Premium
Glucagon‐Like Peptide‐2 Alters Bile Acid Metabolism in Parenteral Nutrition–Associated Liver Disease
Author(s) -
Lim David W.,
Wales Paul W.,
Mi Si,
Yap Jason Y. K.,
Curtis Jonathan M.,
Mager Diana R.,
Mazurak Vera C.,
Wizzard Pamela R.,
Sigalet David L.,
Turner Justine M.
Publication year - 2016
Publication title -
journal of parenteral and enteral nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.935
H-Index - 98
eISSN - 1941-2444
pISSN - 0148-6071
DOI - 10.1177/0148607115595596
Subject(s) - bile acid , farnesoid x receptor , lithocholic acid , medicine , cholesterol 7 alpha hydroxylase , cholestasis , neonatal cholestasis , endocrinology , parenteral nutrition , glucagon like peptide 2 , chenodeoxycholic acid , liver disease , biology , biochemistry , peptide , gene , nuclear receptor , biliary atresia , liver transplantation , transplantation , transcription factor
Background : We aim to study the mechanisms underlying our previous finding that exogenous glucagon‐like peptide‐2 (GLP‐2) treatment in a preclinical model of neonatal parenteral nutrition–associated liver disease (PNALD) improves cholestasis. Methods : Neonatal piglets received 17 days of parenteral nutrition (PN) therapy and either saline control (PN/Saline n = 8) or GLP‐2 treatment at 11 nmol/kg/d (PN/GLP‐2, n = 7). At terminal laparotomy, bile and liver samples were collected. The relative gene expression of enzymes involved in bile acid synthesis, regulation, and transport was measured in liver by reverse‐transcriptase quantitative polymerase chain reaction. Bile acid composition in bile was determined using tandem mass spectrometry. Data were analyzed using 1‐way analysis of variance (ANOVA) or Kruskal‐Wallis ANOVA. Results : GLP‐2 increased the expression of bile acid export genes: multidrug resistance–associated proteins 2 (MRP2) ( P = .002) and 3 (MRP3) ( P = .037) over saline control. GLP‐2 increased expression of Farnesoid X receptor (FXR) ( P < .001) and CYP7A1 (cytochrome P450, family 7, subfamily A, polypeptide 1) ( P = .03). GLP‐2 treatment was associated with decreased concentrations of taurohyocholic acid and conjugates of toxic lithocholic acid ( P < .01). GLP‐2 treatment increased the liver bile acid content. Conclusions : GLP‐2 treatment was associated with alterations in the hepatic expression of genes involved in bile acid metabolism. The transcriptomic results indicate the mechanisms at the transcriptional level acting to regulate bile acid synthesis and increase bile acid export. Differences in bile acid profiles further support a beneficial role for GLP‐2 therapy in PNALD.