Intake Of Essential Amino Acids Stimulates Mtorc1 Signaling And Inhibits Autophagy Following Glycogen-depleted Resistance Exercise

Abstract

Autophagy is responsible for degrading and recycling cellular proteins under conditions of energetic stress and low nutrient availability. Activation of autophagy is mediated by AMPK which is activated by high-intensity exercise and low glycogen availability and performing resistance exercise with low glycogen levels may result in enhanced autophagy activation which in turn may have negative effects on muscle protein balance. Autophagy is inhibited by mTORC1 which is potently activated by essential amino acids (EAA). 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 EAA intake. PURPOSE: To study the effect of EAA intake on autophagy and mTORC1 signaling following resistance exercise with high and low glycogen availability. METHODS: Using a unilateral study design in which one leg was glycogen loaded and the other leg was glycogen depleted, men and women underwent two experimental trials wherein they consumed either a placebo (PLA) or an EAA drink after resistance exercise. Unilateral differences in muscle glycogen content were achieved through glycogen loading and subsequent one-legged glycogen depleting exercise the evening prior to each experimental trial. Muscle biopsies were collected at baseline, post exercise and 1 and 3 h after drink intake in both legs in both trials. RESULTS: Mean glycogen content was ~69 % lower in the depleted leg compared to the loaded leg (228 vs 724 mmol/kg dry weight) across all time points in both trials. Phosphorylation of ULK1 at the AMPK-specific site S317 was elevated ~5-fold immediately post exercise in the depleted leg while remaining unchanged in the loaded leg with no differences between trials. In the PLA-trial, S317 phosphorylation remained elevated 60 min post drink ingestion, while in the EAA trial at the same time point, it had returned to baseline values. Phosphorylation of S6K1 at the mTORC1-specific site T389 remained largely unchanged at all time-points in the PLA-trial while being increased by ~33-fold in both legs at 60 min in the EAA-trial. CONCLUSIONS: Intake of EAA blunt the elevations in autophagy signaling induced by resistance exercise performed in a glycogen-depleted state while simultaneously stimulating the mTORC1 pathway.