title: Increased hepatic CD36 expression with age is associated with enhanced susceptibility to nonalcoholic fatty liver disease.
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.
authors.affiliation: University of Groningen, University Medical Center Groningen, Molecular Genetics, Groningen, The Netherlands.
authors.forename: Fareeba
authors.initials: F
authors.lastname: Sheedfar
authors.forename: Miranda My
authors.initials: MM
authors.lastname: Sung
authors.forename: Marcela
authors.initials: M
authors.lastname: Aparicio-Vergara
authors.forename: Niels J
authors.initials: NJ
authors.lastname: Kloosterhuis
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Miquilena-Colina
authors.forename: Javier
authors.initials: J
authors.lastname: Vargas-Castrillón
authors.forename: Maria
authors.initials: M
authors.lastname: Febbraio
authors.forename: René L
authors.initials: RL
authors.lastname: Jacobs
authors.forename: Alain
authors.initials: A
authors.lastname: de Bruin
authors.forename: Manlio
authors.initials: M
authors.lastname: Vinciguerra
authors.forename: Carmelo
authors.initials: C
authors.lastname: García-Monzón
authors.forename: Marten H
authors.initials: MH
authors.lastname: Hofker
authors.forename: Jason Rb
authors.initials: JR
authors.lastname: Dyck
authors.forename: Debby P Y
authors.initials: DP
authors.lastname: Koonen
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D000818:Animals; D018955:CD36 Antigens / Q000096:biosynthesis*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D018955:CD36 Antigens
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