Passive dehydration increases oxidative stress and mTOR signalling pathway activation in young men following...

Dehydration is prevalent and adversely affects exercise performance; however, its influence on cellular responses to exercise remains unclear. Thus, this study examined the intramuscular responses to resistance-exercise (RE) in RE-trained men under dehydrated and euhydrated states. Eleven men (21 ± 1 years, 175.9 ± 6.2 cm, 79.2 ± 12.3 kg, 18.4% ± 6.7% fat) completed two identical lower-body RE sessions, either with (DEHY) or without (EUHY) fluid-restriction from 24 h before to 3 h after RE. At pre-RE (PRE), 1 h, and 3 h post-RE, muscle samples were collected and analysed for protein content of AKT/mTOR/p70S6K/rpS6 and their corresponding phosphorylation sites, REDD1 and selected autophagy markers, cathepsin L, H₂O₂ concentration, fibre cross-sectional area (CSA), and muscle water content. Significant time × condition interaction effects revealed that p-rpS6^S240/244 was greater in DEHY than EUHY at PRE and increased from PRE to 1 h and 3 h in both conditions. In DEHY, REDD1 increased from PRE to 1 h and 3 h, active-cathepsin L decreased from 1 h to 3 h and was greater than EUHY at 1 h, and muscle water content increased from 1 h to 3 h. Significant condition main effects revealed that p-S6K^T389 and H₂O₂ were greater, and CSA was smaller, in DEHY versus EUHY. Significant time main effects revealed that p-AKT^S473 and p-mTOR^S2448 increased from PRE to 1 h and 3 h, LC3-I decreased from PRE and 1 h to 3 h, LC3-II decreased from PRE to 1 h and 3 h, and LC3-II/LC3-I decreased from PRE to 1 h and increased from 1 h to 3 h. These results suggest that performing RE in a dehydrated state imposes additional stress on the muscle, leading to greater cellular stress and growth signalling. KEY POINTS: Dehydration can negatively impact exercise performance, overall health, and cognitive function in humans. Water makes up about 70% of muscle mass, and dehydration has been shown to decrease muscle size in humans. However, the mechanisms by which dehydration affects muscle response on anabolic and catabolic signalling have only been observed in in vitro studies, leaving the processes in humans still not fully understood. Following 24 h of dehydration, there was an increase in the activation of rpS6 at rest. Additionally, young men exhibited greater activation of S6K during resistance exercise (RE) while dehydrated compared to when they were adequately hydrated. Concurrently, stress (H₂O₂ and REDD1) and proteolytic (active-cathepsin L) responses were elevated after RE in a dehydrated state compared to an adequately hydrated state. Our research offers new insights into the importance of hydration in muscle responses to exercise, particularly for individuals who are frequently dehydrated.