Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by lipoprotein lipase in wild-type and apoE knockout mice

• Main Authors: Miek C. Jong, Patrick C.N. Rensen, Vivian E.H. Dahlmans, Hans van der Boom, Theo J.C. van Berkel, Louis M. Havekes
• Format: Article
• Language: English
• Published: Elsevier 2001-10-01
• Series: Journal of Lipid Research
• Subjects: hypercholesterolemia; transgenic mice; triglyceride metabolism
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520322112

Previous studies with hypertriglyceridemic APOC3 transgenic mice have suggested that apolipoprotein C-III (apoC-III) may inhibit either the apoE-mediated hepatic uptake of TG-rich lipoproteins and/or the lipoprotein lipase (LPL)-mediated hydrolysis of TG. Accordingly, apoC3 knockout (apoC3−/−) mice are hypotriglyceridemic. In the present study, we attempted to elucidate the mechanism(s) underlying these phenomena by intercrossing apoC3−/− mice with apoE−/− mice to study the effects of apoC-III deficiency against a hyperlipidemic background. Similar to apoE+/+ apoC3−/− mice, apoE−/−apoC3−/− mice exhibited a marked reduction in VLDL cholesterol and TG, indicating that the mechanism(s) by which apoC-III deficiency exerts its lipid-lowering effect act independent of apoE. On both backgrounds, apoC3−/− mice showed normal intestinal lipid absorption and hepatic VLDL TG secretion. However, turnover studies showed that TG-labeled emulsion particles were cleared much more rapidly in apoC3−/− mice, whereas the clearance of VLDL apoB, as a marker for whole particle uptake by the liver, was not affected. Furthermore, it was shown that cholesteryl oleate-labeled particles were also cleared faster in apoC3−/− mice. Thus the mechanisms underlying the hypolipidemia in apoC3−/− mice involve both a more efficient hydrolysis of VLDL TG as well as an enhanced selective clearance of VLDL cholesteryl esters from plasma.In summary, our studies of apoC3−/− mice support the concept that apoC-III is an effective inhibitor of VLDL TG hydrolysis and reveal a potential regulating role for apoC-III with respect to the selective uptake of cholesteryl esters.