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1 Department of Clinical Cell Biology, Chiba University, Graduate School of Medicine, Chiba, Japan
2 Department of Genome Research and Clinical Application, Chiba University, Graduate School of Medicine, Chiba, Japan
3 Division of Applied Translational Research, Chiba University, Graduate School of Medicine, Chiba, Japan
* To whom correspondence should be addressed. E-mail: kazuot{at}intmed02.m.chiba-u.ac.jp.
Vascular endothelial growth factor (VEGF) is an important angiogenic factor and expressed in wide variety of cell types. In this study, we investigated the mechanism of VEGF production in adipocytes in three sets of experiments. First, to clarify the relation between plasma VEGF concentrations and its expressions in adipose tissues, we investigated the genetically obese db/db and KK-Ay mice. Plasma VEGF concentrations in obese mice were significantly higher than in control and related with adiposity. VEGF expressions in visceral fat were enhanced during growth and related with fat deposition. Next, to demonstrate the relation between VEGF production and lipid accumulation in adipocytes, we analyzed VEGF mRNA expression and its protein secretion in 3T3-L1 cells. VEGF production was enhanced during lipid accumulation in 3T3-L1 cells after adipocyte conversion. Next, to clarify the role of anatomical localization on VEGF expression in adipocytes, we implanted 3T3-L1 cells into visceral or subcutaneous fat in athymic mice. 3T3-L1 cells implanted into mesenteric area expressed more VEGF mRNA than that into subcutaneous area. Plasma VEGF concentration in the mice implanted into visceral fat was higher than control. These results suggest both the anatomical localization and the lipid accumulation are important for the VEGF production in adipocytes.
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