A few months ago a Norwegian-German research team published a study in Biochemical and Biophysical Research Communications about which in a quarter of a century we might say: this was the start of a new era in bodybuilding. The study suggests that the protein decorin plays a key role in muscle growth.
In fact it may just be the case that decorin plays an even more fundamental role in muscle growth than myostatin and follistatin.
The structural formula of decorin is shown above. It is a relatively small glycoprotein, which also contains a relatively large number of leucine units. It is a dimer, but in a fluid the two parts of the molecule attach themselves to each other.
Decorin is a myokine, a protein that muscle cells produce. Researchers have known for 15 years that decorin plays a significant role in muscle growth. [J Biol Chem. 2001 Feb 2;276(5):3589-96.] If you genetically modify mice so that they produce more decorin, their muscles recover faster from injury and damage. [Mol Ther. 2007 Sep;15(9):1616-22.] This is partly because decorin sabotages myostatin, and as a result enables stem cells to grow into mature muscle cells more quickly. [J Cell Physiol. 2008 Jun;215(3):856-67.]
Myostatin is a protein that muscle cells synthesise and with which they inhibit their own growth. Decorin probably renders the myostatin molecules harmless before they attach themselves to their receptor. One theory is that decorin stimulates muscle cells to make follistatin, a protein that gobbles up myostatin as it were – thereby preventing myostatin from doing its work.
Until now decorin research had only been done on muscle cells in vitro and lab animals, but the Norwegians and Germans also looked at humans in their study. They got 10 students who already did weight training to do a full-body workout, performing 8 basic exercises: leg press, leg curls, bench press, pulldown, sitting shoulder press, cable-flies, and low rowing. For each exercise they did 3 sets of 8 reps.
The figure below shows that the workout boosted the concentration of decorin in the blood.
The heavier the weights the students used, the bigger the increase in concentration of decorin in their blood. The figure above shows the relationship between the concentration of decorin and the number of kilograms the students could shift on the leg press.
In a second experiment the researchers got 26 men with a sedentary lifestyle, aged between 40 and 65, to do weight training for 12 weeks. Before and after the training period the researchers took samples of muscle tissue from the men’s leg muscles and measured the concentration of decorin in them.
At the end of the 12 weeks the men had gained strength and were capable of shifting more kilograms on the leg press machine. And their leg muscles had started to produce more decorin. And hey presto: the bigger the increase in the synthesis of decorin in the muscles, the bigger the increase in body strength.
The researchers also did an animal study in which they inserted artificial decorin genes with electrical pulses in the mice’s leg muscles. This boosted the activity of the Mighty gene, which counteracts the effects of myostatin. In addition, the new decorin genes boosted the activity of the follistatin gene, and reduced the effects of the muscle atrophy genes Atrogin-1 and MuRF1.
“We hypothesize that decorin secreted from skeletal muscle cells in response to exercise is involved in restructuring of muscle during hypertrophy”, the researchers write.
The myokine decorin is regulated by contraction and involved in muscle hypertrophy.
The health-promoting effects of regular exercise are well known, and myokines may mediate some of these effects. The small leucine-rich proteoglycan decorin has been described as a myokine for some time. However, its regulation and impact on skeletal muscle has not been investigated in detail. In this study, we report decorin to be differentially expressed and released in response to muscle contraction using different approaches. Decorin is released from contracting human myotubes, and circulating decorin levels are increased in response to acute resistance exercise in humans. Moreover, decorin expression in skeletal muscle is increased in humans and mice after chronic training. Because decorin directly binds myostatin, a potent inhibitor of muscle growth, we investigated a potential function of decorin in the regulation of skeletal muscle growth. In vivo overexpression of decorin in murine skeletal muscle promoted expression of the pro-myogenic factor Mighty, which is negatively regulated by myostatin. We also found Myod1 and follistatin to be increased in response to decorin overexpression. Moreover, muscle-specific ubiquitin ligases atrogin1 and MuRF1, which are involved in atrophic pathways, were reduced by decorin overexpression. In summary, our findings suggest that decorin secreted from myotubes in response to exercise is involved in the regulation of muscle hypertrophy and hence could play a role in exercise-related restructuring processes of skeletal muscle.
PMID: 24996176 [PubMed – indexed for MEDLINE]