The present study investigated whether exercise induces the expression of PGC-1α splice variants in human skeletal muscle and the possible influence of metabolic perturbation on this response. The subjects exercised one leg for 45 min with restricted blood flow (R-leg), followed by 45 min of exercise using the other leg at the same absolute workload but with normal blood flow (NR-leg). This ischemic model (R-leg) has been shown previously to induce a greater metabolic perturbation and enhance the expression of PGC-1α beyond that observed in the NR-leg. Cultured human myotubes were used to test suggested exercise-induced regulatory stimuli of PGC-1α. We showed, for the first time, that transcripts from both the canonical promoter (PGC-1α-a) and the proposed upstream-located promoter (PGC-1α-b) are present in human skeletal muscle. Both transcripts were upregulated after exercise in the R-leg, but the fold change increase of PGC-1α-b was much greater than that of PGC-1α-a. No differences were observed between the two conditions regarding the marker for calcineurin activation, MCIP1, or p38 phosphorylation. AMPK phosphorylation increased to a greater extent in the R-leg, and AICAR stimulation of cultured human myotubes induced the expression of PGC-1α-a and PGC-1α-b. AICAR combined with norepinephrine yielded an additive effect on the PGC-1α-b expression only. Our results indicate clearly that exercise can activate an upstream promoter in humans and support AMPK as a major regulator of transcripts from the canonical PGC-1α promoter and the involvement of β-adrenergic stimulation in combination with AMPK in the regulation of PGC-1α-b.

In response to exercise, muscles adapt with a multitude of gene expression changes and protein modifications. One of the most profound changes is an increased mitochondrial biogenesis. The co‐repressor RIP140 interacts with several nuclear receptors and is recruited by transcription factors and co‐activators such as PGC‐1α and NRF‐1. Therefore, RIP140 may take part in the regulation of mitochondrial biogenesis.PurposeTo investigate 1. if an acute bout of exercise reduces the inhibitory action of RIP140 through translocation from the nucleus to the cytoplasm and 2. the temporal resolution of RIP140 mRNA expression before and up to 24h after exercise.MethodsHealthy men (n=4) and women (n=3) performed 1h of cycling exercise at 70 % of VO2max. Skeletal muscle biopsies were obtained before and after exercise (pre, 30′, 2h, 6h and 24h).ResultsRIP140 protein abundance increased in the cytoplasmic fraction 24h after exercise (n=3). RIP140 mRNA expression (n=7) was significantly increased 6h after exercise and returned to baseline values at 24h.ConclusionAn acute bout of exercise appears to translocate RIP140 protein from the nucleus to the cytoplasm. This would decrease the inhibitory action of RIP140 on nuclear genes encoding mitochondrial proteins and might therefore be part of the adaptive mitochondrial response seen with training.

No abstract

No abstract