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HUI SHU-PING

Faculty of Health Sciences Health Sciences Medical Laboratory ScienceProfessor
Center for Environmental and Health SciencesProfessor

Researcher basic information

■ Nickname etc.
  • HUI SP
■ Degree
  • 医学博士, 北海道大学
■ URL
researchmap URLホームページURL■ Various IDs
Researcher number
  • 90337030
■ Research Keywords and Fields
Research Keyword
  • 抗酸化物質
  • リポタンパク質
  • 酸化ストレス
  • 糖尿病腎症
  • Medium chain fatty acids
  • Lipid hydroperoxide
  • 酸化リポ蛋白
  • 過酸化脂質
Research Field
  • Life Science, Pathological biochemistry, Laboratory medicine
  • Life Science, Nutrition science and health science, 臨床栄養学
  • Life Science, Nephrology
  • Others, Others, 臨床化学・分析化学・病態検査学
■ Educational Organization

Career

■ Career
Career
  • Aug. 2014 - Present
    Hokkaido University, Faculty of Health Sciences, 教授
  • Apr. 2012 - Jul. 2014
    Hokkaido University, 准教授
  • Nov. 2010 - Mar. 2012
    北海道大学 大学院保健科学研究院 健康科学分野, 特任准教授
  • Mar. 2006 - Sep. 2010
    北海道医療大学 薬学部 生命物理科学講座, 講師
  • Feb. 2001 - Mar. 2006
    北海道医療大学 薬学部 生命物理科学講座, 助教
  • Jan. 1999 - Jan. 2001
    日本学術振興会 外国人特別研究員 (北海道医療大学 薬学部 生命物理科学講座)
Educational Background
  • Apr. 1994 - Jun. 1997, Hokkaido University, School of Medicine, 医学部 医学博士号取得
  • Sep. 1981 - Jul. 1986, 中国西安医科大学, 医学部 卒業
Committee Memberships
  • Sep. 2025 - Present
    日本医用マススペクトル学会, 理事, 日本医用マススペクトル学会, 理事
  • Apr. 2021 - Present
    日本臨床化学会, 理事, Society
  • Nov. 2019 - Present
    日本未病学会, 理事, Society
  • Oct. 2015 - Present
    日本医用マススペクトル学会東日本支部, 幹事
  • Aug. 2015 - Present
    日本過酸化脂質・抗酸化物質学会, 幹事, Society
  • Nov. 2014 - Present
    日本未病学会, 評議員, Society
  • Apr. 2013 - Present
    日本臨床化学会, 評議員, Society
  • Sep. 2012 - Present
    日本臨床検査医学会, 北海道支部幹事, Society
  • Apr. 2012 - Present
    日本医用マス学会, 評議員, Society
  • Apr. 2010 - Present
    日本臨床化学会北海道支部, 幹事, Society
  • Sep. 2009 - Present
    日本医用マススペクトル学会, 評議員, Society
  • Sep. 2019 - Sep. 2023
    日本医用マススペクトル学会, 理事, Society
  • Apr. 2021 - Mar. 2023
    北海道大学 国際連携機構中国北京オフィス, 所長, Others
  • Apr. 2018 - Mar. 2022
    日本臨床化学会 北海道支部, 支部長, Society
  • Apr. 2016 - Mar. 2020
    北海道大学 保健科学研究院, 研究院長補佐
  • Jan. 2015 - Dec. 2019
    日本臨床検査医学会, 評議員, Society
  • Apr. 2015 - Mar. 2019
    日本臨床化学会, 理事, Society
  • Apr. 2011 - Mar. 2019
    日本臨床化学会, 国際交流委員会, Society

Research activity information

■ Awards
  • Dec. 2025, 北海道大学, 2025年度北海道大学桂田芳枝賞
  • May 2022, 令和3年度 北海道大学保健科学研究院長賞
  • Sep. 2021, by the Lipoprotein and Vascular Disease Division of AACC, USA, Zak Award, AACC, USA, 2021
    Shu-Ping Hui
  • Jun. 2020, 令和元年度 北海道大学保健科学研究院長賞
  • May 2018, 平成29年度 北海道大学保健科学研究院長賞
    惠 淑萍
  • Nov. 2014, 第21回日本未病システム学会優秀賞
    惠 淑萍
  • Aug. 2011, 2011年度 日本臨床化学会 学術賞
    惠 淑萍
■ Papers
  • Development of analytical methods for the quantification and enhanced detection of unsaturated short-chain FAHFAs
    Rachana M. Gangadhara; Perumalsamy Parasuraman; Divyavani Gowda; Hariom Yadav; Ganesh V. Halade; Shu-Ping Hui; Siddabasave Gowda B. Gowda
    Analytica Chimica Acta, 1404, 345435, 345435, Jun. 2026, [International Magazine]
    English, Scientific journal, Short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs) comprise a novel class of endogenous lipids predominantly localized in the gut and play essential roles in metabolic and inflammatory regulation. Previous studies have enabled chemical synthesis and quantitative analysis of saturated SFAHFAs using validated analytical methods. However, the detection and quantification of unsaturated SFAHFAs remains challenging because of their synthetic complexity and inherently low abundance in biological matrices. In this study, a comprehensive in-house library comprising thirty isomeric unsaturated SFAHFAs was synthesized to facilitate the development of two LC-MS/MS based analytical approaches: (i) direct analysis without derivatization for reliable quantification and (ii) a sensitivity-enhanced method based on 2-(2-pyridyl) ethylamine derivatization. Liquid chromatography-tandem mass spectrometry was optimized for sensitive and selective quantification, demonstrating excellent linearity with limits of detection between 0.5 and 5 fmol and limits of quantification between 5 and 50 fmol. The non-derivatized method was used to profile fecal SFAHFAs in murine and human samples. In mice, exercise increased the levels of both saturated and unsaturated SFAHFAs, whereas an obesogenic diet selectively reduced saturated SFAHFA levels. By contrast, analysis of fecal samples from humans with mild cognitive impairment revealed no significant differences from those of healthy controls, suggesting potential disease- and matrix-specific variability. A chemical derivatization approach using 2-(2-pyridyl) ethylamine enhanced detection sensitivity by approximately 1000-fold with LOD between 0.0005 and 0.001 fmol and LOQ 0.005 and 0.01 fmol. This study presents an analytical approach for the synthesis, quantification, and improved detection of unsaturated SFAHFAs, establishing a foundation for the further exploration of their roles in metabolic disorders associated with gut dysbiosis.
  • Comprehensive lipidomic profiling of dietary Indian millets and identification of fatty acid esters of hydroxy fatty acids by untargeted LC/MS.
    Kumari Suraksha; Divyavani Gowda; Chandra Nayaka Siddaiah; Tara Satyavathi Chellapilla; Shu-Ping Hui; Siddabasave Gowda B Gowda
    Food chemistry, 511, 148792, 148792, 15 May 2026, [International Magazine]
    English, Scientific journal, Millets are small-seeded coarse cereals gaining attention for their nutraceutical potential in managing metabolic disorders. Although millets are widely consumed in South Asia and Africa, their bioactive lipid composition remains largely unexplored. In this study, nontargeted lipidomics analysis was performed on 59 varieties from six Indian millet species using liquid chromatography/mass spectrometry. A total of 219 lipid species were identified, with glycerolipids being most abundant, followed by glycerophospholipids. Foxtail millet showed the highest ratio of polyunsaturated to saturated fatty acids and the highest total lipid content. Little millet exhibited the highest health promotion index, whereas finger millet demonstrated elevated polyunsaturated fatty acid levels, reflecting improved favorable nutritional composition. This study provides the first identification of fatty acid esters of hydroxy fatty acids in Indian millets. This lipid profiling highlights the potential of millets as functional foods and underscores the need for further research on bioactive lipids for metabolic health applications.
  • Hyperlipidemia promotes neutrophil extracellular trap-mediated osteonecrosis of the femoral head following methylprednisolone pulse in lupus mice.
    Hodaka Ogawa; Naho Ogawa; Mizuki Fukuyama; Shota Homma; Suishin Arai; Momo Uchizawa; Riku Manabe; Koki Takai; China Washio; Ikuma Hori; Yuka Nishibata; Sakiko Masuda; Toshihiro Sakurai; Shu-Ping Hui; Kanako Watanabe-Kusunoki; Daigo Nakazawa; Utano Tomaru; Tomohiro Shimizu; Norimasa Iwasaki; Akihiro Ishizu
    Immunobiology, 231, 3, 153178, 153178, 09 Apr. 2026, [International Magazine]
    English, Scientific journal, Methylprednisolone (mPSL) pulse therapy is an essential treatment for systemic lupus erythematosus (SLE); however, it carries a risk of osteonecrosis of the femoral head (ONFH). The pathogenesis of ONFH involves neutrophil extracellular trap (NET)-mediated microcirculation disorders. In BALB/c mice with imiquimod (IMQ)-induced lupus, mPSL pulse elevated serum levels of prenylcysteine oxidase 1 (PCYOX1), an enzyme that produces NET inducers hydrogen peroxide and farnesal, resulting in increased NETs in vivo. Although ischemia was observed in the femoral head, IMQ + mPSL-treated BALB/c mice did not develop ONFH. PCYOX1 is abundant in very-low-density lipoproteins. This study aimed to demonstrate that hyperlipidemia exacerbates NET-mediated microcirculation disorders and leads to ONFH development following mPSL pulse in lupus mice. To address this, ApoE mutant hyperlipidemic and BALB/c mice with IMQ-induced lupus received mPSL pulse. NET-forming neutrophils in peripheral blood were detected by flow cytometry. ONFH was assessed microscopically. As a result, IMQ + mPSL-treated ApoE mutant but not BALB/c mice developed ONFH, exhibiting higher levels of PCYOX1 and NET-forming neutrophils in circulation. In addition, NET-forming neutrophils accumulated in the vessels surrounding the femoral head, accompanied by osteocyte necrosis. This study demonstrated that mPSL pulse in lupus mice with hyperlipidemia enhanced PCYOX1 levels and NET formation, resulting in ONFH development, suggesting that hyperlipidemia may be a risk factor for ONFH following mPSL pulse therapy in SLE.
  • Hydrogen gas with hypothermic machine perfusion induces lipidomic alterations in donation-after-cardiac-death rat livers
    Yusuke Minami; Siddabasave Gowda B. Gowda; Kengo Shibata; Sodai Sakamoto; Divyavani Gowda; Tsuyoshi Shimamura; Akinobu Taketomi; Hitoshi Chiba; Moto Fukai; Shu-Ping Hui
    Journal of Lipid Research, 101040, 101040, Apr. 2026, [International Magazine]
    English, Scientific journal, Hypothermic machine perfusion (HMP) combined with hydrogen gas has previously been shown to mitigate ischemia-reperfusion injury (IRI) in rat liver, but without full recovery of function. This study examined how hydrogen gas modulates hepatic lipid metabolism during HMP using donation after cardiac death (DCD) rat livers. Untargeted liquid chromatography-mass spectrometry was employed to perform comprehensive lipidomic profiling of liver samples. The analysis results revealed distinct lipid metabolic alterations across cold storage (CS), machine perfusion (MP), and hydrogen-supplemented perfusion (MP-H2) groups compared to healthy controls. Compared with MP, MP-H2 treatment reduced lysophosphatidylinositol (LPI) levels and the LPI/phosphatidylinositol (PI) ratio while increasing phosphatidic acid (PA) species such as PA (18:0/18:1) and PA (18:0/20:4). Elevated lysophosphatidylethanolamine (LPE) and ceramide (Cer) in MP-H2 suggested adaptive remodeling of membrane lipids. The ratio of monolysocardiolipin to cardiolipin increased in the MP group but was reduced following hydrogen gas treatment. These lipidomic shifts imply that hydrogen gas attenuates IRI by stabilizing lipid homeostasis and may improve DCD graft viability. Furthermore, the restoration of key lipid species associated with mitochondrial integrity and membrane remodeling suggests that hydrogen gas supports bioenergetic recovery and limits oxidative membrane damage during reperfusion. Overall, these findings highlight the potential of hydrogen-enriched perfusion as a metabolic intervention to enhance organ preservation, reduce mitochondrial dysfunction, and extend the usable lifespan of DCD liver grafts for transplantation.
  • Development of a Lipidomics-Based Cell Screening Platform for Indirect Antioxidants Targeting Oxidized Lipid Droplet Formation and Mitochondrial Membrane Abnormality
    Yuzu Shibata; Toshihiro Sakurai; Akiko Sakurai; Misuzu Sato; Shu-Ping Hui
    Nutrients, 18, 5, 24 Feb. 2026, [International Magazine]
    English, Scientific journal, Background/Objectives: Oxidized lipid droplet formation and cardiolipin (CL) profile abnormality in mitochondrial membranes are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). However, studies on cell models to easily and simultaneously assess the preventive effects on oxidized lipid droplet formation and CL abnormality by indirect antioxidants are limited. Here, we aimed to develop a lipidomics-based cell screening platform to simultaneously evaluate the preventive effects of indirect antioxidants on oxidized lipid droplet formation and mitochondrial membrane lipid abnormalities. Methods: We created a novel lipidomics-based cell screening platform using oxidized low-density lipoprotein (oxLDL) and a human liver-derived cell line (C3A), and screened indirect antioxidants to promote the expression of cellular antioxidant enzymes, preventing oxidized lipid droplet formation. Results: Mass spectrometry revealed that oxLDL increased the levels of cholesteryl ester hydroperoxides. Thus, oxidized lipid droplet formation was confirmed. Three indirect antioxidants (kaempferol, quercetin, and hesperetin) were examined in the lipidomics-based platform. Consequently, quercetin significantly decreased major lipids and lipid hydroperoxide species, particularly triglycerides and triglyceride hydroperoxides with five or more double bonds. Furthermore, fluorescence microscopy revealed that quercetin reduced the size of small oxidized lipid droplets; it also decreased monolysocardiolipin, which could be associated with mitochondrial dysfunction. Conclusions: Overall, we demonstrated that this method could be useful for screening indirect antioxidants with excellent preventive effects against oxidized lipid droplet formation and CL abnormality by simultaneously analyzing various lipids.
  • Lipidomic signatures reveal biomarkers of mild cognitive impairment.
    Jayashankar Jayaprakash; Siddabasave Gowda B Gowda; Divyavani Gowda; Shalini Jain; Hariom Yadav; Shu-Ping Hui
    Translational psychiatry, 16, 1, 16 Feb. 2026, [International Magazine]
    English, Scientific journal, Mild cognitive impairment (MCI) is an early stage in the progression toward dementia. Lipids are central to neurodegeneration, yet the biomarker potential of lipidomics from saliva, plasma, and feces remains underexplored. As part of the Microbiome in Aging Gut and Brain (MiaGB) consortium, saliva, plasma, and fecal samples were collected from older adults with MCI and healthy controls. Samples were analyzed by high-performance liquid chromatography coupled with high-resolution mass spectrometry (LC/MS), to profile lipidomic alterations and identify candidate biomarkers. Lipidomic profiling annotated over 200 molecular species spanning five major lipid classes. Compared with controls, MCI patients exhibited increased oxidized triacylglycerols (oxTGs) in saliva, reduced cholesteryl linoleate (CE 18:2) in plasma, and decreased fatty acid esters of hydroxy fatty acids (FAHFAs) in feces. Receiver operating characteristic (ROC) analysis identified α-linolenic acid (FA 18:3), docosapentaenoic acid (FA 22:5), and CE 18:2 as discriminatory metabolites with notable diagnostic performance. Moreover, elevated fecal triacylglycerols containing medium-chain fatty acids (TG-MCFAs) were observed in MCI, suggesting impaired lipid absorption or altered metabolism. This multi-sample lipidomics strategy highlights TG-MCFAs as fecal biomarkers for MCI detection, supporting further mechanistic and longitudinal validation.
  • Lysophosphatidylethanolamine Degradation Associated with Upregulation of Pnpla6/7 in a Murine Model of Metabolic Dysfunction-Associated Steatohepatitis
    Nao Inoue; Hsin-Jung Ho; Siddabasave Gowda B. Gowda; Miki Eguchi; Minato Masamura-Takeuchi; Hitoshi Chiba; Shu-Ping Hui
    International Journal of Molecular Sciences, 27, 4, 15 Feb. 2026, [International Magazine]
    English, Scientific journal, Metabolic dysfunction-associated steatohepatitis (MASH) is a form of fatty liver disease characterized by fat accumulation, hepatic inflammation, and fibrosis. Lysophosphatidylethanolamine (LPE), a partially deacylated product of phosphatidylethanolamine, plays significant roles in anti-inflammatory responses and mitochondrial homeostasis. Although serum LPE levels are reduced in patients with MASH, the underlying mechanisms remain unclear. In this study, we investigated LPE metabolism using liquid chromatography-tandem mass spectrometry and protein expressions in MASH mice. Male C57BL/6J mice were fed a high-fat, high-cholesterol, and cholic acid diet, along with 2% hydroxypropyl-β-cyclodextrin in drinking water (HFCC/CDX) for three weeks to induce MASH. LPE was primarily distributed in the liver and kidneys, with lower levels in the white adipose tissue. HFCC/CDX mice exhibited accumulation of cholesterols and oxidized triglycerides, accompanied by inflammation and fibrosis in the liver. In the plasma and liver of HFCC/CDX mice, most LPE species were decreased and showed negative correlations with hepatic inflammation, with the exception of LPE 18:1. Mechanistically, enhanced degradation of LPE to glycerophosphorylethanolamine was associated with upregulation of Pnpla6/7 in the liver. These findings suggest that Pnpla6/7-driven LPE catabolism is contributing to LPE depletion. This study provides a new perspective to understand the association between disrupted phospholipid metabolism and MASH pathogenesis.
  • Brain lipidomics for region-specific biomarker discovery in neurodegenerative diseases
    Jayashankar Jayaprakash; Solomon Tebeje Gizaw; Divyavani Gowda; Hiroshi Hinou; Shin-Ichiro Nishimura; Shu-Ping Hui; Siddabasave Gowda B. Gowda
    FRONTIERS IN AGING NEUROSCIENCE, 18, 1757306, 1757306, 11 Feb. 2026, [International Magazine]
    English, Scientific journal
  • Lipidomic profiling of 56 japonica rice cultivars and identification of novel fatty acid esters of hydroxy fatty acids.
    Lipsa Rani Nath; Siddabasave Gowda B Gowda; Divyavani Gowda; Perumalsamy Parasuraman; Wei Qin; Shu-Ping Hui
    Food research international (Ottawa, Ont.), 223, Pt 2, 117895, 117895, 15 Jan. 2026, [International Magazine]
    English, Scientific journal
  • Sex- and Regio-Specific Lipid Profiling of Shishamo and Capelin Fish by Nontargeted Liquid Chromatography/Mass Spectrometry
    Yusuke Minami; Siddabasave Gowda B. Gowda; Divyavani Gowda; Hitoshi Chiba; Shu-Ping Hui
    Foods, 15, 2, 14 Jan. 2026, [International Magazine]
    English, Scientific journal
  • Antioxidant Clove Extract Inhibits Lipid Droplet Accumulation and Lipid Oxidation in Hepatocytes
    Satomi Monde; Dya Fita Dibwe; Shion Iwasaki; Shu-Ping Hui
    Metabolites, 16, 1, 22 Dec. 2025, [International Magazine]
    English, Scientific journal, BACKGROUND: Recent studies have shown that plant-based dietary extracts can prevent the formation of lipid droplets (LDs) and oxidized lipid droplets (oxLDs) in liver cells. These results indicate that these extracts might be useful in addressing metabolic dysfunction-associated fatty liver disease (MAFLD) and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH). In our ongoing study, we evaluated the potential of various food extracts to inhibit the accumulation and oxidation of LDs in liver cells to prevent metabolic MAFLD and MASH. METHODS: The antioxidant activity index was determined using the DPPH assay, cell viability was assessed via cytotoxicity and lipotoxicity, and lipid droplet accumulation inhibition (LDAI) assays were performed. Metabolome analysis was performed using 1D-NMR [1H, 13C, DEPT 90, and 135] techniques. RESULTS: Dietary clove (Syzygium aromaticum) extract exhibited antioxidant properties and inhibited linoleic acid-induced lipid droplet (LD) accumulation (LDA) and oxidized LDA (oxLDA) in HepG2 cells. Additionally, an analysis of the metabolome of dietary clove bioactive LDAI using 1D-NMR showed that clove extract (CE) mainly consists of hydroxybenzoic acids (HBAs) and hydroxycinnamic acids (HCAs), along with minor amounts of carbohydrates, coumarins, polyphenolic compounds, and small quantities of polyols, fatty acyls, small peptides, and amino acids. This suggests that CE could be a promising resource for developing functional foods and nutraceuticals and discovering drugs for treating MAFLD, MASH, and related conditions.
  • Effects of Yomogi Tea on Lipid Metabolism in Renal Tubular HK-2 Cells
    Wei Qin; Hsin-Jung Ho; Xun-Zhi Wu; Miki Eguchi; Manami Uchita; Minato Takeuchi; Shu-Ping Hui
    Foods, 14, 22, 07 Nov. 2025, [International Magazine]
    English, Scientific journal, Excessive accumulation of lipid droplets (LDs), their dynamics, and lipotoxicity are critical factors in the progression of metabolic disorders, including diabetic nephropathy. This study investigates the effects of yomogi tea (Mugwort tea), specifically its leaf infusion (YL) and powdered infusion (YP), on lipid metabolism in human kidney proximal tubular epithelial HK-2 cells under lipotoxic conditions induced by palmitic acid (PA). Both YL and YP significantly reduced intracellular triglyceride (TG) and free fatty acid (FFA) levels, with YP showing a trend toward greater efficacy. Mechanistic analysis revealed that yomogi tea regulates lipid metabolism by significantly downregulating mRNA expression of FAS and upregulating that of the lipolytic ATGL, while SCD-1 mRNA expression remained largely unchanged. Furthermore, yomogi tea reduced LD size and neutral lipid content, potentially enhancing lipid hydrolysis efficiency and mitigating lipotoxic effects. These findings highlight the potential of yomogi tea as a natural agent for regulating lipid metabolism and reducing lipotoxicity, offering promise for managing lipid metabolism-related disorders.
  • Effect of exercise on multi-compartment lipid metabolism in murine models fed an obesogenic diet using non-targeted LC/MS
    Rachana M. Gangadhara; Divyavani Gowda; Siddabasave Gowda B. Gowda; Gunjan Upadhyay; Nikhil Chainani; Vasundara Kain; Ganesh V. Halade; Shu-Ping Hui
    Frontiers in Nutrition, 12, 1673002, 1673002, Frontiers Media SA, 23 Oct. 2025, [International Magazine]
    English, Scientific journal, Background

    Chronic inflammation from obesogenic diets (OBD) disrupts lipid metabolism and contributes to non-communicable metabolic diseases. Exercise is a non-drug intervention that reduces inflammatory metabolic diseases by improving lipid metabolism. However, there are research gaps in understanding how the lipid metabolites are altered by exercise under an OBD.

    Methods

    Two-month-old male C57BL/6 J mice were fed a control (CON diet-Standard Lab Chaw-3.4%w/w Teklad Global #2918) or OBD for 10 months, then assigned to sedentary (Sed) or exercise (Exe) groups for 2 weeks. This study aims to examine changes in lipid metabolites in plasma, tissues, and feces of mice using untargeted liquid chromatography/mass spectrometry (LC/MS). Echocardiography was used to assess the impact of OBD on heart function.

    Results

    A total of 363 lipid molecular species were identified and characterized in the murine samples by retention time behavior and MS/MS spectral annotation. Multivariate analysis showed a distinct group separation between CON and OBD groups in both Sed and Exe groups. Phospholipids acylated with docosahexaenoic acid (DHA) are the key metabolites responsible for group separation in tissues and plasma, whereas in feces, glycerolipids, mainly monoacylglycerols. Lysophosphatidylethanolamine (LPE 22:5) was significantly upregulated in the liver, plasma, and left ventricle of the OBD mice in both Sed and Exe groups, contradictorily DHA containing phosphatidylglycerol [PG (22:6/22:6)] was significantly downregulated. Exercise modestly modulated the lipid profile under OBD, lowering plasma ceramides and partially reversing lipid alterations in feces. Interestingly, exercise combined with a control diet led to an increase in gut-microbiota-derived short-chain fatty acid esters of hydroxy fatty acids.

    Conclusion

    Chronic OBD induces distinct lipid alterations across multiple biological compartments. Short-term exercise provides modest improvements, with stronger benefits when combined with a balanced diet.
  • Development of a Liquid Chromatography–Tandem Mass Spectrometry Method for Oxylipin Analysis and Its Application to Children’s Plasma
    Yonghan Li; Siddabasave Gowda B. Gowda; Divyavani Gowda; Atsuko Ikeda; Yu Ait Bamai; Rahel Mesfin Ketema; Reiko Kishi; Hitoshi Chiba; Shu-Ping Hui
    Diagnostics, 15, 15, 25 Jul. 2025, [International Magazine]
    English, Scientific journal, Background/Objectives: Oxylipins, a family of oxygenated natural products derived from polyunsaturated fatty acids (PUFAs), play crucial roles in various physiological processes. Evaluating their levels in vivo helps to reveal their roles in health and disease. Because of the numerous isomers of oxylipins, it is essential to develop efficient and precise analytical methods for their identification and quantification. The objective of this study is to establish a quantitative method for oxylipin analysis and its application to the assessment of oxylipins in children's plasma, with potential implications for diagnostic use in pediatric populations. Methods: A liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed to quantify 64 oxylipins and four precursor PUFAs within 36 min. The limits of quantification ranged from 0.25 to 50 pg, with most analytes showing recoveries and matrix effects between 85 and 110% and between 90 and 110%, respectively. Intra- and inter-day precision values were within 15%. The established method was applied to plasma samples from children aged 9-12 years (boys = 181; girls = 161) in Hokkaido, Japan, to assess the relation between plasma oxylipin and PUFA levels and age, sex, and body mass index. Results: There was no significant correlation between oxylipin levels and age, sex, or body mass index. However, among the PUFAs, boys had higher eicosapentaenoic acid and arachidonic acid levels than those of girls, with a significant increase in eicosapentaenoic acid levels in the overweight group compared with those in the underweight group. Conclusions: We successfully developed a simple and highly selective method for the analysis of oxylipins in preadolescent children's plasma samples. Thus, this study provides a foundation for broader application of the developed method to different biological samples in future studies.
  • Lipidomic Profiling of Edible Japanese Sea Urchins by LC–MS
    Sahana Amai; Kisara Yuki; Siddabasave Gowda B. Gowda; Divyavani Gowda; Shu-Ping Hui
    Foods, 14, 13, 26 Jun. 2025, [International Magazine]
    English, Scientific journal, Sea urchins (Echinoidea) are marine echinoderms commonly consumed as seafood in East Asia. To date, various metabolic components of sea urchins have been analyzed, and their health benefits for humans have also been attracting attention. Lipids are the major biomolecules present in sea urchins. However, the comprehensive lipid profiling of sea urchins is limited. In this study, we aimed to perform the comprehensive lipid profiling of six types of sea urchins using liquid chromatography-mass spectrometry (LC/MS). The application of untargeted lipidomics led to the identification of 281 lipid molecular species in six varieties of fresh sea urchin gonads. Each lipid metabolite was identified based on its retention time and MS/MS fragmentation pattern. The results of the analysis showed the highest abundance of lipid percentage in Kitamurasakiuni (14.3%), followed by Hokuyobafununi (12.4%). In all the analyzed sea urchins, glycerolipids such as triacylglycerols were found to be the most abundant lipid components. Multivariate analysis revealed that Murasakiuni showed a different lipid profile from the other types. Interestingly, the polyunsaturated fatty acid to saturated fatty acid ratios and health-related nutritional indices factors were found to be higher in Hokuyobafununi compared to other varieties. The ω-3 fatty acids, such as docosapentaenoic acid (FA 22:6) and eicosapentaenoic acid (FA 20:5), were also abundant in Hokuyobafununi. Lipids such as ether and N-acyl-type lysophosphatidylethanolamines were detected for the first time in sea urchins. This study highlights the nutritional significance of sea urchins and their potential use in the development of functional foods.
  • Inhibition of Triacylglycerol Accumulation and Oxidized Hydroperoxides in Hepatocytes by Allium cepa (Bulb)
    Dya Fita Dibwe; Saki Oba; Satomi Monde; Shu-Ping Hui
    Antioxidants, 14, 6, 29 May 2025, [International Magazine]
    English, Scientific journal, Recent studies have demonstrated that dietary plant extracts can inhibit the development of lipid droplets (LDs) and oxidized LDs (oxLDs) in hepatic cells. These findings suggest that such extracts may be beneficial in combating metabolic dysfunction-associated fatty liver disease (MAFLD) and its more advanced stage, metabolic dysfunction-associated steatohepatitis (MASH). We examined nine Allium extracts (ALs: AL1-9) to assess their capacity to decrease lipid droplet accumulation (LDA) and oxidative stress by suppressing lipid formation and oxidation in liver cells. Among the Allium extracts tested, AL6 exhibited significant inhibitory effects against LDA. Furthermore, we employed our lipidomic method to assess the accumulation and suppression of intracellular triacylglycerol (TAG) and oxidized TAG hydroperoxide [TG (OOH) n = 3] by AL6 in liver cells under oleic acid (OA) and linoleic acid (LA) loading conditions. These findings indicate that foods derived from Allium species prevent the formation of lipid droplets by decreasing intracellular lipids and lipid hydroperoxides in the hepatocytes. Analysis of the metabolome of bioactive lipid droplet accumulation inhibition (LDAI) AL6 using LC-MS/MS and 1D-NMR [1H, 13C, DEPT 90, and 135] techniques revealed that AL6 is primarily composed of carbohydrates, glucosidic metabolites, and organosulfur compounds, with small amounts of polyols, fatty acyls, small peptides, and amino acids. This implies that AL6 could be a valuable resource for developing functional foods and drug discovery targeting metabolic dysfunction-associated fatty liver disease (MAFLD)/metabolic dysfunction-associated steatohepatitis (MASH) and related disorders.
  • Vitamin K2 Attenuates Mitochondrial Damage in Renal Proximal Tubular Cells.
    Hsinjung Ho; Natsumi Aoki; Miki Eguchi; Mingchen Gao; Hirotaka Suzuki; Mao Mikami; Hitoshi Chiba; Shu-Ping Hui
    Journal of agricultural and food chemistry, 73, 35, 21857, 21868, 21 May 2025, [International Magazine]
    English, Scientific journal, Excessive reactive oxygen species (ROS) levels cause oxidative stress, which can lead to various diseases. Renal failure is associated with oxidative stress and mitochondrial dysfunction. Vitamin K1 (phylloquinone) and K2 (menaquinone) are essential for blood coagulation and bone formation. Vitamin K has been shown to have anti-inflammation, glucose metabolism regulation, and antiferroptosis functions. We investigated the impact of menaquinone-4 (MK-4) on oxidative stress and mitochondrial dysfunction in human renal proximal tubular cells. MK-4 protected cells from oxidative damage induced by l-buthionine-(S,R)-sulfoximine (BSO), a selective inhibitor of glutathione metabolism, by inhibiting cell death, mitochondrial ROS production, and lipid peroxidation. MK-4 also reduced lactate production, prevented mitochondrial fragmentation, and improved mitochondrial respiratory function, indicating cytoprotective effects. Moreover, it enhanced intracellular ATP production and respiratory capacity, even in the absence of oxidative stress. Thus, MK-4 plays an important role in mitochondrial function in renal proximal tubular cells.
  • Discovering Novel Short- and Medium-Chain Esters of Hydroxy Fatty Acids in Human Fecal Samples Using Untargeted Liquid Chromatography/Mass Spectrometry.
    Jayashankar Jayaprakash; Divyavani Gowda; Rachana M Gangadhara; Shalini Jain; Hariom Yadav; Siddabasave Gowda B Gowda; Shu-Ping Hui
    Rapid communications in mass spectrometry : RCM, 39, 12, e10032, 30 Apr. 2025, [International Magazine]
    English, Scientific journal, RATIONALE: Exploring novel metabolites produced by host gut microbiome communication is crucial for understanding their roles in various disease pathologies. We previously uncovered a novel class of lipids, short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs), in mouse fecal samples and demonstrated their promising physiological functions in mammals. However, the discovery of SFAHFAs in human samples remains unexplored. METHODS: This study aimed to analyze the SFAHFAs and their structural analogs in human fecal samples using liquid chromatography/mass spectrometry. RESULTS: We identified 26 isomeric lipid species, including SFAHFAs and novel medium-chain fatty acid esters of hydroxy fatty acids (MFAHFAs). The detected SFAHFAs and MFAHFAs were characterized by accurate mass measurements using MSn analysis. The results were validated by matching the mass spectral fragmentation and retention time with authentic standards. Two new MFAHFAs, enanthic acid and caprylic acid esters of long-chain hydroxy fatty acids (C24 and C26), were detected and characterized for the first time in human fecal samples. Among the 26 isomeric lipid species, SFAHFA 2:0/24:0 or 4:0/22:0 and SFAHFA 2:0/24:1 were most abundant among the saturated and unsaturated SFAHFAs, respectively. CONCLUSIONS: This study offers the first insights into detecting and characterizing novel gut microbial lipids in human fecal samples. Further investigations are essential to recognize the metabolism and function of these lipids in the human gut.
  • Comparative Study of Total Polyphenol Content and Antioxidant Activity of Yomogi Tea and Green Tea during Simulated In Vitro Gastrointestinal Digestion
    Wei Qin; Fei-fei Hu; Shu-ping Hui
    ACS Food Science & Technology, 5, 4, 1392, 1399, American Chemical Society (ACS), 18 Mar. 2025, [Peer-reviewed], [Last author, Corresponding author]
    Scientific journal
  • Long-term survival and durable recovery of heart failure in patients with triglyceride deposit cardiomyovasculopathy treated with tricaprin.
    Ken-Ichi Hirano; Satomi Okamura; Koichiro Sugimura; Hideyuki Miyauchi; Yusuke Nakano; Kotaro Nochioka; Chikako Hashimoto; Yoshitaka Iwanaga; Kenichi Nakajima; Satoshi Yamaguchi; Yoko Yasui; Shinsaku Shimamoto; Makito Hirano; Mana Okune; Yuki Nishimura; Hisashi Shimoyama; Yasuyuki Nagasawa; Tetsuya Amano; Shimpei Kuniyoshi; Shu-Ping Hui; Nobuhiro Zaima; Yoshihiko Ikeda; Tomomi Yamada; Shinichiro Fujimoto; Yasuhiko Sakata; Kunihisa Kobayashi
    Nature cardiovascular research, 4, 3, 266, 274, Mar. 2025, [International Magazine]
    English, Scientific journal, Heart disease is a major global threat. Triglyceride deposit cardiomyovasculopathy (TGCV) is an emerging, noncommunicable, adult-onset heart disease, first identified in Japanese patients with heart failure (HF) requiring cardiac transplantation1-3. In TGCV, defective intracellular lipolysis of long-chain triglycerides (TGs) results in cellular steatosis and energy failure mainly in cardiomyocytes4 and smooth muscle cells5, leading to HF, diffuse coronary artery disease with TG deposition and ventricular arrhythmias with high mortality6. Tricaprin, a class of medium-chain TGs, recently corrected myocardial TG lipolysis7. Here we report remarkable long-term survival and durable recovery of HF in patients with TGCV treated with supplemental tricaprin in registry studies. Our study offers a classification of heart disease caused by defective lipolysis and its possible practical treatment. Because myocardial lipid droplets are a common feature in HF and their potential as therapeutic targets has been discussed worldwide, our findings warrant investigation into other ethnicities.
  • Application of Liquid Chromatography/Tandem Mass Spectrometry for Quantitative Analysis of Plasmalogens in Preadolescent Children—The Hokkaido Study
    Yifan Chen; Siddabasave Gowda B. Gowda; Divyavani Gowda; Jayashankar Jayaprakash; Lipsa Rani Nath; Atsuko Ikeda; Yu Ait Bamai; Rahel Ketema; Reiko Kishi; Hitoshi Chiba; Shu-Ping Hui
    Diagnostics, 15, 6, Mar. 2025, [International Magazine]
    English, Scientific journal, Background: Plasmalogens (Pls) are phospholipids with a unique structure, abundant in the brain and heart. Due to their chemical instability and analytical difficulties, less information is available compared to other phospholipids. The importance of Pls in several cellular processes is known, one of which is their protective effect against oxidative damage. The physiological role of Pls in human development has not been elucidated. Despite their clinical importance, the quantitative analysis of Pls in children's plasma has been limited. Methods: This study aims to determine the plasma levels of Pls in prepubertal children using liquid chromatography/tandem mass spectrometry (LC-MS/MS). The plasma samples used were obtained from 9- to 12-year-old girls (n = 156) and boys (n = 178), n = 334 in total, who participated in the Hokkaido study. Results: Ethanolamine plasmalogen (PlsEtn) and choline plasmalogen (PlsCho), both carrying eicosapentaenoic acid, were significantly lower in girls than in boys. In both sexes, the plasmalogen levels for the 12-year-old children were lower than those for the 9-year-old children. PlsCho (16:0/18:2) was lower in the overweight children than in the normal-weight children for both sexes. PlsEtn (18:0/20:4) was the most abundant ethanolamine-type plasmalogen in both sexes. Conclusions: This study is the first report on plasmalogen levels and molecular types in children's plasma. This study provides the information needed to understand the role of Pls in human developmental processes and may open up new opportunities in the future to control age-related changes in Pls.
  • Plasma Lipidomics of Preadolescent Children: A Hokkaido Study
    Jayashankar Jayaprakash; Siddabasave Gowda B. Gowda; Divyavani Gowda; Atsuko Ikeda; Yu Ait Bamai; Rahel Mesfin Ketema; Reiko Kishi; Yifan Chen; Hitoshi Chiba; Shu-Ping Hui
    Journal of Lipids, 2025, 3106145, 3106145, Jan. 2025, [International Magazine]
    English, Scientific journal, Lipids are the most abundant biomolecules of human plasma, and their balance plays a significant role in health and disease management. Despite the importance of lipids, the studies focused on the comprehensive determination of the plasma lipidome in children are limited. In this study, we investigated the sex, age, and weight-specific changes in the plasma lipidome of nonfasting preadolescent children aged 9-12 years (n = 342) using a nontargeted liquid chromatography-mass spectrometry technique. A total of 219 lipid species were characterized in the plasma samples. Multivariate analysis revealed that boys and girls have similar lipid profiles, but relatively higher levels of capric acid-composed triacylglycerols (TGs) were observed in plasma samples of boys. Saturated fatty acids are the most abundant fatty acyls followed by mono- and polyunsaturated fatty acids in the plasma of both boys and girls. Sphingolipids such as ceramides, hexosylceramides, sphingomyelin, and a phospholipid (phosphatidylinositol) were relatively higher in the plasma of a 10-year-old group than other age groups. Plasma levels of TG and phosphatidylserine were increased within age from 9 to 12 years. Furthermore, most of the TG molecular species were increased in the plasma of overweight children compared to the normal range groups. The receiver operating characteristic analysis results show that TG (10:0/10:0/18:1) could be a specific marker for childhood obesity (area under the curve (AUC) = 0.72). Overall, this study highlights the altered plasma lipidome in preadolescent children for sex, age, and percentage of overweight. Early detection of lipid markers for obesity would be a promising target for developing therapeutic strategies.
  • Relationships of the Surface Charge of Low-Density Lipoprotein (LDL) with the Serum LDL-Cholesterol and Atherosclerosis Levels in a Japanese Population: The DOSANCO Health Study
    Nakamura Koshi; Nakamura Koshi; Takeda Seiji; Takeda Seiji; Sakurai Toshihiro; Ukawa Shigekazu; Ukawa Shigekazu; Okada Emiko; Okada Emiko; Nakagawa Takafumi; Imae Akihiro; Hui Shu-Ping; Chiba Hitoshi; Chiba Hitoshi; Tamakoshi Akiko
    Journal of Atherosclerosis and Thrombosis (Web), 32, 1, 34, 47, 2025, [Domestic magazines]
    English, AIM: This study investigated the associations of the surface charge of low-density lipoprotein (LDL) with the serum LDL-cholesterol and atherosclerosis levels in a community-based Japanese population. METHODS: The study had a cross-sectional design and included 409 community residents aged 35-79 years who did not take medications for dyslipidemia. The potential electric charge of LDL and the zeta potential, which indicate the surface charge of LDL, were measured by laser Doppler microelectrophoresis. The correlations of the zeta potential of LDL (-mV) with the serum LDL-cholesterol levels (mg/dL), cardio-ankle vascular index (CAVI), and serum high-sensitivity C-reactive protein (hsCRP) levels (log-transformed values, mg/L) were examined using Pearson's correlation coefficient (r). Linear regression models were constructed to examine these associations after adjusting for potential confounding factors. RESULTS: A total of 201 subjects with correctly stored samples were included in the primary analysis for zeta potential measurement. An inverse correlation was observed between the LDL zeta potential and the serum LDL-cholesterol levels (r=-0.20; p=0.004). This inverse association was observed after adjusting for sex, age, dietary cholesterol intake, smoking status, alcohol intake, body mass index, and the serum levels of the major classes of free fatty acids (standardized β=-6.94; p=0.005). However, the zeta potential of LDL showed almost no association with CAVI or the serum hsCRP levels. Similar patterns were observed in the 208 subjects with compromised samples as well as all the original 409 subjects. CONCLUSION: A higher electronegative surface charge of LDL was associated with lower serum LDL-cholesterol levels in the general Japanese population.
  • Integration of lipidomics with targeted, single cell, and spatial transcriptomics defines an unresolved pro-inflammatory state in colon cancer.
    Ramani Soundararajan; Michelle M Maurin; Jetsen Rodriguez-Silva; Gunjan Upadhyay; Ashley J Alden; Siddabasave Gowda B Gowda; Michael J Schell; Mingli Yang; Noah Jhad Levine; Divyavani Gowda; Punith M Sundaraswamy; Shu-Ping Hui; Lance Pflieger; Heiman Wang; Jorge Marcet; Carolina Martinez; Robert David Bennett; Allen Chudzinski; Andreas Karachristos; Timothy M Nywening; Paul M Cavallaro; Matthew Linley Anderson; Robert J Coffey; Michael V Nebozhyn; Andrey Loboda; Domenico Coppola; Warren Jackson Pledger; Ganesh V Halade; Timothy J Yeatman
    Gut, 74, 4, 586, 602, 20 Dec. 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: Over a century ago, Virchow proposed that cancer represents a chronically inflamed, poorly healing wound. Normal wound healing is represented by a transitory phase of inflammation, followed by a pro-resolution phase, with prostaglandin (PGE2/PGD2)-induced 'lipid class switching' producing inflammation-quenching lipoxins (LXA4, LXB4). OBJECTIVE: We explored if lipid dysregulation in colorectal cancers (CRCs) is driven by a failure to resolve inflammation. DESIGN: We performed liquid chromatography and tandem mass spectrometry (LC-MS/MS) untargeted analysis of 40 human CRC and normal paired samples and targeted, quantitative analysis of 81 human CRC and normal paired samples. We integrated analysis of lipidomics, quantitative reverse transcription-PCR, large scale gene expression, and spatial transcriptomics with public scRNASEQ data to characterize pattern, expression and cellular localisation of genes that produce and modify lipid mediators. RESULTS: Targeted, quantitative LC-MS/MS demonstrated a marked imbalance of pro-inflammatory mediators, with a dearth of resolving lipid mediators. In tumours, we observed prominent over-expression of arachidonic acid derivatives, the genes encoding their synthetic enzymes and receptors, but poor expression of genes producing pro-resolving synthetic enzymes and resultant lipoxins (LXA4, LXB4) and associated receptors. These results indicate that CRC is the product of defective lipid class switching likely related to inadequate or ineffective levels of PGE2/PGD2. CONCLUSION: We show that the lipidomic profile of CRC tumours exhibits a distinct pro-inflammatory bias with a deficiency of endogenous resolving mediators secondary to defective lipid class switching. These observations pave the way for 'resolution medicine', a novel therapeutic approach for inducing or providing resolvins to mitigate the chronic inflammation driving cancer growth and progression.
  • Targeted Circulating Lipid Mediators and Immune Cell Gene Transcripts After ST-Elevation Myocardial Infarction
    Dae Hyun Lee; Gunjan Upadhyay; Siddabasave Gowda B. Gowda; Vasundhara Kain; MD Abdul Malek; Nicholas Carris; Samip Vasaiwala; Timothy Yeatman; Guilherme Oliveira; Shu-Ping Hui; Ganesh V Halade
    American Journal of Physiology-Heart and Circulatory Physiology, 328, 6, H1351-H1360, 20 Dec. 2024, [International Magazine]
    English, Scientific journal, Residual inflammation drives atherogenesis to atherosclerosis and myocardial infarction, which triggers acute inflammation. In preclinical studies, polyunsaturated fatty acids-derived specialized pro-resolving mediators (SPMs) have been shown to promote recovery after MI, in contrast to pro-inflammatory lipid mediators (PIMs). However, the dynamic changes of lipid mediators after ST-elevation myocardial infarction (STEMI), particularly after percutaneous coronary intervention (PCI) and respective gene transcripts, are poorly understood. Therefore, the study aimed to assess the early dynamic changes in circulating lipid mediators and lipid pathway transcripts in STEMI patients who undergo PCI. In this prospective observational clinical study, patients with STEMI (n=10) and control subjects (n=6) were included. Plasma samples for lipid mediator profiling (targeted oxylipids) and whole blood for inflammation-related transcript expression were collected at baseline before PCI, 2 hours, and 24 hours post-PCI. A total of 10 STEMI patients received PCI with a mean age of 53.3 years, 90% male. Linoleic acid and DPA levels were higher in STEMI patients. A subset of PIM levels (HETEs, PGE2) were elevated at the baseline, with a subsequent decrease in circulating levels at 2 hours after PCI (TXB2, LTB4, 20-OH-LTB4). A subset of SPM levels (HEPEs) were elevated at the baseline of STEMI suggestive overlap of inflammation-resolution signaling. The temporal kinetics of LMs showed that both the initiation of inflammation and the resolution process start simultaneously and continue as an endogenous repair mechanism during STEMI. Therefore, approaches to increase these endogenous bioactive resolution mediators content and/or efficacy before PCI should be considered in treating MI patients.
  • Inhibition of Accumulation of Neutral Lipids and Their Hydroperoxide Species in Hepatocytes by Bioactive Allium sativum Extract
    Dya Fita Dibwe; Saki Oba; Satomi Monde; Shu-Ping Hui
    Antioxidants, 13, 11, 1310, 1310, MDPI AG, 28 Oct. 2024, [International Magazine]
    English, Scientific journal, Our ongoing research suggests that extracts from plant-based foods inhibit the accumulation of lipid droplets (LDs) and oxidized lipid droplets (oxLDs) in liver cells. These findings suggest their potential use in the alleviation of metabolic dysfunction-associated fatty liver disease (MAFLD) and its most severe manifestation, metabolic dysfunction-associated steatohepatitis (MASH). Allium extracts (ALs: AL1–AL9) were used to assess their ability to reduce lipid droplet accumulation (LDA) and oxidized lipid droplet accumulation (oxLDA) by inhibiting neutral lipid accumulation and oxidation in LD. Among the tested Allium extracts, AL1, AL3, and AL6 demonstrated substantial inhibitory effects on the LDA. Furthermore, AL1 extract showed real-time inhibition of LDA in HepG2 cells in DMEM supplemented with oleic acid (OA) within 12 h of treatment. Our lipidomic approach was used to quantify the accumulation and inhibition of intracellular triacylglycerol (TAG) and oxidized TAG hydroperoxide [TG (OOH) n = 3] species in hepatocytes under OA and linoleic acid loading conditions. These results suggest that Allium-based foods inhibit LD accumulation by decreasing intracellular lipids and lipid hydroperoxides in the hepatocytes. The metabolomic analysis of AL1—the bioactive LDAI extract—using both LC-MS/MS and 1D-NMR [1H, 13C, and Dept (135 and 90)] approaches revealed that AL1 contains mainly carbohydrates and glucoside metabolites, including iridoid glucosides, as well as minor amino acids, organosulfur compounds, and organic acids such as the antioxidant ascorbic acid (KA2 = S13), and their derivatives, suggesting that AL1 could be a potential resource for the development of functional foods and in drug discovery targeting MAFLD/MASH and other related diseases.
  • Analysis and functions of bioactive lipids in food
    Jayashankar Jayaprakash; Lipsa Rani Nath; Siddabasave Gowda B. Gowda; Divyavani Gowda; Shu-Ping Hui
    Discover Food, 4, 1, Springer Science and Business Media LLC, 14 Oct. 2024
    Scientific journal
  • Nontargeted Lipidomics of Sorghum Grain Reveals Novel Fatty Acid Esters of Hydroxy Fatty Acids and Cultivar Differences in Lipid Profiles
    Lipsa Rani Nath; Siddabasave Gowda B. Gowda; Thomas H. Roberts; Divyavani Gowda; Ali Khoddami; Shu-Ping Hui
    Journal of Agricultural and Food Chemistry, 72, 37, 20690, 20703, American Chemical Society (ACS), 04 Sep. 2024, [International Magazine]
    English, Scientific journal, Sorghum, a globally grown gluten-free cereal, is used mainly as an animal feed in developed countries regardless of its potential for human consumption. In this study, we utilized nontargeted lipidomics to thoroughly analyze, compare, and characterize whole-grain lipids in six sorghum cultivars (cv) grown in a single field trial in Australia: Buster, Bazley, Cracker, Liberty, MR43, and Tiger. In total, 194 lipid molecular species representing five major lipid classes were identified. Multivariate analysis unveiled distinct lipid profiles among the cultivars. The most distinct lipid profile belonged to cv. MR43. The lower ω-6 to ω-3 ratio and optimal P/S ratio in cv. Bazley reflect this as a valuable source of balanced essential fatty acids in the diet. The novel bioactive lipids known as FAHFAs (fatty acid esters of hydroxy fatty acids) were identified and characterized in sorghum grains. These findings further emphasize the potential of whole-grain sorghum as a basis for new health-promoting food products.
  • Lipidomics of herbal tea revealed their potential lipid nutrients including novel fatty acid esters of hydroxy fatty acids
    Rachana M. Gangadhara; Siddabasave Gowda B. Gowda; Kota Yanagimoto; Divyavani Gowda; Hitoshi Chiba; Shu-Ping Hui
    Journal of Food Measurement and Characterization, Springer Science and Business Media LLC, 30 Aug. 2024
    Scientific journal
  • Determination of plasma lysophosphatidylethanolamines (lyso-PE) by LC-MS/MS revealed a possible relation between obesity and lyso-PE in Japanese preadolescent children: the Hokkaido study.
    Nao Inoue; Siddabasave Gowda B Gowda; Divyavani Gowda; Toshihiro Sakurai; Atsuko Ikeda-Araki; Yu Ait Bamai; Rahel Mesfin Ketema; Reiko Kishi; Hitoshi Chiba; Shu-Ping Hui
    Annals of clinical biochemistry, 62, 1, 45632241280352, 45632241280352, 21 Aug. 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: Lysophosphatidylethanolamines (lyso-PEs) are the partial hydrolysis products of phosphatidylethanolamine. Although lyso-PEs are important biomarkers in various diseases, their determination is limited by the lack of simple and efficient quantification methods. This study aims to develop an improved quantitative method for the determination of lyso-PEs and its application to an epidemiological study. METHODS: Single reaction monitoring channels by collision-induced dissociation for seven lyso-PEs were established using liquid chromatography-tandem mass spectrometry. Plasma lyso-PEs were extracted with a single-phase method using an isotopically labeled internal standard for quantification. The proposed method was adopted to define lyso-PEs in plasma samples of children aged 9-12 years living in Sapporo, Japan. RESULTS: The limit of detection and limit of quantification for each lyso-PE ranged between 0.001-0.015 and 0.002-0.031 pmol/μL, respectively. Recoveries were found to be > 91% for all the species. The analysis results of children's plasma showed that the total lyso-PE concentrations in boys (n = 181) and girls (n = 161) were 11.53 and 11.00 pmol/μL (median), respectively. Participants were further classified by the percentage of overweight and subgrouped as underweight (n = 12), normal range (n = 292), or overweight (n = 38). Interestingly, the reduction of lyso-PE 16:0 and increased lyso-PE 22:6 were observed in overweight children compared with normal range (Fold change: 0.909 and 1.174, respectively). CONCLUSIONS: This study successfully established a simple quantitative method to determine lyso-PE concentrations. Furthermore, our method revealed the possible relation between plasma lyso-PEs and overweight status.
  • Quantitative determination of plasma cholesteryl ester levels in Japanese preadolescents from the Hokkaido study using liquid chromatography/tandem mass spectrometry.
    Divyavani Gowda; Siddabasave Gowda B Gowda; Atsuko Ikeda; Rahel Mesfin Ketema; Yu Ait Bamai; Reiko Kishi; Hitoshi Chiba; Shu-Ping Hui
    Steroids, 211, 109498, 109498, 13 Aug. 2024, [International Magazine]
    English, Scientific journal, Cholesteryl esters (CE) are sterols comprising various fatty acyl chains attached to a cholesterol hydroxyl moiety. CEs are often considered plasma biomarkers of liver function; however, their absolute concentrations in the plasma of Japanese preadolescents have not been well explored. This study aimed to determine the plasma CE levels in Japanese preadolescents of different sexes, ages, and body weights living in Hokkaido, Japan using targeted liquid chromatography/tandem mass spectrometry. The analysis was performed on the non-fasting plasma of preadolescents aged 9-12 years (n = 339 healthy volunteers; 178 boys and 161 girls) from Sapporo, Hokkaido, Japan. The analysis results showed that the total CE levels in boys and girls were 871 ± 153 and 862 ± 96 pmol/μL, respectively. CE 18:2 (41 ± 2.9 %) was found to be the most abundant species followed by CE 18:1 (16 ± 1.5 %) and CE 16:0 (13 ± 1.1 %). The ω-3 fatty acid-containing CEs such as CE 18:3 and CE 20:5 were significantly lower in girls than in boys. Despite the different ages, CEs were tightly regulated in the plasma of children's, and the total CEs ranged between 844 and 906 pmol/μL in boys and 824 and 875 pmol/μL in girls. The participants were further classified into three groups based on their body mass index underweight (n = 237), normal weight (n = 94), and overweight (n = 8). Most of the quantified CEs were accumulated in the overweight group. Interestingly, CE 18:3 was significantly upregulated in the overweight group compared to that in the normal range, and the area under the receiver operating characteristic curve was 0.73, suggesting that it could be a possible marker for obesity. This study marks the initial investigation of absolute CE levels in the plasma of children and can help elucidate the relationship between CEs and childhood obesity.
  • Lipidomic study of kidney in a mouse model with urine flow obstruction.
    Divyavani Gowda; Md Abdul Masum; Siddabasave Gowda B Gowda; Chandra Shekhar; Md Zahir Uddin Rubel; Shunnosuke Kira; Osamu Ichii; Yasuhiro Kon; Hitoshi Chiba; Shu-Ping Hui
    Scientific reports, 14, 1, 18042, 18042, 05 Aug. 2024, [International Magazine]
    English, Scientific journal, Obstructed urine flow is known to cause structural and functional kidney damage leading to renal fibrosis. However, limited information is available on the change in kidney lipids during urinary tract obstruction. In this study, we investigated the change in lipidome in a mouse model with unilateral ureteral obstruction (UUO). The establishment of the UUO model was confirmed by histopathological examination using transmission electron microscopy. Untargeted liquid chromatography/mass spectrometry was carried out over a time course of 4 and 7 days. Compared to the sham control, the UUO kidney at 7 days showed dilatation of the renal tubule with loss of brush borders and thickening of the capillary endothelium. In the kidney lipidomes obtained from the UUO 7 days group compared to the control, a significant decrease of ceramide, sphingomyelin, phosphatidylcholine, lysophospholipids, and phosphatidylethanolamine was observed, whereas cholesteryl esters, free fatty acids, phosphatidylglycerol, and cardiolipins were significantly increased. The present study revealed the disturbed lipid metabolism in the UUO model, which may provide a clue to potential lipid pathways and therapeutic targets for the early stage of renal fibrosis.
  • Targeted and untargeted lipidomics with integration of liver dynamics and microbiome after dietary reversal of obesogenic diet targeting inflammation-resolution signaling in aging mice.
    Gunjan Upadhyay; Siddabasave Gowda B Gowda; Sidharth P Mishra; Lipsa Rani Nath; Adewale James; Alisha Kulkarni; Yuktee Shrikant; Rohitram Upendram; MathanKumar Marimuthu; Shu-Ping Hui; Shalini Jain; Kain Vasundhara; Hariom Yadav; Ganesh V Halade
    Biochimica et biophysica acta. Molecular and cell biology of lipids, 1869, 8, 159542, 159542, 02 Aug. 2024, [International Magazine]
    English, Scientific journal, Obesity, a global epidemic linked to around 4 million deaths yearly, arises from lifestyle imbalances impacting inflammation-related conditions like non-alcoholic fatty liver disease and gut dysbiosis. But the long-term effects of inflammation caused by lifestyle-related dietary changes remain unexplained. In this study, we used young male C57Bl/6 mice which were fed either an obesogenic diet (OBD) or a control diet (CON) for six months. Later, a group of mice from the OBD group were intervened to the CON diet (OBD-R) for four months, while another OBD group remained on the OBD diet. The OBD induced distinct changes in gut microbial, notably elevating Firmicutes and Actinobacteria, while reducing Bacteroidetes and Tenericutes. OBD-R restored microbial abundance like CON. Analyzing liver, plasma, and fecal samples revealed OBD-induced alterations in various structural and bioactive lipids, which were normalized to CON in the OBD-R, showcasing lipid metabolism flexibility and adaptability to dietary shifts. OBD increased omega 6 fatty acid, Arachidonic Acid (AA) and decreased omega 3-derived lipid mediators in the OBD mimicking non-alcoholic fatty liver disease thus impacting inflammation-resolution pathways. OBD also induced hepatic inflammation via increasing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and proinflammatory markers CCR2, TNF-α, and IL-1β in liver. Transitioning from OBD to CON mitigated inflammatory gene expression and restored lipid and cholesterol networks. This study underscores the intricate interplay between lifestyle-driven dietary changes, gut microbiota, lipid metabolism, and liver health. Notably, it suggests that shift from an OBD (omega-6 enriched) to CON partially alleviates signs of chronic inflammation during aging. Understanding these microbial, lipidomic, and hepatic inflammatory dynamics reveals potential therapeutic avenues for metabolic disorders induced by diet, emphasizing the pivotal role of diet in sustaining metabolic health.
  • Dissecting new lipids and their composition in herbal tea using untargeted LC/MS.
    Lipsa Rani Nath; Siddabasave Gowda B Gowda; Divyavani Gowda; Fengjue Hou; Hitoshi Chiba; Shu Ping Hui
    Food chemistry, 447, 138941, 138941, 30 Jul. 2024, [International Magazine]
    English, Scientific journal, Herbal teas and beverages have gained global attention because they are rich in natural bioactive compounds, which are known to have diverse biological effects, including antioxidant and anticarcinogenic properties. However, the lipidomic profiles of herbal teas remain unclear. In this study, we applied an untargeted lipidomics approach using high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry to comprehensively profile, compare, and identify unknown lipids in four herbal teas: dokudami, kumazasa, sugina, and yomogi. A total of 341 molecular species from five major classes of lipids were identified. Multivariate principal component analysis revealed distinct lipid compositions for each of the herbs. The fatty acid α-linolenic acid (FA 18:3) was found to be abundant in kumazasa, whereas arachidonic acid (FA 20:4) was the most abundant in sugina. Interestingly, novel lipids were discovered for the first time in plants; specifically, short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs) with 4-hydroxy phenyl nonanoic acid as the structural core. This study provides insight into the lipidomic diversity and potential bioactive lipid components of herbal teas, offering a foundation for further research into their health-promoting properties and biological significance.
  • Exploration of New Lipid Nutrients and Their Characterization in Herbal Teas Using Non-Targeted Liquid Chromatography-Mass Spectrometry.
    Md Abdul Malek; Siddabasave Gowda B Gowda; Rachana M Gangadhara; Divyavani Gowda; Shu-Ping Hui
    Foods (Basel, Switzerland), 13, 12, 14 Jun. 2024, [International Magazine]
    English, Scientific journal, Herbal teas are blends of leaves, seeds, fruits, and flowers from various plants that provide relaxation, anti-inflammatory benefits, and immune system support for conditions such as diabetes and asthma. Despite their health benefits, comprehensive lipidomic data on herbal teas are limited in the literature. We used non-targeted liquid chromatography-linear ion trap orbitrap mass spectrometry to identify and correlate the lipid species in the following six herbal tea samples: fennel, ginger, juniper, lemon peel, orange peel, and rosehip. A total of 204 lipid molecular species were identified, and multivariate analysis revealed a significant difference between lipid species in herbal teas. Saturated fatty acids (SFAs) and polyunsaturated fatty acids (PUFAs) are significantly abundant in juniper, including ω-3 and ω-6 fatty acids, followed by fennel. Cluster correlations showed that ginger contained mainly sphingolipids and lysophospholipids, whereas fennel was rich in phospholipids. No significant variations in the content of triacylglycerols were observed in any of the herbal teas analyzed. The ratio of PUFAs to SFAs in herbal teas showed that orange peel had the highest ratio, followed by lemon peel and fennel, indicating their potential health benefits. In addition, using high-resolution mass spectrometry, various lipids such as fatty acid esters of hydroxy fatty acids and N-acyl-lysophosphatidylethanolamines were identified and characterized in these herbal teas. This study provides a comprehensive lipid analysis and detailed characterization of lipids in six herbal teas, highlighting their plausible applications in the field of nutrition and various food industries for the development of functional foods.
  • Alterations in plasma short-chain fatty acids in preadolescence children: The Hokkaido study
    Yonghan Li; Siddabasave Gowda B. Gowda; Divyavani Gowda; Atsuko Ikeda; Yu Ait Bamai; Rahel Mesfin Ketema; Reiko Kishi; Hitoshi Chiba; Shu-Ping Hui
    Journal of Chromatography B, 1242, 124191, 124191, Elsevier BV, Jun. 2024, [International Magazine]
    English, Scientific journal, The purpose of this study is to explore the plasma short-chain fatty acid (SCFA) concentrations in 9-12-year-old Japanese children collected in the Hokkaido study, focusing on how factors such as age, sex, and body mass index (BMI) correlate with these levels. The Hokkaido Study on Children's Health is an ongoing longitudinal study since 2002, encompassing 20,926 pregnant women in Hokkaido Prefecture, Japan, between 2003 and 2012. We contacted 1881 children aged 9-12 born between April 2006 and January 2010, and 342 non-fasting plasma samples (boys = 181, girls = 161) were obtained from this cohort, alongside assessments of their height and weight. Plasma SCFA concentrations were determined using N,N-dimethylethylenediamine derivatization method coupled with liquid chromatography-mass spectrometry. Ethyl acetate was used to extract SCFAs from plasma, and the recovery ranged from 83 % to 108 %. Our findings indicate that acetic acid had the highest concentration across all age groups and sexes. The concentrations of butyric acid, valeric acid, and hexanoic acid increased with age, peaking in 12-year-old children. Conversely, the level of 4-hydroxy valeric acid showed a decreasing trend with increasing age groups. This study also explored the correlation between BMI and SCFA concentrations, comparatively higher level of propionic acid was observed in the overweight group. The results obtained in this study enhance our understanding of the role of SCFAs in the growth and development of children and provide a foundation for future nutritional intervention and health promotion strategies.
  • Increased phosphatidylcholine and its hydroperoxides in serum low-density lipoproteins from patients with non-alcoholic steatohepatitis.
    Nanao Murakami; Toshihiro Sakurai; Arisa Yamahata; Akiko Sakurai; Kazuhiro Nouso; Yuki Fujii; Hitoshi Chiba; Shu-Ping Hui
    Annals of clinical biochemistry, 61, 5, 45632241259658, 45632241259658, 23 May 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: Non-alcoholic fatty liver disease is classified into simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) according to histological findings from liver biopsies. Phosphatidylcholine (PC), the main component of phospholipids in serum lipoproteins, is easily oxidized to phosphatidylcholine hydroperoxide (PC-OOH). Although a lipid composition in the low-density lipoproteins (LDL) from patients with NASH could be abnormal, it remains unclear. Here, to better understand the characteristics of lipids in the LDL from NASH and SS, we compared the composition of PC and PC-OOH species in LDL particles (LDL-PC, LDL-PCOOH) from these patients, then clarified the association between these lipids and NASH severity. METHODS: The serum samples from patients with NASH (female, n = 9) and SS (female, n = 4; male, n = 2) were used for isolation of LDL. Total lipids were extracted from isolated LDL, and the species of PC and PC-OOH were measured using liquid chromatography-mass spectrometry/mass spectrometry. RESULTS: The sum of LDL-PC and the sum of LDL-PCOOH were significantly higher in NASH than in SS. Several LDL-PC (PC 32:0, 32:1, 32:2, 34:3, 36:2, sum of PC with saturated fatty acyl chains and sum of LDL-PC with polyunsaturated fatty acyl chains) and several LDL-PCOOH (34:2, 36:2, 36:3 and total) were increased significantly with increasing fibrosis score. In particular, a series of LDL-PCOOH were more reflective of the severity of fibrosis score. CONCLUSIONS: LDL-PC and LDL-PCOOH species were strongly correlated with the fibrosis score in NASH, which suggests that abnormal LDL is involved in the development of liver fibrosis.
  • A facile method for monitoring sphingomyelin synthase activity in HeLa cells using liquid chromatography/mass spectrometry.
    Punith M Sundaraswamy; Yusuke Minami; Jayashankar Jayaprakash; Siddabasave Gowda B Gowda; Hiroyuki Takatsu; Divyavani Gowda; Hye-Won Shin; Shu-Ping Hui
    The Analyst, 07 May 2024, [International Magazine]
    English, Scientific journal, Sphingomyelin synthase (SMS) is a sphingolipid-metabolizing enzyme involved in the de novo synthesis of sphingomyelin (SM) from ceramide (Cer). Recent studies have indicated that SMS is a key therapeutic target for metabolic diseases such as fatty liver, type 2 diabetes, atherosclerosis, and colorectal cancer. However, very few SMS inhibitors have been identified because of the limited sensitivity and selectivity of the current fluorescence-based screening assay. In this study, we developed a simple cell-based assay coupled with liquid chromatography/tandem mass spectrometry (LC-MS/MS) to screen for SMS inhibitors. HeLa cells stably expressing SMS1 or SMS2 were used for the screening. A non-fluorescent unnatural C6-Cer was used as a substrate for SMS to produce C6-SM. C6-Cer and C6-SM levels in the cells were monitored and quantified using LC-MS/MS. The activity of ginkgolic acid C15:1 (GA), a known SMS inhibitor, was measured. GA had half-maximal inhibitory concentrations of 5.5 μM and 3.6 μM for SMS1 and SMS2, respectively. To validate these findings, hSMS1 and hSMS2 proteins were optimized for molecular docking studies. In silico analyses were conducted to assess the interaction of GA with SMS1 and SMS2, and its binding affinity. This study offers an analytical approach for screening novel SMS inhibitors and provides in silico support for the experimental findings.
  • Regio-specific lipid fingerprinting of edible sea cucumbers using LC/MS
    Yusuke Minami; Siddabasave Gowda B. Gowda; Divyavani Gowda; Hitoshi Chiba; Shu-Ping Hui
    Food Research International, 184, 114253, 114253, May 2024, [International Magazine]
    English, Scientific journal, Sea cucumbers are a rich source of bioactive compounds and are gaining popularity as nutrient-rich seafood. They are consumed as a whole organism in Pacific regions. However, limited data are available on the comparison of their lipid composition and nutritional value. In this study, untargeted liquid chromatography/mass spectrometry was applied to comprehensively profile lipids in the skin, meat, and intestinal contents of three color-distinct edible sea cucumbers. Multivariate principal component analysis revealed that the lipid composition of the intestinal contents of red, black, and blue sea cucumbers differs from that of skin, and meats. Polyunsaturated fatty acids (PUFAs) are abundant in the intestinal contents, followed by meats of sea cucumber. Lipid nutritional quality assessments based on fatty acid composition revealed a high P:S ratio, low index of atherogenicity, and high health promotion indices for the intestinal contents of red sea cucumber, suggesting its potential health benefits. In addition, hierarchical cluster analysis revealed that the intestinal contents of sea cucumbers were relatively high in PUFA-enriched phospholipids and lysophospholipids. Ceramides are abundant in black skin, blue meat, and red intestinal content samples. Overall, this study provides the first insights into a comprehensive regio-specific profile of the lipid content of sea cucumbers and their potential use as a source of lipid nutrients in food and nutraceuticals.
  • Inhibition of Lipid Accumulation and Oxidation in Hepatocytes by Bioactive Bean Extracts
    Dya Fita Dibwe; Emi Kitayama; Saki Oba; Nire Takeishi; Hitoshi Chiba; Shu-Ping Hui
    Antioxidants, 13, 5, 25 Apr. 2024, [International Magazine]
    English, Scientific journal, During our search for natural resources that can inhibit lipid droplet accumulation (LDA) and potentially prevent metabolic dysfunction-associated fatty liver disease (MAFLD) and its progressive stages, such as metabolic dysfunction-associated steatohepatitis (MASH), eight bean extracts (BE1-BE8) were tested for their ability to inhibit lipid accumulation and oxidation in hepatocytes. Substantial inhibitory effects on LDA with bean extracts (BEs) BE2, BE4, BE5, and BE8 were demonstrated. An advanced lipidomic approach was used to quantify the accumulation and inhibition of intracellular triacylglycerol (TAG) and its oxidized species, TAG hydroperoxide (TGOOH), in hepatocytes under fatty acid-loading conditions. The results show that the antioxidants BE2 and BE8 are potential candidates for regulating TAG and TGOOH accumulation in fatty acid-induced lipid droplets (LDs). This study suggests that bean-based foods inhibit LDs formation by decreasing intracellular lipids and lipid hydroperoxides in the hepatocytes. The metabolic profiling of BEs revealed that BE2 and BE8 contained polyphenolic compounds. These may be potential resources for the development of functional foods and drug discovery targeting MAFLD/MASH.
  • Sex-Specific Effect of Ethanol on Colon Content Lipidome in a Mice Model Using Nontargeted LC/MS.
    Jayashankar Jayaprakash; Siddabasave Gowda B Gowda; Pradeep K Shukla; Divyavani Gowda; Lipsa Rani Nath; Hitoshi Chiba; Radhakrishna Rao; Shu-Ping Hui
    ACS omega, 9, 14, 16044, 16054, 09 Apr. 2024, [International Magazine]
    English, Scientific journal, Consumption of alcohol has widespread effects on the human body. The organs that are most significantly impacted are the liver and digestive system. When alcohol is consumed, it is absorbed in the intestines and processed by the liver. However, excessive alcohol use may affect gut epithelial integrity, microbiome composition, and lipid metabolism. Despite past studies investigating the effect of ethanol on hepatic lipid metabolism, the focus on colonic lipid metabolism has not been well explored. In this study, we investigated the sex-specific effect of ethanol on the colonic content lipidome in a mouse model using nontargeted liquid chromatography-mass spectrometry. Comprehensive lipidome analysis of colonic flush samples was performed using ethanol-fed (EF) and pair-fed (PF) mice of each sex. Partial least-squares discriminant analysis revealed that ethanol altered colonic lipid composition largely in male mice compared with female mice. A significant increase in free fatty acids, ceramides, and hexosylceramides and decreased phosphatidylglycerols (PG) was observed in the EF group compared to the PF group in male mice. Phosphatidylethanolamine (PE) levels were increased significantly in the EF group of both sexes compared to the PF group. The volcanic plot shows that PG (O-15:1/15:0) and PE (O-18:2/15:0) are common markers that are increased in both sexes of the EF group. In addition, decreased fatty acid esters of hydroxy fatty acids (FAHFA) were observed specifically in the EF group of female mice. Overall, a significant variation in the mice colonic content lipidome between the EF and PF groups was observed. Target pathways, such as sphingolipid metabolism in males, FAHFA in females, and PE metabolism in both sexes, were suggested. This study provides new insight into the sex-dependent lipid change associated with alcohol-induced gut-microbiota dysfunction and its potential health impacts.
  • Glucosylceramide flippases contribute to cellular glucosylceramide homeostasis.
    Natsuki Kita; Asuka Hamamoto; Siddabasave Gowda B Gowda; Hiroyuki Takatsu; Kazuhisa Nakayama; Makoto Arita; Shu-Ping Hui; Hye-Won Shin
    Journal of lipid research, 65, 3, 100508, 100508, Mar. 2024, [International Magazine]
    English, Scientific journal, Lipid transport is an essential cellular process with importance to human health, disease development, and therapeutic strategies. Type IV P-type ATPases (P4-ATPases) have been identified as membrane lipid flippases by utilizing nitrobenzoxadiazole (NBD)-labeled lipids as substrates. Among the 14 human type IV P-type ATPases, ATP10D was shown to flip NBD-glucosylceramide (GlcCer) across the plasma membrane. Here, we found that conversion of incorporated GlcCer (d18:1/12:0) to other sphingolipids is accelerated in cells exogenously expressing ATP10D but not its ATPase-deficient mutant. These findings suggest that 1) ATP10D flips unmodified GlcCer as well as NBD-GlcCer at the plasma membrane and 2) ATP10D can translocate extracellular GlcCer, which is subsequently converted to other metabolites. Notably, exogenous expression of ATP10D led to the reduction in cellular hexosylceramide levels. Moreover, the expression of GlcCer flippases, including ATP10D, also reduced cellular hexosylceramide levels in fibroblasts derived from patients with Gaucher disease, which is a lysosomal storage disorder with excess GlcCer accumulation. Our study highlights the contribution of ATP10D to the regulation of cellular GlcCer levels and maintaining lipid homeostasis.
  • Kaempferol Improves Cardiolipin and ATP in Hepatic Cells: A Cellular Model Perspective in the Context of Metabolic Dysfunction-Associated Steatotic Liver Disease
    Akiko Sakurai; Toshihiro Sakurai; Hsin-Jung Ho; Hitoshi Chiba; Shu-Ping Hui
    Nutrients, 11 Feb. 2024
    Scientific journal
  • Synthesis and quantification of short-chain fatty acid esters of hydroxy fatty acids in rat intestinal contents and fecal samples by LC-MS/MS
    Siddabasave Gowda B. Gowda; Fengjue Hou; Divyavani Gowda; Hitoshi Chiba; Kentaro Kawakami; Satoru Fukiya; Atsushi Yokota; Shu-Ping Hui
    Analytica Chimica Acta, 1288, 342145, 342145, Elsevier BV, Feb. 2024, [International Magazine]
    English, Scientific journal, Short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs) are a new class of endogenous lipids belonging to the fatty acid esters of the hydroxy fatty acid family. We previously uncovered their chemical structure and discussed their potential biological significance. We anticipate an increased need for SFAHFA measurements as markers of metabolic and inflammatory health. In this study, we synthesized sixty isomeric SFAHFAs by combining 12 hydroxy fatty acids (C16-C24) and five short-chain fatty acids (C2-C6) including a labelled internal standard. SFAHFA enrichment was achieved by solid-phase extraction and established a sensitive method for their quantitation by targeted LC-MS/MS. The method was applied to profile SFAHFAs in intestinal contents and fecal samples collected from rats fed a high-fat diet (HFD). The results demonstrated a significant decrease in SFAHFAs in the intestinal contents of the HFD group compared with the control group. The fecal time course (0-8 weeks) profile of SFAHFAs showed significant downregulation of acetic and propanoic acid esters in just 2 weeks after HFD administration. This study offers the first synthesis and quantitation method for SFAHFAs, demonstrating their potential use in elucidating SFAHFA sources, their role in various diseases, and potential biochemical signalling pathways.
  • Lysosomal membrane integrity in fibroblasts derived from patients with Gaucher disease.
    Asuka Hamamoto; Natsuki Kita; Siddabasave Gowda B Gowda; Hiroyuki Takatsu; Kazuhisa Nakayama; Makoto Arita; Shu-Ping Hui; Hye-Won Shin
    Cell structure and function, 49, 1, 1, 10, Japan Society for Cell Biology, 23 Jan. 2024, [Domestic magazines]
    English, Gaucher disease (GD) is a recessively inherited lysosomal storage disorder characterized by a deficiency of lysosomal glucocerebrosidase (GBA1). This deficiency results in the accumulation of its substrate, glucosylceramide (GlcCer), within lysosomes. Here, we investigated lysosomal abnormalities in fibroblasts derived from patients with GD. It is noteworthy that the cellular distribution of lysosomes and lysosomal proteolytic activity remained largely unaffected in GD fibroblasts. However, we found that lysosomal membranes of GD fibroblasts were susceptible to damage when exposed to a lysosomotropic agent. Moreover, the susceptibility of lysosomal membranes to a lysosomotropic agent could be partly restored by exogenous expression of wild-type GBA1. Here, we report that the lysosomal membrane integrity is altered in GD fibroblasts, but lysosomal distribution and proteolytic activity is not significantly altered.Key words: glucosylceramide, lysosome, Gaucher disease, lysosomotropic agent.
  • Identification of a β-Carboline Alkaloid from Chemoselectively Derived Vanilla Bean Extract and Its Prevention of Lipid Droplet Accumulation in Human Hepatocytes (HepG2)
    Dya Fita Dibwe; Nire Takeishi; Saki Oba; Akiko Sakurai; Toshihiro Sakurai; Takayuki Tsukui; Hitoshi Chiba; Shu-Ping Hui
    Molecules, 144th, 09 Dec. 2023
    Scientific journal
  • Regiospecific analysis of lipidome in the brain from mammals of land and aquatic habitats-by liquid chromatography-mass spectrometry
    Siddabasave Gowda B. Gowda; Divyavani Gowda; Fengjue Hou; Chandra Shekhar; Hitoshi Chiba; Nina Patzke; Shu-Ping Hui
    Heliyon, 9, 12, e22959, e22959, Elsevier BV, Dec. 2023
    Scientific journal
  • Flazin improves mitochondrial dynamics in renal tubular epithelial cells under oxidative stress
    Xun-Zhi Wu; Hsin-Jung Ho; Miki Eguchi; Zhen Chen; Hitoshi Chiba; Shu-Ping Hui
    Food Bioscience, Dec. 2023
    Scientific journal
  • Crosstalk between Lipids and Non-Alcoholic Fatty Liver Disease
    Divyavani Gowda; Chandra Shekhar; Siddabasave Gowda B. Gowda; Yifan Chen; Shu-Ping Hui
    Livers, 23 Nov. 2023
    Scientific journal
  • The elucidation of plasma lipidome profiles during severe influenza in a mouse model.
    Marumi Ohno; Siddabasave Gowda B Gowda; Toshiki Sekiya; Naoki Nomura; Masashi Shingai; Shu-Ping Hui; Hiroshi Kida
    Scientific reports, 13, 1, 14210, 14210, 30 Aug. 2023, [International Magazine]
    English, Scientific journal, Although influenza virus infection has been shown to affect lipid metabolism, details remain unknown. Therefore, we elucidated the kinetic lipid profiles of mice infected with different doses of influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) by measuring multiple lipid molecular species using untargeted lipidomic analysis. C57BL/6 male mice were intranasally infected with PR8 virus at 50 or 500 plaque-forming units to cause sublethal or lethal influenza, respectively. Plasma and tissue samples were collected at 1, 3, and 6 days post-infection (dpi), and comprehensive lipidomic analysis was performed using high-performance liquid chromatography-linear trap quadrupole-Orbitrap mass spectrometry, as well as gene expression analyses. The most prominent feature of the lipid profile in lethally infected mice was the elevated plasma concentrations of phosphatidylethanolamines (PEs) containing polyunsaturated fatty acid (PUFA) at 3 dpi. Furthermore, the facilitation of PUFA-containing phospholipid production in the lungs, but not in the liver, was suggested by gene expression and lipidomic analysis of tissue samples. Given the increased plasma or serum levels of PUFA-containing PEs in patients with other viral infections, especially in severe cases, the elevation of these phospholipids in circulation could be a biomarker of infection and the severity of infectious diseases.
  • Plasmalogen Profiling in Porcine Brain Tissues by LC-MS/MS.
    Yue Wu; Yifan Chen; Min Zhang; Hitoshi Chiba; Shu-Ping Hui
    Foods (Basel, Switzerland), 12, 16, 08 Aug. 2023, [International Magazine]
    English, Scientific journal, Plasmalogen, a functional glycerophospholipid, is known for its beneficial nutritional effects, such as anti-oxidation and anti-inflammation. As the porcine brain is a plasmalogen-rich resource, this study aimed to explore its potential for plasmalogen-based health food product development, with special attention on whether and how the industrial production processes influence the plasmalogen content and composition. In the present work, plasmalogens from different porcine brain products were investigated using liquid chromatography-tandem mass spectrometry. The results indicated that all the porcine brain products showed abundant total plasmalogens, of which more than 95% were ethanolamine plasmalogen species. Acetone precipitation, ethanol extraction, and drying did not significantly affect the plasmalogen content, whereas repeated freeze-thaw cycles in the production process led to noticeable loss. The chemometric investigation suggested that raw products and glycerophospholipid products exhibited different profiles; furthermore, the concentration step seemed to impact the plasmalogen composition. The nutritional assessment revealed that porcine brain products showed favorable values of multiple indexes, including PUFA/SFA ratio, n-6/n-3 ratio, thrombogenicity index, and unsaturation index, suggesting a health-beneficial value. The current study not only shows the feasibility of producing porcine brain-derived plasmalogens, but also provides possible strategies for developing and quality-controlling dietary plasmalogen supplements and healthcare products.
  • Lipid Composition Analysis and Characterization of Acyl Sterol Glycosides in Adzuki and Soybean Cultivars by Non-Targeted LC-MS.
    Rachana M Gangadhara; Siddabasave Gowda B Gowda; Divyavani Gowda; Ken Inui; Shu-Ping Hui
    Foods (Basel, Switzerland), 12, 14, 21 Jul. 2023, [International Magazine]
    English, Scientific journal, Beans, a globally significant economic and nutritional food crop, are rich in polyphenolic chemicals with potential health advantages, providing high protein, fiber, minerals, and vitamins. However, studies on the global profiling of lipids in beans are limited. We applied a non-targeted lipidomic approach based on high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (HPLC/LTQ-Orbitrap-MS) to comprehensively profile and compare the lipids in six distinct bean cultivars, namely, adzuki red beans-adzuki cultivar (ARB-AC), adzuki red beans-Benidainagon cultivar (ARB-BC), adzuki red beans-Erimoshouzu cultivar (ARB-EC), soybean-Fukuyutaka cultivar 2021 (SB-FC21), soybean-Fukuyutaka cultivar 2022 (SB-FC22), and soybean-Oosuzu cultivar (SB-OC). MS/MS analysis defined 144 molecular species from four main lipid groups. Multivariate principal component analysis indicated unique lipid compositions in the cultivars except for ARB-BC and ARB-EC. Evaluation of the concentrations of polyunsaturated fatty acid to saturated fatty acid ratio among all the cultivars showed that SB-FC21 and SB-FC22 had the highest value, suggesting they are the most beneficial for health. Furthermore, lipids such as acyl sterol glycosides were detected and characterized for the first time in these bean cultivars. Hierarchical cluster correlations revealed the predominance of ceramides in ARB-EC, lysophospholipids in SB-FC21, and glycerophospholipids in SB-OC. This study comprehensively investigated lipids and their compositions in beans, indicating their potential utility in the nutritional evaluation of beans as functional foods.
  • A Pacific Oyster-Derived Antioxidant, DHMBA, Protects Renal Tubular HK-2 Cells against Oxidative Stress via Reduction of Mitochondrial ROS Production and Fragmentation.
    Hsin-Jung Ho; Natsumi Aoki; Yi-Jou Wu; Ming-Chen Gao; Karin Sekine; Toshihiro Sakurai; Hitoshi Chiba; Hideaki Watanabe; Mitsugu Watanabe; Shu-Ping Hui
    International journal of molecular sciences, 24, 12, 13 Jun. 2023, [International Magazine]
    English, Scientific journal, The kidney contains numerous mitochondria in proximal tubular cells that provide energy for tubular secretion and reabsorption. Mitochondrial injury and consequent excessive reactive oxygen species (ROS) production can cause tubular damage and play a major role in the pathogenesis of kidney diseases, including diabetic nephropathy. Accordingly, bioactive compounds that protect the renal tubular mitochondria from ROS are desirable. Here, we aimed to report 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), isolated from the Pacific oyster (Crassostrea gigas) as a potentially useful compound. In human renal tubular HK-2 cells, DHMBA significantly mitigated the cytotoxicity induced by the ROS inducer L-buthionine-(S, R)-sulfoximine (BSO). DHMBA reduced the mitochondrial ROS production and subsequently regulated mitochondrial homeostasis, including mitochondrial biogenesis, fusion/fission balance, and mitophagy; DHMBA also enhanced mitochondrial respiration in BSO-treated cells. These findings highlight the potential of DHMBA to protect renal tubular mitochondrial function against oxidative stress.
  • Sleep deprivation in obesogenic setting alters lipidome and microbiome toward suboptimal inflammation in acute heart failure.
    Ganesh V Halade; Yusuf Mat; Siddabasave Gowda B Gowda; Shalini Jain; Shu-Ping Hui; Hariom Yadav; Vasundhara Kain
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 37, 5, e22899, May 2023, [International Magazine]
    English, Scientific journal, Sleep is a fundamental medicine for cardiac homeostasis, and sleep-deprived individuals are prone to higher incidences of heart attack. The lipid-dense diet (obesogenic diet-OBD) is a cumulative risk factor for chronic inflammation in cardiovascular disease; thus, understanding how sleep fragmentation (SF) in an obesity setting impacts immune and cardiac health is an unmet medical need. We hypothesized whether the co-existence of SF with OBD dysregulates gut homeostasis and leukocyte-derived reparative/resolution mediators, thereby impairing cardiac repair. Two-month-old male C57BL/6J mice were randomized first into two groups, then four groups; Control, control + SF, OBD, and OBD + SF mice subjected to myocardial infarction (MI). OBD mice had higher levels of plasma linolenic acid with a decrease in eicosapentaenoic and docosahexaenoic acid. The OBD mice had lower Lactobacillus johnsonii indicating a loss of probiotic microbiota. SF in OBD mice increased Firmicutes/Bacteroidetes ratio indicative of a detrimental change in SF-directed microbiome. OBD + SF group increased in the neutrophil: lymphocyte ratio suggestive of suboptimal inflammation. As a result of SF, resolution mediators (RvD2, RvD3, RvD5, LXA4 , PD1, and MaR1) decreased and inflammatory mediators (PGD2 , PGE2 , PGF2a , 6k-PGF1a ) were increased in OBD mice post-MI. At the site of infarction, the proinflammatory cytokines Ccl2, IL1β, and IL-6 were amplified in OBD + SF indicating a robust proinflammatory milieu post-MI. Also, brain circadian genes (Bmal1, Clock) were downregulated in SF-subjected control mice, but remained elevated in OBD mice post-MI. SF superimposed on obesity dysregulated physiological inflammation and disrupted resolving response thereby impaired cardiac repair and signs of pathological inflammation.
  • Mass spectrometric approaches in discovering lipid biomarkers for COVID-19 by lipidomics: Future challenges and perspectives.
    Siddabasave Gowda B Gowda; Chandra Shekhar; Divyavani Gowda; Yifan Chen; Hitoshi Chiba; Shu-Ping Hui
    Mass spectrometry reviews, 27 Apr. 2023, [International Magazine]
    English, Scientific journal, Coronavirus disease 2019 (COVID-19) has emerged as a global health threat and has rapidly spread worldwide. Significant changes in the lipid profile before and after COVID-19 confirmed the significance of lipid metabolism in regulating the response to viral infection. Therefore, understanding the role of lipid metabolism may facilitate the development of new therapeutics for COVID-19. Owing to their high sensitivity and accuracy, mass spectrometry (MS)-based methods are widely used for rapidly identifying and quantifying of thousands of lipid species present in a small amount of sample. To enhance the capabilities of MS for the qualitative and quantitative analysis of lipids, different platforms have been combined to cover a wide range of lipidomes with high sensitivity, specificity, and accuracy. Currently, MS-based technologies are being established as efficient methods for discovering potential diagnostic biomarkers for COVID-19 and related diseases. As the lipidome of the host cell is drastically affected by the viral replication process, investigating lipid profile alterations in patients with COVID-19 and targeting lipid metabolism pathways are considered to be crucial steps in host-directed drug targeting to develop better therapeutic strategies. This review summarizes various MS-based strategies that have been developed for lipidomic analyzes and biomarker discoveries to combat COVID-19 by integrating various other potential approaches using different human samples. Furthermore, this review discusses the challenges in using MS technologies and future perspectives in terms of drug discovery and diagnosis of COVID-19.
  • Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets.
    Iku Sazaki; Toshihiro Sakurai; Arisa Yamahata; Sumire Mogi; Nao Inoue; Koutaro Ishida; Ami Kikkai; Hana Takeshita; Akiko Sakurai; Yuji Takahashi; Hitoshi Chiba; Shu-Ping Hui
    International journal of molecular sciences, 24, 5, 4281, 4281, MDPI AG, 21 Feb. 2023, [International Magazine]
    English, Scientific journal, Oxidized low-density lipoproteins (oxLDLs) induce oxidative stress in the liver tissue, leading to hepatic steatosis, inflammation, and fibrosis. Precise information on the role of oxLDL in this process is needed to establish strategies for the prevention and management of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Here, we report the effects of native LDL (nLDL) and oxLDL on lipid metabolism, lipid droplet formation, and gene expression in a human liver-derived C3A cell line. The results showed that nLDL induced lipid droplets enriched with cholesteryl ester (CE) and promoted triglyceride hydrolysis and inhibited oxidative degeneration of CE in association with the altered expression of LIPE, FASN, SCD1, ATGL, and CAT genes. In contrast, oxLDL showed a striking increase in lipid droplets enriched with CE hydroperoxides (CE-OOH) in association with the altered expression of SREBP1, FASN, and DGAT1. Phosphatidylcholine (PC)-OOH/PC was increased in oxLDL-supplemented cells as compared with other groups, suggesting that oxidative stress increased hepatocellular damage. Thus, intracellular lipid droplets enriched with CE-OOH appear to play a crucial role in NAFLD and NASH, triggered by oxLDL. We propose oxLDL as a novel therapeutic target and candidate biomarker for NAFLD and NASH.
  • Extraction and Quantitation of Phytosterols from Edible Brown Seaweeds: Optimization, Validation, and Application.
    Zhen Chen; Nianqiu Shen; Xunzhi Wu; Jiaping Jia; Yue Wu; Hitoshi Chiba; Shuping Hui
    Foods (Basel, Switzerland), 12, 2, 05 Jan. 2023, [International Magazine]
    English, Scientific journal, Brown seaweeds are known as important marine food sources, from which phytosterols have been recognized as functional food components with multiple health-beneficial effects. However, studies on phytosterol extraction and quantitation from edible brown seaweeds are limited. In the present work, extraction methods for seaweed phytosterols were compared and optimized by one-factor-at-one-time method and response surface methodology. Moreover, the quantitation method of total sterols and major sterol components, including fucosterol, saringosterol, and ostreasterol, was established and validated using 1H NMR. Furthermore, the developed extraction and determination methods were applied to investigate three common edible seaweeds from Japan (Hijiki, Wakame, and Kombu). As a result, the finally optimized conditions were ultrasound-assisted extraction with CHCl3-MeOH 2:3 for 15 min followed by saponification with 1.65 mL of 1.85 M KOH for 14.5 h. Based on the developed methods, phytosterols in three seaweeds were compared, and Hijiki showed an abundant total sterol amount (2.601 ± 0.171 mg/g DW), significantly higher than Wakame (1.845 ± 0.137 mg/g DW) and Kombu (1.171 ± 0.243 mg/g DW). Notably, the composition of the sterol components varied in different seaweeds. These findings might help the nutritional investigation and functional food development concerning phytosterols from seaweeds.
  • Distinctive serum lipidomic profile of IVIG-resistant Kawasaki disease children before and after treatment.
    Zhen Chen; Shuji Sai; Kiyoshi Nagumo; Yue Wu; Hitoshi Chiba; Shu-Ping Hui
    PloS one, 18, 3, e0283710, 2023, [International Magazine]
    English, Scientific journal, Kawasaki Disease (KD) is an acute inflammatory disorder associated with systemic vasculitis. Intravenous immunoglobulin (IVIG) is an effective therapy for KD, yet, about 20% of cases show IVIG resistance with persistent inflammation. The lipid profile in IVIG-resistant KD patients and the relationship between lipid characteristics and IVIG resistance remain unknown. In this study, serum samples from twenty KD patients with different IVIG responses (sensitive, intermediate, or resistant) were collected both before and after treatment, and lipidomic analysis was performed using high-performance liquid chromatography-mass spectrometry. As a result, before treatment, six lipid species were found as the most variant features, in which all the top decreased lipids in the IVIG-resistant group were lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), suggesting the potential to be IVIG-resistant markers in pretreatment diagnosis. During treatment, lipidomic changes showed a weaker response in the IVIG-resistant group. After treatment, LPC and LPE species exhibited lower in the IVIG-resistant group and negative correlation with the inflammatory markers, indicating that the unique metabolism may occur among IVIG-responsiveness. These results might contribute to diagnosing IVIG-resistant patients more accurately for alternative therapy and to a better understanding of how lipid metabolism is associated with IVIG sensitiveness/resistance in KD.
  • Temporal lipid profiling in the progression from acute to chronic heart failure in mice and ischemic human hearts.
    Siddabasave Gowda B Gowda; Divyavani Gowda; Fengjue Hou; Hitoshi Chiba; Vibhu Parcha; Pankaj Arora; Ganesh V Halade; Shu-Ping Hui
    Atherosclerosis, 363, 30, 41, Elsevier BV, Dec. 2022, [International Magazine]
    English, Scientific journal, BACKGROUND AND AIMS: Myocardial infarction (MI) is a leading cause of heart failure (HF). After MI, lipids undergo several phasic changes implicated in cardiac repair if inflammation resolves on time. However, if inflammation continues, that leads to end stage HF progression and development. Numerous studies have analyzed the traditional risk factors; however, temporal lipidomics data for human and animal models are limited. Thus, we aimed to obtain sequential lipid profiling from acute to chronic HF. METHODS: Here, we report the comprehensive lipidome of the hearts from diseased and healthy subjects. To induce heart failure in mice, we used a non-reperfused model of coronary ligation, and MI was confirmed by echocardiography and histology, then temporal kinetics of lipids in different tissues (heart, spleen, kidney), and plasma was quantitated from heart failure mice and compared with naïve controls. For lipid analysis in mouse and human samples, untargeted liquid chromatography-linear trap quadrupole orbitrap mass spectrometry (LC-LTQ-Orbitrap MS) was performed. RESULTS: In humans, multivariate analysis revealed distinct cardiac lipid profiles between healthy and ischemic subjects, with 16 lipid species significantly downregulated by 5-fold, mainly phosphatidylethanolamines (PE), in the ischemic heart. In contrast, PE levels were markedly increased in mouse tissues and plasma in chronic MI, indicating possible cardiac remodeling. Further, fold change analysis revealed site-specific lipid biomarkers for acute and chronic HF. A significant decrease in sulfatides (SHexCer (34:1; 2O)) and sphingomyelins (SM (d18:1/16:0)) was observed in mouse tissues and plasma in chronic HF. CONCLUSIONS: Overall, a significant decreased lipidome in human ischemic LV and differential lipid metabolites in the transition of acute to chronic HF with inter-organ communication could provide novel insights into targeting integrative pathways for the early diagnosis or development of novel therapeutics to delay/prevent HF.
  • Simultaneous free fatty acid elevations and accelerated desaturation in plasma and oocytes in early postpartum dairy cows under intensive feeding management.
    Eri Furukawa; Zhen Chen; Tomoaki Kubo; Yue Wu; Koichiro Ueda; Madalitso Chelenga; Hitoshi Chiba; Yojiro Yanagawa; Seiji Katagiri; Masashi Nagano; Shu-Ping Hui
    Theriogenology, 193, 20, 29, Elsevier BV, Nov. 2022, [International Magazine]
    English, Scientific journal, A severe negative energy balance and high circulating free fatty acids (FFA) in postpartum cows impair fertility. The lipotoxicity of FFA has been shown to decrease the quality of bovine oocytes in vitro. Therefore, excess FFA in cells is converted to triacylglycerol (TAG), a non-toxic form, to avoid lipotoxicity. We recently reported that the TAG content in oocytes was higher in postpartum lactating cows subjected to grazing management than in heifers (Theriogenology 176: 174-182, 2021). The present study investigated the compositions of the energy metabolism-related lipids, FFA and TAG, in the plasma and oocytes of cows at different lactation stages under indoor intensive feeding management in order to obtain insights into lipotoxicity in oocytes, particularly those in early postpartum cows. Blood and oocytes were collected from 20 lactating cows categorized into the following lactation groups: 20-30 days in milk (DIM) (n = 5), 40-50 DIM (n = 5), 60-80 DIM (n = 5), and 130-160 DIM (n = 5). Daily energy balance data were obtained for 3 weeks prior to oocyte collection using the ovum pick up (OPU) method. The contents and compositions of FFA and TAG in plasma and oocytes were analyzed using liquid chromatography-mass spectrometry. As expected, plasma FFA was high at 20-30 DIM, decreased by 50 DIM, and was maintained at a low level for the remainder of the experimental period. Similar changes were observed in oocyte FFA and TAG with DIM as plasma FFA. Oocyte FFA positively correlated with plasma FFA (P < 0.05), but negatively correlated with the mean energy balance 1 and 21 days before OPU (P < 0.05). Relationships were noted between the composition and content of FFA in plasma and oocytes, with the FFA 16:1/16:0 and 18:1/18:0 ratios positively correlating with the total amount of FFA (P < 0.05). Elevated oocyte FFA in cows in the early postpartum period under intensive feeding management suggested that oocytes were at a high risk of FFA lipotoxicity. Furthermore, the present results implied that the severe negative energy balance in the previous few weeks was closely related to increases in oocyte FFA, which supports the importance of long-term cow feeding management for preserving the quality of oocytes in the early postpartum period. The present results provide insights into the effects of high circulating FFA on the fertility of postpartum cows.
  • Detection and characterization of lipids in eleven species of fish by non-targeted liquid chromatography/mass spectrometry
    Siddabasave Gowda B. Gowda; Yusuke Minami; Divyavani Gowda; Hitoshi Chiba; Shu-Ping Hui
    Food Chemistry, 393, 133402, 133402, Elsevier BV, Nov. 2022
    Scientific journal
  • Analysis of Antioxidant Lipids in Five Species of Dietary Seaweeds by Liquid Chromatography/Mass Spectrometry
    Siddabasave Gowda B. Gowda; Chen Yifan; Divyavani Gowda; Yui Tsuboi; Hitoshi Chiba; Shu-Ping Hui
    Antioxidants, 11, 8, 1538, 1538, MDPI AG, 08 Aug. 2022
    English, Seaweeds are a good source of bioactive lipids and are known for their nutritional benefits, making them a valuable food source. Despite their dietary significance and nutritional importance, there are limited reports on comprehensive lipidome analysis of lipids with antioxidant properties. Therefore, this study aimed to compare the lipid profiles of five commonly consumed Japanese dietary seaweeds using non-targeted liquid chromatography/mass spectrometry (LC/MS). A total, of 304 molecular species from four major lipid classes were detected and characterized by MS/MS analysis. Multivariate statistical analysis revealed distinct lipid molecular compositions in kombu and sea mustard compared to hijiki, mozuku, and laver seaweeds. Kombu has been shown to contain large amounts of antioxidants, such as polyunsaturated fatty acids (PUFAs), and a high health promotion index compared to other seaweeds. Hierarchical cluster correlations indicated the predominance of glycerophospholipids (GPs) and glycerolipids (GLs) in sea mustard and kombu. As a result, dietary seaweeds have great potential as antioxidants and health-promoting foods for human consumption due to their high levels of PUFA-rich GPs and GLs. Unsaturated triacylglycerols are predominant in hijiki, whereas other health-beneficial lipids, such as monogalactosyldiacylglycerol and sulfoquinovosyl diacylglycerols, are predominant in sea mustard. This study provides a detailed characterization of lipids and their comparative fingerprints in seaweeds, demonstrating the potential use of dietary seaweeds in biotechnological and industrial applications involving the development of functional food products.
  • Oxidative Stress and Lipid Dysregulation in Lipid Droplets: A Connection to Chronic Kidney Disease Revealed in Human Kidney Cells.
    Zhen Chen; Rojeet Shrestha; Xiaoyue Yang; Xunzhi Wu; Jiaping Jia; Hitoshi Chiba; Shu-Ping Hui
    Antioxidants (Basel, Switzerland), 11, 7, 18 Jul. 2022, [International Magazine]
    English, Scientific journal, Chronic kidney disease (CKD), which is defined as a condition causing the gradual loss of kidney function, shows renal lipid droplet (LD) accumulation that is associated with oxidative damage. There is a possibility that an LD abnormality in quality plays a role in CKD development. This study aimed to explore the chemical composition of LDs that are induced in human kidney cells during exposure to free fatty acids as an LD source and oxidized lipoproteins as oxidative stress. The LDs were aspirated directly from cells using nanotips, followed by in-tip microextraction, and the LD lipidomic profiling was conducted using nanoelectrospray mass spectrometry. As a result, the free fatty acids increased the LD lipid content and, at the same time, changed their composition significantly. The oxidized lipoproteins caused distorted proportions of intact lipids, such as triacylglycerols (TG), phosphatidylcholines (PC), phosphatidylethanolamines (PE), and cholesteryl esters (CE). Notably, the oxidized lipids, including the hydroperoxides of TG, PC, and PE, exhibited significant elevations in dose-dependent manners. Furthermore, the dysregulation of intact lipids was paralleled with the accumulation of lipid hydroperoxides. The present study has revealed that the oxidation of lipids and the dysregulation of the lipid metabolism coexisted in LDs in the kidney cells, which has provided a potential new target for diagnosis and new insights into CKD.
  • Determination of short-chain fatty acids by N,N-dimethylethylenediamine derivatization combined with liquid chromatography/mass spectrometry and their implication in influenza virus infection.
    Divyavani Gowda; Yonghan Li; Siddabasave Gowda B Gowda; Marumi Ohno; Hitoshi Chiba; Shu-Ping Hui
    Analytical and bioanalytical chemistry, 414, 22, 6419, 6430, 16 Jul. 2022, [International Magazine]
    English, Scientific journal, Short-chain fatty acids (SCFAs) are the end products of the fermentation of complex carbohydrates by the gut microbiota. Although SCFAs are recognized as important markers to elucidate the link between gut health and disease, it has been difficult to analyze SCFAs with mass spectrometry technologies due to their poor ionization efficiency and high volatility. Here, we present a novel and sensitive method for the quantification of SCFAs, including C2-C6 SCFAs and their hydroxy derivatives, by liquid chromatography/tandem mass spectrometry (LC-MS/MS) upon N,N-dimethylethylenediamine (DMED) derivatization with a run time of 10 min. Moreover, the quantification method of DMED-derivatized SCFAs in intestinal contents using isotope-labeled internal standards was also established. The method validation was performed by analyzing spiked intestinal samples; the limits of detection and quantification of SCFAs with this method were found to be 0.5 and 5 fmol, respectively; the recovery was greater than 80% and good linearity (0.9932 to 0.9979) of calibration curves was obtained over the range from 0.005 to 5000 pmol/μL; the intraday and interday precisions were achieved in the range of 1-5%. Furthermore, the validated method was applied to analyze SCFAs in the cecum and colon contents of mice infected with the influenza virus. The results showed that the concentration of most of the SCFAs tested here decreased significantly in a time-dependent manner after the infection, suggesting a possibility that SCFAs in intestinal samples could be used as severe disease markers. Overall, we here successfully developed a simple, fast, and sensitive method for SCFA analysis by LC-MS/MS combined with DMED derivatization. The method for the quantification of SCFAs will be a useful tool for both basic research and clinical studies.
  • Profiling of lysophosphatidylethanolamine molecular species in human serum and in silico prediction of the binding site on albumin.
    Nao Inoue; Toshihiro Sakurai; Yusuke Yamamoto; Hitoshi Chiba; Shu-Ping Hui
    BioFactors (Oxford, England), 48, 5, 1076, 1088, 10 Jun. 2022, [International Magazine]
    English, Scientific journal, Lysophosphatidylethanolamine (LPE) is a major lysophospholipid produced by phospholipids and binds to human serum albumin (HSA). LPEs may play various roles in vivo depending on the differences in their acyl chains. However, only few reports have been published on the biological functions of LPEs. Hence, we determined the exact relative abundance of the major LPEs in the serum of healthy participants (n = 8) using liquid chromatography-tandem mass spectrometry. Consequently, LPE 18:2 (24.1 ± 5.2%) was found to be the most abundant in serum. To understand the distribution of LPEs, the serum separated via gel-filtration high-performance liquid chromatography was subjected to quantitative measurement. LPEs were more observed in the albumin fraction than the lipoprotein fraction. We also performed a fluorescence displacement assay and an in silico molecular docking experiment using AutoDock to confirm the affinity and binding sites of the LPEs on HSA. The binding affinities of the LPEs for drug sites 1 and 2 on HSA were relatively low, with Ki values of approximately 11 and 3.8 μM, respectively. AutoDock analysis revealed the conformation of the LPEs bound to drug sites and the possibility of LPEs binding to other HSA sites. These findings could help to elucidate the biological and pathological functions of LPEs.
  • Quantitative Evaluation on the Degradation Process of the Pulmonary Surfactant Monolayer When Exposed to Low-Level Ozone of Ambient Environment.
    Lin Qiao; Zhen Chen; Chunji Takada; Hitoshi Chiba; Ken-Ichi Inoue; Shu-Ping Hui; Shen Ye
    Analytical chemistry, 94, 24, 8651, 8658, 23 May 2022, [International Magazine]
    English, Scientific journal, Ozone is a potent environmental oxidant with high chemical reactivity and is present in the ambient environment at a low level of a few tens of ppb. However, only limited information is known about low-level ozone's influence on the respiratory system. In the present study, we systematically investigated the degradation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), which is one of the major components of the pulmonary surfactant (PS), enabling breath function of the lung exposed to low ambient-level ozone (40 ± 10 ppb). Using the liquid chromatography-mass spectrometry technique combined with the Langmuir-Blodgett approach, we first tracked the degradation process of POPC molecules by determining the degradation products during exposure to the ambient environment. As a result, we found that the POPC molecules can be readily degraded from the C═C moiety in 45 min, yielding an aldehyde-type product of 1-palmitoyl-2-(9'-oxo-nonanoyl)-sn-glycero-3-phosphocholine (POnPC) and a trace amount of an acid-type one of 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PAzPC), as well as a pair of secondary ozonide (SOZ) isomers. Furthermore, with prolonged exposure, the SOZ stayed constant but the yield of PAzPC significantly increased with the decrease in POnPC. The low-level ozone-induced oxidation mechanisms for unsaturated lipids are discussed based on the quantitative analyses of these experimental observations. The present results demonstrate that the ground-level ozone is strong enough to induce dramatic oxidation damage to the unsaturated lipids of the PS. These oxidized species may trigger the lung's inflammatory response and be used as biomarkers for oxidative stress and inflammation.
  • Food-Derived β-Carboline Alkaloids Ameliorate Lipid Droplet Accumulation in Human Hepatocytes.
    Dya Fita Dibwe; Saki Oba; Nire Takeishi; Toshihiro Sakurai; Takayuki Tsukui; Hitoshi Chiba; Shu-Ping Hui
    Pharmaceuticals (Basel, Switzerland), 15, 5, 212, 212, (一社)日本臨床化学会, 05 May 2022, [International Magazine]
    English, Lipid droplet accumulation (LDA) in hepatocytes is the initial stage of nonalcoholic fatty liver disease (NAFLD). In the search for natural compounds for the prevention of NAFLD, a series of β-carboline alkaloid derivatives, inspired by flazin and its derivative, newly identified in Crassostrea gigas Thunberg. extracts, were examined for LDA inhibition (LDAI) activity in oleic acid-loaded hepatocytes (HepG2). Eight compounds with a piperidine or pyridine C-ring were chemically synthesized (1-8). Among them, compounds 2 and 4 (flazin) with a carboxy group at C-3 and furfuryl alcohol moiety at C-1 showed low cytotoxicity and they exhibited significant LDAI activity. Compound 2 with piperidine C-ring was identified for the first time in C. gigas extract, and ameliorated the lipid accumulation with the LDAI value of 25.4%. Active compounds 2 and 4 significantly inhibited triacylglycerol species accumulation in cells. These compounds upregulated ATGL and downregulated SREBP1, FASN, and SCD1 genes, suggesting that they activated lipolysis and suppressed lipogenesis, respectively. These results suggest that β-carboline alkaloids, especially compounds 2 and 4, might be potentially useful for preventing NAFLD.
  • Flazin as a Lipid Droplet Regulator against Lipid Disorders.
    Xunzhi Wu; Zhen Chen; Yue Wu; Yifan Chen; Jiaping Jia; Nianqiu Shen; Hitoshi Chiba; Shu-Ping Hui
    Nutrients, 14, 7, 03 Apr. 2022, [International Magazine]
    English, Scientific journal, Lipid disorders are closely related to numerous metabolic diseases, and lipid droplets (LDs) have been considered as a new target for regulating lipid metabolism. Dietary intervention and nutraceuticals provide safe and long-term beneficial effects for treating metabolic diseases. Flazin is a diet-derived bioactive constituent mainly existing in fermented foods, of which the lipid metabolism improvement function has not been studied. In this study, the effect of flazin on lipid regulation at both cell level and organelle level was investigated. Lipidomic profiling showed that flazin significantly decreased cellular triglyceride (TG) by 12.0-22.4% compared with modeling groups and improved the TG and free fatty acid profile. LD staining revealed that flazin efficiently reduced both cellular neutral lipid content by 17.4-53.9% and LD size by 10.0-35.3%. Furthermore, nanoelectrospray ionization mass spectrometry analysis proved that flazin exhibited a preferential suppression of LD TG and regulated LD morphology, including a size decrease and surface property improvement. An evaluation of related gene expression suggested the mechanism to be lipolysis promotion and lipogenesis inhibition. These findings indicated that flazin might be an LD regulator for reversing lipid metabolism disturbance. Moreover, the strategy proposed in this study may contribute to developing other nutraceuticals for treating lipid disorder-related metabolic diseases.
  • Effect of charcoal grilling on polycyclic aromatic hydrocarbons (PAHs): content, composition, and health risk in edible fish in Japan.
    Zijun Gao; Zhen Chen; Shu-Ping Hui
    Analytical sciences : the international journal of the Japan Society for Analytical Chemistry, 38, 3, 515, 523, Mar. 2022, [International Magazine]
    English, Scientific journal, The content and composition of polycyclic aromatic hydrocarbons (PAHs) induced by charcoal grilling of fish were determined in this study. Using HPLC-DAD, the simultaneously quantitative method for 16 priority PAHs was developed and applied to three common Japanese fish: mackerel, pacific saury, and sardine. Charcoal grilling largely increased the content of both total and representative PAHs. Moreover, all of the three fish showed a similar PAH composition under the effect of charcoal grilling: in raw samples, naphthalene was observed as the dominant PAH, while in charcoal-grilled samples, phenanthrene, fluoranthene, and pyrene served as the major PAHs. Furthermore, a health risk assessment showed that charcoal grilling resulted in high levels of the toxic equivalence quotients, the daily dietary intake exposure to PAHs, and the incremental lifetime cancer risk in three fish, which outclassed the raw samples and exceeded the recommended limitations. The results suggested that charcoal grilling-induced accumulation of PAHs and their potential health risk on human health should be of great concern, which might contribute to the dietary guidance and risk management of food-contained PAHs.
  • LC/MS analysis of storage-induced plasmalogen loss in ready-to-eat fish.
    Zhen Chen; Jiaping Jia; Yue Wu; Hitoshi Chiba; Shu-Ping Hui
    Food chemistry, 383, 132320, 132320, 02 Feb. 2022, [International Magazine]
    English, Scientific journal, Plasmalogens are functional and oxidation-sensitive phospholipids abundant in fish. Chilling and freezing are common storage methods for maintaining the quality of fish, but their effect on plasmalogen preservation has not been studied. Therefore, plasmalogen loss in ready-to-eat tuna meat during storage under different conditions was investigated. LC/MS was used to analyze the time- and temperature-dependent changes of plasmalogens, which was the most evident for the species with an ethanolamine headgroup and polyunsaturated fatty acyl chains. Moreover, a series of oxidized plasmalogen molecules were identified, and their storage-induced accumulation was observed. Plasmalogen loss was strongly correlated with total lipid oxidation and phospholipid degradation. Repeated freeze-thaw cycles were found to accelerate the loss of plasmalogens, whereas the different thawing methods did not. The present study provides a deeper understanding of changes in lipid nutrients from fish meat during storage and demonstrates the importance of using advanced strategies to maintain food quality.
  • Lysophosphatidylethanolamine Affects Lipid Accumulation and Metabolism in a Human Liver-Derived Cell Line.
    Yusuke Yamamoto; Toshihiro Sakurai; Zhen Chen; Nao Inoue; Hitoshi Chiba; Shu-Ping Hui
    Nutrients, 14, 3, 28 Jan. 2022, [International Magazine]
    English, Scientific journal, The physiological functions of lysophosphatidylethanolamine (lysoPE) have not been fully elucidated. In this study, the effects of lysoPE on lipogenesis and lipolysis were investigated in a cultured human liver-derived cell line. The intracellular lipid profile was investigated in detail using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to better understand the underlying mechanism. The expression of genes related to lipid metabolism and catabolism was analyzed using real-time PCR. LysoPE supplementation induced cellular lipid droplet formation and altered triacylglycerol (TAG) profiles. Furthermore, lysoPE downregulated expression of the TAG hydrolyzation regulation factor ATGL, and reduced the expression of fatty acid biosynthesis-related genes SREBP1 and SCD1. LC-MS/MS-based lipidomic profiling revealed that the addition of lysoPE 18:2 increased the PE species containing linoleic acyl, as well as the CE 18:2 species, likely due to the incorporation of linoleic acyl from lysoPE 18:2. Collectively, these findings suggest that lysoPE 18:2 is involved in lipid droplet formation by suppressing lipolysis and fatty acid biosynthesis. Thus, lysoPE might play a pathological role in the induction of fatty liver disease.
  • Simple and Sensitive Method for the Quantitative Determination of Lipid Hydroperoxides by Liquid Chromatography/Mass Spectrometry.
    Chongsheng Liang; Siddabasave Gowda B Gowda; Divyavani Gowda; Toshihiro Sakurai; Iku Sazaki; Hitoshi Chiba; Shu-Ping Hui
    Antioxidants (Basel, Switzerland), 11, 2, 25 Jan. 2022, [International Magazine]
    English, Scientific journal, Lipid hydroperoxides (LOOH) are the initial products of the peroxidation of unsaturated lipids and play a crucial role in lipid oxidation due to their ability to decompose into free radicals and cause adverse effects on human health. Thus, LOOHs are commonly considered biomarkers of oxidative stress-associated pathological conditions. Despite their importance, the sensitive and selective analytical method for determination is limited, due to their low abundance, poor stability, and low ionizing efficiency. To overcome these limitations, in this study, we chemically synthesized eight fatty acid hydroperoxides (FAOOH), including FA 18:1-OOH, FA 18:2-OOH, FA 18:3-OOH, FA 20:4-OOH, FA 20:5-OOH, FA 22:1-OOH, FA 22:6-OOH as analytes, and FA 19:1-OOH as internal standard. Then, they were chemically labeled with 2-methoxypropene (2-MxP) to obtain FAOOMxP by one-step derivatization (for 10 min). A selected reaction monitoring assisted targeted analytical method was developed using liquid chromatography/tandem mass spectrometry (LC-MS/MS). The MxP-labelling improved the stability and enhanced the ionization efficiency in positive mode. Application of reverse-phase chromatography allowed coelution of analytes and internal standards with a short analysis time of 6 min. The limit of detection and quantification for FAOOH ranged from 0.1-1 pmol/µL and 1-2.5 pmol/µL, respectively. The method was applied to profile total FAOOHs in chemically oxidized human serum samples (n = 5) and their fractions of low and high-density lipoproteins (n = 4). The linoleic acid hydroperoxide (FA 18:2-OOH) and oleic acid hydroperoxide (FA 18:1-OOH) were the most abundant FAOOHs in human serum and lipoproteins. Overall, our validated LC-MS/MS methodology features enhanced detection and rapid separation that enables facile quantitation of multiple FAOOHs, therefore providing a valuable tool for determining the level of lipid peroxidation with potential diagnostic applications.
  • Adverse Effects of Chrysene on Human Hepatocytes via Inducement of Oxidative Stress and Dysregulation of Xenobiotic Metabolism
    Zijian Zhu; Zhen Chen; Toshihiro Sakurai; Hitoshi Chiba; Shu-Ping Hui
    POLYCYCLIC AROMATIC COMPOUNDS, Dec. 2021
    English, Scientific journal
  • Oxidative Stress Linked Organ Lipid Hydroperoxidation and Dysregulation in Mouse Model of Nonalcoholic Steatohepatitis: Revealed by Lipidomic Profiling of Liver and Kidney.
    Yue Wu; Zhen Chen; Hirotoshi Fuda; Takayuki Tsukui; Xunzhi Wu; Nianqiu Shen; Natsuki Saito; Hitoshi Chiba; Shu-Ping Hui
    Antioxidants (Basel, Switzerland), 10, 10, 12 Oct. 2021, [International Magazine]
    English, Scientific journal, Nonalcoholic steatohepatitis (NASH) is a prevalent disease related to lipid metabolism disorder and oxidative stress. Lipid hydroperoxidation is known to be a critical driving force of various disorders and diseases. However, the combination of both intact and hydroperoxidized lipids in NASH has not yet been studied. In this work, the liver and kidney samples from NASH-model mice were comprehensively investigated by using the LC/MS-based lipidomic analysis. As a result, triglycerides showed the amount accumulation and the profile alteration for the intact lipids in the NASH group, while phosphatidylethanolamines, lysophosphatidylethanolamines, plasmalogens, and cardiolipins largely depleted, suggesting biomembrane damage and mitochondria dysfunction. Notably, the lipid hydroperoxide species of triglyceride and phosphatidylcholine exhibited a significant elevation in both the liver and the kidney of the NASH group and showed considerable diagnostic ability. Furthermore, the relationship was revealed between the lipid metabolism disturbance and the lipid hydroperoxide accumulation, which played a key role in the vicious circle of NASH. The present study suggested that the omics approach to the lipid hydroperoxide profile might be the potential diagnostic marker of NASH and other oxidative stress-related diseases, as well as the evaluative treatment index of antioxidants.
  • Defining the kinetic effects of infection with influenza virus A/PR8/34 (H1N1) on sphingosine-1-phosphate signaling in mice by targeted LC/MS.
    Divyavani Gowda; Marumi Ohno; Siddabasave Gowda B Gowda; Hitoshi Chiba; Masashi Shingai; Hiroshi Kida; Shu-Ping Hui
    Scientific reports, 11, 1, 20161, 20161, 11 Oct. 2021, [International Magazine]
    English, Scientific journal, Influenza remains a world-wide health concern, causing 290,000-600,000 deaths and up to 5 million cases of severe illnesses annually. Noticing the host factors that control biological responses, such as inflammatory cytokine secretion, to influenza virus infection is important for the development of novel drugs. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite and has essential biological functions in inflammation. However, the kinetic effects of influenza virus infection on physiological S1P levels and their signaling in multiple tissues remain unknown. In this study, we utilized a mouse model intranasally infected with 50 or 500 plaque forming units (PFU) of A/Puerto Rico/8/34 (H1N1; PR8) virus to investigate how S1P levels and expression of its regulating factors are affected by influenza virus infection by the liquid-chromatography/mass spectrometry and real-time PCR, respectively. The S1P level was significantly high in the plasma of mice infected with 500 PFU of the virus than that in control mice at 6 day-post-infection (dpi). Elevated gene expression of sphingosine kinase-1 (Sphk1), an S1P synthase, was observed in the liver, lung, white adipose tissue, heart, and aorta of infected mice. This could be responsible for the increased plasma S1P levels as well as the decrease in the hepatic S1P lyase (Sgpl1) gene in the infected mice. These results indicate modulation of S1P-signaling by influenza virus infection. Since S1P regulates inflammation and leukocyte migration, it must be worth trying to target this signaling to control influenza-associated symptoms.
  • Postpartum cows showed high oocyte triacylglycerols concurrently with high plasma free fatty acids.
    Eri Furukawa; Zhen Chen; Hiroki Ueshiba; Yue Wu; Hitoshi Chiba; Yojiro Yanagawa; Seiji Katagiri; Masashi Nagano; Shu-Ping Hui
    Theriogenology, 176, 174, 182, 02 Oct. 2021, [International Magazine]
    English, Scientific journal, Impaired oocyte quality is one of the main causes of low fertility in modern high-yielding dairy cows. One of the potential factors of the impaired oocyte quality is the effects of free fatty acids (FFA). In fact, high FFA supplementation to culture media exacerbated oocyte developmental competence in vitro. Meanwhile, artificially induced high blood FFA levels in heifers did not affect the lipid composition of oocytes in vivo; however, the oocyte lipid profile of postpartum cows has not yet been investigated. Therefore, the profile of lipids involved in energy metabolism, including FFA and triacylglycerols (TAG), and their relationship between plasma and oocytes were compared among cows at different lactation stages. Heifers were used as a control group that was not affected by lactation. Plasma and oocytes were collected from heifers (n = 4) and 14 Holstein cows categorized to the early lactation stage: 25-47 days in milk (DIM) (n = 6), peak lactation stage: 61-65 DIM (n = 4), and middle lactation stage: 160-202 DIM (n = 4). The FFA and TAG profiles of plasma and oocytes were examined by liquid chromatography mass spectrometry. Plasma FFA positively correlated with oocyte TAG (P < 0.05). Plasma FFA and oocyte TAG were significantly higher in cows in the early lactation stage than in heifers (P < 0.05), while the peak and middle lactation stage groups had intermediate levels. The proportion of oleic acid in plasma increased concurrently with elevations in total FFA, while the compositions of oocyte FFA and TAG fatty acyls were constant regardless of plasma FFA concentration or oocyte TAG content. The present results suggest that high postpartum plasma FFA concentrations affect the quantity of oocyte TAG. Taken together with the adverse effects of high FFA concentrations on oocyte developmental competence in vitro, oocyte quality in postpartum cows may be impaired due to high circulating FFA concentrations. These results provide a more detailed understanding of the effects of postpartum high circulating FFA concentrations on the low fertility of cows.
  • Serum 25-hydroxyvitamin D3 Levels and Diabetes in a Japanese Population: The DOSANCO Health Study.
    Koshi Nakamura; Shu-Ping Hui; Shigekazu Ukawa; Emiko Okada; Takafumi Nakagawa; Akihiro Imae; Hiroaki Okabe; Zhen Chen; Yusuke Miura; Hitoshi Chiba; Akiko Tamakoshi
    Journal of epidemiology, 33, 1, 31, 37, 28 Sep. 2021, [Domestic magazines]
    English, Scientific journal, BACKGROUND: Both decreased insulin sensitivity and impaired insulin secretion are common in Asian populations with diabetes, in contrast to Western populations. There is limited evidence regarding the association between insulin response in diabetes in Asian populations and serum 25-hydroxyvitamin D3 (25[OH]D3) insufficiency. METHODS: The present cross-sectional study compared the prevalence of diabetes, defined as a fasting plasma glucose level ≥126 mg/dL and/or a HbA1c level ≥6.5%, among 480 participants aged 35-79 years not taking anti-diabetes medications, based on serum 25(OH)D3 levels. A logistic regression model was used to calculate the odds ratios for diabetes in each serum 25(OH)D3 group. Furthermore, this study examined the association between serum 25(OH)D3 levels and the index of homeostasis model assessment of insulin resistance (HOMA-IR) using a linear regression model. RESULTS: The prevalence of diabetes was 7.29% in the study population, and was higher in lower serum 25(OH)D3 quartile groups. The odds ratios for diabetes in the first, second, and third serum 25(OH)D3 quartile groups (25[OH]D3: ≤18.10, 18.11-22.90, and 22.91-28.17 ng/mL) were 4.02 (95% confidence interval [CI], 1.25-12.92), 2.50 (95% CI, 0.77-8.10), and 1.91 (95% CI, 0.60-6.09), respectively, with the fourth quartile group (≽28.18 ng/mL) serving as the reference group, after adjusting for sociodemographic, lifestyle, physical and environmental factors. Serum 25(OH)D3 levels showed an inverse association with log-transformed HOMA-IR after adjusting for similar factors (standardized β = -0.08; 95% CI, -0.14 to -0.02). CONCLUSIONS: Serum 25(OH)D3 levels were inversely associated with diabetes prevalence in a general Japanese population, with a slight inverse association between serum 25(OH)D3 levels and HOMA-IR.
  • Comparison of dimension reduction methods on fatty acids food source study.
    Yifan Chen; Yusuke Miura; Toshihiro Sakurai; Zhen Chen; Rojeet Shrestha; Sota Kato; Emiko Okada; Shigekazu Ukawa; Takafumi Nakagawa; Koshi Nakamura; Akiko Tamakoshi; Hitoshi Chiba; Hideyuki Imai; Hiroyuki Minami; Masahiro Mizuta; Shu-Ping Hui
    Scientific reports, 11, 1, 18748, 18748, 21 Sep. 2021, [International Magazine]
    English, Scientific journal, Serum fatty acids (FAs) exist in the four lipid fractions of triglycerides (TGs), phospholipids (PLs), cholesteryl esters (CEs) and free fatty acids (FFAs). Total fatty acids (TFAs) indicate the sum of FAs in them. In this study, four statistical analysis methods, which are independent component analysis (ICA), factor analysis, common principal component analysis (CPCA) and principal component analysis (PCA), were conducted to uncover food sources of FAs among the four lipid fractions (CE, FFA, and TG + PL). Among the methods, ICA provided the most suggestive results. To distinguish the animal fat intake from endogenous fatty acids, FFA variables in ICA and factor analysis were studied. ICA provided more distinct suggestions of FA food sources (endogenous, plant oil intake, animal fat intake, and fish oil intake) than factor analysis. Moreover, ICA was discovered as a new approach to distinguish animal FAs from endogenous FAs, which will have an impact on epidemiological studies. In addition, the correlation coefficients between a published dataset of food FA compositions and the loading values obtained in the present ICA study suggested specific foods as serum FA sources. In conclusion, we found that ICA is a useful tool to uncover food sources of serum FAs.
  • HPLC with spectrophotometric or mass spectrometric detection for quantifying very-long chain fatty acids in human plasma and its association with cardiac risk factors.
    Rojeet Shrestha; Zhen Chen; Zijun Gao; Yifan Chen; Emiko Okada; Shigekazu Ukawa; Takafumi Nakagawa; Koshi Nakamura; Akiko Tamakoshi; Hitoshi Chiba; Shu-Ping Hui
    Annals of clinical biochemistry, 58, 5, 400, 410, Sep. 2021, [International Magazine]
    English, BACKGROUND: We developed and compared two liquid chromatography methods, one with UV/Visible spectrophotometric detection (HPLC) and the other with mass spectrometric detection (LC-MS), for quantifying very-long chain fatty acids (VLCFA) in human plasma. Association of VLCFA with various cardiovascular risk factors were evaluated. METHOD: Fasting blood samples were collected from 541 human volunteers (242 men and 299 women; mean age ±SD, 58.9 ± 12.4 years), including 429 and 112 individuals with and without hypertriglyceridemia, respectively. Esterified VLCFA were saponified and derivatized with 2-nitrophenylhydrazine. Separation of VLCFA species was achieved with C4 Mightysil column (HPLC) and Ascentis Express Phenyl-Hexyl column (LC-MS) followed by spectrophotometric and selected-reaction monitoring mode of mass spectrometric detection, respectively. RESULTS: The HPLC assay of VLCFA was precise with intra-assay imprecision of 2.5% to 6.9% and inter-assay imprecision of 3.2% to 9.5%. Moreover, there was an excellent correlation (r > 0.96) between HPLC and LC-MS methods. The 95 percentile reference intervals (RI; upper limit) of VLCFA were determined to be 41.3 µmol/L in healthy volunteers. Plasma VLCFA were significantly correlated with triglycerides (Spearman's ρ = 0.306, P < 0.001) and total cholesterol (Spearman's ρ = 0.251, P < 0.001). All species of VLCFA were significantly elevated in hypertriglyceridaemic individuals compared with control. CONCLUSION: We established LC-based assays of VLCFA with either spectrophotometry or mass spectrometry as a detection system. Hypertriglyceridaemia is significantly associated with elevated concentration of each species of VLCFA.
  • Sphingosine-1-phosphate interactions in the spleen and heart reflect extent of cardiac repair in mice and failing human hearts.
    SiddabasaveGowda B Gowda; Divyavani Gowda; Vasundhara Kain; Hitoshi Chiba; Shu-Ping Hui; Charles E Chalfant; Vibhu Parcha; Pankaj Arora; Ganesh V Halade
    American journal of physiology. Heart and circulatory physiology, 321, 3, H599-H611, 01 Sep. 2021, [International Magazine]
    English, Scientific journal, Sphingosine-1-phosphate (S1P) is a bioactive mediator in inflammation. Dysregulated S1P is demonstrated as a cause of heart failure (HF). However, the time-dependent and integrative role of S1P interaction with receptors in HF is unclear after myocardial infarction (MI). In this study, the sphingolipid mediators were quantified in ischemic human hearts. We also measured the time kinetics of these mediators post-MI in murine spleen and heart as an integrative approach to understand the interaction of S1P and respective S1P receptors in the transition of acute (AHF) to chronic HF (CHF). Risk-free 8-12 wk male C57BL/6 mice were subjected to MI surgery, and MI was confirmed by echocardiography and histology. Mass spectrometry was used to quantify sphingolipids in plasma, infarcted heart, spleen of mice, and ischemic and healthy human heart. The physiological cardiac repair was observed in mice with a notable increase of S1P quantity (pmol/g) in the heart and spleen significantly reduced in patients with ischemic HF. The circulating murine S1P levels were increased during AHF and CHF despite lowered substrate in CHF. The S1PR1 receptor expression was observed to coincide with the respective S1P quantity in mice and human hearts. Furthermore, selective S1P1 agonist limited inflammatory markers CCL2 and TNF-α and accelerated reparative markers ARG-1 and YM-1 in macrophages in the presence of Kdo2-Lipid A (KLA; potent inflammatory stimulant). This report demonstrated the importance of S1P/S1PR1 signaling in physiological inflammation during cardiac repair in mice. Alteration in these axes may serve as the signs of pathological remodeling in patients with ischemia.NEW & NOTEWORTHY Previous studies indicate that sphingosine-1-phosphate (S1P) has some role in cardiovascular disease. This study adds quantitative and integrative systems-based approaches that are necessary for discovery and bedside translation. Here, we quantitated sphinganine, sphingosine, sphingosine-1-phosphate (S1P) in mice and human cardiac pathobiology. Interorgan S1P quantity and respective systems-based receptor activation suggest cardiac repair after myocardial infarction. Thus, S1P serves as a therapeutic target for cardiac protection in clinical translation.
  • Effect of charcoal grilling on polycyclic aromatic hydrocarbons (PAHs): content, composition, and health risk in edible fish in Japan.
    Zijun Gao; Zhen Chen; Shu-Ping Hui
    Analytical sciences : the international journal of the Japan Society for Analytical Chemistry, 20 Aug. 2021, [Domestic magazines]
    English, Scientific journal
  • Detection and Structural Characterization of SFAHFA Homologous Series in Mouse Colon Contents by LTQ-Orbitrap-MS and Their Implication in Influenza Virus Infection.
    Siddabasave Gowda B Gowda; Divyavani Gowda; Marumi Ohno; Chongsheng Liang; Hitoshi Chiba; Shu-Ping Hui
    Journal of the American Society for Mass Spectrometry, 32, 8, 2196, 2205, 04 Aug. 2021, [International Magazine]
    English, Scientific journal, Fatty acid esters of hydroxy fatty acids (FAHFAs) are a new class of endogenous lipids with promising physiological functions in mammals. We previously introduced a new type of lipids to this family called short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs), branching specific to the C2 carbon of a long-chain fatty acid (≥C20). In this study, we discovered a homologous series of SFAHFAs comprising C16-C26 hydroxy fatty acids esterified with short-chain fatty acids (C2-C5) in mouse colon contents. The detected SFAHFAs were characterized by high-resolution mass spectrometry with MSn analysis. The double-bond position of monounsaturated SFAHFAs was determined by the epoxidation reaction of samples with m-chloroperoxybenzoic acid and their MSn analysis. Further, the measurement of SFAHFA concentration in the colon contents of mice infected with influenza A/Puerto Rico/8/34 (H1N1; PR8) virus revealed a significant increase in their levels compared to native control. A strong correlation was observed between hydroxy fatty acid and SFAHFAs. Detection, characterization, and profiling of these new SFAHFA levels in relation with pandemic H1N1; PR8 influenza virus will contribute to the in-depth study of their function and metabolism.
  • Docosahexaenoic Acid Esters of Hydroxy Fatty Acid Is a Novel Activator of NRF2.
    Siddabasave Gowda B Gowda; Takayuki Tsukui; Hirotoshi Fuda; Yusuke Minami; Divyavani Gowda; Hitoshi Chiba; Shu-Ping Hui
    International journal of molecular sciences, 22, 14, 15 Jul. 2021, [International Magazine]
    English, Scientific journal, Fatty acid esters of hydroxy fatty acids (FAHFAs) are a new class of endogenous lipids with interesting physiological functions in mammals. Despite their structural diversity and links with nuclear factor erythroid 2-related factor 2 (NRF2) biosynthesis, FAHFAs are less explored as NRF2 activators. Herein, we examined for the first time the synthetic docosahexaenoic acid esters of 12-hydroxy stearic acid (12-DHAHSA) or oleic acid (12-DHAHOA) against NRF2 activation in cultured human hepatoma-derived cells (C3A). The effect of DHA-derived FAHFAs on lipid metabolism was explored by the nontargeted lipidomic analysis using liquid chromatography-mass spectrometry. Furthermore, their action on lipid droplet (LD) oxidation was investigated by the fluorescence imaging technique. The DHA-derived FAHFAs showed less cytotoxicity compared to their native fatty acids and activated the NRF2 in a dose-dependent pattern. Treatment of 12-DHAHOA with C3A cells upregulated the cellular triacylglycerol levels by 17-fold compared to the untreated group. Fluorescence imaging analysis also revealed the suppression of the degree of LDs oxidation upon treatment with 12-DHAHSA. Overall, these results suggest that DHA-derived FAHFAs as novel and potent activators of NRF2 with plausible antioxidant function.
  • Lipidomic analysis of non-esterified furan fatty acids and fatty acid compositions in dietary shellfish and salmon by UHPLC/LTQ-Orbitrap-MS.
    Siddabasave Gowda B Gowda; Yusuke Minami; Divyavani Gowda; Daisuke Furuko; Hitoshi Chiba; Shu-Ping Hui
    Food research international (Ottawa, Ont.), 144, 110325, 110325, Jun. 2021, [International Magazine]
    English, Scientific journal, Lipids such as furan fatty acids (F-acids) are the valuable minor bioactive components of food such as fatty fish and plants. They are reported to have positive health benefits, including antioxidant and anti-inflammatory activities. Despite their importance, limited studies are focusing on F-acid determination in dietary seafood. This study aimed to identify and profile non-esterified F-acids and free fatty acids in total lipid extract of seafood such as shellfish and salmon. The lipidomic analysis using liquid chromatography-linear trap quadrupole-orbitrap mass spectrometry led to identifying seven types of free F-acids in shellfish (n = 5) and salmon (n = 4). The identified F-acids were confirmed by their high-resolution masses and acquired mass spectra. The relative concentrations of F-acids in shellfish range from 0.01 to 10.93 mg/100 g of the fillet, and in salmon, 0.01 to 14.21 mg/100 g of the fillet. The results revealed the highest abundance of F-acids in Sakhalin surf clam, Japanese scallop, and a fatty salmon trout. Besides, relative levels of saturated, monounsaturated, and polyunsaturated fatty acids (PUFAs) in these seafoods were compared with each other, suggesting basket clams and salmon trout to have significantly higher levels of PUFAs. The dietary seafoods enriched with F-acids and PUFAs may have possible health benefits. Hence, the applied technique could be a promising tool for rapid detection and analysis of non-esterified fatty acids in food.
  • The Phenolic Antioxidant 3,5-dihydroxy-4-methoxybenzyl Alcohol (DHMBA) Prevents Enterocyte Cell Death under Oxygen-Dissolving Cold Conditions through Polyphyletic Antioxidant Actions.
    Moto Fukai; Takuya Nakayabu; Shintaro Ohtani; Kengo Shibata; Shingo Shimada; Soudai Sakamoto; Hirotoshi Fuda; Takayuki Furukawa; Mitsugu Watanabe; Shu-Ping Hui; Hitoshi Chiba; Tsuyoshi Shimamura; Akinobu Taketomi
    Journal of clinical medicine, 10, 9, 04 May 2021, [International Magazine]
    English, Scientific journal, Cold preservation in University of Wisconsin (UW) solution is not enough to maintain the viability of the small intestine, due to the oxidative stress. The novel phenolic antioxidant 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) has dual properties to reduce oxidative stress, radical scavenging, and antioxidant protein induction, in other cells. This study was designed to determine whether DHMBA reduces cold preservation injury of enterocytes, and to identify the effector site. Enterocytes were subjected to 48-h cold preservation under atmosphere in UW solution (±DHMBA), and then returned to normal culture to replicate reperfusion of the small intestine after cold preservation. At the end of cold preservation (ECP) and at 1, 3, 6, and 72 h after rewarming (R1h, R3h, R6h, and R72h), we evaluated cell function and the injury mechanism. The results showed that DHMBA protected mitochondrial function mainly during cold preservation, and suppressed cell death after rewarming, as shown by the MTT, ATP, mitochondrial membrane potential, LDH, and lipid peroxidation assays, together with enhanced survival signals (PI3K, Akt, p70S6K) and induction of antioxidant proteins (HO-1, NQO-1, TRX-1). We found that DHMBA mitigates the cold-induced injury of enterocytes by protecting the mitochondria through direct and indirect antioxidative activities.
  • Branched-chain amino acids and l-carnitine attenuate lipotoxic hepatocellular damage in rat cirrhotic liver.
    Yasuyuki Tamai; Zhen Chen; Yue Wu; Jun Okabe; Yoshinao Kobayashi; Hitoshi Chiba; Shu-Ping Hui; Akiko Eguchi; Motoh Iwasa; Masaaki Ito; Yoshiyuki Takei
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 135, 111181, 111181, Mar. 2021, [International Magazine]
    English, Scientific journal, Branched-chain amino acids (BCAA) reverse malnutrition and l-carnitine leads to the reduction of hyperammonemia and muscle cramps in cirrhotic patients. BCAA and l-carnitine are involved in glucose and fatty acid metabolism, however their mechanistic activity in cirrhotic liver is not fully understood. We aim to define the molecular mechanism(s) and combined effects of BCAA and l-carnitine using a cirrhotic rat model. Rats were administered carbon tetrachloride for 10 weeks to induce cirrhosis. During the last 6 weeks of administration, cirrhotic rats received BCAA, l-carnitine or a combination of BCAA and l-carnitine daily via gavage. We found that BCAA and l-carnitine treatments significantly improved hepatocellular function associated with reduced triglyceride level, lipid deposition and adipophilin expression, in cirrhotic liver. Lipidomic analysis revealed dynamic changes in hepatic lipid composition by BCAA and l-carnitine administrations. BCAA and l-carnitine globally increased molecular species of phosphatidylcholine. Liver triacylglycerol and phosphatidylcholine hydroperoxides were significantly decreased by BCAA and l-carnitine. Furthermore, serum and liver ATP levels were significantly increased in all treatments, which were attributed to the elevation of mature cardiolipins and mitochondrial component gene expressions. Finally, BCAA and l-carnitine dramatically reduced hepatocellular death. In conclusion, BCAA and l-carnitine treatments attenuate hepatocellular damage through the reduction of lipid peroxides and the overall maintenance of mitochondrial integrity within the cirrhotic liver. These effectiveness of BCAA and l-carnitine support the therapeutic strategies in human chronic liver diseases.
  • A mouse model of short-term, diet-induced fatty liver with abnormal cardiolipin remodeling via downregulated Tafazzin gene expression.
    Toshihiro Sakurai; Zhen Chen; Arisa Yamahata; Takahiro Hayasaka; Hiroshi Satoh; Hirotaka Sekiguchi; Hitoshi Chiba; Shu-Ping Hui
    Journal of the science of food and agriculture, 101, 12, 4995, 5001, 05 Feb. 2021, [International Magazine]
    English, Scientific journal, BACKGROUND: Cardiolipin (CL) helps maintain mitochondrial structure and function. Here we investigated whether a high carbohydrate diet (HCD) fed to mice for a short period (5 days) could modulate the CL level, including that of monolysoCL (MLCL) in the liver. RESULTS: Total CL in the HCD group was 22% lower than that in the normal chow diet (NCD) group (P < 0.05). The CL72:8 level strikingly decreased by 93% (P < 0.0001), whereas total nascent CLs (CLs other than CL72:8) increased (P < 0.01) in the HCD group. The total MLCL in the HCD group increased by 2.4-fold compared with that in the NCD group (P < 0.05). Tafazzin expression in the HCD group was significantly downregulated compared with that in the NCD group (P < 0.05). A strong positive correlation between nascent CL and total MLCL (r = 0.955, P < 0.0001), and a negative correlation between MLCL and Tafazzin expression (r = -0.593, P = 0.0883) were observed. CONCLUSION: A HCD modulated the fatty acid composition of CL and MLCL via Tafazzin in the liver, which could lead to mitochondrial dysfunction. This model may be useful for elucidating the relationship between fatty liver and mitochondrial dysfunction. © 2021 Society of Chemical Industry.
  • Quantitative and Comparative Investigation of Plasmalogen Species in Daily Foodstuffs.
    Yue Wu; Zhen Chen; Jiaping Jia; Hitoshi Chiba; Shu-Ping Hui
    Foods (Basel, Switzerland), 10, 1, 08 Jan. 2021, [International Magazine]
    English, Scientific journal, Plasmalogens are an animal-derived functional phospholipid increasingly known as a safe and effective nutritional ingredient, however, the quantitation and comparison of plasmalogen species in foods is limited. In the present work, determination methods for dietary plasmalogens using liquid chromatography-tandem mass spectroscopy under positive and negative ionization modes were compared. The negative-mode method, which showed better selectivity, sensitivity, and accuracy, was then applied in 14 kinds of livestock, poultry, and seafood samples. Livestock and poultry showed abundant total plasmalogen (530.83-944.94 nmol/g), higher than fish (46.08-399.75 nmol/g) and mollusk (10.00-384.76 nmol/g). While fish and mollusk samples expressed healthier fatty acyl composition, with higher eicosapentaenoyl and more beneficial n-6/n-3 ratio than the land animal meats, especially for squid and octopus, with eicosapentaenoyl of 98.4% and 94.5%, respectively. The correlations among plasmalogen species varied in different foodstuffs with distinguishing patterns, suggesting the customizable strategies for achieving targeted plasmalogen species. These findings not only provided fundamental comparison of plasmalogen among daily foodstuffs, but also contributed to extend the dietary plasmalogen sources for health food development.
  • Analysis of serum lysophosphatidylethanolamine levels in patients with non-alcoholic fatty liver disease by liquid chromatography-tandem mass spectrometry.
    Yusuke Yamamoto; Toshihiro Sakurai; Zhen Chen; Takayuki Furukawa; Siddabasave Gowda B Gowda; Yue Wu; Kazuhiro Nouso; Yuki Fujii; Yuki Yoshikawa; Hitoshi Chiba; Shu-Ping Hui
    Analytical and bioanalytical chemistry, 413, 1, 245, 254, Jan. 2021, [International Magazine]
    English, Scientific journal, Lysophosphatidylethanolamines (LysoPEs) are the partial hydrolysis products of phosphatidylethanolamine. Despite the unique in vitro bioactivities of LysoPEs, there are limited reports on the pathophysiological role of LysoPEs in the serum, due to the lack of sensitive analytical methods for determination of each molecular species in clinical samples. Herein, we developed a highly sensitive quantitative method to profile the serum LysoPE species by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with selected reaction monitoring (SRM). The internal standard (IS), chemically synthesized in-house, and the lineup of seven major LysoPE species were used in this study. The limits of detection and quantification for each LysoPE species ranged within 0.5-3.3 pmol/mL and 1.0-5.0 pmol/mL, respectively. The combined concentrations of LysoPEs in the serum from healthy subjects (n = 8) and the patients with non-alcoholic fatty liver diseases (NAFLD) including simple steatosis (SS, n = 9) and non-alcoholic steatohepatitis (NASH, n = 27) were 18.030 ± 3.832, 4.867 ± 1.852, and 5.497 ± 2.495 nmol/mL, respectively. The combined and individual concentrations of LysoPEs, except for LysoPE 18:0, significantly decreased in the patients with NAFLD compared with those for the healthy subjects. However, no significant difference was observed between the SS and NASH groups. Our proposed LC-MS/MS method is valid and has advantages of small sample volume, high sensitivity, and simultaneous absolute quantitation for multiple molecular species. This method may enable diagnostic evaluation and elucidation of the as-yet uncovered pathophysiological role of LysoPEs.
  • Comparison of anthocyanin distribution in berries of Haskap (Lonicera caerulea subsp. edulis (Turcz. ex. Herder) Hultén), Miyama-uguisukagura (Lonicera gracilipes Miq.), and their interspecific hybrid using imaging mass spectrometry.
    Ryohei Fujita; Takahiro Hayasaka; Shigeki Jin; Shu-Ping Hui; Yoichiro Hoshino
    Plant science : an international journal of experimental plant biology, 300, 110633, 110633, Nov. 2020, [International Magazine]
    English, Scientific journal, Haskap (Lonicera caerulea subsp. edulis), a shrub with violet-blue fruits, is distributed mainly in Hokkaido, Japan. Miyama-uguisukagura (Lonicera gracilipes), a species related to Haskap, produces red fruits. Interspecific hybridization of Miyama-uguisukagura and Haskap was performed to introduce novel characteristics in the resulting hybrids. The shape and color of the interspecific hybrid fruits differed from those of the parent fruits. A comparison of anthocyanin distribution among these three fruit types by imaging mass spectrometry (IMS) revealed the presence of five different anthocyanins. The average cyanidin 3,5-diglucoside and peonidin 3,5-diglucoside intensities in the interspecific hybrid fruit were higher than those of the parent fruits, whereas the average pelargonidin 3-glucoside, cyanidin 3-glucoside, and peonidin 3-glucoside intensities were the highest in Haskap. All anthocyanins were mainly accumulated in the inner and outer skins of Haskap and interspecific hybrid fruits, and in the skin of Miyama-uguisukagura fruits. The order of signal intensities of all anthocyanins among the three fruits was unchanged in different regions. Additionally, a comparison of IMS and LC/MS data from our previous study confirmed the possibility of comparing multiple fruits in the same plate by IMS. Thus, we elucidated anthocyanin distribution patterns of the interspecific hybrid and parent fruits by IMS.
  • Low-Density Lipoprotein (LDL)-Triglyceride and Its Ratio to LDL-Cholesterol as Diagnostic Biomarkers for Nonalcoholic Steatohepatitis.
    Yuki Fujii; Kazuhiro Nouso; Hiroshi Matsushita; Kazuya Kariyama; Toshihiro Sakurai; Yuji Takahashi; Hitoshi Chiba; Shu-Ping Hui; Yasuki Ito; Motoko Ohta; Hiroyuki Okada
    The journal of applied laboratory medicine, 5, 6, 1206, 1215, 01 Nov. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease, but it is difficult to distinguish its pathogenic phenotype, nonalcoholic steatohepatitis (NASH), from nonalcoholic fatty liver (NAFL) without a liver biopsy. We analyzed serum lipids, including low-density lipoprotein triglyceride (LDL-TG), to elucidate their usefulness for diagnosing NASH. PATIENTS AND METHODS: Serum samples obtained from 35 NASH and 9 NAFL biopsy-confirmed patients and 6 healthy volunteers (HLT) were studied for 13 lipid-related markers and compared between HLT, NAFL, and NASH groups. The relationship between histological findings and the lipid markers was also analyzed. RESULTS: There were significant differences in triglyceride, LDL-TG, the ratio of LDL-TG to the LDL-cholesterol (LDL-TG/LDL-C), small dense LDL-C, and apolipoprotein E between the three groups. Among the 5 lipid components, serum LDL-TG level and the ratio of LDL-TG to the LDL-cholesterol (LDL-TG/LDL-C) were significantly elevated in NASH. The median concentrations of LDL-TG in HLT, NAFL, and NASH were 9, 15, and 20 mg/dL (P < 0.001), and those of LDL-TG/LDL-C were 0.097, 0.102, and 0.173 (P < 0.001), respectively. Although the degree of steatosis was not correlated with the LDL-TG/LDL-C, the ratio was significantly higher in patients with lobular inflammation (P = 0.071), ballooning (P = 0.031), and fibrosis (P < 0.001). The area under the receiver operating characteristic curve of the ratio for distinguishing NASH from NAFL was 0.857. The rest of studied markers showed no significant utility. CONCLUSION: Serum LDL-TG levels and the LDL-TG/LDL-C ratio might serve as simple and noninvasive diagnostic biomarkers for NASH.
  • Comprehensive lipidomic profiling in serum and multiple tissues from a mouse model of diabetes.
    Zhen Chen; Qiangrong Liang; Yue Wu; Zijun Gao; Satoru Kobayashi; Joy Patel; Cairong Li; Fei Cai; Youhua Zhang; Chongsheng Liang; Hitoshi Chiba; Shu-Ping Hui
    Metabolomics : Official journal of the Metabolomic Society, 16, 11, 115, 115, 16 Oct. 2020, [International Magazine]
    English, Scientific journal, INTRODUCTION: Diabetes mellitus is a serious metabolic disorder causing multiple organ damage in human. However, the lipidomic profiles in different organs and their associations are rarely studied in either diabetic patients or animals. OBJECTIVES: To evaluate and compare the characteristics of lipid species in serum and multiple tissues in a diabetic mouse model. METHODS: Semi-quantitative profiling analyses of intact and oxidized lipids were performed in serum and multiple tissues from a diabetic mouse model fed a high fat diet and treated with streptozotocin by using LC/HRMS and MS/MS. The total content of each lipid class, and the tissue-specific lipid species in all tissue samples were determined and compared by multivariate analyses. RESULTS: The diabetic mouse model displayed characteristic differences in serum and multiple organs: the brain and heart showed the largest reduction in cardiolipin, while the kidney had more alterations in triacylglycerol. Interestingly, the lipidomic differences also existed between different regions of the same organ: cardiolipin species with highly polyunsaturated fatty acyls decreased only in atrium but not in ventricle, while renal cortex showed longer fatty acyl chains for both increased and decreased triacylglycerol species than renal medulla. Importantly, diabetes caused an accumulation of lipid hydroperoxides, suggesting that oxidative stress was induced in all organs except for the brain during the development of diabetes. CONCLUSIONS: These findings provided novel insight into the organ-specific relationship between diabetes and lipid metabolism, which might be useful for evaluating not only diabetic tissue injury but also the effectiveness of diabetic treatments.
  • Chemical Labeling Assisted Detection and Identification of Short Chain Fatty Acid Esters of Hydroxy Fatty Acid in Rat Colon and Cecum Contents.
    Siddabasave Gowda B Gowda; Divyavani Gowda; Chongsheng Liang; Yonghan Li; Kentaro Kawakami; Satoru Fukiya; Atsushi Yokota; Hitoshi Chiba; Shu-Ping Hui
    Metabolites, 10, 10, 08 Oct. 2020, [International Magazine]
    English, Scientific journal, Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are novel endogenous lipids with important physiological functions in mammals. We previously identified a new type of FAHFAs, named short-chain fatty acid esterified hydroxy fatty acids (SFAHFAs), with acetyl or propyl esters of hydroxy fatty acids of carbon chains, C ≥ 20. However, sensitive determination of SFAHFAs is still a challenge, due to their high structural similarity and low abundance in biological samples. This study employs one-step chemical derivatization following total lipid extraction using 2-dimethylaminoethylamine (DMED) for enhanced detection of SFAHFAs. The labeled extracts were subjected to ultrahigh performance liquid chromatography coupled to linear ion trap quadrupole-Orbitrap mass spectrometry (UHPLC/LTQ-Orbitrap MS). Our results demonstrated that the detection sensitivities of SFAHFAs increased after DMED labeling, and is highly helpful in discovering six additional novel SFAHFAs in the cecum and colon contents of WKAH/HKmSlc rats fed with normal and high-fat diet (HFD). The identified DMED labeled SFAHFAs were characterized by their detailed MS/MS analysis, and their plausible fragmentation patterns were proposed. The concentrations of SFAHFAs were significantly reduced in the cecum of HFD group compared to the control. Hence, the proposed method could be a promising tool to apply for the enhanced detection of SFAHFAs in various biological matrices, which in turn facilitate the understanding of their sources, and physiological functions of these novel lipids.
  • IVIG感受性川崎病患児と抵抗性患児との間にみられる脂質の特徴の違い(Differential lipid characteristics in Kawasaki disease between IVIG sensitive and resistant children)
    陳 震; 齋 秀二; Wu Yue; 千葉 仁志; 惠 淑萍
    臨床化学, 49, Suppl.1, 215, 215, (一社)日本臨床化学会, Oct. 2020
    English
  • Identification of short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs) in a murine model by nontargeted analysis using ultra-high-performance liquid chromatography/linear ion trap quadrupole-Orbitrap mass spectrometry.
    Siddabasave Gowda B Gowda; Chongsheng Liang; Divyavani Gowda; Fengjue Hou; Kentaro Kawakami; Satoru Fukiya; Atsushi Yokota; Hitoshi Chiba; Shu-Ping Hui
    Rapid communications in mass spectrometry : RCM, 34, 17, e8831, 15 Sep. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, RATIONALE: Fatty acid esters of hydroxy fatty acids (FAHFAs) are recently discovered endogenous lipids with outstanding health benefits. FAHFAs are known to exhibit antioxidant, antidiabetic and anti-inflammatory properties. The number of known long-chain FAHFAs in mammalian tissues and dietary resources increased recently because of the latest developments in high-resolution tandem mass spectrometry techniques. However, there are no reports on the identification of short-chain fatty acid esterified hydroxy fatty acids (SFAHFAs). METHODS: Intestinal contents, tissues, and plasma of rats fed with high-fat diet (HFD) and normal diet (ND) were analyzed for fatty acids, hydroxy fatty acids, and FAHFAs using ultra-high-performance liquid chromatography (UHPLC) and linear trap quadrupole-Orbitrap mass spectrometry (LTQ Orbitrap MS) with negative heated electrospray ionization. RESULTS: Untargeted analysis of total lipid extracts from murine samples (male 13-week-old WKAH/HKmSlc rats) led to the identification of several new SFAHFAs of acetic acid or propanoic acid esterified long-chain (>C20)-hydroxy fatty acids. Furthermore, MS3 analysis revealed the position of the hydroxyl group in the long-chain fatty acid as C-2. The relative amounts of SFAHFAs were quantified in intestinal contents and their tissues (Cecum, small intestine, and large intestine), liver, and plasma of rats fed with HFD and ND. The large intestine showed the highest abundance of SFAHFAs with a concentration range from 0.84 to 57 pmol/mg followed by the cecum with a range of 0.66 to 28.6 pmol/mg. The SFAHFAs were significantly altered between the HFD and ND groups, with a strong decreasing tendency under HFD conditions. CONCLUSIONS: Identification of these novel SFAHFAs can contribute to a better understanding of the chemical and biological properties of individual SFAHFAs and their possible sources in the gut, which in turn helps us tackle the role of these lipids in various metabolic diseases.
  • Plasmalogen fingerprint alteration and content reduction in beef during boiling, roasting, and frying.
    Yue Wu; Zhen Chen; Hitoshi Chiba; Shu-Ping Hui
    Food chemistry, 322, 126764, 126764, 30 Aug. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Plasmalogens are dietary phospholipids with beneficial health effects. In this work, plasmalogen characteristics and changes in beef during boiling, frying, and roasting were comprehensively investigated by liquid-chromatography-mass spectrometry. The alteration of plasmalogen fingerprint during cooking processes was found by untargeted omics approach, in which time of boiling, temperature of roasting, and meat core/surface of frying were responsible for the observed variations. Moreover, the targeted determination of representative plasmalogen species showed significant loss with a temperature- and time-dependent manner in roasting and frying. And frying even showed an extra loss in meat surface compared with core. Furthermore, an artificial neural network-based predictive model elucidated the dynamics of plasmalogen species during cooking. Finally, batter-coating pretreatment was performed to show its protection against plasmalogens loss during frying. These results might provide a potential strategy to better control and improve the quality of functional foodstuffs during cooking processes.
  • Correction to: Deoxynivalenol-induced alterations in the redox status of HepG2 cells: identification of lipid hydroperoxides, the role of Nrf2-Keap1 signaling, and protective effects of zinc
    Wageh Sobhy Darwish; Zhen Chen; Yonghan Li; Hui Tan; Hitoshi Chiba; Shu-Ping Hui
    Mycotoxin Research, Aug. 2020
    Scientific journal
  • Untargeted Lipidomic Analysis of Plasma from High-fat Diet-induced Obese Rats Using UHPLC-Linear Trap Quadrupole-Orbitrap MS
    GOWDA Siddabasave Gowda B.; GAO Zi-Jun; CHEN Zhen; ABE Takayuki; HORI Shota; FUKIYA Satoru; ISHIZUKA Satoshi; YOKOTA Atsushi; CHIBA Hitoshi; HUI Shu-Ping
    Analytical Sciences, 36, 7, 821, 828, 10 Jul. 2020, [Peer-reviewed], [Domestic magazines]
    English, High-fat diet (HFD)-induced obesity is a primary risk factor for serious health problems. Although much research has been performed at the genomic level, lipidomic studies were limited. In this study, we aim to obtain a comprehensive profile of circulating plasma lipids, which are altered in rodent rat obesity by untargeted liquid chromatography-mass spectrometry. Rats fed with HFD for 8 weeks had increased body weight, liver and adipose tissue weight. The analysis results revealed that polyunsaturated fatty acids (PUFAs) and their corresponding phosphatidylcholine, phosphatidylinositol, and phosphatidylserine were significantly decreased in rats fed with HFD. In contrast, less unsaturated and ether type phosphatidylglycerols were increased. The triacylglycerides (TAGs) having saturated FA were increased in the HFD condition, whereas TAGs having PUFA were decreased. The levels of many plasma lipids were altered, and interestingly PUFA derived lipids were negatively associated with obesity. This signifies the importance of a PUFAs enriched diet to overwhelm obesity associated diseases.
  • A Simple and Efficient Method for Synthesis of sn-Glycero-Phosphoethanolamine.
    Siddabasave Gowda B Gowda; Hirotoshi Fuda; Yusuke Yamamoto; Hitoshi Chiba; Shu-Ping Hui
    Lipids, 55, 4, 395, 401, Jul. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, An efficient three-step strategy for the convenient synthesis of Sn-glycero-3-phosphoethanolamine (GroPEtn) from a commercially available 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) is reported. Direct hydrolysis of DPPE produces a complex inseparable mixture, hence a protection and deprotection strategy is employed to prepare GroPEtn. The primary amine of DPPE is protected with a highly stable acid-labile trityl group, followed by strong base hydrolysis of N-trityl-DPPE gives N-trityl-GroPEtn. Further a mild, rapid, and efficient deprotection method is established using trifluoroacetic acid to remove N-trityl moiety, affords GroPEtn as a single product. This is the first semisynthetic approach and efficient method to produce GroPEtn with a total yield of 66% in three steps. GroPEtn did not show any cytotoxicity against human kidney (HK-2) cells and reporter gene assay for activation of Keap1-Nrf2-mediated antioxidant defense mechanism showed no significant effects.
  • Oxidized lipid species in lipoproteins: Significance and analytical considerations
    Rojeet Shrestha; Hitoshi Chiba; Shu-Ping Hui
    Medical Mass Spectrometry, 4, 1, 1, 22, Japanese Society for Biomedical Mass Spectrometry, Jun. 2020, [Peer-reviewed], [Domestic magazines]
    English
  • Discovery of Eicosapentaenoic Acid Esters of Hydroxy Fatty Acids as Potent Nrf2 Activators.
    Siddabasave Gowda B Gowda; Hirotoshi Fuda; Takayuki Tsukui; Hitoshi Chiba; Shu-Ping Hui
    Antioxidants (Basel, Switzerland), 9, 5, 08 May 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are a recently discovered class of biologically active lipids with anti-inflammatory and anti-diabetic properties. Despite the possible link between endogenous FAHFA levels and nuclear factor erythroid 2-related factor 2 (Nrf2), their possible function as antioxidants and the mechanisms involved in this are unknown. Here, we investigate FAHFAs' plausible antioxidant potential with reference to their effect on the Nrf2 levels, oxidative stress, and lipid droplet oxidation in human hepatocytes (C3A). Six authentic FAHFAs were chemically synthesized and performed activity-based screening by reporter gene assay. Among them, eicosapentaenoic acid (EPA) esterified 12-hydroxy stearic acid (12-HSA) and 12-hydroxy oleic acid (12-HOA) FAHFAs showed less cytotoxicity compared to their free fatty acids and potent activators of Nrf2. To define their mode of action, relative levels of nuclear Nrf2 were determined, which found a higher amount of Nrf2 in nucleus of cells treated with 12-EPAHSA compared to the control. Furthermore, 12-EPAHSA increased the expression of Nrf2-dependent antioxidant enzyme genes (NQO1, GCLM, GCLC, SOD-1, and HO-1). Fluorescence imaging analysis of linoleic-acid-induced lipid droplets (LDs) in C3A cells treated with 12-EPAHSA revealed the strong inhibition of small-size LD oxidation. These results suggest that EPA-derived FAHFAs as a new class of lipids with less cytotoxicity, and strong Nrf2 activators with plausible antioxidant effects via the induction of cytoprotective proteins against oxidative stress, induced cellular damage.
  • Identification of novel biomarkers of hepatocellular carcinoma by high-definition mass spectrometry: Ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry and desorption electrospray ionization mass spectrometry imaging.
    Koshi Nagai; Baasanjav Uranbileg; Zhen Chen; Amane Fujioka; Takahiro Yamazaki; Yotaro Matsumoto; Hiroki Tsukamoto; Hitoshi Ikeda; Yutaka Yatomi; Hitoshi Chiba; Shu-Ping Hui; Toru Nakazawa; Ritsumi Saito; Seizo Koshiba; Junken Aoki; Daisuke Saigusa; Yoshihisa Tomioka
    Rapid communications in mass spectrometry : RCM, 34 Suppl 1, Suppl 1, e8551, Apr. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, RATIONALE: Hepatocellular carcinoma (HCC) is a highly malignant disease for which the development of prospective or prognostic biomarkers is urgently required. Although metabolomics is widely used for biomarker discovery, there are some bottlenecks regarding the comprehensiveness of detected features, reproducibility of methods, and identification of metabolites. In addition, information on localization of metabolites in tumor tissue is needed for functional analysis. Here, we developed a wide-polarity global metabolomics (G-Met) method, identified HCC biomarkers in human liver samples by high-definition mass spectrometry (HDMS), and demonstrated localization in cryosections using desorption electrospray ionization MS imaging (DESI-MSI) analysis. METHODS: Metabolic profiling of tumor (n = 38) and nontumor (n = 72) regions in human livers of HCC was performed by an ultrahigh-performance liquid chromatography quadrupole time-of-flight MS (UHPLC/QTOFMS) instrument equipped with a mixed-mode column. The HCC biomarker candidates were extracted by multivariate analyses and identified by matching values of the collision cross section and their fragment ions on the mass spectra obtained by HDMS. Cryosections of HCC livers, which included both tumor and nontumor regions, were analyzed by DESI-MSI. RESULTS: From the multivariate analysis, m/z 904.83 and m/z 874.79 were significantly high and low, respectively, in tumor samples and were identified as triglyceride (TG) 16:0/18:1(9Z)/20:1(11Z) and TG 16:0/18:1(9Z)/18:2(9Z,12Z) using the synthetic compounds. The TGs were clearly localized in the tumor or nontumor areas of the cryosection. CONCLUSIONS: Novel biomarkers for HCC were identified by a comprehensive and reproducible G-Met method with HDMS using a mixed-mode column. The combination analysis of UHPLC/QTOFMS and DESI-MSI revealed that the different molecular species of TGs were associated with tumor distribution and were useful for characterizing the progression of tumor cells and discovering prospective biomarkers.
  • Multivariate Analysis for Molecular Species of Cholesteryl Ester in the Human Serum.
    Yifan Chen; Shu-Ping Hui; Yusuke Miura; Sota Kato; Toshihiro Sakurai; Zhen Chen; Emiko Okada; Shigekazu Ukawa; Takafumi Nakagawa; Koshi Nakamura; Akiko Tamakoshi; Hitoshi Chiba; Hiroyuki Minami; Masahiro Mizuta
    Analytical sciences : the international journal of the Japan Society for Analytical Chemistry, 36, 3, 373, 378, 10 Mar. 2020, [Peer-reviewed], [Domestic magazines]
    English, Cholesteryl ester (CE) is an ester of cholesterol and fatty acid (FA). Plasma CE reflects complicated metabolisms of cholesterol, phospholipids, lipoproteins, and dietary FAs. An informatics approach could be useful for analysis of the CE species. In this study, two basic dimension reduction methods, principal component analysis (PCA) and factor analysis, were applied to serum CE species determined by LC-MS/MS in a Japanese population (n = 545). PCA and factor analysis both reflected the size (concentration), food source, fat solubility, and biological aspect of the CE species. In a comparison between PCA (PC4) and factor analysis (factor 4), the latter was found to be more suggestive from a biological aspect of n-6 FAs. Cholesteryl docosahexaenoate (DHA) was found to be unique by a factor analysis, possibly relevant to the unique accumulation of DHA in the brain. An informatics approach, especially factor analysis, might be useful for the analysis of complicated metabolism of CE species in the serum.
  • Lipidomic profiling of dairy cattle oocytes by high performance liquid chromatography-high resolution tandem mass spectrometry for developmental competence markers.
    Zhen Chen; Yue Wu; Masashi Nagano; Kouki Ueshiba; Eri Furukawa; Yusuke Yamamoto; Hitoshi Chiba; Shu-Ping Hui
    Theriogenology, 144, 56, 66, 01 Mar. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, A comparative lipidomic profiling analysis of dairy cattle oocytes with different developmental competences was performed using a combination of high performance liquid chromatography-high resolution tandem mass spectrometry and multivariate statistical analysis. Significant lipidomic changes were identified in degenerating oocytes. Total triacylglycerol in the degenerating oocytes was 1.8-fold higher than that in the normal oocytes; however, total cardiolipin was 53.5% lesser than that in the normal oocytes, which indicated attenuation of energy metabolism. Compared to those in the normal oocytes, triacylglycerols in the degenerating oocytes were composed of longer and more unsaturated acyl chains. In contrast, the acyl chains in free fatty acids present in the degenerating oocytes were shorter and with lesser degree of unsaturation compared to those in the normal oocytes. Moreover, a significant decrease in degenerating oocytes were found in total phosphatidylinositol (14.8 ± 7.6 pmol vs. 24.8 ± 5.5 pmol), total phosphatidylcholine (20.8 ± 8.7 pmol vs. 33.5 ± 7.2 pmol), and total plasmalogen ethanolamine (9.0 ± 4.7 pmol vs. 16.8 ± 5.2 pmol), which indicated dysfunction of lipid-metabolizing enzymes in oocytes during degeneration. Thus, increase of triacylglycerols together with the decrease of certain phospholipid species could be potential markers of oocyte developmental competence. In addition to providing a new approach to investigate the lipidomic changes in oocyte development, the lipidomic profiling in the present study has revealed insights that hold potential to unravel the role of lipid metabolism in oocyte developmental competence in cattle.
  • Identification of molecular species of phosphatidylcholine hydroperoxides in native and copper-oxidized triglyceride-rich lipoproteins in humans.
    Rojeet Shrestha; Zhen Chen; Yusuke Miura; Yusuke Yamamoto; Toshihiro Sakurai; Hitoshi Chiba; Shu-Ping Hui
    Annals of clinical biochemistry, 57, 1, 95, 98, Jan. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Identification of cadmium-produced lipid hydroperoxides, transcriptomic changes in antioxidant enzymes, xenobiotic transporters, and pro-inflammatory markers in human breast cancer cells (MCF7) and protection with fat-soluble vitamins.
    Wageh Sobhy Darwish; Zhen Chen; Yonghan Li; Yue Wu; Hitoshi Chiba; Shu-Ping Hui
    Environmental science and pollution research international, 27, 2, 1978, 1990, Jan. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Cadmium (Cd) is a toxic metal that is regarded as a metallohormone with estrogen-like properties. The present study aimed at identification of lipid hydroperoxides produced in human breast cancer (MCF7) exposed to cadmium (Cd) at environmentally relevant levels. Cd induced cytotoxicity and oxidative stress and produced a series of 26 lipid hydroperoxide species including 14 phosphatidylcholine hydroperoxides (PC-OOH), 9 triacylglycerol hydroperoxides (TG-OOH), and 3 cholesteryl ester hydroperoxides (CE-OOH). Among these hydroperoxides, PC34:2-OOH, PC34:3-OOH, TG60:14-OOH, TG48:5-OOH, TG60:15-OOH, and CE20:4-OOH were produced in a dose-dependent manner, suggesting these as possible biomarkers for Cd exposure in MCF7 cells. In addition, Cd led to significant decreases in the gene expressions of antioxidants, detoxification enzymes, and xenobiotic transporters. In a protection trial, co-exposure of MCF7 cells to fat-soluble vitamins including vitamin A, D, and E reduced Cd-induced cytotoxicity, lipid peroxidation, oxidative stress, and inflammatory responses. Fat-soluble vitamins upregulated antioxidant and detoxification enzymes, and xenobiotic transporters. Therefore, dietary supplementation of such micronutrients is recommended for people at risk for exposure to Cd.
  • Author Correction: Circulating Apolipoprotein L1 is associated with insulin resistance-induced abnormal lipid metabolism (Scientific Reports, (2019), 9, 1, (14869), 10.1038/s41598-019-51367-7)
    Kenji Nishimura; Taichi Murakami; Toshihiro Sakurai; Masashi Miyoshi; Kiyoe Kurahashi; Seiji Kishi; Masanori Tamaki; Tatsuya Tominaga; Sumiko Yoshida; Kojiro Nagai; Hideharu Abe; Shu-Ping Hui; Kazuhiko Kotani; Toshio Doi
    Scientific Reports, 9, 1, Nature Research, 01 Dec. 2019
    English, Scientific journal
  • Identification of lead-produced lipid hydroperoxides in human HepG2 cells and protection using rosmarinic and ascorbic acids with a reference to their regulatory roles on Nrf2-Keap1 antioxidant pathway
    Yonghan Li; Wageh Sobhy Darwish; Zhen Chen; Tan Hui; Yue Wu; Suzuki Hirotaka; Hitoshi Chiba; Shu-Ping Hui
    Chemico-Biological Interactions, 314, Elsevier Ireland Ltd, 01 Dec. 2019
    English, Scientific journal
  • Flazin as a Promising Nrf2 Pathway Activator.
    Hirotoshi Fuda; Satoshi Miyanaga; Takayuki Furukawa; Satomi Umetsu; Sae Joko; Yuning Roan; Hirotaka Suzuki; Shu-Ping Hui; Mitsugu Watanabe; Hitoshi Chiba
    Journal of agricultural and food chemistry, 67, 46, 12844, 12853, 20 Nov. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Flazin is a β-carboline-derived alkaloid found in Japanese fermented foods. Here, the potential of flazin as an antioxidant food was studied with particular reference to its effect on the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) system in human hepatocytes (C3A). Flazin and flazin analogues including the decarboxylated derivative perlolyrine were chemically synthesized and compared with each other and with chlorogenic acid and curcumin. Among these compounds, flazin showed the lowest cytotoxicity (IC50 < 500 μM) and the highest capacity to activate the Keap1-Nrf2 system. It provided the largest (>3-fold of the control) cytoprotection ability against a pro-oxidant, although its radical absorbance capacity was relatively low. Flazin increased the expressions of Nrf2-dependent phase II enzyme genes and their products (NQO1, GSTP, and GSH proteins). The strong cytoprotection ability of flazin associated with low log P (0-3) is shared by sulforaphane and 3,5-dihydroxy-4-methoxybenzyl alcohol, suggesting the potential value of flazin and flazin-rich foods for the prevention of oxidation-related health disorders.
  • A phase II, open-label clinical trial on the combination therapy with medium-chain triglycerides and ghrelin in patients with chronic obstructive pulmonary disease.
    Keisuke Miki; Seigo Kitada; Mari Miki; Shu-Ping Hui; Rojeet Shrestha; Kenji Yoshimura; Kazuyuki Tsujino; Hiroyuki Kagawa; Yohei Oshitani; Hiroshi Kida; Ryoji Maekura; Kenji Kangawa
    The journal of physiological sciences : JPS, 69, 6, 969, 979, Nov. 2019, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, The aim of this study was to investigate the effect of activated ghrelin with dietary octanoic acids or medium-chain triglyceride (MCT) administration to underweight patient with chronic obstructive pulmonary disease (COPD). Eleven severe and very severe COPD patients received a 5-day treatment with edible MCT. Sequentially, 10 patients received a 3-week combination treatment with MCT and intravenous acyl ghrelin. Five-day MCT treatment increased endogenous acyl ghrelin (p = 0.0049), but the total ghrelin level was unchanged. MCT-ghrelin combination treatment improved the peak oxygen uptake (p = 0.0120) during whole treatment course. This effect was attributed to the resultant improvements in cardiac function by O2 pulse, and to the difference between inspired and expired oxygen concentration rather than minute ventilation. Addition of dietary MCT to ghrelin treatment improved the aerobic capacity of underweight COPD patients, likely by mechanisms of increased O2 delivery through improvements in primary cardiocirculatory and muscular crosstalk.
  • Circulating Apolipoprotein L1 is associated with insulin resistance-induced abnormal lipid metabolism.
    Kenji Nishimura; Taichi Murakami; Toshihiro Sakurai; Masashi Miyoshi; Kiyoe Kurahashi; Seiji Kishi; Masanori Tamaki; Tatsuya Tominaga; Sumiko Yoshida; Kojiro Nagai; Hideharu Abe; Shu-Ping Hui; Kazuhiko Kotani; Toshio Doi
    Scientific reports, 9, 1, 14869, 14869, 16 Oct. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Circulating ApolipoproteinL1 (ApoL1) is a component of pre-β-high-density lipoprotein (HDL), however little is known about the relationship of ApoL1 with cardiometabolic factors. Considering previous studies reporting the correlation of ApoL1 to triglyceride, we have hypothesized that ApoL1 associates with insulin-related metabolism. The current study examined their associations in 126 non-diabetic subjects and 36 patients with type 2 diabetes (T2DM). Non-diabetic subjects demonstrated triglyceride (standardized coefficients [s.c.] = 0.204, p < 0.05), body mass index (s.c. =0.232, p < 0.05) and HDL cholesterol (s.c. = -0.203, p < 0.05) as independent determinant of ApoL1 levels, and the significant elevation of ApoL1 in metabolic syndrome. Lipoprotein fractionation analysis revealed the predominant distribution of ApoL1 in large HDL fraction, and the significant increase of ApoL1 in large LDL fraction in high ApoL1 samples with insulin resistance. In T2DM, ApoL1 was higher in T2DM with metabolic syndrome, however ApoL1 was lower with β cell dysfunction. Insulin significantly promotes ApoL1 synthesis and secretion in HepG2 cells. In conclusion, circulating ApoL1 may be associated with abnormal HDL metabolism in insulin resistant status. This may suggest a regulation of insulin signal on the ApoL1 level, leading to offer a novel insight to the ApoL1 biology.
  • Postgraduate education constructs the base of clinical chemistry
    Hitoshi Chiba; Shu-Ping Hui
    Japanese Journal of Clinical Chemistry, 48, 4, 321, 327, Japanese Journal of Clinical Chemistry, 01 Oct. 2019
    Japanese, Scientific journal
  • Development of a simultaneous quantitation for short-, medium-, long-, and very long-chain fatty acids in human plasma by 2-nitrophenylhydrazine-derivatization and liquid chromatography-tandem mass spectrometry.
    Zhen Chen; Zijun Gao; Yue Wu; Rojeet Shrestha; Hiromitsu Imai; Naoto Uemura; Ken-Ichi Hirano; Hitoshi Chiba; Shu-Ping Hui
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 1126-1127, 121771, 121771, 15 Sep. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Fatty acids (FA) have been important in clinical diagnosis for long, which makes the increasing need for a fast, reliable, and economic approach to determine FA of short-, medium-, long-, and very long-chain by widely available equipment and with high-throughput capacity. In the present work, 2‑nitrophenylhydrazine derivatization coupling with LC-MS/MS detection was utilized to simultaneously quantitate 18 FAs ranging from C4 to C26 in human plasma. The sample preparation protocol was optimized and extracting with diethyl ether‑potassium phosphate buffer twice was found as the highest efficiency along with economic feasibility. Under the optimized conditions, all the FA showed excellent linearity (R2 > 0.999 for each), sufficient sensitivity (LOD 0.2-330 fmol and LOQ 2.3-660 fmol for all), favorable accuracy (recovery ranged from 98.1 ± 3.6% to 104.9 ± 5.5% with coefficient of variation no >8.6% for all), and negligible matrix effect. In the clinical application on 30 healthy subjects, compared with the previous HPLC-UV method, the developed method showed high reliability, as well as reduced time and reagent costs. The established method showed the potential to apply to not only diagnostic practice, but also nutritional and epidemiological studies.
  • Novel Fluorescence-Based Method To Characterize the Antioxidative Effects of Food Metabolites on Lipid Droplets in Cultured Hepatocytes.
    Tsukui T; Chen Z; Fuda H; Furukawa T; Oura K; Sakurai T; Hui SP; Chiba H
    Journal of agricultural and food chemistry, 67, 35, 9934, 9941, Sep. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, A fluorescence microscopic method for characterizing size, quantity, and oxidation of lipid droplets (LDs) in HepG2 cells was developed. LDs were induced by palmitic (PA), oleic (OA), or linoleic acids (LA) and stained with two fluorescent probes for neutral lipids and lipid peroxides. Each fatty acid increased the number of LDs and oxidized LDs (oxLDs) and the degree of LD oxidation time dependently, as well as increased intracellular triglyceride hydroperoxides. LDs induced by LA without 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) showed the most significant oxidation degree over PA and OA, especially in large LDs (area ≥ 3 μm2, oxLD/LD = 52.3 ± 21.7%). Under this condition, two food-derived antioxidants were evaluated, and both of them significantly improved the LD characteristics. Moreover, chlorogenic acid reduced the quantity of large LDs by 74.0-87.6% in a dose-dependent manner. The proposed method provides a new approach to evaluate the effect of dietary antioxidants on LD characteristics.
  • Identification of novel biomarkers of hepatocellular carcinoma by a high definition mass spectrometry; UHPLC-QTOF/MS and DESI-MSI.
    Nagai K; Uranbileg B; Chen Z; Fujioka A; Yamazaki T; Matsmoto Y; Tsukamoto H; Ikeda H; Yatomi Y; Chiba H; Hui SP; Nakazawa T; Saito R; Koshiba S; Aoki J; Saigusa D; Tomioka Y
    Rapid communications in mass spectrometry : RCM, 34, Aug. 2019, [Peer-reviewed]
    English, Scientific journal
  • Determination of polycyclic aromatic hydrocarbon content in heat-treated meat retailed in Egypt: Health risk assessment, benzo[a]pyrene induced mutagenicity and oxidative stress in human colon (CaCo-2) cells and protection using rosmarinic and ascorbic ac
    Darwish WS; Chiba H; El-Ghareeb WR; Elhelaly AE; Hui SP
    Food chemistry, 290, 114, 124, Aug. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, This study was undertaken to estimate the concentrations of the formed polycyclic aromatic hydrocarbons (PAHs) in heat-treated (boiled, pan-fried and grilled) meats collected from Egypt. Dietary intakes and cancer risks of PAHs among Egyptian adults were calculated. Benzo[a]pyrene (B[a]P)-induced mutagenicity and oxidative stress in human colon (CaCo-2) cell line and mechanisms behind such effects were also investigated. Finally, protection trials using rosmarinic (RMA) and ascorbic acids (ASA) were carried out. The results indicated formation of PAHs at high levels in the heat-treated meats. Calculated incremental life time cancer risk among Egyptian adults were 7.05179E-07, 7.00604 E-06 and 1.86069 E-05 due to ingestion of boiled, pan-fried and grilled meats, respectively. B[a]P-exposed CaCo-2 cells had high abilities for mutagenicity (490.05 ± 21.37 His + revertants) and production of reactive oxygen species. RMA and ASA protected CaCo-2 cells via reduction of B[a]P-induced mutagenicity and oxidative stress and upregulation of phase II detoxification enzymes and xenobiotic transporters.
  • Choline and Ethanolamine Plasmalogens Prevent Lead-Induced Cytotoxicity and Lipid Oxidation in HepG2 Cells.
    Wu Y; Chen Z; Darwish WS; Terada K; Chiba H; Hui SP
    Journal of agricultural and food chemistry, 67, 27, 7716, 7725, Jul. 2019, [Peer-reviewed]
  • Triglyceride deposit cardiomyovasculopathy: a rare cardiovascular disorder.
    Ming Li; Ken-Ichi Hirano; Yoshihiko Ikeda; Masahiro Higashi; Chikako Hashimoto; Bo Zhang; Junji Kozawa; Koichiro Sugimura; Hideyuki Miyauchi; Akira Suzuki; Yasuhiro Hara; Atsuko Takagi; Yasuyuki Ikeda; Kazuhiro Kobayashi; Yoshiaki Futsukaichi; Nobuhiro Zaima; Satoshi Yamaguchi; Rojeet Shrestha; Hiroshi Nakamura; Katsuhiro Kawaguchi; Eiryu Sai; Shu-Ping Hui; Yusuke Nakano; Akinori Sawamura; Tohru Inaba; Yasuhiko Sakata; Yoko Yasui; Yasuyuki Nagasawa; Shintaro Kinugawa; Kazunori Shimada; Sohsuke Yamada; Hiroyuki Hao; Daisaku Nakatani; Tomomi Ide; Tetsuya Amano; Hiroaki Naito; Hironori Nagasaka; Kunihisa Kobayashi
    Orphanet journal of rare diseases, 14, 1, 134, 134, 11 Jun. 2019, [Peer-reviewed], [International Magazine]
    English, Triglyceride deposit cardiomyovasculopathy (TGCV) is a phenotype primarily reported in patients carrying genetic mutations in PNPLA2 encoding adipose triglyceride lipase (ATGL) which releases long chain fatty acid (LCFA) as a major energy source by the intracellular TG hydrolysis. These patients suffered from intractable heart failure requiring cardiac transplantation. Moreover, we identified TGCV patients without PNPLA2 mutations based on pathological and clinical studies. We provided the diagnostic criteria, in which TGCV with and without PNPLA2 mutations were designated as primary TGCV (P-TGCV) and idiopathic TGCV (I-TGCV), respectively. We hereby report clinical profiles of TGCV patients. Between 2014 and 2018, 7 P-TGCV and 18 I-TGCV Japanese patients have been registered in the International Registry. Patients with I-TGCV, of which etiologies and causes are not known yet, suffered from adult-onset severe heart disease, including heart failure and coronary artery disease, associated with a marked reduction in ATGL activity and myocardial washout rate of LCFA tracer, as similar to those with P-TGCV. The present first registry-based study showed that TGCV is an intractable, at least at the moment, and heterogeneous cardiovascular disorder.
  • Analysis of molecular species of phosphatidylcholine hydroperoxide in human native and copper-oxidized triglyceride-rich lipoproteins
    Shrestha Rojeet; Chen Z; Miura Y; Yamamoto Y; Sakurai T; Chiba H; Hui SP
    Clinica Chimica Acta, 439, S82, S83, Elsevier BV, Jun. 2019, [Peer-reviewed]
    English, International conference proceedings
  • Composition of plasmalogens in serum lipoproteins from patients with non-alcoholic steatohepatitis and their susceptibility to oxidation
    Akiko Ikuta; Toshihiro Sakurai; Megumi Nishimukai; Yuji Takahashi; Atsushi Nagasaka; Shu-Ping Hui; Hiroshi Hara; Hitoshi Chiba
    Clinica Chimica Acta, 493, 1, 7, Jun. 2019, [Peer-reviewed]
    Scientific journal
  • Interaction between LDL-mimetic liposomes and acid-treated carbon nanotube electrode during Cu2+-mediated oxidation
    Seiji Takeda; Koichi Mukasa; Shu-Ping Hui; Hitoshi Chiba
    Biochemical and Biophysical Research Communications, 513, 1, 275, 279, May 2019, [Peer-reviewed]
    Scientific journal
  • Serum 25-hydroxyvitamin D3 levels and poor sleep quality in a Japanese population: the DOSANCO Health Study.
    Koshi Nakamura; Shu-Ping Hui; Shigekazu Ukawa; Emiko Okada; Takafumi Nakagawa; Hiroaki Okabe; Zhen Chen; Yusuke Miura; Hitoshi Chiba; Akiko Tamakoshi
    Sleep medicine, 57, 135, 140, May 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, OBJECTIVE: The present cross-sectional study investigated the relationship between serum 25-hydroxyvitamin D3 (25[OH]D3) levels and the presence of poor sleep quality in a community-based Japanese adult population. METHODS: Poor sleep quality, defined as poor subjective sleep quality and/or use of sleep medications, was assessed using a self-administered questionnaire. The prevalence of poor sleep quality was compared among 512 Japanese participants aged 35-79 years, based on serum 25(OH)D3 levels, which were determined using tandem mass spectrometry. A logistic regression model was used to calculate the odds ratios (ORs) for the presence of poor sleep quality in each group with the highest quartile of 25(OH)D3 serving as the reference group. RESULTS: Poor sleep quality was reported by 33.2% of the total study population. The prevalence of poor sleep quality was higher in the first quartile group (25[OH]D3: 2.08-18.13 ng/mL) than in the second, third and fourth quartile groups (18.14-23.07 ng/mL, 23.08-28.32 ng/mL, and 28.33-78.83 ng/mL, respectively). The ORs for poor sleep quality were 1.86 (95% confidence interval, 1.08-3.20) for the first quartile group, 0.73 (0.41-1.29) for the second quartile group, and 0.73 (0.42-1.27) for the third quartile group after adjusting for age, sex, and sociodemographic, lifestyle, physical and environmental factors, while the ORs were 1.68 (0.96-2.95), 0.69 (0.39-1.24), and 0.65 (0.37-1.15) after further adjustment for overall health status and depression status. CONCLUSIONS: The first quartile group of serum 25(OH)D3 was associated with the presence of poor sleep quality.
  • Separating and Profiling Phosphatidylcholines and Triglycerides from Single Cellular Lipid Droplet by In-Tip Solvent Microextraction Mass Spectrometry.
    Zhao Y; Chen Z; Wu Y; Tsukui T; Ma X; Zhang X; Chiba H; Hui SP
    Analytical chemistry, 91, 7, 4466, 4471, Apr. 2019, [Peer-reviewed]
  • Estimation of cadmium content in Egyptian foodstuffs: health risk assessment, biological responses of human HepG2 cells to food-relevant concentrations of cadmium, and protection trials using rosmarinic and ascorbic acids.
    Darwish WS; Chiba H; Elhelaly AE; Hui SP
    Environmental science and pollution research international, 26, 15, 15443, 15457, Apr. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Cadmium (Cd) is an environmental pollutant that can get entry into human body via ingestion of contaminated foods causing multiple organ damage. This study aimed at monitoring Cd residues in 20 foodstuffs of animal origin that are commonly consumed in Egypt. Health risk assessment was conducted via calculation of Cd dietary intakes and non-carcinogenic target hazard quotient. An in vitro approach was performed to investigate the constitutive effects of Cd on human hepatoma (HepG2) cells under food-relevant concentrations. Trials to reduce Cd-induced adverse effects on HepG2 cells were done using rosmarinic (RMA) and ascorbic acids (ASA). The achieved results indicated contamination of the tested foodstuffs with Cd at high levels with potential human health hazards. Cd at food-relevant concentrations caused significant cytotoxicity to HepG2 cells. This may be attributed to induction of oxidative stress and inflammation, as indicated by the overexpression of stress and inflammatory markers. At the same time, Cd downregulated xenobiotic transporters and upregulated the proliferation factors. Co-exposure of HepG2 cells to Cd and micronutrients such as RMA and ASA led to recovery of cells from the oxidative damage, and subsequently cell viability was strongly improved. RMA and ASA ameliorated the biological responses of HepG2 cells to Cd exposure.
  • Determination of total, free and esterified short-chain fatty acid in human serum by liquid chromatography-mass spectrometry.
    Chen Z, Wu Y; Shrestha R; Gao Z; Zhao Y; Miura Y; Tamakoshi A; Chiba H; Hui SP
    Annals of clinical biochemistry, 56, 2, 190, 197, Mar. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Short-chain fatty acids are primarily absorbed through the portal vein during lipid digestion, which is utilized as the energy source, as well as prevent type 2 diabetes and some cancers. However, reports on the determination of these short-chain fatty acids in human serum are limited. METHODS: Blood samples from human subjects ( n = 547, male/female = 246/301, age 58.85 ± 12.57) were collected. Saponification was applied to obtain total fatty acid. After derivatization by 2-nitrophenylhydrazine, fatty acid 4:0 and fatty acid 6:0 were measured by liquid chromatography-mass spectrometry. RESULTS: The developed method exhibited good linearity (R2 = 0.9996 for both). All the coefficients of variation of reproducibility and accuracy for fatty acid 4:0 and fatty acid 6:0 ranged 3.0%-6.1%, with the average recoveries of 87.8%-102.4% and 92.2%-98.2%, respectively. In all the samples, the concentration of fatty acid 4:0 (162.4 ± 76.4 μmol/L) was significantly higher than fatty acid 6:0 (2.0 ± 2.5 μmol/L, P < 0.001). Furthermore, the esterified form was predominant in both fatty acid 4:0 and fatty acid 6:0 (98.2% and 82.4% of total fatty acids, respectively). Besides, short-chain fatty acids showed no significant differences with regard to sex or age differences. CONCLUSION: This developed liquid chromatography-mass spectrometry method is convenient and reliable, which might be useful for monitoring the variations of short-chain fatty acids in blood.
  • Dietary salmon milt extracts attenuate hepatosteatosis and liver dysfunction in diet-induced fatty liver model.
    Sakurai T; Hayasaka T; Sekiguchi H; Satoh H; Chen Z; Chiba H; Hui SP
    Journal of the science of food and agriculture, 99, 4, 1675, 1681, Mar. 2019, [Peer-reviewed]
  • Microbiome Alteration in Type 2 Diabetes Mellitus Model of Zebrafish.
    Fumiyoshi Okazaki; Liqing Zang; Hiroko Nakayama; Zhen Chen; Zi-Jun Gao; Hitoshi Chiba; Shu-Ping Hui; Takahiko Aoki; Norihiro Nishimura; Yasuhito Shimada
    Scientific reports, 9, 1, 867, 867, 29 Jan. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Understanding the gut microbiota in metabolic disorders, including type 2 diabetes mellitus (T2DM), is now gaining importance due to its potential role in disease risk and progression. We previously established a zebrafish model of T2DM, which shows glucose intolerance with insulin resistance and responds to anti-diabetic drugs. In this study, we analysed the gut microbiota of T2DM zebrafish by deep sequencing the 16S rRNA V3-V4 hypervariable regions, and imputed a functional profile using predictive metagenomic tools. While control and T2DM zebrafish were fed with the same kind of feed, the gut microbiota in T2DM group was less diverse than that of the control. Predictive metagenomics profiling using PICRUSt revealed functional alternation of the KEGG pathways in T2DM zebrafish. Several amino acid metabolism pathways (arginine, proline, and phenylalanine) were downregulated in the T2DM group, similar to what has been previously reported in humans. In summary, we profiled the gut microbiome in T2DM zebrafish, which revealed functional similarities in gut bacterial environments between these zebrafish and T2DM affected humans. T2DM zebrafish can become an alternative model organism to study host-bacterial interactions in human obesity and related diseases.
  • Examining the effect of regioisomerism on the physico-chemical properties of lysophosphatidylethanolamine-containing liposomes using fluoro probes.
    Yamamoto Y; Furukawa T; Takeda S; Kashida H; Chiba H; Hui SP
    Chemistry and physics of lipids, 216, 9, 16, Nov. 2018, [Peer-reviewed]
  • Lipidomic Profiling on Oxidized Phospholipids in Type 2 Diabetes Mellitus Model Zebrafish.
    Zhen Chen; Liqing Zang; Yue Wu; Hiroko Nakayama; Yasuhito Shimada; Rojeet Shrestha; Yaoyao Zhao; Yusuke Miura; Hitoshi Chiba; Shu-Ping Hui; Norihiro Nishimura
    Analytical sciences : the international journal of the Japan Society for Analytical Chemistry, 34, 10, 1201, 1208, 10 Oct. 2018, [Peer-reviewed], [Domestic magazines]
    English, Type 2 diabetes mellitus is a serious metabolic disorder in the world. Oxidative stress, as a key role on the pathogenesis of diabetes, also results in the oxidation of phospholipids. However, studies on phospholipid oxidation in diabetes, especially directly focusing on oxidized and degraded phospholipid species, are quite limited. In this study, phospholipid profiles of diabetic zebrafish plasma were characterized by LC-HRMS and MS/MS, and the total amounts of each lipid class were compared. Furthermore, the key molecular species as biomarkers in distinguishing control and diabetic samples were investigated by orthogonal partial least squares discriminant analysis. Among the identified 114 phospholipid species in total, there were 11 hydroperoxides, 7 aldehydes, and 19 lysophospholipids found significantly elevated along with the increasing blood glucose, which were known as oxidation or degradation products. Furthermore, lysophosphatidylcholine 20:5 and lysophosphatidylcholine 22:6 were assessed as potential biomarkers in diabetic zebrafish. The current work would not only help to gain further insights into diabetes, but also contribute to find new clinical parameters for the screening of the promising antioxidant agents for its therapies.
  • Determination of Total, Free, and Esterified Short-Chain Fatty Acid in Human Serum by LC-MS/MS.
    Chen Z, Wu Y; Shrestha R; Gao Z; Zhao Y; Miura Y; Tamakoshi A; Chiba H; Hui SP
    Annals of clinical biochemistry, 4563218801393, {SAGE} Publications, Sep. 2018, [Peer-reviewed]
  • Determination of Serum 25-Hydroxyvitamin D3 by LC/MS/MS and Its Monthly Variation in Sapporo Indoor Workers.
    Okabe H; Shimizu C; Yamamoto M; Kikuchi R; Minami A; Chen YF; Imai H; Mizuta M; Chen Z; Chiba H; Hui SP
    Analytical sciences : the international journal of the Japan Society for Analytical Chemistry, 34, 9, 1043, 1047, Sep. 2018, [Peer-reviewed], [Domestic magazines]
    English, 25-Hydroxyvitamin D3 (25(OH)D3) as the metabolite of vitamin D, is connected with various of diseases, and important to people with limited sunshine. Thus, the investigation of serum 25-hydroxyvitamin D and its variation in these people is necessary. In this study, a simple, precise, and accurate method for serum 25(OH)D3 determination by LC/MS/MS was developed. Serum samples were obtained monthly for one year from 11 male and 11 female indoor workers in Sapporo, Japan, and the overall 25(OH)D3 concentration was 12.9 ± 4.7 ng/mL. The 25(OH)D3 in females was significantly lower than that in males (14.0 ± 5.0 vs. 11.9 ± 4.3 ng/mL). The serum 25(OH)D3 concentration in males and females were both strongly correlated to UV-B radiation (r2 = 0.8477 and 0.7384, respectively), with a two-month's lag. Also the monthly change in 25(OH)D3 in males was more significant than that in females.
  • A two-step homogeneous assay for apolipoprotein E-containing high-density lipoprotein-cholesterol.
    Takahashi Y; Ito Y; Sakurai T; Wada N; Nagasaka A; Fujikawa M; Chiba H; Hui SP
    Annals of clinical biochemistry, 56, 1, 4563218795212, 132, Aug. 2018, [Peer-reviewed]
  • Effects of enzymes on elastic modulus of low-density lipoproteins were investigated using atomic force microscopy
    Seiji Takeda; Toshihiro Sakurai; Shu-Ping Hui; Hirotoshi Fuda; Hitoshi Chiba
    Biochemical and Biophysical Research Communications, 501, 3, 607, 611, Elsevier B.V., 27 Jun. 2018, [Peer-reviewed]
    English, Scientific journal
  • Microwave-assisted Derivatization of Fatty Acids for Its Measurement in Milk Using High-Performance Liquid Chromatography.
    Rojeet Shrestha; Yusuke Miura; Ken-Ichi Hirano; Zhen Chen; Hiroaki Okabe; Hitoshi Chiba; Shu-Ping Hui
    Analytical sciences : the international journal of the Japan Society for Analytical Chemistry, 34, 5, 575, 582, Japan Society for Analytical Chemistry, 2018, [Peer-reviewed], [Domestic magazines]
    English
  • Identification and Quantitation of C=C Location Isomers of Unsaturated Fatty Acids by Epoxidation Reaction and Tandem Mass Spectrometry
    Yaoyao Zhao; Hansen Zhao; Xu Zhao; Jia Jia; Qiang Ma; Sichun Zhang; Xinrong Zhang; Hitoshi Chiba; Shu-Ping Hui; Xiaoxiao Ma
    ANALYTICAL CHEMISTRY, 89, 19, 10270, 10278, Oct. 2017, [Peer-reviewed]
    English, Scientific journal
  • An Efficient Glycoblotting-Based Analysis of Oxidized Lipids in Liposomes and a Lipoprotein
    Takayuki Furukawa; Hiroshi Hinou; Seiji Takeda; Hitoshi Chiba; Shin-Ichiro Nishimura; Shu-Ping Hui
    CHEMBIOCHEM, 18, 19, 1903, 1909, Oct. 2017, [Peer-reviewed]
    English, Scientific journal
  • Profiling of cardiolipins and their hydroperoxides in HepG2 cells by LC/MS
    Zhen Chen; Yue Wu; Yi-Shing Ma; Yuu Kobayashi; Yao-Yao Zhao; Yusuke Miura; Hitoshi Chiba; Shu-Ping Hui
    ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 409, 24, 5735, 5745, Sep. 2017, [Peer-reviewed]
    English, Scientific journal
  • Comparison of chemical structures and cytoprotection abilities between direct and indirect antioxidants
    Sae Joko; Mitsugu Watanabe; Hirotoshi Fuda; Seiji Takeda; Takayuki Furukawa; Shu-Ping Hui; Rojeet Shrestha; Hitoshi Chiba
    JOURNAL OF FUNCTIONAL FOODS, 35, 245, 255, Aug. 2017, [Peer-reviewed]
    English, Scientific journal
  • Absolute quantification of cholesteryl esters using liquid chromatography-tandem mass spectrometry uncovers novel diagnostic potential of urinary sediment
    Yusuke Miura; Takayuki Furukaw; Miho Kobayashi; Rojeet Shrestha; Ryoji Takahashi; Chikara Shimizu; Hitoshi Chiba; Shu-Ping Hui
    STEROIDS, 123, 43, 49, Jul. 2017, [Peer-reviewed]
    English, Scientific journal
  • Selective improvement of peptides imaging on tissue by supercritical fluid wash of lipids for matrix-assisted laser desorption/ionization mass spectrometry
    Shoko Matsushita; Noritaka Masaki; Kohei Sato; Takahiro Hayasaka; Eiji Sugiyama; Shu-Ping Hui; Hitoshi Chiba; Nobuyuki Mase; Mitsutoshi Setou
    ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 409, 6, 1475, 1480, Feb. 2017, [Peer-reviewed]
    English, Scientific journal
  • Change in Plasma Total, Esterified and Non-esterified Capric Acid Concentrations during a Short-term Oral Administration of Synthetic Tricaprin in Dogs.
    Rojeet Shrestha; Ken-Ichi Hirano; Akira Suzuki; Satoshi Yamaguchi; Yusuke Miura; Yi-Fan Chen; Masahiro Mizuta; Hitoshi Chiba; Shu-Ping Hui
    Analytical sciences : the international journal of the Japan Society for Analytical Chemistry, 33, 11, 1297, 1303, 2017, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal
  • Rapid tin-mediated access to a lysophosphatidylethanolamine (LPE) library: Application to positional LC/MS analysis for hepatic LPEs in non-alcoholic steatohepatitis model mice
    Takayuki Furukawa; Hirotoshi Fuda; Satoshi Miyanaga; Chinatsu Watanabe; Hitoshi Chiba; Shu-Ping Hui
    CHEMISTRY AND PHYSICS OF LIPIDS, 200, 133, 138, Oct. 2016, [Peer-reviewed]
    English, Scientific journal
  • A fatty acid profiling method using liquid chromatography-high resolution mass spectrometry for improvement of assisted reproductive technology
    Akiko Yagi; Satoshi Miyanaga; Rojeet Shrestha; Seiji Takeda; Seiichi Kobayashi; Hitoshi Chiba; Hirobumi Kamiya; Shu-Ping Hui
    CLINICA CHIMICA ACTA, 456, 100, 106, May 2016, [Peer-reviewed]
    English, Scientific journal
  • Imaging Mass Spectrometry Reveals a Decrease of Cardiolipin in the Kidney of NASH Model Mice
    Takahiro Hayasaka; Hirotoshi Fuda; Shu-Ping Hui; Hitoshi Chiba
    ANALYTICAL SCIENCES, 32, 4, 473, 476, Apr. 2016, [Peer-reviewed]
    English, Scientific journal
  • Synthesis of (2 beta,3 alpha,6-H-2(3))cholesteryl linoleate and cholesteryl oleate as internal standards for mass spectrometry
    Yusuke Miura; Shu-Ping Hui; Rojeet Shrestha; Takahisa Hiruma; Seiji Takeda; Hirotoshi Fuda; Shigeo Ikegawa; Ken-ichi Hirano; Hitoshi Chiba
    STEROIDS, 107, 1, 9, Mar. 2016, [Peer-reviewed]
    English, Scientific journal
  • Development of homogeneous assay for simultaneous measurement of apoE-deficient, apoE-containing, and total HDL-cholesterol
    Yuji Takahashi; Yasuki Ito; Norio Wada; Atsushi Nagasaka; Masato Fujikawa; Toshihiro Sakurai; Rojeet Shrestha; Shu-Ping Hui; Hitoshi Chiba
    CLINICA CHIMICA ACTA, 454, 135, 142, Feb. 2016, [Peer-reviewed]
    English, Scientific journal
  • Improvement of Mitochondrial Function and Lipid Utilization by 3,5-dihydroxy-4-methoxybenzyl Alcohol, an Oyster-derived polyphenol, in Oleate-loaded C2C12 Myotubes.
    Ma YS; Yoshida S; Kobayashi Y; Kawanishi N; Furukawa T; Fuda H; Hui SP; Chiba H
    Journal of Food and Nutrition Research, 4, 8, 498, 507, Science & Education Publishing, 2016, [Peer-reviewed]
    English, Anti-oxidative effects of the Pacific oyster-derived phenolic antioxidant, 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), has been documented in hepatocytes. Additionally, DHMBA-rich oyster extracts significantly attenuated obesity in a non-alcoholic steatohepatitis mouse model. Whether the administration of DHMBA might improve muscular mitochondrial function was investigated. The mouse C2C12-derived myotubes were loaded with oleic acid (400μM) and cultured for 24 hours in the presence of DHMBA (500μM) with or without electrical stimulation (ES), where ES was given as exercise mimic. The fatty acid uptake, lipid accumulation, and mitochondrial function were subsequently accessed. DHMBA and ES increased fatty acid uptake, TG contents, mitochondrial membrane potential, intracellular level of H2O2, and mitochondrial O2 consumption rate. Intracellular ATP content was significantly increased when both DHMBA and ES were loaded at the same time, suggesting their synergic action. Phosphorylated AMPKα, AMPKβ1, and acetyl-CoA carboxylase were increased by DHMBA, indicating a possible role for DHMBA for activation of metabolic adaptation system and consequent increase of fatty acid oxidation. In conclusion, DHMBA solely or in collaboration with exercise might possibly serve as a fitness food for obese persons by stimulating muscular fatty acid utilization and mitochondrial energy production. This assumption must be verified by animal experiment.
  • Oyster extracts attenuate pathological changes in non-alcoholic steatohepatitis (NASH) mouse model
    Mitsugu Watanabe; Hirotoshi Fuda; Hiroaki Okabe; Sae Joko; Yusuke Miura; Shu-Ping Hui; Yimin; Naohiro Hamaoka; Emiko Miki; Hitoshi Chiba
    JOURNAL OF FUNCTIONAL FOODS, 20, 516, 531, Jan. 2016, [Peer-reviewed]
    English, Scientific journal
  • Mass Spectrometric Quantification of Amphipathic, Polyphenolic Antioxidant of the Pacific Oyster (Crassostrea Gigas)
    Hiroaki Okabe; Shu-Ping Hui; Hirotoshi Fuda; Takayuki Furukawa; Seiji Takeda; Rojeet Shrestha; Yusuke Miura; Mitsugu Watanabe; Hitoshi Chiba
    ANALYTICAL SCIENCES, 31, 12, 1341, 1344, Dec. 2015, [Peer-reviewed]
    English, Scientific journal
  • Elastic modulus of low-density lipoprotein as potential indicator of its oxidation
    Seiji Takeda; Agus Subagyo; Shu-Ping Hui; Hirotoshi Fuda; Rojeet Shrestha; Kazuhisa Sueoka; Hitoshi Chiba
    ANNALS OF CLINICAL BIOCHEMISTRY, 52, 6, 647, 653, Nov. 2015, [Peer-reviewed]
    English, Scientific journal
  • Identification of molecular species of oxidized triglyceride in plasma and its distribution in lipoproteins
    Rojeet Shrestha; Shu-Ping Hui; Yusuke Miura; Akiko Yagi; Yuji Takahashi; Seiji Takeda; Hirotoshi Fuda; Hitoshi Chiba
    CLINICAL CHEMISTRY AND LABORATORY MEDICINE, 53, 11, 1859, 1869, Oct. 2015, [Peer-reviewed]
    English, Scientific journal
  • Plasma capric acid concentrations in healthy subjects determined by high-performance liquid chromatography
    Rojeet Shrestha; Shu-Ping Hui; Hiromitsu Imai; Satoru Hashimoto; Naoto Uemura; Seiji Takeda; Hirotoshi Fuda; Akira Suzuki; Satoshi Yamaguchi; Ken-ichi Hirano; Hitoshi Chiba
    ANNALS OF CLINICAL BIOCHEMISTRY, 52, 5, 588, 596, Sep. 2015, [Peer-reviewed]
    English, Scientific journal
  • Synergistic Costimulatory Effect of Chlamydia pneumoniae with Carbon Nanoparticles on NLRP3 Inflammasome-Mediated Interleukin-1 beta Secretion in Macrophages
    Junji Matsuo; Shinji Nakamura; Seiji Takeda; Kasumi Ishida; Tomohiro Yamazaki; Mitsutaka Yoshida; Hitoshi Chiba; Shu-Ping Hui; Hiroyuki Yamaguchi
    INFECTION AND IMMUNITY, 83, 7, 2917, 2925, Jul. 2015, [Peer-reviewed]
    English, Scientific journal
  • Anti-apoptotic effects of novel phenolic antioxidant isolated from the Pacific oyster (Crassostrea gigas) on cultured human hepatocytes under oxidative stress
    Hirotoshi Fuda; Mitsugu Watanabe; Shu-Ping Hui; Sae Joko; Hiroaki Okabe; Shigeki Jin; Seiji Takeda; Emiko Miki; Takayuki Watanabe; Hitoshi Chiba
    FOOD CHEMISTRY, 176, 226, 233, Jun. 2015, [Peer-reviewed]
    English, Scientific journal
  • Serum choline plasmalogens-those with oleic acid in sn-2-are biomarkers for coronary artery disease
    Megumi Nishimukai; Ryouta Maeba; Akiko Ikuta; Naoya Asakawa; Kiwamu Kamiya; Shiro Yamada; Takashi Yokota; Mamoru Sakakibara; Hiroyuki Tsutsui; Toshihiro Sakurai; Yuji Takahashi; Shu-Ping Hui; Hitoshi Chiba; Tomoki Okazaki; Hiroshi Hara
    CLINICA CHIMICA ACTA, 437, 147, 154, Nov. 2014, [Peer-reviewed]
    English, Scientific journal
  • Identification of molecular species of cholesteryl ester hydroperoxides in very low-density and intermediate-density lipoproteins
    Rojeet Shrestha; Shu-Ping Hui; Toshihiro Sakurai; Akiko Yagi; Yuji Takahashi; Seiji Takeda; Shigeki Jin; Hirotoshi Fuda; Hitoshi Chiba
    ANNALS OF CLINICAL BIOCHEMISTRY, 51, 6, 662, 671, Nov. 2014, [Peer-reviewed]
    English, Scientific journal
  • Changes of lipoproteins in phenylalanine hydroxylase-deficient children during the first year of life
    Hironori Nagasaka; Hirokazu Tsukahara; Yoshiyuki Okano; Ken-ichi Hirano; Toshihiro Sakurai; Shu-Ping Hui; Toshihiro Ohura; Hiromi Usui; Tohru Yorifuji; Satoshi Hirayama; Akira Ohtake; Takashi Miida
    CLINICA CHIMICA ACTA, 433, C, 1, 4, Jun. 2014, [Peer-reviewed]
    English, Scientific journal
  • Serum choline plasmalogens, particularly those with oleic acid in sn-2, are associated with proatherogenic state
    Megumi Nishimukai; Ryouta Maeba; Yuya Yamazaki; Toru Nezu; Toshihiro Sakurai; Yuji Takahashi; Shu-Ping Hui; Hitoshi Chiba; Tomoki Okazaki; Hiroshi Hara
    JOURNAL OF LIPID RESEARCH, 55, 5, 956, 965, May 2014, [Peer-reviewed]
    English, Scientific journal
  • Evaluation of Antioxidant Activity of Natural and Synthetic Compounds Against LDL Oxidation Using CNT Electrode
    Futaba Ohkawa; Seiji Takeda; Shu-Ping Hui; Toshihiro Sakurai; Shigeki Jin; Hirotoshi Fuda; Kazuhisa Sueoka; Hitoshi Chiba
    IEEE SENSORS JOURNAL, 14, 2, 532, 537, Feb. 2014, [Peer-reviewed]
    English, Scientific journal
  • Peripheral leukocyte anomaly detected with routine automated hematology analyzer sensitive to adipose triglyceride lipase deficiency manifesting neutral lipid storage disease with myopathy/triglyceride deposit cardiomyovasculopathy
    Akira Suzuki; Hironori Nagasaka; Yasuhiro Ochi; Kazuhiro Kobayashi; Hiroshi Nakamura; Daisaku Nakatani; Satoshi Yamaguchi; Shinobu Yamaki; Atsushi Wada; Yoshihisa Shirata; Shu-Ping Hui; Tatsushi Toda; Hiroshi Kuroda; Hitoshi Chiba; Ken-Ichi Hirano
    Molecular Genetics and Metabolism Reports, 1, 1, 249, 253, Elsevier Inc., 2014, [Peer-reviewed]
    English, Scientific journal
  • Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-gamma in patients with triglyceride deposit cardiomyovasculopathy
    Ken-ichi Hirano; Tatsuya Tanaka; Yoshihiko Ikeda; Satoshi Yamaguchi; Nobuhiro Zaima; Kazuhiro Kobayashi; Akira Suzuki; Yasuhiko Sakata; Yasushi Sakata; Kunihisa Kobayashi; Tatsushi Toda; Norihide Fukushima; Hatsue Ishibashi-Ueda; Daniela Tavian; Hironori Nagasaka; Shu-Ping Hui; Hitoshi Chiba; Yoshiki Sawa; Masatsugu Hori
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 443, 2, 574, 579, Jan. 2014, [Peer-reviewed]
    English, Scientific journal
  • Measurement of single low-density lipoprotein particles by atomic force microscopy
    Toshihiro Sakurai; Seiji Takeda; Jun-ya Takahashi; Yuji Takahashi; Norio Wada; Suchin Trirongjitmoah; Takeshi Namita; Shigeki Jin; Akiko Ikuta; Hiroaki Furumaki; Shu-Ping Hui; Hirotoshi Fuda; Masato Fujikawa; Koichi Shimizu; Hitoshi Chiba
    ANNALS OF CLINICAL BIOCHEMISTRY, 50, 6, 564, 570, Nov. 2013, [Peer-reviewed]
    English, Scientific journal
  • Evaluation of Oxidized-Low-Density Lipoproteins Using Kelvin Force Microscopy
    Seiji Takeda; Futaba Ohkawa; Shu-Ping Hui; Toshihiro Sakurai; Shigeki Jin; Hirotoshi Fuda; Kazuhisa Sueoka; Hitoshi Chiba
    IEEE SENSORS JOURNAL, 13, 9, 3449, 3453, Sep. 2013, [Peer-reviewed]
    English, Scientific journal
  • Quantification of urinary 18-hydroxycortisol using LC-MS/MS
    Shigeki Jin; Norio Wada; Yuji Takahashi; Shu-Ping Hui; Toshihiro Sakurai; Hirotoshi Fuda; Seiji Takeda; Masato Fujikawa; Katsuyuki Yanagisawa; Shigeo Ikegawa; Takao Kurosawa; Hitoshi Chiba
    ANNALS OF CLINICAL BIOCHEMISTRY, 50, 5, 450, 456, Sep. 2013, [Peer-reviewed]
    English, Scientific journal
  • Immunological detection of large oxidized lipoproteins in hypertriglyceridemic serum
    Toshihiro Sakurai; Norio Wada; Yuji Takahashi; Ayako Ichikawa; Akiko Ikuta; Hiroaki Furumaki; Shu-Ping Hui; Shigeki Jin; Seiji Takeda; Hirotoshi Fuda; Masato Fujikawa; Chikara Shimizu; Hironori Nagasaka; Hiroyuki Furukawa; Seiichi Kobayashi; Hitoshi Chiba
    ANNALS OF CLINICAL BIOCHEMISTRY, 50, 5, 465, 472, Sep. 2013, [Peer-reviewed]
    English, Scientific journal
  • Evaluation of various electrode materials for detection of oxidized low-density lipoproteins
    Seiji Takeda; Shu-Ping Hui; Hirotoshi Fuda; Shigeki Jin; Toshihiro Sakurai; Atsushi Ishii; Koichi Mukasa; Kazuhisa Sueoka; Hitoshi Chiba
    Journal of Biomedical Nanotechnology, 9, 2, 303, 306, Feb. 2013, [Peer-reviewed]
    English, Scientific journal
  • Effects of acid oxidation on carbon nanotube based electrodes for detection of oxidized LDL
    Seiji Takeda; Toshihiro Sakurai; Futaba Ohkawa; Shigeki Jin; Shu-Ping Hui; Hirotoshi Fuda; Koichi Mukasa; Hitoshi Chiba; Kazuhisa Sueoka
    2013 IEEE SENSORS, 1038, 1041, 2013, [Peer-reviewed]
    English, International conference proceedings
  • Analysis of triacylglycerol hydroperoxides in human lipoproteins by Orbitrap mass spectrometer
    Shu-Ping Hui; Toshihiro Sakurai; Seiji Takeda; Shigeki Jin; Hirotoshi Fuda; Takao Kurosawa; Hitoshi Chiba
    Analytical and Bioanalytical Chemistry, 405, 14, 4981, 4987, 2013, [Peer-reviewed]
    English, Scientific journal
  • 過酸化脂質の分析―質量分析法を中心に―
    HUI Shu‐Ping; 千葉仁志
    JSBMS Lett, 37, 3, 38, 43, 30 Nov. 2012
    Japanese
  • A phenolic antioxidant from the Pacific oyster (Crassostrea gigas) inhibits oxidation of cultured human hepatocytes mediated by diphenyl-1-pyrenylphosphine
    Mitsugu Watanabe; Hirotoshi Fuda; Shigeki Jin; Toshihiro Sakurai; Shu-Ping Hui; Seiji Takeda; Takayuki Watanabe; Takao Koike; Hitoshi Chiba
    FOOD CHEMISTRY, 134, 4, 2086, 2089, Oct. 2012, [Peer-reviewed]
    English, Scientific journal
  • LC‐MS/MSで測定した血清,尿18‐hydroxycortisolによる原発性アルドステロン症の診断
    和田典男; 神繁樹; 藤谷昴文; 惠淑萍; 柳澤克之; 黒澤隆夫; 千葉仁志
    日本内分泌学会雑誌, 88, 2, 695, 20 Sep. 2012
    Japanese
  • Novel monoclonal antibody recognizing triglyceride-rich oxidized LDLs associated with severe liver disease and small oxidized LDLs in normal subjects
    Toshihiro Sakurai; Ayako Ichikawa; Hiroyuki Furukawa; Norio Wada; Atsushi Nagasaka; Yuji Takahashi; Masato Fujikawa; Akiko Ikuta; Hiroaki Furumaki; Maiko Shiga; Chikara Shimizu; Shu-Ping Hui; Shigeki Jin; Seiji Takeda; Hirotoshi Fuda; Hironori Nagasaka; Seiichi Kobayashi; Hitoshi Chiba
    ANNALS OF CLINICAL BIOCHEMISTRY, 49, Pt5, 456, 462, Sep. 2012, [Peer-reviewed]
    English, Scientific journal
  • Methods for determination of lipid peroxides
    惠 淑萍; 千葉 仁志
    細胞, 44, 8, 370, 373, ニューサイエンス社, Jul. 2012
    Japanese
  • Detection and characterization of cholesteryl ester hydroperoxides in oxidized LDL and oxidized HDL by use of an Orbitrap mass spectrometer
    Shu-Ping Hui; Toshihiro Sakurai; Futaba Ohkawa; Hiroaki Furumaki; Shigeki Jin; Hirotoshi Fuda; Seiji Takeda; Takao Kurosawa; Hitoshi Chiba
    ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 404, 1, 101, 112, Jul. 2012, [Peer-reviewed]
    English, Scientific journal
  • Quantitative determination of phosphatidylcholine hydroperoxides during copper oxidation of LDL and HDL by liquid chromatography/mass spectrometry
    Shu-Ping Hui; Yudai Taguchi; Seiji Takeda; Futaba Ohkawa; Toshihiro Sakurai; Shinobu Yamaki; Shigeki Jin; Hirotoshi Fuda; Takao Kurosawa; Hitoshi Chiba
    ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 403, 7, 1831, 1840, Jun. 2012, [Peer-reviewed]
    English, Scientific journal
  • Detection of oxidized LDL using a carbon nanotube electrode
    Seiji Takeda; Shu-Ping Hui; Keisuke Fukuda; Hirotoshi Fuda; Shigeki Jin; Toshihiro Sakurai; Atsushi Ishii; Koichi Mukasa; Kazuhisa Sueoka; Hitoshi Chiba
    SENSORS AND ACTUATORS B-CHEMICAL, 166, 5, 833, 836, May 2012
    English, Scientific journal
  • 血中,尿中18‐hydroxycortisol測定による原発性アルドステロン症の鑑別診断
    和田典男; 神繁樹; 惠淑萍; 柳澤克之; 黒澤隆夫; 千葉仁志
    日本内分泌学会雑誌, 88, 1, 302, 01 Apr. 2012
    Japanese
  • Clinical chemical studies of lipid peroxides and plasmalogens
    Shu-Ping Hui
    Japanese Journal of Clinical Chemistry, 41, 1, 54, 61, 31 Jan. 2012
    Japanese, Scientific journal
  • 過酸化脂質およびプラズマローゲンに関する臨床化学的研究
    HUI Shu‐Ping
    臨床化学, 41, 1, 54, 61, 31 Jan. 2012
    Japanese
  • Isolation and Characterization of a Phenolic Antioxidant from the Pacific Oyster (Crassostrea gigas)
    Mitsugu Watanabe; Hirotoshi Fuda; Shigeki Jin; Toshihiro Sakurai; Futaba Ohkawa; Shu-Ping Hui; Seiji Takeda; Takayuki Watanabe; Takao Koike; Hitoshi Chiba
    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 60, 3, 830, 835, Jan. 2012, [Peer-reviewed]
    English, Scientific journal
  • Application of Kelvin force microscopy for evaluation of oxidized low-density lipoprotein
    Seiji Takeda; Futaba Ohkawa; Toshihiro Sakurai; Shigeki Jin; Hirotoshi Fuda; Shu-Ping Hui; Hitoshi Chiba; Kazuhisa Sueoka
    2012 IEEE SENSORS PROCEEDINGS, 1751, 1754, 2012, [Peer-reviewed]
    English, International conference proceedings
  • 過酸化脂質及び抗酸化脂質に関する研究
    惠淑萍
    臨床化学, 40, 79, 80, 31 Jul. 2011
    Japanese
  • CD36 deficiency predisposing young children to fasting hypoglycemia
    Hironori Nagasaka; Tohru Yorifuji; Tomozumi Takatani; Yoshiyuki Okano; Hirokazu Tsukahara; Hidekatsu Yanai; Ken-ichi Hirano; Shu-Ping Hui; Satoshi Hirayama; Tetsuya Ito; Hitoshi Chiba; Takashi Miida
    METABOLISM-CLINICAL AND EXPERIMENTAL, 60, 6, 881, 887, Jun. 2011, [Peer-reviewed]
    English, Scientific journal
  • Liquid chromatography-mass spectrometric determination of plasmalogens in human plasma
    Shu-Ping Hui; Hitoshi Chiba; Takao Kurosawa
    ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 400, 7, 1923, 1931, Jun. 2011, [Peer-reviewed]
    English, Scientific journal
  • Chiral Separation, Determination of Absolute Configuration, and High-performance Liquid Chromatography Detection of Enantiomeric 3-hydroxyhexadecanoyl-CoA
    Shirou Tsuchida; Koutarou Kawamoto; Kana Nunome; Naoya Hamaue; Shu-Ping Hui; Tsuyoshi Murai; Takashi Aoki; Takao Kurosawa
    JOURNAL OF OLEO SCIENCE, 60, 2, 87, 92, Feb. 2011, [Peer-reviewed]
    English, Scientific journal
  • Cellular response after crush injury in adult zebrafish spinal cord.
    Hui SP; Dutta A; Ghosh S
    Developmental dynamics : an official publication of the American Association of Anatomists, 239, 11, 2962, 2979, 11, Nov. 2010, [Peer-reviewed]
  • Measurement of lipoprotein particle sizes using dynamic light scattering
    Toshihiro Sakurai; Suchin Trirongjitmoah; Yuka Nishibata; Takeshi Namita; Masahiro Tsuji; Shu-Ping Hui; Shigeki Jin; Koichi Shimizu; Hitoshi Chiba
    ANNALS OF CLINICAL BIOCHEMISTRY, 47, 5, 476, 481, Sep. 2010, [Peer-reviewed]
    English, Scientific journal
  • Analyses for phosphatidylcholine hydroperoxides by LC/MS
    Shu-Ping Hui; Hitoshi Chiba; Shigeki Jin; Hironori Nagasaka; Takao Kurosawa
    JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 878, 20, 1677, 1682, Jun. 2010, [Peer-reviewed]
    English, Scientific journal
  • Measurement of the Transport Activities of Bile Salt Export Pump Using Chemiluminescence Detection Method
    Kana Yamaguchi; Tsuyoshi Murai; Hikaru Yabuuchi; Shu-Ping Hui; Takao Kurosawa
    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 130, 5, 755, 761, May 2010, [Peer-reviewed]
    Japanese, Scientific journal
  • 生化学的検査[2]A.脂質関係 過酸化脂質
    HUI ShuPing
    日本臨床, 68, 120, 124, 28 Jan. 2010
    Japanese
  • Lipid peroxide
    惠 淑萍
    Japanese journal of clinical medicine, 68, 0, 120, 124, 日本臨床社, Jan. 2010
    Japanese
  • Measurement of Bile Salt Export Pump Transport Activities using a Fluorescent Bile Acid Derivative
    Kana Yamaguchi; Tsuyoshi Murai; Hikaru Yabuuchi; Shu-Ping Hui; Takao Kurosawa
    DRUG METABOLISM AND PHARMACOKINETICS, 25, 2, 214, 219, 2010, [Peer-reviewed]
    English, Scientific journal
  • Improved LC/MS Analytical Method for PC Hydroperoxides in Human Plasma
    Shuping Hui; Hitoshi Chiba; Takao Kurosawa
    FREE RADICAL BIOLOGY AND MEDICINE, 49, S211, S211, 2010, [Peer-reviewed]
    English
  • Increased Plasma TG Hydroperoxide in Advanced Liver Disease
    Shuping Hui; Hitoshi Chiba; Takao Kurosawa
    FREE RADICAL BIOLOGY AND MEDICINE, 47, S188, S188, 2009, [Peer-reviewed]
    English
  • Fluctuation of lipoprotein metabolism linked with bile acid-activated liver nuclear receptors in Alagille syndrome
    Hironori Nagasaka; Takashi Miida; Ken-ichi Hirano; Akemi Ota; Kei Murayama; Tohru Yorifuji; Kunihiko Kobayashi; Tornommi Takatani; Hirokazu Tsukahara; Shu-Ping Hui; Masaki Takayanagi; Hitoshi Chiba
    ATHEROSCLEROSIS, 198, 2, 434, 440, Jun. 2008, [Peer-reviewed]
    English, Scientific journal
  • Reduced apolipoprotein E-rich high-density lipoprotein level at birth is restored to the normal range in patients with familial Hypercholesterolemia in the first year of life
    Hironori Nagasaka; Takashi Miida; Kenichi Hirano; Akemi Ota; Tohru Yorifuji; Tomozumi Takatani; Hirokazu Tsukahara; Masaki Takayanagi; Shu-Ping Hui; Kunihiko Kobayashi; Hitoshi Chiba
    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 93, 3, 779, 783, Mar. 2008, [Peer-reviewed]
    English, Scientific journal
  • An improved HPLC assay for phosphatidylcholine hydroperoxides (PCOOH) in human plasma with synthetic PCOOH as internal standard
    Shu-Ping Hui; Hitoshi Chiba; Toshihiro Sakurai; Chitose Asakawa; Hironori Nagasaka; Tsuyoshi Murai; Hajime Ide; Takao Kurosawa
    JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 857, 1, 158, 163, Sep. 2007, [Peer-reviewed]
    English, Scientific journal
  • Attenuated aerobic exercise capacity in CD36 deficiency
    Hidekatsu Yanai; Ichiro Watanabe; Kojiro Ishii; Mie Morimoto; Hironobu Fujiwara; Shigeru Yoshida; Shu-Ping Hui; Kazuhiko Matsuno; Hitoshi Chiba
    JOURNAL OF MEDICAL GENETICS, 44, 7, 445, 447, Jul. 2007, [Peer-reviewed]
    English, Scientific journal
  • Depletion of high-density lipoprotein and appearance of triglyceride-rich low-density lipoprotein in a Japanese patient with FIC1 deficiency manifesting benign recurrent intrahepatic cholestasis
    Hironori Nagasaka; Hitoshi Chiba; Shu-Ping Hui; Hajime Takikawa; Takashi Miida; Masaki Takayanagi; Tohru Yorifuji; Makoto Hasegawa; Akemi Ota; Ken-ichi Hirano; Hideaki Kikuchi; Hirokazu Tsukahara; Kunihiko Kobayashi
    JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 45, 1, 96, 105, Jul. 2007, [Peer-reviewed]
    English, Scientific journal
  • Improved HPLC assay for lipid peroxides in human plasma using the internal standard of hydroperoxide
    SP Hui; T Murai; T Yoshimura; H Chiba; H Nagasaka; T Kurosawa
    LIPIDS, 40, 5, 515, 522, May 2005, [Peer-reviewed]
    English, Scientific journal
  • Oxidized low-density lipoprotein upregulates GM2 activator protein gene expression
    Yanai H; Yoshida H; Fujiwara H; Yoshida S; Fuda H; Shu-Ping Hui; Nagasaka H; Tada N; Chiba H
    Am J Biochem Biotechnol, 1, 2, 90, 94, May 2005, [Peer-reviewed]
    English, Scientific journal
  • Simple chemical syntheses of TAG monohydroperoxides
    SP Hui; T Murai; T Yoshimura; H Chiba; T Kurosawa
    LIPIDS, 38, 12, 1287, 1292, Dec. 2003, [Peer-reviewed]
    English, Scientific journal
  • Unique character and metabolism of high. density lipoprotein (HDL) in fetus
    H Nagasaka; H Chiba; H Kikuta; H Akita; Y Takahashi; H Yanai; SP Hui; H Fuda; H Fujiwara; K Kobayashi
    ATHEROSCLEROSIS, 161, 1, 215, 223, Mar. 2002, [Peer-reviewed]
    English, Scientific journal
  • Metabolic changes in human CD36 deficiency displayed by glucose loading
    H Yanai; H Chiba; H Fujiwara; M Morimoto; Y Takahashi; SP Hui; H Fuda; H Akita; T Kurosawa; K Kobayashi; K Matsuno
    THROMBOSIS AND HAEMOSTASIS, 86, 4, 995, 999, Oct. 2001, [Peer-reviewed]
    English, Scientific journal
  • Phenotype-genotype correlation in CD36 deficiency types I and II
    H Yanai; H Chiba; H Fujiwara; M Morimoto; K Abe; S Yoshida; Y Takahashi; H Fuda; SP Hui; H Akita; K Kobayashi; K Matsuno
    THROMBOSIS AND HAEMOSTASIS, 84, 3, 436, 441, Sep. 2000, [Peer-reviewed]
    English, Scientific journal
  • Human CD36 deficiency is associated with elevation in low-density lipoprotein-cholesterol
    H Yanai; H Chiba; M Morimoto; K Abe; H Fujiwara; H Fuda; SP Hui; Y Takahashi; H Akita; GA Jamieson; K Kobayashi; K Matsuno
    AMERICAN JOURNAL OF MEDICAL GENETICS, 93, 4, 299, 304, Aug. 2000, [Peer-reviewed]
    English, Scientific journal
  • Quantitative and compositional changes in high density lipoprotein subclasses in patients with various genotypes of cholesteryl ester transfer protein deficiency
    H Chiba; H Akita; K Tsuchihashi; SP Hui; Y Takahashi; H Fuda; H Suzuki; H Shibuya; M Tsuji; K Kobayashi
    JOURNAL OF LIPID RESEARCH, 38, 6, 1204, 1216, Jun. 1997, [Peer-reviewed]
    English, Scientific journal
  • Frequency and Effect on Plasma Lipoprotein Metabolism of a Mutation in the Cholesteryl Ester Transfer Protein Gene in the Chinese
    HUI Shu-Ping
    北海道醫學雜誌 = Acta medica Hokkaidonensia, 72, 3, 319, 327, 01 May 1997
    Japanese
  • [Frequency and effect on plasma lipoprotein metabolism of a mutation in the cholesteryl ester transfer protein gene in the Chinese].
    Hui SP
    [Hokkaido igaku zasshi] The Hokkaido journal of medical science, 72, 3, 319, 327, 3, May 1997, [Peer-reviewed]
    Japanese
  • Effects of triamcinolone on brain and cerebrospinal fluid apolipoprotein E levels in rats
    H Chiba; H Akita; SP Hui; Y Takahashi; H Nagasaka; H Fuda; K Kobayashi
    LIFE SCIENCES, 60, 20, 1757, 1761, Apr. 1997, [Peer-reviewed]
    English, Scientific journal
  • Lipoprotein(a), apolipoprotein(a) phenotypes, and nephropathy in NIDDM patients
    H Akita; H Chiba; M Noritake; Y Katsura; Y Udo; H Shibuya; SP Hui; Y Takahashi; H Nagasaka
    DIABETES CARE, 19, 9, 1036, 1037, Sep. 1996, [Peer-reviewed]
    English
  • Native lipoproteins inhibit platelet activation induced by oxidized lipoproteins
    Y Takahashi; H Chiba; K Matsuno; H Akita; SP Hui; H Nagasaka; H Nakamura; K Kobayashi; NN Tandon; GA Jamieson
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 222, 2, 453, 459, May 1996, [Peer-reviewed]
    English, Scientific journal
  • EVALUATION OF G-TO-A SUBSTITUTION IN THE APOLIPOPROTEIN-A-I GENE PROMOTER AS A DETERMINANT OF HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL LEVEL IN SUBJECTS WITH AND WITHOUT CHOLESTERYL ESTER TRANSFER PROTEIN-DEFICIENCY
    H AKITA; H CHIBA; M TSUJI; SP HUI; Y TAKAHASHI; K MATSUNO; K KOBAYASHI
    HUMAN GENETICS, 96, 5, 521, 526, Nov. 1995, [Peer-reviewed]
    English, Scientific journal
  • CHOLESTERYL ESTER TRANSFER PROTEIN-DEFICIENCY - IDENTIFICATION IN THE CHINESE
    H AKITA; H CHIBA; SP HUI; Y TAKAHASHI; K MATSUNO; K KOBAYASHI
    AMERICAN JOURNAL OF MEDICAL GENETICS, 59, 3, 399, 400, Nov. 1995, [Peer-reviewed]
    English
■ Other Activities and Achievements
■ Books and other publications
  • バイオセンサの迅速・簡易・高機能化技術と課題解決書:過酸化脂質・酸化LDL測定のためのバイオセンサ
    武田 晴治; 惠 淑萍; 千葉 仁志
    (株)技術情報協会, Apr. 2014, [Joint work]
  • 医用質量分析ガイド 内分泌・代謝疾患,診断と治療
    千葉仁志; 惠 淑萍
    診断と治療社, Dec. 2013, [Joint work]
  • “パザパ”薬学演習シリーズ7
    黒澤隆夫; 豊田栄子; 村井毅; 惠 淑萍
    京都廣川書店, Apr. 2010, [Joint work]
■ Lectures, oral presentations, etc.
  • 臨床化学者の異分野連携研究
    日本臨床化学第62回年次学術集会, 02 Oct. 2022, Invited oral presentation
    [Invited]
  • From the standpoint of a lipid researcher, strategic measures for pre-illness with an eye on the next era
    Shu-Ping Hui
    第27回 日本未病学会学術総会 シンポジウム8(次の時代を見据えた戦略的未病対策とは ), 01 Nov. 2020
    [Invited]
  • Analyses of hydroperoxide lipids in human lipoprotein and cell by mass spectrometry
    SHU-PING HUI
    2018 Annual Medical Laboratory Forum (Taipei Medical University), 29 Oct. 2018, English, Invited oral presentation
    [Invited], [International presentation]
  • 異所性脂肪蓄積と酸化ストレス
    惠 淑萍
    第31回日本小児脂質研究会学術集会 特別講演, 05 Nov. 2017
    [Invited], [Domestic Conference]
  • 体外受精における使用済み胚培養液の組成と胚発育の関係
    第57 回日本臨床化学会 年次学術集会, 07 Oct. 2017
    [Invited]
  • 質量分析による分子レベルの脂質研究
    惠 淑萍
    第56回日本臨床化学会年次学術集会(教育講演), Dec. 2016
    [Invited], [Domestic Conference]
  • 質量分析法による種々の脂質分子の定性及び定量分析
    第62 回日本臨床検査医学 会学術集会,, 20 Nov. 2015
    [Invited]
  • 脂肪滴の分析技術
    第22 回日本未病システム学会学術総会,, 11 Oct. 2015
    [Invited]
  • タンデム型質量分析計による臨床サンプルの定量分析」:LC/MSを用いた過酸化脂質 および生理活性脂質の分析
    第60回日本臨床検査医学会,, 01 Nov. 2013
    [Invited]
  • 臨床現場で活躍する分析科学」:「疾患と酸化ストレス・過酸化脂質分析
    第23 回バイ オメディカル分析科学シンポジウム, 22 Jul. 2010
    [Invited]
  • 臨床化学の若い力で発信しつつある新たな検査, 病態解析法:「欲速則不達:急がば 回れの過酸化脂質研究の道」
    第49 回日本臨床化学会年次学術集会, 22 Aug. 2009
    [Invited]
■ Syllabus
  • 検査機器学Ⅱ, 2024年, 学士課程, 医学部
  • 代謝分析化学特論, 2024年, 修士課程, 保健科学院
  • 代謝分析化学演習, 2024年, 修士課程, 保健科学院
  • 大学院共通授業科目(教育プログラム):JICA開発大学院連携プログラム, 2024年, 修士課程, 大学院共通科目
  • 先端検査医学特論, 2024年, 修士課程, 保健科学院
  • 生体情報機能解析学特講, 2024年, 博士後期課程, 保健科学院
  • 生体情報機能解析学特講演習, 2024年, 博士後期課程, 保健科学院
  • 技能修得到達度評価, 2024年, 学士課程, 医学部
  • 臨地実習(検体・病理検査), 2024年, 学士課程, 医学部
  • 検査機器学, 2024年, 学士課程, 医学部
  • 臨床化学実習Ⅱ, 2024年, 学士課程, 医学部
  • 代謝生化学, 2024年, 学士課程, 医学部
  • 臨床化学実習, 2024年, 学士課程, 医学部
  • 臨床化学実習Ⅰ, 2024年, 学士課程, 医学部
  • 生体分析学, 2024年, 学士課程, 医学部
  • 臨床化学Ⅰ, 2024年, 学士課程, 医学部
  • 臨床化学Ⅱ, 2024年, 学士課程, 医学部
  • 臨床栄養学, 2024年, 学士課程, 医学部
  • 臨床病態学Ⅱ, 2024年, 学士課程, 医学部
  • 健康食品学, 2024年, 学士課程, 医学部
  • 臨床病態学Ⅰ, 2024年, 学士課程, 医学部
■ Affiliated academic society
  • THE MASS SPECTOMETRY SOCIETY OF JAPAN
  • JAPANESE SOCIETY FOR BIOMEDICAL MASS SPECTROMETRY
  • Society for Free Radical Biology and Medicine, USA
  • JAPANESE SOCIETY OF LABORATORY MEDICINE
  • SOCIETY FOR FREE RADICAL RESEARCH JAPAN
  • THE JAPAN SOCIETY FOR ANALYTICAL CHEMISTRY
  • 日本臨床化学会
  • THE PHARMACEUTICAL SOCIETY OF JAPAN
  • 日本未病システム学会
■ Research Themes
  • 網羅的リピドミクスによって糖・脂質代謝異常などと関連する脂質種を探索する疫学研究
    科学研究費助成事業
    01 Apr. 2025 - 31 Mar. 2029
    中村 幸志; 惠 淑萍
    日本学術振興会, 基盤研究(B), 琉球大学, 25K03033
  • Proton isotope effect as the method to repair marginal liver graft by extracorporeal perfusion
    Grants-in-Aid for Scientific Research
    01 Apr. 2023 - 31 Mar. 2026
    嶋村 剛; 深井 原; 暮地本 宙己; 亀田 浩之; 西川 祐司; 惠 淑萍
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23K28467
  • Proton isotope effect as the method to repair marginal liver graft by extracorporeal perfusion
    Grants-in-Aid for Scientific Research
    01 Apr. 2023 - 31 Mar. 2026
    嶋村 剛; 深井 原; 惠 淑萍; 暮地本 宙己; 亀田 浩之; 西川 祐司
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23H03779
  • 新規抗酸化物質の糖尿病性腎症の有効性に関する研究
    科学研究費助成事業
    01 Apr. 2023 - 31 Mar. 2026
    惠 淑萍
    日本学術振興会, 基盤研究(C), 北海道大学, 23K06861
  • Development and application of novel technique for evaluation of mitochondrial function
    Grants-in-Aid for Scientific Research
    01 Apr. 2023 - 31 Mar. 2026
    千葉 仁志; 櫻井 俊宏; 惠 淑萍
    カルジオリピン(CL)及びその前駆物質のモノリゾカルジオリピン(MLCL)はそれぞれ4種類、3種類の脂肪酸が結合するリン脂質である。アシル基(脂肪酸)の組み合わせで様々なCL分子種、MLCL分子種が存在する。CL及びMLCLはミトコンドリア内膜に特異的に局在することが特徴的である。CLの合成では、はじめに鎖長の短い脂肪酸が結合した未熟なCLが産生され、一本のアシル基(脂肪酸)が酵素的に切断されてMLCLになる。MLCLは酵素的に一本のアシル基(脂肪酸)が付加されて、CLになる。その繰り返しを経て、成熟CLが完成する。この過程をCLのリモデリングと呼ぶ。成熟CLはミトコンドリア内膜の構造やエネルギー産生を含むミトコンドリア機能の維持に重要な役割を果たす。一方でMLCLの増加は、CLのリモデリング異常(CL代謝の異常)を意味し、ミトコンドリア機能の低下と関連があると考えられてきた。しかしながら、機能や役割についての全容の解明には至っていない。申請者らの先行研究で、MLCLが脂肪肝で増加するという知見を得た(Sakurai T, Chiba H, Hui SP, et al., J Sci Food Agric, 2021)。この結果はMLCLが生活習慣病など様々な疾患で変動する可能性を示唆する。
    しかし、MLCLの網羅的解析及び定量系は未だ確立されていない。そこで本申請課題では、MLCLの測定系の開発とその応用を目的とし、MLCLの標準物質や内部標準物質を用いる質量分析による測定系を分析化学的に構築する。このMLCLの新たな解析手法が確立されれば、将来的にそれらの測定系が様々な病態解明に応用される可能性が期待される。よって、本研究は健康科学領域での大きな波及効果があると考えられる。現在までにMLCLの網羅的測定系の構築を順調に進めている。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 23K06881
  • 化学物質の次世代影響-出生から青年期の脂質代謝やエピゲノムの作用機序
    科学研究費助成事業
    01 Apr. 2023 - 31 Mar. 2026
    宮下 ちひろ; 池田 敦子; 田村 菜穂美; 山口 健史; 惠 淑萍
    日本学術振興会, 基盤研究(C), 北海道大学, 23K09641
  • Elucidation of oxidized HDL and NASH pathogenesis focusing on mitochondrial dysfunction
    Grants-in-Aid for Scientific Research
    01 Apr. 2022 - 31 Mar. 2025
    櫻井 俊宏; 惠 淑萍
    非アルコール性脂肪性肝炎(NASH)は酸化ストレスや肥満、生活習慣病が関与する疾患であり、患者数が世界的に増加している。これまでに申請者は、酸化高比重リポタンパク質(酸化HDL)がNASH発症に深く関わることを示唆する知見を得た。例えば、酸化HDLは肝細胞での炎症、線維化、脂肪滴形成に関与した。また、脂肪滴の酸化を明らかにし、さらに血中酸化HDLはNASHで高値であることを見いだした。一方で近年のNASH研究で、酸化ストレスとミトコンドリア機能異常がNASHの発症や進展に関わることが示唆されている。
    以上から本研究では、酸化ストレスの一因としての酸化HDLがミトコンドリア機能障害を引き起こしてNASH発症に関与するかどうかを明らかにすることを目的とし、肝培養細胞を用いて酸化HDLのミトコンドリア機能への影響を生化学的に調査することとした。当該年度の研究はミトコンドリアの膜脂質に着目し、カルジオリピンとその代謝関連物質の網羅的な分析を行い、酸化HDLにおいてカルジオリピンのプロフィール異常を調査した。今回使用したOrbitrap LC-MS/MSを用いるリピドミクス解析(一斉分析)ではCL及びMLCLの半定量的な測定が可能であり、多くの分子種が存在するCL及びMLCLのプロフィールを調査でき、当研究室においては既に確立された手法であった。発見は、ミトコンドリア機能低下の指標としたMLCL/CL比が酸化HDL添加群でのみ有意な増加を示したことであった。この結果は将来的に酸化HDLの生理学的機能の解明に役立ち、健康科学的に大きな波及効果が期待される。計画は概ね順調に進んだ。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 22K11797
  • Adverse health effects of environmental chemical exposure: elucidation of mechanisms via human and animal studies
    Grants-in-Aid for Scientific Research
    05 Apr. 2021 - 31 Mar. 2025
    池田 敦子; 小島 弘幸; 池中 良徳; Goudarzi Houman; 山口 健史; 惠 淑萍; 中村 明枝; アイツバマイ ゆふ; 増田 秀幸; POUDEL KRITIKA
    疫学研究では、「北海道スタディ」に参加する9-11歳の前思春期児から収集した血漿を用いて、性ステロイドホルモン14物質の一斉分析、LH、FSH、Inhibin B、INSL3の測定を行った。曝露評価として尿中フタル酸エステル類代謝物、ノニルフェノールを測定した。フタル酸エステル類代替物質DINCH、DEHTP、DEHA代謝物分析に向けた条件検討を実施し、ピークが得られることを確認した。
    曝露と健康を介在するバイオマーカーの測定に向けて、96穴プレートを用いて一度に数十種類のたんぱく質やペプチドを、20μLという非常に少量の検体を用いて分析できるBio-Plex200 multiplexアッセイシステムを購入した。機器メーカによるトレーニングに加えて、ヒトテストサンプルを用いて、Th1/Th2サイトカインにエオタキシンを加えたテストアッセイを実施し、手技や分析に問題がないことを確認し、子どもから収集した血漿を用いた測定に向けて準備を整えた。
    子ども血中総IgE、好酸球、気道炎症マーカーFeNO値について、一般子ども集団のアレルギー有となしの子どもの比較により、成人のカットオフ値の妥当性について検討した。
    動物・細胞実験分担研究においては、ヒト肝細胞に近い性質を示すHepaRG細胞株に0.1% DMSO(対照群)、MEHP 3 microM(低用量群)、MEHP 30 microM(高用量群)をそれぞれ24時間曝露してmRNAを採取した。GeneChip解析を用いた網羅的遺伝子発現解析を行い、核内受容体PPARalpha活性化に伴う遺伝子発現変化を認めた。さらに、妊娠ICRマウスに、0.1%DMSOを含む水(対照群)、DEHP 0.3 mg/kg(低用量群)及びDEHP 3 mg/kg(高用量群)を妊娠期間中経口曝露した。それぞれ出生後7日目の仔マウス肝臓からmRNAを採取した。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 21H04843
  • プラスチックによる脂質代謝異常およびNASHや発癌との関連性に関する研究
    科学研究費助成事業 基盤研究(C)
    01 Apr. 2020 - 31 Mar. 2023
    DARWISH WAGEH・SOBHY・ABDELRAHEM・ABDALLAH; 津久井 隆行; 惠 淑萍
    日本学術振興会, 基盤研究(C), 北海道大学, 20K12205
  • Effects of feeding management on bovine fertility and ovarian function: relationship between lipid profile and developmental competence of oocytes
    Grants-in-Aid for Scientific Research
    01 Apr. 2019 - 31 Mar. 2022
    Nagano Masashi
    Oocyte triacylglycerols (TAG) were significantly higher in cows in the early lactation stage than in heifers. Plasma free fatty acids (FFA) were high at 20-30 after days in milk (DIM). Oocyte FFA positively correlated with plasma FFA, but negatively correlated with the mean energy balance and 21 days before oocyte collection. Elevated oocyte FFA in cows in the early ostpartum period under intensive feeding management suggested that oocytes were at a high risk of FFA lipotoxicity.
    In addition, the effects modulated (5-20%) oxygen environments on the in vitro development of bovine oocyte-cumulus-granulosa cell complexes (OCGCs) cultured in the presence or absence of an antioxidant (astaxanthin: Ax) were evaluated by using gas permeable culture wells. The presence of Ax in the 5-20% O2 condition promoted oocyte nuclear maturation and development of OCGCS.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Kitasato University, 19H03117
  • 糖尿病性腎症発症メカニズムの解明と制御:コレステリルエステル蓄積からのアプローチ
    科学研究費助成事業 基盤研究(C)
    01 Apr. 2019 - 31 Mar. 2022
    惠 淑萍
    糖尿病性腎症は、先進国における末期腎臓病の主な原因であり、活性酸素種(ROS)が極めて重要な役割を果たすことが知られている。本研究課題は、糖尿病性腎症を、近位尿細管細胞への脂肪酸流入とコレステリルエステル(CE)蓄積を発端に始まり、ミトコンドリアを巻き込んで進行する酸化的悪性サイクルとして理解し、それを制御する手段を提案することを目的とする。
    2019年度はまず、化学合成により得られた8種類CE標準物質およびそれぞれ8種類の重水素標識CEの内部標準物質を用いて、液体クロマトグラフィー質量分析定量法(LC/MS)を確立した。また、ヒト腎近位尿細管上皮細胞由来であるHK-2細胞に脂肪酸添加を行い、オレイン酸(FA18:1),リノール酸(FA18:2),アラキドン酸(FA20:4),エイコサペンタエン酸(FA20:5),およびドコサヘキサエン酸(FA22:6)添加群において脂肪滴の形成を確認した。しかし,パルミチン酸(FA16:0)添加群では脂肪滴は確認されなかった。なお、脂肪酸の添加による脂肪滴形成時のCEをLC/MS定量法により分析した。同様に不飽和脂肪酸添加群においてCEの有意な増加が確認された。
    さらに、CE代謝酵素とトリグリセリド(TG)の合成系酵素を評価した。HK-2細胞(健常成人腎臓由来の近位尿細管上皮細胞株)への脂肪酸の過剰流入により、Sterol regulatory element-binding proteinの発現が低下した。HK-2細胞への脂肪酸負荷により、Diacylglycerol acyltransferaseおよびAdipose triglyceride lipaseの変化はなかった。
    日本学術振興会, 基盤研究(C), 北海道大学, 19K07861
  • A community-based epidemiological study on the links between characteristics of low-density lipoprotein and lifestyles/metabolic disorders/arteriosclerosis.
    Grants-in-Aid for Scientific Research
    Apr. 2017 - Mar. 2022
    Nakamura Koshi
    A community-based epidemiological study was conducted to examine the association between serum low-density lipoprotein (LDL) cholesterol concentration and arteriosclerosis in the general population, with consideration of characteristics of LDL. Indices of arteriosclerosis of interest were cardio ankle vascular index (CAVI) and ankle brachial pressure index (ABI). When the study population was stratified by the median values of LDL characteristics (i.e., particle size, zeta-potential, hardness, and height), there were no associations between serum LDL cholesterol concentration and CAVI/ABI in each stratum.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), 北海道大学, 17H04120
  • 中性脂肪蓄積心筋血管症の診断に直結するエビデンス創出研究
    2020 - 2022
    惠 淑萍
    日本医療研究開発機構(AMED), Coinvestigator
  • Study of Rapid Detection Technology for Oil Quality and Toxicological Evaluation of Frying Oil
    Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS Fellows
    10 Nov. 2017 - 31 Mar. 2020
    惠 淑萍; 張 函; MA JIN-KUI
    It was established that an effective and rapid detection method based on the odor fingerprint of frying oil for a real-time detection and monitoring of frying oil quality. The potential toxicities of frying oils' polar substances and oxidative products (hydroperoxides) to cells in vivo were investigated. The major primary oxidative products of the linoleic acid, 9 and 13-Hydroxyoctadecadienoic acid (9 and 13-HPODE), were synthesized using soybean lipoxygenase I-B. The 9 and 13-HPODE were also subjected to HepG 2 cells to evaluate its possible adverse effects (cell viability, changes in the enzyme expression, lipidomic analysis) . The research results of 2019 are summarized as follows:
    1.The synthesized hydroperoxides have been identified by the Mass spectroscopy and NMR. Results showed that the purity of the synthesized 13-HPODE was around 95% and the yield rate was 70% above which implies the method is successful and was feasible for preparing 9 and 13-HPODE in a regular laboratory.
    2.In the cells’ experiments, there were two parallel experiments carried out: one is for the PAHs and another is for the HPODEs using target cell line- HepG 2 cells. Results showed that the mRNA expression of GSTO1, SOD2, and HO-1 have increased when the cells were treated with high HPODEs concentration (100 uM), while the GPX mRNA expression was inhibited after the treatment. Results also indicated that the expression level of CYP1A1 mRNA has been significantly increased after the cells treated with high concentration of HPODEs.
    Japan Society for the Promotion of Science, Grant-in-Aid for JSPS Fellows, 17F17751
  • Study on the Oxidation and Inhibition of Unsaturated Lipid s and
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    01 Apr. 2017 - 31 Mar. 2020
    Ye Shen
    In the present study, we demonstrated the risk that the unsaturated lipids in the lung surfactants could be oxidized by the low-level ozone in the ambient environment. The oxidation products of the unsaturated lipid monolayers have been quantitatively characterized by surface isotherm, liquid chromatography-mass spectrometry (LC-MS), and heterodyne-detected sum frequency generation (HD-SFG) spectroscopy. It was found that the unsaturated lipid molecules of the lung surfactants were quickly oxidized from its C=C moiety to form the aldehyde and acid terminated lipid derivatives with a trace amount of secondary ozonide. Detailed reaction mechanisms and kinetics have been discussed based on the experimental results. Furthermore, oxidation inhibition effects by adding ascorbic acid or 3,5-dihydroxy-4-methoxybenzyl alcohol in the subphase have been partially confirmed.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Tohoku University, 17H01879
  • System development to realize transillumination and functional imaging of animal body using safe light
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    01 Apr. 2017 - 31 Mar. 2020
    Shimizu Koichi
    To realize 3D transillumination imaging of internal body structure and physiological function, we integrated our principles to establish a new technique, and developed a test system. Through this study, we achieved the following results.
    (1) An inverse scattering problem was solved to obtain internal structure in a turbid medium using scattered light from the medium. (2) Blurred transillumination image could be improved by the deconvolution with a point spread function. (3) The problem of image blur was resolved using the convolutional neural network obtained by deep learning. (4) The feasibility of 3D transillumination imaging was confirmed using a tissue-simulated model phantom. (5) A test system was designed and manufactured. (6) The feasibility of functional imaging was confirmed in the identification of vein and artery in a transillumination image. (7) 3D functional transillumination imaging was achieved in animal experiments.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Waseda University, 17H02112
  • Novel biomarker for atherosclerosis: clinical significance of isoprostanes analyzed by LC-MS/MS
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2017 - 31 Mar. 2020
    Segawa Namiko
    Oxidative stress is linked with many diseases including atherosclerosis and Alzheimer disease. Urine 8-isoprostaglandin F2α (8-iso-PGF2α) was established as a biomarker of oxidative stress. However, reactive oxygen species (ROS) affects the polyunsaturated fatty acid (PUFA) arachidonic acid to produces many isoforms of 8-iso-PGF2α, the biological significance of which is unclear. To explore the diagnosis marker of atherosclerosis, the relation between atherosclerosis and 8-iso-PGF2αisoforms was examined using multivariate data analysis methods including principal component analysis (PCA).
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Fukuoka University, 17K09001
  • Exploration of graft conditioning methods during machine perfusion to augment mitochondrial function and antioxidant ability in steatotic liver graft
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    01 Apr. 2016 - 31 Mar. 2020
    Shimamura Tsuyoshi
    To establish the methods for pre-conditioning the steatotic graft by machine perfusion, and to find out the reliable marker to predict later severity of ischemia and reperfusion injury (IRI), we explored the following issues. Using steatotic rat livers and hepatocytes cell line treated by fatty acids-rich culture, they were subjected to cold storage and/or machine perfusion (or mimicking conditions) in various temperatures, preservation and perfusion solutions commercially available, with or without supplementation of antioxidant and other agents to augment some protective proteins. We found that pre-conditioning during machine perfusion with antioxidant and some agents, having property to induce expression of protective proteins and to activate protective transcription factors, effectively prevent progression of IRI. These results indicate that properly pre-conditioned steatotic graft could become a safe source of liver transplantation.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 16H05398
  • 安全な光による生体透視と機能イメージングを実現するシステムの創成
    科学研究費助成事業 基盤研究(B)
    Apr. 2017 - Mar. 2020
    分担者; 惠 淑萍
    文部科学省, Principal investigator, Competitive research funding
  • 極低濃度オゾン曝露における不飽和脂質とヒトリポ蛋自の酸化及び抑制に関する研究
    科学研究費助成事業 基盤研究(B)
    Apr. 2017 - Mar. 2020
    分担者; 惠 淑萍
    文部科学省, Principal investigator, Competitive research funding
  • 血中低比重リポ蛋自の性質と生活習慣・代謝異常・動脈硬化に関する地域疫学研究
    科学研究費助成事業 基盤研究(B)
    Apr. 2017 - Mar. 2020
    分担者; 惠 淑萍
    文部科学省, Principal investigator, Competitive research funding
  • 脂肪肝グラフトのミトコンドリア機能と抗酸化能を増強する画期的な肝体外灌流法の開発
    科学研究費助成事業 基盤研究B
    Apr. 2016 - Mar. 2020
    分担者; 惠 淑萍
    文部科学省, Principal investigator, Competitive research funding
  • Impact of the fraction of serum fatty acids on health and regulatory role of foods and gastrointestinal microbiota on them
    Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
    01 Apr. 2016 - 31 Mar. 2018
    Tamakoshi Akiko
    We investigated the impact of fraction of serum fatty acids on body mass, body composition and hypertension and their relationship with food intake and gastrointestinal microbiota among the population in a town in Hokkaido, Japan. From previous studies, excessive intake of SFA and MUFA from foods increase the risk of various disease such as obesity and arteriosclerotic disease. In addition to these knowledge, this study newly revealed that the concentrations of some serum fatty acids were related to the risk of obesity and arteriosclerotic disease. Besides, the relationship between the fraction of serum fatty acids and a particular gastrointestinal bacterial species which affect host body mass and body composition was also observed. Further analysis is needed to examine these relations comprehensively
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 16K15353
  • Effect of dietary patterns and blood vitamin D levels on sarcopenia
    Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
    01 Apr. 2016 - 31 Mar. 2018
    Okada Emiko; TAMAKOSHI Akiko; NAKAMURA Koshi; UKAWA Shigekazu; SASAKI Sachiko; HUI Shu-ping
    This study aimed to investigate the effect of blood vitamin D levels and dietary patterns on sarcopenia among community-dwelling people enrolled the Dynamics of lifestyle and Neighborhood Community (DOSANCO) on Health Study.
    The serum 25-hydroxyvitamin D levels in participants was 24.8 ng/mL for males and 22.5 ng/mL for females. Three dietary patterns were identified from the results of factor analysis: vegetable, traditional Japanese, and low-confectionery. The higher vitamin D levels was significantly associated with the higher muscle strength. However, regarding three dietary patterns, no significant associations were observed with muscle mass, muscular strength, and sarcopenia.
    This study is limited to cross-sectional study. Further study is needed that follow-up of participants and investigate to effect of vitamin D levels and dietary patterns on the long-term care and mortality.
    Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), 16K16272
  • 血中脂肪酸分画の健康影響ならびにその規定要因としての摂取食物と腸内細菌叢の関与
    科学研究費助成事業 挑戦的萌芽研究
    Apr. 2016 - Mar. 2018
    分担者; 惠 淑萍
    文部科学省, Principal investigator, Competitive research funding
  • 中性脂肪蓄積心筋血管症に対する中鎖脂肪酸を含有する医薬品の開発
    難治性疾患実用化研究事業
    Apr. 2015 - Mar. 2018
    分担者; 惠 淑萍
    日本医療研究開発機構, Principal investigator, Competitive research funding
  • Possibility of a new biomarker in the diagnosis of primary aldosteronism
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2013 - 31 Mar. 2017
    JIN SHIGEKI; CHIBA Hitoshi; HUI Shu-Ping; WADA Norio
    Primary aldosteronism is considered as approximately 10% of the causes of hypertension, so the diagnosis of its subtype is crucially important issue because cures are required on different kind of subtype. In this study, we found the substance which was detected more amount in the aldosterone-producing adenoma (APA) patient urine than that in the other subtypes of primary aldosteronism. We investigated the possibility of employing this substance as a new biomarker. The substance was detected as 1.5-2.0 fold amount in APA against essential hypertension and idiopathic hyperaldosteronism (IHA). However, its isolation and the structural analysis had not been executed until now.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 25460668
  • Comprehensive analyses and development of immunometric assay for plasmalogen
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2013 - 31 Mar. 2016
    Hui Shu-Ping
    Plasmalogens (Pls) are glycerophospholipids owning antioxidative effect, so it is conceivable that Pls may prevent arteriosclerosis and Alzheimer's disease. In our study, chemical synthesis method for choline Pls (PlsCho) has been improved; chemical synthesis method for ethanolamine Pls (PlsEtn) has been established.
    Comprehensively qualitative and quantitative analyses of Pls in human serum have been carried out by LC-MS/MS using the synthetic Pls standards. The concentration ofPlsEtn18:0/20:4shows higher than that of PlsCho18:0/20:4 in human serum. Some mouses were immunized with BSA-plasmalogens obtained from chemical synthesis.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 25460669
  • 地域イノベーション戦略支援プログラム(国際競争力強化地域)(機器共用化)
    地域産学官連携科学技術振興事業費補助金・イノベーションシステム整備事業
    2013 - 2016
    惠 淑萍
    科学技術振興機構, Principal investigator, Competitive research funding
  • 地域イノベーション戦略支援プログラム(国際競争力強化地域)(研究者集積)
    地域産学官連携科学技術振興事業費補助金・イノベーションシステム整備事業
    2013 - 2016
    惠 淑萍
    科学技術振興機構, Principal investigator, Competitive research funding
  • プラズマローゲンの網羅的解析と免疫測定法の開発
    科学研究費助成事業基盤研究C
    2013 - 2016
    惠 淑萍
    文部科学省, Principal investigator, Competitive research funding
  • 中性脂肪蓄積心筋血管症に対する中鎖脂肪酸を含有する医薬品の開発(分担者)
    難治性疾患克服研究経費・難治性疾患等克服研究事業
    2013 - Mar. 2015
    惠 淑萍
    厚生労働省, Principal investigator, Competitive research funding
  • 新規サケ白子加水分解物の機能性分析と血中動態
    中小企業競争力強化促進事業
    2013 - Mar. 2014
    惠 淑萍
    北海道中小企業総合支援センター, Principal investigator, Competitive research funding
  • 食・運動・健康・医療をつなぐ知で家庭に拓く次世代健康生活創造の国際拠点
    研究成果展開事業センター・オブ・イノベーション(COI)プログラム・COI-トライアル
    2013 - 2014
    惠 淑萍
    科学技術振興機構, Principal investigator, Competitive research funding
  • 中性脂肪蓄積心筋血管症に対する中鎖脂肪酸を含有する医薬品の開発 (分担者)
    Sep. 2012 - Mar. 2013
    惠 淑萍
    平成 24 年度厚生労働科学研究費補助金(難治性疾患等克服研究事業), Principal investigator, Competitive research funding
  • 細胞内脂肪滴の酸化評価系の作製と食品開発への応用
    産学が連携した研究開発成果の展開 研究成果展開事業 研究成果最適展開支援プログラム(A-STEP) 探索タイプ
    2013 - 2013
    惠 淑萍
    針で採取した細胞の脂肪滴の量をモニターし、内標準法で脂質を定量できた時に、評価法の知財化と技術移転が可能になる。また、脂肪滴の酸化を阻止しミトコンドリア機能維持に役立つ物質が同定された時、最大の知財と技術移転の可能性が生じる。技術的課題、1)培養細胞に脂肪滴を形成、脂肪滴を定量的に評価、2)ミトコンドリア機能評価(膜電位測定)と脂肪滴との関係把握、3)脂肪滴採取と脂肪滴脂質(過酸化脂質を含む)の定量質量分析、以上の問題の解決に取り組み、1)、2)は実施できたが、3)は脂肪滴採取と内標準物質(安定同位体)合成までで時間切れとなった。達成率は90%。今後は現状の評価系での目的の食品成分の探索と、評価系の完成度向上に努め、両面で技術移転の可能性を追求する。
    北海道大学
  • Study of lipid hydroperoxides in metabolic syndrome
    Grants-in-Aid for Scientific Research
    2010 - 2012
    HUI Shu-ping
    Cholesterylester monohydroperoxides (CEOOH), triglyceride monohydroperoxides (TGOOH, and phosphatidylcholine monohydroperoxide (PCOOH) were chemically synthesized. oxLDL was prepared by incubating native LDL from human plasma with CuSO4 for up to 4 h. The PCOOH levels during oxidation were determined and showed time course consisted of three phases. We then immunized five mice using the synthetic PCOOH and oxLDL, and antibody titers were measured. For synthetic PCOOH, the antibody titer did not show increase, but significant increase for oxLDL.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, Competitive research funding, 22590534
  • 地域ノベーションクラスタープログラム(分担者)
    Apr. 2010 - Mar. 2011
    惠 淑萍
    地域産学官連携科学技術振興事業費補助金 イノベーションシステム整備事業, Principal investigator, Competitive research funding
  • 特別研究員奨励費
    Jan. 1999 - Mar. 2001
    惠 淑萍
    文部省科学研究補助基金, Principal investigator, Competitive research funding
■ Industrial Property Rights
  • ミトコンドリア機能活性化剤
    Patent right
    特願2020-120617, 14 Jul. 2020
    特許第7620270号
    惠 淑萍、櫻井俊宏、千葉仁志、佐藤浩志
  • フェロトーシス抑制剤
    Patent right, 惠 淑萍; 何 欣蓉; 千葉 仁志; 渡辺 貢; 渡辺 秀明, 北海道大学
    特願2024-196430, 11 Nov. 2024
  • コレステロール合成経路抑制、阻害剤
    Patent right, 渡辺 貢; 千葉仁志; 惠淑萍; 何欣蓉; 櫻井俊宏; 渡辺 秀明
    特願2024-129775, 06 Aug. 2024
  • 非アルコール性脂肪性肝炎の判定を補助する方法および非アルコール性脂肪性肝炎の判定を補助するためのデータを得る方法
    Patent right, 櫻井俊宏; 惠淑萍; 千葉仁志; 板井友和; 大窪喜丸
    特願2024-068144, 19 Apr. 2024
  • ミトコンドリア機能向上用剤
    Patent right
    特願2023-165920, Sep. 2023
  • 細胞保護用剤
    Patent right, 惠 淑萍; 櫻井 俊宏; 千葉 仁志; 佐藤 浩志; 盛 孝男, 国立大学法人北海道大学, 日生バイオ株式会社
    特願2021-127042, 03 Aug. 2021
    特開2023-022363, 15 Feb. 2023
    202303011329545757
  • Keap1-Nrf2システムによる生体防御遺伝子発現の活性化用剤
    Patent right, 惠 淑萍; 千葉 仁志; 布田 博敏; 陳 震; 佐藤 浩志, 国立大学法人北海道大学, 日生バイオ株式会社
    特願2018-124331, 29 Jun. 2018
    特開2020-002082, 09 Jan. 2020
    特許第7201164号
    202303007910252313
  • ミトコンドリア成分であるカルジオリピン分子種の増加剤
    Patent right
    特願2022-126781, Aug. 2022
  • 非アルコール性脂肪性肝炎の診断方法
    Patent right, 櫻井 俊宏; 惠 淑萍; 千葉 仁志, 国立大学法人北海道大学
    特願2020-149798, 07 Sep. 2020
    特開2022-044259, 17 Mar. 2022
    202203001827564731
  • ミトコンドリア機能活性化剤
    Patent right, 惠 淑萍; 櫻井 俊宏; 千葉 仁志; 佐藤 浩志, 国立大学法人北海道大学, 日生バイオ株式会社
    特願2020-120617, 14 Jul. 2020
    特開2022-017829, 26 Jan. 2022
    202203001556225251
  • ATP産生促進用剤
    Patent right, 惠 淑萍; 馬 逸興; 陳 震; 布田 博敏; 佐藤 浩志, 国立大学法人北海道大学, 日生バイオ株式会社
    特願2017-200782, 17 Oct. 2017
    特開2019-073476, 16 May 2019
    特許第6964290号
    202103002742300521
  • Method for aiding detection of nonalcoholic steatohepatitis
    Patent right, 櫻井俊宏; 水田 正弘; 惠淑萍; 能祖一裕; 岡田裕之; 佐藤 謙亨; 伊藤康樹
    特願PCT/JP2021/004008, 04 Feb. 2021
    北海道大学、岡山大学、デンカ生研株式会社
  • 抗酸化能測定用リポソーム
    Patent right, 武田晴治; 千葉仁志; 惠淑萍, 国立大学法人北海道大学
    特願2015-249328, 22 Dec. 2015
    特開2017-116308, 29 Jun. 2017
    特許第6692089号
    202003011814405260
  • 非アルコール性脂肪肝炎の検出を補助する方法
    Patent right, 櫻井俊宏; 水田 正弘; 惠淑萍; 能祖一裕; 岡田裕之; 佐藤 謙亨; 伊藤康樹, 北海道大学、岡山大学、デンカ生研株式会社
    特願2020- 16820, 04 Feb. 2020
  • Keap1-Nrf2システムによる生体防御遺伝子発現の活性化用剤
    Patent right, 惠 淑萍; 千葉 仁志; 布田 博敏; 陳 震; 佐藤 浩志, 国立大学法人北海道大学, 日生バイオ株式会社
    特願2018-124331, 29 Jun. 2018
    特開2020-002082, 09 Jan. 2020
    202003011226334241
  • 低密度リポタンパク質酸化抑制剤
    Patent right, 惠 淑萍; 武田晴治; 佐藤浩志, 国立大学法人北海道大学, 日生バイオ株式会社, 株式会社エル・エスコーポレーション
    特願2015-091804, 28 Apr. 2015
    特開2016-204340, 10 Dec. 2016
    特許第6628071号
    国立大学法人北海道大学,日生バイオ株式会社
    202003004721253693
  • ATP産生促進用剤
    Patent right, 惠 淑萍; 馬 逸興; 陳 震; 布田 博敏; 佐藤 浩志, 国立大学法人北海道大学, 日生バイオ株式会社
    特願2017-200782, 17 Oct. 2017
    特開2019-073476, 16 May 2019
    201903010526815163
  • 抗酸化能測定用リポソーム、抗酸化能測定方法及びリポソーム
    Patent right, 武田 晴治; 千葉 仁志; 惠 淑萍, 国立大学法人北海道大学
    特願2015-249328, 22 Dec. 2015
    特開2017-116308, 29 Jun. 2017
    201703018950381340
  • 低密度リポタンパク質酸化抑制剤
    Patent right, 惠 淑萍; 武田 晴治; 佐藤 浩志, 国立大学法人北海道大学, 日生バイオ株式会社, 株式会社エル・エスコーポレーション
    特願2015-091804, 28 Apr. 2015
    特開2016-204340, 08 Dec. 2016
    201703002913011520
  • カプリン酸定量方法
    Patent right, 惠 淑萍; 平野 賢一, 国立大学法人北海道大学, 興和株式会社
    特願2013-224897, 30 Oct. 2013
    特開2015-087199, 07 May 2015
    201503084209484465
  • CNTセンサーによる過酸化物を電気的に測定する方法
    Patent right, 千葉 仁志; 武田 晴治; 石井 睦; 中村 基訓; 武笠 幸一; 惠 淑萍; 黒澤 隆夫, 国立大学法人北海道大学, 学校法人東日本学園
    特願2011-522742, 16 Jul. 2010
    特許第5433839号
    20 Dec. 2013
    201403022970417426
  • プラズマローゲンの分析方法
    Patent right, 西向 めぐみ; 千葉 仁志; 原 博; 惠 淑萍; 黒澤 隆夫, 国立大学法人北海道大学, 惠 淑萍, 黒澤 隆夫
    特願2009-296744, 28 Dec. 2009
    特開2011-136926, 14 Jul. 2011
    201103095521466523
  • CNTセンサーによる過酸化物を電気的に測定する方法
    Patent right, 千葉 仁志; 武田 晴治; 石井 睦; 中村 基訓; 武笠 幸一; 惠 淑萍; 黒澤 隆夫, 国立大学法人北海道大学, 学校法人東日本学園・北海道医療大学
    JP2010004624, 16 Jul. 2010
    WO2011-007582, 20 Jan. 2011
    WO2011-007582, 20 Jan. 2011
    201303065579784108
  • CNTセンサーによる過酸化物を電気的に測定する方法
    Patent right, 千葉 仁志; 武田 晴治; 石井 睦; 中村 基訓; 武笠 幸一; 惠 淑萍; 黒澤 隆夫, 国立大学法人北海道大学, 学校法人東日本学園・北海道医療大学
    JP2010004624, 16 Jul. 2010
    WO2011-007582, 20 Jan. 2011
    201303065579784108