Resistance exercise decreases eIF2Bε phosphorylation and potentiates the feeding-induced stimulation of p70^S6K1 and rpS6 in young men

Abstract

We investigated the effect of resistance exercise and feeding on the activation of signaling proteins involved in translation initiation. Nine young men (23.7+/-0.41 yr; BMI=25.5+/-1.0 kg/m2; means+/-SE) were tested twice after they performed a strenuous bout of unilateral resistance exercise, such that their contralateral leg acted as a nonexercised comparator, in either the fasted and fed [1,000 kJ, each 90 min (3 doses): 10 g protein, 41 g carbohydrate, 4 g fat] states. Muscle biopsies were obtained 6 h postexercise from both legs, resulting in four experimental conditions: rest-fasted, rest-fed, exercise-fasted, and exercise-fed. Feeding increased PKB/Akt (Ser473) phosphorylation (P<0.05), while exercise increased the phosphorylation of Akt and the downstream 70 kDa S6 protein kinase (p70S6K1, Thr389) and ribosomal protein S6 (rpS6, Ser235/236, Ser240/244; all P<0.05). The combination of resistance exercise and feeding increased the phosphorylation of p70S6K1 (Thr389) and rpS6 (Ser240/244) above exercise alone (P<0.05). Exercise also reduced phosphorylation of the catalytic epsilon subunit of eukaryotic initiation factor 2B (eIF2Bepsilon, Ser540; P<0.05). Mammalian target of rapamycin (mTOR, Ser2448), glycogen synthase kinase-3beta (GSK-3beta, Ser9), and focal adhesion kinase (FAK, Tyr576/577) phosphorylation were unaffected by either feeding or resistance exercise (all P>0.14). In summary, feeding resulted in phosphorylation of Akt, while resistance exercise stimulated phosphorylation of Akt, p70S6K1, rpS6, and dephosphorylation eIF2Bepsilon with a synergistic effect of feeding and exercise on p70(S6K1) and its downstream target rpS6. We conclude that resistance exercise potentiates the effect of feeding on the phosphorylation and presumably activation of critical proteins involved in the regulation of muscle protein synthesis in young men.

Whey and casein labeled withl-[1-13C]leucine and muscle protein synthesis: effect of resistance exercise and protein ingestion

“…Because of this fact, the relative importance of total vs. phosphorylated amounts in relation to inhibitory binding of eIF4E also remains unknown. Our results on GSK-3␤ did not show any significant changes, which is in line with previous findings (25) indicating minor importance of the Akt-GSK-3␤ pathway (7).…”

Neuromuscular electrical stimulation increases muscle protein synthesis in elderly type 2 diabetic men

“…5B) but, perhaps unsurprisingly, did not observe any differences in either the stimulated or control leg following NMES. In support of this observation, the protein abundance of these intramuscular anabolic signaling proteins tends to remain static after acute anabolic stimuli in younger subjects (29), and muscle protein synthesis rates have been reported to increase in response to physical exercise well before any measurable changes in total mRNA content (68). However, we provide additional evidence in a sedentary population of type 2 diabetics that the transcriptional regulation of these signaling proteins has little influence on the acute stimulation of muscle protein synthesis rates.…”

The order of concurrent endurance and resistance exercise modifies mTOR signaling and protein synthesis in rat skeletal muscle

“…In the present study, EE also increased phosphorylation of Akt, an upstream stimulator of mTORC1. Although animal data regarding post-EE Akt activation especially under fasting conditions are limited, an increase in Akt phosphorylation has been reported previously in humans after fasting (7, 13) and after RE under fasting conditions (22). Further studies are warranted to investigate the effect of specific EE protocol or fasting state on RE-induced anabolic responses.…”

“…Numerous studies have reported an increase in mTORC1 signaling (e.g., an increase in phosphorylation of downstream targets of mTORC1 such as p70S6K) after RE in both animal and human models (4,15,16,20,22,49,51), and some studies have reported that muscle contraction-induced increases in muscle protein synthesis and subsequent muscle hypertrophy are almost fully dependent on the activation of mTORC1 within the skeletal muscle (17,23). On the other hand, AMP-activated protein kinase (AMPK), which is a key sensor of cellular energy status, is known to be partly responsible for skeletal muscle adaptations to EE training (31,38,66,67).…”