Difference between revisions of "Aop:58"

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__NOTOC__
 
__NOTOC__
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= Status =
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<span style="color:#FF0000">
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This is a legacy representation of this AOP. Please see the current version here:
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[//{{SERVERNAME}}/aops/58 https://{{SERVERNAME}}/aops/58]
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</span>
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== AOP Title ==
 
== AOP Title ==
 
<div id='longTitle' class='Title'> NR1I3 (CAR) suppression leading to hepatic steatosis </div>
 
<div id='longTitle' class='Title'> NR1I3 (CAR) suppression leading to hepatic steatosis </div>
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== Status ==
 
== Status ==
'''Under development:  Do not distribute or cite.'''
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'''Please follow the link to [//{{SERVERNAME}}/aops/{{PAGENAMEE}}/snapshots snapshots page] to view and create Snapshots of this AOP.'''
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[http://www.oecd.org/env/ehs/testing/listsofprojectsontheaopdevelopmentprogrammeworkplan.htm 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]
 
[http://www.oecd.org/env/ehs/testing/listsofprojectsontheaopdevelopmentprogrammeworkplan.htm 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]
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'''Under development:  Do not distribute or cite.'''
  
 
This AOP page was last modified on {{REVISIONMONTH1}}/{{REVISIONDAY}}/{{REVISIONYEAR}}.
 
This AOP page was last modified on {{REVISIONMONTH1}}/{{REVISIONDAY}}/{{REVISIONYEAR}}.
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== Summary of the AOP ==
 
== Summary of the AOP ==
 
[[Category:Adverse Outcome Pathway]]
 
[[Category:Adverse Outcome Pathway]]
Please follow link to [//{{SERVERNAME}}/aopportal/aops/{{PAGENAMEE}} widget page] to edit this section.
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Please follow link to [//{{SERVERNAME}}/aops/{{PAGENAMEE}} widget page] to edit this section.
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<span style="color:#FF0000">'''If you manually enter text in this section, it will get automatically altered or deleted in subsequent edits using the widgets.'''</span>
  
 
=== Molecular Initiating Event ===
 
=== Molecular Initiating Event ===
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|-
 
|-
  
|[[Event:228|PPAR gamma, Activation]]||
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|[[Event:228|PPARγ, Activation]]||
  
 
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|[[Event:327|Fatty acid, Accumulation]]||
 
|[[Event:327|Fatty acid, Accumulation]]||
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|[[Event:470|Acetyl-CoA carboxylase-1 (ACC-1), Up Regulation]]||[[Aop:58#Essentiality of the Key Events|Strong]]
  
 
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|[[Event:456|Constitutive androstane receptor, NR1l3, Suppression]]||[[Relationship:477|Directly Leads to]]||[[Event:228|PPAR gamma, Activation]]||[[Relationship:477#Weight of Evidence|Strong]]||[[Relationship:477#Quantitative Understanding of the Linkage|Strong]]
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|[[Event:456|Constitutive androstane receptor, NR1l3, Suppression]]||[[Relationship:477|Directly Leads to]]||[[Event:228|PPARγ, Activation]]||[[Relationship:477#Weight of Evidence|Strong]]||[[Relationship:477#Quantitative Understanding of the Linkage|Strong]]
  
 
|-
 
|-
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|[[Event:66|ChREBP, Activation]]||[[Relationship:483|Directly Leads to]]||[[Event:458|De Novo FA synthesis, Increased]]||[[Relationship:483#Weight of Evidence|Strong]]||[[Relationship:483#Quantitative Understanding of the Linkage|Strong]]
 
|[[Event:66|ChREBP, Activation]]||[[Relationship:483|Directly Leads to]]||[[Event:458|De Novo FA synthesis, Increased]]||[[Relationship:483#Weight of Evidence|Strong]]||[[Relationship:483#Quantitative Understanding of the Linkage|Strong]]
 
|-
 
 
|[[Event:460|Fatty acid uptake, Increased]]||[[Relationship:485|Directly Leads to]]||[[Event:454|Triglyceride formation, Increased]]||[[Relationship:485#Weight of Evidence|Strong]]||[[Relationship:485#Quantitative Understanding of the Linkage|Strong]]
 
  
 
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|[[Event:228|PPAR gamma, Activation]]||[[Relationship:487|Directly Leads to]]||[[Event:457|SREBF1, Activation]]||[[Relationship:487#Weight of Evidence|Moderate]]||[[Relationship:487#Quantitative Understanding of the Linkage|Moderate]]
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|[[Event:228|PPARγ, Activation]]||[[Relationship:487|Directly Leads to]]||[[Event:457|SREBF1, Activation]]||[[Relationship:487#Weight of Evidence|Moderate]]||[[Relationship:487#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:228|PPARγ, 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:458|De Novo FA synthesis, Increased]]||[[Relationship:512|Directly Leads to]]||[[Event:327|Fatty acid, Accumulation]]||[[Relationship:512#Weight of Evidence|Strong]]||
 
|[[Event:458|De Novo FA synthesis, Increased]]||[[Relationship:512|Directly Leads to]]||[[Event:327|Fatty acid, Accumulation]]||[[Relationship:512#Weight of Evidence|Strong]]||
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|-
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|[[Event:460|Fatty acid uptake, Increased]]||[[Relationship:513|Directly Leads to]]||[[Event:327|Fatty acid, Accumulation]]||[[Relationship:513#Weight of Evidence|Strong]]||
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|-
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|[[Event:327|Fatty acid, Accumulation]]||[[Relationship:514|Directly Leads to]]||[[Event:454|Triglyceride formation, Increased]]||||
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|-
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|[[Event:327|Fatty acid, Accumulation]]||[[Relationship:515|Directly Leads to]]||[[Event:459|Liver Steatosis, Increased]]||||
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|-
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|[[Event:451|Mitochondrial fatty acid beta-oxidation, Inhibition]]||[[Relationship:475|Directly Leads to]]||[[Event:327|Fatty acid, Accumulation]]||||
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|-
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|[[Event:167|LXR, Activation]]||[[Relationship:516|Directly Leads to]]||[[Event:470|Acetyl-CoA carboxylase-1 (ACC-1), Up Regulation]]||[[Relationship:516#Weight of Evidence|Strong]]||
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|-
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|[[Event:470|Acetyl-CoA carboxylase-1 (ACC-1), Up Regulation]]||[[Relationship:517|Indirectly Leads to]]||[[Event:458|De Novo FA synthesis, Increased]]||[[Relationship:517#Weight of Evidence|Strong]]||
  
 
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| human, mouse, rat || || [[Aop:58#Domain of Applicability|Moderate]] || [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id= NCBI]
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|human, mouse, rat||||[[Aop:58#Domain of Applicability|Moderate]]||
  
 
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Latest revision as of 19:06, 11 December 2016

Status

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

https://aopwiki.org/aops/58


AOP Title

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

Authors

Michelle Angrish, Brian Chorley

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

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
PPAR alpha, Inhibition
LXR, Activation
PPARγ, Activation

Key Events

Event Support for Essentiality
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
Mitochondrial fatty acid beta-oxidation, Inhibition
Fatty acid, Accumulation
Acetyl-CoA carboxylase-1 (ACC-1), 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 PPARγ, Activation 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
Triglyceride formation, Increased Directly Leads to Liver Steatosis, Increased Strong Strong
PPARγ, Activation Directly Leads to SREBF1, Activation Moderate Moderate
PPARγ, Activation Directly Leads to Fatty acid uptake, Increased Moderate Moderate
SREBF1, Activation Directly Leads to SCD-1, Up Regulation Strong Strong
LXR, Activation Directly Leads to CD36, Up Regulation Strong Strong
LXR, Activation Directly Leads to FAS, Up Regulation Strong Strong
LXR, Activation Directly Leads to SCD-1, Up Regulation Strong Strong
FAS, Up Regulation Directly Leads to De Novo FA synthesis, Increased Strong Strong
SCD-1, Up Regulation Directly Leads to Triglyceride formation, Increased Strong Strong
CD36, Up Regulation Directly Leads to Fatty acid uptake, Increased Strong Strong
LXR, Activation Indirectly Leads to PPAR alpha, Inhibition
PPAR alpha, Inhibition Directly Leads to Mitochondrial fatty acid beta-oxidation, Inhibition Strong
De Novo FA synthesis, Increased Directly Leads to Fatty acid, Accumulation Strong
Fatty acid uptake, Increased Directly Leads to Fatty acid, Accumulation Strong
Fatty acid, Accumulation Directly Leads to Triglyceride formation, Increased
Fatty acid, Accumulation Directly Leads to Liver Steatosis, Increased
Mitochondrial fatty acid beta-oxidation, Inhibition Directly Leads to Fatty acid, Accumulation
LXR, Activation Directly Leads to Acetyl-CoA carboxylase-1 (ACC-1), Up Regulation Strong
Acetyl-CoA carboxylase-1 (ACC-1), Up Regulation Indirectly Leads to De Novo FA synthesis, Increased Strong

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Life Stage Applicability

Life Stage Evidence Links

Taxonomic Applicability

Name Scientific Name Evidence Links
human, mouse, rat Moderate

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
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Weight of Evidence Summary

Summary Table
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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