Characterizing the obesogenic and fatty liver-inducing effects of Acetyl tributyl citrate (ATBC) plasticizer using both in vivo and in vitro models.

The global incidence of obesity and non-alcoholic fatty liver disease (NAFLD) is rising rapidly in recent years. Environmental factors including usage of plastics and exposure to chemicals have been proposed as important contributors to the obesity pandemic. Acetyl tributyl citrate (ATBC) is a non-phthalate plasticizer widely used in food packaging, personal care products, medical devices and children's toys etc. Due to its high leakage rate from plastics, exposure risk of ATBC keeps increasing. Although there are some studies investigating the safety of ATBC on human health, these studies mainly focused on high dosages and information regarding ATBC safety at environmental-relevant low levels is still limited. In this study, we aimed to evaluate the safety of subchronic exposure to environmentally-relevant concentrations of ATBC. C57BL/6J mice were orally exposed to ATBC for 6 or 14 weeks. Results indicated that ATBC exposure increased the body weight gain, the body fat content and the size of adipocytes, induced liver steatosis in mice. Consistent with in vivo effects, ATBC treatment increased the intracellular lipid accumulation in vitro hepatocytes. Transcriptome sequencing, qRT-PCR analysis and western blotting revealed that ATBC exposure affected the expression of genes involved in de novo lipogenesis and lipid uptake. Therefore, based on our subchronic and in vitro results, it suggested that ATBC might be a potential environmental obesogen with metabolism-disturbing and fatty liver-inducing risk, and its application in many consumer products should be carefully re-evaluated. [Display omitted] • Subchronic exposure to environmentally-relevant low dosages of ATBC induced obesity and liver steatosis in C57BL/6J mice. • ATBC treatment increased intracellular lipid accumulation in both mouse hepatocytes and human macrophages. • ATBC treatment induced the expression of genes regulating de novo lipogenesis and lipid uptake. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Hazardous Materials is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)