Placental lipid processing in response to a maternal high-fat diet and diabetes in rats

BACKGROUND: Diabetes and obesity during pregnancy impact 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. METHODS: We 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. RESULTS: Maternal HF diet exaggerated hyperlipidemia of pregnancy; with diabetes marked dyslipidemia developed in dams but not 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 diabetes-exposed pregnancies which could not be explained by differences in hormone production. Although not confirmed, inflammation may play a role. CONCLUSION: Maternal hyperlipidemia contributes to placental lipid droplet accumulation, perinatal mortality, and aberrant FA profiles that may influence the health of the developing offspring.