title: Antenatal exposure to chorioamnionitis affects lipid metabolism in 7-week-old sheep.
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.
authors.affiliation: 1Department 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.
authors.forename: E
authors.initials: E
authors.lastname: Vlassaks
authors.affiliation: 1Department 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.
authors.forename: A W D
authors.initials: AW
authors.lastname: Gavilanes
authors.affiliation: 2Department of Molecular Genetics and Pathology, Nutrition and Toxicology Research Institute (NUTRIM) and Cardiovascular Research Institute (CARIM) of Maastricht University, Maastricht, The Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: Bieghs
authors.affiliation: 3Department of Pathology, University Hospital Aachen, Aachen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Reinartz
authors.affiliation: 3Department of Pathology, University Hospital Aachen, Aachen, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Gassler
authors.affiliation: 2Department of Molecular Genetics and Pathology, Nutrition and Toxicology Research Institute (NUTRIM) and Cardiovascular Research Institute (CARIM) of Maastricht University, Maastricht, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Van Gorp
authors.affiliation: 2Department of Molecular Genetics and Pathology, Nutrition and Toxicology Research Institute (NUTRIM) and Cardiovascular Research Institute (CARIM) of Maastricht University, Maastricht, The Netherlands.
authors.forename: M J J
authors.initials: MJ
authors.lastname: Gijbels
authors.affiliation: 4Department of Clinical Chemistry, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: O
authors.initials: O
authors.lastname: Bekers
authors.affiliation: 1Department 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.
authors.forename: L J I
authors.initials: LJ
authors.lastname: Zimmermann
authors.affiliation: 5School of Women's and Infants' Health, University of Western Australia, Crawley, Western Australia.
authors.forename: J J
authors.initials: JJ
authors.lastname: Pillow
authors.affiliation: 5School of Women's and Infants' Health, University of Western Australia, Crawley, Western Australia.
authors.forename: G R
authors.initials: GR
authors.lastname: Polglase
authors.affiliation: 5School of Women's and Infants' Health, University of Western Australia, Crawley, Western Australia.
authors.forename: I
authors.initials: I
authors.lastname: Nitsos
authors.affiliation: 5School of Women's and Infants' Health, University of Western Australia, Crawley, Western Australia.
authors.forename: J P
authors.initials: JP
authors.lastname: Newnham
authors.affiliation: 6Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Kallapur
authors.affiliation: 6Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Jobe
authors.affiliation: 2Department of Molecular Genetics and Pathology, Nutrition and Toxicology Research Institute (NUTRIM) and Cardiovascular Research Institute (CARIM) of Maastricht University, Maastricht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Shiri-Sverdlov
authors.affiliation: 1Department 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.
authors.forename: B W
authors.initials: BW
authors.lastname: Kramer