Peroxisome proliferator-activated receptor gamma

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

ENSG00000132170

ENSMUSG00000000440

UniProt

P37231

P37238

RefSeq (mRNA)

NM_001127330
NM_011146
NM_001308352
NM_001308354

RefSeq (protein)

NP_001120802
NP_001295281
NP_001295283
NP_035276

Location (UCSC)Chr 3: 12.29 – 12.43 MbChr 6: 115.34 – 115.47 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Peroxisome proliferator-activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone reverse insulin resistance receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor functioning as a transcription factor that in humans is encoded by the PPARG gene.[5][6][7]

Tissue distribution

PPARG is mainly present in adipose tissue, colon and macrophages. Two isoforms of PPARG are detected in the human and in the mouse: PPAR-γ1 (found in nearly all tissues except muscle) and PPAR-γ2 (mostly found in adipose tissue and the intestine).[8][9]

Gene expression

This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte differentiation. Alternatively spliced transcript variants that encode different isoforms have been described.[10]

The activity of PPARG can be regulated via phosphorylation through the MEK/ERK pathway. This modification decreases transcriptional activity of PPARG and leads to diabetic gene modifications, and results in insulin insensitivity. For example, the phosphorylation of serine 112 will inhibit PPARG function, and enhance adipogenic potential of fibroblasts.[11]

Function

PPARG regulates fatty acid storage and glucose metabolism. The genes activated by PPARG stimulate lipid uptake and adipogenesis by fat cells. PPARG knockout mice are devoid of adipose tissue, establishing PPARG as a master regulator of adipocyte differentiation.[12]

PPARG increases insulin sensitivity by enhancing storage of fatty acids in fat cells (reducing

FGF21,[12] and by enhancing nicotinic acid adenine dinucleotide phosphate production through upregulation of the CD38 enzyme.[13]

PPARG promotes anti-inflammatory M2 macrophage activation in mice.[14]

Adiponectin induces ABCA1-mediated reverse cholesterol transport by activation of PPAR-γ and LXRα/β.[15]

Many naturally occurring agents directly bind with and activate PPAR gamma. These agents include various

ajulemic acid (AJA).[20] The activation of PPAR gamma by these and other ligands may be responsible for inhibiting the growth of cultured human breast, gastric, lung, prostate and other cancer cell lines.[21][22]

During embryogenesis, PPARG first substantially expresses in interscapular brown fat pad.[23] The depletion of PPARG will result in embryonic lethality at E10.5, due to the vascular anomalies in placenta, with no permeation of fetal blood vessels and dilation and rupture of maternal blood sinuses.[24] The expression PPARG can be detected in placenta as early as E8.5 and through the remainder of gestation, mainly located in the primary trophoblast cell in the human placenta.[23] PPARG is required for epithelial differentiation of trophoblast tissue, which is critical for proper placenta vascularization. PPARG agonists inhibit extravillous cytotrophoblast invasion. PPARG is also required for the accumulation of lipid droplets by the placenta.[11]

Interactions

Peroxisome proliferator-activated receptor gamma has been shown to

interact
with:

Research

PPAR-gamma

hyperlipidaemia and hyperglycemia.[36][37]

Many

thiazolidinediones) used in the treatment of diabetes activate PPARG as a means to lower serum glucose without increasing pancreatic insulin secretion. Activation of PPARG is more effective for skeletal muscle insulin resistance than for insulin resistance of the liver.[38]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000132170 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000440 – 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. PMID 7787419
    .
  6. PMID 8702406
    .
  7. S2CID 2240461
    .
  8. PMID 9228052
    .
  9. PMID 27777310
    .
  10. ^ "Entrez Gene: PPARG peroxisome proliferator-activated receptor gamma".
  11. ^
    PMID 16753211
    .
  12. ^
    PMID 23652116
    .
  13. PMID 23177620
    .
  14. ^
    PMID 23061409
    .
  15. S2CID 203413137
    .
  16. S2CID 10746292
    .
  17. PMID 16154383
    .
  18. S2CID 30996954
    .
  19. PMID 16213464
    .
  20. S2CID 22671555
    .
  21. PMID 17896990
    .
  22. S2CID 232300877
    .
  23. ^
    PMID 10549290
    .
  24. S2CID 54322301
    .
  25. PMID 12040021
    .
  26. S2CID 20343538
    .
  27. PMID 10882139
    .
  28. ^
    PMID 12479814
    .
  29. ^
    PMID 10944516
    .
  30. S2CID 19487189
    .
  31. PMID 10347167
    .
  32. PMID 11696534
    .
  33. PMID 14636573
    .
  34. PMID 10558993
    .
  35. S2CID 221017099
    .
  36. S2CID 18526710
    .
  37. S2CID 12296573
    .
  38. PMID 16644654
    .

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

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