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Apolipoprotein A5, a Crucial Determinant of Plasma Triglyceride Levels, Is Highly Responsive to Peroxisome Proliferator-activated Receptor α Activators
Open accessAbstract
The recently discovered APOA5 gene has been shown in humans and mice to be important in determining plasma triglyceride levels, a major cardiovascular disease risk factor. apoAV represents the first described apolipoprotein where overexpression lowers triglyceride levels. Since fibrates represent a commonly used therapy for lowering plasma triglycerides in humans, we investigated their ability to modulate APOA5 gene expression and consequently influence plasma triglyceride levels. Human primary hepatocytes treated with Wy 14,643 or fenofibrate displayed a strong induction of APOA5 mRNA. Deletion and mutagenesis analyses of the proximal APOA5 promoter firmly demonstrate the presence of a functional peroxisome proliferator-activated receptor response element. These findings demonstrate that APOA5 is a highly responsive peroxisome proliferator-activated receptor alpha target gene and support its role as a major mediator for how fibrates reduce plasma triglycerides in humans.
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Cited by
Pawlak, M., Lefebvre, P., & Staels, B. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2014.10.039 · Cited by 1,578
Self-citationPeroxisome Proliferator-Activated Receptor Alpha Target Genes
Rakhshandehroo, M., Knoch, B., Müller, M., & Kersten, S. (2010) · PPAR Research · doi:10.1155/2010/612089 · Cited by 1,020
Sorting out the roles of PPAR in energy metabolism and vascular homeostasis
Lefebvre, P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27989 · Cited by 962
Molecular Actions of PPARα in Lipid Metabolism and Inflammation
Bougarne, N., Weyers, B., Desmet, S. J., Deckers, J., Ray, D. W., Staels, B., & De Bosscher, K. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00064 · Cited by 898
Self-citationPPARs in Obesity-Induced T2DM, Dyslipidaemia and NAFLD
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Metadata
- Authors
- Vu-Dac, N., Gervois, P., Jakel, H., Nowak, M., Baugé, E., Dehondt, H., Staels, B., Pennacchio, L. A., Rubin, E. M., Fruchart-Najib, J., & Fruchart, J.-C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-05
- Volume
- 278
- Issue
- 20
- Pages
- 17982-17985
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2132198142
- Cited by
- 206
- References
- 5
- FWCI
- 7.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- creativecommons.org/licenses/by/4.0/ (vor, 6364 d)
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- Vu-Dac, N., Gervois, P., Jakel, H., Nowak, M., Baugé, E., Dehondt, H., Staels, B., Pennacchio, L. A., Rubin, E. M., Fruchart-Najib, J., & Fruchart, J.-C. (2003). Apolipoprotein A5, a Crucial Determinant of Plasma Triglyceride Levels, Is Highly Responsive to Peroxisome Proliferator-activated Receptor α Activators. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m212191200
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