Theabrownin inhibits obesity and non-alcoholic fatty liver disease in mice via serotonin-related signaling pathways and gut-liver axis

Hang-Yu Li; Si-Yu Huang; Dan-Dan Zhou; Ruo-Gu Xiong; Min Luo; Adila Saimaiti; Mu-Ke Han; Ren-You Gan; Hui-Lian Zhu; Hua-Bin Li

doi:10.1016/j.jare.2023.01.008

Theabrownin inhibits obesity and non-alcoholic fatty liver disease in mice via serotonin-related signaling pathways and gut-liver axis

J Adv Res. 2023 Oct:52:59-72. doi: 10.1016/j.jare.2023.01.008. Epub 2023 Jan 11.

Authors

Affiliations

¹ Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China.
² School of Public Health, Capital Medical University, Beijing 100069, China.
³ Research Center for Plants and Human Health, Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, National Agricultural Science & Technology Center, Chengdu 610213, China. Electronic address: ganrenyou@caas.cn.
⁴ Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China. Electronic address: lihuabin@mail.sysu.edu.cn.

Abstract

Introduction: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Anti-obesity; Gut microbiota; Non-alcoholic fatty liver disease; Serotonin; Theabrownin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Mice
Non-alcoholic Fatty Liver Disease* / drug therapy
Non-alcoholic Fatty Liver Disease* / metabolism
Non-alcoholic Fatty Liver Disease* / pathology
Obesity / drug therapy
Obesity / metabolism
Obesity / microbiology
RNA, Ribosomal, 16S
Serotonin / pharmacology
Serotonin / therapeutic use
Signal Transduction
Tea

Substances

Serotonin
RNA, Ribosomal, 16S
theabrownin
Tea