Roles of PPARs in health and disease
Abstract
In developed societies, chronic diseases such as diabetes, obesity, atherosclerosis and cancer are responsible for most deaths. These ailments have complex causes involving genetic, environmental and nutritional factors. There is evidence that a group of closely related nuclear receptors, called peroxisome proliferator-activated receptors (PPARs), may be involved in these diseases. This, together with the fact that PPAR activity can be modulated by drugs such as thiazolidinediones and fibrates, has instigated a huge research effort into PPARs. Here we present the latest developments in the PPAR field, with particular emphasis on the physiological function of PPARs during various nutritional states, and the possible role of PPARs in several chronic diseases.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PPARγ and LXRs are ligand-activated transcription factors that act as fatty acid and cholesterol sensors.
“The nuclear receptors, peroxisome proliferator-activated receptor-γ (PPARγ) and Liver X receptors (LXRs) are ligand-activated transcription factors that act as fatty acid and cholesterol sensors (Forman et al., 1997; Kersten et al., 2000).”
From Mechanisms Underlying the Rapid Peroxisome Proliferator-Activated Receptor-γ-Mediated Amyloid Clearance and Reversal of Cognitive Deficits in a Murine Model of Alzheimer's Disease (2012) · cites this paper as Kersten et al., 2000
Cites
Delerive, P., De Bosscher, K., Besnard, S., Vanden Berghe, W., Peters, J. M., Gonzalez, F. J., Fruchart, J.-C., Tedgui, A., Haegeman, G., & Staels, B. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.45.32048 · Cited by 1,089 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915 · see citing works
Ecotoxicology of human pharmaceuticals
Fent, K., Weston, A. A., & Caminada, D. (2006) · Aquatic Toxicology · doi:10.1016/j.aquatox.2005.09.009 · Cited by 3,223 · see citing works
Damiola, F., Le Minh, N., Preitner, N., Kornmann, B., Fleury-Olela, F., & Schibler, U. (2000) · Genes & Development · doi:10.1101/gad.183500 · Cited by 2,394 · see citing works
Inagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.003 · Cited by 1,504 · see citing works
Yamauchi, T., Nio, Y., Maki, T., Kobayashi, M., Takazawa, T., Iwabu, M., Okada-Iwabu, M., Kawamoto, S., Kubota, N., Kubota, T., et al. (2007) · Nature Medicine · doi:10.1038/nm1557 · Cited by 1,396 · see citing works
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 · see citing works
Adiponectin and AdipoR1 Regulate PGC-1α and Mitochondria by Ca2+ and AMPK/SIRT1
Iwabu, M., Yamauchi, T., Okada-Iwabu, M., Sato, K., Nakagawa, T., Funata, M., Yamaguchi, M., Namiki, S., Nakayama, R., Tabata, M., et al. (2010) · Nature · doi:10.1038/nature08991 · Cited by 971 · see citing works
Coregulator Function: A Key to Understanding Tissue Specificity of Selective Receptor Modulators
Smith, C. L., & O’Malley, B. W. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0023 · Cited by 931 · see citing works
Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis
Yamauchi, T., Kamon, J., Waki, H., Imai, Y., Shimozawa, N., Hioki, K., Uchida, S., Ito, Y., Takakuwa, K., Matsui, J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209033200 · Cited by 911 · see citing works
A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity
Okada-Iwabu, M., Yamauchi, T., Iwabu, M., Honma, T., Hamagami, K.-I., Matsuda, K., Yamaguchi, M., Tanabe, H., Kimura-Someya, T., Shirouzu, M., et al. (2013) · Nature · doi:10.1038/nature12656 · Cited by 757 · see citing works
Mechanisms of nutritional and hormonal regulation of lipogenesis
Kersten, S. (2001) · The EMBO Reports · doi:10.1093/embo-reports/kve071 · Cited by 700 · see citing works
Self-citationAlternative macrophage activation and metabolism
Odegaard, J. I., & Chawla, A. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130138 · Cited by 640 · see citing works
Targeting fibrosis: mechanisms and clinical trials
Zhao, M., Wang, L., Wang, M., Zhou, S., Lu, Y., Cui, H., Racanelli, A. C., Zhang, L., Ye, T., Ding, B., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01070-3 · Cited by 547 · see citing works
Tan, N.-S., Shaw, N. S., Vinckenbosch, N., Liu, P., Yasmin, R., Desvergne, B., Wahli, W., & Noy, N. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.14.5114-5127.2002 · Cited by 499 · see citing works
Self-citationMarra, F., Efsen, E., Romanelli, R. G., Caligiuri, A., Pastacaldi, S., Batignani, G., Bonacchi, A., Caporale, R., Laffi, G., Pinzani, M., et al. (2000) · Gastroenterology · doi:10.1053/gast.2000.9365 · Cited by 409 · see citing works
Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration
Feher, J., Kovacs, I., Artico, M., Cavallotti, C., Papale, A., & Balacco Gabrieli, C. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.05.012 · Cited by 388 · see citing works
Buzzai, M., Bauer, D. E., Jones, R. G., DeBerardinis, R. J., Hatzivassiliou, G., Elstrom, R. L., & Thompson, C. B. (2005) · Oncogene · doi:10.1038/sj.onc.1208622 · Cited by 357 · see citing works
Mandrekar-Colucci, S., Karlo, J. C., & Landreth, G. E. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5268-11.2012 · Cited by 355 · see citing works
“The nuclear receptors, peroxisome proliferator-activated receptor- (PPAR ) and Liver X receptors (LXRs) are ligandactivated transcription factors that act as fatty acid and cholesterol sensors (Forman et al., 1997; Kersten et al., 2000).”
BackgroundYoon, M. (2009) · Pharmacological Research · doi:10.1016/j.phrs.2009.02.004 · Cited by 336 · see citing works
Lipid accumulation induced by APOE4 impairs microglial surveillance of neuronal-network activity
Victor, M. B., Leary, N., Luna, X., Meharena, H. S., Scannail, A. N., Bozzelli, P. L., Samaan, G., Murdock, M. H., von Maydell, D., Effenberger, A. H., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.07.005 · Cited by 316 · see citing works
Regulation of Ketone Body Metabolism and the Role of PPARα
Grabacka, M., Pierzchalska, M., Dean, M., & Reiss, K. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17122093 · Cited by 305 · see citing works
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 · see citing works
The ROR nuclear orphan receptor subfamily: Critical regulators of multiple biological processes
Jetten, A. M., Kurebayashi, S., & Ueda, E. (2001) · Progress in Nucleic Acid Research and Molecular Biology · doi:10.1016/s0079-6603(01)69048-2 · Cited by 232 · see citing works
Burstein, H. J., Demetri, G. D., Mueller, E., Sarraf, P., Spiegelman, B. M., & Winer, E. P. (2003) · Breast Cancer Research and Treatment · doi:10.1023/a:1024038127156 · Cited by 228 · see citing works
Hardy, T., Zeybel, M., Day, C. P., Dipper, C., Masson, S., McPherson, S., Henderson, E., Tiniakos, D., White, S., French, J., et al. (2017) · Gut · doi:10.1136/gutjnl-2016-311526 · Cited by 216 · see citing works
Prieur, X., Coste, H., & Rodríguez, J. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301302200 · Cited by 194 · see citing works
Khandoudi, N., Delerive, P., Berrebi-Bertrand, I., Buckingham, R. E., Staels, B., & Bril, A. (2002) · Diabetes · doi:10.2337/diabetes.51.5.1507 · Cited by 174 · see citing works
Goya, K., Sumitani, S., Xu, X., Kitamura, T., Yamamoto, H., Kurebayashi, S., Saito, H., Kouhara, H., Kasayama, S., & Kawase, I. (2004) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000118682.58708.78 · Cited by 174 · see citing works
Sidell, R. J., Cole, M. A., Draper, N. J., Desrois, M., Buckingham, R. E., & Clarke, K. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1110 · Cited by 165 · see citing works
PEX11β Deficiency Is Lethal and Impairs Neuronal Migration but Does Not Abrogate Peroxisome Function
Li, X., Baumgart, E., Morrell, J. C., Jimenez-Sanchez, G., Valle, D., & Gould, S. J. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.12.4358-4365.2002 · Cited by 165 · see citing works
Scuderi, C., Steardo, L., & Esposito, G. (2014) · Phytotherapy Research · doi:10.1002/ptr.5095 · Cited by 161 · see citing works
Angiopoietin-Related/Angiopoietin-Like Proteins Regulate Angiogenesis
Oike, Y., Yasunaga, K., & Suda, T. (2004) · International Journal of Hematology · doi:10.1532/ijh97.04034 · Cited by 160 · see citing works
Arlt, W., Auchus, R. J., & Miller, W. L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100040200 · Cited by 157 · see citing works
Aasum, E., Belke, D. D., Severson, D. L., Riemersma, R. A., Cooper, M., Andreassen, M., & Larsen, T. S. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00226.2001 · Cited by 154 · see citing works
Dobrosi, N., Tóth, B. I., Nagy, G., Dózsa, A., Géczy, T., Nagy, L., Zouboulis, C. C., Paus, R., Kovács, L., & Bíró, T. (2008) · The FASEB Journal · doi:10.1096/fj.07-104877 · Cited by 142 · see citing works
Signalling mechanisms linking hepatic glucose and lipid metabolism
Weickert, M. O., & Pfeiffer, A. F. H. (2006) · Diabetologia · doi:10.1007/s00125-006-0295-3 · Cited by 127 · see citing works
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 · see citing works
Fibroblast growth factor 21: a regulator of metabolic disease and health span
Xie, T., & Leung, P. S. (2017) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00101.2017 · Cited by 121 · see citing works
Chong, H. C., Tan, M. J., Philippe, V., Tan, S. H., Tan, C. K., Ku, C. W., Goh, Y. Y., Wahli, W., Michalik, L., & Tan, N. S. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200809028 · Cited by 107 · see citing works
Self-citation15-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 · see citing works
Rodríguez-Vilarrupla, A., Laviña, B., García-Calderó, H., Russo, L., Rosado, E., Roglans, N., Bosch, J., & García-Pagán, J. C. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2011.12.008 · Cited by 90 · see citing works
Peroxisome proliferator-activated receptor-γ ligands for the treatment of breast cancer
Fenner, M. H., & Elstner, E. (2005) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.14.6.557 · Cited by 88 · see citing works
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 · see citing works
Dietary Oleic Acid Increases M2 Macrophages in the Mesenteric Adipose Tissue
Camell, C., & Smith, C. W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075147 · Cited by 76 · see citing works
Meta-analysis of primary target genes of peroxisome proliferator-activated receptors
Heinäniemi, M., Uski, J. O., Degenhardt, T., & Carlberg, C. (2007) · Genome Biology · doi:10.1186/gb-2007-8-7-r147 · Cited by 71 · see citing works
Clay, C. E., Namen, A. M., Atsumi, G.-I., Trimboli, A. J., Fonteh, A. N., High, K. P., & Chilton, F. H. (2001) · Journal of Investigative Medicine · doi:10.2310/6650.2001.33786 · Cited by 67 · see citing works
Wan Ibrahim, W. N., Tofighi, R., Onishchenko, N., Rebellato, P., Bose, R., Uhlén, P., & Ceccatelli, S. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.03.003 · Cited by 65 · see citing works
Domi, E., Uhrig, S., Soverchia, L., Spanagel, R., Hansson, A. C., Barbier, E., Heilig, M., Ciccocioppo, R., & Ubaldi, M. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.4127-15.2016 · Cited by 61 · see citing works
Non-genomic effects of nuclear receptors: insights from the anucleate platelet
Unsworth, A. J., Flora, G. D., & Gibbins, J. M. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy044 · Cited by 54 · see citing works
Nuclear receptor superfamily: Principles of signaling
Germain, P., Altucci, L., Bourguet, W., Rochette-Egly, C., & Gronemeyer, H. (2003) · Pure and Applied Chemistry · doi:10.1351/pac200375111619 · Cited by 53 · see citing works
Shen, W., Hao, J., Feng, Z., Tian, C., Chen, W., Packer, L., Shi, X., Zang, W., & Liu, J. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01134.x · Cited by 52 · see citing works
Peroxisome proliferator-activated receptor and age-related macular degeneration
Herzlich, A. A., Tuo, J., & Chan, C.-C. (2008) · PPAR Research · doi:10.1155/2008/389507 · Cited by 43 · see citing works
Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis
BIANCHI, E., SCARINCI, F., RIPANDELLI, G., FEHER, J., PACELLA, E., MAGLIULO, G., GABRIELI, C. B., PLATEROTI, R., PLATEROTI, P., MIGNINI, F., et al. (2013) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2012.1164 · Cited by 40 · see citing works
Use of Thiazolidinediones and the Risk of Colorectal Cancer in Patients With Diabetes
Chen, S.-W., Tsan, Y.-T., Chen, J.-D., Hsieh, H.-I., Lee, C.-H., Lin, H.-H., Wang, J.-D., Chen, P.-C., & Health Data Analysis in Taiwan Research Group (2013) · Diabetes Care · doi:10.2337/dc11-2197 · Cited by 37 · see citing works
Aasum, E., Cooper, M., Severson, D. L., & Larsen, T. S. (2005) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y04-139 · Cited by 37 · see citing works
Song, N., Zhang, L., Chen, W., Zhu, H., Deng, W., Han, Y., Guo, J., & Qin, C. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.05.016 · Cited by 36 · see citing works
Controversies in the Use of Omega-3 Fatty Acids to Prevent Atherosclerosis
Quispe, R., Alfaddagh, A., Kazzi, B., Zghyer, F., Marvel, F. A., Blumenthal, R. S., Sharma, G., & Martin, S. S. (2022) · Current Atherosclerosis Reports · doi:10.1007/s11883-022-01031-9 · Cited by 17 · see citing works
- Authors
- Kersten, S., Desvergne, B., & Wahli, W.
- Affiliations
- University of Lausanne (CH)
- Corresponding author
- Wahli, Walter
- Venue
- Nature
- Published
- 2000-05
- Volume
- 405
- Issue
- 6785
- Pages
- 421-424
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1647126819
- Cited by
- 1,956
- References
- 1
- Citations by year
- 2026: 25 · 2025: 34 · 2024: 34 · 2023: 44 · 2022: 55 · 2021: 55 · 2020: 54 · 2019: 63 · 2018: 74 · 2017: 55 · 2016: 75 · 2015: 72 · 2014: 74 · 2013: 91 · 2012: 90
- FWCI
- 7.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- peroxisome proliferator-activated receptors, nuclear receptors, chronic disease, diabetes mellitus, obesity, atherosclerosis, cancer, thiazolidinediones, fibrates, nutritional status, physiological function
- MeSH terms
- Animals, Arteriosclerosis, Chronic Disease, Humans, Ligands, Metabolic Diseases, Neoplasms, Nutritional Status, Transcription Factors, Receptors, Cytoplasmic and Nuclear, Gene Targeting
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
