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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Lycopene Biodistribution Is Altered in 15,15'-Carotenoid Monooxygenase Knockout Mice^1–3,

⁴ Division of Nutritional Sciences, and ⁵ Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL 61801; and ⁶ DSM Nutritional Products, CH-4303 Kaiseraugst n. Basel, Switzerland

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, 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 β-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 β-carotene (βC-KO) had significantly lower hepatic vitamin A concentrations (17% of WT mice fed β-carotene [βC-WT]). Concordantly, βC-KO mice had higher serum and tissue β-carotene concentrations than βC-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 β-carotene to vitamin A at appreciable levels.

^* To whom correspondence should be addressed. E-mail: jwerdman{at}illinois.edu.

Manuscript received 15 September 2008. Initial review completed 22 September 2008. Revision accepted 3 October 2008.