Obesity has emerged as one of the key health concerns of this century due to its prevalence and resistance to treatment. Specifically, more than 60% of people within the UK are currently overweight or obese. Recently, significant progress has been made in clarifying brain neurochemicals and regions regulating energy intake and energy expenditure. Among these neurochemicals is the precursor polypeptide pro-opiomelanocortin (Pomc) localised within the homeostatic brain region the arcuate nucleus of the hypothalamus (ARC). A new medication for obesity treatment named lorcaserin was recently launched in the USA. However, mechanism through which lorcaserins therapeutic benefit is achieved remained to be clarified. Using a combination of viral and genetic technology, we uncovered the specific brain circuits through which lorcaserin reduces food intake. We reveal that lorcaserin suppresses appetite via action at Pomc neurons signaling to melanocortin4 receptors. These findings illustrate that the brain circuits controlling appetite may be pharmacologically harnessed to improve obesity and health.