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 f at Zucker rat that carries a mutation in the leptin receptor. gene. In the present study. we studied the regulation of hepatic low density l ipoprotein (LDL) receptor expression in lean and fat Zucker rats. Comp ared with lean rats, the fat ones had a pronounced (similar to 60%) re duction in hepatic LDL receptor expression, whereas the levels of rece ptor messenger RNA (mRNA) were not reduced. Fat rats had increased lev els of very low density lipoproteins and high density lipoproteins, bu t their plasma apo B100 within LDL was reduced. Challenge with 2% diet ary cholesterol for 8 days suppressed hepatic LDL receptor expression in lean animals to similar levels as seen in Fat ones, whereas the red uction in mRNA levels was much less pronounced. Treatment with ethynyl estradiol (5 mg/kg BW.day) for 4 days strongly stimulated hepatic LDL receptor expression in both lean and fat rats: this treatment also inc reased LDL receptor rRNA levels, but to a lesser extent. In conclusion . the basal expression of hepatic LDL receptors is reduced in fat Zuck er rats, but the capacity for the regulation of the receptors remains intact.