Difference between revisions of "Aop:58"

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|[[Event:228|PPAR gamma, Activation]]||[[Relationship:488|Directly Leads to]]||[[Event:460|Fatty acid uptake, Increased]]||[[Relationship:488#Weight of Evidence|Moderate]]||[[Relationship:488#Quantitative Understanding of the Linkage|Moderate]]
 
|[[Event:228|PPAR gamma, Activation]]||[[Relationship:488|Directly Leads to]]||[[Event:460|Fatty acid uptake, Increased]]||[[Relationship:488#Weight of Evidence|Moderate]]||[[Relationship:488#Quantitative Understanding of the Linkage|Moderate]]
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|[[Event:457|SREBF1, Activation]]||[[Relationship:489|Directly Leads to]]||[[Event:462|SCD-1, Up Regulation]]||[[Relationship:489#Weight of Evidence|Strong]]||[[Relationship:489#Quantitative Understanding of the Linkage|Strong]]
  
 
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Revision as of 19:22, 12 March 2015

AOP Title

NR1I3 (CAR) suppression leading to hepatic steatosis
Short name: NR1I3 suppression to steatosis

Authors

Michelle Angrish, Brian Chorley

Status

Under development: Do not distribute or cite. 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

This AOP page was last modified on 3/12/2015.

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Abstract

Background (optional)

Summary of the AOP

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Molecular Initiating Event

Molecular Initiating Event Support for Essentiality
Constitutive androstane receptor, NR1l3, Suppression Moderate

Key Events

Event Support for Essentiality
LXR, Activation Strong
PPAR gamma, Activation Strong
SREBF1, Activation Moderate
ChREBP, Activation Moderate
De Novo FA synthesis, Increased Strong
Fatty acid uptake, Increased Strong
Triglyceride formation, Increased Moderate
CD36, Up Regulation Strong
SCD-1, Up Regulation Strong
FAS, Up Regulation Strong

Adverse Outcome

Adverse Outcome
Liver Steatosis, Increased

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
Constitutive androstane receptor, NR1l3, Suppression Directly Leads to LXR, Activation Strong Strong
Constitutive androstane receptor, NR1l3, Suppression Directly Leads to PPAR gamma, Activation Strong Strong
LXR, Activation Directly Leads to Fatty acid uptake, Increased Strong Strong
LXR, Activation Directly Leads to SREBF1, Activation Strong Strong
LXR, Activation Directly Leads to ChREBP, Activation Strong Strong
ChREBP, Activation Directly Leads to De Novo FA synthesis, Increased Strong Strong
De Novo FA synthesis, Increased Directly Leads to Triglyceride formation, Increased Strong Strong
Fatty acid uptake, Increased Directly Leads to Triglyceride formation, Increased Strong Strong
Triglyceride formation, Increased Directly Leads to Liver Steatosis, Increased Strong Strong
PPAR gamma, Activation Directly Leads to SREBF1, Activation Moderate Moderate
PPAR gamma, Activation Directly Leads to Fatty acid uptake, Increased Moderate Moderate
SREBF1, Activation Directly Leads to SCD-1, Up Regulation Strong Strong

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Life Stage Applicability

Life Stage Evidence Links

Taxonomic Applicability

Name Scientific Name Evidence Links
human, mouse, rat Moderate NCBI

Sex Applicability

Sex Evidence Links

Graphical Representation

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Overall Assessment of the AOP

Domain of Applicability

Life Stage Applicability, Taxonomic Applicability, Sex Applicability
Elaborate on the domains of applicability listed in the summary section above. Specifically, provide the literature supporting, or excluding, certain domains.

Essentiality of the Key Events

Molecular Initiating Event Summary, Key Event Summary
Provide an overall assessment of the essentiality for the key events in the AOP. Support calls for individual key events can be included in the molecular initiating event, key event, and adverse outcome tables above.

Weight of Evidence Summary

Summary Table
Provide an overall summary of the weight of evidence based on the evaluations of the individual linkages from the Key Event Relationship pages.

Quantitative Considerations

Summary Table
Provide an overall discussion of the quantitative information available for this AOP. Support calls for the individual relationships can be included in the Key Event Relationship table above.

Considerations for Potential Applications of the AOP (optional)

References