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dc.contributor.authorAnzai, Alvaro
dc.contributor.authorMarcondes, Rodrigo R.
dc.contributor.authorGoncalves, Thiago H.
dc.contributor.authorCarvalho, Katia C.
dc.contributor.authorSimoes, Manuel J. [UNIFESP]
dc.contributor.authorGarcia, Natalia
dc.contributor.authorSoares, Jose M., Jr.
dc.contributor.authorPadmanabhan, Vasantha
dc.contributor.authorBaracat, Edmund C.
dc.contributor.authorda Silva, Ismael D. C. G. [UNIFESP]
dc.contributor.authorMaciel, Gustavo A. R.
dc.date.accessioned2020-08-04T13:39:51Z
dc.date.available2020-08-04T13:39:51Z
dc.date.issued2017
dc.identifierhttp://dx.doi.org/10.1038/s41598-017-13451-8
dc.identifier.citationScientific Reports. London, v. 7, p. -, 2017.
dc.identifier.issn2045-2322
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/57151
dc.description.abstractPolycystic 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 (Testosen
dc.description.abstractn = 10), 0.5 mg estradiol benzoate (E2en
dc.description.abstractn = 10), or vehicle (control group, CNTen
dc.description.abstractn = 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.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.format.extent-
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofScientific Reports
dc.rightsAcesso aberto
dc.titleImpaired branched-chain amino acid metabolism may underlie the nonalcoholic fatty liver disease-like pathology of neonatal testosterone-treated female ratsen
dc.typeArtigo
dc.description.affiliationUniv Sao Paulo, Fac Med FMUSP, Disciplina Ginecol, Lab Ginecol Estrutural & Mol LIM 58, BR-01246903 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Disciplina Histol & Biol Estrutural, Dept Morfol & Genet, BR-04023900 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Michigan, Dept Pediat, Ann Arbor, MI 48109 USA
dc.description.affiliationUniv Fed Sao Paulo, Dept Ginecol, Lab Ginecol Mol & Prote, BR-04024002 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Disciplina Histol & Biol Estrutural, Dept Morfol & Genet, BR-04023900 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Ginecol, Lab Ginecol Mol & Prote, BR-04024002 Sao Paulo, SP, Brazil
dc.description.sponsorshipIDFAPESP: 2010/17417-3
dc.identifier.fileWOS000412956900057.pdf
dc.identifier.doi10.1038/s41598-017-13451-8
dc.description.sourceWeb of Science
dc.identifier.wosWOS:000412956900057
dc.coverageLondon
dc.citation.volume7


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