(OR23-02-25) Polyunsaturated Fatty Acid Concentrations Are Reduced in the Cerebral Cortex of Mice When Fed an Alpha-Tocopherol Deficient Diet

Objectives: Alpha-tocopherol (αT) deficiency causes increased lipid peroxidation, the process by which reactive oxygen species attack membrane lipids, particularly polyunsaturated fatty acids (PUFAs) that are abundant in the brain. We utilize αT transfer protein knockout (Ttpa-/-) mice that are unable to transport hepatic αT to other tissues to deplete αT in the brain. This study evaluated the impact of αT deficiency on brain PUFA composition.

Methods: Male wild-type (WT) and Ttpa-/- weanling littermates (n= 4-8/group) were fed an αT-deficient diet (VED) or -sufficient diet (VES, 60 mg αT acetate/kg) ad libitum for 9 weeks (Study 1). In addition, mice of the same genotypes were fed an αT-deficient diet for 12 weeks (Study 2). αT in tissues was measured by HPLC. Brain lipids were extracted from the cerebral cortex, derivatized into fatty acid methyl esters, and quantified using GC-FID.

Results: (Study 1) Concentrations of αT in the brain, serum, and liver were significantly lower/undetectable in VED mice compared to VES mice, but genotype differences were only observed in the brain and serum. Arachidonic, adrenic, linoleic, and α-linolenic acid concentrations were significantly reduced in VED mice, with lower arachidonic, adrenic, and linoleic acid levels in WT mice. Docosahexaenoic acid concentrations trended lower in VED mice (p=0.053).

(Study 2) αT concentrations in the brain, serum, and liver were significantly lower/undetectable in Ttpa-/- mice compared to WT mice. Docosahexaenoic acid was significantly reduced in Ttpa-/- mice, however no other differences in PUFA concentrations were observed.

Conclusions: Low αT status negatively impacts the concentration of PUFAs in the murine cerebral cortex, especially in WT mice, which may be more responsive to changes in dietary αT. Docosahexaenoic acid may be especially sensitive to changes in cerebral αT concentrations, as evidenced by the reductions seen in both studies based on diet and genotype. The impact of αT status on oxidative stress and inflammatory responses will be evaluated in future studies.

Funding Sources: Abbott Nutrition via the Center for Nutrition, Learning, and Memory, University of Illinois; Division of Nutritional Sciences Vision 20/20, University of Illinois.