Modulation of angiogenesis during adipose tissue development in murine models of obesity.
Development of vasculature and mRNA expression of 17 pro- or antiangiogenic factors were studied during adipose tissue development in nutritionally induced or genetically determined murine obesity models. Subcutaneous (SC) and gonadal (GON) fat pads were harvested from male C57Bl/6 mice kept on standard chow [standard fat diet (SFD)] or on high-fat diet for 0-15 wk and from male ob/ob mice kept on SFD. Ob/ob mice and C57Bl/6 mice on high-fat diet had significantly larger SC and GON fat pads, accompanied by significantly higher blood content, increased total blood vessel volume, and higher number of proliferating cells. mRNA and protein levels of angiopoietin (Ang)-1 were down-regulated, whereas those of thrombospondin-1 were up-regulated in developing adipose tissue in both obesity models. Ang-1 mRNA levels correlated negatively with adipose tissue weight in the early phase of nutritionally induced obesity as well as in genetically determined obesity. Placental growth factor and Ang-2 expression were increased in SC adipose tissue of ob/ob mice, and thrombospondin-2 was increased in both their SC and GON fat pads. mRNA levels of vascular endothelial growth factor (VEGF)-A isoforms VEGF-B, VEGF-C, VEGF receptor-1, -2, and -3, and neuropilin-1 were not markedly modulated by obesity. This modulation of angiogenic factors during development of adipose tissue supports their important functional role in obesity.
Voros
Gabor
G
Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs en Navorsing, Herestraat 49, B-3000 Leuven, Belgium.
Maquoi
Erik
E
Demeulemeester
Diego
D
Clerx
Natalie
N
Collen
Désiré
D
Lijnen
H Roger
HR
D016475:3T3 Cells; D000273:Adipose Tissue / Q000098:blood supply* / Q000254:growth & development; D000818:Animals; D017931:DNA Primers; D004041:Dietary Fats; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018919:Neovascularization, Physiologic; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012259:Ribonuclease, Pancreatic / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D042561:Vascular Endothelial Growth Factor B / Q000235:genetics
D017931:DNA Primers; D004041:Dietary Fats; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; C046366:angiogenin; D012259:Ribonuclease, Pancreatic