Increased intake of omega-6 rich plant oils such as soybean and corn oil over the past few decades has inadvertently tripled the amount of n-6 linoleic acid (LA, 18:2n-6) in the diet. Although LA is nutritionally “essential”, very little is known about how it affects the brain when present in excess. This review provides an overview on the metabolism of LA by the brain and the effects of excess dietary LA intake on brain function. Pre-clinical evidence suggests that excess dietary LA increases the brain’s vulnerability to inflammation and likely acts via its oxidized metabolites. In humans, excess maternal LA intake has been linked to atypical neurodevelopment, but underlying mechanisms are unknown. It is concluded that excess dietary LA may adversely affect the brain. The potential neuroprotective role of reducing dietary LA merits clinical evaluation in future studies.

Several oxylipins are potent lipid mediators that regulate diverse aspects of health and disease and whose quantitative analysis by liquid chromatography–mass spectrometry (LC-MS) presents substantial technical challenges. As members of the lipidomics community, we developed technical recommendations to ensure best practices when quantifying oxylipins by LC-MS.

Linoleic acid (LA; 18:2 n-6), the most abundant polyunsaturated fatty acid in the US diet, is a precursor to oxidized metabolites that have unknown roles in the brain. Here, we show that oxidized LA-derived metabolites accumulate in several rat brain regions during CO₂-induced ischemia and that LA-derived 13-hydroxyoctadecadienoic acid, but not LA, increase somatic paired-pulse facilitation in rat hippocampus by 80%, suggesting bioactivity. This study provides new evidence that LA participates in the response to ischemia-induced brain injury through oxidized metabolites that regulate neurotransmission. Targeting this pathway may be therapeutically relevant for ischemia-related conditions such as stroke.