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J. Biol. Chem., Vol. 283, Issue 19, 13108-13115, May 9, 2008

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CD36 Mediates Both Cellular Uptake of Very Long Chain Fatty Acids and Their Intestinal Absorption in Mice^*

Victor A. Drover¹², David V. Nguyen, Claire C. Bastie, Yolanda F. Darlington³, Nada A. Abumrad^¶, Jeffrey E. Pessin, Erwin London^||, Daisy Sahoo¹, and Michael C. Phillips

From the Departments of Pharmacology and ^||Biochemistry and Cell Biology, State University of New York, Stony Brook, New York 11794, the GI/Nutrition Division, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, and the ^¶Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110

The intestine has an extraordinary capacity for fatty acid (FA) absorption. Numerous candidates for a protein-mediated mechanism of dietary FA absorption have been proposed, but firm evidence for this process has remained elusive. Here we show that the scavenger receptor CD36 is required both for the uptake of very long chain FAs (VLCFAs) in cultured cells and the absorption of dietary VLCFAs in mice. We found that the fraction of CD36-dependent saturated fatty acid association/absorption in these model systems is proportional to the FA chain length and specific for fatty acids and fatty alcohols containing very long saturated acyl chains. Moreover, intestinal VLCFA absorption is completely abolished in CD36-null mice fed a high fat diet, illustrating that the predominant mechanism for VLCFA absorption is CD36-dependent. Together, these findings represent the first direct evidence for protein-facilitated FA absorption in the intestine and identify a novel therapeutic target for the treatment of diseases characterized by elevated VLCFA levels.

Received for publication, September 27, 2007 , and in revised form, February 22, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grants DK060022 (to N. A. A.), HL22633 (to M. C. P.), and HL63768 (to E. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1.

¹ Current address: Dept. of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226.

³ Current address: Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.

² To whom correspondence should be addressed: H4880 Health Research Center, 8701 Watertown Plank Rd., Milwaukee, WI 53089. Tel.: 414-456-4607; Fax: 414-456-6570; E-mail: victor.drover{at}mcw.edu.

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