Hypoxia-inducible factor-1α (HIF-1α), which is a transcription factor that 
enhances glycolysis in cells in response to hypoxia, is induced in hypertrophied 
adipocytes in obesity. Recent studies have shown that growth factors are able to 
induce HIF-1α by mechanisms independent of hypoxia. Since basic fibroblast 
growth factor (bFGF), an angiogenic factor, is concentrated in expanding adipose 
tissue, the possible effects of bFGF on regulation of HIF-1α in adipocytes were 
investigated. Treatment of differentiated 3T3-L1 adipocytes with bFGF induced 
HIF-1α. Concomitantly, glucose transporter 1 (GLUT1), which is a target gene of 
HIF-1α, was induced at both mRNA and protein levels and was translocated to the 
plasma membrane. A chromatin immunoprecipitation assay and an RNA interference 
study indicated that bFGF-induced HIF-1α directly upregulates GLUT1. In 
addition, it was observed that bFGF increases lactate production of adipocytes. 
This result indicates that bFGF reprograms the metabolism toward glycolysis. 
Intraperitoneal injection of bFGF into mice upregulated HIF-1α and GLUT1 in 
adipose tissues, suggesting that bFGF regulates the metabolism of adipocytes via 
HIF-1α-GLUT1 regulation in vivo. We also found that bFGF inhibits 
insulin-induced phosphorylation of insulin receptor substrate-1 and Akt, 
suggesting that bFGF attenuates the insulin signal in adipocytes. Taken 
together, the findings suggest that bFGF has a harmful effect on the development 
of type 2 diabetes through metabolism reprogramming and attenuation of the 
insulin signal.