Investigating the Combined Effect of Acute Energy Deficit and Aerobic Exercise Training on Muscle Quality in Healthy Adult Males

Justification for the research:

Weight-loss strategies that use energy restriction alone can lead to impaired muscle mass, which can also further impair health of individuals with metabolic conditions, such as type 2 diabetics. Skeletal muscle mass and function are key to maintaining a healthy metabolism and quality of life throughout the lifespan. The combination of exercise and calorie restriction is a powerful intervention for reducing body weight and improving the metabolism and health status of healthy, overweight and obese individuals. The investigators have previously shown that skeletal muscle protein synthesis is reduced with energy restriction and that resistance-type exercise can reverse this negative effect. Aerobic-type exercise also has the capacity to stimulate muscle protein synthesis and improve the quality of muscle by increasing mitochondrial protein synthesis. Nonetheless, how energy deficit overlayed on top of aerobic exercise modulates skeletal muscle quality is not well characterised. Furthermore, existing studies have looked only into mixed (unspecific) protein synthesis of different intracellular compartments without providing details on how protein synthesis for specific proteins is regulated.

This project will provide novel data to unravel the mechanisms behind the positive effect of energy restriction and concomitant aerobic exercise on skeletal muscle quality.

Aerobic exercise alone is a well-established intervention to increase mitochondrial capacity and skeletal muscle function, but the effect on skeletal muscle of overlaying energy restriction while performing aerobic exercise is not well characterised. Recent findings in Rhesus monkeys, whose physiology responds in a very similar way to that of humans, has shown that life-long caloric restriction has a profound positive effect on skeletal muscle. These findings show that caloric restriction not only maintains contractile content of muscle, but also rescues the age-related decline of skeletal muscle mitochondrial content and capacity. However, physical activity in this study was not controlled and appeared to be higher in the caloric restriction group, representing an important confounding factor. Research in humans addressing similar questions so far has been less clear. Pronounced weight loss through energy restriction alone (10% total body weight in ~7.5 wk) in obese women lead to a decrease in muscle mitochondrial content. In stark contrast, using a milder restriction of 25% of total energy alone or combined with exercise during 6 months in overweight individuals showed increased expression of genes encoding mitochondrial proteins in both groups. However, despite these promising findings suggesting that weight-loss combined with exercise will enhance skeletal muscle metabolism, there are currently no strong data to provide support on the use of concomitant energy restriction and aerobic exercise with in-depth analysis of its physiological and molecular effects in humans.

The proposed study herein will include a short period of tightly controlled exercise and dietary intake to show that energy deficit while performing aerobic exercise results in further benefits to muscle metabolic adaptation. The current project builds on from the investigator's previous and recent research findings to directly address this question. This research has shown that resistance exercise during 30% daily energy deficit rescues the decrease in mixed (unspecific) myofibrillar protein synthesis observed with energy deficit alone. Moreover, the investigator's research has shown that aerobic exercise up-regulates specific proteins in skeletal muscle mitochondria in rodents; that skeletal muscle lipid droplet profile is responsive to exercise and nutrition; that nutrition modulates the cellular response to aerobic exercise and, importantly; that aerobic exercise after short-term (~14 hours) energy deficit can up-regulate markers of mitochondrial biogenesis in skeletal muscle and improve metabolic control in humans.