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

Abstract

A B S T R A C TBackground: 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.

A single meal has the potential to alter brain oxylipin content

“…In conclusion, while it has previously been shown that the oxylipin content of the brain can be modified by changes in the composition of a chronically consumed diet [12][13][14][15][16][17], in this study we demonstrate that a single meal exposure is sufficient to produce differences in oxylipin content. We also demonstrate that fasting alters brain oxylipin content.…”

“…In previous work conducted in our laboratory, we found that the consumption of a Western diet over the period of three months increased arachidonic acid derived oxylipins and altered the fatty acid profiles of the brains of mice [12]. Further, others have shown that various modifications of a chronically consumed diet have the potential to modify brain oxylipin levels [13][14][15][16][17].…”

Linoleic acid‐derived metabolites constitute the majority of oxylipins in the rat pup brain and stimulate axonal growth in primary rat cortical neuron‐glia co‐cultures in a sex‐dependent manner

“…There is limited information on brain LA and OXLAM metabolism in developing rats. In adult mice, brain OXLAM concentrations were increased with dietary LA levels, but were unaffected by feeding oxidized corn oil (enriched with OXLAMs) for 8 weeks (Ramsden et al ). The fact that pup brain LA was the least abundant fatty acid relative to others (not detected or <3% composition in the lipid pools analyzed), while its metabolites constituted approximately half of the measured oxylipins, suggests that LA entering the brain is likely metabolized into OXLAMs instead of being retained.…”

Importance of the Role of ω-3 and ω-6 Polyunsaturated Fatty Acids in the Progression of Brain Cancer

“…The plasma non esterified-DHA (NE-DHA) is the main contributor to brain DHA [ 51 , 52 ]. Significantly, LA and EPA are highly represented in the cerebellum, while ARA and DHA are in the cerebrum [ 53 ]. ω-3 PUFAs play a fundamental role in maintaining the membrane integrity and fluidity, which is crucial for neurotransmitter binding, and signaling [ 54 ].…”