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

To evaluate the impact of gender and ablation of β-carotene oxygenase 1 (BCO1), β-carotene oxygenase 2(BCO2) or both on tissue accumulation of lycopene dosed transgenic mice. Previous work from our laboratories suggests that BCO2 appears to be the primary carotenoid cleavage enzyme for lycopene in vivo. Three-week old C57BL/6 male and female mice (wild type [WT], Bco1-/-, Bco2-/-, Bco1-/- X Bco2-/- double knock out [DKO]) were divided into groups based on genotype (n = 8 per group/per gender) and fed a powdered AIN 93G diet for 2 weeks. The mice were gavaged daily for 2 weeks with 1 mg of lycopene dissolved in cottonseed oil after which they were fasted and sacrificed. Liver, serum, and extra-hepatic tissues were harvested. Lycopene concentration was measured with high-performance liquid chromatography. Data analyses were performed using one-way ANOVA. On a concentration basis, liver, duodenum and adrenal lycopene were higher than other tissues. Serum and tissues of DKO mice accumulated the highest lycopene. DKO mice had significantly higher lycopene than Bco1-/- mice in the liver (P < .002), heart (P < .004), adipose (P < .03), and the testes (P < .004). Compared to Bco2-/- mice, DKO mice had greater accumulation in the serum (P < .001), intestine (P < .04), heart (P < .0001), kidneys (P < .0001), adipose (P < .04), and testes (P < .0001). Liver (P < .007) and adrenal (ns) tissues in Bco2-/- mice had higher levels of lycopene than Bco1-/- mice whereas Bco1-/- mice had significantly higher levels in the kidneys (P < .001) and tended to have greater accumulation in other tissues. Accumulation of lycopene in tissues depended upon gender, genotype and tissue type. The abolition of both enzymes and mice of a female sex generated a higher accumulation. We are probing whether tissue-specific expression levels of BCO1, BCO2 or carotenoid transport proteins explain differential tissue accumulation across genotypes. N/A.