GDF15 is a heart‐derived hormone that regulates body growth
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 01, 2017
- Source ID
- 10.15252/emmm.201707604
Entities
People
- Benjamin J. Wilkins
- Caitlin Mcdonald
- Hakon Hakonarson
- Jian Liu
- Katherine Lupino
- Liming Pei
- Ting Wang
- Xiandun Zhai
Organizations
- Children's Hospital of Philadelphia
- Henan University of Science and Technology
- National Institutes of Health
- United States Department of Defense
- University of Pennsylvania
- W. W. Smith Charitable Trust