Lipid oxidation is reduced in obese human skeletal muscle.
The purpose of this study was to discern cellular mechanisms that contribute to the suppression of lipid oxidation in the skeletal muscle of obese individuals. 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 oxidation was studied by measuring (14)CO(2) production from (14)C-labeled fatty acids. Palmitate oxidation, which is at least partially dependent on carnitine palmitoyltransferase-1 (CPT-1) activity, was depressed (P < 0.05) by approximately 50% with obesity (6.8 +/- 2.2 vs. 13.7 +/- 1.4 nmole CO(2).g(-1).h(-1)). The CPT-1-independent event of palmitoyl carnitine oxidation was also depressed (P < 0.01) by approximately 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 synthase activity, an index of mitochondrial content, were also significantly (P < 0.05) reduced ( approximately 35%) with obesity. CPT-1 (r = -0.48) and citrate synthase (r = -0.65) activities were significantly (P < 0.05) related to adiposity. These data suggest that lesions at CPT-1 and post-CPT-1 events, such as mitochondrial content, contribute to the reduced reliance on fat oxidation evident in human skeletal muscle with obesity.
Kim
J Y
JY
Department of Biochemistry, East Carolina University, Greenville, North Carolina 27858, USA.
Hickner
R C
RC
Cortright
R L
RL
Dohm
G L
GL
Houmard
J A
JA
D000328:Adult; D015992:Body Mass Index; D002210:Caprylates / Q000378:metabolism; D002247:Carbon Isotopes; D002331:Carnitine / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism; D010732:Phosphofructokinase-1 / Q000378:metabolism
D002210:Caprylates; D002247:Carbon Isotopes; D005227:Fatty Acids; D019308:Palmitic Acid; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase; D010732:Phosphofructokinase-1; C031492:octanoic acid; D002331:Carnitine