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Severe energy deficit at high altitude inhibits skeletal muscle mTORC1‐mediated anabolic signaling without increased ubiquitin proteasome activity
Author(s) -
Margolis Lee M.,
Carbone John W.,
Berryman Claire E.,
Carrigan Christopher T.,
Murphy Nancy E.,
Ferrando Arny A.,
Young Andrew J.,
Pasiakos Stefan M.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201800163rr
Subject(s) - anabolism , mtorc1 , p70 s6 kinase 1 , medicine , endocrinology , chemistry , skeletal muscle , ribosomal protein s6 , pi3k/akt/mtor pathway , acclimatization , catabolism , biology , biochemistry , signal transduction , metabolism , botany
Muscle loss at high altitude (HA) is attributable to energy deficit and a potential dysregulation of 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 at HA is unknown. To address this, muscle obtained from lowlanders ( n = 8 males) at SL, acute HA (3 h, 4300 m), and chronic HA (21 d, ‐1766 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 ingesting whey 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‐mTOR Ser2448 and Post and REC p‐p70S6K Ser424/421 were not different from Base and lower than SL ( P < 0.05). At chronic HA, Post and Rec p‐mTOR Ser2448 and p‐p70S6K Ser424/421 were not different from Base and lower than SL, and, independent of time, p‐rpS6 Ser235/236 was lower than SL ( P < 0.05). Post proteasome activity was lower ( P < 0.05) than Base and Rec, independent of phase. Our findings suggest that HA exposure induces muscle anabolic resistance that is exacerbated by energy deficit during acclimatization, with no change in proteolysis.—Margolis, L. M., Carbone, J. W., Berryman, C. E., Carrigan, C. T., Murphy, N. E., Ferrando, A. A., Young, A. J., Pasiakos, S. M. Severe energy deficit at high altitude inhibits skeletal muscle mTORC1‐mediated anabolic signaling without increased ubiquitin proteasome activity. FASEB J. 32, 5955–5966 (2018). www.fasebj.org