LBODP003 Effects Of 4-weeks’ Treatment With Intraperitoneal Colchicine On Metabolic And Inflammatory Outcomes In Mice Fed A High-fat Diet

Abstract Health-deteriorating effects of obesity include chronic inflammation and insulin resistance (IR). A recent pilot human trial reported reduced IR in colchicine-treated vs. placebo-treated adults with obesity. Thus, we examined anti-inflammatory and metabolic effects of two commonly employed dosing regimens of colchicine, 0.2 mg/kg and 0. 02mg/kg, in a high-fat diet (HFD; 45%) mouse obesity model. We placed male C57BL/6J mice on HFD from ages 8 through 16 weeks. At age 12 weeks, mice were randomized to: high-dose colchicine (CHD 0.2 mg/kg, n=28), low dose colchicine (CLD, 0. 02mg/kg, n=26) or vehicle (V, n=26), injected intraperitoneally (IP) for 4 weeks. Serum CRP was measured by ELISA. Dual-energy X-ray absorptiometry (DXA) scans and fasting IP glucose tolerance (GTT) and insulin-tolerance (ITT) tests were performed at baseline and following treatment. Hepatic tissue was processed for immunoblotting to determine expression of NLRP3 and caspase-1. Changes in pre- vs. post-treatment serum CRP were significantly different in the CHD group (Mean±SD: -0.57±3.1µg/mL) vs. V (+3.64±2.9µg/mL; p