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Event: 89
Key Event Title
Synthesis, De Novo FA
Short name
Biological Context
Level of Biological Organization |
---|
Cellular |
Cell term
Cell term |
---|
hepatocyte |
Organ term
Key Event Components
Process | Object | Action |
---|---|---|
fatty acid biosynthetic process | fatty acid | increased |
Key Event Overview
AOPs Including This Key Event
AOP Name | Role of event in AOP | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|
LXR Activation to Liver Steatosis | KeyEvent | Marina Goumenou (send email) | Not under active development | |
LXR activation leads to liver steatosis | KeyEvent | John Frisch (send email) | Under development: Not open for comment. Do not cite |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
---|---|---|---|
Vertebrates | Vertebrates | High | NCBI |
Life Stages
Life stage | Evidence |
---|---|
Adult | High |
Juvenile | Moderate |
Sex Applicability
Term | Evidence |
---|---|
Unspecific | High |
Key Event Description
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.
How It Is Measured or Detected
Increases in fatty acid synthesis are generally measured by increases in triglycerides, fatty acids, cholesterols, and similar compounds in cells. In addition, assessment is generally made for cellular components such as mitochondria and/or gene expression increases with genes associated with synthesis, to associate the increase in fatty acid compounds with synthesis rather than other pathways (ex. influx).
Domain of Applicability
Life Stage: Older individuals are more likely to manifest this adverse outcome pathway (adults > juveniles) due to accumulation of triglycerides.
Sex: Applies to both males and females.
Taxonomic: Appears to be present broadly in vertebrates, with most representative studies in mammals (humans, lab mice, lab rats).
References
- ↑ 1.0 1.1 Postic & Girard 2008 - Postic C., Girard J., Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice, J. Clin. Invest. 118 (No 3), 829–838, 2008
- Diraison et al 1997 - Diraison F., et al, Role of human liver lipogenesis and re-esterification in triglycerides secretion and in FFA re-esterification. Am J Physiol., 274 (2 Pt 1), E321-327, 1998
NOTE: Italics symbolize edits from John Frisch