Host‐related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans
In vitro studies have suggested that lycopene is an efficient substrate for carotenoid 9'10'-monooxygenase II (CMO2) but an inhibitor of carotenoid 15,15'-monooxygenase I (CMO1). The objectives of this study were to clone the rat CMO2 gene, determine whether feeding lycopene for different lengths of time (3-37 d) altered the expression of genes related to carotenoid cleavage [CMO1, CMO2 and peroxisomal proliferator-activated receptor gamma (PPAR-gamma)] or increased the activity of selected phase I and phase II detoxification enzymes in rat tissues. The cloned rat CMO2 gene was 92 and 82% homologous to the mouse and human CMO2 nucleotide sequence, respectively. The relative abundance of CMO1, CMO2, and PPAR-gamma were differentially expressed among rat tissues. CMO1 and PPAR-gamma expression were decreased in the kidney and adrenal with lycopene intake (P < 0.05), whereas CMO2 expression was reduced only in the kidney. Lycopene did not alter hepatic phase I activity, but hepatic quinone reductase activity increased after 3 and 7 d of lycopene feeding (P < 0.05). Lycopene intake decreased a PPAR-gamma target gene, fatty acid binding protein 3 (FABP3), in the kidney and adrenal (P < 0.05). Thus, these data show that although the intake of 0.25 g lycopene/kg diet does not induce hepatic P450 detoxification enzymes, lycopene feeding alters CMO1, PPAR-gamma, and FABP3 mRNA expression in selected rat tissues with a moderate effect on kidney CMO2 expression. These data suggest that lycopene may play an important role in the modulation of beta-carotene, retinoid, and/or lipid metabolism.