GDF 15 is a heart‐derived hormone that regulates body growth

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 ( GDF 15) as a heart‐derived hormone that regulates body growth. We show that pediatric heart disease induces GDF 15 synthesis and secretion by cardiomyocytes. Circulating GDF 15 in turn acts on the liver to inhibit growth hormone ( GH ) signaling and body growth. We demonstrate that blocking cardiomyocyte production of GDF 15 normalizes circulating GDF 15 level and restores liver GH signaling, establishing GDF 15 as a bona fide heart‐derived hormone that regulates pediatric body growth. Importantly, plasma GDF 15 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 . image In paediatric cardiac disorders, the heart can secrete GDF 15 as a hormone to modulate liver growth hormone ( GH ) signaling and regulate body growth, establishing GDF 15 as a bona fide heart‐derived hormone and linking body growth to cardiac function. Pediatric heart disease induces GDF15 synthesis and secretion by cardiomyocytes. GDF15 inhibits liver GH signaling and body growth. Blocking cardiac GDF15 production restores circulating GDF15 and liver GH signaling. Plasma GDF15 is increased in children with concomitant heart disease and FTT.