High Fat Diet Increases Hippocampal Oxidative Stress and Cognitive Impairment in Aged Mice: Implications for decreased Nrf2 signaling.

MORRISON, CHRISTOPHER D.; PISTELL, PAUL J.; INGRAM, DONALD K.; JOHNSON, WILLIAM D.; LIU, YING; FERNANDEZ-KIM, SUN OK; WHITE, CHRISTY L.; PURPERA, MEGAN N.; URANGA, ROMINA M.; BRUCE-KELLER, ANNADORA J.; KELLER, JEFFREY N.

JOURNAL OF NEUROCHEMISTRY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2010 vol. 114 p. 1581 - 1589

0022-3042

Long term consumption of a high fat diet (HFD) contributes to increased morbidity andmortality. Yet the specific effects of HFD consumption on brain aging are poorlyunderstood. In the present study 20-month old male C57Bl/6 mice were fed either“Western Diet” (WD, 41% fat), very high fat lard diet (HFL, 60% fat), or correspondingcontrol diets for 16 weeks and then assessed for changes in metabolism and brainhomeostasis. Although both HFDs increased adiposity and fasting blood glucose, onlythe HFL diet increased age-related oxidative damage (protein carbonyls) and impairedretention in the behavioral test. This selective increase in oxidative damage andcognitive decline was also associated with a decline in Nrf2 levels and Nrf2 activity,suggesting a potential role for decreased antioxidant response. Taken together, thesedata suggest that while adiposity and insulin resistance following HFD consumption arelinked to increased morbidity, the relationship between these factors and brainhomeostasis during aging is not a linear relationship. More specifically, these dataimplicate impaired Nrf2 signaling and increased cerebral oxidative stress asmechanisms underlying HFD-induced declines in cognitive performance in the agedbrain.