Skeletal muscle responses to negative energy balance: effects of dietary protein

Abstract

Sustained periods of negative energy balance decrease body mass due to losses of both fat and skeletal muscle mass. Decreases in skeletal muscle mass are associated with a myriad of negative consequences, including suppressed basal metabolic rate, decreased protein turnover, decreased physical performance, and increased risk of injury. Decreases in skeletal muscle mass in response to negative energy balance are due to imbalanced rates of muscle protein synthesis and degradation. However, the underlying physiological mechanisms contributing to the loss of skeletal muscle during energy deprivation are not well described. Recent studies have demonstrated that consuming dietary protein at levels above the current recommended dietary allowance (0.8 g · kg(-1) · d(-1)) may attenuate the loss of skeletal muscle mass by affecting the intracellular regulation of muscle anabolism and proteolysis. However, the specific mechanism by which increased dietary protein spares skeletal muscle through enhanced molecular control of muscle protein metabolism has not been elucidated. This article reviews the available literature related to the effects of negative energy balance on skeletal muscle mass, highlighting investigations that assessed the influence of varying levels of dietary protein on skeletal muscle protein metabolism. Further, the molecular mechanisms that may contribute to the regulation of skeletal muscle mass in response to negative energy balance and alterations in dietary protein level are described.

Conflict of interest statement

Author disclosures: J. W. Carbone, J. P. McClung, and S. M. Pasiakos, no conflicts of interest.

Figures

Figure 1

In response to negative energy balance, mRNA translation and muscle protein synthesis may be down-regulated as a result of decreased nutrient and growth factor availability, causing reduced mTORC1 activation. Decreased mTORC1 activation and subsequent decreases in muscle protein synthesis, coupled with increased FOXO nuclear localization, increased transcription of atrophy-related genes, with up-regulated caspase 3 activation and muscle protein ubiquitylation provide a possible mechanism contributing to skeletal muscle loss in response to periods of negative energy balance. Synthetic stimulators are depicted in gray, whereas inhibitors of synthesis are shown in black. Akt, protein kinase B; AMPK, AMP-activated protein kinase; eEF2, eukaryotic elongation factor 2; eEF2K, eukaryotic elongation factor 2 kinase; eIF4E-BP1, eukaryotic translation initiation factor 4E-binding protein 1; FOXO, forkhead box O; IRS-1, insulin receptor substrate 1; MAFbx, muscle atrogin F-box protein; mTORC1, mammalian target of rapamycin complex 1; MuRF1, muscle RING-finger protein 1; p70S6K, 70-kDa S6 kinase; PI3K, phosphatidylinositol 3-kinase; Rheb, ras homolog enriched in brain; rpS6, ribosomal protein S6; TSC, tuberous sclerosis complex; Ub, ubiquitin.