Bisphenol A Coupled with a High-Fat Diet Promotes Hepatosteatosis through Reactive-Oxygen-Species-Induced CD36 Overexpression
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-ex...
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MDPI AG
2022-04-01
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| Online Access: | https://www.mdpi.com/2305-6304/10/5/208 |
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| author | Jyun-Lin Lee Yao-Chien Wang Yu-An Hsu Chih-Sheng Chen Rui-Cian Weng Yen-Pei Lu Chun-Yu Chuang Lei Wan |
| author_facet | Jyun-Lin Lee Yao-Chien Wang Yu-An Hsu Chih-Sheng Chen Rui-Cian Weng Yen-Pei Lu Chun-Yu Chuang Lei Wan |
| author_sort | Jyun-Lin Lee |
| collection | DOAJ |
| description | 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 (α-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. |
| first_indexed | 2024-03-10T01:42:48Z |
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| id | doaj.art-f5153b8c6fb84f778d5671d3df9a9474 |
| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-10T01:42:48Z |
| publishDate | 2022-04-01 |
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| record_format | Article |
| series | Toxics |
| spelling | doaj.art-f5153b8c6fb84f778d5671d3df9a94742023-11-23T13:21:10ZengMDPI AGToxics2305-63042022-04-0110520810.3390/toxics10050208Bisphenol A Coupled with a High-Fat Diet Promotes Hepatosteatosis through Reactive-Oxygen-Species-Induced CD36 OverexpressionJyun-Lin Lee0Yao-Chien Wang1Yu-An Hsu2Chih-Sheng Chen3Rui-Cian Weng4Yen-Pei Lu5Chun-Yu Chuang6Lei Wan7Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, TaiwanDepartment of Emergency Medicine, Taichung Tzu Chi Hospital, Taichung 427, TaiwanSchool of Chinese Medicine, China Medical University, Taichung 404, TaiwanDivision of Chinese Medicine, Asia University Hospital, Taichung 413, TaiwanGraduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 106, TaiwanNational Applied Research Laboratories, Taiwan Instrument Research Institute (TIRI), Hsinchu 300, TaiwanDepartment of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, TaiwanSchool of Chinese Medicine, China Medical University, Taichung 404, TaiwanBisphenol 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 (α-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.https://www.mdpi.com/2305-6304/10/5/208bisphenol Areactive oxygen speciesendocrine-disrupting chemicalCD36non-alcoholic fatty liver diseasefatty acid uptake |
| spellingShingle | Jyun-Lin Lee Yao-Chien Wang Yu-An Hsu Chih-Sheng Chen Rui-Cian Weng Yen-Pei Lu Chun-Yu Chuang Lei Wan Bisphenol A Coupled with a High-Fat Diet Promotes Hepatosteatosis through Reactive-Oxygen-Species-Induced CD36 Overexpression Toxics bisphenol A reactive oxygen species endocrine-disrupting chemical CD36 non-alcoholic fatty liver disease fatty acid uptake |
| title | Bisphenol A Coupled with a High-Fat Diet Promotes Hepatosteatosis through Reactive-Oxygen-Species-Induced CD36 Overexpression |
| title_full | Bisphenol A Coupled with a High-Fat Diet Promotes Hepatosteatosis through Reactive-Oxygen-Species-Induced CD36 Overexpression |
| title_fullStr | Bisphenol A Coupled with a High-Fat Diet Promotes Hepatosteatosis through Reactive-Oxygen-Species-Induced CD36 Overexpression |
| title_full_unstemmed | Bisphenol A Coupled with a High-Fat Diet Promotes Hepatosteatosis through Reactive-Oxygen-Species-Induced CD36 Overexpression |
| title_short | Bisphenol A Coupled with a High-Fat Diet Promotes Hepatosteatosis through Reactive-Oxygen-Species-Induced CD36 Overexpression |
| title_sort | bisphenol a coupled with a high fat diet promotes hepatosteatosis through reactive oxygen species induced cd36 overexpression |
| topic | bisphenol A reactive oxygen species endocrine-disrupting chemical CD36 non-alcoholic fatty liver disease fatty acid uptake |
| url | https://www.mdpi.com/2305-6304/10/5/208 |
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