Adiponectin Corrects High-Fat Diet–Induced Disturbances in Muscle Metabolomic Profile and Whole-Body Glucose Homeostasis

  1. Gary Sweeney1
  1. 1Department of Biology, York University, Toronto, Ontario, Canada
  2. 2Department of Life Science, Gachon University, Sungnam, Republic of Korea
  3. 3School of Biomedical Sciences, University of Newcastle, Newcastle, U.K.
  4. 4Université Laval, Québec City, Canada
  5. 5Department of Pharmacology, University of Hong Kong, Hong Kong, China
  1. Corresponding author: Gary Sweeney, gsweeney{at}yorku.ca

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 Rd 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.

Footnotes

  • Received May 27, 2012.
  • Accepted September 7, 2012.

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  1. Diabetes vol. 62 no. 3 743-752
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