Summary of Follistatin
Primary Information, Benefits, Effects, and Important Facts
Follistatin is a negative regulatory protein. It works to regulate the body by suppressing the actions of other proteins and hormones.
When overexpressed, it can cause excessive suppression of these proteins. One of these proteins, Myostatin, is itself a negative regulatory of muscle protein synthesis. Thus, increases in follistatin expression indirectly promote muscle protein synthesis by eliminating a 'lock' on protein synthesis.
Follistatin overexposure (typically though injections) mimics myostatin deficiency, which is colloquially known as 'double muscling' and is the cause of hypermuscularity seen in Belgian Blue Cattle.
Follistatin also has interactions with reproductive health, and may have far-reaching effects due to its suppression of proteins that are not myostatin; namely Activins.
Research Breakdown on Follistatin
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Follistatin is a glycosylated protein found in plasma that was named due to its ability to suppress Follicle-Stimulating Hormone (FSH). It is a member of the Transforming Growth Factor Beta (TGF-b) superfamily of proteins.
Follistatin seems to be able to bind to and inactivate proteins through preventing said proteins from acting on their receptors. This is seen with:
Myostatin is the prototypical negative muscle mass regulator, GDF11 is unlikely to regulate muscle mass as it is more involved with skeleton and kidney regulation and activins regulate muscle mass in addition to a pleiotropic effect on many other organs such as brain and ovaries. An increase in follistatin levels may cause a decrease in the activity of the above proteins.
Follistatin gene expression appears to be reduced during menopause, and is elevated with Hormone-Replacement Therapy.
Follistatin manipulations have been looked at indirectly through its ability to block Myostatin signalling. Myostatin is a negative regulator (suppressor) of muscle protein synthesis, and thus inhibiting the negative regulation allows for muscle protein synthesis to accelerate. Administration of a drug that works vicariously through follistatin has been shown in mice to enhance muscle growth long-term.
Follistatin works via suppressing Myostatin, but also seems to suppress activin. Even in myostatin deficient mice, follistatin overexpression can further increase protein synthesis (suggesting suppression of other negative regulatory factors). The end result is more satellite cell recruitment.
Follistatin increases seen during exercise seem to originate from the liver, and are independent of related exericse-induced factors IL-6 and adrenaline.
Mouse models with Follistatin-derived peptides (to create selectivity for Myostatin over other activins) tends to result in increased muscle mass and less fat mass with smaller adipocytes. Myostatin deficiency, either by follistatin intervention or genetic knockout, results in an inability to store excessive fat.
Genetic manipulations into myostatin (used as a model for lack of myostatin activity on its receptors) seems to result in muscle growth across species. The above mouse models, cattle,, dog, sheep, and a genetic abnormality case study in a human. Using follistatin gene transplantation, a 20% reduction of myostatin's effects is able to confer significant muscle growth in primates.
Follistatin mRNA increases after eccentric exercise in menopausal women by 2.1-fold, and 5.8-fold with Hormone Replacement therapy.
When mRNA is measured 24 hours after the eccentric exercise, it is not significantly different from baseline values.
In healthy males, 3 hours of cardiovascular exercise at 50% VO2 max or 2 hours of intermittent eccentric activity (weightlifting) was able to increase follistatin 7-fold relative to fasting. However, this increase was noted 5-6 hours after the start of exercise, and not during. It seems that the follistatin is created in the liver and not muscles; this was supported by a mouse model showing a 21.5-fold increase in liver mRNA of follistatin.
In muscle tissue, follistatin seems to be created in response to necrosis (damage) from either exercise or chemical agents.
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