scholarly journals Effects of the PPARG Gene Polymorphisms on Markers of Obesity and the Metabolic Syndrome in Bosnian Subjects

2014 ◽  
Vol 33 (4) ◽  
pp. 323-332 ◽  
Author(s):  
Tanja Dujić ◽  
Tamer Bego ◽  
Barbara Mlinar ◽  
Sabina Semiz ◽  
Maja Malenica ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Metabolic Phenotype ◽  
Polymorphism Analysis ◽  
Peroxisome Proliferator ◽  
Nucleotide Polymorphisms ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Metabolic Syndrome ◽  
Obesity And Diabetes ◽  
Pparg Gene ◽  
Relationship Of

Summary Background: Peroxisome proliferator-activated receptor gamma (PPARg) is a key transcription factor in adipogene-sis, and also regulates a number of genes associated with lipid storage and insulin sensitivity. Single nucleotide polymorphisms (SNPs) in the PPARG gene have been associated with obesity and diabetes. In this study, we explored the relationship of three PPARG gene variants with the metabolic syndrome (MetS) and related traits in a population from Bosnia and Herzegovina. Methods: Anthropometric and biochemical parameters were measured in 43 patients with MetS and 43 healthy controls. Subjects were genotyped for Pro12Ala (rs1801282) and 1431C>T (rs3856806) SNPs by classic PCR–restriction fragment length polymorphism analysis, and for-681C>G (rs10865710) variant by real-time PCR. Results: The genotype distributions for the three polymorphisms were not significantly different between MetS patients and controls. The Pro12Ala and 1431C>T variants were associated with lower body mass index in the control subjects (p=0.012 and p=0.049, respectively). In this group, the carriers of Pro12Ala had also lower waist circumference compared to the wild-type homozygotes (p=0.045). Conclusions: Results of our preliminary study indicate a beneficial effect of a common Pro12Ala variant on the metabolic phenotype in healthy non-obese subjects.

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 Peroxisome Proliferator–Activated Receptors and The Metabolic Syndrome

2009 ◽  
Vol 1 (1) ◽  
pp. 4 ◽  
Author(s):  
Anna Meiliana ◽  
Andi Wijaya
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Energy Balance ◽  
Glucose Homeostasis ◽  
Gene Activation ◽  
Sugar Metabolism ◽  
Endocrine Function ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Metabolic Syndrome

BACKGROUND: Obesity is a growing threat to global health by virtue of its association with insulin resistance, inflammation, hypertension, and dyslipidemia, collectively known as the metabolic syndrome (MetS). The nuclear receptors PPARα and PPARγ are therapeutic targets for hypertriglyceridemia and insulin resistance, respectively, and drugs that modulate these receptors are currently in clinical use. More recent work on the PPARδ has uncovered a dual benefit for both hypertriglyceridemia and insulin resistance, highlighting the broad potential of PPARs in the treatment of metabolic disease.CONTENT: We have learned much about PPARs, the metabolic fat sensors, and the molecular pathways they regulate. Through their distinct tissue distribution and specific target gene activation, the three PPARs together control diverse aspects of fatty acid metabolism, energy balance, insulin sensitivity glucose homeostasis, inflammation, hypertension and atherosclerosis. These studies have advanced our understanding of the etiology for the MetS. Mechanisms revealed by these studies highlight the importance of emerging concepts, such as the endocrine function of adipose tissue, tissue-tissue cross-talk and lipotoxicity, in the pathogenesis of type 2 diabetes mellitus and CVD.SUMMARY: The elucidation of key regulators of energy balance and insulin signaling have revolutionized our understanding of fat and sugar metabolism and their intimate link. The three ‘lipidsensing’ (PPARα, PPARγ and PPARδ) exemplify this connection, regulating diverse aspects of lipid and glucose homeostasis, and serving as bonafide therapeutic targets.KEYWORDS: Peroxisome Proliferator, Activated Receptor, Metabolic Syndrome

scholarly journals Screening of Peroxisome Proliferator-activated Receptors (PPARs) α, γ and δ Gene Polymorphisms for Obesity and Metabolic Syndrome Association in the Multi-ethnic Malaysian Population

2015 ◽  
Vol 25 (4) ◽  
pp. 383 ◽  
Author(s):  
Phee-Phee Chia ◽  
Sook-Ha Fan ◽  
Yee-How Say
Keyword(s):  
Metabolic Syndrome ◽  
Demographic Data ◽  
Plasma Lipid ◽  
Peroxisome Proliferator ◽  
Nucleotide Polymorphisms ◽  
Ethnic Population ◽  
Single Nucleotide ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ethnic Chinese ◽  
Peroxisome Proliferator Activated Receptors

<p class="Pa7"><strong>Objective: </strong>This study aimed to investigate the association of peroxisome proliferator-activated receptor (PPAR) genes <em>PPAR</em>α L162V, <em>PPAR</em><em>γ</em><em>2 </em>C161T and <em>PPAR</em><em>δ </em>T294C single nucleotide polymorphisms (SNPs) with obesity and metabolic syndrome (Met- S) in a multi-ethnic population in Kampar, Malaysia.</p><p class="Pa7"><strong>Methods: </strong>Socio-demographic data, anthropometric and biochemical measure­ments (plasma lipid profile, adiponectin and interleukin-6 [IL-6] levels) were taken from 307 participants (124 males; 180 obese; 249 Met-S; 97 Malays, 85 ethnic Chinese, 55 ethnic Indians).</p><p class="Pa7"><strong>Results: </strong>The overall minor allele frequen­cies were .08, .22 and .30 for <em>PPAR </em>α L162V, γ C161T, δ T294C, respectively. All SNPs were not associated with obesity, Met-S and obesity with/without Met-S by χ2 analysis, ethnicity-stratified and logistic re­gression analyses. Nevertheless, participants with V162 allele of <em>PPAR</em><em>α </em>had significantly higher IL-6, while those with T161 allele of <em>PPAR</em><em>γ</em><em>2 </em>had significantly lower HOMA-IR.</p><p><strong>Conclusions: </strong>All <em>PPAR </em>SNPs were not associated with obesity and Met-S in the suburban population of Kampar, Malay­sia, where only <em>PPAR</em><em>α </em>V162 and <em>PPAR</em><em>γ</em><em>2 </em>T161 alleles were associated with plasma IL-6 and HOMA-IR, respectively. <em>Ethn Dis. </em>2015;25(4):383-390; doi:10.18865/ ed.25.4.383</p>

scholarly journals Sirt1-PPARS Cross-Talk in Complex Metabolic Diseases and Inherited Disorders of the One Carbon Metabolism

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1882 ◽  
Author(s):  
Viola J. Kosgei ◽  
David Coelho ◽  
Rosa-Maria Guéant-Rodriguez ◽  
Jean-Louis Guéant
Keyword(s):  
Metabolic Syndrome ◽  
Vitamin B12 ◽  
Metabolic Diseases ◽  
Preclinical Study ◽  
Peroxisome Proliferator ◽  
Inherited Disorders ◽  
Peroxisome Proliferator Activated Receptor ◽  
Altered Expression ◽  
The Metabolic Syndrome ◽  
Pregnancy And Lactation

Sirtuin1 (Sirt1) has a NAD (+) binding domain and modulates the acetylation status of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and Fork Head Box O1 transcription factor (Foxo1) according to the nutritional status. Sirt1 is decreased in obese patients and increased in weight loss. Its decreased expression explains part of the pathomechanisms of the metabolic syndrome, diabetes mellitus type 2 (DT2), cardiovascular diseases and nonalcoholic liver disease. Sirt1 plays an important role in the differentiation of adipocytes and in insulin signaling regulated by Foxo1 and phosphatidylinositol 3′-kinase (PI3K) signaling. Its overexpression attenuates inflammation and macrophage infiltration induced by a high fat diet. Its decreased expression plays a prominent role in the heart, liver and brain of rat as manifestations of fetal programming produced by deficit in vitamin B12 and folate during pregnancy and lactation through imbalanced methylation/acetylation of PGC1α and altered expression and methylation of nuclear receptors. The decreased expression of Sirt1 produced by impaired cellular availability of vitamin B12 results from endoplasmic reticulum stress through subcellular mislocalization of ELAVL1/HuR protein that shuttles Sirt1 mRNA between the nucleus and cytoplasm. Preclinical and clinical studies of Sirt1 agonists have produced contrasted results in the treatment of the metabolic syndrome. A preclinical study has produced promising results in the treatment of inherited disorders of vitamin B12 metabolism.

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