title: Tissue- and sex-specific effects of β-carotene 15,15' oxygenase (BCO1) on retinoid and lipid metabolism in adult and developing mice.
abstract: In mammals, β-carotene-15,15'-oxygenase (BCO1) is the main enzyme that cleaves β-carotene, the most abundant vitamin A precursor, to generate retinoids (vitamin A derivatives), both in adult and developing tissues. We previously reported that, in addition to this function, BCO1 can also influence the synthesis of retinyl esters, the storage form of retinoids, in the mouse embryo at mid-gestation. Indeed, lack of embryonic BCO1 impaired both lecithin-dependent and acyl CoA-dependent retinol esterification, mediated by lecithin:retinol acyltransferase (LRAT) and acyl CoA:retinol acyltransferase (ARAT), respectively. Furthermore, embryonic BCO1 also influenced the ester pools of cholesterol and diacylglycerol. In this report, we gained novel insights into this alternative function of BCO1 by investigating whether BCO1 influenced embryonic retinoid and lipid metabolism in a tissue-dependent manner. To this end, livers and brains from wild-type and BCO1-/- embryos at mid-gestation were analyzed for retinoid and lipid content, as well as gene expression levels. We also asked whether or not the role of BCO1 as a regulator of lecithin- and acyl CoA-dependent retinol esterification was exclusively restricted to the developing tissues. Thus, a survey of retinol and retinyl ester levels in adult tissues of wild-type, BCO1-/-, LRAT-/- and LRAT-/-BCO1-/- mice was performed. We showed that the absence of BCO1 affects embryonic retinoid and lipid homeostasis in a tissue-specific manner and that retinyl ester formation is also influenced by BCO1 in a few adult tissues (pancreas, lung, heart and adipose) in a sex-dependent manner.
authors.affiliation: Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08091, USA.
authors.forename: Youn-Kyung
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08091, USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Zuccaro
authors.affiliation: Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08091, USA.
authors.forename: Brianna K
authors.initials: BK
authors.lastname: Costabile
authors.affiliation: Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08091, USA.
authors.forename: Rebeka
authors.initials: R
authors.lastname: Rodas
authors.affiliation: Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08091, USA. Electronic address: quadro@aesop.rutgers.edu.
authors.forename: Loredana
authors.initials: L
authors.lastname: Quadro
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D049308:Dioxygenases / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D005838:Genotype; D006706:Homeostasis; D050356:Lipid Metabolism; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008297:Male; D051379:Mice; D009928:Organ Specificity; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism*; D012727:Sex Characteristics; D050559:beta-Carotene 15,15'-Monooxygenase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D012176:Retinoids; D049308:Dioxygenases; C481678:Bco2 protein, mouse; D050559:beta-Carotene 15,15'-Monooxygenase
keywords: Adult organs; Embryonic organs; Retinoid metabolism; β-Carotene 15,15′ oxygenase (BCO1 or CMOI or BCMO1); β-Carotene metabolism