Curcuma longa rhizome extract activates brown adipocytes and inhibits lipogenesis in high-fat diet-fed mice

• In obese mice, Curcuma longa rhizome extract (CRE) prevented metabolic endotoxemia and de novo lipogenesis. • CRE induced the browning of adipocytes via thermogenesis-related markers. • CRE improved intestinal status and obesity/NAFLD symptoms. Interactions between the gut, adipose, and liver tissues play important roles in metabolic endotoxemia and gut dysbiosis. This study explored the effectiveness of Curcuma longa rhizome extract (CRE) in improving high-fat diet (HFD)-induced metabolic disorders and modulating gut environments. CRE treatment inhibited lipid accumulation in 3T3-L1 white adipocytes and activated thermogenesis-related genes in T37i brown adipocytes. CRE was administered to HFD-fed mice for 8 weeks, and serum, feces, colon, white adipose, and liver tissue were analyzed. CRE ameliorated the symptoms of metabolic disorders in mice with HFD-induced obesity by suppressing body weight and fat mass gain, adipocyte size, insulin resistance, and hepatic steatosis. CRE regulated gut axis-based mechanisms by inhibiting gut permeability, metabolic endotoxemia, and de novo lipogenesis, and promoting gut barrier integrity. Serum metabolites were negatively correlated with most biomarkers for metabolic disorders. Therefore, CRE could alleviate metabolic disorders by improving the intestinal environment and modulating the gut axis.