Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5
| Autor: | Bryan H. Brewer, Tatiana Pham, Benoit Thomas, Len A. Pennacchio, Jean-Charles Fruchart, Corinne Rommens, Zouher Majd, Loredan-Stefan Niculescu, Jamila Fruchart-Najib, Eric Bauge |
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| Rok vydání: | 2004 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty Very low-density lipoprotein Apolipoprotein B Transgene Lipolysis Cholesterol VLDL Biophysics Enzyme-Linked Immunosorbent Assay Mice Transgenic Biochemistry chemistry.chemical_compound Mice Internal medicine medicine Animals Humans Apolipoproteins C Molecular Biology Apolipoproteins A Triglycerides Apolipoproteins B Lipoprotein lipase Apolipoprotein C-III biology Triglyceride Cholesterol nutritional and metabolic diseases Cell Biology Postprandial Period Dietary Fats Enzyme Activation Lipoprotein Lipase Postprandial Endocrinology Apolipoproteins chemistry Apolipoprotein A-V biology.protein lipids (amino acids peptides and proteins) |
| Zdroj: | Biochemical and biophysical research communications. 319(2) |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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