title: Effect of vascular endothelial growth factor receptor 2 antagonism on adiposity in obese mice.
abstract: Development and maintenance of fat depots require angiogenesis, in which vascular endothelial growth factor (VEGF) and its receptors play a crucial role. We have evaluated the effect of blocking VEGF receptor 2 (VEGF-R2) with a MAB (DC101) on adipose tissue of mice with established obesity. Therefore, obese male wild-type C57B1/6 mice were treated with i.p. injection of DC101 (40 mg/kg body weight, twice weekly during 13 weeks) or of the control antibody 1C8. Treatment with DC101 resulted in a slightly lower body weight but had no effect on subcutaneous (SC) or gonadal (GON) white adipose tissue mass, as monitored by MRI. Histochemical analysis of isolated SC and GON fat pads did not reveal significant effects of DC101 treatment on adipocyte or blood vessel size or density. Plasma levels of the liver enzymes aspartate aminotransferase and alanine aminotransferase as well as liver triglyceride levels were significantly decreased following DC101 treatment. Plasma glucose levels were markedly lower upon DC101 treatment, whereas insulin and adiponectin levels were not affected. Furthermore, Akt phosphorylation in adipose tissues was not affected. Thus, in vivo VEGF-R2 blockade in mice with established nutritionally induced obesity did not significantly affect insulin signaling in adipose tissue or adiposity.
authors: Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, KU Leuven, Campus Gasthuisberg, Onderwijs & Navorsing 1, Herestraat 49, Box 911, B-3000 Leuven, Belgium. roger.lijnen@med.kuleuven.be
authors: H Roger
authors: HR
authors: Lijnen
authors: Ilse
authors: I
authors: Scroyen
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; C511761:DC101 monoclonal antibody; D040301:Vascular Endothelial Growth Factor Receptor-2