Water deprivation induces a systemic procatabolic state that differentially affects oxidative and glycolytic skeletal muscles in male mice

Dehydration, characterized by the loss of total body water and/or electrolytes due to diseases or inadequate fluid intake, is prevalent globally but often underestimated. Its contribution to long-term chronic diseases and sarcopenia is recognized, yet the mechanisms involved in systemic and muscle protein metabolism during dehydration remain unclear. This study investigated metabolic adaptations in a 36-h water deprivation (WD) model of mice. Male C57BL/6 mice underwent 36-h WD or pair-feeding at rest, with assessments of motor skills along with biochemical and metabolic parameters. Dehydration was confirmed by hypernatremia, body mass loss, hyporexia, and increased activity of vasopressinergic and oxytocinergic neurons compared with controls. These results were associated with liver mass loss, decreased glycemia, and increased cholesterolemia. In addition, increased V̇o₂ and a decreased respiratory exchange ratio indicated reduced carbohydrate consumption and potentially increased protein use during dehydration. Thus, skeletal muscle protein metabolism was evaluated due to its high protein content. In the oxidative muscles of the WD group, total and proteasomal proteolysis increased, which was associated with decreased Akt-mediated intracellular signaling. Interestingly, there was an increase in fiber cross-sectional area, likely due to higher muscle water content caused by increased intracellular osmolality induced by protein catabolism products. Conversely, no changes were observed in protein turnover or water content in glycolytic muscles. These findings suggest that short-term WD imposes a procatabolic state, depleting protein content in skeletal muscle. However, skeletal muscle may respond differently to dehydration based on its phenotype and might adapt for a limited time.<b>NEW & NOTEWORTHY</b> This study investigated the effects of WD on mouse homeostasis, focusing on energy substrates and skeletal muscle protein metabolism. Our findings revealed a shift toward reduced dependence on carbohydrate degradation and increased reliance on lipid oxidation, or even protein oxidation, as energy sources, since we observed increased proteolysis in one muscle phenotype. Despite body mass loss, soleus and EDL muscle masses were differently affected. These results indicate the procatabolic potential of short-term WD in mice.