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

Mika Silvennoinen,Tanja Laine,Satu Pekkala,Heikki Kyröläinen,Keijo Häkkinen,Bradley C Nindl,Juha P Ahtiainen,Heikki Kainulainen,Ritva S Taipale,Juha J Hulmi,Harri Selänne

doi:10.14814/phy2.12563

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.

Highlights

Skeletal muscle comprises about 40–50% of body mass in humans and plays significant roles in locomotion, heat production, and whole-body metabolism
To increase knowledge of early signaling events that drive the exercise mode-specific adaptations, and to confirm previous findings with well-defined primers, the present study aimed to investigate the acute gene expression responses of different PGC-1 isoforms after a single bout of high-load resistance exercise or moderate intensity endurance exercise in human skeletal muscle
The main findings of this study were that (1) both exercise group (EE) and resistance exercise group (RE) induced significant increase in the gene expression of alternative promoter originated PGC-1a exon 1band 1b’-derived isoforms, whereas the proximal promoter originated PGC-1a exon 1a-derived transcripts were less inducible and were upregulated only after EE; (2) truncated PGC-1a transcripts were upregulated markedly after RE and slightly after EE; (3) based on the marker gene expression changes, EE induced responses typical for angiogenesis and mitochondrial biogenesis, while RE induced responses typical for angiogenesis and muscle

Summary

Introduction

Skeletal muscle comprises about 40–50% of body mass in humans (lean) and plays significant roles in locomotion, heat production, and whole-body metabolism. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. The question remains, Which specific mechanisms are involved in the response to different types of physical activities? There have been attempts to identify single signaling cascades or molecules that could work as a master regulator for controlling exercise-specific adaptations (Atherton et al 2005; Baar and Esser 1999). PGC-1a has been identified as a regulator of mitochondrial biogenesis, angiogenesis, antioxidant defense, and inflammatory proteins (Olesen et al 2010)

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