Anti-Adipogenic Effect of Theabrownin Is Mediated by Bile Acid Alternative Synthesis via Gut Microbiota Remodeling

Abstract

Theabrownin is one of the most bioactive compounds in Pu-erh tea. Our previous study revealed that the hypocholesterolemic effect of theabrownin was mediated by the modulation of bile salt hydrolase (BSH)-enriched gut microbiota and bile acid metabolism. In this study, we demonstrated that theabrownin ameliorated high-fat-diet (HFD)-induced obesity by modifying gut microbiota, especially those with 7α-dehydroxylation on the species level, and these changed microbes were positively correlated with secondary bile acid (BA) metabolism. Thus, altered intestinal BAs resulted in shifting bile acid biosynthesis from the classic to the alternative pathway. This shift changed the BA pool by increasing non-12α-hydroxylated-BAs (non-12OH-BAs) and decreasing 12α-hydroxylated BAs (12OH-BAs), which improved energy metabolism in white and brown adipose tissue. This study showed that theabrownin was a potential therapeutic modality for obesity and other metabolic disorders via gut microbiota-driven bile acid alternative synthesis.

The role of bile acids in carcinogenesis

“…Secondary BAs can be resorbed to the portal circulation and are transported to the liver, where, however, hydroxylation and conjugation needs to be restored for reuse. The main secondary BAs in humans are lithocholic acid (LCA), deoxycholic acid (DCA) and to a lesser extent, ursodeoxycholic acid (UDCA) [ 24 , 25 ].…”

Theabrownin-targeted regulation of intestinal microorganisms to improve glucose and lipid metabolism in Goto-Kakizaki rats

“…27 Its medical activities include inducing significant weight loss, lowering blood lipid and blood glucose levels, regulating intestinal microorganisms, 28 and improving the metabolic syndrome. 29 Although TB has a preventive effect on hyperglycemia in rats that are fed a high-glucose and high-fat diet, 30 the direct impact of TB on the treatment of diabetes and its mechanism of action are still unclear. In particular, the interaction between TB and intestinal microorganisms and whether TB has a targeted regulation need to be further studied.…”

Theabrownin and Poria cocos Polysaccharide Improve Lipid Metabolism via Modulation of Bile Acid and Fatty Acid Metabolism

“…The effect of TB + PCP on reducing lipid has not been explained although previous studies revealed that TB and PCP could alleviate hyperlipidemia through several mechanisms ( Huang et al, 2019a ; Huang et al, 2019b ; Kim et al, 2019 ; Kuang et al, 2020 ). In the current study, the combination of TB and PCP was found to significantly reduce body weight, adipose tissue weight, and lipid levels (e.g., TG, TC, and LDL in the liver).…”

“…Theabrownin (TB) is a kind of water-soluble polyphenols produced through pu-erh tea fermentation ( Huang et al, 2019a ; Kuang et al, 2020 ). Our previous study has proved that after TB treatment, the body weight, blood and liver lipid levels are reduced in humans and mice ( Huang et al, 2019b ).…”

“…Our previous study has proved that after TB treatment, the body weight, blood and liver lipid levels are reduced in humans and mice ( Huang et al, 2019b ). TB could promote cholesterol degradation, insulin sensitivity, energy consumption, and white adipose tissue browning by altering the composition of gut microbiome and bile acid metabolism ( Kuang et al, 2020 ). Poria cocos , is a dried sclerotia of P. cocos wolf, which is often parasitic on pine roots.…”