An Acute Increase in Skeletal Muscle Carnitine Content Alters Fuel Metabolism in Resting Human Skeletal Muscle

Context: Carnitine plays an essential role in the integration of fat and carbohydrate oxidation in skeletal muscle, which is impaired in obesity and type 2 diabetes. Objective: The aim of the present study was to investigate the effect of an increase in skeletal muscle total carnitine (TC) content on muscle fuel metabolism. Design: A 5-h iv infusion of saline (control) or l-carnitine was administered while serum insulin was maintained at a physiologically high concentration during two randomized visits. Participants: Seven healthy, nonvegetarian young men (body mass index, 26.1 ± 1.6 kg/m2) participated in the present study at the University of Nottingham. Main Outcome Measures: Skeletal muscle pyruvate dehydrogenase complex (PDC) activity and associated muscle metabolites were measured. Results: The combination of hypercarnitinemia (600 μmol/liter) and hyperinsulinemia (160 mU/liter) increased muscle TC content by 15% (P < 0.01) and was associated with decreased pyruvate dehydrogenase complex activity (P < 0.05) and muscle lactate content (P < 0.05) by 30 and 40%, respectively, and an overnight increase in muscle glycogen (P < 0.01) and long-chain acyl-coenzyme A content (P < 0.05) by 30 and 40%, respectively, compared with control. Conclusions: These results suggest that an acute increase in human skeletal muscle TC content results in an inhibition of carbohydrate oxidation in conditions of high carbohydrate availability, possibly due to a carnitine-mediated increase in fat oxidation. These novel findings may have important implications for our understanding of the regulation of muscle fat oxidation, particularly during exercise, when carnitine availability may limit fat oxidation, and in obesity and type 2 diabetes where it is known to be impaired.