Sexual Dimorphism in Coping/Despair‐Like Response to High Fat Diet in Heterogeneous Stock Rats

Abstract

Obesity is a growing epidemic associated with a range of comorbidities, including heart disease, diabetes, and mental health. Studies suggest underlying genetics may be contributing to both adiposity and anxiety/depression, in addition to environmental factors, such as diet, contributing to both. To better understand the shared genetic factors involved in obesity and mental health, we used the Heterogeneous Stock (HS) rat, a population created from 8 inbred strains outbred to maximize genetic diversity, resulting in genetically and phenotypically unique individual rats. In this study, we investigated metabolic and behavioral responses to high fat diet (HFD) or low fat diet (LFD) in male and female HS rats. Metabolic phenotypes include body weight, fat pad weight, glucose tolerance, and fasting insulin. Behavioral phenotypes include anxiety-like (elevated plus maze and open field test) and coping/despair-like behaviors (splash test and forced swim test). Both male and female rats showed worsened metabolic outcomes, including increased body weight and fat pad weight and decreased glucose tolerance, following HFD compared to LFD. In behavioral outcomes, HFD males showed increased immobility in the FST as well as anxiety-like behavior in the OFT compared to LFD. However, no effect of diet was found on behavioral phenotypes in females. In conclusion, sexual dimorphism in response to diet was seen for behavioral, but not metabolic traits. Future work will investigate what is driving the diet-induced behavioral response in males.