Platycodonis Radix Polysaccharides Suppress Progression of High-Fat-induced Obesity Through Modulation of Intestinal Microbiota and Metabolites
Background Obesity is a prevalent chronic condition worldwide, posing a significant risk to public health. Polysaccharides derived from Platycodonis Radix (PR) have been identified as the primary bioactive compounds in combating obesity, although the underlying molecular mechanisms remain inadequately understood. Purpose The purpose of the research is to analyze the potential anti-obesity influnces within PR polysaccharides (PG: PG1 and PG2) by analyzing their impact on gut microbiota (GM) composition, SCFA and BA metabolism, and the regulation of associated gene and protein expression. Study Design and Methods In this research, 7-week-old male C57BL/6 mice were assigned to a HFD or a control chow diet for 90 days to evaluate the therapeutic effects of PG intervention. Metagenomic analysis was performed to assess GM alterations, while GC-MS and LC-MS were used to quantify SCFA and BA concentrations in cecal contents, respectively. Furthermore, the effects of PG on SCFA- and BA-associated metabolic pathways were examined through qRT-PCR and WB. Results PG1 demonstrated superior efficacy compared to PG2 in reducing HFD-induced obesity and associated metabolic disturbances. High-dose PG1 treatment effectively inhibited weight gain, dyslipidemia, inflammation, liver damage, and fat deposition caused by the HFD. Additionally, PG1 treatment primarily promoted the abundance of SCFA-producing bacteria, enhanced the expression of GPR41 and GPR43 genes, significantly elevated levels of GLP-1 and PYY, and improved circulating leptin and adiponectin levels. The intervention with PG1 notably enhanced the relative abundances of bacteria involved in the production of secondary BAs, such as Lachnospiraceae_NK4A136 and Eubacterium coprostanoligenes . This augmentation facilitated the transformation of primary BAs into secondary forms, diminished the relative expression of intestinal FXR and FGF15, and reduced FGFR4 levels. Consequently, this led to an upregulation of hepatic CYP7A1, accelerating liver cholesterol metabolism and the synthesis of new BAs. Conclusion Supplementation with PG1 protects mice from obesity induced by an HFD. The observed protective effects of PG1 appear to be primarily mediated through the activation of the GM-SCFA-GPR pathway and the inhibition of the GM-BAs-FXR-FGF15 signaling pathway.
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