Aop:61

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Status

This is a legacy representation of this AOP. Please see the current version here:

https://aopwiki.org/aops/61


AOP Title

NFE2L2/FXR activation leading to hepatic steatosis
Short name: NRF2/FXR to steatosis

Authors

Michelle Angrish, Brian Chorley, U.S. EPA

Status

Please follow the link to snapshots page to view and create Snapshots of this AOP.

OECD Project 1.29: A catalog of putative AOPs that will enhance the utility of US EPA Toxcast high throughput screening data for hazard identification

Under development: Do not distribute or cite.

This AOP page was last modified on 12/11/2016.

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Abstract

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Summary of the AOP

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Molecular Initiating Event

Molecular Initiating Event Support for Essentiality
NRF2, Activation
NR1H4, Activation

Key Events

Event Support for Essentiality
SHP, Activation
PPARα, Activation
DHB4/HSD17B4, Decreased
Mitochondrial fatty acid beta-oxidation, Inhibition
LXR alpha, Activation
SREBP1c, Inhibition
MTTP, Activation
ApoB100, Increased
Triglyceride, Increased
De Novo FA synthesis, Decreased

Adverse Outcome

Adverse Outcome
Liver Steatosis, Increased

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
NRF2, Activation Directly Leads to NR1H4, Activation
NR1H4, Activation Directly Leads to SHP, Activation
NR1H4, Activation Directly Leads to PPARα, Activation
PPARα, Activation Directly Leads to LXR alpha, Activation
LXR alpha, Activation Directly Leads to De Novo FA synthesis, Increased
De Novo FA synthesis, Increased Indirectly Leads to Liver Steatosis, Increased
DHB4/HSD17B4, Decreased Directly Leads to Mitochondrial fatty acid beta-oxidation, Inhibition
Mitochondrial fatty acid beta-oxidation, Inhibition Directly Leads to Liver Steatosis, Increased
SHP, Activation Directly Leads to SREBP1c, Inhibition

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Life Stage Applicability

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Taxonomic Applicability

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Sex Applicability

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Overall Assessment of the AOP

Domain of Applicability

Life Stage Applicability, Taxonomic Applicability, Sex Applicability
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Essentiality of the Key Events

Molecular Initiating Event Summary, Key Event Summary
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Weight of Evidence Summary

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Quantitative Considerations

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Considerations for Potential Applications of the AOP (optional)

References