IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35317-y.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35317-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-35317-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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. 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.
    3. 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.
    4. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Lin-lin Zhao & Ru Chen & Ziyu Bai & Junyi Liu & Yuhao Zhang & Yicheng Zhong & Meng-xiang Sun & Peng Zhao, 2024. "Autophagy-mediated degradation of integumentary tapetum is critical for embryo pattern formation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Hong Huang & Qinqin Ouyang & Min Zhu & Haijia Yu & Kunrong Mei & Rong Liu, 2021. "mTOR-mediated phosphorylation of VAMP8 and SCFD1 regulates autophagosome maturation," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    3. Elodie Mailler & Carlos M. Guardia & Xiaofei Bai & Michal Jarnik & Chad D. Williamson & Yan Li & Nunziata Maio & Andy Golden & Juan S. Bonifacino, 2021. "The autophagy protein ATG9A enables lipid mobilization from lipid droplets," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    4. Wenjun Wang & Junyang Tan & Xiaomin Liu & Wenqi Guo & Mengmeng Li & Xinjie Liu & Yanyan Liu & Wenyu Dai & Liubing Hu & Yimin Wang & Qiuxia Lu & Wen Xing Lee & Hong-Wen Tang & Qinghua Zhou, 2023. "Cytoplasmic Endonuclease G promotes nonalcoholic fatty liver disease via mTORC2-AKT-ACLY and endoplasmic reticulum stress," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Yun Seok Kim & Bongsub Ko & Da Jung Kim & Jihoon Tak & Chang Yeob Han & Joo-Youn Cho & Won Kim & Sang Geon Kim, 2022. "Induction of the hepatic aryl hydrocarbon receptor by alcohol dysregulates autophagy and phospholipid metabolism via PPP2R2D," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    6. Denisa Margină & Anca Ungurianu & Carmen Purdel & Dimitris Tsoukalas & Evangelia Sarandi & Maria Thanasoula & Fotios Tekos & Robin Mesnage & Demetrios Kouretas & Aristidis Tsatsakis, 2020. "Chronic Inflammation in the Context of Everyday Life: Dietary Changes as Mitigating Factors," IJERPH, MDPI, vol. 17(11), pages 1-27, June.
    7. Hejazi Keyvan & Fathi Mehrdad & Salkhord Mahsa & Dastani Maryam, 2021. "The Effect of Eight Weeks of Combined Training (Endurance-Intermittent Resistance and Endurance-Continuous Resistance) on Coagulation, Fibrinolytic and Lipid Profiles of Overweight Women," Polish Journal of Sport and Tourism, Sciendo, vol. 28(4), pages 3-9, December.
    8. Zhen Yuan & Kun Cai & Jiajia Li & Ruifeng Chen & Fuhai Zhang & Xuan Tan & Yaming Jiu & Haishuang Chang & Bing Hu & Weiyi Zhang & Binbin Ding, 2024. "ATG14 targets lipid droplets and acts as an autophagic receptor for syntaxin18-regulated lipid droplet turnover," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    9. Yan-Xin Zhang & Xin Yang & Pan Zou & Peng-Fei Du & Jing Wang & Fen Jin & Mao-Jun Jin & Yong-Xin She, 2016. "Nonylphenol Toxicity Evaluation and Discovery of Biomarkers in Rat Urine by a Metabolomics Strategy through HPLC-QTOF-MS," IJERPH, MDPI, vol. 13(5), pages 1-17, May.
    10. King Hang Tommy Mau & Donja Karimlou & David Barneda & Vincent Brochard & Christophe Royer & Bryony Leeke & Roshni A. Souza & Mélanie Pailles & Michelle Percharde & Shankar Srinivas & Alice Jouneau & , 2022. "Dynamic enlargement and mobilization of lipid droplets in pluripotent cells coordinate morphogenesis during mouse peri-implantation development," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    11. Odeta Meçe & Diede Houbaert & Maria-Livia Sassano & Tania Durré & Hannelore Maes & Marco Schaaf & Sanket More & Maarten Ganne & Melissa García-Caballero & Mila Borri & Jelle Verhoeven & Madhur Agrawal, 2022. "Lipid droplet degradation by autophagy connects mitochondria metabolism to Prox1-driven expression of lymphatic genes and lymphangiogenesis," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    12. Xiaowei Sun & Jie Shen & Norbert Perrimon & Xue Kong & Dan Wang, 2023. "The endoribonuclease Arlr is required to maintain lipid homeostasis by downregulating lipolytic genes during aging," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    13. Zhenzhen Zi & Zhuzhen Zhang & Qiang Feng & Chiho Kim & Xu-Dong Wang & Philipp E. Scherer & Jinming Gao & Beth Levine & Yonghao Yu, 2022. "Quantitative phosphoproteomic analyses identify STK11IP as a lysosome-specific substrate of mTORC1 that regulates lysosomal acidification," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    14. 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.
    15. Scotland E. Farley & Jennifer E. Kyle & Hans C. Leier & Lisa M. Bramer & Jules B. Weinstein & Timothy A. Bates & Joon-Yong Lee & Thomas O. Metz & Carsten Schultz & Fikadu G. Tafesse, 2022. "A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    16. Yoshito Minami & Atsushi Hoshino & Yusuke Higuchi & Masahide Hamaguchi & Yusaku Kaneko & Yuhei Kirita & Shunta Taminishi & Toshiyuki Nishiji & Akiyuki Taruno & Michiaki Fukui & Zoltan Arany & Satoaki , 2023. "Liver lipophagy ameliorates nonalcoholic steatohepatitis through extracellular lipid secretion," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    17. Liang Yang & Junfeng Shen & Chunhua Liu & Zhonghua Kuang & Yong Tang & Zhengjiang Qian & Min Guan & Yongfeng Yang & Yang Zhan & Nan Li & Xiang Li, 2023. "Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    18. Donghai Cui & Zixiang Wang & Qianli Dang & Jing Wang & Junchao Qin & Jianping Song & Xiangyu Zhai & Yachao Zhou & Ling Zhao & Gang Lu & Hongbin Liu & Gang Liu & Runping Liu & Changshun Shao & Xiyu Zha, 2023. "Spliceosome component Usp39 contributes to hepatic lipid homeostasis through the regulation of autophagy," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    19. Jialiu Zeng & Rebeca Acin-Perez & Essam A. Assali & Andrew Martin & Alexandra J. Brownstein & Anton Petcherski & Lucía Fernández-del-Rio & Ruiqing Xiao & Chih Hung Lo & Michaël Shum & Marc Liesa & Xue, 2023. "Restoration of lysosomal acidification rescues autophagy and metabolic dysfunction in non-alcoholic fatty liver disease," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    20. Leslie A. Rowland & Adilson Guilherme & Felipe Henriques & Chloe DiMarzio & Sean Munroe & Nicole Wetoska & Mark Kelly & Keith Reddig & Gregory Hendricks & Meixia Pan & Xianlin Han & Olga R. Ilkayeva &, 2023. "De novo lipogenesis fuels adipocyte autophagosome and lysosome membrane dynamics," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35317-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.