β-Carotene-9′,10′-Oxygenase Status Modulates the Impact of Dietary Tomato and Lycopene on Hepatic Nuclear Receptor–, Stress-, and Metabolism-Related Gene Expression in Mice

Abstract

Tomato and lycopene (ψ,ψ-carotene) consumption is hypothesized to protect against nonalcoholic steatohepatitis and hepatocarcinogenesis, processes that may depend upon diet and gene interactions. To investigate the interaction of tomato or lycopene feeding with β-carotene-9',10'-monooxygenase (Bco2) on hepatic metabolic and signaling pathways, male wild-type (WT) and Bco2(-/-) mice (3-wk-old; n = 36) were fed semi-purified control, 10% tomato powder-containing, or 0.25% lycopene beadlet-containing diets for 3 wk. Serum lycopene concentrations were higher in lycopene- and tomato-fed Bco2(-/-) mice compared with WT (P = 0.03). Tomato- and lycopene-fed mice had detectable hepatic apolipoprotein (apo)-6'-, apo-8'-, and apo-12'-lycopenal concentrations. Hepatic expression of β-carotene-15,15'-monooxygenase was increased in Bco2(-/-) mice compared with WT (P = 0.02), but not affected by diet. Evaluation of hepatic gene expression by focused quantitative reverse transcriptase-polymerase chain reaction arrays for nuclear receptors and coregulators (84 genes) and stress and metabolism (82 genes) genes indicates that tomato feeding affected 31 genes (≥1.5-fold, P < 0.05) and lycopene feeding affected 19 genes, 16 of which were affected by both diets. Lycopene down-regulation of 7 nuclear receptors and coregulators, estrogen-related receptor-α, histone deacetylase 3, nuclear receptor coactivator 4, RevErbA-β, glucocorticoid receptor, peroxisome proliferator-activated receptor (PPAR)-α, and PPAR-γ, coactivator 1 β was dependent upon interaction with Bco2 status. Lycopene and tomato feeding induced gene expression patterns consistent with decreased lipid uptake, decreased cell proliferation and mitosis, down-regulated aryl hydrocarbon receptor signaling, and decreased expression of genes involved in retinoid X receptor heterodimer activation. Tomato feeding also caused expression changes consistent with down-regulation of DNA synthesis and terpenoid metabolism. These data suggest tomato components, particularly lycopene, affect hepatic gene expression, potentially affecting hepatic responses to metabolic, infectious, or chemical stress.

Lycopene and Apo-10′-lycopenoic Acid Have Differential Mechanisms of Protection against Hepatic Steatosis in β-Carotene-9′,10′-oxygenase Knockout Male Mice

“…Nevertheless, it should be noted that lycopene effects on PPARa-and PPARg-mediated signaling were relatively modest; thus, this might explain why lycopene did not reduce final BW. Lycopene modulations in PPAR-associated signaling were observed in the adrenal glands, liver, and kidney of rodents in previous studies (16,50,51). During the preparation of this manuscript, a recent publication by Tan et al (50) showed that 3wk-old BCO2-KO male mice on a lycopene-supplemented (250 mg/ kg diet) AIN-93G semipurified diet for 3 wk modulated hepatic PPAR-associated signaling that could potentially affect hepatic responses to metabolic, infectious, or chemical stress.…”

Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-Related Gene Expression during Early TRAMP Prostate Carcinogenesis

“…Male TRAMP (+/-) C57BL/6×FVB/N hybrid and male C57BL/6 controls (Jackson Laboratory, Bar Harbor, ME) were used. Tomato and lycopene diets were formulated to provide blood and tissue concentrations of lycopene similar to humans (19). TRAMP mice weaned at 4 wk-of-age were randomized to one of three semi-purified AIN-93G-based diets (ResearchDiets, New Brunswick, NJ) with either 0.25% ( w/w ) placebo beadlets (DSM, Basel, Switzerland), 10% ( w/w ) tomato powder providing 384 mg lycopene/kg diet (FutureCeuticals, Momence, IL ) [with 0.25% ( w/w ) placebo beadlets], or 0.25% ( w/w ) lycopene beadlets (RediVivo 10% lycopene, DSM) providing 462 mg lycopene/kg diet, as previously described (19).…”

Cardiovascular benefits of lycopene: fantasy or reality?

“…The induction of cell differentiation (52) via the restoration of gap junctions (57) has also been suggested. Other mechanisms include prevention of oxidative damage (58,59) , inhibition of angiogenesis (59,60) , induction of phase II enzymes (61)(62)(63) , interaction with growth factors and sex hormones (64) and the induction of nuclear receptors activation (65)(66)(67) . Lycopene has also been found to confer photoprotection (68) .…”