ESPE Abstracts (2015) 84 PL5

Ontogeny of FGF21 in the Human: Implications for Metabolic Health

Francesc Villarroyaa,b

aUniversity of Barcelona, Barcelona, Spain; bCIBER Fisiopatologia de la Obesidad y Nutrición, Barcelona, Spain

Background: FGF21 is a hormonal factor with powerful anti-diabetic and anti-obesity properties in adults\. Studies in rodent models indicated that hepatic FGF21 expression and blood FGF21 levels are strongly induced after birth in response to fat provided by milk ingestion. Moreover, preliminary data indicate that FGF21 is present in maternal milk.

Objective and hypotheses: Our objective is to determine, using human samples and pre-clinical experimental models, the role of FGF21, both endogenously produced and transferred from the mother, in neonatal metabolism.

Methods: Determination of the ontogeny of FGF21 levels and FGF21 gene expression in human early life, using blood samples as well as hepatic and adipose samples from necropsies. Determination of the alterations in neonatal metabolism in mice with targeted invalidation of the FGF21 gene. Characterization of FGF21 in maternal milk in humans and rodents. Determination of the physiological role of the FGF21 present in maternal milk on neonatal development.

Results: FGF21 levels are induced after birth in human neonates, thus resulting in a surge of FGF21 from infra- to supra-adult concentrations in the neonate. Changes in FGF21 levels in blood appear to reflect mainly hepatic FGF21 expression changes in the neonatal period. Brown but not white adipose tissue expresses FGF21 in human neonates. Maternal milk, either from humans and rodents, contains FGF21 that is essentially originating in maternal blood. Rodent studies indicate that FGF21 from milk is essential for appropriate neonatal development. FGF21 in milk is retained in neonatal gut and does not cross to neonatal circulation. Small intestine is a target of FGF21 action in neonates, in contrast with adults in which intestine is not sensitive to FGF21. FGF21 acts on neonatal intestine promoting the expression of digestive enzymes, such as lactase, and intestinal hormones such as GIP and GLP-1. FGF21 in neonatal intestine induces lactose digestion.

Conclusion: FGF21 is an important hormonal factor in neonates. The role of FGF21 involves both endogenous regulation of expression and levels in the neonate and the action of FGF21 present in maternal milk on neonatal intestine function and maturation.

Funding: This work is supported by MINECO (Grant SAF2011-2636), Recercaixa Foundation, Instituto Danone and Generalitat de Catalunya (Grant 2009SGR00284), Spain.

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