CD36-deficient Mice Are Resistant to Alcohol- and High-carbohydrate-induced Hepatic Steatosis

Overview

Journal J Lipid Res

Publisher Elsevier

Specialty Biochemistry

Date 2013 Nov 28

PMID 24280415

Citations 42

Authors

Robin D Clugston

Jason J Yuen

Yunying Hu

Nada A Abumrad

Paul D Berk

Ira J Goldberg

William S Blaner

Li-Shin Huang

Affiliations

Soon will be listed here.

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.

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