Web of Science: 2 citas, Scopus: 2 citas, Google Scholar: citas
AAV8-mediated Sirt1 gene transfer to the liver prevents high carbohydrate diet-induced nonalcoholic fatty liver disease
Vilà, Laia (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Elias, Ivet (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Roca, Carles (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Ribera, Albert (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Ferré, Tura (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Casellas, Alba (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Lage, Ricardo (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Franckhauser, Sylvie (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Bosch, Fatima (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)

Fecha: 2014
Resumen: Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease worldwide, and evidence suggests that it promotes insulin resistance and type 2 diabetes. Caloric restriction (CR) is the only available strategy for NAFLD treatment. The protein deacetylase Sirtuin1 (SIRT1), which is activated by CR, increases catabolic metabolism and decreases lipogenesis and inflammation, both involved in the development of NAFLD. Here we show that adeno-associated viral vectors of serotype 8 (AAV8)-mediated liver-specific Sirt1 gene transfer prevents the development of NAFLD induced by a high carbohydrate (HC) diet. Long-term hepatic SIRT1 overexpression led to upregulation of key hepatic genes involved in β-oxidation, prevented HC diet-induced lipid accumulation and reduced liver inflammation. AAV8- Sirt1 –treated mice showed improved insulin sensitivity, increased oxidative capacity in skeletal muscle and reduced white adipose tissue inflammation. Moreover, HC feeding induced leptin resistance, which was also attenuated in AAV8- Sirt1 –treated mice. Therefore, AAV-mediated gene transfer to overexpress SIRT1 specifically in the liver may represent a new gene therapy strategy to counteract NAFLD and related diseases such as type 2 diabetes.
Derechos: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-nd/3.0/ Creative Commons
Lengua: Anglès.
Documento: article ; recerca ; publishedVersion
Publicado en: Molecular Therapy. Methods & Clinical Development, Vol. 1 (october 2014) , p. 14039, ISSN 2329-0501

PMID: 26015978
DOI: 10.1038/mtm.2014.39


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