scholarly journals The Role of PPARs in Cancer

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-15 ◽  
Author(s):  
Keisuke Tachibana ◽  
Daisuke Yamasaki ◽  
Kenji Ishimoto ◽  
Takefumi Doi
Keyword(s):  
Fatty Acid ◽  
Density Lipoprotein ◽  
Nuclear Hormone Receptor ◽  
Keratinocyte Differentiation ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Cancer Cell Growth ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. PPAR is mainly expressed in the liver, where it activates fatty acid catabolism. PPAR activators have been used to treat dyslipidemia, causing a reduction in plasma triglyceride and elevation of high-density lipoprotein cholesterol. PPAR is expressed ubiquitously and is implicated in fatty acid oxidation and keratinocyte differentiation. PPAR activators have been proposed for the treatment of metabolic disease. PPAR2 is expressed exclusively in adipose tissue and plays a pivotal role in adipocyte differentiation. PPAR is involved in glucose metabolism through the improvement of insulin sensitivity and represents a potential therapeutic target of type 2 diabetes. Thus PPARs are molecular targets for the development of drugs treating metabolic syndrome. However, PPARs also play a role in the regulation of cancer cell growth. Here, we review the function of PPARs in tumor growth.

scholarly journals The PPARδ Agonist GW501516 Improves Lipolytic/Lipogenic Balance through CPT1 and PEPCK during the Development of Pre-Implantation Bovine Embryos

2019 ◽  
Vol 20 (23) ◽  
pp. 6066 ◽  
Author(s):  
Muhammad Idrees ◽  
Lianguang Xu ◽  
Marwa El Sheikh ◽  
Tabinda Sidrat ◽  
Seok-Hwan Song ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Embryo Development ◽  
Embryo Quality ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Bovine Embryo ◽  
Bovine Embryos ◽  
Peroxisome Proliferator Activated Receptors

The PPARs (peroxisome proliferator-activated receptors) play critical roles in the regulation of lipid and glucose metabolism. PPARδ, a member of the PPARs family, is associated with decreased susceptibility to ectopic lipid deposition and is implicated in the regulation of mitochondrial processes. The current study aimed to determine the role of PPARδ in fatty acid β-oxidation and its influence on PEPCK for the lipogenic/lipolytic balance during in vitro bovine oocyte maturation and embryo development. Activation of PPARδ by GW501516, but not 2-BP, was indicated by intact embryonic PEPCK (cytosolic) and CPT1 expression and the balance between free fatty acids and mitochondrial β-oxidation that reduced ROS and inhibited p-NF-κB nuclear localization. Genes involved in lipolysis, fatty acid oxidation, and apoptosis showed significant differences after the GW501516 treatment relative to the control- and 2-BP-treated embryos. GSK3787 reversed the PPARδ-induced effects by reducing PEPCK and CPT1 expression and the mitochondrial membrane potential, revealing the importance of PPARδ/PEPCK and PPARδ/CPT1 for controlling lipolysis during embryo development. In conclusion, GW501516-activated PPARδ maintained the correlation between lipolysis and lipogenesis by enhancing PEPCK and CPT1 to improve bovine embryo quality.

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 PPARα: Energy Combustion, Hypolipidemia, Inflammation and Cancer

2010 ◽  
Vol 8 (1) ◽  
pp. nrs.08002 ◽  
Author(s):  
Sean R. Pyper ◽  
Navin Viswakarma ◽  
Songtao Yu ◽  
Janardan K. Reddy
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Gene Knockout ◽  
Nuclear Hormone Receptor ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Synthetic Chemicals ◽  
Gene Knockout Mouse ◽  
Lipid Sensor

The peroxisome proliferator-activated receptor α (PPARα, or NR1C1) is a nuclear hormone receptor activated by a structurally diverse array of synthetic chemicals known as peroxisome proliferators. Endogenous activation of PPARα in liver has also been observed in certain gene knockout mouse models of lipid metabolism, implying the existence of enzymes that either generate (synthesize) or degrade endogenous PPARα agonists. For example, substrates involved in fatty acid oxidation can function as PPARα ligands. PPARα serves as a xenobiotic and lipid sensor to regulate energy combustion, hepatic steatosis, lipoprotein synthesis, inflammation and liver cancer. Mainly, PPARα modulates the activities of all three fatty acid oxidation systems, namely mitochondrial and peroxisomal β-oxidation and microsomal co-oxidation, and thus plays a key role in energy expenditure. Sustained activation of PPARα by either exogenous or endogenous agonists leads to the development of hepatocellular carcinoma resulting from sustained oxidative and possibly endoplasmic reticulum stress and liver cell proliferation. PPARα requires transcription coactivator PPAR-binding protein (PBP)/mediator subunit 1(MED1) for its transcriptional activity.

scholarly journals PPARδActivity in Cardiovascular Diseases: A Potential Pharmacological Target

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Angela Tesse ◽  
Ramaroson Andriantsitohaina ◽  
Thierry Ragot
Keyword(s):  
Metabolic Diseases ◽  
Peroxisome Proliferator ◽  
In Vivo Models ◽  
Pharmacological Target ◽  
Cardiovascular Cells ◽  
Peroxisome Proliferator Activated Receptors

Activation of peroxisome proliferator-activated receptors (PPARs), and particularly of PPARαand PPARγ, using selective agonists, is currently used in the treatment of metabolic diseases such as hypertriglyceridemia and type 2 diabetes mellitus. PPARαand PPARγanti-inflammatory, antiproliferative and antiangiogenic properties in cardiovascular cells were extensively clarified in a variety of in vitro and in vivo models. In contrast, the role of PPARδin cardiovascular system is poorly understood. Prostacyclin, the predominant prostanoid released by vascular cells, is a putative endogenous agonist for PPARδ, but only recently PPARδselective synthetic agonists were found, improving studies about the physiological and pathophysiological roles of PPARδactivation. Recent reports suggest that the PPARδactivation may play a pivotal role to regulate inflammation, apoptosis, and cell proliferation, suggesting that this transcriptional factor could become an interesting pharmacological target to regulate cardiovascular cell apoptosis, proliferation, inflammation, and metabolism.

scholarly journals AMPK Phosphorylates Desnutrin/ATGL and Hormone-Sensitive Lipase To Regulate Lipolysis and Fatty Acid Oxidation within Adipose Tissue

2016 ◽  
Vol 36 (14) ◽  
pp. 1961-1976 ◽  
Author(s):  
Sun-Joong Kim ◽  
Tianyi Tang ◽  
Marcia Abbott ◽  
Jose A. Viscarra ◽  
Yuhui Wang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Hydrolase Activity ◽  
Hormone Sensitive Lipase ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Hormone Sensitive

The role of AMP-activated protein kinase (AMPK) in promoting fatty acid (FA) oxidation in various tissues, such as liver and muscle, has been well understood. However, the role of AMPK in lipolysis and FA metabolism in adipose tissue has been controversial. To investigate the role of AMPK in the regulation of adipose lipolysisin vivo, we generated mice with adipose-tissue-specific knockout of both the α1 and α2 catalytic subunits of AMPK (AMPK-ASKO mice) by using aP2-Cre and adiponectin-Cre. Both models of AMPK-ASKO ablation show no changes in desnutrin/ATGL levels but have defective phosphorylation of desnutrin/ATGL at S406 to decrease its triacylglycerol (TAG) hydrolase activity, lowering basal lipolysis in adipose tissue. These mice also show defective phosphorylation of hormone-sensitive lipase (HSL) at S565, with higher phosphorylation at protein kinase A sites S563 and S660, increasing its hydrolase activity and isoproterenol-stimulated lipolysis. With higher overall adipose lipolysis, both models of AMPK-ASKO mice are lean, having smaller adipocytes with lower TAG and higher intracellular free-FA levels. Moreover, FAs from higher lipolysis activate peroxisome proliferator-activated receptor delta to induce FA oxidative genes and increase FA oxidation and energy expenditure. Overall, for the first time, we providein vivoevidence of the role of AMPK in the phosphorylation and regulation of desnutrin/ATGL and HSL and thus adipose lipolysis.

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 Nuclear Control of the Inflammatory Response in Mammals by Peroxisome Proliferator-Activated Receptors

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-23 ◽  
Author(s):  
Stéphane Mandard ◽  
David Patsouris
Keyword(s):  
Inflammatory Response ◽  
Protective Role ◽  
Peroxisome Proliferator ◽  
Nuclear Control ◽  
Inflammatory Bowel ◽  
Peroxisome Proliferator Activated Receptors ◽  
Ppar Ligands ◽  
The Impact

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that play pivotal roles in the regulation of a very large number of biological processes including inflammation. Using specific examples, this paper focuses on the interplay between PPARs and innate immunity/inflammation and, when possible, compares it among species. We focus on recent discoveries establishing how inflammation and PPARs interact in the context of obesity-induced inflammation and type 2 diabetes, mostly in mouse and humans. We illustrate that PPARγability to alleviate obesity-associated inflammation raises an interesting pharmacologic potential. In the light of recent findings, the protective role of PPARαand PPARβ/δagainst the hepatic inflammatory response is also addressed. While PPARs agonists are well-established agents that can treat numerous inflammatory issues in rodents and humans, surprisingly very little has been described in other species. We therefore also review the implication of PPARs in inflammatory bowel disease; acute-phase response; and central, cardiac, and endothelial inflammation and compare it along different species (mainly mouse, rat, human, and pig). In the light of the data available in the literature, there is no doubt that more studies concerning the impact of PPAR ligands in livestock should be undertaken because it may finally raise unconsidered health and sanitary benefits.

The Role of Peroxisome Proliferator-Activated Receptor in Addiction: A Novel Drug Target

2021 ◽  
Vol 21 ◽  
Author(s):  
Carla Quiroga ◽  
Juan José Barberena ◽  
Jocelyne Alcaraz-Silva ◽  
Sérgio Machado ◽  
Claudio Imperatori ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Acid Oxidation ◽  
Critical Element ◽  
Peroxisome Proliferator ◽  
Addictive Behaviors ◽  
Health Issues ◽  
Peroxisome Proliferator Activated Receptor ◽  
Peroxisome Proliferator Activated Receptors ◽  
Novel Drug

: The peroxisome proliferator activated receptors (PPARs) are a superfamily of well-recognized ligand-binding nuclear receptors comprising three isoforms: PPARα, PPARγ, and PPARβ/δ. In response to endogenous lipid messengers, PPARs trigger the transcription of genes related to a wider spectrum of physiological phenomena, including fatty acid oxidation, inflammation, and adipogenesis among many others. Thus, the importance of PPARs as putative protective therapy in health issues has increased the interest in studying these nuclear receptors, including the management of neurodegenerative disorders, multiple sclerosis, and likely addiction. In recent years, several pieces of evidence from animal models have demonstrated the promising role of PPARs as a critical element for interventions in addictive behaviors by reducing the reinforcing properties of addictive substances such as alcohol. However, there is a lack of data in scope and has so far been unexplored the function of PPARs in additional drugs such as cannabis, opioids, methamphetamine, or cocaine. Similar scenario has been found for the management of binge-type eating disorders. Thus, here we review recent advances in understanding the relevance of the PPAR controlling addiction.

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