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

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

Abbreviations: BMT, bone marrow transplantation; ELISA, enzyme-linked immunosorbent assay; mAb, monoclonal antibody; PlGF, placental growth factor; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor

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.

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