Fibroblast Growth Factor 1

Abstract

Obesity, with its related problems, is recognized as the fastest growing disease epidemic facing the world, yet we still have limited insight into the regulation of adipose tissue mass in humans. We have previously shown that adipose-derived microvascular endothelial cells (MVECs) secrete a factor(s) that increases proliferation of human preadipocytes. We now demonstrate that coculture of human preadipocytes with MVECs significantly increases preadipocyte differentiation, evidenced by dramatically increased triacylglycerol accumulation and glycerol-3-phosphate dehydrogenase activity compared with controls. Subsequent analysis identified fibroblast growth factor (FGF)-1 as an adipogenic factor produced by MVECs. Expression of FGF-1 was demonstrated in MVECs but not in preadipocytes, while preadipocytes were shown to express FGF receptors 1-4. The proliferative effect of MVECs on human preadipocytes was blocked using a neutralizing antibody specific for FGF-1. Pharmacological inhibition of FGF-1 signaling at multiple steps inhibits preadipocyte replication and differentiation, supporting the key adipogenic role of FGF-1. We also show that 3T3-L1 cells, a highly efficient murine model of adipogenesis, express FGF-1 and, unlike human preadipocytes, display no increased differentiation potential in response to exogenous FGF-1. Conversely, FGF-1-treated human preadipocytes proliferate rapidly and differentiate with high efficiency in a manner characteristic of 3T3-L1 cells. We therefore suggest that FGF-1 is a key human adipogenic factor, and these data expand our understanding of human fat tissue growth and have significant potential for development of novel therapeutic strategies in the prevention and management of human obesity. Diabetes 53: [3097][3098][3099][3100][3101][3102][3103][3104][3105][3106] 2004

Fibroblast growth factor 1 levels are elevated in newly diagnosed type 2 diabetes compared to normal glucose tolerance controls

“…Inhibition of FGFR activation during proliferation decreased FGF1 priming and differentiation potential of human PA [29]. This priming effect of preadipocytes was more apparent if the cells were differentiated exposed to a PPAR-γ ligand [27]. Jonker et al also verified that FGF1 was a direct target of PPARγ in HFD-fed mice.…”

“…Subjects in the upper serum FGF1 tertile had higher levels of BMI, [17]. So far, mounting evidence from previous studies highlighted an essential role of FGF1 in proliferation and differentiation of primary human preadipocytes (phPA) [23,27]. Louise et al showed that the proliferation rate of phPA was increased in the presence of FGF1, and this effect can be blocked by addition of a neutralizing antibody raised against FGF1 [27].…”

“…So far, mounting evidence from previous studies highlighted an essential role of FGF1 in proliferation and differentiation of primary human preadipocytes (phPA) [23,27]. Louise et al showed that the proliferation rate of phPA was increased in the presence of FGF1, and this effect can be blocked by addition of a neutralizing antibody raised against FGF1 [27]. Additionally, FGF1 treated phPA differentiated to a greater extent in comparison with untreated PA and FGF1 up-regulated the expression of peroxisome proliferators activator receptor γ (PPARγ) in phPA [23].…”

The role of growth factors in extraction wound healing

“…Kiseli fibroblastni faktor rasta (aFGF-1) i bazni fibroblastni faktor rasta (bFGF-2) identifikovani su u fluidu rane, naročito u najranijim fazama zarastanja 41 . Uloga FGF u zarastanju rane je dokazana in vitro i in vivo kroz akciju u ranoj aktivaciji makrofaga, povećanju komponenti ekstracelularnog matriksa, povećanju proliferacije i diferencijacije neuroektodermalnih i mezodermalnih derivata, endotelnoj ćelijskoj proliferaciji, adipogenezi, angiogenezi i reepitelizaciji 42,43 . Najveću ulogu u procesu zarastanja rane ima kiseli fibroblastni faktor rasta (aFGF-1) koji utiče na proliferaciju fibroblasta i endotela, promovišući zarastanje rane i angiogenezu.…”

The PPARγ-FGF1 axis: an unexpected mediator of adipose tissue homeostasis

“…Treatment of endothelial cells with FGF1 causes microvascular branching, suggesting a possible role in angiogenesis [8]. Intriguingly, as a proliferative factor, FGF1 may also play an important role in adipogenesis [9]. Due to its beneficial impact on the circulatory system, FGF1 has been tested for clinical applications in cardiovascular diseases npg [7].…”