PDF(Pubmed)
Abstract：
Obesity is associated with alterations in lipid metabolism and gut microbiota dysbiosis. This study investigated the effects of puerarin, a bioactive isoflavone, on lipid metabolism disorders and gut microbiota in high-fat diet (HFD)-induced obese mice. Supplementation with puerarin reduced plasma alanine aminotransferase, liver triglyceride, liver free fatty acid (FFA), and improved gut microbiota dysbiosis in obese mice. Puerarin\'s beneficial metabolic effects were attenuated when farnesoid X receptor (FXR) was antagonized, suggesting FXR-mediated mechanisms. In hepatocytes, puerarin ameliorated high FFA-induced sterol regulatory element-binding protein (SREBP) 1 signaling, inflammation, and mitochondrial dysfunction in an FXR-dependent manner. In obese mice, puerarin reduced liver damage, regulated hepatic lipogenesis, decreased inflammation, improved mitochondrial function, and modulated mitophagy and ubiquitin-proteasome pathways, but was less effective in FXR knockout mice. Puerarin upregulated hepatic expression of FXR, bile salt export pump (BSEP), and downregulated cytochrome P450 7A1 (CYP7A1) and sodium taurocholate transporter (NTCP), indicating modulation of bile acid synthesis and transport. Puerarin also restored gut microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of Clostridium celatum and Akkermansia muciniphila. This study demonstrates that puerarin effectively ameliorates metabolic disturbances and gut microbiota dysbiosis in obese mice, predominantly through FXR-dependent pathways. These findings underscore puerarin\'s potential as a therapeutic agent for managing obesity and enhancing gut health, highlighting its dual role in improving metabolic functions and modulating microbial communities.
摘要：
肥胖与脂质代谢和肠道微生物群失调的改变有关。本研究调查了葛根素的作用，一种生物活性异黄酮,高脂饮食（HFD）诱导的肥胖小鼠的脂质代谢紊乱和肠道菌群。补充葛根素可降低血浆丙氨酸转氨酶，肝脏甘油三酯，肝脏游离脂肪酸（FFA），和改善肥胖小鼠的肠道微生物群失调。拮抗法尼醇X受体（FXR）时，葛根素的有益代谢作用减弱，提示FXR介导的机制。在肝细胞中，葛根素改善高FFA诱导的固醇调节元件结合蛋白（SREBP）1信号，炎症,和线粒体功能障碍以FXR依赖的方式。在肥胖小鼠中，葛根素减少肝损伤，调节肝脏脂肪生成，减少炎症，改善线粒体功能，调节线粒体自噬和泛素-蛋白酶体途径，但在FXR基因敲除小鼠中效果较差。葛根素上调FXR的肝脏表达，胆盐出口泵（BSEP），下调细胞色素P4507A1（CYP7A1）和牛磺胆酸钠转运蛋白（NTCP），指示胆汁酸合成和运输的调节。葛根素还恢复了肠道微生物多样性，Firmicutes/拟杆菌比率，以及丰富的clostriumcelatum和Akkermansiamuiniphila。这项研究表明，葛根素有效改善肥胖小鼠的代谢紊乱和肠道菌群失调，主要通过FXR依赖性途径。这些发现强调了葛根素作为治疗肥胖和增强肠道健康的潜在作用。强调其在改善代谢功能和调节微生物群落方面的双重作用。
