Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland..
Doctoral School, Medical University of Warsaw, 02-091 Warsaw, Poland.
Int J Mol Sci. 2024 Aug 29;25(17):9391. doi: 10.3390/ijms25179391.
Obesity, which leads to metabolic dysregulation and body function impairment, emerges as one of the pressing health challenges worldwide. Excessive body fat deposits comprise a dynamic and biologically active organ possessing its own endocrine function. One of the mechanisms underlying the pathophysiology of obesity is low-grade systemic inflammation mediated by pro-inflammatory factors such as free fatty acids, lipopolysaccharides, adipokines (including leptin, resistin and visfatin) and cytokines (TNF-α, IL-1β, Il-6), which are secreted by adipose tissue. Together with obesity-induced insulin resistance and hyperandrogenism, the exacerbated immune response has a negative impact on the hypothalamic-pituitary-gonadal axis at all levels and directly affects reproduction. In women, it results in disrupted ovarian function, irregular menstrual cycles and anovulation, contributing to infertility. This review focuses on the abnormal intracellular communication, altered gene expression and signaling pathways activated in obesity, underscoring its multifactorial character and consequences at a molecular level. Extensive presentation of the complex interplay between adipokines, cytokines, immune cells and neurons may serve as a foundation for future studies in search of potential sites for more targeted treatment of reproductive disorders related to obesity.
肥胖会导致代谢失调和身体功能障碍,成为全球紧迫的健康挑战之一。过多的体脂沉积构成了一个动态且具有生物活性的器官,具有自身的内分泌功能。肥胖症病理生理学的机制之一是由脂肪组织分泌的促炎因子(如游离脂肪酸、脂多糖、脂肪因子(包括瘦素、抵抗素和内脂素)和细胞因子(TNF-α、IL-1β、IL-6)介导的低度系统性炎症。与肥胖引起的胰岛素抵抗和高雄激素血症一起,加剧的免疫反应对下丘脑-垂体-性腺轴的各个层面都有负面影响,并直接影响生殖。在女性中,它会导致卵巢功能紊乱、月经周期不规律和无排卵,导致不孕。本综述重点关注肥胖症中异常的细胞内通讯、改变的基因表达和信号通路,强调其在分子水平上的多因素特征和后果。详细介绍脂肪因子、细胞因子、免疫细胞和神经元之间的复杂相互作用,可以为未来研究寻找与肥胖相关的生殖障碍的更有针对性的治疗靶点奠定基础。