Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic Nephropathy

NMN Treatment Shows Promise in Preventing Diabetic Nephropathy

Introduction: Nicotinamide mononucleotide (NMN), a precursor of NAD+ and activator of Sirtuin1 (Sirt1), has been studied for its potential anti-aging effects. While NMN treatment has shown positive outcomes in various disease models, its effects on diabetic nephropathy (DN) have not been extensively explored. In a recent study, researchers investigated the effects of NMN treatment in a murine model of early DN and found that it had a long-lasting renoprotective effect.

Key Findings:

• NMN treatment did not have an impact on metabolic parameters but attenuated the decrease in Sirt1 levels.
• NMN treatment also reduced foot-process effacement of podocytes and decreased albuminuria, even after the cessation of NMN treatment.
• These findings indicate that NMN has the potential to be used as a preventive treatment for diabetic nephropathy.

Study Methodology:

• Male diabetic db/db mice and nondiabetic db/m mice were used in the study.
• The mice were divided into two groups: one treated with vehicle (normal saline) and the other treated with NMN at a dosage of 500 mg/kg per day.
• Treatment was administered intraperitoneally every day for 14 consecutive days.
• Kidneys were harvested after 14 days of treatment for analysis.
• Blood and urine examinations were performed to evaluate renal function.
• Kidney histology, immunohistochemistry, and electron microscopy were used to evaluate kidney tissues.
• NAD+ metabolite measurement was conducted using liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) techniques.

Summary of Results:

• NMN treatment improved kidney function and attenuated histological changes in diabetic nephropathy.
• NMN treatment increased the expression of Sirt1, Nampt, and Nmnat1 in the kidneys.
• NMN treatment also increased kidney concentrations of NAD+.
• The renoprotective effects of NMN treatment persisted even after the termination of treatment.

Conclusion:

The study demonstrates that short-term NMN administration can effectively treat early-stage diabetic nephropathy. NMN treatment improves kidney function and histological changes, increases Sirt1 expression, and maintains kidney NAD+ levels. These findings suggest that NMN supplementation could be a potential preventive strategy for diabetic nephropathy.

Disclaimer: The research was supported by the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Keio University Doctoral Student Grant-in-Aid Program. The authors have disclosed potential conflicts of interest. Supplemental material including methods and figures can be found online.

Title of paper: Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic Nephropathy

Author(s): Yasuda I, Hasegawa K, Sakamaki Y, Muraoka H, Kawaguchi T, Kusahana E, Ono T, Kanda T, Tokuyama H, Wakino S, Itoh H.

Year published: 2021

Published in: J Am Soc Nephrol

Original article can be found here.