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A transcriptomics study on hepatic lipid metabolism in mice exposed to contaminated drinking water

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Abstract

DNA microarray was used to analyze hepatic transcriptional profile of male mice (Mus musculus) after the mice were fed with Yangtze River (China) source water (NJS) and tap water (NJT) for 90 days. Chemical analysis demonstrated that NJS and NJT contained various trace-level pollutants including polycyclic aromatic hydrocarbons, phthalate ethers and inorganic contaminants. DNA microarray revealed occurrence of 5,042 differentially expressed genes (DEGs) in the mice fed with NJS and 828 DEGs in the mice fed with NJT, indicating that NJS posed greater influence on liver transcriptome. Annotation against Kyoto Encyclopedia of Genes and Genomes pathway database showed that the DEGs in NJS group were mostly involved in lipid metabolism (51 DEGs), followed by neurodegenerative diseases (47 DEGs), energy metabolism (41 DEGs) and endocrine system (38 DEGs). NJT exposure was found to affect lipid metabolism (14 DEGs), xenobiotics biodegradation and metabolism (6 DEGs), and cofactors and vitamins metabolism (5 DEGs). Annotation against Gene Ontology database confirmed that lipid metabolism among the altered pathways was most susceptible to both NJS and NJT exposure. The DEGs were involved in 6 lipid metabolic pathways including fatty acid metabolism, glycerophospholipid metabolism, unsaturated fatty acid biosynthesis, steroid biosynthesis, primary bile acid biosynthesis and steroid hormone biosynthesis. Although both NJS and NJT might cause no obvious liver tissue damages, the lipid metabolic disturbance induced by trace-level pollutants still deserves public health concern.

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References

  • Axmon A, Rylander L, Rignell-Hydbom A (2008) Reproductive toxicity of seafood contaminants: prospective comparisons of Swedish east and west coast fishermen’s families. Environ Health 7:1–10

    Article  Google Scholar 

  • Bechmann LP, Hannivoort RA, Gerken G, Hotamisligil GS, Trauner M, Canbay A (2012) The interaction of hepatic lipid and glucose metabolism in liver diseases. J Hepatol 56(4):952–964

    Article  CAS  Google Scholar 

  • Carman GM, Han GS (2009) Phosphatidic acid phosphatase, a key enzyme in the regulation of lipid synthesis. J Biol Chem 284:2593–2597

    Article  CAS  Google Scholar 

  • Chen YJ, Zhang XX, Wu B, Liu B, Xiao L, Li AM, Cheng SP (2012) Semivolatile organic compounds removal and health risk reduction in drinking water treatment biofilters applying different backwashing strategies. Int J Environ Sci Technol 9:661–670

    Article  CAS  Google Scholar 

  • Currie RA, Orphanides G, Moggs JG (2005) Mapping molecular responses to xenoestrogens through Gene Ontology and pathway analysis of toxicogenomic data. Reprod Toxicol 20:433–440

    Article  CAS  Google Scholar 

  • CWRC (Changjiang Water Resources Commission) (2011) Report on water resources in the Yangtze River. Available at http://202.103.33.45:8380/templet/default/ShowArticle.jsp?id=3348 on 10 Jan 2013

  • Dai GD, Cui LB, Song L, Liu R, He J, Wang YB, Cheng JF, Chang HC, Wang XR (2006) Effects of terephthalic acid on rat lipid metabolism. Biomed Environ Sci 19:273–276

    CAS  Google Scholar 

  • Euling SY, White LD, Kim AS, Sen B, Wilson VS, Keshava C, Keshava N, Hester S, Ovacik AM, Ierapetritou MG, Androulakis IP, Gaido KW (2011) Use of genomic data in risk assessment case study: II. Evaluation of the dibutyl phthalate toxicogenomic data set. Toxicol Appl Pharmacol 271(3):249–262

  • Gant TW, Baus PR, Clothier B, Riley J, Davies R, Judah DJ, Edwards RE, George E, Greaves P, Smith AG (2003) Gene expression profiles associated with inflammation, fibrosis, and cholestasis in mouse liver after griseofulvin. Environ Health Perspect 111(6):847–853

    CAS  Google Scholar 

  • Hunt MC, Yamada J, Maltais LJ, Wright MW, Podesta EJ, Alexson SE (2005) A revised nomenclature for mammalian acyl-CoA thioesterases/hydrolases. J Lipid Res 46(9):2029–2032

    Article  CAS  Google Scholar 

  • Kawano Y, Nishiumi S, Tanaka S, Nobutani K, Miki A, Yano Y, Seo Y, Kutsumi H, Ashida H, Azuma T, Yoshida M (2010) Activation of the aryl hydrocarbon receptor induces hepatic steatosis via the upregulation of fatty acid transport. Arch Biochem Biophys 504(2):221–227

    Article  CAS  Google Scholar 

  • Keshavarzi B, Moore F, Najmeddin A, Rahmani F, Malekzadeh A (2012) Quality of drinking water and high incidence rate of esophageal cancer in Golestan Province of Iran: a probable link. Environ Geochem Health 34(1):15–26

    Article  CAS  Google Scholar 

  • Kosmehl T, Otte JC, Yang L, Legradi J, Bluhm K, Zinsmeister C, Keiter SH, Reifferscheid G, Manz W, Braunbeck T, Straehle U, Hollert H (2012) A combined DNA-microarray and mechanism-specific toxicity approach with zebrafish embryos to investigate the pollution of river sediments. Reprod Toxicol 33(2):245–253

    Article  CAS  Google Scholar 

  • Kozul-Horvath CD, Zandbergen F, Jackson BP, Enelow RI, Hamilton JW (2012) Effects of low-dose drinking water arsenic on mouse fetal and postnatal growth and development. PLoS One 7(5):e38249

    Article  CAS  Google Scholar 

  • Larregle EV, Varas SM, Oliveros LB, Martinez LD, Anton R, Marchevsky E, Gimenez MS (2008) Lipid metabolism in liver of rat exposed to cadmium. Food Chem Toxicol 46(5):1786–1792

    Article  CAS  Google Scholar 

  • Lee BM, Koo HJ (2007) Hershberger assay for antiandrogenic effects of phthalates. J Toxicol Environ Health A 70:1365–1370

    Article  CAS  Google Scholar 

  • Lin J, Fu C, Zhang X, Xie K, Yu Z (2012) Heavy metal contamination in the water-level fluctuating zone of the Yangtze River within Wanzhou Section, China. Biol Trace Res 145(2):268–272

    Article  CAS  Google Scholar 

  • Maranghi F, Lorenzetti S, Tassinari R, Moracci G, Tassinari V, Marcoccia D, Di VA, Eusepi A, Romeo A, Magrelli A, Salvatore M, Tosto F, Viganotti M, Antoccia A, Di MA, Azzalin G, Tanzarella C, Macino G, Taruscio D, Mantovani A (2010) In utero exposure to di-(2-ethylhexyl) phthalate affects liver morphology and metabolism in post-natal CD-1 mice. Reprod Toxicol 29(4):427–432

    Article  CAS  Google Scholar 

  • Marchitti SA, Brocker C, Stagos D, Vasiliou V (2008) Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily. Expert Opin Drug Metab Toxicol 4(6):697–720

    Article  CAS  Google Scholar 

  • Mashek DG, Bomfeldt KE, Coleman RA, Berger J, Bernlohr DA, Black P, DiRusso CC, Farber SA, Guo W, Hashimoto N, Khodiyar V, Kuypers FA, Maltais LJ, Nebert DW, Renieri A, Schaffer JE, Stahl A, Watkins PA, Vasiliou V, Yamamoto TT (2005) Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family. J Lipid Res 45(10):1958–1961

    Article  Google Scholar 

  • Modi HR, Patil N, Katyare S (2008) Effect of treatment with cadmium on kinetic properties of Na+, K+-ATPase and glucose-6-phosphatase activity in rat liver microsomes: a correlative study on influence of lipid/phospholipid make-up. Toxicology 254(1–2):29–41

    Article  CAS  Google Scholar 

  • Nguyen P, Leray V, Diez M, Serisier S, Le Bloćh J, Siliart B, Dumon H (2008) Liver lipid metabolism. J Anim Physiol Anim Nutr 92(3):272–283

    Article  CAS  Google Scholar 

  • Oh JH, Moon HB, Choe ES (2012) Alterations in differentially expressed genes by exposure to a mixture of carcinogenic polycyclic aromatic hydrocarbons in the liver of Oryzias latipes. Environ Toxicol Pharmacol 33(3):403–407

    Article  CAS  Google Scholar 

  • Ozaki H, Kitamura S, Sugihara K, Ohta S (2006) Inhibitory effect of phthalate diesters on the cytochrome P450 system. Drug Metab Rev 38(3):123

    Google Scholar 

  • Pelkonen O, Turpeinen M, Hakkola J, Honkakoski P, Hukkanen J, Raunio H (2008) Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol 82(10):667–715

    Article  CAS  Google Scholar 

  • Podechard N, Tekpli X, Catheline D, Holme JA, Rioux V, Legrand P, Rialland M, Fardel O, Lagadic-Gossmann D, Lecureur V (2012) Mechanisms involved in lipid accumulation and apoptosis induced by 1-nitropyrene in Hepa1c1c7 cells. Toxicol Lett 206(3):289–299

    Article  Google Scholar 

  • Qin WD, Yang LY, Zhang XX, Zhang ZY, Xu LZ, Wu J, An J, Wang YP (2012) Cyanobacteria-blooming water samples from Lake Taihu induce endoplasmic reticulum stress in liver and kidney of mice. Ecotoxicology 21:1495–1503

    Article  CAS  Google Scholar 

  • Rebola M, Silva MJ, Antunes AM, Jose SS, Silva ZI, Cardoso AS (2011) Contribution to risk assessment of chlorinated polycyclic aromatic hydrocarbons associated with drinking water chlorination: formation, occurrence and genotoxic effects. Eur J Public Health 20(1):175

    Google Scholar 

  • Shi P, Zhang XX, Zhang ZY, Zhang Y, Wu B, Cheng SP, Li AM (2012) Chronic exposure to contaminated drinking water stimulates PPAR expression in mice livers. Chemosphere 88(4):407–412

    Article  CAS  Google Scholar 

  • Silverio R, Laviano A, Fanelli FR, Seelaender M (2012) L-Carnitine induces recovery of liver lipid metabolism in cancer cachexia. Amino Acids 42(5):1783–1792

    Article  CAS  Google Scholar 

  • Sun J, Cheng SP, Li AM, Zhang R, Wu B, Zhang Y, Zhang XX (2011) Integration of gene chip and topological network techniques to screen a candidate biomarker gene (CBG) for predication of the source water carcinogenesis risks on mouse Mus musculus. Ecotoxicology 20:1026–1032

    Article  CAS  Google Scholar 

  • Vanhove GF, Van Veldhoven PP, Fransen M, Denis S, Eyssen HJ, Wanders RJ, Mannaerts GP (1993) The CoA esters of 2-methyl-branched chain fatty acids and of the bile acid intermediates di- and trihydroxycoprostanic acids are oxidized by one single peroxisomal branched chain acyl-CoA oxidase in human liver and kidney. J Biol Chem 268(14):10335–10344

    CAS  Google Scholar 

  • Welsch F, Nemec MD, Lawrence WB (2008) Two-generation reproductive toxicity study of resorcinol administered via drinking water to Crl:CD(SD) rats. Int J Toxicol 27:43–57

    Article  CAS  Google Scholar 

  • Wong JS, Gill SS (2002) Gene expression changes induced in mouse liver by di(2-ethylhexyl) phthalate. Toxicol Appl Pharmacol 185:180–196

    Article  CAS  Google Scholar 

  • Wu B, Cheng SP, Li YQ, Kong J, Zhao DY, Zhang Y, Zhang XX (2009) Transcriptional toxicity of the Yangtze River source water on mouse (Mus musculus) detected by cDNA microarray. Ecotoxicology 18:715–721

    Article  CAS  Google Scholar 

  • Xu Y, Knipp GT, Cook TJ (2006) Effects of di-(2-ethylhexyl)-phthalate and its metabolites on the lipid profiling in rat HRP-1 trophoblast cells. Arch Toxicol 80(5):293–298

    Article  CAS  Google Scholar 

  • Yamaori S, Koeda K, Kushihara M, Hada Y, Yamamoto I, Watanabe K (2012) Comparison in the in vitro inhibitory effects of major phytocannabinoids and polycyclic aromatic hydrocarbons contained in marijuana smoke on cytochrome P450 2C9 activity. Drug Metab Pharmacokinet 27(3):294–300

    Article  CAS  Google Scholar 

  • Yang H, Zhuo S, Xue B, Zhang C, Liu W (2012) Distribution, historical trends and inventories of polychlorinated biphenyls in sediments from Yangtze River Estuary and adjacent East China Sea. Environ Pollut 169:20–26

    Article  CAS  Google Scholar 

  • Yi YJ, Zhang SH (2012) Heavy metal (Cd, Cr, Cu, Hg, Pb, Zn) concentrations in seven fish species in relation to fish size and location along the Yangtze River. Environ Sci Pollut Res 19(9):3989–3996

    Article  CAS  Google Scholar 

  • Zhang WG, Feng H, Chang JN, Qu JG, Xie HX, Yu LZ (2009) Heavy metal contamination in surface sediments of Yangtze River intertidal zone: an assessment from different indexes. Environ Pollut 157:1533–1543

    Article  CAS  Google Scholar 

  • Zhang ZY, Ma LP, Zhang XX, Li WX, Zhang Y, Wu B, Yang LY, Cheng SP (2010) Genomic expression profiles in liver of mice exposed to purified terephthalic acid manufacturing wastewater. J Hazard Mater 181:1121–1126

    Article  CAS  Google Scholar 

  • Zhang R, Cheng SP, Li AM, Sun J, Zhang Y, Zhang XX (2011a) Genome-wide screening of indicator genes for assessing the potential carcinogenic risk of Nanjing City drinking water. Ecotoxicology 20:1033–1040

    Article  CAS  Google Scholar 

  • Zhang Y, Li WX, Zhang R, Sun J, Wu B, Zhang XX, Cheng SP (2011b) Preliminary evaluation of gene expression profiles in liver of mice exposed to Taihu Lake drinking water for 90 days. Ecotoxicology 20:1071–1077

    Article  CAS  Google Scholar 

  • Zhang Y, Wu B, Zhang XX, Li AM, Cheng SP (2011c) Metabolic profiles in serum of mouse after chronic exposure to drinking water. Hum Exp Toxicol 30(8):1088–1095

    Article  Google Scholar 

  • Zhang Y, Zhang ZY, Zhao YP, Cheng SP, Ren HQ (2013) Identifying health effects of exposure to trichloroacetamide using transcriptomics and metabonomics in mice (Mus musculus). Environ Sci Technol 47:2918–2924

  • Zhao DY, Cheng SP, Wu B, Zhang Y, Zhang XX, Li WX, Cui Y (2009) Toxicity of the Yangtze River source of drinking water on reproductive system of male mice (Mus musculus). Ecotoxicology 18:729–735

    Article  CAS  Google Scholar 

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Acknowledgments

This study was financially supported by National Natural Science Foundation of China (No. 51290282 and 51278240).

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Authors and Affiliations

  1. State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, 163 Xianlin Road, Nanjing, 210023, China

    J. Yin, F. Zhao, X.-X. Zhang, Y. Chen, B. Wu & H. Ren

  2. Nanjing Institute of Environmental Sciences, Ministry of Environmental Protection of China, 8 Jiangwangmiao Street, Nanjing, 210042, China

    W. Li

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  1. J. Yin
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Correspondence to X.-X. Zhang.

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Yin, J., Zhao, F., Zhang, XX. et al. A transcriptomics study on hepatic lipid metabolism in mice exposed to contaminated drinking water. Int. J. Environ. Sci. Technol. 12, 847–856 (2015). https://doi.org/10.1007/s13762-013-0424-8

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  • DOI: https://doi.org/10.1007/s13762-013-0424-8

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