NOX activity in brain aging: exacerbation by high fat diet.

ABSTRACT

This study describes how age and high fat diet affect the profile of NADPH oxidase (NOX). Specifically, NOX activity and subunit expression were evaluated in the frontal cerebral cortex of 7-, 16-, and 24-month old mice following a 4-month exposure to either Western diet (WD, 41% calories from fat) or very high fat lard diet (VHFD, 60% calories from fat). Data reveal a significant effect of age in on NOX activity, and show that NOX activity was only increased by VHFD, and only in 24-month old mice. NOX subunit expression was also increased by diet only in older mice. Quantification of protein carbonyls revealed significant age-related increases in protein oxidation, and indicate that only aged mice respond to high fat diet with enhanced protein oxidation. Histological analyses indicate prominent neuronal localization of both NOX subunits and protein carbonylation. Finally, data indicate that changes in reactive microgliosis, but not astrocytosis, mirror the pattern of diet-induced NOX activation and protein oxidation. Collectively, these data show that both age and dietary fat drive NOX activation, and further indicate that aged mice are preferentially sensitive to the effects of high fat diet. These data also suggest that high fat diets might exacerbate age-related oxidative stress in the brain via increased NOX.