1. Increased hepatic CD36 expression with age is associated with enhanced susceptibility to nonalcoholic fatty liver disease
- Author
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Sheedfar, Fareeba, Sung, Miranda My, Aparicio-Vergara, Marcela, Kloosterhuis, Niels J, Miquilena-Colina, Maria Eugenia, Vargas-Castrillón, Javier, Febbraio, Maria, Jacobs, René L, de Bruin, Alain, Vinciguerra, Manlio, García-Monzón, Carmelo, Hofker, Marten H, Dyck, Jason Rb, Koonen, Debby P Y, LS Pathobiologie, PB TR, Tissue Repair, Center for Liver, Digestive and Metabolic Diseases (CLDM), Vascular Ageing Programme (VAP), Cardiovascular Centre (CVC), LS Pathobiologie, PB TR, and Tissue Repair
- Subjects
CD36 Antigens ,Male ,Aging ,obesity ,CD36 ,CARDIAC MYOCYTES ,Antigens, CD36 ,Inbred C57BL ,STEATOHEPATITIS ,Mice ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Nonalcoholic fatty liver disease ,steatosis ,0303 health sciences ,INSULIN-RESISTANCE ,medicine.diagnostic_test ,biology ,NASH ,Middle Aged ,Immunohistochemistry ,Liver ,030220 oncology & carcinogenesis ,Liver biopsy ,SKELETAL-MUSCLE ,Female ,Research Paper ,Adult ,medicine.medical_specialty ,SARCOLEMMAL FAT/CD36 ,Immunoblotting ,Real-Time Polymerase Chain Reaction ,liver ,OBESE ZUCKER RATS ,DIET ,03 medical and health sciences ,Young Adult ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,NAFLD ,medicine ,Animals ,Humans ,Antigens ,030304 developmental biology ,Aged ,Cell Membrane ,aging ,nutritional and metabolic diseases ,Cell Biology ,medicine.disease ,Obesity ,Mice, Inbred C57BL ,MICE ,Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] ,Endocrinology ,ACID TRANSPORT ,inflammation ,PLASMA-MEMBRANE ,biology.protein ,Hepatocytes ,Steatohepatitis ,Steatosis - Abstract
Item does not contain fulltext 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.
- Published
- 2014
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