Historical Background
The first peroxisome proliferator-activated receptor or PPAR was discovered as hormone receptor that was activated by rodent hepatocarcinogens that induced peroxisome proliferation (Issemann and Green 1990). PPARs are now known as a group of transcription factors that are able to induce transcription of genes that contain PPAR responsive elements (PPREs). The PPAR family of transcription factors consist of PPARα, β of δ (or nuclear receptor subfamily 1, group C, member 2 (NR1C2)), and γ (or nuclear receptor subfamily 1, group C, member 3 NR1C3). Here the focus is on PPARα that, in humans, is mainly expressed in tissue with high fatty acid oxidation like liver, muscle, heart, and kidney though also many other tissues do show expression of this family member. PPARα is thought to be a master regulator of lipid metabolism. It does so by...
This is a preview of subscription content, log in via an institution.
References
Agarwal S, Yadav A, Chaturvedi RK. Peroxisome proliferator-activated receptors (PPARs) as therapeutic target in neurodegenerative disorders. Biochem Biophys Res Commun. 2016. doi:10.1016/j.bbrc.2016.08.043.
Ballestri S, Nascimbeni F, Romagnoli D, Baldelli E, Lonardo A. The role of nuclear receptors in the pathophysiology, natural course, and drug treatment of NAFLD in humans. Adv Ther. 2016;33:291–319. doi:10.1007/s12325-016-0306-9.
Bilandzic A, Fitzpatrick T, Rosella L, Henry D. Risk of bias in systematic reviews of non-randomized studies of adverse cardiovascular effects of thiazolidinediones and cyclooxygenase-2 inhibitors: application of a new cochrane risk of bias tool. PLoS Med. 2016;13:e100e1987. doi:10.1371/journal.pmed.1001987.
Bragt MC, Popeijus HE. Peroxisome proliferator-activated receptors and the metabolic syndrome. Physiol Behav. 2008;94:187–97. doi:10.1016/j.physbeh.2007.11.053.
Gao Q, Jia Y, Yang G, Zhang X, Boddu PC, Petersen B, et al. PPARalpha-deficient ob/ob obese mice become more obese and manifest severe hepatic steatosis due to decreased fatty acid oxidation. Am J Pathol. 2015;185:1396–408. doi:10.1016/j.ajpath.2015.01.018.
Huang D, Zhao Q, Liu H, Guo Y, Xu H. PPAR-alpha agonist WY-14643 inhibits LPS-induced inflammation in synovial fibroblasts via NF-kB pathway. J Mol Neurosci. 2016;59:544–53. doi:10.1007/s12031-016-0775-y.
Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 1990;347:645–50. doi:10.1038/347645a0.
Janssen AW, Betzel B, Stoopen G, Berends FJ, Janssen IM, Peijnenburg AA, et al. The impact of PPARalpha activation on whole genome gene expression in human precision cut liver slices. BMC Genomics. 2015;16:760. doi:10.1186/s12864-015-1969-3.
Krey G, Braissant O, L’Horset F, Kalkhoven E, Perroud M, Parker MG, et al. Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Mol Endocrinol. 1997;11:779–91. doi:10.1210/mend.11.6.0007.
Mansour M. The roles of peroxisome proliferator-activated receptors in the metabolic syndrome. Prog Mol Biol Transl Sci. 2014;121:217–66. doi:10.1016/B978-0-12-800101-1.00007-7.
Mochizuki K, Suruga K, Fukami H, Kiso Y, Takase S, Goda T. Selectivity of fatty acid ligands for PPARalpha which correlates both with binding to cis-element and DNA binding-independent transactivity in Caco-2 cells. Life Sci. 2006;80:140–5. doi:10.1016/j.lfs.2006.08.029.
Pawlak M, Lefebvre P, Staels B. Molecular mechanism of PPARalpha action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. J Hepatol. 2015;62:720–33. doi:10.1016/j.jhep.2014.10.039.
Popeijus HE, Saris WH, Mensink RP. Role of stearoyl-CoA desaturases in obesity and the metabolic syndrome. Int J Obes. 2008;32:1076–82. doi:10.1038/ijo.2008.55.
Popeijus HE, van Otterdijk SD, van der Krieken SE, Konings M, Serbonij K, Plat J, et al. Fatty acid chain length and saturation influences PPARalpha transcriptional activation and repression in HepG2 cells. Mol Nutr Food Res. 2014;58:2342–9. doi:10.1002/mnfr.201400314.
Shipman KE, Strange RC, Ramachandran S. Use of fibrates in the metabolic syndrome: a review. World J Diabetes. 2016;7:74–88. doi:10.4239/wjd.v7.i5.74.
Thomas M, Bayha C, Klein K, Muller S, Weiss TS, Schwab M, et al. The truncated splice variant of peroxisome proliferator-activated receptor alpha, PPARalpha-tr, autonomously regulates proliferative and pro-inflammatory genes. BMC Cancer. 2015;15:488. doi:10.1186/s12885-015-1500-x.
Yan F, Wang Q, Xu C, Cao M, Zhou X, Wang T, et al. Peroxisome proliferator-activated receptor alpha activation induces hepatic steatosis, suggesting an adverse effect. PLoS One. 2014;9:e99245. doi:10.1371/journal.pone.0099245.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media LLC
About this entry
Cite this entry
Popeijus, H.E. (2016). Peroxisome Proliferator-Activated Receptor Alpha (PPAR-Alpha). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101552-1
Download citation
DOI: https://doi.org/10.1007/978-1-4614-6438-9_101552-1
Received:
Accepted:
Published:
Publisher Name: Springer, New York, NY
Online ISBN: 978-1-4614-6438-9
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences