Editing Peroxisome proliferator-activated receptor (section)

== History ==
These agents, [[pharmacology|pharmacologically]] related to the [[fibrate]]s, were discovered in the early 1980s.

PPARs were originally identified in ''[[Xenopus]]'' frogs as receptors that induce the proliferation of [[peroxisome]]s in cells in 1992.<ref name="pmid1312391">{{cite journal | vauthors = Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, Wahli W | title = Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors | journal = Cell | volume = 68 | issue = 5 | pages = 879–87 | year = 1992 | pmid = 1312391 | doi = 10.1016/0092-8674(92)90031-7 | s2cid = 3148132 }}</ref> The first PPAR (PPARα) was discovered in 1990 during the search for a molecular target of a group of agents then referred to as ''peroxisome proliferators'', as they increased peroxisomal numbers in rodent liver tissue, apart from improving [[insulin resistance|insulin sensitivity]].<ref name="pmid2129546">{{cite journal | vauthors = Issemann I, Green S | title = Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators | journal = Nature | volume = 347 | issue = 6294 | pages = 645–50 | year = 1990 | pmid = 2129546 | doi = 10.1038/347645a0 | bibcode = 1990Natur.347..645I | s2cid = 4306126 }}</ref>  

When it turned out that PPARs played a versatile role in biology, the agents were in turn termed ''PPAR ligands''. The best-known PPAR ligands are the [[thiazolidinedione]]s.

After PPARδ (delta) was identified in humans in 1992,<ref name="pmid1333051">{{cite journal | vauthors = Schmidt A, Endo N, Rutledge SJ, Vogel R, Shinar D, Rodan GA | title = Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids | journal = Mol. Endocrinol. | volume = 6 | issue = 10 | pages = 1634–41 | year = 1992 | doi = 10.1210/mend.6.10.1333051 | pmid = 1333051 | s2cid = 23506853 | doi-access = free }}</ref> it turned out to be closely related to PPARβ (beta), previously described during the same year in an [[amphibian]], ''[[Xenopus]]''. The term "PPARδ" is generally used in the US, while "PPARβ" has remained in Europe, where this receptor was initially discovered.

PPARs were named because they induce peroxisome proliferation in rodents, but this induction has not been verified in humans.<ref name="pmid29197930">{{cite journal | vauthors=Corton JC, Peters JM, Klaunig JE | title=The PPARα-dependent rodent liver tumor response is not relevant to humans: addressing misconceptions | journal=[[Journal of Molecular Endocrinology]] | volume=92 | issue=1 | pages=83–119 | year=2018 | doi = 10.1007/s00204-017-2094-7 | pmc=6092738 | pmid=29197930 | bibcode=2018ArTox..92...83C }}</ref><ref> {{cite book |chapter=Peroxisome Proliferator-Activated Receptors |vauthors=Sugden MC, Caton PW, Holness MJ, Miller JJ |title= Reference Module in Life Sciences|doi=10.1016/B978-0-12-819460-7.00200-0|chapter-url=https://www.sciencedirect.com/science/article/pii/B9780128194607002000|date=2021|volume=17|issue= 6|pages= 574–583 |publisher= Elsevier|isbn= 9780128096338|s2cid= 241510571}}</ref>