High-fat diet negatively impacts both metabolic and behavioral health in outbred heterogeneous stock rats

Abstract

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.

A new experimental design to study inflammation-related versus non-inflammation-related depression in mice

“…Further ruling out potential interferences of motor impairment in the FST, we previously showed that changes in immobility can be reported in this test without general locomotion necessarily being altered [ 30 – 33 ]. In line with this, HFD-induced anxiety-like behavior, as assessed in behavioral tests involving locomotor response, were also independent of overall locomotion [ 45 ]. Akin to these findings, we showed here that both HFD and UCMS mice displayed prolonged latency to eat in the NSFT only when conducted in the new environment, which reflects increased anxiety-like behaviors unrelated to changes in appetite or locomotion [ 37 , 47 , 48 , 50 , 62 ].…”

“…As previously shown [ 44 , 50 , 61 , 62 ], UCMS and HFD notably increased immobility in the FST. Although it could be postulated that HFD-related locomotor impairment may be a confounding factor in this test [ 45 ], changes in immobility likely reflected depressive-like behavior, consistent with impaired sucrose preference in the SPT, a reward-based test modeling anhedonia, which does not rely on locomotor response. Further ruling out potential interferences of motor impairment in the FST, we previously showed that changes in immobility can be reported in this test without general locomotion necessarily being altered [ 30 – 33 ].…”

“…HFD models therefore recapitulate most of the neurobiological alterations linked to inflammation. Accordingly, they appear as particularly suitable to study the involvement of affected systems in the development of associated depressive symptoms, while offering the opportunity of considering the potential impact of obesity-related metabolic dysregulations [ 45 ].…”

Stress Alters the Effect of Alcohol on Catecholamine Dynamics in the Basolateral Amygdala

“…Day 2 (test day) recordings were analyzed by an experimenter blinded to the condition and scored for bouts of immobility. The experimenter evaluated behavior every 5 s for the duration of the test (5 min) as either swimming or immobile (Deal A. W. et al, 2020).…”

The Effect of High Fat Diet on Cerebrovascular Health and Pathology: A Species Comparative Review

“…Other factors related to HFD are also predictors of cerebrovascular disease, including aging, hypertension, elevated cholesterol, diabetes, obesity, and atherosclerosis [ 39 ]. In addition, there may be complex interactions with behavior that moderate some of the effects of HFD, such as stress and inactivity [ 113 , 114 , 115 , 116 ]. Obesity is associated with the development of many systemic diseases, including diabetes mellitus, hypertension, dyslipidemia, as well as ischemic heart disease [ 117 ].…”