mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer.

Tontonoz, Peter; Hu, Erding; Graves, Reed A.; Budavari, Adriane I.; Spiegelman, Bruce M.

doi:10.1101/gad.8.10.1224

Cited by 2,061 publications

(1,610 citation statements)

References 40 publications

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“…We also investigated a possible cooperation between hSNF5/INI1 and PPARg2 to activate the aP2 target gene, the promoter of which has been shown to contain PPARg2-responsive elements (Tontonoz et al, 1994). In both MON and KD, PPARg2 expression alone was not sufficient to induce aP2 (Figure 6a).…”

Section: Requirement For Snf5/ini1 In Adipogenic Differentiation Modelsmentioning

confidence: 99%

The requirement for SNF5/INI1 in adipocyte differentiation highlights new features of malignant rhabdoid tumors

et al. 2007

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ATP-dependent SWI/SNF chromatin remodeling complexes regulate cell-cycle and play critical roles in a variety of differentiation pathways. The core subunit SNF5/INI1 is a tumor suppressor that is inactivated in a highly aggressive childhood cancer of unknown cellular origin, termed malignant rhabdoid tumor (MRT). The highly undifferentiated phenotype of this tumor suggests that the loss-of-function of hSNF5/INI1 impairs specific differentiation programs of the MRT parental cell. Based on the hypothesis that these programs might be reinitialized upon hSNF5/INI1 re-expression in MRTs, we show that some MRT cell lines can differentiate toward the adipogenic lineage. We further show that the knock down of the SNF5/INI1 subunit abrogates adipocyte differentiation of murine 3T3-L1 preadipocytes and of human mesenchymal stem cells. Finally, we provide evidence that hSNF5/INI1 cooperates with C/EBPb and PPARc2 transcriptional regulators to activate the expression of adipocyte-specific genes. These data indicate that not only the ATPase subunit of the SWI/SNF complex, but also SNF5/INI1 is required for adipocyte differentiation. They further show that MRT cell lines harbor an adipogenic differentiation potential and that the tumor suppressor role of the SNF5/INI1 subunit may rely on its ability to regulate the balance between cell proliferation and differentiation.

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Section: Requirement For Snf5/ini1 In Adipogenic Differentiation Modelsmentioning

confidence: 99%

The requirement for SNF5/INI1 in adipocyte differentiation highlights new features of malignant rhabdoid tumors

et al. 2007

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“…Both a small molecule antagonist, GW9662, and overexpression of dominant-negative PPARg were effective in blocking ligand-mediated repression of MCM7 transcription. In NIH3T3 fibroblasts, which do not express detectable levels of PPARg, 17 PPARg ligands also had no effect on MCM expression. Thus, in these experimental systems corresponding to a loss of PPARg function, PPARg ligands failed to repress MCM7 transcription.…”

mentioning

confidence: 94%

New targets for PPARγ in the vessel wall: implications for restenosis

2005

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Peroxisome proliferator-activated receptor {gamma} (PPARg), the nuclear receptor that binds the insulin-sensitizing thiazolidinediones (TZDs), is prominently upregulated in intimal vascular smooth muscle cells (VSMC) after mechanical injury to the vessel wall. Several TZD PPARg ligands have been shown to inhibit neointima formation in both normal and insulinresistant vasculature. The suppression of intimal hyperplasia by TZD PPARg ligands probably results from their activity to inhibit VSMC growth and promote apoptosis. TZDs prevent VSMC proliferation by blocking the activity of regulatory proteins, such as phosphorylation of the retinoblastoma protein (Rb). Rb functions as a G 1 gatekeeper by controlling S phase gene expression mediated by the E2F transcription factor. Consistent with their effect on Rb phosphorylation, PPARg ligands inhibit the mitogenic induction of minichromosome maintenance (MCM) proteins 6 and 7, two E2F-regulated S phase genes essential for DNA replication. PPARg ligands also induced apoptosis in VSMC, which correlated with a potent induction of GADD45, a gene implicated in controlling cell growth and survival. A constitutively active form of PPARg targeted the same cell cycle regulators as did PPARg ligands, consistent with a nuclear-receptor-dependent mechanism of action. This review will summarize mechanisms through which PPARg modulates VSMC proliferation and apoptosis suggesting that PPARg itself is a novel important regulator of cell cycle and apoptosis and may provide a new therapeutic approach to prevent restenosis. Keywords: PPARg; thiazolidinedione; vascular smooth muscle; proliferation; minichromosome maintenance protein; GADD45Peroxisome proliferator-activated receptor {gamma} (PPARg) ligands have been shown to inhibit growth of vascular and cancer cells by interfering with the expression and function of multiple cell cycle regulators. 1-6 Although many studies have focused on alterations in the regulation of cell growth as a fundamental feature during atherogenesis and neointimal hyperplasia after percutaneous coronary revascularization, it is becoming increasingly evident that perturbations in the regulation of cell death may be of equal importance. 7 In vascular smooth muscle cells (VSMC), we have previously reported that the thiazolidinedione (TZD) PPARg ligands, troglitazone (TRO) and rosiglitazone (RSG), inhibit exit from G1 into S phase of the cell cycle by attenuating retinoblastoma protein (Rb) phosphorylation. 4 As illustrated in Figure 1 decreased phosphorylation of Rb by TRO and RSG likely results from their effect to elevate levels of the cyclindependent kinase inhibitor (CDKI) p27 kip1 and reduce the activity of cyclin D-and cyclin E-dependent kinases (CDK). 4 In addition, recent studies have shown that TZDs not only inhibit cell growth, but they can also induce apoptosis in VSMC. 8,9 The molecular mechanisms by which TZDs induce apoptosis in VSMC and whether they involve a PPARgdependent pathway also remain unclear.Using DNA microarray analysis, we have identifi...

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“…One was Pparg2 (Peroxisome Proliferator Activated Receptor gamma 2), a transcription factor closely related to adipocyte differentiation, 23 also discussed concerning brown adipocytes. 24 The other was Fabp4 (fatty acid binding protein 4, also known as aP2).…”

Section: Resultsmentioning

confidence: 99%

Promotion of lipid storage rather than of thermogenic competence by fetal versus newborn calf serum in primary cultures of brown adipocytes

2018

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Much current understanding of brown adipocyte development comes from in-vitro cell models. Serum type may affect the behavior of cultured cells and thus conclusions drawn. Here, we investigate effects of serum type (“fetal bovine” versus “newborn calf”) on responses to differentiation inducers (the PPARγ agonist rosiglitazone or the neurotransmitter norepinephrine) in cultured primary brown adipocytes. Lipid storage was enhanced by fetal versus newborn serum. However, molecular adipose conversion (Pparg2 and Fabp4 expression) was not affected by serum type. Rosiglitazone-induced (7-days) expression of thermogenic genes (i.e. Ucp1, Pgc1a, Dio2 and Elovl3) was not systematically affected by serum type. However, importantly, acute (2 h) norepinephrine-induced thermogenic gene expression was overall markedly higher (and adipose genes somewhat lower) in cells cultured in newborn serum. Thus, newborn serum promotes thermogenic competence, and the use of fetal serum in brown adipocyte cultures (as is often routine) counteracts adequate differentiation. Agents that counteract this inhibition may therefore confoundingly be ascribed genuine thermogenic competence-inducing properties.

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mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer.

Cited by 2,061 publications

References 40 publications

The requirement for SNF5/INI1 in adipocyte differentiation highlights new features of malignant rhabdoid tumors

The requirement for SNF5/INI1 in adipocyte differentiation highlights new features of malignant rhabdoid tumors

New targets for PPARγ in the vessel wall: implications for restenosis

Promotion of lipid storage rather than of thermogenic competence by fetal versus newborn calf serum in primary cultures of brown adipocytes

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