Peroxisome proliferator-activated receptor delta

Source: Wikipedia, the free encyclopedia.
PPARD
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000112033

ENSMUSG00000002250

UniProt

Q03181

P35396

RefSeq (mRNA)

NM_001171818
NM_001171819
NM_001171820
NM_006238
NM_177435

NM_011145

RefSeq (protein)

NP_001165289
NP_001165290
NP_001165291
NP_006229
NP_803184

NP_035275

Location (UCSC)Chr 6: 35.34 – 35.43 MbChr 17: 28.23 – 28.3 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Peroxisome proliferator-activated receptor delta (PPAR-delta), or (PPAR-beta), also known as Nuclear hormone receptor 1 (NUC1) is a nuclear receptor that in humans is encoded by the PPARD gene.[5]

This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. It was first identified in Xenopus in 1993.[6]

Function

PPAR-delta 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.[7][8]

In muscle PPARD

type I fibers.[9] Both PPAR-delta and AMPK agonists are regarded as exercise mimetics.[10] In adipose tissue PPAR-β/δ increases both oxidation as well as uncoupling of oxidative phosphorylation.[9]

PPAR-delta may function as an integrator of

epidermal cell proliferation, and glucose[12] and lipid metabolism.[13]

This protein has been shown to be involved in differentiation, lipid accumulation,[14] directional sensing, polarization, and migration in keratinocytes.[15]

Role in cancer

Studies into the role of PPAR-delta in cancer have produced contradictory results. Although there is some controversy, the majority of studies have suggested that PPAR-delta activation could result in changes that are favorable to cancer progression.[16] PPAR-delta favours tumour angiogenesis.[17]

Tissue distribution

PPAR-delta is highly expressed in many tissues, including

keratinocytes, as well as in heart, spleen, skeletal muscle, lung, brain and thymus.[18]

Knockout studies

postnatally. In addition, fat stores in the gonads of the mutants are smaller. The mutants also display increased epidermal hyperplasia upon induction with TPA.[19]

Ligands

PPAR-delta is activated in the cell by various fatty acids and fatty acid derivatives.

15-hydroxyicosatetraenoic acid family of arachidonic acid metabolites including 15(S)-HETE, 15(R)-HETE, and 15-HpETE.[20] Several high affinity ligands for PPAR-delta 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.[21] Initially, PPAR-delta agonists were considered promising therapies as an exercise mimetic that could treat metabolic syndrome, but later on more evidence was uncovered about their possible pro-cancer effects.[16]

Agonists

Although its drug development was discontinued due to animal studies suggesting an increased risk of cancer, GW501516 has been used as a

performance enhancing drug.[24] It and other PPAR-delta agonists are banned in sports.[25][26]

Interactions

Peroxisome proliferator-activated receptor delta has been shown to

interact with HDAC3[27][28] and NCOR2.[28]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000112033 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000002250 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. S2CID 23506853
    .
  6. S2CID 25098754
    .
  7. ^
    PMID 11818483
    .
  8. PMID 16476485
    .
  9. ^
    PMID 25945080
    .
  10. PMID 18674809
    .
  11. PMID 16969348
    .
  12. PMID 16492734
    .
  13. ^ "Entrez Gene: PPARD peroxisome proliferator-activated receptor delta".
  14. PMID 15102088
    .
  15. PMID 17682064
    .
  16. ^
    PMID 32375405
    .
  17. PMID 31842402
    .
  18. PMID 18442472
    .
  19. PMID 10866668
    .
  20. ^ Mol. Pharmacol. 77:171-184, 2010
  21. PMID 16960684
    .
  22. S2CID 261023817
    .
  23. PMID 37386786
    .
  24. ^ Koh B (22 March 2013). "Anti-doping agency warns cheats on the health risks of Endurobol". The Conversation. Retrieved 5 September 2023.
  25. S2CID 231899376
    .
  26. PMID 22977012
    .
  27. S2CID 19487189
    .
  28. ^
    PMID 11867749
    .

Further reading

External links

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

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