title: Cardiac dysfunction in β-carotene-15,15'-dioxygenase-deficient mice is associated with altered retinoid and lipid metabolism.
abstract: Dietary carotenoids like β-carotene are converted within the body either to retinoid, via β-carotene-15,15'-dioxygenase (BCO1), or to β-apo-carotenoids, via β-carotene-9',10'-oxygenase 2. Some β-apo-carotenoids are potent antagonists of retinoic acid receptor (RAR)-mediated transcriptional regulation, which is required to ensure normal heart development and functions. We established liquid chromatography tandem mass spectrometery methods for measuring concentrations of 10 β-apo-carotenoids in mouse plasma, liver, and heart and assessed how these are influenced by Bco1 deficiency and β-carotene intake. Surprisingly, Bco1(-/-) mice had an increase in heart levels of retinol, nonesterified fatty acids, and ceramides and a decrease in heart triglycerides. These lipid changes were accompanied by elevations in levels of genes important to retinoid metabolism, specifically retinol dehydrogenase 10 and retinol-binding protein 4, as well as genes involved in lipid metabolism, including peroxisome proliferator-activated receptor-γ, lipoprotein lipase, Cd36, stearoyl-CoA desaturase 1, and fatty acid synthase. We also obtained evidence of compromised heart function, as assessed by two-dimensional echocardiography, in Bco1(-/-) mice. However, the total absence of Bco1 did not substantially affect β-apo-carotenoid concentrations in the heart. β-Carotene administration to matched Bco1(-/-) and wild-type mice elevated total β-apo-carotenal levels in the heart, liver, and plasma and total β-apo-carotenoic acid levels in the liver. Thus, BCO1 modulates heart metabolism and function, possibly by altering levels of cofactors required for the actions of nuclear hormone receptors.
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York;
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York;
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York;
authors.forename: Chad M
authors.initials: CM
authors.lastname: Trent
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York;
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Yuen
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, Ohio; and Department of Human Nutrition, The Ohio State University, Columbus, Ohio.
authors.forename: Sureshbabu
authors.initials: S
authors.lastname: Narayanasamy
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, Ohio; and.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Curley
authors.affiliation: Department of Human Nutrition, The Ohio State University, Columbus, Ohio.
authors.forename: Earl H
authors.initials: EH
authors.lastname: Harrison
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York;
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York;
authors.forename: Mathew S
authors.initials: MS
authors.lastname: Maurer
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York; wsb2@columbia.edu.
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
mesh_terms: D000818:Animals; D002338:Carotenoids / Q000378:metabolism; D006331:Heart Diseases / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D006706:Homeostasis; D050356:Lipid Metabolism / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000172:deficiency* / Q000235:genetics*
chemical_list: D012176:Retinoids; D002338:Carotenoids; C493359:Bco1 protein, mouse; D050559:beta-Carotene 15,15'-Monooxygenase
keywords: heart; liquid chromatography tandem mass spectrometry; retinoic acid; retinoid; β-carotene