Aop:57

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Status

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

https://aopwiki.org/aops/57


AOP Title

AhR activation leading to hepatic steatosis
Short name: AhR activation to steatosis

Authors

Michelle Angrish

Status

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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
AHR, Activation Strong

Key Events

Event Support for Essentiality
VLDL secretion, Suppression Strong
Mitochondrial fatty acid beta-oxidation, Inhibition Strong
Fatty acid, Accumulation Strong
PCK1 expression (control point for glycolysis/gluconeogenesis pathway), Decreased Strong
Triglyceride, Accumulation Strong
CD36, Up Regulation Strong
SCD-1, Increased Moderate
FA Influx, Increased Strong
LDLR (low density lipoprotein receptor), Up Regulation Strong
LDL uptake, Increased
CYP1A1, Up Regulation Strong

Adverse Outcome

Adverse Outcome
Liver lipid, Accumulation

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
VLDL secretion, Suppression Directly Leads to Liver lipid, Accumulation Strong Strong
AHR, Activation Indirectly Leads to Mitochondrial fatty acid beta-oxidation, Inhibition Moderate Moderate
Triglyceride, Accumulation Directly Leads to Liver lipid, Accumulation Strong Strong
Mitochondrial fatty acid beta-oxidation, Inhibition Directly Leads to Fatty acid, Accumulation Strong Strong
AHR, Activation Directly Leads to CD36, Up Regulation Strong Strong
AHR, Activation Directly Leads to SCD-1, Increased Moderate
AHR, Activation Directly Leads to PCK1 expression (control point for glycolysis/gluconeogenesis pathway), Decreased Strong Strong
SCD-1, Increased Directly Leads to Triglyceride, Accumulation Strong
CD36, Up Regulation Directly Leads to FA Influx, Increased Strong
Fatty acid, Accumulation Directly Leads to Liver lipid, Accumulation Strong Strong
PCK1 expression (control point for glycolysis/gluconeogenesis pathway), Decreased Indirectly Leads to Fatty acid, Accumulation
FA Influx, Increased Directly Leads to Fatty acid, Accumulation
AHR, Activation Directly Leads to LDLR (low density lipoprotein receptor), Up Regulation Strong
LDLR (low density lipoprotein receptor), Up Regulation Directly Leads to LDL uptake, Increased
LDL uptake, Increased Directly Leads to Fatty acid, Accumulation
AHR, Activation Indirectly Leads to VLDL secretion, Suppression
AHR, Activation Directly Leads to CYP1A1, Up Regulation Strong

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Life Stage Applicability

Life Stage Evidence Links

Taxonomic Applicability

Name Scientific Name Evidence Links
mouse Mus musculus Strong NCBI

Sex Applicability

Sex Evidence Links

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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

Summary Table
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Quantitative Considerations

Summary Table
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Considerations for Potential Applications of the AOP (optional)

References