Pre-emptive short-term nicotinamide mononucleotide treatment in a mouse model of diabetic nephropathy

Itaru Yasuda, Kazuhiro Hasegawa, Yusuke Sakamaki, Hirokazu Muraoka, Takahisa Kawaguchi, Ei Kusahana, Takashi Ono, Takeshi Kanda, Hirobumi Tokuyama, Shu Wakino, Hiroshi Itoh

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Background The activation of NAD1-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 NAD1 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 NAD1 salvage pathway, both of which indicate NMN legacy effects on DN.

Original languageEnglish
Pages (from-to)1355-1370
Number of pages16
JournalJournal of the American Society of Nephrology
Volume32
Issue number6
DOIs
Publication statusPublished - 2021 Jun
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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