Exploring Hipothalamic GPR139 Signal Transduction Pathways For Novel Obesity Therapeutics

• Grant number: 24/14339-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: January 03, 2025
• End date: July 01, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Licio Augusto Velloso
• Grantee: Ester dos Santos Alves
• Supervisor: Davide Calebiro
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Birmingham, England
• Associated to the scholarship: 23/00848-1 - Characterization of the GPR139 Receptor as a Potential Target for Obesity Treatment, BP.DR

Abstract

Obesity affects over 600 million people worldwide and, despite recent therapeutic advance in the field, projections estimate a continuous increase of its prevalence over the next decade. In this context, the identification of new targets could improve therapeutic strategies and contribute to revert the current epidemiological scenario. G protein-coupled receptors (GPCRs) are the targets for over 35% of all drugs approved for the treatment of several human diseases. Orphan GPCRs are of particular interest as novel drug targets, and, in a recent exploratory study, we identified GPR139, which is expressed in hypothalamic neurons, to be involved the regulation of food intake and energy balance. The inhibition of hypothalamic GPR139 in mice resulted in increased food intake and body mass. Therefore, in this project, we plan to dissect the signal transduction pathway driving the effects of GPR139 in hypothalamic neurons. For this purpose, we will employ innovative microscopy approaches and bioluminescence energy transfer (BRET) probes that allow monitoring GPCR signalling in living cells with high spatio-temporal resolution. Using these approaches, we will clarify the signalling pathways that are activated by GPR139 in a hypothalamic neuronal cell line. Upon completion, the study will advance our understating of how hypothalamic GPR139 regulates body energy balance. This could open new opportunities for exploiting GPR139 as a novel therapeutic target for obesity.