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Clin Sci (Lond). 2019 Feb 5;133(3):409-423. doi: 10.1042/CS20171039. Print 2019 Feb 14.

Hepatic accumulation of S-adenosylmethionine in hamsters with non-alcoholic fatty liver disease associated with metabolic syndrome under selenium and vitamin E deficiency.

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Eurecat, Centre Tecnològic de Catalunya, Technological Unit of Nutrition and Health, Reus, Spain.
Eurecat, Centre Tecnològic de Catalunya, Nutrition and Health Research Group (GRNS), Reus, Spain.
R&D Department, Quantitative Genomic Medicine Laboratories (qGenomics), Barcelona, Spain.
Centre for Omic Sciences, Joint Unit Universitat Rovira i Virgili-Eurecat, Centre Tecnològic de Catalunya, Unique Scientific and Technical Infrastructures, Reus, Spain.
Centre for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra (UPF), CIBER Epidemiología y Salud Pública (CIBERESP), 08003 Barcelona, Spain.
Grups de Recerca d'Àfrica i Amèrica Llatines (GRAAL), Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain.
Eurecat, Centre Tecnològic de Catalunya, Technological Unit of Nutrition and Health, Reus, Spain
Universitat Rovira i Virgili, Nutrigenomics Research Group; Department of Biochemistry and Biotechnology, Campus Sescelades, Tarragona, Spain.


Progression of non-alcoholic fatty liver disease (NAFLD) in the context of metabolic syndrome (MetS) is only partially explored due to the lack of preclinical models. In order to study the alterations in hepatic metabolism that accompany this condition, we developed a model of MetS accompanied by the onset of steatohepatitis (NASH) by challenging golden hamsters with a high-fat diet low in vitamin E and selenium (HFD), since combined deficiency results in hepatic necroinflammation in rodents. 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.


metabolic syndromes; non alcoholic fatty liver disease; nutrition


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