Dietary fatty acids regulate Acyl-CoA:cholesterol acyltransferase and cytosolic cholesteryl ester hydrolase in hamsters

To investigate the effects of dietary fatty acids on acyl-CoA: cholesterol acyltransferase (ACAT) and cytosolic cholesteryl ester hydrolase (cCEH), male Syrian hamsters (F₁B hybrid) were fed a modified version of the NIH-07 open formula, cereal-based rodent diet enriched with one of the following 4 dietary fatty acids: palmitic acid (16:0), trans fatty acids (18:1t), oleic acid (18:1c), or linoleic acid (18:2). Hamsters fed 16:0 and 18:1t had significantly higher plasma non-HDL cholesterol concentrations compared with those fed 18:1c and 18:2. However, differences in plasma apolipoprotein (apo)B₁₀₀ concentration, hepatic cCEH mRNA abundance, and hepatic ACAT activity between 16:0- and 18:1t-fed hamsters suggest that the hypercholesterolemic effects are achieved by different mechanisms. Specifically, an increase in ACAT activity by 16:0 may induce enrichment of cholesteryl esters in apoB₁₀₀-containing particles, whereas 18:1t may increase the number of the particles. Hepatic cholesteryl esters accumulated in the 18:1c- and 18:2-fed groups with no differences in hepatic ACAT activity and cCEH mRNA abundance among hamsters fed unsaturated fatty acids (i.e., 18:1t, 18:1c, and 18:2). Considering the lack of change in free cholesterol concentration and increased cholesteryl esters in the liver, the hypocholesterolemic effect of 18:1c and 18:2 compared with 18:1t may be attributed to decreased production of apoB₁₀₀-containing particles. ACAT-1 was expressed in all the tissues examined; in contrast, ACAT-2 was highly expressed in the liver and small intestine. Hepatic ACAT activity was disproportionate to the levels of ACAT-1 and ACAT-2 mRNA and protein, indicating post-transcriptional regulation of ACAT by dietary fatty acids. The data suggest that cholesterolemic effects of individual dietary fatty acids can be achieved through their independent modulation of pathways regulating assembly and secretion of apoB ₁₀₀-containing particles.