API

Event: 54

Key Event Title

?

Up Regulation, CD36

Short name

?

Up Regulation, CD36

Key Event Component

?

Process Object Action
gene expression platelet glycoprotein 4 increased

Key Event Overview


AOPs Including This Key Event

?


Stressors

?



Level of Biological Organization

?

Biological Organization
Molecular

Cell term

?

Cell term
hepatocyte


Organ term

?



Taxonomic Applicability

?



Life Stages

?



Sex Applicability

?



How This Key Event Works

?


Fatty acid translocase CD36 (FAT/CD36) is a scavenger protein mediating uptake and intracellular transport of long-chain fatty acids (FA) in diverse cell types [1], [2]. In addition, CD36 can bind a variety of molecules including acetylated low density lipoproteins (LDL), collagen and phospholipids [3]. CD36 has been shown to be expressed in liver tissue [4], [5]. It is located in lipid rafts and non-raft domains of the cellular plasma membrane and most likely facilitates LCFA transport by accumulating LCFA on the outer surface [6], [7], [8].

FAT/CD36 gene is a liver specific target of LXR activation [9]. Studies have confirmed that the lipogenic effect of LXR and activation of FAT/CD36 was not a simple association, since the effect of LXR agonists on increasing hepatic and circulating levels of triglycerides and free fatty acids (FFAs) was largely abolished in FAT/CD36 knockout mice suggesting that intact expression and/or activation of FAT/CD36 is required for the steatotic effect of LXR agonists [10], [11]. In addition to the well-defined pathogenic role of FAT/CD36 in hepatic steatosis in rodents the human up-regulation of the FAT/CD36 in NASH patients is confirmed [12]. There are now findings that can accelerate the translation of FAT/CD36 metabolic functions determined in rodents to humans [13] and suggest that the translocation of this fatty acid transporter to the plasma membrane of hepatocytes may contribute to liver fat accumulation in patients with NAFLD and HCV [14]. In addition, hepatic FAT/CD36 up-regulation is significantly associated with insulin resistance, hyperinsulinaemia and increased steatosis in patients with NASH and HCV G1 (Hepatitis C Virus Genotype1) with fatty liver. Recent data show that CD36 is also increased in the liver of morbidly obese patients and correlated to free FA levels [15].


How It Is Measured or Detected

?



Evidence Supporting Taxonomic Applicability

?



References

?


  1. Su & Abumrad 2009
  2. He et al. 2011
  3. Krammer 2011
  4. Pohl et al. 2005
  5. Cheung et al. 2007
  6. Ehehalt et al. 2008
  7. Pohl et al. 2005
  8. Krammer 2011
  9. Zhou 2008
  10. Febbraio et al. 1999
  11. Lee et al. 2008
  12. Zhu et al. 2011
  13. Love-Gregory et al. 2011
  14. Miquilena-Colina et al. 2011
  15. Bechmann et al. 2010