Role of follistatin in promoting adipogenesis in women.
BACKGROUND
Follistatin is a glycoprotein that binds and neutralizes biological activities of TGFbeta superfamily members including activin and myostatin. We previously identified by expression profiling that follistatin levels in white adipose tissue (WAT) were regulated by obesity.


OBJECTIVE
The objective of the study was to elucidate the role of follistatin in human WAT and obesity.


METHODS
We measured secreted follistatin protein from WAT biopsies and fat cells in vitro. We also quantified follistatin mRNA expression in sc and visceral WAT and in WAT-fractionated cells and related it to obesity status, body region, and cellular origin. We investigated the effects of follistatin on adipocyte differentiation of progenitor cells in vitro.


METHODS
Women (n = 66) with a wide variation in body mass index were recruited by advertisement and from a clinic for weight-reduction therapy.


RESULTS
WAT secreted follistatin in vitro. Follistatin mRNA levels in sc but not visceral WAT were decreased in obesity and restored to nonobese levels after weight reduction. Follistatin mRNA levels were high in the stroma-vascular fraction of WAT and low in adipocytes. Recombinant follistatin treatment promoted adipogenic differentiation of progenitor cells and neutralized the inhibitory action of myostatin on differentiation in vitro. Moreover, activin and myostatin signaling receptors were detected in WAT and adipocytes.


CONCLUSIONS
Follistatin is a new adipokine important for adipogenesis. Down-regulated WAT expression of follistatin in obesity may counteract adiposity but could, by inhibiting adipogenesis, contribute to hypertrophic obesity (large fat cells) and insulin resistance.
Flanagan
John N
JN
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
Linder
Kristina
K
Mejhert
Niklas
N
Dungner
Elisabeth
E
Wahlen
Kerstin
K
Decaunes
Pauline
P
Rydén
Mikael
M
Björklund
Peyman
P
Arver
Stefan
S
Bhasin
Shalender
S
Bouloumie
Anne
A
Arner
Peter
P
Dahlman
Ingrid
I
D030301:Activin Receptors, Type II / Q000235:genetics; D050156:Adipogenesis; D052436:Adipose Tissue, White / Q000378:metabolism; D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005260:Female; D038681:Follistatin / Q000235:genetics / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics
C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D038681:Follistatin; D047495:PPAR gamma; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030301:Activin Receptors, Type II; D000077293:Receptor, Transforming Growth Factor-beta Type I; C425584:activin receptor type II-B