scholarly journals Molecular Mechanisms and Genome-Wide Aspects of PPAR Subtype Specific Transactivation

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Anne Bugge ◽  
Susanne Mandrup
Keyword(s):  
Energy Homeostasis ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Fat Metabolism ◽  
Special Focus ◽  
Peroxisome Proliferator ◽  
Subtype Specificity ◽  
Genome Wide ◽  
Peroxisome Proliferator Activated Receptors

The peroxisome proliferator-activated receptors (PPARs) are central regulators of fat metabolism, energy homeostasis, proliferation, and inflammation. The three PPAR subtypes, PPAR, /, and activate overlapping but also very different target gene programs. This review summarizes the insights into PPAR subtype-specific transactivation provided by genome-wide studies and discusses the recent advances in the understanding of the molecular mechanisms underlying PPAR subtype specificity with special focus on the regulatory role of AF-1.

scholarly journals PPARs, Obesity, and Inflammation

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-10 ◽  
Author(s):  
Rinke Stienstra ◽  
Caroline Duval ◽  
Michael Müller ◽  
Sander Kersten
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Vascular Wall ◽  
Peroxisome Proliferator ◽  
Proinflammatory Mediators ◽  
Inflammatory Status ◽  
Prevalence Of Obesity ◽  
Peroxisome Proliferator Activated Receptors

The worldwide prevalence of obesity and related metabolic disorders is rising rapidly, increasing the burden on our healthcare system. Obesity is often accompanied by excess fat storage in tissues other than adipose tissue, including liver and skeletal muscle, which may lead to local insulin resistance and may stimulate inflammation, as in steatohepatitis. In addition, obesity changes the morphology and composition of adipose tissue, leading to changes in protein production and secretion. Some of these secreted proteins, including several proinflammatory mediators, may be produced by macrophages resident in the adipose tissue. The changes in inflammatory status of adipose tissue and liver with obesity feed a growing recognition that obesity represents a state of chronic low-level inflammation. Various molecular mechanisms have been implicated in obesity-induced inflammation, some of which are modulated by the peroxisome proliferator-activated receptors (PPARs). PPARs are ligand-activated transcription factors involved in the regulation of numerous biological processes, including lipid and glucose metabolism, and overall energy homeostasis. Importantly, PPARs also modulate the inflammatory response, which makes them an interesting therapeutic target to mitigate obesity-induced inflammation and its consequences. This review will address the role of PPARs in obesity-induced inflammation specifically in adipose tissue, liver, and the vascular wall.

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.

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 The Role of Peroxisome Proliferator-Activated Receptors in Colorectal Cancer

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Joo-In Park ◽  
Jong-Young Kwak
Keyword(s):  
Colorectal Cancer ◽  
Dietary Fat ◽  
Energy Homeostasis ◽  
Hormone Receptors ◽  
Clinical Implications ◽  
Peroxisome Proliferator ◽  
Fat Intake ◽  
Nutrient Metabolism ◽  
Peroxisome Proliferator Activated Receptors

Colorectal cancer is one of the most common cancers in the world. Dietary fat intake is a major risk factor for colorectal cancer. Some nuclear hormone receptors play an important role in regulating nutrient metabolism and energy homeostasis. Among these receptors, special attention has been focused on the role of peroxisome proliferator-activated receptors (PPARs) in colorectal cancer, because PPARs are involved in regulation of lipid and carbohydrate metabolism. PPARs are ligand-activated intracellular transcription factors. The PPAR subfamily consists of three subtypes encoded by distinct genes named PPARα, PPARβ/δ, and PPARγ. PPARγis the most extensively studied subtype of PPARs. Even though many investigators have studied the expression and clinical implications of PPARs in colorectal cancer, there are still many controversies about the role of PPARs in colorectal cancer. In this paper, the recent progresses in understanding the role of PPARs in colorectal cancer are summarized.

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 Thyroid hormone receptors regulate adipogenesis and carcinogenesis via crosstalk signaling with peroxisome proliferator-activated receptors

2009 ◽  
Vol 44 (3) ◽  
pp. 143-154 ◽  
Author(s):  
Changxue Lu ◽  
Sheue-Yann Cheng
Keyword(s):  
Thyroid Hormone ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptors ◽  
Peroxisome Proliferator ◽  
Cellular Functions ◽  
Biological Impact ◽  
Hormone Response Elements ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) and thyroid hormone receptors (TRs) are members of the nuclear receptor superfamily. They are ligand-dependent transcription factors that interact with their cognate hormone response elements in the promoters to regulate respective target gene expression to modulate cellular functions. While the transcription activity of each is regulated by their respective ligands, recent studies indicate that via multiple mechanisms PPARs and TRs crosstalk to affect diverse biological functions. Here, we review recent advances in the understanding of the molecular mechanisms and biological impact of crosstalk between these two important nuclear receptors, focusing on their roles in adipogenesis and carcinogenesis.

scholarly journals The role of peroxisome proliferator-activated receptor in the treatment of non-alcoholic fatty liver disease

2017 ◽  
Vol 67 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Xin Sun ◽  
Yan Zhang ◽  
Meilin Xie
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Fatty Liver ◽  
Peroxisome Proliferator Activated Receptors ◽  
Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) has been defined as a spectrum of histological abnormalities and is characterized by significant and excessive accumulation of triglycerides in the hepatocytes in patients without alcohol consumption or other diseases. Current studies are targeting new molecular mechanisms that underlie NAFLD and associated metabolic disorders. Many therapeutic targets have been found and used in clinical studies. Peroxisome proliferator-activated receptors (PPARs) are among the potential targets and have been demonstrated to exert a pivotal role in modulation of NAFLD. Many drugs developed so far are targeted at PPARs. Thus, the aim of this paper is to summarize the roles of PPARs in the treatment of NAFLD.

scholarly journals The Molecular Mechanisms Underlying the Proinflammatory Actions of Thiazolidinediones in Human Macrophages

2007 ◽  
Vol 21 (8) ◽  
pp. 1756-1768 ◽  
Author(s):  
Julie M. Hall ◽  
Donald P. McDonnell
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Systemic Exposure ◽  
Receptor Subtype ◽  
Peroxisome Proliferator ◽  
Independent Manner ◽  
Subtype Specificity ◽  
Monocytes And Macrophages ◽  
Peroxisome Proliferator Activated Receptors

Abstract It is hypothesized that the antiinflammatory actions of peroxisome proliferator-activated receptors (PPARs) may explain the protective effect of these receptors in diabetes, atherosclerosis, cancer, and other inflammatory diseases. However, emerging evidence for proinflammatory activities of activated PPARs is concerning in light of new studies that associate PPAR modulators with an increased incidence of both cardiovascular events in humans and the sporadic formation of tumors in rodents. In an attempt to define the role of each PPAR subtype in inflammation, we made the unexpected observation that human PPARδ is a positive regulator of inflammatory responses in both monocytes and macrophages. Notably, TNFα-stimulated cells administered PPARδ agonists express and secrete elevated levels of inflammatory cytokines. Most surprising, however, was the finding that thiazolidinediones (TZDs) and other known PPARγ ligands display different degrees of proinflammatory activities in a PPARγ- and PPARα-independent manner via their ability to augment PPARδ signaling. A series of mechanistic studies revealed that TZDs, at clinically relevant concentrations, bind and activate the transcriptional activity of PPARδ. Collectively, these studies suggest that the observed proinflammatory and potentially deleterious effects of PPARγ ligands may be mediated through an off-target effect on PPARδ. These studies highlight the need for PPAR modulators with increased receptor subtype specificity. Furthermore, they suggest that differences in systemic exposure and consequently in the activation of PPARγ and PPARδ may explain why TZDs can exhibit both inflammatory and antiinflammatory activities in humans.

scholarly journals PPAR-γ: Therapeutic Potential for Multiple Sclerosis

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Paul D. Drew ◽  
Jihong Xu ◽  
Michael K. Racke
Keyword(s):  
Multiple Sclerosis ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Peroxisome Proliferator ◽  
Autoimmune Encephalomyelitis ◽  
Ppar Γ ◽  
Peroxisome Proliferator Activated Receptors ◽  
Experimental Autoimmune

The role of peroxisome proliferator-activated receptors (PPARs) in altering lipid and glucose metabolism is well established. More recent studies indicate that PPARs also play critical roles in controlling immune responses. We and others have previously demonstrated that PPAR-γagonists modulate the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). This review will discuss the cellular and molecular mechanisms by which these agonists are believed to modulate disease. The therapeutic potential of PPAR-γagonists in the treatment of multiple sclerosis will also be considered.

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