Developmental regulation of the intestinal FGF19 system in domestic pigs

Fibroblast growth factor-19 (FGF19) is an emerging endocrine factor involved in the regulation of bile acid homeostasis and energy metabolism in rodents and humans. In pigs, however, the FGF19 system remains largely unexplored. This study was designed to investigate the developmental regulation of the FGF19 system in domestic pigs. Samples of intestinal sections, liver, and plasma were collected from 24 pigs ( n = 6) at four developmental stages (birth, preweaning, postweaning, and adulthood). In the intestine, expression of the farnesoid X receptor (FXR) and FGF19 showed a congruent time- and region-dependent regulation, beginning soon after birth to achieve maximal expression in ileum during adulthood. The same temporal pattern was followed by the circulating concentration of FGF19, and these changes were accompanied by a time-related increase in the ileal proportion of bile acids that potently activate FXR. Conversely, genes belonging to the FGF19 signaling machinery achieved maximal expression in the small intestine at birth to decrease sharply afterward. In the liver, gene expression of FGF19 receptors and enzymes involved in bile acid biosynthesis paralleled after-birth changes in plasma concentration of this enterokine and attained a maximum during postweaning when plasma FGF19 was the lowest. Although detectable at birth, the hepatic expression of genes belonging to the bile acid-FXR-FGF19 pathway was low before the onset of enteral feeding. In summary, the porcine FGF19 system is present from birth, operative before the onset of enteral feeding, and regulated in a temporal and section-specific manner. NEW & NOTEWORTHY Fibroblast growth factor-19 (FGF19) is an emerging endocrine factor. The domestic pig is a translational model of value in biomedical research. We show for the first time that in pigs the intestinal FGF19 system is present from birth, operative before the onset of enteral feeding, and regulated in a temporal and section-specific manner. This work identifies pigs as a suitable model for investigating the implications of FGF19 signaling within and beyond the gut-liver axis.