Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is a major health problem worldwide and constitutes a sanitary emergency in Mexico, especially childhood obesity. Several studies have proved the relationship between obesity and oxidative stress and the influence of genetic predisposition. This work was aimed to analyze the association of antioxidant enzyme polymorphisms with overweight and obesity in Mexican children and adolescents. A case-control study was performed in 585 children and adolescents aged 3 to 17 years, using two criteria to classify obesity: body mass index (BMI) and body fat percentage (BFP). Anthropometric and biochemical measurements were carried out, and malondialdehyde serum levels were determined. Genotyping was done with the Axiom Genome-Wide LAT microarray, including 68 single nucleotide polymorphisms (SNPs) of the glutathione peroxidase (GPX) and paraoxonase (PON) families. We found six haplotypes associated with obesity-two of them (one in GPX3 and the other in GPX5 and GPX6) in a protective direction when obesity was classified by BMI. The other four haplotypes were associated with obesity when classification was based on BFP-one of them in GPX3 in a protective direction and the others in PON genes conferring obesity risk. In addition, two SNPs, GPX3 rs922429 and GPX4 rs2074451 showed protection against obesity classified by BFP. This study showed genetic susceptibility to oxidative stress in relation to obesity in Mexican children and opens up the possibility that some genetic loci related to obesity are not identified when weight classification is based on BMI.
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PMID:Antioxidant Enzymes Haplotypes and Polymorphisms Associated with Obesity in Mexican Children. 3275 12

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight-loss procedures, but how severe obesity and RYGB affects circulating HDL-associated microRNAs (miRNAs) remains unclear. Here, we aim to investigate how HDL-associated miRNAs are regulated in severe obesity and how weight loss after RYGB surgery affects HDL-miRNAs. Plasma HDL were isolated from patients with severe obesity (n=53) before, 6 and 12 months after RYGB by immunoprecipitation using goat anti-human apoA-I microbeads. HDL were also isolated from 18 healthy participants. miRNAs were extracted from isolated HDL and levels of miR-24, miR-126, miR-222 and miR-223 were determined by TaqMan miRNA assays. We found that HDL-associated miR-126, miR-222 and miR-223 levels, but not miR-24 levels, were significantly higher in patients with severe obesity when compared with healthy controls. There were significant increases in HDL-associated miR-24, miR-222 and miR-223 at 12 months after RYGB. Additionally, cholesterol efflux capacity and paraoxonase (PON1) activity were increased and intracellular adhesion molecule-1 (ICAM-1) levels decreased. The increases in HDL-associated miR-24 and miR-223 were positively correlated with increase in cholesterol efflux capacity (r=0.326, P=0.027 and r=0.349, P=0.017 respectively). An inverse correlation was observed between HDL-associated miR-223 and ICAM-1 at baseline. Together, these findings show that HDL-associated miRNAs are differentially regulated in healthy versus patients with severe obesity and are altered after RYGB. These findings provide insights into how miRNAs are regulated in obesity before and after weight reduction, and may lead to the development of novel treatment strategies for obesity and related metabolic disorders.
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PMID:High-density lipoprotein-associated miRNA is increased following Roux-en-Y gastric bypass surgery for severe obesity. 3309 36

Paraoxonase 1 (PON1) enzyme has antioxidative properties and is present in mammalian blood and several other body fluids. In blood, PON1 is usually integrated into the high-density lipoprotein (HDL) cholesterol. PON1 is a highly versatile enzyme displaying diverse functions such as arylesterase, lactonase, and paraoxonase, among others. PON1 activities are usually investigated with artificial substrates, for example, dihydrocoumarin and thiobutyl butyrolactone for lactonase activity. The PON1 enzyme activities measured with different substrates tend to be falsely assumed as being equivalent in the literature, although there are poor or weak correlations among the PON1 enzyme activities with different substrates. In addition, and despite our knowledge of the factors influencing PON1 paraoxonase and arylesterase activities, there is little knowledge of PON1 lactonase activity variations and attendant mechanisms. This is important considering further that the lactonase activity is the native activity of PON1. We report here a multi-omics analysis of PON1 lactonase activity. The influence of genetic variations, particularly of single nucleotide polymorphisms and epigenetic, proteomic, and lipidomic variations on PON1 lactonase activity are reviewed. In addition, the influence of various environmental, clinical, and demographic variables on PON1 lactonase activity is discussed. Finally, we examine the associations between PON1 lactonase activity and health states and common complex diseases such as atherosclerosis, dementias, obesity, and diabetes. To the best of our knowledge, this is the first multi-omics analysis of PON1 lactonase activity with an eye to future applications in basic life sciences and translational medicine and the nuances of critically interpreting PON1 function with lactones as substrates.
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PMID:A Multi-Omics Analysis of PON1 Lactonase Activity in Relation to Human Health and Disease. 3330 25


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