| First Author | Jong MC | Year | 2001 |
| Journal | J Lipid Res | Volume | 42 |
| Issue | 10 | Pages | 1578-85 |
| PubMed ID | 11590213 | Mgi Jnum | J:72320 |
| Mgi Id | MGI:2152463 | Citation | Jong MC, et al. (2001) Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by lipoprotein lipase in wild-type and apoE knockout mice. J Lipid Res 42(10):1578-85 |
| abstractText | 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. - Jong, M. C., P. C. N. Rensen, V. E. H. Dahlmans, H. van der Boom, T. J. C. van Berkel, and L. M. Havekes. Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by lipoprotein lipase in wild-type and apoE knockout mice. J. Lipid Res. 2001. 42: 1578;-1585. |
