During the past few decades, the rate of obesity has tripled worldwide. This is detrimental as obesity is a major risk factor for many non-communicable diseases including type 2 diabetes, cardiovascular diseases, and some cancers. Despite the prevalence of obesity, there are few therapeutic interventions available for individuals. Bodyweight is controlled by the brain, specifically by appetite-promoting or appetite-suppressing brain cells that are found in the hypothalamus. We have found that a group of appetite-promoting brain cells called melanin-concentrating hormone (MCH) neurons become active after eating high-fat diet (HFD). This activation is due to prostaglandin E2, a molecule involved in inflammation. Therefore, my project focuses on (1) further investigating the inflammatory effect of HFD on the hypothalamus, (2) understanding the way HFD activates MCH neurons, and lastly (3) testing whether preventing the effect of prostaglandin E2 on MCH neurons can be protective against obesity. Overall, this research aims to identify a novel therapeutic intervention for individuals with obesity.