title: Retinoid absorption and storage is impaired in mice lacking lecithin:retinol acyltransferase (LRAT).
abstract: Lecithin:retinol acyltransferase (LRAT) is believed to be the predominant if not the sole enzyme in the body responsible for the physiologic esterification of retinol. We have studied Lrat-deficient (Lrat-/-) mice to gain a better understanding of how these mice take up and store dietary retinoids and to determine whether other enzymes may be responsible for retinol esterification in the body. Although the Lrat-/- mice possess only trace amounts of retinyl esters in liver, lung, and kidney, they possess elevated (by 2-3-fold) concentrations of retinyl esters in adipose tissue compared with wild type mice. These adipose retinyl ester depots are mobilized in times of dietary retinoid insufficiency. We further observed an up-regulation (3-4-fold) in the level of cytosolic retinol-binding protein type III (CRBPIII) in adipose tissue of Lrat-/- mice. Examination by electron microscopy reveals a striking total absence of large lipid-containing droplets that normally store hepatic retinoid within the hepatic stellate cells of Lrat-/- mice. Despite the absence of significant retinyl ester stores and stellate cell lipid droplets, the livers of Lrat-/- mice upon histologic analysis appear normal and show no histological signs of liver fibrosis. Lrat-/- mice absorb dietary retinol primarily as free retinol in chylomicrons; however, retinyl esters are also present within the chylomicron fraction obtained from Lrat-/- mice. The fatty acyl composition of these (chylomicron) retinyl esters suggests that they are synthesized via an acyl-CoA-dependent process suggesting the existence of a physiologically significant acyl-CoA:retinol acyltransferase.
authors.affiliation: Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Sheila M
authors.initials: SM
authors.lastname: O'Byrne
authors.forename: Nuttaporn
authors.initials: N
authors.lastname: Wongsiriroj
authors.forename: Jenny
authors.initials: J
authors.lastname: Libien
authors.forename: Silke
authors.initials: S
authors.lastname: Vogel
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baehr
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
mesh_terms: D000217:Acyltransferases / Q000235:genetics* / Q000502:physiology*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D002914:Chylomicrons / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008862:Microsomes, Liver / Q000378:metabolism; D011863:Radioimmunoassay; D012737:Sex Factors; D013997:Time Factors; D014018:Tissue Distribution; D014212:Tretinoin / Q000378:metabolism* / Q000493:pharmacokinetics*; D014801:Vitamin A / Q000737:chemistry
chemical_list: D002914:Chylomicrons; D008055:Lipids; D014801:Vitamin A; D014212:Tretinoin; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase