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Exposure to endocrine disrupting chemicals (EDCs) used in plastic manufacturing processes may be contributing to the current increase in metabolic disorders. Here, we determined that benzyl butyl phthalate (BBP), a common EDC and food packaging plasticizer, mixed into chow diet (CD) and high fat diets (HFD) at varying concentrations (4 μg/kg body weight (bw)/day, 169 μg/kg bw/day, 3 mg/kg bw/day, 50 mg/kg bw/day) produced a number of detrimental and sex-specific metabolic effects in C57BL/6 male and female mice after 16 weeks. Male mice exposed to moderate (3 mg/kg bw/day) concentrations of BBP in an HFD were especially affected, with significant increases in body weight due to significant increases in weight of liver and adipose tissue. Other doses did not show any significant changes when compared to only CD or HFD alone. HFD in the presence of 3 mg/kg bw/day BBP showed significant increases in fasting blood glucose, glucose intolerance, and insulin intolerance when compared to HFD alone. Furthermore, this group significantly alters transcriptional regulators involved in hepatic lipid synthesis and its downstream pathway. Interestingly, most of the BBP doses had no phenotypic effect when mixed with CD and compared to CD alone. The female mice did not show a similar response as the male population even though they consumed a similar amount of food. Overall, these data establish a dose which can be used for a BBP-induced metabolic research model and suggest that a moderate dosage level of EDC exposure can contribute to widely ranging metabolic effects.

A moderate physiological dose of benzyl butyl phthalate exacerbates the high fat diet-induced diabesity in male mice