Endogenous GLP-1 plays an important biological role in regulating metabolism and agonists that target the GLP-1 receptor have been recently approved as treatment of obesity. Studies in mice have shown that activation of hypothalamic pro-opiomelanocortin (POMC) neurons by GLP-1 receptor agonists promote weight loss by reducing food intake. POMC neurons are known to mediate weight loss by releasing melanocyte-stimulating hormone (MSH) upon excitation,. However, the molecular mechanisms on how the GLP-1 R agonists excite POMC neurons, and whereas this excitation enhance the release of MSH hormone is unknown. This MPhil research will provide essential mechanistic insight on the role of GLP-1 receptor in human POMC neurons, which may reveal new molecular targets for further enhancing the appetite-reducing action of GLP-1 receptor agonists.
