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

Abstract

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.

The Acute Effects of Exercise and Temperature on Regional mtDNA

“…Further, both mRNA expression and mtDNA damage, in response to exercise, seem to be improved in cooler temperatures. Taken together, these results may provide a potential explanation for differences in mitochondrial related gene expression results that we have consistently found with our exercise and temperature investigations [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. However, the exact relationship between mtDNA and exercise induced mRNA expression is not clear and the mechanisms for each appear independent.…”

“…Previous works suggest exercise can induce mtDNA damage manifested as a reduction of mtDNA copy number [ 7 , 8 , 9 , 18 , 19 , 27 , 28 ], which is an established marker for mitochondrial dysfunction in many disease processes [ 1 , 2 , 3 , 4 ]. Exercising in cold ambient temperatures have demonstrated the potential to upregulate gene expression related to mitochondrial biogenesis [ 10 , 11 , 13 , 14 , 15 , 16 ]. Whereas, in hot ambient temperatures, there is a post-exercise blunted gene response [ 10 , 12 , 17 ].…”

“…The experimental cycling trial was performed at 50% Wpeak for 60 min and conducted in a temperature- and humidity-controlled (40% relative humidity) chamber (Darwin Chambers Co., St. Louis, MO, USA) within the designated temperatures, either cold (7 °C), room temperature (20 °C), or hot (33 °C). These combinations of temperatures and relative intensity were chosen based upon previous works demonstrating altered mitochondrial gene expression [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ] and to make sure all participants were able to complete the full trial, specifically those within the 33 °C cycling group. All subjects wore short-sleeved T-shirt and standard cycling shorts to maintain consistency among the groups.…”

“…Mitochondria are highly concentrated in skeletal muscle and can undergo damage when the ATP demand is elevated (e.g., a stressor like exercise and/or temperature) via increased production of ROS. Gene expression data has suggested that exercise, when paired with cold and hot ambient temperatures, may have different transcriptional influences [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. More specifically, the pairing of exercise and cold ambient temperature may act in a mitochondrial-enhancing manner through the upregulation of the gene PGC1α and its mitochondrial biogenesis-related downstream targets [ 10 , 11 , 15 , 16 ].…”

“…Gene expression data has suggested that exercise, when paired with cold and hot ambient temperatures, may have different transcriptional influences [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. More specifically, the pairing of exercise and cold ambient temperature may act in a mitochondrial-enhancing manner through the upregulation of the gene PGC1α and its mitochondrial biogenesis-related downstream targets [ 10 , 11 , 15 , 16 ]. Whereas exercise in hot ambient conditions may blunt these same mitochondrial-related benefits [ 10 , 11 , 12 , 17 ].…”