期刊
EMBO MOLECULAR MEDICINE
卷 9, 期 8, 页码 1150-1164出版社
WILEY
DOI: 10.15252/emmm.201707604
关键词
body growth; failure to thrive; GDF15; heart disease; heart-derived hormone
资金
- Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program [W81XWH-16-1-0400]
- W.W. Smith Charitable Trust [H1407]
- Diabetes Research Center at the University of Pennsylvania from NIH [DK 19525]
- NIH [DK111495, DK099379, HG008684, MH096891]
- China Scholarship Council
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 30years 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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