scholarly journals Peroxisome Proliferator-Activated Receptors and the Heart: Lessons from the Past and Future Directions

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-18 ◽  
Author(s):  
Wang-Soo Lee ◽  
Jaetaek Kim
Keyword(s):  
Nuclear Family ◽  
Current Knowledge ◽  
Therapeutic Option ◽  
Lessons Learned ◽  
Peroxisome Proliferator ◽  
Main Role ◽  
Future Directions ◽  
Drug Candidates ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear family of ligand activated transcriptional factors and comprise three different isoforms, PPAR-α, PPAR-β/δ, and PPAR-γ. The main role of PPARs is to regulate the expression of genes involved in lipid and glucose metabolism. Several studies have demonstrated that PPAR agonists improve dyslipidemia and glucose control in animals, supporting their potential as a promising therapeutic option to treat diabetes and dyslipidemia. However, substantial differences exist in the therapeutic or adverse effects of specific drug candidates, and clinical studies have yielded inconsistent data on their cardioprotective effects. This review summarizes the current knowledge regarding the molecular function of PPARs and the mechanisms of the PPAR regulation by posttranslational modification in the heart. We also describe the results and lessons learned from important clinical trials on PPAR agonists and discuss the potential future directions for this class of drugs.

scholarly journals PPAR Regulation of Inflammatory Signaling in CNS Diseases

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-12 ◽  
Author(s):  
John J. Bright ◽  
Saravanan Kanakasabai ◽  
Wanida Chearwae ◽  
Sharmistha Chakraborty
Keyword(s):  
Hormone Receptors ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Signaling Networks ◽  
Peroxisome Proliferator ◽  
Inflammatory Signaling ◽  
Cns Diseases ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Privileged Site

Central nervous system (CNS) is an immune privileged site, nevertheless inflammation associates with many CNS diseases. Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors that regulate immune and inflammatory responses. Specific ligands for PPAR, , and isoforms have proven effective in the animal models of multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, and trauma/stroke, suggesting their use in the treatment of neuroinflammatory diseases. The activation of NF-B and Jak-Stat signaling pathways and secretion of inflammatory cytokines are critical in the pathogenesis of CNS diseases. Interestingly, PPAR agonists mitigate CNS disease by modulating inflammatory signaling network in immune cells. In this manuscript, we review the current knowledge on how PPARs regulate neuroinflammatory signaling networks in CNS diseases.

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 Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
White Adipocyte ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

scholarly journals PPARs in Liver Diseases and Cancer: Epigenetic Regulation by MicroRNAs

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Marion Peyrou ◽  
Pierluigi Ramadori ◽  
Lucie Bourgoin ◽  
Michelangelo Foti
Keyword(s):  
Liver Diseases ◽  
Metabolic Diseases ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Hepatocellular Adenoma ◽  
Peroxisome Proliferator ◽  
Cancer Therapies ◽  
Ppar Agonists ◽  
Expression And Activity

Peroxisome-proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that exert in the liver a transcriptional activity regulating a whole spectrum of physiological functions, including cholesterol and bile acid homeostasis, lipid/glucose metabolism, inflammatory responses, regenerative mechanisms, and cell differentiation/proliferation. Dysregulations of the expression, or activity, of specific PPAR isoforms in the liver are therefore believed to represent critical mechanisms contributing to the development of hepatic metabolic diseases, disorders induced by hepatic viral infections, and hepatocellular adenoma and carcinoma. In this regard, specific PPAR agonists have proven to be useful to treat these metabolic diseases, but for cancer therapies, the use of PPAR agonists is still debated. Interestingly, in addition to previously described mechanisms regulating PPARs expression and activity, microRNAs are emerging as new important regulators of PPAR expression and activity in pathophysiological conditions and therefore may represent future therapeutic targets to treat hepatic metabolic disorders and cancers. Here, we reviewed the current knowledge about the general roles of the different PPAR isoforms in common chronic metabolic and infectious liver diseases, as well as in the development of hepatic cancers. Recent works highlighting the regulation of PPARs by microRNAs in both physiological and pathological situations with a focus on the liver are also discussed.

scholarly journals The Renoprotective Actions of Peroxisome Proliferator-Activated Receptors Agonists in Diabetes

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
M. C. Thomas ◽  
K. A. Jandeleit-Dahm ◽  
C. Tikellis
Keyword(s):  
Cardiovascular Effects ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Oral Hypoglycaemic Agents ◽  
Diabetic Kidney ◽  
Critical Pathways ◽  
Patients With Diabetes ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
In The Diabetic Kidney

Pharmaceutical agonists of peroxisome proliferator-activated receptors (PPARs) are widely used in the management of type 2 diabetes, chiefly as lipid-lowering agents and oral hypoglycaemic agents. Although most of the focus has been placed on their cardiovascular effects, both positive and negative, these agents also have significant renoprotective actions in the diabetic kidney. Over and above action on metabolic control and effects on blood pressure, PPAR agonists also appear to have independent effects on a number of critical pathways that are implicated in the development and progression of diabetic kidney disease, including oxidative stress, inflammation, hypertrophy, and podocyte function. This review will examine these direct and indirect actions of PPAR agonists in the diabetic kidney and explore recent findings of clinical trials of PPAR agonists in patients with diabetes.

scholarly journals PPAR Action in Human Placental Development and Pregnancy and Its Complications

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-14 ◽  
Author(s):  
Fritz Wieser ◽  
Leslie Waite ◽  
Christophe Depoix ◽  
Robert N. Taylor
Keyword(s):  
Gestational Diabetes ◽  
Metabolic Regulation ◽  
Current Knowledge ◽  
Clinical Pregnancy ◽  
Trophoblast Invasion ◽  
Peroxisome Proliferator ◽  
Placental Development ◽  
Human Trophoblast ◽  
Peroxisome Proliferator Activated Receptors ◽  
Specific Disorders

During pregnancy crucial anatomic, physiologic, and metabolic changes challenge the mother and the fetus. The placenta is a remarkable organ that allows the mother and the fetus to adapt to the new metabolic, immunologic, and angiogenic environment imposed by gestation. One of the physiologic systems that appears to have evolved to sustain this metabolic regulation is mediated by peroxisome proliferator-activated receptors (PPARs). In clinical pregnancy-specific disorders, including preeclampsia, gestational diabetes, and intrauterine growth restriction, aberrant regulation of components of the PPAR system parallels dysregulation of metabolism, inflammation and angiogenesis. This review summarizes current knowledge on the role of PPARs in regulating human trophoblast invasion, early placental development, and also in the physiology of clinical pregnancy and its complications. As increasingly indicated in the literature, pregnancy disorders, such as preeclampsia and gestational diabetes, represent potential targets for treatment with PPAR ligands. With the advent of more specific PPAR agonists that exhibit efficacy in ameliorating metabolic, inflammatory, and angiogenic disturbances, further studies of their application in pregnancy-related diseases are warranted.

scholarly journals The endocannabinoid pathway and the female reproductive organs

2012 ◽  
Vol 50 (1) ◽  
pp. R1-R9 ◽  
Author(s):  
Anna Maria Di Blasio ◽  
Michele Vignali ◽  
Davide Gentilini
Keyword(s):  
Signal Transduction ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Reproductive Organs ◽  
Signal Transduction Pathways ◽  
Peroxisome Proliferator ◽  
Pathological Conditions ◽  
Peroxisome Proliferator Activated Receptors ◽  
Synthesis And Degradation ◽  
Female Reproductive Organs

Endocannabinoids are endogenous ligands of cannabinoid, vanilloid and peroxisome proliferator-activated receptors that activate multiple signal transduction pathways. Together with their receptor and the enzymes responsible for their synthesis and degradation, these compounds constitute the endocannabinoid system that has been recently shown to play, in humans, an important role in modulating several central and peripheral functions including reproduction. Given the relevance of the system, drugs that are able to interfere with the activity of endocannabinoids are currently considered as candidates for the treatment of various diseases. In this review, we will summarise the current knowledge regarding the effects of endocannabinoids in female reproductive organs. In particular, we will focus on some newly reported mechanisms that can affect endometrial plasticity both in physiological and in pathological conditions.

scholarly journals Peroxisome Proliferator-Activated Receptors (PPARs) as Potential Inducers of Antineoplastic Effects in CNS Tumors

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Lars Tatenhorst ◽  
Eric Hahnen ◽  
Michael T. Heneka
Keyword(s):  
Central Nervous System ◽  
Hormone Receptors ◽  
Tumor Therapy ◽  
Peroxisome Proliferator ◽  
Ppar Agonists ◽  
The Central Nervous System ◽  
Peroxisome Proliferator Activated Receptors ◽  
Underlying Mechanisms

The peroxisome proliferator-activated receptors (PPARs) are ligand-inducible transcription factors which belong to the superfamily of nuclear hormone receptors. In recent years it turned out that natural as well as synthetic PPAR agonists exhibit profound antineoplastic as well as redifferentiation effects in tumors of the central nervous system (CNS). The molecular understanding of the underlying mechanisms is still emerging, with partially controverse findings reported by a number of studies dealing with the influence of PPARs on treatment of tumor cells in vitro. Remarkably, studies examining the effects of these drugs in vivo are just beginning to emerge. However, the agonists of PPARs, in particular the thiazolidinediones, seem to be promising candidates for new approaches in human CNS tumor therapy.

scholarly journals Mitochondria, PPARs, and Cancer: Is Receptor-Independent Action of PPAR Agonists a Key?

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-10 ◽  
Author(s):  
Roberto Scatena ◽  
Patrizia Bottoni ◽  
Bruno Giardina
Keyword(s):  
Cell Differentiation ◽  
Side Effects ◽  
Nuclear Receptors ◽  
Cancer Biology ◽  
Experimental Models ◽  
Peroxisome Proliferator ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Reciprocal Influences ◽  
Ppar Ligands

Before the discovery of peroxisome proliferator activated receptors (PPARs), it was well known that certain drugs considered as classical PPAR-alpha agonists induced hepatocarcinoma or peroxisome proliferation in rodents. These drugs were derivatives of fibric acid, and they included clofibrate, bezafibrate, and fenofibrate. However, such toxicity has never been observed in human patients treated with these hypolipidemic drugs. Thiazolidinediones are a new class of PPAR activators showing greater specificity for the isoform of PPARs. These drugs are used as insulin sensitizers in the treatment of type II diabetes. In addition, they have been shown to induce cell differentiation or apoptosis in various experimental models of cancer. PPAR- ligands have also been shown to induce cancer cell differentiation and, paradoxically, PPAR- drug activators have been reported to act as carcinogens. The confusing picture that emerges from these data is further complicated by the series of intriguing side effects observed following administration of pharmacological PPAR ligands (rhabdomyolysis, liver and heart toxicity, anemia, leucopenia). These side effects cannot be easily explained by simple interactions between the drug and nuclear receptors. Rather, these side effects seem to indicate that the ligands have biological activity independent of the nuclear receptors. Considering the emerging role of mitochondria in cancer and the potential metabolic connections between this organelle and PPAR physiology, characterization of the reciprocal influences is fundamental not only for a better understanding of cancer biology, but also for more defined pharmacotoxicological profiles of drugs that modulate PPARs.

scholarly journals PPARs and Myocardial Infarction

2020 ◽  
Vol 21 (24) ◽  
pp. 9436
Author(s):  
Kay-Dietrich Wagner ◽  
Nicole Wagner
Keyword(s):  
Myocardial Infarction ◽  
Therapeutic Potential ◽  
Pathological Condition ◽  
Expression Patterns ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Specific Expression ◽  
Ppar Agonists ◽  
Cell Type Specific Expression ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family. They are ligand-activated transcription factors and exist in three different isoforms, PPARα (NR1C1), PPARβ/δ (NR1C2), and PPARγ (NR1C3). PPARs regulate a variety of functions, including glucose and lipid homeostasis, inflammation, and development. They exhibit tissue and cell type-specific expression patterns and functions. Besides the established notion of the therapeutic potential of PPAR agonists for the treatment of glucose and lipid disorders, more recent data propose specific PPAR ligands as potential therapies for cardiovascular diseases. In this review, we focus on the knowledge of PPAR function in myocardial infarction, a severe pathological condition for which therapeutic use of PPAR modulation has been suggested.

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