目的:多囊卵巢综合征(PCOS)是一种复杂的遗传性状,是女性最常见的内分泌疾病,在全球5%-15%的育龄女性中具有临床意义,与相关的心脏代谢功能障碍。脂肪组织(AT)功能障碍似乎在PCOS的病理生理学中起重要作用,即使在没有过度肥胖的患者中也是如此。
方法:我们对PCOS患者AT功能障碍进行了系统评价,以及直接评估AT功能的优先研究。我们还探索了针对AT功能障碍的治疗PCOS的疗法。
结果:确定了PCOS中AT功能障碍的各种机制,包括储存能力失调,缺氧,和增生;脂肪生成受损;胰岛素信号传导和葡萄糖转运受损;脂解和非酯化游离脂肪酸(NEFA)动力学失调;脂肪因子和细胞因子失调和亚急性炎症;表观遗传失调;以及线粒体功能障碍和ER和氧化应激。GLUT-4在脂肪细胞中的表达和含量降低,导致AT中胰岛素介导的葡萄糖转运减少,尽管胰岛素结合或IRS/PI3K/Akt信号没有改变,但仍是一致的异常。与对照相比,PCOS中响应于细胞因子/趋化因子的脂联素分泌受到影响。有趣的是,通过DNA甲基化和miRNA调节的表观遗传调节似乎是PCOS中AT功能障碍的重要机制。
结论:AT功能障碍,超过AT分布和过度肥胖,导致PCOS的代谢和炎症异常。尽管如此,许多研究提供了矛盾的,不清楚,或有限的数据,强调迫切需要在这一重要领域进行更多研究。
OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity.
METHODS: We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS.
RESULTS: Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS.
CONCLUSIONS: AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.