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Liver Derived FGF21 Maintains Core Body Temperature During Acute Cold Exposure

Fibroblast Growth Factor 21 (FGF21) elicits an array of metabolic effects. However, the physiological role of FGF21 during thermal challenges is not clear. In this study, we assessed the tissue source of FGF21 and its site of action to regulate core body temperature in response to cold. Using mice l...

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Autores principales: Ameka, Magdalene, Markan, Kathleen R., Morgan, Donald A., BonDurant, Lucas D., Idiga, Sharon O., Naber, Meghan C., Zhu, Zhiyong, Zingman, Leonid V., Grobe, Justin L., Rahmouni, Kamal, Potthoff, Matthew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345819/
https://www.ncbi.nlm.nih.gov/pubmed/30679672
http://dx.doi.org/10.1038/s41598-018-37198-y
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author Ameka, Magdalene
Markan, Kathleen R.
Morgan, Donald A.
BonDurant, Lucas D.
Idiga, Sharon O.
Naber, Meghan C.
Zhu, Zhiyong
Zingman, Leonid V.
Grobe, Justin L.
Rahmouni, Kamal
Potthoff, Matthew J.
author_facet Ameka, Magdalene
Markan, Kathleen R.
Morgan, Donald A.
BonDurant, Lucas D.
Idiga, Sharon O.
Naber, Meghan C.
Zhu, Zhiyong
Zingman, Leonid V.
Grobe, Justin L.
Rahmouni, Kamal
Potthoff, Matthew J.
author_sort Ameka, Magdalene
collection PubMed
description Fibroblast Growth Factor 21 (FGF21) elicits an array of metabolic effects. However, the physiological role of FGF21 during thermal challenges is not clear. In this study, we assessed the tissue source of FGF21 and its site of action to regulate core body temperature in response to cold. Using mice lacking FGF21 specifically in the liver (FGF21 LivKO) or adipose tissues (FGF21 AdipoKO), we performed a series of cold exposure studies to examine the tissue specific induction of FGF21 in response to cold. We also examined the physiological site of FGF21 action during cold exposure by impairing FGF21 signaling to adipose tissues or the central nervous system (CNS) using genetic ablation of the FGF21 co-receptor β-klotho in adipose tissues (KLB AdipoKO) or pharmacological blockage of FGF21 signaling. We found that only liver-derived FGF21 enters circulation during acute cold exposure and is critical for thermoregulation. While FGF21 signaling directly to adipose tissues during cold is dispensable for thermoregulation, central FGF21 signaling is necessary for maximal sympathetic drive to brown adipose tissue to maintain thermoregulation during cold. These data demonstrate a previously unrecognized role for FGF21 in the maintenance of body temperature in response to cold.
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spelling pubmed-63458192019-01-29 Liver Derived FGF21 Maintains Core Body Temperature During Acute Cold Exposure Ameka, Magdalene Markan, Kathleen R. Morgan, Donald A. BonDurant, Lucas D. Idiga, Sharon O. Naber, Meghan C. Zhu, Zhiyong Zingman, Leonid V. Grobe, Justin L. Rahmouni, Kamal Potthoff, Matthew J. Sci Rep Article Fibroblast Growth Factor 21 (FGF21) elicits an array of metabolic effects. However, the physiological role of FGF21 during thermal challenges is not clear. In this study, we assessed the tissue source of FGF21 and its site of action to regulate core body temperature in response to cold. Using mice lacking FGF21 specifically in the liver (FGF21 LivKO) or adipose tissues (FGF21 AdipoKO), we performed a series of cold exposure studies to examine the tissue specific induction of FGF21 in response to cold. We also examined the physiological site of FGF21 action during cold exposure by impairing FGF21 signaling to adipose tissues or the central nervous system (CNS) using genetic ablation of the FGF21 co-receptor β-klotho in adipose tissues (KLB AdipoKO) or pharmacological blockage of FGF21 signaling. We found that only liver-derived FGF21 enters circulation during acute cold exposure and is critical for thermoregulation. While FGF21 signaling directly to adipose tissues during cold is dispensable for thermoregulation, central FGF21 signaling is necessary for maximal sympathetic drive to brown adipose tissue to maintain thermoregulation during cold. These data demonstrate a previously unrecognized role for FGF21 in the maintenance of body temperature in response to cold. Nature Publishing Group UK 2019-01-24 /pmc/articles/PMC6345819/ /pubmed/30679672 http://dx.doi.org/10.1038/s41598-018-37198-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ameka, Magdalene
Markan, Kathleen R.
Morgan, Donald A.
BonDurant, Lucas D.
Idiga, Sharon O.
Naber, Meghan C.
Zhu, Zhiyong
Zingman, Leonid V.
Grobe, Justin L.
Rahmouni, Kamal
Potthoff, Matthew J.
Liver Derived FGF21 Maintains Core Body Temperature During Acute Cold Exposure
title Liver Derived FGF21 Maintains Core Body Temperature During Acute Cold Exposure
title_full Liver Derived FGF21 Maintains Core Body Temperature During Acute Cold Exposure
title_fullStr Liver Derived FGF21 Maintains Core Body Temperature During Acute Cold Exposure
title_full_unstemmed Liver Derived FGF21 Maintains Core Body Temperature During Acute Cold Exposure
title_short Liver Derived FGF21 Maintains Core Body Temperature During Acute Cold Exposure
title_sort liver derived fgf21 maintains core body temperature during acute cold exposure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345819/
https://www.ncbi.nlm.nih.gov/pubmed/30679672
http://dx.doi.org/10.1038/s41598-018-37198-y
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