Xu Wei, Kong Yingying, Zhang Tuo, Gong Zhihua, Xiao Wenjun
Key Lab of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha, China.
National Research Center of Engineering Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha, China.
J Sci Food Agric. 2023 Feb;103(3):1283-1293. doi: 10.1002/jsfa.12222. Epub 2022 Sep 23.
l-Theanine (LTA) is a biologically active ingredient in tea that shows great potential for regulating lipid metabolism. Bile acids (BA), an important end-product of cholesterol catabolism, participate in the regulation of lipid metabolism and gut microbiota. Here, we investigated the effect of LTA on lipid metabolism and the mechanism by which it regulates BA metabolism and gut microbiota. Male BALB/c mice were treated with LTA for 28 days.
Daily LTA doses of 100 and 300 mg kg d altered the gut microbiota in mice, predominantly by decreasing Lactobacillus, Streptococcus, Bacteroides, Clostridium and Enterorhabdus microbes associated with bile-salt hydrolase (BSH) activity, thereby decreasing the activity of BSH and increasing the levels of ileum conjugated BA (such as glycocholic acid (GCA) and lithocholic acid), thereby inhibiting the intestinal farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling pathway. Inhibition of FXR-FGF15 signaling was accompanied by upregulation of cholesterol 7α-hydroxylase (CYP7A1) mRNA and protein expression and increased hepatic production of cholic acid, deoxycholic acid, GCA, glycine cholic acid and glycine ursodeoxycholic acid. Meanwhile, increasing hepatic unconjugated BA upregulated the mRNA and protein expression of liver 3-hydroxy-3-methylglutaryl-CoA reductase and downregulated the mRNA and protein expression of stearoyl-CoA desaturase-1, liver low-density lipoprotein receptor and type B scavenger receptor. Therefore, the serum levels of cholesterol and triglycerides decreased.
Our findings indicate that LTA regulates lipid metabolism by modulating the gut microbiota and BA metabolism via the FXR-FGF15-CYP7A1 pathway. © 2022 Society of Chemical Industry.
L-茶氨酸（LTA）是茶叶中的一种生物活性成分，在调节脂质代谢方面具有巨大潜力。胆汁酸（BA）是胆固醇分解代谢的重要终产物，参与脂质代谢和肠道微生物群的调节。在此，我们研究了LTA对脂质代谢的影响及其调节BA代谢和肠道微生物群的机制。雄性BALB/c小鼠接受LTA治疗28天。
每日100和300 mg/kg剂量的LTA改变了小鼠的肠道微生物群，主要是通过减少与胆汁盐水解酶（BSH）活性相关的乳酸杆菌、链球菌、拟杆菌、梭菌和肠杆菌属微生物，从而降低BSH的活性并增加回肠结合BA（如甘氨胆酸（GCA）和石胆酸）的水平，进而抑制肠道法尼醇X受体（FXR）-成纤维细胞生长因子15（FGF15）信号通路。FXR-FGF15信号通路的抑制伴随着胆固醇7α-羟化酶（CYP7A1）mRNA和蛋白表达的上调以及肝脏胆酸、脱氧胆酸、GCA、甘氨酸胆酸和甘氨酸熊去氧胆酸生成的增加。同时，肝脏未结合BA的增加上调了肝脏3-羟基-3-甲基戊二酰辅酶A还原酶的mRNA和蛋白表达，并下调了硬脂酰辅酶A去饱和酶-1、肝脏低密度脂蛋白受体和B型清道夫受体的mRNA和蛋白表达。因此，血清胆固醇和甘油三酯水平降低。
我们的研究结果表明，LTA通过FXR-FGF15-CYP7A1途径调节肠道微生物群和BA代谢来调节脂质代谢。©2022化学工业协会。
