Gestational bisphenol A exposure induces fatty liver development in male offspring mice through the inhibition of HNF1b and upregulation of PPARγ

• DOI: 10.1007/s10565-020-09535-3
• Publication Date: 2020-07-04T08:03:39Z
• Authors: Zi Long; Junshu Fan; Guangyuan Wu; Xiyu Liu; Hao Wu; Jiangzheng Liu; Yao Chen; Shuhao Su; Xiaodong Cheng; Zhongrui Xu; Hongfei Su; Meng Cao; Chunping Zhang; Chunxu Hai; Xin Wang
• Keywords: Male; 0301 basic medicine; Transcription, Genetic; Down-Regulation; Estrogens; Lipid Metabolism; Up-Regulation; Fatty Liver; Mice, Inbred C57BL; PPAR gamma; 03 medical and health sciences; Glucose; Gene Expression Regulation; Liver; Phenols; Pregnancy; Prenatal Exposure Delayed Effects; Animals; Original Article; Female; Benzhydryl Compounds; Triglycerides; Hepatocyte Nuclear Factor 1-beta

Abstract Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) associated with non-alcoholic fatty liver disease (NAFLD). The effects of gestational BPA exposure on hepatic lipid accumulation in offspring are not fully understood. Here, we investigate the sex-dependent and glucose metabolism mice to reveal mechanisms underlying exposure-associated NAFLD. Pregnant were administered gavage or without 1 μg kg −1 day at embryonic 7.5 (E7.5)–E16.5. Hepatic evaluated these models. Both male female exhibited after treatment. Lipid dysfunction observed offspring. We revealed abnormal expression regulators that inhibition peroxisome proliferator-activated receptor γ (PPARγ) repressed induced by exposure. also found a decrease hepatocyte nuclear factor 1b (HNF1b) transcriptional repression PPARγ HNF1b was confirmed L02 cells. Downregulation HNF1b, upregulation PPARγ, subsequent essential for NAFLD development gestationally exposed as well BPA-exposed adult mice. Dysregulation HNF1b/PPARγ pathway may be involved exposure-induced These data provide new insights into mechanism metabolic dysfunction.