Ask about this productRelated genes to: GPR75 Blocking Peptide
- Gene:
- GPR75 NIH gene
- Name:
- G protein-coupled receptor 75
- Previous symbol:
- -
- Synonyms:
- WI-31133
- Chromosome:
- 2p16.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-10-22
- Date modifiied:
- 2016-10-05
Related products to: GPR75 Blocking Peptide
Related articles to: GPR75 Blocking Peptide
- Gestational diabetes mellitus (GDM) is a common pregnancy complication associated with significant maternal and fetal risks. The 20-hydroxyeicosatetraenoic acid (20-HETE) and its receptor GPR75 have been implicated in metabolic dysregulation, but their role in GDM remains unclear. This study investigated the pathophysiological role of the 20-HETE/GPR75 axis in GDM and evaluated the therapeutic potential of a GPR75 antagonist. In a mouse model of GDM, we found significantly elevated levels of 20-HETE in plasma (2.4-fold) and placental tissue (1.6-fold), alongside increased GPR75 expression at both mRNA (2.3-fold, P < 0.01) and protein levels (2.1-fold). Administration of the GPR75 antagonist AAA (10 mg/kg/day) markedly attenuated hyperglycemia (143.3 ± 14.2 vs. 195.2 ± 21.3 mg/dL, P < 0.01), improved insulin levels (5.7 ± 0.59 vs. 3.9 ± 0.39 mg/dL, P < 0.01), corrected dyslipidemia (TC: 113.5 ± 15.1 vs. 168.7 ± 20.2 mg/dL, P < 0.01; TG: 124.9 ± 13.8 vs. 215.3 ± 23.6 mg/dL, P < 0.01), and improved fetal survival rate (97.2% vs. 81.2%, P < 0.05). Mechanistically, the antagonist reduced oxidative stress (TBARS decreased by 58%, ROS levels reduced by approximately 42%, both P < 0.01), suppressed NLRP3 inflammasome activation (NLRP3 expression reduced by 48%, P < 0.01; IL-1β: 1.7 ± 0.16 vs. 3.5 ± 0.37 ng/g protein, P < 0.01), and inhibited the MAPK p38/NF-κB signaling pathway (p-p38/p38 ratio reduced from 2.8 ± 0.25-1.3 ± 0.13, p-NF-κB p65 from 2.3 ± 0.24-1.2 ± 0.11, both P < 0.01) in the placenta. Our findings demonstrate that the 20-HETE/GPR75 pathway is upregulated in GDM and contributes to its pathophysiology. Targeting GPR75 represents a promising therapeutic strategy for mitigating GDM symptoms and improving placental function. - Source: PubMed
Publication date: 2026/04/02
Tong QiaolingHu ManGuan YuanSong Fang - The G-protein-coupled receptor 75 (GPR75) emerged as a promising therapeutic target for treating diet-induced obesity (DIO). Loss-of-function mutations of GPR75 in humans are associated with reduced body mass index (BMI). Also, Gpr75-deficient mice are protected from DIO. Here, we generated genetically modified mice that enable us to selectively delete or reactivate Gpr75 in a Cre-dependent manner. Loss of Gpr75 in vGlut2+ glutamatergic neurons (Gpr75) results in protection against high-fat diet (HFD)-induced weight gain, whereas loss of Gpr75 in GABAergic neurons shows no protection against DIO. Furthermore, male Gpr75 mice have reduced food intake on HFD without a change in energy expenditure. Reactivation of Gpr75 only in vGlut2-expressing cells in a Gpr75 null mouse (Gpr75) completely rescues the HFD-induced weight gain, whereas reactivation in GABAergic cells has no effect on body weight or adiposity. These complementary results demonstrate the importance of glutamatergic neurons in GPR75's regulation of food intake and protection from obesity. - Source: PubMed
Publication date: 2026/02/20
Wyler Steven CGahlot SurbhiBideyan LaraBrown KyleSchiavo Jennifer KGalvan MarcoThomas ShreyaTinajero ArelyKhan AdanMerchant WardaGautron LaurentYou Young-JaiMastaitis Jason WAltarejos Judith YFujikawa TeppeiElmquist Joel K - G-protein coupled receptor (GPCR) 75 (GPR75) is a 540 amino acid member of the G class of GPCRs, with no homology with other classic GPCRs. The current focus on GPR75 has centred on its potential role in metabolic disorders and cancer. GPR75 expression is abundant in the central nervous system (CNS) more so than in the peripheral tissues; however, much remains unknown about the distribution and role of this receptor throughout the CNS. In this study, we quantified GPR75 mRNA expression in the mouse CNS using RNAscope fluorescent in situ hybridization (FISH) technology, combined with immunohistochemistry (IHC) to detect GPR75 transcripts in specific neuronal cell types. GPR75 knockout (KO) mice were used as controls and specificity of hybridization. Our results show that GPR75 mRNA expression occurs in several neuronal populations including GABAergic and glutamatergic neurons. In select areas, such as the substantia nigra/ventral tegmental area, locus coeruleus and raphe nucleus, GPR75 mRNA is also highly expressed in monoaminergic neurons. Moreover, we found high expression of GPR75 mRNA in the cerebellum, in both GABAergic and glutamatergic neurons, suggesting a potential role for this receptor in motor/equilibrium activity. Indeed, GPR75 KO mice perform significantly better than wild-type littermates on the rotarod test. Our data suggest that this receptor may play an important role in brain physiology and function. - Source: PubMed
Becher Melanie KKnox TessaWilson KaelaKromer Lawrence FMocchetti Italo - Loss of function G-protein coupled receptor 75 (GPR75) variants in humans are associated with leanness, and Gpr75 null mice are protected from diet-induced obesity (DIO). However, the mechanisms underlying this protection are largely unknown. Here, we investigated the contribution of adipocyte-derived Gpr75 to DIO. Adipocyte-specific Gpr75 knockout (adipo-Gpr75) male and female mice and their wild-type (WT) littermates were placed on a high-fat diet (HFD) for 14 weeks. Metabolic parameters including body weight, energy intake and expenditure, activity, and glucose metabolism were monitored before and after diet feeding. While WT mice obtained a diabetogenic phenotype on HFD, the adipo-Gpr75 counterparts were protected. This protection showed sexual dimorphism. Female adipo-Gpr75 mice displayed a 50% (p < 0.001) decrease in weight gain and adiposity compared to WT, whereas male adipo-Gpr75 gained weight like WT mice. Interestingly, both male and female adipo-Gpr75 mice exhibited improved glucose handling compared to WT, which was correlated to decreased adiposity, abrogated adipose tissue inflammation, and increased insulin sensitivity in skeletal muscle. Importantly, no differences in food intake were observed; however, adipo-Gpr75 mice exhibited increased activity and energy expenditure, regardless of sex. Taken together, these findings demonstrate that deletion of GPR75 specifically in adipocytes is sufficient to confer protection against DIO and suggest that adipocyte-derived GPR75 contributes importantly to the pathogenesis of DIO potentially by mechanisms that may include promotion of inflammation, impairment of insulin signaling, and disruption of metabolic homeostasis. - Source: PubMed
Hossain SakibVillegas ElizabethLiapes CatherineSultana NahidKrasniqi DorinaDiegisser DanielleCastro AnaWilliams ComfortGruzdev ArtiomZeldin Darryl CGarcia VictorSchwartzman Michal Laniado - Metabolic dysfunction-associated steatotic liver disease (MASLD), including its more severe form, metabolic dysfunction-associated steatohepatitis (MASH), is increasingly recognized as a critical global health challenge. This study investigates the role of hepatic GPR75 in MASH progression. - Source: PubMed
Publication date: 2026/02/03
Yang XuleYang NaCheng ZhihaoZhang RuiFan HuiLiu DongshengAa JiyeWang GuangjiXie Yuan