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 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.

scholarly journals Integrating nuclear receptor mobility in models of gene regulation

2006 ◽  
Vol 4 (1) ◽  
pp. nrs.04010 ◽  
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 ◽  
Peroxisome Proliferator Activated Receptors

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.

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.

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.

Effects of DHEA on metabolic and endocrine functions of adipose tissue

2013 ◽  
Vol 14 (2) ◽  
Author(s):  
Joanna Karbowska ◽  
Zdzislaw Kochan
Keyword(s):  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Tissue Mass ◽  
Triacylglycerol Hydrolysis ◽  
Proliferation And Differentiation ◽  
Hormone Sensitive ◽  
Hormone Biosynthesis ◽  
Peroxisome Proliferator Activated Receptors

AbstractDehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS, are the major circulating adrenal steroids and serve as substrates for sex hormone biosynthesis. DHEA is effectively taken up by adipose tissue, where the concentrations of free DHEA are four to ten times higher than those found in the circulation. DHEA reduces adipose tissue mass and inhibits the proliferation and differentiation of adipocytes; it may also protect against obesity by lowering the activity of stearoyl-CoA desaturase 1 in fat cells. Recent studies demonstrate that DHEA stimulates triacylglycerol hydrolysis in adipose tissue by increasing the expression and activity of adipose triglyceride lipase and hormone-sensitive lipase, the key enzymes of lipolysis. DHEA has been shown to modulate insulin signaling pathways, enhance glucose uptake in adipocytes, and increase insulin sensitivity in patients with DHEA deficiency or abnormal glucose tolerance. Additionally, by suppressing the activity of 11β-hydroxysteroid dehydrogenase 1 in adipocytes, DHEA may promote intra-adipose inactivation of cortisol to cortisone. Several studies have demonstrated that DHEA may also regulate the expression and secretion of adipokines such as leptin, adiponectin, and resistin. The effects of DHEA on adipokine expression in adipose tissue are depot-specific, with visceral fat being the most responsive. The mechanisms underlying DHEA actions in adipose tissue are still unclear; however, they involve nuclear receptors such as androgen receptor and peroxisome proliferator-activated receptors γ and α. Because clinical trials investigating the effects of DHEA failed to yield consistent results, further studies are needed to clarify the role of DHEA in the regulation of human adipose tissue physiology.

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 Peroxisome Proliferator-Activated Receptors in Female Reproduction and Fertility

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Maurizio Vitti ◽  
Giovanna Di Emidio ◽  
Michela Di Carlo ◽  
Gaspare Carta ◽  
Andrea Antonosante ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Energy Homeostasis ◽  
Therapeutic Potential ◽  
Environmental Pollutants ◽  
Peroxisome Proliferator ◽  
Female Reproduction ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Exogenous Agents ◽  
Peroxisome Proliferator Activated Receptors

Reproductive functions may be altered by the exposure to a multitude of endogenous and exogenous agents, drug or environmental pollutants, which are known to affect gene transcription through the peroxisome proliferator-activated receptors (PPARs) activation. PPARs act as ligand activated transcription factors and regulate metabolic processes such as lipid and glucose metabolism, energy homeostasis, inflammation, and cell proliferation and differentiation. All PPARs isotypes are expressed along the hypothalamic-pituitary-gonadal axis and are strictly involved in reproductive functions. Since female fertility and energy metabolism are tightly interconnected, the research on female infertility points towards the exploration of potential PPARs activating/antagonizing compounds, mainly belonging to the class of thiazolidinediones (TZDs) and fibrates, as useful agents for the maintenance of metabolic homeostasis in women with ovarian dysfunctions. In the present review, we discuss the recent evidence about PPARs expression in the hypothalamic-pituitary-gonadal axis and their involvement in female reproduction. Finally, the therapeutic potential of their manipulation through several drugs is also discussed.

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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