3P-0713 Analysis of peroxisome proliferator-activated receptors (PPARs) target genes in the HepG2 cells overexpressing each PPAR isoform in the tetracycline (Tet)-regulated system

2003 ◽  
Vol 4 (2) ◽  
pp. 218
Author(s):  
K. Tachibana ◽  
T. Tanaka ◽  
M. Tagami ◽  
Y. Kobayashi ◽  
T. Katayama ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Target Genes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors

scholarly journals PPARgene: A Database of Experimentally Verified and Computationally Predicted PPAR Target Genes

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Li Fang ◽  
Man Zhang ◽  
Yanhui Li ◽  
Yan Liu ◽  
Qinghua Cui ◽  
...  
Keyword(s):  
In Silico ◽  
Target Gene ◽  
Target Genes ◽  
Prediction Method ◽  
Peroxisome Proliferator ◽  
Physiological Processes ◽  
Peroxisome Proliferator Activated Receptors ◽  
High Throughput Gene Expression ◽  
Responsive Element ◽  
Target Gene Transcription

The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear receptor superfamily. Upon ligand binding, PPARs activate target gene transcription and regulate a variety of important physiological processes such as lipid metabolism, inflammation, and wound healing. Here, we describe the first database of PPAR target genes, PPARgene. Among the 225 experimentally verified PPAR target genes, 83 are for PPARα, 83 are for PPARβ/δ, and 104 are for PPARγ. Detailed information including tissue types, species, and reference PubMed IDs was also provided. In addition, we developed a machine learning method to predict novel PPAR target genes by integratingin silicoPPAR-responsive element (PPRE) analysis with high throughput gene expression data. Fivefold cross validation showed that the performance of this prediction method was significantly improved compared to thein silicoPPRE analysis method. The prediction tool is also implemented in the PPARgene database.

scholarly journals Peroxisome Proliferator-Activated Receptor Subtype- and Cell-Type-Specific Activation of Genomic Target Genes upon Adenoviral Transgene Delivery

2006 ◽  
Vol 26 (15) ◽  
pp. 5698-5714 ◽  
Author(s):  
Ronni Nielsen ◽  
Lars Grøntved ◽  
Hendrik G. Stunnenberg ◽  
Susanne Mandrup
Keyword(s):  
Target Genes ◽  
Receptor Subtype ◽  
Peroxisome Proliferator ◽  
Cell Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Molecular Events ◽  
Adenoviral Delivery ◽  
Cell Type Specific ◽  
Peroxisome Proliferator Activated Receptors ◽  
The Individual

ABSTRACT Investigations of the molecular events involved in activation of genomic target genes by peroxisome proliferator-activated receptors (PPARs) have been hampered by the inability to establish a clean on/off state of the receptor in living cells. Here we show that the combination of adenoviral delivery and chromatin immunoprecipitation (ChIP) is ideal for dissecting these mechanisms. Adenoviral delivery of PPARs leads to a rapid and synchronous expression of the PPAR subtypes, establishment of transcriptional active complexes at genomic loci, and immediate activation of even silent target genes. We demonstrate that PPARγ2 possesses considerable ligand-dependent as well as independent transactivation potential and that agonists increase the occupancy of PPARγ2/retinoid X receptor at PPAR response elements. Intriguingly, by direct comparison of the PPARs (α, γ, and β/δ), we show that the subtypes have very different abilities to gain access to target sites and that in general the genomic occupancy correlates with the ability to activate the corresponding target gene. In addition, the specificity and potency of activation by PPAR subtypes are highly dependent on the cell type. Thus, PPAR subtype-specific activation of genomic target genes involves an intricate interplay between the properties of the subtype- and cell-type-specific settings at the individual target loci.

scholarly journals Improved Insulin Resistance and Lipid Metabolism by Cinnamon Extract through Activation of Peroxisome Proliferator-Activated Receptors

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaoyan Sheng ◽  
Yuebo Zhang ◽  
Zhenwei Gong ◽  
Cheng Huang ◽  
Ying Qin Zang
Keyword(s):  
Insulin Resistance ◽  
Target Genes ◽  
Water Extract ◽  
Food Preparation ◽  
Peroxisome Proliferator ◽  
Cinnamon Extract ◽  
Diet Induced Obesity ◽  
Peroxisome Proliferator Activated Receptors ◽  
High Caloric Diet

Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors involved in the regulation of insulin resistance and adipogenesis. Cinnamon, a widely used spice in food preparation and traditional antidiabetic remedy, is found to activate PPARγandα, resulting in improved insulin resistance, reduced fasted glucose, FFA, LDL-c, and AST levels in high-caloric diet-induced obesity (DIO) anddb/dbmice in its water extract form. In vitro studies demonstrate that cinnamon increases the expression of peroxisome proliferator-activated receptorsγandα(PPARγ/α) and their target genes such as LPL, CD36, GLUT4, and ACO in 3T3-L1 adipocyte. The transactivities of both full length and ligand-binding domain (LBD) of PPARγand PPARαare activated by cinnamon as evidenced by reporter gene assays. These data suggest that cinnamon in its water extract form can act as a dual activator of PPARγandα, and may be an alternative to PPARγactivator in managing obesity-related diabetes and hyperlipidemia.

scholarly journals Structural Basis for PPARs Activation by the Dual PPARα/γ Agonist Sanguinarine: A Unique Mode of Ligand Recognition

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 6012
Author(s):  
Siyu Tian ◽  
Rui Wang ◽  
Shuming Chen ◽  
Jialing He ◽  
Weili Zheng ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Target Genes ◽  
Binding Pocket ◽  
Binding Mode ◽  
Structural Basis ◽  
Peroxisome Proliferator ◽  
Functional Studies ◽  
Glucose And Lipid Metabolism ◽  
Peroxisome Proliferator Activated Receptors ◽  
Dual Agonist

Peroxisome proliferator-activated receptors (PPARs) play crucial roles in glucose and lipid metabolism and inflammation. Sanguinarine is a natural product that is isolated from Sanguinaria Canadensis, a potential therapeutic agent for intervention in chronic diseases. In this study, biochemical and cell-based promoter-reporter gene assays revealed that sanguinarine activated both PPARα and PPARγ, and enhanced their transcriptional activity; thus, sanguinarine was identified as a dual agonist of PPARα/γ. Similar to fenofibrate, sanguinarine upregulates the expression of PPARα-target genes in hepatocytes. Sanguinarine also modulates the expression of key PPARγ-target genes and promotes adipocyte differentiation, but with a lower adipogenic activity compared with rosiglitazone. We report the crystal structure of sanguinarine bound to PPARα, which reveals a unique ligand-binding mode of sanguinarine, dissimilar to the classic Y-shaped binding pocket, which may represent a new pharmacophore that can be optimized for selectively targeting PPARα. Further structural and functional studies uncover the molecular basis for the selectivity of sanguinarine toward PPARα/γ among all three PPARs. In summary, our study identifies a PPARα/γ dual agonist with a unique ligand-binding mode, and provides a promising and viable novel template for the design of dual-targeting PPARs ligands.

scholarly journals Meta-analysis of primary target genes of peroxisome proliferator-activated receptors

2007 ◽  
Vol 8 (7) ◽  
pp. R147 ◽  
Author(s):  
Merja Heinäniemi ◽  
J Oskari Uski ◽  
Tatjana Degenhardt ◽  
Carsten Carlberg
Keyword(s):  
Target Genes ◽  
Meta Analysis ◽  
Peroxisome Proliferator ◽  
Primary Target ◽  
Peroxisome Proliferator Activated Receptors

The metabolic coregulator RIP140: an update

2010 ◽  
Vol 299 (3) ◽  
pp. E335-E340 ◽  
Author(s):  
Asmaà Fritah ◽  
Mark Christian ◽  
Malcolm G. Parker
Keyword(s):  
Nuclear Receptors ◽  
Posttranslational Modifications ◽  
Energy Homeostasis ◽  
Target Genes ◽  
Peroxisome Proliferator ◽  
Transcriptional Coregulator ◽  
Peroxisome Proliferator Activated Receptors ◽  
Direct Regulation

RIP140 is a transcriptional coregulator highly expressed in metabolic tissues where it has important and diverse actions. RIP140-null mice show that it plays a crucial role in the control of lipid metabolism in adipose tissue, skeletal muscle, and the liver and is essential for female fertility. RIP140 has been shown to act as a ligand-dependent transcriptional corepressor for metabolic nuclear receptors such as estrogen-related receptors and peroxisome proliferator-activated receptors. The role of RIP140 as a corepressor has been strengthened by the characterization of RIP140-overexpressing mice, although it emerges through several studies that RIP140 can also behave as a coactivator. Nuclear localization of RIP140 is important for controlling transcription of target genes and is subject to regulation by posttranslational modifications. However, cytoplasmic RIP140 has been shown to play a role in the control of metabolism through direct regulation of glucose transport in adipocytes. In this review, we focus on recent advances highlighting the growing importance of RIP140 as a regulator of energy homeostasis.

How nuclear receptors tell time

2009 ◽  
Vol 107 (6) ◽  
pp. 1965-1971 ◽  
Author(s):  
Michèle Teboul ◽  
Aline Gréchez-Cassiau ◽  
Fabienne Guillaumond ◽  
Franck Delaunay
Keyword(s):  
Nuclear Receptors ◽  
Target Genes ◽  
Clock Genes ◽  
Estrogen Receptor Α ◽  
Nuclear Hormone Receptor ◽  
Circadian Clocks ◽  
Orphan Receptor ◽  
Peroxisome Proliferator ◽  
Peripheral Clocks ◽  
Peroxisome Proliferator Activated Receptors

Most organisms adapt their behavior and physiology to the daily changes in their environment through internal (∼24 h) circadian clocks. In mammals, this time-keeping system is organized hierarchically, with a master clock located in the suprachiasmatic nuclei of the hypothalamus that is reset by light, and that, in turn, coordinates the oscillation of local clocks found in all cells. Central and peripheral clocks control, in a highly tissue-specific manner, hundreds of target genes, resulting in the circadian regulation of most physiological processes. A great deal of knowledge has accumulated during the last decade regarding the molecular basis of mammalian circadian clocks. These studies have collectively demonstrated how a set of clock genes and their protein products interact together in complex feedback transcriptional/translational loops to generate 24-h oscillations at the molecular, cellular, and organism levels. In recent years, a number of nuclear receptors (NRs) have been implicated as important regulators of the mammalian clock mechanism. REV-ERB and retinoid-related orphan receptor NRs regulate directly the core feedback loop and increase its robustness. The glucocorticoid receptor mediates the synchronizing effect of glucocorticoid hormones on peripheral clocks. Other NR family members, including the orphan NR EAR2, peroxisome proliferator activated receptors-α/γ, estrogen receptor-α, and retinoic acid receptors, are also linked to the clockwork mechanism. These findings together establish nuclear hormone receptor signaling as an integral part of the circadian timing system.

Peroxisome proliferator-activated receptors and cardiovascular remodeling

2005 ◽  
Vol 288 (3) ◽  
pp. H1037-H1043 ◽  
Author(s):  
Ernesto L. Schiffrin
Keyword(s):  
Cardiovascular Disease ◽  
Target Genes ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Fat Cell ◽  
Ppar Γ ◽  
Peroxisome Proliferator Activated Receptors ◽  
Prevention Of Cardiovascular Disease

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that heterodimerize with the retinoid X receptor and then modulate the function of many target genes. Three PPARs are known: α, β/δ, and γ. The better known are PPAR-α and PPAR-γ, which may be activated by different synthetic agonists, although the endogenous ligands are unknown. PPAR-α is involved in fatty acid oxidation and expressed in the liver, kidney, and skeletal muscle, whereas PPAR-γ is involved in fat cell differentiation, lipid storage, and insulin sensitivity. However, both have been shown to be present in variable amounts in cardiovascular tissues, including endothelium, smooth muscle cells, macrophages, and the heart. The activators of PPAR-α (fibrates) and PPAR-γ (thiazolidinediones or glitazones) antagonized the actions of angiotensin II in vivo and in vitro and exerted cardiovascular antioxidant and anti-inflammatory effects. PPAR activators lowered blood pressure, induced favorable effects on the heart, and corrected vascular structure and endothelial dysfunction in several rodent models of hypertension. Activators of PPARs may become therapeutic agents useful in the prevention of cardiovascular disease beyond their effects on carbohydrate and lipid metabolism. Some side effects, such as weight gain, as well as documented aggravation of advanced heart failure through fluid retention by glitazones, may, however, limit their therapeutic application in prevention of cardiovascular disease.

scholarly journals PPARdelta in Affected Atopic Dermatitis and Psoriasis: A Possible Role in Metabolic Reprograming

2021 ◽  
Vol 22 (14) ◽  
pp. 7354
Author(s):  
Stefan Blunder ◽  
Petra Pavel ◽  
Deborah Minzaghi ◽  
Sandrine Dubrac
Keyword(s):  
Atopic Dermatitis ◽  
Hormone Receptors ◽  
Target Genes ◽  
Skin Diseases ◽  
Retinoic Acid Receptor ◽  
Skin Inflammation ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Keratinocyte Proliferation ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors expressed in the skin. Three PPAR isotypes, α (NRC1C1), β or δ (NRC1C2) and γ (NRC1C3), have been identified. After activation through ligand binding, PPARs heterodimerize with the 9-cis-retinoic acid receptor (RXR), another nuclear hormone receptor, to bind to specific PPAR-responsive elements in regulatory regions of target genes mainly involved in organogenesis, cell proliferation, cell differentiation, inflammation and metabolism of lipids or carbohydrates. Endogenous PPAR ligands are fatty acids and fatty acid metabolites. In past years, much emphasis has been given to PPARα and γ in skin diseases. PPARβ/δ is the least studied PPAR family member in the skin despite its key role in several important pathways regulating inflammation, keratinocyte proliferation and differentiation, metabolism and the oxidative stress response. This review focuses on the role of PPARβ/δ in keratinocytes and its involvement in psoriasis and atopic dermatitis. Moreover, the relevance of targeting PPARβ/δ to alleviate skin inflammation is discussed.

scholarly journals The PPARα and PPARγ Epigenetic Landscape in Cancer and Immune and Metabolic Disorders

2021 ◽  
Vol 22 (19) ◽  
pp. 10573
Author(s):  
Jesús Porcuna ◽  
Jorge Mínguez-Martínez ◽  
Mercedes Ricote
Keyword(s):  
Metabolic Disorders ◽  
Target Genes ◽  
Dna Methyltransferases ◽  
Nutrient Sensing ◽  
Peroxisome Proliferator ◽  
Obesity And Diabetes ◽  
Histone Modifiers ◽  
Non Coding Rnas ◽  
Peroxisome Proliferator Activated Receptors ◽  
Epigenetic Modulation

Peroxisome proliferator-activated receptors (PPARs) are ligand-modulated nuclear receptors that play pivotal roles in nutrient sensing, metabolism, and lipid-related processes. Correct control of their target genes requires tight regulation of the expression of different PPAR isoforms in each tissue, and the dysregulation of PPAR-dependent transcriptional programs is linked to disorders, such as metabolic and immune diseases or cancer. Several PPAR regulators and PPAR-regulated factors are epigenetic effectors, including non-coding RNAs, epigenetic enzymes, histone modifiers, and DNA methyltransferases. In this review, we examine advances in PPARα and PPARγ-related epigenetic regulation in metabolic disorders, including obesity and diabetes, immune disorders, such as sclerosis and lupus, and a variety of cancers, providing new insights into the possible therapeutic exploitation of PPAR epigenetic modulation.

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