scholarly journals Peroxisome-proliferator-activated receptor γ suppresses Wnt/β-catenin signalling during adipogenesis

2003 ◽  
Vol 376 (3) ◽  
pp. 607-613 ◽  
Author(s):  
Marthe MOLDES ◽  
Ying ZUO ◽  
Ron F. MORRISON ◽  
David SILVA ◽  
Bae-Hang PARK ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Ectopic Expression ◽  
Reciprocal Relationship ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Activation Of Transcription ◽  
Undifferentiated State ◽  
Ectopic Production ◽  
Pparγ Expression

The Wnt/β-catenin signalling pathway appears to operate to maintain the undifferentiated state of preadipocytes by inhibiting adipogenic gene expression. To define the mechanisms regulating suppression of Wnt/β-catenin signalling, we analysed the β-catenin expression in response to activation of transcription factors that regulate adipogenesis. The results show an extensive down-regulation of nuclear β-catenin that occurs during the first few days of differentiation of 3T3-L1 preadipocytes and coincides with the induction of the adipogenic transcription factors, C/EBPβ (CCAAT-enhancer-binding protein) and PPARγ (peroxisome-proliferator-activated receptor). To assess the role of each of these factors in this process, we conditionally overexpressed C/EBPβ in Swiss mouse fibroblasts using the TET-off system. Abundant expression of C/EBPβ alone had minimal effect on β-catenin expression, whereas expression of C/EBPβ, in the presence of dexamethasone, induced PPARγ expression and caused a measurable decrease in β-catenin. In addition, exposure of cells expressing both C/EBPβ and PPARγ to a potent PPARγ ligand resulted in an even greater decrease in β-catenin by mechanisms that involve the proteasome. Our studies also suggest a reciprocal relationship between PPARγ activity and β-catenin expression, since ectopic production of Wnt-1 in preadipocytes blocked the induction of PPARγ gene expression. Moreover, by suppressing β-catenin expression, ectopic expression of PPARγ in Wnt-1-expressing preadipocytes rescued the block in adipogenesis after their exposure to the PPARγ ligand, troglitazone.

scholarly journals Increasing Fat Deposition via Upregulates the Transcription of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in Native Crossbred Chicken

2020 ◽  
Author(s):  
Supanon Tunim ◽  
Yupin Phasuk ◽  
Samuel E. Aggrey ◽  
Monchai Duangjinda
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Intramuscular Fat ◽  
Abdominal Fat ◽  
Fat Deposition ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Chicken Breeds ◽  
Pparγ Expression ◽  
Pparγ Gene

Abstract Background: Crossbreeding using exotic breeds is usually employed to improve the growth characteristics of indigenous chickens. This mating not only provides growth but affect adversely to fat deposition as well. We studied the growth, abdominal, subcutaneous and intramuscular fat and mRNA expression of peroxisome proliferator-activated receptor (PPAR) α and PPARγ in adipose and muscle tissues of four chicken breeds [Chee breed (CH) (100% Thai native chicken), Kaimook e-san1 (KM1; 50% CH background), Kaimook e-san2 (KM2; 25% CH background), and broiler (BR)]. This study was aim to study role of PPARs on fat deposition in native crossbred chicken.Results: The BR chickens had higher abdominal fat than other breeds (P<0.05) and the KM2 had an abdominal fat percentage higher than KM1 and CH respectively (P<0.05). The intramuscular fat (IMF) of BR was greater than KM1 and CH (P<0.05). In adipose tissue, PPARα transcription expression was different among the chicken breeds. However, there were breed differences in PPARγ gene expression. Study of abdominal fat PPARγ gene expression showed the BR breed, KM1, and KM2 breed significantly greater (P<0.05) than CH. In 8 to 12 weeks of age, the result shows that the PPARγ expression of the CH breed is less than (P<0.05) KM2. The result of PPARs expression in muscle tissue was similar result in adipose tissue.Conclusion: Crossbreeding improved the growth of the Thai native breed, there was also a corresponding increase in carcass fatness. However, there appears to be a relationship between PPARγ expression and fat deposition traits. therefore, PPARγ activity plays a key role in lipid accumulation by up-regulation.

scholarly journals Retinoic acid blocks adipogenesis by inhibiting C/EBPbeta-mediated transcription.

1997 ◽  
Vol 17 (3) ◽  
pp. 1552-1561 ◽  
Author(s):  
E J Schwarz ◽  
M J Reginato ◽  
D Shao ◽  
S L Krakow ◽  
M A Lazar
Keyword(s):  
Transcription Factors ◽  
Retinoic Acid ◽  
Transcriptional Activation ◽  
Adipocyte Differentiation ◽  
Ectopic Expression ◽  
Transient Transfection ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Necessary And Sufficient ◽  
Sequential Induction

Adipocyte differentiation is thought to involve sequential induction of the transcription factors C/EBPbeta, peroxisome proliferator-activated receptor gamma (PPARgamma), and C/EBPalpha. C/EBPalpha expression is both necessary and sufficient for adipocyte differentiation. Here we report that ectopic expression of either C/EBPalpha or C/EBPbeta induces PPARgamma expression and adipogenesis and that retinoic acid (RA) completely inhibits adipogenesis by either form of C/EBP. In studies of normal preadipocytes, RA does not prevent C/EBPbeta induction but blocks induction of PPARgamma, C/EBPalpha, and adipogenesis. In transient transfection studies, liganded RA receptor (RAR) specifically blocks transcriptional activation by either C/EBPalpha or C/EBPbeta. These results strongly suggest that C/EBPalpha substitutes for C/EBPbeta to induce adipocyte differentiation and that liganded RAR inhibits adipogenesis by blocking C/EBPbeta-mediated induction of downstream genes.

scholarly journals Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids.

1996 ◽  
Vol 16 (8) ◽  
pp. 4128-4136 ◽  
Author(s):  
Z Wu ◽  
N L Bucher ◽  
S R Farmer
Keyword(s):  
Gene Expression ◽  
Expression System ◽  
Ectopic Expression ◽  
Response To Treatment ◽  
Peroxisome Proliferator ◽  
Differentiation Process ◽  
Peroxisome Proliferator Activated Receptor ◽  
Initial Exposure ◽  
3T3 Fibroblasts ◽  
Nih 3T3

The differentiation of 3T3 preadipocytes into adipocytes is accompanied by a transient induction of C/EBPbeta and C/EBPdelta expression in response to treatment of the cells with methylisobutylxanthine (MIX) and dexamethasone (DEX), respectively. In this report, we demonstrate that peroxisome proliferator-activated receptor gamma (PPARgamma) expression in 3T3-L1 preadipocytes is induced by MIX and DEX, suggesting that C/EBPbeta and C/EBPdelta may be involved in this process. Using a tetracycline-responsive expression system, we have recently shown that the conditional ectopic expression of C/EBPbeta in NIH 3T3 fibroblasts (beta2 cells) in the presence of DEX activates the synthesis of peroxisome PPARgamma mRNA. Subsequent exposure of these cells to PPAR activators stimulates their conversion into adipocytes; however, neither the expression of C/EBPbeta nor exposure to DEX alone is capable of inducing PPARgamma expression in the beta2 cell line. We find that unlike the case for 3T3 preadipocytes, C/EBPdelta is not induced by DEX in these 3T3 fibroblasts and therefore is not relaying the effect of this glucocorticoid to the PPARgamma gene. To define the role of glucocorticoids in regulating PPARgamma expression and the possible involvement of C/EBPdelta, we have established an additional set of NIH 3T3 cell lines expressing either C/EBPdelta alone (delta23 cells) or C/EBPdelta and C/EBPbeta together (beta/delta39 cells), using the tetracycline-responsive system. Culture of these cells in tetracycline-deficient medium containing DEX, MIX, insulin, and fetal bovine serum shows that the beta/delta39 cells express PPARgamma and aP2 mRNAs at levels that are almost equivalent to those observed in fully differentiated 3T3-L1 adipocytes. These levels are approximately threefold higher than their levels of expression in the beta2 cells. Despite the fact that these beta/delta39 cells produce abundant amounts of C/EBPbeta and C/EBPdelta (in the absence of tetracycline), they still require glucocorticoids to attain maximum expression of PPARgamma mRNA. Furthermore, the induction of PPARgamma mRNA by exposure of these cells to DEX occurs in the absence of ongoing protein synthesis. The delta23 cells, on the other hand, are not capable of activating PPARgamma gene expression when exposed to the same adipogenic inducers. Finally, attenuation of ectopic C/EBPbeta production at various stages during the differentiation process results in a concomitant inhibition of PPARgamma and the adipogenic program. These data strongly suggest that the induction of PPARgamma gene expression in multipotential mesenchymal stem cells (NIH 3T3 fibroblasts) is dependent on elevated levels of C/EBPbeta throughout the differentiation process, as well as an initial exposure to glucocorticoids. C/EBPdelta may function by synergizing with C/EBPbeta to enhance the level of PPARgamma expression.

scholarly journals C/EBP transcription factors regulate SREBP1c gene expression during adipogenesis

2009 ◽  
Vol 425 (1) ◽  
pp. 215-224 ◽  
Author(s):  
Victoria A. Payne ◽  
Wo-Shing Au ◽  
Christopher E. Lowe ◽  
Shaikh M. Rahman ◽  
Jacob E. Friedman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Binding Protein ◽  
Regulatory Element ◽  
Dominant Negative ◽  
Peroxisome Proliferator ◽  
Small Interfering Rnas ◽  
Inhibitory Protein ◽  
Intact Cells ◽  
Peroxisome Proliferator Activated Receptor

The transcription factor SREBP1c (sterol-regulatory-element-binding protein 1c) is highly expressed in adipose tissue and plays a central role in several aspects of adipocyte development including the induction of PPARγ (peroxisome-proliferator-activated receptor γ), the generation of an endogenous PPARγ ligand and the expression of several genes critical for lipid biosynthesis. Despite its significance, the regulation of SREBP1c expression during adipogenesis is not well characterized. We have noted that in several models of adipogenesis, SREBP1c expression closely mimics that of known C/EBPβ (CCAAT/enhancer-binding protein β) targets. Inhibition of C/EBP activity during adipogenesis by expressing either the dominant-negative C/EBPβ LIP (liver-enriched inhibitory protein) isoform, the co-repressor ETO (eight-twenty one/MTG8) or using siRNAs (small interfering RNAs) targeting either C/EBPβ or C/EBPδ significantly impaired early SREBP1c induction. Furthermore, ChIP (chromatin immunoprecipitation) assays identified specific sequences in the SREBP1c promoter to which C/EBPβ and C/EBPδ bind in intact cells, demonstrating that these factors may directly regulate SREBP1c expression. Using cells in which C/EBPα expression is inhibited using shRNA (short hairpin RNA) and ChIP assays we show that C/EBPα replaces C/EBPβ and C/EBPδ as a regulator of SREBP1c expression in maturing adipocytes. These results provide novel insight into the induction of SREBP1c expression during adipogenesis. Moreover, the findings of the present study identify an important additional mechanism via which the C/EBP transcription factors may control a network of gene expression regulating adipogenesis, lipogenesis and insulin sensitivity.

scholarly journals MLL3/MLL4-Associated PAGR1 Regulates Adipogenesis by Controlling Induction of C/EBPβ and C/EBPδ

2020 ◽  
Vol 40 (17) ◽  
Author(s):  
Ji-Eun Lee ◽  
Young-Wook Cho ◽  
Chu-Xia Deng ◽  
Kai Ge
Keyword(s):  
Transcription Factors ◽  
Muscle Development ◽  
Critical Role ◽  
Ectopic Expression ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Histone Methyltransferases ◽  
Brown Adipose ◽  
Phosphorylated Creb

ABSTRACT Transcription factors C/EBPβ and C/EBPδ are induced within hours after initiation of adipogenesis in culture. They directly promote the expression of master adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and C/EBPα and are required for adipogenesis in vivo. However, the mechanism that controls the induction of C/EBPβ and C/EBPδ remains elusive. We previously showed that histone methyltransferases MLL3/MLL4 and associated PTIP are required for the induction of PPARγ and C/EBPα during adipogenesis. Here, we show MLL3/MLL4/PTIP-associated protein PAGR1 (also known as PA1) cooperates with phosphorylated CREB and ligand-activated glucocorticoid receptor to directly control the induction of C/EBPβ and C/EBPδ in the early phase of adipogenesis. Deletion of Pagr1 in white and brown preadipocytes prevents the induction of C/EBPβ and C/EBPδ and leads to severe defects in adipogenesis. Adipogenesis defects in PAGR1-deficient cells can be rescued by the ectopic expression of C/EBPβ or PPARγ. Finally, the deletion of Pagr1 in Myf5+ precursor cells impairs brown adipose tissue and muscle development. Thus, by controlling the induction of C/EBPβ and C/EBPδ, PAGR1 plays a critical role in adipogenesis.

FOOD SECURITY: EFFECT ON PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA (PPARY) AND BMI AMONG YOUNG ADULT

2016 ◽  
Vol 78 (6-8) ◽  
Author(s):  
Nur Atiqah Alias ◽  
Norazmir Md Nor ◽  
Mohd Fahmi Mastuki ◽  
Khairil Anuar Md Isa
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Food Security ◽  
Adipocyte Differentiation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Food Security Status ◽  
Metabolic Indices ◽  
Pparγ Expression ◽  
Sensitivity Increase

Food security status is a method used to differentiate food secure and food insecure experience. Throughout our lives, nutritious food and lifestyle are closely related with most lifestyle-associated illness. This study investigated young adults in both groups to determine molecular changes on gene expression of peroxisome proliferator-activated receptor-gamma (PPARγ). PPARγ plays an important role in adipocyte differentiation, fatty acids, and insulin sensitivity. Increase of PPARγ expression help to improve metabolic indices in dysregulated metabolism associated with obesity, diabetes, and cardiovascular disease. There are no significant differences (P>0.05) of PPARγ expression and BMI for both groups. However, expression of PPARγ is detected in earlier amplification for food insecure group. Mean of BMI (20.70± 3.025) is also slightly higher in food insecure group than food secure. Conclusively, there are some effects on expression of PPARγ and BMI based on food security status. 

scholarly journals Regulation of Peroxisome Proliferator-Activated Receptor γ Expression by Adipocyte Differentiation and Determination Factor 1/Sterol Regulatory Element Binding Protein 1: Implications for Adipocyte Differentiation and Metabolism

1999 ◽  
Vol 19 (8) ◽  
pp. 5495-5503 ◽  
Author(s):  
Lluis Fajas ◽  
Kristina Schoonjans ◽  
Laurent Gelman ◽  
Jae B. Kim ◽  
Jamila Najib ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Adipocyte Differentiation ◽  
Binding Protein ◽  
Regulatory Element ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Pparγ Expression

ABSTRACT Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor implicated in adipocyte differentiation and insulin sensitivity. We investigated whether PPARγ expression is dependent on the activity of adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1 (ADD-1/SREBP-1), another transcription factor associated with both adipocyte differentiation and cholesterol homeostasis. Ectopic expression of ADD-1/SREBP-1 in 3T3-L1 and HepG2 cells induced endogenous PPARγ mRNA levels. The related transcription factor SREBP-2 likewise induced PPARγ expression. In addition, cholesterol depletion, a condition known to result in proteolytic activation of transcription factors of the SREBP family, induced PPARγ expression and improved PPRE-driven transcription. The effect of the SREBPs on PPARγ expression was mediated through the PPARγ1 and -3 promoters. Both promoters contain a consensus E-box motif that mediates the regulation of the PPARγ gene by ADD-1/SREBP-1 and SREBP-2. These results suggest that PPARγ expression can be controlled by the SREBP family of transcription factors and demonstrate new interactions between transcription factors that can regulate different pathways of lipid metabolism.

scholarly journals Intake of Watermelon and Watermelon Byproducts in Male Mice Fed a Western-Style Obesogenic Diet Alters Hepatic Gene Expression Patterns, as Determined by RNA Sequencing

2020 ◽  
Vol 4 (8) ◽  
Author(s):  
Mariana Buranelo Egea ◽  
Gavin Pierce ◽  
Alexandra R Becraft ◽  
Marlena Sturm ◽  
Wesley Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Rna Sequencing ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Hepatic Gene Expression ◽  
Peroxisome Proliferator Activated Receptor ◽  
Expression Levels

ABSTRACT Background Consumption of watermelon has been associated with beneficial effects on metabolism, including reductions in systolic blood pressure, improved fasting blood glucose levels, and changes in hepatic metabolite accumulation. Objectives In the present study, we investigated the impact of consumption of watermelon flesh (WF), watermelon rind (WR), and watermelon skin (WS) on hepatic gene expression patterns in an obesogenic mouse model. Methods Hepatic RNA was isolated and RNA sequencing was performed following a 10-week feeding trial during which C57BL/6 J mice were provided either a low-fat diet (LF), high-fat diet (HF; controls), or HF plus either WS, WR, or WF. Bioinformatic approaches were used to determine changes in the canonical pathways and gene expression levels for lipid- and xenobiotic-regulating nuclear hormone receptors and other related transcription factors, including the aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), farnesyl X receptor, peroxisome proliferator–activated receptor alpha (PPARα), peroxisome proliferator–activated receptor gamma, liver X receptor, pregnane X receptor, and nuclear factor erythroid 2–related factor 2. Results There were 9394 genes that had unchanged expression levels between all 5 diet groups, and 247, 58, and 34 genes were uniquely expressed in the WF, WR, and WS groups, respectively. The relative levels of mRNAs regulated by AhR, CAR, and PPARα were upregulated in mice in the WF group, as compared to the HF control mice; in comparison, mRNAs regulated mainly by CAR were upregulated in mice in the WR and WS groups, compared to those in the HF control group. Conclusions At modest levels of intake reflective of typical human consumption, mice in the WF, WS, and WR groups exhibited hepatic gene expression profiles that were altered when compared to mice in the HF control group. Several of these changes involve genes regulated by ligand-responsive transcription factors implicated in xenobiotic and lipid metabolisms, suggesting that the modulation of these transcription factors occurred in response to the consumption of WS, WR, and WF. Some of these changes are likely due to nuclear hormone receptor–mediated changes involved in lipid and xenobiotic metabolisms.

scholarly journals Exercise training impacts skeletal muscle gene expression related to the kynurenine pathway

2019 ◽  
Vol 316 (3) ◽  
pp. C444-C448 ◽  
Author(s):  
David J. Allison ◽  
Joshua P. Nederveen ◽  
Tim Snijders ◽  
Kirsten E. Bell ◽  
Dinesh Kumbhare ◽  
...  
Keyword(s):  
Gene Expression ◽  
Older Adults ◽  
Skeletal Muscle ◽  
Transcription Factors ◽  
Exercise Training ◽  
Kynurenine Pathway ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Muscle Gene Expression ◽  
Muscle Gene

Exercise positively impacts mood and symptoms of depression; however, the mechanisms underlying these effects are not fully understood. Recent evidence highlights a potential role for skeletal muscle-derived transcription factors to influence tryptophan metabolism, along the kynurenine pathway, which has important implications in depression. This has important consequences for older adults, whose age-related muscle deterioration may influence this pathway and may increase their risk for depression. Although exercise training has been shown to improve skeletal muscle mass in older adults, whether this also translates into improvements in transcription factors and metabolites related to the kynurenine pathway has yet to be examined. The aim of the present study was to examine the influence of a 12-wk exercise program on skeletal muscle gene expression of transcription factors, kynurenine aminotransferase (KAT) gene expression, and plasma concentrations of tryptophan metabolites (kynurenines) in healthy older men over 65 yr of age. Exercise training significantly increased skeletal muscle gene expression of transcription factors (peroxisome proliferator-activated receptor-γ coactivator 1α, peroxisome proliferator-activated receptor-α, and peroxisome proliferator-activated receptor-δ: 1.77, 1.99, 2.18-fold increases, respectively, P < 0.01] and KAT isoforms 1–4 (6.5, 2.1, 2.2, and 2.6-fold increases, respectively, P ≤ 0.01). Concentrations of plasma kynurenines were not altered. These results demonstrate that 12 wk of exercise training significantly altered skeletal muscle gene expression of transcription factors and gene expression related to the kynurenine pathway, but not circulating kynurenine metabolites in older men. These findings warrant future research to determine whether distinct exercise modalities or varying intensities could induce a shift in the kynurenine pathway in depressed older adults.

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