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Papers In Press, published online ahead of print November 1, 2009
J. Lipid Res., doi:10.1194/jlr.M900054-JLR200

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Journal of Lipid Research, Vol. 50, 2278-2289, November 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Hepatic retinol secretion and storage are altered by dietary CLA: common and distinct actions of CLA c9,t11 and t10,c12 isomers^[S]

Berenice Ortiz^1,*, Lesley Wassef^1,*, Elena Shabrova^*, Lina Cordeddu, Sebastiano Banni^2, and Loredana Quadro^2,*

^* Department of Food Science and Rutgers Center for Lipid Research, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ, 08901
Department of Experimental Biology, University of Cagliari, Cagliari, 09042 Italy

² To whom correspondence should be addressed. e-mail: quadro{at}aesop.rutgers.edu or banni{at}unica.it

Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid obtained from ruminant products. Previous studies in rats and pigs showed that a dietary equimolar mixture of c9,t11 and t10,c12 CLA isomers induces changes in serum and tissue levels of retinoids (vitamin A derivatives). However, the mechanism(s) responsible for these actions remain(s) unexplored. Given the numerous crucial biological functions regulated by retinoids, it is key to establish whether the perturbations in retinoid metabolism induced by dietary CLA mediate some of the beneficial effects associated with intake of this fatty acid or, rather, have adverse consequences on health. To address this important biological question, we began to explore the mechanisms through which dietary CLA alters retinoid metabolism. By using enriched preparations of CLA c9,t11 or CLA t10,c12, we uncoupled the effects of these two CLA isomers on retinoid metabolism. Specifically, we show that both isomers induce hepatic retinyl ester accumulation. However, only CLA t10,c12 enhances hepatic retinol secretion, resulting in increased serum levels of retinol and its specific carrier, retinol-binding protein (RBP). Dietary CLA t10,c12 also redistributes retinoids from the hepatic stores toward the adipose tissue and possibly stimulates hepatic retinoid oxidation. Using mice lacking RBP, we also demonstrate that this key protein in retinoid metabolism mediates hepatic retinol secretion and its redistribution toward fat tissue induced by CLA t10,c12 supplementation.

Supplementary key words conjugated linoleic acid • retinol • retinyl ester • retinol-binding protein

Abbreviations: CLA, conjugated linoleic acid; LRAT, lecithin:retinol acyltransferase; RBP, retinol-binding protein; TTR, transthyretin

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