2018 Fiscal Year Final Research Report
Effect of adipose tissue localization and gene expression pattern on the development of obesity and diabetes
| Project/Area Number |
16K16614
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied health science
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| Research Institution | National Center for Global Health and Medicine |
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Principal Investigator |
Udagawa Haruhide 国立研究開発法人国立国際医療研究センター, 代謝疾患研究部, 上級研究員 (50533882)
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| Research Collaborator |
Yasuda Kazuki
Nammo Takao
Funahashi Nobuaki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 内臓脂肪 / 皮下脂肪 / 転写因子 / Gata5 / 高度肥満 |
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| Outline of Final Research Achievements |
In this study, we aimed to elucidate the pathogenic mechanism of obesity and type 2 diabetes by identifying functional and pathological roles of genes differentially expressed in visceral fat and subcutaneous fat of morbidly obese subjects. We focused on transcription factor Gata5 which is predominantly expressed in visceral fat from transcriptome analysis of visceral fat and subcutaneous fat of morbidly obese subjects. Expression of Gata5 mRNA in epididymal fat was significantly higher in SV fraction than in adipocyte fraction and significantly decreased in high fat mice. In overexpression of Gata5 gene in C3H10T1/2 cells (G5-C3H), the differentiation efficiency was significantly decreased. The expression of Cebpb, Cebpd, Pparg and Cebpa in Gata5-C3H cells were significantly decreased on the first day of differentiation. These results suggest that Gata5 is expressed predominantly in preadipocyte of visceral fat, and is a transcription factor regulating adipocyte differentiation.
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| Free Research Field |
糖尿病・代謝学
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| Academic Significance and Societal Importance of the Research Achievements |
内臓脂肪・皮下脂肪など各脂肪組織の違いにおける生物学的・機能的意義を解明することは、生命予後の不良な高度肥満の病態解明とともに、日本人肥満・糖尿病の本質的な治療法開発にも貢献できる。本研究では高脂肪食マウスの内臓脂肪と皮下脂肪組織を採取し、各部位の脂肪細胞の遺伝子発現量の差が肥満・糖尿病の病態に関わる意義について探索した。ヒトおよびマウス内臓脂肪で共通して皮下脂肪と発現が異なる遺伝子群（内臓脂肪遺伝子群）および内臓脂肪優位な遺伝子Gata5を同定した。今後候補遺伝子の脂肪細胞における機能や標的遺伝子を探索することで創薬や肥満病態の解明に繋がる可能性がある。
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