scholarly journals Role of peroxisome proliferator-activated receptors in the control of alcohol dependence and concomitant liver pathology

2019 ◽  
Vol 16 (2) ◽  
pp. 244-256
Author(s):  
I. N. Semenenya ◽  
A. H. Shlyahtun ◽  
H. F. Raduta
Keyword(s):  
Liver Disease ◽  
Alcohol Dependence ◽  
Alcoholic Liver Disease ◽  
Therapeutic Potential ◽  
Scattered Data ◽  
Peroxisome Proliferator ◽  
Liver Pathology ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

The article is aimed to summarize the scattered data on the role of peroxisome proliferator-activated receptors (PPAR) and the possibility of using PPAR’s agonists for treatment of alcohol dependence and alcoholic liver disease. Earlier it was shown that some PPAR agonists can reduce ethanol consumption and preference in rodents. Several hypotheses considering the antialcoholic activity of PPAR agonists and the roles of PPAR in the development of alcohol dependence were discussed. In light of these data, the therapeutic potential of PPARs agonists as an agent for the treatment of alcoholism, has been reviewed.

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 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.

scholarly journals New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue Injury

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Miriam D. Neher ◽  
Sebastian Weckbach ◽  
Markus S. Huber-Lang ◽  
Philip F. Stahel
Keyword(s):  
Inflammatory Response ◽  
Major Trauma ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Healing Process ◽  
Wound Healing Process ◽  
Peroxisome Proliferator ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

Major trauma results in a strong inflammatory response in injured tissue. This posttraumatic hyperinflammation has been implied in the adverse events leading to a breakdown of host defense mechanisms and ultimately to delayed organ failure. Ligands to peroxisome proliferator-activated receptors (PPARs) have recently been identified as potent modulators of inflammation in various acute and chronic inflammatory conditions. The main mechanism of action mediated by ligand binding to PPARs is the inhibition of the nuclear transcription factor NF-κB, leading to downregulation of downstream gene transcription, such as for genes encoding proinflammatory cytokines. Pharmacological PPAR agonists exert strong anti-inflammatory properties in various animal models of tissue injury, including central nervous system trauma, ischemia/reperfusion injury, sepsis, and shock. In addition, PPAR agonists have been shown to induce wound healing process after tissue trauma. The present review was designed to provide an up-to-date overview on the current understanding of the role of PPARs in the pathophysiology of the inflammatory response after major trauma. Therapeutic options for using recombinant PPAR agonists as pharmacological agents in the management of posttraumatic inflammation will be discussed.

scholarly journals The lymphatic system in alcohol-associated liver disease

2020 ◽  
Vol 26 (4) ◽  
pp. 633-638
Author(s):  
Reiichiro Kondo ◽  
Yasuko Iwakiri
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Fluid Balance ◽  
Interstitial Fluid ◽  
Lymphatic System ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Review Article ◽  
Related Disease

The lymphatic system plays vital roles in interstitial fluid balance and immune cell surveillance. The effect of alcohol on the lymphatic system is poorly understood. This review article explores the role of the lymphatic system in the pathogenesis of alcohol-related disease including alcoholic liver disease (ALD) and the therapeutic potential of targeting hepatic lymphatics for the treatment of ALD.

scholarly journals Enhanced Hepatocarcinogenicity Due to Agonists of Peroxisome Proliferator-Activated Receptors in Senescent Rats: Role of Peroxisome Proliferation, Cell Proliferation, and Apoptosis

2002 ◽  
Vol 2 ◽  
pp. 1491-1500 ◽  
Author(s):  
Jihan Youssef ◽  
Mostafa Badr
Keyword(s):  
Cell Proliferation ◽  
Peroxisome Proliferator ◽  
Carcinogenic Effect ◽  
Peroxisome Proliferator Activated Receptor ◽  
New Findings ◽  
Proliferation And Apoptosis ◽  
Ppar Agonists ◽  
Old Rats ◽  
Peroxisome Proliferator Activated Receptors

Exposure to agonists of peroxisome proliferator-activated receptor alpha (PPARα) causes liver cancer in rodents, with aged animals being more susceptible than their younger counterparts to this effect. Treatment with these chemicals produced a five- to sevenfold higher yield of grossly visible hepatic tumors in old rats compared to young animals. The enhanced susceptibility of the aged livers to the carcinogenic effect of PPAR agonists could not be explained by differences in levels of peroxisomal and/or cell proliferation between young and old animals, as neither of these responses was exaggerated with aging. Reported studies have shown that activating PPARa results in the suppression of hepatic apoptosis. This effect is expected to diminish the ability of the liver to purge itself of pre-existing neoplastic cells, allowing them to progress to tumors. New findings from our laboratories show that the aged liver is exceedingly sensitive to the antiapoptotic effect of PPAR agonists. In addition, aged livers showed remarkably higher levels of the antiapoptotic protein Bcl-2 than livers of young, adult, and middle-aged animals. Interestingly, the PPARa agonist Wy-14,643 significantly diminished elements of the proapoptotic machinery (e.g., Bax, caspases, and fas) in the aged liver, while remarkably increasing elements of this machinery in younger animals. Taken together, while activation of PPARs appears to inhibit apoptosis in livers of senescent animals, activating these receptors seems to stimulate the apoptotic machinery in young animals. This paradoxical effect may be responsible for the exaggerated sensitivity of the aged liver to the carcinogenic effect of agents that activate PPARs.

scholarly journals Peroxisome Proliferator-Activated Receptors in Diabetic Nephropathy

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-11 ◽  
Author(s):  
Shinji Kume ◽  
Takashi Uzu ◽  
Keiji Isshiki ◽  
Daisuke Koya
Keyword(s):  
Diabetic Nephropathy ◽  
Therapeutic Potential ◽  
Experimental Studies ◽  
Renin Angiotensin System ◽  
Pressure Control ◽  
Peroxisome Proliferator ◽  
Patients With Diabetes ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Stage Renal Disease

Diabetic nephropathy is a leading cause of end-stage renal disease, which is increasing in incidence worldwide, despite intensive treatment approaches such as glycemic and blood pressure control in patients with diabetes mellitus. New therapeutic strategies are needed to prevent the onset of diabetic nephropathy. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostases. These agents might prevent the progression of diabetic nephropathy, since PPAR agonists improve dyslipidemia and insulin resistance. Furthermore, data from murine models suggest that PPAR agonists also have independent renoprotective effects by suppressing inflammation, oxidative stress, lipotoxicity, and activation of the renin-angiotensin system. This review summarizes data from clinical and experimental studies regarding the relationship between PPARs and diabetic nephropathy. The therapeutic potential of PPAR agonists in the treatment of diabetic nephropathy is also discussed.

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 Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1638 ◽  
Author(s):  
Anne Fougerat ◽  
Alexandra Montagner ◽  
Nicolas Loiseau ◽  
Hervé Guillou ◽  
Walter Wahli
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Peroxisome Proliferator ◽  
Biological Processes ◽  
Alcoholic Fatty Liver ◽  
Glucose And Lipid Metabolism ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, frequently associated with obesity and type 2 diabetes. Steatosis is the initial stage of the disease, which is characterized by lipid accumulation in hepatocytes, which can progress to non-alcoholic steatohepatitis (NASH) with inflammation and various levels of fibrosis that further increase the risk of developing cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is influenced by interactions between genetic and environmental factors and involves several biological processes in multiple organs. No effective therapy is currently available for the treatment of NAFLD. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate many functions that are disturbed in NAFLD, including glucose and lipid metabolism, as well as inflammation. Thus, they represent relevant clinical targets for NAFLD. In this review, we describe the determinants and mechanisms underlying the pathogenesis of NAFLD, its progression and complications, as well as the current therapeutic strategies that are employed. We also focus on the complementary and distinct roles of PPAR isotypes in many biological processes and on the effects of first-generation PPAR agonists. Finally, we review novel and safe PPAR agonists with improved efficacy and their potential use in the treatment of NAFLD.

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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