Impaired Adipose Tissue Development in Mice With Inactivation of Placental Growth Factor Function

Impaired Adipose Tissue Development in Mice With Inactivation of Placental Growth Factor Function H. Roger Lijnen 1 , Valerie Christiaens 1 , Ilse Scroyen 1 , Gabor Voros 1 , Marc Tjwa 2 , Peter Carmeliet 2 and Désiré Collen 1 2 1 Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Leuven, Belgium 2 Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Leuven, Belgium Address correspondence and reprint requests to H.R. Lijnen, Center for Molecular and Vascular Biology, KU Leuven, Campus Gasthuisberg, O & N 1, Box 911, Herestraat 49, B-3000 Leuven, Belgium. E-mail: roger.lijnen{at}med.kuleuven.be Abstract Placental growth factor (PlGF)-deficient (PlGF −/− ) and wild-type mice were kept on a standard-fat or high-fat diet for 15 weeks. With the standard-fat diet, the body weights of PlGF −/− and wild-type mice were comparable, whereas the combined weight of subcutaneous and gonadal adipose tissues was lower in PlGF −/− mice ( P = 0.02). With the high-fat diet, PlGF −/− mice had a lower body weight ( P < 0.05) and less total subcutaneous plus gonadal adipose tissue ( P < 0.0001). Blood vessel size was lower in gonadal adipose tissue of PlGF −/− mice with both the standard-fat and high-fat diet ( P < 0.05). Blood vessel density, normalized to adipocyte number, was significantly lower in subcutaneous adipose tissue of PlGF −/− mice fed the high-fat diet ( P < 0.01). De novo adipose tissue development in nude mice injected with 3T3-F442A preadipocytes was reduced ( P < 0.005) by administration of a PlGF-neutralizing antibody. Bone marrow transplantation from wild-type or PlGF −/− mice to wild-type or PlGF −/− recipient mice revealed significantly lower blood vessel density in PlGF −/− recipient mice without an effect on adipose tissue growth. Thus, in murine models of diet-induced obesity, inactivation of PlGF impairs adipose tissue development, at least in part as a result of reduced angiogenesis. BMT, bone marrow transplantation ELISA, enzyme-linked immunosorbent assay mAb, monoclonal antibody PlGF, placental growth factor VEGF, vascular endothelial growth factor VEGFR, VEGF receptor Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted July 11, 2006. Received April 19