Isolating the effects of carbohydrate and lipid availability on exercise-induced skeletal muscle signalling in males

Training with low carbohydrate availability can increase AMP-activated protein kinase (AMPK) activation, but whether increased AMPK activation is the result of low carbohydrate availability per se or concurrent increases in fatty acid availability/oxidation is unclear. This study assessed the independent effects of carbohydrate and fatty acid availability on exercise-induced skeletal muscle AMPK activation and downstream signalling. Eight active males who were aged between 18 and 60 years with a body mass index in the range 18.0-30.0 kg m^-2 cycled on three occasions for 60 min at 95% of lactate threshold 1 with ingestion of either carbohydrate (CARB), niacin (NIACIN) or placebo (FAST) in a crossover design (11 ± 6 days washout). Blood and exhaled breath were sampled throughout exercise and muscle was sampled pre- and post-exercise. Fat oxidation and plasma non-esterified fatty acid concentrations were both lower in CARB vs. FAST with negligible difference between CARB vs. NIACIN. Plasma insulin concentrations were higher in CARB compared with both FAST and NIACIN. Net muscle glycogen use was greater with NIACIN vs. CARB. Although no evidence for differences were observed for phosphorylated AMPK, the downstream target, phosphorylated acetyl-CoA carboxylase was decreased with CARB vs. both FAST (-0.7 ± 0.6 fold, P = 0.04) and NIACIN (-1.0 ± 0.8 fold, P = 0.02). RNA-sequencing displayed several canonical changes with exercise but little difference between conditions. These data suggest carbohydrate ingestion suppresses exercise-induced phosphorylation of acetyl-CoA carboxylase independent of fatty acid availability. KEY POINTS: It is currently unknown whether the enhanced physiological adaptation to regularly exercising in a fasted-state are explained by low carbohydrate availability and/or the concomitant increase in fatty acid availability. This study used fasted exercise with niacin ingestion to reduce the lipaemic response associated with fasted exercise to isolate the effects of carbohydrate vs. fatty acid availability on exercise-induced skeletal muscle signalling. Our data show niacin ingestion increases muscle glycogen utilisation compared to carbohydrate ingestion during exercise, but both niacin and carbohydrate ingestion suppress fatty acid availability and fat oxidation to a similar extent. Our data demonstrate carbohydrate ingestion during exercise suppresses acetyl-CoA carboxylase phosphorylation compared to both niacin ingestion and extended overnight fasting. These data suggest that high carbohydrate availability inhibits exercise-induced acetyl-CoA carboxylase phosphorylation in human skeletal muscle, independent of circulating fatty acid concentrations.