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

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

Author Anzai, Alvaro Google Scholar
Marcondes, Rodrigo R. Google Scholar
Goncalves, Thiago H. Google Scholar
Carvalho, Katia C. Google Scholar
Simoes, Manuel J. Autor UNIFESP Google Scholar
Garcia, Natalia Google Scholar
Soares, Jose M., Jr. Google Scholar
Padmanabhan, Vasantha Google Scholar
Baracat, Edmund C. Google Scholar
da Silva, Ismael D. C. G. Autor UNIFESP Google Scholar
Maciel, Gustavo A. R. Google Scholar
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.
xmlui.dri2xhtml.METS-1.0.item-coverage London
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Grant number FAPESP: 2010/17417-3
Date 2017
Published in Scientific Reports. London, v. 7, p. -, 2017.
ISSN 2045-2322 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent -
Origin http://dx.doi.org/10.1038/s41598-017-13451-8
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000412956900057
URI https://repositorio.unifesp.br/handle/11600/57151

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