(OR19-01-26) Depleting Brain α-tocopherol Reduces Concentrations of Unsaturated and Saturated Fatty Acids in the Cerebral Cortex in Mice

Objectives: α-tocopherol (αT), the most biologically active form of Vitamin E, is a lipophilic antioxidant that protects membrane unsaturated fatty acids from reactive oxygen species attack. Polyunsaturated fatty acids (PUFAs) comprise a large portion of brain fatty acids, and their degradation has been linked to negative impacts on brain health. Mice lacking the αT transfer protein (Ttpa^-/-), a protein which facilitates transport of hepatic αT to peripheral tissues, were used to model αT deficiency. The goal of this study was to evaluate the impact of 9- or 12-week dietary αT depletion on PUFA composition in the cerebral cortex.

Methods: For both genotypes, male and female wild-type (WT) and Ttpa^-/- weanling littermates were fed either an αT-deficient (0 mg αTA/kg) or an αT-sufficient diet (60 mg αTA/kg) ad libitum for 9 or 12 weeks. The αT-sufficient diet served as a control in both genotypes. αT tissue content was measured by HPLC. Cerebral cortex lipids were extracted, derivatized into fatty acid methyl esters, and quantified using GC-FID.

Results: Concentrations of αT in the brain and liver were significantly lower/undetectable in mice fed the αT-deficient diet for both 9 and 12 weeks when compared to mice fed the αT-sufficient diet. Ttpa^-/- mice had significantly reduced serum and brain αT compared to WT mice. Mice fed the αT-deficient diet for 9 weeks had significant reductions in saturated and monounsaturated fatty acids compared to mice fed the αT-sufficient diet. When fed the αT-deficient diet for 12 weeks, there were significant reductions in saturated, monounsaturated, PUFA, and total fatty acids compared to mice fed the αT-sufficient diet.

Conclusions: αT depletion decreases fatty acid levels in the cerebral cortex. This effect was exacerbated at 12 weeks compared to 9 weeks with changes in total, PUFA, monounsaturated, and saturated fatty acid profiles. Alterations in lipid content in the murine brain may negatively influence neurological function. The 12-week αT depletion protocol will be used to assess the effects of vitamin E depletion on brain lipid oxidation products and other metabolic outcomes in future studies.

Funding Sources: Abbott Nutrition; Division of Nutritional Sciences Vision 20/20, Margin of Excellence Research Programs at the University of Illinois; USDA Hatch.