Roles of Peroxisome proliferator-activated receptors（PPARs）

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms20215422 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5422 ◽

Cited By ~ 4

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 (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.

PPARs in Calorie Restricted and Genetically Long-Lived Mice

PPAR Research ◽

10.1155/2007/28436 ◽

2007 ◽

Vol 2007 ◽

pp. 1-7 ◽

Cited By ~ 40

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 (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.

Integrating nuclear receptor mobility in models of gene regulation

Nuclear Receptor Signaling ◽

10.1621/nrs.04010 ◽

2006 ◽

Vol 4 (1) ◽

pp. nrs.04010 ◽

Cited By ~ 4

Author(s):

Laurent Gelman ◽

Jerome N. Feige ◽

Cicerone Tudor ◽

Yves Engelborghs ◽

Walter Wahli ◽

...

Keyword(s):

Gene Regulation ◽

Fluorescence Microscopy ◽

Nuclear Receptors ◽

Transcriptional Activity ◽

Molecular Mechanisms ◽

Living Cells ◽

Chromatin Interaction ◽

Peroxisome Proliferator ◽

The mode of action of nuclear receptors in living cells is an actively investigated field but much remains hypothetical due to the lack, until recently, of methods allowing the assessment of molecular mechanisms in vivo. However, these last years, the development of fluorescence microscopy methods has allowed initiating the dissection of the molecular mechanisms underlying gene regulation by nuclear receptors directly in living cells or organisms. Following our analyses on peroxisome proliferator activated receptors (PPARs) in living cells, we discuss here the different models arising from the use of these tools, that attempt to link mobility, DNA binding or chromatin interaction, and transcriptional activity.

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

Nuclear Receptor Signaling ◽

10.1621/nrs.13001 ◽

2015 ◽

Vol 13 (1) ◽

pp. nrs.13001 ◽

Cited By ~ 9

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 ◽

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.

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

Current Medicinal Chemistry ◽

10.2174/1570162x18666201123114934 ◽

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 ◽

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.

PPAR-δin Vascular Pathophysiology

PPAR Research ◽

10.1155/2008/164163 ◽

2008 ◽

Vol 2008 ◽

pp. 1-10 ◽

Cited By ~ 16

Author(s):

Nanping Wang

Keyword(s):

Transcription Factors ◽

Cell Growth ◽

Glucose Metabolism ◽

Nuclear Receptor ◽

Therapeutic Intervention ◽

Peroxisome Proliferator ◽

Cardiovascular Disorders ◽

Direct Effects ◽

Cell Growth And Differentiation ◽

Peroxisome proliferator-activated receptors belong to the superfamily of ligand-dependent nuclear receptor transcription factors, which include three subtypes: PPAR-α,β/δ, andγ. PPAR-δ, play important roles in the regulation of cell growth and differentiation as well as tissue wound and repair. Emerging evidence has also demonstrated that PPAR-δis implicated in lipids and glucose metabolism. Most recently, the direct effects of PPAR-δon cardiovascular processes such as endothelial function and angiogenesis have also been investigated. Therefore, it is suggested that PPAR-δmay have critical roles in cardiovascular pathophysiology and is a potential target for therapeutic intervention of cardiovascular disorders such as atherosclerosis.

Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues

Cells ◽

10.3390/cells8111373 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1373 ◽

Cited By ~ 11

Author(s):

Herring ◽

Elison ◽

Tessem

Keyword(s):

Transcription Factors ◽

Family Member ◽

Nuclear Receptors ◽

Hormone Receptors ◽

Cellular Proliferation ◽

Nuclear Hormone Receptors ◽

Fuel Utilization ◽

Orphan Nuclear Receptors ◽

Tissue Specific ◽

Specific Effects

The Nr4a family of nuclear hormone receptors is composed of three members—Nr4a1/Nur77, Nr4a2/Nurr1 and Nr4a3/Nor1. While currently defined as ligandless, these transcription factors have been shown to regulate varied processes across a host of tissues. Of particular interest, the Nr4a family impinge, in a tissue dependent fashion, on cellular proliferation, apoptosis and fuel utilization. The regulation of these processes occurs through both nuclear and non-genomic pathways. The purpose of this review is to provide a balanced perspective of the tissue specific and Nr4a family member specific, effects on cellular proliferation, apoptosis and fuel utilization.

Nuclear Receptors as Autophagy-Based Antimicrobial Therapeutics

Cells ◽

10.3390/cells9091979 ◽

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 ◽

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.

Peroxisome Proliferator-Activated Receptors and Shock State

The Scientific World JOURNAL ◽

10.1100/tsw.2006.298 ◽

2006 ◽

Vol 6 ◽

pp. 1770-1782 ◽

Cited By ~ 7

Author(s):

Emanuela Esposito ◽

Salvatore Cuzzocrea ◽

Rosaria Meli

Keyword(s):

Transcription Factors ◽

Energy Homeostasis ◽

Hormone Receptors ◽

Inflammatory Responses ◽

Nuclear Hormone Receptor ◽

Peroxisome Proliferator ◽

Shock State ◽

Anti Inflammatory ◽

Inflammatory Molecules

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid, and thyroid hormone receptors. Three isotypes of PPARs have been identified: alpha, beta/delta, and gamma, encoded by different genes and distributed in various tissues. PPARs are implicated in the control of inflammatory responses and in energy homeostasis and, thus, can be defined as metabolic and anti-inflammatory transcription factors. They exert anti-inflammatory effects by inhibiting the induction of proinflammatory cytokines, adhesion molecules, and extracellular matrix proteins, or by stimulating the production of anti-inflammatory molecules. Moreover, PPARs modulate the proliferation, differentiation, and survival of immune cells. This review presents the current state of knowledge regarding the involvement of PPARs in the control of inflammatory response, and their potential therapeutic applications in several types of shock, as well as hemorrhagic, septic, and nonseptic shock.

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

Current Pharmaceutical Design ◽

10.2174/1381612825666190716094852 ◽

2019 ◽

Vol 25 (23) ◽

pp. 2540-2554 ◽

Cited By ~ 5

Author(s):

Waquar Ahsan

Keyword(s):

Peroxisome Proliferator ◽

Expression Of Genes ◽

Current Perspective ◽

Drug Designing ◽

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.