Metabolic and molecular basis for adaptation to resistance-type exercise Flashcards
-What is resistance (type) exercise, and what are the major adaptations it elicits? Why is it critical for us to understand how resistance training leads to adaptation? -What are the responses to a single bout of resistance-type exercise at different levels of physiology: o Physiological (protein metabolism) o Cellular (cellular protein turnover and role of satellite cells) o Molecular (anabolic signalling pathways) -How do these acute responses accumulate into adaptation?
Why do we resistance train?
o Bone mineral density increase
o Increased insulin sensitivity
o Increased brain health
Who (should?) resistance train(s)?
o We know that it is important for health, as those who are stronger typically live longer and healthier lives.
o As well as improving our health, people train to become more aesthetic
o Game related sports require strength and power.
What are the major adaptations to resistance training?
o Hypertrophy of muscle
o Tendon adaptations
o Cardiac adaptations
How does resistance exercise tip the balance? (MPS/MPB)
o 1-2 % per day (300-600 g muscle tissue) (0.04 – 0.14 %.h-1) without resistance training
o Following resistance training? 2-3 % per day (600-900 g muscle tissue)
How is protein metabolism affected by training status?
Fundamental physiological process by which muscle (and other tissues) grow and strengthen is improved protein balance, mainly driven by increased muscle protein synthesis. The latter is achieved by the synergy between the potent effect of a single bout of resistance exercise, and the consequent sensitisation of tissue to the (in comparison more mild) anabolic effects of nutrition.
So what is protein synthesis?
Key is to remember this happens with every single protein! We can talk about individuals proteins (~molecular biology) We can talk about groups of proteins (~physiology)
How is protein synthesis regulated?
Transcription:
• within the genome (nucleus) an mRNA chain is generated from from the DNA using RNA polymerase with each protein being regulated by different transcription factors.
• the single stranded mRNA then migrates from the nucleus into the cytoplasm.
Translation:
• Translation takes place in the cytoplasm where the ribosomes exist
• The specific mRNA is then decoded to form a sequence of amino acids as a polypeptide/protein
• Three steps: 1) Initiation (initiation factors allow the ribosome subunit to bind to the mRNA) 2) Elongation (refers to the tRNA binding to the ribosome) 3) Termination (when a stop codon forces the ribosome to release the polypeptide)
What is mTOR signalling?
Mammalian/mechanistic target of rapamycin
Serine/threonine kinase of the phosphatidylinositol kinaserelated kinase family
Expressed in all cell types
Discovered in the 1990s by utilising the drug rapamycin
A complex of proteins including 2 major subgroups: mTORC1 and mTORC2.
Major regulator of cell growth and proliferation.
What is the significance of mTOR signalling to in vivo human physiology research?
mTOR is activated in animal and human skeletal muscle following resistance exercise or nutritional stimuli
mTOR clearly associated with resistance exercise?
o Rapamycin blocks mTOR and MPS in response to amino acid or exercise stimuli in rodents
o Rapamycin is capable of blocking hypertrophy without affecting atrophy in rodents
How do we establish causality of a single protein kinase? Ablation? Stimulation?
Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis.
A phosphatidylinositol 3-kinase/protein kinase B-independent activation of mammalian target of rapamycin signalling is sufficient to induce skeletal muscle hypertrophy.
Regulation of mTOR
o Akt/IGF1?
Overexpression of Akt in mice leads to huge hypertrophy (Bodine et al., 2001).
Can be activated independently by insulin (Greenhaff at al., 2008) and other studies also show a disassociation between Akt, mTOR and protein synthesis (e.g. Wilkinson et al., 2008, Drummond et al., 2009, Timmerman et al., 2010)
IGF1 is increased in blood with exercise, but its knockout doesn’t prevent hypertrophy.
o EAA/Leucine?
Certainly activates mTOR in vitro and in vivo but (alone) does not translate to long term gains in muscle mass (Leenders et al., 2011)
o Contraction?
Most potent stimulus for protein synthesis and hypertrophy but how does contraction regulate mTOR ? FAK? AMPK? ERK/MAPK? Also there is a disassociation between mTOR signalling and type of exercise (Wilkinson et al., 2008).
Also, without nutrition, translation initiation/protein synthesis cannot be fully activated (Koopman et al., 2005)
Are satellite cells (and their regulation) critical to muscle growth with resistance training?
o Essential for myofiber maintenance
o Essential for muscle growth, repair, regeneration
Mixed muscle protein synthesis and breakdown after resistance exercise in humans (Phillips et al., 1997)
We conclude that exercise resulted in an increase in muscle net protein balance that persisted for up to 48 h after the exercise bout and was unrelated to the type of muscle contraction performed.
Rapamycin administration in humans blocks the contraction induced increase in skeletal muscle protein synthesis (Drummond et al., 2009)
We conclude that mTORC1 signalling is, in part, playing a key role in regulating the contraction‐induced stimulation of muscle protein synthesis in humans, while dual activation of mTORC1 and ERK1/2 stimulation may be required for full stimulation of human skeletal muscle protein synthesis.
