peroxisome proliferator-activated receptor gamma; PPAR-gamma; nuclear receptor subfamily 1 group C member 3 (PPARG, NR1C3)
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Function
- activated by fatty acids & peroxisome proliferators
- binds to DNA as heterodimer with RXRA
- regulates transcription of acyl-CoA oxidase thus peroxisomal beta-oxidation pathway of fatty acids
- regulates transcription of insulin-responsive genes
- dUTPase prevents PPAR-RXR heterodimerization[4]
- interacts with FAM120B (putative)
- interacts with NOCA7 (ligand-inducible)
- interacts with NCOA1 LXXLL motifs
- interacts with TGFB1I1
- interacts with DNTTIP2
Physiologic roles:[4]
- adipocyte differentiation
- down-regulation of inflammation
- increases fat storage in liver
- decreases volume of brown fat & white fat
- increases efficiency of energy metabolism
- improves insulin sensitivity
- suppresses weight gain induced by high-fat diet
- physiologic effects of PPAR-gamma2 may depend upon afferent vagal stimulation from liver to CNS[5]
Endogenous ligands (activators)
- monounsaturated fatty acids
- palmitoleic acid [16:1] (2+)
- oleic acid [18:1] (3+)
- elaidic acid [20:1] (+)
- polyunsaturated fatty acids
- linoleic acid [18:2, n-6] (+)
- alpha-linolenic acid [18:3, n-3] (2+)
- gamma-linolenic acid [18:3, n-6] (2+)
- dihomo-gamma-linolenic acid [20:3, n-6] (3+)
- arachidonic acid [20:4, n-6] (3+)
- eicosapentaenoic acid [22:5, n-3] (3+)
- docosahexaenoic acid [22:6, n-3] (+/-)
- eicosanoids
* HODE = hydroxyoctadecadienoic acid
- p300/CBP
- PPAR-binding protein
- PGC-1*
- PGC-2*
- Ara70*
- steroid coactivator-1 (SRC-1)
- NCOA6 > PPARBP [4]
* uncertain as to identity of these proteins
Corepressors:
Structure
- belongs to the nuclear hormone receptor family, NR1 subfamily
- contains 1 nuclear receptor DNA-binding domain
Compartment
Alternative splicing
-named isoforms=2
Expression
- adipose tissue (4+) > skeletal muscle, spleen (3+), heart & liver > placenta, lung & ovary
- intestine (2+), kidney (+/-)
Pathology
- defects in PPARG may be associated with
- severe insulin resistance & marked hypertension
- susceptibility to obesity
- colon cancer
- familial partial lipodystrophy
Polymorphism
- variation in PPARG
- is associated with carotid intimal medial thickness 1
- may influence body mass index
- may influence abdominal body fat distribution
Pharmacology
- target of thiazolidinediones (glitazones) which are agonists
Exogenous agonists: (peroxisome proliferators)[1]
- hypolipidemic drugs
- WY-14-643 (2+)
- clofibrate (1+)
- ciprofibrate (1+)
- gemfibrozil (1+)
- GW2331 (2+)
- non-steroidal anti-inflammatory drugs (NSAIDs)
- indomethacin (3+)
- ibuprofen (1+)
- fenoprofen (1+)
- GW0072 (1+)
- L-764406 (3+)
- L-165041 (1+)
- thiazolidinediones
- BRL-49653 (3+)
- pioglitazone (2+)
- ciglitazone (2+)
- englitazone (1+)
- KRP-297 (2+)
- MCC-555 (2+)
- other
- monoethylhexyl phthalate (3+)
- trichloroacetic acid (1+)
- eicosatetraynoic acid (ETYA) (3+)
- LTB4 antagonists
- MK-571 (2+)
- LY-171883 (2+)
More general terms
Additional terms
References
- ↑ 1.0 1.1 UniProt http://www.uniprot.org/uniprot/P37231.html
- ↑ Journal Watch 20(3):25-26, 2000
- ↑ Barroso et al Nature 402:880, 1999
- ↑ 4.0 4.1 4.2 4.3 Corton JC et al, Central role of peroxisome proliferator-activated receptors in the actions of peroxisome proliferators Ann Rev Pharmacol Toxicol 2000; 40:491 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10836145
- ↑ 5.0 5.1 Uno K et al, Neuronal pathway from the liver modulates energy expenditure and systemic insulin sensitivity. Science 2006; 312:1656 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16778057
- ↑ Wikipedia; peroxisome proliferator-activated receptor entry http://en.wikipedia.org/wiki/peroxisome_proliferator-activated_receptor
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=PPARG
- ↑ SeattleSNPs http://pga.gs.washington.edu/data/pparg/
- ↑ SHMPD; The Singapore human mutation and polymorphism database http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=PPARG
- ↑ UniProt http://www.uniprot.org/uniprot/P37231.html
Database
- OMIM: https://mirror.omim.org/entry/601487
- OMIM: https://mirror.omim.org/entry/601665
- OMIM: https://mirror.omim.org/entry/604367
- OMIM: https://mirror.omim.org/entry/606641
- OMIM: https://mirror.omim.org/entry/609338
- OMIM: https://mirror.omim.org/entry/609830
- UniProt: http://www.uniprot.org/uniprot/P37231.html