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

Abstract

BACKGROUND:

The activation of NAD+-dependent deacetylase, Sirt1, by the administration of nicotinamide mononucleotide (NMN) ameliorates various aging-related diseases.

METHODS:

Diabetic db/db mice were treated with NMN transiently for 2 weeks and observed for effects on diabetic nephropathy (DN).

RESULTS:

At 14 weeks after the treatment period, NMN attenuated the increases in urinary albumin excretion in db/db mice without ameliorating hemoglobin A1c levels. Short-term NMN treatment mitigated mesangium expansion and foot process effacement, while ameliorating decreased Sirt1 expression and increased claudin-1 expression in the kidneys of db/db mice. This treatment also improved the decrease in the expression of H3K9me2 and DNMT1. Short-term NMN treatment also increased kidney concentrations of NAD+ and the expression of Sirt1 and nicotinamide phosphoribosyltransferase (Nampt), and it maintained nicotinamide mononucleotide adenyltransferase1 (Nmnat1) expression in the kidneys. In addition, survival rates improved after NMN treatment.

CONCLUSIONS:

Short-term NMN treatment in early-stage DN has remote renal protective effects through the upregulation of Sirt1 and activation of the NAD+ salvage pathway, both of which indicate NMN legacy effects on DN.

• Authors: Itaru Yasuda, Kazuhiro Hasegawa, Yusuke Sakamaki, Hirokazu Muraoka, Takahisa Kawaguchi, Ei Kusahana, Takashi Ono, Takeshi Kanda, Hirobumi Tokuyama, Shu Wakino, Hiroshi Itoh
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 32 Issue 6 Pg. 1355-1370 (06 01 2021) ISSN: 1533-3450 [Electronic] United States
• PMID: 33795425 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 by the American Society of Nephrology.

Chemical References

• Claudin-1
• Cldn1 protein, mouse
• Cytokines
• Glycated Hemoglobin A
• Histones
• NAD
• Nicotinamide Mononucleotide
• DNA (Cytosine-5-)-Methyltransferase 1
• Dnmt1 protein, mouse
• Nicotinamide Phosphoribosyltransferase
• nicotinamide phosphoribosyltransferase, mouse
• Nicotinamide-Nucleotide Adenylyltransferase
• Nmnat1 protein, mouse
• Sirt1 protein, mouse
• Sirtuin 1

Topics

• Albuminuria (etiology, urine)
• Animals
• Claudin-1 (metabolism)
• Cytokines (metabolism)
• DNA (Cytosine-5-)-Methyltransferase 1 (metabolism)
• Diabetic Nephropathies (complications, drug therapy, metabolism, pathology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Epigenesis, Genetic (drug effects)
• Glomerular Mesangium (pathology)
• Glycated Hemoglobin (metabolism)
• Histones (metabolism)
• Male
• Mice
• Mice, Knockout
• NAD (metabolism)
• Nicotinamide Mononucleotide (administration & dosage, therapeutic use)
• Nicotinamide Phosphoribosyltransferase (metabolism)
• Nicotinamide-Nucleotide Adenylyltransferase (metabolism)
• Podocytes (pathology)
• Sirtuin 1 (genetics, metabolism)
• Survival Rate
• Time Factors