Modulation of hepatic apolipoprotein B, 3-hydroxy-3-methylglutaryl-CoA reductase and low-density lipoprotein receptor mRNA and plasma lipoprotein concentrations by defined dietary fats. Comparison of trimyristin, tripalmitin, tristearin and triolein

Abstract

Different dietary fatty acids exert specific effects on plasma lipids but the mechanism by which this occurs is unknown. Hamsters were fed on low-cholesterol diets containing triacylglycerols enriched in specific saturated fatty acids, and effects on plasma lipids and the expression of genes involved in hepatic lipoprotein metabolism were measured. Trimyristin and tripalmitin caused significant rises in low-density lipoprotein (LDL) cholesterol which were accompanied by significant reductions in hepatic LDL receptor mRNA levels. Tripalmitin also increased hepatic expression of the apolipoprotein B gene, implying an increased production of LDL via very-low-density lipoprotein (VLDL) and decreased removal of LDL in animals fed this fat. Hepatic levels of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA did not vary significantly between the groups. Compared with triolein, tristearin had little effect on hepatic gene expression or total plasma cholesterol. However, it caused a marked decrease in VLDL cholesterol and a rise in LDL cholesterol such that overall it appeared to be neutral. Lipid analysis suggested a rapid desaturation of much of the dietary stearate. The differential changes in plasma lipids and hepatic mRNA levels induced by specific dietary fats suggests a role for fatty acids or a metabolite thereof in the regulation of the expression of genes involved in lipoprotein metabolism.

Increasing amounts of dietary myristic acid modify the plasma cholesterol level and hepatic mass of Scavenger receptor BI without affecting bile acid biosynthesis in hamsters

“…In the present study, different levels of myristic acid (0.03 to 4.2%) do not alter the biosynthesis of bile acids or that of cholesterol since no differences in the HMGCoA activity of the different dietary groups was detected. These last data are similar to those found in previous studies [2,38].…”

“…2 The abbreviations used are: CH: total cholesterol in plasma, EC: esterified cholesterol in liver, TG: hepatic triglycerides, HMG-CoA-R: 3-hydroxy-3-methyl glutaryl coenzyme A reductase, CYP7A1: cholesterol 7 alpha hydroxylase, CYP27A1: sterol 27 hydroxylase, LDL-R: low density lipoprotein receptor, SR-BI: scavenger receptor class B type I, AU: arbitrary units, SFA: saturated fatty acids, MUFA: monounsaturated fatty acids, PUFA: polyunsaturated fatty acids, P/S: ratio of polyunsaturated fatty acids to saturated fatty acids, ns: no significant. A significant decrease in the liver triglyceride concentration was seen after feeding the MI, LA and SA diets while phospholipid concentrations were lower in the LA and MI groups only.…”

Hepatic microsomal triglyceride transfer protein messenger RNA concentrations are increased by dietary cholesterol in hamsters

“…VLDL, low density lipoprotein (LDL) and high density lipoprotein (HDL) were separated by preparative ultracentrifugation at density ranges of <: 1.006, 1.02 1.06 g/ml and > 1.06 g/ml, respectively, as previously described [9,10]. Cholesterol and triacylglycerol concentrations were determined automatically using the Olympus system reagent 5000 cholesterol and GPO Trinder triacylglycerol kits, respectively.…”

“…Hepatic free and esterified cholesterol were extracted, separated by thin-layer chromatography and assayed as previously described [9] 2.4. Isolation of hepatic" total RNA and determination of MTP and apoB mRNA concentrations Total hepatic RNA was isolated by the guanidinium thiocyanate method essentially according to Chomczynski and Sacchi [11].…”

“…Isolation of hepatic" total RNA and determination of MTP and apoB mRNA concentrations Total hepatic RNA was isolated by the guanidinium thiocyanate method essentially according to Chomczynski and Sacchi [11]. The mRNA concentrations for hepatic MTP and apoB genes were determined by a solution hybridization/RNAse protection assay as described previously [6,9]. Results were corrected for variation in the mRNA content of total RNA samples by quantitation of poly(A) RNA using oligo-dTls hybridization [12].…”