|Tissue distribution of follistatin and its induction during adipogenic differentiation of mouse brown preadipocyte cells. (A) Real-time quantitative PCR analysis of follistatin gene expression in mouse tissue panel (n=3). (B) Photomicrographs of mouse brown pre-adipocyte cells grown either in regular growth medium (undifferentiated) or in BAT-specific adipogenic medium (differentiated) for 8 days
Nary a week goes by without a new fad diet limiting or directing the intake of sugars, fats or proteins — or a combination of any or all three. So it’s rather interesting that a study in the March issue of the Journal of Lipid Research seems to indicate that a glycoprotein known to be involved with promoting growth of muscle mass may have an unexpected relationship with brown adipose tissue, more commonly known as brown fat.
Brown fat generates and maintains body heat in warm-blooded animals, and its activity affects energy metabolism and therefore could be a determinant in predicting obesity and metabolic syndrome. In an article by Melissa Braga of the Charles R. Drew University of Medicine and Science and colleagues, the activity of a glycoprotein called follistatin in brown fat was examined.
Braga et al. had noted that follistatin expression levels are significant in some brown adipose tissue and wanted to know its functions there. So first, they examined mouse brown pre-adipocytes allowed to differentiate under controlled conditions; follistatin levels went from undetectable from baseline to substantial levels once the adipocytes differentiated.
From there, the team looked at adipogenesis in vitro in mouse embryonic fibroblasts, comparing the differences between those isolated from wild-type embryos or embryos in which the follistatin gene had been knocked out. The levels of key brown adipocyte proteins, including uncoupling protein 1, or UCP1, were found to be much lower in the knockout mouse fibroblasts compared with wild type. The decrease in the amounts of these proteins suggests that follistatin influences adipogenesis and differentiation of brown adipocytes and that severe metabolic defects may occur without normal follistatin function, including defects that could prove fatal.
By treating both kinds of cells with follistatin, the researchers confirmed it was the lack of the glycoprotein that was causing the decreased levels of key brown adipocyte proteins. Addition of the glycoprotein to follistatin-deficient fibroblasts also increased cellular respiration.
Global gene-expression profiling also was conducted on fibroblasts of both types during the early stages of brown adipocyte induction. Expression levels of genes were reduced by 3.5-fold or more in the knockout fibroblasts compared with the wild-type cells and indicated that follistatin is a key modulator of lipid and energy metabolism.
The researchers say more detailed studies of follistatin’s functional role in vivo are the next logical step. The development of in vivo models hopefully will help identify potential tissue targets of follistatin and therefore provide novel therapeutic approaches for treating obesity, diabetes and metabolic syndrome.
Mary L. Chang (email@example.com
) is publications manager for the Journal of Lipid Research.