Fiber type dependent upregulation of human skeletal muscle UCP2 and UCP3 mRNA expression by high-fat diet

OBJECTIVE: To test the hypothesis that consumption of a high-fat diet leads to an increase in UCP mRNA expression in human skeletal muscle. In a group of endurance athletes, with a range in fiber type distribution, we hypothe sized that the effect of the high-fat diet on UCP2 and UCP3 mRNA expression is more pronounced in muscle fibers which are known to have a high capacit y to shift from carbohydrate to fat oxidation (type IIA fibers). DESIGN: Ten healthy trained athletes (five males, five females) consumed a low-fat diet (17 +/- 0.9 en% of fat) and high-fat diet (41.4 +/- 1.4 en% fa t) for 4 weeks, separated by a 4 week wash-out period. Muscle biopsies were collected at the end of both dietary periods. MEASUREMENTS: Using RT-PCR, levels of UCP2 and UCP3 mRNA expression were me asured and the percentage of type I, IIA and IIB fibers were determined usi ng the myofibrillar ATPase method in all subjects. RESULTS: UCP3L mRNA expression tended to be higher on the high-fat diet, an effect which reached significance when only males were considered (P=0.037 ). Furthermore, diet-induced change in mRNA expression of UCP3T (r: 0.66, P =0.037), UCP3L (r: 0.61, P=0.06) and UCP2 (r: 0.70, P=0.025), but not UCP3S , correlated significantly with percentage dietary fat on the high-fat diet . Plasma FFA levels were not different during the two diets. Finally, the p ercentage of type IIA fibers was positively correlated with the diet-induce d change in mRNA expression for UCP2 (r: 0.7, P=0.03), UCP3L (r: 0.73, P=0. 016) and UCP3T (r: 0.68, P=0.03) but not with UCP3S (r: 0.06, NS) CONCLUSION: UCP2 and UCP3 mRNAs are upregulated by a high-fat diet. This up regulation is more pronounced in humans with high proportions of type IIA f ibers, suggesting a role for UCPs in lipid utilization.