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dc.contributor.author
Pirola, Carlos José
dc.contributor.author
Fernández Gianotti, Tomás
dc.contributor.author
Burgueño, Adriana Laura
dc.contributor.author
Rey Funes, Manuel
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Loidl, Cesar Fabian
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Mallardi, Pablo
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San Martino, Julio
dc.contributor.author
Castaño, Gustavo Osvaldo
dc.contributor.author
Sookoian, Silvia Cristina
dc.date.available
2019-01-08T20:39:55Z
dc.date.issued
2013-09
dc.identifier.citation
Pirola, Carlos José; Fernández Gianotti, Tomás; Burgueño, Adriana Laura; Rey Funes, Manuel; Loidl, Cesar Fabian; et al.; Epigenetic modification of liver mitochondrial DNA is associated with histological severity of nonalcoholic fatty liver disease; B M J Publishing Group; Gut; 62; 9; 9-2013; 1356-1363
dc.identifier.issn
0017-5749
dc.identifier.uri
http://hdl.handle.net/11336/67707
dc.description.abstract
Objective & design: Nonalcoholic fatty liver disease (NAFLD) is a clinical condition that refers to progressive histological changes ranging from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH). We evaluated the status of cytosine methylation (5mC) of liver mitochondrial DNA (mtDNA) in selected regions of the mtDNA genome, such as D-loop control region, and mitochondrially encoded NADH dehydrogenase 6 (MT-ND6) and cytochrome C oxidase I (MT-CO1), to contrast the hypothesis that epigenetic modifications play a role in the phenotypic switching from SS to NASH. Methods: We studied liver biopsies obtained from patients with NAFLD in a case-control design; 45 patients and 18 near-normal liver-histology subjects. Results: MT-ND6 methylation was higher in the liver of NASH than SS patients (p<0.04) and MT-ND6 methylated DNA/unmethylated DNA ratio was significantly associated with NAFLD activity score (p<0.02). Liver MT-ND6 mRNA expression was significantly decreased in NASH patients (0.26±0.30) versus SS (0.74±0.48), p<0.003, and the protein level was also diminished. The status of liver MT-ND6 methylation in NASH group was inversely correlated with the level of regular physical activity (R=-0.54, p<0.02). Hepatic methylation levels of D-Loop and MT-CO1 were not associated with the disease severity. DNA (cytosine-5) methyltransferase 1 was significantly upregulated in NASH patients (p<0.002). Ultrastructural evaluation showed that NASH is associated with mitochondrial defects and peroxisome proliferation. Conclusion: Hepatic methylation and transcriptional activity of the MT-ND6 are associated with the histological severity of NAFLD. Epigenetic changes of mtDNA are potentially reversible by interventional programs, as physical activity could modulate the methylation status of MT-ND6.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
B M J Publishing Group
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Epigenetics
dc.subject
Mitochondrial Dysfunction
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Mt-Nd6
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Nafld
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Dna Methylation
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Nash
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Otros tipos de Medicina Clínica
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Medicina Clínica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Epigenetic modification of liver mitochondrial DNA is associated with histological severity of nonalcoholic fatty liver disease
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-01-02T19:52:38Z
dc.journal.volume
62
dc.journal.number
9
dc.journal.pagination
1356-1363
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
dc.description.fil
Fil: Fernández Gianotti, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
dc.description.fil
Fil: Burgueño, Adriana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
dc.description.fil
Fil: Rey Funes, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
dc.description.fil
Fil: Loidl, Cesar Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
dc.description.fil
Fil: Mallardi, Pablo. Municipio de San Martín. Hospital Municipal "Diego Thompson"; Argentina
dc.description.fil
Fil: San Martino, Julio. Municipio de San Martín. Hospital Municipal "Diego Thompson"; Argentina
dc.description.fil
Fil: Castaño, Gustavo Osvaldo. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
dc.journal.title
Gut
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1136/gutjnl-2012-302962
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://gut.bmj.com/content/62/9/1356


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