Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise

Exercise training elicits a number of adaptive changes in skeletal muscle t hat result in an improved metabolic efficiency. The molecular mechanisms me diating the cellular adaptations to exercise training in human skeletal mus cle are unknown. To test the hypothesis that recovery from exercise is asso ciated with transcriptional activation of specific genes, six untrained mal e subjects completed 60-90 min of exhaustive one-legged knee extensor exerc ise for five consecutive days. On day 5, nuclei were isolated from biopsies of the vastus lateralis muscle of the untrained and the trained leg before exercise and from the trained leg immediately after exercise and after 15 min, 1 h, 2 h, and 4 h of recovery. Transcriptional activity of the uncoupl ing protein 3 (UCP3), pyruvate dehydrogenase kinase 4 (PDK4), and heme oxyg enase-1 (HO-1) genes (relative to beta-actin) increased by three- to sevenf old in response to exercise, peaking after 1-2 h of recovery. Increases in mRNA levels followed changes in transcription, peaking between 2 and 4 h af ter exercise. Lipoprotein lipase and carnitine pamitoyltransferase I gene t ranscription and mRNA levels showed similar but less dramatic induction pat terns, with increases ranging from two- to threefold. In a separate study, a single 4-h bout of cycling exercise (n = 4) elicited from 5 to >20-fold i ncreases in UCP3, PDK4, and HO-1 transcription, suggesting that activation of these genes may be related to the duration or intensity of exercise. The se data demonstrate that exercise induces transient increases in transcript ion of metabolic genes in human skeletal muscle. Moreover, the findings sug gest that the cumulative effects of transient increases in transcription du ring recovery from consecutive bouts of exercise may represent the underlyi ng kinetic basis for the cellular adaptations associated with exercise trai ning.