Korean J Sports Med.  2022 Sep;40(3):151-169. 10.5763/kjsm.2022.40.3.151.

From Barbells to Brawns: The Physiology of Resistance Exercise and Skeletal Muscle Growth

• Park J
• Mcllvain V
• Rosenberg J
• Donovan L
• Desai P
• Kim JY

• KMID: 2532893
• DOI: http://doi.org/10.5763/kjsm.2022.40.3.151

Abstract

A complex network of biochemical pathways carries out the process of muscle regeneration/growth following resistance exercise. The initial inflammatory response following muscle damage is primarily mediated by the nuclear factor κ -light-chain-enhancer of activated B cells (NF-κ B), cyclooxygenase enzymes, and prostaglandins. Muscle damage also stimulates the activation, proliferation, differentiation, migration, and fusion of satellite cells onto damaged myofibers, resulting in myofibrillar hypertrophy. The progression of the myogenic lineage is predominantly coordinated by the wingless/integrated family of glycoproteins which engages in crosstalk with NF-κ B and the mitogen-activated protein kinase (MAPK)/extracellular signaling-regulated kinase network. The MAPK cascade is essential for mechanotransduction, the process of converting mechanical stimuli into biochemical responses such as accelerated protein synthesis and satellite cell activation. Muscle protein synthesis is primarily governed by the insulin-like growth factor 1/phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway. Several calcium-dependent pathways are also integrated into the process of myogenesis and influence skeletal muscle plasticity. These dynamic interactions are part of the anabolic priming by resistance exercise effect, which defines resistance exercise as an acute catabolic event that potentiates multiple downstream anabolic pathways. Plateaus in muscle growth are attributed to deteriorating inflammatory signaling with repeated bouts of muscle damage as well as increasing thresholds for continuous adaptations, which ultimately become unreachable beyond a certain point. The physiological ceiling of skeletal muscle mass is also credited to myostatin. However, recent discoveries suggest the role of myostatin is not limited to preventing excessive skeletal muscle hypertrophy.

Keyword

Resistance training; Skeletal muscle satellite cells; Myostatin

Figure

• 

  Fig. 1 The biochemical transduction of resistance exercise. Resistance exercise stimulates calcium mobilization, AMPK and Wnt signaling, and growth hormone release while also causing metabolic stress, mechanical tension, and muscle damage. Crosstalk between the Wnt, MAPK (particularly the JNK subpathway), and NF-κB pathways coordinates satellite cell activation and the subsequent myonuclear accretion. It is suggested that the retention of such myonuclei is responsible for the muscle memory phenomenon. The MAPK pathway also increases fatty acid oxidation to improve body composition. Growth hormone causes the release of multiple pro-IGF-1s, while mechanical tension preferentially upregulates the MGF isoform. Pro-IGF-1s exert their own independent effects, while generating E-peptides and mature IGF-1. IGF-1, insulin, nutrients/amino acids, and other growth factors can stimulate the Akt/mTOR pathway. mTOR induces MPS and blocks FOXO signaling to inhibit MPB. Food ingestion demarcates a critical early checkpoint in the postexercise recovery period and is responsible for providing adequate nutrients as well as a stimulus for insulin secretion. AMPK signaling during exercise activates autophagic processes necessary for health and longevity. As part of the anabolic priming by resistance exercise effect, AMPK also abruptly inhibits mTOR and enhances insulin sensitivity, hyper-sensitizing the cell to anabolic stimuli during the subsequent postexercise recovery period. Metabolic stress during exercise causes skeletal muscle perfusion, defined as a transient increase in muscle blood flow and thickening of the sarcoplasm and/or sarcolemma. Like the insulin/mTOR sensitizing effect of AMPK, increased muscle blood flow promotes nutrient uptake and primes downstream anabolism via spatial priming. The combination of myonuclear accretion, MPS, and spatial priming yields myofibrillar hypertrophy. This increase in contractile tissue mass, in addition to increased glycogen synthesis via Wnt inhibition of GSK3-β, enhances insulin sensitivity and optimizes nutrient partitioning in the long-term. Exercise-induced calcium mobilization activates calcium-dependent pathways. In turn, transcription factors, such as NFAT and MEF2, induce transcriptional activity. Calcium signaling also promotes oxidative adaptations. The combination of optimized nutrient partitioning (i.e., larger/more receptive glycogen stores), increased contractile tissue mass, and oxidative adaptations results in greater exercise capacity. Thus, performance improvements are demonstrated in resistance training. Continuous skeletal muscle anabolism is limited by myostatin and the depletion of AA. However, these factors also appear to be attributed to the maintenance of tendon integrity and the anti-inflammatory effects of exercise, respectively. In summary, several interrelated routes govern skeletal muscle adaptations following resistance exercise. Note: Some relationships and signaling pathways are not shown for the purpose of simplicity. AMPK: AMP-activated protein kinase, MAPK: mitogen-activated protein kinase, JNK: c-Jun N-terminal kinase, NF-κB: nuclear factor κ-light-chain-enhancer of activated B cells, IGF-1: insulin-like growth factor 1, MGF: mechano growth factor, mTOR: mammalian target of rapamycin, MPS: muscle protein synthesis, FOXO: forkhead box O, MPB: muscle protein breakdown, GSK3-β: glycogen synthase kinase 3-β, NFAT: nuclear factor of activated T cells, MEF2: myocyte-enhancing factor 2, AA: arachidonic acid.

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