Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD+ synthesis via enterohepatic circulation

被引:0
|
作者
Yaku, Keisuke [1 ]
Palikhe, Sailesh [1 ,7 ]
Iqbal, Tooba [1 ]
Hayat, Faisal [2 ]
Watanabe, Yoshiyuki [3 ]
Fujisaka, Shiho [3 ]
Izumi, Hironori [4 ,5 ]
Yoshida, Tomoyuki [4 ,5 ]
Karim, Mariam [1 ]
Uchida, Hitoshi [1 ]
Nawaz, Allah [1 ]
Tobe, Kazuyuki [3 ,6 ]
Mori, Hisashi [4 ,5 ]
Migaud, Marie E. [2 ]
Nakagawa, Takashi [1 ,6 ]
机构
[1] Univ Toyama, Fac Med, Dept Mol & Med Pharmacol, 2630 Sugitani, Toyama, Toyama 9300194, Japan
[2] Univ S Alabama, Dept Pharmacol, Mitchell Canc Inst, 1660 Springhill Ave, Mobile, AL 36693 USA
[3] Univ Toyama, Fac Med, Dept Internal Med 1, 2630 Sugitani, Toyama, Toyama 9300194, Japan
[4] Univ Toyama, Fac Med, Dept Mol Neurosci, 2630 Sugitani, Toyama, Toyama 9300194, Japan
[5] Univ Toyama, Res Ctr Idling Brain Sci RCIBS, 2630 Sugitani, Toyama, Toyama 9300194, Japan
[6] Univ Toyama, Res Ctr Predis Sci, 2630 Sugitani, Toyama 9300194, Japan
[7] Univ Kansas, Med Ctr, Dept Cell Biol & Physiol, Kansas City, KS USA
来源
SCIENCE ADVANCES | 2025年 / 11卷 / 12期
基金
美国国家卫生研究院;
关键词
EXTRACELLULAR-PRECURSORS; SKELETAL-MUSCLE; ACID RIBOSIDE; MITOCHONDRIAL; BIOSYNTHESIS; METABOLISM; INSULIN; SALVAGE; DIET; SUPPLEMENTATION;
D O I
10.1126/sciadv.adr1538
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Decreased nicotinamide adenine dinucleotide (oxidized form) (NAD+) levels are reportedly associated with several aging-related disorders. Thus, supplementation with NAD+ precursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), exhibits beneficial effects against these disorders. However, the in vivo metabolic pathways of NMN and NR remain to be elucidated. In this study, we comprehensively analyzed the fate of orally and intravenously administered NMN and NR in mice using NAD+ metabolomics. We found that only a small portion of orally administered NMN and NR was directly absorbed from the small intestine and that most of them underwent gut microbiota-mediated deamidation and conversion to nicotinic acid (NA). Moreover, intravenously administered NMN and NR were rapidly degraded into nicotinamide and secreted to bile followed by deamidation to NA by gut microbiota. Thus, enterohepatic circulated NA is preferentially used in the liver. These findings showed that NMN and NR are indirectly converted to NAD+ via unexpected metabolic pathways.
引用
收藏
页数:16
相关论文
共 50 条
  • [31] NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells
    Joanna Ratajczak
    Magali Joffraud
    Samuel A. J. Trammell
    Rosa Ras
    Núria Canela
    Marie Boutant
    Sameer S. Kulkarni
    Marcelo Rodrigues
    Philip Redpath
    Marie E. Migaud
    Johan Auwerx
    Oscar Yanes
    Charles Brenner
    Carles Cantó
    Nature Communications, 7
  • [32] NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells
    Ratajczak, Joanna
    Joffraud, Magali
    Trammell, Samuel A. J.
    Ras, Rosa
    Canela, Nuria
    Boutant, Marie
    Kulkarni, Sameer S.
    Rodrigues, Marcelo
    Redpath, Philip
    Migaud, Marie E.
    Auwerx, Johan
    Yanes, Oscar
    Brenner, Charles
    Canto, Carles
    NATURE COMMUNICATIONS, 2016, 7
  • [33] NAD+ augmentation with nicotinamide riboside improves lymphoid potential of Atm−/− and old mice HSCs
    Le Zong
    Mayuri Tanaka-Yano
    Bongsoo Park
    Hagai Yanai
    Ferda T. Turhan
    Deborah L. Croteau
    Jane Tian
    Evandro F. Fang
    Vilhelm A. Bohr
    Isabel Beerman
    npj Aging and Mechanisms of Disease, 7
  • [34] Induction of the nicotinamide riboside kinase NAD+ salvage pathway in a model of sarcoplasmic reticulum dysfunction
    Craig L. Doig
    Agnieszka E. Zielinska
    Rachel S. Fletcher
    Lucy A. Oakey
    Yasir S. Elhassan
    Antje Garten
    David Cartwright
    Silke Heising
    Ahmed Alsheri
    David G. Watson
    Cornelia Prehn
    Jerzy Adamski
    Daniel A. Tennant
    Gareth G. Lavery
    Skeletal Muscle, 10
  • [35] Induction of the nicotinamide riboside kinase NAD+ salvage pathway in a model of sarcoplasmic reticulum dysfunction
    Doig, Craig L.
    Zielinska, Agnieszka E.
    Fletcher, Rachel S.
    Oakey, Lucy A.
    Elhassan, Yasir S.
    Garten, Antje
    Cartwright, David
    Heising, Silke
    Alsheri, Ahmed
    Watson, David G.
    Prehn, Cornelia
    Adamski, Jerzy
    Tennant, Daniel A.
    Lavery, Gareth G.
    SKELETAL MUSCLE, 2020, 10 (01)
  • [36] NAD+ modulation with nicotinamide mononucleotide coated 3D printed microneedle implants
    Ali, Masood
    Huang, Wenhao
    Huang, Yicheng
    Wu, Xiaoxin
    Namjoshi, Sarika
    Prasadam, Indira
    Benson, Heather A. E.
    Kumeria, Tushar
    Mohammad, Yousuf
    JOURNAL OF MATERIALS CHEMISTRY B, 2025, 13 (11) : 3564 - 3580
  • [37] Yeast Cell Surface Engineering of a Nicotinamide Riboside Kinase for the Production of β-Nicotinamide Mononucleotide via Whole- Cell Catalysis
    He, Zhonghui
    Yang, Xiaosong
    Tian, Xin
    Li, Lujun
    Liu, Mengyuan
    ACS SYNTHETIC BIOLOGY, 2022, 11 (10): : 3451 - 3459
  • [38] ANALOGS OF NICOTINAMIDE AND NAD+ AND DRUG METABOLISM
    BEDERKA, JP
    MINTRANU.W
    FEDERATION PROCEEDINGS, 1970, 29 (02) : A858 - +
  • [39] Enzymatic synthesis of high-titer nicotinamide mononucleotide with a new nicotinamide riboside kinase and an efficient ATP regeneration system
    Qian, Xiao-Long
    Dai, Yi-Si
    Li, Chun-Xiu
    Pan, Jiang
    Xu, Jian-He
    Mu, Bozhong
    BIORESOURCES AND BIOPROCESSING, 2022, 9 (01)
  • [40] Simultaneous quantitation of nicotinamide riboside, nicotinamide mononucleotide and nicotinamide adenine dinucleotide in milk by a novel enzyme-coupled assay
    Ummarino, Simone
    Mozzon, Massimo
    Zamporlini, Federica
    Amici, Adolfo
    Mazzola, Francesca
    Orsomando, Giuseppe
    Ruggieri, Silverio
    Raffaelli, Nadia
    FOOD CHEMISTRY, 2017, 221 : 161 - 168