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Hepatic fatty acid translocase CD36 upregulation is associated with insulin resistance, hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C
  1. María Eugenia Miquilena-Colina1,2,
  2. Elena Lima-Cabello3,
  3. Sonia Sánchez-Campos2,3,
  4. María Victoria García-Mediavilla2,3,
  5. Miguel Fernández-Bermejo4,
  6. Tamara Lozano-Rodríguez1,2,
  7. Javier Vargas-Castrillón1,2,
  8. Xabier Buqué5,
  9. Begoña Ochoa5,
  10. Patricia Aspichueta5,
  11. Javier González-Gallego2,3,
  12. Carmelo García-Monzón1,2
  1. 1Liver Research Unit, University Hospital Santa Cristina, Instituto de Investigación Sanitaria Princesa, Madrid, Spain
  2. 2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
  3. 3Institute of Biomedicine (IBIOMED), University of León, León, Spain
  4. 4Gastroenterology Service, San Pedro de Alcántara Hospital, Cáceres, Spain
  5. 5Department of Physiology, School of Medicine and Dentistry, University of Basque Country, Leioa, Spain
  1. Correspondence to Dr Carmelo García-Monzón, Liver Research Unit, University Hospital Santa Cristina, Instituto de Investigación Sanitaria Princesa, Maestro Vives 2, 28009 Madrid, Spain; cgarcia.hscr{at}salud.madrid.org

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.

Patients 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.

  • Fatty acids
  • fatty acid transporters
  • nonalcoholic fatty liver disease
  • hepatitis C virus
  • insulin
  • fatty liver
  • hepatitis C
  • nonalcoholic steatohepatitis

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Footnotes

  • Funding This work was supported by grants to CG-M from Instituto de Salud Carlos III (PI06/0221 and PI10/00067), Fundación Eugenio Rodríguez Pascual, and Universidad Europea de Madrid, Spain; to JG-G and SS-C from Junta de Castilla y León (G/467B01/64000/3 and SAN673/LE06/08) and Ministerio de Educación y Ciencia (BFU2007-62977); and to PA and BO from Basque government (IT-336-10 and S-PE09UN28) and Ministerio de Educación y Ciencia (SAF2007-60211). MVG-M and TL-R were supported by CIBERehd contracts. CIBERehd is funded by the Instituto de Salud Carlos III, Spain.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the ethics committee of University Hospital Santa Cristina, as commissioned by University Hospital La Princesa, Madrid, Spain.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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