title: Behavioral changes in male mice fed a high-fat diet are associated with IL-1β expression in specific brain regions.
abstract: 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.
authors.affiliation: Military and Emergency Medicine, Consortium for Health and Military Performance, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: camila.almeida.ctr@usuhs.edu.
authors.forename: Camila P
authors.initials: CP
authors.lastname: Almeida-Suhett
authors.affiliation: Military and Emergency Medicine, Consortium for Health and Military Performance, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Graham
authors.affiliation: Military and Emergency Medicine, Consortium for Health and Military Performance, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Military and Emergency Medicine, Consortium for Health and Military Performance, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Deuster
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005951:Glucose Tolerance Test; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D013550:Swimming / Q000523:psychology
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D008840:Microfilament Proteins
keywords: Amygdala; Anxiety-like behavior; Cognitive deficit; High-fat diet; Hippocampus; Interleukin-1β