A single day of reduced activity alters the next day's transcriptomic and metabolic exercise response

Regular aerobic exercise decreases the risk of metabolic diseases; however, reduced physical activity may attenuate these beneficial adaptations. This study investigated the influence of a single day of reduced activity on the skeletal muscle transcriptome (RNA-Seq) and systemic metabolism surrounding an acute bout of aerobic exercise. Using a crossover design, subjects [n = 9 (7 M, 2 F), 24 ± 1 yr] exercised at 65% maximal oxygen consumption for 60 min following a day of reduced activity (IN; 3,581 ± 1,185 steps) and normal activity (A; 11,069 ± 3,631 steps). RNA-Seq from skeletal muscle biopsies was taken before and 4 h postexercise. Respiratory gas exchange analysis was completed at 20, 40, and 60 min of exercise. Blood samples for select metabolites were collected before, during, and throughout the 4 h recovery. Inactivity resulted in nine differentially expressed genes at rest, whereas exercise altered 793 and 1,403 genes in A and IN, respectively. Gene set enrichment analysis revealed an interaction of exercise and trial, which were related to inflammation, metabolism, cell cycle, and innate immunity. Respiratory exchange ratio (0.93 ± 0.04 vs. 0.91 ± 0.03; P < 0.05) and carbohydrate utilization (2.16 ± 0.79 vs. 1.96 ± 0.72 g/min; P = 0.09) were higher in the IN versus A trial at 60 min of exercise. Triglycerides were higher in the IN trial (P < 0.05), with no differences between trials observed in other measured metabolites. These findings indicate that a single day of reduced physical activity can elicit modest but significant changes in the metabolic and transcriptomic exercise response. Such alterations have implications for exercise guidelines and underscore the importance of controlling for daily step count when assessing exercise responses.NEW & NOTEWORTHY This investigation shows modest differences in the metabolic demands of an acute bout of exercise following a day of inactivity. In addition, there are differences in the skeletal muscle transcriptome at rest and in the exercise response with decreased physical activity before exercise. This study highlights the need for more research on the role of physical inactivity in the exercise response, as well as the need to control for step count before exercise response studies.