API

Aop: 57

AOP Title

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AhR activation leading to hepatic steatosis

Short name:

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AhR activation to steatosis

Authors

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Michelle Angrish

Point of Contact

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Michelle Angrish

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 Do not cite Under Development 1.29 Included in OECD Work Plan


This AOP was last modified on February 26, 2017 20:09

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Revision dates for related pages

Page Revision Date/Time
Activation, AhR June 12, 2017 15:14
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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Stressors

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Molecular Initiating Event

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Title Short name
Activation, AhR Activation, AhR

Key Events

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Title Short name
Suppression, VLDL secretion Suppression, VLDL secretion
Inhibition, Mitochondrial fatty acid beta-oxidation Inhibition, Mitochondrial fatty acid beta-oxidation
Accumulation, Fatty acid Accumulation, Fatty acid
Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway) Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway)
Accumulation, Triglyceride Accumulation, Triglyceride
Up Regulation, CD36 Up Regulation, CD36
Increased, FA Influx Increased, FA Influx
Up Regulation, LDLR (low density lipoprotein receptor) Up Regulation, LDLR (low density lipoprotein receptor)
Increased, LDL uptake Increased, LDL uptake
Up Regulation, CYP1A1 Up Regulation, CYP1A1
Up Regulation, SCD-1 Up Regulation, SCD-1

Adverse Outcome

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Title Short name
Accumulation, Liver lipid Accumulation, Liver lipid

Relationships Between Two Key Events (Including MIEs and AOs)

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Title Directness Evidence Quantitative Understanding
Suppression, VLDL secretion leads to Accumulation, Liver lipid Directly leads to Strong Strong
Activation, AhR leads to Inhibition, Mitochondrial fatty acid beta-oxidation Indirectly leads to Moderate Moderate
Accumulation, Triglyceride leads to Accumulation, Liver lipid Directly leads to Strong Strong
Inhibition, Mitochondrial fatty acid beta-oxidation leads to Accumulation, Fatty acid Directly leads to Strong Strong
Activation, AhR leads to Up Regulation, CD36 Directly leads to Strong Strong
Activation, AhR leads to Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway) Directly leads to Strong Strong
Up Regulation, CD36 leads to Increased, FA Influx Directly leads to Strong
Accumulation, Fatty acid leads to Accumulation, Liver lipid Directly leads to Strong Strong
Decreased, PCK1 expression (control point for glycolysis/gluconeogenesis pathway) leads to Accumulation, Fatty acid Indirectly leads to
Increased, FA Influx leads to Accumulation, Fatty acid Directly leads to
Activation, AhR leads to Up Regulation, LDLR (low density lipoprotein receptor) Directly leads to Strong
Up Regulation, LDLR (low density lipoprotein receptor) leads to Increased, LDL uptake Directly leads to
Increased, LDL uptake leads to Accumulation, Fatty acid Directly leads to
Activation, AhR leads to Suppression, VLDL secretion Indirectly leads to
Activation, AhR leads to Up Regulation, CYP1A1 Directly leads to Strong
Activation, AhR leads to Up Regulation, SCD-1 Directly leads to Moderate
Up Regulation, SCD-1 leads to Accumulation, Triglyceride Directly leads to Strong

Network View

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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 Strong NCBI

Sex Applicability

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Graphical Representation

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Click to download graphical representation template

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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Weight of Evidence Summary

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Quantitative Considerations

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Considerations for Potential Applications of the AOP (optional)

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References

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