Cholinergic Activation by Galantamine Suppresses Obesity-Associated Inflammation in Mice (54.4)

Abstract Low-grade systemic inflammation is a central event in obesity and mediates insulin resistance and other complications. Previously we discovered a role for neural cholinergic signaling in controlling inflammation (Nature, 2000, 405, 6785; Proc Natl Acad Sci USA, 2006, 5219) and demonstrated that the acetylcholinesterase inhibitor galantamine suppresses systemic lethal inflammation (Brain Behav Immun, 2009, 4; 1). Here we tested the efficacy of galantamine in alleviating obesity-associated inflammation. C57BL/6J mice with high fat-diet induced (for 8 weeks) obesity were treated with either galantamine (4 mg/kg daily, i.p.), or saline for 4 weeks while on the high-fat diet. Galantamine treatment of obese mice resulted in lower body weight and abdominal adiposity as compared to saline treatment. Galantamine significantly decreased systemic levels of characteristic pro-inflammatory cytokines/adipokines, including IL-6, MCP-1, resistin and leptin and increased adiponectin levels, accompanied by alleviated hyperglycemia, hyperinsulinemia, insulin resistance and hepatosteatosis. These results demonstrate that galantamine reduces obesity-associated inflammation and alleviates obesity-related complications and provide a rationale for further mechanistic studies and novel therapeutic implications. Translational aspects of these studies will be additionally facilitated by the fact that galantamine is a FDA approved (for the treatment of Alzheimer’s disease) cholinergic agent.