Fatty liver and fibrosis in glycine N-methyltransferase knockout mice is prevented by nicotinamide
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Fatty liver and fibrosis in glycine N-methyltransferase knockout mice is prevented by nicotinamide

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Fatty liver and fibrosis in glycine N-methyltransferase knockout mice is prevented by nicotinamide

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dc.contributor.author Varela-Rey, Marta es_ES
dc.contributor.author Martínez-López, Nuria es_ES
dc.contributor.author Fernández-Ramos, David es_ES
dc.contributor.author Embade, Nieves es_ES
dc.contributor.author Calvisi, Diego F. es_ES
dc.contributor.author Woodhoo, Aswhin es_ES
dc.contributor.author Rodríguez, Juan es_ES
dc.contributor.author Fraga, Mario F. es_ES
dc.contributor.author Julve, Josep es_ES
dc.contributor.author Rodríguez-Millán, Elisabeth es_ES
dc.contributor.author Frades, Itziar es_ES
dc.contributor.author Torres, Luís es_ES
dc.contributor.author Luka, Zigmund es_ES
dc.contributor.author Wagner, Conrad es_ES
dc.contributor.author Esteller Badosa, Manel es_ES
dc.contributor.author Lu, Shelly C es_ES
dc.contributor.author Martínez Chantar, María es_ES
dc.contributor.author Mato, José M. es_ES
dc.date.accessioned 2015-06-29T10:32:26Z
dc.date.available 2015-06-29T10:32:26Z
dc.date.issued 2010 es_ES
dc.identifier.uri http://hdl.handle.net/10550/44788
dc.description.abstract Deletion of glycine N-methyltransferase (GNMT) in mice, the main gene involved in liver S-adenosylmethionine (SAMe) catabolism, leads to the hepatic accumulation of this molecule and the development of fatty liver and fibrosis. To demonstrate that the excess of hepatic SAMe is the main agent contributing to liver disease in GNMT-KO mice, we treated 1.5-month old GNMT-KO mice for 6 weeks with nicotinamide (NAM), a substrate of the enzyme NAM N-methyltransferase. NAM administration markedly reduced hepatic SAMe content, prevented DNA-hypermethylation and normalized the expression of critical genes involved in fatty acid metabolism, oxidative stress, inflammation, cell proliferation, and apoptosis. More important, NAM treatment prevented the development of fatty liver and fibrosis in GNMT-KO mice. Because GNMT expression is down-regulated in patients with cirrhosis and there are subjects with GNMT mutations who have spontaneous liver disease, the clinical implication of the present findings is obvious at least with respect to these latter individuals. Especially since NAM has been used for many years to treat a broad spectrum of diseases including pellagra and diabetes without significant side effects, it should be considered in subjects with GNMT mutations.ConclusionsThese results indicate that the anomalous accumulation of SAMe in GNMT-KO mice can be corrected by NAM treatment leading to the normalization of the expression of many genes involved in fatty acid metabolism, oxidative stress, inflammation, cell proliferation and apoptosis, and to the reversion of the appearance of the pathologic phenotype. es_ES
dc.source Vol. 52 Issue 1: pp. 105-114 es_ES
dc.subject S-Adenosylmethionine es_ES
dc.subject DNA methylation es_ES
dc.subject Ras signaling es_ES
dc.subject JAK/STAT signaling es_ES
dc.subject hepatocytes es_ES
dc.title Fatty liver and fibrosis in glycine N-methyltransferase knockout mice is prevented by nicotinamide es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.identifier.doi 10.1002/hep.23639 es_ES
dc.identifier.idgrec 060182 es_ES

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