研究者データベース

岡松 優子(オカマツ ユウコ)
獣医学研究院 獣医学部門 基礎獣医科学分野
准教授

基本情報

所属

  • 獣医学研究院 獣医学部門 基礎獣医科学分野

職名

  • 准教授

学位

  • 博士(獣医学)(北海道大学)

ホームページURL

J-Global ID

研究キーワード

  • 冬眠・休眠   メタボリックシンドローム   細胞増殖   体温調節   褐色脂肪   脂肪細胞   肥満   代謝   

研究分野

  • ライフサイエンス / 代謝、内分泌学
  • ライフサイエンス / 生理学
  • ライフサイエンス / 獣医学

職歴

  • 2018年11月 - 現在 北海道大学 大学院獣医学研究院 生化学教室 准教授
  • 2015年09月 - 2018年10月 北海道大学 大学院獣医学研究院 生化学教室 講師
  • 2008年06月 - 2015年08月 北海道大学 大学院獣医学研究科 生化学教室 助教
  • 2008年04月 - 2008年05月 日本学術振興会 特別研究員 (PD)
  • 2007年04月 - 2008年03月 日本学術振興会 特別研究員 (DC2)

学歴

  • 2004年04月 - 2008年03月   北海道大学   獣医学研究科
  • 1998年04月 - 2004年03月   北海道大学   獣医学部

所属学協会

  • 日本獣医学会   日本肥満学会   日本生化学会   日本分子生物学会   日本生理学会   

研究活動情報

論文

  • Junnosuke Mae, Kazuki Nagaya, Yuko Okamatsu-Ogura, Ayumi Tsubota, Shinya Matsuoka, Junko Nio-Kobayashi, Kazuhiro Kimura
    Frontiers in Cell and Developmental Biology 9 2021年07月05日 [査読有り]
     
    Brown adipose tissue (BAT) is a specialized tissue that regulates non-shivering thermogenesis. In Syrian hamsters, interscapular adipose tissue is composed primarily of white adipocytes at birth, which is converted to BAT through the proliferation and differentiation of brown adipocyte progenitors and the simultaneous disappearance of white adipocytes. In this study, we investigated the regulatory mechanism of brown adipogenesis during postnatal BAT formation in hamsters. Interscapular adipose tissue of a 10-day-old hamster, which primarily consists of brown adipocyte progenitors and white adipocytes, was digested with collagenase and fractioned into stromal–vascular (SV) cells and white adipocytes. SV cells spontaneously differentiated into brown adipocytes that contained multilocular lipid droplets and expressed uncoupling protein 1 (Ucp1), a marker of brown adipocytes, without treatment of adipogenic cocktail such as dexamethasone and insulin. The spontaneous differentiation of SV cells was suppressed by co-culture with adipocytes or by the addition of white adipocyte-conditioned medium. Conversely, the addition of SV cell-conditioned medium increased the expression of Ucp1. These results indicate that adipocytes secrete factors that suppress brown adipogenesis, whereas SV cells secrete factors that promote brown adipogenesis. Transcriptome analysis was conducted; however, no candidate suppressing factors secreted from adipocytes were identified. In contrast, 19 genes that encode secretory factors, including bone morphogenetic protein (BMP) family members, BMP3B, BMP5, and BMP7, were highly expressed in SV cells compared with adipocytes. Furthermore, the SMAD and MAPK signaling pathways, which represent the major BMP signaling pathways, were activated in SV cells, suggesting that BMPs secreted from SV cells induce brown adipogenesis in an autocrine manner through the SMAD/MAPK signaling pathways. Treatment of 5-day-old hamsters with type I BMP receptor inhibitor, LDN-193189, for 5 days reduced p38 MAPK phosphorylation and drastically suppressed BAT formation of interscapular adipose tissue. In conclusion, adipocytes and stromal cells regulate brown adipogenesis through secretory factors during the postnatal white-to-brown conversion of adipose tissue in Syrian hamsters.
  • Okamatsu-Ogura Yuko, Masayuki Saito
    Diabetes & Metabolism Journal 2021年06月25日 [査読有り]
  • Tussapon Boonyarattanasoonthorn, Keisuke Sato, Yuko Okamatsu-Ogura, Masami Morimatsu, Takashi Agui
    The Journal of veterinary medical science 83 3 403 - 411 2021年03月11日 
    Adipose tissues in mammals are categorized into white and brown adipose tissues in which cellular morphology, cell functions, and tissue distribution are different. White adipose tissue (WAT) plays a major role in energy reservation, while brown adipose tissue (BAT) mainly relates to the thermoregulation of the body. One interesting function of adipose tissue is the response to the infection, especially the pathogens that cause pneumonia. We have previously reported that DBA/2 (D2) mice are susceptible to pathogens causing pneumonia, Mycoplasma (M.) pulmonis and Sendai virus (SeV), whereas C57BL/6 (B6) mice are resistant to them. Furthermore, morphological alteration of mediastinal fat tissue (MFT) was seen after infection of M. pulmonis in D2 mice but not in B6 mice. In this study, we aimed to exhibit the difference in adipose tissue response in other areas, including interscapular brown adipose tissue (iBAT), inguinal white adipose tissue (ingWAT), and perigonadal WAT (perigoWAT) between resistant strain, B6 and susceptible strain, D2 after challenging them with M. pulmonis and SeV. Compared with B6 mice, D2 mice showed an increase in fat-associated lymphoid cluster in MFT, an increase in BAT in both iBAT and ingWAT after M. pulmonis and SeV infection. The results of this study indicate that pneumonia caused by M. pulmonis and SeV infection induces browning of adipocyte, suggesting that BAT plays a role in pathogen infection and inflammation.
  • Kazuhei Nishida, Michito Shimozuru, Yuko Okamatsu-Ogura, Mitsunori Miyazaki, Tsukasa Soma, Mariko Sashika, Toshio Tsubota
    Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology 191 2 397 - 409 2021年03月 
    Hibernating bears survive up to 6 months without feeding while yet maintaining metabolic homeostasis. We previously reported expression changes in energy metabolism-related genes in the liver of hibernating Japanese black bears. The present study examined the role of microRNAs in the regulation of hepatic gene expression during hibernation. The quantitative analyses revealed significant increases in the expression of 4 microRNAs (miR-221-3p, miR-222-3p, miR-455-3p, and miR-195a-5p) and decreases of 2 microRNAs (miR-122-5p and miR-7a-1-5p) during hibernation. RNA sequencing and in silico target prediction regarding 3 upregulated microRNAs (miR-221-3p, miR-222-3p and miR-455-3p) found 13 target mRNAs with significantly decreased expression during hibernation. The transfection of microRNA mimics into cells showed that miR-222 and miR-455 reduced solute carrier family 16 member 4 (SLC16A4) and fatty acid synthase (FASN) mRNA expression, respectively. Our results suggest that the increased levels of hepatic miRNA during hibernation (miR-222-3p and miR-455-3p) negatively regulate the expression of targeted genes predicted to be involved in the transport of energy source and de novo fatty acid synthesis, is consistent with a regulatory role of these miRNAs in energy metabolism in hibernating black bears.
  • Taisuke Kitano, Ryota Eguchi, Yuko Okamatsu-Ogura, Soichiro Yamaguchi, Ken-Ichi Otsuguro
    Journal of pharmacological sciences 145 3 228 - 240 2021年03月 
    Astrocytes are glial cells with numerous fine processes which are important for the functions of the central nervous system. The activation of β-adrenoceptors induces process formation of astrocytes via cyclic AMP (cAMP) signaling. However, the role of α-adrenoceptors in the astrocyte morphology has not been elucidated. Here, we examined it by using cultured astrocytes from neonatal rat spinal cords and cortices. Exposure of these cells to noradrenaline and the β-adrenoceptor agonist isoproterenol increased intracellular cAMP levels and induced the formation of processes. Noradrenaline-induced process formation was enhanced with the α1-adrenoceptor antagonist prazosin and α2-adrenoceptor antagonist atipamezole. Atipamezole also enhanced noradrenaline-induced cAMP elevation. Isoproterenol-induced process formation was not inhibited by the α1-adrenoceptor agonist phenylephrine but was inhibited by the α2-adrenoceptor agonist dexmedetomidine. Dexmedetomidine also inhibited process formation induced by the adenylate cyclase activator forskolin and the membrane-permeable cAMP analog dibutyryl-cAMP. Moreover, dexmedetomidine inhibited cAMP-independent process formation induced by adenosine or the Rho-associated kinase inhibitor Y27632. In the presence of propranolol, noradrenaline inhibited Y27632-induced process formation, which was abolished by prazosin or atipamezole. These results demonstrate that α-adrenoceptors inhibit both cAMP-dependent and -independent astrocytic process formation.
  • Collins Nimako, Yoshinori Ikenaka, Yuko Okamatsu-Ogura, Jussiaea V Bariuan, Atsushi Kobayashi, Ryo Yamazaki, Kumiko Taira, Nobuhiko Hoshi, Tetsushi Hirano, Shouta M M Nakayama, Mayumi Ishizuka
    The Journal of veterinary medical science 2021年01月25日 
    Hepatic steatosis is known to precede a continuum of events that lead to hepatic metabolic dysfunction, inflammation and carcinogenesis. Recently, studies have linked xenobiotic exposures to hepatic steatogenesis and its associated metabolic disorders; however, the underlying mechanisms remain elusive. This study aimed to elucidate the mechanistic role of imidacloprid in the prevalence of high fat diet (HFD)-induced liver steatosis, using a C57BL/6J mice model. Mice (3 weeks old) were fed with HFD and treated with 0.6 mg/kg bw/day (one-tenth of the NOAEL) of imidacloprid through water or diet, for 24 weeks. In a controlled group, mice were fed with only HFD. At the end of the study, imidacloprid treatment significantly potentiated HFD-induced body weight gain in mice. Also, imidacloprid increased the liver weights of mice, with complimentary reductions in mesenteric and gonadal white adipose tissue weights. Histopathological analysis of liver revealed a drastic steatosis in imidacloprid treated mice. Following a real-time qPCR analysis, imidacloprid upregulated transcriptions of hepatic fatty acid biosynthesis-related transcription factors and genes. Imidacloprid also induced hepatic expression of the gene encoding pregnane X receptor; but had no significant effect on hepatic expressions of liver X receptor and aryl hydrocarbon receptor. The imidacloprid treatment further enhanced serum alanine aminotransferase levels but downregulated hepatic antioxidant mRNA expressions. Ultimately, this study suggested an imidacloprid-potentiation effects on prevalence of HFD-induced liver steatosis via transcriptional modulations of the hepatic FA biosynthesis pathway.
  • Yuko Nabatame, Tetsuya Hosooka, Chikako Aoki, Yusei Hosokawa, Makoto Imamori, Yoshikazu Tamori, Yuko Okamatsu-Ogura, Takeshi Yoneshiro, Shingo Kajimura, Masayuki Saito, Wataru Ogawa
    Journal of diabetes investigation 2021年01月21日 
    AIMS/INTRODUCTION: Brown adipose tissue (BAT) utilizes large amounts of fuel for thermogenesis, but the mechanism by which fuel substrates are switched in response to changes in energy status is poorly understood. We have now investigated the role of Kruppel-like factor 15 (KLF15), a transcription factor expressed at a high level in adipose tissue, in the regulation of fuel utilization in BAT. MATERIALS AND METHODS: Depletion or overexpression of KLF15 in HB2 differentiated brown adipocytes was achieved by adenoviral infection. Glucose and fatty acid oxidation were measured with radioactive substrates, pyruvate dehydrogenase complex activity was determined with a colorimetric assay, and gene expression was examined by reverse transcription and real-time polymerase chain reaction analysis. RESULTS: Knockdown of KLF15 in HB2 cells attenuated fatty acid oxidation in association with downregulation of the expression of genes related to this process including Acox1 and Fatp1, whereas it increased glucose oxidation. Expression of the gene for pyruvate dehydrogenase kinase 4 (PDK4), a negative regulator of pyruvate dehydrogenase complex, was increased or decreased by KLF15 overexpression or knockdown, respectively, in HB2 cells, with these changes being accompanied by a respective decrease or increase in pyruvate dehydrogenase complex activity. Chromatin immunoprecipitation showed that Pdk4 is a direct target of KLF15 in HB2 cells. Finally, fasting increased expression of KLf15, Pdk4 and genes involved in fatty acid utilization in BAT of mice, whereas refeeding suppressed Klf15 and Pdk4 expression. CONCLUSIONS: Our results implicate KLF15 in the regulation of fuel switching between glucose and fatty acids in response to changes in energy status in BAT.
  • Yuko Okamatsu-Ogura, Masashi Kuroda, Rie Tsutsumi, Ayumi Tsubota, Masayuki Saito, Kazuhiro Kimura, Hiroshi Sakaue
    Metabolism: clinical and experimental 113 154396 - 154396 2020年12月 
    BACKGROUND: Brown adipose tissue (BAT) is a site of metabolic thermogenesis mediated by mitochondrial uncoupling protein 1 (UCP1) and represents a target for a therapeutic intervention in obesity. Cold exposure activates UCP1-mediated thermogenesis in BAT and causes drastic changes in glucose, lipid, and amino acid metabolism; however, the relationship between these metabolic changes and UCP1-mediated thermogenesis is not fully understood. METHODS: We conducted metabolomic and GeneChip array analyses of BAT after 4-h exposure to cold temperature (10 °C) in wild-type (WT) and UCP1-KO mice. RESULTS: Cold exposure largely increased metabolites of the glycolysis pathway and lactic acid levels in WT, but not in UCP1-KO, mice, indicating that aerobic glycolysis is enhanced as a consequence of UCP1-mediated thermogenesis. GeneChip array analysis of BAT revealed that there were 2865 genes upregulated by cold exposure in WT mice, and 838 of these were upregulated and 74 were downregulated in UCP1-KO mice. Pathway analysis revealed the enrichment of genes involved in fatty acid (FA) β oxidation and triglyceride (TG) synthesis in both WT and UCP1-KO mice, suggesting that these metabolic pathways were enhanced by cold exposure independently of UCP1-mediated thermogenesis. FA and cholesterol biosynthesis pathways were enhanced only in UCP1-KO mice. Cold exposure also significantly increased the BAT content of proline, tryptophan, and phenylalanine amino acids in both WT and UCP1-KO mice. In WT mice, cold exposure significantly increased glutamine content and enhanced the expression of genes related to glutamine metabolism. Surprisingly, aspartate was almost completely depleted after cold exposure in UCP1-KO mice. Gene expression analysis suggested that aspartate was actively utilized after cold exposure both in WT and UCP1-KO mice, but it was replenished from intracellular N-acetyl-aspartate in WT mice. CONCLUSIONS: These results revealed that cold exposure induces UCP1-mediated thermogenesis-dependent glucose utilization and UCP1-independent active lipid metabolism in BAT. In addition, cold exposure largely affects amino acid metabolism in BAT, especially UCP1-dependently enhances glutamine utilization. These results contribute a comprehensive understanding of UCP1-mediated thermogenesis-dependent and thermogenesis-independent metabolism in BAT.
  • Yuki Oiwa, Kaori Oka, Hironobu Yasui, Kei Higashikawa, Hidemasa Bono, Yoshimi Kawamura, Shingo Miyawaki, Akiyuki Watarai, Takefumi Kikusui, Atsushi Shimizu, Hideyuki Okano, Yuji Kuge, Kazuhiro Kimura, Yuko Okamatsu-Ogura, Kyoko Miura
    Scientific reports 10 1 19488 - 19488 2020年11月10日 
    The naked mole-rat (NMR) is a heterothermic mammal that forms eusocial colonies consisting of one reproductive female (queen), several reproductive males, and subordinates. Despite their heterothermy, NMRs possess brown adipose tissue (BAT), which generally induces thermogenesis in cold and some non-cold environments. Previous studies suggest that NMR-BAT induces thermogenesis by cold exposure. However, detailed NMR-BAT characteristics and whether NMR-BAT thermogenesis occurs in non-cold environments are unknown. Here, we show beta-3 adrenergic receptor (ADRB3)-dependent thermogenic potential of NMR-BAT, which contributes to thermogenesis in the isolated queen in non-cold environments (30 °C). NMR-BAT expressed several brown adipocyte marker genes and showed noradrenaline-dependent thermogenic activity in vitro and in vivo. Although our ADRB3 inhibition experiments revealed that NMR-BAT thermogenesis slightly delays the decrease in body temperature in a cold environment (20 °C), it was insufficient to prevent the decrease in the body temperatures. Even at 30 °C, NMRs are known to prevent the decrease of and maintain their body temperature by heat-sharing behaviors within the colony. However, isolated NMRs maintained their body temperature at the same level as when they are in the colony. Interestingly, we found that queens, but not subordinates, induce BAT thermogenesis in this condition. Our research provides novel insights into NMR thermoregulation.
  • Naoki Takatani, Yuka Kono, Fumiaki Beppu, Yuko Okamatsu-Ogura, Yumiko Yamano, Kazuo Miyashita, Masashi Hosokawa
    Biochemical and biophysical research communications 528 2 305 - 310 2020年07月23日 [査読有り][通常論文]
     
    Nonalcoholic steatohepatitis (NASH) is associated with hepatocyte injury, excessive oxidative stress, and chronic inflammation in fatty liver, and can progress to more severe liver diseases, such as cirrhosis and hepatocellular carcinoma. However, currently there are no effective therapies for NASH. Marine carotenoid, fucoxanthin (Fx), abundant in brown seaweeds, has variable biological properties, such as anti-cancer, anti-inflammatory, anti-oxidative and anti-obesity. However, the effect of Fx on the development of NASH has not been explored. We investigated the protective effects of Fx in diet-induced NASH model mice fed choline-deficient L-amino acid-defined high fat diet (CDAHFD). Fx administration significantly attenuated liver weight gain and hepatic fat accumulation, resulting in the alleviation of hepatic injury. Furthermore, the Fx-fed mice, not only exhibited reduced hepatic lipid oxidation, but also decreased mRNA expression levels of inflammation and infiltration-related genes compared to that of the CDAHFD-fed mice. Moreover, fucoxanthinol and amarouciaxanthin A, two Fx metabolites exerted anti-inflammatory effects in the liver via inhibiting the chemokine production in hepatocytes. In case of fibrosis, one of the features of advanced NASH, the expression of fibrogenic factors including activated-hepatic stellate cell marker was significantly decreased in the liver of Fx-fed mice. Thus, the present study elucidated that dietary Fx not only inhibited hepatic oxidative stress and inflammation but also prevented early phase of fibrosis in the diet-induced NASH model mice.
  • The effect of temperature acclimation on torpor expression pattern in mice.
    Sakamoto KQ, Okamatsu-Ogura Y
    68 1 55 - 62 2020年
  • Masayuki Saito, Mami Matsushita, Takeshi Yoneshiro, Yuko Okamatsu-Ogura
    Frontiers in endocrinology 11 222 - 222 2020年 
    Since the recent rediscovery of brown adipose tissue (BAT) in adult humans, this thermogenic tissue has been attracting increasing interest. The inverse relationship between BAT activity and body fatness suggests that BAT, because of its energy dissipating activity, is protective against body fat accumulation. Cold exposure activates and recruits BAT, resulting in increased energy expenditure and decreased body fatness. The stimulatory effects of cold exposure are mediated through transient receptor potential (TRP) channels and the sympathetic nervous system (SNS). Most TRP members also function as chemesthetic receptors for various food ingredients, and indeed, agonists of TRP vanilloid 1 such as capsaicin and its analog capsinoids mimic the effects of cold exposure to decrease body fatness through the activation and recruitment of BAT. The antiobesity effect of other food ingredients including tea catechins may be attributable, at least in part, to the activation of the TRP-SNS-BAT axis. BAT is also involved in the facultative thermogenesis induced by meal intake, referred to as diet-induced thermogenesis (DIT), which is a significant component of the total energy expenditure in our daily lives. Emerging evidence suggests a crucial role for the SNS in BAT-associated DIT, particularly during the early phase, but several gut-derived humoral factors may also participate in meal-induced BAT activation. One intriguing factor is bile acids, which activate BAT directly through Takeda G-protein receptor 5 (TGR5) in brown adipocytes. Given the apparent beneficial effects of some TRP agonists and bile acids on whole-body substrate and energy metabolism, the TRP/TGR5-BAT axis represents a promising target for combating obesity and related metabolic disorders in humans.
  • Alireza Nasoori, Yuko Okamatsu-Ogura, Michito Shimozuru, Mariko Sashika, Toshio Tsubota
    PloS one 15 8 e0238132  2020年 
    Bears do not suffer from osteoporosis during hibernation, which is associated with long-term inactivity, lack of food intake, and cold exposure. However, the mechanisms involved in bone loss prevention have scarcely been elucidated in bears. We investigated the effect of serum from hibernating Japanese black bears (Ursus thibetanus japonicus) on differentiation of peripheral blood mononuclear cells (PBMCs) to osteoclasts (OCs). PBMCs collected from 3 bears were separately cultured with 10% serum of 4 active and 4 hibernating bears (each individual serum type was assessed separately by a bear PBMCs), and differentiation were induced by treatment with macrophage colony stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL). PBMCs that were cultured with the active bear serum containing medium (ABSM) differentiated to multi-nucleated OCs, and were positive for TRAP stain. However, cells supplemented with hibernating bear serum containing medium (HBSM) failed to form OCs, and showed significantly lower TRAP stain (p < 0.001). On the other hand, HBSM induced proliferation of adipose derived mesenchymal stem cells (ADSCs) similarly to ABSM (p > 0.05), indicating no difference on cell growth. It was revealed that osteoclastogenesis of PBMCs is hindered by HBSM, implying an underlying mechanism for the suppressed bone resorption during hibernation in bears. In addition, this study for the first time showed the formation of bears' OCs in-vitro.
  • Tsolmon Chuluunbaatar, Osamu Ichii, Teppei Nakamura, Takao Irie, Takashi Namba, Md Rashedul Islam, Yuki Otani, Md Abdul Masum, Yuko Okamatsu-Ogura, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Frontiers in physiology 11 587214 - 587214 2020年 
    Cotton rats are one of the experimental rodents used for testing different infectious and non-infectious diseases, including gastrointestinal tract pathology. However, their intestinal morphological characteristics are still poorly understood. Here, we clarified the anatomical and histological characteristics of the cecum and ascending colon (AC) of young (1-3-month old), adult (4-6-month old), and old (10-12-month old) cotton rats. The large intestine (LI) in cotton rats is composed of the cecum, AC, transverse and descending colons, and rectum, and is similar to that of other mammals. The AC begins with a double or triple spiral loop-like flexure (SLLF) and ends with a coupled horseshoe-like flexure (HSLF). A single longitudinal mucosal fold (SLMF) was found at the beginning of the AC along the mesentery line and developed with age. Furthermore, the SLMF contained several lymphatic nodules (LNs), indicating their role in digestive and immunological functions. Small and large protuberant LNs were found in the cecum and SLLF, respectively, whereas thin and flat LNs were observed in the HSLF and transverse colon, respectively. Regarding sex-related differences, adult females had a significantly longer AC with a higher number of SLLFs compared to males. The SLMF length and LN number were also longer and higher, respectively, in adult females compared to adult males. These are crucial findings, indicating the presence of sex-related differences in the morphology of the LI in cotton rats, and ours is the first study to discover a sex difference in the mammalian LI lining. Our study clarified the unique morphology of the LI in cotton rats, which could serve as the principal model for elucidating species-specific digestive tract functions and gastrointestinal disorders.
  • Nakajima S, Nishimoto Y, Tateya S, Iwahashi Y, Okamatsu-Ogura Y, Saito M, Ogawa W, Tamori Y
    J Diabetes Investig 10 6 1419 - 1429 2019年11月 [査読有り][通常論文]
     
    AIMS/INTRODUCTION: Fat-specific protein 27 (FSP27) α is the major isoform of FSP27 in white adipose tissue (WAT), and is essential for large unilocular lipid droplet (LD) formation in white adipocytes. In contrast, FSP27β is abundantly expressed in brown adipose tissue (BAT), and plays an important role in small multilocular LD formation. In FSP27 KO mice in which FSP27α and β are both depleted, WAT is characterized by multilocular LD formation, and by increased mitochondrial abundance and energy expenditure, whereas BAT conversely manifests large oligolocular LDs and reduced energy expenditure. MATERIALS AND METHODS: We investigated the effects of autophagy in WAT and BAT of wild type (WT) and FSP27 knockout (KO) mice. In addition, we examined the effects of FSP27α and FSP27β to the induction of autophagy in COS cells. RESULTS: Food deprivation induced autophagy in BAT of WT mice, as well as in WAT of FSP27 KO mice, suggesting that enhanced autophagy is characteristic of adipocytes with small multilocular LDs. Pharmacological inhibition of autophagy attenuated the fasting-induced loss of LD area in adipocytes with small multilocular LDs (BAT of WT mice and WAT of FSP27 KO mice), without affecting that in adipocytes with large unilocular or oligolocular LDs (WAT of WT mice or in BAT of FSP27 KO mice). Overexpression of FSP27α inhibited autophagy induction by serum deprivation in COS cells, whereas that of FSP27β had no such effect. CONCLUSIONS: The present results thus showed that FSP27α inhibits autophagy and might thereby contribute to the energy-storage function of WAT.
  • Ayumi Tsubota, Yuko Okamatsu-Ogura, Jussiaea Valente Bariuan, Junnosuke Mae, Shinya Matsuoka, Junko Nio-Kobayashi, Kazuhiro Kimura
    The Journal of veterinary medical science 81 10 1461 - 1467 2019年10月24日 
    Brown adipose tissue (BAT) contributes to non-shivering thermogenesis and plays an important role in body temperature control. The contribution of BAT thermogenesis to body temperature control in a non-cold environment was evaluated using developing hamsters. Immunostaining for uncoupling protein 1 (UCP1), a mitochondrial protein responsible for BAT thermogenesis, indicated that interscapular fat tissue had matured as BAT at day 14. When pups were placed on a thermal plate kept at 23°C, the body surface temperature decreased in day 7- and 10-day-old pups but was maintained at least for 15 min in 14-day-old pups, indicating that hamsters are unable to maintain their body temperature until around day 14 even in a non-cold environment. Body temperature maintenance was also evaluated in UCP1-deficient mice. BAT analysis showed that the UCP1 protein level in Ucp1+/- Hetero mice was 61.3 ± 1.4% of that in wild-type (WT) mice and was undetected in Ucp1-/- knockout (KO) mice. When 12-day-old pups were place on a thermal plate at 23°C, body surface temperature was maintained for at least 15 min in WT and Hetero mice but gradually dropped by 2.4 ± 0.2°C in 15 min in KO mice. It is concluded that BAT thermogenesis is indispensable for body temperature maintenance in pups of hamsters and mice, even in the non-cold circumstances. The early life poikilothermy and the later acquirement of homeothermy in hamsters may be because of the postnatal development of BAT.
  • Yuko Okamatsu-Ogura, Mami Matsushita, Jussiaea Valente Bariuan, Kazuki Nagaya, Ayumi Tsubota, Masayuki Saito
    Scientific reports 9 1 13243 - 13243 2019年09月13日 [査読有り][通常論文]
     
    Brown adipose tissue (BAT) plays an important role in body fat accumulation and the regulation of energy expenditure. Since the role of miRNAs in the pathogenesis of obesity and related metabolic diseases is contentious, we analyzed exosomal miRNAs in serum of healthy subjects with special references to BAT activity and body fat level. Forty male volunteers aged 20-30 years were recruited. Their BAT activity was assessed by fluorodeoxyglucose positron emission tomography and computed tomography after 2 h of cold exposure and expressed as a maximal standardized uptake value (SUVmax). Exosomal miRNA levels was analyzed using microarray and real-time PCR analyses. The miR-122-5p level in the high BAT activity group (SUV ≧ 3) was 53% lower than in the low BAT activity group (SUVmax <3). Pearson's correlation analysis revealed that the serum miR-122-5p level correlated negatively with BAT activity and the serum HDL-cholesterol, and it correlated positively with age, BMI, body fat mass, and total cholesterol and triglyceride serum levels. Multivariate regression analysis revealed that BAT activity was associated with the serum miR-122-5p level independently of the other parameters. These results reveal the serum exosomal miR-122-5p level is negatively associated with BAT activity independently of obesity.
  • Woongchul Shin, Yuko Okamatsu-Ogura, Shinya Matsuoka, Ayumi Tsubota, Kazuhiro Kimura
    The Journal of veterinary medical science 81 6 799 - 807 2019年06月06日 [査読有り][通常論文]
     
    Brown adipocytes, which exist in brown adipose tissue (BAT), are activated by adrenergic stimulation, depending on the activity of uncoupling protein 1 (UCP1). Beige adipocytes emerge from white adipose tissue (WAT) in response to chronic adrenergic stimulation. We investigated obesity-related changes in responses of both types of adipocytes to adrenergic stimulation in mice. Feeding of mice with high-fat diets (HFD: 45%-kcal fat) for 14 weeks resulted in significantly higher body and WAT weight compared to feeding with normal diets (ND: 10%-kcal fat). Injection with β3-adrenergic receptor agonist CL316,243 (CL; 0.1 mg/kg, once a day) for one week elevated the mRNA and protein expression levels of UCP1 in BAT, irrespective of diet. In WAT, CL-induced UCP1 expression in ND mice; however, the responses to CL treatment were attenuated in HFD mice, indicating that CL-induced browning of WAT was impaired in obese mice. Flow cytometric analysis revealed a significant decrease in platelet-derived growth factor receptor (PDGFR) α-expressing beige adipocyte progenitors in WAT of HFD mice compared with those of ND mice. Expression of PDGF-B, a PDGFRα ligand, increased in WAT following CL-injection in ND mice, but not in HFD mice. Treatment of mice with a PDGFR inhibitor significantly decreased CL-dependent UCP1 protein induction in WAT. Our study demonstrates that β3-adrenergic stimulation-dependent beige adipocyte induction in WAT is impaired by obesity in mice, potentially due to obesity-dependent reduction in the number of PDGFRα-expressing progenitors and decreased PDGF-B expression.
  • Narumi Kubo, Mio Kawahara, Yuko Okamatsu-Ogura, Yosuke Miyazaki, Ryuto Otsuka, Kazuki Fukuchi
    Molecular imaging and biology 21 2 249 - 256 2019年04月 
    PURPOSE: Regulation of metabolic activity in adipose tissue is of great concern for treating obesity. This study aimed to evaluate the adrenergic regulation of glucose uptake and the thermogenic program in adipose tissues in mouse models of both type 1 and 2 diabetes mellitus (DM). PROCEDURES: Male mice were treated with streptozotocin to induce type 1 (T1) DM, and obese ob/ob mice were used for the type 2 (T2) DM model. After selective β3-adrenoreceptor stimulation by CL 316,243 (CL) treatment, 2-deoxy-D-[14C]glucose ([14C]DG) was administered to DM and corresponding control mice. Radioactivity and uncoupling protein 1 (UCP1) expression were measured and analyzed in adipose tissues. RESULTS: In T1DM, [14C]DG uptake in brown adipose tissue (BAT) decreased both at rest and upon CL stimulation, and UCP1 expression was preserved. However, CL treatment enhanced [14C]DG uptake without impairing UCP1 expression in inguinal white adipose tissue (iWAT). In this model, CL could not alter blood glucose levels. In T2DM mice, the blood glucose level was significantly lowered by CL treatment. There was no decrease in CL-induced [14C]DG uptake in BAT, and UCP1 expression was maintained. However, [14C]DG uptake was not increased in iWAT and no UCP1 expression was observed in iWAT (browning). CONCLUSIONS: The metabolic response against adrenergic stimulation varied depending on the type of adipose tissue and DM. This could be important for the therapeutic activation of adipose tissue metabolism in obese diabetic patients.
  • Yoneshiro T, Shin W, Machida K, Fukano K, Tsubota A, Chen Y, Yasui H, Inanami O, Okamatsu-Ogura Y, Kimura K
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 4 5196 - 5207 2019年04月 [査読有り][通常論文]
     
    Bone marrow provides progenitors of several types of cells, including muscle and white adipocytes, ensuring peripheral tissue homeostasis. However, the role of bone marrow-derived cells (BMCs) in induction of thermogenic adipocytes is unresolved. The purpose of this study is to examine whether BMCs are involved in the emergence of thermogenic adipocytes through adrenergic activation. Irradiation of mice with 8 Gy of X-ray-depleted BMCs and peripheral blood mononucleated cells (PBMCs), which in turn impaired induction of uncoupling protein 1 (UCP1) through administration of β3 adrenergic receptor agonist, CL 316,243 (CL), in inguinal white adipose tissue (iWAT). In contrast, CL-induced UCP1 induction in brown adipose tissue was unaffected by BMC depletion. Transplantation of normal BMCs into mice depleted of BMCs recovered PBMC levels and rescued the ability of iWAT browning by CL. Furthermore, analyses of mice transplanted with green fluorescent protein (GFP)-labeled BMCs revealed that the number of GFP-positive BMCs and PBMCs were significantly decreased by CL and that GFP-positive stromal cells and GFP-positive UCP1-expressing multilocular adipocytes appeared in iWAT after CL administration, demonstrating differentiation of BMC-derived preadipocytes into UCP1-expressing thermogenic adipocytes. These results unveiled a crucial role of the BMC as a nonresident origin for a subset of thermogenic adipocytes, contributing to browning of white adipose tissue.-Yoneshiro, T., Shin, W., Machida, K., Fukano, K., Tsubota, A., Chen, Y., Yasui, H., Inanami, O., Okamatsu-Ogura, Y., Kimura, K. Differentiation of bone marrow-derived cells toward thermogenic adipocytes in white adipose tissue induced by the β3 adrenergic stimulation.
  • Okura Y, Imao T, Murashima S, Shibata H, Kamikavwa A, Okamatsu-Ogura Y, Saito M, Kimura K
    International journal of molecular sciences 20 7 2019年03月27日 [査読有り][通常論文]
     
    Both adiponectin and secreted protein, acidic and rich in cysteine (SPARC) inhibit platelet-derived growth factor-BB (PDGF-BB)-induced and basic fibroblast growth factor (FGF2)-induced angiogenic activities through direct and indirect interactions. Although SPARC enhances nerve growth factor (NGF)-dependent neurogenesis, the physical interaction of NGFβ with adiponectin and SPARC remains obscure. Therefore, we first examined their intermolecular interaction by surface plasmon resonance method. NGFβ bound to immobilized SPARC with the binding constant of 59.4 nM, comparable with that of PDGF-BB (24.5 nM) but far less than that of FGF2 (14.4 µM). NGFβ bound to immobilized full length adiponectin with the binding constant of 103 nM, slightly higher than those of PDGF-BB (24.3 nM) and FGF2 (80.2 nM), respectively. Treatment of PC12 cells with SPARC did not cause mitogen-activated protein kinase (MAPK) activation and neurite outgrowth. However, simultaneous addition of SPARC with NGFβ enhanced NGFβ-induced MAPK phosphorylation and neurite outgrowth. Treatment of the cells with adiponectin increased AMP-activated protein kinase (AMPK) phosphorylation but failed to induce neurite outgrowth. Simultaneous treatment with NGFβ and adiponectin significantly reduced cell size and the number of cells with neurite, even after silencing the adiponectin receptors by their siRNA. These results indicate that NGFβ directly interacts with adiponectin and SPARC, whereas these interactions oppositely regulate NGFβ functions.
  • Cold Exposure Increases Circulating miR-122 Levels via UCP1-Dependent Mechanism in Mice.
    Bariuan JV, Okamatsu-Ogura Y, Tsubota A, Matsuoka S, Saito M, Kimura K
    Japanese Journal of Veterinary Research 68 3 187 - 195 2019年
  • Takeshi Yoneshiro, Ryuji Kaede, Kazuki Nagaya, Manami Saito, Julia Aoyama, Mohamed Elfeky, Yuko Okamatsu-Ogura, Kazuhiro Kimura, Akira Terao
    Nutrition research (New York, N.Y.) 58 17 - 25 2018年10月 [査読有り][通常論文]
     
    Dietary supplementation with melinjo (Gnetum gnemon L.) seed extract (MSE) has been proposed as an anti-obesity strategy. However, it remains unclear how MSE modulates energy balance. We tested the hypothesis that dietary MSE reduces energy intake and/or increases physical activity and metabolic thermogenesis in brown and white adipose tissue (BAT and WAT) in mice. Twenty-four C57BL/6 J mice were provided with normal diet, high-fat diet (HFD), or HFD with 1% MSE added, for 17 weeks. Food intake, spontaneous locomotor activity, hepatic triglyceride (TG) content, and blood parameters were examined. Mitochondrial thermogenesis-associated molecule and inflammatory marker expression levels in BAT and WAT were examined by quantitative PCR and western blotting. Dietary MSE did not affect energy intake or spontaneous locomotor activity, but significantly suppressed HFD-induced fat accumulation, hyperglycemia, and hyperinsulinemia. Homeostasis model assessment of insulin resistance score and hepatic TG content were both lower in the MSE-supplemented HFD-fed group than in the HFD-fed group, indicating reduced insulin resistance and a less fatty liver. Dietary MSE upregulated thermogenic uncoupling protein 1 (UCP1) and mitochondrial marker cytochrome c oxidase subunit IV protein expression in BAT; this was closely associated with sirtuin 1 mRNA induction. mRNAs of adipose inflammatory markers, such as monocyte chemotactic 1 and interleukin-1, were induced by HFD but suppressed by MSE. Considering that UCP1 protein expression is the most physiologically relevant parameter to assess the thermogenic capacities of BAT, our results indicate that dietary MSE supplementation induces BAT thermogenesis and reduces obesity-associated adipose tissue inflammation, hepatic steatosis, and insulin resistance.
  • Masako Yudasaka, Yohei Yomogida, Minfang Zhang, Masako Nakahara, Norihiko Kobayashi, Takeshi Tanaka, Yuko Okamatsu-Ogura, Kumiko Saeki, Hiromichi Kataura
    Scientific reports 8 1 14446 - 14446 2018年09月27日 
    Brown adipose tissue (BAT), which is composed of thermogenic brown adipocytes (BA) and non-parenchymal components including vasculatures and extracellular matrix, contribute to the maintenance of body temperature. BAT distribution is detected by positron emission tomography-computed tomography (PET/CT) using 18F-fluorodeoxy glucose (18F-FDG) or single-photon-emission computed tomography-computed tomography (SPECT/CT) using [123/125I]-beta-methyl-p-iodophenyl-pentadecanoic acid. Although sympathetic nerve activity and thermogenic capacity of BA is downregulated under fasting conditions in mice, fasting-dependent structural changes and fluid kinetics of BAT remain unknown. Here we show that the fasting induces fine and reversible structural changes in the non-parenchymal region in murine BAT with widened intercellular spaces and deformed collagen bands as revealed by electron microscopy. Interestingly, a newly introduced near infrared fluorescent probe of single-walled carbon nanotubes (CNTs) coated with phospholipid polyethylene glycol (PLPEG) easily demonstrated enhanced vascular permeability in BAT by the fasting. PLPEG-CNTs extravasated and remained in intercellular spaces or further redistributed in parenchymal cells in fasted mice, which is a previously unknown phenomenon. Thus, PLPEG-CNTs provide a powerful tool to trace fluid kinetics in sub-tissue levels.
  • Kazuki Nagaya, Yuko Okamatsu-Ogura, Junko Nio-Kobayashi, Shohei Nakagiri, Ayumi Tsubota, Kazuhiro Kimura
    Journal of Physiological Sciences 1 - 8 2018年04月02日 [査読有り][通常論文]
     
    In Syrian hamsters, brown adipose tissue (BAT) develops postnatally through the proliferation and differentiation of brown adipocyte progenitors. In the study reported here, we investigated how ambient temperature influenced BAT formation in neonatal hamsters. In both hamsters raised at 23 or 30 °C, the interscapular fat changed from white to brown coloration in an age-dependent manner and acquired the typical morphological features of BAT by day 16. However, the expression of uncoupling protein 1, a brown adipocyte marker, and of vascular endothelial growth factor α were lower in the group raised at 30 °C than in that raised at 23 °C. Immunofluorescent staining revealed that the proportion of Ki67-expressing progenitors and endothelial cells was lower in the 30 °C group than in the 23 °C group. These results indicate that warm ambient temperature suppresses the proliferation of brown adipocyte progenitors and endothelial cells and negatively affects the postnatal development of BAT in Syrian hamsters.
  • Mohamed Elfeky, Takeshi Yoneshiro, Yuko Okamatsu-Ogura, Kazuhiro Kimura
    Journal of Biochemistry 163 2 143 - 153 2018年02月01日 [査読有り][通常論文]
     
    High-mobility group protein B1 (HMGB1) is a late inflammatory mediator released from inflammatory cells when stimulated, resulting in exaggerating septic symptoms. We recently demonstrated that full-length adiponectin, a potent anti-inflammatory adipokine, inhibits lipopolysaccharide-induced HMGB1 release. However, the effects of adiponectin on HMGB1-induced exaggerating signals currently remain unknown. This study aimed to investigate the effects of adiponectin on the pro-inflammatory function of HMGB1 in RAW264 macrophage cells. The treatment of RAW264 cells with HMGB1 significantly up-regulated the mRNA expression of tumour necrosis factor-α, interleukin-1β and C-X-C motif chemokine 10. HMGB1-induced cytokine expression was markedly suppressed by a toll-like receptor 4 (TLR4) antagonist and slightly suppressed by an antagonist of the receptor for advanced glycation end products. A prior treatment with full-length or globular adiponectin dose-dependently suppressed all types of HMGB1-induced cytokine expression, and this suppression was abolished by compound C, an AMPK inhibitor, but not by the haem oxygenase (HO)-1 inhibitor, zinc protoporphyrin IX. Both forms of adiponectin also reduced the mRNA expression of TLR4. These results suggest that full-length and globular adiponectin suppress HMGB1-induced cytokine expression through an AMPK-mediated HO-1-independent pathway.
  • Yuko Okamatsu-Ogura, Junko Nio-Kobayashi, Kazuki Nagaya, Ayumi Tsubota, Kazuhiro Kimura
    Journal of Applied Physiology 124 1 99 - 108 2018年01月01日 [査読有り][通常論文]
     
    To investigate the postnatal development of brown adipose tissue (BAT) in Syrian hamsters, we histologically examined interscapular fat tissue from 5-16-day-old pups, focusing on how brown adipocytes arise. Interscapular fat of 5-day-old hamsters mainly consisted of white adipocytes containing large unilocular lipid droplets, as observed in typical white adipose tissue (WAT). On day 7, clusters of small, proliferative nonadipocytes with a strong immunoreactivity for Ki67 appeared near the edge of the interscapular fat tissue. The area of the Ki67-positive regions expanded to ~50% of the total tissue area by day 10.The interscapular fat showed the typical BAT feature by day 16. A brown adipocyte-specific marker, uncoupling protein-1, was clearly detected on day 10 and thereafter, while not detected on day 7. During conversion of interscapular fat from WAT to BAT, unilocular adipocytes completely and rapidly disappeared without obvious apoptosis. Dual immunofluorescence staining for Ki67 and monocarboxylate transporter 1 (MCT1), another selective marker for brown adipocytes, revealed that most of the proliferating cells were of the brown adipocyte lineage. Electron microscopic examination showed that some of the white adipocytes contained small lipid droplets in addition to the large droplet and expressed MCT1 as do progenitor and mature brown adipocytes, implying a direct conversion from white to brown adipocytes. These results suggest that BAT of Syrian hamsters develops postnatally through two different pathways: The proliferation and differentiation of brown adipocyte progenitors and the conversion of unilocular adipocytes to multilocular brown adipocytes.
  • Role of macrophages in depot-dependent browning of white adipose tissue.
    Machida K, Okamatsu-Ogura Y, Shin W, Matsuoka S, Tsubota A, Kimura K
    J Physiol Sci 68 5 601 - 608 2018年 [査読有り][通常論文]
  • Yoneshiro T, Kaede R, Nagaya K, Aoyama J, Saito M, Okamatsu-Ogura Y, Kimura K, Terao A
    Obes Res Clin Prac 12 1 127 - 137 2018年01月 [査読有り][通常論文]
  • Yamaji, D, Soliman, M.M, Kamikawa, A, Ito, T, Ahmed, M.M, Okamatsu-Ogura, Y, Saito, M, Kimura, K
    Domestic Animal Endocrinology 62 39 - 48 2018年 [査読有り][通常論文]
  • Yuko Okamatsu-Ogura, Keigo Fukano, Ayumi Tsubota, Junko Nio-Kobayashi, Kyoko Nakamura, Masami Morimatsu, Hiroshi Sakaue, Masayuki Saito, Kazuhiro Kimura
    SCIENTIFIC REPORTS 7 1 6648  2017年07月 [査読有り][通常論文]
     
    We previously reported brown adipocytes can proliferate even after differentiation. To test the involvement of mature adipocyte proliferation in cell number control in fat tissue, we generated transgenic (Tg) mice over-expressing cell-cycle inhibitory protein p27 specifically in adipocytes, using the aP2 promoter. While there was no apparent difference in white adipose tissue (WAT) between wild-type (WT) and Tg mice, the amount of brown adipose tissue (BAT) was much smaller in Tg mice. Although BAT showed a normal cellular morphology, Tg mice had lower content of uncoupling protein 1 (UCP1) as a whole, and attenuated cold exposure-or beta 3-adrenergic receptor (AR) agonist-induced thermogenesis, with a decrease in the number of mature brown adipocytes expressing proliferation markers. An agonist for the beta 3-AR failed to increase the number of proliferating brown adipocytes, UCP1 content in BAT, and oxygen consumption in Tg mice, although the induction and the function of beige adipocytes in inguinal WAT from Tg mice were similar to WT mice. These results show that brown adipocyte proliferation significantly contributes to BAT development and adaptive thermogenesis in mice, but not to induction of beige adipocytes.
  • Mabrouk Attia Abd Eldaim, Shinya Matsuoka, Yuko Okamatsu-Ogura, Akihiro Kamikawa, Mohamed Mohamed Ahmed, Akira Terao, Kei-ichi Nakajima, Kazuhiro Kimura
    GENES TO CELLS 22 6 568 - 582 2017年06月 [査読有り][通常論文]
     
    It is well known that retinoic acid (RA) suppresses adipogenesis, although there are some contradicting reports. In this study, we examined the effect of extracellular glucose on RA-induced suppression of adipogenesis in 3T3L1 cell culture. When the cells were cultured in normal glucose medium (NG), the addition of RA suppressed lipid accumulation. However, when cultured in high glucose medium (HG), addition of RA to the cells enhanced lipid accumulation. These changes were accompanied by parallel alterations in fatty acid synthase (FAS) and sterol regulatory element-binding protein (SREBP)-1 gene expression. Transfection of SREBP-1 siRNA suppressed RA-induced enhancement of lipid accumulation and FAS expression in the cells cultured with HG. Transfection of the nuclear form of SREBP-1a cDNA into the cells cultured with NG inhibited RA-induced suppression of lipid accumulation and FAS expression. Moreover, RA- and HG-induced SREBP-1a expression occurred at the early phase of adipogenesis and was dependent on glucocorticoid to induce liver X receptor (LXR) , peroxisomal proliferator-activated receptor (PPAR) and retinoid X receptor (RXR), the key nuclear factors influencing the SREBP-1a gene expression. These results suggest that RA suppresses and enhances lipid accumulation through extracellular glucose concentration-dependent modulation of SREBP-1 expression.
  • Masako Yudasaka, Yohei Yomogida, Minfang Zhang, Takeshi Tanaka, Masako Nakahara, Norihiko Kobayashi, Yuko Okamatsu-Ogura, Ken Machida, Kazuhiko Ishihara, Kumiko Saeki, Hiromichi Kataura
    Scientific Reports 7 2017年03月20日 [査読有り][通常論文]
     
    Near-infrared photoluminescent single-walled carbon nanotubes (CNTs) are expected to provide effectual bio-imaging tools, although, as yet, only limited applications have been reported. Here, we report that CNTs coated with an amphiphilic and biocompatible polymer, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate PMB), generate high-quality images of brown fat. Brown fat is a heat-productive adipose tissue, which is attracting increasing attention as a new therapeutic target for obesity-associated metabolic disorders. Its brown colour is mainly attributed to densely packed capillaries, which facilitate its high heat-exchanging efficiency. Currently, positron emission tomography-computed tomography is the only practical technique to identify brown fat distribution in the living body however, it is expensive to use. By virtue of their high affinity to apolipoproteins and exemption from macrophage phagocytosis, PMB-CNTs selectively accumulate on capillary endothelial cells but not larger vessels in adipose tissue. Therefore, the image brightness of adipose tissue can directly reflect the capillary density, and indirectly the thermogenic capability and brownness. PMB-CNTs provide clearer images than conventional organic dyes, as the high level of transmitted light passes through the body with less light scattering. Thus, PMB-CNT-based imaging methods could open a new phase in thermogenic adipose tissue research.
  • Woongchul Shin, Yuko Okamatsu-Ogura, Ken Machida, Ayumi Tsubota, Junko Nio-Kobayashi, Kazuhiro Kimura
    OBESITY 25 2 417 - 423 2017年02月 [査読有り][通常論文]
     
    Objective: There are two types of thermogenic adipocytes expressing uncoupling protein ( UCP)-1: the brown adipocyte activated by adrenergic stimulation and the beige adipocyte that appears within the white adipose tissue ( WAT) in response to chronic adrenergic stimulation. This study examined age-related changes in responses of both types of adipocytes to adrenergic stimulation in mice. Methods: Aged ( age 20 months) and young ( 4 months) mice were injected daily with either saline or beta 3-adrenergic receptor agonist CL316,243 ( CL; 0.1 mg/kg, once a day) for 1 week. Results: The body and WAT weight tended to be higher in aged mice. CL treatment increased UCP-1 protein amounts in both brown adipose tissue and inguinal WAT, suggesting activation of brown and beige adipocytes. However, induction of beige adipocytes was impaired in aged mice, whereas brown adipocyte activation was comparable to young mice. The number of platelet-derived growth factor receptor alpha-expressing progenitor cells, which were reported to differentiate into beige adipocytes, significantly decreased in inguinal WAT of aged mice compared with that of young mice. Conclusions: Inductive ability of beige adipocytes in WAT declines with aging in mice. It may be partly because of a decreased number of progenitor cells associated with aging.
  • Tomoki Ito, Daisuke Yamaji, Akihiro Kamikawa, Mabrouk Attia Abd Eldaim, Yuko Okamatsu-Ogura, Akira Terao, Masayuki Saito, Kazuhiro Kimura
    ENDOCRINE JOURNAL 64 8 777 - 785 2017年 [査読有り][通常論文]
     
    It is well documented that estrogen is predominant inducer of hepatocyte growth factor (HGF) in a variety of cell types. However, the effect of progesterone (P) remains to be elusive. Thus, in the present study, we examined the effect of P and combined effect of P and 17 beta-estradiol (E2) on HGF expression and production in 3T3-L1 fibroblastic preadipocytes and mature adipocytes, as a model of stromal cells. Northern blot analysis showed that hgf mRNA expressed in preadipocytes was notably higher than that of mature adipocytes, and increased by treatment of preadipocytes with E2 or 10 nM P, but not with 1,000 nM P. The E2-induced hgf mRNA expression was enhanced by 10 nM P, but suppressed by 1,000 nM P. Western blot analysis revealed that biological active forms of HGF protein was found in the preadipocyte culture medium, while the lesser amount of HGF precursor protein was detected in the mature adipocyte culture medium. The amounts of HGF were changed dependently on the hgf mRNA expression levels. These results indicate that HGF production is intricately regulated by E2 and P at the transcriptional levels in 3T3-L1 cells, and may explain the changes in the HGF production during the mammary gland development, especially decrease in HGF expression during pregnancy when P concentration is high.
  • Keigo Fukano, Yuko Okamatsu-Ogura, Ayumi Tsubota, Junko Nio-Kobayashi, Kazuhiro Kimura
    PLOS ONE 11 11 e0166579 - e0166579 2016年11月15日
  • Mohamed Elfeky, Ryuji Kaede, Yuko Okamatsu-Ogura, Kazuhiro Kimura
    MEDIATORS OF INFLAMMATION 2016年 [査読有り][通常論文]
     
    High mobility group protein B1 (HMGB1) is a late inflammatory mediator that exaggerates septic symptoms. Adiponectin, an adipokine, has potent anti-inflammatory properties. However, possible effects of adiponectin on lipopolysaccharide-(LPS-) induced HMGB1 release are unknown. The aim of this study was to investigate effects of full length adiponectin on HMGB1 release in LPS-stimulated RAW 264 macrophage cells. Treatment of the cells with LPS alone significantly induced HMGB1 release associated with HMGB1 translocation from the nucleus to the cytosol. However, prior treatment with adiponectin suppressed LPS-induced HMGB1 release and translocation. The anti-inflammatory cytokine interleukin-(IL-) 10 similarly suppressed LPS-induced-HMGB1 release. Adiponectin treatment decreased toll-like receptor 4 (TLR4) mRNA expression and increased heme oxygenase-(HO-) 1 mRNA expression without inducing IL-10 mRNA, while IL-10 treatment decreased TLR2 and HMGB1 mRNA expression and increased the expression of IL-10 andHO-1mRNA. Treatment with the HO-1 inhibitor ZnPP completely prevented the suppression of HMGB1 release by adiponectin but only partially inhibited that induced by IL-10. Treatment with compound C, an AMP kinase (AMPK) inhibitor, abolished the increase in HO-1 expression and the suppression of HMGB1 release mediated by adiponectin. In conclusion, our results indicate that adiponectin suppresses HMGB1 release by LPS through an AMPK-mediated and HO-1-dependent IL-10-independent pathway.
  • Yuko Okamatsu-Ogura, Ayumi Tsubota, Kana Ohygma, Yoshihito Nogusa, Masayuki Saito, Kazuhiro Kimura
    JOURNAL OF FUNCTIONAL FOODS 19 1 - 9 2015年12月 [査読有り][通常論文]
     
    Capsinoids are less pungent capsaicin analogues that increase whole body energy expenditure and hence reduce fat. Several studies have suggested that capsinoids activate brown adipose tissue (BAT), a major site of adaptive thermogenesis, but the actual contribution of BAT and uncoupling protein 1 (UCP1), a thermogenic protein expressed in BAT, to the fat-reducing effect of capsinoids has not yet been determined. Here, we investigated the effect of capsinoids on high-fat diet (HFD)-induced obesity using wild-type (WT) and UCP1-deficient (KO) mice. Capsinoids feeding potently suppressed HFD-induced increase in body weight, adiposity, and fatty liver development in WT mice. In contrast, such effects of capsinoids were completely abolished in UCP1-KO mice. Moreover, capsinoids significantly increased UCP1 protein expression in BAT without its apparent induction in white adipose tissue (WAT) in WT mice. These results indicate that capsinoids suppress diet-induced obesity of mice through the UCP1 function in BAT but not in WAT. (C) 2015 Elsevier Ltd. All rights reserved.
  • Yuta Sakurai, Yuko Okamatsu-Ogura, Masayuki Saito, Kazuhiro Kimura, Ryo Nakao, Aiko Ohnuma, Mari Kobayashi
    MARINE MAMMAL SCIENCE 31 2 818 - 827 2015年04月 [査読有り][通常論文]
  • Yasufumi Teramura, Akira Terao, Yuko Okada, Junichi Tomida, Yuko Okamatsu-Ogura, Kazuhiro Kimura
    JAPANESE JOURNAL OF VETERINARY RESEARCH 62 3 117 - 127 2014年08月 [査読有り][通常論文]
     
    The effects of three stressors of different categories, namely cold exposure, immobilization, and lipopolysaccharide (LPS) treatment, on sympathetic nerve activity were examined by assessing its biochemical index norepinephrine (NE) turnover in peripheral organs of C57BL/6 mice. NE turnover was assessed by measuring the decrease in the organ NE concentration 3 h after inhibition of catecholamine biosynthesis with alpha-methyl-p-tyrosine. NE turnover in brown adipose tissue (BAT) in the room temperature (23 degrees C) control group was as high as that in the cold exposure (4 degrees C) group. Similarly, the mRNA level of the thermogenic marker uncoupling protein 1 (UCP1) in the room temperature control group was as high as that in the cold exposure group. As sympathetic stimulation upregulates the UCP1 mRNA level, we thought that sympathetic nerve tonus in BAT was already accelerated at room temperature. To exclude factors affecting basal sympathetic nerve activity, mice housed at thermoneutral temperature (30 degrees C) were used as controls for the subsequent experiments. In this condition, cold exposure accelerated NE turnover in the BAT, as well as heart and pancreas. The corticosterone level showed a higher trend in the cold exposure group in comparison to the control group. Immobilization accelerated NE turnover in the spleen, pancreas, and white adipose tissue and elevated the corticosterone level. LPS (3 mg/kg, i.p.) did not affect NE turnover in all peripheral organs but elevated the corticosterone level. In summary, the sympathetic nervous and adrenocortical responses to three stressors differed greatly. In particular, sympathetic responses showed clear organ-specific acceleration patterns. This important feature may improve our understanding of the multiplicity of biological responses.
  • Masaaki K. Sato, Masaya Toda, Naoki Inomata, Hisataka Maruyama, Yuko Okamatsu-Ogura, Fumihito Arai, Takahito Ono, Akihiko Ishijima, Yuichi Inoue
    Biophysical Journal 106 11 2458 - 2464 2014年06月03日 [査読有り][通常論文]
     
    Mammalian cells must produce heat to maintain body temperature and support other biological activities. Methods to measure a cell's thermogenic ability by inserting a thermometer into the cell or measuring the rate of oxygen consumption in a closed vessel can disturb its natural state. Here, we developed a noninvasive system for measuring a cell's heat production with a bimaterial microcantilever. This method is suitable for investigating the heat-generating properties of cells in their native state, because changes in cell temperature can be measured from the bending of the microcantilever, without damaging the cell and restricting its supply of dissolved oxygen. Thus, we were able to measure increases in cell temperature of <1 K in a small number of murine brown adipocytes (n = 4-7 cells) stimulated with norepinephrine, and observed a slow increase in temperature over several hours. This long-term heat production suggests that, in addition to converting fatty acids into heat energy, brown adipocytes may also adjust protein expression to raise their own temperature, to generate more heat. We expect this bimaterial microcantilever system to prove useful for determining a cell's state by measuring thermal characteristics. © 2014 Biophysical Society.
  • Hiyoshi, H, Terao, A, Okamatsu-Ogura, Y, Kimura, K
    Experimental Animals 62 205 - 213 2014年 [査読有り][通常論文]
  • Ting Wang, Tatsuya Kusudo, Tamaki Takeuchi, Yukari Yamashita, Yasuhide Kontani, Yuko Okamatsu, Masayuki Saito, Nozomu Mori, Hitoshi Yamashita
    PLOS ONE 8 12 2013年12月 [査読有り][通常論文]
     
    Evodiamine, an alkaloid extracted from the dried unripe fruit of the tree Evodia rutaecarpa Bentham (Rutaceae), reduces obesity and insulin resistance in obese/diabetic mice; however, the mechanism underlying the effect of evodiamine on insulin resistance is unknown. This study investigated the effect of evodiamine on signal transduction relating to insulin resistance using obese/diabetic KK-Ay mice and an in vitro adipocyte culture. There is a significant decrease in the mammalian target of rapamycin (mTOR) and ribosomal S6 protein kinase (S6K) signaling in white adipose tissue (WAT) in KK-Ay mice treated with evodiamine, in which glucose tolerance is improved. In addition, reduction of insulin receptor substrate 1 (IRS1) serine phosphorylation, an indicator of insulin resistance, was detected in their WAT, suggesting suppression of the negative feedback loop from S6K to IRS1. As well as the stimulation of IRS1 and Akt serine phosphorylation, insulin-stimulated phosphorylation of mTOR and S6K is time-dependent in 3T3-L1 adipocytes, whereas evodiamine does not affect their phosphorylation except for an inhibitory effect on mTOR phosphorylation. Moreover, evodiamine inhibits the insulin-stimulated phosphorylation of mTOR and S6K, leading to down-regulation of IRS1 serine phosphorylation in the adipocytes. Evodiamine also stimulates phosphorylation of AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, which may cause down-regulation of mTOR signaling in adipocytes. A similar effect on AMPK, mTOR and IRS1 phosphorylation was found in adipocytes treated with rosiglitazone. These results suggest evodiamine improves glucose tolerance and prevents the progress of insulin resistance associated with obese/diabetic states, at least in part, through inhibition of mTOR-S6K signaling and IRS1 serine phosphorylation in adipocytes.
  • Yuko Okamatsu-Ogura, Keigo Fukano, Ayumi Tsubota, Akihiro Uozumi, Akira Terao, Kazuhiro Kimura, Masayuki Saito
    PLOS ONE 8 12 e84229  2013年12月 [査読有り][通常論文]
     
    Chronic adrenergic activation leads to the emergence of beige adipocytes in some depots of white adipose tissue in mice. Despite their morphological similarities to brown adipocytes and their expression of uncoupling protein 1 (UCP1), a thermogenic protein exclusively expressed in brown adipocytes, the beige adipocytes have a gene expression pattern distinct from that of brown adipocytes. However, it is unclear whether the thermogenic function of beige adipocytes is different from that of classical brown adipocytes existing in brown adipose tissue. To examine the thermogenic ability of UCP1 expressed in beige and brown adipocytes, the adipocytes were isolated from the fat depots of C57BL/6J mice housed at 24 degrees C (control group) or 10 degrees C (cold-acclimated group) for 3 weeks. Morphological and gene expression analyses revealed that the adipocytes isolated from brown adipose tissue of both the control and cold-acclimated groups consisted mainly of brown adipocytes. These brown adipocytes contained large amounts of UCP1 and increased their oxygen consumption when stimulated with norepinephirine. Adipocytes isolated from the perigonadal white adipose tissues of both groups and the inguinal white adipose tissue of the control group were white adipocytes that showed no increase in oxygen consumption after norepinephrine stimulation. Adipocytes isolated from the inguinal white adipose tissue of the cold-acclimated group were a mixture of white and beige adipocytes, which expressed UCP1 and increased their oxygen consumption in response to norepinephrine. The UCP1 content and thermogenic ability of beige adipocytes estimated on the basis of their abundance in the cell mixture were similar to those of brown adipocytes. These results revealed that the inducible beige adipocytes have potent thermogenic ability comparable to classical brown adipocytes.
  • Tanno S, Terao A, Okamatsu-Ogura Y, Kimura K
    Obes Res Clin Pract 7 e251 - e257 2013年07月 [査読有り][通常論文]
  • Toda C, Shiuchi T, Kageyama H, Okamoto S, Coutinho EA, Sato T, Okamatsu-Ogura Y, Yokota S, Takagi K, Tang L, Saito K, Shioda S, Minokoshi Y
    Diabetes 62 7 2295 - 2307 2013年07月 [査読有り][通常論文]
  • Tsutomu Sasaki, Mayumi Shimpuku, Tomoya Kitazumi, Haruna Hiraga, Yuko Nakagawa, Hiroshi Shibata, Yuko Okamatsu-Ogura, Osamu Kikuchi, Hye-Jin Kim, Yuki Fujita, Jun Maruyama, Vina Yanti Susanti, Hiromi Yokota-Hashimoto, Masaki Kobayashi, Masayuki Saito, Tadahiro Kitamura
    Endocrine Journal 60 10 1117 - 1129 2013年 [査読有り][通常論文]
     
    Miglitol is an alpha-glucosidase inhibitor that improves post-prandial hyperglycemia, and it is the only drug in its class that enters the bloodstream. Anecdotally, miglitol lowers patient body weight more effectively than other alphaglucosidase inhibitors, but the precise mechanism has not been addressed. Therefore, we analyzed the anti-obesity effects of miglitol in mice and in the HB2 brown adipocyte cell line. Miglitol prevented diet-induced obesity by stimulating energy expenditure without affecting food intake in mice. Long-term miglitol treatment dose-dependently prevented dietinduced obesity and induced mitochondrial gene expression in brown adipose tissue. The anti-obesity effect was independent of preventing carbohydrate digestion in the gastrointestinal tract. Miglitol effectively stimulated energy expenditure in mice fed a high-fat high-monocarbohydrate diet, and intraperitoneal injection of miglitol was sufficient to stimulate energy expenditure in mice. Acarbose, which is a non-absorbable alpha glucosidase inhibitor, also prevented diet-induced obesity, but through a different mechanism: it did not stimulate energy expenditure, but caused indigestion, leading to less energy absorption. Miglitol promoted adrenergic signaling in brown adipocytes in vitro. These data indicate that circulating miglitol stimulates brown adipose tissue and increases energy expenditure, thereby preventing diet-induced obesity. Further optimizing miglitol's effect on brown adipose tissue could lead to a novel anti-obesity drug. © The Japan Endocrine Society.
  • Ishii T, Fukano K, Shimada K, Kamikawa A, Okamatsu-Ogura Y, Terao A, Yoshida T, Saito M, Kimura K
    Journal of biochemistry 152 1 53 - 62 1 2012年07月 [査読有り][通常論文]
  • Kohei Shimada, Yuta Ohno, Yuko Okamatsu-Ogura, Masahiro Suzuki, Akihiro Kamikawa, Akira Terao, Kazuhiro Kimura
    PEPTIDES 34 2 336 - 342 2012年04月 [査読有り][通常論文]
     
    The thermogenic function of brown adipose tissue (BAT) is increased by norepinephrine (NE) released from sympathetic nerve endings, but the roles of NPY released along with NE are poorly elucidated. Here, we examined effect of NPY on basal and NE-enhanced thermogenesis in isolated brown adipocytes that express Y1 and Y5 receptor mRNA. Treatment of cells with NPY did not influence the basal and NE-enhanced rates of oxygen consumption and cAMP accumulation. Treatment with NPY also failed to induce ERK (Thr202/Tyr204) phosphorylation in the brown adipocytes. In contrast, treatment with NPY increased ERK phosphorylation in cultured stromal vascular cells from the BAT that express Y1 receptor mRNA. In the latter treatment with NPY also increased STAT3 (Ser727) phosphorylation. These results suggest that NPY mainly acts on stromal vascular cells in BAT and plays roles in the regulation of their gene transcription through ERK and STAT3 pathways, while NPY does not affect the thermogenic function of brown adipocytes. (C) 2012 Elsevier Inc. All rights reserved.
  • Yuko Okamatsu-Ogura, Junko Nio-Kobayashi, Toshihiko Iwanaga, Akira Terao, Kazuhiro Kimura, Masayuki Saito
    EXPERIMENTAL BIOLOGY AND MEDICINE 236 11 1274 - 1281 2011年11月 [査読有り][通常論文]
     
    Leptin reduces body fat by decreasing food intake and increasing energy expenditure. Uncoupling protein (UCP) 1, a key molecule for brown adipose tissue (BAT) thermogenesis, was reported to contribute to the stimulatory effect of leptin on energy expenditure. To clarify whether UCP1 is also involved in the anorexigenic effect of leptin, in this study we examined the effect of leptin on food intake using wild-type (WT) and UCP1-deficient (UCP1-KO) mice. Repeated injection of leptin decreased food intake more markedly in WT mice than in UCP1-KO mice, while a single injection of leptin showed similar effects in the two groups of mice. As chronic leptin stimulation induces UCP1 expression in BAT and ectopically in white adipose tissue (WAT), we mimicked the UCP1 induction by repeated injection of CL316,243 (CL), a highly specific beta 3-adrenoceptor agonist, and measured food intake in response to a single injection of leptin. Two-week treatment with CL enhanced the anorexigenic effect of leptin in WT mice, but not in UCP1-KO mice. Three-day treatment with CL in WT mice also enhanced the anorexigenic effect of leptin and leptin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) in the arcuate nucleus of the hypothalamus, without any notable change in adiposity. These results indicate that UCP1 enhances leptin action at the hypothalamus level, suggesting UCP1 contributes to the control of energy balance not only through the regulation of energy expenditure but also through appetite control by modulating leptin action.
  • Shimba S, Ogawa T, Hitosugi S, Ichihashi Y, Nakadaira Y, Kobayashi M, Tezuka M, Kosuge Y, Ishige K, Ito Y, Komiyama K, Okamatsu-Ogura Y, Kimura K, Saito M
    PloS one 6 9 e25231  9 2011年09月22日 [査読有り][通常論文]
  • Takeshi Yoneshiro, Sayuri Aita, Mami Matsushita, Yuko Okamatsu-Ogura, Toshimitsu Kameya, Yuko Kawai, Masao Miyagawa, Masayuki Tsujisaki, Masayuki Saito
    OBESITY 19 9 1755 - 1760 2011年09月 [査読有り][通常論文]
     
    Brown adipose tissue (BAT) can be identified by (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with X-ray computed tomography (CT) in adult humans. The objective of this study was to clarify the relationship between BAT and adiposity in healthy adult humans, particularly to test the idea that decreased BAT activity may be associated with body fat accumulation with age. One hundred and sixty-two healthy volunteers aged 20-73 years (103 males and 59 females) underwent FDG-PET/CT after 2-h cold exposure at 19 degrees C with light clothing. Cold-activated BAT was detected in 41% of the subjects (BAT-positive). Compared with the BAT-negative group, the BAT-positive group was younger (P < 0.01) and showed a lower BMI (P < 0.01), body fat content (P < 0.01), and abdominal fat (P < 0.01). The incidence of cold-activated BAT decreased with age (P < 0.01), being more than 50% in the twenties, but less than 10% in the fifties and sixties. The adiposity-related parameters showed some sex differences, but increased with age in the BAT-negative group (P < 0.01), while they remained unchanged from the twenties to forties in the BAT-positive group, in both sexes. These results suggest that decreased BAT activity may be associated with accumulation of body fat with age.
  • Abd Eldaim MA, Okamatsu-Ogura Y, Terao A, Kimura K
    The Japanese journal of veterinary research 58 3-4 149 - 154 3-4 2010年11月 [査読有り][通常論文]
  • Takashi Sawada, Hideaki Miyoshi, Kohei Shimada, Akira Suzuki, Yuko Okamatsu-Ogura, James W. Perfield, Takuma Kondo, So Nagai, Chikara Shimizu, Narihito Yoshioka, Andrew S. Greenberg, Kazuhiro Kimura, Takao Koike
    PLOS ONE 5 11 e14006  2010年11月 [査読有り][通常論文]
     
    Background: Perilipin A (PeriA) exclusively locates on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Previously, we reported that adipocyte specific overexpression of PeriA caused resistance to diet-induced obesity and resulted in improved insulin sensitivity. In order to better understand the biological basis for this observed phenotype, we performed additional studies in this transgenic mouse model. Methodology and Principal Findings: When compared to control animals, whole body energy expenditure was increased in the transgenic mice. Subsequently, we performed DNA microarray analysis and real-time PCR on white adipose tissue. Consistent with the metabolic chamber data, we observed increased expression of genes associated with fatty acid beta-oxidation and heat production, and a decrease in the genes associated with lipid synthesis. Gene expression of Pgc1a, a regulator of fatty acid oxidation and Ucp1, a brown adipocyte specific protein, was increased in the white adipose tissue of the transgenic mice. This observation was subsequently verified by both Western blotting and histological examination. Expression of RIP140, a regulator of white adipocyte differentiation, and the lipid droplet protein FSP27 was decreased in the transgenic mice. Importantly, FSP27 has been shown to control gene expression of these crucial metabolic regulators. Overexpression of PeriA in 3T3-L1 adipocytes also reduced FSP27 expression and diminished lipid droplet size. Conclusions: These findings demonstrate that overexpression of PeriA in white adipocytes reduces lipid droplet size by decreasing FSP27 expression and thereby inducing a brown adipose tissue-like phenotype. Our data suggest that modulation of lipid droplet proteins in white adipocytes is a potential therapeutic strategy for the treatment of obesity and its related disorders.
  • Abd Eldaim MA, Kamikawa A, Soliman MM, Ahmed MM, Okamatsu-Ogura Y, Terao A, Miyamoto T, Kimura K
    The Journal of dairy research 77 1 27 - 32 1 2010年02月 [査読有り][通常論文]
  • Masayuki Saito, Yuko Okamatsu-Ogura, Mami Matsushita, Kumiko Watanabe, Takeshi Yoneshiro, Junko Nio-Kobayashi, Toshihiko Iwanaga, Masao Miyagawa, Toshimitsu Kameya, Kunihiro Nakada, Yuko Kawai, Masayuki Tsujisaki
    DIABETES 58 7 1526 - 1531 2009年07月 [査読有り][通常論文]
     
    OBJECTIVE-The significant roles of brown adipose tissue (BAT) in the regulation of energy expenditure and adiposity are established in small rodents but have been controversial in humans. The objective is to examine the prevalence of metabolically active BAT in healthy adult humans and to clarify the effects of cold exposure and adiposity. RESEARCH DESIGN AND METHODS-In vivo 2-[(18)F]fluoro-2-deoxyglucose (FDG) uptake into adipose tissue was measured in 56 healthy volunteers (31 male and 25 female subjects) aged 23-65 years by positron emission tomography (PET) combined with X-ray computed tomography (CT). RESULTS-When exposed to cold (19 C) for 2 h, 17 of 32 younger subjects (aged 23-35 years) and 2 of 24 elderly subjects (aged 38-65 years) showed a substantial FDG uptake into adipose tissue of the supraclavicular and paraspinal regions, whereas they showed no detectable uptake when kept warm (27 C). Histological examinations confirmed the presence of brown adipocytes in these regions. The cold-activated FDG uptake was increased in winter compared with summer (P < 0.001) and was inversely related to BMI (P < 0.001) and total (P < 0.01) and visceral (P < 0.001) fat areas estimated from CT image at the umbilical level. CONCLUSIONS-Our findings, being against the conventional view, indicate the high incidence of metabolically active BAT in adult humans and suggest a role in the control of body temperature and adiposity. Diabetes 58:1526-1531, 2009
  • Akihiro Kamikawa, Osamu Ichii, Daisuke Yamaji, Takeshi Imao, Chihairu Suzuki, Yuko Okamatsu-Ogura, Akira Terao, Yasuhiro Kon, Kazuhiro Kimura
    DEVELOPMENTAL DYNAMICS 238 5 1092 - 1099 2009年05月 [査読有り][通常論文]
     
    Mammary glands develop postnatally in response to the hypothalamic-pituitary-gonadal axis. Obesity-induced changes in the local environment, however, retard mammary gland development during late pregnancy and lactation. To clarify the effects of obesity on fundamental duct development, we compared the mammary glands of nulliparous nonpregnant obese mice fed a high-fat diet with those of lean mice fed a normal diet. Obese mice had enlarged mammary glands, reflecting fat pad size, whereas the ducts in obese mice showed a less dense distribution with less frequent branching. Additionally, the ducts were surrounded by thick collagen layers, and were incompletely lined with myoepithelium. Because leptin receptors were localized in the epithelium region and leptin that was highly expressed in the obese glands suppressed mammary epithelial cell proliferation in vitro, the present results suggest that obesity disrupts mammary ductal development, possibly by remodeling the mammary microenvironment and promoting the expression of such paracrine factors as leptin. Developmental Dynamics 238:1092-1099, 2009. (C) 2009 Wiley-Liss, Inc.
  • Ahmed M, Kimura K, Soliman M, Yamaji D, Okamatsu-Ogura Y, Ishioka K, Makondo K, Hagiwara K, Saito M
    Veterinary journal (London, England : 1997) 176 3 361 - 8 2008年06月 [査読有り][通常論文]
     
    This study examined the mitogenic response of bovine peripheral T lymphocytes to leptin, a pleiotropic hormone regulating food intake and energy expenditure. Leptin alone slightly suppressed proliferation of T lymphocytes in the presence of concanavalin A (ConA). Leptin also inhibited proliferation of T lymphocytes induced by anti-CD3 antibody. ConA treatment activated some protein kinases, including p44/p42(MAPK) and Akt/PKB, while anti-CD3 antibody treatment increased mRNA expression of suppressor of cytokine signalling (SOCS) 3, interferon (IFN)gamma, interleukin (IL) 2 and IL4 in T lymphocytes. Leptin alone increased only SOCS3 mRNA expression. Simultaneous treatment with mitogens and leptin enhanced IFNgamma mRNA expression but decreased IL2 mRNA expression, without any synergistic effect on phosphorylation of protein kinases or mRNA expression of SOCS3 and IL4. These results suggest that leptin modulates bovine T lymphocyte functions.
  • Yuko Okamatsu-Ogura, Akihiro Uozumi, Chitoku Toda, Kazuhiro Kimura, Hitoshi Yamashita, Masayuki Saito
    OBESITY RESEARCH & CLINICAL PRACTICE 1 4 233 - 241 2007年12月 [査読有り][通常論文]
     
    Leptin is proposed to reduce body fat by increasing energy expenditure, in addition to decreasing food intake, through the activation of brown adipose tissue (BAT) thermogenesis. To confirm this, we investigated the effects of leptin on whole body energy expenditure, BAT functions and adiposity in wild-type (WT) mice, and compared with those in mice deficient in uncoupling protein 1 (UCP1), a key molecule for BAT thermogenesis. Chronic hyperleptinemia induced by adenovirus gene transfer reduced food intake in both WT and UCP1-KO mice. WT mice with hyperleptinemia, compared to pair-fed controls, showed increased oxygen consumption, elevated UCP1 expression in BAT, ectopic UCP1 induction in white adipose tissue (WAT), and reduced body fat content. These effects of chronic hyperleptinemia were not observed in UCP1-KO mice. It was concluded that the fat-reducing effect of leptin is due to not only decreased food intake, but also increased UCP1-dependent energy expenditure. (c) 2007 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
  • Mohamed Soliman, Kazuhiro Kimura, Mohamed Ahmed, Daisuke Yamaji, Yukiko Matsushita, Yuko Okamatsu-Ogura, Kennedy Makondo, Masayuki Saito
    DOMESTIC ANIMAL ENDOCRINOLOGY 33 4 400 - 409 2007年11月 [査読有り][通常論文]
     
    Leptin is an adipose tissue-derived cytokine plays key roles in the regulation of food intake and energy expenditure. However, regulatory mechanisms of leptin gene expression are not fully elucidated in ruminants that utilize short-chain fatty acids (SCFA), known as volatile fatty acids, as principal energy sources. In this study, we determined effects of SCFA and long-chain fatty acids (LCFA) on leptin expression in bovine adipocytes. Bovine stromal vascular cells isolated from subcutaneous adipose tissue of Holstein cows were cultured to confluence and treated sequentially with dexamethasone and isobutylmethylxanthine for 2 days and insulin and troglitazone for 12 days to achieve full differentiation to adipocytes. The cells started to accumulate lipids 4 days after the onset of treatment, with increased mRNA expression of leptin, as well as aP2, adiponectin, and PPAR-gamma. Removal of fetal calf serum and reduction of glucose in the culture medium of differentiated adipocytes decreased leptin mRNA expression. Subsequent addition of acetate, butyrate, or propionate dose-dependently restored and rather increased leptin expression, while addition of LCFA suppressed it. The stimulatory effect of acetate was abolished by prior treatment of the cells with pertussis toxin and by addition of LCFA. Furthermore, cows fasted for 48 h and fed thereafter, elaborate reduced and increased plasma leptin levels, respectively. Thus. these results suggest that plasma leptin levels in cows are inversely controlled at the transcription level by VFA and LCFA, and that the effects of SCFA possibly act through a G protein-coupled receptor for SCFA. (c) 2006 Elsevier Inc. All rights reserved.
  • Naoya Kitao, Takahiro Yahata, Takaaki Matsumoto, Yuko Okamatsu-Ogura, Asako Omachi, Kazuhiro Kimura, Masayuki Saito
    The Journal of veterinary medical science 69 10 1065 - 8 2007年10月 [査読有り][通常論文]
     
    Uncoupling protein 1 (UCP1) is present exclusively in brown adipose tissue, and contributes to body temperature control during cold exposure. We cloned UCP1 cDNA of plateau pika (Ochotona dauurica), a small, non-hibernating, diurnal lagomorph that inhabits in relatively cold climates and at high altitudes in Mongolia and in northern China. The nucleotide sequence of pika UCP1 was highly homologous to UCP1 of other species, and the deduced amino acid sequence had some common domains for UCP, including six mitochondrial carrier protein motifs and a putative purine-nucleotide binding site. RT-PCR and Western blot analyses revealed that both UCP1 mRNA and protein were expressed exclusively in the interscapular adipose tissue. These results suggest that pika UCP1 contributes to heat production in brown adipose tissue, as do those in other species.
  • Yuko Okamatsu-Ogura, Naoya Kitao, Kazuhiro Kimura, Masayuki Saito
    INTERNATIONAL JOURNAL OF OBESITY 31 S58 - S58 2007年05月 [査読有り][通常論文]
  • Ahmed M, Shaban Z, Yamaji D, Okamatsu-Ogura Y, Soliman M, Abd Eldaim M, Ishioka K, Makondo K, Saito M, Kimura K
    The Journal of veterinary medical science / the Japanese Society of Veterinary Science 69 5 509 - 514 5 2007年05月 [査読有り][通常論文]
  • Okamatsu-Ogura Y, Kitao N, Kimura K, Saito M
    Am J Physiol Endocrinol Metab 292 4 E1135 - E1139 2007年04月 [査読有り][通常論文]
     
    Brown fat UCP1 is not involved in the febrile and thermogenic responses to IL-1 beta in mice. Am J Physiol Endocrinol Metab 292: E1135-E1139, 2007. First published December 12, 2006; doi:10.1152/ajpendo.00425.2006. - The activity of brown adipose tissue (BAT), a site of nonshivering metabolic thermogenesis, has been reported to increase after interleukin (IL)-1 beta/lipopolysaccharide injection. To clarify the possible contribution of BAT thermogenesis to whole body febrile response, we investigated febrile and thermogenic response to IL-1 beta using mice deficient in uncoupling protein-1 (UCP1), a key molecule for BAT thermogenesis. In wild-type (WT) mice, IL-1 beta injection (5 mu g/kg ip) increased body temperature (+1.82 degrees C at 20 min), decreased physical activity (-37% at 1 h), and produced a slight and insignificant rise (+15% at 1 h) in oxygen consumption (V-O2). V-O2 dependent on metabolic thermogenesis (Delta V-O2 thermogenesis) calculated by correcting the effect of physical activity was increased after IL-1 beta injection (726 +/- 200 ml center dot h(-1)center dot kg(-1) at 1 h). Almost the same responses were observed in UCP1-deficient mice, showing 638 +/- 87 ml center dot h(-1)center dot kg(-1) of Delta V-O2 (thermogenesis) at 1 h. In contrast, CL316,243, a selective activator of BAT thermogenesis, increased body temperature, decreased physical activity, and produced a significant rise in V-O2 in WT mice, showing 1,229 +/- 35 ml center dot h(-1)center dot kg(-1) of Delta V-O2 thermogenesis at 1 h. These changes were not observed in UCP1-deficient mice. These results, conflicting with a previously proposed idea of a role of BAT in fever, suggest a minor contribution of BAT thermogenesis to IL-1 beta-induced fever. In support of this, we found no effect of IL-1 beta on triglyceride content and UCP1 mRNA level in BAT, in contrast with apparent effects of CL316,243.
  • Ahmed M, Kimura K, Soliman M, Yamaji D, Okamatsu-Ogura Y, Makondo K, Inanami O, Saito M
    The Journal of veterinary medical science 69 2 125 - 131 2007年02月 [査読有り][通常論文]
  • Okamatsu-Ogura Y, Uozumi A, Kitao N, Kimura K, Saito M
    Obes Res Clin Prac 1 1 61 - 67 2007年01月 [査読有り][通常論文]
     
    beta 3-adrenergic receptor (beta 3-AR) agonist, a drug that reduces body fat, stimulates lipomobilization from white adipose tissue (WAT) and thermogenesis in brown adipose tissue (BAT). To test the day-night difference in the effects of beta 3-AR agonist, in the present study, we examined the responses of lipomobitization and energy expenditure to CL316,243 (CL) during the daytime at 10:00 and nighttime at 22:00 in mice kept in a 12 h light-dark cycle with lights on from 07:00. CL injection increased plasma free fatty acid to the same extent at 10:00 and 22:00. In contrast, CL injection increased total oxygen consumption more markedly at 10:00 than 22:00. Physical activity was suppressed by CL injection especially at 22:00. Correcting total oxygen consumption by the suppressive effect on physical activity, oxygen consumption dependent on BAT thermogenesis was estimated. This revealed that the effect of CL on BAT thermogenesis was not different between 10:00 and 22:00. Thus, we concluded that there is no day-night difference in the CL effects on lipomobilization from WAT and thermogenesis in BAT. The stronger effect of CL on total energy expenditure in the daytime was largely due to a more suppressive effect on physical activity in the nighttime. (C) 2006 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
  • Inokuma K, Okamatsu-Ogura Y, Omachi A, Matsushita Y, Kimura K, Yamashita H, Saito M
    Am J Physiol Endocrinol Metab 290 5 E1014 - E1021 2006年05月 [査読有り][通常論文]
     
    Mitochondrial uncoupling protein-1 ( UCP1) has been thought to be a key molecule for thermogenesis during cold exposure and spontaneous hyperphagia and thereby in the autonomic regulation of energy expenditure and adiposity. However, UCP1 knockout ( KO) mice were reported to be cold intolerant but unexpectedly did not get obese even after hyperphagia, implying that UCP1 may not be involved in the regulation of adiposity. Treatment of obese animals with beta(3)-adrenergic agonists is known to increase lipid mobilization, induce UCP1, and, finally, reduce body fat content. To obtain direct evidence for the role of UCP1 in the anti-obesity effect of beta(3)-adrenergic stimulation, in the present study, UCP1-KO and wild-type ( WT) mice were fed on cafeteria diets for 8 wk and then given a beta(3)-adrenergic agonist, CL-316,243 ( CL), or saline for 2 wk. A single injection of CL increased whole body oxygen consumption and brown fat temperature in WT mice but not in KO mice, and it elicited almost the same plasma free fatty acid response in WT and KO mice. WT and KO mice increased similarly their body and white fat pad weights on cafeteria diets compared with those on laboratory chow. Daily treatment with CL resulted in a marked reduction of white fat pad weight and the size of adipocytes in WT mice, but not in KO mice. Compared with WT mice, KO mice expressed increased levels of UCP2 in brown fat but decreased levels in white fat and comparable levels of UCP3. It was concluded that the anti-obesity effect of beta(3)-adrenergic stimulation is largely attributable to UCP1, but less to UCP2 and UCP3, and thereby to UCP1-dependent degradation of fatty acids released from white adipose tissue.
  • K Inokuma, Y Ogura-Kamatsu, C Toda, K Kimura, H Yamashita, M Saito
    DIABETES 54 5 1385 - 1391 2005年05月 [査読有り][通常論文]
     
    Sympathetic stimulation activates glucose utilization in parallel with fatty acid oxidation and thermogenesis in brown adipose tissue (BAT) through the beta-adrenergic receptors. To clarify the roles of the principal thermogenic molecule mitochondrial uncoupling protein 1 (UCP1) in the sympathetically stimulated glucose utilization, we investigated the uptake of 2-deoxyglucose (2-DG) into BAT and some other tissues of UCP1-knockout (KO) mice in vivo. In wild-type (WT) mice, administration of norepinephrine (NE) accelerated the disappearance of plasma 2-DG and increased 2-DG uptake into BAT and heart without any rise of plasma insulin level. In UCP1-KO mice, the stimulatory effect of NE on 2-DG uptake into BAT, but not into heart, disappeared completely. Insulin administration increased 2-DG uptake into BAT and also heart similarly in WT and UCP1-KO mice. NE also increased the activity of AMP-activated protein kinase (AMP kinase) in BAT of WT but not UCP1-KO mice. Our results, together with reports that the activation of AMP kinase increases glucose transport in myocytes, suggest that the sympathetically stimulated glucose utilization in BAT is due to the serial activation of UCP1 and AMP kinase.

書籍

  • 獣医生化学
    (担当:分担執筆範囲:11章「代謝の臓器特異性とその相関」)
    朝倉書店 2014年
  • ここまでわかった燃える褐色脂肪の不思議
    岡松 優子 (担当:分担執筆範囲:いろいろな動物の褐色脂肪組織とその役割)
    有限会社ナップ 2013年
  • 体と温度の辞典
    岡松優子, 斉藤昌之 (担当:分担執筆範囲:熱産生機構2 褐色脂肪組織)
    朝倉書店 2010年
  • 肥満と脂肪エネルギー代謝
    岡松優子, 斉藤昌之 (担当:分担執筆範囲:褐色脂肪と肥満・メタボリックシンドローム:実験動物からヒトへ)
    建帛社 2008年
  • 糖尿病カレントライブラリー7 脂肪細胞と脂肪組織
    岡松優子, 斉藤昌之, 辻崎正幸 (担当:分担執筆範囲:白色脂肪と褐色脂肪の代謝特性)
    文光堂 2007年
  • 別冊医学の歩み『糖尿病・代謝症候群ムstate of arts 2004-2006』
    小倉優子, 猪熊健一 (担当:分担執筆範囲:エネルギー消費における脱共役蛋白質UCP1の役割)
    医歯薬出版 2004年

講演・口頭発表等

  • 冬眠動物ハムスターにおける褐色脂肪組織の形成プログラミング機構  [招待講演]
    岡松優子
    日本獣医学会学術集会(第162回大会)生理学・生化学分科会シンポジウム 2018年
  • 母マウスへの高脂肪食の給餌が乳仔期のベージュ脂肪細胞誘導に与える影響  [招待講演]
    岡松優子
    日本栄養・食糧学会北海道支部(第48回大会)・東北支部(第52回大会)合同支部大会公開シンポジウム 2016年
  • 褐色脂肪細胞の増殖と適応熱産生adaptive thermogenesisにおける役割  [招待講演]
    岡松優子
    第37回日本肥満学会 2016年
  • 肥満対策のターゲットとしての褐色脂肪組織:実験動物を用いた検討  [招待講演]
    岡松 優子
    第157回日本獣医学会 2014年09月 シンポジウム・ワークショップパネル(指名)
  • 食品成分カプシノイドの抗肥満作用  [招待講演]
    岡松 優子
    第34回日本肥満学会 2013年10月 シンポジウム・ワークショップパネル(指名)
  • 褐色脂肪細胞の増殖とその病態生理学的意義  [招待講演]
    岡松 優子
    第18回アディポサイエンス・シンポジウム 2013年08月 シンポジウム・ワークショップパネル(指名)
  • 褐色脂肪細胞の増殖と意義  [招待講演]
    岡松 優子
    第33回日本肥満学会 2012年10月 シンポジウム・ワークショップパネル(指名)
  • Roles of UCP1 in the regulation of energy metabolism  [招待講演]
    岡松 優子
    Brown Adipose Tissue 2011 Update 2011年03月 シンポジウム・ワークショップパネル(指名)
  • Protective roles of brown adipose tissue against age-related development of obesity  [招待講演]
    岡松 優子
    14th International Congress of Endocrinology Official Satellite Symposium 2010年03月 シンポジウム・ワークショップパネル(指名)

その他活動・業績

  • 食と栄養による脂肪組織の機能制御
    岡松優子 生化学 93 (1) 22 -34 2021年 [招待有り]
  • 褐色脂肪細胞によるエネルギー代謝調節
    岡松優子 FOOD STYLE 21 21 (8) 60 -63 2017年 [招待有り]
  • 膵臓の内分泌生理
    岡松優子 SURGEON 129 22 (3) 12 -19 2016年 [招待有り]
  • 犬と猫の肥満研究の最前線「摂食と栄養代謝」
    岡松優子 J-VET 29 (10) 8 -18 2016年 [招待有り]
  • 脂肪燃焼組織・褐色脂肪の食品成分による活性化と抗肥満効果
    岡松優子 New Food Industry 58 (10) 21 -25 2015年 [査読無し][招待有り]
  • 褐色脂肪細胞の増殖とその生理的意義
    岡松優子, 深野圭吾 医学のあゆみ 250 (9) 822 -826 2014年 [査読無し][招待有り]
  • 褐色/ベージュ脂肪細胞の発生機構と生理的役割
    岡松優子, 木村和弘 バイオインダストリー 30 (11) 4 -10 2013年 [査読無し][招待有り]
  • UCP1の機能と比較生物学
    岡松 優子 The Lipid 25 (1) 29 -35 2013年 [査読無し][招待有り]
  • 褐色脂肪細胞によるエネルギー代謝制御におけるPGC-1 の役割
    岡松優子, 木村和弘 内分泌・糖尿病科 29 (2) 109 -116 2009年 [査読無し][招待有り]
  • レプチンの体脂肪減少効果にUCP1は貢献しているのか?
    岡松優子, 斉藤昌之 肥満研究 12 73 -75 2006年 [査読無し][招待有り]
  • 褐色脂肪細胞の起源と分化制御
    岡松優子, 斉藤昌之 The Lipid 17 65 -71 2006年 [査読無し][招待有り]
  • 褐色脂肪の機能と分化機構
    岡松優子, 斉藤昌之 細胞 38 14 -18 2006年 [査読無し][招待有り]
  • 褐色脂肪によるエネルギー代謝の調節
    岡松優子, 斉藤昌之 Clinical Neuroscience 24 914 -916 2006年 [査読無し][招待有り]
  • 褐色脂肪と白色脂肪:エネルギー代謝における役割
    岡松優子, 大町麻子, 斉藤昌之 分子細胞治療 5 28 -34 2006年 [査読無し][招待有り]

受賞

  • 2021年03月 日本生理学会 入澤彩記念女性生理学者奨励賞
  • 2020年09月 日本獣医学会 日本獣医学会賞
  • 2019年11月 日本肥満学会 学術奨励賞
  • 2008年03月 北海道大学 大塚賞
  • 2005年10月 日本肥満学会 若手研究奨励賞
  • 2004年08月 アディポサイエンス研究会シンポジウム 若手優秀ポスター賞

共同研究・競争的資金等の研究課題

  • 体温制御システム構築の細胞分子基盤:ハムスターの恒温性獲得機構をモデルとして
    日本学術振興会:科学研究費助成事業(科学研究費補助金) 基盤(C)
    研究期間 : 2017年 -2019年 
    代表者 : 岡松 優子
  • 母乳の質がもたらす乳児期の脂肪組織リモデリングと成長後のメタボリックシンドロームの発症しやすさとの関わりの解明
    森永奉仕会:研究奨励
    研究期間 : 2019年 
    代表者 : 岡松 優子
  • 冬眠動物における体温制御システム構築の分子基盤:発熱細胞プロジェニターの同定と局所環境の役割
    内藤記念科学振興財団:内藤記念女性研究者研究助成
    研究期間 : 2015年 -2017年 
    代表者 : 岡松 優子
  • 乳幼児期のベージュ脂肪細胞の誘導と消失に母乳の摂取が与える影響の解明
    糧食研究会:一般公募研究
    研究期間 : 2017年 
    代表者 : 岡松 優子
  • 生体のエネルギー消費能力を増大させる褐色脂肪由来アディポカインの同定
    日本学術振興会:科学研究費助成事業(科学研究費補助金) 若手研究(B)
    研究期間 : 2014年 -2016年 
    代表者 : 岡松 優子
  • 冬眠動物の体温を制御する熱産生脂肪細胞の発生・誘導機構の解明
    秋山記念生命科学振興財団:奨励助成
    研究期間 : 2014年 
    代表者 : 岡松 優子
  • アザラシはどのように脂肪を蓄えるのか —皮下脂肪の重度蓄積と内臓脂肪の欠損の謎に迫る—
    栗林育英学術財団:研究助成
    研究期間 : 2012年 -2013年 
    代表者 : 岡松 優子
  • 乳腺組織形成における脂肪細胞分泌因子レプチンの役割
    森永奉仕会:研究奨励
    研究期間 : 2012年 
    代表者 : 岡松 優子
  • 食品成分を利用した肥満対策法の開発に向けた褐色脂肪増加機構の解析
    ノーステック財団:フードイノベーション創造支援事業 研究シーズ発掘補助金
    研究期間 : 2012年 
    代表者 : 岡松 優子
  • 白色脂肪の褐色化機構の解明:新規肥満治療法の開発に向けた基礎研究
    日本学術振興会:科学研究費助成事業(科学研究費補助金) 若手研究(B)
    研究期間 : 2009年 -2010年 
    代表者 : 岡松 優子
  • 褐色脂肪の増殖及び機能におけるp27Kip1の役割
    秋山記念生命科学振興財団:奨励助成
    研究期間 : 2009年 
    代表者 : 岡松 優子
  • エネルギー消費組織:褐色脂肪の増殖・機能分化機構の解明
    北海道大学:公募型プロジェクト研究等支援経費(若手研究者自立支援)
    研究期間 : 2009年 
    代表者 : 岡松 優子
  • 白色脂肪の褐色化 -太りにくい体質の獲得に向けて-
    日本学術振興会:科学研究費助成事業(科学研究費補助金) (特別研究員奨励費)
    研究期間 : 2007年 -2008年 
    代表者 : 岡松 優子
  • レプチンの作用におけるUCP1の役割
    伊藤医薬学術交流財団:海外研究交流助成
    研究期間 : 2006年 
    代表者 : 岡松 優子

教育活動情報

主要な担当授業

  • 獣医科学基礎科目B 生命科学特論Ⅰ:実験の原理
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • 先端生命科学特論Ⅲ
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 代謝生化学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 生命科学特論
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 生化学実習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 生化学実習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 溶液とpH、蛋白質の定量、糖質の定量、脂質の定量、核酸の定量、酵素反応速度
  • アドバンスト演習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
  • 代謝生化学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 酵素学、糖質・脂質・アミノ酸代謝,臓器相関,比較生化学


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