This liver steatosis AOP starts from the top with different molecular initiating events going down towards liver steatosis. The black nodes are Key Events and green nodes are molecular pathways. Adverse outcome pathway liver steatosis; the accumulation of lipids in hepatocytes, caused either by over-nutrition, visceral obesity, metabolic syndrome, or environmental toxins. Liver steatosis can be divided into three main categories: alcoholic liver disease (ALD), non-alcoholic liver disease (NAFLD), and toxicant-associated liver disease (TAFLD).[Review on liver steatosis](https://pubmed.ncbi.nlm.nih.gov/28210688/). ca3 a4f d68 dfc eb7 b6a a2e ed4 a7b ec2 e5d a45 d50 df0 cd6 be4 c02 a33 ce9 disease pathway PW:0000013 Pathway Ontology 21908933 PubMed Crosstalk of thyroid hormone receptor and liver X receptor in lipid metabolism and beyond [Review]. Endocr J 2011 Hashimoto K Mori M 21420387 PubMed From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans. Biochem Pharmacol 2011 Bock KW 16873678 PubMed Liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistance in ob/ob mice. Diabetes 2006 Dentin R Benhamed F Hainault I Fauveau V Foufelle F Dyck JR Girard J Postic C 1844873 PubMed Human AH locus polymorphism and cancer: inducibility of CYP1A1 and other genes by combustion products and dioxin. Pharmacogenetics 1991 Nebert DW Petersen DD Puga A 10398686 PubMed p27(Kip1) induction and inhibition of proliferation by the intracellular Ah receptor in developing thymus and hepatoma cells. Genes Dev 1999 Kolluri SK Weiss C Koff A Göttlicher M 19129222 PubMed Identification of pregnane-X receptor target genes and coactivator and corepressor binding to promoter elements in human hepatocytes. Nucleic Acids Res 2009 Hariparsad N Chu X Yabut J Labhart P Hartley DP Dai X Evers R 18288955 PubMed Xenobiotic-induced transcriptional regulation of xenobiotic metabolizing enzymes of the cytochrome P450 superfamily in human extrahepatic tissues. Curr Drug Metab 2008 Pavek P Dvorak Z 26451809 PubMed The identification of nuclear receptors associated with hepatic steatosis to develop and extend adverse outcome pathways. Crit Rev Toxicol 2016 Mellor CL Steinmetz FP Cronin MT 15340055 PubMed Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes Mol Cell Biol 2004 Kodama S 15581595 PubMed Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR. Arch Biochem Biophys 2005 Handschin C Meyer UA 11343253 PubMed The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR. Hepatology 2001 Sugatani J Kojima H Ueda A Kakizaki S Yoshinari K Gong QH Owens IS Negishi M Sueyoshi T 12611900 PubMed Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes. J Biol Chem 2003 Maglich JM Parks DJ Moore LB Collins JL Goodwin B Billin AN Stoltz CA Kliewer SA Lambert MH Willson TM Moore JT 11502724 PubMed Metabolic activation of polycyclic aromatic hydrocarbons and other procarcinogens by cytochromes P450 1A1 and P450 1B1 allelic variants and other human cytochromes P450 in Salmonella typhimurium NM2009. Drug Metab Dispos 2001 Shimada T Oda Y Gillam EM Guengerich FP Inoue K 8120057 PubMed The human CYP1A2 gene and induction by 3-methylcholanthrene. A region of DNA that supports AH-receptor binding and promoter-specific induction. J Biol Chem 1994 Quattrochi LC Vu T Tukey RH fatty liver disease DOID:9452 Disease hepatocyte CL:0000182 Cell Type 8910454 PubMed Isolation and characterization of the human cytochrome P450 CYP1B1 gene. J Biol Chem 1996 Tang YM Wo YY Stewart J Hawkins AL Griffin CA Sutter TR Greenlee WF 15004031 PubMed The nuclear receptor CAR is a regulator of thyroid hormone metabolism during caloric restriction. J Biol Chem 2004 Maglich JM Watson J McMillen PJ Goodwin B Willson TM Moore JT 9789279277443 ISBN Description of Prototype Modes-of-Action Related to Repeated Dose Toxicity http://publications.jrc.ec.europa.eu/repository/bitstream/JRC75689/lb-na-25631-en-n.pdf 2012 Brigitte Landesmann Marina Goumenou Sharon Munn Maurice Whelan 15581595 PubMed Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR. Arch Biochem Biophys 2005 Handschin C Meyer UA 17595319 PubMed The xenobiotic-sensing nuclear receptors pregnane X receptor, constitutive androstane receptor, and orphan nuclear receptor hepatocyte nuclear factor 4alpha in the regulation of human steroid-/bile acid-sulfotransferase. Mol Endocrinol 2007 Echchgadda I Song CS Oh T Ahmed M De La Cruz IJ Chatterjee B