Impact of dietary fat type within the context of altered cholesterol homeostasis on cholesterol and lipoprotein metabolism in the F1B hamster

Cholesterol status and dietary fat alter several metabolic pathways reflected in lipoprotein profiles. To assess plasma lipoprotein response and mechanisms by which cholesterol and dietary fat type regulate expression of genes involved in lipoprotein metabolism, we developed an experimental model system using F1B hamsters fed diets (12 weeks) enriched in 10% (wt/wt) coconut, olive, or safflower oil with either high cholesterol (0.1%; cholesterol supplemented) or low cholesterol coupled with cholesterol-lowering drugs 10 days before killing (0.01% cholesterol, 0.15% lovastatin, 2% cholestyramine; cholesterol depleted). Irrespective of dietary fat, cholesterol depletion, relative to supplementation, resulted in lower plasma non–high-density lipoprotein (non-HDL) and HDL cholesterol, and triglyceride concentrations (all Ps < .05). In the liver, these differences were associated with higher sterol regulatory element binding protein–2, low-density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and 7α-hydroxylase messenger RNA (mRNA) levels; higher scavenger receptor B1 and apolipoprotein A-I mRNA and protein levels; lower apolipoprotein E protein levels; and in intestine, modestly lower sterol transporters adenosine triphosphate–binding cassette (ABC) A1, ABCG5, and ABCG8 mRNA levels. Irrespective of cholesterol status, coconut oil, relative to olive and safflower oils, resulted in higher non-HDL cholesterol and triglyceride concentrations (both Ps < .05) and modestly higher sterol regulatory element binding protein–2 mRNA levels. These data suggest that, in F1B hamsters, differences in plasma lipoprotein profiles in response to cholesterol depletion are associated with changes in the expression of genes involved in cholesterol metabolism, whereas the effect of dietary fat type on gene expression was modest, which limits the usefulness of the experimental animal model.