Dokumentenart: | Artikel | ||||||
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Titel eines Journals oder einer Zeitschrift: | Laboratory Investigation | ||||||
Verlag: | Nature Publishing Group | ||||||
Band: | 94 | ||||||
Seitenbereich: | S. 394-408 | ||||||
Datum: | 3 Februar 2014 | ||||||
Zusätzliche Informationen (Öffentlich): | Advance online publication 3 February 2014 | ||||||
Institutionen: | Medizin > Lehrstuhl für Innere Medizin I Medizin > Lehrstuhl für Pathologie Medizin > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) Informatik und Data Science > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) | ||||||
Identifikationsnummer: |
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Stichwörter / Keywords: | AP-1; c-Jun; metabolic syndrome; NAFLD; NASH Animals; Dietary Fats, adverse effects; Disease Models, Animal; Fatty Liver, etiology/metabolism/pathology; Fibrosis; Gene Expression; Humans; Lipid Metabolism; Liver, pathology; Male; Metabolic Syndrome X, etiology; Mice; Mice, Inbred C57BL; Obesity, etiology; Oxidative Stress; Proto-Oncogene Proteins c-jun, metabolism; Sucrose, adverse effects | ||||||
Dewey-Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik > 500 Naturwissenschaften 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||||
Status: | Veröffentlicht | ||||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||||
An der Universität Regensburg entstanden: | Zum Teil | ||||||
Dokumenten-ID: | 30490 |
Zusammenfassung
Overnutrition is the major cause of nonalcoholic fatty liver disease (NAFLD) and its advanced form nonalcoholic steatohepatitis (NASH). We aimed to develop and characterize a murine model, which resembles both the pathology and nutritional situation, of NASH patients in Western societies. Mice were fed with a NASH-inducing diet (ND) containing sucrose, cholesterol and fats rich in saturated fatty ...
Zusammenfassung
Overnutrition is the major cause of nonalcoholic fatty liver disease (NAFLD) and its advanced form nonalcoholic steatohepatitis (NASH). We aimed to develop and characterize a murine model, which resembles both the pathology and nutritional situation, of NASH patients in Western societies. Mice were fed with a NASH-inducing diet (ND) containing sucrose, cholesterol and fats rich in saturated fatty acids in a composition, which mimics Western food. After 12 weeks, ND-fed mice revealed obesity and impaired glucose tolerance. In the liver, ND-feeding led to marked steatosis, hepatocellular damage, inflammation and beginning fibrosis. Transcriptome-wide gene expression analysis and search for over-represented transcription factor target sites among the differentially expressed genes identified activator protein-1 (AP-1) as the most likely factor to cause the transcriptional changes in ND livers. Combining differentially expressed gene and protein-protein interaction network analysis identified c-Jun as hub in the largest connected deregulated sub-network in ND livers. Accordingly, ND livers revealed c-Jun-phosphorylation and nuclear translocation. Moreover, hepatic c-Jun expression was enhanced in ND-fed mice. Combined tissue microarray technology and immunohistochemical analysis confirmed enhanced hepatic c-Jun levels in NAFLD patients, which correlated with inflammation, and notably, with the degree of hepatic steatosis. In summary, our new mouse model shows important pathological changes also found in human NASH and indicates c-Jun/AP-1 activation as critical regulator of hepatic alterations. Abundance of c-Jun in NAFLD likely facilitates development and progression of NASH.
Metadaten zuletzt geändert: 29 Sep 2021 07:40