Pronounced Effects of Acute Endurance Exercise on Gene Expression in Resting and Exercising Human Skeletal Muscle

Abstract

Regular physical activity positively influences whole body energy metabolism and substrate handling in exercising muscle. While it is recognized that the effects of exercise extend beyond exercising muscle, it is unclear to what extent exercise impacts non-exercising muscles. Here we investigated the effects of an acute endurance exercise bouts on gene expression in exercising and non-exercising human muscle. To that end, 12 male subjects aged 44–56 performed one hour of one-legged cycling at 50% Wmax. Muscle biopsies were taken from the exercising and non-exercising leg before and immediately after exercise and analyzed by microarray. One-legged cycling raised plasma lactate, free fatty acids, cortisol, noradrenalin, and adrenalin levels. Surprisingly, acute endurance exercise not only caused pronounced gene expression changes in exercising muscle but also in non-exercising muscle. In the exercising leg the three most highly induced genes were all part of the NR4A family. Remarkably, many genes induced in non-exercising muscle were PPAR targets or related to PPAR signalling, including PDK4, ANGPTL4 and SLC22A5. Pathway analysis confirmed this finding. In conclusion, our data indicate that acute endurance exercise elicits pronounced changes in gene expression in non-exercising muscle, which are likely mediated by changes in circulating factors such as free fatty acids. The study points to a major influence of exercise beyond the contracting muscle.

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Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

“…One-legged cycling allows the direct analysis of the effects of acute exercise in exercising muscle, with the nonexercising leg serving as control leg. Microarray analysis was performed on all four muscle biopsies of nine subjects (4). Microarrays from two subjects failed to meet quality control criteria and were excluded from analysis, and one subject refused to have biopsies taken.…”

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