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

• Published in: The Journal of clinical investigation 2005-08, Vol.115 (8), p.2214-2222
• Main Authors: Seo, Toru, Qi, Kemin, Chang, Chuchun, Liu, Ying, Worgall, Tilla S, Ramakrishnan, Rajasekhar, Deckelbaum, Richard J
• Format: Article
• Language: English
• Subjects: Animals; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; Arteries - metabolism; Arteriosclerosis - blood; Atherosclerosis; Biomedical research; Cholesterol; Cholesterol Esters - blood; Cholesterol, LDL - blood; Diet; Diet, Atherogenic; Dietary Fats - blood; Fatty acids; Fatty Acids - blood; High density lipoprotein; Humans; Lipids; Lipoprotein Lipase - metabolism; Low density lipoprotein; Membrane Proteins - metabolism; Mice; Mice, Knockout; Oils & fats; Plasma; Receptors, Lipoprotein - metabolism; Scavenger Receptors, Class B
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI24327

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.