IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-44866-3.html
   My bibliography  Save this article

Short-term hypercaloric carbohydrate loading increases surgical stress resilience by inducing FGF21

Author

Listed:
  • Thomas Agius

    (University Hospital of Lausanne (CHUV)
    Harvard Medical School
    Massachusetts General Hospital, Harvard Medical School)

  • Raffaella Emsley

    (University Hospital of Lausanne (CHUV))

  • Arnaud Lyon

    (University Hospital of Lausanne (CHUV))

  • Michael R. MacArthur

    (Princeton University)

  • Kevin Kiesworo

    (University Hospital of Lausanne (CHUV))

  • Anna Faivre

    (University of Geneva
    University Hospital of Geneva)

  • Louis Stavart

    (University of Lausanne (UNIL))

  • Martine Lambelet

    (University Hospital of Lausanne (CHUV))

  • David Legouis

    (University of Geneva
    University Hospital of Geneva)

  • Sophie Seigneux

    (University of Geneva
    University Hospital of Geneva)

  • Déla Golshayan

    (University of Lausanne (UNIL))

  • Francois Lazeyras

    (University of Geneva
    Center for Biomedical Imaging (CIBM))

  • Heidi Yeh

    (Harvard Medical School
    Massachusetts General Hospital, Harvard Medical School)

  • James F. Markmann

    (Harvard Medical School
    Massachusetts General Hospital, Harvard Medical School)

  • Korkut Uygun

    (Harvard Medical School
    Massachusetts General Hospital, Harvard Medical School)

  • Alejandro Ocampo

    (University of Lausanne)

  • Sarah J. Mitchell

    (Princeton University)

  • Florent Allagnat

    (University Hospital of Lausanne (CHUV)
    University of Lausanne)

  • Sébastien Déglise

    (University Hospital of Lausanne (CHUV))

  • Alban Longchamp

    (University Hospital of Lausanne (CHUV)
    Harvard Medical School
    Massachusetts General Hospital, Harvard Medical School)

Abstract

Dietary restriction promotes resistance to surgical stress in multiple organisms. Counterintuitively, current medical protocols recommend short-term carbohydrate-rich drinks (carbohydrate loading) prior to surgery, part of a multimodal perioperative care pathway designed to enhance surgical recovery. Despite widespread clinical use, preclinical and mechanistic studies on carbohydrate loading in surgical contexts are lacking. Here we demonstrate in ad libitum-fed mice that liquid carbohydrate loading for one week drives reductions in solid food intake, while nearly doubling total caloric intake. Similarly, in humans, simple carbohydrate intake is inversely correlated with dietary protein intake. Carbohydrate loading-induced protein dilution increases expression of hepatic fibroblast growth factor 21 (FGF21) independent of caloric intake, resulting in protection in two models of surgical stress: renal and hepatic ischemia-reperfusion injury. The protection is consistent across male, female, and aged mice. In vivo, amino acid add-back or genetic FGF21 deletion blocks carbohydrate loading-mediated protection from ischemia-reperfusion injury. Finally, carbohydrate loading induction of FGF21 is associated with the induction of the canonical integrated stress response (ATF3/4, NF-kB), and oxidative metabolism (PPARγ). Together, these data support carbohydrate loading drinks prior to surgery and reveal an essential role of protein dilution via FGF21.

Suggested Citation

  • Thomas Agius & Raffaella Emsley & Arnaud Lyon & Michael R. MacArthur & Kevin Kiesworo & Anna Faivre & Louis Stavart & Martine Lambelet & David Legouis & Sophie Seigneux & Déla Golshayan & Francois Laz, 2024. "Short-term hypercaloric carbohydrate loading increases surgical stress resilience by inducing FGF21," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44866-3
    DOI: 10.1038/s41467-024-44866-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-44866-3
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-44866-3?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. Martin Holzenberger & Joëlle Dupont & Bertrand Ducos & Patricia Leneuve & Alain Géloën & Patrick C. Even & Pascale Cervera & Yves Le Bouc, 2003. "IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice," Nature, Nature, vol. 421(6919), pages 182-187, January.
    2. Cristal M. Hill & Diana C. Albarado & Lucia G. Coco & Redin A. Spann & Md Shahjalal Khan & Emily Qualls-Creekmore & David H. Burk & Susan J. Burke & J. Jason Collier & Sangho Yu & David H. McDougal & , 2022. "FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Edward T. Chouchani & Victoria R. Pell & Edoardo Gaude & Dunja Aksentijević & Stephanie Y. Sundier & Ellen L. Robb & Angela Logan & Sergiy M. Nadtochiy & Emily N. J. Ord & Anthony C. Smith & Filmon Ey, 2014. "Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS," Nature, Nature, vol. 515(7527), pages 431-435, November.
    4. Alison K Gosby & Namson S Lau & Charmaine S Tam & Miguel A Iglesias & Christopher D Morrison & Ian D Caterson & Jennie Brand-Miller & Arthur D Conigrave & David Raubenheimer & Stephen J Simpson, 2016. "Raised FGF-21 and Triglycerides Accompany Increased Energy Intake Driven by Protein Leverage in Lean, Healthy Individuals: A Randomised Trial," PLOS ONE, Public Library of Science, vol. 11(8), pages 1-16, August.
    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. Peter Kip & Thijs J. Sluiter & Michael R. MacArthur & Ming Tao & Nicky Kruit & Sarah J. Mitchell & Jonathan Jung & Sander Kooijman & Josh Gorham & Jonathan G. Seidman & Paul H. A. Quax & Julius L. Dec, 2024. "Preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male mice," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Chris G. Faulkes & Thomas R. Eykyn & Jan Lj. Miljkovic & James D. Gilbert & Rebecca L. Charles & Hiran A. Prag & Nikayla Patel & Daniel W. Hart & Michael P. Murphy & Nigel C. Bennett & Dunja Aksentije, 2024. "Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Yu Jin Chung & Zoe Hoare & Friedrich Baark & Chak Shun Yu & Jia Guo & William Fuller & Richard Southworth & Doerthe M. Katschinski & Michael P. Murphy & Thomas R. Eykyn & Michael J. Shattock, 2024. "Elevated Na is a dynamic and reversible modulator of mitochondrial metabolism in the heart," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Maithily S. Nanadikar & Ana M. Vergel Leon & Jia Guo & Gijsbert J. Belle & Aline Jatho & Elvina S. Philip & Astrid F. Brandner & Rainer A. Böckmann & Runzhu Shi & Anke Zieseniss & Carla M. Siemssen & , 2023. "IDH3γ functions as a redox switch regulating mitochondrial energy metabolism and contractility in the heart," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    5. Joy Edwards-Hicks & Huizhong Su & Maurizio Mangolini & Kubra K. Yoneten & Jimi Wills & Giovanny Rodriguez-Blanco & Christine Young & Kevin Cho & Heather Barker & Morwenna Muir & Ania Naila Guerrieri &, 2022. "MYC sensitises cells to apoptosis by driving energetic demand," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Jiayi Wang & Mengke Zhao & Meina Wang & Dong Fu & Lin Kang & Yu Xu & Liming Shen & Shilin Jin & Liang Wang & Jing Liu, 2024. "Human neural stem cell-derived artificial organelles to improve oxidative phosphorylation," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    7. Reji Babygirija & Michelle M. Sonsalla & Jericha Mill & Isabella James & Jessica H. Han & Cara L. Green & Mariah F. Calubag & Gina Wade & Anna Tobon & John Michael & Michaela M. Trautman & Ryan Matosk, 2024. "Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    8. Xiaoduo Tang & Jingyan Ren & Xin Wei & Tao Wang & Haiqiu Li & Yihan Sun & Yang Liu & Mingli Chi & Shoujun Zhu & Laijin Lu & Junhu Zhang & Bai Yang, 2023. "Exploiting synergistic effect of CO/NO gases for soft tissue transplantation using a hydrogel patch," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    9. Masataka Kawamura & Catherine Parmentier & Samrat Ray & Sergi Clotet-Freixas & Sharon Leung & Rohan John & Laura Mazilescu & Emmanuel Nogueira & Yuki Noguchi & Toru Goto & Bhranavi Arulratnam & Sujani, 2024. "Normothermic ex vivo kidney perfusion preserves mitochondrial and graft function after warm ischemia and is further enhanced by AP39," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    10. Yan-Ping Zhang & Wen-Hong Zhang & Pan Zhang & Qi Li & Yue Sun & Jia-Wen Wang & Shaobing O. Zhang & Tao Cai & Cheng Zhan & Meng-Qiu Dong, 2022. "Intestine-specific removal of DAF-2 nearly doubles lifespan in Caenorhabditis elegans with little fitness cost," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    11. Wang Yuan & Yi M. Weaver & Svetlana Earnest & Clinton A. Taylor & Melanie H. Cobb & Benjamin P. Weaver, 2023. "Modulating p38 MAPK signaling by proteostasis mechanisms supports tissue integrity during growth and aging," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    12. Xueqiang Wang & Xing Zhang & Ke Cao & Mengqi Zeng & Xuyang Fu & Adi Zheng & Feng Zhang & Feng Gao & Xuan Zou & Hao Li & Min Li & Weiqiang Lv & Jie Xu & Jiangang Long & Weijin Zang & Jinghai Chen & Fen, 2022. "Cardiac disruption of SDHAF4-mediated mitochondrial complex II assembly promotes dilated cardiomyopathy," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    13. Lianghui Cheng & Zhiyong Zhuang & Mingming Yin & Yuan Lu & Sujuan Liu & Minle Zhan & Liyuan Zhao & Zhenyan He & Fanling Meng & Sidan Tian & Liang Luo, 2024. "A microenvironment-modulating dressing with proliferative degradants for the healing of diabetic wounds," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    14. Pankaj Sharma & Elena Maklashina & Markus Voehler & Sona Balintova & Sarka Dvorakova & Michal Kraus & Katerina Hadrava Vanova & Zuzana Nahacka & Renata Zobalova & Stepana Boukalova & Kristyna Cunatova, 2024. "Disordered-to-ordered transitions in assembly factors allow the complex II catalytic subunit to switch binding partners," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    15. John O. Onukwufor & M. Arsalan Farooqi & Anežka Vodičková & Shon A. Koren & Aksana Baldzizhar & Brandon J. Berry & Gisela Beutner & George A. Porter & Vsevolod Belousov & Alan Grossfield & Andrew P. W, 2022. "A reversible mitochondrial complex I thiol switch mediates hypoxic avoidance behavior in C. elegans," Nature Communications, Nature, vol. 13(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:15:y:2024:i:1:d:10.1038_s41467-024-44866-3. 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.