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EMBO Mol Med. 2017 Aug;9(8):1150-1164. doi: 10.15252/emmm.201707604.

GDF15 is a heart-derived hormone that regulates body growth.

Wang T1,2, Liu J1,2, McDonald C1,2, Lupino K1,2, Zhai X1,2,3, Wilkins BJ2,4, Hakonarson H5,6, Pei L7,2,4.

Author information

1
Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
2
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
3
Institute of Forensic Medicine, Henan University of Science and Technology, Luoyang Henan, China.
4
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
5
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
6
Department of Pediatrics, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, USA.
7
Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA lpei@mail.med.upenn.edu.

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.

KEYWORDS:

GDF15; body growth; failure to thrive; heart disease; heart‐derived hormone

PMID:
28572090
PMCID:
PMC5538424
DOI:
10.15252/emmm.201707604
[Indexed for MEDLINE]
Free PMC Article

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