High fat diet increases hippocampal oxidative stress and cognitive impairment in aged mice: implications for decreased Nrf2 signaling - PubMed (original) (raw)

High fat diet increases hippocampal oxidative stress and cognitive impairment in aged mice: implications for decreased Nrf2 signaling

Christopher D Morrison et al. J Neurochem. 2010 Sep.

Abstract

Long term consumption of a high fat diet (HFD) contributes to increased morbidity and mortality. Yet the specific effects of HFD consumption on brain aging are poorly understood. In the present study 20-month old male C57Bl/6 mice were fed either 'western diet' (41% fat), very high fat lard diet (60% fat), or corresponding control diets for 16 weeks and then assessed for changes in metabolism and brain homeostasis. Although both HFDs increased adiposity and fasting blood glucose, only the high fat lard diet increased age-related oxidative damage (protein carbonyls) and impaired retention in the behavioral test. This selective increase in oxidative damage and cognitive decline was also associated with a decline in NF-E2-related factor 2 (Nrf2) levels and Nrf2 activity, suggesting a potential role for decreased antioxidant response. Taken together, these data suggest that while adiposity and insulin resistance following HFD consumption are linked to increased morbidity, the relationship between these factors and brain homeostasis during aging is not a linear relationship. More specifically, these data implicate impaired Nrf2 signaling and increased cerebral oxidative stress as mechanisms underlying HFD-induced declines in cognitive performance in the aged brain.

© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.

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Figures

Figure 1

Figure 1. Changes in body weight and total adiposity

Twenty-month old male C57Bl/6 mice were placed on Western diet (WD), High Fat Lard diet (HFL), or their respective control diets (WD-C,HFL-C) for 16 weeks and analyzed for changes in body weight (A) or total body fat using NMR (B). Data are presented as the mean and S.E.M. from 12 animals per group. *P < 0.01 for each high fat diet vs. its control; †P < 0.01 for HFL vs. WD.

Figure 2

Figure 2. Changes in individual fat pad weight

Twenty month old male C57Bl/6 mice were placed on Western diet (WD), High Fat Lard diet (HFL), or the respective control diets (WD-C,HFL-C) for 16 weeks and analyzed for changes in fat pad weight, which were manually dissected and weighed. Animals were analyzed for total fad pad weight (A), retroperitoneal fat pad (B), epididymal fat pad (C), and visceral fat pad weight (D). Data are presented as the mean and S.E.M. from 12 animals per group. *P < 0.01 for each high fat diet vs. its control; †P < 0.01 for HFL vs. WD.

Figure 3

Figure 3. Changes in fasting insulin, glucose, and leptin levels

Twenty month old male C57Bl/6 mice were placed on Western diet (WD), High Fat Lard diet (HFL), or the respective control diets (WD-C,HFL-C) for 16 weeks and analyzed for changes in fasting glucose (measured at 13 weeks; A), fasting insulin (B), and fasting leptin levels (C). Data are presented as the mean and S.E.M. from 12 animals per group. *P < 0.01 for each high fat diet vs. its control; †P < 0.01 for HFL vs. WD.

Figure 4

Figure 4. High fat lard, but not Western diet, consumption promotes increased oxidative stress

Twenty month old male C57Bl/6 mice were placed on Western diet (WD), High Fat Lard diet (HFL), or the respective control diets (WD-C,HFL-C) for 16 weeks and analyzed for changes in protein oxidation (protein carbonyls) within the hippocampus. Data are presented as the mean and S.E.M. from 8 animals per group. *P < 0.01 for HFL vs. its control diet.

Figure 5

Figure 5. High fat lard, but not Western diet, consumption promotes decreases in Nrf2 levels and Nrf2 DNA binding activity

Twenty month old male C57Bl/6 mice were placed on Western diet (WD), High Fat Lard diet (HFL), or the respective control diets (WD-C,HFL-C) for 16 weeks and analyzed for changes in Nrf2 protein levels (A), in the NRF2 responsive proteins HO-1 and NQO-1 (B), or changes in Nrf2 DNA binding activity (C). *P < 0.01 for HFL vs. control.

Figure 6

Figure 6. High fat lard, but not Western diet, consumption promotes increased cognitive decline

Twenty month old male C57Bl/6 mice were placed on Western diet (WD), High Fat Lard diet (HFL), or the respective control diets (WD-C,HFL-C) and cognitive performance was assessed in a 14-Unit T-maze. A. Mean errors during the acquisition training across 15 trials (collapsed into 3 trial blocks). B. Mean errors during the final acquisition trial. C. Mean errors during the retention trial, 7 days following acquisition. *P < 0.05 vs control.

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References

    1. Barbieri M, Gambardella A, Paolisso G, Varricchio M. Metabolic aspects of the extreme longevity. Exp Gerontol. 2008;43:74–78. - PubMed
    1. Barbieri M, Rizzo MR, Manzella D, Paolisso G. Age-related insulin resistance: is it an obligatory finding? The lesson from healthy centenarians. Diabetes Metab Res Rev. 2001;17:19–26. - PubMed
    1. Bruce-Keller AJ, Keller JN, Morrison CD. Obesity and vulnerability of the CNS. Biochim Biophys Acta. 2009;1792:395–400. - PMC - PubMed
    1. Cecarini V, Gee J, Fioretti E, Amici M, Angeletti M, Eleuteri AM, Keller JN. Protein oxidation and cellular homeostasis: Emphasis on metabolism. Biochim Biophys Acta. 2007;1773:93–104. - PubMed
    1. Cornier MA, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR, Van Pelt RE, Wang H, Eckel RH. The metabolic syndrome. Endocr Rev. 2008;29:777–822. - PMC - PubMed

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