Inhibition of intestinal cholesterol absorption by surfomer [alpha-olefin maleic acid] affects hepatic cholesterol synthesis and low density lipoprotein transport in hamsters fed a fat-enriched diet

Background, Surfomer (alpha -olefin maleic acid) reduces intestinal cholesterol absorption. Aims. This study was performed to investigate the effect of surfomer on cholesterol synthesis and low density lipoprotein in hamsters fed a hypercholesterolaemic, lipid-enriched diet. Animals and methods. Male hamsters were fed a diet enriched in cholesterol (0.07%) and saturated fatty acids (coconut oil 20%); the diet was supplemented with 3% surfomer: for 1-4 weeks. Cholesterol synthesis was assessed measuring incorporation of [H-3]water into tissue sterols; low density lipoprotein clearance was determined using a primed-continuous infusion of [I-125]tyramine-cellobiose lipoprotein. Results. Cholesterol synthesis was suppressed after 3 weeks of hyperlipidaemic diet in liver and small bowel (by 88% and 38%, respectively) and was significantly increased by supplementing the fat-enriched diet with surfomer. Low density lipoprotein-cholesterol was increased by 44% after 4 weeks of hyperlipidaemic diet, in parallel with a decrease in hepatic low density lipoprotein clearance rates (48 +/-3 vs 68 +/-7 mul of plasma/h per g of tissue). Concurrent treatment with surfomer for 1, P or 4 weeks prevented the decrease of clearance and maintained normal low density lipoprotein-cholesterol levels at all time points, Conclusions. Surfomer represents a powerful tool to investigate the impact of cholesterol absorption on sterol homeostasis. Furthermore, since surfomer appears to normalize low density lipoprotein transport in hamsters fed a diet comparable to a lipid-rich western-style regimen, this drug may deserve consideration as an adjunct treatment for hypercholesterolaemia in selected patient groups.