Abbreviations used: ALA, alpha lipoic acid; ACC, acetyl-coenzyme A

Prevention of high-fat diet-induced muscular lipid accumulation in rats by alpha lipoic acid is not mediated by AMPK activation

Silvie Timmers1,2, Johan de Vogel-van den Bosch1,2, Mhairi C. Towler3, Gert Schaart4, Esther Moonen-Kornips2,4, Ronald P. Mensink1,2, Matthijs K. Hesselink4, D. Grahame Hardie3 and Patrick Schrauwen1,2

1

Top Institute Food and Nutrition (TIFN), 6700 AN, Wageningen, The

Netherlands

2

Department of Human Biology, School for Nutrition, Toxicology

Netherlands

3

Division of Molecular Physiology, College of Life Sciences,

University of Dundee, DD1 5EH, Dundee, Scotland

4

Department of Human

Movement Sciences, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, 6200 MD, Maastricht, The Netherlands Running head: alpha lipoic acid, muscle lipid accumulation Address correspondence to: Patrick Schrauwen Department of Human Biology Maastricht University P.O. Box 616 6200 MD Maastricht, The Netherlands Phone: +31 (0) 43 3881502 Fax: +31 (0) 43 3670976 E-mail: [email protected]

Abbreviations used: ALA, alpha lipoic acid; ACC, acetyl-coenzyme A carboxylase; AMPK, AMP-activated protein kinase; AUC, area under the concentration-time curve; HFD, high-fat diet; HFD+ALA, high-fat diet supplemented with 0.5% of alpha lipoic acid; LFD, low-fat diet; LFD+ALA, lowfat diet supplemented with 0.5% of alpha lipoic acid; IMCL, intramyocellular lipid(s); ipGTT, intraperitoneal glucose tolerance test.

1

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and Metabolism (NUTRIM), Maastricht University, 6200 MD, Maastricht, The

Abstract

Skeletal muscle triglyceride accumulation is associated with insulin resistance in obesity. Recently, it has been suggested that alpha lipoic acid (ALA) improves insulin sensitivity by lowering triglyceride accumulation in nonadipose tissues via activation of skeletal muscle AMP-activated protein kinase (AMPK). We examined whether chronic ALA supplementation prevents muscular lipid accumulation that is associated with high-fat diets via activation of AMPK. In addition, we tested if ALA supplementation was able to improve

Supplementing male Wistar rats with 0.5% ALA for eight weeks significantly reduced body weight, both on low- and high-fat diets (-24% LFD+ALA vs. LFD, p