Fibroblast growth factor 19 secretion and function in perinatal development

Abstract

Limited work has focused on fibroblast growth factor-19 (FGF19) secretion and function in the perinatal period. FGF19 is a potent growth factor that coordinates development of the brain, eye, inner ear, and skeletal system in the embryo, but after birth, FGF19 transitions to be an endocrine regulator of the classic pathway of hepatic bile acid synthesis. FGF19 has emerged as a mediator of metabolism and bile acid synthesis in aged animals and adults in the context of liver disease and metabolic dysfunction. FGF19 has also been shown to have systemic insulin-sensitizing and skeletal muscle hypertrophic effects when induced or supplemented at supraphysiological levels in adult rodent models. These effects could be beneficial to improve growth and nutritional outcomes in preterm infants, which are metabolically resistant to the anabolic effects of enteral nutrition. Existing clinical data on FGF19 secretion and function in the perinatal period in term and preterm infants has been equivocal. Studies in pigs show that FGF19 expression and secretion are upregulated with gestational age and point to molecular and endocrine factors that may be involved. Work focused on FGF19 in pediatric diseases suggests that augmentation of FGF19 secretion by activation of gut FXR signaling is associated with benefits in diseases such as short bowel syndrome, parenteral nutrition-associated liver disease, and biliary atresia. Future work should focus on characterization of FGF19 secretion and the mechanism underpinning the transition of FGF19 function as an embryological growth factor to metabolic and bile acid regulator.