Elevated serum vascular endothelial growth factor is associated with visceral fat accumulation in human obese subjects.
OBJECTIVE
Adipose tissue expresses some bioactive molecules, which may be involved in the development of obesity-associated metabolic disorders and cardiovascular diseases. Vascular endothelial growth factor (VEGF) an important angiogenic factor is implicated in normal and pathological vessel formation. The aim of this study is to investigate clinically the association between blood serum VEGF concentrations and body fat accumulation as well as distribution. The study also aims to show the effect of serum VEGF protein on gene expression of transcriptional factor E26 transformation-specific-1 (Ets-1) and matrix metalloproteinase (MMP)-3.


METHODS
Serum VEGF concentrations were measured in 38 overweight or obese subjects. Fat distribution in the abdominal subcutaneous as well as visceral fat areas was assessed by computed tomography scans at umbilical level. Furthermore, the changes of serum VEGF concentrations following body weight reduction therapy were analyzed in eight subjects recruited from the original pool of subjects. Semi-purified circulating VEGF proteins were obtained by heparin-sepharose and its biological activities were shown to alter gene expressions in human aortic endothelial cells.


RESULTS
Serum VEGF concentrations were positively correlated with BMI (r=0.433, p=0.007) and visceral fat area (r=0.488, p=0.002). Stepwise regression analysis showed the visceral fat area as the most important determinant factor for VEGF circulating levels. Following body weight reduction therapy, VEGF concentrations as well as visceral fat area were decreased. The serum semi-purified VEGF protein enhanced expressions of Ets-1 and MMP-3 in human aortic endothelial cells.


CONCLUSIONS
Increased serum VEGF concentrations associated with visceral fat accumulation could influence vascular endothelial function.
Miyazawa-Hoshimoto
S
S
Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chuo-ku, Japan.
Takahashi
K
K
Bujo
H
H
Hashimoto
N
N
Saito
Y
Y
D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D001483:Base Sequence; D015992:Body Mass Index; D017931:DNA Primers; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin; D014057:Tomography, X-Ray Computed; D014157:Transcription Factors / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D014781:Viscera
D017931:DNA Primers; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D019278:Matrix Metalloproteinase 3