期刊
JOURNAL OF NEUROSCIENCE
卷 36, 期 4, 页码 1324-1335出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1934-15.2016
关键词
DNA methylation; epigenetics; high-fat diet; memory; obesity; Sirt1
资金
- National Heart, Lung, and Blood Institute [T32HL105349]
- National Institutes of Health [MH57014]
- UAB Diabetes and Research Training Center [P60DK079626]
- Nutrition Obesity Research Center [P30DK56336]
- United Negro College Fund (UNCF)/Merck Graduate Science Research Dissertation Fellowship
Aberrant gene expression within the hippocampus has recently been implicated in the pathogenesis of obesity-induced memory impairment. Whether a dysregulation of epigenetic modifications mediates this disruption in gene transcription has yet to be established. Here we report evidence of obesity-induced alterations in DNA methylation of memory-associated genes, including Sirtuin 1 (Sirt1), within the hippocampus, and thus offer a novel mechanism by which SIRT1 expression within the hippocampus is suppressed during obesity. Forebrain neuron-specific Sirt1 knock-out closely recapitulated the memory deficits exhibited by obese mice, consistent with the hypothesis that the high-fat diet-mediated reduction of hippocampal SIRT1 could be responsible for obesity-linked memory impairment. Obese mice fed a diet supplemented with the SIRT1-activating molecule resveratrol exhibited increased hippocampal SIRT1 activity and preserved hippocampus-dependent memory, further strengthening this conclusion. Thus, our findings suggest that the memory-impairing effects of diet-induced obesity may potentially be mediated by neuroepigenetic dysregulation of SIRT1 within the hippocampus.
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