GDF15 is a heart‐derived hormone that regulates body growth

Autor: Ting Wang, Jian Liu, Caitlin McDonald, Katherine Lupino, Xiandun Zhai, Benjamin J Wilkins, Hakon Hakonarson, Liming Pei
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 9, Iss 8, Pp 1150-1164 (2017)
Druh dokumentu: article
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.201707604
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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