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dc.contributor.authorDagdeviren, Sezin
dc.contributor.authorJung, Dae Young
dc.contributor.authorLee, Eunjung
dc.contributor.authorFriedline, Randall H.
dc.contributor.authorNoh, Hye Lim
dc.contributor.authorKim, Jong Hun.
dc.contributor.authorPatel, Payal R.
dc.contributor.authorTsitsilianos, Nicholas
dc.contributor.authorTsitsilianos, Andrew V.
dc.contributor.authorTran, Duy A.
dc.contributor.authorTsougranis, George H.
dc.contributor.authorKearns, Caitlyn C.
dc.contributor.authorUong, Cecilia P.
dc.contributor.authorKwon, Jung Yeon.
dc.contributor.authorMuller, Werner
dc.contributor.authorLee, Ki Won.
dc.contributor.authorKim, Jason K.
dc.date2022-08-11T08:08:19.000
dc.date.accessioned2022-08-23T15:51:03Z
dc.date.available2022-08-23T15:51:03Z
dc.date.issued2016-11-14
dc.date.submitted2016-12-06
dc.identifier.citationMol Cell Biol. 2016 Nov 14;36(23):2956-2966. Print 2016 Dec 1. <a href="http://dx.doi.org/10.1128/MCB.00181-16">Link to article on publisher's site</a>
dc.identifier.issn0270-7306 (Linking)
dc.identifier.doi10.1128/MCB.00181-16
dc.identifier.pmid27644327
dc.identifier.urihttp://hdl.handle.net/20.500.14038/28804
dc.description.abstractSkeletal 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27644327&dopt=Abstract">Link to Article in PubMed</a>
dc.rightsCopyright © 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.
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectEndocrinology, Diabetes, and Metabolism
dc.subjectMolecular Biology
dc.titleAltered Interleukin-10 Signaling in Skeletal Muscle Regulates Obesity-Mediated Inflammation and Insulin Resistance
dc.typeJournal Article
dc.source.journaltitleMolecular and cellular biology
dc.source.volume36
dc.source.issue23
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2045&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1042
dc.identifier.contextkey9445251
refterms.dateFOA2022-08-23T15:51:03Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathfaculty_pubs/1042
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages2956-2966


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