Research Paper Volume 6, Issue 4 pp 281—295
Increased hepatic CD36 expression with age is associated with enhanced susceptibility to nonalcoholic fatty liver disease
- 1 University of Groningen, University Medical Center Groningen, Molecular Genetics, Groningen, The Netherlands
- 2 Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
- 3 Liver Research Unit, University Hospital Santa Cristina, Instituto de Investigación Sanitaria Princesa, CIBERehd, Madrid, Spain
- 4 Department of Dentistry, University of Alberta, Edmonton, AB, Canada
- 5 Agricultural, Department of Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
- 6 Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
- 7 IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy
- 8 UCL - Institute of Liver and Digestive Health, Royal Free Hospital, UK
Received: March 4, 2014 Accepted: April 4, 2014 Published: April 9, 2014
https://doi.org/10.18632/aging.100652How to Cite
Abstract
CD36 has been associated with obesity and diabetes in human liver diseases, however, its role in age-associated nonalcoholic fatty liver disease (NAFLD) is unknown. Therefore, liver biopsies were collected from individuals with histologically normal livers (n=30), and from patients diagnosed with simple steatosis (NAS; n=26). Patients were divided into two groups according to age and liver biopsy samples were immunostained for CD36. NAFLD parameters were examined in young (12-week) and middle-aged (52-week) C57BL/6J mice, some fed with chow-diet and some fed with low-fat (LFD; 10% kcal fat) or high-fat diet (HFD; 60% kcal fat) for 12-weeks. CD36 expression was positively associated with age in individuals with normal livers but not in NAS patients. However, CD36 was predominantly located at the plasma membrane of hepatocytes in aged NAS patients as compared to young. In chow-fed mice, aging, despite an increase in hepatic CD36 expression, was not associated with the development of NAFLD. However, middle-aged mice did exhibit the development of HFD-induced NAFLD, mediated by an increase of CD36 on the membrane. Enhanced CD36-mediated hepatic fat uptake may contribute to an accelerated progression of NAFLD in mice and humans. Therapies to prevent the increase in CD36 expression and/or CD36 from anchoring at the membrane may prevent the development of NAFLD.
Abbreviations
(NAFLD): Nonalcoholic fatty liver disease; (NAS): nonalcoholic steatosis; (NASH): nonalcoholic steatohepatitis; (HFD): high-fat diet; (LFD): low-fat diet; (qRT-PCR): Quantitative real-time polymerase chain reaction; (TG): triglycerides; (OXPHOS): oxidative phosphorylation; (HCV G1): hepatitis C virus infected with genotype 1.