Differential bioavailability, clearance, and tissue distribution of the acyclic tomato carotenoids lycopene and phytoene in mongolian gerbils.

Lycopene (LYC) is the major tomato carotenoid and is the focus of substantial research. Phytoene (PE), a minor tomato carotenoid, is found in human blood and tissues in similar concentrations to LYC. To determine which metabolic differences underlie this phenomenon, Mongolian gerbils (Meriones unguiculatus, n = 56) were fed control or tomato powder (TP)-containing diets (to establish steady-state serum and tissue carotenoid concentrations similar to tomato-fed humans) for 26 d. The TP-fed gerbils were then provided either a single, oral, cottonseed oil (CO) vehicle dose and tissues were collected at 6 h or they were provided unlabeled PE or LYC in CO and tissues were evaluated at 6, 12, or 24 h. In vehicle-dosed, TP-fed gerbils, LYC was the major carotenoid (≥ 55% carotenoids) in liver, spleen, testes, and the prostate-seminal vesicle complex, whereas PE was the major serum and adipose carotenoid (≥ 37% total carotenoid) and phytofluene was the major carotenoid (≥ 38%) in adrenals and lungs. PE dosing increased hepatic, splenic, and serum PE concentrations compared with vehicle dosing (P < 0.05) from 6 to 24 h, whereas LYC dosing increased only serum LYC at 6 and 12 h (P < 0.05) compared with vehicle dosing. This suggested PE was more bioavailable and cleared more slowly than LYC. To precisely track absorptive and distributive differences, (14)C-PE or (14)C-LYC (n = 2/group) was provided to TP-fed gerbils. Bioavailability assessed by carcass (14)C-content was 23% for PE and 8% for LYC. Nearly every extra-hepatic tissue accumulated greater dose radioactivity after (14)C-PE than (14)C-LYC dosing. Thus, LYC and PE, which structurally differ only by saturation, pharmacokinetically differ in bioavailability, tissue deposition, and clearance.

Biosynthesis of highly enriched 13C-lycopene for human metabolic studies using repeated batch tomato cell culturing with 13C-glucose.

While putative disease-preventing lycopene metabolites are found in both tomato (Solanum lycopersicum) products and in their consumers, mammalian lycopene metabolism is poorly understood. Advances in tomato cell culturing techniques offer an economical tool for generation of highly-enriched (13)C-lycopene for human bioavailability and metabolism studies. To enhance the (13)C-enrichment and yields of labelled lycopene from the hp-1 tomato cell line, cultures were first grown in (13)C-glucose media for three serial batches and produced increasing proportions of uniformly labelled lycopene (14.3±1.2%, 39.6±0.5%, and 48.9±1.5%) with consistent yields (from 5.8 to 9 mg/L). An optimised 9-day-long (13)C-loading and 18-day-long labelling strategy developed based on glucose utilisation and lycopene yields, yielded (13)C-lycopene with 93% (13)C isotopic purity, and 55% of isotopomers were uniformly labelled. Furthermore, an optimised acetone and hexane extraction led to a fourfold increase in lycopene recovery from cultures compared to a standard extraction.

An interaction between carotene-15,15'-monooxygenase expression and consumption of a tomato or lycopene-containing diet impacts serum and testicular testosterone.

Lycopene, the red pigment of tomatoes, is hypothesized to reduce prostate cancer risk, a disease strongly dependent upon testosterone. In this study, mice lacking the expression of carotene-15,15'-monooxygenase (CMO-I(-/-) ) or wild-type mice were fed either a 10% tomato powder (TP), lycopene-containing (248 nmol/g diet) or their respective control diets for 4 days, after which serum testosterone was measured. A significant diet × genotype interaction (p = 0.02) suggests that the TP reduces serum testosterone concentrations in CMO-I(-/-) mice but not in wild-type mice. Similarly, testicular testosterone was lowered in TP-fed CMO-I(-/-) mice (p = 0.01), suggesting that testosterone synthesis may be inhibited in this group. A similar pattern was also observed for lycopene fed mice. Interestingly, the CMO-I(-/-) mice showed a greater expression of the gene encoding the CMO-II enzyme responsible for eccentric oxidative carotenoid cleavage in the testes. Therefore, we hypothesize that serum testosterone is reduced by lycopene metabolic products of oxidative cleavage by CMO-II in the testes. Overall, these findings suggest that genetic polymorphisms impacting CMO-I expression and its interaction with CMO-II, coupled with variations in dietary lycopene, may modulate testosterone synthesis and serum concentrations. Furthermore, carefully controlled studies with tomato products and lycopene in genetically defined murine models may elucidate important diet × genetic interactions that may impact prostate cancer risk.