Rosmarinic Acid Ameliorates Obesity-Associated Metabolic Disturbances and Hepatic Steatosis in Mice with High-Fat Diet-Induced Obesity.

Obesity and obesity-associated hepatic steatosis represent major metabolic health challenges, yet effective pharmacological interventions remain limited. Rosmarinic acid (RA), a natural polyphenol, has been reported to exert anti-obesity effects; however, its specific roles in restoring hepatic lipid homeostasis and modulating glucose metabolism under diet-induced obesity remain unclear. In this study, we investigated the metabolic effects and underlying mechanisms of RA in mice with high-fat diet (HFD)-induced obesity. RA significantly reduced body weight gain and adipose tissue mass without altering total energy intake, accompanied by increased nocturnal energy expenditure and fecal lipid excretion. RA restored hepatic lipid homeostasis by improving circulating lipid profiles and markedly attenuating hepatic steatosis, fibrosis, and hepatocellular injury. These effects were associated with increased fecal lipid excretion, suppression of hepatic lipogenesis, and enhancement of fatty acid oxidation-related markers. Furthermore, RA reduced fasting blood glucose levels and modulated the expression of hepatic glucose metabolism-related genes. Pancreatic immunohistochemistry showed morphological changes in insulin-positive and glucagon-positive cells following RA supplementation. Collectively, these findings indicate that RA ameliorates obesity-associated metabolic disturbances and hepatic steatosis through coordinated regulation of lipid metabolism and hepatic glucose metabolism-related pathways, highlighting its potential relevance for obesity-associated fatty liver conditions.