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

Oliveira, Monique Cristine de; Campos-Shimada, Lilian Brites; Marçal-Natali, Maria Raquel; Ishii-Iwamoto, Emy Luiza; Salgueiro-Pagadigorria, Clairce Luzia

doi:10.1055/s-0038-1666856

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Revista Brasileira de Ginecologia e Obstetrícia

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Sumário

Original Article • Rev. Bras. Ginecol. Obstet. 40 (05) • May 2018 • https://doi.org/10.1055/s-0038-1666856 copy

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

Deficiência de estrogênio em longo prazo em camundongas ovarietcomizadas está associada a distúrbios na oxidação de ácidos graxos e estresse oxidativo

Authorship SCIMAGO INSTITUTIONS RANKINGS

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 andmitochondria 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.

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

Variable	SHAM (n= 6)	OVX (n= 6)
Glucose (mmol/L)	4.79 ± 0.27	6.30 ± 0.71*
Total cholesterol (mmol/L)	2.93 ± 0.30	5.83 ± 0.65*
HDL cholesterol (mmol/L)	1.53 ± 0.33	1.83 ± 0.23
LDL cholesterol (mmol/L)	1.29 ± 0.21	3.88 ± 0.63*
VLDL cholesterol (mmol/L)	0.11 ± 0.04	0.12 ± 0.03
Triacylglycerols (mmol/L)	0.56 ± 0.19	0.63 ± 0.16
Liver total lipid content (%)	5.59 ± 0.78	8.06 ± 0.48*

Variable	SHAM (n= 15)	OVX (n= 15)
Body weight (g)	34.66 ± 3.73	49.40 ± 3.39*
Food intake (g/day/kg BW)	186.485 ± 21.77	160.369 ± 15.39
Uterus/BW (%)	0.39 ± 0.07	0.094 ± 0.06*
Liver/BW (%)	3.30 ± 0.23	3.59 ± 0.15
PUAT/BW (%)	2.61 ± 0.38	5.46 ± 0.90*

Variable	SHAM (n= 5)	OVX (n= 5)
Homogenate GSH	3.19 ± 0.24	1.59 ± 0.64***
Mitochondrial GSH	0.94 ± 0.02	0.74 ± 0.03**
Homogenate MDA	4.03 ± 0.23	14.08 ± 1.89***
Mitochondrial MDA	1.50 ± 0.15	4.29 ± 0.45***

Antioxidant Enzyme (per mg protein)	SHAM (n= 6)	OVX (n= 6)
SOD1 (U)	1.20 ± 0.22	0.80 ± 0.17*
SOD2 (U)	1.57 ± 0.13	0.92 ± 0.07***
CT (µmol/min)	18.35 ± 1.26	10.7 ± 0.92**
GSSG-Red (nmol/min)	53.4 ± 4.29	32.55 ± 2.86**
GSH-Px (nmol/min)	173.4 ± 14.51	293.15 ± 30.62*
G6PD (nmol/min)	6.18 ± 0.56	4.15 ± 0.48*

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[1] Address for correspondence Monique Cristine de Oliveira, Centro Universitário de Ingá, Rod. PR 317, 6114, Parque Industrial, 200, Maringá, PR, 87035-510, Brazil (e-mail: prof.moniqueoliveira@uninga.edu.br).