Lipoprotein Metabolism in the Fat Zucker Rat: Reduced Basal Expression but Normal Regulation of Hepatic Low Density Lipoprotein Receptors*

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 (approximately 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 per 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.