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.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Wang T,Liu J,McDonald C,Lupino K,Zhai X,Wilkins BJ,Hakonarson H,Pei Ldoi
10.15252/emmm.201707604subject
Has Abstractpub_date
2017-08-01 00:00:00pages
1150-1164issue
8eissn
1757-4676issn
1757-4684pii
emmm.201707604journal_volume
9pub_type
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