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Type: Journal article
Title: Impact of maternal overnutrition on gluconeogenic factors and methylation of the phosphoenolpyruvate carboxykinase promoter in the fetal and postnatal liver
Author: Rattanatray, L.
Muhlhausler, B.
Nicholas, L.
Morrison, J.
McMillen, I.
Citation: Pediatric Research, 2014; 75(1):14-21
Publisher: Nature Publishing Group
Issue Date: 2014
ISSN: 0031-3998
Statement of
Leewen Rattanatray, Beverly S. Muhlhausler, Lisa M. Nicholas, Janna L. Morrison and I. Caroline McMillen
Abstract: BACKGROUND: Exposure to maternal obesity or hyperglycemia increases the risk of obesity and poor glucose tolerance in the offspring. We hypothesized that maternal overnutrition in late pregnancy would result in (i) lower methylation in the promoter region of the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK-C; PCK1) and (ii) higher expression of hepatic gluconeogenic factors in the fetal and postnatal lamb. METHODS: Ewes were fed 100% (n = 18) or ~155% (n = 17) of energy requirements from 115 d gestation, and livers were collected at ~140 d gestation or 30 d postnatal age. RESULTS: Maternal overnutrition resulted in a decrease in hepatic expression of the mitochondrial form of PEPCK (PEPCK-M; PCK2) but not of PEPCK-C or glucose-6-phosphatase (G6PHOS) before and after birth. Hepatic expression of peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1), peroxisome proliferator-activated receptor α (PPARα), PEPCK-C, G6PHOS, and 11β hydroxysteroid dehydrogenase type 1 (11βHSD1), but not PEPCK-M, was higher in the postnatal lamb compared with that in the fetal lamb. The level of PCK1 methylation was paradoxically approximately twofold higher in the postnatal liver compared with that in the fetal liver. CONCLUSION: Maternal overnutrition programs a decrease in hepatic PEPCK-M in the offspring and as ~50% of total hepatic PEPCK is PEPCK-M, the longer-term consequences of this decrease may be significant.
Keywords: Liver
Description: Advance online publication 22 January 2014
Rights: Copyright © 2014 International Pediatric Research Foundation, Inc.
RMID: 0030016871
DOI: 10.1038/pr.2013.178
Appears in Collections:Obstetrics and Gynaecology publications

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