be kept at extremely low basal levels until there is a thermogenic demand. Mimicking the cold induction of Gpr3 is then sufficient to drive and maintain elevated BAT activity even under conditions of little or no sympathetic tone. To prove this, OS Johansen and colleagues developed a conditional gain-of-function model (Gpr3 TTG) for robust and sustained genetic manipulation of Gpr3 in vitro and in vivo. Gpr3 TTG mice were crossed with mice to facilitate overexpression of Gpr3 in isolated primary brown and subcutaneous white adipocytes. Gpr3 overexpression significantly increased the expression of thermogenic genes, fatty acid uptake, and basal and leak mitochondrial respiration. Gpr3 overexpression in their primary adipocyte model suppressed expression of the β-adrenergic receptors, further supporting a counter-regulatory interaction between GPR3 and other Gs-coupled receptors. BAT-specific overexpression of Gpr3 (C-3BO) mice were completely protected from developing diet-induced obesity despite maintaining comparable levels of food intake, C-3BO mice maintained elevated whole-body energy expenditure as well as darker brown BAT depots and higher thermogenic gene expression. Reproductive system In mammalian oocytes, the process of meiotic arrest and meiotic maturation is controlled by in large part by cAMP concentrations in the cell. When cAMP levels in the cell decrease the process of miosis resumes and this precedes germinal vesicle breakdown. It is proposed That GPR3 is implicated in cAMP signaling in oocytes since it is consistent with the observation that their mRNA expression is reduced when cAMP is chronically increased in oocytes. The constitutive activity of these receptors is sufficient to prevent maturation in mouse oocytes, it is shown that their activity is also sufficient for maintaining the meiotic arrest in the follicle. Brain cells GPR3 mRNA is broadly expressed in neurons in various brain regions, including the cortex, thalamus, hypothalamus, amygdala, hippocampus, pituitary, and cerebellum. Notably, the GPR3 protein is overexpressed in neurons in post-mortem brain tissue sections from individuals afflicted by Alzheimer's disease. In a study on mice with Alzheimer's disease, it was shown that the disruption of the expression of GPR3 has affected the overgrowth of amyloid plaque on neurons, helping symptoms of Alzheimer's disease. Ligands GPR3 is largely known as an orphan G protein-coupled receptor. Even though it does not have any endogenous ligands there is research being conducted to find non-endogenous agonists for the receptor. Agonists Sphingosine 1-phosphate The molecule Sphingosine 1-phosphate (S1P) is a signaling lipid that exists in the extracellular plasma, its synthesis is