Gpr27, an orphan G protein-coupled receptor, is a member of the "Super-Conserved Receptors Expressed in the Brain" (SREB) family [8]. It has been postulated to be involved in key physiological processes such as insulin production, secretion, lipid metabolism, neuronal plasticity, and L-lactate homeostasis [6,7,8]. Gpr27 may function through pathways like MAPK/ERK, though its exact signaling mechanisms are still being explored [1].

In gene knockout studies, deletion of Gpr27 in mice reduced insulin and Pdx1 mRNA by 30% in islets, with slightly worsened glucose tolerance but no diabetes development [4]. In zebrafish, gpr27 knockout potentiated glucose elevation, elevated medium-chain acylcarnitines associated with insulin resistance, abrogated insulin-dependent Akt phosphorylation and glucose utilization, and increased expression of key enzymes in the carnitine shuttle complex [5]. In cancer research, in hepatocellular carcinoma (HCC), GPR27 knockdown inhibited proliferation, colony formation, cell viability, and induced cell S-phase arrest by blocking the MAPK/ERK pathway [1]. In gliomas, GPR27 expression was negatively correlated with WHO grade, and lower levels were associated with higher death possibilities, while in vitro experiments showed it inhibited glioma cell growth [2]. In gastric cancer, lower GPR27 mRNA expression was related to better survival, and it had an interaction with immune cell infiltration [3].

In summary, Gpr27 plays significant roles in metabolism-related processes like insulin regulation, glucose homeostasis, and lipid metabolism. In disease contexts, especially in various cancers, Gpr27 shows potential as a prognostic biomarker and therapeutic target. Gene knockout models in mice and zebrafish have been crucial in uncovering these functions, helping to understand the biological processes and disease mechanisms related to Gpr27 [1,2,3,4,5].

References:

1. Wang, Hongxv, Du, Danyu, Huang, Jianwen, Yuan, Shengtao, Xiao, Jing. 2022. GPR27 Regulates Hepatocellular Carcinoma Progression via MAPK/ERK Pathway. In Cancer management and research, 14, 1165-1177. doi:10.2147/CMAR.S335749. https://pubmed.ncbi.nlm.nih.gov/35330739/

2. Cai, Changcheng, Hu, Libo, Wu, Ke, Liu, Yinggang. 2024. GPR27 expression correlates with prognosis and tumor progression in gliomas. In PeerJ, 12, e17024. doi:10.7717/peerj.17024. https://pubmed.ncbi.nlm.nih.gov/38638156/

3. Pan, Jun, Gao, Yuanjun. 2023. Prognostic significance and immune characteristics of GPR27 in gastric cancer. In Aging, 15, 9144-9166. doi:10.18632/aging.205023. https://pubmed.ncbi.nlm.nih.gov/37702614/

4. Chopra, Deeksha G, Yiv, Nicholas, Hennings, Thomas G, Zhang, Yaohuan, Ku, Gregory M. 2020. Deletion of Gpr27 in vivo reduces insulin mRNA but does not result in diabetes. In Scientific reports, 10, 5629. doi:10.1038/s41598-020-62358-4. https://pubmed.ncbi.nlm.nih.gov/32221326/

5. Nath, Anjali K, Ma, Junyan, Chen, Zsu-Zsu, Gerszten, Robert E, Yeh, Jing-Ruey J. 2019. Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34, 1546-1557. doi:10.1096/fj.201901466R. https://pubmed.ncbi.nlm.nih.gov/31914600/

6. Pillaiyar, Thanigaimalai, Wozniak, Monika, Abboud, Dayana, Laufer, Stefan A, Hanson, Julien. 2023. Development of Ligands for the Super Conserved Orphan G Protein-Coupled Receptor GPR27 with Improved Efficacy and Potency. In Journal of medicinal chemistry, 66, 17118-17137. doi:10.1021/acs.jmedchem.3c02030. https://pubmed.ncbi.nlm.nih.gov/38060818/

7. Pillaiyar, Thanigaimalai, Rosato, Francesca, Wozniak, Monika, Müller, Christa E, Hanson, Julien. 2021. Structure-activity relationships of agonists for the orphan G protein-coupled receptor GPR27. In European journal of medicinal chemistry, 225, 113777. doi:10.1016/j.ejmech.2021.113777. https://pubmed.ncbi.nlm.nih.gov/34454125/

8. Bayrak, Alp, Hanson, Julien, Laufer, Stefan, Pillaiyar, Thanigaimalai. 2022. Super-conserved receptors expressed in the brain: biology and medicinal chemistry efforts. In Future medicinal chemistry, 14, 899-913. doi:10.4155/fmc-2022-0006. https://pubmed.ncbi.nlm.nih.gov/35535715/