TY - JOUR
T1 - Pre-emptive short-term nicotinamide mononucleotide treatment in a mouse model of diabetic nephropathy
AU - Yasuda, Itaru
AU - Hasegawa, Kazuhiro
AU - Sakamaki, Yusuke
AU - Muraoka, Hirokazu
AU - Kawaguchi, Takahisa
AU - Kusahana, Ei
AU - Ono, Takashi
AU - Kanda, Takeshi
AU - Tokuyama, Hirobumi
AU - Wakino, Shu
AU - Itoh, Hiroshi
N1 - Funding Information:
This work was supported by the Scientific Research Fund of the Ministry of Education, Culture, Sports, Science, and Technology of Japan (19K08732) and Keio University Doctoral Student Grant-in-Aid Program.
Funding Information:
H. Tokuyama reports being a scientific advisor or member as councilor of the Japanese Society of Hypertension and councilor of the Japanese Society of Nephrology. T. Kanda reports receiving research funding from Shionogi. T. Ono is employed by Shionogi & Co., Ltd. All remaining authors have nothing to disclose.
Publisher Copyright:
© 2021 by the American Society of Nephrology
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
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U2 - 10.1681/ASN.2020081188
DO - 10.1681/ASN.2020081188
M3 - Article
C2 - 33795425
AN - SCOPUS:85107319498
SN - 1046-6673
VL - 32
SP - 1355
EP - 1370
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 6
ER -
