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.
Highlights
Regular exercise training is generally recognized as a powerful preventive and therapeutic strategy for diseases such as type 2 diabetes, obesity and cardiovascular disease
The results reveal 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 (FFA)
Plasma glucose and triglyceride (TG) levels were not altered by one-legged cycling, while plasma FFA and lactate increased at T3, but mostly returned to baseline at T3
Summary
Regular exercise training is generally recognized as a powerful preventive and therapeutic strategy for diseases such as type 2 diabetes, obesity and cardiovascular disease. Upon initiation of exercise, local demand for ATP, oxygen, glucose and fatty acids increases dramatically These demands are accommodated by rapid changes in skeletal muscle activity of key enzymes and transporters involved in glucose and fatty acid oxidation via allosteric regulation and phosphorylation of rate-limiting enzymes. Exercise may elicit changes in gene expression in non-exercising muscle via circulating mediators and metabolites. Such a mechanism may provide a conceptual framework for the impact of exercise on non-contractile tissues such as liver. The results reveal 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 (FFA)
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