Mechanisms underlying the regulation of human skeletal muscle protein turnover by omega-3 fatty acids.

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Skeletal muscle is a critical organ serving as a major contributor to whole-body metabolism and provides the necessary force to support movement and breathing. The size of skeletal muscle is underpinned by changes in rates of muscle protein synthesis (MPS) and rates of muscle protein breakdown (MPB). When MPS exceeds MPB skeletal muscle will grow (hypertrophy) and when MPB exceeds MPS skeletal muscle will reduce in size (atrophy). Both MPS and MPB are energetically expensive processes utilizing energy produced in the mitochondria. However, the cellular and molecular mechanisms that integrate the regulation of MPS, MPB, and mitochondrial energy production in humans remains largely unknown. What is known is that MPS and MPB are sensitive to contractile activity and nutrition. Resistance exercise and protein feeding increase MPS with repeated bouts of resistance exercise and protein feeding leading to skeletal muscle hypertrophy. Endurance exercise will also stimulate MPS and over time lead to increased mitochondrial protein content. Conversely, we have recently shown that a period of muscle-disuse reduces MPS initiating in a decline in mitochondrial protein content, and skeletal muscle atrophy even when protein intakes are above the recommended dietary allowance. Intriguingly, our recent work has shown that the provision of omega-3 fatty acids, commonly known as fish oils, protect against declines in rates of MPS, mitochondrial protein content, and skeletal muscle size during a period of muscle-disuse by unidentified mechanism(s). The overarching aim of my research program is to build on my previous work to understand the biological mechanisms that mediate the anabolic influence of omega-3 fatty acids on skeletal muscle in women and men. This work will employ a range of biochemical techniques including isotopic labelling of skeletal muscle proteins, measurement of mitochondrial respiration kinetics, and assessment of changes in gene expression and protein kinase activity. Specifically, I will utilize exercise and muscle-disuse to disrupt rates of MPS, and MPB following a period of omega-3 fatty acid feeding and probe for changes in anabolic signalling molecules to pinpoint mechanistic actions of omega-3 fatty acids in skeletal muscle. The work proposed in this Discovery Grant will have a number of implications for Canadian research and innovation. Primarily, the knowledge gained will deliver a basic, mechanistic understanding of how omega-3 fatty acid exposure influences the regulation of human skeletal muscle mass. In turn, this new knowledge may be applied in the development of therapies to reduce muscle wasting, enhance muscle size, and combat disorders associated with metabolic dysfunction in humans. Lastly, this program of work will serve as a training vehicle for a number of HQP that will acquire a unique and cross-disciplinary skillset ready to be deployed in either the academic or private sector.