Ellagic Acid Promotes Lipid Reduction in High‐Fat Diet‐Induced Obese Mice by Remodeling the Gut Microbiota and Activating PPAR Pathways and Retinol Metabolism in Adipose Tissue

ABSTRACT Ellagic acid (EA), a bioactive polyphenol abundant in pomegranate and berries, exhibits potential in metabolic regulation. This study investigates EA's anti‐obesity mechanisms, focusing on its effects on gut microbiota and transcriptional regulation in adipose tissue. After a 9‐week high‐fat diet feeding, mice were divided into groups and treated with low‐dose EA (10 mg/kg/day), high‐dose EA (30 mg/kg/day), or urolithin A (20 mg/kg/day) for 7 weeks, with healthy and obese controls included. In diet‐induced obese mice, a 7‐week EA intervention (10 mg/kg/day) significantly reduced adiposity (−46.96%, p < 0.01) and improved serum lipid profiles. Transcriptome analysis revealed PPARγ upregulation (380.34%, p < 0.001) and retinol metabolism activation (Rdh11, 1.51‐fold) in white adipose tissue. Gut microbiota analysis showed that low‐dose EA inhibited Mailhella massiliensis abundance (73.64%, p < 0.001). It also enhanced nocturnal energy expenditure (56.79%, p < 0.05) and improved antioxidant capacity. In contrast, high‐dose EA and UroA neither activated these pathways nor suppressed harmful bacteria, and physical activity levels remained unchanged. Low‐dose EA ameliorates obesity via PPARγ‐mediated lipid metabolism, retinol metabolism activation, and gut microbiota modulation ( M. massiliensis suppression). EA‐rich foods may serve as functional dietary strategies for obesity management.