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Metabolomics and transcriptomics integrated analyses of livers revealed an unexpected accumulation of hepatic S-Adenosylmethionine (SAM) when compared with healthy livers likely due to diminished methylation reactions and repression of GNMT. SAM plays a key role in the maintenance of cellular homeostasis and cell cycle control. In agreement, analysis of over-represented transcription factors revealed a central role of c-myc and c-Jun pathways accompanied by negative correlations between SAM concentration, MYC expression and AMPK phosphorylation. These findings point to a drift of cell cycle control toward senescence in livers of HFD animals, which could explain the onset of NASH in this model. In contrast, hamsters with NAFLD induced by a conventional high-fat diet did not show SAM accumulation, suggesting a key role of selenium and vitamin E in SAM homeostasis. In conclusion, our results suggest that progression of NAFLD in the context of MetS can take place even in a situation of hepatic SAM excess and that selenium and vitamin E status might be considered in current therapies against NASH based on SAM supplementation.<\/jats:p>","DOI":"10.1042\/cs20171039","type":"journal-article","created":{"date-parts":[[2017,11,10]],"date-time":"2017-11-10T01:55:25Z","timestamp":1510278925000},"page":"409-423","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Hepatic accumulation of S-adenosylmethionine in hamsters with non-alcoholic fatty liver disease associated with metabolic syndrome under selenium and vitamin E deficiency"],"prefix":"10.1042","volume":"133","author":[{"given":"Josep","family":"Maria del Bas","sequence":"first","affiliation":[{"name":"Eurecat, Centre Tecnol\u00f2gic de Catalunya, Technological Unit of Nutrition and Health, Reus, Spain"},{"name":"Eurecat, Centre Tecnol\u00f2gic de Catalunya, Nutrition and Health Research Group (GRNS), Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjam\u00edn","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"R&D Department, Quantitative Genomic Medicine Laboratories (qGenomics), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Puiggr\u00f2s","sequence":"additional","affiliation":[{"name":"Eurecat, Centre Tecnol\u00f2gic de Catalunya, Technological Unit of Nutrition and Health, Reus, Spain"},{"name":"Eurecat, Centre Tecnol\u00f2gic de Catalunya, Nutrition and Health Research Group (GRNS), Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Marin\u00e9","sequence":"additional","affiliation":[{"name":"Centre for Omic Sciences, Joint Unit Universitat Rovira i Virgili-Eurecat, Centre Tecnol\u00f2gic de Catalunya, Unique Scientific and Technical Infrastructures, Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel\u00a0Angel","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Centre for Omic Sciences, Joint Unit Universitat Rovira i Virgili-Eurecat, Centre Tecnol\u00f2gic de Catalunya, Unique Scientific and Technical Infrastructures, Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mori\u00f1a","sequence":"additional","affiliation":[{"name":"Centre for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra (UPF), CIBER Epidemiolog\u00eda y Salud P\u00fablica (CIBERESP), 08003 Barcelona, Spain"},{"name":"Grups de Recerca d\u2019\u00c0frica i Am\u00e8rica Llatines (GRAAL), Unitat de Bioestad\u00edstica, Facultat de Medicina, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Llu\u00eds","family":"Armengol","sequence":"additional","affiliation":[{"name":"R&D Department, Quantitative Genomic Medicine Laboratories (qGenomics), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"Caimari","sequence":"additional","affiliation":[{"name":"Eurecat, Centre Tecnol\u00f2gic de Catalunya, Technological Unit of Nutrition and Health, Reus, Spain"},{"name":"Eurecat, Centre Tecnol\u00f2gic de Catalunya, Nutrition and Health Research Group (GRNS), Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Llu\u00eds","family":"Arola","sequence":"additional","affiliation":[{"name":"Eurecat, Centre Tecnol\u00f2gic de Catalunya, Technological Unit of Nutrition and Health, Reus, Spain"},{"name":"Universitat Rovira i Virgili, Nutrigenomics Research Group; Department of Biochemistry and Biotechnology, Campus Sescelades, Tarragona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2019,2,5]]},"reference":[{"key":"2021113011092413900_B1","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1097\/01.ALC.0000108654.77178.03","article-title":"Abnormal hepatic methionine and glutathione metabolism in patients with alcoholic hepatitis","volume":"28","author":"Lee","year":"2004","journal-title":"Alcohol Clin. 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