{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:03:49Z","timestamp":1790402629136,"version":"4.1.0"},"reference-count":25,"publisher":"American Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"vor","delay-in-days":76,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:p>Adipose tissue macrophages (ATMs) are involved in the development of insulin resistance in obesity. We have recently shown that myeloid cell\u2013specific reduction of HMG-CoA reductase (Hmgcrm\u2212\/m\u2212), 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 Hmgcrm\u2212\/m\u2212 mice than in control Hmgcrfl\/fl mice in the setting of obesity. To test this hypothesis, we fed Hmgcrm\u2212\/m\u2212 and Hmgcrfl\/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\u2013specific 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\u2013specific 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.<\/jats:p>","DOI":"10.2337\/db19-0076","type":"journal-article","created":{"date-parts":[[2019,11,5]],"date-time":"2019-11-05T21:45:24Z","timestamp":1572990324000},"page":"158-164","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":25,"title":["Myeloid HMG-CoA Reductase Determines Adipose Tissue Inflammation, Insulin Resistance, and Hepatic Steatosis in Diet-Induced Obese Mice"],"prefix":"10.2337","volume":"69","author":[{"given":"Akihito","family":"Takei","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and 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