scholarly journals PPARs: Protectors or Opponents of Myocardial Function?

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-19 ◽  
Author(s):  
Christine J. Pol ◽  
Melissa Lieu ◽  
Konstantinos Drosatos
Keyword(s):  
Myocardial Function ◽  
The United States ◽  
Review Article ◽  
Peroxisome Proliferator ◽  
Metabolic Complications ◽  
Research Findings ◽  
Peroxisome Proliferator Activated Receptors ◽  
Nuclear Receptor Family ◽  
Pharmacologic Agents ◽  
Receptor Family

Over 5 million people in the United States suffer from the complications of heart failure (HF), which is a rapidly expanding health complication. Disorders that contribute to HF include ischemic cardiac disease, cardiomyopathies, and hypertension. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family. There are three PPAR isoforms: PPARα, PPARγ, and PPARδ. They can be activated by endogenous ligands, such as fatty acids, as well as by pharmacologic agents. Activators of PPARs are used for treating several metabolic complications, such as diabetes and hyperlipidemia that are directly or indirectly associated with HF. However, some of these drugs have adverse effects that compromise cardiac function. This review article aims to summarize the current basic and clinical research findings of the beneficial or detrimental effects of PPAR biology on myocardial function.

scholarly journals Placental Implications of Peroxisome Proliferator-Activated Receptors in Gestation and Parturition

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Valerie Borel ◽  
Denis Gallot ◽  
Geoffroy Marceau ◽  
Vincent Sapin ◽  
Loïc Blanchon
Keyword(s):  
Nuclear Receptor ◽  
Metabolic Disorders ◽  
Peroxisome Proliferator ◽  
Placental Development ◽  
Early Stages ◽  
Peroxisome Proliferator Activated Receptors ◽  
Nuclear Receptor Family ◽  
Amniotic Membranes ◽  
Late Stages ◽  
Receptor Family

The placenta is a transitory structure indispensable for the proper development of the embryo and fetus during mammalian gestation. Like other members of the nuclear receptor family, the peroxisome proliferator-activated receptors (PPARs) are known to be involved in the physiological and pathological events occurring during the placentation. This placental involvement has been recently reviewed focusing on the early stages of placental development (implantation and invasion, etc.), mouse PPARs knockout phenotypes, and cytotrophoblast physiology. In this review, we describe the placental involvement of PPARs (e.g., fat transport and metabolism, etc.) during the late stages of gestation and in the amniotic membranes, highlighting their roles in the inflammation process (e.g., chorioamnionitis), metabolic disorders (e.g., diabetes), and parturition.

scholarly journals PPARs and Microbiota in Skeletal Muscle Health and Wasting

2020 ◽  
Vol 21 (21) ◽  
pp. 8056 ◽  
Author(s):  
Ravikumar Manickam ◽  
Kalina Duszka ◽  
Walter Wahli
Keyword(s):  
Skeletal Muscle ◽  
Gut Microbiota ◽  
Muscle Wasting ◽  
Fiber Type ◽  
Low Grade ◽  
Peroxisome Proliferator ◽  
Growth Factor Signaling ◽  
Peroxisome Proliferator Activated Receptors ◽  
Nuclear Receptor Family ◽  
Aging Muscle

Skeletal muscle is a major metabolic organ that uses mostly glucose and lipids for energy production and has the capacity to remodel itself in response to exercise and fasting. Skeletal muscle wasting occurs in many diseases and during aging. Muscle wasting is often accompanied by chronic low-grade inflammation associated to inter- and intra-muscular fat deposition. During aging, muscle wasting is advanced due to increased movement disorders, as a result of restricted physical exercise, frailty, and the pain associated with arthritis. Muscle atrophy is characterized by increased protein degradation, where the ubiquitin-proteasomal and autophagy-lysosomal pathways, atrogenes, and growth factor signaling all play an important role. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family of transcription factors, which are activated by fatty acids and their derivatives. PPARs regulate genes that are involved in development, metabolism, inflammation, and many cellular processes in different organs. PPARs are also expressed in muscle and exert pleiotropic specialized responses upon activation by their ligands. There are three PPAR isotypes, viz., PPARα, -β/δ, and -γ. The expression of PPARα is high in tissues with effective fatty acid catabolism, including skeletal muscle. PPARβ/δ is expressed more ubiquitously and is the predominant isotype in skeletal muscle. It is involved in energy metabolism, mitochondrial biogenesis, and fiber-type switching. The expression of PPARγ is high in adipocytes, but it is also implicated in lipid deposition in muscle and other organs. Collectively, all three PPAR isotypes have a major impact on muscle homeostasis either directly or indirectly. Furthermore, reciprocal interactions have been found between PPARs and the gut microbiota along the gut–muscle axis in both health and disease. Herein, we review functions of PPARs in skeletal muscle and their interaction with the gut microbiota in the context of muscle wasting.

scholarly journals Common Drug Pipelines for the Treatment of Diabetic Nephropathy and Hepatopathy: Can We Kill Two Birds with One Stone?

2020 ◽  
Vol 21 (14) ◽  
pp. 4939
Author(s):  
Yoshio Sumida ◽  
Masashi Yoneda ◽  
Hidenori Toyoda ◽  
Satoshi Yasuda ◽  
Toshifumi Tada ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
The United States ◽  
Severe Form ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Cross Sectional ◽  
Common Drug ◽  
Glucagon Like Peptide 1 ◽  
Peroxisome Proliferator Activated Receptors ◽  
Stage Renal Disease

Type 2 diabetes (T2D) is associated with diabetic nephropathy as well as nonalcoholic steatohepatitis (NASH), which can be called “diabetic hepatopathy or diabetic liver disease”. NASH, a severe form of nonalcoholic fatty disease (NAFLD), can sometimes progress to cirrhosis, hepatocellular carcinoma and hepatic failure. T2D patients are at higher risk for liver-related mortality compared with the nondiabetic population. NAFLD is closely associated with chronic kidney disease (CKD) or diabetic nephropathy according to cross-sectional and longitudinal studies. Simultaneous kidney liver transplantation (SKLT) is dramatically increasing in the United States, because NASH-related cirrhosis often complicates end-stage renal disease. Growing evidence suggests that NAFLD and CKD share common pathogenetic mechanisms and potential therapeutic targets. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and diabetic nephropathy/CKD. There are no approved therapies for NASH, but a variety of drug pipelines are now under development. Several agents of them can also ameliorate diabetic nephropathy/CKD, including peroxisome proliferator-activated receptors agonists, apoptosis signaling kinase 1 inhibitor, nuclear factor-erythroid-2-related factor 2 activator, C-C chemokine receptor types 2/5 antagonist and nonsteroidal mineral corticoid receptor antagonist. This review focuses on common drug pipelines in the treatment of diabetic nephropathy and hepatopathy.

A Mechanistic approach of Peroxisome Proliferator-Activated Receptors and its subtypes on Clinical and preclinical model of Neurodegenerative disorders

2021 ◽  
pp. 3967-3975
Author(s):  
Jinu Avarachan ◽  
Anitta Augustine ◽  
Pallavi Mahadev Shinde ◽  
Venkatesh Gunasekaran
Keyword(s):  
Neurodegenerative Disorders ◽  
Symptomatic Relief ◽  
Preclinical Model ◽  
Peroxisome Proliferator ◽  
Mechanistic Approach ◽  
Peroxisome Proliferator Activated Receptors ◽  
Nuclear Receptor Family ◽  
Preclinical And Clinical Studies ◽  
Ppar Ligands

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, belonging to the nuclear receptor family, which has high expression of three structurally homologous PPARs isotypes (PPARα, PPARβ/δ, and PPARγ) in brain. Several studies have discovered role of PPARs in oxidative stress, mitochondrial dysfunction, neuroinflammation and production of the toxic proteins in various neurodegenerative disorders such as Parkinson disease, Alzheimer’s disease, Huntington disease, Amyotrophic Lateral Sclerosis, Multiple sclerosis etc. Currently available drugs provide symptomatic relief, but disease progression cannot be stopped, because of their unclear molecular approach. The ability of PPAR to modulate the pathways involved in these conditions paved a path for future studies. Due to increasing challenges to treat central nervous system related disorders, hence PPARs have attracted much attention nowadays. In this review, we discussed various mechanisms of PPARs subtypes in neurodegenerative disorders. We congregate the molecular evidences which support PPARs as a therapeutic target to treat neurodegenerative disorders from preclinical and clinical studies and provide a basis for the potential therapeutic use of PPAR ligands in human diseases.

scholarly journals Bezafibrate, a Peroxisome Proliferator-Activated Receptors Agonist, Decreases Body Temperature and Enhances Electroencephalogram Delta-Oscillation during Sleep in Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 5262-5271 ◽  
Author(s):  
Sachiko Chikahisa ◽  
Kumiko Tominaga ◽  
Tomoko Kawai ◽  
Kazuyoshi Kitaoka ◽  
Katsutaka Oishi ◽  
...  
Keyword(s):  
Body Temperature ◽  
Eye Movement ◽  
Control Diet ◽  
Critical Role ◽  
Pcr Analysis ◽  
Peroxisome Proliferator ◽  
Sleep Regulation ◽  
Delta Power ◽  
Peroxisome Proliferator Activated Receptors ◽  
Nuclear Receptor Family

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor family. PPARs play a critical role in lipid and glucose metabolism. We examined whether chronic treatment with bezafibrate, a PPAR agonist, would alter sleep and body temperature (BT). Mice fed with a control diet were monitored for BT, electroencephalogram (EEG), and electromyogram for 48 h under light-dark conditions. After obtaining the baseline recording, the mice were provided with bezafibrate-supplemented food for 2 wk, after which the same recordings were performed. Two-week feeding of bezafibrate decreased BT, especially during the latter half of the dark period. BT rhythm and sleep/wake rhythm were phase advanced about 2–3 h by bezafibrate treatment. Bezafibrate treatment also increased the EEG delta-power in nonrapid eye movement sleep compared with the control diet attenuating its daily amplitude. Furthermore, bezafibrate-treated mice showed no rebound of EEG delta-power in nonrapid eye movement sleep after 6 h sleep deprivation, whereas values in control mice largely increased relative to baseline. DNA microarray, and real-time RT-PCR analysis showed that bezafibrate treatment increased levels of Neuropeptide Y mRNA in the hypothalamus at both Zeitgeber time (ZT) 10 and ZT22, and decreased proopiomelanocortin-α mRNA in the hypothalamus at ZT10. These findings demonstrate that PPARs participate in the control of both BT and sleep regulation, which accompanied changes in gene expression in the hypothalamus. Activation of PPARs may enhance deep sleep and improve resistance to sleep loss.

scholarly journals PPAR-Mediated Toxicology and Applied Pharmacology

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 352 ◽  
Author(s):  
Yue Xi ◽  
Yunhui Zhang ◽  
Sirui Zhu ◽  
Yuping Luo ◽  
Pengfei Xu ◽  
...  
Keyword(s):  
Multiple Organ ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Pharmacological Agents ◽  
Peroxisome Proliferator Activated Receptors ◽  
Systematic Understanding ◽  
Approved Drugs ◽  
Receptor Family

Peroxisome proliferator-activated receptors (PPARs), members of the nuclear hormone receptor family, attract wide attention as promising therapeutic targets for the treatment of multiple diseases, and their target selective ligands were also intensively developed for pharmacological agents such as the approved drugs fibrates and thiazolidinediones (TZDs). Despite their potent pharmacological activities, PPARs are reported to be involved in agent- and pollutant-induced multiple organ toxicity or protective effects against toxicity. A better understanding of the protective and the detrimental role of PPARs will help to preserve efficacy of the PPAR modulators but diminish adverse effects. The present review summarizes and critiques current findings related to PPAR-mediated types of toxicity and protective effects against toxicity for a systematic understanding of PPARs in toxicology and applied pharmacology.

scholarly journals The Role of PPARαActivation in Liver and Muscle

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Lena Burri ◽  
G. Hege Thoresen ◽  
Rolf K. Berge
Keyword(s):  
Target Gene ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ligand Activation ◽  
Risks And Benefits ◽  
Physiological Homeostasis ◽  
Nuclear Receptor Family ◽  
Target Gene Transcription ◽  
Receptor Family

PPARαis one of three members of the soluble nuclear receptor family called peroxisome proliferator-activated receptor (PPAR). It is a sensor for changes in levels of fatty acids and their derivatives that responds to ligand binding with PPAR target gene transcription, inasmuch as it can influence physiological homeostasis, including lipid and carbohydrate metabolism in various tissues. In this paper we summarize the involvement of PPARαin the metabolically active tissues liver and skeletal muscle and provide an overview of the risks and benefits of ligand activation of PPARα, with particular consideration to interspecies differences.

scholarly journals Parsing the Role of PPARs in Macrophage Processes

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel Toobian ◽  
Pradipta Ghosh ◽  
Gajanan D. Katkar
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Disease ◽  
Peroxisome Proliferator ◽  
Microbial Infection ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Nuclear Receptor Family

Cells are richly equipped with nuclear receptors, which act as ligand-regulated transcription factors. Peroxisome proliferator activated receptors (PPARs), members of the nuclear receptor family, have been extensively studied for their roles in development, differentiation, and homeostatic processes. In the recent past, there has been substantial interest in understanding and defining the functions of PPARs and their agonists in regulating innate and adaptive immune responses as well as their pharmacologic potential in combating acute and chronic inflammatory disease. In this review, we focus on emerging evidence of the potential roles of the PPAR subtypes in macrophage biology. We also discuss the roles of dual and pan PPAR agonists as modulators of immune cell function, microbial infection, and inflammatory 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.

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