Muscle Protein Turnover and the Molecular Regulation of Muscle Mass during Hypoxia

It has been frequently reported that myostatin inhibition increases muscle mass, but decreases muscle quality (i.e., strength/muscle mass). Resistance exercise training (RT) and essential amino acids (EAAs) are potent anabolic stimuli that synergistically increase muscle mass through changes in muscle protein turnover. In addition, EAAs are known to stimulate mitochondrial biogenesis. We have investigated if RT amplifies the anabolic potential of myostatin inhibition while EAAs enhance muscle quality through stimulations of mitochondrial biogenesis and/or muscle protein turnover. Mice were assigned into ACV (myostatin inhibitor), ACV+EAA, ACV+RT, ACV+EAA +RT, or control (CON) over 4 weeks. RT, but not EAA, increased muscle mass above ACV. Despite differences in muscle mass gain, myofibrillar protein synthesis was stimulated similarly in all vs. CON, suggesting a role for changes in protein breakdown in muscle mass gains. There were increases in MyoD expression but decreases in Atrogin-1/MAFbx expression in ACV+EAA, ACV+RT, and ACV+EAA+RT vs. CON. EAA increased muscle quality (e.g., grip strength and maximal carrying load) without corresponding changes in markers of mitochondrial biogenesis and neuromuscular junction stability. In conclusion, RT amplifies muscle mass and strength through changes in muscle protein turnover in conjunction with changes in implicated signaling, while EAAs enhance muscle quality through unknown mechanisms.

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Resistance exercise and the mechanisms of muscle mass regulation in humans: Acute effects on muscle protein turnover and the gaps in our understanding of chronic resistance exercise training adaptation

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2013.07.005 ◽

2013 ◽

Vol 45 (10) ◽

pp. 2209-2214 ◽

Cited By ~ 18

Author(s):

A.J. Murton ◽

P.L. Greenhaff

Keyword(s):

Exercise Training ◽

Resistance Exercise ◽

Muscle Mass ◽

Protein Turnover ◽

Muscle Protein ◽

Acute Effects ◽

Resistance Exercise Training ◽

Muscle Protein Turnover ◽

Training Adaptation

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A Muscle-Centric Perspective on Intermittent Fasting: A Suboptimal Dietary Strategy for Supporting Muscle Protein Remodeling and Muscle Mass?

Frontiers in Nutrition ◽

10.3389/fnut.2021.640621 ◽

2021 ◽

Vol 8 ◽

Author(s):

Eric Williamson ◽

Daniel R. Moore

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Protein Turnover ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Insulin Response ◽

Intermittent Fasting ◽

Muscle Protein Turnover ◽

Healthy Humans ◽

Dietary Strategy

Muscle protein is constantly “turning over” through the breakdown of old/damaged proteins and the resynthesis of new functional proteins, the algebraic difference determining net muscle gain, maintenance, or loss. This turnover, which is sensitive to the nutritional environment, ultimately determines the mass, quality, and health of skeletal muscle over time. Intermittent fasting has become a topic of interest in the health community as an avenue to improve health and body composition primarily via caloric deficiency as well as enhanced lipolysis and fat oxidation secondary to attenuated daily insulin response. However, this approach belies the established anti-catabolic effect of insulin on skeletal muscle. More importantly, muscle protein synthesis, which is the primary regulated turnover variable in healthy humans, is stimulated by the consumption of dietary amino acids, a process that is saturated at a moderate protein intake. While limited research has explored the effect of intermittent fasting on muscle-related outcomes, we propose that infrequent meal feeding and periods of prolonged fasting characteristic of models of intermittent fasting may be counter-productive to optimizing muscle protein turnover and net muscle protein balance. The present commentary will discuss the regulation of muscle protein turnover across fasted and fed cycles and contrast it with studies exploring how dietary manipulation alters the partitioning of fat and lean body mass. It is our position that intermittent fasting likely represents a suboptimal dietary approach to remodel skeletal muscle, which could impact the ability to maintain or enhance muscle mass and quality, especially during periods of reduced energy availability.

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Skeletal and cardiac muscle protein turnover during cold acclimation in young rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.278.3.r705 ◽

2000 ◽

Vol 278 (3) ◽

pp. R705-R711 ◽

Cited By ~ 8

Author(s):

T. A. McAllister ◽

J. R. Thompson ◽

S. E. Samuels

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Cardiac Muscle ◽

Cold Acclimation ◽

Protein Turnover ◽

Muscle Protein ◽

Muscle Protein Turnover ◽

Protein Mass ◽

The Absolute

The effect of long-term cold exposure on skeletal and cardiac muscle protein turnover was investigated in young growing animals. Two groups of 36 male 28-day-old rats were maintained at either 5°C (cold) or 25°C (control). Rates of protein synthesis and degradation were measured in vivo on days 5, 10, 15, and 20. Protein mass by day 20 was ∼28% lower in skeletal muscle (gastrocnemius and soleus) and ∼24% higher in heart in cold compared with control rats ( P < 0.05). In skeletal muscle, the fractional rates of protein synthesis ( k syn) and degradation ( k deg) were not significantly different between cold and control rats, although k syn was lower (approximately −26%) in cold rats on day 5; consequent to the lower protein mass, the absolute rates of protein synthesis (approximately −21%; P < 0.05) and degradation (approximately −13%; P < 0.1) were lower in cold compared with control rats. In heart, overall, k syn(approximately +12%; P < 0.1) and k deg(approximately +22%; P < 0.05) were higher in cold compared with control rats; consequently, the absolute rates of synthesis (approximately +44%) and degradation (approximately +54%) were higher in cold compared with control rats ( P < 0.05). Plasma triiodothyronine concentration was higher ( P < 0.05) in cold compared with control rats. These data indicate that long-term cold acclimation in skeletal muscle is associated with the establishment of a new homeostasis in protein turnover with decreased protein mass and normal fractional rates of protein turnover. In heart, unlike skeletal muscle, rates of protein turnover did not appear to immediately return to normal as increased rates of protein turnover were observed beyond day 5. These data also indicate that increased rates of protein turnover in skeletal muscle are unlikely to contribute to increased metabolic heat production during cold acclimation.

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