Fiona Murray
Senior Lecturer, University of Aberdeen
Presentation: GPR75: Orphan to Opportunity in Metabolic Syndrome
The orphan G protein-coupled receptor (GPCR), GPR75, has recently emerged as a novel target for metabolic syndrome (MetS): analysis of the UK Biobank revealed that loss-of-function variants in GPR75 are associated with lower body mass index and a reduced likelihood of hepatic steatosis. Building on this genetic evidence, we demonstrated that deletion of GPR75 protects against high-fat-diet–induced MetS [Leeson-Payne et al., 2024]. However, orphan GPCRs are challenging to study as without an endogenous ligand their pharmacology is difficult to define, and it is harder to link receptor expression to cellular function and disease. Our group has undertaken the complex task of dissecting the signalling, regulation, sex-dependent effects, and tissue-specific roles of GPR75 , revealing both the obstacles and opportunities this orphan GPCR presents for MetS.
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