Behavioral changes in male mice fed a high-fat diet are associated with IL-1β expression in specific brain regions

Physiol Behav. 2017 Feb 1;169:130-140. doi: 10.1016/j.physbeh.2016.11.016. Epub 2016 Nov 19.


High-fat diet (HFD)-induced obesity is associated with not only increased risk of metabolic and cardiovascular diseases, but cognitive deficit, depression and anxiety disorders. Obesity also leads to low-grade peripheral inflammation, which plays a major role in the development of metabolic alterations. Previous studies suggest that obesity-associated central inflammation may underlie the development of neuropsychiatric deficits, but further research is needed to clarify this relationship. We used 48 male C57BL/6J mice to investigate whether chronic consumption of a high-fat diet leads to increased expression of interleukin-1β (IL-1β) in the hippocampus, amygdala and frontal cortex. We also determined whether IL-1β expression in those brain regions correlates with changes in the Y-maze, open field, elevated zero maze and forced swim tests. After 16weeks on dietary treatments, HFD mice showed cognitive impairment on the Y-maze test, greater anxiety-like behavior during the open field and elevated zero maze tests, and increased depressive-like behavior in the forced swim test. Hippocampal and amygdalar expression of IL-1β were significantly higher in HFD mice than in control mice fed a standard diet (SD). Additionally, hippocampal GFAP and Iba1 immunoreactivity were increased in HFD mice when compared to SD controls. Cognitive performance negatively correlated with level of IL-1β in the hippocampus and amygdala whereas an observed increase in anxiety-like behavior was positively correlated with higher expression of IL-1β in the amygdala. However, we observed no association between depressive-like behavior and IL-1β expression in any of the brain regions investigated. Together our data provide evidence that mice fed a HFD exhibit cognitive deficits, anxiety and depressive-like behaviors. Our results also suggest that increased expression of IL-1β in the hippocampus and amygdala may be associated with the development of cognitive deficits and anxiety-like behavior, respectively.

Keywords: Amygdala; Anxiety-like behavior; Cognitive deficit; High-fat diet; Hippocampus; Interleukin-1β.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Body Weight / physiology
  • Brain / metabolism*
  • Brain / physiopathology*
  • Calcium-Binding Proteins / metabolism
  • Cognition Disorders / etiology*
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Exploratory Behavior / physiology
  • Gene Expression Regulation*
  • Glial Fibrillary Acidic Protein / metabolism
  • Glucose Tolerance Test
  • Interleukin-1beta / genetics*
  • Interleukin-1beta / metabolism
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / metabolism
  • Swimming / psychology


  • Aif1 protein, mouse
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Interleukin-1beta
  • Microfilament Proteins