Lycopene Accumulation in Transgenic Mice Lacking One or Both Carotenoid Cleaving Enzymes

Background: β-carotene oxygenase 1 (BCO1) and β-carotene oxygenase 2 (BCO2) are responsible for the cleavage of carotenoids in mammals. Objective: The goals of this study were to (1) establish the relative contribution of each enzyme on lycopene accumulation in mice and (2) examine the role of lycopene on gene expression in the gut of wild type (WT) mice. Methods: We utilized male and female WT, Bco1^-/-, Bco2^-/-, and Bco1^-/- Bco2^-/- double knockout (DKO) mice. We gavaged the mice with either 1 mg of lycopene resuspended in cottonseed oil or vehicle as a control group daily for 2 wk. In a second study, we evaluated the effect of dietary vitamin A on lycopene absorption and intestinal gene expression by RT-PCR. We also quantified lycopene concentration isomer distribution by high performance liquid chromatography. Results: Of the 11 tissues measured, the liver accounted for 94 to 98% of the lycopene content across genotypes. We did not observe sex differences between genotypes, although hepatic lycopene levels in Bco1^-/- mice were approximately half in comparison to the other genotypes; Bco1^-/- verses Bco2^-/- (P < 0.0001), DKO mice (P < 0.001), WT (ns). Analyses of mitochondrial lycopene content revealed a 3- to 5-fold enrichment compared with total hepatic content (P < 0.05) in all genotypes and sexes. In our second study, WT mice fed a vitamin A-deficient diet (VAD) accumulated greater amounts of lycopene in the liver than those fed a vitamin A-sufficient diet (VAS) (P < 0.01). These changes were accompanied by an upregulation of the vitamin A-responsive transcription factor intestine specific homeobox (ISX) in mice fed VAD + lycopene and VAS + lycopene diets compared with VAD control-fed mice (P < 0.05). Conclusions: Our data suggest that BCO2 is the primary lycopene cleavage enzyme in mice. Lycopene concentration was enriched in the mitochondria of hepatocytes independently of genotype, and lycopene stimulated vitamin A signaling in WT mice.