Low glycogen availability induces superior autophagy activation in type II fibers after exercise

Nutrient and energy availability plays a central role in exercise adaptations. Considerable effort has been aimed at examining the impact of low glycogen availability and studies have shown that manipulation of glycogen content can modulate molecular pathways regulating exercise adaptations. However, the focus has been on endurance exercise and mitochondrial biogenesis and very little is known about glycogen availability and resistance exercise adaptations.

The process of autophagy is responsible for degrading and recycling cellular proteins under conditions of energetic stress and poor nutrient availability. Activation of autophagy is largely mediated by the energy sensing protein AMPK which is activated by high-intensity exercise and low glycogen availability. Thus, performing resistance exercise with low glycogen levels may result in enhanced activation of autophagy. As autophagy is a degradative process, potent activation of this pathway may have a negative effect on muscle protein balance. Autophagy is inhibited by mTORC1, which is a key mediator of resistance exercise adaptations and is potently activated by amino acids. The opposing effects of AMPK and mTORC1 on autophagy suggests that any potential negative effects of performing resistance exercise with low glycogen availability may be rescued by amino acid intake.

The main aims of this project are
1) to study if resistance exercise with low glycogen increases autophagy versus high glycogen levels in a fiber type-specific manner and
2) if this increase is mitigated by amino acid intake in a fiber type-specific manner.

Individual muscle fibers will be dissected out from muscle biopsies collected from participants who have performed resistance exercise with either high or low muscle glycogen and with or without amino acid intake during recovery. To define potential sex-differences, individual muscle fibers from both men and women will be studied. Autophagy is slowly emerging as an important mediator of skeletal muscle remodelling and exercise adaptations, but studies in humans are scarce and the role of glycogen availability in this context has never been studied previously. Thus, the project is highly novel and employs a study design which specifically allows the study of autophagy signalling at the level of individual muscle fibers. The outcome of the project is likely to influence nutritional recommendations for optimal exercise adaptations, potentially in a sport- and sex-specific manner.