36 | The effects of heat stress and exercise on skeletal muscle

Chiara Malerba¹, A. Laurino¹, M. Serano, C. Pranzo¹, F. Fiore¹, E. Pierantozzi¹, D. Rossi^1|2, V. Sorrentino^1|2 | ¹Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy; ²Azienda Ospedaliero Universitaria Senese, Siena, Italy.

Skeletal muscle constitutes approximately 40% of total body mass and is highly susceptible to environmental stressors. Climate change and the increasing frequency of heat waves represent a growing threat to public health. Damage due to heat stress to this tissue can therefore have widespread effects on overall health and systemic functions. However, the effects of acute heat exposure on skeletal muscle function remain poorly characterized. Indeed, several stimuli, among which heat exposure, can perturb endoplasmic/sarcoplasmic reticulum (ER/SR) homeostasis in skeletal muscle, leading to ER stress and the subsequent activation of the unfolded protein response (UPR). The aim of this study was to evaluate the impact of heat stress on in vivo muscle performance in mice and to determine whether heat exposure induces ER stress and/or activates the UPR in skeletal muscle. Additionally, with the goal of identifying strategies to protect muscle from heat-induced damage, we investigated the potential preventive role of voluntary exercise. Four experimental groups were tested: control mice (CTR), mice exposed to 39.5°C for 3 hours (heat-stressed, HS), mice allowed voluntary wheel running for 4 weeks (exercised, EX), and exercised mice subsequently exposed to heat stress (EX+HS). After 4 weeks from the start of the experiment, mice underwent functional assessment by grip strength and hanging wire tests. Gastrocnemius and soleus muscles were collected for ER stress/UPR analysis by RT-qPCR. We observed that acute heat stress significantly reduced muscle strength and increased BiP and Gadd34 mRNA levels in the soleus but not in gastrocnemius muscle. In exercised mice, these functional and transcriptional changes were prevented. Moreover, exercise alone improved muscular endurance. These findings indicate that physical exercise might represent a protective strategy to preserve skeletal muscle function under heat stress conditions.