Impact of Maternal Obesity on Liver Disease in the Offspring: A Comprehensive Transcriptomic Analysis and Confirmation of Results in a Murine Model
Beat Moeckli,
Vaihere Delaune,
Julien Prados,
Matthieu Tihy,
Andrea Peloso,
Graziano Oldani,
Thomas Delmi,
Florence Slits,
Quentin Gex,
Laura Rubbia-Brandt,
Nicolas Goossens,
Stéphanie Lacotte,
Christian Toso
Affiliations
Beat Moeckli
Hepatology and Transplantation Laboratory, Department of Surgery, Faculty of Medicine, Division of Visceral Surgery, University of Geneva, 1206 Geneva, Switzerland
Vaihere Delaune
Hepatology and Transplantation Laboratory, Department of Surgery, Faculty of Medicine, Division of Visceral Surgery, University of Geneva, 1206 Geneva, Switzerland
Julien Prados
Bioinformatics Support Platform, Services Communs de la Faculté, University of Geneva, 1206 Geneva, Switzerland
Matthieu Tihy
Division of Clinical Pathology, Geneva University Hospitals, 1205 Geneva, Switzerland
Andrea Peloso
Hepatology and Transplantation Laboratory, Department of Surgery, Faculty of Medicine, Division of Visceral Surgery, University of Geneva, 1206 Geneva, Switzerland
Graziano Oldani
Hepatology and Transplantation Laboratory, Department of Surgery, Faculty of Medicine, Division of Visceral Surgery, University of Geneva, 1206 Geneva, Switzerland
Thomas Delmi
Hepatology and Transplantation Laboratory, Department of Surgery, Faculty of Medicine, Division of Visceral Surgery, University of Geneva, 1206 Geneva, Switzerland
Florence Slits
Hepatology and Transplantation Laboratory, Department of Surgery, Faculty of Medicine, Division of Visceral Surgery, University of Geneva, 1206 Geneva, Switzerland
Quentin Gex
Hepatology and Transplantation Laboratory, Department of Surgery, Faculty of Medicine, Division of Visceral Surgery, University of Geneva, 1206 Geneva, Switzerland
Laura Rubbia-Brandt
Division of Clinical Pathology, Geneva University Hospitals, 1205 Geneva, Switzerland
Nicolas Goossens
Division of Gastroenterology, Geneva University Hospitals, 1205 Geneva, Switzerland
Stéphanie Lacotte
Hepatology and Transplantation Laboratory, Department of Surgery, Faculty of Medicine, Division of Visceral Surgery, University of Geneva, 1206 Geneva, Switzerland
Christian Toso
Hepatology and Transplantation Laboratory, Department of Surgery, Faculty of Medicine, Division of Visceral Surgery, University of Geneva, 1206 Geneva, Switzerland
The global obesity epidemic particularly affects women of reproductive age. Offspring of obese mothers suffer from an increased risk of liver disease but the molecular mechanisms involved remain unknown. We performed an integrative genomic analysis of datasets that investigated the impact of maternal obesity on the hepatic gene expression profile of the offspring in mice. Furthermore, we developed a murine model of maternal obesity and studied the development of liver disease and the gene expression profile of the top dysregulated genes by quantitative real-time polymerase chain reaction (qPCR). Our data are available for interactive exploration on our companion webpage. We identified five publicly available datasets relevant to our research question. Pathways involved in metabolism, the innate immune system, the clotting cascade, and the cell cycle were consistently dysregulated in the offspring of obese mothers. Concerning genes involved in the development of liver disease, Egfr, Vegfb, Wnt2,Pparg and six other genes were dysregulated in multiple independent datasets. In our own model, we observed a higher tendency towards the development of non-alcoholic liver disease (60 vs. 20%) and higher levels of alanine aminotransferase (41.0 vs. 12.5 IU/l, p = 0.008) in female offspring of obese mothers. Male offspring presented higher levels of liver fibrosis (2.4 vs. 0.6% relative surface area, p = 0.045). In a qPCR gene expression analysis of our own samples, we found Fgf21, Pparg, Ppard, and Casp6 to be dysregulated by maternal obesity. Maternal obesity represents a looming threat to the liver health of future generations. Our comprehensive transcriptomic analysis will help to better understand the mechanisms of the development of liver disease in the offspring of obese mothers and can give rise to further explorations.
