Ovariectomy decreases plasma triglyceride levels in analbuminaemic rats by lowering hepatic triglyceride secretion

Abstract

In mutant analbuminaemic rats (NAR), females demonstrate a more marked hypertriglyceridaemia than males. Ovariectomy decreases triglyceride levels in female NAR. We measured triglyceride secretion rates in vivo as well as the activity of acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS) in hepatic cytosol obtained from female control Sprague-Dawley (SD) rats and NAR with or without ovariectomy. NAR were severely hyperlipidaemic, and triglyceride, cholesterol, apolipoprotein A-I and plasma protein concentrations levels were decreased (all P < 0.01) by ovariectomy. Only triglyceride levels were decreased by ovariectomy in the SD rats ( P < 0.05). Oestradiol treatment in ovariectomized NAR restored plasma protein and triglyceride concentrations to levels similar to those observed in intact female NAR and caused a marked increase in plasma cholesterol. Ovariectomy in NAR reduced lipoprotein triglycerides and cholesterol in VLDL, IDL and LDL1, but had little effect on the triglyceride-cholesterol ratio of these particles. Both ACC and FAS activities were markedly increased in NAR vs. SD rats ( P < 0.01). This increase was partially corrected by ovariectomy. There was no significant effect of ovariectomy on ACC or FAS activity in the SD rats. Triglyceride secretion rates were significantly increased in NAR vs. SD rats (135 ± 10 vs. 103 ± 12 nmol/min per 100 g body weight; P < 0.05). Ovariectomy markedly decreased triglyceride secretion rate in NAR to 69 ± 6 ( P < 0.01), but not in SD rats (92 ± 8 nmol/min per 100 g body weight, NS). Oestradiol treatment in ovariectomized SD rats restored triglyceride levels but had no significant effect on triglyceride secretion rate (106 ± 23 nmol/min per 100 g). However, oestradiol treatment in ovariectomized NAR caused a marked increase in plasma triglycerides and triglyceride secretion rate (188 ± 24 nmol/min per 100 g; P < 0.01). Thus, hypertriglyceridaemia in female NAR is partly determined by a quantitative increase in the secretion of triglyceride-rich lipoproteins by the liver. The increased triglyceride secretion is largely dependent on oestrogens because ovariectomy causes a marked decrease in plasma triglycerides and triglyceride secretion, and oestradiol treatment restores plasma triglyceride levels to levels normally found in female NAR. The enhanced secretion is associated with an increase in synthesis of fatty acids in the liver as assessed by activities of ACC and FAS. These data indicate that there may be a specific interaction of albumin and oestrogen in the regulation of hepatic lipid metabolism.