This Event is licensed under the Creative Commons BY-SA license. This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.

Event: 233

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Decreased, PPAR-gamma activation

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

Explore in a Third Party Tool

Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Cell term
hepatocyte

Organ term

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
peroxisome proliferator activated receptor signaling pathway	peroxisome proliferator-activated receptor gamma	decreased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
Peroxisomal Fatty Acid Beta-Oxidation Inhibition Leading to Steatosis	MolecularInitiatingEvent	Michelle Angrish (send email)	Under Development: Contributions and Comments Welcome
ROS formation leads to cancer via PPAR pathway	KeyEvent	John Frisch (send email)	Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
human	Homo sapiens	Not Specified	NCBI
mouse	Mus musculus	Not Specified	NCBI
rat	Rattus norvegicus	Not Specified	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
All life stages	Not Specified

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Unspecific	Not Specified

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

The Peroxisome Proliferator-Activated Receptors (PPAR) family of genes involved in regulation of lipid metabolism and energy pathways (Desvergne and Wahli 1999, Hihi et al. 2002, Ahmed et al. 2007). Fatty acids stimulate the expression of PPAR genes, which initiate a variety of cellular responses focused on lipid metabolism, but also inflammation and apoptosis pathways. Decreases in PPAR-gamma expression are associated with disruption of adipocyte differentiation and glucose homeostasis.

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Peroxisome proliferation-activated receptors are investigated by changes in gene expression and protein levels. X-ray crystallography can be used to determine molecular structure. Effects of PPAR gamma on expression of downstream genes can be investigating using metabolomics and RT-qPCR approaches.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Life Stage: All life stages.

Sex: Applies to both males and females.

Taxonomic: Appears to be present broadly, with representative studies in mammals.

References

List of the literature that was cited for this KE description. More help

Ahmed, W., Ziouzenkova, O., Brown, J. Devchand, P. Francis, S., Kadakia, M., Kanda, T., Orasanu, G., Sharlach, M., Zandbergen, F., and Plutzky, J. 2007. PPARs and their metabolic modulation: new mechanisms for transcriptional regulation? Journal of Internal Medicine 262: 184-198.

Desvergne, B. and Wahli, W. 1999. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocrine Reviews 20(5): 649-688.

Hihi, A.K., Michalik, L., Wahli, W. 2002. PPARs: transcriptional effectors of fatty acids and their derivatives. Cellular and Molecular Life Sciences 59: 790-798.