scholarly journals PPARs Integrate the Mammalian Clock and Energy Metabolism

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Lihong Chen ◽  
Guangrui Yang
Keyword(s):  
Energy Metabolism ◽  
Nuclear Receptors ◽  
Essential Role ◽  
Target Gene ◽  
Target Genes ◽  
Circadian Regulation ◽  
Peroxisome Proliferator ◽  
Mouse Tissues ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that function as transcription factors regulating the expression of numerous target genes. PPARs play an essential role in various physiological and pathological processes, especially in energy metabolism. It has long been known that metabolism and circadian clocks are tightly intertwined. However, the mechanism of how they influence each other is not fully understood. Recently, all three PPAR isoforms were found to be rhythmically expressed in given mouse tissues. Among them, PPARαand PPARγare direct regulators of core clock components, Bmal1 and Rev-erbα, and, conversely, PPARαis also a direct Bmal1 target gene. More importantly, recent studies using knockout mice revealed that all PPARs exert given functions in a circadian manner. These findings demonstrated a novel role of PPARs as regulators in correlating circadian rhythm and metabolism. In this review, we summarize advances in our understanding of PPARs in circadian regulation.

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.

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 PPARs in Calorie Restricted and Genetically Long-Lived Mice

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-7 ◽  
Author(s):  
Michal M. Masternak ◽  
Andrzej Bartke
Keyword(s):  
Transcription Factors ◽  
Energy Metabolism ◽  
Nuclear Receptors ◽  
Calorie Restriction ◽  
Insulin Action ◽  
Peroxisome Proliferator ◽  
Physiological Functions ◽  
Multiple Organs ◽  
Longevity Genes ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors superfamily. The three subtypes, PPARα, PPARγ, and PPARβ/δ, are expressed in multiple organs. These transcription factors regulate different physiological functions such as energy metabolism (including lipid and carbohydrate metabolism), insulin action, and immunity and inflammation, and apparently also act as important mediators of longevity and aging. Calorie restriction (CR) is the most effective intervention known to delay aging and increase lifespan. Calorie restriction affects the same physiological functions as PPARs. This review summarizes recent findings on the effects of CR and aging on the expression of PPARγ,α, andβ/δin mice and discusses possible involvement of PPARs in mediating the effects of murine longevity genes. The levels of PPARs change with age and CR appears to prevent these alterations which make “PPARs-CR-AGING” dependence of considerable interest.

scholarly journals Molecular Mechanisms and Genome-Wide Aspects of PPAR Subtype Specific Transactivation

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Anne Bugge ◽  
Susanne Mandrup
Keyword(s):  
Energy Homeostasis ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Fat Metabolism ◽  
Special Focus ◽  
Peroxisome Proliferator ◽  
Subtype Specificity ◽  
Genome Wide ◽  
Peroxisome Proliferator Activated Receptors

The peroxisome proliferator-activated receptors (PPARs) are central regulators of fat metabolism, energy homeostasis, proliferation, and inflammation. The three PPAR subtypes, PPAR, /, and activate overlapping but also very different target gene programs. This review summarizes the insights into PPAR subtype-specific transactivation provided by genome-wide studies and discusses the recent advances in the understanding of the molecular mechanisms underlying PPAR subtype specificity with special focus on the regulatory role of AF-1.

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.

The Role of Peroxisome Proliferator-Activated Receptor in Addiction: A Novel Drug Target

2021 ◽  
Vol 21 ◽  
Author(s):  
Carla Quiroga ◽  
Juan José Barberena ◽  
Jocelyne Alcaraz-Silva ◽  
Sérgio Machado ◽  
Claudio Imperatori ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Acid Oxidation ◽  
Critical Element ◽  
Peroxisome Proliferator ◽  
Addictive Behaviors ◽  
Health Issues ◽  
Peroxisome Proliferator Activated Receptor ◽  
Peroxisome Proliferator Activated Receptors ◽  
Novel Drug

: The peroxisome proliferator activated receptors (PPARs) are a superfamily of well-recognized ligand-binding nuclear receptors comprising three isoforms: PPARα, PPARγ, and PPARβ/δ. In response to endogenous lipid messengers, PPARs trigger the transcription of genes related to a wider spectrum of physiological phenomena, including fatty acid oxidation, inflammation, and adipogenesis among many others. Thus, the importance of PPARs as putative protective therapy in health issues has increased the interest in studying these nuclear receptors, including the management of neurodegenerative disorders, multiple sclerosis, and likely addiction. In recent years, several pieces of evidence from animal models have demonstrated the promising role of PPARs as a critical element for interventions in addictive behaviors by reducing the reinforcing properties of addictive substances such as alcohol. However, there is a lack of data in scope and has so far been unexplored the function of PPARs in additional drugs such as cannabis, opioids, methamphetamine, or cocaine. Similar scenario has been found for the management of binge-type eating disorders. Thus, here we review recent advances in understanding the relevance of the PPAR controlling addiction.

scholarly journals Regulation of Peroxisome Proliferator-Activated Receptors by E6-Associated Protein

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Lakshmi Gopinathan ◽  
Daniel B. Hannon ◽  
Russell W. Smith ◽  
Jeffrey M. Peters ◽  
John P. Vanden Heuvel
Keyword(s):  
Ubiquitin Ligase ◽  
Target Genes ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Independent Manner ◽  
Coordinate Regulation ◽  
Protein Levels ◽  
Ubiquitin Ligase Activity ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors (NRs) that regulate genes involved in lipid and glucose metabolism. PPAR activity is regulated by interactions with cofactors and of interest are cofactors with ubiquitin ligase activity. The E6-associated protein (E6-AP) is an E3 ubiquitin ligase that affects the activity of other NRs, although its effects on PPARs have not been examined. E6-AP inhibited the ligand-independent transcriptional activity of PPARαand PPARβ, with marginal effects on PPARγ, and decreased basal mRNA levels of PPARαtarget genes. Inhibition of PPARαactivity required the ubiquitin ligase function of E6-AP, but occurred in a proteasome-independent manner. PPARαinteracted with E6-AP, and in mice treated with PPARαagonist clofibrate, mRNA and protein levels of E6-AP were increased in wildtype, but not in PPARαnull mice, indicating a PPARα-dependent regulation. These studies suggest coordinate regulation of E6-AP and PPARα, and contribute to our understanding of the role of PPARs in cellular metabolism.

scholarly journals The Role of PPARs in Disease

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2367
Author(s):  
Nicole Wagner ◽  
Kay-Dietrich Wagner
Keyword(s):  
Target Genes ◽  
Peroxisome Proliferator ◽  
Downstream Target ◽  
Novel Approach ◽  
Pparγ Agonists ◽  
Cell Type Specific ◽  
Peroxisome Proliferator Activated Receptors ◽  
Specific Regulation ◽  
X Receptors

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that function as ligand-activated transcription factors. They exist in three isoforms: PPARα, PPARβ/δ, and PPARγ. For all PPARs, lipids are endogenous ligands, linking them directly to metabolism. PPARs form heterodimers with retinoic X receptors, and upon ligand binding, they modulate the gene expression of downstream target genes, depending on the presence of co-repressors or co-activators. This results in a complex, cell type-specific regulation of proliferation, differentiation, and cell survival. PPARs are linked to metabolic disorders and are interesting pharmaceutical targets. PPARα and PPARγ agonists are already in clinical use for the treatment of hyperlipidemia and type 2 diabetes, respectively. More recently, PPARβ/δ activation came into focus as an interesting novel approach for the treatment of metabolic syndrome and associated cardiovascular diseases; however, this has been limited due to the highly controversial function of PPARβ/δ in cancer. This Special Issue of Cells brings together the most recent advances in understanding the various aspects of the action of PPARs, and it provides new insights into our understanding of PPARs, implying also the latest therapeutic perspectives for the utility of PPAR modulation in different disease settings.

scholarly journals Nutrigenomic Functions of PPARs in Obesogenic Environments

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Soonkyu Chung ◽  
Young Jun Kim ◽  
Soo Jin Yang ◽  
Yunkyoung Lee ◽  
Myoungsook Lee
Keyword(s):  
Target Genes ◽  
Current Knowledge ◽  
Critical Role ◽  
Bioactive Molecules ◽  
Metabolic Adaptation ◽  
Peroxisome Proliferator ◽  
Beige Adipocytes ◽  
Peroxisome Proliferator Activated Receptors ◽  
Obesogenic Environments

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that mediate the effects of several nutrients or drugs through transcriptional regulation of their target genes in obesogenic environments. This review consists of three parts. First, we summarize current knowledge regarding the role of PPARs in governing the development of white and brown/beige adipocytes from uncommitted progenitor cells. Next, we discuss the interactions of dietary bioactive molecules, such as fatty acids and phytochemicals, with PPARs for the modulation of PPAR-dependent transcriptional activities and metabolic consequences. Lastly, the effects of PPAR polymorphism on obesity and metabolic outcomes are discussed. In this review, we aim to highlight the critical role of PPARs in the modulation of adiposity and subsequent metabolic adaptation in response to dietary challenges and genetic modifications. Understanding the changes in obesogenic environments as a consequence of PPARs/nutrient interactions may help expand the field of individualized nutrition to prevent obesity and obesity-associated metabolic comorbidities.

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