Truncated splice variant PGC-1α4 is not associated with exercise-induced human muscle hypertrophy

Introduction: A truncated PGC-1 alpha splice variant (PGC-1 alpha 4) has been implicated in the regulation of resistance exercise (RE)-induced muscle hypertrophy, and basal expression levels said to be augmented in response to concurrent aerobic (AE) and RE training. Aim: The current study investigated human muscle truncated and non-truncated PGC-1a transcripts in response to both acute and chronic RE, and with or without preceding AE (AE+RE). Methods: Ten men performed 5 weeks of unilateral AE+RE and RE training. Before (untrained) and after (trained) this intervention, PGC-1a transcripts were assessed in vastus lateralis muscle biopsies obtained before and 3 h after acute RE, with or without preceding AE. Additionally, samples were collected 72 h after the last exercise bout of the training programme. Results: The truncated splice variant increased (P < 0.05) its expression after acute exercise regardless of mode. However, the expression was greater (P < 0.05) after AE+RE than RE. Other PGC-1a transcripts showed similar response. Truncated transcripts originated from both the alternative and proximal promoter, and AE+RE increased PGC-1 alpha expression from both promoter sites. RE induced transcripts from the alternative promoter only. PGC-1 alpha expressions after acute exercise were comparable across isoforms in both untrained and trained muscle. Steady-state levels of isoforms were unchanged after 5-week training (P > 0.05). Exercise-induced expression of PGC-1a variants did not correlate with changes in muscle size or strength (P > 0.05). Conclusion: Our results do not support the view that truncated PGC-1a coordinates exercise-induced hypertrophy in human skeletal muscle. Rather, all PGC-1 alpha isoforms appear to be regulated transiently in response to acute exercise and regardless of mode.