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Event: 89
Key Event Title
A descriptive phrase which defines a discrete biological change that can be measured.
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Synthesis, De Novo FA
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.
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Synthesis, De Novo FA
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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.
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A number of pathways and a great number of enzymes like GK, L-PK, ACC, FAS and SCD-1 are involved in the de novo FA synthesis [1]. As it is already discussed above these enzymes are induced by LXR agonists (FAS, SCD1), the SREBP-1c (GK, ACC, FAS) and the ChREBP (L-PK, ACC, FAS) leading to enhancement of the de novo FA synthesis.
Figure 1. Metabolic pathway for de novo FA synthesis and TG formation [1]
As proposed from Diraison et al 1997 the de novo FA synthesis contributes maximum 5% to the synthesis of FA and TG under normal conditions. Conditions associated with high rates of lipogenesis, such as low fat - high carbohydrate (LF/HC) diet, hyperglycemia, and hyperinsulinemia are associated with a shift in cellular metabolism from lipid oxidation to TG esterification, thereby increasing the availability of TGs derived from VLDL synthesis and secretion.
In the context of the EMOD/M2AOP prototyping, there are 2 components to the How it is Measured or Detected field, a structured component for adding Assay information and a free text component for unstructured descriptive information.In the free text field, include 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.
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Observed meausures are instances of assay results that support this Key Event
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| ID | Experimental Effect | Biological Object | Biological Process | Method of Measurement | Notes | Evidence Source ID | Citation (first author, year) |
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Observed meausures are instances of assay results that support this Key Event
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| ID | Stressor | Sample (short_name) | Assay | Effect |
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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.
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| Process | Object | Action |
|---|---|---|
| fatty acid biosynthetic process | fatty acid | increased |
Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE.
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| Level of Biological Organization |
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| Cellular |
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.
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| Cell term |
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| hepatocyte |
Organ 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.
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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.
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| AOP Name | Role of event in AOP | Point of Contact | Author Status | OECD Status |
|---|---|---|---|---|
| LXR Activation to Liver Steatosis | KeyEvent | Agnes Aggy (send email) | Not under active development |
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.
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Life Stages
An indication of the the relevant life stage(s) for this KE.
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Sex Applicability
An indication of the the relevant sex for this KE.
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A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).
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List of the literature that was cited for this KE description.
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