Increased hepatic CD36 expression with age is associated with enhanced susceptibility to nonalcoholic fatty liver disease

Fareeba Sheedfar, Miranda My Sung, Marcela Aparicio-Vergara, Niels J Kloosterhuis, Maria Eugenia Miquilena-Colina, Javier Vargas-Castrillón, Maria Febbraio, René L Jacobs, Alain de Bruin, Manlio Vinciguerra, Carmelo García-Monzón, Marten H Hofker, Jason Rb Dyck, Debby P Y Koonen

    Research output: Contribution to journalArticleAcademicpeer-review

    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.

    Original languageEnglish
    Pages (from-to)281-95
    Number of pages15
    JournalAging
    Volume6
    Issue number4
    DOIs
    Publication statusPublished - Apr 2014

    Keywords

    • Adult
    • Aged
    • Aging
    • Animals
    • Antigens, CD36
    • Cell Membrane
    • Female
    • Hepatocytes
    • Humans
    • Immunoblotting
    • Immunohistochemistry
    • Liver
    • Male
    • Mice
    • Mice, Inbred C57BL
    • Middle Aged
    • Non-alcoholic Fatty Liver Disease
    • Real-Time Polymerase Chain Reaction
    • Young Adult

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