Effects of diets enriched in linoleic acid and its peroxidation products on brain fatty acids, oxylipins, and aldehydes in mice

Christopher E Ramsden, Marie Hennebelle, Susanne Schuster, Gregory S Keyes, Casey D Johnson, Irina A Kirpich, Jeff E Dahlen, Mark S Horowitz, Daisy Zamora, Ariel E Feldstein, Craig J McClain, Beverly S Muhlhausler, Maria Makrides, Robert A Gibson, Ameer Y Taha

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BACKGROUND: Linoleic acid (LA) is abundant in modern industrialized diets. Oxidized LA metabolites (OXLAMs) and reactive aldehydes, such as 4-hydroxy-2-nonenal (4-HNE), are present in heated vegetable oils and can be endogenously synthesized following consumption of dietary LA. OXLAMs have been implicated in cerebellar degeneration in chicks; 4-HNE is linked to neurodegenerative conditions in mammals. It unknown whether increasing dietary LA or OXLAMs alters the levels of oxidized fatty acids (oxylipins), precursor fatty acids, or 4-HNE in mammalian brain.

OBJECTIVES: To determine the effects of increases in dietary OXLAMs and dietary LA, on levels of fatty acids, oxylipins, and 4-HNE in mouse brain tissues.

METHODS: Mice (n = 8 per group) were fed one of three controlled diets for 8 weeks: (1) a low LA diet, (2) a high LA diet, or (3) the low LA diet with added OXLAMs. Brain fatty acids, oxylipins, and 4-HNE were quantified in mouse cerebellum and cerebral cortex by gas chromatography-flame ionization detection, liquid chromatography-tandem mass spectrometry, and immunoblot, respectively.

RESULTS: Increasing dietary LA significantly increased omega-6 fatty acids, decreased omega-3 fatty acids, and increased OXLAMs in brain. Dietary OXLAMs had minimal effect on oxidized lipids but did decrease both omega-6 and omega-3 fatty acids. Neither dietary LA nor OXLAMs altered 4-HNE levels.

CONCLUSION: Brain fatty acids are modulated by both dietary LA and OXLAMs, while brain OXLAMs are regulated by endogenous synthesis from LA, rather than incorporation of preformed OXLAMs.

Original languageEnglish
Pages (from-to)1206-1213
Number of pages8
JournalBiochimica et biophysica acta
Issue number10
Publication statusE-pub ahead of print - 25 Jul 2018


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Ramsden, C. E., Hennebelle, M., Schuster, S., Keyes, G. S., Johnson, C. D., Kirpich, I. A., ... Taha, A. Y. (2018). Effects of diets enriched in linoleic acid and its peroxidation products on brain fatty acids, oxylipins, and aldehydes in mice. Biochimica et biophysica acta, 1863(10), 1206-1213. https://doi.org/10.1016/j.bbalip.2018.07.007