Academic Journal
Hepatocyte-specific loss of GPS2 in mice reduces non-alcoholic steatohepatitis via activation of PPARα
| العنوان: | Hepatocyte-specific loss of GPS2 in mice reduces non-alcoholic steatohepatitis via activation of PPARα |
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| المؤلفون: | Liang, Ning, Damdimopoulos, Anastasius, Goñi, Saioa, Huang, Zhiqiang, Vedin, Lise-Lotte, Jakobsson, Tomas, Giudici, Marco, Ahmed, Osman, Pedrelli, Matteo, Barilla, Serena, Alzaid, Fawaz, Mendoza, Arturo, Schröder, Tarja, Kuiper, Raoul, Parini, Paolo, Hollenberg, Anthony, Lefebvre, Philippe, Francque, Sven, van Gaal, Luc, Staels, Bart, Venteclef, Nicolas, Treuter, Eckardt, Fan, Rongrong |
| المساهمون: | Karolinska Institutet Stockholm, Department of Laboratory Medicine Karolinska Institutet, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Weill Medical College of Cornell University New York, Inflammation and Infection Theme Karolinska University Hospital, Karolinska University Hospital Stockholm, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), Department of Gastroenterology and Hepatology, University of Antwerp (UA), Laboratory of Experimental Medicine and Pediatrics, Department of Endocrinology, Diabetology and Metabolism, E.T. was supported by grants from the Center for Innovative Medicine (CIMED) at the Karolinska Institutet, the Swedish Research Council, the Swedish Cancer Society, the Swedish Diabetes Foundation, the Novo Nordisk Foundation, and the European Union FP7 HEALTH project HUMAN. R.F. was supported by the European Foundation for the Study of Diabetes (EFSD)/Lilly research fellowship, Junior Diabetes Wellness Sverige grant and KI research foundation grants. R.K. and T.S. were supported by KI/SL and grants from CIMED. N.L. received a doctoral education grant (KID) from Karolinska Institutet. Z.H. was supported by Chinese Government Scholarship (CSC). N.V. was supported by grants from the French National Agency of Research (CONRAD and PROVIDE), Region Ile de France (CORDDIM), Paris city (EMERGENCE), the French Foundation for Diabetes (SFD), and the European Union H2020 framework (ERC-EpiFAT 725790). The human liver transcriptome study performed by P.L., F.A., N.V., and B.S. was supported by EU HEPADIP (Contract LSHM-CT-2005-018734) and RESOLVE (Contract FP7-305707) , the European Research Council (ERC Grant Immunobile, contract 694717), Fondation pour la Recherche Médicale (Equipe labellisée, DEQ20150331724) and Agence Nationale pour la Recherche (ANR-10-LBEX-46). B.S. is a recipient of an Advanced ERC Grant (694717), ANR-12-JSV1-0007,CONRAD,Le complexe répresseur SMRT-GPS2: senseur moléculaire de l'inflammation du tissu adipeux dans l'obésité humaine(2012), ANR-15-CE14-0029,PROVIDE,Compréhension des mécanismes inflammatoires protecteurs dans le diabète(2015), European Project: 694717,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,ImmunoBile(2016) |
| المصدر: | ISSN: 2041-1723. |
| بيانات النشر: | CCSD Nature Publishing Group |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | MESH: Animals, MESH: Biopsy, MESH: Non-alcoholic Fatty Liver Disease, MESH: PPAR alpha, MESH: Datasets as Topic, MESH: Diet, High-Fat, MESH: Disease Models, Animal, MESH: Disease Progression, MESH: Epigenesis, Genetic, MESH: Fibrosis, MESH: HEK293 Cells, MESH: Hepatocytes, MESH: Humans, MESH: Intracellular Signaling Peptides and Proteins, MESH: Lipid Metabolism, MESH: Liver, MESH: Male, MESH: Mice, Inbred C57BL, Knockout, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Obesity triggers the development of non-alcoholic fatty liver disease (NAFLD), which involves alterations of regulatory transcription networks and epigenomes in hepatocytes. Here we demonstrate that G protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor (NCOR) and histone deacetylase 3 (HDAC3) complex, has a central role in these alterations and accelerates the progression of NAFLD towards non-alcoholic steatohepatitis (NASH). Hepatocyte-specific Gps2 knockout in mice alleviates the development of diet-induced steatosis and fibrosis and causes activation of lipid catabolic genes. Integrative cistrome, epigenome and transcriptome analysis identifies the lipid-sensing peroxisome proliferator-activated receptor α (PPARα, NR1C1) as a direct GPS2 target. Liver gene expression data from human patients reveal that Gps2 expression positively correlates with a NASH/fibrosis gene signature. Collectively, our data suggest that the GPS2-PPARα partnership in hepatocytes coordinates the progression of NAFLD in mice and in humans and thus might be of therapeutic interest. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/30975991; info:eu-repo/grantAgreement//694717/EU/Bile acid, immune-metabolism, lipid and glucose homeostasis/ImmunoBile; PUBMED: 30975991; PUBMEDCENTRAL: PMC6459876 |
| DOI: | 10.1038/s41467-019-09524-z |
| الاتاحة: | https://inserm.hal.science/inserm-02154801 https://inserm.hal.science/inserm-02154801v1/document https://inserm.hal.science/inserm-02154801v1/file/Liang%20Nat%20Commun.pdf https://doi.org/10.1038/s41467-019-09524-z |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.4E15A0F2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-019-09524-z |
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