Genetic Factors and Nutritional Influences on Muscle

Genetic Factors and Nutritional Influences

  • Exercise upregulates gene expression of genes encoding proteins in skeletal muscle, meeting exercise demands.
  • Nutrition alters gene expression at rest and with exercise.
  • Low glycogen and high-fat diets enhance mRNA content of genes involved in exercise metabolism (e.g., AMPK pathway, mitochondrial biogenesis).

Muscle Loss

  • Inactivity, anabolic resistance, and inflammation are underlying causes of muscle mass loss.
  • The relative importance of each cause varies with the condition.
    • Inactivity plays a large role in age-related sarcopenia.
    • Inflammation plays a large role in acute, rapid wasting disorders (sepsis, cancer).
  • Age-related sarcopenia is a gradual decline, while acute wasting disorders lead to rapid muscle loss.
  • Maintaining muscle integrity during aging is crucial, intervening early (40-50s) to prevent later-life problems.

mTOR Pathway and Muscle Protein Synthesis

  • mTOR plays a key role in integrating the stimulating effects of amino acids, insulin, and muscle contraction on muscle protein synthesis.
  • Amino acids upregulate mTOR. Insulin can upregulate through PI3K and the AKT pathway. Resistance training can as well through the AKT pathway.
    • Resistance training can also block TORC signaling one and two, which if it's phosphorylated will have negative impacts on mTOR.
  • The process increases translational machinery and initiation, resulting in net muscle protein synthesis.

Muscle Protein Balance

  • In a fed state (adequate amino acids, especially leucine, and carbohydrates), muscle protein synthesis increases.
  • In a fasted state, muscle protein degradation occurs.
  • Ideally, synthesis and degradation balance, maintaining stable muscle protein.
  • Impaired synthesis and increased degradation lead to net muscle protein loss.

Impact of Resistance Training

  • Under healthy conditions, resistance training with adequate nutrition further increases muscle protein synthesis in the fed state.
  • It also attenuates muscle protein loss in the fasted state.
  • Even with impaired muscle protein synthesis (e.g., aging), resistance exercise can still increase synthesis and reduce degradation.
  • Adequate nutrition and resistance exercise can offset or attenuate muscle loss with aging.

mTOR Pathway Activation

  • Leucine is crucial for upregulating mTOR, as are the effects of insulin and insulin-like growth factor 1.
  • This results in protein synthesis and ribosome biogenesis.

Factors Influencing mTOR

  • Appropriately programmed resistance training stimulates the AKT pathway.
  • Excessive endurance activity activates the AMPK pathway.
  • Hypoxia phosphorylates REDD1/2 and inhibits TORC1/2, negatively impacting mTOR.
  • Leucine & insulin positively impact mTOR.
  • Energy availability (ATP, glycogen) impacts AMPK.

ERK Signaling Pathway

  • Contraction affects the ERK signaling pathway, related to work and fuel sensing.
  • Resistance training and appropriate insulin/IGF-1 activate the AKT pathway, positively affecting mTOR signaling & protein synthesis.

Timing of Nutrient Ingestion

  • Nutrient ingestion after resistance exercise results in the greatest muscle protein synthesis rate.
  • The timing of nutrient intake relative to resistance training is important.

Systemic Factors

  • Glucose, glycogen, insulin, and lipids affect cellular pathways, leading to hypertrophy and mTOR activation.
  • Amino acids also play a role.

Gene Expression Time Course (Hawley, 2006)

  • Acute exercise increases cytosolic and mitochondrial calcium and Na+/K+ pump activity; decreases phosphocreatine (PCr) and increases AMP.
  • Within minutes, metabolic and mechanical activation of key kinases/phosphatases occurs (AMPK, MAP kinases).
  • Within hours, mRNA expression of transcription factors promotes mitochondrial biogenesis and myogenesis.
  • Within hours to days, increased expression of genes encoding mitochondrial and myogenic proteins and increased satellite cell proliferation/differentiation occur.
  • Within days to weeks, increased protein expression and assembly of respiratory complexes occur.

Training, Diet, and mRNA Expression

  • Both training and diet impact mRNA expression and protein synthesis.

Omega-3 Fatty Acids

  • Omega-3 fatty acids may have roles in muscle protein fractional synthesis rate.
  • Mixed muscle protein fractional synthesis rate was increased with the supplementation of omega-three fatty acids compared to corn oil.
  • Omega-3 fatty acids increase mTOR and p70S6K phosphorylation compared to corn oil.
  • Supplementation (e.g., 4g Lovaza/day with 1.86g EPA and 1.5g DHA for eight weeks) increases muscle protein fractional synthesis rate and omega-3 PUFA concentration.
  • Omega-3 PUFAs enhance anabolic processes.
  • There was significant improvement after the supplementation period with omega-three fatty acids.

Omega-3s and Inflammation

  • Omega-3s have anti-inflammatory effects, competing with arachidonic acid for eicosanoid production.
  • They can reduce joint pain.
  • Omega-3s may offer athletes an alternative to NSAIDs, which impair muscle protein synthesis.

Key Takeaways

  • Review DNA components, transcription, and translation.
  • Understand the heritability and trainability of athletic traits.
  • Review how genes dictate responses to strength and endurance training.
  • Understand how genes and polymorphisms relate to muscle growth, power, and endurance (e.g., ACTN3).
  • Exercise and nutrition impact gene expression and cell signaling.
  • Omega-3 supplementation can positively impact muscle protein synthesis.