Transcription of the ADIPOQ gene, encoding a fat-derived hor...
| created | [InstanceEdit:9856210] Orlic-Milacic, Marija, 2023-12-13 |
| dbId | 9856209 |
| displayName | Transcription of the ADIPOQ gene, encoding a fat-derived hor... |
| literatureReference |
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| modified | [InstanceEdit:9971485] Orlic-Milacic, Marija, 2025-11-06 |
| schemaClass | Summation |
| text | Transcription of the ADIPOQ gene, encoding a fat-derived hormone with antidiabetic and anti-atherogenic properties, is positively regulated by the PPARG:RXRA heterodimer and KMT2C (MLL3)/KMT2D (MLL4) histone methyltransferase complexes. Administration of synthetic agonists of PPARG increases plasma ADIPOQ protein levels in both insulin resistant humans and mice (Maeda et al. 2001). In cultured mouse 3T3-L1 white preadipocytes, PPARG synthetic agonists enhance mRNA transcription and secretion of Adipoq protein (Maeda et al. 2001). In 3T3-L1 cells, PPARG synthetic agonists stimulate activation of the luciferase reporter containing the human ADIPOQ gene promoter (Maeda et al. 2001). In obese diabetic mice chronically treated with PPARG synthetic agonists (11-day treatment window), mean plasma Adipoq protein levels increase (Combs et al. 2002). A two-week treatment of normal human subjects with the PPARG synthetic agonist rosiglitazone leads to increased circulating ADIPOQ protein (Combs et al. 2002). ADIPOQ serum levels are 5-fold suppressed in patients with severe insulin resistance caused by dominant-negative mutations in the PPARG gene (Combs et al. 2002). The human PPARG:RXRA heterodimer was shown by EMSA to directly bind to peroxisome proliferator response element (PPRE) in the promoter of the human ADIPOQ gene to increase its transcription (Iwaki et al. 2003). The human ADIPOQ gene promoter contains a responsive element for the liver receptor homolog-1 (LRH1, officially known as NR5A2) in the vicinity of the PPRE and direct NR5A2 binding to the ADIPOQ gene promoter facilitates PPARG:RXRA-mediated induction of the ADIPOQ gene transcription (Iwaki et al. 2003). Expression of ADIPOQ is significantly down-regulated in WAT of Kmt2c delta/delta mice that express a H3K4 methyltransferase-inactive Kmt2c mutant (Lee et al. 2008). Treatment of mouse white preadipocyte cell line 3T3-L1 with PPARG agonists results in increased Adipoq mRNA levels (Bhalla et al. 2011). Expression of the ADIPOQ gene is severely reduced in differentiating mouse brown preadipocytes expressing histone H3.3 K4M mutant or Kmt2c and Kmt2d with deleted SET domains (Jang et al. 2019: RNA-seq, supplementary information). |
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