Key Event Overview
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AOPs Including This Key Event
|AOP Name||Event Type||Essentiality|
|LXR activation leading to hepatic steatosis||KE|
|NR1I3 (CAR) suppression leading to hepatic steatosis||KE||Moderate|
Level of Biological Organization
How this Key Event works
ChREBP is an LXR target that independently enhances the up-regulation of select lipogenic genes. The up-regulation of the ChREBP target gene is through liver-type pyruvate kinase (L-PK). Therefore, activation of LXR not only increases ChREBP mRNA via enhanced transcription but also modulates its activity . In the liver, ChREBP mediates activation of several regulatory enzymes of glycolysis and lipogenesis including L-PK, acetyl CoA carboxylase (ACC), and fatty acid synthase (FAS). However, according to the study of Denechaud increase in the glucose flux in the cell is a prerequisite for ChREBP activation from T0901317 in mice .
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
- Cha & Repa 2007
- Denechaud et al. 2008