Exercise May Promote Skeletal Muscle Hypertrophy via Enhancing Leucine-Sensing: Preliminary Evidence

Abstract

Several studies have indicated a positive effect of exercise (especially resistance exercise) on the mTOR signaling that control muscle protein synthesis and muscle remodeling. However, the relationship between exercise, mTOR activation and leucine-sensing requires further clarification. Two month old Sprague-Dawley rats were subjected to aerobic exercise (treadmill running at 20 m/min, 6° incline for 60 min) and resistance exercise (incremental ladder climbing) for 4 weeks. The gastrocnemius muscles were removed for determination of muscle fibers diameter, cross-sectional area (CSA), protein concentration and proteins involved in muscle leucine-sensing and protein synthesis. The results show that 4 weeks of resistance exercise increased the diameter and CSA of gastrocnemius muscle fibers, protein concentration, the phosphorylation of mTOR (Ser2448), 4E-BP1(Thr37/46), p70S6K (Thr389), and the expression of LeuRS, while aerobic exercise just led to a significant increase in protein concentration and the phosphorylation of 4E-BP1(Thr37/46). Moreover, no difference was found for Sestrin2 expression between groups. The current study shows resistance exercise, but not aerobic exercise, may increase muscle protein synthesis and protein deposition, and induces muscle hypertrophy through LeuRS/mTOR signaling pathway. However, further studies are still warranted to clarify the exact effects of vary intensities and durations of aerobic exercise training.

Mild Endurance Exercise during Fasting Increases Gastrocnemius Muscle and Prefrontal Cortex Thyroid Hormone Levels through Differential BHB and BCAA-Mediated BDNF-mTOR Signaling in Rats

“…Our study reveals that when combined with fasting, mild endurance exercise can result in activation of mTOR signaling in response to tissue BCAA levels including leucine, which does not occur under fed conditions. In line with our results, gastrocnemius muscle sensitivity to leucine-dependent mTOR activation has very recently been shown to occur only through intense resistance exercise under fed conditions [ 34 ]. Supporting evidence for a functional association between the observed increased tissue BCAA levels, especially those of leucine and isoleucine, and re-activation of gastrocnemius muscle mTOR signaling comes from a study showing that exogenous leucine administration during fasting rapidly induces mTOR signaling in rat gastrocnemius muscle [ 15 ].…”

Resistance exercise enhances long-term mTORC1 sensitivity to leucine

“…To explore the potential mechanisms underlying the exercise-induced increase in leucine sensitivity, we decided to assess intramuscular leucine levels, since those critically control mTORC1 activity [ 43 ]. Exercise acutely increases amino acid uptake in the muscle [ 2 , 44 ], but whether this effect is still present 48 h after exercise cessation, and how it is related to mTORC1 activation, is unknown.…”

Protein Turnover in Skeletal Muscle: Looking at Molecular Regulation towards an Active Lifestyle

“…1) and sestrin2, which were identified as Leu sensors [139,140]. Four weeks of resistance exercise training was reported to promote gastrocnemius hypertrophy, which was associated with the enhanced phosphorylation of mTOR, p70S6K and 4E-BP1, and the upregulation of LeuRS but not of sestrin2 [141]. Some authors reported that ses-trin1, instead of sestrin2, is highly expressed in the SkM and mediates Leu activation of mTORC1 [142].…”