Abstract 18507: Icosabutate, a Novel Structurally Enhanced Fatty-acid Increases Hepatic Uptake of Cholesterol and Triglycerides in Conjunction With Increased Hepatic LDL Receptor Expression

Background: At a tenth of the dose of unmodified omega-3 fatty acids, Icosabutate (a structurally modified omega-3 fatty acid) achieves potent lowering of both plasma triglycerides (TG) and non-HDL cholesterol (C) in APOE*3Leiden.CETP transgenic mice. The mechanism/s by which Icosabutate exerts its hypolipidemic effect was investigated. Methods: Male APOE*3Leiden.CETP mice were fed a semi-synthetic Western-type diet (WTD, 15% cocoa butter, 40% sucrose and 0.25% cholesterol; all w/w) without or with Icosabutate (112 mg/kg bw/day). Hepatic production and clearance of lipids/lipoproteins, lipolytic activity, hepatic lipids and expression of LDL receptor protein (LDLr) were assessed. Results: After 4 to 6 weeks of treatment Icosabutate lowered both plasma TG and C, confined to the non-HDL particles, by 68% (p<0.001 vs. control). No significant effects were seen in lipoprotein lipase and hepatic lipase activity. However, hepatic uptake of VLDL-like 14C-cholesteryl oleate particles (as marker for VLDL-CE) and 3...