Recent advances in understanding resistance exercise training-induced skeletal muscle hypertrophy in humans

Abstract

Skeletal muscle plays a pivotal role in the maintenance of physical and metabolic health and, critically, mobility. Accordingly, strategies focused on increasing the quality and quantity of skeletal muscle are relevant, and resistance exercise is foundational to the process of functional hypertrophy. Much of our current understanding of skeletal muscle hypertrophy can be attributed to the development and utilization of stable isotopically labeled tracers. We know that resistance exercise and sufficient protein intake act synergistically and provide the most effective stimuli to enhance skeletal muscle mass; however, the molecular intricacies that underpin the tremendous response variability to resistance exercise-induced hypertrophy are complex. The purpose of this review is to discuss recent studies with the aim of shedding light on key regulatory mechanisms that dictate hypertrophic gains in skeletal muscle mass. We also aim to provide a brief up-to-date summary of the recent advances in our understanding of skeletal muscle hypertrophy in response to resistance training in humans.

Keywords: hypertrophy; muscle; protein; resistance exercise.

Figure 1.. Current understanding of the relationship between exogenous and endogenous variables for skeletal muscle hypertrophy.

Appropriate exogenous stimuli are required to modulate endogenous variables related to muscle protein synthesis and induce skeletal muscle hypertrophy. Resistance exercise and nutrition variables such as dietary protein (especially leucine) as well as anabolic supplements are considered to be the most reliable exogenous variables for skeletal muscle hypertrophy. However, the red arrow-headed line and red dotted line illustrate that exogenous variables do not induce skeletal muscle hypertrophy independently of the endogenous variable modulation. Therefore, endogenous variables are affected by exogenous variables, such as modification to histones, transcription factors, satellite cells, and/or androgen receptor content, which are key determinants of skeletal muscle hypertrophy. The blue arrow-headed line describes the exogenous stimuli that must act through endogenous variables, as represented by thin blue lines, to induce skeletal muscle hypertrophy. Furthermore, depending on the extent of the endogenous variables’ response to exogenous stimuli, higher responders may have greater skeletal muscle hypertrophy compared to lower responders.

Figure 2.. Current understanding of changes in muscle protein turnover with chronic resistance exercise training.

Skeletal muscle hypertrophy can occur only under periods of positive protein balance: that is, when relative rates of muscle protein synthesis (MPS) (blue line) exceed that of muscle protein breakdown (MPB) (red line). In the fasted state, rates of MPB exceed those of MPS, resulting in a negative net protein balance (NPB). Compared to untrained individuals ( A), trained individuals ( B) display higher fasted rates of MPS; however, protein balance remains negative because of the concomitant elevation of MPB in the trained state. Regardless of training status, nutritional and contractile stimuli are potent regulators of MPS and, to a lesser extent, MPB. Resistance exercise (RE) stimulates increases in both MPS and MPB, and NPB remains negative. Ingestion of dietary protein—in particular, essential amino acids—in close temporal proximity to RE augments MPS and attenuates the exercise-induced increase in MPB, resulting in a temporary state of positive protein balance. Chronic RE training (RET) modulates the time course of the increase in MPS following a bout of RE. Specifically, the initial increase in MPS following a bout of RE is less pronounced in the untrained state than in the trained state; however, it is longer lived and peaks later in the untrained than the trained state. MPS, MPB, and NPB during periods of ( B) RE+Fasted and ( C) RE+Fed in the untrained and trained state.