| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| 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.
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