G-Protein Coupled Receptor 19 (Gpr19) Knockout Mice Display Sex-Dependent Metabolic Dysfunction

Abstract

G-protein coupled receptors (GPCRs) mediate signal transduction from the cellular surface to intracellular metabolic pathways. While the function of many GPCRs has been delineated previously, a significant number require further characterization to elucidate their cellular function. G-protein coupled receptor 19 (GPR19) is a poorly characterized class A GPCR which has been implicated in the regulation of circadian rhythm, tumor metastasis, and mitochondrial homeostasis. In this report, we use a novel knockout (KO) mouse model to examine the role of GPR19 in whole-body metabolic regulation. We show that loss of GPR19 promotes increased energy expenditure and decreased activity in both male and female mice. However, only male GPR19 KO mice display glucose intolerance in response to a high fat diet (HFD). Loss of GPR19 expression in male mice, but not female mice, resulted in diet-induced hepatomegaly, which was associated with decreased expression of key fatty acid oxidation genes in male GPR19 KO livers. Overall, our data suggest that loss of GPR19 impacts whole-body energy metabolism in diet-induced obese mice in a sex-dependent manner.

WITHDRAWN: Novel splicing variants in ARR3 gene cause the female- limited early-onset high myopia

“…The ARR3 gene encodes a 388-amino acid protein belonging to the arrestin family of proteins [9]. Arrestins play a role in regulating the signaling and tra cking of G protein-coupled receptors (GPCRs), which are essential for various cellular processes including vision, smell, hormone response, and neurotransmission [10,11]. ARR3 gene expression is speci cally observed in the retina and pineal gland, where it facilitates the desensitization and internalization of light-activated rhodopsin, a GPCR that initiates the phototransduction cascade [12][13][14].…”