Omega-6 linoleic acid (LA) is a polyunsaturated fatty acid that has become ubiquitous in our diets due to agricultural shifts towards high LA soybean and corn oils. Despite accounting for approximately 7% of daily calories, little is known about the role of this abundant dietary fatty acid on neurodevelopment. There is reason to believe that excess maternal LA intake may adversely impact brain development based on 1) a few correlative clinical reports showing an association between maternal breast milk LA levels and adverse neurodevelopmental outcomes in children, and 2) our recent preliminary studies in rats showing that LA is a precursor to bioactive oxidized linoleic acid metabolites (OXLAMs), which make up the majority (40%) of oxidized lipids in the brain, and regulate neuronal signaling and morphogenesis in young pups. The goal of the present exploratory proposal is to test the hypothesis that excess maternal LA intake increases brain OXLAM concentrations in developing rat pups, and that these OXLAMs directly alter neurodevelopment. Understanding the role of maternal LA intake on neurodevelopment is important for assessing risks associated with excess maternal LA consumption.
Demonstrating that excess maternal LA intake alters the trajectory of neurodevelopment will provide proof-of- concept justification for conducting appropriately designed clinical studies that directly address the impact of excess dietary LA on brain development. This will ultimately lead to establishing scientifically valid LA consumption guidelines during pregnancy and lactation. The proposed work may also underscore an important and under-recognized link between dietary LA and the rising prevalence of neurodevelopmental disorders such as autism.