Fritillaria thunbergii Miq. (FTM), a traditional medicinal and edible herb, has shown promise in alleviating metabolic disturbances, yet its mechanistic basis remains unclear. In this study, we investigated the therapeutic effects of FTM aqueous extract in a male KM mouse model of obesity induced by a high‐sugar, high‐fat diet (HSFD). A 7‐week intervention with FTM significantly ameliorated obesity‐related phenotypes, including weight gain, insulin resistance, hyperlipidemia, and histopathological damage in the liver and pancreas. Comprehensive RT‐qPCR profiling of 38 hepatic genes revealed coordinated modulation of lipid metabolism (e.g., SREBP1 and FAS), insulin signaling (e.g., IRS1 and GLUT2), inflammation (e.g., NF‐κB and IL‐10), and mitochondrial function (e.g., PGC‐1α), indicating transcriptional reprogramming as a core mechanism. UPLC‐QTOF‐MS identified eight cevanine‐type alkaloids—including peimine, peiminine, and their glycosides—as major constituents, potentially contributing to the observed bioactivity via anti‐inflammatory and metabolic regulatory pathways. Moreover, 16S rRNA sequencing demonstrated that FTM reshaped gut microbiota composition by enriching SCFA‐producing taxa such as Lachnospiraceae and Faecalibaculum while suppressing Akkermansia overgrowth. Functional predictions further indicated normalization of microbial metabolic pathways disrupted by HSFD. These findings demonstrate that FTM exerts systemic benefits through the integrated modulation of hepatic gene networks, bioactive phytochemicals, and gut microbial communities, supporting its development as a multitarget functional food for the management of glycolipid metabolic disorders.
Zou et al. (Thu,) studied this question.