Recent Advances in the Characterization of Skeletal Muscle and Whole-Body Protein Responses to Dietary Protein and Exercise during Negative Energy Balance.

In a review published in 2012, we concluded that higher-protein diets preserve muscle mass during energy deficit via stimulated mammalian target of rapamycin complex 1 signaling, coincident increased muscle protein synthesis (PS), inhibited ubiquitin-mediated proteolysis, and suppressed muscle protein breakdown (PB). Since then, there have been significant advances in understanding the fundamental effects of higher-protein diets, with or without exercise training, on muscle and whole-body protein homeostasis during negative energy balance. Therefore, an update on the evolution of this field of research is warranted to better inform recommendations on best practices for healthy weight loss and muscle preservation. We will review the most recent studies examining the effects of higher-protein diets and negative energy balance on body composition, muscle PS, muscle PB, associated intracellular regulatory pathway activities, and whole-body protein homeostasis. In addition to critically analyzing contemporary findings, knowledge gaps and opportunities for continued research will be identified. Overall, the newest research confirms that consuming higher-protein diets, particularly when coupled with resistance exercise, preserves muscle mass and maintains whole-body protein homeostasis during moderate energy deficits (i.e., normal weight loss). However, these newer findings also indicate that as the magnitude of energy deficit increases, the efficacy of higher-protein diets for mitigating losses of fat-free mass is diminished. Further, recent results suggest that alterations in muscle PS, more so than muscle PB, may be primarily responsible for changes in muscle mass that occur in response to negative energy balance.