Dietary Dependent Alteration of Blood‐Brain Barrier Tight Junctional Protein Expression

Abstract

The impact of diet on brain health extends to the blood‐brain barrier (BBB). Western diets high in saturated fatty acids, such as lard, increase the risk for neurodegenerative disease and cerebrovascular dysfunction. Whereas, fish‐oil (FO) diets containing long‐chain polyunsaturated fatty acids can form products that reduce inflammation and have been identified to have cerebrovascular benefit. However, the impact of dietary fats on the BBB endothelial cell tight junctions remains unclear. BBB tight junction integrity is governed by key proteins, including claudin‐5, occludin, and zonula occluden‐1 (ZO1). This study examined the effect of lard and FO based diets on these key tight junctional proteins.Male C57BL/6J mice received a diet containing either 10% lard, 10% FO, 41% lard or 41% FO over 32 weeks. Cortical brain tissue was harvested at conclusion of treatment, with protein (Western blot) and mRNA (RT‐qPCR) expression analyses performed. Body weights and blood chemistry measures were also evaluated. Two‐way ANOVAs performed, with Tukey post‐hoc test used to determine if means significantly differed, with significance set at P<0.05.No differences in mRNA expression were observed across diets. Neither the type or percentage of fat had any impact on occludin protein expression. ZO1 protein expression was significantly higher with FO compared to lard. A significant interaction was found between the type and percentage of fat on claudin‐5 protein expression. Respective to lard, claudin‐5 protein expression significantly decreased as the percentage of fat increased from 10 to 41%. Respective to FO, claudin‐5 protein expression significantly increased as the percentage of fat increased from 10 to 41%. Respective to 10% fat, claudin‐5 protein expression was significantly lower in FO compared to lard. Respective to 41% fat, claudin‐5 protein expression was significantly lower in lard compared to FO.Study identified ZO1 and Claudin‐5 protein expression changes within the brain are linked to diet. Data supports that diets high in FO have a greater expression of key tight junctional proteins, which suggests enhanced BBB integrity.Support or Funding InformationSupported by the NIH, National Institute of Neurological Disorders and Stroke (grant R21NS090282).