Liupao tea alleviates high-fat diet-induced obesity by re-establishing metabolic homeostasis of short-chain fatty acids and chenodeoxycholic acid

LPTe alleviates HFD-induced obesity, hepatic steatosis, and inflammation. • Five circulating LPTe-derived constituents were identified in vivo . • LPTe restores CDCA homeostasis through gut–liver bile acid remodeling. • LPTe strengthens intestinal barrier function via SCFA–GPCR signaling. • LPTe anti-obesity efficacy is gut microbiota-dependent. Metabolic dyshomeostasis of bile acid (BA) and microbiota-derived short-chain fatty acid (SCFA) is a critical driver of obesity pathogenesis. Liupao tea (LPT) has garnered attention for its anti-obesity potential, owing to potent lipid-lowering, microbiota- and BA metabolism-regulatory properties. However, whether LPT coordinately modulates BA and SCFA homeostasis remains unclear. This study investigated the therapeutic potential of LPT extract (LPTe) in alleviating obesity by focusing on the host–microbial re-establishment of SCFA and BA homeostasis. Results showed that five potential bioactive LPTe-derived constituents were identified in vivo. LPTe intervention effectively attenuated body weight gain, dyslipidemia, hepatic steatosis, intestinal barrier dysfunction, and systemic inflammation in HFD mice. LPTe treatment was associated with a shift in BA biosynthesis toward a chenodeoxycholic acid (CDCA)-enriched profile and with altered enterohepatic BA circulation. This shift coincided with increased fecal BA excretion and diminished lithocholic acid (LCA) accumulation, ultimately mitigating hepatic inflammation and lipotoxicity. LPTe altered gut microbial composition, reducing the relative abundances of genera potentially associated with secondary BA metabolism, in parallel with lower LCA levels. Simultaneously, increased SCFA levels were accompanied by higher colonic mRNA expression of GPR41 and GPR109A , increased ZO-1 and Occludin protein expression, and improved mucosal barrier-related indices. Crucially, antibiotic-mediated microbiota depletion abolished these metabolic benefits. Collectively, LPTe alleviated HFD-induced obesity through microbiota-dependent remodeling of the gut–liver axis, driven by the coordinated restoration of SCFA and CDCA homeostasis. These findings offer a theoretical basis for leveraging LPTe as a functional dietary intervention for obesity management. Download: Download high-res image (432KB) Download: Download full-size image