Mapping of the fibroblast growth factors in human white adipose tissue.
BACKGROUND
Fibroblast growth factors (FGFs) regulate the development of white adipose tissue (WAT). However, the secretion and cellular origin of individual FGFs in WAT as well as the influence of obesity are unknown.


OBJECTIVE
Our objective was to map FGFs in human sc WAT, the cellular source, and association with obesity.


METHODS
Secretion, mRNA, and circulatory levels of FGFs in human abdominal sc WAT from nonobese and obese donors were examined by microarray, real-time quantitative PCR, and ELISA. The activity of FGFs in cultured human adipocytes was determined by phosphorylation assays.


RESULTS
Expression of five FGFs (FGF1, FGF2, FGF7, FGF9, and FGF18) and FGF homologous factor (FHF2) was identified in WAT. Only FGF1 was released in a time-dependent manner from sc WAT, and fat cells were the major source of FGF1 secretion. FGF1 expression increased and FGF2 decreased during adipocyte differentiation. Furthermore, FGF1 was not secreted into the circulation. Although FGF1 levels were 2-fold increased in obesity, they were unaltered by weight reduction. Only FGF1 and FGF2 induced a marked concentration-dependent phosphorylation of p44/42 in cultured human adipocytes.


CONCLUSIONS
Of the investigated FGFs, only FGF1 is secreted from sc WAT and predominantly so from the adipocyte fraction. The activity in adipocyte cultures and lack of secretion into the circulation suggest that FGF1 acts as an auto- or paracrine factor. FGF1 levels are increased in obesity but unaffected by weight reduction, suggesting a primary defect in obese individuals. In conclusion, FGF1 may play a superior role among the FGFs in sc WAT and obesity development.
Mejhert
Niklas
N
Karolinska Institutet, Department of Medicine, Huddinge, Lipid Laboratory, Stockholm, Sweden. niklas.mejhert@ki.se
Galitzky
Jean
J
Pettersson
Amanda T
AT
Bambace
Clara
C
Blomqvist
Lennart
L
Bouloumié
Anne
A
Frayn
Keith N
KN
Dahlman
Ingrid
I
Arner
Peter
P
Rydén
Mikael
M
D000005:Abdomen; D052436:Adipose Tissue, White / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D002874:Chromosome Mapping; D004797:Enzyme-Linked Immunosorbent Assay; D005346:Fibroblast Growth Factors / Q000235:genetics*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D009765:Obesity / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D050177:Overweight / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
D047495:PPAR gamma; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D006493:Heparin