Maternal immune activation disrupts maternal and offspring lipid signalling in association with reduced PPARα-FGF21 expression

Maternal immune activation (MIA) during gestation increases neurodevelopmental disorder risk, but its metabolic mechanisms remain unclear. Given the role of lipid metabolism in fetal brain development and endocannabinoid signaling, we investigated whether MIA is associated with alteration in maternal and offspring lipid pathways and peroxisome proliferator-activated receptor α (PPARα)-related signaling. Pregnant rats received a single i.v. injection of the viral mimetic polyinosinic: polycytidylic acid [poly (I: C)] at gestational day 15. Lipidomic and gene-expression analyses were conducted in maternal, fetal, and adolescent male and female offspring tissues to assess fatty acid composition, desaturase activity, de novo lipogenesis (DNL), and N -acylethanolamines (NAE) signaling. MIA induced maternal weight loss, and was associated with lower hepatic DNL and Δ5/Δ6-desaturase activities, and decreased Fasn , Pparα , and Fgf21 expression, suggesting alterated PPARα-FGF21 signaling. These alterations were accompanied by reduced hepatic total NAE, including N -oleoylethanolamine (OEA), N -palmitoleoylethanolamine (POEA) and N -docosahexaenoylethanolamine (DHAEA), and hippocampal DHAEA. Fetal tissues showed diminished DHAEA and DNL indices. In adolescence, males displayed cortical decreases in NAE and 2-arachidonoyl-glycerol (2-AG), whereas females exhibited hepatic lipid accumulation but preserved cortical lipid signaling. These findings suggest that altered PPARα-related lipid signaling may contribute to the association between prenatal inflammation and metabolic alterations. Future studies should determine whether targeted nutritional activation of PPARα could mitigate MIA-induced alterations.