Dataset Information

Screening of Peroxisome Proliferator-Activated Receptors (PPARs) ?, ? and ? Gene Polymorphisms for Obesity and Metabolic Syndrome Association in the Multi-Ethnic Malaysian Population.

ABSTRACT: This study aimed to investigate the association of peroxisome proliferator-activated receptor (PPAR) genes PPAR? L162V, PPAR?2 C161T and PPAR? T294C single nucleotide polymorphisms (SNPs) with obesity and metabolic syndrome (Met-S) in a multi-ethnic population in Kampar, Malaysia.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).The overall minor allele frequencies were .08, .22 and .30 for PPAR ? L162V, ? C161T, ? T294C, respectively. All SNPs were not associated with obesity, Met-S and obesity with/without Met-S by ?(2) analysis, ethnicity-stratified and logistic regression analyses. Nevertheless, participants with V162 allele of PPAR? had significantly higher IL-6, while those with T161 allele of PPAR?2 had significantly lower HOMA-IR.All PPAR SNPs were not associated with obesity and Met-S in the suburban population of Kampar, Malaysia, where only PPAR? V162 and PPAR?2 T161 alleles were associated with plasma IL-6 and HOMA-IR, respectively.

SUBMITTER: Chia PP

PROVIDER: S-EPMC4671443 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Screening of Peroxisome Proliferator-Activated Receptors (PPARs) α, γ and α Gene Polymorphisms for Obesity and Metabolic Syndrome Association in the Multi-Ethnic Malaysian Population.

Chia Phee-Phee PP Fan Sook-Ha SH Say Yee-How YH Say Yee-How YH

Ethnicity & disease 20151105 4

<h4>Objective</h4>This study aimed to investigate the association of peroxisome proliferator-activated receptor (PPAR) genes PPARα L162V, PPARγ2 C161T and PPARδ T294C single nucleotide polymorphisms (SNPs) with obesity and metabolic syndrome (Met-S) in a multi-ethnic population in Kampar, Malaysia.<h4>Methods</h4>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 ...[more]

PMID: 26673968

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Project description:BACKGROUND: Megalin is a large endocytic receptor with relevant functions during development and adult life. It is expressed at the apical surface of several epithelial cell types, including proximal tubule cells (PTCs) in the kidney, where it internalizes apolipoproteins, vitamins and hormones with their corresponding carrier proteins and signaling molecules. Despite the important physiological roles of megalin little is known about the regulation of its expression. By analyzing the human megalin promoter, we found three response elements for the peroxisomal proliferator-activated receptor (PPAR). The objective of this study was to test whether megalin expression is regulated by the PPARs. METHODOLOGY/PRINCIPAL FINDINGS: Treatment of epithelial cell lines with PPAR? or PPAR? ligands increased megalin mRNA and protein expression. The stimulation of megalin mRNA expression was blocked by the addition of specific PPAR? or PPAR? antagonists. Furthermore, PPAR bound to three PPAR response elements located in the megalin promoter, as shown by EMSA, and PPAR? and its agonist activated a luciferase construct containing a portion of the megalin promoter and the first response element. Accordingly, the activation of PPAR? and PPAR? enhanced megalin expression in mouse kidney. As previously observed, high concentrations of bovine serum albumin (BSA) decreased megalin in PTCs in vitro; however, PTCs pretreated with PPAR? and PPAR? agonists avoided this BSA-mediated reduction of megalin expression. Finally, we found that megalin expression was significantly inhibited in the PTCs of rats that were injected with BSA to induce tubulointerstitial damage and proteinuria. Treatment of these rats with PPAR? agonists counteracted the reduction in megalin expression and the proteinuria induced by BSA. CONCLUSIONS: PPAR?/? and their agonists positively control megalin expression. This regulation could have an important impact on several megalin-mediated physiological processes and on pathophysiologies such as chronic kidney disease associated with diabetes and hypertension, in which megalin expression is impaired.

Dataset Information

Screening of Peroxisome Proliferator-Activated Receptors (PPARs) ?, ? and ? Gene Polymorphisms for Obesity and Metabolic Syndrome Association in the Multi-Ethnic Malaysian Population.

Publications

Screening of Peroxisome Proliferator-Activated Receptors (PPARs) α, γ and α Gene Polymorphisms for Obesity and Metabolic Syndrome Association in the Multi-Ethnic Malaysian Population.

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