Five days of physical inactivity induced by dry immersion alter skeletal muscle metabolism and whole body glucose tolerance in healthy men

Even brief periods of physical inactivity can induce metabolic disruptions; however, the underlying cellular and molecular mechanisms initiating these alterations remain unclear. We investigated whole-body and skeletal muscle-specific metabolic responses to short-term inactivity induced by dry immersion (DI), a model of rapid physical deconditioning. Eighteen healthy men (age = 33.6 [SD 5.5] years, body mass index (BMI) = 23.3 [1.8] kg/m²) underwent five days of DI in a longitudinal within-subject design, with each participant serving as his own control. DI-induced inactivity reduced V̇o_2max (-7.4%, <i>P</i> = 0.003), fat mass [dual energy X-ray absorptiometry (DXA), -2.6%, <i>P</i> = 0.002], fat-free mass (DXA, -2.6%, <i>P</i> < 0.001), and quadriceps cross-sectional area (MRI, -2.8%, <i>P</i> < 0.001). Fat content increased in the liver (MRI, +21%, <i>P</i> < 0.001), but not in the muscles (MRI, +0.1%, <i>P</i> = 0.218). Urinary nitrogen excretion rose (+28%, <i>P</i> < 0.001), indicating increased whole-body protein catabolism. Fasting insulin (+46%, <i>P</i> = 0.009) and triglycerides (+14%, <i>P</i> = 0.013), as well as postprandial incremental glucose (+49%, <i>P</i> = 0.002) and insulin (+90%, <i>P</i> < 0.001) concentrations following a carbohydrate-rich meal were increased. Fasting and postprandial total lipid and carbohydrate oxidation measured by indirect calorimetry and adjusted for body composition remained unchanged (<i>P</i> > 0.05 for all). In differentiated myotubes isolated from vastus lateralis biopsies, insulin-stimulated Akt Thr308 phosphorylation (<i>P</i> = 0.03), in vitro glycogen synthesis assessed from U-¹⁴C glucose (<i>P</i> < 0.01), and the ability to suppress in vitro palmitate oxidation (1-¹⁴Cpalmitate) following incremental glucose concentrations were impaired (<i>P</i> = 0.02). The ability to increase palmitate oxidation when palmitate availability rises was not significantly altered. These results suggest that early intrinsic skeletal muscle cell changes may contribute to the onset of whole-body metabolic disorders induced by physical inactivity.<b>NEW & NOTEWORTHY</b> Five days of dry immersion led to reduced cardiovascular fitness, muscle atrophy, hepatic fat accumulation, and lower glucose tolerance. These alterations occur despite no detectable changes in whole body fat and carbohydrate oxidation following a carbohydrate-rich meal. In cultured primary myotubes, insulin action and metabolic flexibility (fuel switching) are impaired. Early alterations in intrinsic muscle cell metabolism likely reflect rapid epigenetic imprinting of satellite cells and may contribute to systemic metabolic disturbances induced by physical inactivity.