Event:89

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Event Title

De Novo FA, Synthesis
Short name: De Novo FA, Synthesis

Key Event Overview

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AOPs Including This Key Event

AOP Name Event Type Essentiality
LXR activation leading to hepatic steatosis KE

Taxonomic Applicability

Name Scientific Name Evidence Links

Level of Biological Organization

Biological Organization

How this Key Event works

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.


Metabolic-pathway-for-de-novo-FA-synthesis-and-TG-formation.png


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

Methods that have been previously reviewed and approved by a recognized authority should be included in the Overview section above. All other methods, including those well established in the published literature, should be described here. Consider the following criteria when describing each method: 1. Is the assay fit for purpose? 2. Is the assay directly or indirectly (i.e. a surrogate) related to a key event relevant to the final adverse effect in question? 3. Is the assay repeatable? 4. Is the assay reproducible?

Evidence Supporting Taxonomic Applicability

References

  1. 1.0 1.1 Postic & Girard 2008