title: Adiponectin corrects high-fat diet-induced disturbances in muscle metabolomic profile and whole-body glucose homeostasis.
abstract: We provide here a detailed and comprehensive analysis of skeletal muscle metabolomic profiles in response to adiponectin in adiponectin knockout (AdKO) mice after high-fat-diet (HFD) feeding. Hyperinsulinemic-euglycemic clamp studies showed that adiponectin administration corrected HFD-induced defects in post/basal insulin stimulated R(d) and insulin signaling in skeletal muscle. Lipidomic profiling of skeletal muscle from HFD-fed mice indicated elevated triacylglycerol and diacylglycerol species (16:0-18:1, 18:1, and 18:0-18:2) as well as acetyl coA, all of which were mitigated by adiponectin. HFD induced elevated levels of various ceramides, but these were not significantly altered by adiponectin. Adiponectin corrected the altered branched-chain amino acid metabolism caused by HFD and corrected increases across a range of glycerolipids, fatty acids, and various lysolipids. Adiponectin also reversed induction of the pentose phosphate pathway by HFD. Analysis of muscle mitochondrial structure indicated that adiponectin treatment corrected HFD-induced pathological changes. In summary, we show an unbiased comprehensive metabolomic profile of skeletal muscle from AdKO mice subjected to HFD with or without adiponectin and relate these to changes in whole-body glucose handling, insulin signaling, and mitochondrial structure and function. Our data revealed a key signature of relatively normalized muscle metabolism across multiple metabolic pathways with adiponectin supplementation under the HFD condition.
authors.affiliation: Department of Biology, York University, Toronto, Ontario, Canada.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Subat
authors.initials: S
authors.lastname: Turdi
authors.forename: Taesik
authors.initials: T
authors.lastname: Park
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Morris
authors.forename: Yves
authors.initials: Y
authors.lastname: Deshaies
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Gary
authors.initials: G
authors.lastname: Sweeney
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects*; D004734:Energy Metabolism; D006949:Hyperlipidemias / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D007328:Insulin; D011994:Recombinant Proteins