PGC-1α alternative promoter (Exon 1b) controls augmentation of total PGC-1α gene expression in response to cold water immersion and low glycogen availability

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.

Keywords: CWI; Exon; PGC-1α.

Fig. 1

Overview of the experimental protocol used in each trial. Whilst blood samples were collected in the original studies no new data herein is derived from blood.  HIIT high-intensity intermittent exercise; CON control condition/limb; NOT non-immersed limb; CWI cold water immersion condition/limb; PPO peak power output; LOW low CHO limb; VLOW very low CHO limb

Fig. 2

PGC-1α mRNA and specific to Exon 1a (a) and Exon 1b (b) ^ΔΔCT fold change in expression value with the calibrator as pre-exercise and the reference gene as GAPDH. Values are mean ± SEM. *Significantly different from pre-exercise (P < 0.05). #Significantly different from CON (P < 0.05). $ (P = 0.07) vs CON. + 3 h = 3 h post-exercise. Total PGC-1α mRNA (c) redrawn from Allan et al. (J Appl Physiol. 2017; 123 (2): 451–459) as mean ± SEM

Fig. 3

PGC-1α mRNA specific to Exon 1a (a) and Exon 1b (b) ^ΔΔCT fold change in expression with the calibrator as pre-exercise and the reference gene as GAPDH. Values are mean ± SEM. $ Trend towards increase from pre-exercise (a P = 0.065, b P = 0.057). *Significantly different from corresponding LOW limb (P = 0.025). + Different from corresponding LOW limb (P = 0.062). + 3 h = 3 h post-exercise. Total PGC-1α mRNA (c) redrawn from Allan et al. (Physiol Rep. 2019; 7(11): e14082) as mean ± SEM. ⁱSignificantly less than CON LOW (P < 0.05), ⁱⁱ greater than CON VLOW (P = 0.05), ⁱⁱⁱ Significantly less than CWI LOW (P = 0.019), ^ivSignificantly greater than pre- and post-exercise (P < 0.001)