Abstract

This investigation sought to determine whether post-exercise cold water immersion and low glycogen availability, separately and in combination, would preferentially activate either the Exon 1a or Exon 1b Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) promoter. Through a reanalysis of sample design, we identified that the systemic cold-induced augmentation of total PGC-1α gene expression observed previously (Allan et al. in J Appl Physiol 123(2):451–459, 2017) was largely a result of increased expression from the alternative promoter (Exon 1b), rather than canonical promoter (Exon 1a). Low glycogen availability in combination with local cooling of the muscle (Allan et al. in Physiol Rep 7(11):e14082, 2019) demonstrated that PGC-1α alternative promoter (Exon 1b) expression continued to rise at 3 h post-exercise in all conditions; whilst, expression from the canonical promoter (Exon 1a) decreased between the same time points (post-exercise–3 h post-exercise). Importantly, this increase in PGC-1α Exon 1b expression was reduced compared to the response of low glycogen or cold water immersion alone, suggesting that the combination of prior low glycogen and CWI post-exercise impaired the response in gene expression versus these conditions individually. Data herein emphasise the influence of post-exercise cooling and low glycogen availability on Exon-specific control of total PGC-1 α gene expression and highlight the need for future research to assess Exon-specific regulation of PGC-1α.

Highlights

  • It has been shown that skeletal muscle expresses several different transcript variants that produce different protein isoforms of the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α)

  • Exercise significantly increased the expression of Exon 1a mRNA ~ two–four fold from Pre (Pre–Post-Exercise: P < 0.001, ES 2.50 Very Large, Fig. 2)

  • No significant interaction was seen (P = 0.111). This is the first study to investigate the relative influence of post-exercise cooling as well as the impact of reduced glycogen availability alone, and in combination, on promoterspecific mRNA expression of the transcriptional co-activator PGC-1α

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Summary

Introduction

It has been shown that skeletal muscle expresses several different transcript variants that produce different protein isoforms of the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) (reviewed in Popov et al 2015a). Of particular interest is whether the individual impact of exercise, cold stress and low glycogen would preferentially activate either the Exon 1a or Exon 1b PGC-1α promoter, and whether the combined impact of these stimuli would further enhance PGC-1α gene expression. Such mechanistic information would allow greater support for the application of post-exercise CWI in an applied setting, whilst going some way to assist the correct use and timing of such modalities

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