Nonalcoholic fatty liver disease (WP4396)

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.
last edited

Authors

AlexanderPico and Egonw

Cited In

Organism

Homo sapiens

Communities

Diseases

Annotations

Cell Type Ontology: hepatocyte

Disease Ontology: non-alcoholic fatty liver disease

Pathway Ontology: disease pathway liver disease pathway

Participants

Label Type Compact Identifier
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RELA GeneProduct ncbigene:5970
PIK3CA GeneProduct ncbigene:5290
PIK3CD GeneProduct ncbigene:5293
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PIK3R1 GeneProduct ncbigene:5295
PIK3R2 GeneProduct ncbigene:5296
PIK3R3 GeneProduct ncbigene:8503
AKT1 GeneProduct ncbigene:207
AKT2 GeneProduct ncbigene:208
AKT3 GeneProduct ncbigene:10000
GSK3A GeneProduct ncbigene:2931
GSK3B GeneProduct ncbigene:2932
IL1A GeneProduct ncbigene:3552
IL1B GeneProduct ncbigene:3553
MLX GeneProduct ncbigene:6945
MLXIP GeneProduct ncbigene:22877
MLXIPL GeneProduct ncbigene:51085
ADIPOR1 GeneProduct ncbigene:51094
ADIPOR2 GeneProduct ncbigene:79602
PRKAA1 GeneProduct ncbigene:5562
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PRKAG3 GeneProduct ncbigene:53632
PRKAG2 GeneProduct ncbigene:51422
CDC42 GeneProduct ncbigene:998
RAC1 GeneProduct ncbigene:5879
JNK2 GeneProduct ncbigene:5601
CXCL8 GeneProduct ncbigene:3576
TGFB1 GeneProduct ncbigene:7040
CASP3 GeneProduct ncbigene:836
CASP7 GeneProduct ncbigene:840
NDUFV1 GeneProduct ncbigene:4723
NDUFV2 GeneProduct ncbigene:4729
NDUFV3 GeneProduct ncbigene:4731
NDUFA1 GeneProduct ncbigene:4694
NDUFA2 GeneProduct ncbigene:4695
NDUFA3 GeneProduct ncbigene:4696
NDUFA4 GeneProduct ncbigene:4697
NDUFA4L2 GeneProduct ncbigene:56901
NDUFA5 GeneProduct ncbigene:4698
NDUFA6 GeneProduct ncbigene:4700
NDUFA7 GeneProduct ncbigene:4701
NDUFA8 GeneProduct ncbigene:4702
NDUFA9 GeneProduct ncbigene:4704
NDUFA10 GeneProduct ncbigene:4705
NDUFAB1 GeneProduct ncbigene:4706
NDUFA11 GeneProduct ncbigene:126328
NDUFA12 GeneProduct ncbigene:55967
NDUFA13 GeneProduct ncbigene:51079
NDUFB1 GeneProduct ncbigene:4707
NDUFB2 GeneProduct ncbigene:4708
NDUFB3 GeneProduct ncbigene:4709
NDUFB4 GeneProduct ncbigene:4710
NDUFB5 GeneProduct ncbigene:4711
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NDUFB8 GeneProduct ncbigene:4714
NDUFB9 GeneProduct ncbigene:4715
NDUFB10 GeneProduct ncbigene:4716
NDUFB11 GeneProduct ncbigene:54539
NDUFS1 GeneProduct ncbigene:4719
NDUFS2 GeneProduct ncbigene:4720
NDUFS3 GeneProduct ncbigene:4722
NDUFS4 GeneProduct ncbigene:4724
NDUFS5 GeneProduct ncbigene:4725
NDUFS6 GeneProduct ncbigene:4726
NDUFS7 GeneProduct ncbigene:374291
NDUFS8 GeneProduct ncbigene:4728
NDUFC1 GeneProduct ncbigene:4717
NDUFC2 GeneProduct ncbigene:4718
NDUFC2-KCTD14 GeneProduct ncbigene:100532726
SDHA GeneProduct ncbigene:6389
SDHB GeneProduct ncbigene:6390
SDHC GeneProduct ncbigene:6391
SDHD GeneProduct ncbigene:6392
UQCRFS1 GeneProduct ncbigene:7386
CYTB GeneProduct ncbigene:4519
CYC1 GeneProduct ncbigene:1537
UQCRC1 GeneProduct ncbigene:7384
UQCRC2 GeneProduct ncbigene:7385
UQCRH GeneProduct ncbigene:7388
UQCRHL GeneProduct ncbigene:440567
UQCRB GeneProduct ncbigene:7381
UQCRQ GeneProduct ncbigene:27089
UQCR10 GeneProduct ncbigene:29796
UQCR11 GeneProduct ncbigene:10975
COX3 GeneProduct ncbigene:4514
COX1 GeneProduct ncbigene:4512
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COX6C GeneProduct ncbigene:1345
COX7A1 GeneProduct ncbigene:1346
COX7A2 GeneProduct ncbigene:1347
COX7A2L GeneProduct ncbigene:9167
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COX7B2 GeneProduct ncbigene:170712
COX7C GeneProduct ncbigene:1350
COX8C GeneProduct ncbigene:341947
COX8A GeneProduct ncbigene:1351
TRAF2 GeneProduct ncbigene:7186
oxysterols Metabolite chebi:53030
Oxidative Phosphorylation Pathway wikipathways:WP623
ROS Metabolite chebi:26523
SREBF1 GeneProduct ncbigene:6720
IRS1 GeneProduct ncbigene:3667
CYCS GeneProduct ncbigene:54205
TNF GeneProduct ncbigene:7124
FXR GeneProduct ncbigene:9971
EIF2AK3 GeneProduct ncbigene:9451
BAK1 GeneProduct ncbigene:578
XBP1 GeneProduct ncbigene:7494
ATF4 GeneProduct ncbigene:468
CEBPA GeneProduct ncbigene:1050
NR1H3 GeneProduct ncbigene:10062
PKLR GeneProduct ncbigene:5313
INS GeneProduct ncbigene:3630
mir21 Rna ncbigene:406991
BAX GeneProduct ncbigene:581
DDIT3 GeneProduct ncbigene:1649
IL6R GeneProduct ncbigene:3570
Fatty Acid Biosynthesis Pathway wikipathways:WP357
Lipogenic Enzymes GeneProduct None
FASLG GeneProduct ncbigene:356
Insulin Signaling Pathway wikipathways:WP481
Apoptosis Pathway wikipathways:WP254
LEPR GeneProduct ncbigene:3953
LEP GeneProduct ncbigene:3952
CxI GeneProduct None
MAP3K5 GeneProduct ncbigene:4217
CASP8 GeneProduct ncbigene:841
TNF Signaling Pathway wikipathways:WP231
EIF2S1 GeneProduct ncbigene:1965
ERN1 GeneProduct ncbigene:2081
selonsertib Metabolite wikidata:Q27088777
INSR GeneProduct ncbigene:3643
PPAR Signaling Pathway wikipathways:WP3942
D-glucose Metabolite chebi:42758
BID GeneProduct ncbigene:637
IKBKB GeneProduct ncbigene:3551
fatty acids Metabolite chebi:35366
FAS GeneProduct ncbigene:355
PPARA GeneProduct ncbigene:5465
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MAP3K11 GeneProduct ncbigene:4296
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PI3K-AKT Signaling Pathway wikipathways:WP3844
SOCS3 GeneProduct ncbigene:9021
ADIPOQ GeneProduct ncbigene:9370
IL6 GeneProduct ncbigene:3569
IL6 GeneProduct ncbigene:3569
CxII GeneProduct None
CxIII GeneProduct None
CxIV GeneProduct None
IL1A GeneProduct ncbigene:3552
TNF GeneProduct ncbigene:7124
TNF GeneProduct ncbigene:7124
FASLG GeneProduct ncbigene:356
IL1B GeneProduct ncbigene:3553
BIM GeneProduct ncbigene:10018
TCA Cycle Pathway wikipathways:WP78
CCL2 GeneProduct ncbigene:6347
VCAM1 GeneProduct ncbigene:7412
SMAD7 GeneProduct ncbigene:4092

References

  1. Feldstein AE, Canbay A, Angulo P, Taniai M, Burgart LJ, Lindor KD, et al. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology. 2003 Aug;125(2):437–43. PubMed Europe PMC Scholia
  2. Larter CZ, Farrell GC. Insulin resistance, adiponectin, cytokines in NASH: Which is the best target to treat? J Hepatol. 2006 Feb;44(2):253–61. 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 Apr 1;44(7):1259–72. PubMed Europe PMC Scholia
  4. Malaguarnera M, Di Rosa M, Nicoletti F, Malaguarnera L. Molecular mechanisms involved in NAFLD progression. J Mol Med (Berl). 2009 Jul;87(7):679–95. PubMed Europe PMC Scholia
  5. Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010 Mar 19;140(6):900–17. PubMed Europe PMC Scholia
  6. Malhi H, Kaufman RJ. Endoplasmic reticulum stress in liver disease. J Hepatol. 2011 Apr;54(4):795–809. PubMed Europe PMC Scholia
  7. Farrell GC, van Rooyen D, Gan L, Chitturi S. NASH is an Inflammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications. Gut Liver. 2012 Apr;6(2):149–71. PubMed Europe PMC Scholia
  8. 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 Aug;143(2):307–20. PubMed Europe PMC Scholia
  9. Dattaroy D, Pourhoseini S, Das S, Alhasson F, Seth RK, Nagarkatti M, et al. 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 Feb 15;308(4):G298-312. PubMed Europe PMC Scholia
  10. Loomba R, Lawitz E, Mantry PS, Jayakumar S, Caldwell SH, Arnold H, et al. The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial. Hepatology. 2018 Feb;67(2):549–59. PubMed Europe PMC Scholia
  11. Armstrong LE, Guo GL. Role of FXR in Liver Inflammation during Nonalcoholic Steatohepatitis. Curr Pharmacol Rep. 2017 Apr;3(2):92–100. PubMed Europe PMC Scholia