Pomegranate seed oil alleviates renal lipid deposition and fibrosis in diabetic kidney disease mice

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes, with renal lipid deposition being a key pathogenic driver. Pomegranate seed oil (PSO) has a variety of health benefits, but the specific mechanism for alleviating DKD in mice has not been fully elucidated. This study found PSO reduced blood glucose levels and alleviated insulin resistance. Histological staining revealed PSO attenuated mesangial matrix deposition and fibrosis. PSO significantly reduced serum uric acid, creatinine, and the urine albumin/creatinine ratio, increased anti-oxidative stress indicators total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the kidney of diabetic mice, and significantly inhibited the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) ( P < 0.05). Non-targeted metabolomics indicated that PSO mainly affected pantothenate and coenzyme A biosynthesis and unsaturated fatty acid biosynthesis. PSO intervention was associated with increased expression of G protein-coupled receptor 120 and β-arrestin2, reduced phosphorylation of extracellular signal-regulated kinase 1/2, and upregulated expression of peroxisome proliferator-activated receptor α and fatty acid β-oxidation-related proteins. PSO also significantly downregulated fibrosis-related proteins, including transforming growth factor-β1, α-smooth muscle actin, and type IV collagen, indicating attenuation of renal fibrosis. This study provided a theoretical foundation for the use of PSO in alleviating DKD.