Effects of exercise followed by a low-carbohydrate diet on peak fat oxidation and mitochondrial coupling control and efficiency in healthy trained men

Whole-body fat oxidation correlates with mitochondrial oxidative capacity, emphasizing the role of mitochondrial function in systemic and skeletal muscle substrate utilization during exercise - a relationship that may be modulated by the prevailing fuel availability. Muscle glycogen is an important fuel during exercise due to its effects on substrate metabolism, but its influence on peak fat oxidation (PFO) and mitochondrial coupling control and efficiency (MCCE) remains unclear. The aim of the study was to investigate the influence of muscle glycogen content on PFO, the intensity eliciting PFO (Fat_max) and MCCE. Ten trained men participated in a randomized crossover study comprising two interventions conducted over two consecutive days. Day 1 included anthropometric assessments, blood sampling, a muscle biopsy and a graded exercise test followed by a glycogen depletion protocol. The following day blood sampling, muscle biopsy and the graded exercise test were repeated. A diet high or low in carbohydrate was consumed between the days to manipulate glycogen levels. The experiment was repeated after 7-14 days. Muscle samples were analysed for glycogen and triacylglycerol content and MCCE. PFO increased after both interventions and was further enhanced by the combined exercise and low-carbohydrate intervention, where muscle glycogen was low. Fat_max increased only following the combined exercise and low-carbohydrate intervention. MCCE was unaffected by the interventions. The study concludes that exercise-induced glycogen depletion together with a low-carbohydrate diet increases PFO and Fat_max but does not influence MCCE. These findings have implications towards understanding and optimizing fat oxidation and as a potential read out of metabolic flexibility. KEY POINTS: Whole-body fat oxidation is linked to mitochondrial capacity, yet the role of endogenous fuel availability in this relationship has not been studied. Muscle glycogen is a primary exercise fuel, but its specific influence on peak fat oxidation (PFO), the exercise intensity that elicits PFO (Fat_max) and mitochondrial coupling control and efficiency (MCCE) is unclear. Ten trained men completed a randomized crossover study using glycogen depletion and dietary intervention to alter glycogen levels, with exercise tests and muscle biopsies performed at baseline and postintervention. Exercise-induced glycogen depletion combined with a low-carbohydrate diet increased both PFO and Fat_max, whereas there was no effect on MCCE. These findings clarify the regulation of PFO and the combined effect of exercise-induced glycogen depletion and low carbohydrate diet, and that this is not regulated through changes in mitochondrial function.