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Aop: 57

AOP Title

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AhR activation leading to hepatic steatosis

Short name:

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AhR activation to steatosis

Graphical Representation

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Click to download graphical representation template

Authors

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Michelle Angrish

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: Contributions and Comments Welcome 1.29 Under Development

This AOP was last modified on February 07, 2020 14:15

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Revision dates for related pages

Page Revision Date/Time
Activation, AhR March 22, 2018 14:00
Suppression, VLDL secretion September 16, 2017 10:15
Inhibition, Mitochondrial fatty acid beta-oxidation September 16, 2017 10:15
Accumulation, Fatty acid September 16, 2017 10:14
Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway) December 03, 2016 16:37
Accumulation, Triglyceride September 16, 2017 10:14
Accumulation, Liver lipid December 03, 2016 16:37
Up Regulation, CD36 September 16, 2017 10:14
Increased, FA Influx September 16, 2017 10:15
Up Regulation, LDLR (low density lipoprotein receptor) September 16, 2017 10:15
Increased, LDL uptake September 16, 2017 10:15
Up Regulation, CYP1A1 September 16, 2017 10:15
Up Regulation, SCD-1 September 16, 2017 10:15
Suppression, VLDL secretion leads to Accumulation, Liver lipid December 03, 2016 16:37
Activation, AhR leads to Inhibition, Mitochondrial fatty acid beta-oxidation December 03, 2016 16:37
Accumulation, Triglyceride leads to Accumulation, Liver lipid December 03, 2016 16:37
Inhibition, Mitochondrial fatty acid beta-oxidation leads to Accumulation, Fatty acid December 03, 2016 16:37
Activation, AhR leads to Up Regulation, CD36 December 03, 2016 16:37
Activation, AhR leads to Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway) December 03, 2016 16:37
Up Regulation, CD36 leads to Increased, FA Influx December 03, 2016 16:37
Accumulation, Fatty acid leads to Accumulation, Liver lipid December 03, 2016 16:37
Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway) leads to Accumulation, Fatty acid December 03, 2016 16:37
Increased, FA Influx leads to Accumulation, Fatty acid December 03, 2016 16:37
Activation, AhR leads to Up Regulation, LDLR (low density lipoprotein receptor) December 03, 2016 16:37
Up Regulation, LDLR (low density lipoprotein receptor) leads to Increased, LDL uptake December 03, 2016 16:37
Increased, LDL uptake leads to Accumulation, Fatty acid December 03, 2016 16:37
Activation, AhR leads to Suppression, VLDL secretion December 03, 2016 16:37
Activation, AhR leads to Up Regulation, CYP1A1 December 03, 2016 16:37
Activation, AhR leads to Up Regulation, SCD-1 August 31, 2017 09:20
Up Regulation, SCD-1 leads to Accumulation, Triglyceride August 31, 2017 09:20

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 18 Activation, AhR Activation, AhR
2 KE 450 Suppression, VLDL secretion Suppression, VLDL secretion
3 KE 451 Inhibition, Mitochondrial fatty acid beta-oxidation Inhibition, Mitochondrial fatty acid beta-oxidation
4 KE 327 Accumulation, Fatty acid Accumulation, Fatty acid
5 KE 216 Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway) Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway)
6 KE 291 Accumulation, Triglyceride Accumulation, Triglyceride
7 KE 54 Up Regulation, CD36 Up Regulation, CD36
8 KE 465 Increased, FA Influx Increased, FA Influx
9 KE 466 Up Regulation, LDLR (low density lipoprotein receptor) Up Regulation, LDLR (low density lipoprotein receptor)
10 KE 467 Increased, LDL uptake Increased, LDL uptake
11 KE 80 Up Regulation, CYP1A1 Up Regulation, CYP1A1
12 KE 462 Up Regulation, SCD-1 Up Regulation, SCD-1
13 AO 455 Accumulation, Liver lipid Accumulation, Liver lipid

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Suppression, VLDL secretion leads to Accumulation, Liver lipid adjacent High High
Accumulation, Triglyceride leads to Accumulation, Liver lipid adjacent High High
Inhibition, Mitochondrial fatty acid beta-oxidation leads to Accumulation, Fatty acid adjacent High High
Activation, AhR leads to Up Regulation, CD36 adjacent High High
Activation, AhR leads to Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway) adjacent High High
Up Regulation, CD36 leads to Increased, FA Influx adjacent High
Accumulation, Fatty acid leads to Accumulation, Liver lipid adjacent High High
Increased, FA Influx leads to Accumulation, Fatty acid adjacent
Activation, AhR leads to Up Regulation, LDLR (low density lipoprotein receptor) adjacent High
Up Regulation, LDLR (low density lipoprotein receptor) leads to Increased, LDL uptake adjacent
Increased, LDL uptake leads to Accumulation, Fatty acid adjacent
Activation, AhR leads to Up Regulation, CYP1A1 adjacent High
Activation, AhR leads to Up Regulation, SCD-1 adjacent Moderate
Up Regulation, SCD-1 leads to Accumulation, Triglyceride adjacent High
Activation, AhR leads to Inhibition, Mitochondrial fatty acid beta-oxidation non-adjacent Moderate Moderate
Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway) leads to Accumulation, Fatty acid non-adjacent
Activation, AhR leads to Suppression, VLDL secretion 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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Term Scientific Term Evidence Link
mouse Mus musculus High 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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