Journal article
AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice
HM O'Neill, JS Lally, S Galic, M Thomas, PD Azizi, MD Fullerton, BK Smith, T Pulinilkunnil, Z Chen, MC Samaan, SB Jorgensen, JRB Dyck, GP Holloway, TJ Hawke, BJ Van Denderen, BE Kemp, GR Steinberg
Diabetologia | Published : 2014
Abstract
Aims/hypothesis: Obesity is characterised by lipid accumulation in skeletal muscle, which increases the risk of developing insulin resistance and type 2 diabetes. AMP-activated protein kinase (AMPK) is a sensor of cellular energy status and is activated in skeletal muscle by exercise, hormones (leptin, adiponectin, IL-6) and pharmacological agents (5-amino-4-imidazolecarboxamide ribonucleoside [AICAR] and metformin). Phosphorylation of acetyl-CoA carboxylase 2 (ACC2) at S221 (S212 in mice) by AMPK reduces ACC activity and malonyl-CoA content but the importance of the AMPK-ACC2-malonyl-CoA pathway in controlling fatty acid metabolism and insulin sensitivity is not understood; therefore, we ch..
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Funding Acknowledgements
These studies were supported by grants and fellowships from the Australian Research Council and CSIRO (BEK), National Health and Medical Research Council (BEK, GRS, BJvD), the Canadian Diabetes Association (JRBD, GRS) and the Canadian Institutes of Health Research (CIHR) (JRBD, GRS). Support in part was received from the Victorian Government's OIS Program (BEK) and Canadian Foundation for Innovation (GRS). MDF is a CIHR Banting Postdoctoral Fellow and GRS holds a Canada Research Chair in Metabolism and Obesity.