Exercise- and Cold-Induced Human PGC-1α mRNA Isoform Specific Responses

Int J Environ Res Public Health. 2020 Aug 8;17(16):5740. doi: 10.3390/ijerph17165740.


Cold exposure in conjunction with aerobic exercise stimulates gene expression of PGC-1α, the master regulator of mitochondrial biogenesis. PGC-1α can be expressed as multiple isoforms due to alternative splicing mechanisms. Among these isoforms is NT-PGC-1α, which produces a truncated form of the PGC-1α protein, as well as isoforms derived from the first exon of the transcript, PGC-1α-a, PGC-1α-b, and PGC-1α-c. Relatively little is known about the individual responses of these isoforms to exercise and environmental temperature. Therefore, we determined the expression of PGC-1α isoforms following an acute bout of cycling in cold (C) and room temperature (RT) conditions. Nine male participants cycled for 1h at 65% Wmax at -2 °C and 20 °C. A muscle biopsy was taken from the vastus lateralis before and 3h post-exercise. RT-qPCR was used to analyze gene expression of PGC-1α isoforms. Gene expression of all PGC-1α isoforms increased due to the exercise intervention (p < 0.05). Exercise and cold exposure induced a greater increase in gene expression for total PGC-1α (p = 0.028) and its truncated isoform, NT-PGC-1α (p = 0.034), but there was no temperature-dependent response in the other PGC-1α isoforms measured. It appears that NT-PGC-1α may have a significant contribution to the reported alterations in the exercise- and temperature-induced PGC-1α response.

Keywords: RT-qPCR; alternate promoter; primary promoter; transcription; truncated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cold Temperature*
  • Exercise*
  • Humans
  • Male
  • Muscle, Skeletal*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha* / metabolism
  • Protein Isoforms / genetics
  • RNA Isoforms*
  • RNA, Messenger / genetics
  • Transcription Factors / genetics


  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Protein Isoforms
  • RNA Isoforms
  • RNA, Messenger
  • Transcription Factors