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Publication
Altered Interleukin-10 Signaling in Skeletal Muscle Regulates Obesity-Mediated
Inflammation and Insulin Resistance.
Authors Dagdeviren S, Jung DY, 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
Submitted By Submitted Externally on 4/12/2017
Status Published
Journal Molecular and cellular biology
Year 2016
Date Published 12/1/2016
Volume : Pages 36 : 2956 - 2966
PubMed Reference 27644327
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(IL10)). After 16 weeks of a high-fat diet (HFD), M(IL10) 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(ob/ob)) did not affect spontaneous obesity, but MCK-IL10(ob/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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