MATERNAL WESTERN DIET IMPAIRS CARDIOVASCULAR FUNCTION AND MODULATES NEUROBEHAVIORAL OUTCOMES IN FEMALE OFFSPRING

Recent evidence suggests that early-life exposure to a Western diet may lead to persistent neurodevelopmental impairments that could predispose offspring to severe neurological dysfunctions, including an increased risk of neurodegenerative disorders, in a sex-specific manner. In the present work, female Wistar Han rats were exposed to either a control diet (CD) or a Western diet (WD) during gestation and lactation (14 weeks). After weaning, all females were maintained on a CD and evaluated at postnatal days (PND) 30, 60, and 90. Behavioral tests included locomotion, open field (OF), elevated zero maze (EZM), novelty-suppressed feeding, self-grooming, novel object recognition, and social interaction. Vascular function was examined in third-order branches of the superior mesenteric artery, along with blood pressure measurements. Molecular mechanisms underlying observed changes were investigated in the prefrontal cortex and hippocampus (HIP) using RNA sequencing and ELISA. Maternal WD induced an increase in adiposity, accompanied by reduced acetylcholine responsiveness, which was associated with altered contractile responses to endothelin-1 at PND30 and elevated systolic blood pressure at PND90. Additionally, maternal WD exposure resulted in a higher number of line crossings in the OF test and increased head-dipping behavior in the EZM at PND60. Furthermore, maternal WD downregulated eNOS and VEGF-B gene and protein expression in the HIP at PND60. Altered expression of genes involved in cardiovascular regulation and inflammatory signaling observed after early-life exposure to a maternal Western diet suggests the presence of early molecular changes that could contribute to long-term vulnerability of the nervous and cardiovascular systems.