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The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction

Author

Listed:
  • Guanlan Hu

    (University of Toronto
    The Hospital for Sick Children)

  • Catriona Ling

    (University of Toronto
    The Hospital for Sick Children)

  • Lijun Chi

    (The Hospital for Sick Children)

  • Mehakpreet K. Thind

    (University of Toronto
    The Hospital for Sick Children)

  • Samuel Furse

    (University of Cambridge
    Biological Chemistry Group, Royal Botanic Gardens, Kew, Kew Green)

  • Albert Koulman

    (University of Cambridge)

  • Jonathan R. Swann

    (University of Southampton
    Imperial College London)

  • Dorothy Lee

    (The Hospital for Sick Children)

  • Marjolein M. Calon

    (The Hospital for Sick Children)

  • Celine Bourdon

    (The Hospital for Sick Children
    The Childhood Acute Illness & Nutrition Network (CHAIN))

  • Christian J. Versloot

    (University of Groningen, University Medical Center Groningen)

  • Barbara M. Bakker

    (University of Groningen, University Medical Center Groningen)

  • Gerard Bryan Gonzales

    (The Hospital for Sick Children
    Wageningen University)

  • Peter K. Kim

    (University of Toronto
    The Hospital for Sick Children)

  • Robert H. J. Bandsma

    (University of Toronto
    The Hospital for Sick Children
    The Childhood Acute Illness & Nutrition Network (CHAIN)
    University of Groningen, University Medical Center Groningen)

Abstract

Mortality in children with severe malnutrition is strongly related to signs of metabolic dysfunction, such as hypoglycemia. Lower circulating tryptophan levels in children with severe malnutrition suggest a possible disturbance in the tryptophan-nicotinamide adenine dinucleotide (TRP-NAD+) pathway and subsequently in NAD+ dependent metabolism regulator sirtuin1 (SIRT1). Here we show that severe malnutrition in weanling mice, induced by 2-weeks of low protein diet feeding from weaning, leads to an impaired TRP-NAD+ pathway with decreased NAD+ levels and affects hepatic mitochondrial turnover and function. We demonstrate that stimulating the TRP-NAD+ pathway with NAD+ precursors improves hepatic mitochondrial and overall metabolic function through SIRT1 modulation. Activating SIRT1 is sufficient to induce improvement in metabolic functions. Our findings indicate that modulating the TRP-NAD+ pathway can improve liver metabolic function in a mouse model of severe malnutrition. These results could lead to the development of new interventions for children with severe malnutrition.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35317-y
    DOI: 10.1038/s41467-022-35317-y
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    1. Tatsuo Hashimoto & Thomas Perlot & Ateequr Rehman & Jean Trichereau & Hiroaki Ishiguro & Magdalena Paolino & Verena Sigl & Toshikatsu Hanada & Reiko Hanada & Simone Lipinski & Birgit Wild & Simone M. , 2012. "ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation," Nature, Nature, vol. 487(7408), pages 477-481, July.
    2. Rajat Singh & Susmita Kaushik & Yongjun Wang & Youqing Xiang & Inna Novak & Masaaki Komatsu & Keiji Tanaka & Ana Maria Cuervo & Mark J. Czaja, 2009. "Autophagy regulates lipid metabolism," Nature, Nature, vol. 458(7242), pages 1131-1135, April.
    3. 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.
    4. Joseph T. Rodgers & Carlos Lerin & Wilhelm Haas & Steven P. Gygi & Bruce M. Spiegelman & Pere Puigserver, 2005. "Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1," Nature, Nature, vol. 434(7029), pages 113-118, March.
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