Status
Please wait ...

Details for receptor: PPARgamma1

  • Top
  • General information
  • Subunits
    •
  • External resources
  • General information
  • Hormones
  • Anatomical structures
  • Click to access the toolbox
EndoNet ID: ENR00118

To link to the content of EndoNet use the EndoNet ID that is given on the detail pages in the format ENX0000, where X is a place holder for the type of the component (e. g. R for receptor or C for anatomical structure).
As URL for the linking append this ID to the detail page for this type of component.
For an hormone that would be: 

http://endonet.bioinf.med.uni-goettingen.de/hormone/ENH00000

It is also possible to use the search of EndoNet to link to the right detail page. The URL should look like 

http://endonet.bioinf.med.uni-goettingen.de/search/ENC00000
If the search pattern is unambigious the user is directed to the corresponding detail page.

Synonyms

  • PPARG
  • peroxisome proliferator-activated receptor gamma
  • NR1C3
  • PPARgamma1
  • PPAR gamma1
  • glitazone receptor
  • peroxisome proliferative activated receptor gamma isoform 1

General information

  • The nuclear hormone receptor PPAR gamma promotes adipogenesis and macrophage differentiation and is a primary pharmacological target in the treatment of type II diabetes. [1]
  • The PPAR gamma receptor is important in the control of insulin sensitivity, glucose homeostasis and blood pressure in man. [2]
  • Terminal differentiation of human breast cancer through PPAR gamma. [3]
  • Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma. [4]
  • The nuclear receptor peroxisome proliferator-activated receptor gamma regulates adipose differentiation and systemic insulin signaling via ligand-dependent transcriptional activation of target genes. [5]
  • In the absence of ligand, PPAR gamma has the potential to actively silence genes to which it is bound by recruiting transcriptional corepressor complexes containing nuclear receptor corepressor (N-CoR) or SMRT (silencing mediator of retinoid and thyroid receptors). [6]
  • Combined treatment of PPARgamma and cytokines (IL-1 or TNF-alpha) inhibited adipogenesis and induced osteoblastgenesis in bone marrow-derived mesenchymal stem cells. [7]
  • The ligand dependent transactivation function of PPARgamma was suppressed by IL-1 and TNF-alpha. [7]
  • The highest levels of PPARG are found in adipose tissue and large intestine, with intermediate levels in kidney, liver, and small intestine, and barely detectable levels in muscle. [8]
  • PPARgamma is expressed in many cell types including mammary epithelium, ovary, macrophages, and B- and T-cells. [9]
  • PPAR gamma is essential for the formation of fat. [10]
  • PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. [11]
  • PPARgamma/RXRalpha heterodimers control human trophoblast invasion. [11]
  • PPAR-gamma, is a potent inhibitor of microglial cell activation. [12]
  • A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. [13]
  • Critical physiological role for PPAR gamma function in beta-cell proliferation. [14]
  • Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. [15]
  • Two PPARgamma isoforms created by differential promoter usage and splicing (gamma1 and gamma2) are found in adipocytes. [6]
  • Fluid shear stress decreases the expression of PPARgamma in endothelial cells and that loss of PPARgamma expression characterizes an abnormal, proliferating, apoptosis-resistant endothelial cell phenotype. [16]
  • Ubiquitous PPARgamma expression in normal lungs, and in contrast, a reduced lung tissue PPARgamma gene and protein expression in the lungs from patients with severe PH and loss of PPARgamma expression in their complex vascular lesions. [16]
  • PPAR gamma is required for placental, cardiac, and adipose tissue development. [1]
  • Muscle-specific Pparg deletion causes insulin resistance. [17]
  • A genetic polymorphism of the peroxisome proliferator-activated receptor gamma gene influences plasma leptin levels in obese humans. [18]
  • PPARgamma is an essential regulator of adipogenesis and modulator of fat cell function. [19]
  • PPARgamma is a member of the nuclear receptor family that includes 48 human transcription factors whose activity is regulated by direct binding of steroid and thyroid hormones, vitamins, lipid metabolites, and xenobiotics. [6]
  • PPARgamma is expressed in blood cells and induced during macrophage differentiation. [6]
  • PPARgamma is a ligand-dependent nuclear receptor and regulates adipogenesis and fat metabolism. PPARgamma is activated by fatty acid derivatives and some synthetic compounds such as the thiazolidinediones. [7]
  • PPAR gamma induces expression of Scavenger receptor class B, type I (SR-BI) in rat hepatocytes, liver endothelial cells, and Kupffer cells. [20]
  • The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor subfamily of transcription factors. [8]
  • Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle. [21]
  • PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. [22]
  • Highest expression in adipose tissue. Lower in skeletal muscle, spleen, heart and liver. Also are detectable in placenta, lung and ovary. [15]
  • PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. [23]
  • Lipodystrophy and insulin resistance are the core features of human PPARgamma deficiency states. [24]
  • Cyclin D1 repression of peroxisome proliferator-activated receptor gamma expression and transactivation. [25]
  • Thiazolidinedione (TZD) antidiabetic drugs are high-affinity agonist ligands for PPAR gamma. [6]
  • HSC activated both in vitro and in vivo have reduced expression of PPAR-gamma. The treatment of culture-activated HSC with the PPAR-gamma ligands restores its expression. [26]
  • Two isoforms of PPARg, g1 and g2, have been found in mice [2]. The expression of these 2 isotypes results from differential promoter use and alternative RNA splicing [9]
  • As previously reported in the mouse [2], the coding sequences for PPARg1 and PPARg2 are identical with the exception that PPARg2 contains an additional 84 nucleotides (90 for the mouse) at its 5* end encoding an N-terminal 28 amino acid extension [9]
  • Insulin itself decrease PPAR gamma mRNA expression. [27]

Links to other resources

UniProt P37231
Ensembl ENST00000455517

Subunit information

PPARG isoform 1

  • PPAR gamma1 and gamma3 mRNA code for the same protein, while PPAR gamma2 codes for a different protein containing 28 additional amino acids at the N-terminus. [28]
Sequence 
MTMVDTEMP FWPTNFGIS SVDLSVMED 
HSHSFDIKP FTTVDFSSI STPHYEDIP 
FTRTDPVVA DYKYDLKLQ EYQSAIKVE 
PASPPYYSE KTQLYNKPH EEPSNSLMA 
IECRVCGDK ASGFHYGVH ACEGCKGFF 
RRTIRLKLI YDRCDLNCR IHKKSRNKC 
QYCRFQKCL AVGMSHNAI RFGRMPQAE 
KEKLLAEIS SDIDQLNPE SADLRALAK 
HLYDSYIKS FPLTKAKAR AILTGKTTD 
KSPFVIYDM NSLMMGEDK IKFKHITPL 
QEQSKEVAI RIFQGCQFR SVEAVQEIT 
EYAKSIPGF VNLDLNDQV TLLKYGVHE 
IIYTMLASL MNKDGVLIS EGQGFMTRE 
FLKSLRKPF GDFMEPKFE FAVKFNALE 
LDDSDLAIF IAVIILSGD RPGLLNVKP 
IEDIQDNLL QALELQLKL NHPESSQLF 
AKLLQKMTD LRQIVTEHV QLLQVIKKT 
ETDMSLHPL LQEIYKDLY
UniProt P37231-2

Binding hormones

  • free fatty acid
  • 15d-PGJ2

Anatomical structures with this receptor

  • adipose_tissue

    Influences

    • haptoglobin
    • resistin
      • PPAR-gamma agonists were initially reported to suppress resistin expression in murine adipocytes, although a second study suggested that PPAR-gamma agonists increase adipose tissue resistin mRNA levels. [29]
    • positive adiponectin
      • Adiponectin secretion is stimulated by exposure of adipocytes to PPAR-gamma agonists. [30]
    • negative leptin
      • Catecholamines (beta 2 adrenoreceptor), cAMP agonists, and peroxisome proliferator-activated receptor gamma (PPAR-gamma) inhibit leptin synthesis and secretion. [31]

    Induced phenotypes

    • regulation of fat cell differentiation
      • PPARγ expression is observed in adipose tissue in rodents. Its expression is induced early in differentiation of 3T3-L1 preadipocytes into adipocytes, and its overexpression in fibroblasts induces them to differentiate into adipocytes. [32]
    • negative regulation of transcription
      • Insulin decrease PPAR gamma mRNA expression. [27]
    • regulation of glucose homeostasis
      • PPAR-gamma is expressed in human fat, one tissue where most of the insulin-stimulated glucose uptake occurs. [33]
    • PPARγ1 had the broadest tissue expression(...)PPARγ1 mRNA was found in the heart, large and small intestines, colon, kidney, pancreas, spleen and skeletal muscle. [28]
    • The peroxisome proliferation-activated receptor gamma (PPARγ)1 is a member of the nuclear receptor superfamily. It is expressed in many cell types, including adipocytes, epithelial cells, B- and T-cells, macrophages, endothelial cells, neutrophils, and smooth muscle cells [9]

  • large_intestine

    • PPARγ1 had the broadest tissue expression(...)PPARγ1 mRNA was found in the heart, large and small intestines, colon, kidney, pancreas, spleen and skeletal muscle. [28]

  • kidney

    • PPARγ1 had the broadest tissue expression(...)PPARγ1 mRNA was found in the heart, large and small intestines, colon, kidney, pancreas, spleen and skeletal muscle. [28]

  • small_intestine

    • PPARγ1 had the broadest tissue expression(...)PPARγ1 mRNA was found in the heart, large and small intestines, colon, kidney, pancreas, spleen and skeletal muscle. [28]

  • bone_marrow

    • mRNA being detectable in spleen, bone marrow, liver, testis, skeletal muscle and brain [34]

  • lung

    • In this paper it is not clear whether it is γ1 or another γ receptor isoform it only says: " PPARγ expression occurs in the lung in alveolar type II cells" [16]

  • placenta

    • In this paper it is not clear whether it is γ1 or another γ receptor isoform it only says: " PPARγ regulates terminal epithelial differentiation of the trophoblast, which, given the ubiquitous expression of PPARγ in epithelia of endocrine and exocrine tissues, could apply to additional organs. Most importantly, we unravel the existence of a previously unrecognized functional link between the placenta and the developing heart, which could shed new light on the origins of congenital cardiomyopathies [1]

  • heart

    Induced phenotypes

    • regulation of glucose homeostasis
      • PPAR-gamma is expressed in the heart, one tissue where most of the insulin-stimulated glucose uptake occurs. [33]
    • In this paper it is not clear whether it is γ1 or another γ receptor isoform it only says: " PPARγ regulates terminal epithelial differentiation of the trophoblast, which, given the ubiquitous expression of PPARγ in epithelia of endocrine and exocrine tissues, could apply to additional organs. Most importantly, we unravel the existence of a previously unrecognized functional link between the placenta and the developing heart, which could shed new light on the origins of congenital cardiomyopathies [1]
    • PPARγ1 had the broadest tissue expression(...)PPARγ1 mRNA was found in the heart, large and small intestines, colon, kidney, pancreas, spleen and skeletal muscle. [28]

  • ovary

    • The peroxisome proliferation-activated receptor gamma (PPARγ) is expressed in many cell types including mammary epithelium, ovary, macrophages, and B- and T-cells [9]

  • breast

    • The peroxisome proliferation-activated receptor gamma (PPARγ) is expressed in many cell types including mammary epithelium, ovary, macrophages, and B- and T-cells [9]

  • smooth_muscle

    • The peroxisome proliferation-activated receptor gamma (PPARγ)1 is a member of the nuclear receptor superfamily. It is expressed in many cell types, including adipocytes, epithelial cells, B- and T-cells, macrophages, endothelial cells, neutrophils, and smooth muscle cells [9]

  • smooth_muscle_cell

    • PPARγ is expressed in endothelium and smooth muscle in the blood vessel wall [35]

  • macrophage

    • The peroxisome proliferation-activated receptor gamma (PPARγ) is expressed in many cell types including mammary epithelium, ovary, macrophages, and B- and T-cells [9]

  • spleen

    • PPARγ1 had the broadest tissue expression(...)PPARγ1 mRNA was found in the heart, large and small intestines, colon, kidney, pancreas, spleen and skeletal muscle. [28]
    • mRNA being detectable in spleen, bone marrow, liver, testis, skeletal muscle and brain [34]

  • testis

    • mRNA being detectable in spleen, bone marrow, liver, testis, skeletal muscle and brain [34]

  • skeleton_muscle

    Induced phenotypes

    • regulation of glucose and lipid metabolism
      • Co-activation of PPAR gamma and RXR results in additive or synergistic effects on glucose and lipid metabolism in skeletal muscle. [36]
    • regulation of glucose metabolic process
      • PPAR-gamma directly coordinates glucoregulatory responses in skeletal muscle. [17]
    • PPARγ1 had the broadest tissue expression(...)PPARγ1 mRNA was found in the heart, large and small intestines, colon, kidney, pancreas, spleen and skeletal muscle. [28]
    • mRNA being detectable in spleen, bone marrow, liver, testis, skeletal muscle and brain [34]

  • brain

    • PPARγ1 has a broader expression pattern that extends to settings such as the gut, brain, vascular cell and specific kinds of immune and inflammatory cells. [37]

  • B-lymphocyte

    • The peroxisome proliferation-activated receptor gamma (PPARγ)1 is a member of the nuclear receptor superfamily. It is expressed in many cell types, including adipocytes, epithelial cells, B- and T-cells, macrophages, endothelial cells, neutrophils, and smooth muscle cells [9]

  • colon

    • PPARγ1 had the broadest tissue expression(...)PPARγ1 mRNA was found in the heart, large and small intestines, colon, kidney, pancreas, spleen and skeletal muscle. [28]

  • immune_system

    • PPARγ1 has a broader expression pattern that extends to settings such as the gut, brain, vascular cell and specific kinds of immune and inflammatory cells. [37]

  • retina

    • PPARγ has been shown to be expressed in the RPE(retinal pigmented epithelium), and phagocytosis of photoreceptor outer segments increases PPARγ expression in these cells. [38]

  • microglial_cell_in_central_nervous_system

    • The observation that PPAR-gamma is involved in the regulation of macrophage differentiation and activation in the peripheral organs has prompted the investigation of the functional role of PPAR-gamma in microglial cells, the main macrophage population of the CNS. [39]

  • T-lymphocyte

    • The peroxisome proliferation-activated receptor gamma (PPARγ)1 is a member of the nuclear receptor superfamily. It is expressed in many cell types, including adipocytes, epithelial cells, B- and T-cells, macrophages, endothelial cells, neutrophils, and smooth muscle cells [9]

  • lipocyte_of_liver

    Induced phenotypes

    • involvement in liver steatosis
      • Among genes involved in lipid metabolism, adipogenesis-related genes, PPARgamma and its targeted gene, CD36 mRNA expression is specifically up-regulated in the liver by high fat diet for 2 weeks. Protein expression of cAMP response element-binding protein (CREB), an upstream molecule of PPARgamma, in the liver was drastically suppressed by high fat diet. [40]
      • CREB-PPARgamma signaling pathway could be involved in the high fat diet-induced liver steatosis. [40]

  • monocyte

    Influences

    • positive FABP4
      • FABP4, a known PPAR-gamma target, was strikingly increased by 24 h of treatment with two independent PPAR-gamma agonists. [29]
    • positive resistin

  • vascularendothelial_cell

    • PPARγ1 has a broader expression pattern that extends to settings such as the gut, brain, vascular cell and specific kinds of immune and inflammatory cells. [37]
Reference