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Aop: 58

AOP Title

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NR1I3 (CAR) suppression leading to hepatic steatosis

Short name:

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NR1I3 suppression to steatosis

Graphical Representation

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Click to download graphical representation template

Authors

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Michelle Angrish, Brian Chorley

Point of Contact

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Michelle Angrish   (email point of contact)

Contributors

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  • Brian Chorley
  • Michelle Angrish
  • Lyle Burgoon

Status

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 Do not cite 1.29 Under Development


This AOP was last modified on January 27, 2018 15:34

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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 November 27, 2017 12:48
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

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Background (optional)

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Summary of the AOP

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
1 MIE 456 Suppression, Constitutive androstane receptor, NR1l3 Suppression, Constitutive androstane receptor, NR1l3
2 MIE 468 Inhibition, PPAR alpha Inhibition, PPAR alpha
3 MIE 167 Activation, LXR Activation, LXR
4 MIE 228 peroxisome proliferator activated receptor promoter demethylation demethylation, PPARg promoter
5 KE 457 Activation, SREBF1 Activation, SREBF1
6 KE 66 Activation, ChREBP Activation, ChREBP
7 KE 458 Increased, De Novo FA synthesis Increased, De Novo FA synthesis
8 KE 454 Increased, Triglyceride formation Increased, Triglyceride formation
9 KE 54 Up Regulation, CD36 Up Regulation, CD36
10 KE 462 Up Regulation, SCD-1 Up Regulation, SCD-1
11 KE 463 Up Regulation, FAS Up Regulation, FAS
12 KE 451 Inhibition, Mitochondrial fatty acid beta-oxidation Inhibition, Mitochondrial fatty acid beta-oxidation
13 KE 327 Accumulation, Fatty acid Accumulation, Fatty acid
14 KE 470 Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1) Up Regulation, Acetyl-CoA carboxylase-1 (ACC-1)
15 KE 465 Increased, FA Influx Increased, FA Influx
16 AO 459 Increased, Liver Steatosis Increased, Liver Steatosis

Relationships Between Two Key Events
(Including MIEs and AOs)

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

Network View

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Stressors

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Life Stage Applicability

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Taxonomic Applicability

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

Sex Applicability

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Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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