Follistatin and Brown Fat

In this weeks study review, we are looking at some new findings that I am sure you have not heard of amist the recent craze over Follistatin and Brown Fat. Within the last few years, the research industry boomed with talk of this amazing new peptide that was responsible for promoting huge muscular growth (seriously, obsurd growth). Here is a small overview I wrote when it first hit the market; Follistatin, simply put, it a protein that is a myostatin antagonist (or myostatin-binding protein). Myostatin, as we know, regulates muscle growth, kind of like a governor in cars. Myostatin is produced naturally to limit skeletal muscle growth, so that muscles grow “in proportion” in mammalian bodies.

Thus, circulating in the blood stream, a gene that will literally inhibit growth naturally. Not something we want in our research subjects right? Also, myostatin levels have been seen to be dramatically higher in later weeks of anabolic conjunct anabolic research subjects. This is believed to be the reason as to why most myofibril proliferation is usually seen in the first few weeks of research, because after that, myostatin levels peak and really limit tissue growth. But what if that could be changed? If we could block myostatin, we could potentially see these 12 to 15 week studies making constant gains, which would be something that is rarely to never seen. “In (subjects) treated with graded doses of testosterone, myostatin levels were significantly higher on day 56 than baseline in both young and older (subjects); changes in myostatin levels were significantly correlated with changes in total and free testosterone in young (subjects).”This is where follistatin comes in.

Follistatin Skeletal Muscle Growth

Follistatin is used to inhibit myostatin activity in vitro resulting in skeletal muscle growth in vivo. Simply, when follistatin is introduced, a shortage in myostatin is seen which results muscle growth. Studies have backed up this, and research on monkeys and other mammals began after rodent trials were shown successful. The result of follistatin treatment was a significant increase in muscle mass and strength. In one study I paid particular attention to, Follistatin over expression increased the muscle weight by about 37% in control animals! Another study looked at, showed not only an increase in skeletal muscle, but a decrease in fat accumulation! What we also found interesting is that subjects already produce an increased amount of follistatin with exercise! I see this as another one of the ways the subject is kind of “turned-on” to muscle growth in retaliation of exercise. After many trials, it was conclusive that follistatin seems to be quite successful in inhibiting myostatin, which results in these muscle and strength gains.

So what we have here is, a protein that binds with another which limits subject muscle growth, that is naturally released with exercise, which induces an increase in muscle mass and a decrease in fat storage. A way for us to take our longer cycles to full potential, and see gains past week 10, while off cycle still pushing our bodies to produce gains that have normally been inhibited. But with its potential to be a staple in long research studies, and off-cycle growth, it may just be gold. With all these amazing benefits, its seems as though this drug could not get any better; but it does. A recent study has linked folliststin to adipocyte differentiation, browning, and promoting energy metabolism. For those who are unfamiliar with brown adipose tissue, it has a remarkable energy dissipating capacity and actively promotes triglyceride clearance, glucose disposal, and generation of heat for thermogenesis- all incredibly desirable effects.

So what exactly is follistatin and brown fat, and why are we suddenly hearing so much about it if we have known about it existence for years? Brown fat has a large quantity of iron-containing mitochondria in the cells, has only become a hot research topic in the past few years because of our new understanding of its prevalence in adults. Brown fat cells have a high mitochondrial content and the ability to uncouple cellular respiration through an uncoupling protein. It was previously thought that brown fat was only found in newborns and then disappeared as they grew up and did not rely on thermoregulation.

Then, in a 2009 study published in the New England Journal of Medicine, researchers found that brown fat can indeed still be found in adults. Younger people tend to have more of it than older adults. The same study determined that brown fat appeared to be more abundant in slim people and in women. In infants, brown fats primary role is helping infants stay warm and protecting them from hypothermia once outside of the womb. We now know that in adults, remaining brown fat is located in small amounts on the side of the neck, in the upper back, along the spine and in the dip between the collarbone and the shoulder.

While we know that white fat is mainly used to store energy (fatty acids and glycerol), brown fat keeps the body warm by burning calories once it is activated. Even better, brown fat seems to target calories that come from fat and sugar. This in turn may be particularly helpful in fighting health issues such as diabetes and being overweight. So how can we take advantage of this “fat burning good fat” paradox? Well, it seems as though it responds positively to follistatin, which promoted its differention! Because follistatin is a secreted protein, it was tested whether exogenously added follistatin protein had an effect on brown adipocyte differentiation.

Follistatin Enhanced Thermogenic

Treatment of cells during differentiation with follistatin enhanced thermogenic gene expression 50–80% beyond levels in cultures differentiated without follistatin. Thus, the data indicate a possible functional role of follistatin during brown adipocyte differentiation and regulation of the thermogenic process. This is all amazing news, but remember that this is preliminary research that just came out in the Journal of lipid research. The molecular mechanisms responsible for follistatin-induced brown characteristics of white adipocytes are not known at the moment; however, it is possible that follistatin may antagonize the myostatin/TGF-β signaling pathway during the process.

Myostatin is predominantly expressed in skeletal muscle and plays an important role in regulation of muscle mass and fat deposition. [The study authors] have recently reported that myostatin inactivation in myostatin knockout mice promotes pathways related to lipid metabolism and brown fat differentiation. It will be interesting to explore whether follistatin targets myostatin signaling to promote adipocyte differentiation and browning. So with that, until next time!