Regulation of skeletal muscle UCP-2 and UCP-3 gene expression by exercise and denervation

The factors that regulate gene expression of uncoupling proteins 2 and 3 (U CP-2 and UCP-3) in skeletal muscle are poorly understood, but both genes ar e clearly responsive to the metabolic state of the organism. Therefore, we tested the hypothesis that denervation and acute and/or chronic exercise (f actors that profoundly affect metabolism) would alter UCP-2 and UCP-3 gene expression. For the denervation studies, the sciatic nerve of rat and mouse hindlimb was sectioned in one leg while the contralateral limb served as c ontrol. Northern blot analysis revealed that denervation was associated wit h a 331% increase (P < 0.001) in UCP-3 mRNA and a 200% increase (P < 0.01) in UCP-2 mRNA levels in rat mixed gastrocnemius (MG) muscle. In contrast, d enervation caused a 53% decrease (P < 0.001) in UCP-3 and a 63% increase (P < 0.01) in UCP-2 mRNA levels in mouse MG. After acute exercise (2-h treadm ill running), rat UCP-3 mRNA levels were elevated (vs. sedentary control) 2 52% (P < 0.0001) in white gastrocnemius and 63% (P < 0.05) in red gastrocne mius muscles, whereas UCP-2 levels were unaffected. To a lesser extent, ele vations in UCP-3 mRNA (22%; P < 0.01) and UCP-2 mRNA (55%; P < 0.01) levels were observed after acute exercise in the mouse MG. There were no changes in either UCP-2 or UCP-3 mRNA levels after chronic exercise (9 wk of wheel running). These results indicate that acute exercise and denervation regula te gene expression of skeletal muscle UCPs.