Hexokinase: A central player in the synergism of high-intensity intermittent exercise and every-other-day intermittent fasting regimen on energy metabolism adaptations

Visceral lipid accumulation, organ hypertrophy and a reduction in skeletal muscle strength are all signs associated with the severity of obesity related disease. Intermittent fasting (IF) and high-intensity intermittent exercise (HIIE) are natural strategies that, individually, can prevent and ameliorate obesity along with metabolic syndrome and its associated diseases. However, the combinatorial effect of IF and HIIF on energetic metabolism is currently not well understood. We hypothesized that their combination could have a potential for more than strictly additive benefits. Here, we show that two months of every-other-day intermittent fasting regimen combined with a high-intensity intermittent exercise protocol (IF/HIIE) produce a synergetic effect, preventing fat accumulation, enhancing physical performance and optimizing energy production. The IF/HIIE group presented increased glucose uptake, lower levels of serum insulin and a global activation of hexokinases in skeletal muscle, heart and liver comparing to control, IF and HIIE groups. IF/HIIE synergism led to activation of the FoF1 ATP synthase and promoted a more oxidative profile of mitochondria in observed skeletal muscle. Additionally, high-resolution respirometry of muscle fibers showed that animals in the IF/HIIE group presented characteristics suggestive of augmented mitochondrial mass and efficiency. Finally, an important reduction in serum oxidative stress markers were observed in IF/HIIE group. These findings provide new insights for the implementation of non-pharmaceutical strategies to prevent/treat metabolic syndrome and associated diseases.