| Autor: |
Jong, M.C., Rensen, P.C.N., Dahlmans, V.E.H., Boom, H. van der, Berkel, T.J.C. van, Havekes, L.M. |
| Přispěvatelé: |
Gaubius Instituut TNO |
| Jazyk: |
angličtina |
| Rok vydání: |
2001 |
| Předmět: |
|
| Zdroj: |
Journal of Lipid Research, 10, 42, 1578-1585 |
| ISSN: |
1578-1585 |
| Popis: |
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 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
