Authors: Hayley M O’Neill James S Lally Sandra Galic Melissa Thomas Paymon D Azizi Morgan D Fullerton Brennan K Smith Thomas Pulinilkunnil Zhiping Chen M Constantine Samaan Sebastian B Jorgensen Jason R B Dyck Graham P Holloway Thomas J Hawke Bryce J van Denderen Bruce E Kemp Gregory R Steinberg
Publish Date: 2014/06/10
Volume: 57, Issue: 8, Pages: 1693-1702
Abstract
Obesity is characterised by lipid accumulation in skeletal muscle which increases the risk of developing insulin resistance and type 2 diabetes AMPactivated protein kinase AMPK is a sensor of cellular energy status and is activated in skeletal muscle by exercise hormones leptin adiponectin IL6 and pharmacological agents 5amino4imidazolecarboxamide ribonucleoside AICAR and metformin Phosphorylation of acetylCoA carboxylase 2 ACC2 at S221 S212 in mice by AMPK reduces ACC activity and malonylCoA content but the importance of the AMPK–ACC2–malonylCoA pathway in controlling fatty acid metabolism and insulin sensitivity is not understood therefore we characterised Acc2 S212A knockin ACC2 KI miceACC2 KI mice were resistant to increases in skeletal muscle fatty acid oxidation elicited by AICAR These mice had normal adiposity and liver lipids but elevated contents of triacylglycerol and ceramide in skeletal muscle which were associated with hyperinsulinaemia glucose intolerance and skeletal muscle insulin resistance
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