Cholesterol-lowering and anti-atherogenic effects of oats in mice

Sammanfattning: The cholesterol-lowering effect of oats is well established, but the crucial properties eliciting this effect need to be further investigated to optimize the use of oats as functional foods. Furthermore, there are almost no reports investigating the effect of oats on atherosclerosis development. This thesis describes our work with finding suitable mouse models to study cholesterol-lowering and anti-atherogenic effects of oats, the mechanism behind, and how processing of oat foods might interfere with these beneficial effects. We found that supplementation of oat bran to an atherogenic diet significantly reduced plasma cholesterol and LDL+VLDL concentrations in C57BL/6 mice. The responsiveness to oats did however differ between two substrain of mice. Oat intake resulted in reduced plasma cholesterol, increased faecal excretion of bile acids and cholesterol, and increased expression of the bile acid producing enzyme CYP7A1 in the C57BL/6NCrl substrain. None of these parameters were altered in the C57BL/6JBomTac mice. The different expression of CYP7A1 in the two substrains of C57BL/6 strongly supports the importance of increased bile acid excretion, together with increase of bile acid synthesis from cholesterol, for oats to reduce levels of cholesterol in plasma. To address how processing of oats might interfere with its cholesterol-lowering properties, oat beta-glucans were enzymatically digested to different molecular weights and then fed to C57BL/6NCrl mice. Reducing the molecular weight of the beta-glucans affected its viscous properties in vitro. It also affected the production of short chain fatty acids in caecal contents of the mice, but did not influence the cholesterol-lowering properties. Thus molecular weight and viscous properties of beta-glucans do not seem to be crucial parameters for the cholesterol-lowering properties of oats in the C57BL/6 mice. When studying effects of oats on atherogenesis and inflammation we used a mouse model developing more pronounced hypercholesterolaemia, the LDL-receptor deficient mice. Oats reduced plasma cholesterol and levels of LDL+VLDL in this model too, and also reduced plasma concentrations of the inflammation markers fibrinogen and soluble vascular adhesion molecule-1 (sVCAM-1). Most importantly oat bran in the diet reduced incidence of atherosclerotic lesions in both the aortic root and the descending aorta. These findings demonstrate that oats have anti-atherogenic properties, and support health claims that oats can reduce risk of cardiovascular disease.