High fat diet negatively impacts both metabolic and behavioral health in an outbred rat model.

Obesity is influenced by both genetics and diet and has wide ranging comorbidities, including anxiety and depressive disorders. In this study, outbred Heterogeneous Stock (HS) rats were fed high fat diet (HFD) or low fat diet (LFD) and tested for metabolic and behavioral outcomes. Male HS rats were fed 60% HFD or 10% LFD ad lib for 12-21 weeks. Rats were weighed weekly. We assessed multiple metabolic (glucose tolerance, fasting insulin, fat pad weights) and behavioral (elevated plus maze - EPM, open field test - OFT, splash test - SpT, and forced swim test - FST) measures. We found negative effects of HFD on metabolic outcomes, including increased body weight and fat pad weights, decreased glucose tolerance, and increased fasting insulin. We also found negative effects of HFD on coping response to stress and/or despair- and anxiety-like behaviors, including increased closed arm time and decreased open arm time in the EPM, increased movement and rest episodes and decreased rearing episodes in the OFT, increased SpT grooming time, and increased FST immobility. Positive correlations were found between FST immobility and visceral fat pad weights. We also found diet-dependent correlations between EPM, OFT and SpT measures. HFD negatively affected metabolic and behavioral health in HS rats. Changes in multiple coping/despair-and anxiety-like behaviors, independent of locomotion, indicate a role of HFD on behavioral health beyond just fat mass. This work establishes the HS rat as a model to study gene by diet interactions affecting obesity and behavioral health.