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Significance of this study
What is already known about this subject?
Fatty acid translocase CD36 (FAT/CD36) is the best characterised free fatty acid transporter.
FAT/CD36 plays a key role in the hepatic steatosis set-up in rodents.
Little is known about the significance of FAT/CD36 in human liver diseases.
What are the new findings?
Hepatic FAT/CD36 expression is abnormally increased in non-alcoholic fatty liver disease (NAFLD).
In patients with chronic hepatitis C virus (HCV) infection, FAT/CD36 is largely overexpressed in those with steatosis.
FAT/CD36 is predominantly located at the plasma membrane of hepatocytes in patients with NAFLD and HCV with steatosis.
Hepatic FAT/CD36 upregulation is significantly associated with insulin resistance, hyperinsulinaemia and increased steatosis in patients with NAFLD and HCV with fatty liver.
How might it impact on clinical practice in the foreseeable future?
Modulating FAT/CD36 expression and/or translocation to the plasma membrane of hepatocytes could be useful for the prevention/treatment of liver fat accumulation and its deleterious consequences on the outcome of NAFLD and chronic HCV infection.
Introduction
Non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection are the most prevalent causes of chronic liver disease in developed countries. 1 2 NAFLD comprises a wide spectrum of histological findings ranging from simple steatosis to steatohepatitis with progressive fibrosis. Liver disease induced by persistent HCV infection encompasses conditions ranging from chronic hepatitis, with or without steatosis, to cirrhosis and hepatocellular carcinoma. Although diverse factors play a role in the pathogenesis of hepatic steatosis-exclusively metabolic in NAFLD 3 and both metabolic and viral genotype-specific in HCV-infected patients 4 5 -the increased mobilisation and transport of free fatty acids (FFAs) flux from insulin-resistant adipose tissue to the liver should be the first essential step in the accumulation of fat as triglyceride (TG) in the hepatocytes. 6 In this regard, it has been shown that circulating FFAs are the major source of hepatic lipids in patients with fatty liver, 7 suggesting that the rate of influx of FFAs to the hepatocytes may have a relevant role in the process of fat deposition within the liver cells.
It is well known that FFAs are taken up into cells by passive diffusion and by protein-mediated mechanisms involving a number of fatty acid transporters, of which the fatty...