The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
A selective peroxisome proliferator-activated receptor δ agonist promotes reverse cholesterol transport
Open accessAbstract
The peroxisome proliferator-activated receptors (PPARs) are dietary lipid sensors that regulate fatty acid and carbohydrate metabolism. The hypolipidemic effects of the fibrate drugs and the antidiabetic effects of the glitazone drugs in humans are due to activation of the α (NR1C1) and γ (NR1C3) subtypes, respectively. By contrast, the therapeutic potential of the δ (NR1C2) subtype is unknown, due in part to the lack of selective ligands. We have used combinatorial chemistry and structure-based drug design to develop a potent and subtype-selective PPARδ agonist, GW501516. In macrophages, fibroblasts, and intestinal cells, GW501516 increases expression of the reverse cholesterol transporter ATP-binding cassette A1 and induces apolipoprotein A1-specific cholesterol efflux. When dosed to insulin-resistant middle-aged obese rhesus monkeys, GW501516 causes a dramatic dose-dependent rise in serum high density lipoprotein cholesterol while lowering the levels of small-dense low density lipoprotein, fasting triglycerides, and fasting insulin. Our results suggest that PPARδ agonists may be effective drugs to increase reverse cholesterol transport and decrease cardiovascular disease associated with the metabolic syndrome X.
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The PPARs: From Orphan Receptors to Drug Discovery
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Self-citationMechanism of Action of Fibrates on Lipid and Lipoprotein Metabolism
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Molecular recognition of fatty acids by peroxisome proliferator-activated receptors
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Lipids and Lipid-Based Formulations: Optimizing the Oral Delivery of Lipophilic Drugs
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Peroxisome-Proliferator-Activated Receptor δ Activates Fat Metabolism to Prevent Obesity
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Metadata
- Authors
- Oliver, W. R., Shenk, J. L., Snaith, M. R., Russell, C. S., Plunket, K. D., Bodkin, N. L., Lewis, M. C., Winegar, D. A., Sznaidman, M. L., Lambert, M. H., Xu, H. E., Sternbach, D. D., Kliewer, S. A., Hansen, B. C., & Willson, T. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-04-17
- Volume
- 98
- Issue
- 9
- Pages
- 5306-5311
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2146788074
- Cited by
- 1,046
- References
- 11
- FWCI
- 23.99
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Oliver, W. R., Shenk, J. L., Snaith, M. R., Russell, C. S., Plunket, K. D., Bodkin, N. L., Lewis, M. C., Winegar, D. A., Sznaidman, M. L., Lambert, M. H., Xu, H. E., Sternbach, D. D., Kliewer, S. A., Hansen, B. C., & Willson, T. M. (2001). A selective peroxisome proliferator-activated receptor δ agonist promotes reverse cholesterol transport. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.091021198
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
