The orphan receptor GPR68 is expressed in the hypothalamus and is involved in the regulation of feeding

•Using bioinformatic tools we identified 78 class A orphan GPCRs expressed in the hypothalamus and for most of them there is no known function.•GPR68 is mostly expressed in hypothalamic neurons and undergoes increased expression when mice are fed a high-fat diet.•The allosteric inhibition of GPR68 promotes an increase in the expression of orexigenic neurotransmitters, agouti-related peptide and neuropeptide Y.•The allosteric inhibition of GPR68 promotes an increase in food intake.