Effects of Intraperitoneal Colchicine on the Metabolic Consequences of High Fat Diet-Induced Obesity in Mice

INTRODUCTION: Obesity-associated inflammation promotes metabolic dysregulation and insulin resistance. Colchicine, a potent microtubule inhibitor, suppresses NLRP3 inflammasome activity and acts proximally to inhibit the inflammatory pathway. The primary objective was to evaluate the impact of intraperitoneal (IP) colchicine administration on inflammation and metabolic parameters in mice with high-fat diet-induced obesity. METHODS: C57BL/6 mice consumed a 45% fat diet from age 8 weeks to 16 weeks to induce obesity and inflammation. From weeks 12-16, 39 male and 29 female mice were randomized 1:1 to IP vehicle or IP colchicine 0.2 mg/kg/d. Glucose and insulin tolerance tests were performed, and CRP was measured to evaluate systemic inflammation. NLRP3 and Caspase-1 expression were assessed to evaluate hepatic inflammation. RESULTS: Body weight was lower for both male and female mice administered colchicine versus placebo (p