Liver steatosis adverse outcome pathway (Homo sapiens)

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13, 1713, 171413, 1713, 17Fatty acid lysisgenesCAR Target genesMitochondrialBeta-oxidationgenesCAR coregulatorsAhR Target genesFAS genesLXR Target genesChREBPCD36KE(KE:10106)Fatty LivercellsKE(KE:466)MIE(KE:18)LDLRMIE(KE:245KE(KE:291)KE(KE:10201)NucleusdistortionKE(KE:471)PPARDPPARAKE(KE:116)KE(KE:66)CPT1AMIE(KE:227)FOXA2PXR activationMitochondrialBeta-oxidationDe novoFA synthesisKE(KE:10201)CAR activationPPARGFA influxKE(KE:472)Liver SteatosisLXR activationHSD17B10KE(KE:10201)FASKE(KE:89)KE(KE:258)MitochondrialdisruptionFatty acid lysisMIE(KE:10101)MIE(KE:228)KE(KE:10201)MIE(KE:167)CytoplasmdisplacementTriglyceride accumulationin LivercellsKE(KE:10110)AO(KE:345)KE(KE:1214)KE(KE:264)KE(KE:54)Endoplasmicreticulum stressSCDKE(KE:10102)KE(KE:474)HMGCS2KE(KE:115)SREBP-1cAhR activationKE(KE:860)CYP2C911ABCB115UGT1A1ABCC2168CYP2A6CYP4A11158CYP2C19SULT1A111GSTA2315CYP3A511SULT2A1CYP3A418ALAS111EHHADH158CYP2B6ABCC3118UGT1A4UGT1A612UGT1A912UGT1A31212FOXO16NCOA6SP1NCOA1PPARGC1ANCOA2SMC1Ap27Kip12CYP1A1CYP1A29CYP1B17p21cip15, 19ABCG8CYP3A44ABCG510CYP2B64CYP7A110SREBF11010FASN10SCDPXR Target genesPXR coregulatorsCYP3A711UGT1A6UGT1A31212UGT1A912CYP2A6UGT1A41112SLCO1B1SRPX21NCOA3FOXO16CYP4F121CYP3A4UGT1A1111ABCC4NRIP11CYP2B611GSTA21PSMC5PPARGC1ANCOA1NCOA2ABCB1CYP2C9111CYP3A511CYP2C1911SULT2A118ABCC2ABCC31010SRCNCOA2NCOA3PSMC5NRIP1SRPX2PPARGC1AACSL4SCP2CPT2EHHADHACSL1DCIACADSHADHACPT1AACSL2ACSL3ACADLACADMACADVLHADHSCSLC25A20PECRECHS1ACSL5PECRECHDC2ACACAECHDC1ACSL4ACAS2ECHDC3ACLYFASNACSL3HADHSCACACBACSL1ACAA2MECRDECR1ACSL6ECH1PRKAR1BPRKAR2BATGLHSLPRKAG3PRKAG1ABHD5PRKACGPRKACAPRKAA1PRKACBPRKAB2PRKAB1PRKAA2PRKAG2PRKAR1APRKAR2Ade novoFA synthesisECHS1ACSL5PECRECHDC2ACACAECHDC1ACSL4ACAS2ECHDC3ACLYFASNACSL3HADHSCACACBACSL1ACAA2MECRDECR1ACSL6ECH1


Description

Liver steatosis AOP

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Bibliography

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  1. Quattrochi LC, Vu T, Tukey RH; ''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 PubMed Europe PMC Scholia
  2. Shimada T, Oda Y, Gillam EM, Guengerich FP, Inoue K; ''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 PubMed Europe PMC Scholia
  3. Kolluri SK, Weiss C, Koff A, Göttlicher M; ''p27(Kip1) induction and inhibition of proliferation by the intracellular Ah receptor in developing thymus and hepatoma cells.''; Genes Dev, 1999 PubMed Europe PMC Scholia
  4. Hariparsad N, Chu X, Yabut J, Labhart P, Hartley DP, Dai X, Evers R; ''Identification of pregnane-X receptor target genes and coactivator and corepressor binding to promoter elements in human hepatocytes.''; Nucleic Acids Res, 2009 PubMed Europe PMC Scholia
  5. Maglich JM, Parks DJ, Moore LB, Collins JL, Goodwin B, Billin AN, Stoltz CA, Kliewer SA, Lambert MH, Willson TM, Moore JT; ''Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes.''; J Biol Chem, 2003 PubMed Europe PMC Scholia
  6. Handschin C, Meyer UA; ''Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR.''; Arch Biochem Biophys, 2005 PubMed Europe PMC Scholia
  7. Pavek P, Dvorak Z; ''Xenobiotic-induced transcriptional regulation of xenobiotic metabolizing enzymes of the cytochrome P450 superfamily in human extrahepatic tissues.''; Curr Drug Metab, 2008 PubMed Europe PMC Scholia
  8. Hashimoto K, Mori M; ''Crosstalk of thyroid hormone receptor and liver X receptor in lipid metabolism and beyond [Review].''; Endocr J, 2011 PubMed Europe PMC Scholia
  9. Bock KW; ''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 PubMed Europe PMC Scholia
  10. Dentin R, Benhamed F, Hainault I, Fauveau V, Foufelle F, Dyck JR, Girard J, Postic C; ''Liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistance in ob/ob mice.''; Diabetes, 2006 PubMed Europe PMC Scholia
  11. Nebert DW, Petersen DD, Puga A; ''Human AH locus polymorphism and cancer: inducibility of CYP1A1 and other genes by combustion products and dioxin.''; Pharmacogenetics, 1991 PubMed Europe PMC Scholia
  12. Tang YM, Wo YY, Stewart J, Hawkins AL, Griffin CA, Sutter TR, Greenlee WF; ''Isolation and characterization of the human cytochrome P450 CYP1B1 gene.''; J Biol Chem, 1996 PubMed Europe PMC Scholia
  13. Mellor CL, Steinmetz FP, Cronin MT; ''The identification of nuclear receptors associated with hepatic steatosis to develop and extend adverse outcome pathways.''; Crit Rev Toxicol, 2016 PubMed Europe PMC Scholia
  14. Kodama S; ''Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes''; Mol Cell Biol, 2004 PubMed Europe PMC Scholia
  15. Handschin C, Meyer UA; ''Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR.''; Arch Biochem Biophys, 2005 PubMed Europe PMC Scholia
  16. Sugatani J, Kojima H, Ueda A, Kakizaki S, Yoshinari K, Gong QH, Owens IS, Negishi M, Sueyoshi T; ''The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR.''; Hepatology, 2001 PubMed Europe PMC Scholia
  17. Echchgadda I, Song CS, Oh T, Ahmed M, De La Cruz IJ, Chatterjee B; ''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 PubMed Europe PMC Scholia
  18. Brigitte Landesmann, Marina Goumenou, Sharon Munn, Maurice Whelan; ''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
  19. Maglich JM, Watson J, McMillen PJ, Goodwin B, Willson TM, Moore JT; ''The nuclear receptor CAR is a regulator of thyroid hormone metabolism during caloric restriction.''; J Biol Chem, 2004 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
135423view20:56, 5 September 2024AlexanderPicoadded BiopaxRefs for each of the PublicationXrefs
135422view20:42, 5 September 2024AlexanderPicoremoved duplicate bp:ID in rdf:id="dfc"
135414view20:54, 4 September 2024Khanspersminor layout update
135411view19:20, 3 September 2024Khanspersminor layout change to trigger update
129354view09:32, 27 March 2024MkutmonOntology Term : 'disease pathway' added !
128765view13:41, 21 February 2024Marvin M2Reverted to version '11:25, 23 June 2021' by Marvin M2
128764view13:41, 21 February 2024MysticArchers
128763view13:39, 21 February 2024Marvin M2Reverted to version '11:25, 23 June 2021' by Marvin M2
128762view13:38, 21 February 2024Marvin M2
119296view11:25, 23 June 2021FinterlyAdded ISBN for book citation
118491view08:46, 28 May 2021FinterlyReplace DataNode Type "Key Event" with "Event"
116509view10:44, 7 May 2021EweitzModified title
115813view20:37, 14 March 2021ChesdeWindtFixed incorrect reference on KE 860
115727view08:51, 9 March 2021Marvin M2Updated PPARa and b/d KE pathways, and cleaned the AOP
115692view17:12, 4 March 2021Jkearns445Fixed interactions
115688view10:40, 4 March 2021ChesdeWindtModified description
115648view14:35, 3 March 2021Jkearns445
115644view14:28, 3 March 2021Jkearns445
115643view14:27, 3 March 2021Jkearns445
115642view14:10, 3 March 2021Jkearns445
115627view18:32, 2 March 2021ChesdeWindt
115626view17:12, 2 March 2021ChesdeWindtAdded KE479 to KE227
115578view22:58, 27 February 2021ChesdeWindtModified description
115545view15:10, 26 February 2021Jkearns445
115544view15:08, 26 February 2021Jkearns445
115543view15:06, 26 February 2021Jkearns445Cleaned up the patway, added a new pathway
115542view14:59, 26 February 2021Jkearns445
115540view14:19, 26 February 2021Jkearns445
115539view14:14, 26 February 2021Jkearns445
115526view13:24, 25 February 2021Jkearns445
115525view13:13, 25 February 2021Jkearns445
115524view12:54, 25 February 2021Marvin M2Ontology Term : 'hepatocyte' added !
115523view12:52, 25 February 2021Marvin M2Ontology Term : 'fatty liver disease' added !
115522view22:17, 24 February 2021ChesdeWindtModified description
115495view07:22, 24 February 2021Jkearns445
115494view07:20, 24 February 2021Jkearns445
115346view09:56, 15 February 2021Jkearns445
115332view18:56, 13 February 2021Jkearns445
115331view18:54, 13 February 2021Jkearns445
115330view18:53, 13 February 2021Jkearns445
115327view11:17, 13 February 2021Jkearns445
115326view11:03, 13 February 2021Jkearns445Cleaned up the pathway and added pathways to KE nodes
115314view07:28, 12 February 2021Jkearns445
115313view07:18, 12 February 2021Jkearns445
115310view17:13, 11 February 2021Marvin M2updated KE title of KE66
115309view17:11, 11 February 2021Marvin M2Added Key Event type to KE66
115304view13:11, 11 February 2021Jkearns445
115303view12:43, 11 February 2021Jkearns445Added database IDs for more Key Events
115302view12:24, 11 February 2021Jkearns445Added database IDs for Key Events and changed the shape of the pathway nodes
115301view10:49, 11 February 2021Marvin M2

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ABCB1GeneProduct5243 (Entrez Gene) ATP-binding cassette, sub-family B (MDR/TAP), member 1
ABCB1GeneProductENSG00000085563 (Ensembl)
ABCC2GeneProduct1244 (Entrez Gene) ATP-binding cassette, sub-family C (CFTR/MRP), member 2
ABCC2GeneProductENSG00000023839 (Ensembl)
ABCC3GeneProduct8714 (Entrez Gene) ATP-binding cassette, sub-family C (CFTR/MRP), member 3
ABCC3GeneProductENSG00000108846 (Ensembl)
ABCC4GeneProductENSG00000125257 (Ensembl)
ABCG5GeneProduct64240 (Entrez Gene) ATP-binding cassette, sub-family G (WHITE), member 5
ABCG8GeneProduct64241 (Entrez Gene) ATP-binding cassette, sub-family G (WHITE), member 8
ABHD5GeneProductENSG00000011198 (Ensembl)
ACAA2GeneProduct10449 (Entrez Gene)
ACACAGeneProduct31 (Entrez Gene)
ACACBGeneProduct32 (Entrez Gene)
ACADLGeneProduct33 (Entrez Gene)
ACADMGeneProduct34 (Entrez Gene)
ACADSGeneProduct35 (Entrez Gene)
ACADVLGeneProduct37 (Entrez Gene)
ACAS2GeneProduct55902 (Entrez Gene)
ACLYGeneProduct47 (Entrez Gene)
ACSL1GeneProduct2180 (Entrez Gene)
ACSL2GeneProduct80221 (Entrez Gene)
ACSL3GeneProduct2181 (Entrez Gene)
ACSL4GeneProduct2182 (Entrez Gene)
ACSL5GeneProduct51703 (Entrez Gene)
ACSL6GeneProduct23305 (Entrez Gene)
ALAS1GeneProductENSG00000023330 (Ensembl)
AO (KE:345)
ATGLGeneProductENSG00000177666 (Ensembl)
AhR activationPathwayWP2586 (WikiPathways)
CAR activationPathwayWP2875 (WikiPathways)
CD36GeneProductENSG00000135218 (Ensembl)
CPT1AGeneProduct1374 (Entrez Gene)
CPT1AGeneProductENSG00000110090 (Ensembl)
CPT2GeneProduct1376 (Entrez Gene)
CYP1A1GeneProduct1543 (Entrez Gene)
CYP1A2GeneProduct1544 (Entrez Gene)
CYP1B1GeneProduct1545 (Entrez Gene)
CYP2A6GeneProduct1548 (Entrez Gene) cytochrome P450, family 2, subfamily A, polypeptide 6
CYP2A6GeneProductENSG00000255974 (Ensembl)
CYP2B6GeneProduct1555 (Entrez Gene) cytochrome P450, family 2, subfamily B, polypeptide 6
CYP2B6GeneProductENSG00000197408 (Ensembl)
CYP2C19GeneProduct1557 (Entrez Gene) cytochrome P450, family 2, subfamily C, polypeptide 19
CYP2C19GeneProductENSG00000165841 (Ensembl)
CYP2C9GeneProduct1559 (Entrez Gene) cytochrome P450, family 2, subfamily C, polypeptide 9
CYP2C9GeneProductENSG00000138109 (Ensembl)
CYP3A4GeneProduct1576 (Entrez Gene) cytochrome P450, family 3, subfamily A, polypeptide 4
CYP3A4GeneProductENSG00000160868 (Ensembl)
CYP3A5GeneProduct1577 (Entrez Gene) cytochrome P450, family 3, subfamily A, polypeptide 5
CYP3A5GeneProductENSG00000106258 (Ensembl)
CYP3A7GeneProductENSG00000160870 (Ensembl)
CYP4A11GeneProductENSG00000187048 (Ensembl)
CYP4F12GeneProductENSG00000186204 (Ensembl)
CYP7A1GeneProduct1581 (Entrez Gene) cytochrome P450, family 7, subfamily A, polypeptide 1 , is not affected in human
ChREBPGeneProductENSG00000009950 (Ensembl)
Cytoplasm displacement
DCIGeneProduct1632 (Entrez Gene)
DECR1GeneProduct1666 (Entrez Gene)
De novo FA synthesisPathwayWP357 (WikiPathways)
ECH1GeneProduct1891 (Entrez Gene)
ECHDC1GeneProduct55862 (Entrez Gene)
ECHDC2GeneProduct55268 (Entrez Gene)
ECHDC3GeneProduct79746 (Entrez Gene)
ECHS1GeneProduct1892 (Entrez Gene)
EHHADHGeneProduct1962 (Entrez Gene)
EHHADHGeneProductENSG00000113790 (Ensembl)
Endoplasmic reticulum stress
FA influx
FASNGeneProduct2194 (Entrez Gene)
FASPathwayWP357 (WikiPathways)
FOXA2GeneProductENSG00000125798 (Ensembl)
FOXO1GeneProductENSG00000150907 (Ensembl)
Fatty Liver cells
Fatty acid lysisPathwayWP3965 (WikiPathways)
GSTA2GeneProduct2939 (Entrez Gene) glutathione S-transferase alpha 2
GSTA2GeneProductENSG00000244067 (Ensembl)
HADHAGeneProduct3030 (Entrez Gene) similiar to: ECHA RAT
HADHSCGeneProduct3033 (Entrez Gene)
HMGCS2GeneProductENSG00000134240 (Ensembl)
HSD17B10GeneProductENSG00000072506 (Ensembl)
HSLGeneProductENSG00000079435 (Ensembl)
KE (KE:10102)
KE (KE:10106)
KE (KE:10110)
KE (KE:10201)GeneProduct
KE (KE:115)GeneProduct
KE (KE:116)GeneProduct
KE (KE:1214)
KE (KE:258)GeneProduct
KE (KE:264)GeneProduct
KE (KE:291)
KE (KE:466)
KE (KE:471)
KE

(KE:472)

KE

(KE:474)

KE (KE:54)GeneProduct
KE (KE:66)
KE (KE:860)
KE (KE:89)
LDLRGeneProductENSG00000130164 (Ensembl)
LXR activationPathwayWP2874 (WikiPathways)
Liver Steatosis
MECRGeneProduct51102 (Entrez Gene)
MIE (KE:10101)
MIE (KE:167)
MIE (KE:18)
MIE (KE:227)
MIE (KE:228)
MIE (KE:245
Mitochondrial Beta-oxidationPathwayWP368 (WikiPathways)
Mitochondrial disruption
NCOA1GeneProduct8648 (Entrez Gene) nuclear receptor coactivator 1
NCOA1GeneProductENSG00000084676 (Ensembl)
NCOA2GeneProduct10499 (Entrez Gene) nuclear receptor coactivator 2
NCOA2GeneProductENSG00000140396 (Ensembl)
NCOA3GeneProductENSG00000124151 (Ensembl)
NCOA6GeneProduct23054 (Entrez Gene) nuclear receptor coactivator 6
NRIP1GeneProductENSG00000180530 (Ensembl)
Nucleus distortion
PECRGeneProduct55825 (Entrez Gene)
PPARAGeneProductENSG00000186951 (Ensembl)
PPARDGeneProductENSG00000112033 (Ensembl)
PPARGC1AGeneProduct10891 (Entrez Gene) peroxisome proliferator-activated receptor gamma, coactivator 1 alpha
PPARGC1AGeneProductENSG00000109819 (Ensembl)
PPARGGeneProductENSG00000132170 (Ensembl)
PRKAA1GeneProductENSG00000132356 (Ensembl)
PRKAA2GeneProductENSG00000162409 (Ensembl)
PRKAB1GeneProductENSG00000111725 (Ensembl)
PRKAB2GeneProductENSG00000131791 (Ensembl)
PRKACAGeneProductENSG00000072062 (Ensembl)
PRKACBGeneProductENSG00000142875 (Ensembl)
PRKACGGeneProductENSG00000165059 (Ensembl)
PRKAG1GeneProductENSG00000181929 (Ensembl)
PRKAG2GeneProductENSG00000106617 (Ensembl)
PRKAG3GeneProductENSG00000115592 (Ensembl)
PRKAR1AGeneProductENSG00000108946 (Ensembl)
PRKAR1BGeneProductENSG00000188191 (Ensembl)
PRKAR2AGeneProductENSG00000114302 (Ensembl)
PRKAR2BGeneProductENSG00000005249 (Ensembl)
PSMC5GeneProductENSG00000087191 (Ensembl)
PXR activationPathwayWP2876 (WikiPathways)
SCDGeneProduct6319 (Entrez Gene)
SCDGeneProductENSG00000099194 (Ensembl)
SCP2GeneProduct6342 (Entrez Gene)
SLC25A20GeneProduct788 (Entrez Gene)
SLCO1B1GeneProductENSG00000134538 (Ensembl)
SMC1AGeneProduct8243 (Entrez Gene) structural maintenance of chromosomes 1A
SP1GeneProduct6667 (Entrez Gene) Sp1 transcription factor
SRCGeneProductENSG00000197122 (Ensembl)
SREBF1GeneProduct6720 (Entrez Gene) sterol regulatory element binding transcription factor 1
SREBP-1cGeneProductENSG00000072310 (Ensembl)
SRPX2GeneProductENSG00000102359 (Ensembl)
SULT1A1GeneProductENSG00000196502 (Ensembl) during fasting
SULT2A1GeneProductENSG00000105398 (Ensembl)
Triglyceride accumulation in Livercells
UGT1A1GeneProductENSG00000241635 (Ensembl)
UGT1A3GeneProductENSG00000243135 (Ensembl)
UGT1A4GeneProductENSG00000244474 (Ensembl)
UGT1A6GeneProductENSG00000167165 (Ensembl)
UGT1A9GeneProductENSG00000241119 (Ensembl)
p21cip1GeneProduct1026 (Entrez Gene)
p27Kip1GeneProduct1027 (Entrez Gene)

Annotated Interactions

No annotated interactions

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