By Dr. Nicola Sacchi - Author of the book: Drugs and doping in sport -
Pgc1-α (coactivator 1 of the peroxisome gamma proliferator) is a transcription coactivator. It is a protein that promotes transcription, hence the expression of numerous genes, including those responsible for the regulation of mitochondrial biogenesis and fat oxidation. It also seems to play a role, not yet completely clear, in the differentiation of the two types of muscle cells. This protein is mostly expressed in type I fibers and promotes angiogenesis induced by physical activity. It also seems likely that it is responsible for the conversion of type IIb fibers into fibers with greater oxidative capacity.
Pgc1-α is also involved in energy production systems and also plays a role in the production of the GLUT-4 receptor; in fact it is assumed that it may be involved in pathologies related to insulin resistance, ie the low sensitivity of cells to the action of insulin.
Pgc1-α is expressed in all tissues with high energy consumption: cardiac and skeletal striated muscle, brown fat, liver and brain.
In skeletal muscle, Pgc1-α acts as a sensor of the intracellular calcium signals induced by the motor neuron activity at the level of the neuromuscular junction; therefore its expression is influenced by muscular contractions induced by physical activity. This protein is a mediator of motoneuron activity in skeletal muscle and through interaction with MEF2 and calcineurin increases the oxidative capacity of muscle fiber by promoting mitochondrial biogenesis.
During exercise the combination of neuromuscular stimulation and contraction promotes the expression of Pgc1-α; in fact this protein is more present in the muscles of people who regularly perform physical activity and seems to be responsible for the muscular adaptations linked to endurance activity, such as the increase in oxidative capacities and a probable conversion of IIb fibers into the more oxidative IIa.
The suppression of Pgc1-α in different forms of atrophy suggests a contribution in maintaining muscle mass, but not only: this suppression produced a marked production of inflammatory substances such as IL-6, TNF-α and therefore Pgc1-α appears to be involved in the regulation of phlogistic processes and its reduced expression is assumed to play a role in sedentary pathologies such as obesity and type 2 diabetes.
The expression of this protein, which increases following physical activity, also appears to have trophic activity on the muscle tissue, activating the genes of protein synthesis and thus preventing catabolism; in fact, in some experiments on mice, inducing their expression, the symptoms of a particular form of dystrophy have been improved.
In further experiments it was seen that the activation of the Pgc1-α gene induces a greater production of type IIx muscle fibers, which are fast fibers with intermediate characteristics between the 2 best known subtypes A and B. this overproduction has made the mice of the experiment faster and more resistant than the control group.
In the light of these findings, possible applications will be sought in pathologies such as amyotrophic sclerosis, type 2 diabetes and muscular dystrophy and it can be assumed that in the future we will seek ways to promote the production of Pgc1-α in athletes to improve performance, given that it is already possible to modulate pharmacologically the expression of its gene.
