title: 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.
authors.affiliation: The Interdisciplinary Program in Nutrition.
authors.forename: Hsueh-Li
authors.initials: HL
authors.lastname: Tan
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Moran
authors.forename: Morgan J
authors.initials: MJ
authors.lastname: Cichon
authors.forename: Ken M
authors.initials: KM
authors.lastname: Riedl
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Schwartz
authors.forename: John W
authors.initials: JW
authors.lastname: Erdman
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Pearl
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Thomas-Ahner
authors.forename: Steven K
authors.initials: SK
authors.lastname: Clinton
mesh_terms: D000818:Animals; D002338:Carotenoids / Q000008:administration & dosage / Q000627:therapeutic use*; D004247:DNA / Q000096:biosynthesis; D019587:Dietary Supplements; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005638:Fruit / Q000737:chemistry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease; D056918:Nuclear Receptor Coactivators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011897:Random Allocation; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D056918:Nuclear Receptor Coactivators; D018160:Receptors, Cytoplasmic and Nuclear; D014280:Triglycerides; D002338:Carotenoids; D004247:DNA; D049308:Dioxygenases; C481678:Bco2 protein, mouse; D000077276:Lycopene