Abstract：This study utilized data mining from public databases, such as CTD and GEO, to demonstrate that EHDPP has the risk of inducing metabolic diseases by modulating various cell membrane receptor-mediated biological signaling pathways, which are related to the development of metabolic disorders and inflammation. Then, zebrafish larvae were utilized as models and exposed to a sublethal dose of EHDPP in order to validate the aforementioned findings. The findings revealed that after 5days of 500μg/L-EHDPP exposure, the content of triglycerides and total cholesterol in zebrafish larvae increased by 53.8% and 32.1%, respectively. Additionally, qRT-PCR results indicated that the lipid metabolism pathway mediated by Pparγ may serve as a potential pivotal mechanism for the induction of abnormal lipid accumulation in zebrafish caused by EHDPP.
倪安煜, 李金芸, 方露, 万可维, 陈泱, 王慧利, 闫瑾. 生物信息辅助斑马鱼模型揭示EHDPP诱发代谢疾病的机制[J]. 中国环境科学, 2023, 43(9): 4942-4950.
NI An-yu, LI Jin-yun, FANG Lu, WAN Ke-wei, CHEN Yang, WANG Hui-li, YAN Jin. Bioinformatics-assisted zebrafish model reveals the mechanism of EHDPP-induced metabolic disease. CHINA ENVIRONMENTAL SCIENCECE, 2023, 43(9): 4942-4950.
Kumar R, Priyadarshi R N, Anand U. Non-alcoholic fatty liver disease:growing burden, adverse outcomes and associations[J]. Journal of Clinical and Translational Hepatology, 2020,8(1):76.
[2]
张绪超,赵力,陈懿,等.环境持久性自由基及其介导的生物学损伤[J]. 中国环境科学, 2019,39(5):2180-2189. Zhang X C, Zhao L, Chen Y, et al. Overlooked risks and influences of environmentally persistent free radicals in the ambient media[J]. China Environmental Science, 2019,39(5):2180-2189.
[3]
Cristale J, Belé T G A, Lacorte S, et al. Occurrence and human exposure to brominated and organophosphorus flame retardants via indoor dust in a Brazilian city[J]. Environmental Pollution, 2018, 237:695-703.
[4]
Kim U J, Oh J K, Kannan K. Occurrence, removal, and environmental emission of organophosphate flame retardants/plasticizers in a wastewater treatment plant in New York State[J]. Environmental Science & Technology, 2017,51(14):7872-7880.
[5]
Loos R, Carvalho R, António D C, et al. EU-wide monitoring survey on emerging polar organic contaminants in wastewater treatment plant effluents[J]. Water Research, 2013,47(17):6475-6487.
[6]
Wang X, Liu J, Yin Y. Development of an ultra-high-performance liquid chromatography-tandem mass spectrometry method for high throughput determination of organophosphorus flame retardants in environmental water[J]. Journal of Chromatography A, 2011,1218(38):6705-6711.
[7]
Lee S, Cho H J, Choi W, et al. Organophosphate flame retardants (OPFRs) in water and sediment:Occurrence, distribution, and hotspots of contamination of Lake Shihwa, Korea[J]. Marine Pollution Bulletin, 2018,130:105-112.
[8]
Sundkvist A M, Olofsson U, Haglund P. Organophosphorus flame retardants and plasticizers in marine and fresh water biota and in human milk[J]. Journal of Environmental Monitoring, 2010,12(4):943-951.
[9]
Yang R, Wang X, Wang J, et al. Insights into the sex-dependent reproductive toxicity of 2-ethylhexyl diphenyl phosphate on zebrafish (Danio rerio)[J]. Environment International, 2022,158:106928.
[10]
Shen J, Zhang Y, Yu N, et al. Organophosphate ester, 2-ethylhexyl diphenyl phosphate (EHDPP), elicits cytotoxic and transcriptomic effects in chicken embryonic hepatocytes and its biotransformation profile compared to humans[J]. Environmental Science & Technology, 2019,53(4):2151-2160.
[11]
Schang G, Robaire B, Hales B F. Organophosphate flame retardants act as endocrine-disrupting chemicals in MA-10mouse tumor Leydig cells[J]. Toxicological Sciences, 2016,150(2):499-509.
[12]
Sun W, Duan X, Chen H, et al. Adipogenic activity of 2-ethylhexyl diphenyl phosphate via peroxisome proliferator-activated receptor γ pathway[J]. Science of the Total Environment, 2020,711:134810.
[13]
Zhu L, Huang X, Li Z, et al. Evaluation of hepatotoxicity induced by 2-ethylhexyldiphenyl phosphate based on transcriptomics and its potential metabolism pathway in human hepatocytes[J]. Journal of Hazardous Materials, 2021,413:125281.
[14]
陈铭.大数据时代的整合生物信息学[J]. 生物信息学, 2022, 20(2):75-83. Chen M. Integrative bioinformatics in the big data era[J]. Chinese Journal of Bioinformatics, 2022,20(2):75-83.
[15]
Davis A P, Grondin C J, Johnson R J, et al. Comparative toxicogenomics database (CTD):update 2021[J]. Nucleic acids research, 2021,49(D1):D1138-D1143.
[16]
Huerta-Cepas J, Forslund K, Coelho L P, et al. Fast genome-wide functional annotation through orthology assignment by eggNOG-mapper[J]. Molecular biology and evolution, 2017,34(8):2115-2122.
[17]
Chen C, Chen H, Zhang Y, et al. TBtools:an integrative toolkit developed for interactive analyses of big biological data[J]. Molecular Plant, 2020,13(8):1194-1202.
[18]
辛友志.基于RNA-Seq的3T3-L1前脂肪细胞分化过程中差异表达基因研究[D]. 聊城:聊城大学, 2019. Xin Y Z. RNA-Seq Analysis Reveals a Critical Role of Differentially Expressed Genes during Adipogenesis of 3T3-L1[D]. Liaocheng:Liaocheng University, 2019.
[19]
Latruffe N, Vamecq J. Peroxisome proliferators and peroxisome proliferator activated receptors (PPARs) as regulators of lipid metabolism[J]. Biochimie, 1997,79(2/3):81-94.
[20]
Menendez J A, Vazquez-Martin A, Ortega F J, et al. Fatty acid synthase:association with insulin resistance, type 2diabetes, and cancer[J]. Clinical Chemistry, 2009,55(3):425-438.
[21]
Wang Z V, Scherer P E. Adiponectin, the past two decades[J]. Journal of molecular cell biology, 2016,8(2):93-100.
[22]
Merkel M, Eckel R H, Goldberg I J. Lipoprotein lipase[J]. Journal of Lipid Research, 2002,43(12):1997-2006.
[23]
Santos J, Leitão-Correia F, Sousa M J, et al. Dietary restriction and nutrient balance in aging[J]. Oxidative Medicine and Cellular Longevity, 2016,2016:4010357.
[24]
de Mello A H, Costa A B, Engel J D G, et al. Mitochondrial dysfunction in obesity[J]. Life Sciences, 2018,192:26-32.
[25]
Chen G, Goeddel D V. TNF-R1signaling:a beautiful pathway[J]. Science, 2002,296(5573):1634-1635.
[26]
Ohlrogge J, Browse J. Lipid biosynthesis[J]. The Plant Cell, 1995, 7(7):957.
[27]
Gyamfi D, Awuah E O, Owusu S. Lipid metabolism:an overview[J]. The Molecular Nutrition of Fats, 2019:17-32.
[28]
Koyama-Honda I, Fujiwara T K, Kasai R S, et al. High-speed single-molecule imaging reveals signal transduction by induced transbilayer raft phases[J]. Journal of Cell Biology, 2020,219(12):e202006125.
[29]
Shi Y, Ruan H. Toward a membrane-centric biology[J]. Frontiers in Immunology, 2020,11:1909.
[30]
Ouweneel A B, Thomas M J, Sorci-Thomas M G. The ins and outs of lipid rafts:Functions in intracellular cholesterol homeostasis, microparticles, and cell membranes:Thematic review series:Biology of lipid rafts[J]. Journal of lipid research, 2020,61(5):676-686.
[31]
Subramanian A, Tamayo P, Mootha V K, et al. Gene set enrichment analysis:a knowledge-based approach for interpreting genome-wide expression profiles[J]. Proceedings of the National Academy of Sciences, 2005,102(43):15545-15550.
[32]
Bloch K. Sterol molecule:structure, biosynthesis, and function[J]. Steroids, 1992,57(8):378-383.
[33]
Gill S, Chow R, Brown A J. Sterol regulators of cholesterol homeostasis and beyond:the oxysterol hypothesis revisited and revised[J]. Progress in Lipid Research, 2008,47(6):391-404.
[34]
Di L, Balesano A, Jordan S, et al. The role of alcohol dehydrogenase in drug metabolism:beyond ethanol oxidation[J]. The AAPS Journal, 2021,23(1):1-21.
[35]
Siersbæk R, Nielsen R, Mandrup S. PPARγ in adipocyte differentiation and metabolism-novel insights from genome-wide studies[J]. FEBS Letters, 2010,584(15):3242-3249.
[36]
Ma S, Zhou B, Yang Q, et al. A transcriptional regulatory loop of master regulator transcription factors, PPARG, and fatty acid synthesis promotes esophageal adenocarcinoma[J]. Cancer Research, 2021, 81(5):1216-1229.
[37]
Dorn C, Riener M O, Kirovski G, et al. Expression of fatty acid synthase in nonalcoholic fatty liver disease[J]. International Journal of Clinical and Experimental Pathology, 2010,3(5):505.
[38]
Fhu C W, Ali A. Fatty acid synthase:an emerging target in cancer[J]. Molecules, 2020,25(17):3935.
[39]
王杨,吴国辉,钱秋慧,等.三氯生对斑马鱼发育和脂质代谢的影响[J]. 中国环境科学, 2022,42(3):1394-1400. Wang Y, Wu G H, Qian Q H, et al. Effects of triclosan environmental exposure on zebrafish development and lipid metabolism[J]. China Environmental Science, 2022,42(3):1394-1400.
[40]
Zhang X, Cao Y J, Zhang H Y, et al. Associations between ADIPOQ polymorphisms and coronary artery disease:a meta-analysis[J]. BMC Cardiovascular Disorders, 2019,19(1):1-8.
