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Project Publications: Michigan State University: TCDD-Elicited Steatosis: The Role of Aryl Hydrocarbon Receptor Regulation in Lipid Uptake, Metabolism, and Transport

Superfund Research Program

TCDD-Elicited Steatosis: The Role of Aryl Hydrocarbon Receptor Regulation in Lipid Uptake, Metabolism, and Transport

Project Leader: Timothy R. Zacharewski
Grant Number: P42ES004911
Funding Period: 2006-2021

Project-Specific Links



  • Cholico G, Nault R, Zacharewski TR. 2022. Genome-wide ChIPseq analysis of AhR, COUP-TF, and HNF4 enrichment in TCDD-treated mouse liver. Int J Mol Sci 23(3):1558. doi:10.3390/ijms23031558 PMID:35163483 PMCID:PMC8836158
  • Nault R, Saha S, Bhattacharya S, Dodson J, Sinha S, Maiti T, Zacharewski TR. 2022. Benchmarking of a Bayesian single cell RNAseq differential gene expression test for dose-response study designs. Nucleic Acids Res doi:10.1093/nar/gkac019 PMID:35061903
  • Orlowska K, Fling RR, Nault R, Sink WJ, Schilmiller AL, Zacharewski TR. 2022. Dioxin-elicited decrease in cobalamin redirects propionyl-CoA metabolism to the beta-oxidation-like pathway resulting in acrylyl-CoA conjugate buildup. J Biol Chem 298(9):102301. doi:10.1016/j.jbc.2022.102301 PMID:35931118 PMCID:PMC9418907



  • Doskey CM, Fader KA, Nault R, Lydic TA, Matthews J, Potter D, Sharratt B, Williams K, Zacharewski TR. 2020. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters hepatic polyunsaturated fatty acid metabolism and eicosanoid biosynthesis in female Sprague-Dawley rats. Toxicol Appl Pharmacol 398:14. doi:10.1016/j.taap.2020.115034 PMID:32387183 PMCID:PMC7294678
  • Fling RR, Doskey CM, Fader KA, Nault R, Zacharewski TR. 2020. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) dysregulates hepatic one carbon metabolism during the progression of steatosis to steatohepatitis with fibrosis in mice. Sci Rep 10:14831. doi:10.1038/s41598-020-71795-0 PMID:32908189 PMCID:PMC7481292


  • Dornbos P, Jurgelewicz A, Fader KA, Williams K, Zacharewski TR, LaPres JJ. 2019. Characterizing the role of HMG-CoA reductase in aryl hydrocarbon receptor-mediated liver injury in C57BL/6 mice. Sci Rep 9(1):15828. doi:10.1038/s41598-019-52001-2 PMID:31676775 PMCID:PMC6825130
  • Fader KA, Nault R, Doskey CM, Fling RR, Zacharewski TR. 2019. 2,3,7,8-Tetrachlorodibenzo-p-dioxin abolishes circadian regulation of hepatic metabolic activity in mice. Sci Rep 9:6514. doi:10.1038/s41598-019-42760-3 PMID:31015483 PMCID:PMC6478849
  • Josyula N, Andersen ME, Kaminski NE, Dere E, Zacharewski TR, Bhattacharya S. 2019. Gene co-regulation and co-expression in the aryl hydrocarbon receptor-mediated transcriptional regulatory network in the mouse liver. Arch Toxicol 94:113-126. doi:10.1007/s00204-019-02620-5 PMID:31728591


  • Fader KA, Nault R, Raehtz S, McCabe LR, Zacharewski TR. 2018. 2,3,7,8-Tetrachlorodibenzo-p-dioxin dose-dependently increases bone mass and decreases marrow adiposity in juvenile mice. Toxicol Appl Pharmacol 348:85-98. doi:10.1016/j.taap.2018.04.013 PMID:29673856 PMCID:PMC5984050
  • Nault R, Doskey CM, Fader KA, Rockwell CE, Zacharewski TR. 2018. Comparison of hepatic NRF2 and aryl hydrocarbon receptor binding in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated mice demonstrates NRF2-independent PKM2 induction. Mol Pharmacol 94(2):876-884. doi:10.1124/mol.118.112144 PMID:29752288 PMCID:6022803



  • Nault R, Fader KA, Ammendolia DA, Dornbos P, Potter D, Sharratt B, Kumagai K, Harkema JR, Lunt SY, Matthews J, Zacharewski TR. 2016. Dose-dependent metabolic reprogramming and differential gene expression in TCDD-elicited hepatic fibrosis. Toxicol Sci 154(2):253-266. doi:10.1093/toxsci/kfw163 PMID:27562557 PMCID:PMC5139066
  • Nault R, Fader KA, Kirby MP, Ahmed S, Matthews J, Jones AD, Lunt SY, Zacharewski TR. 2016. Pyruvate kinase isoform switching and hepatic metabolic reprogramming by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci 149(2):358-371. doi:10.1093/toxsci/kfv245 PMID:26582802 PMCID:PMC4900217
  • Nault R, Fader KA, Kopec AK, Harkema JR, Zacharewski TR, Luyendyk J. 2016. From the cover: coagulation-driven hepatic fibrosis requires protease activated receptor-1 (PAR-1) in a mouse model of TCDD-elicited steatohepatitis. Toxicol Sci 154(2):381-391. doi:10.1093/toxsci/kfw175 PMID:27613713 PMCID:PMC5139072


  • Fader KA, Nault R, Ammendolia DA, Harkema JR, Williams KJ, Crawford RB, Kaminski NE, Potter D, Sharratt B, Zacharewski TR. 2015. 2,3,7,8-Tetrachlorodibenzo-p-dioxin alters lipid metabolism and depletes immune cell populations in the jejunum of C57BL/6 mice. Toxicol Sci 148(2):567-580. doi:10.1093/toxsci/kfv206 PMID:26377647 PMCID:PMC5009443
  • Nault R, Colbry D, Brandenberger C, Zacharewski TR, Harkema JR. 2015. Development of a computational high-throughput tool for the quantitative examination of dose-dependent histological features. Toxicol Pathol 43(3):366-375. doi:10.1177/0192623314544379 PMID:25274660 PMCID:PMC4382446
  • Nault R, Fader KA, Zacharewski TR. 2015. RNA-Seq versus oligonucleotide array assessment of dose-dependent TCDD-elicited hepatic gene expression in mice. BMC Genomics 16:373. doi:10.1186/s12864-015-1527-z PMID:25958198 PMCID:PMC4456707



  • Angrish MM, Jones AD, Harkema JR, Zacharewski TR. 2011. Aryl hydrocarbon receptor-mediated induction of stearoyl-CoA desaturase 1 alters hepatic fatty acid composition in TCDD-elicited steatosis. Toxicol Sci 124(2):299-310. doi:10.1093/toxsci/kfr226 PMID:21890736 PMCID:PMC3216411
  • Dere E, Forgacs AL, Zacharewski TR, Burgoon LD. 2011. Genome-wide computational analysis of dioxin response element location and distribution in the human, mouse, and rat genomes. Chem Res Toxicol 24:494-504. doi:10.1021/tx100328r PMID:21370876 PMCID:PMC4038167
  • Dere E, Lee AW, Burgoon LD, Zacharewski TR. 2011. Differences in TCDD-elicited gene expression profiles in human HepG2, mouse Hepa1c1c7 and rat H4IIE hepatoma cells. BMC Genomics 12:doi:10.1186/1471-2164-12-193 PMID:21496263 PMCID:PMC3089798
  • Dere E, Lo R, Celius T, Matthews J, Zacharewski TR. 2011. Integration of genome-wide computation DRE search, AhR ChIP-chip and gene expression analyses of TCDD-elicited responses in the mouse liver. BMC Genomics 12:365. doi:10.1186/1471-2164-12-365 PMID:21762485 PMCID:PMC3160422
  • Kopec AK, D'Souza ML, Mets BD, Burgoon LD, Reese SE, Archer KJ, Potter D, Tashiro C, Sharratt B, Harkema JR, Zacharewski TR. 2011. Non-additive hepatic gene expression elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,2 ',4,4 ',5,5 '-hexachlorobiphenyl (PCB153) co-treatment in C57BL/6 mice. Toxicol Appl Pharmacol 256:154-167. doi:10.1016/j.taap.2011.08.002 PMID:21851831 PMCID:PMC4126514
  • Lo R, Celius T, Dere E, MacPherson L, Harper PA, Zacharewski TR, Matthews J. 2011. Identification of aryl hydrocarbon receptor binding targets in mouse hepatic tissue treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Appl Pharmacol 257:38-47. doi:10.1016/j.taap.2011.08.016 PMID:21889950


  • Forgacs AL, Burgoon LD, Lynn SG, LaPres JJ, Zacharewski TR. 2010. Effects of TCDD on the expression of nuclear encoded mitochondrial genes. Toxicol Appl Pharmacol 246(1-2):58-65. doi:10.1016/j.taap.2010.04.006 PMID:20399798 PMCID:PMC4030424
  • Kopec AK, Burgoon LD, Ibrahim-Aibo D, Burg AR, Lee AW, Tashiro C, Sharratt B, Harkema JR, Rowlands C, Budinsky R, Zacharewski TR. 2010. Automated dose-response analysis and comparative toxicogenomic evaluation of the hepatic effects elicited by TCDD, TCDF, and PCB126 in C57BL/6 mice. Toxicol Sci 118(1):286-297. doi:10.1093/toxsci/kfq236 PMID:20702594 PMCID:PMC2955213
  • Kopec AK, Burgoon LD, Ibrahim-Aibo D, Mets BD, Tashiro C, Potter D, Sharratt B, Harkema JR, Zacharewski TR. 2010. PCB153-elicited hepatic responses in the immature, ovariectomized C57BL/6 mice: comparative toxicogenomic effects of dioxin and non-dioxin-like ligands. Toxicol Appl Pharmacol 243(3):359-371. doi:10.1016/j.taap.2009.12.003 PMID:20005886 PMCID:PMC3987113


  • Boverhof DR, Burgoon LD, Williams KJ, Zacharewski TR. 2008. Inhibition of estrogen-mediated uterine gene expression responses by dioxin. Mol Pharmacol 73(1):82-93. doi:10.1124/mol.107.040451 PMID:17942748
  • Kopec AK, Boverhof DR, Burgoon LD, Ibrahim-Aibo D, Harkema JR, Tashiro C, Chittim B, Zacharewski TR. 2008. Comparative toxicogenomic examination of the hepatic effects of PCB126 and TCDD in immature, ovariectomized C57BL/6 mice. Toxicol Sci 102(1):61-75. doi:10.1093/toxsci/kfm289 PMID:18042819
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