Broussoflavonol F Alleviates Obesity-Associated Metabolic Syndrome in Obese Mice by Modulating Gut Microbiota

Abstract

Obesity is a global health challenge associated with gut microbiota dysbiosis, which contributes to metabolic dysfunction and fat accumulation. This study explored the anti-obesity effects of Broussonetia flavonol F (BPF) and its ability to modulate gut microbiota in high-fat diet (HFD)-induced obese mice. After 6 weeks of BPF treatment, obese mice exhibited significant reductions in body weight, adipose tissue mass, and serum lipid levels (TC, TG, and LDL-C), alongside improved glucose tolerance. BPF inhibited fat deposition by downregulating key adipogenic and lipogenic genes in both inguinal adipose tissue (i-WAT) and epididymal adipose tissue (e-WAT). Additionally, BPF improved gut barrier function and reduced TNF-α and IL-6 levels. 16S rRNA sequencing revealed that BPF restored gut microbiota diversity, increasing the abundance of beneficial bacteria such as Lactobacillus, while decreasing the Firmicutes/Bacteroidetes ratio, a marker of obesity-related dysbiosis. Mechanistically, the anti-obesity effects of BPF were abolished in antibiotic-treated mice and were reproduced by FMT from BPF-treated donors, confirming a gut microbiota-dependent mechanism. Our findings demonstrate that BPF alleviates obesity by reshaping gut microbiota structure and suppressing metabolic inflammation, highlighting its potential as a therapeutic agent for obesity management.