CD36 deficiency impairs intestinal lipid secretion and clearance of chylomicrons from the blood. J Clin Invest 2005 May;115(5):1290-7
Date
04/21/2005Pubmed ID
15841205Pubmed Central ID
PMC1074677DOI
10.1172/JCI21514Scopus ID
2-s2.0-18244393432 (requires institutional sign-in at Scopus site) 199 CitationsAbstract
CD36 mediates the transfer of fatty acids (FAs) across the plasma membranes of muscle and adipose cells, thus playing an important role in regulating peripheral FA metabolism in vivo. In the proximal intestine, CD36 is localized in abundant quantities on the apical surface of epithelial cells, a pattern similar to that of other proteins implicated in the uptake of dietary FAs. To define the role of CD36 in the intestine, we examined FA utilization and lipoprotein secretion by WT and CD36-null mice in response to acute and chronic fat feeding. CD36-null mice given a fat bolus by gavage or fed a high-fat diet accumulated neutral lipid in the proximal intestine, which indicated abnormal lipid processing. Using a model in which mice were equipped with lymph fistulae, we obtained evidence of defective lipoprotein secretion by directly measuring lipid output. The secretion defect appeared to reflect an impaired ability of CD36-null enterocytes to efficiently synthesize triacylglycerols from dietary FAs in the endoplasmic reticulum. In the plasma of intact mice, the reduced intestinal lipid secretion was masked by slow clearance of intestine-derived lipoproteins. The impaired clearance occurred despite normal lipoprotein lipase activity and likely reflected feedback inhibition of the lipase by FAs due to their defective removal from the plasma. We conclude that CD36 is important for both secretion and clearance of intestinal lipoproteins. CD36 deficiency results in hypertriglyceridemia both in the postprandial and fasting states and in humans may constitute a risk factor for diet-induced type 2 diabetes and cardiovascular disease.
Author List
Drover VA, Ajmal M, Nassir F, Davidson NO, Nauli AM, Sahoo D, Tso P, Abumrad NAAuthor
Daisy Sahoo PhD Dean, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApolipoproteins C
CD36 Antigens
Chylomicrons
Enterocytes
Fatty Acids
Intestine, Small
Lipid Metabolism
Mice
Mice, Inbred C57BL
RNA, Messenger
Time Factors
Triglycerides
