title: Hepatic fatty acid translocase CD36 upregulation is associated with insulin resistance, hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C.
abstract: BACKGROUND
  Fatty acid translocase CD36 (FAT/CD36) mediates uptake and intracellular transport of long-chain fatty acids in diverse cell types. While the pathogenic role of FAT/CD36 in hepatic steatosis in rodents is well-defined, little is known about its significance in human liver diseases.
  
  
  OBJECTIVE
  To examine the expression of FAT/CD36 and its cellular and subcellular distribution within the liver of patients with non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection.
  
  
  METHODS
  34 patients with non-alcoholic steatosis (NAS), 30 with non-alcoholic steatohepatitis (NASH), 66 with HCV genotype 1 (HCV G1) and 32 with non-diseased liver (NL).
  
  
  METHODS
  Real-time PCR and western blot analysis were used to assess hepatic FAT/CD36 expression. Computational image analysis of immunostained liver biopsy sections was performed to determine subcellular distribution and FAT/CD36 expression index.
  
  
  RESULTS
  Compared with NL, hepatic mRNA and protein levels of FAT/CD36 were significantly higher in patients with NAS (median fold increase 0.84 (range 0.15-1.61) and 0.66 (range 0.33-1.06), respectively); NASH (0.91 (0.22-1.81) and 0.81 (0.38-0.92), respectively); HCV G1 without steatosis (0.30 (0.17-1.59) and 0.33 (0.29-0.52), respectively); and HCV G1 with steatosis (0.85 (0.15-1.98) and 0.87 (0.52-1.26), respectively). In contrast to NL, FAT/CD36 was predominantly located at the plasma membrane of hepatocytes in patients with NAFLD and HCV G1 with steatosis. A significant correlation was observed between hepatic FAT/CD36 expression index and plasma insulin levels, insulin resistance (HOMA-IR) and histological grade of steatosis in patients with NASH (r=0.663, r=0.735 and r=0.711, respectively) and those with HCV G1 with steatosis (r=0.723, r=0.769 and r=0.648, respectively).
  
  
  CONCLUSIONS
  Hepatic FAT/CD36 upregulation is significantly associated with insulin resistance, hyperinsulinaemia and increased steatosis in patients with NASH and HCV G1 with fatty liver. Translocation of this fatty acid transporter to the plasma membrane of hepatocytes may contribute to liver fat accumulation in patients with NAFLD and HCV.
authors.affiliation: Liver Research Unit, University Hospital Santa Cristina, Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Miquilena-Colina
authors.forename: Elena
authors.initials: E
authors.lastname: Lima-Cabello
authors.forename: Sonia
authors.initials: S
authors.lastname: Sánchez-Campos
authors.forename: María Victoria
authors.initials: MV
authors.lastname: García-Mediavilla
authors.forename: Miguel
authors.initials: M
authors.lastname: Fernández-Bermejo
authors.forename: Tamara
authors.initials: T
authors.lastname: Lozano-Rodríguez
authors.forename: Javier
authors.initials: J
authors.lastname: Vargas-Castrillón
authors.forename: Xabier
authors.initials: X
authors.lastname: Buqué
authors.forename: Begoña
authors.initials: B
authors.lastname: Ochoa
authors.forename: Patricia
authors.initials: P
authors.lastname: Aspichueta
authors.forename: Javier
authors.initials: J
authors.lastname: González-Gallego
authors.forename: Carmelo
authors.initials: C
authors.lastname: García-Monzón
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics*; D018450:Disease Progression; D005234:Fatty Liver / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D006946:Hyperinsulinism / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D014178:Translocation, Genetic; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D018955:CD36 Antigens; D012333:RNA, Messenger