Impact of Maternal Obesity on Liver Disease in the Offspring: A Comprehensive Transcriptomic Analysis and Confirmation of Results in a Murine Model

Article Article scientifique Article Impact of Maternal Obesity on Liver Disease in the Offspring: A Comprehensive Transcriptomic Analysis and Confirmation of Results in a Murine Model eng 2022-01-27 2022-01-27 author Moeckli Beat 0000-0002-9020-8416 848954 author Delaune Vaihere 0000-0001-8931-0977 839496 author Prados Julien 0000-0002-8546-241X 561771 author Tihy Matthieu 0000-0002-9314-4657 914217 author Peloso Andréa 0000-0002-3089-0230 878393 author Oldani Graziano 776352 author Delmi Thomas Marino 832604 author Slits Florence 782467 author Gex Quentin 701133 author Rubbia-Brandt Laura 31809 author Goossens Nicolas 509893 author Lacotte Stéphanie 0000-0002-5921-6389 714209 author Toso Christian 0000-0003-1652-4522 92271 294 10.3390/biomedicines10020294 35203502 2227-9059 PMC8869223 https://www.mdpi.com/2227-9059/10/2/294 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. Maternal obesity Liver disease Whole-genome expression analysis Transcriptomics Non-alcoholic fatty liver disease Developmental origins of health and disease Dewey 616 Dewey 616.07 Dewey 617 Swiss National Science Foundation Impact of the gut-liver axis on de novo and recurrent hepatocellular carcinoma in the presence non-alcoholic fatty liver disease 310030_182471 CH Project funding Leenaards Foundation 5489 Fondation Francis & Marie-France Minkoff 57 Département de chirurgie 222 56 Département de médecine 221 137 Département de pathologie et immunologie 21F false 562 Transplantation et hépatologie 905 1329 Chirurgie viscérale (HUG) 48a82112-9f30-4dde-a32a-47c02fceac29 Bioinformatics Support Platform 1323 Création de tissus par bio-ingénieurie et régénération d'organes 1021 0a6434c9-7972-44ea-8708-82e501660dc7 Biomedical Data Science Facility https://github.com/moecklib/IGA_maternalobesity Biomedicines 10 2 8db3ab39-3a63-41ff-9523-06a5729d91e9 Article (Published version) Public Article-scientifique-from-unpaywall.pdf 6022624 application/pdf CC BY-4.0 bd843321-00db-42d4-b66b-e2c7d5c4cd21 Appendix Public biomedicines-10-00294-s001.zip 18727899 application/zip openAccess Faculté de médecine / Section de médecine clinique / Département de chirurgie Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Impact of Maternal Obesity on Liver Disease in the Offspring: A Comprehensive Transcriptomic Analysis and Confirmation of Results in a Murine Model	Biomedicines			2022	503	294

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Delmi, Thomas

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