The signalling pathways behind endurance training adaptations

The signalling pathways of adaptation to endurance training

Everyone knows that regular endurance training improves your endurance capacity. But what adaptations can you expect in your body from endurance training? We'll clear that up for you in this blog.

Regular, training-induced stimuli each improve different components of endurance capacity. These adaptations to endurance training take place both centrally (an improvement in cardiac output) and peripherally in the working muscles (muscle fibre distribution, mitochondrial density, capillarisation). It's especially important to note that central adaptations improve regardless of the training method chosen, whereas peripheral adaptations mainly take place in the muscles actually used. Because of this, the choice of training method should be well considered and, above all, tailored to your individual goal.
How the various types of endurance training lead to specific adaptations, and how these can partly be deliberately controlled through a suitable choice of training method, is part of sports physiology research and is summarised here in a short overview, for a general understanding.

1. Adaptation to endurance training: athlete's heart or pathological cardiac hypertrophy.

The main component of the central adaptation to endurance training is a largely structural change to the heart muscle. These changes can be either positive (athlete's heart) or negative (hypertrophic cardiomyopathy). With an athlete's heart, the left ventricle mainly enlarges and the heart muscle wall thickens in the right proportion, which overall leads to an increased stroke volume (the heart can pump out more blood per beat). In a cardiac patient, on the other hand (for example due to aortic stenosis or long-standing hypertension), the wall thickness increases sharply at the expense of ventricular volume, which ultimately leads to a reduced stroke volume and, after usually years of heart failure caused by the heart muscle failing, ends in cardiac death.
As you might expect, two different molecular signalling pathways lead to the adaptations of the heart muscle mentioned above. Above all, repeated intervals of intense endurance exercise lead to physiological hypertrophy of the heart muscle cells by increasing PI3K and subsequently PKB/Akt concentrations while lowering the C/EBPbeta signalling pathway. Pathological cardiac hypertrophy, on the other hand, is mainly based on an increased calcineurin signal.
Sooner or later, it may become possible to directly influence these signalling pathways using medication or genetic methods.

What is certain, however, is that you can influence this through repeated, intense endurance training or by eliminating the factors that favour hypertrophic cardiomyopathy (blood pressure regulation, aortic stenosis surgery, etc.)

2. Adaptation to endurance training: changes in muscle fibre distribution.

An important structural component at the muscular level for endurance performance is muscle fibre distribution. Human skeletal muscle fibres can basically be divided into slow-contracting type 1 fibres and fast-contracting type 2a (fast) and type 2x (very fast) fibres. This classification is named after the heavy myosin chains that are mainly expressed in skeletal muscle fibres. Type 2x fibres, for example, predominantly express heavy myosin chains of the 2x type.
In this regard, it has been shown that the calcineurin-NFAT signalling pathway is predominantly induced in type 1 muscle fibres. If this signal is weakened by a specific inhibitor, the ratio of type 1 to type 2 fibres decreases. This signal is also increased by prolonged electrical stimulation in model organisms, which indicates a link between muscle fibre distribution and physical training. In type 2 fibres, a shift from type 2x to type 2a fibres induced by endurance training has been found, suggesting a slight slowing at the fibre level. Overall, of course, the muscle doesn't become slower as a result of training-induced stimuli. A shift from type 1 to type 2 fibres and vice versa can theoretically be encouraged through years of training, but the evidence for this is very limited, so no definitive statement can be made.
What could, however, be shown with certainty is that the individual heavy myosin chain types mutually suppress each other's gene expression. This explains the fact that, within a given muscle fibre type, only one type of heavy myosin chain is expressed at a time, while all the others are suppressed.

3. Adaptation to endurance training: training-induced mitochondrial biogenesis.

Over time, regular endurance training increases the density of mitochondria in the muscle. This adaptation to endurance training is called mitochondrial biogenesis and can basically be explained by two signalling pathways. Prolonged, slow endurance training activates CaMK through the release of calcium. During high-intensity interval training (HIIT), on the other hand, AMPK registers the low concentrations of AMP and ADP. It also registers the drop in glycogen.
AMPK and CaMK increase the expression of the transcription factor PGC-1alpha, which in turn improves mitochondrial biogenesis by increasing the expression of nuclear and mitochondrial DNA.

4. Adaptation to endurance training: training-induced angiogenesis.

As already described, a performance-limiting factor in endurance sports is not only maximal oxygen uptake but also peripheral oxygen utilisation. In this respect, the density of the muscular capillary network is of central importance.
Via the CaMK/AMPK-PGC-1alpha signalling pathway, hypoxia-induced HIF-1 and shear-stress-induced NO, angiogenic growth factors (which promote capillary growth) are upregulated. One of the most important of these factors is VEGF (vascular endothelial growth factor).
In addition, endurance training increases the expression of metalloproteinases, which prepare the extracellular matrix for capillary sprouting by forming tunnels.

Summary

As described above, you can basically expect 4 adaptations to endurance training:

1. Adaptation of the heart: enlargement of the left ventricle and the heart muscle wall. This leads to an increased stroke volume.
2. Changes in muscle fibre distribution: the muscle fibres become more resistant to fatigue (a change from type IIx to type IIa)
3. Mitochondrial biogenesis: an increase in the density of mitochondria in the muscle. Mitochondria are the powerhouses of the cell.
4. Angiogenesis: an increase in the density of the muscular capillary network. Capillaries are the finest branches of the blood vessels).

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