Gpr149 is involved in energy homeostasis in the male mouse.

GPR149 is an orphan receptor about which little is known. Accordingly, in the present study, we mapped the tissue expression of in mice using three complementary approaches: quantitative PCR, hybridization, and a newly generated Gpr149-Cre reporter mouse model. The strongest expressions of were observed in neurons of the islands of Calleja, the ventromedial hypothalamus, and the rostral interpeduncular nucleus. Moderate-to-low expression was also observed in the basal forebrain, striatum, hypothalamus, brainstem, and spinal cord. Some expression was also detected in the primary afferent neurons, enteric neurons, and pituitary endocrine cells. This expression pattern is consistent with the involvement of GPR149 signaling in the regulation of energy balance. To explore the physiological function of GPR149 , we used CRISPR-Cas9 to generate a global knockout allele with mice lacking exon 1. Preliminary metabolic findings indicated that mice partially resist weight gain when fed with a high-fat diet and have greater sensitivity to insulin than control mice. In summary, our data may serve as a resource for future studies on GPR149 in the context of diet-induced obesity.