Nonalcoholic fatty liver disease (Homo sapiens)

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1-4, 8-11Insulin ResistanceCxIER StressUQCRBADIPOR2BIDNDUFA8UQCRC1IL6selonsertibNDUFB8JUNPRKAA1NDUFA2TGF SignalingCOX8AApoptosisSDHBCOX7CIL6RPIK3R1UQCR10MAP3K11UQCRQNDUFA11PIK3R3INSXBP1NDUFB2NDUFA4PRKAG3NDUFA3RELACASP8LEPRCxINDUFA1CYC1PIK3R2CASP3COX7B2COX5BNDUFB1INSRCOX6A2PPARAPRKAG2ITCHNDUFA9SREBF1COX6B2NDUFV2NDUFS7PRKAA2mir21COX6CoxysterolsNFKB1MLXIPADIPOR1SDHDAKT1ADIPOQCOX7A1COX4I2SDHCTRAF2JNK2NDUFB6PRKAG1SDHANDUFS4FASNDUFA10IRS2GSK3BTNFNDUFB3PRKAB2LEPATF4COX6A1Oxidative PhosphorylationCOX7A2CEBPAUQCR11NDUFS3GSK3ACOX4I1MLXPPAR SignalingLipogenic EnzymesEIF2AK3COX8CCYP2E1FXRNDUFA6NDUFB10NDUFS1NDUFC2NDUFA5COX7A2LIL1BTGFB1NDUFA4L2PIK3CANDUFS8ERN1CYCSMLXIPLCOX3DDIT3UQCRC2PI3K-AKT SignalingNDUFAB1UQCRHTNFR1AKT3BAXRXRATNF SignalingNDUFC1FASLGIRS1NDUFA13AKT2IKBKBRAC1CXCL8COX7BPIK3CDCOX1COX2Fatty Acid BiosynthesisNDUFB11NDUFA12JNK1NDUFB4NDUFS5NDUFS2NDUFV3UQCRHLNDUFA7CDC42IL1ABBC3PIK3CBCYTBPKLRROSEIF2S1NDUFC2-KCTD14Insulin SignalingD-glucoseNDUFB7NDUFB9NDUFV1COX6B1MAP3K5NDUFB5NDUFS6fatty acidsSOCS3PRKAB1UQCRFS1BAK1COX5ANR1H3CASP7P675HepatocyteIL6CxIICxIIICxIVCxIICxIIICxIVIL1ATNFTNFFASLGGlucose UptakeFatty Acid OxidationDevelopment of NAFLDDevelopment of SteatoheptisisHepatocyte InjuryMitochondriadysfunctionIL1BBIMTCA CycleCCL2VCAM1NASHFibrogenesisSMAD7


Description

Nonalcoholic fatty liver disease (NAFLD) is a condition in which too much fat is stored in the liver. Nonalcoholic steatohepatitis (NASH) is a type of NAFLD marked by liver inflammation, which may progress to scarring and irreversible damage similar to that caused by heavy alcohol use. Components of glucose matabolism, insulin signaling, inflammation, oxidative stress, ER sgtress and apoptosis are all involved and interconnected in the progression of this disease.

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Bibliography

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  1. Larter CZ, Farrell GC; ''Insulin resistance, adiponectin, cytokines in NASH: Which is the best target to treat?''; J Hepatol, 2006 PubMed Europe PMC
  2. Seki E, Brenner DA, Karin M; ''A liver full of JNK: signaling in regulation of cell function and disease pathogenesis, and clinical approaches.''; Gastroenterology, 2012 PubMed Europe PMC
  3. Mantena SK, King AL, Andringa KK, Eccleston HB, Bailey SM; ''Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases.''; Free Radic Biol Med, 2008 PubMed Europe PMC
  4. Feldstein AE, Canbay A, Angulo P, Taniai M, Burgart LJ, Lindor KD, Gores GJ; ''Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis.''; Gastroenterology, 2003 PubMed Europe PMC
  5. Armstrong LE, Guo GL; ''Role of FXR in Liver Inflammation during Nonalcoholic Steatohepatitis.''; Curr Pharmacol Rep, 2017 PubMed Europe PMC
  6. Loomba R, Lawitz E, Mantry PS, Jayakumar S, Caldwell SH, Arnold H, Diehl AM, Djedjos CS, Han L, Myers RP, Subramanian GM, McHutchison JG, Goodman ZD, Afdhal NH, Charlton MR; ''Selonsertib (GS-4997), an ASK1 inhibitor, antagonizes multidrug resistance in ABCB1- and ABCG2-overexpressing cancer cells.''; Cancer Lett, 2018 PubMed Europe PMC
  7. Dattaroy D, Pourhoseini S, Das S, Alhasson F, Seth RK, Nagarkatti M, Michelotti GA, Diehl AM, Chatterjee S; ''Micro-RNA 21 inhibition of SMAD7 enhances fibrogenesis via leptin-mediated NADPH oxidase in experimental and human nonalcoholic steatohepatitis.''; Am J Physiol Gastrointest Liver Physiol, 2015 PubMed Europe PMC
  8. Malaguarnera M, Di Rosa M, Nicoletti F, Malaguarnera L; ''Molecular mechanisms involved in NAFLD progression.''; J Mol Med (Berl), 2009 PubMed Europe PMC
  9. Hotamisligil GS; ''Endoplasmic reticulum stress and the inflammatory basis of metabolic disease.''; Cell, 2010 PubMed Europe PMC
  10. Farrell GC, van Rooyen D, Gan L, Chitturi S; ''NASH is an Inflammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications.''; Gut Liver, 2012 PubMed Europe PMC
  11. Malhi H, Kaufman RJ; ''Endoplasmic reticulum stress in liver disease.''; J Hepatol, 2011 PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
98945view17:56, 16 October 2018AlexanderPicoOntology Term : 'liver disease pathway' added !
98944view17:55, 16 October 2018AlexanderPicoOntology Term : 'disease pathway' added !
98943view17:55, 16 October 2018AlexanderPicoOntology Term : 'nonalcoholic fatty liver disease' added !
98942view17:55, 16 October 2018AlexanderPicoOntology Term : 'hepatocyte' added !
98933view10:52, 16 October 2018EgonwReplaced a secondary ChEBI identifier.
98932view10:50, 16 October 2018EgonwRemoved funny chars in identifier.
98931view06:46, 16 October 2018AlexanderPicoModified description
98930view06:35, 16 October 2018AlexanderPicofixed paste characters in IDs
98929view06:31, 16 October 2018AlexanderPiconew pathway
98917view18:21, 15 October 2018AlexanderPicoNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADIPOQGeneProduct9370 (Entrez Gene)
ADIPOR1GeneProduct51094 (Entrez Gene)
ADIPOR2GeneProduct79602 (Entrez Gene)
AKT1GeneProduct207 (Entrez Gene)
AKT2GeneProduct208 (Entrez Gene)
AKT3GeneProduct10000 (Entrez Gene)
ATF4GeneProduct468 (Entrez Gene)
ApoptosisPathwayWP254 (WikiPathways)
BAK1GeneProduct578 (Entrez Gene)
BAXGeneProduct581 (Entrez Gene)
BBC3GeneProduct27113 (Entrez Gene)
BIDGeneProduct637 (Entrez Gene)
BIMGeneProduct10018 (Entrez Gene)
CASP3GeneProduct836 (Entrez Gene)
CASP7GeneProduct840 (Entrez Gene)
CASP8GeneProduct841 (Entrez Gene)
CCL2GeneProduct6347 (Entrez Gene)
CDC42GeneProduct998 (Entrez Gene)
CEBPAGeneProduct1050 (Entrez Gene)
COX1GeneProduct4512 (Entrez Gene)
COX2GeneProduct4513 (Entrez Gene)
COX3GeneProduct4514 (Entrez Gene)
COX4I1GeneProduct1327 (Entrez Gene)
COX4I2GeneProduct84701 (Entrez Gene)
COX5AGeneProduct9377 (Entrez Gene)
COX5BGeneProduct1329 (Entrez Gene)
COX6A1GeneProduct1337 (Entrez Gene)
COX6A2GeneProduct1339 (Entrez Gene)
COX6B1GeneProduct1340 (Entrez Gene)
COX6B2GeneProduct125965 (Entrez Gene)
COX6CGeneProduct1345 (Entrez Gene)
COX7A1GeneProduct1346 (Entrez Gene)
COX7A2GeneProduct1347 (Entrez Gene)
COX7A2LGeneProduct9167 (Entrez Gene)
COX7BGeneProduct1349 (Entrez Gene)
COX7B2GeneProduct170712 (Entrez Gene)
COX7CGeneProduct1350 (Entrez Gene)
COX8AGeneProduct1351 (Entrez Gene)
COX8CGeneProduct341947 (Entrez Gene)
CXCL8GeneProduct3576 (Entrez Gene)
CYC1GeneProduct1537 (Entrez Gene)
CYCSGeneProduct54205 (Entrez Gene)
CYP2E1GeneProduct1571 (Entrez Gene)
CYTBGeneProduct4519 (Entrez Gene)
CxIGeneProduct
CxIIGeneProduct
CxIIIGeneProduct
CxIVGeneProduct
D-glucoseMetaboliteCHEBI:42758 (ChEBI)
DDIT3GeneProduct1649 (Entrez Gene)
EIF2AK3GeneProduct9451 (Entrez Gene)
EIF2S1GeneProduct1965 (Entrez Gene)
ERN1GeneProduct2081 (Entrez Gene)
FASGeneProduct355 (Entrez Gene)
FASLGGeneProduct356 (Entrez Gene)
FXRGeneProduct9971 (Entrez Gene)
Fatty Acid BiosynthesisPathwayWP357 (WikiPathways)
GSK3AGeneProduct2931 (Entrez Gene)
GSK3BGeneProduct2932 (Entrez Gene)
IKBKBGeneProduct3551 (Entrez Gene)
IL1AGeneProduct3552 (Entrez Gene)
IL1BGeneProduct3553 (Entrez Gene)
IL6GeneProduct3569 (Entrez Gene)
IL6RGeneProduct3570 (Entrez Gene)
INSGeneProduct3630 (Entrez Gene)
INSRGeneProduct3643 (Entrez Gene)
IRS1GeneProduct3667 (Entrez Gene)
IRS2GeneProduct8660 (Entrez Gene)
ITCHGeneProduct83737 (Entrez Gene)
Insulin SignalingPathwayWP481 (WikiPathways)
JNK1GeneProduct5599 (Entrez Gene)
JNK2GeneProduct5601 (Entrez Gene)
JUNGeneProduct3725 (Entrez Gene)
LEPGeneProduct3952 (Entrez Gene)
LEPRGeneProduct3953 (Entrez Gene)
Lipogenic EnzymesGeneProduct
MAP3K11GeneProduct4296 (Entrez Gene)
MAP3K5GeneProduct4217 (Entrez Gene)
MLXGeneProduct6945 (Entrez Gene)
MLXIPGeneProduct22877 (Entrez Gene)
MLXIPLGeneProduct51085 (Entrez Gene)
NDUFA10GeneProduct4705 (Entrez Gene)
NDUFA11GeneProduct126328 (Entrez Gene)
NDUFA12GeneProduct55967 (Entrez Gene)
NDUFA13GeneProduct51079 (Entrez Gene)
NDUFA1GeneProduct4694 (Entrez Gene)
NDUFA2GeneProduct4695 (Entrez Gene)
NDUFA3GeneProduct4696 (Entrez Gene)
NDUFA4GeneProduct4697 (Entrez Gene)
NDUFA4L2GeneProduct56901 (Entrez Gene)
NDUFA5GeneProduct4698 (Entrez Gene)
NDUFA6GeneProduct4700 (Entrez Gene)
NDUFA7GeneProduct4701 (Entrez Gene)
NDUFA8GeneProduct4702 (Entrez Gene)
NDUFA9GeneProduct4704 (Entrez Gene)
NDUFAB1GeneProduct4706 (Entrez Gene)
NDUFB10GeneProduct4716 (Entrez Gene)
NDUFB11GeneProduct54539 (Entrez Gene)
NDUFB1GeneProduct4707 (Entrez Gene)
NDUFB2GeneProduct4708 (Entrez Gene)
NDUFB3GeneProduct4709 (Entrez Gene)
NDUFB4GeneProduct4710 (Entrez Gene)
NDUFB5GeneProduct4711 (Entrez Gene)
NDUFB6GeneProduct4712 (Entrez Gene)
NDUFB7GeneProduct4713 (Entrez Gene)
NDUFB8GeneProduct4714 (Entrez Gene)
NDUFB9GeneProduct4715 (Entrez Gene)
NDUFC1GeneProduct4717 (Entrez Gene)
NDUFC2-KCTD14GeneProduct100532726 (Entrez Gene)
NDUFC2GeneProduct4718 (Entrez Gene)
NDUFS1GeneProduct4719 (Entrez Gene)
NDUFS2GeneProduct4720 (Entrez Gene)
NDUFS3GeneProduct4722 (Entrez Gene)
NDUFS4GeneProduct4724 (Entrez Gene)
NDUFS5GeneProduct4725 (Entrez Gene)
NDUFS6GeneProduct4726 (Entrez Gene)
NDUFS7GeneProduct374291 (Entrez Gene)
NDUFS8GeneProduct4728 (Entrez Gene)
NDUFV1GeneProduct4723 (Entrez Gene)
NDUFV2GeneProduct4729 (Entrez Gene)
NDUFV3GeneProduct4731 (Entrez Gene)
NFKB1GeneProduct4790 (Entrez Gene)
NR1H3GeneProduct10062 (Entrez Gene)
Oxidative PhosphorylationPathwayWP623 (WikiPathways)
PI3K-AKT SignalingPathwayWP3844 (WikiPathways)
PIK3CAGeneProduct5290 (Entrez Gene)
PIK3CBGeneProduct5291 (Entrez Gene)
PIK3CDGeneProduct5293 (Entrez Gene)
PIK3R1GeneProduct5295 (Entrez Gene)
PIK3R2GeneProduct5296 (Entrez Gene)
PIK3R3GeneProduct8503 (Entrez Gene)
PKLRGeneProduct5313 (Entrez Gene)
PPAR SignalingPathwayWP3942 (WikiPathways)
PPARAGeneProduct5465 (Entrez Gene)
PRKAA1GeneProduct5562 (Entrez Gene)
PRKAA2GeneProduct5563 (Entrez Gene)
PRKAB1GeneProduct5564 (Entrez Gene)
PRKAB2GeneProduct5565 (Entrez Gene)
PRKAG1GeneProduct5571 (Entrez Gene)
PRKAG2GeneProduct51422 (Entrez Gene)
PRKAG3GeneProduct53632 (Entrez Gene)
RAC1GeneProduct5879 (Entrez Gene)
RELAGeneProduct5970 (Entrez Gene)
ROSMetaboliteCHEBI:26523 (ChEBI)
RXRAGeneProduct6256 (Entrez Gene)
SDHAGeneProduct6389 (Entrez Gene)
SDHBGeneProduct6390 (Entrez Gene)
SDHCGeneProduct6391 (Entrez Gene)
SDHDGeneProduct6392 (Entrez Gene)
SMAD7GeneProduct4092 (Entrez Gene)
SOCS3GeneProduct9021 (Entrez Gene)
SREBF1GeneProduct6720 (Entrez Gene)
TCA CyclePathwayWP78 (WikiPathways)
TGF SignalingPathwayWP560 (WikiPathways)
TGFB1GeneProduct7040 (Entrez Gene)
TNF SignalingPathwayWP231 (WikiPathways)
TNFGeneProduct7124 (Entrez Gene)
TNFR1GeneProduct7132 (Entrez Gene)
TRAF2GeneProduct7186 (Entrez Gene)
UQCR10GeneProduct29796 (Entrez Gene)
UQCR11GeneProduct10975 (Entrez Gene)
UQCRBGeneProduct7381 (Entrez Gene)
UQCRC1GeneProduct7384 (Entrez Gene)
UQCRC2GeneProduct7385 (Entrez Gene)
UQCRFS1GeneProduct7386 (Entrez Gene)
UQCRHGeneProduct7388 (Entrez Gene)
UQCRHLGeneProduct440567 (Entrez Gene)
UQCRQGeneProduct27089 (Entrez Gene)
VCAM1GeneProduct7412 (Entrez Gene)
XBP1GeneProduct7494 (Entrez Gene)
fatty acidsMetaboliteCHEBI:35366 (ChEBI)
mir21Rna406991 (Entrez Gene)
oxysterolsMetaboliteCHEBI:53030 (ChEBI)
selonsertibMetaboliteQ27088777 (Wikidata)

Annotated Interactions

No annotated interactions

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