GPR119

Description

The GPR119 (G protein-coupled receptor 119) is a protein-coding gene located on chromosome X.

G protein-coupled receptor 119, also known as GPR119, is a G protein-coupled receptor encoded by the GPR119 gene in humans. Along with GPR55 and GPR18, it has been suggested as a novel cannabinoid receptor.

GPR119 is primarily found in the pancreas and gastrointestinal tract of both rodents and humans, and is also present in the rodent brain. Activation of the receptor leads to a decrease in food intake and body weight gain in rats. GPR119 also regulates the secretion of incretin and insulin hormones. Consequently, new drugs targeting this receptor have been proposed as potential treatments for obesity and diabetes.

Several endogenous, synthetic, and plant-derived ligands for GPR119 have been identified:

2-Oleoylglycerol (2OG)
Anandamide
AR-231,453
MBX-2982
Oleoylethanolamide (OEA) (Endogenous Ligand)
PSN-375,963
PSN-632,408

Commensal bacteria play a crucial role in human health. Bacterial metabolites are likely key components in host interactions that influence mammalian physiology. N-acyl amide synthase genes, found in abundance within gastrointestinal bacteria, produce lipids that interact with GPCRs, regulating gastrointestinal tract physiology. Cell-based models have shown that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as effectively as human ligands. The most significant overlap in structure and function between bacterial and human GPCR-active ligands is observed for the endocannabinoid receptor GPR119.

Experiments have isolated both palmitoyl and oleoyl analogs of N-acyl serinol. The oleoyl analog differs from 2-OG: C21H40O4 only by the presence of an amide instead of an ester, and from OEA: C20H39NO2 by the presence of an additional ethanol substituent. N-oleoyl serinol (C21H41NO3; 18:1,n-9) is a potent GPR119 agonist similar to the endogenous ligand OEA (EC50 12 μM vs. 7 μM), but it elicits nearly twice the maximum activation. This suggests that chemical mimicry of eukaryotic signaling molecules may be common among commensal bacteria, which communicate through interactions between these two fundamental systems—forming the gut microbiota-endocannabinoidome axis.

GPR119 is also known as GPCR2.

Associated Diseases

WES Whole Exome Sequencing