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‐2H5]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‐BP1Thr37/46 and rpS6ser240/244 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.

Altered anabolic signalling and reduced stimulation of myofibrillar protein synthesis after feeding and resistance exercise in people with obesity

“…The cellular mechanisms that regulate myofibrillar protein synthesis rates are assumed to be centered on anabolic pathways such as mTORC1 signalling (Abou Sawan et al . ). We previously showed dysregulated mTORC1 signalling in muscles of obese vs .…”

“…Given that the synthesis rates of myofibrillar protein fraction were robustly stimulated in the NW group at 0-2 h compared to the OB group, it appears that perhaps with resistance exercise the dietary amino acids remained confined to the more rapidly turning over sarcoplasmic pool in obese muscles as opposed to being used for post-exercise myofibrillar protein accretion. J Physiol 596.21 The cellular mechanisms that regulate myofibrillar protein synthesis rates are assumed to be centered on anabolic pathways such as mTORC1 signalling (Abou Sawan et al 2018). We previously showed dysregulated mTORC1 signalling in muscles of obese vs. normal weight adults (Beals et al 2016).…”

Dose-response effects of dietary protein on muscle protein synthesis during recovery from endurance exercise in young men: a double-blind randomized trial

“…In the present study, protein co-ingestion did not result in greater MitoPS rates than 0 g PRO ( Figure 11A , B ). MitoPS rates increase in response to intravenous infusion of amino acids ( 19 , 20 ), and the ingestion of larger (i.e., 36 g) ( 21 ), but not smaller (i.e., 18 g) ( 18 ) doses of protein at rest. Our finding that protein co-ingestion did not result in greater MitoPS rates than 0 g PRO aligns with previous studies that reported no further increase in MitoPS rates after protein intake compared with a nonprotein control during recovery from endurance exercise ( 13 , 14 ) or combined endurance and resistance exercise ( 22–24 ).…”

“…Our finding that protein co-ingestion did not result in greater MitoPS rates than 0 g PRO aligns with previous studies that reported no further increase in MitoPS rates after protein intake compared with a nonprotein control during recovery from endurance exercise ( 13 , 14 ) or combined endurance and resistance exercise ( 22–24 ). Studies to date examining the impact of protein ingestion on MitoPS rates after an acute bout of endurance exercise or combined endurance and resistance exercise have provided protein doses < 30 g ( 13 , 14 , 18 , 22–24 ). Our results show that even relatively large doses of protein (45 g or ∼0.58 g protein/kg) do not increase MitoPS rates more than the ingestion of carbohydrate only during the first few hours of recovery from a single bout of endurance exercise.…”

“…The majority of ( 13–17 ), but not all ( 2 , 18 ), studies to date examining the effect of protein ingestion on MPS rates during recovery from an acute bout of endurance exercise have found that protein intake results in higher mixed MPS ( 15 , 16 ) and MyoPS ( 13 , 14 , 17 ) rates than does a nonprotein control treatment. Intravenously infused amino acids ( 19 , 20 ) and protein ingestion ( 21 ) stimulate increased MitoPS rates at rest; however, protein ingestion does not appear to enhance MitoPS rates during recovery from endurance exercise ( 13 , 14 , 18 ) or combined endurance and resistance exercise ( 22–24 ). The dose of ingested protein is a key factor determining the magnitude of increase in whole-body net protein balance ( 25 ) and MPS rates ( 26 , 27 ) during recovery from resistance exercise.…”