TY - JOUR

T1 - Rapid Postnatal Upregulation of Intestinal FXR-FGF19 Signalling in Premature Pigs

AU - Smith, Victoria

AU - Jiang, Yanjun

AU - Thymann, Thomas

AU - Sangild, Per

AU - Maj, Magdalena

AU - Manjarin, Rodrigo

AU - Burrin, Douglas

PY - 2020

Y1 - 2020

N2 - OBJECTIVES: Bile acid (BA) homeostasis is regulated by intestinal cellular signaling involving the farnesoid X receptor (FXR) and fibroblast growth factor 19 (FGF19) secretion. Using preterm and term pigs as a model, we examined postnatal changes in expression of the FXR-FGF19 axis that is poorly characterized in human infants.METHODS: Pigs delivered by cesarean-section at 10 d preterm and near full term (115 d gestation) were fitted with orogastric and umbilical arterial catheters. Pigs were fed combined parenteral nutrition and minimal enteral nutrition for 5 d, followed by milk formula until 26 d. Plasma and tissue samples were collected at d 0, 5, 11, and 26. Plasma FGF19 concentration and liver and distal intestinal gene expression of FGF19 and other FXR target genes were quantified.RESULTS: Plasma FGF19 levels were lower in preterm vs. term newborn pigs (P < 0.05), increased markedly by 5 d, especially in preterm pigs, and decreased in both groups until d 26. Likewise, intestinal FXR and FGF19 expression was lower (P ≤ 0.05) in premature vs term newborn pigs and decreased (P ≤ 0.05) between d 5 and 26. Hepatic expression of cholesterol 7α-hydroxylase (CYP7A1) was inversely correlated with plasma FGF19 in both groups.CONCLUSIONS: We conclude that the activity of FXR-FGF19 axis is lower in preterm than in term newborn pigs but increases transiently and then declines by the first month of age. We also provide supportive evidence of negative feedback between plasma FGF19 and hepatic CYP7A1 expression.

AB - OBJECTIVES: Bile acid (BA) homeostasis is regulated by intestinal cellular signaling involving the farnesoid X receptor (FXR) and fibroblast growth factor 19 (FGF19) secretion. Using preterm and term pigs as a model, we examined postnatal changes in expression of the FXR-FGF19 axis that is poorly characterized in human infants.METHODS: Pigs delivered by cesarean-section at 10 d preterm and near full term (115 d gestation) were fitted with orogastric and umbilical arterial catheters. Pigs were fed combined parenteral nutrition and minimal enteral nutrition for 5 d, followed by milk formula until 26 d. Plasma and tissue samples were collected at d 0, 5, 11, and 26. Plasma FGF19 concentration and liver and distal intestinal gene expression of FGF19 and other FXR target genes were quantified.RESULTS: Plasma FGF19 levels were lower in preterm vs. term newborn pigs (P < 0.05), increased markedly by 5 d, especially in preterm pigs, and decreased in both groups until d 26. Likewise, intestinal FXR and FGF19 expression was lower (P ≤ 0.05) in premature vs term newborn pigs and decreased (P ≤ 0.05) between d 5 and 26. Hepatic expression of cholesterol 7α-hydroxylase (CYP7A1) was inversely correlated with plasma FGF19 in both groups.CONCLUSIONS: We conclude that the activity of FXR-FGF19 axis is lower in preterm than in term newborn pigs but increases transiently and then declines by the first month of age. We also provide supportive evidence of negative feedback between plasma FGF19 and hepatic CYP7A1 expression.

U2 - 10.1097/MPG.0000000000002645

DO - 10.1097/MPG.0000000000002645

M3 - Journal article

C2 - 31990866

VL - 70

SP - e94-e99

JO - Journal of Pediatric Gastroenterology and Nutrition

JF - Journal of Pediatric Gastroenterology and Nutrition

SN - 0277-2116

IS - 5

ER -