Interrogation of Neuromedin U Receptor 2/Neuromedin U as a Novel Therapeutic Target for the Treatment of Obesity
Obesity is a growing public health concern, with 42.4% of the adult population considered obese. Obesity has many comorbidities associated with it, including diabetes, cancer, and heart disease. These comorbidities increase the likelihood of mortality and increase the individual medical costs of the obese population. Obesity is a disease commonly characterized by an overconsumption of energy dense foods leading to an increase in adiposity. The rate at which obesity is growing has demanded a better understanding of the disease and better pharmacotherapies. Currently, the pharmacotherapies available to treat obesity have modest efficacy which highlights the need for more effective pharmacotherapies to treat obesity. The identification of key neural pathways that play a role in food consumption have helped highlight the Neuromedin U Receptor 2 (NMUR2) as a promising target that can regulate body weight and food intake. NMUR2 is activated by the endogenous ligand, Neuromedin U (NMU), which then causes a downstream signaling cascade that leads to neuronal activation or inhibition. This dissertation aims to explore the role of the NMUR2/NMU signaling complex in vitro and identify the physiological role of NMU when examined in the neural pathways in which regulate food intake and body weight. Once identifying NMU as a mediator of food intake and body weight, we then explored the effect of small molecule NMUR2 agonists and their ability to decrease body weight, adiposity, and improve metabolic measures in diet induced obese animals.