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

Frankie D. Heyward, R. Grace Walton, Matthew S. Carle, Mark A. Coleman, W. Timothy Garvey, J. David Sweatt

Research output: Contribution to journalArticlepeer-review

136 Scopus citations


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.

Original languageEnglish
Pages (from-to)25-32
Number of pages8
JournalNeurobiology of Learning and Memory
Issue number1
StatePublished - Jul 2012

Bibliographical note

Funding Information:
We would like to thank Erin Johnson and Alicia Hall who were instrumental in our optimizing the novel object paradigms, and Dr. Erik Roberson for allowing us to use his behavioral apparatus. This work was supported by a Grant award from the National Heart, Lung, and Blood Institute (T32HL105349) to FDH, by the NIH (MH57014 to JDS; DK038765 and DK083562 to WTG) and the Merit Review program of the Department of Veterans Affairs (to WTG). We also acknowledge support from the UAB Diabetes and Research Training Center (P60DK079626) and the Nutrition Obesity Research Center (P30DK56336).


  • Insulin resistance
  • Memory
  • Obesity
  • Object location memory
  • SIRT1

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience


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