Glucagon-Like Peptide 2 Improves Cholestasis in Parenteral Nutrition–Associated Liver Disease

• Published in: JPEN. Journal of parenteral and enteral nutrition 2016-01, Vol.40 (1), p.14-21
• Main Authors: Lim, David W., Wales, Paul W., Josephson, Jessica K., Nation, Patrick N., Wizzard, Pamela R., Sergi, Consolato M., Field, Catherine J., Sigalet, David L., Turner, Justine M.
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Animals; Animals, Newborn; Bilirubin - blood; C-Reactive Protein - metabolism; cholestasis; Cholestasis - complications; Cholestasis - drug therapy; Female; Glucagon-Like Peptide 2 - pharmacology; glucagon‐like peptide 2; intestinal failure; Liver - drug effects; Liver - metabolism; Liver Diseases - complications; Liver Diseases - drug therapy; Male; neonate; Organ Size - drug effects; parenteral nutrition; Parenteral Nutrition - adverse effects; parenteral nutrition associated liver disease; Swine
• ISSN: 0148-6071; 1941-2444
• DOI: 10.1177/0148607114551968

Background: Parenteral nutrition-associated liver disease (PNALD) remains a significant cause of morbidity and mortality in neonates with intestinal failure. Although glucagon-like peptide-2 (GLP-2) is being advanced as therapy, the effect of GLP-2 treatment on PNALD is unknown. We aim to investigate the effect of exogenous GLP-2 administration on hepatic function in a neonatal piglet model of PNALD. Methods: Neonatal piglets (aged 2–6 days) underwent jugular venous catheterization to receive isonitrogenous, isocaloric parenteral nutrition (PN). Piglets were allocated to 2 groups: group 1 (n = 8) received saline while group 2 (n = 7) received GLP-2 (at 11 nmol/kg/d). After 17 days, piglets underwent terminal laparotomy, and bile flow was measured. Liver specimens were analyzed histologically and with immunoperoxidase staining. Age-matched sow-reared control piglets (group 3, n = 8) were used for comparison. Results: Both groups 1 and 2 receiving PN developed cholestasis relative to sow-reared controls, as evidenced by a decrease in bile flow and increase in serum total bilirubin. However, group 2 had improved bile flow (1.35 vs 0.73 µL/g; P = .02) and diminished bilirubin (38.0 vs 78.5 µmol/L; P = .008) compared with group 1. Group 2 also had lower serum alanine aminotransferase levels, a marker of liver injury. Histologically, the liver specimens in group 1 had marked hepatocyte pigmentation, which was decreased in group 2 specimens. Conclusions: The exogenous administration of GLP-2 is associated with the improvement of cholestasis and liver injury. This study introduces a novel role for GLP-2 in improving PNALD in the setting of prolonged PN duration.