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dc.contributor.author
Sookoian, Silvia Cristina  
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Castaño, Gustavo Osvaldo  
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Scian, Romina  
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Fernández Gianotti, Tomás  
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Dopazo, Hernán Javier  
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Rohr, Cristian Oscar  
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Gaj, Graciela  
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San Martino, Julio  
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Sevic, Ina  
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Flichman, Diego Martin  
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Pirola, Carlos José  
dc.date.available
2018-03-19T19:50:53Z  
dc.date.issued
2016-01  
dc.identifier.citation
Sookoian, Silvia Cristina; Castaño, Gustavo Osvaldo; Scian, Romina; Fernández Gianotti, Tomás; Dopazo, Hernán Javier; et al.; Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level; American Society for Nutrition; American Journal of Clinical Nutrition; 103; 2; 1-2016; 422-434  
dc.identifier.issn
0002-9165  
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http://hdl.handle.net/11336/39259  
dc.description.abstract
Background: Extensive epidemiologic studies have shown that cardiovascular disease and the metabolic syndrome (MetS) are associated with serum concentrations of liver enzymes; however, fundamental characteristics of this relation are currently unknown. Objective: We aimed to explore the role of liver aminotransferases in nonalcoholic fatty liver disease (NAFLD) and MetS. Design: Liver gene- and protein-expression changes of aminotransferases, including their corresponding isoforms, were evaluated in a case-control study of patients with NAFLD (n = 42), which was proven through a biopsy (control subjects: n = 10). We also carried out a serum targeted metabolite profiling to the glycolysis, gluconeogenesis, and Krebs cycle (n = 48) and an exploration by the next-generation sequencing of aminotransferase genes (n = 96). An in vitro study to provide a biological explanation of changes in the transcriptional level and enzymatic activity of aminotransferases was included. Results: Fatty liver was associated with a deregulated liver expression of aminotransferases, which was unrelated to the disease severity. Metabolite profiling showed that serum aminotransferase concentrations are a signature of liver metabolic perturbations, particularly at the amino acid metabolism and Krebs cycle level. A significant and positive association between systolic hypertension and liver expression levels of glutamic-oxaloacetic transaminase 2 (GOT2) messenger RNA (Spearman R = 0.42, P = 0.03) was observed. The rs6993 located in the 3′ untranslated region of the GOT2 locus was significantly associated with features of the MetS, including arterial hypertension [P = 0.028; OR: 2.285 (95% CI: 1.024, 5.09); adjusted by NAFLD severity] and plasma lipid concentrations. Conclusions: In the context of an abnormal hepatic triglyceride accumulation, circulating aminotransferases rise as a consequence of the need for increased reactions of transamination to cope with the liver metabolic derangement that is associated with greater gluconeogenesis and insulin resistance. Hence, to maintain homeostasis, the liver upregulates these enzymes, leading to changes in the amounts of amino acids released into the circulation.  
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application/pdf  
dc.language.iso
eng  
dc.publisher
American Society for Nutrition  
dc.rights
info:eu-repo/semantics/openAccess  
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https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Fatty Liver  
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Gene Expression  
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Liver Injury  
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Metabolomics  
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Transaminases  
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Nutrición, Dietética  
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Ciencias de la Salud  
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CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
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info:eu-repo/semantics/publishedVersion  
dc.date.updated
2018-03-14T17:08:09Z  
dc.identifier.eissn
1938-3207  
dc.journal.volume
103  
dc.journal.number
2  
dc.journal.pagination
422-434  
dc.journal.pais
Estados Unidos  
dc.journal.ciudad
Maryland  
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  
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Fil: Castaño, Gustavo Osvaldo. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina  
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Fil: Scian, Romina. 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  
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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  
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Fil: Dopazo, Hernán Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina  
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Fil: Rohr, Cristian Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina  
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Fil: Gaj, Graciela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Diego Thompson; Argentina  
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Fil: San Martino, Julio. Provincia de Buenos Aires. Ministerio de Salud. Hospital Diego Thompson; Argentina  
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Fil: Sevic, Ina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina  
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Fil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina  
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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.journal.title
American Journal of Clinical Nutrition  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3945/ajcn.115.118695  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/ajcn/article/103/2/422/4564731