PGC-1 isoforms and their target genes are expressed differently in human skeletal muscle following resistance and endurance exercise

Abstract

The primary aim of the present study was to investigate the acute gene expression responses of PGC-1 isoforms and PGC-1α target genes related to mitochondrial biogenesis (cytochrome C), angiogenesis (VEGF-A), and muscle hypertrophy (myostatin), after a resistance or endurance exercise bout. In addition, the study aimed to elucidate whether the expression changes of studied transcripts were linked to phosphorylation of AMPK and MAPK p38. Nineteen physically active men were divided into resistance exercise (RE, n = 11) and endurance exercise (EE, n = 8) groups. RE group performed leg press exercise (10 × 10 RM, 50 min) and EE walked on a treadmill (∼80% HRmax, 50 min). Muscle biopsies were obtained from the vastus lateralis muscle before, 30 min, and 180 min after exercise. EE and RE significantly increased the gene expression of alternative promoter originated PGC-1α exon 1b- and 1bxs’-derived isoforms, whereas the proximal promoter originated exon 1a-derived transcripts were less inducible and were upregulated only after EE. Truncated PGC-1α transcripts were upregulated both after EE and RE. Neither RE nor EE affected the expression of PGC-1β. EE upregulated the expression of cytochrome C and VEGF-A, whereas RE upregulated VEGF-A and downregulated myostatin. Both EE and RE increased the levels of p-AMPK and p-MAPK p38, but these changes were not linked to the gene expression responses of PGC-1 isoforms. The present study comprehensively assayed PGC-1 transcripts in human skeletal muscle and showed exercise mode-specific responses thus improving the understanding of early signaling events in exercise-induced muscle adaptations.

Intake of branched-chain or essential amino acids attenuates the elevation in muscle levels of PGC-1α4 mRNA caused by resistance exercise

“…1). This is in agreement with some previous reports (27,29), but in contrast to another (33). Moreover, both isoforms were elevated 90 min after exercise, PGC-1␣1 by ϳ60% and PGC-1␣4 by three-to fivefold (P Ͻ 0.05 in both cases), but only the expression of PGC-1␣4 was further elevated (10-fold; P Ͻ 0.05) at 180 min of recovery.…”

“…Interestingly, Ruas and colleagues (28) found that a novel isoform of PGC-1␣ (PGC-1␣4), transcribed from the alternative promoter, is involved in regulating muscle hypertrophy in experimental animals, possibly through induction of the insulin-like growth factor I and downregulation of myostatin. However, follow-up studies have revealed that PGC-1␣4 is induced not only by resistance exercise, but also by endurance training (17,29,33), emphasizing the need for further investigations of the cellular mechanisms underlying the potential involvement of PGC-1␣4 in regulating skeletal muscle growth in humans.…”

Peroxisome Proliferator-activated Receptor γ Coactivator-1 α Isoforms Selectively Regulate Multiple Splicing Events on Target Genes

“…The importance of alternative promoter usage in the expression of PGC-1␣ isoforms has been clearly demonstrated (3,6,16). In addition, we have found that, in murine skeletal muscle, ␤ 2 -adrenergic stimulation with clenbuterol results in differential PGC-1␣ promoter regulation as it increases the levels of alternative isoforms but represses PGC-1␣1 expression (Fig.…”

Endoplasmic Reticulum Stress of Skeletal Muscle and Exercise Training Effects in Aging and Obesity

“…Furthermore, ATF6 and IRE1α have also been observed in human skeletal muscle following acute resistance exercise, whereas PERK, eIF2v and CHOP were not increased [49]. Resistance exercise also increases PGC-1α [50], indicating that both of acute aerobic and resistance exercise increase UPR through PGC-1α. Interestingly, these results indicate that differential UPR pathway by ER stress might be triggered by different by exercise type such as endurance and resistance.…”