Genetic determinants of plasma lipoprotein levels and their dietary response.

Hamsters were fed diets containing fat (5-20%, w/w) consisting of triolein (TO) alone or 50% triolein plus 50% trimyristin (TM), tripalmitin (TP) or tristearin (TS) for 28 days. Each fat had unique effects on lipoprotein concentrations which were related to changes in the expression of hepatic genes. Tripalmitin was the most hypercholesterolaemic of the saturated fats, causing dose-dependent increases in LDL and HDL cholesterol which correlated with decreases in the expression of HMGCoA reductase and LDL receptor genes. Tripalmitin also increased the expression of the apoB gene. It seems likely that fatty acids may regulate genes which are involved both in the synthesis and clearance of plasma lipoproteins. Inclusion of increasing amounts of cholesterol in diets containing 20% fat (50% TO plus 50% TP or TS) caused down-regulation of HMGCoAR and LDLR genes and up-regulation of the microsomal triglyceride transfer protein (MTP) gene for both fats. This was accompanied by increased LDL-cholesterol in the TP but not the TS group. In all experiments the concentration of VLDL-cholesterol correlated with the hepatic cholesterylester and MTP mRNA concentrations.