Circadian regulation of the S1PR1-P2X7 signalling axis in obesity-associated metabolic inflammation: molecular crosstalk and therapeutic perspectives.

IF 2.5 4区医学 Q2 NEUROSCIENCES

Purinergic Signalling Pub Date : 2026-10-20 DOI:10.1007/s11302-026-10194-y

Alka Patel, Parag Jain, Hina Sahu

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引用次数: 0

Abstract

Obesity is a chronic, low-grade inflammatory condition expressed by inflammation and immune damage that mediates component(s) of insulin resistance and cardiometabolic syndrome in the presence of disruption of circadian rhythms. Primary research data indicate that the interplay between biological timing and immunological signalling occurs in a synchronised manner to govern metabolic homeostasis, thereby leading us to coin the term Circadian regulation of metabolic inflammation. These signalling pathways directly affect immune cell trafficking and endothelial integrity in sphingosine-1-phosphate receptor 1 (S1PR1) or purinergic P2X7 receptor (P2X7)-mediated regulation, and inflammasome activation. This review highlights a new molecular link establishing the S1PR1-P2X7 axis between circadian rhythm and obesity-linked immunometabolic disorders. We discuss the interplay of lipid and purinergic signalling, focusing on their convergence at nuclear factor kappa B (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), signal transducer and activator of transcription 3 (STAT3), reactive oxygen species (ROS), and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) activation pathways that act in concert to exacerbate both fatty tissue inflammation and systemic insulin metabolic resistance. Altogether, we summarise the latest advances in receptor-based pharmacotherapy, chronotherapy, and nanomedicine-guided drug delivery aimed at restoring circadian homeostasis and metabolic balance. Understanding the circadian regulation of the S1PR1-P2X7 axis may inform new precision treatment strategies for obesity-linked metabolic diseases.

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S1PR1-P2X7信号轴在肥胖相关代谢炎症中的昼夜调节：分子串扰和治疗观点

肥胖是一种慢性、低度炎症，由炎症和免疫损伤表达，在昼夜节律紊乱的情况下介导胰岛素抵抗和心脏代谢综合征的组成部分。初步研究数据表明，生物计时和免疫信号之间的相互作用以同步的方式发生，以控制代谢稳态，从而使我们创造了代谢性炎症的昼夜节律调节这一术语。这些信号通路在鞘氨醇-1-磷酸受体1 （S1PR1）或嘌呤能P2X7受体（P2X7）介导的调控和炎性体激活中直接影响免疫细胞运输和内皮完整性。这篇综述强调了在昼夜节律和肥胖相关的免疫代谢紊乱之间建立S1PR1-P2X7轴的新分子联系。我们讨论了脂质和嘌呤能信号传导的相互作用，重点讨论了它们在核因子κB （NF-κB）、磷酸肌肽3-激酶/蛋白激酶B （PI3K/Akt）、转录信号传导和激活因子3 （STAT3）、活性氧（ROS）以及NOD-、LRR-和pyrin结构域蛋白3 （NLRP3）激活途径上的收敛，这些途径协同作用，加剧了脂肪组织炎症和全身胰岛素代谢抵抗。总之，我们总结了以受体为基础的药物治疗、时间疗法和纳米医学指导的药物递送的最新进展，旨在恢复昼夜节律稳态和代谢平衡。了解S1PR1-P2X7轴的昼夜节律调节可能为肥胖相关代谢疾病提供新的精确治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Purinergic Signalling 医学-神经科学

CiteScore

6.60

自引率

17.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.