The Effect of Graded Skeletal Muscle Glycogen Depletion on Whole‐body and Skeletal Muscle Metabolic Regulation

Exercise training repeatedly exposes skeletal muscle to cyclical periods of glycogen depletion and re‐synthesis. There is evidence to suggest that signal transduction pathways central in driving exercise adaptation are enhanced when exercise is performed in a glycogen depletion state. The purpose of the current study was to use exercise and carbohydrate re‐feeding strategies to manipulate glycogen content in skeletal muscle, allowing examination as to whether a critical level of glycogen depletion is required to promote whole body and skeletal muscle metabolic adaptation. Eight recreationally active males (mean ± SD: age 25 ± 2 yrs; height 176.3 ± 7.7 cm; body mass 78.7 ± 12.8 kg; VO 2peak 45.6 ± 4.2 ml·kg‐1·min‐1) each completed three trials in a randomized crossover design. On each occasion, participants undertook an evening bout of muscle glycogen depleting cycle ergometry (~4–6 pm, intervals of 90, 80, 70 or 60 % peak power output (PPO) alternated with recovery intervals at 50% PPO), before consuming carbohydrate (CHO) jelly and beverages at rates of: 0.0 g.kg.h‐1 (LOW), 0.6 g.kg.h‐1 (MED) or 1.2 g.kg.h‐1 (HIG) for 7 hours before returning to the laboratory the following morning (~8 am) after an overnight fast to perform 1 h steady‐state (SS) cycling at 57% PPO. Skeletal muscle biopsies were obtained immediately prior to glycogen depleting exercise (‘resting muscle glycogen’) during trial 2 and pre‐ and immediately‐post each SS exercise session. Three minute expired gas samples were collected prior to and every 15 min during SS exercise to determine O 2 , CO 2 , ventilatory exchange (VE), respiratory exchange ratio (RER), CHO (CHO‐ox) and fat oxidation (fat‐ox). The exercise and nutritional model successfully achieved three statistically (p < 0.05) ‘graded’ levels of pre‐exercise glycogen: LOW: 194.6 ± 52.3 μmol·g‐1·dw, MED: 351.7 ± 68.6 μmol·g‐1·dw, HIGH: 475.3 ± 43.9 μmol·g‐1·dw (representing 37.9 ± 8.9, 69.8 ± 15.4 and 94.1 ± 12.5 % of ‘normal resting’ stores: 511.6 ± 69.8 μmol·g‐1·dw). During SS exercise muscle glycogen decreased to a comparable extent in each trial (p < 0.01), however, by the end of exercise concentrations were similar between the MED and HIG trials (p > 0.05). After 15 min of SS exercise, three levels of CHO‐ox and two levels of fat‐ox (MED and HIGH similar) were evident (p < 0.05). As SS exercise continued RER and CHO‐ox were lower (p < 0.05) and fat‐ox greater at every time point in LOW compared to the HIG trial (p < 0.05), while substrate utilization was similar between MED and HIG trials for the remainder of exercise. In conclusion, we provide evidence of a working model to assess the role of skeletal muscle glycogen content on resting and exercise‐induced signaling responses in human skeletal muscle. Support or Funding Information This study was funded in part by a BBSRC New Investigator Award BB/L023547/1 to AP