Offspring of Normal and Diabetic Rats Fed Saturated Fat in Pregnancy Demonstrate Vascular Dysfunction

Background — Disturbances of the in utero environment may “program” for disease in later life. In this study, we determined whether dietary fat supplementation and/or diabetes in pregnancy can adversely affect vascular function in the offspring. Methods and Results —Female Sprague-Dawley rats were fed a breeding diet or a diet high in saturated fat (30% wt/wt) for 10 days before mating, throughout pregnancy, and postpartum. Endothelium-dependent relaxation to acetylcholine was blunted in isolated femoral arteries of 15-day-old weanling pups from dams fed the 30%-fat diet. Endothelial dysfunction and enhanced constrictor responses to norepinephrine were also observed in an additional study of 60-day-old offspring of dams fed 20% saturated fat. Rats with streptozotocin-induced diabetes were also fed saturated fat during pregnancy. Femoral arteries from their 15-day-old offspring showed impairment of endothelium-dependent dilation and enhanced constrictor responses to norepinephrine and the thromboxane mimetic U46619 compared with young offspring of high-fat-fed normal dams. The 30%-fat diet was also deleterious to vascular function in the maternal diabetic animals when assessed in mesenteric arteries 16 days postpartum. Conclusions —A high-fat diet in pregnancy led to vascular dysfunction in rat weanlings and young adult offspring. Vascular function further deteriorated in weanlings if the maternal rat was diabetic.