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Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage

Author

Listed:
  • Audrey Sambeat

    (Nestlé Research)

  • Joanna Ratajczak

    (Nestlé Research
    Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Magali Joffraud

    (Nestlé Research)

  • José L. Sanchez-Garcia

    (Nestlé Research)

  • Maria P. Giner

    (Nestlé Research)

  • Armand Valsesia

    (Nestlé Research)

  • Judith Giroud-Gerbetant

    (Nestlé Research)

  • Miriam Valera-Alberni

    (Nestlé Research
    Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Angelique Cercillieux

    (Nestlé Research
    Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Marie Boutant

    (Nestlé Research)

  • Sameer S. Kulkarni

    (Nestlé Research)

  • Sofia Moco

    (Nestlé Research)

  • Carles Canto

    (Nestlé Research
    Ecole Polytechnique Fédérale de Lausanne (EPFL))

Abstract

Supplementation with the NAD+ precursor nicotinamide riboside (NR) ameliorates and prevents a broad array of metabolic and aging disorders in mice. However, little is known about the physiological role of endogenous NR metabolism. We have previously shown that NR kinase 1 (NRK1) is rate-limiting and essential for NR-induced NAD+ synthesis in hepatic cells. To understand the relevance of hepatic NR metabolism, we generated whole body and liver-specific NRK1 knockout mice. Here, we show that NRK1 deficiency leads to decreased gluconeogenic potential and impaired mitochondrial function. Upon high-fat feeding, NRK1 deficient mice develop glucose intolerance, insulin resistance and hepatosteatosis. Furthermore, they are more susceptible to diet-induced liver DNA damage, due to compromised PARP1 activity. Our results demonstrate that endogenous NR metabolism is critical to sustain hepatic NAD+ levels and hinder diet-induced metabolic damage, highlighting the relevance of NRK1 as a therapeutic target for metabolic disorders.

Suggested Citation

  • Audrey Sambeat & Joanna Ratajczak & Magali Joffraud & José L. Sanchez-Garcia & Maria P. Giner & Armand Valsesia & Judith Giroud-Gerbetant & Miriam Valera-Alberni & Angelique Cercillieux & Marie Boutan, 2019. "Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12262-x
    DOI: 10.1038/s41467-019-12262-x
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    Cited by:

    1. Guanlan Hu & Catriona Ling & Lijun Chi & Mehakpreet K. Thind & Samuel Furse & Albert Koulman & Jonathan R. Swann & Dorothy Lee & Marjolein M. Calon & Celine Bourdon & Christian J. Versloot & Barbara M, 2022. "The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Quetzalcoatl Escalante-Covarrubias & Lucía Mendoza-Viveros & Mirna González-Suárez & Román Sitten-Olea & Laura A. Velázquez-Villegas & Fernando Becerril-Pérez & Ignacio Pacheco-Bernal & Erick Carreño-, 2023. "Time-of-day defines NAD+ efficacy to treat diet-induced metabolic disease by synchronizing the hepatic clock in mice," Nature Communications, Nature, vol. 14(1), pages 1-24, December.

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