Pregnancy-induced metabolic changes are regulated by signals from an expanded adipose organ. Placental growth factor (PlGF), acting through vascular endothelial growth factor receptor-1 (VEGFR-1), may be among those signals. There is a steep rise in circulating PlGF during normal pregnancy, which is repressed in gravidas who develop preeclampsia. PlGF-deficiency in mice impairs adipose vascularization and development. Here, we studied young-adult PlGF-deficient (PlGF^-/-) and wild-type (wt) mice on a high-fat diet in the nongravid state and at E13.5 or E18.5 of gestation. Litter size and weight were normal, but E18.5 placentas were smaller in PlGF^-/- pregnancies. PlGF^-/- mice showed altered intra-adipose dynamics, with 1) less blood vessels and fewer brown, uncoupling protein (UCP-1)-positive, adipocytes in "white" subcutaneous (sc) and perigonadal fat compartments, and 2) white-adipocyte hypertrophy. The mRNA expression of ₃-adrenergic receptors (₃-AR), peroxisome proliferator-activated receptor (PPAR)- coactivator-1 (PGC-1), and UCP-1 was decreased accordingly. Moreover, PlGF^-/- mice showed hyperinsulinemia. Pregnancy-associated changes were largely comparable in PlGF^-/- and wt dams. They included expanded sc fat compartments and adipocyte hypertrophy, whereas adipose expression of key angiogenesis/adipogenesis (VEGFR-1, PPAR-₂) and thermogenesis (₃-AR, PGC-1 and UCP-1) genes was downregulated; circulating insulin levels gradually increased during pregnancy. In conclusion, reduced adipose vascularization in PlGF^-/- mice impairs adaptive thermogenesis in favor of energy storage, thereby promoting insulin resistance and hyperinsulinemia. Pregnancy adds to these changes by PlGF-independent mechanisms. Disturbed intra-adipose dynamics is a novel mechanism to explain metabolic changes in late pregnancy in general, and preeclamptic pregnancy in particular.