Exercise attenuates the fasting-induced transcriptional activation of metabolic genes in skeletal muscle.

Fasting elicits a progressive increase in lipid metabolism within skeletal muscle. To determine the effects of fasting on the transcriptional regulation of genes important for metabolic control in skeletal muscle composed of different fiber types, nuclei from control and fasted (24 and 72 h) rats were subjected to nuclear run-on analysis using an RT-PCR-based technique. Fasting increased (P < 0.05) transcription rate of the muscle-specific uncoupling protein-3 gene (UCP3) 14.3- to 21.1-fold in white gastrocnemius (WG; fast-twitch glycolytic) and 5.5- to 7.5-fold in red gastrocnemius (RG; fast-twitch oxidative) and plantaris (PL; mixed) muscles. No change occurred in soleus (slow-twitch oxidative) muscle. Fasting also increased transcription rate of the lipoprotein lipase (LPL), muscle carnitine palmitoyltransferase I (CPT I), and long-chain acyl-CoA dehydrogenase (LCAD) genes 1.7- to 3.7-fold in WG, RG, and PL muscles. Transcription rate responses were similar after 24 and 72 h of fasting. Surprisingly, increasing metabolic demand during the initial 8 h of starvation (two 2-h bouts of treadmill running) attenuated the 24-h fasting-induced transcriptional activation of UCP3, LPL, CPT I, and LCAD in RG and PL muscles, suggesting the presence of opposing regulatory mechanisms. These data demonstrate that fasting elicits a fiber type-specific coordinate increase in the transcription rate of several genes involved in and/or required for lipid metabolism and indicate that exercise may attenuate the fasting-induced transcriptional activation of specific metabolic genes.