Thermotolerance and heat acclimation may share a common mechanism in humans

Abstract

Thermotolerance and heat acclimation are key adaptation processes that have been hitherto viewed as separate phenomena. Here, we provide evidence that these processes may share a common basis, as both may potentially be governed by the heat shock response. We evaluated the effects of a heat shock response-inhibitor (quercetin; 2,000 mg/day) on established markers of thermotolerance [gastrointestinal barrier permeability, plasma TNF-α, IL-6, and IL-10 concentrations, and leukocyte heat shock protein 70 (HSP70) content]. Heat acclimation reduced body temperatures, heart rate, and physiological strain during exercise/heat stress) in male subjects (n = 8) completing a 7-day heat acclimation protocol. These same subjects completed an identical protocol under placebo supplementation (placebo). Gastrointestinal barrier permeability and TNF-α were increased on the 1st day of exercise/heat stress in quercetin; no differences in these variables were reported in placebo. Exercise HSP70 responses were increased, and plasma cytokines (IL-6, IL-10) were decreased on the 7th day of heat acclimation in placebo; with concomitant reductions in exercise body temperatures, heart rate, and physiological strain. In contrast, gastrointestinal barrier permeability remained elevated, HSP70 was not increased, and IL-6, IL-10, and exercise body temperatures were not reduced on the 7th day of heat acclimation in quercetin. While exercise heart rate and physiological strain were reduced in quercetin, this occurred later in exercise than with placebo. Consistent with the concept that thermotolerance and heat acclimation are related through the heat shock response, repeated exercise/heat stress increases cytoprotective HSP70 and reduces circulating cytokines, contributing to reductions in cellular and systemic markers of heat strain. Exercising under a heat shock response-inhibitor prevents both cellular and systemic heat adaptations.

Repeated muscle damage blunts the increase in heat strain during subsequent exercise heat stress

“…There may be shared pathways with the concept of cross-tolerance, where adaptations to one stressor confer protection via molecular, cellular and neural interactions to other forms of stressor (Horowitz 2014;Horowitz and Robinson 2007). This process is thought to be mediated, in part, by intra-cellular heat shock proteins (Hsp's), and it has been suggested that acquired thermotolerance (the accumulation of protective Hsp's within cells following heat exposure), and systemic adaptations to heat acclimation share a common pathway (Kuennen et al 2011). This may be pertinent since EIMD has been shown to increase Hsp72 and Hsp27 expression within muscle cells following EIMD (Paulsen et al 2009;Thompson et al 2001), and that the changes we observed during HS on EIMD trial 2, reflect similar adaptations to that observed during heat acclimation (reduced exercising Tre, earlier sweating onset, reduced thermal sensation).…”

Heat acclimation: Gold mines and genes

“…In a recent human study by Kuennen et al, 36 the administration of 2,000 mg/day of quercetin, an HSP pathway inhibitor, prevented the thermal responses and the improved intestinal permeability seen during a program of heat acclimation. On the other hand, ingestion of glutamine which increases HSP70 synthesis, prevented endotoxin release and the inflammatory response seen in the same unacclimated subjects without glutamine supplementation during an acute exercise bout in the heat.…”

“…36 If the HSP pathway is a major trigger for heat acclimation adaptations, then a malfunction in this system should have serious consequences for heat tolerance. In a study by Moran et al, 33 soldiers who failed to upregulate HSP during heat acclimation had more severe heart rate and body temperature responses during a HTT and were therefore classified as heat intolerant.…”

Heat shock response and autophagy—cooperation and control

“…Ryan et al showed that treadmill exercise results in no apparent increase in HSP70 protein expression in human leukocytes. 142 Similarly, 2 50-min bouts of moderate intensity aerobic exercise 143,144 do not affect HSP70 levels in peripheral blood mononuclear cells (PBMCs). In our recent studies, strenuous treadmill running (rectal temperature of 40 C) produces a timedependent increase in HSP70 protein expression in peripheral leukocytes, but the difference did not reach statistical significance.…”

“…[158][159][160][161][162][163][164][165][166] When examining exercise training effects on HSP70 protein expression in humans, it has been shown that a 7-d heat acclimation protocol consisting of 2 50-min exercise bouts in a warm environmental chamber elevates subjects' core temperature to 39 C and results in a significant increase in HSP70 protein expression in peripheral leukocytes at 4-h post-exercise. 144 Similarly, a 10-d acclimation program involving treadmill walking or running in a hot environment augments HSP70 content in peripheral blood mononuclear cells. 143,167,168 Elevation of HSP70 in response to high-intensity and long-term training is also found after an 11-d training program, but not in response to short or moderate intensity exercise.…”