Alternative splice variant PGC-1 alpha-b is strongly induced by exercise in human skeletal muscle

作者：Norrbom J^*; Sallstedt E K; Fischer H; Sundberg C J; Rundqvist H; Gustafsson T

来源：American Journal of Physiology - Endocrinology And Metabolism, 2011, 301(6): E1092-E1098.

DOI：10.1152/ajpendo.00119.2011

• peroxisome proliferator-activated receptor-gamma coactivator-1 alpha-b

Norrbom J, Sallstedt EK, Fischer H, Sundberg CJ, Rundqvist H, Gustafsson T. Alternative splice variant PGC-1 alpha-b is strongly induced by exercise in human skeletal muscle. Am J Physiol Endocrinol Metab 301: E1092-E1098, 2011. First published August 23, 2011; doi: 10.1152/ajpendo.00119.2011.-The present study investigated whether exercise induces the expression of PGC-1 alpha 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-1 alpha beyond that observed in the NR-leg. Cultured human myotubes were used to test suggested exercise-induced regulatory stimuli of PGC-1 alpha. We showed, for the first time, that transcripts from both the canonical promoter (PGC-1 alpha-a) and the proposed upstream-located promoter (PGC-1 alpha-b) are present in human skeletal muscle. Both transcripts were upregulated after exercise in the R-leg, but the fold change increase of PGC-1 alpha-b was much greater than that of PGC-1 alpha-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-1 alpha-a and PGC-1 alpha-b. AICAR combined with norepinephrine yielded an additive effect on the PGC-1 alpha-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-1 alpha promoter and the involvement of beta-adrenergic stimulation in combination with AMPK in the regulation of PGC-1 alpha-b.

• 出版日期2011-12