A single day of bed rest, irrespective of energy balance, does not affect skeletal muscle gene expression or insulin sensitivity

New Findings What is the central question of this study? What are the initial metabolic and molecular events that underpin bed rest‐induced skeletal muscle deconditioning, and what is the contribution of energy balance? What is the main finding and its importance? A single day of bed rest, irrespective of energy balance, did not lead to overt changes in skeletal muscle gene expression or insulin sensitivity. More than 1 day of physical inactivity is required to observe the insulin resistance and robust skeletal muscle transcriptional responses associated with bed rest and consequent alterations in energy balance. The initial metabolic and molecular events that underpin disuse‐induced skeletal muscle deconditioning, and the contribution of energy balance, remain to be investigated. Ten young, healthy men (age 25 ± 1 years; body mass index 25.3 ± 0.8 kg·m−2) underwent three 24 h laboratory‐based experimental periods in a randomized, crossover manner: (i) controlled habitual physical activity with an energy‐balanced diet (CON); (ii) strict bed rest with a diet to maintain energy balance (BR‐B); and (iii) strict bed rest with a diet identical to CON, consequently resulting in positive energy balance. Continuous glucose monitoring was performed throughout each visit, with vastus lateralis muscle biopsies and an oral glucose tolerance test performed before and after. In parallel with muscle samples collected from a previous 7 day bed rest study, biopsies were used to examine the expression of genes associated with the regulation of muscle mass and insulin sensitivity. A single day of bed rest, irrespective of energy balance, did not lead to overt changes in whole‐body substrate oxidation, indices of insulin sensitivity [i.e. homeostatic model assessment of insulin resistance, BR‐B from 2.7 ± 1.7 to 3.1 ± 1.5 (P > 0.05) and Matsuda index, BR‐B from 5.9 ± 3.3 to 5.2 ± 2.9 (P > 0.05)] or 24 h glycaemic control/variability compared with CON. Seven days of bed rest led to ∼30–55% lower expression of genes involved in insulin signalling, lipid storage/oxidation and muscle protein breakdown, whereas no such changes were observed after 1 day of bed rest. In conclusion, more than a single day of physical inactivity is required to observe the insulin resistance and robust skeletal muscle transcriptional responses associated with bed rest and consequent alterations in energy balance.