Severe energy deficit at high altitude inhibits skeletal muscle mTORC1-mediated anabolic signaling without increased ubiquitin proteasome activity

Abstract

Muscle loss athighaltitude (HA) is attributable to energydeficit andapotentialdysregulationof anabolic signaling. Exercise and protein ingestion can attenuate the effects of energy deficit on muscle at sea level (SL). Whether these effects are observed when energy deficit occurs atHAis unknown. To address this,muscle obtained from lowlanders (n = 8 males) at SL, acute HA (3 h, 4300 m), and chronic HA (21 d, 21766 kcal/d energy balance) before [baseline (Base)] and after 80 min of aerobic exercise followed by a 2-mile time trial [postexercise (Post)] and 3 h into recovery (Rec) after ingestingwhey protein (25 g)were analyzed using standard molecular techniques. At SL, Post, and REC, p-mechanistic target of rapamycin (mTOR)Ser2448, p-p70 ribosomal protein S6 kinase (p70S6K)Ser424/421, and p-ribosomal protein S6 (rpS6)Ser235/236 were similar and higher (P > 0.05) than Base. At acute HA, Post p-mTORSer2448 and Post and REC p-p70S6KSer424/421 were not different from Base and lower than SL (P < 0.05). At chronicHA, Post and Rec p-mTORSer2448 and p-p70S6KSer424/421 were not different from Base and lower than SL, and, independent of time, p-rpS6Ser235/236 was lower than SL (P < 0.05). Post proteasome activity was lower (P < 0.05) than BaseandRec, independent of phase.Our findings suggest thatHAexposure inducesmuscle anabolic resistance that is exacerbated by energy deficit during acclimatization, with no change in proteolysis.