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

• DOI: 10.2337/db06-0526
• Publication Date: 2006-09-26T19:57:52Z
• Authors: H. Roger Lijnen; Valerie Christiaens; Ilse Scroyen; Gabor Voros; Marc Tjwa; Peter Carmeliet; Désiré Collen
• Keywords: Male; 0301 basic medicine; 2. Zero hunger; Antibodies, Monoclonal; Mice, Nude; Pregnancy Proteins; Dietary Fats; Mice; 03 medical and health sciences; Adipose Tissue; Adipocytes; Animals; Bone Marrow Transplantation; Placenta Growth Factor

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.