Mechanism of lipid lowering in mice expressing human apolipoprotein A5

Journal Article · Thu Jan 15 04:00:00 EST 2004 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2004.05.003· OSTI ID:838186

Fruchart-Najib, Jamila ^[1]; Bauge, Eric; Niculescu, Loredan-Stefan; Pham, Tatiana; Thomas, Benoit; Rommens, Corinne; Majd, Zouher; Brewer, Bryan; Rubin, Edward M; Pennacchio, Len A; Fruchart, Jean-Charles

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1. LBNL Library

Recently, we reported that apoAV plays key role in triglycerides lowering. Here, we attempted to determine the mechanism underlying this hypotriglyceridemic effect. We showed that triglyceride turnover is faster in hAPOA5 transgenic compared to wild type mice. Moreover, both apoB and apoCIII are decreased and LPL activity is increased in postheparin plasma of hAPOA5 transgenic mice. These data suggest a decrease in size and number of VLDL. To further investigate the mechanism of hAPOA5 in hyperlipidemic background, we intercrossed hAPOA5 and hAPOC3 transgenic mice. The effect resulted in a marked decreased of VLDL triglyceride, cholesterol, apolipoproteins B and CIII. In postprandial state, the triglyceride response is abolished in hAPOA5 transgenic mice. We demonstrated that in response to the fat load in hAPOA5XhAPOC3 mice, apoAV shifted from HDL to VLDL, probably to limit the elevation of triglycerides. In vitro, apoAV activates lipoprotein lipase. However, apoAV does not interact with LPL but interacts physically with apoCIII. This interaction does not seem to displace apoCIII from VLDL but may induce conformational change in apoCIII and consequently change in its function leading the activation of lipoprotein lipase.

• Research Organization: Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (US)
• Sponsoring Organization: US Department of Energy; National Institutes of Health Grants HL66681 and HL071954A (US)
• DOE Contract Number: AC03-76SF00098
• OSTI ID: 838186
• Report Number(s): LBNL--55258
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 319
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
APOAV APOCIII LIPOPROTEIN LIPASE TRIGLYCERIDE TURNOVER POSTPRANDIA
APOLIPOPROTEINS
CHOLESTEROL
CONFORMATIONAL CHANGES
FATS
IN VITRO
LIPASES
LIPIDS
LIPOPROTEINS
MICE
PLASMA
TRANSGENIC MICE
TRIGLYCERIDES