scholarly journals Integrative and Systemic Approaches for Evaluating PPARβ/δ (PPARD) Function

2015 ◽  
Vol 13 (1) ◽  
pp. nrs.13001 ◽  
Author(s):  
Greta MP Giordano Attianese ◽  
Béatrice Desvergne
Keyword(s):  
Cell Fate ◽  
Nuclear Receptors ◽  
Peroxisome Proliferator ◽  
Independent Manner ◽  
Post Translational Modifications ◽  
Tissue Specific ◽  
Expression Of Genes ◽  
Pathway Function ◽  
Peroxisome Proliferator Activated Receptors ◽  
Systems View

The peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that function as transcription factors regulating the expression of genes involved in cellular differentiation, development, metabolism and also tumorigenesis. Three PPAR isotypes (α, β/δ and γ) have been identified, among which PPARβ/δ (PPARD) is the most difficult to functionally examine due to its tissue-specific diversity in cell fate determination, energy metabolism and housekeeping activities. PPARβ/δ acts both in a ligand-dependent and -independent manner. The specific type of regulation, activation or repression, is determined by many factors, among which the type of ligand, the presence/absence of PPARβ/δ-interacting corepressor or coactivator complexes and PPARβ/δ protein post-translational modifications play major roles. Recently, new global approaches to the study of nuclear receptors have made it possible to evaluate their molecular activity in a more systemic fashion, rather than deeply digging into a single pathway/function. This systemic approach is ideally suited for studying PPARβ/δ, due to its ubiquitous expression in various organs and its overlapping and tissue-specific transcriptomic signatures. The aim of the present review is to present in detail the diversity of PPARβ/δ function, focusing on the different information gained at the systemic level, and describing the global and unbiased approaches that combine a systems view with molecular understanding.

scholarly journals Lifestyle and Food Habits Impact on Chronic Diseases: Roles of PPARs

2019 ◽  
Vol 20 (21) ◽  
pp. 5422 ◽  
Author(s):  
Michele d’Angelo ◽  
Vanessa Castelli ◽  
Maria Grazia Tupone ◽  
Mariano Catanesi ◽  
Andrea Antonosante ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Food Habits ◽  
Transcriptional Activity ◽  
Cellular Proliferation ◽  
Peroxisome Proliferator ◽  
Food Components ◽  
Expression Of Genes ◽  
Proliferation And Differentiation ◽  
Exogenous Factors ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that exert important functions in mediating the pleiotropic effects of diverse exogenous factors such as physical exercise and food components. Particularly, PPARs act as transcription factors that control the expression of genes implicated in lipid and glucose metabolism, and cellular proliferation and differentiation. In this review, we aim to summarize the recent advancements reported on the effects of lifestyle and food habits on PPAR transcriptional activity in chronic disease.

scholarly journals Multiple Interactions between Peroxisome Proliferators-Activated Receptors and the Ubiquitin-Proteasome System and Implications for Cancer Pathogenesis

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-11 ◽  
Author(s):  
Davide Genini ◽  
Giuseppina M. Carbone ◽  
Carlo V. Catapano
Keyword(s):  
Cell Fate ◽  
Nuclear Receptors ◽  
Current Knowledge ◽  
Ubiquitin Proteasome System ◽  
Peroxisome Proliferator ◽  
Protein Levels ◽  
Cancer Pathogenesis ◽  
Ubiquitin Proteasome ◽  
Peroxisome Proliferator Activated Receptors ◽  
Peroxisome Proliferators Activated Receptors

The peroxisome proliferator-activated receptors (PPAR)α, β/δ, andγare ligand-activated nuclear receptors involved in a number of physiological processes, including lipid and glucose homeostasis, inflammation, cell growth, differentiation, and death. PPAR agonists are used in the treatment of human diseases, like type 2 diabetes and dyslipidemia, and PPARs appear as promising therapeutic targets in other conditions, including cancer. A better understanding of the functions and regulation of PPARs in normal and pathological processes is of primary importance to devise appropriate therapeutic strategies. The ubiquitin-proteasome system (UPS) plays an important role in controlling level and activity of many nuclear receptors and transcription factors. PPARs are subjected to UPS-dependent regulation. Interestingly, the three PPAR isotypes are differentially regulated by the UPS in response to ligand-dependent activation, a phenomenon that may be intrinsically connected to their distinct cellular functions and behaviors. In addition to their effects ongene expression, PPARs appear to affect protein levels and downstream pathways also by modulating the activity of the UPS in target-specific manners. Here we review the current knowledge of the interactions between the UPS and PPARs in light of the potential implications for their effects on cell fate and tumorigenesis.

scholarly journals Roles of Peroxisome proliferator-activated receptors（PPARs）

2019 ◽  
Author(s):  
Elisabetta Benedetti
Keyword(s):  
Transcription Factors ◽  
Nuclear Receptors ◽  
Food Habits ◽  
Transcriptional Activity ◽  
Cellular Proliferation ◽  
Peroxisome Proliferator ◽  
Food Components ◽  
Expression Of Genes ◽  
Exogenous Factors ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that exert important functions in mediating the pleiotropic effects of diverse exogenous factors such as  physical exercise and food components. Particularly, PPARs act as transcription factors that control the expression of genes implicated in lipid and glucose metabolism, and cellular proliferation and  differentiation.  In this review, we aimed to summarize recent advancements reported on the effects of lifestyle and food habits on PPAR transcriptional activity.

New trends in the pharmacological intervention of PPARs in obesity: Role of natural and synthetic compounds_

2020 ◽  
Vol 28 ◽  
Author(s):  
Seyed Mohammad Nabavi ◽  
Kasi Pandima Devi ◽  
Sethuraman Sathya ◽  
Ana Sanches-Silva ◽  
Listos Joanna ◽  
...  
Keyword(s):  
Tissue Expression ◽  
Health Concern ◽  
Pharmacological Intervention ◽  
Peroxisome Proliferator ◽  
Expression Of Genes ◽  
Ppar Agonists ◽  
Prevalence Of Obesity ◽  
Peroxisome Proliferator Activated Receptors ◽  
Natural And Synthetic

: Obesity is a major health concern for a growing fraction of the population, with the prevalence of obesity and its related metabolic disorders not being fully understood. Over the last decade, many attempts have been undertaken to understand the mechanisms at the basis of this condition, in which the accumulation of fat occurring in adipose tissue, leads to the pathogenesis of obesity related disorders. Among the most recent studies, those on Peroxisome Proliferator Activated Receptors (PPARs) revealed that these nuclear receptor proteins acting as transcription factors, among others, regulate the expression of genes involved in energy, lipid, and glucose metabolisms, and chronic inflammation. The three different isotypes of PPARs, with different tissue expression and ligand binding specificity, exert similar or overlapping functions directly or indirectly linked to obesity. In this study, we reviewed the available scientific reports concerning the PPARs structure and functions, especially in obesity, considering both natural and synthetic ligands and their role in the therapy of obesity and obesity-associated disorders. In the whole, the collected data show that there are both natural and synthetic compounds that show beneficial promising activity as PPAR agonists in chronic diseases related to obesity.

scholarly journals Post-Translational Modifications of Nuclear Receptors and Human Disease

2012 ◽  
Vol 10 (1) ◽  
pp. nrs.10001 ◽  
Author(s):  
Muralidharan Anbalagan ◽  
Brandy Huderson ◽  
Leigh Murphy ◽  
Brian G. Rowan
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Clinical Outcome ◽  
Nuclear Receptors ◽  
Inflammatory Diseases ◽  
Peroxisome Proliferator ◽  
Additional Measure ◽  
Peroxisome Proliferator Activated Receptor ◽  
Post Translational Modifications ◽  
Pparγ Phosphorylation

Nuclear receptors (NR) impact a myriad of physiological processes including homeostasis, reproduction, development, and metabolism. NRs are regulated by post-translational modifications (PTM) that markedly impact receptor function. Recent studies have identified NR PTMs that are involved in the onset and progression of human diseases, including cancer. The majority of evidence linking NR PTMs with disease has been demonstrated for phosphorylation, acetylation and sumoylation of androgen receptor (AR), estrogen receptor α (ERα), glucocorticoid receptor (GR) and peroxisome proliferator activated receptor γ (PPARΓ). Phosphorylation of AR has been associated with hormone refractory prostate cancer and decreased disease-specific survival. AR acetylation and sumoylation increased growth of prostate cancer tumor models. AR phosphorylation reduced the toxicity of the expanded polyglutamine AR in Kennedy's Disease as a consequence of reduced ligand binding. A comprehensive evaluation of ERα phosphorylation in breast cancer revealed several sites associated with better clinical outcome to tamoxifen therapy, whereas other phosphorylation sites were associated with poorer clinical outcome. ERα acetylation and sumoylation may also have predictive value for breast cancer. GR phosphorylation and acetylation impact GR responsiveness to glucocorticoids that are used as anti-inflammatory drugs. PPARγ phosphorylation can regulate the balance between growth and differentiation in adipose tissue that is linked to obesity and insulin resistance. Sumoylation of PPARγ is linked to repression of inflammatory genes important in patients with inflammatory diseases. NR PTMs provide an additional measure of NR function that can be used as both biomarkers of disease progression, and predictive markers for patient response to NR-directed treatments.

scholarly journals Time-Qualified Patterns of Variation of PPARγ, DNMT1, and DNMT3B Expression in Pancreatic Cancer Cell Lines

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Valerio Pazienza ◽  
Francesca Tavano ◽  
Massimo Francavilla ◽  
Andrea Fontana ◽  
Fabio Pellegrini ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Fate ◽  
Cell Lines ◽  
Expression Profiles ◽  
Dna Methyltransferases ◽  
Nutrient Sensing ◽  
Cell Phenotype ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptors

Carcinogenesis is related to the loss of homeostatic control of cellular processes regulated by transcriptional circuits and epigenetic mechanisms. Among these, the activities of peroxisome proliferator-activated receptors (PPARs) and DNA methyltransferases (DNMTs) are crucial and intertwined. PPARγis a key regulator of cell fate, linking nutrient sensing to transcription processes, and its expression oscillates with circadian rhythmicity. Aim of our study was to assess the periodicity of PPARγand DNMTs in pancreatic cancer (PC). We investigated the time-related patterns ofPPARG, DNMT1, andDNMT3Bexpression monitoring their mRNA levels by qRT-PCR at different time points over a 28-hour span in BxPC-3, CFPAC-1, PANC-1, and MIAPaCa-2 PC cells after synchronization with serum shock.PPARGandDNMT1expression in PANC-1 cells andPPARGexpression in MIAPaCa-2 cells were characterized by a 24 h period oscillation, and a borderline significant rhythm was observed for thePPARG, DNMT1, andDNMT3Bexpression profiles in the other cell lines. The time-qualified profiles of gene expression showed different shapes and phase relationships in the PC cell lines examined. In conclusion,PPARGandDNMTsexpression is characterized by different time-qualified patterns in cell lines derived from human PC, and this heterogeneity could influence cell phenotype and human disease behaviour.

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 Nuclear Receptors as Autophagy-Based Antimicrobial Therapeutics

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1979
Author(s):  
Prashanta Silwal ◽  
Seungwha Paik ◽  
Sang Min Jeon ◽  
Eun-Kyeong Jo
Keyword(s):  
Retinoic Acid ◽  
Nuclear Receptors ◽  
Hormone Receptors ◽  
Emerging Infectious Diseases ◽  
Peroxisome Proliferator ◽  
Vitamin D Receptors ◽  
Gene Sets ◽  
Intracellular Process ◽  
Peroxisome Proliferator Activated Receptors ◽  
X Receptors

Autophagy is an intracellular process that targets intracellular pathogens for lysosomal degradation. Autophagy is tightly controlled at transcriptional and post-translational levels. Nuclear receptors (NRs) are a family of transcriptional factors that regulate the expression of gene sets involved in, for example, metabolic and immune homeostasis. Several NRs show promise as host-directed anti-infectives through the modulation of autophagy activities by their natural ligands or small molecules (agonists/antagonists). Here, we review the roles and mechanisms of NRs (vitamin D receptors, estrogen receptors, estrogen-related receptors, and peroxisome proliferator-activated receptors) in linking immunity and autophagy during infection. We also discuss the potential of emerging NRs (REV-ERBs, retinoic acid receptors, retinoic acid-related orphan receptors, liver X receptors, farnesoid X receptors, and thyroid hormone receptors) as candidate antimicrobials. The identification of novel roles and mechanisms for NRs will enable the development of autophagy-adjunctive therapeutics for emerging and re-emerging infectious diseases.

The Journey of Thiazolidinediones as Modulators of PPARs for the Management of Diabetes: A Current Perspective

2019 ◽  
Vol 25 (23) ◽  
pp. 2540-2554 ◽  
Author(s):  
Waquar Ahsan
Keyword(s):  
Peroxisome Proliferator ◽  
Expression Of Genes ◽  
Current Perspective ◽  
Drug Designing ◽  
Peroxisome Proliferator Activated Receptors ◽  
To Come ◽  
Ppar Ligands ◽  
A Current

Peroxisome Proliferator-Activated Receptors (PPARs) also known as glitazone receptors are a family of receptors that regulate the expression of genes and have an essential role in carbohydrate, lipid and protein metabolism apart from other functions. PPARs come in 3 sub-types: PPAR-α, PPAR-β/δ and PPAR-γ - with PPAR-γ having 2 isoforms - γ1 and γ2. Upon activation, the PPARs regulate the transcription of various genes involved in lipid and glucose metabolism, adipocyte differentiation, increasing insulin sensitivity, prevention of oxidative stress and to a certain extent, modulation of immune responses via macrophages that have been implicated in the pathogenesis of insulin resistance. Hence, PPARs are an attractive molecular target for designing new anti-diabetic drugs. This has led to a boost in the research efforts directed towards designing of PPAR ligands - particularly ones that can selectively and specifically activate one or more of the PPAR subtypes. Though, PPAR- γ full agonists such as Thiazolidinediones (TZDs) are well established agents for dyslipidemia and type 2 diabetes mellitus (T2D), the side effect profile associated with TZDs has potentiated an imminent need to come up with newer agents that act through this pathway. Several newer derivatives having TZD scaffold have been designed using structure based drug designing technique and computational tools and tested for their PPAR binding affinity and efficacy in combating T2D and some have shown promising activities. This review would focus on the role of PPARs in the management of T2D; recently reported TZD derivatives which acted as agonists of PPAR- γ and its subtypes and are potentially useful in the new drug discovery for the disease.

scholarly journals Alteration of a Single Amino Acid in Peroxisome Proliferator-Activated Receptor-α (PPARα) Generates a PPARδ Phenotype

2000 ◽  
Vol 14 (5) ◽  
pp. 733-740 ◽  
Author(s):  
Ichiro Takada ◽  
Ruth T. Yu ◽  
H. Eric Xu ◽  
Millard H. Lambert ◽  
Valerie G. Montana ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nuclear Receptors ◽  
Site Directed Mutagenesis ◽  
Single Amino Acid ◽  
Peroxisome Proliferator ◽  
Transcriptional Responses ◽  
Peroxisome Proliferator Activated Receptor ◽  
Single Amino Acid Change ◽  
Close Relationship ◽  
Peroxisome Proliferator Activated Receptors

Abstract Three pharmacologically important nuclear receptors, the peroxisome proliferator-activated receptors (PPARs α,γ , and δ), mediate key transcriptional responses involved in lipid homeostasis. The PPARα and γ subtypes are well conserved from Xenopus to man, but the β/δ subtypes display substantial species variations in both structure and ligand activation profiles. Characterization of the avian cognates revealed a close relationship between chick (c) α and γ subtypes to their mammalian counterparts, whereas the third chicken subtype was intermediate to Xenopus (x) β and mammalian δ, establishing that β and δ are orthologs. Like xPPARβ, cPPARβ responded efficiently to hypolipidemic compounds that fail to activate the human counterpart. This provided the opportunity to address the pharmacological problem as to how drug selectivity is achieved and the more global evolutionary question as to the minimal changes needed to generate a new class of receptor. X-ray crystallography and chimeric analyses combined with site-directed mutagenesis of avian and mammalian cognates revealed that a Met to Val change at residue 417 was sufficient to switch the human and chick phenotype. These results establish that the genetic drive to evolve a novel and functionally selectable receptor can be modulated by a single amino acid change and suggest how nuclear receptors can accommodate natural variation in species physiology.

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