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Objectives   Previous studies involving mice have demonstrated that a cholesterol-enriched diet evokes liver steatosis, dystrophy, inflammation, and aspects of nonalcoholic fatty liver disease (NAFLD). These changes are accompanied by the activation of pro-inflammatory brain and liver molecular pathways, as well as anxiety and depressive-like behaviors. Given previously reported evidence for the neurobiological relationship between the above-mentioned molecular changes and abnormalities in coping with environmental stimuli, such as interactions with other individuals and new environmental contexts, we hypothesized that novelty exploration and aggressive behavior are affected in a mouse NAFLD model.Methods   To test this hypothesis, young female C57BL/6J mice were fed with a regular chow or a diet containing 0.2% cholesterol for 3 weeks. The mice were then assessed for new object and novel cage exploration, and social interaction in a food competition test.Results   We found reduced object exploration in mice on the cholesterol-enriched diet. This reduction was not related to whether the new object was placed in an anxiogenic or non-anxiogenic environment. These changes were accompanied by diminished exploration of the new environment in a novel cage, and delayed approach to food after a period of food deprivation. Mice on the regular chow or cholesterol-enriched diet showed no differences in aggressive behavior towards a counter-partner in a food competition test. Food intake and body weight did not differ between the groups, thus, excluding their potential as confounders in the measured behaviors.Conclusions   We conclude that a diet enriched with cholesterol reduces novelty exploration irrespective of the anxiogenic level of the environment and does not induce aggressive behavior in female mice.

Behavioral Features of Mice Fed with a Cholesterol-Enriched Diet: Deficient Novelty Exploration and Unaltered Aggressive Behavior