Xanthohumol ameliorates Diet-Induced Liver Dysfunction via Farnesoid X Receptor-Dependent and Independent Signaling.
Xanthohumol ameliorates Diet-Induced Liver Dysfunction via Farnesoid X Receptor-Dependent and Independent Signaling.
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黄腐酚通过Farnesoid X受体依赖和独立信号通路改善饮食诱导的肝功能障碍。
DOI：
10.3389/fphar.2021.643857
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发表时间：
2021
影响因子：
5.6
通讯作者：
Stevens JF
中科院分区：
文献类型：
--
作者：
Paraiso IL;Tran TQ;Magana AA;Kundu P;Choi J;Maier CS;Bobe G;Raber J;Kioussi C;Stevens JF
farnesoid X受体（FXR）在调节脂质和胆汁酸（BA）稳态中起关键作用。肝脏FXR缺失导致脂质和BA积累，并从肝脂肪变性发展为非酒精性脂肪性肝炎（NASH）。本研究旨在评价黄腐酚（XN）对饮食和FXR缺乏引起的小鼠肝损伤的影响。野生型（WT）和肝脏特异性fxr缺失小鼠（FXRLiver - / -）被喂食含有XN的高脂肪饲料（HFD）或载体形成，然后进行组织学表征、脂质、BA和基因分析。HFD添加XN可改善FXRLiver - / -小鼠的肝脏脂肪变性，降低BA浓度，且在雄性小鼠中效果更强。XN诱导FXRLiver - / -小鼠肝脏组成型雄甾烷受体（CAR）、孕激素X受体（PXR）和糖皮质激素受体（GR）基因表达。这些发现表明，激活BA解毒途径是控制FXRLiver - / -小鼠疏水BA浓度的主要机制。总的来说，这些数据表明FXR、脂质和BAs之间存在性别依赖关系，并表明XN通过FXR依赖和独立的信号通路改善hfd诱导的肝功能障碍。
The farnesoid X receptor (FXR) plays a critical role in the regulation of lipid and bile acid (BA) homeostasis. Hepatic FXR loss results in lipid and BA accumulation, and progression from hepatic steatosis to nonalcoholic steatohepatitis (NASH). This study aimed to evaluate the effects of xanthohumol (XN), a hop-derived compound mitigating metabolic syndrome, on liver damage induced by diet and FXR deficiency in mice. Wild-type (WT) and liver-specific FXR-null mice (FXRLiver−/−) were fed a high-fat diet (HFD) containing XN or the vehicle formation followed by histological characterization, lipid, BA and gene profiling. HFD supplemented with XN resulted in amelioration of hepatic steatosis and decreased BA concentrations in FXRLiver−/− mice, the effect being stronger in male mice. XN induced the constitutive androstane receptor (CAR), pregnane X receptor (PXR) and glucocorticoid receptor (GR) gene expression in the liver of FXRLiver−/− mice. These findings suggest that activation of BA detoxification pathways represents the predominant mechanism for controlling hydrophobic BA concentrations in FXRLiver−/− mice. Collectively, these data indicated sex-dependent relationship between FXR, lipids and BAs, and suggest that XN ameliorates HFD-induced liver dysfunction via FXR-dependent and independent signaling.
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影响因子：
5.6
作者：
Garcia M;Thirouard L;Sedès L;Monrose M;Holota H;Caira F;Volle DH;Beaudoin C
通讯作者：
Beaudoin C
影响因子：
4.8
作者：
Guo, GL;Lambert, G;Sinal, CJ
通讯作者：
Sinal, CJ
影响因子：
3.5
作者：
Carazo, Alejandro;Hyrsova, Lucie;Pavek, Petr
通讯作者：
Pavek, Petr
影响因子：
13.5
作者：
Choi, Steve S.;Sicklick, Jason K.;Diehl, Anna Mae
通讯作者：
Diehl, Anna Mae
影响因子：
5.8
作者：
Chiang JY
通讯作者：
Chiang JY