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GDF15 is a heart‐derived hormone that regulates body growth

The endocrine system is crucial for maintaining whole‐body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than atrial/brain natriuretic peptides discovered over 30 years ago. Here, we identify growth differentiation factor 15 (GDF15) as a heart‐derived hormone...

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Autores principales: Wang, Ting, Liu, Jian, McDonald, Caitlin, Lupino, Katherine, Zhai, Xiandun, Wilkins, Benjamin J, Hakonarson, Hakon, Pei, Liming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538424/
https://www.ncbi.nlm.nih.gov/pubmed/28572090
http://dx.doi.org/10.15252/emmm.201707604
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author Wang, Ting
Liu, Jian
McDonald, Caitlin
Lupino, Katherine
Zhai, Xiandun
Wilkins, Benjamin J
Hakonarson, Hakon
Pei, Liming
author_facet Wang, Ting
Liu, Jian
McDonald, Caitlin
Lupino, Katherine
Zhai, Xiandun
Wilkins, Benjamin J
Hakonarson, Hakon
Pei, Liming
author_sort Wang, Ting
collection PubMed
description The endocrine system is crucial for maintaining whole‐body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than atrial/brain natriuretic peptides discovered over 30 years ago. Here, we identify growth differentiation factor 15 (GDF15) as a heart‐derived hormone that regulates body growth. We show that pediatric heart disease induces GDF15 synthesis and secretion by cardiomyocytes. Circulating GDF15 in turn acts on the liver to inhibit growth hormone (GH) signaling and body growth. We demonstrate that blocking cardiomyocyte production of GDF15 normalizes circulating GDF15 level and restores liver GH signaling, establishing GDF15 as a bona fide heart‐derived hormone that regulates pediatric body growth. Importantly, plasma GDF15 is further increased in children with concomitant heart disease and failure to thrive (FTT). Together these studies reveal a new endocrine mechanism by which the heart coordinates cardiac function and body growth. Our results also provide a potential mechanism for the well‐established clinical observation that children with heart diseases often develop FTT.
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spelling pubmed-55384242017-08-04 GDF15 is a heart‐derived hormone that regulates body growth Wang, Ting Liu, Jian McDonald, Caitlin Lupino, Katherine Zhai, Xiandun Wilkins, Benjamin J Hakonarson, Hakon Pei, Liming EMBO Mol Med Research Articles The endocrine system is crucial for maintaining whole‐body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than atrial/brain natriuretic peptides discovered over 30 years ago. Here, we identify growth differentiation factor 15 (GDF15) as a heart‐derived hormone that regulates body growth. We show that pediatric heart disease induces GDF15 synthesis and secretion by cardiomyocytes. Circulating GDF15 in turn acts on the liver to inhibit growth hormone (GH) signaling and body growth. We demonstrate that blocking cardiomyocyte production of GDF15 normalizes circulating GDF15 level and restores liver GH signaling, establishing GDF15 as a bona fide heart‐derived hormone that regulates pediatric body growth. Importantly, plasma GDF15 is further increased in children with concomitant heart disease and failure to thrive (FTT). Together these studies reveal a new endocrine mechanism by which the heart coordinates cardiac function and body growth. Our results also provide a potential mechanism for the well‐established clinical observation that children with heart diseases often develop FTT. John Wiley and Sons Inc. 2017-06-01 2017-08 /pmc/articles/PMC5538424/ /pubmed/28572090 http://dx.doi.org/10.15252/emmm.201707604 Text en © 2017 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Wang, Ting
Liu, Jian
McDonald, Caitlin
Lupino, Katherine
Zhai, Xiandun
Wilkins, Benjamin J
Hakonarson, Hakon
Pei, Liming
GDF15 is a heart‐derived hormone that regulates body growth
title GDF15 is a heart‐derived hormone that regulates body growth
title_full GDF15 is a heart‐derived hormone that regulates body growth
title_fullStr GDF15 is a heart‐derived hormone that regulates body growth
title_full_unstemmed GDF15 is a heart‐derived hormone that regulates body growth
title_short GDF15 is a heart‐derived hormone that regulates body growth
title_sort gdf15 is a heart‐derived hormone that regulates body growth
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538424/
https://www.ncbi.nlm.nih.gov/pubmed/28572090
http://dx.doi.org/10.15252/emmm.201707604
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