PMID- 35622622 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2305-6304 (Electronic) IS - 2305-6304 (Linking) VI - 10 IP - 5 DP - 2022 Apr 22 TI - Bisphenol A Coupled with a High-Fat Diet Promotes Hepatosteatosis through Reactive-Oxygen-Species-Induced CD36 Overexpression. LID - 10.3390/toxics10050208 [doi] LID - 208 AB - Bisphenol A (BPA) is an endocrine-disrupting chemical that affects lipid metabolism and contributes to non-alcoholic fatty liver disease (NAFLD). The mechanism of BPA exposure in hepatic lipid accumulation and its potential effect on NAFLD remain unclear. This study investigated the effect of BPA-exposure-induced hepatic lipid deposition on the pathology of NAFLD and its underlying mechanism in vitro and in vivo. BPA increased intracellular reactive oxygen species (ROS) levels, and promoted fatty acid uptake through upregulation of a free fatty acid uptake transporter, cluster of differentiation 36 (CD36), in HUH-7 cells. Additionally, C57BL/6 mice administered a high-fat/high-cholesterol/high-cholic acid diet (HFCCD) and BPA (50 mg/kg body weight) for 8 weeks developed a steatohepatitis-like phenotype, characterized by alpha-smooth muscle actin (alpha-SMA, an indicator of hepatic fibrosis) and cleaved caspase 3 (an indicator of apoptosis) in hepatic tissue; moreover, they had a higher oxidative stress index of 8-hydroxydeoxyguanosine (8-OHdG) in liver tissue compared to the control group. Treatment with ROS scavenger n-acetylcysteine (NAC) ameliorated BPA-mediated HFCCD-induced lipid accumulation and steatohepatitis in the livers of treated mice. Our study indicates that BPA acts synergistically to increase hepatic lipid uptake and promote NAFLD development by stimulating ROS-induced CD36 overexpression. FAU - Lee, Jyun-Lin AU - Lee JL AD - Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan. FAU - Wang, Yao-Chien AU - Wang YC AD - Department of Emergency Medicine, Taichung Tzu Chi Hospital, Taichung 427, Taiwan. FAU - Hsu, Yu-An AU - Hsu YA AD - School of Chinese Medicine, China Medical University, Taichung 404, Taiwan. FAU - Chen, Chih-Sheng AU - Chen CS AD - Division of Chinese Medicine, Asia University Hospital, Taichung 413, Taiwan. AD - Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 401, Taiwan. AD - Department of Chinese Medicine, China Medicine University Hospital, Taichung 404, Taiwan. FAU - Weng, Rui-Cian AU - Weng RC AD - Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 106, Taiwan. AD - National Applied Research Laboratories, Taiwan Instrument Research Institute (TIRI), Hsinchu 300, Taiwan. FAU - Lu, Yen-Pei AU - Lu YP AD - National Applied Research Laboratories, Taiwan Instrument Research Institute (TIRI), Hsinchu 300, Taiwan. FAU - Chuang, Chun-Yu AU - Chuang CY AUID- ORCID: 0000-0001-8060-192X AD - Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan. FAU - Wan, Lei AU - Wan L AD - School of Chinese Medicine, China Medical University, Taichung 404, Taiwan. AD - Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung 404, Taiwan. AD - Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 413, Taiwan. LA - eng PT - Journal Article DEP - 20220422 PL - Switzerland TA - Toxics JT - Toxics JID - 101639637 PMC - PMC9145332 OTO - NOTNLM OT - CD36 OT - bisphenol A OT - endocrine-disrupting chemical OT - fatty acid uptake OT - non-alcoholic fatty liver disease OT - reactive oxygen species COIS- The authors declare no conflict of interest. EDAT- 2022/05/28 06:00 MHDA- 2022/05/28 06:01 PMCR- 2022/04/22 CRDT- 2022/05/27 13:03 PHST- 2022/03/08 00:00 [received] PHST- 2022/04/13 00:00 [revised] PHST- 2022/04/19 00:00 [accepted] PHST- 2022/05/27 13:03 [entrez] PHST- 2022/05/28 06:00 [pubmed] PHST- 2022/05/28 06:01 [medline] PHST- 2022/04/22 00:00 [pmc-release] AID - toxics10050208 [pii] AID - toxics-10-00208 [pii] AID - 10.3390/toxics10050208 [doi] PST - epublish SO - Toxics. 2022 Apr 22;10(5):208. doi: 10.3390/toxics10050208.