DZQE activates AMPK pathway and regulates lipid metabolism in a rat model of perimenopausal hyperlipidemia

Background: Menopause is an important event in a female's life. During perimenopause, together with osteoporosis and dyslipidemia, ovary function gradually declines. Dyslipidemia is a risk factor for cardiovascular disorder, cerebrovascular disease and breast cancer in postmenopausal women. All of these contribute to impairment of liver function, particularly fatty liver disease. Since liver dysfunction is associated with ovary dysfunction and hyperlipidemia.Thus, this study aims to define a therapeutic approach to improve ovary function and attenuate lipid accumulation in order to prevent perimenopause-induced ovary dysfunction and hyperlipidemia. Methods: Four-week-old female Wistar rats were injected intraperitoneally with 4-VCD and fed with high fat diet (HFD) that served as the model of perimenopause complicated with hyperlipidemia. 4-VCD induced perimenopause whiles HFD caused hyperlipidemia. Five days after administration, the 4-VCD + HFD-treated rats were assessed daily for estrous cycle stage by vaginal cytology. Rats were then assigned into cohorts of groups where 2.5 g kg⁻¹, 5.0 g kg⁻¹, and 10.0 g kg⁻¹ DZQE and EV were administered intragastrically for 8 weeks. Expression levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2) and testosterone (T) by ELISA served as biomarkers for perimenopause and ovary dysfunction. AMPK and ACC expression levels were determined with western blot in the liver whiles AST and ALT were analyzed by automatic biochemical analyzer to examine the liver function. Results: DZQE improved ovary function by up-regulating E2 and T levels in serum and down-regulating FSH and LH serum levels. Moreover, DZQE reduced serum levels of triglyceride (TG), total cholesterol (TC) and low density lipoprotein (LDL) in a dose-dependent manner to regulate lipid level during perimenopause. Furthermore, DZQE increased AMPK in both transcriptional level and translational levels and decreased the expression of SREBP-1c gene as well as its downstream target genes, FAS. DZQE improves dyslipidemia during menopause and further determined its effect on liver function. Conclusion: DZQE is an effective Chinese herbal compound which improves ovary function and lipid metabolism in perimenopause complicated with hyperlipidemia at least in part through AMPK pathway.

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