Vitamin A must be obtained from the diet by intake of either food containing preformed vitamin A (e.g., red meats) or provitamin A carotenoids (e.g., carrots, green leafy vegetables). Most actions of retinol are mediated by its metabolite retinoic acid, which is synthesized intracelluarly in target tissue from retinol [1
]. In the first step, retinol is reversibly oxidized to retinaldehyde. Two major enzyme classes, cytosolic aldehyde dehydrogenases (ADHs) and microsomal short-chain dehydrogenases (SDR) have been proposed to catalyze this reversible reaction [2
]. In the second step, retinaldehyde is irreversibly oxidized to retinoic acid. The enzyme class of cytosolic retinaldehyde dehydrogenases (RALDH) has been clearly identified to catalyze this step [4
Retinoic acid exerts its pleiotropic effects mostly by controlling the expression of over 500 genes through binding to and activating retinoic acid receptors (RAR) and retinoid X receptors (RXR), both of which are members of the nuclear hormone receptor family [5
]. In addition to its oxidation to retinoic acid, retinol can be esterified and stored as retinyl ester in hepatic stellate cells or, to a smaller extent, in extrahepatic tissues including adipose tissue (see below).
The liver plays a central role in vitamin A physiology. Postprandially, vitamin A is delivered to the liver as a constituent of chylomicron remnants. In the liver, retinol is re-esterified to retinyl ester by lecithin:retinol acyltransfrase (LRAT) and stored in hepatic stellate cells, the major storage site for vitamin A in the body [7
]. Retinol bound to retinol-binding protein (RBP; RBP4) is secreted from the liver to maintain serum vitamin A levels and to deliver retinol to extrahepatic target tissues for intracellular retinoic acid synthesis [8
]. RBP contains one binding site for retinol and in plasma RBP circulates as a 1:1 complex with transthyretin. Plasma RBP-retinol levels are under homeostatic regulation and are maintained at levels between 2 and 3 μM [8
Vitamin A, its metabolites, and its synthetic analogs are collectively known as retinoids. The importance and essentiality of retinoids to human health, facilitating normal vision, reproduction, immune function, and cell differentiation have been widely shown and established [9
]. In recent years, the importance of retinoids in adipose tissue biology, obesity and type II diabetes has become apparent. This review will focus on recent new developments within the area of retinoids and adipose tissue biology.