title: Altered Interleukin-10 Signaling in Skeletal Muscle Regulates Obesity-Mediated Inflammation and Insulin Resistance.
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 (MIL10). After 16 weeks of a high-fat diet (HFD), MIL10mice 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/obmice 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.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Sezin
authors.initials: S
authors.lastname: Dagdeviren
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Jung
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|World Class University Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Randall H
authors.initials: RH
authors.lastname: Friedline
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Noh
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|Wellness Emergence Center, Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Jong Hun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Payal R
authors.initials: PR
authors.lastname: Patel
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Tsitsilianos
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Tsitsilianos
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Duy A
authors.initials: DA
authors.lastname: Tran
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: George H
authors.initials: GH
authors.lastname: Tsougranis
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Caitlyn C
authors.initials: CC
authors.lastname: Kearns
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Cecilia P
authors.initials: CP
authors.lastname: Uong
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|Wellness Emergence Center, Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Kwon
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
authors.forename: Werner
authors.initials: W
authors.lastname: Muller
authors.affiliation: World Class University Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.|Wellness Emergence Center, Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA jason.kim@umassmed.edu.|Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|World Class University Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance; D016753:Interleukin-10 / Q000235:genetics*; D020738:Leptin / Q000235:genetics*; D051379:Mice; D018482:Muscle, Skeletal / Q000276:immunology*; D009765:Obesity; D053701:Receptors, Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C556062:IL10 protein, mouse; D020738:Leptin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10; D005947:Glucose