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.


OBJECTIVE
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.


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 [3H]water into tissue sterols; low density lipoprotein clearance was determined using a primed-continuous infusion of (125I)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 microl of plasma/h per g of tissue). Concurrent treatment with surfomer for 1, 2 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.
Bertolotti
M
M
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA. bertolotti.marco@unimo.it
Spady
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D000042:Absorption / Q000187:drug effects; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008078:Cholesterol, LDL / Q000187:drug effects* / Q000378:metabolism*; D006224:Cricetinae; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006937:Hypercholesterolemia / Q000188:drug therapy*; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011108:Polymers / Q000494:pharmacology*; D011336:Probability; D012016:Reference Values; D012680:Sensitivity and Specificity; D013386:Succinates / Q000494:pharmacology*
D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D011108:Polymers; D013386:Succinates; C025487:surfomer