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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:555.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

n-3 Fatty Acids Reduce Arterial LDL-Cholesterol Delivery and Arterial Lipoprotein Lipase Levels and Lipase Distribution

Chuchun L. Chang; Toru Seo; Mika Matsuzaki; Tilla S. Worgall; Richard J. Deckelbaum

From the Institute of Human Nutrition (C.L.C., T.S., M.M., T.S.W., R.J.D.), Department of Pediatrics (T.S., T.S.W., R.J.D.), and the Department of Pathology (T.S.W.), College of Physicians and Surgeons, Columbia University, New York. Current affiliation for T.S.: Merck Banyu Pharmaceutical Co Ltd, Tokyo, Japan.

Correspondence to Richard J. Deckelbaum, Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, 630 W 168th Street, PH1512, New York, NY 10032. E-mail rjd20{at}columbia.edu

Objectives— We previously reported that saturated fat (SAT)-enriched diets increase arterial cholesteryl ester (CE) deposition, especially from LDL-selective uptake (SU), and this was associated with increased arterial lipoprotein lipase (LpL). We now question how n-3 fatty acid rich diets influence arterial cholesterol delivery and arterial LpL levels.

Methods and Results— C57BL/6 mice were fed chow or eucaloric high-fat diets enriched in SAT or fish oil (n-3) for 12 weeks, and then injected with double radiolabeled or fluorescent-labeled human LDL to separately trace LDL-CE and LDL-apoB uptake. SAT and n-3 diets increased plasma cholesterol levels similarly; n-3 diets lowered plasma triglyceride concentrations. SAT increased arterial LDL-SU with significantly higher CE infiltration into aortic media. In contrast, n-3 markedly reduced total LDL uptake and CE deposition and abolished SU with LDL localized only in aortic intima. Disparate patterns of CE deposition between diets were consistent with distribution of arterial LpL—SAT diets induced higher LpL levels throughout the aorta; n-3 diets decreased LpL levels and limited LpL expression to the aortic intima.

Conclusions— n-3 rich diets decrease arterial total LDL delivery and abrogate LDL-SU in parallel with changing arterial wall LpL expression and distribution.

In C57BL/6 mice fed a chow, saturated fatty acid (SAT)-rich, or n-3 diets for 12 weeks, SAT increased arterial LDL-cholesterol uptake. In contrast, n-3 markedly reduced LDL-cholesterol. Patterns of arterial cholesterol deposition parallel distribution and expression of arterial LpL.

Key Words: fatty acids • fish oil • lipoprotein lipase • LDL • atherosclerosis