Regulating body weight by GPR75 in glutamatergic neurons
The G-protein-coupled receptor 75 gene (GPR75) loss of function in humans are associated with reduced body mass index (BMI) and Gpr75-deficient mice are protected from diet induced obesity (DIO).
Using targeted deletion and reactivation of Gpr75 in glutamatergic neurons, the researchers in this study identify a critical neuronal population that is required for GPR75 to exert its obesogenic effects.
The authors show that loss of Gpr75 in vGlut2+ glutamatergic neurons results in protection against high-fat diet (HFD)-induced weight gain, whereas loss of Gpr75 in GABAergic neurons shows no protection against DIO.
The researchers also demonstrate that reactivation of Gpr75 only in vGlut2-expressing cells in a Gpr75 null mouse completely rescues the HFD-induced weight gain, whereas reactivation in GABAergic cells has no effect on body weight or adiposity.
https://www.cell.com/cell-reports/fulltext/S2211-1247(26)00089-6
