ABSTRACT Hyperlipidemia is a major risk factor for cardiovascular disease, yet effective dietary interventions remain underexplored. Pomegranate (POG) has been recognized for its potential lipid‐lowering effects, but its underlying mechanisms require further investigation. To elucidate the therapeutic mechanism of POG in high‐fat diet‐induced hyperlipidemic rats, a comprehensive strategy combining metabolomics and transcriptomics analyses was implemented. Here, we demonstrate that POG exerts hypolipidemic effects through modulation of lipid metabolism and inflammatory pathways. The findings revealed that POG administration significantly reduces body weight gain, liver weight, and adipose tissue accumulation, while alleviating hepatic steatosis. These metabolic improvements were accompanied by ameliorated lipid metabolism, manifested through significant reductions in serum triglycerides, total cholesterol, and low‐density lipoprotein cholesterol, with concurrent elevation of high‐density lipoprotein cholesterol. Metabolomic analysis reveals that POG treatment significantly alters sphingolipid, pyrimidine, and arachidonic acid metabolism, highlighting its role in lipid homeostasis. Furthermore, transcriptomic profiling identifies 440 differentially expressed genes enriched in lipid metabolism and inflammatory pathways, including lipid and atherosclerosis, NF‐κB, and TNF signaling pathways. These findings provide mechanistic insights into the regulatory effects of POG on lipid metabolism and inflammation, rendering it conducive to incorporation into functional foods or pharmaceutical applications.
Wang et al. (Wed,) studied this question.
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