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Characterization of the transcriptional and functional effects of fibroblast growth factor-1 on human preadipocyte differentiation

Felicity S. Newell^*, Hua Su^*, Hans Tornqvist^,, Jonathan P. Whitehead^*, Johannes B. Prins^*,1 and Louise J. Hutley^*

^* Centre for Diabetes and Endocrine Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia;

Diabetes Biology, R&D, Novo Nordisk, Måløv, Denmark; and

Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital MAS, Malmö, Sweden

¹Correspondence: Centres for Health Research, Level 2, Bldg. 35, Princess Alexandra Hospital, Ipswich Rd, Woolloongabba 4102, Australia. E-mail: jprins{at}cder.soms.uq.edu.au

ABSTRACT

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- 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 (ERK 1/2) 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, F. S., Su, H., Tornqvist, H., Whitehead, J. P., Prins, J. B., Hutley, L. J. Characterization of the transcriptional and functional effects of fibroblast growth factor-1 on human preadipocyte differentiation

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