scholarly journals Peroxisome Proliferator-Activated Receptor Agonists: Do They Increase Cardiovascular Risk?

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Ahmad Aljada ◽  
Kshitij Ashwin Shah ◽  
Shaker A. Mousa
Keyword(s):  
Molecular Mechanisms ◽  
Review Article ◽  
Current Evidence ◽  
Peroxisome Proliferator ◽  
Cardiovascular Risks ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonists ◽  
Record Trial ◽  
Meta Analyses

Cardiovascular disease is a major cause of morbidity and mortality among people with type 2 diabetes mellitus. The peroxisome proliferator-activated receptor (PPAR) agonists have a significant role on glucose and fat metabolism. Thiazolidinediones (TZDs) are predominantly PPARγagonists, and their primary benefit appears to be the prevention of diabetic complications by improving glycemic control and lipid profile. Recently, the cardiovascular safety of rosiglitazone was brought to center stage following meta analyses and the interim analysis of the RECORD trial. Current evidence points to rosiglitazone having a greater risk of myocardial ischemic events than placebo, metformin, or sulfonylureas. This review article discusses the mechanism of action of PPAR agonists and correlates it with clinical and laboratory outcomes in the published literature. In addition, this review article attempts to discuss some of the molecular mechanisms regarding the association between TZDs therapy and the nontraditional cardiovascular risks.

scholarly journals PPARγExpression and Function in Mycobacterial Infection: Roles in Lipid Metabolism, Immunity, and Bacterial Killing

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Patricia E. Almeida ◽  
Alan Brito Carneiro ◽  
Adriana R. Silva ◽  
Patricia T. Bozza
Keyword(s):  
Molecular Mechanisms ◽  
Critical Role ◽  
Mycobacterial Infection ◽  
Receptor Activation ◽  
Host Cells ◽  
Current Evidence ◽  
Peroxisome Proliferator ◽  
Bacterial Killing ◽  
Peroxisome Proliferator Activated Receptor ◽  
And Function

Tuberculosis continues to be a global health threat, with drug resistance and HIV coinfection presenting challenges for its control.Mycobacterium tuberculosis, the etiological agent of tuberculosis, is a highly adapted pathogen that has evolved different strategies to subvert the immune and metabolic responses of host cells. Although the significance of peroxisome proliferator-activated receptor gamma (PPARγ) activation by mycobacteria is not fully understood, recent findings are beginning to uncover a critical role for PPARγduring mycobacterial infection. Here, we will review the molecular mechanisms that regulate PPARγexpression and function during mycobacterial infection. Current evidence indicates that mycobacterial infection causes a time-dependent increase in PPARγexpression through mechanisms that involve pattern recognition receptor activation. Mycobacterial triggered increased PPARγexpression and activation lead to increased lipid droplet formation and downmodulation of macrophage response, suggesting that PPARγexpression might aid the mycobacteria in circumventing the host response acting as an escape mechanism. Indeed, inhibition of PPARγenhances mycobacterial killing capacity of macrophages, suggesting a role of PPARγin favoring the establishment of chronic infection. Collectively, PPARγis emerging as a regulator of tuberculosis pathogenesis and an attractive target for the development of adjunctive tuberculosis therapies.

scholarly journals Gynura divaricata ameliorates hepatic insulin resistance by modulating insulin signalling, maintaining glycolipid homeostasis and reducing inflammation in type 2 diabetic mice

2019 ◽  
Vol 8 (6) ◽  
pp. 928-938 ◽  
Author(s):  
Xuan Dong ◽  
Shu-Xiang Zhao ◽  
Bing-Qing Xu ◽  
Yu-Qing Zhang
Keyword(s):  
Insulin Resistance ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Molecular Mechanisms ◽  
Insulin Signalling ◽  
Fasting Blood Glucose ◽  
Hepatic Insulin Resistance ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Insulin Signalling Pathway

Abstract Diabetes mellitus, one of the fastest growing epidemics worldwide, has become a serious health problem in modern society. Gynura divaricata (GD), an edible medicinal plant, has been shown to have hypoglycaemic effects. The molecular mechanisms by which GD improves hepatic insulin resistance (IR) in mice with type 2 diabetes (T2D) remain largely unknown. The aerial parts of GD were prepared in a lyophilized powder, which was added into the diet of T2D mice for 4 weeks. GD could result in an obvious decrease in fasting blood glucose and insulin levels in T2D mice. Meanwhile, the underlying mechanisms involved in the insulin-signalling pathway, glucose metabolism, lipid metabolism and inflammatory reaction in the liver tissue were also investigated by western blot, which indicated that GD further ameliorated hepatic IR by activating the PI3K/p-AKT pathway, decreasing the levels of hepatic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase and increasing the levels of glucokinase and peroxisome proliferator-activated receptor-γ in the livers of T2D mice. GD has the potential to alleviate both hyperglycaemia and hepatic IR in T2D mice. Therefore, GD might be a promising functional food or medicine for T2D treatment.

Role of PPARγ in renoprotection in Type 2 diabetes: molecular mechanisms and therapeutic potential

2008 ◽  
Vol 116 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Jichun Yang ◽  
Dongjuan Zhang ◽  
Jing Li ◽  
Xiaoyan Zhang ◽  
Fenling Fan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Large Body ◽  
Underlying Mechanism ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Underlying Mechanisms ◽  
Stage Renal Disease

DN (diabetic nephropathy) is a chronic disease characterized by proteinuria, glomerular hypertrophy, decreased glomerular filtration and renal fibrosis with loss of renal function. DN is the leading cause of ESRD (end-stage renal disease), accounting for millions of deaths worldwide. TZDs (thiazolidinediones) are synthetic ligands of PPARγ (peroxisome-proliferator-activated receptor γ), which is involved in many important physiological processes, including adipose differentiation, lipid and glucose metabolism, energy homoeostasis, cell proliferation, inflammation, reproduction and renoprotection. A large body of research over the past decade has revealed that, in addition to their insulin-sensitizing effects, TZDs play an important role in delaying and preventing the progression of chronic kidney disease in Type 2 diabetes. Although PPARγ activation by TZDs is in general considered beneficial for the amelioration of diabetic renal complications in Type 2 diabetes, the underlying mechanism(s) remains only partially characterized. In this review, we summarize and discuss recent findings regarding the renoprotective effects of PPARγ in Type 2 diabetes and the potential underlying mechanisms.

scholarly journals PPAR-γ Agonists and Their Role in Primary Cicatricial Alopecia

PPAR Research ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Sarawin Harnchoowong ◽  
Poonkiat Suchonwanit
Keyword(s):  
Clinical Trials ◽  
Review Article ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Biogenesis ◽  
Sebaceous Glands ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lichen Planopilaris ◽  
Ppar Γ ◽  
Ppar Agonists

Peroxisome proliferator-activated receptor γ (PPAR-γ) is a ligand-activated nuclear receptor that regulates the transcription of various genes. PPAR-γ plays roles in lipid homeostasis, sebocyte maturation, and peroxisome biogenesis and has shown anti-inflammatory effects. PPAR-γ is highly expressed in human sebaceous glands. Disruption of PPAR-γ is believed to be one of the mechanisms of primary cicatricial alopecia (PCA) pathogenesis, causing pilosebaceous dysfunction leading to follicular inflammation. In this review article, we discuss the pathogenesis of PCA with a focus on PPAR-γ involvement in pathogenesis of lichen planopilaris (LPP), the most common lymphocytic form of PCA. We also discuss clinical trials utilizing PPAR-agonists in PCA treatment.

scholarly journals Metformin and Fibrosis: A Review of Existing Evidence and Mechanisms

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Maoyan Wu ◽  
Huiwen Xu ◽  
Jingyu Liu ◽  
Xiaozhen Tan ◽  
Shengrong Wan ◽  
...  
Keyword(s):  
Adenosine Monophosphate ◽  
Therapeutic Strategies ◽  
Organ Injury ◽  
Peroxisome Proliferator ◽  
First Line ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonists ◽  
Line Drug ◽  
Organ Fibrosis

Fibrosis is a physiological response to organ injury and is characterized by the excessive deposition of connective tissue components in an organ, which results in the disruption of physiological architecture and organ remodeling, ultimately leading to organ failure and death. Fibrosis in the lung, kidney, and liver accounts for a substantial proportion of the global burden of disability and mortality. To date, there are no effective therapeutic strategies for controlling fibrosis. A class of metabolically targeted chemicals, such as adenosine monophosphate-activated protein kinase (AMPK) activators and peroxisome proliferator-activated receptor (PPAR) agonists, shows strong potential in fighting fibrosis. Metformin, which is a potent AMPK activator and is the only recommended first-line drug for the treatment of type 2 diabetes, has emerged as a promising method of fibrosis reduction or reversion. In this review, we first summarize the key experimental and clinical studies that have specifically investigated the effects of metformin on organ fibrosis. Then, we discuss the mechanisms involved in mediating the antifibrotic effects of metformin in depth.

scholarly journals Inhibition of PPARγ by Natural Compounds as a Promising Strategy in Obesity and Diabetes

2019 ◽  
Vol 13 (1) ◽  
pp. 7-15 ◽  
Author(s):  
Alessandra Ammazzalorso ◽  
Rosa Amoroso
Keyword(s):  
Energy Homeostasis ◽  
Natural Compounds ◽  
Peroxisome Proliferator ◽  
Clinical Role ◽  
Peroxisome Proliferator Activated Receptor ◽  
Obesity And Diabetes ◽  
Ppar Agonists ◽  
Wide Group ◽  
Potential Use

A wide group of natural compounds (flavonoids, stilbenes, neolignans and others) has been identified as Peroxisome Proliferator-Activated Receptor (PPAR) agonists, with a large variety of chemical structure and different activity versus the three PPAR subtypes. These receptors are transcription factors controlling metabolic pathways in the organism, involved in lipid and glucose metabolism, cell differentiation and energy homeostasis. Otherwise, very little is known about natural compounds able to inhibit PPARs. A number of studies demonstrate that PPARγ repression has a beneficial effect in reducing body weight and improving insulin sensitivity, suggesting a potential clinical role in obesity and type 2 diabetes. This review analyzes natural compounds able to repress PPAR activity and their potential use in metabolic disorders.

scholarly journals The Potential of Resveratrol to Act as a Caloric Restriction Mimetic Appears to Be Limited: Insights from Studies in Mice

2020 ◽  
Author(s):  
Kathrin Pallauf ◽  
Ilka Günther ◽  
Gianna Kühn ◽  
Dawn Chin ◽  
Sonia de Pascual-Teresa ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Caloric Restriction ◽  
Gene Transcription ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Laboratory Animals ◽  
Current Evidence ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Age Related

ABSTRACT Caloric restriction (CR) has been shown repeatedly to prolong the lifespan in laboratory animals, with its benefits dependent on molecular targets forming part of the nutrient signaling network, including the NAD-dependent deacetylase silent mating type information regulation 2 homologue 1 (SIRT1). It has been hypothesized that the stilbene resveratrol (RSV) may counteract age- and obesity-related diseases similarly to CR. In yeast and worms, RSV-promoted longevity also depended on SIRT1. While it remains unclear whether RSV can prolong lifespans in mammals, some studies in rodents supplemented with RSV have reported lowered body weight (BW) and fat mass, improved insulin sensitivity, lowered cholesterol levels, increased fitness, and mitochondrial biogenesis. Molecular mechanisms possibly leading to such changes include altered gene transcription and activation of SIRT1, AMP-activated kinase (AMPK), and peroxisome proliferator–activated receptor gamma coactivator 1-alpha (PPARGC1A). However, some mouse models did not benefit from RSV treatment to the same extent as others. We conducted a literature search on PubMed (15 April, 2020) for trials directly comparing RSV application to CR feeding in mice. In most studies retrieved by this systematic PubMed search, mice supplemented with RSV did not show significant reductions of BW, glucose, or insulin. Moreover, in some of these studies, RSV and CR treatments affected molecular targets differently and/or findings on RSV and CR impacts varied between trials. We discuss those RSV-induced changes in gene transcription hypothesized to partly counteract age-related alterations. Although there may be a moderate effect of RSV supplementation on parameters such as insulin sensitivity toward a more CR-like profile in mice, data are inconsistent. Likewise, RSV supplementation trials in humans report controversial findings. While we consider that RSV may, under certain circumstances, moderately mimic some aspects of CR, current evidence does not fully support its use to prevent or treat age- or obesity-related diseases.

Radioprotective effect of pioglitazone against genotoxicity induced by ionizing radiation in human healthy lymphocytes

2020 ◽  
Vol 18 ◽  
Author(s):  
Roya Kazemi ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Ionizing Radiation ◽  
Human Lymphocytes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Mean ◽  
Anti Inflammatory ◽  
Sensitizing Effect ◽  
Binucleated Lymphocytes ◽  
Inflammatory Effect

Objective: Pioglitazone (PG) is used to control high blood sugar in patients with type 2 diabetes mellitus. PG acts as a peroxisome proliferator-activated receptor γ agonist. In addition to the insulin-sensitizing effect, PG possesses anti-inflammatory effect. In this study, the protective effect of PG was evaluated against DNA damage induced by ionizing radiation in human healthy lymphocytes. Methods: The microtubes containing human whole blood were treated with PG at various concentrations (1-50 μM) for three hours. Then, the blood samples were irradiated with X-ray. Lymphocytes were cultured for determining the frequency of micronuclei as a genotoxicity biomarker in binucleated lymphocytes. Results: The mean percentage of micronuclei was significantly increased in human lymphocytes when were exposed to IR, while it was decreased in lymphocytes pre-treated with PG. The maximum reduction in the frequency of micronuclei in irradiated lymphocytes was observed at 5 μM of PG treatment (48% decrease). Conclusion: The anti-inflammatory property is suggested the mechanism action of PG for protection human lymphocytes against genotoxicity induced by ionizing radiation.

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.

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