Peroxisome proliferator-activated receptor gamma (PPARγ) activation and metabolism disturbance induced by bisphenol A and its replacement analog bisphenol S using in vitro macrophages and in vivo mouse models
Bisphenol A (BPA) and its replacement analog, bisphenol S (BPS), have been proposed as environmental obesogen to disrupt the lipid metabolism through regulating peroxisome proliferator-activated receptor gamma (PPARγ) receptor. However, there is a dearth of information on whether this biological eff...
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doaj-26a8af76f23f45349fced857aa9de5112020-11-25T01:53:41ZengElsevierEnvironment International0160-41202020-01-01134Peroxisome proliferator-activated receptor gamma (PPARγ) activation and metabolism disturbance induced by bisphenol A and its replacement analog bisphenol S using in vitro macrophages and in vivo mouse modelsPingshi Gao0Lei Wang1Nanfei Yang2Jingjing Wen3Mengshu Zhao4Guanyong Su5Jianfa Zhang6Dan Weng7School of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing 210094, ChinaSchool of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing 210094, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Department of Rheumatology and Immunology, The Affiliated Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, School of Sciences, Nanjing University, Nanjing 210023, ChinaSchool of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing 210094, ChinaSchool of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing 210094, ChinaSchool of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing 210094, ChinaSchool of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing 210094, China; Corresponding authors.School of Environmental and Biological Engineering, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing 210094, China; Corresponding authors.Bisphenol A (BPA) and its replacement analog, bisphenol S (BPS), have been proposed as environmental obesogen to disrupt the lipid metabolism through regulating peroxisome proliferator-activated receptor gamma (PPARγ) receptor. However, there is a dearth of information on whether this biological effect can occur in human macrophage, a cell type which closely interacts with adipocytes and hepatocytes to control lipid metabolism. Here, we for the first time investigate the activity of BPA and BPS on PPARγ pathway in human macrophages. The results demonstrated that BPA and BPS served as activators of PPARγ in human macrophage cell line, and significantly induced the expression of lipid metabolism-related genes, including fatty acid binding protein 4 (FABP4), cluster of differentiation 36 (CD36) and nuclear receptor subfamily 1 group H member 3 (NR1H3). In PPARγ knockout cells, expression of these genes was down-regulated, suggesting that these genes are dependent on PPARγ. The underlying mechanisms were further investigated using an in vivo mouse model, and the results confirmed the induction of PPARγ and its respective target genes in mice following exposure to BPA or BPS. Moreover, the observed alteration of PPARγ expression highly correlated with the disturbance of metabolism profiles in liver tissues as detected by 1H Nuclear Magnetic Resonance (NMR)-based metabonomics. Overall, this study provided the first evidence that BPA and BPS activated PPARγ and its target genes in human macrophages, and provided comprehensive information to confirm that BPA and BPS disturb the metabolism through targeting PPARγ via both in vitro assays and in vivo animal models.http://www.sciencedirect.com/science/article/pii/S0160412019317192 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pingshi Gao Lei Wang Nanfei Yang Jingjing Wen Mengshu Zhao Guanyong Su Jianfa Zhang Dan Weng |
spellingShingle |
Pingshi Gao Lei Wang Nanfei Yang Jingjing Wen Mengshu Zhao Guanyong Su Jianfa Zhang Dan Weng Peroxisome proliferator-activated receptor gamma (PPARγ) activation and metabolism disturbance induced by bisphenol A and its replacement analog bisphenol S using in vitro macrophages and in vivo mouse models Environment International |
author_facet |
Pingshi Gao Lei Wang Nanfei Yang Jingjing Wen Mengshu Zhao Guanyong Su Jianfa Zhang Dan Weng |
author_sort |
Pingshi Gao |
title |
Peroxisome proliferator-activated receptor gamma (PPARγ) activation and metabolism disturbance induced by bisphenol A and its replacement analog bisphenol S using in vitro macrophages and in vivo mouse models |
title_short |
Peroxisome proliferator-activated receptor gamma (PPARγ) activation and metabolism disturbance induced by bisphenol A and its replacement analog bisphenol S using in vitro macrophages and in vivo mouse models |
title_full |
Peroxisome proliferator-activated receptor gamma (PPARγ) activation and metabolism disturbance induced by bisphenol A and its replacement analog bisphenol S using in vitro macrophages and in vivo mouse models |
title_fullStr |
Peroxisome proliferator-activated receptor gamma (PPARγ) activation and metabolism disturbance induced by bisphenol A and its replacement analog bisphenol S using in vitro macrophages and in vivo mouse models |
title_full_unstemmed |
Peroxisome proliferator-activated receptor gamma (PPARγ) activation and metabolism disturbance induced by bisphenol A and its replacement analog bisphenol S using in vitro macrophages and in vivo mouse models |
title_sort |
peroxisome proliferator-activated receptor gamma (pparγ) activation and metabolism disturbance induced by bisphenol a and its replacement analog bisphenol s using in vitro macrophages and in vivo mouse models |
publisher |
Elsevier |
series |
Environment International |
issn |
0160-4120 |
publishDate |
2020-01-01 |
description |
Bisphenol A (BPA) and its replacement analog, bisphenol S (BPS), have been proposed as environmental obesogen to disrupt the lipid metabolism through regulating peroxisome proliferator-activated receptor gamma (PPARγ) receptor. However, there is a dearth of information on whether this biological effect can occur in human macrophage, a cell type which closely interacts with adipocytes and hepatocytes to control lipid metabolism. Here, we for the first time investigate the activity of BPA and BPS on PPARγ pathway in human macrophages. The results demonstrated that BPA and BPS served as activators of PPARγ in human macrophage cell line, and significantly induced the expression of lipid metabolism-related genes, including fatty acid binding protein 4 (FABP4), cluster of differentiation 36 (CD36) and nuclear receptor subfamily 1 group H member 3 (NR1H3). In PPARγ knockout cells, expression of these genes was down-regulated, suggesting that these genes are dependent on PPARγ. The underlying mechanisms were further investigated using an in vivo mouse model, and the results confirmed the induction of PPARγ and its respective target genes in mice following exposure to BPA or BPS. Moreover, the observed alteration of PPARγ expression highly correlated with the disturbance of metabolism profiles in liver tissues as detected by 1H Nuclear Magnetic Resonance (NMR)-based metabonomics. Overall, this study provided the first evidence that BPA and BPS activated PPARγ and its target genes in human macrophages, and provided comprehensive information to confirm that BPA and BPS disturb the metabolism through targeting PPARγ via both in vitro assays and in vivo animal models. |
url |
http://www.sciencedirect.com/science/article/pii/S0160412019317192 |
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