Adult mice maintained on a high-fat diet exhibit object location memory deficits and reduced hippocampal SIRT1 gene expression

Neurobiol Learn Mem. 2012 Jul;98(1):25-32. doi: 10.1016/j.nlm.2012.04.005. Epub 2012 Apr 21.


Mounting evidence has established that diet-induced obesity (DIO) is associated with deficits in hippocampus-dependent memory. The bulk of research studies dealing with this topic have utilized rats fed a high-fat diet as an experimental model. To date, there has been a paucity of research studies that have established whether the memory deficits exhibited in DIO rats can be recapitulated in mice. Moreover, the majority of experiments that have evaluated memory performance in rodent models of DIO have utilized memory tests that are essentially aversive in nature (i.e., Morris water maze). The current study sought to fill an empirical void by determining if mice maintained on a high-fat diet exhibit deficits in two non-aversive memory paradigms: novel object recognition (NOR) and object location memory (OLM). Here we report that mice fed a high-fat diet over 23 weeks exhibit intact NOR, albeit a marked impairment in hippocampus-dependent OLM. We also determined the existence of corresponding aberrations in gene expression within the hippocampus of DIO mice. DIO mice exhibited significant reductions in both SIRT1 and PP1 mRNA within the hippocampus. Our data suggest that mice maintained on a high-fat diet present with impaired hippocampus-dependent spatial memory and a corresponding alteration in the expression of genes that have been implicated in memory consolidation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Diet, High-Fat / adverse effects*
  • Fear / physiology
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • Male
  • Maze Learning / physiology*
  • Memory / physiology
  • Memory Disorders / etiology*
  • Memory Disorders / genetics
  • Memory Disorders / metabolism
  • Memory Disorders / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Obesity / genetics
  • Obesity / metabolism
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism


  • Sirt1 protein, mouse
  • Sirtuin 1