API

Aop: 58

AOP Title

?


NR1I3 (CAR) suppression leading to hepatic steatosis

Short name:

?

NR1I3 suppression to steatosis

Authors

?


Michelle Angrish, Brian Chorley

Point of Contact

?


Michelle Angrish

Contributors

?


  • Brian Chorley
  • Michelle Angrish
  • Lyle Burgoon

Status

?

Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite Under Development 1.29 Included in OECD Work Plan


This AOP was last modified on February 26, 2017 20:10

?

Revision dates for related pages

Page Revision Date/Time
Suppression, Constitutive androstane receptor, NR1l3 September 16, 2017 10:15
Activation, SREBF1 September 16, 2017 10:15
Activation, ChREBP September 16, 2017 10:14
Increased, De Novo FA synthesis September 16, 2017 10:15
Increased, Liver Steatosis September 16, 2017 10:14
Increased, Triglyceride formation September 16, 2017 10:15
Up Regulation, CD36 September 16, 2017 10:14
Up Regulation, SCD-1 September 16, 2017 10:15
Up Regulation, FAS September 16, 2017 10:15
Inhibition, PPAR alpha September 16, 2017 10:15
Activation, LXR September 16, 2017 10:14
peroxisome proliferator activated receptor promoter demethylation September 16, 2017 10:14
Inhibition, Mitochondrial fatty acid beta-oxidation September 16, 2017 10:15
Accumulation, Fatty acid September 16, 2017 10:14
Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1) September 16, 2017 10:15
Increased, FA Influx September 16, 2017 10:15
Suppression, Constitutive androstane receptor, NR1l3 leads to Activation, LXR December 03, 2016 16:37
Suppression, Constitutive androstane receptor, NR1l3 leads to demethylation, PPARg promoter December 03, 2016 16:37
Activation, LXR leads to Activation, SREBF1 December 03, 2016 16:37
Activation, LXR leads to Activation, ChREBP December 03, 2016 16:37
Activation, ChREBP leads to Increased, De Novo FA synthesis December 03, 2016 16:37
Increased, Triglyceride formation leads to Increased, Liver Steatosis December 03, 2016 16:37
demethylation, PPARg promoter leads to Activation, SREBF1 December 03, 2016 16:37
Activation, SREBF1 leads to Up Regulation, SCD-1 December 03, 2016 16:37
Activation, LXR leads to Up Regulation, CD36 December 03, 2016 16:37
Activation, LXR leads to Up Regulation, FAS December 03, 2016 16:37
Activation, LXR leads to Up Regulation, SCD-1 December 03, 2016 16:37
Up Regulation, FAS leads to Increased, De Novo FA synthesis December 03, 2016 16:37
Up Regulation, SCD-1 leads to Increased, Triglyceride formation December 03, 2016 16:37
Activation, LXR leads to Inhibition, PPAR alpha December 03, 2016 16:37
Inhibition, PPAR alpha leads to Inhibition, Mitochondrial fatty acid beta-oxidation December 03, 2016 16:37
Increased, De Novo FA synthesis leads to Accumulation, Fatty acid December 03, 2016 16:37
Accumulation, Fatty acid leads to Increased, Triglyceride formation December 03, 2016 16:37
Accumulation, Fatty acid leads to Increased, Liver Steatosis December 03, 2016 16:37
Inhibition, Mitochondrial fatty acid beta-oxidation leads to Accumulation, Fatty acid December 03, 2016 16:37
Activation, LXR leads to Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1) December 03, 2016 16:37
Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1) leads to Increased, De Novo FA synthesis December 03, 2016 16:37
demethylation, PPARg promoter leads to Increased, FA Influx August 31, 2017 10:26
Up Regulation, CD36 leads to Increased, FA Influx December 03, 2016 16:37
Increased, FA Influx leads to Accumulation, Fatty acid December 03, 2016 16:37

Abstract

?



Background (optional)

?



Summary of the AOP

?



Stressors

?


Molecular Initiating Event

?

Title Short name
Suppression, Constitutive androstane receptor, NR1l3 Suppression, Constitutive androstane receptor, NR1l3
Inhibition, PPAR alpha Inhibition, PPAR alpha
Activation, LXR Activation, LXR
peroxisome proliferator activated receptor promoter demethylation demethylation, PPARg promoter

Key Events

?

Title Short name
Activation, SREBF1 Activation, SREBF1
Activation, ChREBP Activation, ChREBP
Increased, De Novo FA synthesis Increased, De Novo FA synthesis
Increased, Triglyceride formation Increased, Triglyceride formation
Up Regulation, CD36 Up Regulation, CD36
Up Regulation, SCD-1 Up Regulation, SCD-1
Up Regulation, FAS Up Regulation, FAS
Inhibition, Mitochondrial fatty acid beta-oxidation Inhibition, Mitochondrial fatty acid beta-oxidation
Accumulation, Fatty acid Accumulation, Fatty acid
Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1) Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1)
Increased, FA Influx Increased, FA Influx

Adverse Outcome

?

Title Short name
Increased, Liver Steatosis Increased, Liver Steatosis

Relationships Between Two Key Events (Including MIEs and AOs)

?

Title Directness Evidence Quantitative Understanding
Suppression, Constitutive androstane receptor, NR1l3 leads to Activation, LXR Directly leads to Strong Strong
Suppression, Constitutive androstane receptor, NR1l3 leads to demethylation, PPARg promoter Directly leads to Strong Strong
Activation, LXR leads to Activation, SREBF1 Directly leads to Strong Strong
Activation, LXR leads to Activation, ChREBP Directly leads to Strong Strong
Activation, ChREBP leads to Increased, De Novo FA synthesis Directly leads to Strong Strong
Increased, Triglyceride formation leads to Increased, Liver Steatosis Directly leads to Strong Strong
demethylation, PPARg promoter leads to Activation, SREBF1 Directly leads to Moderate Moderate
Activation, SREBF1 leads to Up Regulation, SCD-1 Directly leads to Strong Strong
Activation, LXR leads to Up Regulation, CD36 Directly leads to Strong Strong
Activation, LXR leads to Up Regulation, FAS Directly leads to Strong Strong
Activation, LXR leads to Up Regulation, SCD-1 Directly leads to Strong Strong
Up Regulation, FAS leads to Increased, De Novo FA synthesis Directly leads to Strong Strong
Up Regulation, SCD-1 leads to Increased, Triglyceride formation Directly leads to Strong Strong
Activation, LXR leads to Inhibition, PPAR alpha Indirectly leads to
Inhibition, PPAR alpha leads to Inhibition, Mitochondrial fatty acid beta-oxidation Directly leads to Strong
Increased, De Novo FA synthesis leads to Accumulation, Fatty acid Directly leads to Strong
Accumulation, Fatty acid leads to Increased, Triglyceride formation Directly leads to
Accumulation, Fatty acid leads to Increased, Liver Steatosis Directly leads to
Inhibition, Mitochondrial fatty acid beta-oxidation leads to Accumulation, Fatty acid Directly leads to
Activation, LXR leads to Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1) Directly leads to Strong
Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1) leads to Increased, De Novo FA synthesis Indirectly leads to Strong
demethylation, PPARg promoter leads to Increased, FA Influx Directly leads to Moderate Moderate
Up Regulation, CD36 leads to Increased, FA Influx Directly leads to Strong Strong
Increased, FA Influx leads to Accumulation, Fatty acid Directly leads to Strong

Network View

?

 

Life Stage Applicability

?


Taxonomic Applicability

?

Term Scientific Term Evidence Link
human, mouse, rat human, mouse, rat Moderate NCBI

Sex Applicability

?


Graphical Representation

?

Click to download graphical representation template

Overall Assessment of the AOP

?



Domain of Applicability

?


Essentiality of the Key Events

?


Weight of Evidence Summary

?


Quantitative Considerations

?


Considerations for Potential Applications of the AOP (optional)

?



References

?