Determinants of cholesterol and lipoprotein metabolism as influenced by dietary fatty acid profile and cholesterol status in the F1B golden-Syrian hamster

Investigated first was the effect of cholesterol status and dietary fatty acid profile on the expression of genes regulating hepatic cholesterol and lipoprotein metabolism. F1B hamsters were fed for 12 weeks diets enriched in 10% (w/w) coconut, olive or safflower oil in combination with either 0.1% cholesterol (cholesterol-supplemented) or 0.01% cholesterol (plus 10 days prior to killing 0.15% lovastatin and 2% cholestyramine) (cholesterol-depleted). Cholesterol depletion resulted in significantly lower plasma non-high density lipoprotein (HDL) cholesterol, HDL cholesterol and triglyceride concentrations. This was associated with up-regulation of genes involved in cholesterol uptake and excretion, and reverse cholesterol transport, and down-regulation of genes involved in de novo lipoprotein and cholesterol synthesis. Coconut oil fed hamsters had significantly higher non-HDL cholesterol and triglyceride concentrations than olive and safflower oil fed hamsters but was not associated with changes in the expression of genes regulating cholesterol and lipoprotein metabolism. Next, the mechanisms by which n-3 PUFA, relative to n-6 PUFA, alter cholesterol and lipoprotein metabolism were assessed using the same hamster model as described. Cholesterol-supplemented hamsters fed fish oil, relative to safflower oil, had higher plasma non-HDL cholesterol and triglyceride concentrations which was associated with down-regulation of genes involved in hepatic cholesterol uptake, and triglyceride and cholesteryl ester synthesis, and up-regulation of genes involved in de novo lipoprotein synthesis. In contrast, cholesterol-depleted hamsters fed fish oil, relative to safflower oil, had lower plasma non-HDL cholesterol and triglyceride concentrations which was associated with lower hepatic SREBP-1 mRNA and protein levels. Independent of cholesterol status, hamsters fed fish oil, relative to safflower oil, had lower HDL cholesterol concentrations and was associated with lower hepatic apo A-1 protein levels. Finally, the effect of dietary fat on aortic lipid composition was assessed in cholesterol-supplemented hamsters fed 10% (w/w) coconut, olive, safflower or fish oil for 12 weeks. Aortic cholesterol accumulation was similar among coconut, olive and safflower oil fed hamsters and significantly higher in fish oil fed hamsters. The fatty acid content of the triglyceride and cholesteryl ester fractions was enriched in the fatty acid class that was predominant in the diet while the phospholipid fraction reflected dietary PUFA.