Torshizi Faeze Fazel, Heravi Reza Majidzadeh, Javadmanesh Ali
Animal Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Animal Sciences Department, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran.
Biol Trace Elem Res. 2025 Jul;203(7):3793-3802. doi: 10.1007/s12011-024-04452-6. Epub 2024 Nov 30.
Zinc (Zn) is a significant element of the reproductive system and is associated with several enzymes that regulate different metabolic pathways. Organic Zn can significantly affect polycystic ovarian syndrome (PCOS) pathogenesis. Insulin resistance (IR) is a common complication of PCOS. Mammalian target of rapamycin (mTOR), which controls crucial cell functions, is regulated by insulin and nutrients. It has two complexes, namely, mTORC1 and mTORC2. mTOR associates with its binding partner's regulatory associated protein of mTOR (Raptor) and rapamycin-insensitive companion of mTOR (Rictor), which form these distinct complexes, respectively, and is activated in PCOS. This research aimed to evaluate the effect of Zn on the expression of mTOR signaling genes (Raptor and Rictor) and IR in PCOS model rats. Different Zn supplements, including standard diet (SD): (control - or + , SD without supplementation), Zn25, Zn75, and Zn175 (daily given three levels of 25, 75, and 175 mg Zn methionine (ZnMet)/kg for 6 weeks, respectively), were applied to the control and PCOS groups. Fasting glucose (FG), fasting insulin (FI), IR indices, and Raptor and Rictor expression levels were measured in both groups. The results showed that PCOS induction dramatically increased FG, FI, IR indices, and mTOR-related gene expression; however, different Zn supplementation concentrations, especially at 75 mg/kg, reduced the effects of PCOS induction. Organic Zn collectively exerted positive effects on Estradiol Valerate (EV)-induced PCOS rats by reducing IR and mTOR signaling gene (i.e., Raptor and Rictor) expression. Moreover, this study revealed a correlation between Zn and IR. Therefore, Zn supplementation could be a valuable therapeutic method for treating PCOS.
锌（Zn）是生殖系统的重要元素，与多种调节不同代谢途径的酶相关。有机锌可显著影响多囊卵巢综合征（PCOS）的发病机制。胰岛素抵抗（IR）是PCOS的常见并发症。哺乳动物雷帕霉素靶蛋白（mTOR）控制着关键的细胞功能，受胰岛素和营养物质调节。它有两个复合物，即mTORC1和mTORC2。mTOR与其结合伙伴mTOR的调节相关蛋白（Raptor）和mTOR的雷帕霉素不敏感伴侣（Rictor）相关联，它们分别形成这些不同的复合物，并在PCOS中被激活。本研究旨在评估锌对PCOS模型大鼠中mTOR信号基因（Raptor和Rictor）表达及IR的影响。将不同的锌补充剂应用于对照组和PCOS组，包括标准饮食（SD）：（对照 - 或 +，不补充的SD）、Zn25、Zn75和Zn175（分别每日给予25、75和175毫克蛋氨酸锌（ZnMet）/千克，持续6周）。测量两组的空腹血糖（FG）、空腹胰岛素（FI）、IR指数以及Raptor和Rictor的表达水平。结果表明，PCOS诱导显著增加了FG、FI、IR指数和mTOR相关基因表达；然而，不同的锌补充浓度，尤其是75毫克/千克时，降低了PCOS诱导的影响。有机锌通过降低IR和mTOR信号基因（即Raptor和Rictor）的表达，对戊酸雌二醇（EV）诱导的PCOS大鼠总体发挥了积极作用。此外，本研究揭示了锌与IR之间的相关性。因此，补充锌可能是治疗PCOS的一种有价值的治疗方法。
