GH1 and heart disorder: They showed that pediatric heart disease induces GDF15 synthesis and secretion by cardiomyocytes, circulating GDF15 in turn acts on the liver to inhibit GH signaling, and specifically knockdown GDF15 in Cre+ cardiomyocytes by AAV9-Sico-mouse Gdf15 shRNA normalizes the circulating GDF15 levels and restores liver GH signaling, establishing GDF15 as a bona fide heart-derived hormone that negatively regulates pediatric body growth via heart-liver axis mediated to suppress hepatic GH signaling [139].