Anabolic Resistance of Muscle Protein Turnover Comes in Various Shapes and Sizes

Abstract

Anabolic resistance is defined by a blunted stimulation of muscle protein synthesis rates (MPS) to common anabolic stimuli in skeletal muscle tissue such as dietary protein and exercise. Generally, MPS is the target of most exercise and feeding interventions as muscle protein breakdown rates seem to be less responsive to these stimuli. Ultimately, the blunted responsiveness of MPS to dietary protein and exercise underpins the loss of the amount and quality of skeletal muscle mass leading to decrements in physical performance in these populations. The increase of both habitual physical activity (including structured exercise that targets general fitness characteristics) and protein dense food ingestion are frontline strategies utilized to support muscle mass, performance, and health. In this paper, we discuss anabolic resistance as a common denominator underpinning muscle mass loss with aging, obesity, and other disease states. Namely, we discuss the fact that anabolic resistance exists as a dimmer switch, capable of varying from higher to lower levels of resistance, to the main anabolic stimuli of feeding and exercise depending on the population. Moreover, we review the evidence on whether increased physical activity and targeted exercise can be leveraged to restore the sensitivity of skeletal muscle tissue to dietary amino acids regardless of the population.

Keywords: chronic kidney disease; dietary protein; exercise; obesity; sarcopenia.

Figure 1

Schematic of muscle protein synthesis rates (MPS) in the basal and postprandial states. Eating a protein meal generally results in a ~2-fold increase in the stimulation of postprandial MPS from basal in healthy muscle. However, a reduced responsiveness of postprandial MPS, or anabolic resistance, to elevated plasma amino acid availability has been detected in older, obese, and adults on maintenance hemodialysis (MHD) (, , –13). Muscle disuse is also a common facilitator of anabolic resistance. Hemodialysis patients have been studied on both dialysis and non-dialysis days. Despite peak inflammation (and presumably catabolism) during dialysis, MPS has been shown to be responsive to intravenous elevation of amino acid availability. However, skeletal muscle is overstimulated in the post-absorptive state on a non-dialysis day, which is associated with inflammation and uremic toxins, to induce overt anabolic resistance. Green indicates “healthy” fed-state MPS response, red indicates anabolically resistant fed-state MPS response. ND, non-dialysis day; ID, intra-dialytic.

Figure 2

Anabolic resistance of muscle protein synthesis rates (MPS) to dietary amino acids exists as a dimmer switch from low to higher levels. Healthy aging muscle has been shown to be quite responsive to the combined stimuli of feeding and exercise in terms of an MPS response (17), but in absence of prior exercise anabolic resistance is detectable (46). Decreasing the physical activity level, which is perhaps exacerbated further when combining increased sedentary behaviors, increases the level of anabolic resistance on MPS (67). Similarly, obesity increases the level of anabolic resistance, regardless of age (3, 74), with the highest level of anabolic resistance on MPS existing in highly catabolic conditions such as end-stage renal disease (4).