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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2021
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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. |
format | Online Article Text |
id | pubmed-8374861 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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