Pharmacological Research· 2026Q1· Derleme
GPR75: Metabolik Hastalıkların Düzenlenmesinde 20-HETE ve CCL5 İçin Çift-Ligandlı Bir Reseptör
GPR75: A dual-ligand receptor for 20-HETE and CCL5 with emerging roles in central and peripheral regulation of metabolic diseases
- 0atıf
- Q1SCImago
- 2026yıl
Kısa özet
G protein-eşleşmeli reseptör 75 (GPR75), metabolik süreçlerin yeni bir düzenleyicisi olarak dikkat çekmekte ve fonksiyon kaybı varyantları obezite, tip 2 diyabet, MASLD ve hipertansiyon riskinin azalmasıyla ilişkilendirilmektedir.
Yapay zekâ ile başlık ve abstract'tan üretildi; tam metin okunmaz.
Ana noktalar
- GPR75, 20-HETE ve CCL5 için çift-ligandlı bir reseptördür.
- 20-HETE, Gαq/11 sinyalini aktive eden güçlü bir GPR75 agonisti olarak görev yapar.
- GPR75'teki fonksiyon kaybı varyantları, obezite, tip 2 diyabet, MASLD ve hipertansiyon riskinin azalmasıyla ilişkilidir.
- GPR75, hipotalamus, yağ dokusu, karaciğer, pankreas ve damar sistemi dahil olmak üzere önemli metabolik dokularda eksprese edilir.
Yapay zekâ ile başlık ve abstract'tan üretildi; tam metin okunmaz.
Özet (abstract)
G protein-coupled receptor 75 (GPR75) has recently attracted considerable attention as a novel regulator of metabolic, immune, and vascular processes. Current evidence suggests that two structurally distinct molecules have been proposed as candidate endogenous ligands for GPR75: 20-hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P450-derived lipid metabolite, and C-C motif chemokine ligand 5 (CCL5; RANTES), a chemokine involved in immune regulation. Among these ligands, 20-HETE functions as a potent agonist of GPR75, leading to activation of Gαq/11-dependent signaling pathways and β-arrestin recruitment. In contrast, although CCL5 has also been reported to interact with GPR75, its role as a direct receptor agonist remains controversial and may be highly context-dependent. Notably, GPR75 is broadly expressed in tissues involved in the regulation of energy homeostasis, including the hypothalamus, adipose tissue, liver, pancreas, and vascular system. Population genetic studies have demonstrated that loss-of-function variants in GPR75 are associated with a reduced risk of obesity, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD), and hypertension. Evidence from animal models further supports a role for GPR75 in the regulation of feeding behavior, insulin sensitivity, lipid metabolism, vascular tone, and inflammatory responses. This review provides a comprehensive overview of the structural characteristics, ligand recognition mechanisms, signaling properties, and tissue distribution of GPR75 and discusses its functions in both the central nervous system and peripheral metabolic tissues. Elucidating how GPR75 integrates, differentiates, and transduces signals derived from these distinct ligands may provide new opportunities for therapeutic intervention in obesity, diabetes, MASLD, and their associated complications.
Yazarların özeti; kaynağından alınmıştır. Pharmacological Research, 2026 · DOI ↗
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Alan: Biyokimya (Biyokimya, Genetik ve Moleküler Biyoloji)
BiochemistryBiochemistry, Genetics and Molecular Biology