Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1324-1335 |
Number of pages | 12 |
Journal | Journal of Neuroscience |
Volume | 36 |
Issue number | 4 |
DOIs | |
State | Published - Jan 27 2016 |
Externally published | Yes |
Keywords
- DNA methylation
- Epigenetics
- High-fat diet
- Memory
- Obesity
- Sirt1
ASJC Scopus subject areas
- General Neuroscience