Characterization of the transcriptional and functional effects of fibroblast growth factor-1 on human preadipocyte differentiation.
We recently established that fibroblast growth factor (FGF)-1 promotes adipogenesis of primary human preadipocytes (phPA). In the current report, we have characterized the adipogenic effects of FGF-1 in phPA and also in a human PA strain derived from an individual with Simpson-Golabi-Behmel syndrome (SGBS PA), which exhibit an intrinsic capacity to differentiate with high efficiency. In further studies, we compared these models with the well-characterized murine 3T3-L1 preadipocyte cell line (3T3-L1 PA). FGF-1 up-regulated the adipogenic program in phPA, with increased expression of peroxisome proliferator-activated receptor-gamma in confluent PA prior to induction of differentiation and increased expression of adipocyte markers during differentiation. Moreover, phPA differentiated in the presence of FGF-1 were more insulin responsive and secreted increased levels of adiponectin. FGF-1 treatment of SGBS PA further enhanced differentiation. For the most part, the adipogenic program in phPA paralleled that observed in 3T3-L1 PA; however, we found no evidence of mitotic clonal expansion in the phPA. Finally, we investigated a role for extracellular regulated kinase 1/2 (ERK1/2) in adipogenesis of phPA. FGF-1 induced robust phosphorylation of ERK1/2 in early differentiation and inhibition of ERK1/2 activity significantly reduced phPA differentiation. These data suggest that FGF-1 treated phPA represent a valuable in vitro model for the study of adipogenesis and insulin action and indicate that ERK1/2 activation is necessary for human adipogenesis in the absence of mitotic clonal expansion.
Newell
Felicity S
FS
Centre for Diabetes and Endocrine Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Su
Hua
H
Tornqvist
Hans
H
Whitehead
Jonathan P
JP
Prins
Johannes B
JB
Hutley
Louise J
LJ
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000502:physiology; D000328:Adult; D000368:Aged; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha; D051743:CCAAT-Enhancer-Binding Protein-delta; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D047495:PPAR gamma; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
D022763:CCAAT-Enhancer-Binding Protein-alpha; D047495:PPAR gamma; D016220:Fibroblast Growth Factor 1; D051743:CCAAT-Enhancer-Binding Protein-delta; D048049:Extracellular Signal-Regulated MAP Kinases