BackgroundDiabetes and obesity during pregnancy have an impact on the health of both mothers and developing babies. Prevention focuses on glycemic control, but increasing evidence implicates a role for lipids. Using a rat model, we showed that a maternal high-fat (HF) diet increased perinatal morbidity and mortality, but lipid processing across the maternal-placental-fetal triad remained unstudied. We hypothesized that HF diet would disrupt placental lipid processing to exaggerate fuel-mediated consequences of diabetic pregnancy.MethodsWe compared circulating lipid profiles, hormones, and inflammatory markers in dams and rat offspring from normal, diabetes-exposed, HF-diet-exposed, and combination-exposed pregnancies. Placentae were examined for lipid accumulation and expression of fuel transporters.ResultsMaternal HF diet exaggerated hyperlipidemia of pregnancy, with diabetes marked dyslipidemia developed in dams but not in offspring. Placentae demonstrated lipid accumulation and lower expression of fatty acid (FA) transporters. Diet-exposed offspring had a lower fraction of circulating essential FAs. Pregnancy loss was significantly higher in diet-exposed but not in diabetes-exposed pregnancies, which could not be explained by differences in hormone production. Although not confirmed, inflammation may play a role.ConclusionMaternal hyperlipidemia contributes to placental lipid droplet accumulation, perinatal mortality, and aberrant FA profiles that may influence the health of the developing offspring.