Peroxisome proliferator-activated receptor delta

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Lua error in Module:Infobox_gene at line 33: attempt to index field 'wikibase' (a nil value). Peroxisome proliferator-activated receptor beta or delta (PPAR-β or PPAR-δ), also known as NR1C2 (nuclear receptor subfamily 1, group C, member 2) is a nuclear receptor that in humans is encoded by the PPARD gene.[1]

This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. It was first identified in Xenopus in 1993.[2]

Function

PPARδ is a nuclear hormone receptor that governs a variety of biological processes and may be involved in the development of several chronic diseases, including diabetes, obesity, atherosclerosis, and cancer.[3][4]

PPARδ may function as an integrator of transcription repression and nuclear receptor signaling. It activates transcription of a variety of target genes by binding to specific DNA elements. Well described target genes of PPARδ include PDK4, ANGPTL4, PLIN2, and CD36. The expression of this gene is found to be elevated in colorectal cancer cells.[5] The elevated expression can be repressed by adenomatosis polyposis coli (APC), a tumor suppressor protein involved in the APC/beta-catenin signaling pathway. Knockout studies in mice suggested the role of this protein in myelination of the corpus callosum, epidermal cell proliferation, and glucose[6] and lipid metabolism.[7]

This protein has been shown to be involved in differentiation, lipid accumulation,[8] directional sensing, polarization, and migration in keratinocytes.[9]

Role in cancer

Studies into the role of PPARδ in cancer have produced contradictory results and there is no scientific consensus on whether it promotes or prevents cancer formation.[10][11]

Pharmacology

Several high affinity ligands for PPARδ have been developed, including GW501516 and GW0742, which play an important role in research. In one study utilizing such a ligand, it has been shown that agonism of PPARδ changes the body's fuel preference from glucose to lipids.[12]

Tissue distribution

PPARδ is highly expressed in many tissues, including colon, small intestine, liver and keratinocytes, as well as in heart, spleen, skeletal muscle, lung, brain and thymus.[13]

Knockout studies

Knockout mice lacking the ligand binding domain of PPARδ are viable. However these mice are smaller than the wild type both neo and postnatally. In addition, fat stores in the gonads of the mutants are smaller. The mutants also display increased epidermal hyperplasia upon induction with TPA.[14]

Ligands

PPARδ is activated in the cell by various fatty acids and fatty acid derivatives.[3] Examples of naturally occurring fatty acids that bind with and activate PPAR delta include arachidonic acid and certain members of the 15-Hydroxyicosatetraenoic acid family of arachidonic acid metabolites including 15(S)-HETE, 15(R)-HETE, and 15-HpETE.[15] Several synthetic ligands have been identified that selectively bind PPARδ.

Agonists

Interactions

Peroxisome proliferator-activated receptor delta has been shown to interact with HDAC3[17][18] and NCOR2.[18]

References

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  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Mol. Pharmacol. 77:171-184, 2010
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Further reading

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External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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