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Translocation and protein complex co-localization of mTOR is associated with postprandial myofibrillar protein synthesis at rest and after endurance exercise

Abstract

Translocation and colocalization of mechanistic target of rapamycin complex 1 (mTORC1) with regulatory proteins represents a critical step in translation initiation of protein synthesis in vitro. However, mechanistic insight into the control of postprandial skeletal muscle protein synthesis rates at rest and after an acute bout of endurance exercise in humans is lacking. In crossover trials, eight endurance-trained men received primed-continuous infusions of L-[ring-(2) H5 ]phenylalanine and consumed a mixed-macronutrient meal (18 g protein, 60 g carbohydrates, 17 g fat) at rest (REST) and after 60 min of treadmill running at 70% VO2peak (EX). Skeletal muscle biopsies were collected to measure changes in phosphorylation and colocalization in the mTORC1-pathway, in addition to rates of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis. MyoPS increased (P < 0.05) above fasted in REST (~2.1-fold) and EX (~twofold) during the 300 min postprandial period, with no corresponding changes in MitoPS (P > 0.05). TSC2/Rheb colocalization decreased below fasted at 60 and 300 min after feeding in REST and EX (P < 0.01). mTOR colocalization with Rheb increased above fasted at 60 and 300 min after feeding in REST and EX (P < 0.01), which was consistent with an increased phosphorylation 4E-BP1(Thr37/46) and rpS6(ser240/244) at 60 min. Our data suggest that MyoPS, but not MitoPS, is primarily nutrient responsive in trained young men at rest and after endurance exercise. The postprandial increase in MyoPS is associated with an increase in mTOR/Rheb colocalization and a reciprocal decrease in TSC2/Rheb colocalization and thus likely represent important regulatory events for in vivo skeletal muscle myofibrillar mRNA translation in humans.

Type Journal
ISBN 2051-817X (Electronic) 2051-817X (Linking)
Authors Abou Sawan, S.; van Vliet, S.; Parel, J. T.; Beals, J. W.; Mazzulla, M.; West, D. W. D.; Philp, A.; Li, Z.; Paluska, S. A.; Burd, N. A.; Moore, D. R.
Responsible Garvan Author Dr Andy Philp
Publisher Name Physiological Reports
Published Date 2018-03-08
Published Volume 6
Published Issue 5
Published Pages e13628
Status Published in-print
DOI 10.14814/phy2.13628
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/29512299