The effects of estradiol valerate and remifemin on liver lipid metabolism

Abstract

To investigate the lipid metabolism dysregulation in the liver of ovariectomized (OVX) rats and effects of estradiol valerate (E) and remifemin (ICR) thereon, forty female Sprague-Dawley rats were randomly divided into sham-operated (SHAM), OVX, OVX+E, and OVX+ICR group. After 4 weeks’ E or ICR treatment, serum estrogen, cholesterol, and triglyceride levels; lipid droplets in hepatocytes; hepatocyte morphology; and the expression of estrogen receptor α (ERα), liver X receptor (LXR), and sterol regulatory element binding proteins (SREBPs) in the liver of the rats were assessed. OVX rats had significantly decreased serum estrogen levels, which significantly increased after treatment with E but not with ICR. Serum triglyceride levels and the amount of lipid droplets in hepatocytes increased after ovariectomy, and significantly decreased after E treatment. In addition, ICR treatment markedly increased serum triglyceride levels and lipid droplet size. No significant differences in the serum cholesterol levels were observed among the four groups. After ovariectomy, hepatocyte mitochondria became hypertrophic and misformed, which were reversed with E or ICR treatment. ICR-treated rats also showed endoplasmic reticulum disorganization. After ovariectomy, ERα and LXR levels significantly decreased while SREBP expression increased. E treatment increased ERα and LXR levels while ICR treatment only increased LXR expression. E treatment decreased SREBP-1c levels, whereas SREBP-1c levels increased with ICR treatment. Treatment with E significantly reversed the ovariectomy-induced dysregulation of hepatocyte lipid metabolism, which was, however, exacerbated with ICR treatment. The effects of E and ICR on hepatocyte lipid metabolism may involve the regulation of LXR and SREBP-1c.