Anti-Obesity and Diuretic Effects of Immature Watermelon Rind Extract in HFD-Induced Obese Mice

<b>Background/Objectives:</b> Immature watermelon (WM) rind contains higher levels of citrulline and potassium than mature fruit and may exert diuretic and metabolic benefits. This study aimed to evaluate the anti-obesity and diuretic effects of WM and salt-treated watermelon rind extract (WMS) in high-fat diet (HFD)-induced obese mice, focusing on changes in lipid metabolism, sodium handling, and tissue-level alterations. <b>Methods:</b> Citrulline concentrations in WM and WMS were quantified using high-performance liquid chromatography with ultraviolet detection (HPLC-UV). Four-week-old male C57BL/6 mice were fed an HFD for 6 weeks and subsequently administered WM (380 mg/kg) or WMS (380 mg/kg) orally for an additional 6 weeks. Body weight, food intake, organ and fat-pad weights, serum biochemical markers, and sodium (Na⁺) levels were measured. Histopathological analyses of liver and epididymal adipose tissue were performed to assess non-alcoholic steatohepatitis (NASH) scores and adipocyte morphology. <b>Results:</b> WM and WMS contained citrulline at levels substantially higher than those reported for mature watermelons. Both treatments significantly reduced body weight, liver weight, and epididymal fat mass compared with the HFD control. Serum total cholesterol and triglyceride levels were lowered in the WM- and WMS-treated groups. Serum Na⁺ concentrations increased by 43.2 ± 7.6% in WM-treated mice and 21.5 ± 6.6% in WMS-treated mice, suggesting enhanced sodium handling. Histological assessment revealed reduced NASH scores and smaller adipocyte sizes in both groups. These improvements are consistent with the known diuretic and metabolic actions of citrulline and potassium. <b>Conclusions:</b> WM and WMS exhibit significant anti-obesity and diuretic effects in HFD-induced obese mice. Their combined actions on sodium excretion, lipid metabolism, and adipose tissue remodeling suggest that immature watermelon rind extracts may serve as promising natural agents for preventing obesity and related metabolic dysfunction.