State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (CAS), Wuhan 430071, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
J Agric Food Chem. 2023 May 24;71(20):7723-7733. doi: 10.1021/acs.jafc.3c00952. Epub 2023 May 11.
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- 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.
异槲皮苷是一种单糖类黄酮，最近有报道称其对高脂肪饮食（HFD）诱导的非酒精性脂肪肝（NAFLD）小鼠具有显著的改善作用。然而，异槲皮苷通过何种机制降低 HFD 喂养小鼠的肝胆固醇和甘油三酯水平仍不清楚。本研究采用 16S rRNA 基因测序、靶向定量分析胆汁酸（BAs）和生物学实验相结合的方法，研究了异槲皮苷对 NAFLD 小鼠的有益作用。结果表明，饮食中的异槲皮苷显著调节了肝脏、血清、肠道和粪便等各种样本中的 BAs 谱。我们发现，饮食中的异槲皮苷通过激活替代途径和抑制肠道 FXR-信号通路促进了 BA 的生物合成，从而降低了 NAFLD 小鼠 13.2%的肝胆固醇和 16.05%的甘油三酯。饮食中的异槲皮苷还调节了一系列受体，介导了 BA 转运、重吸收和排泄的相应过程。值得注意的是，饮食中的异槲皮苷显著调节了 BAs 与 NAFLD 小鼠特定肠道细菌之间的相互作用。这些发现表明，长期摄入异槲皮苷对预防或干预脂肪肝具有有益作用。
