API
Event: 264
Key Event Title
Short name
Activation, SREBP-1cBiological Context
| Level of Biological Organization |
|---|
| Molecular |
Cell term
| Cell term |
|---|
| hepatocyte |
Organ term
Key Event Components
| Process | Object | Action |
|---|---|---|
| SREBP signaling pathway | sterol regulatory element-binding protein 1 | increased |
Key Event Overview
AOPs Including This Key Event
| AOP Name | Role of event in AOP |
|---|---|
| LXR Activation to Liver Steatosis | KeyEvent |
Stressors
Taxonomic Applicability
Life Stages
Sex Applicability
Key Event Description
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 [1], [2], [3], [4].
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 [5]. It is also suggested that for lipogenic genes, SREBP-1c acts together with ChREBP [6]. 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 [7].
Finally there are a number of studies that demonstrated that SREBP-1c is essential for glucokinase (GK) expression and that it is a mediator of insulin action [8], [9].
How It Is Measured or Detected
Domain of Applicability
References
- ↑ 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