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Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5.

Abstract：

:Overexpression of human APOA5 in mice results in dramatically decreased plasma triglyceride levels. In this study we explored the mechanism underlying this hypotriglyceridemic effect. Initially we found that triglyceride turnover was faster in hAPOA5 transgenic mice compared to controls, and this strongly correlated with increased LPL activity in postheparin plasma. Furthermore, we show that in vitro recombinant apoAV interacts physically with lipoprotein lipase and significantly increased its activity. We show that both apoB and apoCIII are decreased in hAPOA5 transgenic mice indicating a decrease in VLDL number. To further investigate the mechanism of hAPOA5 in a hyperlipidemic background, we inter-crossed hAPOA5 and hAPOC3 transgenic mice. We found a marked decrease in VLDL triglyceride and cholesterol, as well as apolipoprotein B and CIII levels. These data indicated that apoAV induces a decrease in VLDL size by activating lipolysis and an increase of VLDL clearance. In a postprandial state, the normal triglyceride response found in wild-type mice was significantly reduced in hAPOA5 transgenics. In addition, we demonstrated that in response to this fat load in hAPOA5xhAPOC3 mice, apoAV, but not apoCIII, was redistributed from primarily HDL to VLDL. This shift of apoAV in VLDL appears to limit the increase of triglyceride by activating the lipoprotein lipase.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Fruchart-Najib J,Baugé E,Niculescu LS,Pham T,Thomas B,Rommens C,Majd Z,Brewer B,Pennacchio LA,Fruchart JC

doi

10.1016/j.bbrc.2004.05.003

subject

Has Abstract

pub_date

2004-06-25 00:00:00

pages

397-404

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006291X04009556

journal_volume

319

pub_type

杂志文章

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