title: Loss of β-carotene 15,15'-oxygenase in developing mouse tissues alters esterification of retinol, cholesterol and diacylglycerols.
abstract: We provide novel insights into the function(s) of β-carotene-15,15'-oxygenase (CMOI) during embryogenesis. By performing in vivo and in vitro experiments, we showed that CMOI influences not only lecithin:retinol acyltransferase but also acyl CoA:retinol acyltransferase reaction in the developing tissues at mid-gestation. In addition, LC/MS lipidomics analysis of the CMOI-/- embryos showed reduced levels of four phosphatidylcholine and three phosphatidylethanolamine acyl chain species, and of eight triacylglycerol species with four or more unsaturations and fifty-two or more carbons in the acyl chains. Cholesteryl esters of arachidonate, palmitate, linoleate, and DHA were also reduced to less than 30% of control. Analysis of the fatty acyl CoA species ruled out a loss in fatty acyl CoA synthetase capability. Comparison of acyl species suggested significantly decreased 18:2, 18:3, 20:1, 20:4, or 22:6 acyl chains within the above lipids in CMOI-null embryos. Furthermore, LCAT, ACAT1 and DGAT2 mRNA levels were also downregulated in CMOI-/- embryos. These data strongly support the notion that, in addition to cleaving β-carotene to generate retinoids, CMOI serves an additional function(s) in retinoid and lipid metabolism and point to its role in the formation of specific lipids, possibly for use in nervous system tissue.
authors.affiliation: Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ 08901, USA; Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901, USA.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Dixon
authors.forename: Youn-Kyung
authors.initials: YK
authors.lastname: Kim
authors.forename: Anita
authors.initials: A
authors.lastname: Brinker
authors.forename: Loredana
authors.initials: L
authors.lastname: Quadro
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D000214:Acyl Coenzyme A / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D051048:Diacylglycerol O-Acyltransferase / Q000096:biosynthesis / Q000235:genetics; D004075:Diglycerides / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D004622:Embryo, Mammalian / Q000201:enzymology*; D004951:Esterification / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009417:Nerve Tissue / Q000196:embryology / Q000201:enzymology; D014801:Vitamin A / Q000235:genetics / Q000378:metabolism*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics / Q000378:metabolism*
chemical_list: D000214:Acyl Coenzyme A; D004075:Diglycerides; D014801:Vitamin A; D002784:Cholesterol; C493359:Bco1 protein, mouse; D050559:beta-Carotene 15,15'-Monooxygenase; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase; C506641:Acat1 protein, mouse; D000101:Acetyl-CoA C-Acetyltransferase
keywords: Acylation reaction; CMOI; CMOII; Gene expression; PC; PE; PI; PS; bC; phosphatidylcholine; phosphatidylethanolamine; phosphatidylinositol; phosphatidylserine; β-Carotene; β-Carotene cleavage enzyme; β-carotene; β-carotene 15,15′-oxygenase; β-carotene-9′,10′-oxygenase