Peroxisome Proliferator Receptor Gamma
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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)
-
- palmitoleic acid [16:1] (2+)
- oleic acid [18:1] (3+)
- elaidic acid [20:1] (+)
- 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] (+/-)
- * HODE = hydroxyoctadecadienoic acid
- Coactivators:
- 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
Pharmacology
- target of thiazoladinediones ( glitazones) which are agonists
- target of thiazoladinediones ( glitazones) which are agonists
- Exogenous agonists: ( peroxisome proliferators) [1]
-
- WY-14-643 (2+)
- clofibrate (1+)
- ciprofibrate (1+)
- gemfibrozil (1+)
- GW2331 (2+)
- indomethacin (3+)
- ibuprofen (1+)
- fenoprofen (1+)
- GW0072 (1+)
- L-764406 (3+)
- L-165041 (1+)
- 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+)
Polymorphism
- variation in PPARG
- is associated with carotid intimal medial thickness 1
- may influence body mass index
- may influence abdominal body fat distribution
More General Terms
Additional Terms
Internet Database
OMIM: 601487
OMIM: 601665
OMIM: 604367
OMIM: 606641
OMIM: 609338
OMIM: 609830
Prosite: [1]
Prosite: [2]
UniProt: [3]
References
- UniProt [4]
- Journal Watch 20(3):25-26, 2000
- Barroso et al Nature 402:880, 1999
- Corton JC et al, Central role of peroxisome proliferator-activated receptors in the actions of peroxisome proliferators Ann Rev Pharmocol Toxicol 2000; 40:491 PMID: [5]
- Uno K et al, Neuronal pathway from the liver modulates energy expenditure and systemic insulin sensitivity. Science 2006; 312:1656 PMID: [6]
- Wikipedia; peroxisome proliferator-activated receptor entry [7]
- GeneReviews [8]
- SeattleSNPs [9]
- SHMPD; The Singapore human mutation and polymorphism database [10]
- UniProt [11]
