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Diabetes 54:3154-3160, 2005
© 2005 by the American Diabetes Association, Inc.

The Stimulatory Effect of Globular Adiponectin on Insulin-Stimulated Glucose Uptake and Fatty Acid Oxidation Is Impaired in Skeletal Muscle From Obese Subjects

Clinton R. Bruce1, Valerie A. Mertz1, George J.F. Heigenhauser2, and David J. Dyck1

1 Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
2 Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Adiponectin is an adipose-derived hormone that plays an important role in regulating insulin sensitivity in rodents. However, little is known regarding the effect of adiponectin on metabolism in human skeletal muscle. Therefore, we examined whether the globular head of adiponectin, gAcrp30, acutely activates fatty acid oxidation and glucose uptake in isolated human skeletal muscle. Furthermore, we aimed to determine whether these effects would differ in muscle from lean versus obese individuals. Treatment with gAcrp30 (2.5 µg/ml) increased fatty acid oxidation in lean muscle (70%, P < 0.0001) and to a lesser extent in obese muscle (30%, P < 0.01). In the absence of insulin, gAcrp30 increased glucose uptake 37% in lean (P < 0.05) and 33% in obese muscle (P < 0.05). Combined exposure of insulin and gAcrp30 demonstrated an additive effect on glucose uptake in lean and obese individuals, but this effect was reduced by 50% in obese muscle (P < 0.05). These metabolic effects were attributable to an increase in AMP-activated protein kinase-{alpha}1 (AMPK{alpha}1) and AMPK{alpha}2 activity. However, in obese muscle the activation of AMPK{alpha}2 by gAcrp30 was blunted. This study provides evidence that gAcrp30 plays a role in regulating fatty acid and glucose metabolism in human skeletal muscle. However, the effects are blunted in obesity, indicating the possible development of adiponectin resistance.

Address correspondence and reprint requests to David J. Dyck, PhD, Department of Human Biology and Nutritional Sciences, 50 Stone Rd. East, University of Guelph, Guelph, ON, N1G 2W1 Canada. E-mail: ddyck{at}uoguelph.ca

Abbreviations: AICAR, 5-amino-imidazole carboxamide riboside; AMPK, AMP-activated protein kinase; DAG, diacylglycerol; HAD, hydroxy-acyl-CoA dehydrogenase; TAG, triacylglycerol


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