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

Five days of dry immersion reduced cardiovascular fitness as measured by VO2max.

• VO2max decreased by 7.4% (P = 0.003)
• Study involved 18 healthy men with mean age 33.6 (SD 5.5) years and BMI 23.3 (1.8) kg/m2
• Longitudinal within-subject design with each participant serving as his own control
• Dry immersion was used as a model of rapid physical deconditioning

Dry immersion induced reductions in both fat mass and fat-free mass, as well as quadriceps cross-sectional area.

• Fat mass decreased by 2.6% (P = 0.002) as measured by DXA
• Fat-free mass decreased by 2.6% (P < 0.001) as measured by DXA
• Quadriceps cross-sectional area decreased by 2.8% (P < 0.001) as measured by MRI
• These changes occurred over only 5 days of inactivity

Dry immersion increased hepatic fat content but did not significantly alter intramuscular fat content.

• Liver fat content increased by 21% (P < 0.001) as measured by MRI
• Muscle fat content increased by only 0.1% (P = 0.218) as measured by MRI
• The differential fat deposition pattern suggests organ-specific responses to short-term inactivity

Urinary nitrogen excretion increased during dry immersion, indicating elevated whole-body protein catabolism.

• Urinary nitrogen excretion rose by 28% (P < 0.001)
• This increase occurred over the 5-day dry immersion period
• Elevated nitrogen excretion is interpreted as a marker of increased whole-body protein catabolism

Fasting insulin and triglyceride concentrations were elevated following dry immersion.

• Fasting insulin increased by 46% (P = 0.009)
• Fasting triglycerides increased by 14% (P = 0.013)
• These changes suggest early onset of metabolic dysregulation with short-term physical inactivity

Postprandial glucose and insulin responses were markedly increased after dry immersion, indicating impaired whole-body glucose tolerance.

• Postprandial incremental glucose concentration increased by 49% (P = 0.002) following a carbohydrate-rich meal
• Postprandial incremental insulin concentration increased by 90% (P < 0.001) following a carbohydrate-rich meal
• These responses were measured following a carbohydrate-rich meal using incremental area under the curve methodology

Whole-body fasting and postprandial fat and carbohydrate oxidation rates, adjusted for body composition, remained unchanged after dry immersion.

• Fasting and postprandial total lipid and carbohydrate oxidation measured by indirect calorimetry remained unchanged (P > 0.05 for all)
• Oxidation rates were adjusted for body composition
• This finding indicates that systemic metabolic flexibility at the whole-body level was not detectably altered despite other metabolic disturbances

Insulin-stimulated Akt Thr308 phosphorylation was impaired in differentiated myotubes isolated after dry immersion.

• Insulin-stimulated Akt Thr308 phosphorylation was significantly reduced (P = 0.03)
• Myotubes were isolated from vastus lateralis biopsies taken before and after dry immersion
• This finding indicates intrinsic changes in insulin signaling within skeletal muscle cells

In vitro glycogen synthesis was impaired in myotubes isolated after dry immersion.

• In vitro glycogen synthesis assessed from U-14C glucose was significantly reduced (P < 0.01)
• Measurements were performed in differentiated myotubes from vastus lateralis biopsies
• This reduction in glycogen synthesis capacity reflects intrinsic cellular changes independent of systemic hormonal environment

The ability of myotubes to suppress palmitate oxidation in response to increasing glucose concentrations was impaired after dry immersion, indicating reduced metabolic flexibility.

• The ability to suppress in vitro palmitate oxidation (1-14C palmitate) following incremental glucose concentrations was impaired (P = 0.02)
• This was assessed in primary differentiated myotubes from vastus lateralis biopsies
• The ability to increase palmitate oxidation when palmitate availability rises was not significantly altered
• Impaired fuel switching (from fat to glucose) in response to glucose represents a cellular marker of metabolic inflexibility

Early intrinsic skeletal muscle cell metabolic changes likely contribute to the onset of whole-body metabolic disorders induced by physical inactivity.

• Cellular-level impairments in insulin signaling, glycogen synthesis, and metabolic flexibility were detected in primary myotubes maintained in culture, removing systemic confounders
• The authors suggest these early alterations may reflect rapid epigenetic imprinting of satellite cells
• Findings support the hypothesis that skeletal muscle cell-intrinsic changes precede or accompany systemic metabolic disturbances during inactivity