scholarly journals PPARs as Nuclear Receptors for Nutrient and Energy Metabolism

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2545 ◽  
Author(s):  
Fan Hong ◽  
Shijia Pan ◽  
Yuan Guo ◽  
Pengfei Xu ◽  
Yonggong Zhai
Keyword(s):  
Energy Metabolism ◽  
Nuclear Receptors ◽  
Metabolic Networks ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Metabolic States ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

It has been more than 36 years since peroxisome proliferator-activated receptors (PPARs) were first recognized as enhancers of peroxisome proliferation. Consequently, many studies in different fields have illustrated that PPARs are nuclear receptors that participate in nutrient and energy metabolism and regulate cellular and whole-body energy homeostasis during lipid and carbohydrate metabolism, cell growth, cancer development, and so on. With increasing challenges to human health, PPARs have attracted much attention for their ability to ameliorate metabolic syndromes. In our previous studies, we found that the complex functions of PPARs may be used as future targets in obesity and atherosclerosis treatments. Here, we review three types of PPARs that play overlapping but distinct roles in nutrient and energy metabolism during different metabolic states and in different organs. Furthermore, research has emerged showing that PPARs also play many other roles in inflammation, central nervous system-related diseases, and cancer. Increasingly, drug development has been based on the use of several selective PPARs as modulators to diminish the adverse effects of the PPAR agonists previously used in clinical practice. In conclusion, the complex roles of PPARs in metabolic networks keep these factors in the forefront of research because it is hoped that they will have potential therapeutic effects in future applications.

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 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.

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 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.

scholarly journals Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Energy Homeostasis of Dairy Animals: Exploiting Their Modulation through Nutrigenomic Interventions

2021 ◽  
Vol 22 (22) ◽  
pp. 12463
Author(s):  
Faiz-ul Hassan ◽  
Asif Nadeem ◽  
Zhipeng Li ◽  
Maryam Javed ◽  
Qingyou Liu ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Metabolic Networks ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Metabolic Stress ◽  
Peroxisome Proliferator ◽  
Dietary Amino Acids ◽  
Dairy Animals ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are the nuclear receptors that could mediate the nutrient-dependent transcriptional activation and regulate metabolic networks through energy homeostasis. However, these receptors cannot work properly under metabolic stress. PPARs and their subtypes can be modulated by nutrigenomic interventions, particularly under stress conditions to restore cellular homeostasis. Many nutrients such as polyunsaturated fatty acids, vitamins, dietary amino acids and phytochemicals have shown their ability for potential activation or inhibition of PPARs. Thus, through different mechanisms, all these nutrients can modulate PPARs and are ultimately helpful to prevent various metabolic disorders, particularly in transition dairy cows. This review aims to provide insights into the crucial role of PPARs in energy metabolism and their potential modulation through nutrigenomic interventions to improve energy homeostasis in dairy animals.

scholarly journals Differential Roles of Peroxisome Proliferator-Activated Receptor-αand Receptor-γon Renal Crystal Formation in Hyperoxaluric Rodents

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Kazumi Taguchi ◽  
Atsushi Okada ◽  
Shuzo Hamamoto ◽  
Rei Unno ◽  
Takahiro Kobayashi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Injury ◽  
Crystal Formation ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tubular Cells ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) and related inflammatory and oxidative molecule expression were investigated in a hyperoxaluric rodent model to evaluate thein vivoefficacy of PPAR agonists in preventing renal crystal formation. PPAR expression was examined in a mouse hyperoxaluria kidney stone model induced by daily intra-abdominal glyoxylate injection. Therapeutic effects of the PPARαagonist fenofibrate and PPARγagonist pioglitazone were also assessed in a 1% ethylene glycol-induced rat model of hyperoxaluria. Crystal formation, inflammation, cell injury, apoptosis, and oxidative stress were compared to those of vehicle-treated controls. Quantitative reverse transcription-polymerase chain reaction revealed that PPARαand PPARγexpression decrease and increase, respectively, during crystal formation in hyperoxaluric kidneys. In addition, PPARαlocalized to the cytoplasm of both proximal and distal tubular cells, whereas PPARγaccumulated in the nucleus of proximal tubular cells. Furthermore, renal crystal formation was significantly less prevalent in pioglitazone-treated rats but higher in the fenofibrate-treated and fenofibrate/pioglitazone-cotreated groups compared to controls, thus indicating that pioglitazone, but not fenofibrate, markedly decreased cell inflammation, oxidative stress, and apoptosis. Collectively, the results demonstrated that PPARγsuppressed renal crystal formation via its antioxidative and anti-inflammatory effects; however, the renotoxicity of PPARαmay elicit the opposite effect.

scholarly journals Role of the Peroxisome Proliferator-Activated Receptors, Adenosine Monophosphate-Activated Kinase, and Adiponectin in the Ovary

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Joëlle Dupont ◽  
Christine Chabrolle ◽  
Christelle Ramé ◽  
Lucie Tosca ◽  
Stéphanie Coyral-Castel
Keyword(s):  
Nuclear Receptors ◽  
Energy Homeostasis ◽  
Integrated Control ◽  
Adenosine Monophosphate ◽  
Peroxisome Proliferator ◽  
The Subject ◽  
Fertility Problems ◽  
Peroxisome Proliferator Activated Receptors ◽  
Biological Actions

The mechanisms controlling the interaction between energy balance and reproduction are the subject of intensive investigations. The integrated control of these systems is probably a multifaceted phenomenon involving an array of signals governing energy homeostasis, metabolism, and fertility. Two fuel sensors, PPARs, a superfamily of nuclear receptors and the kinase AMPK, integrate energy control and lipid and glucose homeostasis. Adiponectin, one of the adipocyte-derived factors mediate its actions through the AMPK or PPARs pathway. These three molecules are expressed in the ovary, raising questions about the biological actions of fuel sensors in fertility and the use of these molecules to treat fertility problems. This review will highlight the expression and putative role of PPARs, AMPK, and adiponectin in the ovary, particularly during folliculogenesis, steroidogenesis, and oocyte maturation.

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.

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