1969-P: Moderate Dosage of Benzyl Butyl Phthalate Synergizes the High-Fat Diet Induced Diabesity in Male Mice

Abstract

There has been a sudden and rapid degradation in global metabolic health over the last decade, due to the progression of the obesity and diabetes epidemic. Exposure to endocrine disrupting chemicals (EDCs) used in plastic manufacturing may be contributing to this increase in metabolic disorders. Previous studies are concentrated on evaluating toxicity of these EDCs in the context of reproductive biology. However, virtually none have been performed with a range of exposure levels in both genders, especially in the context of an obesity-causing Western diet. In this study, we determined that butyl benzyl phthalate (BBP), a common EDC and food packaging plasticizer, mixed into chow (CD) (4% kcal from fat) and high fat diets (HFD) (60% kcal from fat) at varying concentrations (4 µg/kg body weight/day, 169 µg/kg body weight/day, 3 mg/kg body weight/day, 50 mg/kg body weight/day) produced a number of detrimental and sex-specific metabolic effects in C57Bl/6 male and female mouse populations after 16 weeks. Males exposed to moderate (3 mg/kg body weight/day) concentrations of BBP in an HFD were especially affected, with significant increases in body weight due to increases in liver, adipose tissue, kidney, and testes size. Other doses did not show any significant changes when compared to only CD or HFD alone. Furthermore, moderate dosage in HFD showed significant increases in fasting blood glucose, glucose tolerance, and insulin tolerance when compared to HFD alone. This group alters several molecular markers, which regulate hepatic gluconeogenesis and their transcriptional regulators, lipid metabolism, hepatic lipid synthesis, insulin signaling pathways, and inflammation. The female population did not show an intense effect as males even though they consumed similar amounts of food. Overall, these data establish a dose which can be used for a BBP induced metabolic research model, suggesting that a moderate dosage level of EDC exposure can contribute to widely ranging metabolic effects. Disclosure M.K. Kay: None. J. Zhang: None. C. Powell: None. M. Park: None. R. Sonkar: None. S. Meruvu: None. M. Choudhury: None.