1. Adiponectin corrects high-fat diet-induced disturbances in muscle metabolomic profile and whole-body glucose homeostasis.
- Author
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Liu Y, Turdi S, Park T, Morris NJ, Deshaies Y, Xu A, and Sweeney G
- Subjects
- Adiponectin genetics, Adipose Tissue, White metabolism, Adipose Tissue, White ultrastructure, Animals, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 etiology, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 pathology, Hyperlipidemias blood, Hyperlipidemias etiology, Hyperlipidemias metabolism, Hyperlipidemias pathology, Insulin Resistance, Male, Metabolic Syndrome blood, Metabolic Syndrome etiology, Metabolic Syndrome metabolism, Metabolic Syndrome pathology, Metabolomics methods, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Muscle ultrastructure, Muscle, Skeletal ultrastructure, Obesity blood, Obesity etiology, Obesity metabolism, Obesity pathology, Recombinant Proteins metabolism, Adiponectin metabolism, Diet, High-Fat adverse effects, Energy Metabolism, Insulin metabolism, Mitochondria, Muscle metabolism, Muscle, Skeletal metabolism, Signal Transduction
- 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.
- Published
- 2013
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