Effects Of PPARs Research Articles

Peroxisome Proliferator-Activated Receptor γ Dances with Different Partners in Macrophage and Adipocytes

Peroxisome Proliferator-Activated Receptor γ Dances with Different Partners in Macrophage and Adipocytes

PPARs, Cardiovascular Metabolism, and Function: Near- or Far-from-Equilibrium Pathways

Peroxisome proliferator-activated receptors (PPAR α, β/δ and γ) play a key role in metabolic regulatory processes and gene regulation of cellular metabolism, particularly in the cardiovascular system. Moreover, PPARs have various extra metabolic roles, in circadian rhythms, inflammation and oxidative stress. In this review, we focus mainly on the effects of PPARs on some thermodynamic processes, which can behave either near equilibrium, or far-from-equilibrium. New functions of PPARs are reported in the arrhythmogenic right ventricular cardiomyopathy, a human genetic heart disease. It is now possible to link the genetic desmosomal abnormalitiy to the presence of fat in the right ventricle, partly due to an overexpression of PPARγ. Moreover, PPARs are directly or indirectly involved in cellular oscillatory processes such as the Wnt-b-catenin pathway, circadian rhythms of arterial blood pressure and cardiac frequency and glycolysis metabolic pathway. Dysfunction of clock genes and PPARγ may lead to hyperphagia, obesity, metabolic syndrome, myocardial infarction and sudden cardiac death, In pathological conditions, regulatory processes of the cardiovascular system may bifurcate towards new states, such as those encountered in hypertension, type 2 diabetes, and heart failure. Numerous of these oscillatory mechanisms, organized in time and space, behave far from equilibrium and are “dissipative structures”.

PPARs/RXRs in Cardiovascular Physiology and Disease

The PPAR family of nuclear receptor transcription factors are important regulators of cardiovascular function and metabolism. Because of this, PPARs are potentially interesting pharmacologic targets for treating cardiometabolic disease. The reviews in this series discuss the regulatory functions of PPARs in maintaining metabolic and physiologic homeostasis in a variety of cells and tissues. Additionally, the therapeutic potential and mechanisms of action of ligands of the different PPAR isotypes are discussed. The review series is started by an examination of the effects of PPARs on lipoprotein metabolism. This is one of the first identified functions of PPARs. Indeed, ligands for PPARα were in clinical use as lipid-lowering agents even before their pharmacological target, PPARα, were known. The second review evaluates the important anti-inflammatory effects of PPARs in platelets, which is emerging as an important mechanism of their beneficial effects. Next, the critical role that PPARα and its transcriptional coactivator protein PGC-1α play in regulating energy metabolism and function of the myocardium is discussed. Then, a series of reviews focuses on the potentially beneficial effects of PPARγ agonists on the cardiovascular system. Several aspects are presented. The effects of PPAR activation on the cardiovascular system as a whole, on the vascular smooth muscle cell, and in the context of diabetic cardiovascular disease are each discussed at length. A review by Demers et al. also discusses the potential input of the hexarelin signaling pathway in regulating PPARγ activity and its potential impact on cardiometabolic disease. The genes encoding the PPARs are rich with genetic variation and the impact of these polymorphisms and haplotypes on the response to PPAR activators is only beginning to be understood. Thus, the “pharmacogenomics” of PPARs are discussed in a review by Dr. Sharon Cresci. Finally, the potential toxicity and adverse outcomes of PPAR agonism are summarized in detail by Jennifer Robinson. The timeliness of this discussion is outstanding given the recent reports of increased cardiovascular morbidity associated with use of rosiglitazone and the failure of PPAR dual agonists at different stages of development. Several of the other reviews in this series also touch this controversial issue at least briefly. We are also pleased to present two original research reports. The first report found associations between PPARγ gene polymorphisms and several cardiometabolic indices, but found no link with cardiovascular morbidity and mortality. Second, Buroker et al. report an important role for PGC- 1α in postnatal metabolic maturation. This preprogrammed burst in cardiac oxidative metabolism is an important developmental response that also has implications for other physiologic states wherein the demand for ATP production is rapidly induced. We hope that you will find this issue enjoyable and informative. Brian N. Finck Giulia Chinetti Bart Staels

Nutrición molecular, papel del sistema PPAR en el metabolismo lipídico y su importancia en obesidad y diabetes mellitus: regulation of lipid metabolism by peroxisome proliferator activated receptors (PPAR). Their relatioship to obesity and diabetes mellitus

PPARs are transcription factors belonging to the super family of hormonal receptors. Their activity is regulated by fibrates, thiazolidinediones, certain anti inflammatory drugs and fatty acid derivatives, present in food. PPAR isoforms play a central role in lipid homeostasis, regulating anabolic (PPAR gamma) and catabolic (PPAR alpha) pathways of lipid metabolism. Additionally, these receptors participate in glucose homeostasis, influence cellular proliferation and differentiation and participate in inflammatory processes. The effects of PPARs on oxidative substrate partitioning suggests that they have a relevant role in the development of obesity and insulin resistance.

A potential mechanism for anti-inflammatory effects of PPARs

A potential mechanism for anti-inflammatory effects of PPARs