Effects of hepatic HDL-related mRNAs on plasma prebeta HDL in cholesterol-fed rabbits.

Abstract

This study was undertaken to determine; 1) the effect of cholesterol enriched diet on prebeta-migrating (prebeta) HDL levels, 2) the effect of the diet on plasma proteins and/or activities likely associated with prebeta HDL (cholesteryl transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT) and apolipoprotein (apo)A-I), 3) the effect of the diet on the corresponding hepatic mRNAs and 4) the correlation between the hepatic mRNAs and prebeta HDL. Rabbits were fed 0.1% (low) cholesterol (LC group, n = 6) or 0.5% (high) cholesterol diet (HC group, n = 6) for 6 weeks. Plasma CETP activities, plasma total apoA-I and prebeta apoA-I concentrations in the HC group were significantly increased (58.95 +/- 2.37%, 191.52 +/- 13.93 mg/dl, 44.21 +/- 1.14 mg/dl, respectively) compared with the LC group (39.36 +/- 3.62%, 152.85 +/- 8.61 mg/dl, 30.12 +/- 2.79 mg/dl, respectively)(p < 0.05). Plasma LCAT activities did not differ significantly (56.65 +/- 7.19 vs 57.41 +/- 8.21; HC vs LC). Hepatic CETP, LCAT and apoA-I mRNA levels were determined using reverse transcription polymerase chain reaction (RT-PCR). Hepatic CETP mRNA levels, compared to GAPDH mRNA levels as a control, were increased in the HC group (2.226 +/- 0.115) compared with the LC group (1.649 +/- 0.170) (p < 0.05), while hepatic LCAT and apoA-I mRNA levels were unchanged. Thus, plasma concentration of prebeta HDL, CETP activity and the amount of hepatic CETP mRNA were increased in response to the dietary intake of cholesterol. Multiple regression analyses showed that only hepatic CETP mRNA levels had a positive correlation with plasma prebeta HDL concentration (p = 0.04). These results indicate that individual variations in hepatic CETP mRNA levels in rabbits fed a cholesterol diet probably has a major influence on the determination of plasma prebeta HDL concentration.