Lipid oxidation is reduced in obese human skeletal muscle

The purpose of this study was to discern cellular mechanisms that contribut e to the suppression of lipid oxidation in the skeletal muscle of obese ind ividuals. Muscle was obtained from obese [body mass index (BMI), 38.3 +/- 3 .1 kg/m(2)] and lean (BMI, 23.8 +/- 0.9 kg/m(2)) women, and fatty acid oxid ation was studied by measuring (CO2)-C-14 production from C-14-labeled fatt y acids. Palmitate oxidation, which is at least partially dependent on carn itine palmitoyltransferase-1 (CPT-1) activity, was depressed (P < 0.05) by <approximate to>50% with obesity (6.8 +/- 2.2 vs. 13.7 +/- 1.4 nmole CO2.g( -1).h(-1)). The CPT-1-independent event of palmitoyl carnitine oxidation wa s also depressed (P < 0.01) by <approximate to>45%. There were significant negative relationships (P < 0.05) for adiposity with palmitate (r = -0.76) and palmitoyl carnitine (r = 0.82) oxidation. Muscle CPT-1 and citrate synt hase activity, an index of mitochondrial content, were also significantly ( P < 0.05) reduced (approximate to 35%) with obesity. CPT-1 (r = -0.48) and citrate synthase (r = -0.65) activities were significantly (P < 0.05) relat ed to adiposity. These data suggest that lesions at CPT-1 and post-CPT-1 ev ents, such as mitochondrial content, contribute to the reduced reliance on fat oxidation evident in human skeletal muscle with obesity.