title: CD36-deficient mice are resistant to alcohol- and high-carbohydrate-induced hepatic steatosis.
abstract: CD36 is a scavenger receptor with multiple ligands and cellular functions, including facilitating cellular uptake of free fatty acids (FFAs). Chronic alcohol consumption increases hepatic CD36 expression, leading to the hypothesis that this promotes uptake of circulating FFAs, which then serve as a substrate for triglyceride (TG) synthesis and the development of alcoholic steatosis. We investigated this hypothesis in alcohol-fed wild-type and Cd36-deficient (Cd36(-/-)) mice using low-fat/high-carbohydrate Lieber-DeCarli liquid diets, positing that Cd36(-/-) mice would be resistant to alcoholic steatosis. Our data show that the livers of Cd36(-/-) mice are resistant to the lipogenic effect of consuming high-carbohydrate liquid diets. These mice also do not further develop alcoholic steatosis when chronically fed alcohol. Surprisingly, we did not detect an effect of alcohol or CD36 deficiency on hepatic FFA uptake; however, the lower baseline levels of hepatic TG in Cd36(-/-) mice fed a liquid diet were associated with decreased expression of genes in the de novo lipogenesis pathway and a lower rate of hepatic de novo lipogenesis. In conclusion, Cd36(-/-) mice are resistant to hepatic steatosis when fed a high-carbohydrate liquid diet, and they are also resistant to alcoholic steatosis. These studies highlight an important role for CD36 in hepatic lipid homeostasis that is not associated with hepatic fatty acid uptake.
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032.
authors.forename: Robin D
authors.initials: RD
authors.lastname: Clugston
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Yuen
authors.forename: Yunying
authors.initials: Y
authors.lastname: Hu
authors.forename: Nada A
authors.initials: NA
authors.lastname: Abumrad
authors.forename: Paul D
authors.initials: PD
authors.lastname: Berk
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
authors.forename: Li-Shin
authors.initials: LS
authors.lastname: Huang
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000172:deficiency*; D004040:Dietary Carbohydrates / Q000009:adverse effects*; D004041:Dietary Fats / Q000032:analysis; D060467:Disease Resistance / Q000187:drug effects; D005235:Fatty Liver, Alcoholic / Q000209:etiology* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014280:Triglycerides / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D014280:Triglycerides; D005947:Glucose
keywords: alcoholic steatosis; de novo lipogenesis; fatty acid uptake