INTERLEUKIN‐10 DEFICIENCY LIMITS THE DEVELOPMENT OF OBESITY AND INSULIN RESISTANCE PRODUCED BY A HIGH FAT DIET

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The goal of this study was to test the hypothesis that deficiency of immune‐regulating cytokine interleukin‐10 (IL‐10) promotes the development of obesity and insulin resistance. Male C57BL/6 (wild‐type, WT) and IL‐10 deficient (IL‐10−/−) mice were fed either 10% (control) or 60% kcal high fat diet (HFD) for 36 wks. A HFD produced obesity and increased adiposity in both WT and IL‐10−/− mice, however the increases were markedly less (P<0.05) in IL‐10−/−. In addition, the increase in adipocyte size with HFD was less in IL‐10−/− mice as compared to WT. A HFD was associated with the development of insulin resistance in WT mice but not IL‐10−/− mice (eg, glucose levels in WT HFD and IL‐10−/− HFD were 187±47 and 70±44 mg/dl at 120 min following a glucose challenge, respectively). Fasting plasma insulin levels were also higher in WT HFD compared to IL‐10−/− HFD mice (2.6±0.9 vs. 1.0±0.3 ng/ml, respectively). Expression of GLUT4, IRS‐1 and PPARγ in adipose was reduced to a similar extent in response to a HFD in both WT and IL‐10−/− mice. GLUT4 and IRS‐1 expression in skeletal muscle was unaffected by genotype and HFD. Contrary to our hypothesis, these data suggest that IL‐10 contributes to insulin resistance and adiposity produced by a HFD. NIH HL‐089884 & HL‐107632.