Fibroblast growth factor 1: a key regulator of human adipogenesis.
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.
Hutley
Louise
L
Department of Diabetes and Endocrinology, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Australia. lhutley@soms.uq.edu.au
Shurety
Wenda
W
Newell
Felicity
F
McGeary
Ross
R
Pelton
Nicole
N
Grant
Jennifer
J
Herington
Adrian
A
Cameron
Donald
D
Whitehead
Jon
J
Prins
Johannes
J
D017667:Adipocytes / Q000166:cytology* / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D016220:Fibroblast Growth Factor 1 / Q000502:physiology*; D006801:Humans; D051379:Mice; D008833:Microcirculation
D016220:Fibroblast Growth Factor 1