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Aop: 61

AOP Title

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NFE2L2/FXR activation leading to hepatic steatosis

Short name:

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NRF2/FXR to steatosis

Graphical Representation

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Click to download graphical representation template

Authors

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Michelle Angrish, Brian Chorley, U.S. EPA

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 Do not cite 1.29 Under Development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
Activation, NRF2 September 16, 2017 10:15
Activation, NR1H4 September 16, 2017 10:15
Activation, SHP September 16, 2017 10:15
Activation, PPARα September 16, 2017 10:14
Decreased, DHB4/HSD17B4 September 16, 2017 10:15
Inhibition, Mitochondrial fatty acid beta-oxidation September 16, 2017 10:15
Activation, LXR alpha September 16, 2017 10:15
Increased, Liver Steatosis November 27, 2017 12:48
Inhibition, SREBP1c September 16, 2017 10:15
Activation, MTTP September 16, 2017 10:15
Increased, ApoB100 September 16, 2017 10:15
Increased, Triglyceride September 16, 2017 10:15
Increased, De Novo FA synthesis September 16, 2017 10:15
Activation, NRF2 leads to Activation, NR1H4 December 03, 2016 16:37
Activation, NR1H4 leads to Activation, SHP December 03, 2016 16:37
Activation, NR1H4 leads to Activation, PPARα December 03, 2016 16:37
Activation, PPARα leads to Activation, LXR alpha December 03, 2016 16:37
Decreased, DHB4/HSD17B4 leads to Inhibition, Mitochondrial fatty acid beta-oxidation December 03, 2016 16:37
Inhibition, Mitochondrial fatty acid beta-oxidation leads to Increased, Liver Steatosis December 03, 2016 16:37
Activation, SHP leads to Inhibition, SREBP1c December 03, 2016 16:38
Activation, LXR alpha leads to Increased, De Novo FA synthesis July 18, 2017 16:56
Increased, De Novo FA synthesis leads to Increased, Liver Steatosis July 18, 2017 16:57

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 478 Activation, NRF2 Activation, NRF2
2 MIE 479 Activation, NR1H4 Activation, NR1H4
3 KE 480 Activation, SHP Activation, SHP
4 KE 227 Activation, PPARα Activation, PPARα
5 KE 482 Decreased, DHB4/HSD17B4 Decreased, DHB4/HSD17B4
6 KE 451 Inhibition, Mitochondrial fatty acid beta-oxidation Inhibition, Mitochondrial fatty acid beta-oxidation
7 KE 483 Activation, LXR alpha Activation, LXR alpha
8 KE 878 Inhibition, SREBP1c Inhibition, SREBP1c
9 KE 879 Activation, MTTP Activation, MTTP
10 KE 880 Increased, ApoB100 Increased, ApoB100
11 KE 881 Increased, Triglyceride Increased, Triglyceride
12 KE 458 Increased, De Novo FA synthesis Increased, De Novo FA synthesis
13 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
Activation, NRF2 leads to Activation, NR1H4 adjacent
Activation, NR1H4 leads to Activation, SHP adjacent
Activation, NR1H4 leads to Activation, PPARα adjacent
Activation, PPARα leads to Activation, LXR alpha adjacent
Decreased, DHB4/HSD17B4 leads to Inhibition, Mitochondrial fatty acid beta-oxidation adjacent
Inhibition, Mitochondrial fatty acid beta-oxidation leads to Increased, Liver Steatosis adjacent
Activation, SHP leads to Inhibition, SREBP1c adjacent
Activation, LXR alpha leads to Increased, De Novo FA synthesis adjacent
Increased, De Novo FA synthesis leads to Increased, Liver Steatosis non-adjacent

Network View

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Stressors

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Life Stage Applicability

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Taxonomic Applicability

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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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