Differential mechanisms regarding triclosan vs. bisphenol A and fluorene-9-bisphenol induced zebrafish lipid-metabolism disorders by RNA-Seq

Abstract

Exposure of endocrine disrupting chemicals (EDCs) is closely related to induction of obesity, nonalcoholic fatty liver disease (NAFLD) and other lipid-metabolism diseases. Herein, we compared the effects of three EDCs exposure (triclosan, bisphenol A and fluorene-9-bisphenol) on lipid metabolism in zebrfish (Danio rerio). The differential lipid-metabolism disorders were analyzed in depth through RNA-Seq and qRT-PCR, as well as assessment of the relationship between lipid disorder and RNA methylation. Histopathological observation along with varying physiological and biochemical indexes all identified that triclosan and bisphenol A induced liver fat accumulation in acute and chronic exposure. RNA-Seq analysis showed that triclosan exposure disrupted multiple physiological processes including drug metabolism, sucrose metabolism, fat metabolism and bile secretion. The dysregulation of lipid-metabolism related genes indicated that liver steatosis in triclosan and BPA-exposed zebrafish resulted from increased fatty acid synthetase, and uptake and suppression of β-oxidation. Besides, the dysregulation of pro-inflammatory genes and endoplasmic reticulum stress showed that triclosan and bisphenol A exposure not only induced occurrence of NAFLD, but also promoted progression of hepatic inflammation. However, no significant effect on lipid metabolism was observed in fluorene-9-bisphenol-exposed treatment although the larval phenotypic malformation was found compared to the control group. Moreover, EDCs exposure led to decreased global m⁶A level and abnormal expression of m⁶A modulators in larvae. Especially, the expression of demethylase FTO (fat mass and obesity-associated protein) was significantly increased in triclosan-exposure treatment. These findings are conductive for us to deeply understand the underlying molecular mechanisms regarding the obesity and NAFLD from EDCs exposure.

Keywords: Bisphenol A; Lipid-metabolism disorder; Transcriptome sequencing; Triclosan; m(6)A RNA methylation.