Muscle Strength, Lipid Metabolism and Hepatic Steatosis Are Improved with Ursolic Acid Treatment in High-Fat Diet-Induced Obese Mice

Background/Objectives: The prevalence of obesity globally has increased steadily in the past decades. Obesity, sarcopenic obesity (SO) and nonalcoholic fatty liver disease (NAFLD) commonly coexist. Ursolic acid (UA), a natural pentacyclic triterpenoid, has demonstrated potential anti-obesity properties. This study was designed to evaluate the anti-obesity efficacy of UA in a mouse model of high-fat diet (HFD)-induced obesity, with a particular focus on its impact on muscle function and NAFLD. Methods: Male C57BL/6J mice (6 weeks old) were randomly assigned to three groups (n = 20 per group): a control group (CON) fed a normal chow diet, a high-fat diet group (HFD), and a UA treatment group (UA). The HFD and UA groups received a high-fat diet for 10 weeks to induce obesity. Thereafter, mice in the UA group were administered UA orally once daily for 6 weeks. Results: In HFD-induced obese mice, UA administration significantly reduced body weight (BW), abdominal fat weight and liver weight; improved grip strength and muscle weight; and enhanced lipid profiles, including triglycerides, total cholesterol, low-density lipoprotein cholesterol and free fatty acid levels in serum. UA also improved histological changes in the liver and abdominal adipose tissues, regulated serum GH, IGF-1, T3, T4 and leptin levels and downregulated the inflammation-associated gene expression of TNF-α and IL-1β in abdominal adipose tissue. Conclusions: UA could enhance muscle strength, improve lipid metabolism and hepatic steatosis and might be considered a potential therapeutic agent for managing obesity and related metabolic diseases.