title: Lycopene biodistribution is altered in 15,15'-carotenoid monooxygenase knockout mice.
abstract: 15,15'-carotenoid monooxygenase (CMO I) is generally recognized as the central carotenoid cleavage enzyme responsible for converting provitamin A carotenoids to vitamin A, while having little affinity for nonprovitamin A carotenoids, such as lycopene. To investigate the role of CMO I in carotenoid metabolism, approximately 90-d-old C57BL/6 x 129/SvJ [CMO I wild-type (WT)] and B6;129S6-Bcmo1tm1Dnp [CMO I knockout (KO)] mice were fed a high-fat, moderate vitamin A, cholesterol-containing diet supplemented with 150 mg/kg diet of beta-carotene, lycopene, or placebo beadlets for 60 d (n = 12-14). CMO I KO mice fed lycopene (Lyc-KO) exhibited significant decreases in hepatic, spleen, and thymus lycopene concentrations and significant increases in prostate, seminal vesicles, testes, and brain lycopene concentrations compared with WT mice fed lycopene (Lyc-WT). Furthermore, in the serum and all tissues analyzed, excluding the testes, there was a significant increase in the percent lycopene cis isomers in Lyc-KO mice compared with Lyc-WT mice. CMO I KO mice fed beta-carotene (betaC-KO) had significantly lower hepatic vitamin A concentrations (17% of WT mice fed beta-carotene [betaC-WT]). Concordantly, betaC-KO mice had higher serum and tissue beta-carotene concentrations than betaC-WT mice. In addition, phenotypically CMO I KO mice had significantly higher final body weights and CMO I KO female mice had significantly lower uterus weights than CMO I WT mice. In conclusion, CMO I KO mice fed low levels of vitamin A have altered lycopene biodistribution and isomer patterns and do not cleave beta-carotene to vitamin A at appreciable levels.
authors.affiliation: Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Lindshield
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: King
authors.forename: Adrian
authors.initials: A
authors.lastname: Wyss
authors.forename: Regina
authors.initials: R
authors.lastname: Goralczyk
authors.forename: Chi-Hua
authors.initials: CH
authors.lastname: Lu
authors.forename: Nikki A
authors.initials: NA
authors.lastname: Ford
authors.forename: John W
authors.initials: JW
authors.lastname: Erdman
mesh_terms: D000818:Animals; D002338:Carotenoids / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D004032:Diet; D005260:Female; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D000077276:Lycopene; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012176:Retinoids / Q000097:blood / Q000378:metabolism; D014018:Tissue Distribution; D019207:beta Carotene / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D050559:beta-Carotene 15,15'-Monooxygenase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D012176:Retinoids; D019207:beta Carotene; D002338:Carotenoids; D002784:Cholesterol; C493359:Bco1 protein, mouse; D050559:beta-Carotene 15,15'-Monooxygenase; D000077276:Lycopene