Impaired adipose tissue development in mice with inactivation of placental growth factor function.
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.
Lijnen
H Roger
HR
Center for Molecular and Vascular Biology, KU Leuven, Campus Gasthuisberg, O & N 1, Box 911, Herestraat 49, B-3000 Leuven, Belgium. roger.lijnen@med.kuleuven.be
Christiaens
Valerie
V
Scroyen
Ilse
I
Voros
Gabor
G
Tjwa
Marc
M
Carmeliet
Peter
P
Collen
Désiré
D
D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000098:blood supply / Q000254:growth & development*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016026:Bone Marrow Transplantation / Q000502:physiology; D004041:Dietary Fats / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008819:Mice, Nude; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000172:deficiency* / Q000276:immunology
D000911:Antibodies, Monoclonal; D004041:Dietary Fats; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor