A major role of insulin in promoting obesity- associated adipose tissue inflammation

摘要: Objective: Adipose tissue (AT) inflammation is associated with systemic insulin resistance and hyperinsulinemia in obese rodents humans. A longstanding concept that may promote through downregulation of its receptor on target tissues. Here we tested the novel hypothesis also impairs sensitivity by specifically enhancing adipose inflammation. Methods: Circulating levels were reduced about 50% diet-induced genetically mice treatments diazoxide or streptozotocin, respectively. We then examined AT crown-like structures, macrophage markers pro-inflammatory cytokine expression AT. lipogenesis was monitored. Conversely, infused into lean to determine affects above parameters. Results: Lowering circulating streptozotocin treatment decreased content AT, stimulated Akt phosphorylation de novo (DNL). Moreover, responsiveness blood glucose injected improved without changes body weight. Remarkably, even mice, infusion under constant euglycemic conditions cytokines Consistent these findings, 3T3-L1 adipocytes caused a 10-fold increase CCL2 mRNA within 6 h, which blocked ERK inhibitor PD98059. Conclusion: Taken together, results indicate obesity-associated unexpectedly drives turn contributes factors suppress insulin-stimulated adipocyte DNL sensitivity.