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

Lookup NU author(s): Dr Nick Morris

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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. Diabetes 62:743-752, 2013


Publication metadata

Author(s): Liu Y, Turdi S, Park T, Morris NJ, Deshaies Y, Xu AM, Sweeney G

Publication type: Article

Publication status: Published

Journal: Diabetes

Year: 2013

Volume: 62

Issue: 3

Pages: 743-752

Print publication date: 01/03/2013

ISSN (print): 0012-1797

ISSN (electronic): 1939-327X

Publisher: American Diabetes Association

URL: http://dx.doi.org/10.2337/db12-0687

DOI: 10.2337/db12-0687


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Funding

Funder referenceFunder name
Canadian Institutes of Health Research
HKU4/CRF/10Collaborative Research Fund of Hong Kong Research Grant Council

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