The effect of caffeine on skeletal muscle anabolic signaling and hypertrophy

Area of Science:

• Exercise Physiology
• Molecular Biology
• Nutritional Science

Background:

• Caffeine is a popular stimulant known to improve physical performance.
• In vitro studies suggest caffeine may inhibit skeletal muscle anabolic signaling via AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) pathways.
• This inhibition could potentially impede muscle protein synthesis and growth.

Purpose of the Study:

• To investigate the in vivo effects of caffeine on AMPK and mTOR signaling pathways in skeletal muscle.
• To determine caffeine's impact on protein synthesis and muscle growth following exercise.
• To examine the interplay between caffeine, AMPK, and mTOR signaling in muscle adaptation.

Main Methods:

• Assessed caffeine's effect on AMPK and mTOR signaling, protein synthesis, and muscle growth in cultured C2C12 myoblasts and in vivo mouse models.
• Utilized electrically stimulated contractions in mice to mimic exercise stimulus.
• Examined skeletal muscle-specific knockout of LKB1 (AMPK activator) to understand AMPK's role.
• Investigated caffeine's effect on muscle hypertrophy in rats using a tenotomy model.

Main Results:

• Caffeine did not affect mTOR activation, myoblast proliferation, or differentiation in cultured C2C12 cells.
• In mice, caffeine administration did not alter AMPK phosphorylation or inhibit downstream mTOR signaling proteins (p70S6k, S6, 4EBP1) or protein synthesis post-contraction.
• Skeletal muscle-specific knockout of LKB1 abolished contraction-induced AMPK activation and enhanced mTOR signaling.
• Caffeine did not impede plantaris muscle hypertrophy in rats following tenotomy.

Conclusions:

• Caffeine consumption does not impair skeletal muscle load-induced mTOR signaling.
• Caffeine does not negatively affect exercise-induced protein synthesis or muscle hypertrophy.
• The findings suggest caffeine is safe for muscle growth and adaptation in vivo.