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

Autor(es):Mostrar menos -

Anzai, Alvaro ^[1] ; Marcondes, Rodrigo R. ^[1] ; Goncalves, Thiago H. ^[1] ; Carvalho, Katia C. ^[1] ; Simoes, Manuel J. ^[2] ; Garcia, Natalia ^[1] ; Soares, Jr., Jose M. ^[1] ; Padmanabhan, Vasantha ^[3] ; Baracat, Edmund C. ^[1] ; da Silva, Ismael D. C. G. ^[4] ; Maciel, Gustavo A. R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med FMUSP, Disciplina Ginecol, Lab Ginecol Estrutural & Mol LIM 58, BR-01246903 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Disciplina Histol & Biol Estrutural, Dept Morfol & Genet, BR-04023900 Sao Paulo, SP - Brazil

^[3] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 - USA

^[4] Univ Fed Sao Paulo, Dept Ginecol, Lab Ginecol Mol & Prote, BR-04024002 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 7, OCT 13 2017.
• Citações Web of Science: 2

Resumo

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. (AU)

• Processo FAPESP: 10/17417-3 - Expressão de genes relacionados à fisiologia do hormônio liberador de gonadotrofinas (GnRH) em modelo experimental de ratas com síndrome dos ovários policísticos (SOP) induzido por exposição a androgênios
• Beneficiário: Gustavo Arantes Rosa Maciel
• Modalidade de apoio: Auxílio à Pesquisa - Regular