• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2020 Fiscal Year Final Research Report

Molecular mechanism of M2 macrophage activation and insulin resistance associated with obesity

Research Project

  • PDF
Project/Area Number 18H02860
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Kubota Naoto  東京大学, 医学部附属病院, 准教授 (50396719)

Project Period (FY) 2018-04-01 – 2021-03-31
Keywords糖尿病 / 肥満
Outline of Final Research Achievements

We demonstrate that, the IL-4/Irs2/Akt pathway is selectively impaired, along with decreased macrophage Irs2 expression, although IL-4/STAT6 pathway is maintained. Indeed, myeloid cell-specific Irs2-deficient mice show impairment of IL-4-induced M2a-subtype macrophage activation, as a result of stabilization of the FoxO1/HDAC3/NCoR1 corepressor complex, resulting in insulin resistance under the HF diet condition. Moreover, the reduction of macrophage Irs2 expression is mediated by hyperinsulinemia via the insulin receptor (IR). In myeloid cell-specific IR-deficient mice, the IL-4/Irs2 pathway is preserved in the macrophages, which results in a reduced degree of insulin resistance, because of the lack of IR-mediated downregulation of Irs2. We conclude that downregulation of Irs2 in macrophages caused by hyperinsulinemia is responsible for systemic insulin resistance via impairment of M2a-subtype macrophage activation in obesity.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

生理的状態においては、M2a-subtypeマクロファージは脂肪細胞の恒常性維持に重要な役割を果たしていると考えられるが、高インスリン血症が持続すると、病的な脂肪細胞肥大化の亢進は脂肪細胞のインスリン感受性を落としM1マクロファージの浸潤や活性化を惹起し、M2a-subtypeマクロファージの活性化も低下するため、インスリン抵抗性を呈するようになると考えられる。高インスリン血症をきたさない治療が重要であることが示唆された。

URL: 

Published: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi