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

Agius, Thomas; Emsley, Raffaella; Lyon, Arnaud; MacArthur, Michael R.; Kiesworo, Kevin; Faivre, Anna; Stavart, Louis; Lambelet, Martine; Legouis, David; De Seigneux Matthey, Sophie; Golshayan, Déla; Lazeyras, François; Yeh, Heidi; Markmann, James F.; Uygun, Korkut; Ocampo, Alejandro; Mitchell, Sarah J.; Allagnat, Florent; Déglise, Sébastien; Longchamp, Alban

doi:10.1038/s41467-024-44866-3

Scientific article

English

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

Published in

Nature communications, vol. 15, no. 1, 1073

Publication date

2024-02-05

First online date

2024-02-05

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.

UNIGE affiliation entities

UNIGE research groups

Funding

Mendez National Institute of Transplantation Foundation (MNITF) [NA]
Fondation Leenaards
Novartis Foundation
Swiss National Science Foundation - Kidney Preservation with Hydrogen Sulfide and Pre-Transplant Assessment by MRI [182658]
Swiss National Science Foundation - Therapeutic potential of hydrogen sulfide in peripheral vascular diseases [176158]
Swiss National Science Foundation - Role of endogenous hydrogen sulfide in the control of vascular aging [185927]
Mercier Foundation
Fondation pour la recherche en chirurgie thoracique et vasculaire
Union des Sociétés Suisses des Maladies Vasculaires

Citation (ISO format)

AGIUS, Thomas et al. Short-term hypercaloric carbohydrate loading increases surgical stress resilience by inducing FGF21. In: Nature communications, 2024, vol. 15, n° 1, p. 1073. doi: 10.1038/s41467-024-44866-3

Article (Published version)

CC BY-4.0

Supplemental data

Appendix - Reporting Summary

Appendix - Peer Review File

CC BY-4.0

Identifiers

PID : unige:176017
DOI : 10.1038/s41467-024-44866-3
PMID : 38316771
PMCID : PMC10844297

Additional URL for this publication

https://www.nature.com/articles/s41467-024-44866-3

Datasets

Journal ISSN

2041-1723

143views

37downloads

Creation

20/03/2024 17:08:55

First validation

27/03/2024 15:12:19

Update

27/03/2024 15:12:19

Status update

27/03/2024 15:12:19

Last indexation

01/11/2024 09:04:13

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

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Abstract

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Citation (ISO format)

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Additional URL for this publication

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Technical informations

Creation

First validation

Update

Status update

Last indexation