Impaired branched-chain amino acid metabolism may underlie the nonalcoholic fatty liver disease-like pathology of neonatal testosterone-treated female rats

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dc.contributor.author Anzai, Alvaro
dc.contributor.author Marcondes, Rodrigo R.
dc.contributor.author Goncalves, Thiago H.
dc.contributor.author Carvalho, Katia C.
dc.contributor.author Simoes, Manuel J. [UNIFESP]
dc.contributor.author Garcia, Natalia
dc.contributor.author Soares, Jose M., Jr.
dc.contributor.author Padmanabhan, Vasantha
dc.contributor.author Baracat, Edmund C.
dc.contributor.author da Silva, Ismael D. C. G. [UNIFESP]
dc.contributor.author Maciel, Gustavo A. R.
dc.date.accessioned 2020-08-04T13:39:51Z
dc.date.available 2020-08-04T13:39:51Z
dc.date.issued 2017
dc.identifier http://dx.doi.org/10.1038/s41598-017-13451-8
dc.identifier.citation Scientific Reports. London, v. 7, p. -, 2017.
dc.identifier.issn 2045-2322
dc.identifier.uri https://repositorio.unifesp.br/handle/11600/57151
dc.description.abstract 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 en
dc.description.abstract n = 10), 0.5 mg estradiol benzoate (E2 en
dc.description.abstract n = 10), or vehicle (control group, CNT en
dc.description.abstract 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. en
dc.description.sponsorship Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.format.extent -
dc.language.iso eng
dc.publisher Nature Publishing Group
dc.relation.ispartof Scientific Reports
dc.rights Acesso aberto
dc.title Impaired branched-chain amino acid metabolism may underlie the nonalcoholic fatty liver disease-like pathology of neonatal testosterone-treated female rats en
dc.type Artigo
dc.description.affiliation Univ Sao Paulo, Fac Med FMUSP, Disciplina Ginecol, Lab Ginecol Estrutural & Mol LIM 58, BR-01246903 Sao Paulo, SP, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Disciplina Histol & Biol Estrutural, Dept Morfol & Genet, BR-04023900 Sao Paulo, SP, Brazil
dc.description.affiliation Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA
dc.description.affiliation Univ Fed Sao Paulo, Dept Ginecol, Lab Ginecol Mol & Prote, BR-04024002 Sao Paulo, SP, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Disciplina Histol & Biol Estrutural, Dept Morfol & Genet, BR-04023900 Sao Paulo, SP, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Dept Ginecol, Lab Ginecol Mol & Prote, BR-04024002 Sao Paulo, SP, Brazil
dc.description.sponsorshipID FAPESP: 2010/17417-3
dc.identifier.file WOS000412956900057.pdf
dc.identifier.doi 10.1038/s41598-017-13451-8
dc.description.source Web of Science
dc.identifier.wos WOS:000412956900057
dc.coverage London
dc.citation.volume 7



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