Lijnen H Roger, Christiaens Valerie, Scroyen Ilse, Voros Gabor, Tjwa Marc, Carmeliet Peter, Collen Désiré
Center for Molecular and Vascular Biology, KU Leuven, Campus Gasthuisberg, O & N 1, Box 911, Herestraat 49, B-3000 Leuven, Belgium.
Diabetes. 2006 Oct;55(10):2698-704. doi: 10.2337/db06-0526.
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.
将胎盘生长因子（PlGF）缺陷型（PlGF-/-）小鼠和野生型小鼠分别给予标准脂肪饮食或高脂饮食15周。在标准脂肪饮食条件下，PlGF-/-小鼠和野生型小鼠的体重相当，但PlGF-/-小鼠皮下和性腺脂肪组织的总重量较低（P = 0.02）。在高脂饮食条件下，PlGF-/-小鼠体重较低（P < 0.05），皮下和性腺脂肪组织总量也较少（P < 0.0001）。无论标准脂肪饮食还是高脂饮食，PlGF-/-小鼠性腺脂肪组织中的血管大小均较小（P < 0.05）。在高脂饮食喂养的PlGF-/-小鼠皮下脂肪组织中，以脂肪细胞数量标准化后的血管密度显著降低（P < 0.01）。给裸鼠注射3T3-F442A前脂肪细胞后，给予PlGF中和抗体可减少新生脂肪组织的发育（P < 0.005）。将野生型或PlGF-/-小鼠的骨髓移植到野生型或PlGF-/-受体小鼠中，结果显示PlGF-/-受体小鼠的血管密度显著降低，而对脂肪组织生长无影响。因此，在饮食诱导的肥胖小鼠模型中，PlGF失活会损害脂肪组织发育，至少部分原因是血管生成减少。
