The Autophagic Response to Passive and Exercise-induced Increases in Body Core Temperature in Young Adults

Autophagy is an essential cellular survival mechanism that involves the degradation and recycling of aged or damaged organelles and protein aggregates to maintain cellular homeostasis. While autophagic dysfunction occurs with aging and is associated with many disease-related pathologies, methods to modulate autophagic activity remain poorly understood in the context of human physiology. Recently, we demonstrated that autophagy is activated in an intensity-dependent manner during both exercise and passive heat stress, however it is unknown if the autophagic response to elevations in body core temperature (Tcore ) during passive heat exposure are comparable to those elicited through exercise. Therefore, we sought to assess the autophagic response to an elevated state of hyperthermia associated with intense exercise and compare responses to a similar rate and magnitude of increase in Tcore elicited through warm water immersion (WI). We evaluated the hypothesis that autophagic stimulation would occur during both exercise and WI, although responses would be greater during the exercise bout. To assess this hypothesis, 6 young men (mean [SD] 23 [3] years) performed 30 min of intense (70% of maximal oxygen consumption (VO2max )) semi-recumbent cycling. On a separate day (at least 72h after the exercise bout), the same participants were immersed in warm water (up to the clavicle) for 30 min, with the water temperature adjusted to elicit the same relative increase in Tcore (as estimated by rectal temperature) as was achieved during the prior exercise session. Given Tcore during WI was matched to the prior exercise bout, all WI trials were conducted after the exercise session. Autophagic activity was assessed in peripheral blood mononuclear cells prior to, immediately post-exercise or WI, and following a seated recovery (3 and 6h). Western blot was used to assess changes in autophagy via microtubule-associated light chain 3 beta (LC3-II) and normalized to β-actin (expressed as relative fold change to the respective baseline). Area under the curve was used to assess the Tcore response between conditions and protein data were analyzed via a two-way repeated measures ANOVA with Fisher's LSD (α=0.05). A similar average relative increase in Tcore was observed during the exercise and WI bouts (0.65 [0.21]°C vs 0.61 [0.19]°C, respectively; p=0.80) with a return to baseline within 3h in both conditions. In response to 30-min of exercise, LC3-II significantly increased immediately after exercise (1.69 [0.12]; p<0.01) and remained elevated above baseline at 3h (1.51 [0.23]; p<0.01) and 6h (1.38 [0.16]; p<0.01). A similar pattern of response was observed following WI (1.86 [0.77]; p=0.04), however, LC3-II returned to pre-WI levels within the first 3h of recovery. Our preliminary findings show similar increases in autophagy following a similar elevation in core temperature associated induced by exercise and WI. However, the autophagic response only remained elevated after exercise, likely caused by exercise-associated metabolic perturbations. Further research is warranted to delineate the underlying pathways of autophagic activation during these different thermal stressors. © FASEB.