Metabolic and molecular basis for adaptation to endurance-type exercise Flashcards
-What is endurance (type) exercise, and what are the major adaptations it elicits? Why is it critical for us to understand how endurance training leads to adaptation? -What are the responses to endurance-type exercise at different levels of physiology: o Physiological (e.g. aerobic capacity and cardiac output) o Cellular (e.g. cardiac remodelling, angiogenesis, mitochondrial biogenesis) o Molecular (e.g. cellular signalling pathways regulating the above events) -How do these acute responses
What is endurance (type) exercise?
Endurance training is the act of exercising to increase endurance. The term endurance training generally refers to training the aerobic system as opposed to anaerobic.
Why do we endurance train?
There is no consensus on accepted and efficacious (non doping) pharmacological approaches to increase endurance capacity and to support health across the lifespan.
Who (should?) endurance train(s)?
Cardiovascular fitness is associated with cognition in young adulthood
What are the major adaptations to endurance training?
o At rest, whole body oxygen consumption is around 3.5 ml/kg/min (0.2-0.3 L/min)
o 20-25% being used by muscle tissue- so only 40-75 ml/min oxygen consumed by muscle tissue at rest.
o VO2max for a sedentary healthy individual around 40 ml/kg/min with >85% being used by muscle tissue = 2.5-3 L/min
o VO2max for an elite endurance athlete can exceed 80 ml/kg/min with >90% being used by muscle tissue = 5-6 L/min.
o Elite racehorses can have a VO2max of 240 ml/kg/min! (130 L/min)
o VO2max of a COPD patient can be <20ml/kg/min
mTOR ablation/stimulation and cardiac adaption?
o Ablation + Stimulation?
o Used transgenic animals with a KO of PI3K (upstream regulator of mTOR pathway)
o Used cardiac banding (pathological cardiac hypertrophy) and endurance exercise (to induce athlete’s heart).
o Using entire genome and proteome screening, C/EBPβ was detected as downregulated at the mRNA and protein level with endurance exercise, but not pathological cardiac hypertrophy.
o Importantly, they went on to demonstrate that reduction of C/EBPβ mimicked the phenotypic changes of exercise.
Greater cardiac output (due to increased stroke volume) is key…… but then what?
o Oxygen supply to the working muscle is acutely permitted primarily by NO (and numerous other signals) mediated vasodilatation of large and small blood vessels.
o This redistribution of cardiac output is also permitted by vasoconstriction at non-active tissue beds.
However, what are the adaptations to long-term aerobic training?
o Clear artery remodelling (greater diameter with training)
o But not necessarily greater ‘functionality’ of the big vessels.
Blood flow (shear stress), mechanical (stretch) and metabolic factors (Ca+, ADP, AMP, O2 ) play a role in bringing about angiogenesis.
o These are the factors that facilitate O2 (and nutrient) delivery to the working muscle.
o Delivery of O2 generally believed to determine VO2max
Angiogenesis?
Formation of new microvasculature, induced by repeated contraction, and likely primarily sensed by a slight drop in oxygen tension.
Mitochondrial biogenesis?
Aside from increase oxygen delivery to working muscle, increased perfusion of the working muscle, due to increased capiliarisation allows greater oxygen extraction during exercise.
Oxidative capacity?
o Local hypoxia signals via HIFα and VEGF to induce angiogenesis.
o How other upstream effectors of HIFα and VEGF are regulated remains poorly defined and represents important research goals.
o The proportion of ones VO2max that can be exercised at for long periods is mainly due to oxygen utilisation at the muscle.
o Oxygen utilisation by muscle is dictated by oxidative capacity (number and function of mitochondria)
o Endurance exercise increases the synthesis of mitochondrial proteins (mitochondrial biogenesis)
o Endurance training increases mitochondrial biogenesis via PGC1α (due to increased calcium release and greater ATP turnover).
Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle (Perry et al,, 2010
This study has provided the following novel information: (a) the training‐induced increases in transcriptional and mitochondrial proteins appear to result from the cumulative effects of transient bursts in their mRNAs, (b) training‐induced mitochondrial biogenesis appears to involve re‐modelling in addition to increased mitochondrial content, and (c) the ‘transcriptional capacity’ of human muscle is extremely sensitive, being activated by one training bout.
Exercise-induced capillary growth in human skeletal muscle and the dynamics of VEGF (Hoier et al., 2014)
We propose that, during muscle activity, these VEGF‐containing vesicles are redistributed toward the sarcolemma where the contents are secreted into the extracellular fluid. VEGF mRNA expression is increased primarily after exercise, which allows for a more rapid replenishment of VEGF stores lost through secretion during exercise.
Physiological adaptations to low-volume, high-intensity interval training in health and disease (Gibala et al., 2012)
Here we review some of the mechanisms responsible for improved skeletal muscle metabolic control and changes in cardiovascular function in response to low‐volume HIT. We also consider the limited evidence regarding the potential application of HIT to people with, or at risk for, cardiometabolic disorders including type 2 diabetes. Finally, we provide insight on the utility of low‐volume HIT for improving performance in athletes and highlight suggestions for future research.
The critical role of VEGF in skeletal muscle angiogenesis and blood flow. Biochemical society transactions (Wagner, 2011)
VEGF (vascular endothelial growth factor) is well known as an important molecule in angiogenesis. Its inhibition is pursued as an anticancer therapy; its enhancement as therapy for tissue ischaemia. In the present paper, its role in skeletal muscle is explored, both at rest and after exercise. Muscle VEGF mRNA and protein are increased severalfold after heavy exercise. Whereas global VEGF knockout is embryonically lethal, muscle-specific knockout is not, providing models for studying its functional significance. Its deletion in adult mouse skeletal muscle: (i) reduces muscle capillarity by more than 50%, (ii) decreases exercise endurance time by approximately 80%, and (iii) abolishes the angiogenic response to exercise training. What causes VEGF to increase with exercise is not clear. Despite regulation by HIF (hypoxia-inducible factor), increased HIF on exercise, and PO2falling to single digit values during exercise, muscle-specific HIF knockout does not impair performance or capillarity, leaving many unanswered questions.
