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β-胡萝卜素-9',10'-加氧酶状态调节膳食番茄和番茄红素对小鼠肝脏核受体、应激和代谢相关基因表达的影响。

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.

机构信息

The Interdisciplinary Program in Nutrition.

出版信息

J Nutr. 2014 Apr;144(4):431-9. doi: 10.3945/jn.113.186676. Epub 2014 Feb 19.

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.

摘要

番茄和番茄红素(ψ,ψ-胡萝卜素)的摄入被认为可以预防非酒精性脂肪性肝炎和肝癌的发生,而这些过程可能依赖于饮食和基因相互作用。为了研究番茄或番茄红素喂养与β-胡萝卜素-9',10'-单加氧酶(Bco2)对肝代谢和信号通路的相互作用,雄性野生型(WT)和 Bco2(-/-)小鼠(3 周龄;n = 36)分别用半纯化对照、含 10%番茄粉或含 0.25%番茄红素珠的饮食喂养 3 周。与 WT 相比,喂食番茄红素和番茄红素的 Bco2(-/-)小鼠的血清番茄红素浓度更高(P = 0.03)。喂食番茄红素和番茄红素的小鼠可检测到肝载脂蛋白(apo)-6'、apo-8'和 apo-12'-lycopenal 浓度。与 WT 相比,Bco2(-/-)小鼠的β-胡萝卜素-15,15'-单加氧酶表达增加(P = 0.02),但不受饮食影响。通过针对核受体和共激活因子(84 个基因)和应激和代谢(82 个基因)基因的聚焦定量逆转录聚合酶链反应(qRT-PCR)阵列评估肝基因表达表明,番茄喂养影响了 31 个基因(≥1.5 倍,P <0.05),而番茄红素喂养影响了 19 个基因,其中 16 个基因受两种饮食影响。番茄红素下调 7 个核受体和共激活因子、雌激素相关受体-α、组蛋白去乙酰化酶 3、核受体共激活因子 4、RevErbA-β、糖皮质激素受体、过氧化物酶体增殖物激活受体(PPAR)-α和 PPAR-γ、共激活因子 1β,这依赖于与 Bco2 状态的相互作用。番茄红素和番茄红素喂养诱导的基因表达模式与脂质摄取减少、细胞增殖和有丝分裂减少、芳烃受体信号下调以及参与视黄酸 X 受体异二聚体激活的基因表达减少一致。番茄红素喂养还导致 DNA 合成和萜类代谢下调的表达变化。这些数据表明,番茄红素可能影响肝基因表达,从而影响肝对代谢、感染或化学应激的反应。

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