Metabolic Influences of Bisphenol F Exposure in Population‐based Heterogeneous Stock Rats

Abstract

Bisphenol F (BPF) is marketed as a ‘safe’ substitute for bisphenol A (BPA), an endocrine disruptor associated with obesity and heart disease (i.e. cardiometabolic disease), in manufacturing polycarbonates and in common consumer products (e.g. food packaging). BPF's environmental presence is growing rapidly and is detected in over 85% of U.S. adults and children. There is evidence of individual variation in bisphenol levels, suggesting that genetic variation or gene x environment (GxE) interactions influence risk of cardiometabolic disease due to bisphenol exposure.Characterizing the cardiometabolic effects of BPF in either humans or an animal model has not been performed, and the health risks associated with BPF exposure are vastly unknown. Traditional in vivo toxicity studies are performed in genetically undefined, outbred rats or genetically homogeneous, inbred mice, leading to conflicting results possibly due to GxE interactions. The N/NIH Heterogeneous Stock (HS) rats are a genetically heterogeneous rat population that is amenable to genetic study. The overall hypothesis of this project is that BPF‐induced cardiometabolic disease is based on underlying genetic susceptibility which can be identified using the HS rat model.The goal of this pilot project was to determine if BPF exposure influences growth and adiposity in HS rats. Weanling littermate pairs of male HS rats were randomly selected for exposure to either vehicle (0.1% Ethanol) or 1.125 mg/L BPF in 0.1% Ethanol (average dose 154 μg BPF/kg body weight/day) for five weeks in drinking water. Cardiometabolic measures, tissues, urine, and feces were taken.Our studies determined BPF treatment in HS rats significantly increases body growth (Table 1). Heritability estimates of gain in body weight at eight weeks of age were 0.90±0.13 for vehicle‐treated males and 0.67±0.25 for BPF‐treated males (median±SEM). BPF treatment alters body composition seen in nuclear magnetic resonance (NMR) measurements by increasing % fat and decreasing % lean, mirroring the increase in gonadal white adipose tissue (GWAT) mass and the significant increase in perirenal white adipose tissue (PWAT) mass in BPF‐treated males at eight weeks of age (Table 1). Our data suggest that BPF treatment increases body growth and adiposity, which are risk factors for cardiometabolic disease. Future studies will determine if the response to BPF is genetically regulated.Support or Funding InformationUniversity of Iowa Environmental Health Sciences Research Center (NIH P30 ES005605); National Institutes of Health Predoctoral Training Grant T32GM008629, PI Daniel Eberl.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.