Repeated exposure to heat stress induces mitochondrial adaptation in human skeletal muscle

Abstract

The heat stress response is associated with several beneficial adaptations that promote cell health and survival. Specifically, in vitro and animal investigations suggest that repeated exposures to a mild heat stress (~40°C) elicits positive mitochondrial adaptations in skeletal muscle comparable to those observed with exercise. To assess whether such adaptations translate to human skeletal muscle, we produced local, deep tissue heating of the vastus lateralis via pulsed shortwave diathermy in 20 men (n=10) and women (n=10). Diathermy increased muscle temperature by 3.9 °C within 30 minutes of application. Immediately following a single 2-hr heating session, we observed increased phosphorylation of AMPK and ERK1/2, but not of p38 MAPK nor JNK. Following repeated heat exposures (2-hr daily for 6 consecutive days), we observed a significant cellular heat stress response, as heat shock protein 70 and 90 increased 45% and 38%, respectively. In addition, PGC-1α and mitochondrial electron transport protein complexes I and V expression were increased after heating. These increases were accompanied by augmentation of maximal coupled, and uncoupled, respiratory capacity, measured via high-resolution respirometry. Our data provide the first evidence that mitochondrial adaptation can be elicited in human skeletal muscle in response to repeated exposures to mild heat stress.

Skeletal Muscle Signaling Following Whole-Body and Localized Heat Exposure in Humans

“…However, our findings differ from work reporting repressed expression of PGC-1α mRNA expression, or no change in mitochondrial density following acute ( Petrie et al, 2016 ) and longer term heat therapy, respectively ( Hesketh et al, 2019 ). Instead, our findings in general corroborate with data acquired in cell and rodent models showing an increase in markers associated with mitochondrial biogenesis ( Liu and Brooks, 2012 ; Tamura and Hatta, 2017 ), which have been extended to human models demonstrating a HSP-associated increase mitochondrial adaptation in healthy weight-bearing as well as immobilized humans ( Hafen et al, 2018 , 2019 ). We did not observe increased PGC-1α mRNA levels in the current study, despite the increase in gene transcription coding for mitochondria-related proteins.…”

Thermal pretreatment facilitates recovery from prolonged low-frequency force depression in rat fast-twitch muscle

“…Many, if not all , studies have revealed that heat stress and/or vigorous muscle contraction result in the upregulation of HPS70 in fast-and slow-twitch muscles from mammals (Oishi et al 2002;Tupling et al 2007;Tamura et al 2015;Hafen et al 2018). Conversely, the current study showed that neither thermal treatment nor fatiguing stimulation elicited changes in the expression of HSP70 (Fig.…”

“…; Hafen et al. ). Conversely, the current study showed that neither thermal treatment nor fatiguing stimulation elicited changes in the expression of HSP70 (Fig.…”

“…; Hafen et al. ), it seems likely that differences in thermal treatment protocols used, species examined, and/or muscle volumes yield distinct results. The possibility cannot be excluded that in this study, HSP70 was upregulated at the time other than ~24 h after the last thermal treatment, the only time point investigated, and interacted with some proteins critical for excitation–contraction coupling.…”

“…The reasons for the conflicting results remain unclear. However, with the consideration that the extent and time of increases in HSP70 differs between studies (Oishi et al 2002;Touchberry et al 2012;Tamura et al 2015;Hafen et al 2018), it seems likely that differences in thermal treatment protocols used, species examined, and/or muscle volumes yield distinct results. The possibility cannot be excluded that in this study, HSP70 was upregulated at the time other than~24 h after the last thermal treatment, the only time point investigated, and interacted with some proteins critical for excitation-contraction coupling.…”