Abstract
The risk of metabolic abnormalities in menopausal women increases significantly due to the decline in estrogen level. Nuclear factor E2-related factor 2 (NRF2) is an important oxidative stress sensor that plays regulatory role in energy metabolism. Therefore, an ovariectomized menopausal model in Nrf2-knockout (KO) mice was applied to evaluate the effect of Nrf2 deficiency on metabolism in menopausal females. The mice were divided into four groups according to their genotypes and treatments. Blood samples and bodyweights were obtained preoperatively and in the first to ninth postoperative weeks after overnight fasting. Serum levels of triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and glucose (GLU) were measured at postoperative weeks 0, 1, 3, 5, 7, and 9. Neurotransmitter dopamine (DA) and serotonin (5-HT) was analyzed in brain tissues after sacrifice at postoperative week 9. The results demonstrated that, compared with the corresponding wild-type (WT) mice, KO ovariectomized mice had a greater bodyweight gain (P<0.01). Serum analysis showed that the serum GLU, T-CHO, and TG were significantly lower (P<0.05) but LDL was significantly higher (P<0.05) in the KO control mice than that in WT control mice. However, different from the WT counterparts, an increase in blood GLU level (P<0.05), unchanged T-CHO, TG, and HDL levels, and a significant reduction in LDL (P<0.01) was found in the KO ovariectomized mice. In addition, the level of 5-HT was significantly reduced (P<0.05) in the KO mice after ovariectomy. In conclusion, the combination of Nrf2 deletion and a decline in estrogen level induced a significant increase in bodyweight, which may be associated with their altered glucose and LDL metabolism and decreased 5-HT levels. From a clinical perspective, women with antioxidant defense deficiency may have an increased risk of metabolic abnormalities after menopause.
Highlights
Menopause refers to the cessation of ovarian function that leads to the termination of the menstrual cycle and is accompanied by decreased estrogen levels, increased follicle stimulating hormone and luteinizing hormone levels, and significant changes in endocrine secretion [1]
The results showed that the change rate of estrogen levels of the WT-OVX and KO-OVX groups were significantly lower than that of the wild-type control (WT-CON) and KO-CON groups (WT-CON 60.12% ± 124.9%, WT-OVX -21.02% ± 19.32%, KO-CON 34.03% ± 47.50%, and KO-OVX -27.02% ± 14.19, P< 0.05)
Normal estrous changes were observed in the mice of the WT-CON and KO-CON groups, and a large number of keratinized epithelial cells were observed under light microscopy (Fig 1b)
Summary
Menopause refers to the cessation of ovarian function that leads to the termination of the menstrual cycle and is accompanied by decreased estrogen levels, increased follicle stimulating hormone and luteinizing hormone levels, and significant changes in endocrine secretion [1]. This leads to serious pathophysiological changes such as depression, anxiety, sleep disorders, hot flashes, night sweats, and menstrual disorders [2]. A cross-sectional and longitudinal analysis has shown that plasma intermediate-density lipoprotein (IDL) and LDL levels are higher in menopausal women than in women of childbearing age [3]. The decline in estrogen level in menopause is closely related to metabolic abnormalities
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