Resistance exercise increases AMPK activity and reduces 4E‐BP1 phosphorylation and protein synthesis in human skeletal muscle

Abstract

Resistance exercise is a potent stimulator of muscle protein synthesis and muscle cell growth, with the increase in protein synthesis being detected within 2-3 h post-exercise and remaining elevated for up to 48 h. However, during exercise, muscle protein synthesis is inhibited. An increase in AMP-activated protein kinase (AMPK) activity has recently been shown to decrease mammalian target of rapamycin (mTOR) signalling to key regulators of translation initiation. We hypothesized that the cellular mechanism for the inhibition of muscle protein synthesis during an acute bout of resistance exercise in humans would be associated with an activation of AMPK and an inhibition of downstream components of the mTOR pathway (4E-BP1 and S6K1). We studied 11 subjects (seven men, four women) before, during, and for 2 h following a bout of resistance exercise. Muscle biopsy specimens were collected at each time point from the vastus lateralis. We utilized immunoprecipitation and immunoblotting methods to measure muscle AMPKα2 activity, and mTOR-associated upstream and downstream signalling proteins, and stable isotope techniques to measure muscle fractional protein synthetic rate (FSR). AMPKα2 activity (pmol min −1 (mg protein) −1 ) at baseline was 1.7 ± 0.3, increased immediately post-exercise (3.0 ± 0.6), and remained elevated at 1 h post-exercise (P < 0.05). Muscle FSR decreased during exercise and was significantly increased at 1 and 2 h post-exercise (P < 0.05). Phosphorylation of 4E-BP1 at Thr37/46 was significantly reduced immediately post-exercise (P < 0.05). We conclude that AMPK activation and a reduced phosphorylation of 4E-BP1 may contribute to the inhibition of muscle protein synthesis during resistance exercise. However, by 1-2 h post-exercise, muscle protein synthesis increased in association with an activation of protein kinase B, mTOR, S6K1 and eEF2.

mTOR signaling response to resistance exercise is altered by chronic resistance training and detraining in skeletal muscle

“…Previous studies showed elevated 4E-BP1 phosphorylation after resistance exercise (4,38). However, changes in phosphorylation of 4E-BP1 and p70S6K in response to a bout of exercise do not necessarily correspond, and some previous studies have failed to find elevated phosphorylation of 4E-BP1 (9,10,23,29). We also did not detect an elevated rate of 4E-BP1 phosphorylation 24 h after exercise throughout the training and detraining periods, suggesting differential regulation of 4E-BP1 and p70S6K.…”

Heat shock response and autophagy—cooperation and control

“…Resistance exercise is important and well known in development of muscle mass (hypertrophy). In humans, resistance exercise increases protein synthesis [97][98][99][100][101][102][103][104][105][106] and improves protein balance during the recovery phase in the skeletal muscle, 8,107,108 but not during acute bouts of resistance exercise. 109 Similar to resistance exercise, low intensity aerobic training 110 causes a significant increase in fractional synthetic rate in the leg muscle.…”

Free acid gel form of β-hydroxy-β-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt

“…This effect on protein synthesis appears to be shared with the anabolic effects of amino acids (particularly leucine) and insulin (10,11) . In addition, HMB attenuates the induction of the ubiquitin -proteosome proteolytic pathway caused by proteolysis-inducing factor, lipopolysaccharide and angiotensin II, resulting in a decrease in muscle protein breakdown (12 -14) .Human studies have shown a positive effect of resistance exercise on muscle protein synthesis as early as 1 -2 h postexercise and lasting up to 48 h (15,16) . Studies have also shown that the timing of nutrient availability is critical for maximal post-exercise stimulation of protein synthesis as well as blunting of protein breakdown (17) .…”