| Project/Area Number |
17K16141
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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 |
Metabolomics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Toda Gotaro 東京大学, 医学部附属病院, 特任臨床医 (30780332)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 食後糖代謝 / 免疫 / サイトカイン / 肝糖新生 / 食後糖代謝調節 / 腸内細菌叢 / 発現調節 / インスリン / LPS / 代謝 / 環境 |
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| Outline of Final Research Achievements |
Lipopolysaccharide (LPS), which has been reported to drive the pathogenesis of obesity, is also elevated in normal lean mice after feeding, raising the possibility of its role in maintaining postprandial glycemia. Among factors induced in macrophages by LPS, interleukin-10 (IL-10) was elevated in the portal vein after feeding. In vivo the IL-10 signal in liver was shown to suppress postprandial gluconeogenic gene expression. Interestingly, both insulin and LPS stimulation were required for the rapid induction of IL-10 in macrophages. Indeed, myeloid LPS and insulin/Akt/mTOR signaling were shown to be required for the induction of IL-10 in macrophages and the postprandial suppression of gluconeogenic genes in liver. In obese mice, replenishment of IL-10 by adenoviral gene transfer attenuated both postprandial glycemia and hyperinsulinemia. Our results suggested a therapeutic potential of postprandial Akt-mTOR mediated IL-10 production by macrophages in obesity.
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| Academic Significance and Societal Importance of the Research Achievements |
免疫細胞が肥満状態で炎症を引き起こすことにより肥満を増悪させることは数多く報告されてきたが、本研究では正常な状態で免疫が食後の代謝を調節するプロセスを明らかにした。肥満の形成ではこの正常な機能が破綻することにより組織マクロファージでのIL-10欠乏が生じると考えられる。今後の検討によりその過程の詳細が明らかになれば、肥満・インスリン抵抗性に対する新たな治療ターゲットとなることが期待される。
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