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Journal of Lipid Research, Vol. 43, 895-903, June 2002
Copyright © 2002 by Lipid Research, Inc.

Enhanced solubilization and intestinal absorption of cholesterol by oxidized linoleic acid

Meera Penumetcha, Nadya Khan-Merchant and Sampath Parthasarathy1

Department of Gynecology and Obstetrics, Nutrition and Health Sciences Program, Emory University School of Medicine, Atlanta, GA 30322

1 To whom correspondence should be addressed. e-mail: spartha{at}emory.edu

Solubilization of cholesterol in the intestinal lumen by bile acids and the subsequent formation of mixed micelles is an important step in the absorption of cholesterol. We propose that oxidized fatty acids (ox-FA) may mimic bile acids and form mixed micelles with cholesterol much more efficiently, as compared with unoxidized fatty acids, thereby increasing there absorption. In an in vitro assay at concentrations of 1, 5, and 10 mM, oxidized linoleic acid (ox-18:2) increased the solubilization of cholesterol (3.06, 8.16, and 15.46 nmol/ml) in a dose dependent manner compared with a 10 mM unoxidized linoleic acid (unox-18:2 at 0.97 nmol/ml). The uptake of cholesterol solubilized in the presence of ox-18:2 by Caco-2 cells and everted rat intestinal sacs was greater (1.78 and 1.95 nmol/ml respectively) as compared with the cholesterol solubilized in the presence of unox-18:2 (0.29 and 0.61 nmol/ml; P = 0.05). In addition, when LDL receptor deficient mice were fed a high fat diet along with ox-18:2 their plasma cholesterol levels were greater than animals fed the high fat diet alone (1290 mg/dl vs. 1549 mg/dl, P = 0.013).

From these results, we suggest that ox-FA, by enhancing the solubilization of luminal cholesterol, increases the uptake of cholesterol that might lead to hypercholesterolemia and atherosclerosis.

Abbreviations: 13-HODE, 13-hydroxylinoleic acid; ox-FA, oxidized fatty acids; Lyso PtdCho, lyso phosphatidylcholine; ox-18:2, oxidized linoleic acid; unox-18:2, unoxidized linoleic acid; TC, taurocholate; 2-MOG, 2-mono-oleylglycerol

Supplementary key words bile acids • atherosclerosis • lipid peroxides • oxidized fatty acids


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