CD36 mediates both cellular uptake of very long chain fatty acids and their intestinal absorption in mice.
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.
Drover
Victor A
VA
Department of Pharmacology, State University of New York, Stony Brook, New York 11794, USA. victor.drover@mcw.edu
Nguyen
David V
DV
Bastie
Claire C
CC
Darlington
Yolanda F
YF
Abumrad
Nada A
NA
Pessin
Jeffrey E
JE
London
Erwin
E
Sahoo
Daisy
D
Phillips
Michael C
MC
D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D007408:Intestinal Absorption; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013379:Substrate Specificity
D018955:CD36 Antigens; D005227:Fatty Acids; D026901:Membrane Transport Proteins; C482445:Npc1l1 protein, mouse