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Hepatic FGF21 preserves thermoregulation and cardiovascular function during bacterial inflammation

Sickness behaviors, including anorexia, are evolutionarily conserved responses to acute infections. Inflammation-induced anorexia causes dramatic metabolic changes, of which components critical to survival are unique depending on the type of inflammation. Glucose supplementation during the anorectic...

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Autores principales: Huen, Sarah C., Wang, Andrew, Feola, Kyle, Desrouleaux, Reina, Luan, Harding H., Hogg, Richard, Zhang, Cuiling, Zhang, Qing-Jun, Liu, Zhi-Ping, Medzhitov, Ruslan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374861/
https://www.ncbi.nlm.nih.gov/pubmed/34406362
http://dx.doi.org/10.1084/jem.20202151
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author Huen, Sarah C.
Wang, Andrew
Feola, Kyle
Desrouleaux, Reina
Luan, Harding H.
Hogg, Richard
Zhang, Cuiling
Zhang, Qing-Jun
Liu, Zhi-Ping
Medzhitov, Ruslan
author_facet Huen, Sarah C.
Wang, Andrew
Feola, Kyle
Desrouleaux, Reina
Luan, Harding H.
Hogg, Richard
Zhang, Cuiling
Zhang, Qing-Jun
Liu, Zhi-Ping
Medzhitov, Ruslan
author_sort Huen, Sarah C.
collection PubMed
description Sickness behaviors, including anorexia, are evolutionarily conserved responses to acute infections. Inflammation-induced anorexia causes dramatic metabolic changes, of which components critical to survival are unique depending on the type of inflammation. Glucose supplementation during the anorectic period induced by bacterial inflammation suppresses adaptive fasting metabolic pathways, including fibroblast growth factor 21 (FGF21), and decreases survival. Consistent with this observation, FGF21-deficient mice are more susceptible to mortality from endotoxemia and polybacterial peritonitis. Here, we report that increased circulating FGF21 during bacterial inflammation is hepatic derived and required for survival through the maintenance of thermogenesis, energy expenditure, and cardiac function. FGF21 signaling downstream of its obligate coreceptor, β-Klotho (KLB), is required in bacterial sepsis. However, FGF21 modulates thermogenesis and chronotropy independent of the adipose, forebrain, and hypothalamus, which are operative in cold adaptation, suggesting that in bacterial inflammation, either FGF21 signals through a novel, undescribed target tissue or concurrent signaling of multiple KLB-expressing tissues is required.
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spelling pubmed-83748612022-04-04 Hepatic FGF21 preserves thermoregulation and cardiovascular function during bacterial inflammation Huen, Sarah C. Wang, Andrew Feola, Kyle Desrouleaux, Reina Luan, Harding H. Hogg, Richard Zhang, Cuiling Zhang, Qing-Jun Liu, Zhi-Ping Medzhitov, Ruslan J Exp Med Brief Definitive Report Sickness behaviors, including anorexia, are evolutionarily conserved responses to acute infections. Inflammation-induced anorexia causes dramatic metabolic changes, of which components critical to survival are unique depending on the type of inflammation. Glucose supplementation during the anorectic period induced by bacterial inflammation suppresses adaptive fasting metabolic pathways, including fibroblast growth factor 21 (FGF21), and decreases survival. Consistent with this observation, FGF21-deficient mice are more susceptible to mortality from endotoxemia and polybacterial peritonitis. Here, we report that increased circulating FGF21 during bacterial inflammation is hepatic derived and required for survival through the maintenance of thermogenesis, energy expenditure, and cardiac function. FGF21 signaling downstream of its obligate coreceptor, β-Klotho (KLB), is required in bacterial sepsis. However, FGF21 modulates thermogenesis and chronotropy independent of the adipose, forebrain, and hypothalamus, which are operative in cold adaptation, suggesting that in bacterial inflammation, either FGF21 signals through a novel, undescribed target tissue or concurrent signaling of multiple KLB-expressing tissues is required. Rockefeller University Press 2021-08-18 /pmc/articles/PMC8374861/ /pubmed/34406362 http://dx.doi.org/10.1084/jem.20202151 Text en © 2021 Huen et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Report
Huen, Sarah C.
Wang, Andrew
Feola, Kyle
Desrouleaux, Reina
Luan, Harding H.
Hogg, Richard
Zhang, Cuiling
Zhang, Qing-Jun
Liu, Zhi-Ping
Medzhitov, Ruslan
Hepatic FGF21 preserves thermoregulation and cardiovascular function during bacterial inflammation
title Hepatic FGF21 preserves thermoregulation and cardiovascular function during bacterial inflammation
title_full Hepatic FGF21 preserves thermoregulation and cardiovascular function during bacterial inflammation
title_fullStr Hepatic FGF21 preserves thermoregulation and cardiovascular function during bacterial inflammation
title_full_unstemmed Hepatic FGF21 preserves thermoregulation and cardiovascular function during bacterial inflammation
title_short Hepatic FGF21 preserves thermoregulation and cardiovascular function during bacterial inflammation
title_sort hepatic fgf21 preserves thermoregulation and cardiovascular function during bacterial inflammation
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374861/
https://www.ncbi.nlm.nih.gov/pubmed/34406362
http://dx.doi.org/10.1084/jem.20202151
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