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 SOX9
Homo sapiens
 HIF1A
Homo sapiens
 Pax6
Mus musculus
 PAX6
Homo sapiens
 Snai2
Mus musculus
 PPARA
Homo sapiens
 Ppara
Mus musculus
 Thrb
Mus musculus
 SNAI2
Homo sapiens
 Tbr1
Mus musculus
Transcription Factor Encyclopedia  BETA
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Overview
No annotation is available in this section for this article. The content below is taken from a related TF, PPARG (Homo sapiens).

Peroxisome proliferator activated receptor γ (PPARγ) also known as Nuclear Receptor subfamily 1 group C member 3 (NR1C3) is a member of the PPAR subfamily of nuclear receptors. It was first cloned by homology to PPARα and was later identified as a target of thiazolidinedione (TZD) antidiabetic drugs [1][2][3][4]. PPARγ displays a high degree of sequence and structural homology with other members of the PPAR family, i.e. PPARα and PPARβ/δ[5] however, there is only partial overlap in terms of target genes[6][7]. PPARγ exists in two isoforms, γ1 and γ2, which are generated by alternative splicing and promoter usage. PPARγ2 has an additional 30 amino acids in the N-terminal relative to γ1[8]. PPARγ binds as heterodimers with members the retinoid X receptor (RXR) family to PPAR response elements (PPREs) composed of a direct repeat of two half sites of 5’-AGGTCA-3’ separated by one nucleotide. The ligand binding domain of PPARγ binds various polyunsaturated fatty acids, fatty acid derivates and synthetic ligands[9][10], which promote recruitment of transcriptional co-regulators that ultimately regulate recruitment of RNA polymerase II to target promoters[11].

PPARγ is obligate for in vitro as well as in vivo differentiation of adipocytes[12][13][14] and for survival and function of mature adipocytes[15][16][17]. Ectopic expression of PPARγ leads to expression of adipocyte specific genes and accumulation of lipids as triglycerides in numerous non-adipocyte cell types[18][19][6][7]. In addition to its role in adipocyte differentiation, mouse genetic studies have revealed an essential role of PPARγ in several other cell types including macrophages, vascular epithelia and vascular smooth muscle cells[20]. Moreover, PPARγ is regulating gut epithelium differentiation and several lines of evidence show that PPARγ suppresses colon cancer progression[21][22]. Furthermore, activation of PPARγ represses the inflammatory response in several cell types by antagonizing proinflammatory transcription factors[23]. Accordingly agonists of PPARγ have proven to be promising drugs for treatment of diseases such as insulin resistance, atherosclerosis and certain cancers[10].

PPARγ is target for a wide range of synthetic ligands shown to be important for induced insulin sensitivity. However the identity of endogenous ligands is still elusive. Numerous studies have characterized polyunsaturated and oxidized fatty acids as ligands for PPARγ[24]and it has been suggested that endogenous ligands for PPARγ is produced during adipogenesis [25][26]. PPARγ in adipose tissue, rather than liver and skeletal muscle, has been shown to be the major target for TZDs in T2DM treatment, which underscores the importance of PPARγ and adipose tissue in glucose homeostasis and insulin sensitivity. TZDs induce the appearance of small newly differentiated adipocytes and increase WAT mass, which reverse insulin resistance in two ways. First the level of circulating free fatty acids is reduced due to increased expression of genes involved in fatty uptake and storage. Second, TZDs repress adipose tissue specific secretion of TNFalpha and IL-6 and induce secretion of adiponectin, through a mechanism that involves alternative macrophages, which leads to increased insulin sensitivity in liver, muscle and pancreas [27][28][29].

References
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  14. Rosen ED et al. C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway. Genes Dev., 16(1):22-6. (PMID 11782441)
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Figures
No annotation is available in this section for this article. The content below is taken from a related TF, PPARG (Homo sapiens).
FIGURE 1 Figure 1. Structure of PPARγ
PPARγ exists in two isoforms, γ1 and γ2. PPARγ2 has an additional 30 amino acids in the N-terminal relative to γ1 (marked with green). PPARγ has four functional domains (A/B, C, D and E) and is phosphorylated and sumoylated at the indicated residues.
This figure was created by the authors of this article. The authors of this article have provided the assurance that this figure constitutes their original work.