Program in Molecular Medicine; UMass Metabolic Network
Cell Biology | Cellular and Molecular Physiology | Endocrinology, Diabetes, and Metabolism | Molecular Biology
Skeletal muscle insulin resistance is a major characteristic of obesity and type 2 diabetes. Although obesity-mediated inflammation is causally associated with insulin resistance, the underlying mechanism is unclear. Here, we examined the effects of chronic obesity in mice with muscle-specific overexpression of interleukin-10 (MIL10). After 16 weeks of a high-fat diet (HFD), MIL10 mice became markedly obese but showed improved insulin action compared to that of wild-type mice, which was largely due to increased glucose metabolism and reduced inflammation in skeletal muscle. Since leptin regulates inflammation, the beneficial effects of interleukin-10 (IL-10) were further examined in leptin-deficient ob/ob mice. Muscle-specific overexpression of IL-10 in ob/ob mice (MCK-IL10ob/ob) did not affect spontaneous obesity, but MCK-IL10ob/ob mice showed increased glucose turnover compared to that in ob/ob mice. Last, mice with muscle-specific ablation of IL-10 receptor (M-IL10R-/-) were generated to determine whether IL-10 signaling in skeletal muscle is involved in IL-10 effects on glucose metabolism. After an HFD, M-IL10R-/- mice developed insulin resistance with reduced glucose metabolism compared to that in wild-type mice. Overall, these results demonstrate IL-10 effects to attenuate obesity-mediated inflammation and improve insulin sensitivity in skeletal muscle, and our findings implicate a potential therapeutic role of anti-inflammatory cytokines in treating insulin resistance and type 2 diabetes.
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Citation: Mol Cell Biol. 2016 Nov 14;36(23):2956-2966. Print 2016 Dec 1. Link to article on publisher's site. Copyright © 2016, American Society for Microbiology. All Rights Reserved. Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.
Dagdeviren, Sezin; Jung, Dae Young; Lee, Eunjung; Friedline, Randall H.; Noh, Hye Lim; Kim, Jong Hun.; Patel, Payal R.; Tsitsilianos, Nicholas; Tsitsilianos, Andrew V.; Tran, Duy A.; Tsougranis, George H.; Kearns, Caitlyn C.; Uong, Cecilia P.; Kwon, Jung Yeon.; Muller, Werner; Lee, Ki Won.; and Kim, Jason K., "Altered Interleukin-10 Signaling in Skeletal Muscle Regulates Obesity-Mediated Inflammation and Insulin Resistance" (2016). University of Massachusetts Medical School Faculty Publications. 1042.