Please use this identifier to cite or link to this item: https://repositorio.unifesp.br/handle/11600/57151
Title: Impaired branched-chain amino acid metabolism may underlie the nonalcoholic fatty liver disease-like pathology of neonatal testosterone-treated female rats
Authors: Anzai, Alvaro
Marcondes, Rodrigo R.
Goncalves, Thiago H.
Carvalho, Katia C.
Simoes, Manuel J. [UNIFESP]
Garcia, Natalia
Soares, Jose M., Jr.
Padmanabhan, Vasantha
Baracat, Edmund C.
da Silva, Ismael D. C. G. [UNIFESP]
Maciel, Gustavo A. R.
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Scientific Reports. London, v. 7, p. -, 2017.
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
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.
URI: https://repositorio.unifesp.br/handle/11600/57151
ISSN: 2045-2322
Other Identifiers: http://dx.doi.org/10.1038/s41598-017-13451-8
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