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Impaired branched-chain amino acid metabolism may underlie the nonalcoholic fatty liver disease-like pathology of neonatal testosterone-treated female rats.
Anzai, Álvaro; Marcondes, Rodrigo R; Gonçalves, Thiago H; Carvalho, Kátia C; Simões, Manuel J; Garcia, Natália; Soares, José M; Padmanabhan, Vasantha; Baracat, Edmund C; da Silva, Ismael D C G; Maciel, Gustavo A R.
Afiliación
  • Anzai Á; Laboratorio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, 01246903, Brazil.
  • Marcondes RR; Laboratorio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, 01246903, Brazil. marcondes_rr@hotmail.com.
  • Gonçalves TH; Laboratorio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, 01246903, Brazil.
  • Carvalho KC; Laboratorio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, 01246903, Brazil.
  • Simões MJ; Departamento de Morfologia e Genetica, Disciplina de Histologia e Biologia Estrutural, Universidade Federal de Sao Paulo, Sao Paulo, SP, 04023900, Brazil.
  • Garcia N; Laboratorio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, 01246903, Brazil.
  • Soares JM; Laboratorio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, 01246903, Brazil.
  • Padmanabhan V; Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, 48109, USA.
  • Baracat EC; Laboratorio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, 01246903, Brazil.
  • da Silva IDCG; Laboratorio de Ginecologia Molecular e Proteomica, Departamento de Ginecologia, Universidade Federal de Sao Paulo, Sao Paulo, SP, 04024002, Brazil.
  • Maciel GAR; Laboratorio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, 01246903, Brazil. gustavo.maciel@hc.fm.usp.br.
Sci Rep ; 7(1): 13167, 2017 10 13.
Article en En | MEDLINE | ID: mdl-29030588
Polycystic ovary syndrome (PCOS) is frequently associated with non-alcoholic fatty liver disease (NAFLD), but the mechanisms involved in the development of NAFLD in PCOS are not well known. We investigated histological changes and metabolomic profile in the liver of rat models of PCOS phenotype induced by testosterone or estradiol. Two-day old female rats received sc injections of 1.25 mg testosterone propionate (Testos; n = 10), 0.5 mg estradiol benzoate (E2; n = 10), or vehicle (control group, CNT; n = 10). Animals were euthanized at 90-94 d of age and the liver was harvested for histological and metabolomic analyses. Findings showed only Testos group exhibited fatty liver morphology and higher levels of ketogenic and branched-chain amino acids (BCAA). Enrichment analysis showed effects of testosterone on BCAA degradation pathway and mitochondrial enzymes related to BCAA metabolism. Testos group also had a decreased liver fatty acid elongase 2 (ELOVL2) activity. E2 group had reduced lipid and acylcarnitine metabolites in the liver. Both groups had increased organic cation transporters (SLC22A4 and SLC16A9) activity. These findings indicate that neonatal testosterone treatment, but not estradiol, produces histological changes in female rat liver that mimic NAFLD with testosterone-treated rats showing impaired BCAA metabolism and dysfunctions in ELOVL2, SLC22A4 and SLC16A9 activity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome del Ovario Poliquístico / Testosterona / Enfermedad del Hígado Graso no Alcohólico / Aminoácidos de Cadena Ramificada Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome del Ovario Poliquístico / Testosterona / Enfermedad del Hígado Graso no Alcohólico / Aminoácidos de Cadena Ramificada Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido