Maximal lengthening contractions induce different signaling responses in the type I and type II fibers of human skeletal muscle

Abstract

The molecular mechanisms by which resistance exercise enlarges muscle mass, particularly the mass of fast-twitch type II fibers, are likely to involve enhanced phosphorylation/activation of key enzymes regulating protein synthesis. The hypothesis is that resistance exercise influences the phosphorylation of such key signaling proteins to a greater extent in type II than in type I fibers. Six recreationally active male subjects performed four sets of six maximal lengthening contractions with one leg. Muscle biopsies were taken from the vastus lateralis before and immediately after exercise and following 1 and 2 h of recovery. Samples were freeze-dried, and individual muscle fibers were dissected out and identified as type I or type II after staining for myosin ATPase. Phosphorylation of p70(S6k) on Thr(389) and S6 in type II fibers was increased three-to fourfold and six- to ninefold (P < 0.05), respectively, 1 and 2 h after exercise, whereas phosphorylation in type I fibers remained unchanged. Phosphorylation of Akt, mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) was unaltered in both fiber types, whereas that of eukaryotic elongation factor 2 (eEF2) was attenuated 20-45% (P < 0.05) in type II fibers during recovery. Phosphorylation of ERK1/2 was elevated six- to sevenfold (P < 0.05) immediately after exercise, and p38 MAPK phosphorylation was increased three- to fourfold (P < 0.05) for as long as 1 h after exercise in both types of fibers, although the level was markedly higher in type II fibers (P < 0.05). In conclusion, the elevation of p70(S6k) and the reduction of eEF2 phosphorylation in the type II fibers following resistance exercise suggest stimulation of protein synthesis, which may contribute to a more pronounced enlargement of these fibers. Our findings also suggest that p70(S6k) is activated, at least in part, via pathways not involving Akt-mTOR and MAPK.

Effects of time of day on resistance exercise-induced anabolic signaling in skeletal muscle

“…p38 MAPK is responding to both anabolic (e.g., muscle cell stretch, functional overload) and catabolic stimuli (e.g., tumor necrosis factor α) (21,27,44). In the present study, phosphorylated p38 MAPK was elevated after the resistance loading in line with previous reports in humans (4,19,39,41). Interestingly, these changes, when expressed as groups' means were greater in the morning compared to the afternoon in the present study.…”

“…Previous reports on humans have shown increases (e.g., (8), decreases (7,40) but majority of studies reported no change in Akt phosphorylation after exercise (1,11,18,39,41). It can be speculated that low muscle glycogen levels decrease resistance exercise response of Akt phosphorylation (5), and may be thus the reason for the lack of Akt responses in some individuals in the morning in the present study.…”

Cachexia in chronic obstructive pulmonary disease: new insights and therapeutic perspective

“…showed a difference in anabolic response between type‐I and type‐II muscle fibres, with increased AKT phosphorylation and downstream pathway activation in the type‐II fibres 69. In contrast, in COPD, the respiratory muscle with a shift towards more type‐I fibres displayed a larger AKT activation and downstream signalling than the limb muscles with a shift towards more type‐II fibres.…”

Signaling Pathways that Mediate Skeletal Muscle Hypertrophy: Effects of Exercise Training

“…Moreover, differences in type I and type II fibers activated in force development influence the phosphorylation of these key signaling proteins [32,46,47].…”