Angptl4 gene expression is stimulated by Pparg:Rxra and Mll4,(Mll3) complex

Stable Identifier
R-MMU-9907162
Type
Reaction [omitted]
Species
Mus musculus
Compartment
nucleoplasm, extracellular region
ReviewStatus
3/5
General
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PNG
Low
Medium
High
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Angptl4 gene expression is stimulated by Pparg:Rxra and Mll4,(Mll3) complex
In mouse preadipocyte cell line 3T3-L1, Angptl4 expression is rapidly induced upon treatment with PPARG agonists (Yoon et al. 2000, Allen et al. 2006, Bhalla et al. 2011) in the absence of protein synthesis (Yoon et al. 2000). Angptl4 expression in mouse white fat upon treatment with the PPARG agonist rosiglitazone leads to enhanced angiogenesis, which is likely required for adipose tissue growth (Gealekman et al. 2008). Expression of the Angptl4 gene is severely reduced in differentiating mouse brown preadipocytes expressing histone H3.3 K4M mutant or Kmt2c (Mll3) and Kmt2d (Mll4) with deleted SET domains (Jang et al. 2019: RNA-seq, supplementary information). RNA Pol II occupancy at the Angptl4 gene promoter is increased in response to PPARG agonists (Nielsen et al. 2008). Pparg-mediated upregulation of Angptl4 secretion from mouse white fat tissue was shown to specifically promote proliferation of glucagon-secreting alpha-cells of the endocrine pancreas (Ben-Zvi et al. 2015). In mice, it was shown that Angptl4 is involved in regulation of lipid metabolism by inhibiting lipoprotein lipase (Lpl) responsible for the clearance of lipids from the bloodstream, therefore leading to increased blood levels of plasma triglycerides (TG) and fatty acids (Yoshida et al. 2002).
Literature References
PubMed ID Title Journal Year
30335158 H3.3K4M destabilizes enhancer H3K4 methyltransferases MLL3/MLL4 and impairs adipose tissue development

Park, YK, Lee, JE, Froimchuk, E, Jang, Y, Broun, A, Wang, C, Liu, C, Zhuang, L, Ge, K

Nucleic Acids Res 2019
12401877 Angiopoietin-like protein 4 is a potent hyperlipidemia-inducing factor in mice and inhibitor of lipoprotein lipase

Furukawa, H, Shimizugawa, T, Yoshida, K, Ono, M

J Lipid Res 2002
26621734 Angptl4 links α-cell proliferation following glucagon receptor inhibition with adipose tissue triglyceride metabolism

Peterson, QP, Blum, B, Ben-Zvi, D, Barrandon, O, Hadley, S, Melton, DA

Proc Natl Acad Sci U S A 2015
21979952 N-Acetylfarnesylcysteine is a novel class of peroxisome proliferator-activated receptor γ ligand with partial and full agonist activity in vitro and in vivo

Bhalla, K, Choi, JH, Mclenithan, J, Stock, J, Pozharski, E, Hwang, BJ, Girnun, GD, Dewi, R, Twaddel, W, Ou, L

J Biol Chem 2011
27110487 White-to-brite conversion in human adipocytes promotes metabolic reprogramming towards fatty acid anabolic and catabolic pathways

Barquissau, V, Tavernier, G, Beuzelin, D, Guillou, H, Beranger, GE, Amri, EZ, Moro, C, Mairal, A, Roussel, B, Pisani, DF, Langin, D, Montagner, A, Marques, MA

Mol Metab 2016
16936200 Halofenate is a selective peroxisome proliferator-activated receptor gamma modulator with antidiabetic activity

Moodie, SA, Muscat, GE, Gregoire, F, Gustafson, TA, Allen, T, Clemens, LE, Zhang, F, Bell, A, Smith, A

Diabetes 2006
10866690 Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation

Holmes, WE, Dussault, B, Yoon, JC, Qin, Y, Soukas, A, Chickering, TW, Rosen, ED, Spiegelman, BM, Friedman, JM

Mol Cell Biol 2000
18728224 Enhanced angiogenesis in obesity and in response to PPARgamma activators through adipocyte VEGF and ANGPTL4 production

Nicoloro, SM, Chouinard, M, Gealekman, O, Burkart, A, Straubhaar, J, Corvera, S

Am J Physiol Endocrinol Metab 2008
Participants
Input
Output
This event is regulated
Positively by
Regulator
Activated Pparg:Rxra:Angptl4 gene:H3K4me1-Nucleosomes:Mll4,(Mll3)-ASCOM [nucleoplasm] (Mus musculus)
Active Unit
RXRA natural ligands [nucleoplasm]
PPARG natural ligands [nucleoplasm]
Pparg:Rxra [nucleoplasm]
Mll4-ASCOM,(Mll3-ASCOM) [nucleoplasm]
Ncoas (Pparg,Rxra) [nucleoplasm]
Orthologous Events
ANGPTL4 gene expression is stimulated by PPARG:RXRA:MLL4,(MLL3)-ASCOM complex (Homo sapiens)
Authored
Orlic-Milacic, M  (2024-04-04)
Created
Orlic-Milacic, M  (2024-04-04)
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