The Role Of mTOR Signalling In The Regulation Of Skeletal Muscle Mass In A Rodent Model Of Resistance Exercise

Research Summary

A rat study asking what rapamycin-sensitive mTOR signalling actually controls after resistance exercise: the acute activation of muscle protein synthesis, ribosome biogenesis, PGC-1-alpha expression and, after four weeks of training, muscle hypertrophy.

Who Or What Was Studied?

Male Sprague-Dawley rats (about 330 g, 11 weeks old). The gastrocnemius muscle of one leg was electrically stimulated to contract as a resistance-exercise model (five sets of ten 3-second contractions), with the other leg as a non-exercised control. Rapamycin 1.5 mg/kg or placebo was injected intraperitoneally one hour before exercise; muscle was sampled 1, 6 and 24 hours after a single session and after four weeks of training three times a week (n = 5 per time point).

What Did The Research Show?

• Rapamycin fully inhibited the exercise-induced phosphorylation of p70S6K at Thr389, a validated marker of rapamycin-sensitive mTOR signalling, so the dose did block its intended target.
• A single exercise session raised muscle protein synthesis at every time point measured, and rapamycin only partially blocked that rise.
• Acute exercise increased ribosome biogenesis, and rapamycin completely prevented that increase.
• Four weeks of resistance exercise increased muscle wet weight and fibre cross-sectional area in both groups, but the increases were significantly greater in the placebo group – rapamycin only partially blocked hypertrophy.
• Exercise raised PGC-1-alpha mRNA and protein, and rapamycin did not prevent this.
• Chronic rapamycin lowered Akt phosphorylation at Ser473, a marker of mTORC2 signalling.

Limitations And Interpretation

• Animal data, not human: the exercise model is electrical stimulation of rat muscle, not voluntary training in people.
• Rapamycin was given by intraperitoneal injection at 1.5 mg/kg, and chronic treatment also reduced a marker of mTORC2, so the effects seen are not confined to mTORC1.
• The study measured muscle protein synthesis, ribosome biogenesis and hypertrophy only; it says nothing about lifespan, healthspan or human muscle.
• Group sizes were small (n = 5 per time point).