Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA.
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA.
Curr Opin Pharmacol. 2022 Apr;63:102190. doi: 10.1016/j.coph.2022.102190. Epub 2022 Feb 26.
Extracellular uridine nucleotides regulate physiological and pathophysiological metabolic processes through the activation of P2Y, P2Y, P2Y and P2Y purinergic receptors, which play a key role in adipogenesis, glucose uptake, lipolysis and adipokine secretion. Using adipocyte-specific knockout mouse models, it has been demonstrated that lack of the P2YR or P2YR can protect against diet-induced obesity and improve whole-body glucose metabolism. The P2YR facilitated adipogenesis and inflammation, and the loss of P2YR or P2YR raised the levels of the protective endocrine factor adiponectin. Hence, potent antagonists for these receptors may be tested to identify drug candidates for the treatment of obesity and type 2 diabetes. However, future studies are required to provide insight into purinergic regulation of brown adipocytes and their role in thermogenesis. This review summarizes the current studies on uridine nucleotide-activated P2YRs and their role in adipocyte function, diet-induced obesity and associated metabolic deficits.
细胞外尿苷核苷酸通过激活 P2Y、P2Y、P2Y 和 P2Y 嘌呤能受体调节生理和病理生理代谢过程，这些受体在脂肪生成、葡萄糖摄取、脂肪分解和脂肪细胞因子分泌中发挥关键作用。使用脂肪细胞特异性敲除小鼠模型，已经证明缺乏 P2YR 或 P2YR 可以预防饮食诱导的肥胖并改善全身葡萄糖代谢。P2YR 促进脂肪生成和炎症，而 P2YR 或 P2YR 的缺失会提高保护性内分泌因子脂联素的水平。因此，这些受体的有效拮抗剂可能会被测试，以鉴定用于治疗肥胖症和 2 型糖尿病的候选药物。然而，需要进一步的研究来深入了解嘌呤能对棕色脂肪细胞的调节及其在产热中的作用。本综述总结了目前关于尿苷核苷酸激活的 P2YRs 及其在脂肪细胞功能、饮食诱导肥胖和相关代谢缺陷中的作用的研究。
