Prolonged heat stress induces autophagy in mouse skeletal muscle

Environment-induced heat stress (HS) is a significant and expanding threat to human health and efficient agricultural production. In this investigation, we aimed to determine the extent to which HS impacted skeletal muscle health. We hypothesized that HS would decrease autophagosome degradation and autophagic flux in mouse skeletal muscle. To test this hypothesis, female C57 mice were exposed to thermoneutral (TN; 30°C) or heat stress (HS; 37.5°C) conditions for 24 h, and the gastrocnemius, soleus, and diaphragm muscles were immediately collected. A subset of mice was treated with colchicine to assess autophagic flux. Environment-induced HS increased rectal and subcutaneous temperatures by ∼2.0°C and decreased feed intake by 75% and body mass by 14%, without a change in muscle mass. In all muscles, 24 h of HS increased phosphorylated heat shock proteins (HSP) 27 by 1.47-fold to 4.5-fold compared with TN; however, HSPs 27, 60, 72, and 90 were similar between groups. We discovered HS increased autophagic flux in the gastrocnemius and diaphragm, but not soleus, without changes in most key autophagy regulatory proteins. Markers of mitophagy, regulators of mitochondrial architecture, and mitochondrial abundance were largely similar between groups for all muscles. Environment-induced HS increased endoplasmic reticulum (ER) stress regulators, binding immunoglobulin protein by 1.7-fold to 2.9-fold and phosphorylated (p)-inositol-requiring enzyme 1 by 1.84-fold to 2.75-fold in all muscles, and p-eukaryotic initiation factor 2 was increased 3.6-fold in soleus. Counter to our hypothesis, these data demonstrate that 24 h of HS did not decrease autophagosome degradation or flux across a range of muscles in a mouse HS model.NEW & NOTEWORTHY Subheat stroke thermic injury is currently a human and animal health threat that is predicted to rise by environmental forecasting models. The extent to which persistent environment-induced hyperthermia impacts skeletal muscle health is largely unknown. Our findings challenge current knowledge regarding heat stress-induced dysfunction and suggest skeletal muscle mounts muscle-specific response to thermic injury.