Development of anti-diabetic therapy by the elucidation of the mechanism linking microflora and adipose tissue macrophages

Research Project

Project/Area Number	16K15488
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Metabolomics
Research Institution	The University of Tokyo
Principal Investigator	Ueki Kohjiro 東京大学, 医学部附属病院, 客員研究員 (00396714)
Project Period (FY)	2016-04-01 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000) Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords	Akt / マクロファージ / インスリン / LPS / 肥満 / 腸内細菌
Outline of Final Research Achievements	We have found that LPS derived from microflora and insulin induced by feeding stimulates the production of IL-10 in adipose tissue macrophages, and that this production depends on the Akt-mTORC1 pathway. Indeed, mice with disiruption of Akt1 and Akt2 specifically in macrophage (MAktDKO mice) show impaired production of IL-10. MAktDKO mice exhibit impaired glucose tolerance with increased hepatic gluconeogenesis. Adenovirus-mdeiated gene transfer of IL-10 improves glucose tolerance with decreased hepatic gluconeogenesis in MAktDKO mice. Furthermore, MAktDKO mice show more weight gain under the normal chow diet compared to the control mice.

Report

(2 results)