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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.
Keywords
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Article info
Publication history
Accepted:
February 22,
1995
Received in revised form:
February 16,
1995
Received:
October 11,
1994
Identification
Copyright
© 1995 Published by Elsevier Inc.