Work

D2Rs Agonist Ropinirole Cooperates with Metformin to Modulate Thermogenesis and Ameliorate Obesity-Related Metabolic Disorders in Mice

Year: 2026

Type: article

Abstract: Background: Metabolic disorders represent a significant challenge to human health, primarily due to their widespread prevalence and the limited availability of alternative pharmacological interventions. Drug repurposing offers a promising and expedited strategy to address these conditions. Methods: To elucidate the efficacy and underlying mechanism of the combination of metformin with ropinirole on anti-obesity and obesity-related metabolic disorders. Results: The results indicate that the combination treatment led to a significant reduction in body weight and improvements in hyperglycemia, dyslipidemia, and insulin resistance. These enhancements, along with increased energy expenditure, were significantly greater than those achieved with either drug alone. Additionally, we observed the browning of inguinal white adipose tissue (iWAT) and alterations of the whitened-brown adipose tissue (BAT), along with substantial increases in mitochondrial function-related proteins. However, the drug combination did not exhibit any enhanced effect on cell thermogenesis and these proteins in vitro, whereas combination of norepinephrine and metformin-induced an additive upregulation of mitochondrial function-related proteins. Furthermore, pharmacological blockade of the β3 adrenergic receptor inhibited the energy expenditure induced by the combination treatment, etc. Conclusion: Our study underscores the combination of metformin and ropinirole-induced an amplified effectiveness in treating obesity-related metabolic disorders is dependent on the dopamine-control sympathetic nerve activity, and metformin acts directly on BAT and iWAT to improve mitochondrial function, which offering a new perspective for future clinical co-treatment of metabolic disorders with these two drugs.

Source: Diabetes & Metabolism Journal

DOI: 10.4093/dmj.2025.0335