scholarly journals THE METABOLIC SYNDROME: RELATIONSHIP BETWEEN INSULIN SENSITIVITY AND THE ROLE OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPARs) IN SACCHARIDE AND LIPID METABOLISM

2005 ◽  
Vol 149 (2) ◽  
pp. 237-241 ◽  
Author(s):  
Rabha Ben Yahia ◽  
Radka Lichnovska ◽  
Tomas Brychta
Keyword(s):  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Peroxisome Proliferator ◽  
The Metabolic Syndrome ◽  
Peroxisome Proliferator Activated Receptors

scholarly journals Peroxisome Proliferator-Activated Receptors - Alpha in Chronic Inflammation - Mini-Review

2019 ◽  
Vol 12 ◽  
pp. 1-11
Author(s):  
Elena Popa ◽  
Florin Zugun-Eloae ◽  
Mihaela Zlei ◽  
Maria Traian ◽  
Agnes Bacusca ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Transcription Factors ◽  
Lipid Metabolism ◽  
Visceral Obesity ◽  
Peroxisome Proliferator ◽  
Proinflammatory Response ◽  
The Metabolic Syndrome ◽  
Metabolic Complication ◽  
Peroxisome Proliferator Activated Receptors ◽  
Proinflammatory Factors

The pathogeny of the metabolic syndrome (MetS ) is not fully elucidated, but a link between visceral obesity and the increase of the proinflammatory response was proven. Atherosclerosis, perceived as a metabolic complication, draws attention to the peroxisome proliferator-activated receptors- alpha (PPARα). PPARα receptors are transcription factors involved in lipid metabolism, inflammation and atheromatosis. Hence, it interferes in the pathogeny of cardiovascular diseases and other chronic diseases too (neurological, psychical, neoplasical). The study of the expression of PPARα and its modulation on different level may be beneficial in the treatment of metabolic syndrome, intervening in the modulation of another proinflammatory factors.

scholarly journals Preventing type 2 diabetes and cardiovascular disease in metabolic syndrome: the role of PPARα

2007 ◽  
Vol 4 (3_suppl) ◽  
pp. S12-S14 ◽  
Author(s):  
Jorge Plutzky
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Drug Target ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Central Target ◽  
The Metabolic Syndrome

The clustering of cardiovascular risk factors associated with the metabolic syndrome and type 2 diabetes suggests central mechanisms may exist that account for the presence of these abnormalities. Likewise, this clustering also suggests that key therapeutic targets may exist that could allow improvements in many of these parameters. Extensive data implicate peroxisome proliferator-activated receptor-alpha (PPARα) as an important transcriptional regulator of lipid metabolism, energy balance and inflammation. PPARα is also an established drug target. Experimental data show that activation of PPARα by agonists such as fenofibrate improves dyslipidaemia, increases cholesterol efflux and limits inflammation. All of these effects would also be predicted to decrease atherosclerotic risk. Evidence from surrogate markers in humans is also supportive of the concept that PPARα may act as a central target capable of influencing a variety of different pathways involved in lipid metabolism. Thus, fenofibrate offers the potential for inducing a co-ordinated PPARα response that may improve dyslipidaemia, repress inflammation and limit atherosclerosis in patients with the metabolic syndrome or type 2 diabetes.

Evolution of Peroxisome Proliferator-Activated Receptor Agonists

2007 ◽  
Vol 41 (6) ◽  
pp. 973-983 ◽  
Author(s):  
Feng Chang ◽  
Linda A Jaber ◽  
Helen D Berlie ◽  
Mary Beth O'Connell
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Adverse Effects ◽  
Phase Ii ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metabolism Regulation ◽  
Ppar Γ ◽  
The Metabolic Syndrome ◽  
Phase Ii And Iii

OBJECTIVE: To discuss the evolution of peroxisome proliferator-activated receptor (PPAR) agonists from single site to multiple subtype or partial agonists for the treatment of type 2 diabetes, dyslipidemia, obesity, and the metabolic syndrome. DATA SOURCES: Information was obtained from MEDLINE (1966-March 2007) using search terms peroxisome proliferator-activated receptor agonist, PPAR dual agonist, PPAR α/γ agonist, PPAR pan agonist, partial PPAR, and the specific compound names. Other sources included pharmaceutical companies, the Internet, and the American Diabetes Association 64th-66th Scientific Sessions abstract books. STUDY SELECTION AND DATA EXTRACTION: Animal data, abstracts, clinical trials, and review articles were reviewed and summarized. DATA SYNTHESIS: PPAR α, γ, and δ receptors play an important role in lipid metabolism, regulation of adipocyte proliferation and differentiation, and insulin sensitivity. The PPAR dual agonists were developed to combine the triglyceride lowering and high-density lipoprotein cholesterol elevation from the PPAR-α agonists (fibrates) with the insulin sensitivity improvement from the PPAR-γ agonists (thiazolidinediones). Although the dual agonists reduced hemoglobin A1C(A1C) and improved the lipid profile, adverse effects led to discontinued development. Currently, PPAR-γ agonists (GW501516 in Phase I trials), partial PPAR-γ agonists (metaglidasen in Phase II and III trials), and pan agonists (α, γ, δ netoglitazone in Phase II and III trials) with improved cell and tissue selectivity are undergoing investigation to address multiple aspects of the metabolic syndrome with a single medication. By decreasing both A1C and triglycerides, metaglidasen did improve multiple aspects of the metabolic syndrome with fewer adverse effects than compared with placebo. Metaglidasen is now being compared with pioglitazone. CONCLUSIONS: Influencing the various PPARs results in improved glucose, lipid, and weight management, with effects dependent on full or partial agonist activity at single or multiple receptors. Although the dual PPAR compounds have been associated with unacceptable toxicities, new PPAR agonist medications continue to be developed and investigated to discover a safe drug with benefits in multiple disease states.

scholarly journals Zebrafish as a Model to Study the Role of Peroxisome Proliferating-Activated Receptors in Adipogenesis and Obesity

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Marjo J. Den Broeder ◽  
Victoria A. Kopylova ◽  
Leonie M. Kamminga ◽  
Juliette Legler
Keyword(s):  
Lipid Metabolism ◽  
In Silico ◽  
Metabolic Diseases ◽  
Zebrafish Genome ◽  
Peroxisome Proliferator ◽  
Swim Bladder ◽  
Vertebrate Model ◽  
Peroxisome Proliferator Activated Receptors ◽  
Human And Mouse

The Peroxisome Proliferator-Activated Receptors (PPARs) PPARA and PPARD are regulators of lipid metabolism with important roles in energy release through lipid breakdown, while PPARG plays a key role in lipid storage and adipogenesis. The aim of this review is to describe the role of PPARs in lipid metabolism, adipogenesis, and obesity and evaluate the zebrafish as an emerging vertebrate model to study the function of PPARs. Zebrafish are an appropriate model to study human diseases, including obesity and related metabolic diseases, as pathways important for adipogenesis and lipid metabolism which are conserved between mammals and fish. This review synthesizes knowledge on the role of PPARs in zebrafish and focuses on the putative function of PPARs in zebrafish adipogenesis. Usingin silicoanalysis, we confirm the presence of five PPARs (pparaa,pparab,pparda,ppardb, andpparg) in the zebrafish genome with 67–74% identity to human and mouse PPARs. During development,pparda/bparalogs andppargshow mRNA expression around the swim bladder and pancreas, the region where adipocytes first develop, whereasppargis detectable in adipocytes at 15 days post fertilization (dpf). This review indicates that the zebrafish is a promising model to investigate the specific functions of PPARs in adipogenesis and obesity.

scholarly journals Peroxisome Proliferator-Activated Receptor Targets for the Treatment of Metabolic Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Francisco A. Monsalve ◽  
Radha D. Pyarasani ◽  
Fernando Delgado-Lopez ◽  
Rodrigo Moore-Carrasco
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Glucose Homeostasis ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Atherogenic Dyslipidemia ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
The Metabolic Syndrome

Metabolic syndrome is estimated to affect more than one in five adults, and its prevalence is growing in the adult and pediatric populations. The most widely recognized metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a proinflammatory state as well. Peroxisome proliferator-activated receptors (PPARs) may serve as potential therapeutic targets for treating the metabolic syndrome and its related risk factors. The PPARs are transcriptional factors belonging to the ligand-activated nuclear receptor superfamily. So far, three isoforms of PPARs have been identified, namely, PPAR-α, PPAR-β/δ, and PPAR-γ. Various endogenous and exogenous ligands of PPARs have been identified. PPAR-αand PPAR-γare mainly involved in regulating lipid metabolism, insulin sensitivity, and glucose homeostasis, and their agonists are used in the treatment of hyperlipidemia and T2DM. Whereas PPAR-β/δfunction is to regulate lipid metabolism, glucose homeostasis, anti-inflammation, and fatty acid oxidation and its agonists are used in the treatment of metabolic syndrome and cardiovascular diseases. This review mainly focuses on the biological role of PPARs in gene regulation and metabolic diseases, with particular focus on the therapeutic potential of PPAR modulators in the treatment of thrombosis.

Adiponectin, type 2 diabetes and the metabolic syndrome: lessons from human genetic studies

2006 ◽  
Vol 8 (27) ◽  
pp. 1-12 ◽  
Author(s):  
Francis Vasseur ◽  
David Meyre ◽  
Philippe Froguel
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Vascular Complications ◽  
Physiological Role ◽  
Nucleotide Polymorphisms ◽  
The Metabolic Syndrome ◽  
And Function

Adiponectin, a protein exclusively secreted by adipose tissue but present at low levels in obesity, is now widely recognised as a key determinant of insulin sensitivity and of protection against obesity-associated metabolic syndrome. In this review we explain how genetic findings have contributed to a better understanding of the physiological role of adiponectin in humans. The adiponectin-encoding gene, ADIPOQ (ACDC), is very polymorphic: many frequent exonic synonymous, intronic and promoter single-nucleotide polymorphisms (SNPs) have been identified, as well as a few rare exonic amino acid substitutions. Several of these variations additively contribute to the modulation of adiponectin level and function, and associate with insulin sensitivity, type 2 diabetes and vascular complications of obesity.

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