Grant: Project Grant

Obesity poses a major health and economic burden worldwide. Excess consumption of foods high in fat and sugar can elicit inflammation in the brain that contributes to the development of obesity and associated metabolic abnormalities. The last century has witnessed a major increase in the intake of saturated fats along with a decline in essential omega-3 fatty acids that are anti-inflammatory and can protect against metabolic impairments associated with obesity. GPR120 is a receptor activated by omega-3 fatty acids that mediates the antiinflammatory and insulin-sensitizing effects of dietary omega-3 supplementation. In the brain, GPR120 is primarily expressed in microglia (cerebral immune cells) and activation of GPR120 in microglia decreases their inflammatory status. While pharmacological activation of brain GPR120 inhibits feeding, motivation for tasty food and diet-induced hyperglycemia, the role of microglial GPR120 in the neuroimmune and metabolic responses to diet and obesity development are unknown. The proposed project will test the contribution of microglial GPR120 to diet-induced neuroinflammation and obesity susceptibility in mice using a gene intervention approach that will delete GPR120 specifically in microglia. In view of the promising potential of GPR120 agonists to treat obesity and type 2 diabetes, it is critical to understand the role of brain GPR120.