Nonalcoholic fatty liver disease (Homo sapiens)

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1-4, 8-11ER StressInsulin ResistanceCxICASP3UQCR10JUNSDHCLipogenic EnzymesINSRNDUFB2AKT2UQCRFS1NDUFA11TRAF2NDUFC2NDUFB5IRS2COX4I2CDC42NDUFA6ERN1NDUFA3NDUFB8NDUFB3NDUFA2TNFR1RELACEBPAPIK3CAPPARANDUFS5SDHBNDUFB7NDUFA4L2NDUFV2SOCS3NDUFA7NDUFS2COX5ANDUFC1PI3K-AKT SignalingNDUFB11NDUFV1PKLRNFKB1NDUFAB1MLXIPLNDUFS8NDUFS1COX7A1IL6RApoptosisBAK1UQCRBADIPOR2NDUFA13LEPRJNK1UQCRHITCHFASBIDNDUFB4CXCL8JNK2NDUFS7CYTBCOX2NDUFB1SDHASREBF1Fatty Acid BiosynthesisNDUFA9ROSCOX1PRKAA1IRS1ADIPOR1INSNDUFS6NDUFA12oxysterolsCOX7B2ADIPOQCOX6A1Insulin SignalingNDUFA5GSK3ACxINDUFV3BAXIKBKBmir21CASP8NDUFB9UQCRC1NDUFB6TGFB1IL6LEPNDUFA4PIK3R3MAP3K11FXRPRKAG1CYCSIL1ACOX3RXRANDUFA1UQCRQMLXIPEIF2AK3AKT3COX6B2EIF2S1PIK3CBATF4AKT1IL1BBBC3XBP1CYC1NDUFS4DDIT3TNF SignalingCOX8ATGF SignalingMAP3K5COX7BCOX4I1PRKAG3PRKAB2GSK3BPRKAB1TNFCOX8CCASP7COX6A2COX6CPRKAG2NDUFB10UQCR11PRKAA2COX7A2LPIK3R1COX7A2PIK3R2RAC1UQCRHLCOX7CNDUFC2-KCTD14fatty acidsCOX5BD-glucoseNDUFA8FASLGCOX6B1Oxidative PhosphorylationselonsertibNR1H3NDUFS3SDHDNDUFA10PPAR SignalingPIK3CDMLXCYP2E1UQCRC2P675HepatocyteIL6CxIICxIIICxIVCxIICxIIICxIVIL1ATNFTNFFASLGGlucose 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 Scholia
  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 Scholia
  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 Scholia
  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 Scholia
  5. Armstrong LE, Guo GL; ''Role of FXR in Liver Inflammation during Nonalcoholic Steatohepatitis.''; Curr Pharmacol Rep, 2017 PubMed Europe PMC Scholia
  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 Scholia
  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 Scholia
  8. Malaguarnera M, Di Rosa M, Nicoletti F, Malaguarnera L; ''Molecular mechanisms involved in NAFLD progression.''; J Mol Med (Berl), 2009 PubMed Europe PMC Scholia
  9. Hotamisligil GS; ''Endoplasmic reticulum stress and the inflammatory basis of metabolic disease.''; Cell, 2010 PubMed Europe PMC Scholia
  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 Scholia
  11. Malhi H, Kaufman RJ; ''Endoplasmic reticulum stress in liver disease.''; J Hepatol, 2011 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
123350view10:46, 17 July 2022EgonwMade multiple pathways clickable
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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