Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
College of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
Biomed Pharmacother. 2019 May;113:108753. doi: 10.1016/j.biopha.2019.108753. Epub 2019 Mar 9.
The objective of this study was to investigate the effects of ferulic acid (FA) on nonalcoholic fatty liver disease (NAFLD) and gut microbiota, and its regulation mechanism in ApoE mice fed on a high-fat diet (HFD). Liver morphology, blood lipids, gut microbiota and their metabolite indole-3-acetic acid (I3A) were determined in ApoE mice. We also examined the hepatic expression of aryl hydrocarbon receptor (AHR), which inhibits the expression of fatty acid synthase (FASN) and sterol regulatory element-binding protein 1c (SREBP-1c), and ultimately reduces the deposition of triglycerides (TG) and total cholesterol (TC) in the liver. The results of the animal experiment showed that oral administration of FA markedly alleviated the formation of NAFLD and decreased the levels of serum TC, TG and low-density lipoprotein cholesterol (LDL-C). Furthermore, FA supplementation altered the composition of gut microbiota, in particular, modulating the ratio of Firmicutes to Bacteroidetes, and decreased the generation of I3A. Additionally, FA could increase the expression of hepatic AHR and inhibit the expression of FASN and SREBP-1c in the liver. Finally, we found that FA did not have hepatorenal toxicity. The findings above illustrate that FA has the potential to ameliorate NAFLD, some of which are closely related to the modulation of specific gut microbiota and the regulation of genes involved in TG and TC metabolism.
本研究旨在探讨阿魏酸（FA）对高脂饮食（HFD）喂养 ApoE 小鼠非酒精性脂肪肝病（NAFLD）和肠道微生物群的影响及其调控机制。我们检测了 ApoE 小鼠的肝脏形态、血脂、肠道微生物群及其代谢物吲哚-3-乙酸（I3A）。此外，我们还研究了肝脏芳烃受体（AHR）的表达，该受体可抑制脂肪酸合酶（FASN）和固醇调节元件结合蛋白 1c（SREBP-1c）的表达，从而减少肝脏甘油三酯（TG）和总胆固醇（TC）的沉积。动物实验结果表明，FA 可显著减轻 NAFLD 的形成，降低血清 TC、TG 和低密度脂蛋白胆固醇（LDL-C）水平。此外，FA 补充剂改变了肠道微生物群的组成，特别是调节厚壁菌门和拟杆菌门的比例，并降低了 I3A 的生成。此外，FA 可以增加肝脏 AHR 的表达，抑制肝脏中 FASN 和 SREBP-1c 的表达。最后，我们发现 FA 没有肝肾毒性。综上所述，FA 具有改善 NAFLD 的潜力，其中一些与特定肠道微生物群的调节和与 TG 和 TC 代谢相关的基因的调节密切相关。
