Rice protein peptides alleviate lipid accumulation <i>via</i> modulating liver metabolism and remodeling the gut microbiota in HFD-induced mice

Hyperlipidemia is a significant risk factor for lipid metabolism disorder and gut health impairment. Rice protein peptides (RPs) have emerged as promising interventions for hyperlipidemia management, owing to their safety profile, bioavailability, and cost-effectiveness. However, comprehensive investigations into their anti-hyperlipidemic effects and underlying mechanisms remain insufficiently explored. This study aimed to investigate the efficacy of RPs in alleviating hyperlipidemia and hepatic lipid accumulation by lipidomic and microbiome analyses. Results revealed that RP administration significantly ameliorated lipid metabolism disorders by reducing fat accumulation, normalizing blood lipid levels, and inhibiting lipase activity. Additionally, RPs exhibited hepatoprotective effects by increasing antioxidant enzyme activity and decreasing pro-inflammatory cytokines. Lipidomic analysis further revealed that RPs altered lipid metabolic patterns, identifying 10 differentially regulated lipid species that may serve as potential biomarkers for hyperlipidemia. Furthermore, RP supplements significantly regulated the mRNA levels of gene expression (HMGR, SREBP2, CYP7A1, LDLR, PPARα, PPARγ, FAS, and ACS) involved in hepatic lipid metabolism. Metagenomic analysis demonstrated that RPs reversed gut microbiota dysbiosis by reducing the <i>Firmicutes</i>/<i>Bacteroidete</i>s ratio and increasing the abundance of beneficial genera such as <i>Akkermansia</i>, <i>Muribaculaceae</i>, <i>Clostridia_UCG-014</i>, and <i>Blautia</i>. Furthermore, RP intervention significantly elevated fecal short-chain fatty acid (SCFA) content, particularly butyrate, isobutyrate, and isovalerate, suggesting a link between microbial modulation and metabolic improvement. These findings suggested RPs as an effective strategy for improving lipid metabolism and the gut microbiota composition, offering a promising dietary intervention for hyperlipidemia management.