Doping: energy metabolism and fatigue threshold under surveillance

The French Agency against Doping (AFLD) is particularly alert to the emergence of new molecules acting on the energy metabolism of muscles and fatigue threshold, said one of its representatives, Xavier Bigard, when Congress the French Society of Sports Medicine (SFMS).

The different kinds of doping

The Working Group of the AFLD "Muscle, myogenesis and metabolism" is required to conduct a "sharp scientific monitoring" on emerging molecules likely to be doping, to guide research that will enable the agency to " ensure, as far upstream as possible, effective screening, "recalled Xavier Bigard, a member of the working group.

If the agency keeps an eye on the classical pathway stimulators muscle growth, through "an era of renewal," she is also interested in other ways of improving physical performance which appear in recent years, new molecules at the option of decrypting physiological mechanisms showed Xavier Bigard.

One of these ways is to stimulate energy mechanism enabling the development of mitochondria. "In times of energy crisis, during prolonged exercise, the biogenesis of mitochondria is caused by long-term activation of an enzyme called AMP kinase," said the specialist. The objective of new stimulants to trigger this mechanism is premature.

These activators, the best known is the GW1516, acting on the AMP kinase via the transcription cofactor PPAR delta. Overexpression of the transcription cofactor has "increased by almost 50% performance mice in a test that caused a stir in its publication," commented Xavier Bigard.

Another potential way of doping: improving the transfer of calcium between cellular compartments to push the fatigue threshold. Calcium is an essential element in muscle contraction since it is its accumulation in the intracellular environment that maintains the contraction, relaxation being obtained by the reabsorption of calcium from the sarcoplasmic reticulum.

Regulatory proteins channels ensuring the regulation of calcium flux in recent years have become the target of new doping molecules. One of them, named S107, is on calstabines and "keeps longer contraction", backing the threshold of fatigue caused by poor regulation of calcium flux.

New activation of the IGF-1 channels

Regarding modulators of muscle mass, new channels of stimulation are explored, as they have long been at the forefront of performance-enhancing drugs. They therefore continue to be the subject of special attention from the French agency.

One of the main activation pathways modulators of muscle mass is that of IGF-1 (Insulin-like Growth Factor), a hormone secreted by the liver with a stimulatory activity on protein synthesis. "It is a well listed anabolic factor for several years," said Xavier Bigard.

Research has shown that there are regulatory peptides associated with the gene for IGF-1, according to the physiologist, "demonstrate an important functional role in stimulating the penetration level of IGF-1 in muscle fiber" thus accentuating its physiological effect.

MGF (Mechano Growth Factor) is one of these regulatory peptides, which are all the more interesting because they are "easy to synthesize."

Finally, unlike the mechanism of destruction of muscle fibers by proteolysis "also offers guidance on testing strategies for doping," added Xavier Bigard. This is to block myostatin responsible for limiting muscle growth, through molecules similar to its natural inhibitor follistatin.

Remains the only way of increasing the capillary network. "There are quite a few ways to modulate the production of vascular growth factors", represented in particular by the VEGF (Vascular Endothelial Growth Factor). According to Xavier Bigard, "we must remain vigilant because they are also critical of the performance targets"