Vitamin A (retinol) plays an important role in vision and has pleiotropic functions in immune response, hematopoiesis, fertility, cell differentiation, growth, and morphogenesis (1). Both retinol deficiency and excessive doses of retinol cause malformations in the embryos of many vertebrate species, demonstrating that retinol plays an important role in embryogenesis. Retinoic acids, derivatives of retinol, act as the ligands of retinoic acid receptors (RAR) and retinoid X receptors (RXR), which are members of the nuclear receptor superfamily and are ligand-dependent transcriptional factors (2). RAR and RXR have subtypes (a, b, and g), and 9-cis retinoic acid (an isomer of retinoic acid) binds RARs and RXRs, whereas all-trans retinoic acid binds only RARs. Both types of retinoic acid receptors transcriptionally regulate the expression of target genes and exert multiple physiological functions.Dietary retinol has 2 major forms: retinyl esters derived from animal sources and provitamin A carotenoids, mainly in the form of b-carotene, derived from plants (3,4). Dietary retinyl esters are emulsified with fatty acids and bile salts and then micellized before hydrolysis in the lumen of the small intestine for retinol uptake. In the enterocytes, retinol is rapidly re-esterified with long-chain fatty acids. b-Carotene is absorbed in intestinal mucosal cells and then cleaved for retinal formation. b-Carotene 15,15′-monooxygenase (BCMO), the key enzyme of this process, cleaves b-carotene into 2 molecules of retinal, which are then esterified to retinyl ester in the intestine (4). Retinyl esters that are incorporated into chylomicrons are secreted from enterocytes and transferred to the liver through the lymphatic circulation. Chylomicrons containing retinyl esters are taken up by the liver and transferred to hepatic stellate cells (HSCs) for storage. Retinol in the liver is esterified by the enzyme lecithin:retinol acyltransferase (LRAT) to form retinyl esters. The transfer of retinol in the liver is mediated by cellular retinol binding protein (CRBP)-I, which delivers retinol to retinol binding protein (RBP) for secretion into the circulation. Retinoic acid levels are tightly regulated at the biosynthesis and oxidation stages (3). Retinol is reversibly oxidized to retinal by retinol dehydrogenases, and retinal is irreversibly oxidized to retinoic acid by members of the retinal dehydrogenase (ALDH) family. As mentioned above, the biological actions of retinoic acid isomers (all-trans and 9-cis forms) are conducted through their role as RAR and RXR ligands. Retinoic acids are oxidized by the cytochrome P450 26 family (CYP26A1, CYP26B1, and CYP26C1), following which their metabolites are conjugated with glucuronic acid.Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases in developed countries, and Pediatrics, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Kita-ku, Sakai, Osaka 591-8025, Japan (Received October 9, 2013 Summary Retinol and its derivative, retinoic acid, have pleiotropic functions includ...