Key Event Overview
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AOPs Including This Key Event
|AOP Name||Event Type||Essentiality|
|LXR activation leading to hepatic steatosis||KE|
Level of Biological Organization
How this Key Event works
An increase on the mRNA of the SREBP-1c is responsible for an increase of the mRNA of lipogenic enzymes like acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) (Foretz et al. 1999, Foretz et al. 2000). This finding is demonstrated from the absence of triglyceride accumulation on SREBP-1c (-/-) mice , , , .
However there is evidence that this effect is not induced in the embryonic state indicating a different role of the SREBP-1c between embryonic and adult life . It is also suggested that for lipogenic genes, SREBP-1c acts together with ChREBP . In addition, in STZ diabetic mice, adenovirus-mediated over-expression of SREBP-1c in the liver resulted in an increase of lipogenic enzyme expression with an increase of the triglyceride hepatic content and a marked decrease in the hyperglycaemia of diabetic mice mimicking perfectly the effect of an insulin injection .
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
- Liang et al. 2002
- Schultz et al. 2000
- Horton et al. 2002
- Shimano et al. 1999
- Liang et al. 2002
- Ishii et al. 2004
- Bécard et al. 2001
- Ferre 2007
- Fleischmann 1999