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Molecular Nutrition Unit, Center for Nutrition and Toxicology, NOVUM, and Metabolism Unit, Center for Metabolism and Endocrinology, Department of Medicine, Karolinska Institute at Huddinge University Hospital, Huddinge, Sweden
Address all correspondence and requests for reprints to: Wei Liao, M.D., Ph.D., Department of Cell Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030. E-mail: wliao{at}bcm.tmc.edu
Hyperlipoproteinemia is one of the phenotypic characteristics of the
fat Zucker rat that carries a mutation in the leptin receptor gene. In
the present study, we studied the regulation of hepatic low density
lipoprotein (LDL) receptor expression in lean and fat Zucker rats.
Compared with lean rats, the fat ones had a pronounced (
60%)
reduction in hepatic LDL receptor expression, whereas the levels of
receptor messenger RNA (mRNA) were not reduced. Fat rats had increased
levels of very low density lipoproteins and high density lipoproteins,
but their plasma apo B100 within LDL was reduced. Challenge with 2%
dietary cholesterol for 8 days suppressed hepatic LDL receptor
expression in lean animals to similar levels as seen in fat ones,
whereas the reduction in mRNA levels was much less pronounced.
Treatment with ethynylestradiol (5 mg/kg BW·day) for 4 days strongly
stimulated hepatic LDL receptor expression in both lean and fat rats;
this treatment also increased LDL receptor mRNA levels, but to a lesser
extent. In conclusion, the basal expression of hepatic LDL receptors is
reduced in fat Zucker rats, but the capacity for the regulation of the
receptors remains intact.
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