The maintenance of normal retinoid (vitamin A and its derivatives) homeostasis is required to support many crucial biological functions ( 1-3 ). All retinoids in animals are derived from the diet as preformed dietary vitamin A (retinyl esters, retinol, and very small amounts of retinoic acid) from animal products or as ␤ -carotene from vegetables and fruits ( 4 ). Within the intestine, ingested vitamin A is packaged into chylomicrons as retinyl ester regardless of its dietary origin ( 5 ). In the bloodstream, lipolysis of the chylomicrons generates smaller lipoprotein particles called chylomicron remnants, still retaining retinyl ester ( 6, 7 ). Approximately 75% of retinoids within chylomicron remants are cleared by the liver, which is the major site of vitamin A storage and metabolism ( 8-10 ). To meet tissue retinoid needs, the liver secretes retinol into the circulation bound to its sole specifi c transport protein, retinol-binding protein (RBP; also known as RBP4) ( 11,12 ). RBP is a 21 kDa protein with a single binding site for one molecule of all-trans -retinol. It is mainly, but not exclusively, synthesized within the hepatocytes. RBP circulates in the blood as a 1:1 molar complex with another serum protein, transthyretin (TTR), preventing retinol-RBP excretion by the kidney ( 11, 12 ). In the fasting circulation, retinol-RBP represents approximately 99% of all serum retinoids. Blood levels of retinol-RBP in both humans and animals are maintained very constant except in extreme cases of nutritional intake of vitamin A, protein, calories, and zinc or in response to hormonal factors, stress, and in certain disease states ( 11,13,14 ).Abstract 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 benefi cial 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. Specifi cally, 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 specifi c 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 ke...

Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA) is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol) and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4). However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR-α and RXR heterodimer. We also present preliminary data that may position PPAR-α at the crossroads between the metabolism of lipids and vitamin A.

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