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Vonderohe C, Guthrie G, Stoll B, et al. Tissue-specific Mechanisms of Bile Acid Homeostasis and Activation of FXR-FGF19 Signaling in Preterm and Term Neonatal Pigs. Am J Physiol Gastrointest Liver Physiol. 2021;doi: 10.1152/ajpgi.00274.2021.
Vonderohe, C., Guthrie, G., Stoll, B., Chacko, S., Dawson, H., & Burrin, D. G. (2021). Tissue-specific Mechanisms of Bile Acid Homeostasis and Activation of FXR-FGF19 Signaling in Preterm and Term Neonatal Pigs. American journal of physiology. Gastrointestinal and liver physiology, . https://doi.org/10.1152/ajpgi.00274.2021
Vonderohe, Caitlin, et al. "Tissue-specific Mechanisms of Bile Acid Homeostasis and Activation of FXR-FGF19 Signaling in Preterm and Term Neonatal Pigs." American journal of physiology. Gastrointestinal and liver physiology vol. (2021). doi: https://doi.org/10.1152/ajpgi.00274.2021
Vonderohe C, Guthrie G, Stoll B, Chacko S, Dawson H, Burrin DG. Tissue-specific Mechanisms of Bile Acid Homeostasis and Activation of FXR-FGF19 Signaling in Preterm and Term Neonatal Pigs. Am J Physiol Gastrointest Liver Physiol. 2021 Dec 01; doi: 10.1152/ajpgi.00274.2021. Epub 2021 Dec 01. PMID: 34851728.
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Am J Physiol Gastrointest Liver Physiol. 2021 Dec 01; doi: 10.1152/ajpgi.00274.2021. Epub 2021 Dec 01.

Tissue-specific Mechanisms of Bile Acid Homeostasis and Activation of FXR-FGF19 Signaling in Preterm and Term Neonatal Pigs.

American journal of physiology. Gastrointestinal and liver physiology

Caitlin Vonderohe, Gregory Guthrie, Barbara Stoll, Shaji Chacko, Harry Dawson, Douglas G Burrin

Affiliations

  1. USDA-ARS Children's Nutrition Research Center; Pediatrics, Gastroenterology and Nutrition, Baylor College of Medicine, Houston, TX, United States.
  2. USDA-ARS, Beltsville Human Nutrition Research Center, Diet, Genomics and Immunology Laboratory, Beltsville, MD, United States.

PMID: 34851728 DOI: 10.1152/ajpgi.00274.2021

Abstract

BACKGROUND & AIMS: The tissue specific molecular mechanisms involved in perinatal liver and intestinal FXR-FGF19 signaling are poorly defined. Our aim was to establish how gestational age and feeding status affect bile acid synthesis pathway, bile acid pool size, ileal response to bile acid stimulation, genes involved in bile acid-FXR-FGF19 signaling and plasma FGF19 in neonatal pigs. Methods Term (n=23) and preterm (n=33) pigs were born via cesarean section at 100% and 90% gestation, respectively. Plasma FGF19, hepatic bile acid and oxysterol profiles, and FXR target gene expression was assessed in pigs at birth and after a bolus feed on day 3 of life. Pig ileal tissue explants were used to measure signaling response to bile acids. Results Preterm pigs had smaller, more hydrophobic bile acid pools, lower plasma FGF19, and blunted FXR-mediated ileal response to bile acid stimulation than term pigs. GATA-4 expression was higher in jejunum than ileum, and was higher in preterm than term pig ileum. Hepatic oxysterol analysis suggested dominance of the alternative pathway of bile acid synthesis in neonates, regardless of gestational age and persists in preterm pigs after feeding on day 3. Conclusion These results highlight the tissue-specific molecular basis for the immature enterohepatic bile acid signaling via FXR-FGF19 in preterm pigs and may have implications for disturbances of bile acid homeostasis and metabolism in preterm infants.

Keywords: Bile Acid Synthesis; GATA-4; Neonatal; Oxysterols; Premature infants

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