Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China.
School of Public Health, Capital Medical University, Beijing 100069, China.
J Adv Res. 2023 Oct;52:59-72. doi: 10.1016/j.jare.2023.01.008. Epub 2023 Jan 11.
Non-alcoholic fatty liver disease (NAFLD) with obesity seriously threats public health. Our previous studies showed that dark tea had more potential on regulating lipid metabolism than other teas, and theabrownin (TB) was considered to be a main contributor to the bioactivity of dark tea.
This in vivo study aims to reveal the effects and molecular mechanisms of TB on NAFLD and obesity, and the role of the gut-liver axis is explored.
The histopathological examinations, biochemical tests, and nuclear magnetic resonance were applied to evaluate the effects of TB on NAFLD and obesity. The untargeted metabolomics was used to find the key molecule for further exploration of molecular mechanisms. The 16S rRNA gene sequencing was used to assess the changes in gut microbiota. The antibiotic cocktail and fecal microbiota transplant were used to clarify the role of gut microbiota.
TB markedly reduced body weight gain (67.01%), body fat rate (62.81%), and hepatic TG level (51.35%) in the preventive experiment. Especially, TB decreased body weight (32.16%), body fat rate (42.56%), and hepatic TG level (42.86%) in the therapeutic experiment. The mechanisms of action could be the improvement of fatty acid oxidation, lipolysis, and oxidative stress via the regulation of serotonin-related signaling pathways. Also, TB increased the abundance of serotonin-related gut microbiota, such as Akkermansia, Bacteroides and Parabacteroides. Antibiotics-induced gut bacterial dysbiosis disrupted the regulation of TB on serotonin-related signaling pathways in liver, whereas the beneficial regulation of TB on target proteins was regained with the restoration of gut microbiota.
We find that TB has markedly preventive and therapeutic effects on NAFLD and obesity by regulating serotonin level and related signaling pathways through gut microbiota. Furthermore, gut microbiota and TB co-contribute to alleviating NAFLD and obesity. TB could be a promising medicine for NAFLD and obesity.
非酒精性脂肪性肝病（NAFLD）伴肥胖严重威胁公众健康。我们之前的研究表明，黑茶比其他茶类更有调节脂质代谢的潜力，茶褐素（TB）被认为是黑茶生物活性的主要贡献者。
本体内研究旨在揭示 TB 对 NAFLD 和肥胖的作用及分子机制，并探讨肠-肝轴的作用。
采用组织病理学检查、生化检测和磁共振等方法评价 TB 对 NAFLD 和肥胖的作用。采用非靶向代谢组学方法寻找关键分子，进一步探讨分子机制。采用 16S rRNA 基因测序评估肠道微生物群的变化。采用抗生素鸡尾酒和粪便微生物移植来阐明肠道微生物群的作用。
TB 在预防实验中显著降低了体重增加（67.01%）、体脂率（62.81%）和肝甘油三酯水平（51.35%）。特别是，TB 在治疗实验中降低了体重（32.16%）、体脂率（42.56%）和肝甘油三酯水平（42.86%）。作用机制可能是通过调节 5-羟色胺相关信号通路，改善脂肪酸氧化、脂肪分解和氧化应激。此外，TB 增加了 5-羟色胺相关肠道微生物群的丰度，如阿克曼菌、拟杆菌和副拟杆菌。抗生素诱导的肠道细菌失调破坏了 TB 对肝脏中 5-羟色胺相关信号通路的调节作用，而随着肠道微生物群的恢复，TB 对靶蛋白的有益调节作用得以恢复。
我们发现，TB 通过调节肠道微生物群来调节 5-羟色胺水平及相关信号通路，对 NAFLD 和肥胖具有显著的预防和治疗作用。此外，肠道微生物群和 TB 共同减轻 NAFLD 和肥胖。TB 可能是治疗 NAFLD 和肥胖的一种有前途的药物。
