Resistance exercise enhances long-term mTORC1 sensitivity to leucine

Area of Science:

• Exercise physiology
• Molecular biology
• Nutritional biochemistry

Background:

• Exercise increases mammalian target of rapamycin complex 1 (mTORC1) sensitivity to amino acids, particularly leucine.
• The duration and underlying mechanisms of this enhanced sensitivity post-exercise are not fully understood.

Purpose of the Study:

• To investigate the duration of enhanced leucine-mediated mTORC1 activation following exercise.
• To elucidate the mechanisms controlling this enhanced sensitivity, including amino acid transport and sensing pathways.

Main Methods:

• Mice underwent overnight exercise, followed by leucine or saline gavage acutely or 48 hours post-exercise.
• mTORC1 activation was blocked with rapamycin in separate experiments.
• Muscle tissue analysis included immunoblotting, qPCR, and L-[14C(U)]-leucine tracer to assess mTORC1 signaling, protein synthesis, amino acid transporters, and leucine uptake.

Main Results:

• Leucine more potently activated mTORC1 and protein synthesis in acutely exercised soleus muscle, an effect sustained 48 hours post-exercise.
• Exercise increased amino acid transporter expression and leucine uptake, leading to higher intracellular leucine levels.
• Activating transcription factor 4 (ATF4) expression increased, driven by the integrated stress response pathway (eIF2α phosphorylation), not directly by mTORC1.

Conclusions:

• Enhanced mTORC1 sensitivity to leucine persists for at least 48 hours post-exercise, extending the anabolic window.
• Exercise initiates a coordinated muscle program involving increased amino acid uptake and sensing, crucial for stimulating muscle protein synthesis.