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Antenatal exposure to chorioamnionitis affects lipid metabolism in 7-week-old sheep

Published online by Cambridge University Press:  17 February 2012

E. Vlassaks ,
A. W. D. Gavilanes ,
V. Bieghs ,
A. Reinartz ,
N. Gassler ,
P. J. Van Gorp ,
M. J. J. Gijbels ,
O. Bekers ,
L. J. I. Zimmermann  and
J. J. Pillow
...Show all authors
E. Vlassaks
Affiliation:
Department of Pediatrics – Division of Neonatology, Maastricht University Medical Center, School of Mental Health and Neuroscience (MHeNS) and School for Oncology and Developmental Biology Maastricht (GROW), Maastricht, The Netherlands
A. W. D. Gavilanes
Affiliation:
Department of Pediatrics – Division of Neonatology, Maastricht University Medical Center, School of Mental Health and Neuroscience (MHeNS) and School for Oncology and Developmental Biology Maastricht (GROW), Maastricht, The Netherlands
V. Bieghs
Affiliation:
Department of Molecular Genetics and Pathology, Nutrition and Toxicology Research Institute (NUTRIM) and Cardiovascular Research Institute (CARIM) of Maastricht University, Maastricht, The Netherlands
A. Reinartz
Affiliation:
Department of Pathology, University Hospital Aachen, Aachen, Germany
N. Gassler
Affiliation:
Department of Pathology, University Hospital Aachen, Aachen, Germany
P. J. Van Gorp
Affiliation:
Department of Molecular Genetics and Pathology, Nutrition and Toxicology Research Institute (NUTRIM) and Cardiovascular Research Institute (CARIM) of Maastricht University, Maastricht, The Netherlands
M. J. J. Gijbels
Affiliation:
Department of Molecular Genetics and Pathology, Nutrition and Toxicology Research Institute (NUTRIM) and Cardiovascular Research Institute (CARIM) of Maastricht University, Maastricht, The Netherlands
O. Bekers
Affiliation:
Department of Clinical Chemistry, Maastricht University Medical Center, Maastricht, The Netherlands
L. J. I. Zimmermann
Affiliation:
Department of Pediatrics – Division of Neonatology, Maastricht University Medical Center, School of Mental Health and Neuroscience (MHeNS) and School for Oncology and Developmental Biology Maastricht (GROW), Maastricht, The Netherlands
J. J. Pillow
Affiliation:
School of Women's and Infants’ Health, University of Western Australia, Crawley, Western Australia
G. R. Polglase
Affiliation:
School of Women's and Infants’ Health, University of Western Australia, Crawley, Western Australia
I. Nitsos
Affiliation:
School of Women's and Infants’ Health, University of Western Australia, Crawley, Western Australia
J. P. Newnham
Affiliation:
School of Women's and Infants’ Health, University of Western Australia, Crawley, Western Australia
S. G. Kallapur
Affiliation:
Cincinnati Children's Hospital, Cincinnati, Ohio, USA
A. H. Jobe
Affiliation:
Cincinnati Children's Hospital, Cincinnati, Ohio, USA
R. Shiri-Sverdlov
Affiliation:
Department of Molecular Genetics and Pathology, Nutrition and Toxicology Research Institute (NUTRIM) and Cardiovascular Research Institute (CARIM) of Maastricht University, Maastricht, The Netherlands
B. W. Kramer*
Affiliation:
Department of Pediatrics – Division of Neonatology, Maastricht University Medical Center, School of Mental Health and Neuroscience (MHeNS) and School for Oncology and Developmental Biology Maastricht (GROW), Maastricht, The Netherlands
*
*Address for correspondence: Dr B. W. Kramer, MD, PhD, Professor of Experimental Perinatology, Department of Pediatrics, Maastricht University Medical Center, Postbus 5800, 6200MD Maastricht, The Netherlands. (Email [email protected])
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Abstract

Antenatal exposure of the fetus to inflammation may alter postnatal organ development. In our previous work, we demonstrated that the fetal liver is involved in the systemic inflammation associated with chorioamnionitis, leading to metabolic changes. On the basis of these findings, we hypothesized that chorioamnionitis can lead to postnatal inflammation-related liver injury and disturbed lipid metabolism. Chorioamnionitis was induced in sheep by intra-amniotic injection of lipopolysaccharide (LPS) or saline at 90, 100 and 110 days of gestation. Liver homeostasis and lipid metabolism were analyzed at term and at 7 weeks of age. At term, hepatic T-lymphocytes and apoptotic hepatocytes were increased. In addition, hepatic cholesterol and triglyceride levels were decreased in LPS-exposed animals compared with controls. At 7 weeks of age, no hepatic inflammation could be detected. However, liver triglycerides and plasma cholesterol levels were increased in LPS-exposed animals relative to controls. The changes in lipid levels at 7 weeks of age were associated with increased leptin receptor mRNA levels, increased lipid peroxidation, increased expression of cytochrome c oxidase subunit 4 as a marker for mitochondrial function and increased circulating ceramide levels. These findings demonstrate that chorioamnionitis-mediated antenatal inflammation-related liver disturbances have long-lasting postnatal effects on lipid metabolism.

Keywords

fetal origin of adult diseaselipopolysaccharideliver and lipid homeostasis
Type
Original Articles
Information
Journal of Developmental Origins of Health and Disease , Volume 3 , Issue 2 , April 2012 , pp. 103 - 110
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012

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Footnotes

†

Equal contribution of both authors.

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