Front Microbiol. 2026 Jun 19;17:1808318. doi: 10.3389/fmicb.2026.1808318. eCollection 2026.
ABSTRACT
BACKGROUND: Obesity drives chronic diseases such as cardiovascular disease and diabetes. Danlou tablet (DLT), a traditional Chinese medicine formula, is used to treat coronary heart disease by regulating lipid metabolism, suggesting potential for addressing obesity-related metabolic dysfunction. However, its role in obesity and insulin resistance remains unexplored.
OBJECTIVES: We investigated the efficacy and mechanisms of DLT against high-fat diet (HFD)-induced obesity and insulin resistance.
METHODS: C57BL/6N mice were fed an HFD for 22 weeks and treated with DLT. A comprehensive phenotypic assessment was conducted, including body weight, glucose tolerance, insulin sensitivity, serum biochemistry, and histopathology of key tissues. To elucidate the therapeutic mechanism, we integrated 16S rRNA gene sequencing of gut microbiota, serum metabolomics (UPLC-Q-TOF-MS), and hepatic transcriptomics.
RESULTS: DLT treatment counteracted HFD-induced metabolic dysfunction, reducing body weight, adiposity, dyslipidemia, and insulin resistance, while ameliorating hepatic steatosis, inflammation, and oxidative stress. At the microbial level, DLT restored gut microbial diversity, corrected the Firmicutes/Bacteroidota ratio, and modulated key genera. Metabolomics linked these changes to restored fatty acid β-oxidation. In the liver, transcriptomics showed that DLT reversed HFD-induced gene expression, suppressed inflammatory pathways and enhanced fatty acid oxidation and xenobiotic metabolism. Integrated multi-omics analysis revealed a strong correlative relationship that DLT's therapeutic benefits are associated with the modulation of the gut-liver axis, where remodeling of the gut microbiome is closely linked to the reprogramming of hepatic metabolic pathways.
CONCLUSION: DLT counteracts HFD-induced obesity and insulin resistance via a multi-level regulatory mechanism that is closely associated with the modulation of the gut-liver axis, which involves suppressing pathogenic gut microbes, restoring fatty acid metabolism, and enhancing hepatic lipid catabolism and antioxidant defense. This comprehensive preclinical evidence supports the clinical translation of DLT as a novel therapeutic option for obesity and type 2 diabetes mellitus.
PMID:42404798 | PMC:PMC13329814 | DOI:10.3389/fmicb.2026.1808318