Gpr19 encodes an orphan G-protein-coupled receptor (GPCR) [5]. GPCRs are involved in numerous physiological processes, and Gpr19 has been implicated in regulating circadian rhythm, tumor metastasis, mitochondrial homeostasis, and metabolic processes. It may also be associated with the endocannabinoid system and the aging process [1,2,3,5]. Genetic models, such as knockout mice, are valuable for studying its function.

Gpr19 knockout (KO) mouse models have revealed several key functions. Male GPR19 KO mice show glucose intolerance and diet-induced hepatomegaly with decreased fatty acid oxidation gene expression when on a high-fat diet, while both male and female KO mice have increased energy expenditure and decreased activity, indicating a sex-dependent role in whole-body energy metabolism [4]. Gpr19 -/- mice also exhibit a prolonged circadian period, a delayed start of daily locomotor activity, and reduced capacity for light-induced phase-delays in the context of circadian rhythm regulation [5]. In addition, knockdown of GPR19 in melanoma cells reduces their proliferation, migration, and invasive capabilities, suggesting its role in tumor development [6].

In conclusion, Gpr19 plays essential roles in circadian rhythm regulation, metabolic processes, and tumor-related functions. The use of Gpr19 KO mouse models has provided valuable insights into these functions, especially in the context of metabolic diseases and cancer, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Rezende, Bismarck, Alencar, Allan Kardec Nogueira, de Bem, Graziele Freitas, Fontes-Dantas, Fabrícia Lima, Montes, Guilherme Carneiro. 2023. Endocannabinoid System: Chemical Characteristics and Biological Activity. In Pharmaceuticals (Basel, Switzerland), 16, . doi:10.3390/ph16020148. https://pubmed.ncbi.nlm.nih.gov/37017445/

2. Maudsley, Stuart, Schrauwen, Claudia, Harputluoğlu, İrem, Leysen, Hanne, McDonald, Patricia. 2023. GPR19 Coordinates Multiple Molecular Aspects of Stress Responses Associated with the Aging Process. In International journal of molecular sciences, 24, . doi:10.3390/ijms24108499. https://pubmed.ncbi.nlm.nih.gov/37239845/

3. Maudsley, Stuart, Walter, Deborah, Schrauwen, Claudia, Lenaerts, Julia, McDonald, Patricia. 2022. Intersection of the Orphan G Protein-Coupled Receptor, GPR19, with the Aging Process. In International journal of molecular sciences, 23, . doi:10.3390/ijms232113598. https://pubmed.ncbi.nlm.nih.gov/36362387/

4. Mushala, Bellina A S, Xie, Bingxian, Sipula, Ian J, Jurczak, Michael J, Scott, Iain. 2023. G-protein coupled receptor 19 (GPR19) knockout mice display sex-dependent metabolic dysfunction. In Scientific reports, 13, 6134. doi:10.1038/s41598-023-33308-7. https://pubmed.ncbi.nlm.nih.gov/37061564/

5. Yamaguchi, Yoshiaki, Murai, Iori, Goto, Kaoru, Miyake, Takahito, Doi, Masao. 2021. Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock. In Scientific reports, 11, 22406. doi:10.1038/s41598-021-01764-8. https://pubmed.ncbi.nlm.nih.gov/34789778/

6. Song, Binyu, Wang, Kai, Peng, Yixuan, Yu, Zhou, Song, Baoqiang. 2023. Combined signature of G protein-coupled receptors and tumor microenvironment provides a prognostic and therapeutic biomarker for skin cutaneous melanoma. In Journal of cancer research and clinical oncology, 149, 18135-18160. doi:10.1007/s00432-023-05486-4. https://pubmed.ncbi.nlm.nih.gov/38006451/