佛手类黄酮已被证明可以预防代谢综合征,非酒精性脂肪性肝病(NAFLD)并刺激动物模型和患者的自噬。为了进一步研究多酚依赖效应的机制,我们对168种代谢进行了RT2-PCR阵列分析,在暴露于不同饮食14周的大鼠肝脏中表达的转运和自噬相关基因:标准,自助餐厅(CAF)和CAF饮食补充了50mg/kg的佛手多酚部分(BPF)。CAF饮食引起糖异生途径的强烈上调(Gck,Pck2)和调节脂肪生成的基因的中度(>1.7倍)诱导(Srebf1,Pparg,Xbp1),脂质和胆固醇转运或脂解(Fabp3,Apoa1,Lpl)和炎症(Il6,Il10,Tnf)。然而,与对照组相比,CAF大鼠中只有一个β-氧化基因(Cpt1a)和一些自噬基因差异表达。虽然这些转录物大部分被BPF显著调节,我们观察到对脂肪生成基因有特别有效的作用,像Acly,Acaca和Fasn,如基于替代引物的RT2-PCR分析和蛋白质印迹所证实的,其被抑制远低于对照肝脏的mRNA水平。这些作用伴随着促炎细胞因子的下调(Il6,Tnfa,和Il10)和糖尿病相关基因。很少有自噬(Map1Lc3a,与CAF组相比,Dapk)和未观察到β-氧化基因表达变化。总之,慢性BPF补充通过调节肝脏能量代谢和炎症基因表达程序有效预防NAFLD,对β-氧化没有影响,而是对从头脂肪生成的深刻抑制。
Bergamot flavonoids have been shown to prevent metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and stimulate autophagy in animal models and patients. To investigate further the mechanism of polyphenol-dependent effects, we performed a RT2-PCR array analysis on 168 metabolism, transport and autophagy-related genes expressed in rat livers exposed for 14 weeks to different diets: standard, cafeteria (CAF) and CAF diet supplemented with 50 mg/kg of bergamot polyphenol fraction (BPF). CAF diet caused a strong upregulation of gluconeogenesis pathway (Gck, Pck2) and a moderate (>1.7 fold) induction of genes regulating lipogenesis (Srebf1, Pparg, Xbp1), lipid and cholesterol transport or lipolysis (Fabp3, Apoa1, Lpl) and inflammation (Il6, Il10, Tnf). However, only one β-oxidation gene (Cpt1a) and a few autophagy genes were differentially expressed in CAF rats compared to controls. While most of these transcripts were significantly modulated by BPF, we observed a particularly potent effect on lipogenesis genes, like Acly, Acaca and Fasn, which were suppressed far below the mRNA levels of control livers as confirmed by alternative primers-based RT2-PCR analysis and western blotting. These effects were accompanied by downregulation of pro-inflammatory cytokines (Il6, Tnfa, and Il10) and diabetes-related genes. Few autophagy (Map1Lc3a, Dapk) and no β-oxidation gene expression changes were observed compared to CAF group. In conclusion, chronic BPF supplementation efficiently prevents NAFLD by modulating hepatic energy metabolism and inflammation gene expression programs, with no effect on β-oxidation, but profound suppression of de novo lipogenesis.