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, 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 VO 2 max (-7.4%, P=0.003), fat mass (-2.6%, P=0.002), fat-free mass (DXA, -2.6%, P<0.001), and quadriceps cross-sectional area (MRI, -2.8%, P<0.001). Fat content increased in the liver (MRI, +21%, P<0.001), but not in the muscles (MRI, +0.1%, P=0.218). Urinary nitrogen excretion rose (+28%, P<0.001), indicating increased whole-body protein catabolism. Fasting insulin (+46%, P=0.009) and triglycerides (+14%, P=0.013), as well as postprandial incremental glucose (+49%, P=0.002) and insulin (+90%, P<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 (P>0.05 for all). In differentiated myotubes isolated from vastus lateralis biopsies, insulin-stimulated Akt Thr308 phosphorylation (P=0.03), in vitro glycogen synthesis assessed from U- 14 C glucose (P<0.01), and the ability to suppress in vitro palmitate oxidation (1- 14 Cpalmitate) following incremental glucose concentrations were impaired (P=0.02). The ability to increase palmitate oxidation when palmitate availability rises remained preserved. These results suggest that early intrinsic skeletal muscle cell changes may contribute to the onset of whole-body metabolic disorders induced by physical inactivity.