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* Division of Kinesiology, Department of Social and Preventive Medicine, Faculty of Medicine, Laval University, Ste-Foy, Quebec;
Department of Biochemistry, Faculty of Medical Sciences, University of Nijmegen, Nijmegen, The Netherlands;
Department of Exercise Sciences, University of Southern California, Los Angeles, California; and Division of Endocrinology and Metabolism, and
§ Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
2Correspondence: East-1140 Biomedical Science Tower, University of Pittsburgh, Pittsburgh, PA 15213, USA. E-mail: Kelley{at}msx.dept.-med.pitt.edu
A number of biochemical defects have been identified in glucose metabolism within skeletal muscle in obesity, and positive effects of weight loss on insulin resistance are also well established. Less is known about the capacity of skeletal muscle for the metabolism of fatty acids in obesity-related insulin resistance and of the effects of weight loss, though it is evident that muscle contains increased triglyceride. The current study was therefore undertaken to profile markers of human skeletal muscle for fatty acid metabolism in relation to obesity, in relation to the phenotype of insulin-resistant glucose metabolism, and to examine the effects of weight loss. Fifty-five men and women, lean and obese, with normal glucose tolerance underwent percutaneous biopsy of vastus lateralis skeletal muscle for determination of HADH, CPT, heparin-releasable (Hr) and tissue-extractable (Ext) LPL, CS, COX, PFK, and GAPDH enzyme activities, and content of cytosolic and plasma membrane FABP. Insulin sensitivity was measured using the euglycemic clamp method. DEXA was used to measure FM and FFM. In skeletal muscle of obese individuals, CPT, CS, and COX activities were lower while, conversely, they had a higher or similar content of FABPC and FABPPM than in lean individuals. Hr and Ext LPL activities were similar in both groups. In multivariate and simple regression analyses, there were significant correlations between insulin resistance and several markers of FA metabolism, notably, CPT and FABPPM. These data suggest that in obesity-related insulin resistance, the metabolic capacity of skeletal muscle appears to be organized toward fat esterification rather than oxidation and that dietary-induced weight loss does not correct this disposition.—Simoneau, J.-A., Veerkamp, J. H., Turcotte, L. P., Kelley, D. E. Markers of capacity to utilize fatty acids in human skeletal muscle: relation to insulin resistance and obesity and effects of weight loss.
Key Words: carnitine palmitoyl transferase • fatty acid binding proteins • lipoprotein lipase • maximal aerobic power • fatty acid oxidation
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J. He, S. Watkins, and D. E. Kelley Skeletal Muscle Lipid Content and Oxidative Enzyme Activity in Relation to Muscle Fiber Type in Type 2 Diabetes and Obesity Diabetes, April 1, 2001; 50(4): 817 - 823. [Abstract] [Full Text]
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P. Malenfant, A. Tremblay, E. Doucet, P. Imbeault, J.-A. Simoneau, and D. R. Joanisse Elevated intramyocellular lipid concentration in obese subjects is not reduced after diet and exercise training Am J Physiol Endocrinol Metab, April 1, 2001; 280(4): E632 - E639. [Abstract] [Full Text] [PDF]
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R. L. Dobbins, L. S. Szczepaniak, B. Bentley, V. Esser, J. Myhill, and J. D. McGarry Prolonged Inhibition of Muscle Carnitine Palmitoyltransferase-1 Promotes Intramyocellular Lipid Accumulation and Insulin Resistance in Rats Diabetes, January 1, 2001; 50(1): 123 - 130. [Abstract] [Full Text]
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P. Imbeault, A. Tremblay, J.-A. Simoneau, and D. R. Joanisse Weight loss-induced rise in plasma pollutant is associated with reduced skeletal muscle oxidative capacity Am J Physiol Endocrinol Metab, March 1, 2002; 282(3): E574 - E579. [Abstract] [Full Text] [PDF]
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