Saturated fat–rich diet enhances selective uptake of LDL cholesteryl esters in the arterial wall
Toru Seo, … , Rajasekhar Ramakrishnan, Richard J. Deckelbaum
Toru Seo, … , Rajasekhar Ramakrishnan, Richard J. Deckelbaum
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2214-2222. https://doi.org/10.1172/JCI24327.
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Research Article Cardiology

Saturated fat–rich diet enhances selective uptake of LDL cholesteryl esters in the arterial wall

Abstract

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.

Authors

Toru Seo, Kemin Qi, Chuchun Chang, Ying Liu, Tilla S. Worgall, Rajasekhar Ramakrishnan, Richard J. Deckelbaum

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Plasma clearance rate and FCR of LDL-CE core and whole particle of injec...
Plasma clearance rate and FCR of LDL-CE core and whole particle of injected LDL in C57BL/6 and apoE–/– mice fed a chow or SAT diet. Four-week-old C57BL/6 (A) and apoE–/– mice (B) were fed a chow or SAT diet for 12 weeks and then injected with double-labeled LDL as described in Methods. Plasma clearance of 3H and 125I of injected LDL were independently measured to trace clearance of apoB (measured by whole-particle uptake; filled symbols) and clearance of LDL-CE (open symbols). Squares and circles indicate mice fed chow or SAT diet, respectively. Results are expressed as percent injected LDL radioactivity remaining in the plasma at each time point over 24 hours. Each data point indicates the mean radioactivity present in blood measured from a minimum of 5 mice. Insets: FCR determined from blood clearance of 125I (open bars) and 3H (filled bars), using slopes that follow the first-order kinetics.