Nicotinamide Mononucleotide Ameliorates Myocardial Fibrosis in Diabetic Mice Possibly by Modulating SIRT3 to Deacetylate GSK3β and Thereby Reducing the Phosphorylation of Smad3.

This study aims to investigate the therapeutic potential of NMN in alleviating type 2 diabetes-induced myocardial fibrosis.The experiment was comprised of control group, diabetic group, DM + NMN intervention group, and DM + NMN+3-TYP group. Blood glucose level, tibia length, cardiac function, myocardial interstitial fibrosis and ROS level were evaluated. The expression of SIRT3, GSK3β, ac-GSK3β, downstream fibrosis-related proteins and the interaction between SIRT3 and GSK3β were analyzed. Diabetic mice exhibited pronounced myocardial interstitial fibrosis alongside significant alterations in cardiac structure and function. Additionally, the protein expression levels of ac-GSK3β/GSK3β, p-Smad3/t-Smad3, α-SMA, and Collagen I were elevated, while SIRT3 expression was reduced. NMN effectively ameliorated these changes. The therapeutic benefits of NMN were effectively inhibited by 3-TYP. NMN effectively combats diabetes-induced myocardial fibrosis, potentially through upregulating SIRT3 expression. This upregulation may enhance the interaction between SIRT3 and GSK3β, thereby reducing the acetylation of GSK3β. Through this mechanism, NMN ultimately suppresses Smad3 phosphorylation.