Protein synthesis rates in response to exercise and β-adrenergic signaling in human skeletal muscle
Date
2011
Authors
Robinson, Matthew McHutcheson, author
Miller, Benjamin F., advisor
Pagliassotti, Michael J., committee member
Hamilton, Karyn L., committee member
Chicco, Adam J., committee member
Hickey, Matthew S., committee member
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Abstract
Skeletal muscle protein turnover is determined by the synthesis and degradation of skeletal muscle proteins and is the mechanism that determines skeletal muscle protein content. A loss of skeletal muscle mass and function occurs during aging (sarcopenia) due to a net imbalance between synthesis and degradation pathways. Mitochondrial protein turnover, a component of skeletal muscle protein turnover, is decreased with aging. A decline in mitochondrial protein turnover and subsequent decline in mitochondrial function is associated with the progression of chronic diseases associated with aging. Aging populations are commonly prescribed medications to combat age-related chronic diseases. Among commonly prescribed medications are β-adrenergic receptor blockers as anti-hypertensive therapy. Decreased β-adrenergic signaling may impair skeletal muscle adaptations to exercise, particular the mitochondrial fraction, and potentially diminish the benefits of exercise training on skeletal muscle protein synthesis. The regulation of post-exercise mitochondrial protein synthesis by β-adrenergic receptor signaling is not well known in humans. Protein consumption following exercise induces net synthesis of skeletal muscle proteins in younger populations, however the effect appears to be blunted with aging and likely lead to sarcopenia. The net positive protein synthesis following exercise with protein feeding occurs for several hours and may be effective therapy for age-related declines in skeletal muscle mass, yet it is not known whether these short increases will persist over longer periods. The overall objective of our three projects was to investigate the regulation of skeletal muscle protein synthesis in response to exercise, protein consumption, and β-adrenergic signaling in humans. We tested the hypothesis that β-adrenergic signals can regulate mitochondrial biogenesis by examining non-selective β-adrenergic stimulation during resting conditions (Experiment #1) and non-selective β-adrenergic blockade during aerobic exercise (Experiment #2). Furthermore, we tested the hypothesis that protein consumption following exercise can promote skeletal muscle protein synthesis over several weeks of aerobic training (Experiment #3). We used stable isotopic methods to determine rates of skeletal muscle protein synthesis including analysis of the mitochondrial fraction as a measure of mitochondrial biogenesis. Additional measures of mitochondrial biogenesis included mitochondrial DNA content and mRNA content of signaling pathways for mitochondrial adaptations. Deuterium labeling over several weeks was used to measure the synthetic rates of skeletal muscle proteins and DNA during aerobic training. Experiment #1 involved examining the short-term response of skeletal muscle protein synthesis and mitochondrial biogenesis following infusion of a non-selective β-adrenergic agonist. We found that non-selective β-adrenergic activation did not increase skeletal muscle synthesis, whole body protein turnover, or measures of mitochondrial biogenesis. Experiment #2 included investigation of the short-term response of skeletal muscle protein synthesis following infusion of a non-selective β-adrenergic antagonist during a one-hour bout of cycling. Mitochondrial protein fractional synthesis rates were decreased following cycling with non-selective β-adrenergic blockade, yet signals for mitochondrial biogenesis were not different compared to a saline control infusion. Experiment #3 included evaluating the ability for post-exercise protein consumption during aerobic training to stimulate long-term measures of multiple skeletal muscle synthetic processes. We determined that consuming protein compared to carbohydrates after exercise did not lead to differences in protein synthesis or mitochondrial DNA content over several weeks. Interestingly, we measured the amount of newly synthesized DNA in skeletal muscle to be ~5%. Skeletal muscle does not undergo regular cell division, therefore the DNA synthesis was higher than expected. It is likely that the DNA synthesis is due to satellite cell activation. We conclude that β-adrenergic signaling during exercise is a signal for mitochondrial protein synthesis in skeletal muscle. Additionally, the ability for protein consumption following exercise to increase protein synthesis over several hours does not lead to long-term increases in protein synthesis. Collectively, these results provide insight into the regulation of skeletal muscle protein turnover with exercise and β-adrenergic signaling. Understanding potential negative drug and exercise interactions can help improve future therapeutic recommendations for healthy aging.
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Subject
deuterium oxide
stable isotope
protein synthesis
exercise
mitochondria
aging