Abstract
BackgroundCold acclimation and exercise training were previously shown to increase peripheral insulin sensitivity in human volunteers with type 2 diabetes. Although cold is a potent activator of brown adipose tissue, the increase in peripheral insulin sensitivity by cold is largely mediated by events occurring in skeletal muscle and at least partly involves GLUT4 translocation, as is also observed for exercise training.MethodsTo investigate if cold acclimation and exercise training overlap in the molecular adaptive response in skeletal muscle, we performed transcriptomics analysis on vastus lateralis muscle collected from human subjects before and after 10 days of cold acclimation, as well as before and after a 12-week exercise training intervention.ResultsCold acclimation altered the expression of 756 genes (422 up, 334 down, P < 0.01), while exercise training altered the expression of 665 genes (444 up, 221 down, P < 0.01). Principal Component Analysis, Venn diagram, similarity analysis and Rank–rank Hypergeometric Overlap all indicated significant overlap between cold acclimation and exercise training in upregulated genes, but not in downregulated genes. Overlapping gene regulation was especially evident for genes and pathways associated with extracellular matrix remodeling. Interestingly, the genes most highly induced by cold acclimation were involved in contraction and in signal transduction between nerve and muscle cells, while no significant changes were observed in genes and pathways related to insulin signaling or glucose metabolism.ConclusionsOverall, our results indicate that cold acclimation and exercise training have overlapping effects on gene expression in human skeletal muscle, but strikingly these overlapping genes are designated to pathways related to tissue remodeling rather than metabolic pathways.
Highlights
Cold acclimation and exercise training were previously shown to increase peripheral insulin sensitivity in human volunteers with type 2 diabetes
We have previously shown that cold acclimation consisting of daily exposure to 14–15 °C for 6 h for a period of 10 days markedly increased peripheral insulin sensitivity in human volunteers with type 2 diabetes (T2D) [6]
Volcano plot analysis showed that the signal log ratios for the changes in gene expression induced by cold acclimation were larger than the signal log ratios for the changes induced by exercise (Fig. 1a)
Summary
Cold acclimation and exercise training were previously shown to increase peripheral insulin sensitivity in human volunteers with type 2 diabetes. Cold is a potent activator of brown adipose tissue, the increase in peripheral insulin sensitivity by cold is largely mediated by events occurring in skeletal muscle and at least partly involves GLUT4 translocation, as is observed for exercise training. We have previously shown that cold acclimation consisting of daily exposure to 14–15 °C for 6 h for a period of 10 days markedly increased peripheral insulin sensitivity in human volunteers with T2D [6]. The detectability of BAT in human volunteers with T2D was very low or even undetectable by FDGPET/CT, and was only marginally increased after cold acclimation. The molecular pathways triggered by cold acclimation in human skeletal have remained unexplored
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