biostudies-literatureUnknown128(4)Shimobayashi MObesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages. Mechanistically, insulin resistance in adipocytes results in production of the chemokine monocyte chemoattractant protein 1 (MCP1), which recruits monocytes and activatThe Journal of clinical investigation1538-1550https://www.ebi.ac.uk/biostudies/studies/S-EPMC5873875biostudies-literatureInsulin resistance causes inflammation in adipose tissue.PMC5873875Swierczynska MMHall MNJeno PPeterli RClement NWoelnerhanssen BAlbert VWeissenberger DMoes SFrei ICColombi MMeyer-Gerspach ACMeier JAShimobayashi MBeglinger CfalseInsulin resistance causes inflammation in adipose tissue.Obesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages. Mechanistically, insulin resistance in adipocytes results in production of the chemokine monocyte chemoattractant protein 1 (MCP1), which recruits monocytes and activat2018-01-01T00:00:00Z2018 Apr2025-04-26T03:39:10.015Z2019-03-26T23:44:12ZS-EPMC58738752952833510.1172/jci9613910.1172/JCI96139