Dietary Isoquercetin Reduces Hepatic Cholesterol and Triglyceride in NAFLD Mice by Modulating Bile Acid Metabolism via Intestinal FXR-FGF15 Signaling,Journal of Agricultural and Food Chemistry

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Dietary Isoquercetin Reduces Hepatic Cholesterol and Triglyceride in NAFLD Mice by Modulating Bile Acid Metabolism via Intestinal FXR-FGF15 Signaling
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2023-05-11 , DOI: 10.1021/acs.jafc.3c00952
Ce Zhang _{1,

2} , Zunji Shi _{1,

3} , Hehua Lei ₁ , Fang Wu _{1,

2} , Chuan Chen _{1,

2} , Zheng Cao _{1,

2} , Yuchen Song _{1,

2} , Cui Zhang _{1,

2} , Jinlin Zhou _{4,

5} , Yujing Lu _{4,

6} , Limin Zhang _{1,

2}

Affiliation

Isoquercetin, a monosaccharide flavonoid, was recently reported to have significant amelioration effects on high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) of mice. However, the underlying mechanism of hepatic cholesterol and triglyceride improvement in mice fed HFD by isoquercetin remains unclear. Here, a combination of 16S rRNA gene sequencing, targeted quantification of bile acids (BAs), and biological assays was employed to investigate the beneficial effects of isoquercetin on NAFLD in mice. The results showed that dietary isoquercetin markedly modulated the BAs profiling in various samples such as liver, serum, intestine, and feces. We found that dietary isoquercetin promoted BA biosynthesis via the activation of alternative pathways and inhibition of intestinal FXR-Fgf15 signaling, thus reducing 13.2% hepatic cholesterol and 16.05% triglyceride in NAFLD mice. Dietary isoquercetin also regulated a series of receptors mediating correspondent processes of BA transportation, reabsorption, and excretion. Of particular note, dietary isoquercetin significantly modulated cross-talk between BAs and specific gut bacteria of NAFLD mice. These findings revealed that long-term intake of isoquercetin plays beneficial roles in the prevention or intervention of fatty liver disease.

中文翻译：

膳食异槲皮素通过肠道 FXR-FGF15 信号调节胆汁酸代谢降低 NAFLD 小鼠的肝脏胆固醇和甘油三酯

最近报道，异槲皮素是一种单糖类黄酮，对高脂饮食 (HFD) 诱导的小鼠非酒精性脂肪肝 (NAFLD) 具有显着改善作用。然而，异槲皮素喂养 HFD 小鼠肝脏胆固醇和甘油三酯改善的潜在机制仍不清楚。在这里，结合 16S rRNA 基因测序、胆汁酸 (BA) 的靶向定量和生物测定，研究了异槲皮素对小鼠 NAFLD 的有益作用。结果表明，膳食异槲皮素显着调节各种样品（如肝脏、血清、肠道和粪便）中的 BAs 谱。我们发现膳食异槲皮素通过激活替代途径和抑制肠道 FXR- Fgf15促进 BA 生物合成信号，从而降低 NAFLD 小鼠 13.2% 的肝胆固醇和 16.05% 的甘油三酯。膳食异槲皮素还调节一系列受体，介导 BA 运输、重吸收和排泄的相应过程。特别值得注意的是，饮食中的异槲皮素显着调节了 BA 与 NAFLD 小鼠特定肠道细菌之间的相互作用。这些发现表明，长期摄入异槲皮素对预防或干预脂肪肝疾病具有有益作用。

更新日期：2023-05-11

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