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Hepatic transcriptomic responses in mice exposed to arsenic and different fat diet

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Abstract

Chronic exposure to inorganic arsenic (iAs) or a high-fat diet (HFD) can produce liver injury. However, effects of HFD on risk assessment of iAs in drinking water are unclear. In this study, we examined how HFD and iAs interact to alter iAs-induced liver injury in C57BL/6 mice. Mice fed low-fat diet (LFD) or HFD were exposed to 3 mg/L iAs or deionized water for 10 weeks. Results showed that HFD changed intake and excretion of iAs by mice. Then, HFD increased the amount of iAs-induced hepatic DNA damage and amplified changes in pathways related to cell death and growth, signal transduction, lipid metabolism, and insulin signaling. Compared to gene expression profiles caused by iAs alone or HFD alone, insulin signaling pathway might play important roles in the interactive effects of iAs and HFD. Our data suggest that HFD increases sensitivity of mice to iAs in drinking water, resulting in increased hepatotoxicity. This study highlight that HFD might enhance the risk of iAs hepatotoxicity in iAs-polluted regions. The diet should be considered during risk assessment of iAs in drinking water.

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References

  • Ahmed MK et al (2011) Assessing the genotoxic potentials of arsenic in tilapia (Oreochromis mossambicus) using alkaline comet assay and micronucleus test. Chemosphere 84:143–149. doi:10.1016/j.chemosphere.2011.02.025

    Article  CAS  Google Scholar 

  • Alava P, Tack F, Laing GD, de Wiele TV (2012) HPLC-ICP-MS method development to monitor arsenic speciation changes by human gut microbiota. Biomed Chromatogr 26:524–533. doi:10.1002/bmc.1700

    Article  CAS  Google Scholar 

  • Altenburger R, Scholz S, Schmitt-Jansen M, Busch W, Escher BI (2012) Mixture toxicity revisited from a toxicogenomic perspective. Environ Sci Technol 46:2508–2522. doi:10.1021/es2038036

    Article  CAS  Google Scholar 

  • Arteel GE et al (2008) Subhepatotoxic exposure to arsenic enhances lipopolysaccharide-induced liver injury in mice. Toxicol Appl Pharmacol 226:128–139. doi:10.1016/j.taap.2007.08.020

    Article  CAS  Google Scholar 

  • Beyaz S et al (2016) High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature 531:53-+. doi:10.1038/nature17173

    Article  CAS  Google Scholar 

  • Brown KG, Ross GL (2002) Arsenic, drinking water, and health: a position paper of the American council on science and health. Regul Toxicol Pharmacol 36:162–174. doi:10.1006/rtph.2002.1573

    Article  CAS  Google Scholar 

  • Bundschuh J et al (2012) One century of arsenic exposure in Latin America: a review of history and occurrence from 14 countries. Sci Total Environ 429:2–35. doi:10.1016/j.scitotenv.2011.06.024

    Article  CAS  Google Scholar 

  • Collins AR, Ma AG, Duthie SJ (1995) The kinetics of repair of oxidative DNA-damage (strand breaks and oxidized pyrimidines) in human-cells. Mutat Res-DNA Repair 336:69–77

    Article  CAS  Google Scholar 

  • Davis AP, Murphy CG, Rosenstein MC, Wiegers TC, Mattingly CJ (2008) The comparative Toxicogenomics database facilitates identification and understanding of chemical-gene-disease associations: arsenic as a case study. BMC Med Genet 1:48. doi:10.1186/1755-8794-1-48

    Google Scholar 

  • De Vizcaya-Ruiz A, Barbier O, Ruiz-Ramos R, Cebrian ME (2009) Biomarkers of oxidative stress and damage in human populations exposed to arsenic. Mutat Res Genet Toxicol Environ Mutagen 674:85–92. doi:10.1016/j.mrgentox.2008.09.020

    Article  CAS  Google Scholar 

  • Del Razo LM et al (2011) Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: a cross-sectional study in the Zimapan and Lagunera regions in Mexico. Environ Health 10:73. doi:10.1186/1476-069x-10-73

    Article  CAS  Google Scholar 

  • Ditzel EJ, Nguyen T, Parker P, Camenisch TD (2016) Effects of arsenite exposure during fetal development on energy metabolism and susceptibility to diet-induced fatty liver disease in male mice. Environ Health Perspect 124:201–209. doi:10.1289/ehp.1409501

    Google Scholar 

  • Drobna Z, Walton FS, Paul DS, Xing WB, Thomas DJ, Styblo M (2010) Metabolism of arsenic in human liver: the role of membrane transporters. Arch Toxicol 84:3–16. doi:10.1007/s00204-009-0499-7

    Article  CAS  Google Scholar 

  • El-Hachem N et al (2016) Characterization of conserved toxicogenomic responses in chemically exposed hepatocytes across species and platforms. Environ Health Perspect 124:313–320. doi:10.1289/ehp.1409157

    Google Scholar 

  • Franko A et al (2014) Liver adapts mitochondrial function to insulin resistant and diabetic states in mice. J Hepatol 60:816–823. doi:10.1016/j.jhep.2013.11.020

    Article  CAS  Google Scholar 

  • Frost FJ, Muller T, Petersen HV, Thomson B, Tollestrup K (2003) Identifying US populations for the study of health effects related to drinking water arsenic. J Expo Anal Environ Epidemiol 13:231–239. doi:10.1038/sj.jea.7500275

    Article  CAS  Google Scholar 

  • Huang CF et al (2015) Arsenic Exposure and glucose intolerance/insulin resistance in estrogen-deficient female mice. Environ Health Perspect 123:1138–1144. doi:10.1289/ehp.1408663

    Article  Google Scholar 

  • Islam MR et al (2012) Association between type 2 diabetes and chronic arsenic exposure in drinking water: a cross sectional study in Bangladesh. Environ Health 11. doi:10.1186/1476-069x-11-38

  • Jung UJ, Cho YY, Choi MS (2016) Apigenin ameliorates dyslipidemia, hepatic steatosis and insulin resistance by modulating metabolic and transcriptional profiles in the liver of high-fat diet-induced obese mice Nutrients 8. doi:10.3390/nu8050305

  • Liu S, Guo X, Zhang X, Cui Y, Zhang Y, Wu B (2013) Impact of iron precipitant on toxicity of arsenic in water: a combined in vivo and in vitro study. Environ Sci Technol 47:3432–3438

    CAS  Google Scholar 

  • Massey VL et al (2015) Oligofructose protects against arsenic-induced liver injury in a model of environment/obesity interaction. Toxicol Appl Pharm 284:304–314. doi:10.1016/j.taap.2015.02.022

    Article  CAS  Google Scholar 

  • Mazumder DN (2005) Effect of chronic intake of arsenic-contaminated water on liver. Toxicol Appl Pharmacol 206:169–175. doi:10.1016/j.taap.2004.08.025

    Article  Google Scholar 

  • Meliker JR, Wahl RL, Cameron LL, Nriagu JO (2007) Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: a standardized mortality ratio analysis. Environ Health 6:4. doi:10.1186/1476-069x-6-4

    Article  Google Scholar 

  • Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS (2003) Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 289:76–79

    Article  Google Scholar 

  • Navas-Acien A, Silbergeld EK, Streeter RA, Clark JM, Burke TA, Guallar E (2006) Arsenic exposure and type 2 diabetes: a systematic review of the experimental and epidemiologic evidence. Environ Health Perspect 114:641–648. doi:10.1289/ehp.8551

    Article  CAS  Google Scholar 

  • Noeman SA, Hamooda HE, Baalash AA (2011) Biochemical study of oxidative stress markers in the liver, kidney and heart of high fat diet induced obesity in rats. Diabetol Metab Syndr 3:17. doi:10.1186/1758-5996-3-17

    Article  CAS  Google Scholar 

  • Paul DS, Hernandez-Zavala A, Walton FS, Adair BM, Dedina J, Matousek T, Styblo M (2007) Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: development of a mouse model for arsenic-induced diabetes. Toxicol Appl Pharmacol 222:305–314. doi:10.1016/j.taap.2007.01.010

    Article  CAS  Google Scholar 

  • Paul DS, Walton FS, Saunders RJ, Styblo M (2011) Characterization of the impaired glucose homeostasis produced in C57BL/6 mice by chronic exposure to arsenic and high-fat diet. Environ Health Perspect 119:1104–1109. doi:10.1289/ehp.1003324

    Article  CAS  Google Scholar 

  • Petrick JS, Ayala-Fierro F, Cullen WR, Carter DE, Aposhian HV (2000) Monomethylarsonous acid (MMA(III)) is more toxic than arsenite in Chang human hepatocytes. Toxicol Appl Pharmacol 163:203–207. doi:10.1006/taap.1999.8872

    Article  CAS  Google Scholar 

  • Sasaki YF et al (2002) The comet assay with 8 mouse organs: results with 39 currently used food additives. Mutat Res 519:103–119

    Article  CAS  Google Scholar 

  • Schuhmacher-Wolz U, Dieter HH, Klein D, Schneider K (2009) Oral exposure to inorganic arsenic: evaluation of its carcinogenic and non-carcinogenic effects. Crit Rev Toxicol 39:271–298. doi:10.1080/10408440802291505

    Article  CAS  Google Scholar 

  • Smith AH, Steinmaus CM (2009) Health effects of arsenic and chromium in drinking water: recent human findings. Annu Rev Public Health 30:107–122. doi:10.1146/annurev.publhealth.031308.100143

    Article  Google Scholar 

  • Snedeker SM, Hay AG (2012) Do interactions between gut ecology and environmental chemicals contribute to obesity and diabetes? Environ Health Perspect 120:332–339

    Article  CAS  Google Scholar 

  • Tan M, Schmidt RH, Beier JI, Watson WH, Zhong H, States JC, Arteel GE (2011) Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice. Toxicol Appl Pharmacol 257:356–364. doi:10.1016/j.taap.2011.09.019

    Article  CAS  Google Scholar 

  • Tseng CH et al (2000) Long-term arsenic exposure and incidence of non-insulin-dependent diabetes mellitus: a cohort study in arseniasis-hyperendemic villages in Taiwan. Environ Health Perspect 108:847–851. doi:10.1289/ehp.00108847

    Article  CAS  Google Scholar 

  • Wiele TVD et al (2010) Arsenic metabolism by human gut microbiota upon in vitro digestion of contaminated soils. Environ Health Perspect 118:1004–1009

    Article  Google Scholar 

  • Wu J, Liu J, Waalkes MP, Cheng ML, Li L, Li CX, Yang Q (2008) High dietary fat exacerbates arsenic-induced liver fibrosis in mice. Exp Biol Med (Maywood) 233:377–384. doi:10.3181/0710-RM-269

    Article  CAS  Google Scholar 

  • Wu B, Liu S, Guo X, Zhang Y, Zhang X, Li M, Cheng S (2012) Responses of mouse liver to Dechlorane plus exposure by integrative transcriptomic and metabonomic studies. Environ Sci Technol 46:10758–10764

    Article  CAS  Google Scholar 

  • Yoshida T, Yamauchi H, Sun GF (2004) Chronic health effects in people exposed to arsenic via the drinking water: dose-response relationships in review. Toxicol Appl Pharmacol 198:243–252. doi:10.1016/j.taap.2003.10.002

    Article  CAS  Google Scholar 

  • Zhou M et al (2012) Transcriptomic and metabonomic profiling reveal synergistic effects of quercetin and resveratrol supplementation in high fat diet fed mice. J Proteome Res 11:4961–4971. doi:10.1021/pr3004826

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Natural Science Foundation of Jiangsu Province (BK20131270), Foundation of State Key Laboratory of Pollution Control and Resource Reuse, and Science Foundation of Nanjing University.

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Correspondence to Bing Wu.

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Responsible editor: Philippe Garrigues

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Hou, H., Yu, Y., Shen, Z. et al. Hepatic transcriptomic responses in mice exposed to arsenic and different fat diet. Environ Sci Pollut Res 24, 10621–10629 (2017). https://doi.org/10.1007/s11356-017-8743-9

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  • DOI: https://doi.org/10.1007/s11356-017-8743-9

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