| First Author | Takei A | Year | 2020 |
| Journal | Diabetes | Volume | 69 |
| Issue | 2 | Pages | 158-164 |
| PubMed ID | 31690648 | Mgi Jnum | J:283541 |
| Mgi Id | MGI:6385790 | Doi | 10.2337/db19-0076 |
| Citation | Takei A, et al. (2020) Myeloid HMG-CoA Reductase Determines Adipose Tissue Inflammation, Insulin Resistance, and Hepatic Steatosis in Diet-Induced Obese Mice. Diabetes 69(2):158-164 |
| abstractText | Adipose tissue macrophages (ATMs) are involved in the development of insulin resistance in obesity. We have recently shown that myeloid cell-specific reduction of HMG-CoA reductase (Hmgcr (m-/m-) ), which is the rate-limiting enzyme in cholesterol biosynthesis, protects against atherosclerosis by inhibiting macrophage migration in mice. We hypothesized that ATMs are harder to accumulate in Hmgcr (m-/m-) mice than in control Hmgcr (fl/fl) mice in the setting of obesity. To test this hypothesis, we fed Hmgcr (m-/m-) and Hmgcr (fl/fl) mice a high-fat diet (HFD) for 24 weeks and compared plasma glucose metabolism as well as insulin signaling and histology between the two groups. Myeloid cell-specific reduction of Hmgcr improved glucose tolerance and insulin sensitivity without altering body weight in the HFD-induced obese mice. The improvement was due to a decrease in the number of ATMs. The ATMs were reduced by decreased recruitment of macrophages as a result of their impaired chemotactic activity. These changes were associated with decreased expression of proinflammatory cytokines in adipose tissues. Myeloid cell-specific reduction of Hmgcr also attenuated hepatic steatosis. In conclusion, reducing myeloid HMGCR may be a promising strategy to improve insulin resistance and hepatic steatosis in obesity. |
