TitleAltered Interleukin-10 Signaling in Skeletal Muscle Regulates Obesity-Mediated Inflammation and Insulin Resistance.
Publication TypeJournal Article
Year of Publication2016
AuthorsDagdeviren, S, Jung, DYoung, Lee, E, Friedline, RH, Noh, HLim, Kim, JHun, Patel, PR, Tsitsilianos, N, Tsitsilianos, AV, Tran, DA, Tsougranis, GH, Kearns, CC, Uong, CP, Kwon, JYeon, Muller, W, Lee, KWon, Kim, JK
JournalMol Cell Biol
Volume36
Issue23
Pagination2956-2966
Date Published2016 Dec 01
ISSN1098-5549
KeywordsAnimals, Cells, Cultured, Diabetes Mellitus, Type 2, Diet, High-Fat, Disease Models, Animal, Gene Knockout Techniques, Glucose, Insulin Resistance, Interleukin-10, Leptin, Mice, Muscle, Skeletal, Obesity, Receptors, Interleukin-10, Signal Transduction
Abstract

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 (M). After 16 weeks of a high-fat diet (HFD), M 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-IL10) did not affect spontaneous obesity, but MCK-IL10 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.

DOI10.1128/MCB.00181-16
Alternate JournalMol. Cell. Biol.
PubMed ID27644327
PubMed Central IDPMC5108883
Grant ListR01 DK080756 / DK / NIDDK NIH HHS / United States
R24 DK090963 / DK / NIDDK NIH HHS / United States
U24 DK093000 / DK / NIDDK NIH HHS / United States
U2C DK093000 / DK / NIDDK NIH HHS / United States