Contractile and nutritional modulation of human skeletal muscle protein synthesis

Resistance exercise and protein ingestion can act separately and synergistically to stimulate the rate of synthesis of new muscle proteins. The studies reported in this thesis investigated the effects of manipulating skeletal muscle contraction with and without protein ingestion on acute muscle protein synthetic responses. The muscle contraction protocols were aimed to induce muscle fatigue through manipulation of a variety of variables with the overarching thesis that fatigue was associated with recruitment of type II muscle fibres. In Study 1, resistance exercise was performed to failure at two distinct work intensities (30 and 90% of one repetition maximum, 1RM) and both protocols stimulated a similar acute increase in fasting rates of myofibrillar protein synthesis. However, the response only persisted (i.e. 24 h later) after the lower intensity, high volume exercise regimen. In Study 2, we extended these findings into a fed-state condition. Enhanced sensitivity of myofibrillar protein synthesis to protein feeding was apparent after ∼24 h of recovery, only after exercise performed until volitional fatigue. In another investigation we demonstrated that increasing the time that a loaded muscle was under tension resulted in a prolonged stimulation of myofibrillar protein synthesis rates after ∼24 h of recovery. Further, increasing the time under muscle tension affected the acute amplitude of mitochondrial protein synthesis as compared to an external work-matched control. However, the mitochondrial protein synthetic response was elevated in recovery, regardless of time under muscle tension. A separate study demonstrated that stable isotope infusion models that consist of either a single biopsy coupled with baseline enrichments from mixed plasma proteins and/or using crystalline tracer enriched protein drinks are both reliable approaches to calculate muscle protein fractional synthetic rates. In conclusion, the studies in this thesis demonstrate that manipulating load, exercise volume, and/or increasing the time that loaded muscle is under tension to induce fatigue are important variables that can be manipulated and can result in surprisingly robust stimulation of rates of muscle protein synthesis. In addition, certain contraction protocols enhanced the sensitivity of protein synthesis in the myofibrillar protein pool to protein feeding during longer-term exercise recovery. Importantly, many of these results were not seen in mixed muscle protein synthesis. Thus, the studies in this thesis demonstrate that studying the response at the muscle protein-fraction specific (i.e., mitochondrial, myofibrillar, sarcoplasmic) level is important to understand the true phenotypic response.