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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Copyright © 2016, American Society for Microbiology.Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.
DOI of Published Version
Mol Cell Biol. 2016 Nov 14;36(23):2956-2966. Print 2016 Dec 1. Link to article on publisher's site
Molecular and cellular biology
Dagdeviren S, Jung D, Lee E, Friedline RH, Noh HL, Kim JH, Patel PR, Tsitsilianos N, Tsitsilianos AV, Tran DA, Tsougranis GH, Kearns CC, Uong CP, Kwon JY, Muller W, Lee KW, Kim JK. (2016). Altered Interleukin-10 Signaling in Skeletal Muscle Regulates Obesity-Mediated Inflammation and Insulin Resistance. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1128/MCB.00181-16. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1042