| 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. |