Myeliod specific inhibition of cholesterol synthesis ameliorates insulin sensitivity and hepatic steatosis.

2017 Fiscal Year Final Research Report

• Project/Area Number: 26870533
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology; Metabolomics
• Research Institution: Jichi Medical University
• Principal Investigator: NAGASHIMA SHUICHI 自治医科大学, 医学部, 講師 (30406136)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: HMG-CoA還元酵素 / インスリン抵抗性 / 糖尿病 / マクロファージ / スタチン

Outline of Final Research Achievements

HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in cholesterol biosynthesis. HMGCR inhibitors (statins) have been reported to exert cholesterol-lowering independent regression of atherosclerotic plaque by decreasing macrophage accumulation and the inflammatory process in the lesion. We hypothesized that genetically myeloid-specific inhibition of HMGCR would decrease adipose tissue inflammation. As expected, diet-induced obese mice with myeloid-specific HMGCR KO had lesser macrophage accumulation and expression of inflammatory cytokines in the adipose tissue compared with control mice. In insulin tolerance test, obese KO mice demonstrated improved systemic insulin sensitivity with enhanced insulin signaling in the adipose tissue. Moreover, in obese KO mice hepatic steatosis was improved without the change of hepatic inflammatory characteristics. Our data indicate the pivotal role of HMGCR in innate immune cells in regulating systemic insulin sensitivity and hepatic steatosis.

Free Research Field

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