Induction of lipid metabolism dysfunction, oxidative stress and inflammation response by tris(1-chloro-2-propyl)phosphate in larval/adult zebrafish

As an important organophosphate flame retardant, tris(1-chloro-2-propyl)phosphate (TCPP) is ubiquitous in the environment leading to inevitable human exposure. However, there is a paucity of information regarding its acute/chronic effects on obesity, lipid homeostasis, and hepatocellular carcinoma,...

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Main Authors: Jin Yan, Zijia Zhao, Min Xia, Shuya Chen, Xiancheng Wan, Anfei He, Guangyao Daniel Sheng, Xuedong Wang, Qiuhui Qian, Huili Wang
Format: Article
Language:English
Published: Elsevier 2022-02-01
Series:Environment International
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S016041202200006X
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author Jin Yan
Zijia Zhao
Min Xia
Shuya Chen
Xiancheng Wan
Anfei He
Guangyao Daniel Sheng
Xuedong Wang
Qiuhui Qian
Huili Wang
author_facet Jin Yan
Zijia Zhao
Min Xia
Shuya Chen
Xiancheng Wan
Anfei He
Guangyao Daniel Sheng
Xuedong Wang
Qiuhui Qian
Huili Wang
author_sort Jin Yan
collection DOAJ
description As an important organophosphate flame retardant, tris(1-chloro-2-propyl)phosphate (TCPP) is ubiquitous in the environment leading to inevitable human exposure. However, there is a paucity of information regarding its acute/chronic effects on obesity, lipid homeostasis, and hepatocellular carcinoma, especially regarding the underlying molecular mechanisms in humans. Herein, we investigated the effects of TCPP exposure (5–25 mg/L) on lipid homeostasis in larval and adult zebrafish (Danio rerio). TCPP exposure caused remarkable lipid-metabolism dysfunction, which was reflected in obesity and excessive lipid accumulation in zebrafish liver. Mechanistically, TCPP induced the over-expression of adipogenesis genes and suppressed the expression of fatty-acid β-oxidation genes. Consequently, excess lipid synthesis and deficient expenditure triggered oxidative damage and an inflammation response by disrupting the antioxidant system and over-expressing proinflammatory cytokine. Based on high-throughput transcriptome sequencing, we found that TCPP exposure led to enrichment of several pathways involved in lipid metabolism and inflammation, as well as several genes related to pathways of cancer. Notably, increasing expressions of Ki-67 and 53BP1 proteins, which are reliable biomarkers for recognition and risk prediction of cellular proliferation in cancer cells, were observed in liver tissues of adult zebrafish. These results imply that chronic TCPP exposure triggers a potential risk of hepatocellular carcinogenesis (HCC) progression. Collectively, these findings offer new insights into our mechanistic understanding for the health effects of organophosphorus flame retardants on humans.
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spelling doaj.art-b582057fdfc946d7a7eef5212cb239002022-12-22T04:06:11ZengElsevierEnvironment International0160-41202022-02-01160107081Induction of lipid metabolism dysfunction, oxidative stress and inflammation response by tris(1-chloro-2-propyl)phosphate in larval/adult zebrafishJin Yan0Zijia Zhao1Min Xia2Shuya Chen3Xiancheng Wan4Anfei He5Guangyao Daniel Sheng6Xuedong Wang7Qiuhui Qian8Huili Wang9Suzhou University of Science and Technology, National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou 215009, ChinaSuzhou University of Science and Technology, National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou 215009, ChinaSuzhou University of Science and Technology, National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou 215009, ChinaSuzhou University of Science and Technology, National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou 215009, ChinaSuzhou University of Science and Technology, National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou 215009, ChinaSuzhou University of Science and Technology, National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou 215009, ChinaSuzhou University of Science and Technology, National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou 215009, ChinaSuzhou University of Science and Technology, National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou 215009, ChinaSuzhou University of Science and Technology, National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou 215009, ChinaCorresponding author.; Suzhou University of Science and Technology, National and Local Joint Engineering Laboratory of Municipal Sewage Resource Utilization Technology, School of Environmental Science and Engineering, Suzhou 215009, ChinaAs an important organophosphate flame retardant, tris(1-chloro-2-propyl)phosphate (TCPP) is ubiquitous in the environment leading to inevitable human exposure. However, there is a paucity of information regarding its acute/chronic effects on obesity, lipid homeostasis, and hepatocellular carcinoma, especially regarding the underlying molecular mechanisms in humans. Herein, we investigated the effects of TCPP exposure (5–25 mg/L) on lipid homeostasis in larval and adult zebrafish (Danio rerio). TCPP exposure caused remarkable lipid-metabolism dysfunction, which was reflected in obesity and excessive lipid accumulation in zebrafish liver. Mechanistically, TCPP induced the over-expression of adipogenesis genes and suppressed the expression of fatty-acid β-oxidation genes. Consequently, excess lipid synthesis and deficient expenditure triggered oxidative damage and an inflammation response by disrupting the antioxidant system and over-expressing proinflammatory cytokine. Based on high-throughput transcriptome sequencing, we found that TCPP exposure led to enrichment of several pathways involved in lipid metabolism and inflammation, as well as several genes related to pathways of cancer. Notably, increasing expressions of Ki-67 and 53BP1 proteins, which are reliable biomarkers for recognition and risk prediction of cellular proliferation in cancer cells, were observed in liver tissues of adult zebrafish. These results imply that chronic TCPP exposure triggers a potential risk of hepatocellular carcinogenesis (HCC) progression. Collectively, these findings offer new insights into our mechanistic understanding for the health effects of organophosphorus flame retardants on humans.http://www.sciencedirect.com/science/article/pii/S016041202200006XTris(1-chloro-2-propyl)phosphateLipid accumulationInflammation responseHepatocellular carcinogenesisZebrafish
spellingShingle Jin Yan
Zijia Zhao
Min Xia
Shuya Chen
Xiancheng Wan
Anfei He
Guangyao Daniel Sheng
Xuedong Wang
Qiuhui Qian
Huili Wang
Induction of lipid metabolism dysfunction, oxidative stress and inflammation response by tris(1-chloro-2-propyl)phosphate in larval/adult zebrafish
Environment International
Tris(1-chloro-2-propyl)phosphate
Lipid accumulation
Inflammation response
Hepatocellular carcinogenesis
Zebrafish
title Induction of lipid metabolism dysfunction, oxidative stress and inflammation response by tris(1-chloro-2-propyl)phosphate in larval/adult zebrafish
title_full Induction of lipid metabolism dysfunction, oxidative stress and inflammation response by tris(1-chloro-2-propyl)phosphate in larval/adult zebrafish
title_fullStr Induction of lipid metabolism dysfunction, oxidative stress and inflammation response by tris(1-chloro-2-propyl)phosphate in larval/adult zebrafish
title_full_unstemmed Induction of lipid metabolism dysfunction, oxidative stress and inflammation response by tris(1-chloro-2-propyl)phosphate in larval/adult zebrafish
title_short Induction of lipid metabolism dysfunction, oxidative stress and inflammation response by tris(1-chloro-2-propyl)phosphate in larval/adult zebrafish
title_sort induction of lipid metabolism dysfunction oxidative stress and inflammation response by tris 1 chloro 2 propyl phosphate in larval adult zebrafish
topic Tris(1-chloro-2-propyl)phosphate
Lipid accumulation
Inflammation response
Hepatocellular carcinogenesis
Zebrafish
url http://www.sciencedirect.com/science/article/pii/S016041202200006X
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