Mulberry leaf extract ameliorates high-fat diet-induced obesity in mice by regulating the gut microbiota and metabolites

The increasing prevalence of obesity presents a notable challenge to global health. Mulberry leaves enriched with biologically active substances hold promise for alleviating obesity. This research assessed the efficacy of mulberry leaf extract (MLE) in mitigating obesity and metabolic disturbances in mice fed a high-fat diet (HFD). The results demonstrated that MLE, administered at both low (167 mg/kg) and high (333 mg/kg) doses, decreased weight gain and fat accumulation, improved glucose metabolism, enhanced insulin sensitivity, and reduced inflammation. Analysis of fecal samples via 16 S rRNA sequencing revealed that MLE corrected the gut microbiota imbalance caused by HFD, lowering the Firmicutes/Bacteroidota ratio as well as increasing the relative abundances of Bifidobacterium, Faecalibaculum, Coriobacteriaceae_UCG-002, and Dubosiella. Additionally, serum non-targeted metabolomics analysis identified 19 key differential metabolites associated with MLE treatment, which were primarily related to glycerophospholipid metabolism and tryptophan metabolism. Correlation analysis revealed negative associations between Dubosiella and Coriobacteriaceae_UCG-002 with specific phospholipids, and positive associations of 5-hydroxyindoleacetate and quinoline-4,8-diol with Bifidobacterium and Coriobacteriaceae_UCG-002. These findings suggest that MLE is effective in treating obesity and underscores its potential as a functional food.