API

Event: 264

Key Event Title

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Activation, SREBP-1c

Short name

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Activation, SREBP-1c

Key Event Component

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Process Object Action
SREBP signaling pathway sterol regulatory element-binding protein 1 increased

Key Event Overview


AOPs Including This Key Event

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AOP Name Role of event in AOP
LXR activation leading to hepatic steatosis KeyEvent

Stressors

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Level of Biological Organization

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Biological Organization
Molecular

Cell term

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Cell term
hepatocyte


Organ term

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Taxonomic Applicability

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Life Stages

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Sex Applicability

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How This Key Event Works

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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

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Evidence Supporting Taxonomic Applicability

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References

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  1. Liang et al. 2002
  2. Schultz et al. 2000
  3. Horton et al. 2002
  4. Shimano et al. 1999
  5. Liang et al. 2002
  6. Ishii et al. 2004
  7. Bécard et al. 2001
  8. Ferre 2007
  9. Fleischmann 1999