NLRP3 inflammasome activation in PCOS: A novel target for managing insulin resistance and metabolic dysregulation

IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY
Fatemeh Samadi Nasab , Hanie Babei , Mehrnaz Nayebzadeh , Elahe Sadati , Ziba Zahiri , Tayebeh Esfidani , Shabnam Forouzin , Atoosa Etezadi
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引用次数: 0

Abstract

In this comprehensive narrative review, we systematically examine the role of the NLRP3 inflammasome in the pathogenesis of polycystic ovary syndrome (PCOS) and evaluate its potential as a therapeutic target for managing insulin resistance. We performed literature searches in PubMed, Scopus, and Web of Science up to April 2025, using keywords including “PCOS,” “NLRP3 inflammasome,” “insulin resistance,” and “reproductive dysfunction.” Only peer-reviewed studies directly addressing inflammasome activation in PCOS were included, while articles lacking mechanistic or clinical relevance were excluded. PCOS is a highly prevalent and complex endocrine–metabolic disorder characterized by chronic low-grade inflammation, insulin resistance, and reproductive dysfunction, affecting millions of women globally. Despite its widespread impact, current treatments mainly address symptoms rather than underlying disease mechanisms, highlighting the urgent need for novel, targeted therapeutic approaches. Emerging evidence implicates the NLRP3 inflammasome as a central mediator linking immune activation, metabolic dysregulation, and ovarian pathology in PCOS. Activation of NLRP3 triggers release of IL-1β and IL-18, which impair insulin signaling, disrupt glucose homeostasis, and sustain systemic inflammation. Beyond metabolic effects, NLRP3-driven inflammation contributes to anovulation, follicular atresia, and hormonal imbalance. Interactions with mitochondrial dysfunction and endoplasmic reticulum stress further amplify cellular stress responses, accelerating disease progression. This review synthesizes current mechanistic insights into how NLRP3 activation drives both metabolic and reproductive impairments in PCOS, and highlights emerging therapeutic strategies—including pharmacological inhibitors, anti-inflammatory agents, and precision medicine approaches—aimed at disrupting the inflammatory–insulin resistance cycle. By elucidating these immunometabolic mechanisms, our findings support a shift from symptom-based management toward targeted, disease-modifying interventions, advancing precision medicine in women’s health.
多囊卵巢综合征的NLRP3炎性体激活:胰岛素抵抗和代谢失调的新靶点
在这篇全面的叙述性综述中,我们系统地研究了NLRP3炎性体在多囊卵巢综合征(PCOS)发病机制中的作用,并评估了其作为控制胰岛素抵抗的治疗靶点的潜力。截至2025年4月,我们在PubMed、Scopus和Web of Science中进行了文献检索,关键词包括“PCOS”、“NLRP3炎性体”、“胰岛素抵抗”和“生殖功能障碍”。只有同行评审的研究直接涉及多囊卵巢综合征的炎性体激活,而缺乏机制或临床相关性的文章被排除在外。多囊卵巢综合征是一种高度流行和复杂的内分泌代谢紊乱,其特征是慢性低度炎症、胰岛素抵抗和生殖功能障碍,影响全球数百万妇女。尽管其影响广泛,但目前的治疗主要针对症状而不是潜在的疾病机制,因此迫切需要新的靶向治疗方法。新出现的证据表明,NLRP3炎症小体是PCOS中免疫激活、代谢失调和卵巢病理相关的中心介质。NLRP3的激活触发IL-1β和IL-18的释放,从而损害胰岛素信号,破坏葡萄糖稳态并维持全身性炎症。除了代谢作用外,nlrp3驱动的炎症还会导致无排卵、卵泡闭锁和激素失衡。与线粒体功能障碍和内质网应激的相互作用进一步放大细胞应激反应,加速疾病进展。本文综述了目前关于NLRP3激活如何驱动多囊卵巢综合征代谢和生殖损伤的机制见解,并重点介绍了旨在破坏炎症-胰岛素抵抗周期的新兴治疗策略,包括药物抑制剂、抗炎剂和精准医学方法。通过阐明这些免疫代谢机制,我们的研究结果支持从基于症状的管理转向有针对性的疾病改善干预,推进女性健康的精准医学。
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
Tissue & cell
Tissue & cell 医学-解剖学与形态学
CiteScore
3.90
自引率
0.00%
发文量
234
期刊介绍: Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.
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