Skeletal Muscle O-GlcNAc Transferase Action on Global Metabolism Is Partially Mediated Through Interleukin-15

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dc.contributor.authorZumbaugh, Morgan D.en
dc.contributor.authorYen, Con-Ningen
dc.contributor.authorBodmer, Jocelyn S.en
dc.contributor.authorShi, Haoen
dc.contributor.authorGerrard, David E.en
dc.date.accessioned2022-04-08T13:06:45Zen
dc.date.available2022-04-08T13:06:45Zen
dc.date.issued2021-07-13en
dc.description.abstractBesides its roles in locomotion and thermogenesis, skeletal muscle plays a significant role in global glucose metabolism and insulin sensitivity through complex nutrient sensing networks. Our previous work showed that the muscle-specific ablation of O-GlcNAc transferase (OGT) led to a lean phenotype through enhanced interleukin-15 (IL-15) expression. We also showed OGT epigenetically modified and repressed the Il15 promoter. However, whether there is a causal relationship between OGT ablation-induced IL-15 secretion and the lean phenotype remains unknown. To address this question, we generated muscle specific OGT and interleukin-15 receptor alpha subunit (IL-15r alpha) double knockout mice (mDKO). Deletion of IL-15r alpha in skeletal muscle impaired IL-15 secretion. When fed with a high-fat diet, mDKO mice were no longer protected against HFD-induced obesity compared to wild-type mice. After 22 weeks of HFD feeding, mDKO mice had an intermediate body weight and glucose sensitivity compared to wild-type and OGT knockout mice. Taken together, these data suggest that OGT action is partially mediated by muscle IL-15 production and provides some clarity into how disrupting the O-GlcNAc nutrient signaling pathway leads to a lean phenotype. Further, our work suggests that interfering with the OGT-IL15 nutrient sensing axis may provide a new avenue for combating obesity and metabolic disorders.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fphys.2021.682052en
dc.identifier.issn1664-042Xen
dc.identifier.other682052en
dc.identifier.pmid34326778en
dc.identifier.urihttp://hdl.handle.net/10919/109612en
dc.identifier.volume12en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectO-GlcNAc signalingen
dc.subjectinterleukin-15en
dc.subjecttissue cross-talken
dc.subjectinsulin sensitivityen
dc.subjectmyokinesen
dc.titleSkeletal Muscle O-GlcNAc Transferase Action on Global Metabolism Is Partially Mediated Through Interleukin-15en
dc.title.serialFrontiers in Physiologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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