Dehydration Increased Cortisol and Decreased Muscle Size Without Altering the Autophagy Response to Resistance Exercise

The negative impact of dehydration on hemodynamics and endurance exercise is well-established. However, the effect of dehydration on systemic (i.e., cortisol) and mTOR repressor protein (regulated in development and DNA damage-response 1; REDD1), autophagy, and muscle volume) stress responses after resistance exercise (RE) remain unknown. Purpose: To examine the effect of dehydration on stress responses after RE in trained young men. Hypothesis: The stress responses would be greater after RE in a dehydrated than a euhydrated state in young, trained men. Methods: Eleven men (age:21±1yr; height:175.9±6.2cm; weight:79.2±12.3kg) completed two identical bouts of bilateral leg press and knee extensions (5 x 10 reps at 80% of 1RM) either with (DEHY) or without (EUHY) fluid restriction from 24h before to 3h after RE and were separated by 2-3 weeks. Serum cortisol was measured before (PRE), and 5 minutes (m), 15m, 30m, 1 hour (h), and 3h after RE. Muscle samples were collected at PRE and 1h and 3h after RE. Western blots were used to analyze contents of REDD1, microtubule-associated protein 1A/1B-light chain 3 (LC3)-I, LC3-II, and sequestosome-1(p62) and normalized to Ponceau S staining (total protein). Muscle cross-sectional area (CSA) (n=5) was measured as an indicative of muscle volume. Results: REDD1 significantly ( p <0.05) increased from PRE (1.05±0.06) to 1h (1.13±0.21; p =0.032) and 3h (1.19±0.17; p =0.037) in DEHY, and was greater for DEHY(1.13±0.21) than EUHY (1.11±0.12; p =0.043) at 1h (condition x time). LC3-I decreased from PRE (0.81±0.06; p =0.003) and 1h (0.75±0.06; p =0.017) to 3hr (0.69±0.07) (main time). LC3-II decreased from PRE (0.95±0.34) to 1h (0.68±0.14; p =0.005) and 3h (0.91±0.09; p =0.011) (main time). LC3-II/LC3-I decreased from PRE (1.14±0.11) to 1h (0.97±0.30; p =0.007) and increased from 1h to 3h (1.24±0.39; p <0.001) (main time). Cortisol was greater for DEHY (15.09±1.62nmol/L) than EUHY (12.84±1.56 nmol/L; p =0.021) (main condition). CSA was smaller for DEHY (12523±1412mm 2 ) than EUHY (12974±980mm 2 ; p =0.009) (main condition). Conclusion: Stress responses were elevated in young, trained men exposed to mild dehydration during RE. Although autophagy responses did not differ between conditions, dehydration resulted in increased cortisol and REDD1 levels accompanied by reduced muscle volume. These findings suggest that acute dehydration adds an additional stressor during RE, amplifying both systemic and intramuscular stress responses. However, its long-term effect on muscle stress response to exercise warrants further investigation. This project was supported by a grant from the National Strength and Conditioning Association Foundation. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.