| Project/Area Number |
21390021
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
HIRASAWA Akira 京都大学, 大学院・薬学研究科, 准教授 (70242633)
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| Co-Investigator(Renkei-kenkyūsha) |
AWAJI Takeo 埼玉医科大学, 医学部, 講師 (60297546)
KOSHIMIZU Taka-aki 自治医科大学, 医学研究科, 准教授 (20392491)
LIU Ning 京都大学, 大学院・薬学研究科, 研究員 (70464196)
IIDA Keiko 京都大学, 大学院・薬学研究科, 教務補佐 (00422999)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2011: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2009: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
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| Keywords | 薬理学 / GPCR / GPR120 / フローサイトメーター / ゲノム創薬科学 |
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| Research Abstract |
Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. We showed that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. In human, we identified a deleterious non-synonymous mutation(p. R270H) that inhibits GPR120 signalling activity. Furthermore, the p. R270H variant increases the risk of obesity in European populations. We conclude that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.
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