To the extent possible under law, AOP-Wiki has waived all copyright and related or neighboring rights to KE:459
Key Event Title
Increased, Liver Steatosis
Key Event Components
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|NR1I3 suppression to steatosis||AdverseOutcome||Allie Always (send email)||Under Development: Contributions and Comments Welcome|
|PXR activation to steatosis||AdverseOutcome||Cataia Ives (send email)||Under Development: Contributions and Comments Welcome|
|NRF2/FXR to steatosis||AdverseOutcome||Brendan Ferreri-Hanberry (send email)||Under Development: Contributions and Comments Welcome|
|AKT2 activation to steatosis||AdverseOutcome||Arthur Author (send email)||Under Development: Contributions and Comments Welcome|
|Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis||AdverseOutcome||Evgeniia Kazymova (send email)||Under Development: Contributions and Comments Welcome|
|Inhibition fatty acid beta oxidation leading to nonalcoholic steatohepatisis (NASH)||KeyEvent||Arthur Author (send email)||Open for adoption|
|Inhibition of N-linked glycosylation leads to liver injury||KeyEvent||Arthur Author (send email)||Under development: Not open for comment. Do not cite|
|GR activation leading to hepatic steatosis||AdverseOutcome||Agnes Aggy (send email)||Under Development: Contributions and Comments Welcome|
|All life stages||High|
Key Event Description
Biological state: liver steatosis is the inappropriate storage of fat in hepatocytes.
Biological compartment: steatosis is generally an organ-level diagnosis; however, the pathology occurs within the hepatocytes.
Role in biology: steatosis is an adverse endpoint.
Description from EU-ToxRisk:
Activation of stellate cells results in collagen accumulation and change in extracellular matrix composition in the liver causing fibrosis. (Landesmann, 2016)(Koo et al 2016)
How It Is Measured or Detected
Steatosis is measured by lipidomics approaches that measure lipid levels, or by histology.
Domain of Applicability
Steatosis is the result of perturbations in well-known metabolic pathways that are well-studied and well-known in many taxa.
Regulatory Significance of the Adverse Outcome
Steatosis is a regulatory endpoint and has been used as an endpoint in many US EPA assessments, including IRIS assessments.
Landesmann, B. (2016). Adverse Outcome Pathway on Protein Alkylation Leading to Liver Fibrosis, (2).
Koo, J. H., Lee, H. J., Kim, W., & Kim, S. G. (2016). Endoplasmic Reticulum Stress in Hepatic Stellate Cells Promotes Liver Fibrosis via PERK-Mediated Degradation of HNRNPA1 and Up-regulation of SMAD2. Gastroenterology, 150(1), 181–193.e8. https://doi.org/10.1053/j.gastro.2015.09.039