teil 9 und ende
Effects of Resistance Training on the Response of Muscle Protein Turnover
Many of the muscle metabolic systems show adaptations with habitual physical activity. Whether habitual physical activity results in a chronically altered rate of muscle protein turnover is currently the subject of some interest. In diabetic rats trained to perform resistance exercise, Farrell and coworkers demonstrated a reduced response of MPS to exercise after training (161). However, obtaining a clear answer to this question for human muscle is difficult. First, the residual effects of a previous bout of exercise, which may last up to 72 h, depend on intensity. Second, there is the problem of the habitual dietary intake of athletes who are subjected to much marketing and coaching information suggesting that they need to eat large amounts of protein in order to maintain or build muscle mass; this is a problem because habitually high rates of dietary protein intake lead to the induction of amino acid catabolic enzymes (particularly of the branched chain and aromatic amino acids) that decrease the deposition of dietary protein (162, 163). Until this effect abates (after reducing protein intake), there will be a tendency to exhibit negative nitrogen balance, so studies should not be conducted with rapid variation in dietary protein contents.
There is, in fact, little data on the subject in respect to MPS or even muscle mass. Studies of military recruits undergoing intense physical training suggest that there is a loss of body protein over the first few days of training but that adaptation rapidly occurs and nitrogen balance is restored, all at the same rate of dietary protein intake (164). Butterfield & Calloway found that in young men undergoing physical training, exercise increased the efficiency of protein utilization (165), i.e., trained subjects would require less protein. Partial validation of this position was provided by the first of two studies by Phillips and colleagues (166, 167). When two groups of subjects, one strength-trained and the other sedentary, were compared, there were no differences in resting post-absorptive MPS or MPB; also when the post-exercise responses to a single bout of pleiometric exercise at 120% of each subjects concentric 1 RM were compared, the rise in MPS in the trained subjects was 50% less than in the sedentary group, and there was no rise in MPB, which increased by about 40% in the untrained group. Thus net muscle balance (MPS minus MPB) was improved to the same extent in each group. However, a different result was obtained in a second longitudinal study of the effects of 8 weeks of resistance training in young previously untrained men, studied in the fed state at rest and also after a bout of exercise at 80% of their pretraining 1 RM (166). These results suggested that there was no difference in the response of the subjects in the trained and untrained state to acute exercise; also, rather oddly, the trained subjects did now show a marked increase in MPB as a result of exercise. In addition, basal rates of MPS and MPB were in fact now higher in the trained state; one consequence of this was that the effect of training seemed to decrease the relative response to exercise, a result that was consonant with the earlier findingsbut by a different mechanism! All in all, the data on net balance suggest that there was no effect of training tending to confirm the settled views of the present authors (143, 148) (although resisted by many athletes, their trainers, and, of course, sports nutrition companies) that habitual physical activity imposes no greater demands on protein requirements. As Phillips and coworkers (166) point out in their discussion, they did not test whether the same relative workload might affect protein turnover in trained and untrained subjects: It may be that if the above longitudinal studies had been conducted at the same relative intensity, a different result might have been obtained.
In the elderly, the rejuvenating effect of training may confound the issue. There is considerable controversy about whether aging is associated with a fall in muscle protein turnover [see (168) for review of this topic, which will not be dealt with further here]. However if it is true that the frail (as opposed to healthy) elderly show a fall in MPS, as seems likely, then exercise training may normalize it (169). The mechanism may be by decreasing the amount of TNF- in muscle (170).
Effects of Creatine on Human Muscle Protein Turnover
Dietary supplements containing creatine have become popular with athletes and trainers hoping to promote greater increase in muscle mass and strength in resistance training programs (171173). Measurements of myofibrillar protein synthesis (as incorporation of 13C leucine) and forearm protein breakdown (as dilution of deuterated phenylalanine) were unable to discern any differences in subjects studied before and after creatine supplementation, either in the post-absorptive or the fed state, at rest, or immediately after acute exercise (174, 174a). These results appear to rule out any acute effect of creatine alone on translation of pre-existing mRNA or on MPB but do not invalidate the possibility of transcriptional changes or satellite cell activation stimulated by creatine and physical activity.
Effects of Intensity of Contraction and Metabolic Power Output on Muscle Protein Turnover
It seems clear that maneuvers resulting in a relatively rapid rise in muscle mass are all associated with substantial increases, albeit after a short latency, possibly of about one hour, in MPS as a result of translational stimulation produced by changes in 4E-BP1 and p70S6k phosphorylation (176). These changes are followed, probably shortly thereafter, by transcriptional changes associated with intense exercise. Thus questions of the extent and temporal pattern of disturbance need to be addressed.
In human muscle, our group (M.J. Rennie, D.J.R Cuthbertson, K. Esser & M. Fedele, unpublished work) consistently observe a long-lasting rise in p70S6k phosphorylation after acute, high-intensity exercise, with smaller transient rises in PKB (Akt) phosphorylation, which are associated with a consistent rise in incorporation of tracer-labeled amino acid into muscle protein, whether myofibrillar or sarcoplasmic. We find no difference in the extent of stimulation of p70S6k or MPS in different quadriceps in which the same amount of force is applied during stepping exercise (one leg up, one leg down, while carrying 20% of body weight) to exhaustion (81). Because concentric exercise is energetically much less efficient than eccentric exercise and normally requires a higher rate of ATP turnover, this suggests that the crucial factor in determining the extent of the rise of MPS is force or intensity rather than ATP turnover, unless there is some threshold effect beyond which the rise in MPS remains constant.
However, paradoxically, when ATP turnover and the extent of quadriceps motor unit recruitment is kept constant during exercise at 60, 75, and 90% of 1 RM for different numbers of repetitions, the stimulation of MPS is constant (175).
CONCLUSION
As we have seen, our current ability to describe the adaptive responses of skeletal muscle to a wide variety of circumstances with changes in mass, composition, and function is impressive. The time resolution of techniques for measuring changes in muscle mass and composition and rates of protein turnover have increased such that we can now make robust measurements of the time courses of, for example, the rate of myofibrillar protein synthesis, which was impossible 10 years ago. Much information about the interrelationships between signaling pathways, which are important for transcriptional and translational regulation, has been accrued, and we have a much better understanding of the importance of satellite cells for growth and regeneration of muscle. There are, however, a substantial number of gaps that need to be filled. We still have no clear idea of the temporal relationship between the components of amino acid sensing and signaling to the processes of protein synthesis and breakdown and how these are affected by individual amino acids, insulin, and IGF-1. The exact pathways by which anabolic and catabolic steroids affect gene transcription and translation of mRNA remain obscure in human muscle despite the existence of response elements predicted for the muscle genes; the commonality (if any) of the pathways between myofibers and satellite cells is not at all well understood. The nature of the dichotomy of the responses to short-term, high-intensity exercise leading to hypertrophy and long-term low-intensity exercise leading to mitochondriogenesis and fast-to-slow fiber type transition remains a mystery. We still require a good description of the dose-response relationship between exercise intensities and the observed changes in mass and protein composition, and until we have these, it will be difficult to sort out the relative contributions of signaling pathways, their commonality, additivity, or independence from each other in controlling the adaptive responses of muscle.
Nevertheless, the increasing power of post-genomic techniques, particularly the use of transcriptional profiling and subsequent bioinformatics, should enable us to identify previously unknown means of controlling transcriptional and translational events. Perhaps some time in the next 10 years, our view will suddenly snap into focus, and it will become obvious how, for example, changes in the concentrations of Ca2+ or AMP can modulate the size and shape of muscle.
(es folgen noch die ACKNOWLEDGMENTS und 176 literaturangaben. ich bitte um verständnis, wenn ich sie nicht mehr hieherkopiere. wenn jemand ein literaturzitat wissen will, kann er es mir ja mitteilen)
gruß, kurt
