David W Lim1, Paul W Wales2, Jessica K Josephson3, Patrick N Nation4, Pamela R Wizzard3, Consolato M Sergi5, Catherine J Field6, David L Sigalet7, Justine M Turner8. 1. Department of Surgery, University of Alberta, Edmonton, Alberta, Canada. 2. Department of Surgery, University of Alberta, Edmonton, Alberta, Canada Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Department of Surgery, Hospital for Sick Children & University of Toronto, Toronto, Ontario, Canada. 3. Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. 4. Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, Alberta, Canada. 5. Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, Alberta, Canada. 6. Department of Agricultural Food & Nutritional Science, University of Alberta, Edmonton, Alberta, Canada. 7. Department of Surgery, University of Calgary, Calgary, Alberta, Canada. 8. Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Department of Agricultural Food & Nutritional Science, University of Alberta, Edmonton, Alberta, Canada Justine.Turner@albertahealthservices.ca.
Abstract
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.
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.