基本情報

所属

• 保健科学研究院　保健科学部門　健康科学分野

職名

• 助教

科研費研究者番号

• 40875952

ORCID ID

•  https://orcid.org/0000-0001-8102-1302

J-Global ID

• 202101014442020889

研究分野

• 環境・農学 / 化学物質影響

担当教育組織

•  学士課程　医学部（保健学科）
•  修士課程　保健科学院
•  博士課程　保健科学院

学歴

• 2020年03月 - 現在   Assistant professor, Department of Health Science, Hokkaido University.
• 2019年09月 - 2020年02月   Academic Research at Department of Health Science, Hokkaido University.
• 2017年04月 - 2019年05月   Technical assistant at Center for Integrative Medical sciences, Riken Yokohama.
• 2016年10月 - 2017年02月   Postdoctoral fellow at Institute of Low Temperature Science, Hokkaido University
• 2011年07月 - 2012年02月   Lecture at Bharathi Education trust
• 2009年09月 - 2011年06月   Master student, BET, University of Mysore.

研究活動情報

論文

• 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 2024年07月
• 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 2024年05月07日 

  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 (Ottawa, Ont.) 184 114253 - 114253 2024年05月 

  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.
• 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 2024年04月09日 

  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.
• 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 2024年02月
• 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 2023年12月
• Crosstalk between Lipids and Non-Alcoholic Fatty Liver Disease

  Divyavani Gowda, Chandra Shekhar, Siddabasave Gowda B. Gowda, Yifan Chen, Shu-Ping Hui

  Livers 3 4 687 - 708 2023年11月23日 

  Non-alcoholic fatty liver disease (NAFLD), a complex liver disorder that can result in non-alcoholic steatohepatitis, cirrhosis, and liver cancer, is the accumulation of fat in the liver seen in people due to metabolic dysfunction. The pathophysiology of NAFLD is influenced by several variables, such as metabolic dysregulation, oxidative stress, inflammation, and genetic susceptibility. This illness seriously threatens global health because of its link to obesity, insulin resistance, type 2 diabetes, and other metabolic disorders. In recent years, lipid–NAFLD crosstalk has drawn a lot of interest. Through numerous methods, lipids have been connected to the onset and advancement of the illness. The connection between lipids and NAFLD is the main topic of the current review, along with the various therapeutic targets and currently available drugs. The importance of hepatic lipid metabolism in the progression of NAFLD is summarized with the latest results in the field.
• 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 2023年07月21日 

  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.
• Changes in the Size Distributions of Oxalic Acid and Related Polar Compounds Over Northern Japan During Spring

  Dhananjay Kumar Deshmukh, Kimitaka Kawamura, Minoru Kobayashi, Divyavani Gowda

  Journal of Geophysical Research: Atmospheres 128 11 2023年05月31日 

  Abstract Size distributions of chemical species provide evidence for their sources and formation mechanisms. Size‐segregated aerosols with 12 sizes were collected over Northern Japan (Sapporo: 43.07°N and 141.35°E) during the spring (9 April–21 May) of 2001 and analyzed for water‐soluble organic and inorganic species. The dominances of SO₄^2– and NH₄⁺ in submicron (D_a < 1.1 μm) and Na⁺ and Ca²⁺ in supermicron (D_a > 1.1 μm) aerosols suggest substantial contributions from anthropogenic sources, sea‐salt and dust particles via long‐range atmospheric transport. Oxalic acid (C₂) is the dominant organic species followed by malonic (C₃) and succinic (C₄) acid. A supermicron mode enrichment of C₂ is heavily involved with the long‐range transport of dust particles, whereas submicron mode C₂ was influenced by anthropogenic sources from the East Asian continent. The size distributions of shorter‐chain diacids (C₃–C₆), phthalic (Ph) and glyoxylic acid are consistent with those of C₂, whereas azelaic acid (C₉) is enriched in submicron and supermicron modes by the influences of continental and marine air masses. The mass concentration ratios of C₃/C₄ in submicron (1.5–2.3) and supermicron (1.2–1.8) mode demonstrated that water‐soluble organic aerosols in Sapporo were photochemically processed during long‐range transport. The Ph/C₉ ratios show that the influence of anthropogenic sources on 9–28 April samples was pronounced in supermicron (2.5–2.9) than the submicron (1.1–1.2) particles, and vice‐versa on 6–21 May samples. These contrast distributions suggest that the continental air masses from East Asia and marine air masses from the surrounding ocean likely control the chemical composition of aerosols over Northern Japan.
• Sulfate-associated liquid water amplifies the formation of oxalic acid at a semi-arid tropical location over peninsular India during winter

  Suresh K.R. Boreddy, Kimitaka Kawamura, Divyavani Gowda, Dhananjay K. Deshmukh, K. Narasimhulu, K. Ramagopal

  Science of The Total Environment 874 162365 - 162365 2023年05月
• 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 2023年04月27日 

  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.
• Temporal lipid profiling in the progression from acute to chronic heart failure in mice and ischemic human hearts

  Gowda, S.G.B., Gowda, D., Hou, F., Chiba, H., Parcha, V., Arora, P., Halade, G.V., Hui, S.-P.

  Atherosclerosis 363 30 - 41 2022年12月
• 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 2022年11月 

  Fish is an important nutrition source because its lipids, which are rich in ω-3 fatty acids, are beneficial for human health. However, studies focusing on their detection, composition, and nutritional value are limited. In this study, we applied a non-targeted lipidomic approach based on ultra-high performance liquid chromatography coupled with linear-ion trap-Orbitrap mass spectrometry (UHPLC/LTQ-Orbitrap-MS) to comprehensively profile, compare, and detect unknown lipids in eleven types of dietary fish. A total of 287 molecular species from five major lipid classes were characterized by MS/MS analysis. Multivariate principal component analysis revealed the distinct lipid composition in shishamo smelt and Japanese sardine compared to other fish types. The assessment of nutritional indices based on the levels of free fatty acid suggested that among the eleven fish types, shishamo smelt is highly beneficial for health. Further, lipids such as N-acyl lysophosphatidylethanolamine were detected and characterized for the first time in fish fillets. Hierarchical cluster correlations indicated the predominance of glycerophospholipids (GPs) and sphingolipids in sardine, whereas fatty acyls and triacylglycerols (TAGs) were predominant in shishamo smelt. The high levels of polyunsaturated fatty acid-enriched GPs and TAGs in dietary fish endow it with great potential as a health-promoting food for human consumption. This study offers a comprehensive analysis of lipids and their compositions in fish fillets, demonstrating their potential use in the nutritional assessment of functional foods.
• 食事摂取した海藻の脂質に関する液体クロマトグラフィー/質量分析計を利用した探索的なデータ分析研究(Exploratory data analysis on dietary seaweeds lipids by liquid chromatography/mass spectrometry)

  Gowda Siddabasave Gowda B., Yifan Chen, Gowda Divyavani, Tsuboi Yui, Chiba Hitoshi, Hui Shu-Ping

  日本未病学会学術総会抄録集 29回 73 - 73 2022年10月
• 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 2022年09月 

  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.
• 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 2022年08月08日 

  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.
• 食品由来の肥満関連スフィンゴ脂質代謝阻害剤の発見(Discovery of Food Derived Inhibitor for Sphingolipid Metabolism Associated to Obesity)

  Minami Yusuke, Gowda Siddabasave Gowda B., Gowda Divyavani, Chiba Hitoshi, Hui Shu-Ping

  JSBMS Letters 47 Suppl. 80 - 80 2022年08月
• 食用魚11品目の未知の脂質に挑む Untargeted LC/MSによる組成分析(Tackling Unknown Lipids in Eleven Dietary Fish and Their Composition Analysis by Untargeted LC/MS)

  Gowda Siddabasave Gowda B., Minami Yusuke, Gowda Divyavani, Chiba Hitoshi, Hui Shu-Ping

  JSBMS Letters 47 Suppl. 85 - 85 2022年08月
• ヒドロキシ脂肪酸の短鎖脂肪酸エステル類の合成と簡便な分析法の開発(Synthesis and Development of a Facile Analytical Method for Short Chain Fatty Acid Esters of Hydroxy Fatty Acids)

  Hou Fengjue, Gowda Siddabasave Gowda B., Gowda Divyavani, Chiba Hitoshi, Hui Shu-Ping

  JSBMS Letters 47 Suppl. 86 - 86 2022年08月
• 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 11 2 229 - 229 2022年01月25日 

  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.
• 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 2021年12月 

  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.
• 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 2021年09月01日 

  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.
• 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 2021年08月04日 

  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 7598 - 7598 2021年07月15日 

  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 144 110325 - 110325 2021年06月 

  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.
• 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 2020年10月08日 

  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.
• 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  2020年09月15日 

  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.
• Identification of secondary fatty alcohols in atmospheric aerosols in temperate forests

  Yuzo Miyazaki, Divyavani Gowda, Eri Tachibana, Yoshiyuki Takahashi, Tsutom Hiura

  BIOGEOSCIENCES 16 10 2181 - 2188 2019年05月 

  Fatty alcohols (FAs) are major components of surface lipids (waxes) and can act as surface-active organic aerosols in the atmosphere, influencing chemical reactions, particle lifetimes, and the formation of cloud droplets and ice nuclei. However, studies on the composition and source of the FAs in atmospheric aerosols are very limited. In this study, we identified five secondary FAs (SFAs) with C27 and C29 from aerosol samples collected throughout 1 year at two different deciduous forest sites in Japan. Fatty diols, such as n-heptacosan-5,10-diol, were identified in atmospheric aerosols for the first time. Among the identified SFAs, n-nonacosan-10-ol was the most abundant compound, followed by n-nonacosan-5-10-diol at both of the forest sites. Concentrations of the SFAs exhibited distinct seasonal variation, with pronounced peaks during the growing season at each forest site. The SFAs showed significant correlation with sucrose, which is used as a molecular tracer of pollen. A significant fraction of the SFAs was attributed to the submicrometer particles in the growing season. The results indicate that they originated mostly from plant waxes and could be used as useful tracers for primary biological aerosol particles.
• Seasonal variations of low molecular weight hydroxy-dicarboxylic acids and oxaloacetic acid in remote marine aerosols from Chichijima Island in the western North Pacific (December 2010-November 2011)

  Divyavani Gowda, Kimitaka Kawamura

  ATMOSPHERIC RESEARCH 204 128 - 135 2018年05月 

  Concentrations of homologous hydroxy-dicarboxylic acids (diacids) (hC(3)-hC(6)) and keto-diacid (oxaloacetic acid) were measured in the atmospheric aerosols collected at Chichijima Island (27.04 degrees N, 142.13 degrees E) in the western North Pacific from December 2010 to November 2011. The monthly averaged concentrations of hydroxy-diacids and oxaloacetic acid were significantly higher in spring followed by winter and autumn. Molecular distributions of hydroxy-diacids demonstrated that malic acid was the most abundant species in all four seasons, followed by tartronic acid in winter and spring and 3- and 2-hydroxyglutaric acids in summer and autumn. Hydroxy-diacids and keto-diacid maximized in spring and winter when air masses originated from the Asian continent with westerly winds. The concentrations of total hydroxy-diacids and oxaloacetic acid ranged from 0.1 to 27.3 ng m(-3) and < 0.005 to 2 ng m(-3), respectively. The enhanced concentrations of diacids and their intermediates in winter and spring are associated with a long-range atmospheric transport of pollutants from East Asia to remote Chichijima Island followed by photochemical processing of organic aerosols. Seasonal molecular distribution of hydroxy-diacids and oxaloacetic acid was found to be dependent on the source strengths and plausible photochemical processing to form smaller diacids. Moderate to strong correlations among hydroxy-diacids, oxaloacetic acid and low molecular weight (LMW) diacids suggest that hydroxy-diacids and oxaloacetic acid are the intermediates in the photochemical oxidation of LMW diacid. Hence, photochemical formation of the most abundant LMW diacids, i.e., oxalic acid, could be produced from hydroxy- and keto-diacid as intermediates.
• 森林大気エアロゾルにおける脂肪族第二級アルコールの検出

  ディブヤバニ ゴウダ, 宮﨑 雄三, 高橋 善幸, 日浦 勉

  日本地球化学会年会要旨集 64 89 - 89 一般社団法人日本地球化学会 2017年 

  脂肪族アルコールはこれまで、高等植物に由来するワックス成分等として様々な地球化学的試料において分析されているが、大気中においては観測例が極めて限られている。植物から直接放出されるPrimary Biological Aerosol Particles(PBAPs)の起源指標として、その有用性などを実大気から明らかにすることは重要である。本研究では、2か所の国内森林サイトにおいて通年で取得した大気エアロゾル試料を用い、5つの脂肪族第二級アルコールを新たに検出・同定した。脂肪族第二級アルコール濃度は春季に最大を示す明瞭な季節変動を示し、その変動はスクロース(花粉等の起源指標)と類似していた。過去に報告例のあるバイオマス燃焼由来とされる一部の脂肪族アルコール以外に、脂肪族第二級アルコールが植物ワックス由来のPBAPsとして放出されていることが示唆された。

• Identification of hydroxy- and keto-dicarboxylic acids in remote marine aerosols using gas chromatography/quadruple and time-of-flight mass spectrometry

  Divyavani Gowda, Kimitaka Kawamura, Eri Tachibana

  RAPID COMMUNICATIONS IN MASS SPECTROMETRY 30 7 992 - 1000 2016年04月 

  RationaleThe identification of hydroxy- and keto-dicarboxylic acids (diacids) in remote marine aerosol samples is important for a better understanding of the composition of organic particulate matter, as this chemical composition is essential for predicting the effects on climate, air quality, and human health. Molecular characterization of these compounds provides insights into sources and formation pathways of organic aerosols.MethodsThe method of chemical derivatization followed by gas chromatography-flame ionization detection (GC-FID), gas chromatography/quadruple mass spectrometry (GC/QMS) and gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) was used to identify hydroxy- and keto-diacids in remote marine aerosols. Atmospheric samples were collected at Chichijima Island in the western North Pacific and the diacids and related compounds were extracted with organic-free ultrapure water. A two-step derivatization technique was employed, using 14% BF3/n-butanol for the butylation of carboxyl groups and acidic ketones followed by N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) for the trimethylsilylation of hydroxyl groups.ResultsSeveral new peaks were detected in the gas chromatogram after trimethylsilylation of the dibutyl ester fraction. Based on mass spectral interpretation with authentic standards, we successfully identified and quantified a homologous series of hydroxydiacids, including tartaric and oxaloacetic acids. In addition, transformation of oxaloacetic acid into its enol form was elucidated.ConclusionsUtilizing GC-FID, GC/QMS and GC/TOFMS, hydroxy- and keto-diacids were identified in the remote marine aerosols. A complete structural characterization was achieved with extensive mass spectral analysis. Molecular distributions of hydroxydiacids generally showed the predominance of malic acid followed by tartronic acid. We consider that these hydroxydiacids are important intermediates in the atmospheric oxidation of organic aerosols to result in smaller diacids. Copyright (c) 2016 John Wiley & Sons, Ltd.

その他活動・業績

• UHPLC/LTQ Orbitrap MSを用いた日本産魚類における脂質組成の網羅的解析

  MINAMI Yusuke, BOMMEGOWDA Siddabasavegowda, GOWDA Divyavani, CHIBA Hitoshi, HUI Shu-Ping JSBMS Letters 46 (Supplement) 2021年
• LC/MSによる早期疾患バイオマーカー探索のためのグローバル脂質プロファイリング

  BOMMEGOWDA Siddabasavegowda, GOWDA Divyavani, LIANG Chongsheng, CHIBA Hitoshi, HUI Shu-Ping JSBMS Letters 46 (Supplement) 2021年
• 短鎖脂肪酸エステル化ヒドロキシ脂肪酸の合成と分析方法の開発

  HOU Fengjue Hou, BOMMEGOWDA Siddabasavegowda, GOWDA Divyavani, CHIBA Hitoshi, HUI Shu-Ping JSBMS Letters 46 (Supplement) 2021年
• 心筋梗塞におけるスフィンゴシン-1-リン酸塩シグナル伝達の役割(Role of Sphingosine-1-phosphate signalling in myocardial infarction)

  Siddabasavegowda B. Gowda, Gowda Divyavani, 千葉 仁志, Halade Ganesh, 惠 淑萍 臨床化学 49 (Suppl.1) 213 -213 2020年10月

共同研究・競争的資金等の研究課題

• Unrevealing the anti-obesity effects of wakame associated to sphingomyelin synthase inhibition

  2022年度 若手研究：

  研究期間 : 2022年04月 -2024年03月 

  代表者 : Divyavani Gowda
• Analysis of hazardous components(PAHs) and their unknown derivatives in atmospheric PM 2.5 organic aerosols collected over Hokkaido

  日本学術振興会：科学研究費助成事業

  研究期間 : 2020年09月 -2022年03月 

  代表者 : DIVYAVANI

   

  エアロゾルは、気体中に浮遊する微小な粒子から構成されています。近年、粒子状物質（PM）は世界的な健康上の関心事となっています。大気中のPMは気候と健康の両方に影響を与え、PMは喘息や呼吸器疾患など、人間の健康に大きな悪影響を与える可能性があります。したがって、PAHの多様な影響を検討し、制御することができるように、その存在量、化学種、分布、潜在的な発生源を理解することが重要である。
• Analysis of hazardous components(PAHs) and their unknown derivatives in atmospheric PM 2.5 organic aerosols collected over Hokkaido

  Kakehni start up：2020年度 研究活動スタート支援

  研究期間 : 2020年09月 -2022年03月

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