Title
Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by lipoprotein lipase in wild-type and apoE knockout mice
Author
Gaubius Instituut TNO
Jong, M.C.
Rensen, P.C.N.
Dahlmans, V.E.H.
van der Boom, H.
van Berkel, T.J.C.
Havekes, L.M.
Publication year
2001
Abstract
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. Chemicals/CAS: Apolipoprotein C-III; Apolipoproteins C; Apolipoproteins E; Chylomicrons; Lipoprotein Lipase, EC 3.1.1.34; Lipoproteins, VLDL; Triglycerides
Subject
Animals
Apolipoprotein C-III
Apolipoproteins C
Apolipoproteins E
Chylomicrons
Crosses, Genetic
Female
Gene Deletion
Hydrolysis
Lipoprotein Lipase
Lipoproteins, VLDL
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Time Factors
Triglycerides
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TNO identifier
236280
ISSN
0022-2275
Source
Journal of Lipid Research, 42 (42), 1578-1585
Document type
article