Saturated fat-rich diet enhances selective uptake of LDL cholesteryl esters in the arterial wall.
Plasma LDL levels and atherosclerosis both increase on a saturated fat-rich (SAT) diet. LDL cholesterol delivery to tissue may occur via uptake of the LDL particles or via selective uptake (SU), wherein cholesteryl ester (CE) enters cells without concomitant whole-particle uptake. It is not known how dietary fats might directly affect arterial LDL-CE uptake and whether SU is involved. Thus, mice that are relatively atherosclerosis resistant (C57BL/6) or susceptible to atherosclerosis (apoE) were fed a chow or SAT diet and injected with double radiolabeled or fluorescent-labeled human LDL to independently trace LDL-CE core and whole-particle uptake, respectively. Our results show that a SAT diet increased contributions of SU to total arterial LDL-CE delivery in C57BL/6 and apoE mice. The SAT diet increased plasma fatty acid and cholesterol levels; cholesterol, but not fatty acid, levels correlated with SU, as did the degree of atherosclerosis. Increased SU did not correlate with arterial scavenger receptor class B type I levels but paralleled increased lipoprotein lipase (LPL) levels and LPL distribution in the arterial wall. These studies suggest that arterial LDL-CE delivery via SU can be an important mechanism in vivo and that dietary influences on arterial LPL levels and atherogenesis modulate arterial LDL-CE delivery, cholesterol deposition, and SU.
Seo
Toru
T
Department of Pediatrics, Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. ts227@columbia.edu
Qi
Kemin
K
Chang
Chuchun
C
Liu
Ying
Y
Worgall
Tilla S
TS
Ramakrishnan
Rajasekhar
R
Deckelbaum
Richard J
RJ
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001158:Arteries / Q000378:metabolism*; D001161:Arteriosclerosis / Q000097:blood*; D002788:Cholesterol Esters / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000097:blood*; D005227:Fatty Acids / Q000097:blood; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018110:Receptors, Lipoprotein / Q000378:metabolism; D051122:Scavenger Receptors, Class B
D001057:Apolipoproteins E; D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D004041:Dietary Fats; D005227:Fatty Acids; D008565:Membrane Proteins; D018110:Receptors, Lipoprotein; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D008071:Lipoprotein Lipase