A Long-term Estrogen Deficiency in Ovariectomized Mice is Associated with Disturbances in Fatty Acid Oxidation and Oxidative Stress

Abstract

Objective The aim of this work was to evaluate the changes caused by estrogen deficiency in lipid metabolism.

Methods This study encompassed direct measurements of plasma biochemical analyses, liver lipid contents, and assessments of the mitochondrial β-oxidation capacity as well as an evaluation of the liver redox status in an animal model of estrogen deficiency.

Results When compared with control mice, the livers of ovariectomized (OVX) mice presented considerable accretions in their lipid contents, which were accompanied by increased levels of lipid peroxidation in liver homogenates and mitochondria from OVX groups and decreased reduced glutathione (GSH) contents. In isolated mitochondria, estrogen deficiency inhibited mitochondrial β-oxidation of fatty acids irrespective of their chain length. The liver mitochondrial and peroxisomal H₂O₂ generations in OVX mice were increased. Additionally, the activities of all antioxidant enzymes assessed were decreased.

Conclusion These data provide one potential explanation for the increased susceptibility to metabolic diseases observed after menopause.

Resumo

Objetivo O objetivo desse trabalho foi avaliar as alterações causadas pela deficiência estrogênica no metabolismo de lipídeos.

Métodos Este estudo abrangeu análises bioquímicas plasmáticas, verificação de conteúdo lipídico do fígado e avaliações da capacidade de β-oxidação mitocondrial e do estado redox do fígado em um modelo animal de deficiência estrogênica.

Resultados Os fígados das camundongas ovariectomizadas (OVXs) apresentaram acréscimos consideráveis no conteúdo de lipídeos, que foram acompanhados por aumento de peroxidação lipídica em homogenatos e mitocôndrias de fígado e diminuição do conteúdo de glutationa reduzida (GSH) quando comparadas as camundongas do grupo controle. Nas mitocôndrias isoladas, a deficiência estrogênica causou a inibição da β-oxidação mitocondrial independentemente do comprimento da cadeia dos ácidos graxos. A geração mitocondrial e peroxissomal de H₂O₂ apresentou-se aumentada em camundongas OVXs. Além disso, as atividades de todas as enzimas antioxidantes avaliadas foram diminuídas.

Conclusão Esses dados fornecem uma explicação potencial para o aumento da suscetibilidade às doenças metabólicas observadas após a menopausa.

Keywords

mitochondria - non-alcoholic fatty liver disease - obesity - ovariectomy - reactive oxygen species

Descritores

mitocôndrias - doença hepática gordurosa não alcoólica - obesidade - ovariectomia - espécies reativas de oxigênio

Contributions

Oliveira M. C., Shimada L. B. C., Natali M. R. M., Iwamoto E. L. I. and Pagadigorria C. Z. S. contributed to conception and design of the study and the critical review of the intellectual content of the article. All authors approved of the version to be published.

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