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.
Competing interests:The authors have declared that no competing interests exist.serum MDA levels increased in the WT-OVX and KO-CON groups, but decreased in the KO-OVX group, though no statistical significance was reached yet (Fig 2).
Body weight changes in different groups of miceBody weight curves prepared by weighing each group of mice weekly showed that weight gain occurred in the WT-OVX and KO-OVX groups relative to the WT-CON and KO-CON groups (Fig 3b). No significant difference of the weight gain rate was found between the WT-CON and KO-CON groups, but OVX groups had increased weight compared to the counterpart CON groups (Fig 3b and 3a, P < 0.05 and P < 0.01). By calculating the rate of weight gain from the preoperative time to postoperative week 9 in different groups, we found that the weight gain rates of the KO-OVX was significantly higher than that in the corresponding KO-CON and WT-CON groups after postoperative week 4 (Fig 3b), and the weight gain rate of KO-OVX was the greatest and was significantly different from the WT-CON and KO-CON group (WT-CON 6.02% ± 2.95%, WT-OVX 18.55% ...