Anabolic signaling responses to exercise and recovery whey protein are suppressed at high altitude
Authors: Margolis Lee M. , Berryman Claire E. , Carbone John W. , Carrigan Christopher T. , Murphy Nancy E. , Ferrando Arny A. , Young Andrew J. , Pasiakos Stefan M. 
Published: June 2021

Lowlanders sojourning to high‐altitude (HA) often experience muscle mass losses that are attributable to negative energy balance and potential dysregulation of intramuscular anabolic signaling. The combined effects of exercise and high‐quality protein ingestion can ameliorate the effects of short‐term, moderate negative energy balance (10‐d, ≤ 40 % total energy requirements) on intramuscular anabolic signaling at sea level (SL); however, the ability to sustain this effect at HA is unknown. This study examined the combined effects of HA (4300 m) and severe negative energy balance (21‐d, 70% of SL total energy requirements) on mTORC1 signaling responses after aerobic exercise and recovery whey protein (WP) ingestion in recreationally active, native lowlanders (n = 8 males). Total body mass and fat‐free mass were assessed using dual energy x‐ray absorptiometry before and after the 21‐d energy deficit at HA. Muscle biopsies of the vastus lateralis were obtained at SL, acute HA (3‐h HA exposure, day 0), and chronic HA (day 21), before (BASE) and after completing 80‐min of steady‐state aerobic exercise followed by a 2 mile time trial (POST), and 3 h into recovery (REC). In each trial, 25 g WP was consumed as a drink immediately after the POST biopsy. Intramuscular anabolic signaling was determined using Western blot and RT‐qPCR. Participants lost 7.5 ± 0.8 kg of total body mass (4.3 ± 1.0 kg of fat‐free mass, P < 0.05). POST and REC p‐mTORSer2448, p‐70S6KSer424/421 and p‐rpS6Ser235/236 were 2‐, 23‐, and 7‐fold higher (P < 0.05) than BASE at SL. At acute HA, POST p‐mTORSer2448, and POST and REC p‐70S6KSer424/421 were not different (P > 0.05) from BASE and were 1‐ and 20‐fold lower than SL (P < 0.05). However, POST and REC p‐rpS6Ser235/236 at acute HA was 4‐fold higher (P < 0.05) than BASE and not different from SL. At chronic HA, POST and REC p‐mTORSer2448 and p‐70S6KSer424/421 were not different from BASE and were 1‐ and 19‐fold lower (P < 0.05) than SL. POST and REC p‐rpS6Ser235/236 at chronic HA was 2‐fold higher (P < 0.05) than BASE, but overall phosphorylation was 4‐fold lower (P < 0.05) than SL. BASE HIF‐1α mRNA expression tended to be higher (P = 0.07) at acute HA than SL, whereas REC HIF‐1α mRNA expression at acute and chronic HA were lower (P < 0.05) than SL. REDD1 mRNA expression and REDD1/14‐3‐3 coupling were not affected by study phase. These findings indicate that acute HA exposure induces intramuscular anabolic resistance that is further impaired with chronic HA exposure concomitant with severe negative energy balance, suggesting a mechanism for muscle loss at HA.Support or Funding InformationThis material is based on the work supported by US Army Medical Research and Material Command and the US Army Natick Soldier Research Development and Engineering Center. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the US Army.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.