# Zearalenone exposure may increase the risk of non-alcoholic fatty liver disease by activating CYP1B1-SCD1

## TL;DR

Exposure to zearalenone may increase the risk of non-alcoholic fatty liver disease by activating specific liver enzymes.

## Contribution

Identifies CYP1B1-SCD1 as a key pathway linking zearalenone exposure to NAFLD development.

## Key findings

- Zearalenone exposure causes dose-dependent liver toxicity and lipid accumulation in rats.
- Proteomic analysis shows ZEN upregulates ER stress-related enzymes and alters CYP1B1 and SCD1 expression.
- ZEN exposure may increase NAFLD risk via CYP1B1-SCD1 activation, confirmed through clinical and animal data.

## Abstract

•Exposure to the ZEN induces dose-dependent hepatotoxicity and promotes hepatic lipid accumulation in rats.•Proteomic analysis revealed that ZEN exposure upregulates endoplasmic reticulum stress-related enzymes in rat liver.•Toxicological and clinical data demonstrates that ZEN exposure may increase the risk of NAFLD by activating CYP1B1-SCD1.

Exposure to the ZEN induces dose-dependent hepatotoxicity and promotes hepatic lipid accumulation in rats.

Proteomic analysis revealed that ZEN exposure upregulates endoplasmic reticulum stress-related enzymes in rat liver.

Toxicological and clinical data demonstrates that ZEN exposure may increase the risk of NAFLD by activating CYP1B1-SCD1.

Zearalenone (ZEN) is an oestrogen-like mycotoxin that widely contaminates food and feed worldwide. Current research suggests that ZEN causes liver injury by disrupting hepatic lipid metabolism. Furthermore, prolonged disturbances in hepatic lipid metabolism are believed to play a role in the progression of non-alcoholic fatty liver disease (NAFLD). However, the exact association between ZEN exposure and the development of NAFLD is unclear. In this study, we established a rat model of ZEN-induced hepatic lipid accumulation (2.5, 5, 10 mg/kg/d b.w.,14 d, i.g.) to investigate the key targets of ZEN-induced hepatic lipid accumulation and to explore the potential link between ZEN exposure and NAFLD. Histological staining of rat liver showed that ZEN caused significant pathological changes and lipid accumulation; biochemical analysis showed that ZEN significantly and dose-dependently increased serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and disrupted the serum lipid profile in rats; proteomic analysis showed that ZEN significantly altered protein expression levels in rat liver, especially SOAT1, SOAT2, CYP1B1 and SCD1 (p < 0.05). Through bioinformatics analyses, we combined ZEN exposure with a database of NAFLD clinical samples to reveal that ZEN exposure may increase the risk of NAFLD through activation of the CYP1B1-SCD1 pathway, and further animal experiments confirmed this. This study identifies the key target of ZEN-induced lipid accumulation and provides a basis for further research on the intrinsic link between ZEN exposure and NAFLD.