Theabrownin from Pu-erh tea alleviates MAFLD by reducing hepatic serotonin level and utilization in a gut microbiota dependent manner

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a serious threat to public health. We verified that theabrownin from Pu-erh tea possessed preventative and therapeutic effects on MAFLD, meanwhile the gut bacterial-mediated molecular mechanism was revealed. Firstly, theabrownin increased the abundances of metabolic-related gut bacterial genera, such as Akkermansia, Bacteroides and Parabacteroides. Then, theabrownin reduced serotonin level and utilization in liver while increased serotonin level in epididymal adipose tissue. Next, theabrownin alleviated MAFLD by decreasing the levels of serotonin receptor 2A (HTR2A) and serotonin transporter (SERT) in liver while increasing the level of HTR2B in epididymal adipose tissue. Moreover, the regulated effects of theabrownin on serotonin-related signaling pathways in liver relied on the participation of gut microbiota according to antibiotic interference experiment. Furthermore, theabrownin and gut microbiota were interdependent in alleviating MAFLD based on fecal microbiota transplant. Our study suggested that theabrownin might be a novel treatment for MAFLD.