Zearalenone Decreases Food Intake by Disrupting the Gut–Liver–Hypothalamus Axis Signaling via Bile Acids
Peiqiang Yuan, Rongman Ma, Liang Hu, Ran Li, Peng Wang, Sen Lin, Jiancai Huang, Hongmei Wen, Lingjie Huang, Hua Li, Bin Feng, Hong Chen, Yuntao Liu, Xiaoling Zhang, Yan Lin, Shengyu Xu, Jian Li, Yong Zhuo, Lun Hua, Lianqiang Che, De Wu, Zhengfeng Fang
Abstract
Zearalenone (ZEN) is a mycotoxin that is harmful to humans and animals. In this study, female and male rats were exposed to ZEN, and the results showed that ZEN reduced the farnesoid X receptor (FXR) expression levels in the liver and disrupted the enterohepatic circulation of bile acids (BAs). A decrease in food intake induced by ZEN was negatively correlated with an increase in the level of total BAs. BA-targeted metabolomics revealed that ZEN increased glycochenodeoxycholic acid levels and decreased the ratio of conjugated BAs to unconjugated BAs, which further increased the hypothalamic FXR expression levels. Preventing the increase in total BA levels induced by ZEN via Lactobacillus rhamnosus GG intervention restored the appetite. In conclusion, ZEN disrupted the enterohepatic circulation of BAs to decrease the level of food intake. This study reveals a possible mechanism by which ZEN affects food intake and provides a new approach to decrease the toxic effects of ZEN.