Obesity weighs down memory through a mechanism involving the neuroepigenetic dysregulation of Sirt1

Academic Article


  • 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.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Heyward FD; Gilliam D; Coleman MA; Gavin CF; Wang J; Kaas G; Trieu R; Lewis J; Moulden J; David Sweatt J
  • Start Page

  • 1324
  • End Page

  • 1335
  • Volume

  • 36
  • Issue

  • 4