Phorbaketal A inhibits adipogenic differentiation through the suppression of PPARγ-mediated gene transcription by TAZ (original) (raw)
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Journal of Biological Chemistry, 2000
While searching for natural ligands for the peroxisome proliferator-activated receptor (PPAR) ␥, we identified a synthetic compound that binds to this receptor. Bisphenol A diglycidyl ether (BADGE) is a ligand for PPAR␥ with a K d(app) of 100 M. This compound has no apparent ability to activate the transcriptional activity of PPAR␥; however, BADGE can antagonize the ability of agonist ligands such as rosiglitazone to activate the transcriptional and adipogenic action of this receptor. BADGE also specifically blocks the ability of natural adipogenic cell lines such as 3T3-L1 and 3T3-F442A cells to undergo hormone-mediated cell differentiation. These results provide the first pharmacological evidence that PPAR␥ activity is required for the hormonally induced differentiation of adipogenic cells.
International Journal of Molecular Sciences
Understanding the molecular basis of adipogenesis is vital to identify new therapeutic targets to improve anti-obesity drugs. The adipogenic process could be a new target in the management of this disease. Our aim was to evaluate the effect of GMG-43AC, a selective peroxisome proliferator-activated receptor γ (PPARγ) modulator, during adipose differentiation of murine pre-adipocytes and human Adipose Derived Stem Cells (hADSCs). We differentiated 3T3-L1 cells and primary hADSCs in the presence of various doses of GMG-43AC and evaluated the differentiation efficiency measuring lipid accumulation, the expression of specific differentiation markers and the quantification of accumulated triglycerides. The treatment with GMG-43AC is not toxic as shown by cell viability assessments after the treatments. Our findings demonstrate the inhibition of lipid accumulation and the significant decrease in the expression of adipocyte-specific genes, such as PPARγ, FABP-4, and leptin. This effect was...
The elusive endogenous adipogenic PPARγ agonists: Lining up the suspects
Progress in lipid research, 2015
The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is the key decisive factor controlling the development of adipocytes. Ligand-mediated activation of PPARγ occurs early during adipogenesis and is thought to prime adipose conversion. Although several fatty acids and their derivatives are known to bind to and activate PPARγ, the identity of the ligand(s) responsible for initiating adipocyte differentiation is still a matter of debate. Here we review recent data on pathways involved in ligand production as well as possible endogenous, adipogenic PPARγ agonists.
Marine Biotechnology, 2010
In this study, we isolated the phloroglucinol derivative, 1-(3′,5′-dihydroxyphenoxy)-7-(2″,4″,6-trihydroxyphenoxy)-2,4,9-trihydroxydibenzo-1,4-dioxin (1), from Ecklonia cava and evaluated its potential inhibition on adipocyte differentiation in 3T3-L1 cells. Lipid accumulation along with the expression of several genes associated with adipogenesis and lipolysis was examined at the end of differentiation. Lipid accumulation level was examined by measuring triglyceride content and Oil-Red O staining. The expression levels of several genes and proteins were examined using reverse-transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, and Western blot analysis. Compound 1 significantly reduced lipid accumulation and downregulated peroxisome proliferator-activated receptor-γ, sterol regulatory element-binding protein 1c, and CCAAT/enhancer-binding proteins α in a dose-dependent manner. Moreover, the presence of compound 1 induced downregulation of adipogenic target genes such as fatty acid binding protein 4, fatty acid transport protein 1, fatty acid synthase, acyl-CoA synthetase 1, lipoprotein lipase, and leptin. According to the lipolytic response, compound 1 downregulated perilipin and hormone-sensitive lipase while upregulating tumor necrosis factor alpha. Therefore, these results suggest that compound 1 might decrease lipid accumulation during adipocyte differentiation by modulating adipogenesis and lipogenesis. Furthermore, compound 1 could be developed as a functional agent effective in improving obesity.
Endocrinology, 2002
PPAR␥ is an adipocyte-specific nuclear hormone receptor. Agonists of PPAR␥, such as thiazolidinediones (TZDs), promote adipocyte differentiation and have insulin-sensitizing effects in animals and diabetic patients. Affymetrix oligonucleotide arrays representing 6347 genes were employed to profile the gene expression responses of mature 3T3-L1 adipocytes and differentiating preadipocytes to a TZD PPAR␥ agonist in vitro. The expression of 579 genes was significantly up-or down-regulated by more than 1.5-fold during differentiation and/or by treatment with TZD, and these genes were organized into 32 clusters that demonstrated concerted changes in expression of genes controlling cell growth or lipid metabolism. Quantitative PCR was employed to further characterize gene expression and led to the identification of -catenin as a new PPAR␥ target gene. Both mRNA and protein levels for -catenin were down-regulated in 3T3-L1 adipocytes compared with fibroblasts and were further decreased by treatment of adipocytes with PPAR␥ agonists. Treatment of db/db mice with a PPAR␥ agonist also resulted in reduction of -catenin mRNA levels in adipose tissue. These results suggest that -catenin plays an important role in the regulation of adipogenesis. Thus, the transcriptional patterns revealed in this study further the understanding of adipogenesis process and the function of PPAR␥ activation.
Endocrinology, 2002
PPAR gamma is an adipocyte-specific nuclear hormone receptor. Agonists of PPAR gamma, such as thiazolidinediones (TZDs), promote adipocyte differentiation and have insulin-sensitizing effects in animals and diabetic patients. Affymetrix oligonucleotide arrays representing 6347 genes were employed to profile the gene expression responses of mature 3T3-L1 adipocytes and differentiating preadipocytes to a TZD PPAR gamma agonist in vitro. The expression of 579 genes was significantly up- or down-regulated by more than 1.5-fold during differentiation and/or by treatment with TZD, and these genes were organized into 32 clusters that demonstrated concerted changes in expression of genes controlling cell growth or lipid metabolism. Quantitative PCR was employed to further characterize gene expression and led to the identification of beta-catenin as a new PPAR gamma target gene. Both mRNA and protein levels for beta-catenin were down-regulated in 3T3-L1 adipocytes compared with fibroblasts a...
Endocrinology, 2002
PPAR␥ is an adipocyte-specific nuclear hormone receptor. Agonists of PPAR␥, such as thiazolidinediones (TZDs), promote adipocyte differentiation and have insulin-sensitizing effects in animals and diabetic patients. Affymetrix oligonucleotide arrays representing 6347 genes were employed to profile the gene expression responses of mature 3T3-L1 adipocytes and differentiating preadipocytes to a TZD PPAR␥ agonist in vitro. The expression of 579 genes was significantly up-or down-regulated by more than 1.5-fold during differentiation and/or by treatment with TZD, and these genes were organized into 32 clusters that demonstrated concerted changes in expression of genes controlling cell growth or lipid metabolism. Quantitative PCR was employed to further characterize gene expression and led to the identification of -catenin as a new PPAR␥ target gene. Both mRNA and protein levels for -catenin were down-regulated in 3T3-L1 adipocytes compared with fibroblasts and were further decreased by treatment of adipocytes with PPAR␥ agonists. Treatment of db/db mice with a PPAR␥ agonist also resulted in reduction of -catenin mRNA levels in adipose tissue. These results suggest that -catenin plays an important role in the regulation of adipogenesis. Thus, the transcriptional patterns revealed in this study further the understanding of adipogenesis process and the function of PPAR␥ activation.