Polycystic Ovary Syndrome (PCOS), as a common endocrine disorder is accompanied by hyperandrogenism, insulin resistance, ovulation problems, and infertility. Various types of off-label drugs like metformin have been used for the management of targeted problems caused by PCOS such as insulin resistance and hyperandrogenism. Nicotinamide (NAM) acts as a substrate of visfatin and Nicotinamide N-Methyltransferase (NNMT) leading to the generation of Nicotinamide Adenine Dinucleotide (NAD) and N1-Methylnicotinamide (MNAM), respectively. MNAM is known as an anti-inflammatory, anti-thrombosis, and anti-diabetic agent. In this study, the effects of NAM and MNAM on metabolic and endocrine abnormalities were evaluated in the adipose and ovarian tissues of a letrozole-induced rat model of PCOS. Our results showed that MNAM and NAM reversed abnormal estrous cycle and reduced the serum testosterone levels and CYP17A1 gene expression. Furthermore, all therapeutic factors improved HOMA-IR after treatment and NAM significantly increased the expression of GLUT4 and decreased the gene expression of visfatin. Also, MNAM diminished the gene expression of visfatin and resistin. It is noteworthy that all the therapeutic factors successfully activated the AMPK. In summary, this study is the first study reported beneficial effects of NAM and MNAM on the treatment of PCOS. Additionally, the alleviative effects of our therapeutic factors may be partially mediated by the AMPK-dependent manner due to the contribution of the AMPK in the expression of CYP17A1, visfatin, resistin, and GLUT4. Although more studies are required to unravel the exact mode of actions of MNAM and NAM in the PCOS, the findings of the current study shed light on an urgent need for discovering novel therapeutic pharmaceuticals regarding the treatment of PCOS.

中文翻译：

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烟酰胺及其代谢产物N1-甲基烟酰胺可减轻多囊卵巢综合征大鼠模型中脂肪和卵巢组织的内分泌和代谢异常。

多囊卵巢综合症（PCOS）是常见的内分泌疾病，伴有雄激素过多，胰岛素抵抗，排卵问题和不育症。各种标签外药物（如二甲双胍）已用于处理PCOS引起的靶向问题，例如胰岛素抵抗和雄激素过多症。烟酰胺（NAM）充当visfatin和烟酰胺N-甲基转移酶（NNMT）的底物，分别导致烟酰胺腺嘌呤二核苷酸（NAD）和N1-甲基烟酰胺（MNAM）的产生。MNAM被称为抗炎，抗血栓形成和抗糖尿病药。在这项研究中，在来曲唑诱导的PCOS大鼠模型的脂肪和卵巢组织中评估了NAM和MNAM对代谢和内分泌异常的影响。我们的结果表明，MNAM和NAM逆转了异常的发情周期，并降低了血清睾丸激素水平和CYP17A1基因表达。此外，所有治疗因素均能改善治疗后的HOMA-IR，而NAM则显着增加GLUT4的表达并降低visfatin的基因表达。同样，MNAM减少了visfatin和resinin的基因表达。值得注意的是，所有治疗因素均成功激活了AMPK。总而言之，这项研究是第一个报道了NAM和MNAM对PCOS的有益治疗作用的研究。此外，由于AMPK在CYP17A1，visfatin，resistin和GLUT4表达中的贡献，我们的治疗因子的缓解作用可能部分由AMPK依赖性方式介导。