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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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Rubins, H. B., Robins, S. J., Collins, D., Fye, C. L., Anderson, J. W., Elam, M. B., Faas, F. H., Linares, E., Schaefer, E. J., Schectman, G., et al. (1999) · New England Journal of Medicine · doi:10.1056/nejm199908053410604 · Cited by 3,439
Braissant, O., Foufelle, F., Scotto, C., Dauça, M., & Wahli, W. (1996) · Endocrinology · doi:10.1210/endo.137.1.8536636 · Cited by 2,217
Forman, B. M., Chen, J., & Evans, R. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4312 · Cited by 2,116
The PPARs: From Orphan Receptors to Drug Discovery
Willson, T. M., Brown, P. J., Sternbach, D. D., & Henke, B. R. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm990554g · Cited by 1,816
Self-citationMechanism of Action of Fibrates on Lipid and Lipoprotein Metabolism
Staels, B., Dallongeville, J., Auwerx, J., Schoonjans, K., Leitersdorf, E., & Fruchart, J.-C. (1998) · Circulation · doi:10.1161/01.cir.98.19.2088 · Cited by 1,786
Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency
Brooks-Wilson, A., Marcil, M., Clee, S. M., Zhang, L.-H., Roomp, K., van Dam, M., Yu, L., Brewer, C., Collins, J. A., Molhuizen, H. O. F., et al. (1999) · Nature Genetics · doi:10.1038/11905 · Cited by 1,687
Chinetti, G., Lestavel, S., Bocher, V., Remaley, A. T., Neve, B., Torra, I. P., Teissier, E., Minnich, A., Jaye, M., Duverger, N., et al. (2001) · Nature Medicine · doi:10.1038/83348 · Cited by 1,170
Molecular recognition of fatty acids by peroxisome proliferator-activated receptors
Xu, H. E., Lambert, M. H., Montana, V. G., Parks, D. J., Blanchard, S. G., Brown, P. J., Sternbach, D. D., Lehmann, J. M., Wisely, G. B., Willson, T. M., et al. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80467-0 · Cited by 1,169
Self-citationHypertriglyceridemia, atherogenic dyslipidemia, and the metabolic syndrome
Grundy, S. M. (1998) · The American Journal of Cardiology · doi:10.1016/s0002-9149(98)00033-2 · Cited by 525
Staels, B., Vu-Dac, N., Kosykh, V. A., Saladin, R., Fruchart, J. C., Dallongeville, J., & Auwerx, J. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117717 · Cited by 410
Cited by
(1998) · PubMed · Cited by 2,737
The mechanisms of action of PPARs
Berger, J., & Moller, D. E. (2002) · Annual Review of Medicine · doi:10.1146/annurev.med.53.082901.104018 · Cited by 2,659
Lipids and Lipid-Based Formulations: Optimizing the Oral Delivery of Lipophilic Drugs
Porter, C. J. H., Trevaskis, N. L., & Charman, W. N. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2197 · Cited by 1,824
Peroxisome-Proliferator-Activated Receptor δ Activates Fat Metabolism to Prevent Obesity
Wang, Y.-X., Lee, C.-H., Tiep, S., Yu, R. T., Ham, J., Kang, H., & Evans, R. M. (2003) · Cell · doi:10.1016/s0092-8674(03)00269-1 · Cited by 1,296
Varga, T., Czimmerer, Z., & Nagy, L. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.02.014 · Cited by 933
Jin, Q., Yu, L., Wang, L., Zhang, Z., Kasper, L. H., Lee, J., Wang, C., Brindle, P. K., Dent, S. Y. R., & Ge, K. (2011) · The EMBO Journal · doi:10.1038/emboj.2010.318 · Cited by 877
Tanaka, T., Yamamoto, J., Iwasaki, S., Asaba, H., Hamura, H., Ikeda, Y., Watanabe, M., Magoori, K., Ioka, R. X., Tachibana, K., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0306981100 · Cited by 832
PPARs in Obesity-Induced T2DM, Dyslipidaemia and NAFLD
Gross, B., Pawlak, M., Lefebvre, P., & Staels, B. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.135 · Cited by 778
The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21
Kharitonenkov, A., Wroblewski, V. J., Koester, A., Chen, Y.-F., Clutinger, C. K., Tigno, X. T., Hansen, B. C., Shanafelt, A. B., & Etgen, G. J. (2007) · Endocrinology · doi:10.1210/en.2006-1168 · Cited by 738
Self-citationThe macrophage foam cell as a target for therapeutic intervention
Li, A. C., & Glass, C. K. (2002) · Nature Medicine · doi:10.1038/nm1102-1235 · Cited by 700
Kang, K., Reilly, S. M., Karabacak, V., Gangl, M. R., Fitzgerald, K., Hatano, B., & Lee, C.-H. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.04.002 · Cited by 699
Therapeutic roles of peroxisome proliferator-activated receptor agonists
Staels, B., & Fruchart, J.-C. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2460 · Cited by 646
PPAR : a dagger in the heart of the metabolic syndrome
Barish, G. D. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27955 · Cited by 641
Barak, Y., Liao, D., He, W., Ong, E. S., Nelson, M. C., Olefsky, J. M., Boland, R., & Evans, R. M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012610299 · Cited by 586
Subchronic Toxicity Studies on Perfluorooctanesulfonate Potassium Salt in Cynomolgus Monkeys
Seacat, A. M. (2002) · Toxicological Sciences · doi:10.1093/toxsci/68.1.249 · Cited by 564
Peroxisome proliferator‐activated receptor δ controls muscle development and oxydative capability
Luquet, S., Lopez‐Soriano, J., Holst, D., Fredenrich, A., Melki, J., Rassoulzadegan, M., & Grimaldi, P. A. (2003) · The FASEB Journal · doi:10.1096/fj.03-0269fje · Cited by 509
Marx, N., Duez, H., Fruchart, J.-C., & Staels, B. (2004) · Circulation Research · doi:10.1161/01.res.0000127122.22685.0a · Cited by 501
High-Density Lipoprotein as a Therapeutic Target: A Systematic Review
Singh, I. M., Shishehbor, M. H., & Ansell, B. J. (2007) · JAMA · doi:10.1001/jama.298.7.786 · Cited by 468
Critical roles of PPARβ/δ in keratinocyte response to inflammation
Tan, N. S., Michalik, L., Noy, N., Yasmin, R., Pacot, C., Heim, M., Flühmann, B., Desvergne, B., & Wahli, W. (2001) · Genes & Development · doi:10.1101/gad.207501 · Cited by 398
PPARs: diverse regulators in energy metabolism and metabolic diseases
Wang, Y.-X. (2010) · Cell Research · doi:10.1038/cr.2010.13 · Cited by 366
PPAR- and LXR-dependent pathways controlling lipid metabolism and the development of atherosclerosis
Li, A. C., & Glass, C. K. (2004) · Journal of Lipid Research · doi:10.1194/jlr.r400010-jlr200 · Cited by 357
Niemann-Pick C1-Like 1 (NPC1L1) Protein in Intestinal and Hepatic Cholesterol Transport
Jia, L., Betters, J. L., & Yu, L. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-012110-142233 · Cited by 356
Berry, D. C., & Noy, N. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01742-08 · Cited by 345
PPARδ is a very low-density lipoprotein sensor in macrophages
Chawla, A., Lee, C.-H., Barak, Y., He, W., Rosenfeld, J., Liao, D., Han, J., Kang, H., & Evans, R. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0337331100 · Cited by 305
Targeting inflammation in metabolic syndrome
Welty, F. K., Alfaddagh, A., & Elajami, T. K. (2016) · Translational Research · doi:10.1016/j.trsl.2015.06.017 · Cited by 287
Qiu, Y.-Y., Zhang, J., Zeng, F.-Y., & Zhu, Y. Z. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106786 · Cited by 271
The Peroxisome Proliferator-activated Receptor δ Promotes Lipid Accumulation in Human Macrophages
Vosper, H., Patel, L., Graham, T. L., Khoudoli, G. A., Hill, A., Macphee, C. H., Pinto, I., Smith, S. A., Suckling, K. E., Wolf, C. R., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m108482200 · Cited by 268
Nuclear receptors in macrophage biology: at the crossroads of lipid metabolism and inflammation
Castrillo, A., & Tontonoz, P. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.20.012103.134432 · Cited by 260
Coordination of inflammation and metabolism by PPAR and LXR nuclear receptors
Hong, C., & Tontonoz, P. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.07.016 · Cited by 253
Lao, O., de Gruijter, J. M., van Duijn, K., Navarro, A., & Kayser, M. (2007) · Annals of Human Genetics · doi:10.1111/j.1469-1809.2006.00341.x · Cited by 231
Edwards (2002) · doi:10.1016/s1537-1891(02)00175-1 · Cited by 233
PPARs as Nuclear Receptors for Nutrient and Energy Metabolism
Hong, F., Pan, S., Guo, Y., Xu, P., & Zhai, Y. (2019) · Molecules · doi:10.3390/molecules24142545 · Cited by 233
Target Genes of Peroxisome Proliferator-activated Receptor γ in Colorectal Cancer Cells
Gupta, R. A., Brockman, J. A., Sarraf, P., Willson, T. M., & DuBois, R. N. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103779200 · Cited by 215
Self-citationRegulation of Cholesterol Homeostasis by the Liver X Receptors in the Central Nervous System
Whitney, K. D., Watson, M. A., Collins, J. L., Benson, W. G., Stone, T. M., Numerick, M. J., Tippin, T. K., Wilson, J. G., Winegar, D. A., & Kliewer, S. A. (2002) · Molecular Endocrinology · doi:10.1210/mend.16.6.0835 · Cited by 211
Self-citationLuquet, S., Gaudel, C., Holst, D., Lopez-Soriano, J., Jehl-Pietri, C., Fredenrich, A., & Grimaldi, P. A. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.11.011 · Cited by 210
Obesity I: Overview and molecular and biochemical mechanisms
Lustig, R. H., Collier, D., Kassotis, C., Roepke, T. A., Kim, M. J., Blanc, E., Barouki, R., Bansal, A., Cave, M. C., Chatterjee, S., et al. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115012 · Cited by 203
Krämer, D. K., Al-Khalili, L., Guigas, B., Leng, Y., Garcia-Roves, P. M., & Krook, A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702329200 · Cited by 180
Obesity, Peroxisome Proliferator-Activated Receptor, and Atherosclerosis in Type 2 Diabetes
Blaschke, F., Takata, Y., Caglayan, E., Law, R. E., & Hsueh, W. A. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000191663.12164.77 · Cited by 176
PPARδ as a therapeutic target in metabolic disease
Reilly, S. M., & Lee, C.-H. (2008) · FEBS Letters · doi:10.1016/j.febslet.2007.11.040 · Cited by 164
Physiological functions of peroxisome proliferator-activated receptor β
Neels, J. G., & Grimaldi, P. A. (2014) · Physiological Reviews · doi:10.1152/physrev.00027.2013 · Cited by 161
Protection from liver fibrosis by a peroxisome proliferator-activated receptor δ agonist
Iwaisako, K., Haimerl, M., Paik, Y.-H., Taura, K., Kodama, Y., Sirlin, C., Yu, E., Yu, R. T., Downes, M., Evans, R. M., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1202464109 · Cited by 157
Liver X Receptor (LXR) Regulation of the LXRα Gene in Human Macrophages
Whitney, K. D., Watson, M. A., Goodwin, B., Galardi, C. M., Maglich, J. M., Wilson, J. G., Willson, T. M., Collins, J. L., & Kliewer, S. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106155200 · Cited by 154
Self-citationThe Role of Mitochondria in the Pathophysiology of Skeletal Muscle Insulin Resistance
Pagel-Langenickel, I., Bao, J., Pang, L., & Sack, M. N. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0003 · Cited by 154
Krämer, D. K., Al-Khalili, L., Perrini, S., Skogsberg, J., Wretenberg, P., Kannisto, K., Wallberg-Henriksson, H., Ehrenborg, E., Zierath, J. R., & Krook, A. (2005) · Diabetes · doi:10.2337/diabetes.54.4.1157 · Cited by 132
Nuclear receptors as therapeutic targets for Alzheimer's disease
Mandrekar-Colucci, S., & Landreth, G. E. (2011) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.594043 · Cited by 126
15-Deoxy-Δ12,14-prostaglandin J2-induced apoptosis does not require PPARγ in breast cancer cells
Clay, C. E., Monjazeb, A., Thorburn, J., Chilton, F. H., & High, K. P. (2002) · Journal of Lipid Research · doi:10.1194/jlr.m200224-jlr200 · Cited by 103
Raza-Iqbal, S., Tanaka, T., Anai, M., Inagaki, T., Matsumura, Y., Ikeda, K., Taguchi, A., Gonzalez, F. J., Sakai, J., & Kodama, T. (2015) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.28720 · Cited by 100
Akiyama, T. E., Lambert, G., Nicol, C. J., Matsusue, K., Peters, J. M., Brewer, H. B., & Gonzalez, F. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312802200 · Cited by 97
Lee, C.-H., Kang, K., Mehl, I. R., Nofsinger, R., Alaynick, W. A., Chong, L.-W., Rosenfeld, J. M., & Evans, R. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510815103 · Cited by 98
Shan, W., Palkar, P. S., Murray, I. A., McDevitt, E. I., Kennett, M. J., Kang, B. H., Isom, H. C., Perdew, G. H., Gonzalez, F. J., & Peters, J. M. (2008) · Toxicological Sciences · doi:10.1093/toxsci/kfn142 · Cited by 97
Coll, T., Álvarez-Guardia, D., Barroso, E., Gómez-Foix, A. M., Palomer, X., Laguna, J. C., & Vázquez-Carrera, M. (2010) · Endocrinology · doi:10.1210/en.2009-1211 · Cited by 90
Malm, T., Mariani, M., Donovan, L. J., Neilson, L., & Landreth, G. E. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0229-9 · Cited by 77
Remembering your A, B, C's: Alzheimer's disease and ABCA1
Lewandowski, C. T., Laham, M. S., & Thatcher, G. R. J. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.01.011 · Cited by 76
Hellemans, K., Rombouts, K., Quartier, E., Dittié, A. S., Knorr, A., Michalik, L., Rogiers, V., Schuit, F., Wahli, W., & Geerts, A. (2003) · Journal of Lipid Research · doi:10.1194/jlr.m200376-jlr200 · Cited by 64
Biology and Therapeutic Applications of Peroxisome Proliferator- Activated Receptors
P. Menendez-Gutierrez, M., Roszer, T., & Ricote, M. (2012) · Current Topics in Medicinal Chemistry · doi:10.2174/156802612799436669 · Cited by 62
Bouhlel, M. A., Staels, B., & Chinetti‐Gbaguidi, G. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01892.x · Cited by 51
Nuclear Receptors in Nonalcoholic Fatty Liver Disease
López-Velázquez, J. A., Carrillo-Córdova, L. D., Chávez-Tapia, N. C., Uribe, M., & Méndez-Sánchez, N. (2012) · Journal of Lipids · doi:10.1155/2012/139875 · Cited by 48
Dimopoulos, N., Watson, M., Green, C., & Hundal, H. S. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.08.072 · Cited by 36
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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