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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1502.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Fish Oil Promotes Macrophage Reverse Cholesterol Transport in Mice

Tomoyuki Nishimoto; Michael A. Pellizzon; Masakazu Aihara; Ioannis M. Stylianou; Jeffery T. Billheimer; George Rothblat; Daniel J. Rader

From the Institute for Translational Medicine and Therapeutics (T.N., M.A.P., M.A., I.M.S., J.T.B., D.J.R.) and Cardiovascular Institute (D.J.R.), University of Pennsylvania School of Medicine, Philadelphia; and the Children’s Hospital of Philadelphia (G.R), Pa.

Correspondence to Daniel J. Rader, MD, Cardiovascular Institute and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, 654 BRBII/III, 421 Curie Boulevard, Philadelphia, PA 19104. E-mail rader{at}mail.med.upenn.edu

Objective— Fish oil (FO), and specifically omega 3 fatty acids, has favorable effects on cardiovascular outcomes. The aim of this study was to investigate the effects of FO on the process of macrophage reverse cholesterol transport (RCT) in an in vivo mouse model.

Methods and Results— C57BL/6J mice were fed a FO diet, whereas control mice were fed diets containing alternative sources of fats, soybean oil (SO), and coconut oil (CO) for 4 weeks. Macrophage RCT was assessed by injecting [³H]cholesterol-labeled J774 macrophages intraperitoneally into mice. After 48 hours, tissues were harvested and feces were collected. An increase in the excretion of macrophage-derived [³H]-tracer recovered in fecal neutral sterols for FO-fed mice was observed (273% versus SO and 182% versus CO). FO also decreased [³H]-tracer in hepatic cholesteryl ester compared to SO and CO by 76% and 56%, respectively. To specifically determine the effect of FO on the fate of HDL-derived cholesterol, mice fed FO or SO diets were injected with HDL labeled with [³H]cholesteryl oleate, and the disappearance of [³H]-tracer from blood and its excretion in feces was measured. There was no significant difference in the fractional catabolic rate of [³H]cholesteryl oleate-HDL between the 2 groups. However, there was a 242% increase in the excretion of HDL-derived [³H]-tracer recovered in fecal neutral sterols in FO-fed mice, concordant with significantly increased expression of hepatic Abcg5 and Abcg8 mRNA.

Conclusion— As measured by this tracer-based assay, FO promoted reverse cholesterol transport, primarily by enhancement of the hepatic excretion of macrophage-derived and HDL-derived cholesterol.

Fish oil (omega 3 fatty acids) has favorable effects on cardiovascular outcomes. We investigated the effects of fish oil on macrophage reverse cholesterol transport (RCT) in an in vivo mouse model. FO promoted macrophage RCT, primarily by enhancement of the hepatic excretion of macrophage- and HDL-derived cholesterol.

Key Words: HDL • atherosclerosis • nutrition