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© 2001 by the American Diabetes Association, Inc.
Reviews/Commentaries/Position Statements |
Skeletal Muscle Triglyceride
An aspect of regional adiposity and insulin resistance
1 Department of Medicine, University of Pittsburgh School of Medicine
2 Department of Veterans Affairs, Pittsburgh, Pennsylvania
ABSTRACT
Recent evidence derived from four independent methods indicates that an excess triglyceride storage within skeletal muscle is linked to insulin resistance. Potential mechanisms for this association include apparent defects in fatty acid metabolism that are centered at the mitochondria in obesity and in type 2 diabetes. Specifically, defects in the pathways for fatty acid oxidation during postabsorptive conditions are prominent, leading to diminished use of fatty acids and increased esterification and storage of lipid within skeletal muscle. These impairments in fatty acid metabolism during fasting conditions may be related to a metabolic inflexibility in insulin resistance that is not limited to defects in glucose metabolism during insulin-stimulated conditions. Thus, there is substantial evidence implicating perturbations in fatty acid metabolism during accumulation of skeletal muscle triglyceride and in the pathogenesis of insulin resistance. Weight loss by caloric restriction improves insulin sensitivity, but the effects on fatty acid metabolism are less conspicuous. Nevertheless, weight loss decreases the content of triglyceride within skeletal muscle, perhaps contributing to the improvement in insulin action with weight loss. Alterations in skeletal muscle substrate metabolism provide insight into the link between skeletal muscle triglyceride accumulation and insulin resistance, and they may lead to more appropriate therapies to improve glucose and fatty acid metabolism in obesity and in type 2 diabetes.
Abbreviations: CPT, carnitine palmitoyl transferase • CT, computed tomography • FABP, fatty acid–binding protein • FFA, free fatty acid • leg RQ, respiratory quotient across the leg • MRS, magnetic resonance spectroscopy • UCP2, uncoupling protein 2
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