Natália Yumi Noronha

Emerging evidence suggests a link between environmental pollution and epigenetic alterations, prompting the need for comprehensive investigations into the relationship between pollutants and health conditions in human populations. This study investigates the interplay between obesity and exposure to toxic metals, examining clinical, serum metal concentrations, and epigenetic signatures. Our approach included serum metal concentration analysis by inductively coupled plasma mass spectrometry and epigenetic analysis using 450k Illumina BeadChips data. Singular value decomposition and linear regression models were used to identify metal associations with DNA methylation. Marked differences were evident in weight, body mass index, glycaemia, High Density Lipoprotein cholesterol (HDL-c), and triglycerides between patients with obesity and without obesity. Metal serum concentrations revealed higher arsenic levels in participants with obesity, while elevated mercury concentrations were found in individuals without obesity. Epigenetic analysis identified 2045 arsenic-associated differentially methylated positions (DMPs) in individuals with obesity, including 57 hypermethylated and 159 hypomethylated sites in promoter regions. These DMPs demonstrated direct associations of arsenic exposure, and traits such as insufficient sleep, smoking, and diseases such as gestational diabetes. Functional enrichment analysis (using traits, gene ontology, and KEGG pathways) highlighted pathways linking obesity and arsenic exposure, specifically the Wnt and TNF signalling pathways. Additionally, hypermethylated sites were linked with cancer, rheumatoid arthritis, and gestational diabetes, emphasizing the intricate relationship between these conditions. Notably, ABCF1 and BRCA1 showed significant differences in methylation associated with arsenic and obesity. The findings provide valuable insights into unravelling the connections between obesity and arsenic exposure, contributing to understand the potential molecular mechanisms and pathways in these intersecting fields.

Obesity causes metabolic changes, such as the development of cardiovascular diseases. Moreover, physical exercise promotes protection against these diseases. Thus, the objective of the present study was to evaluate whether combined physical training can improve the metabolic system of women with obesity, reducing plasma concentrations of trimethylamine N-oxide (TMAO) and sphingolipids, regardless of weight loss. Fourteen obese women (BMI 30–40 kg/m²), aged 20–40 years, sedentary, were submitted to 8 weeks of combined physical training (strength and aerobic exercises). The training was performed three times/week, 55 min/session, at 75–90% maximum heart rate. All participants were evaluated pre- and post-exercise intervention, and their body composition, plasma TMAO, creatinine, lipid profile, and sphingolipid concentrations were recorded. Maximum oxygen consumption (VO2max), Speed lactate threshold 1 (SpeedLT1), and Speed lactate threshold 2 (SpeedLT2) evaluated physical performance. Results: After combined exercise, it did not change body composition, but TMAO, total cholesterol, and sphingolipid concentrations significantly decreased (p < 0.05). There was an increase in physical performance by improving VO2max, SpeedLT1, and SpeedLT2 (p < 0.05). The combined physical exercise could induce cardiovascular risk protection by decreasing TMAO in obese women, parallel to physical performance improvement, independent of weight loss.

Blood selenium (Se) concentrations differ substantially by population and could be influenced by genetic variants, increasing Se deficiency-related diseases. We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with serum Se deficiency in 382 adults with admixed ancestry. Genotyping arrays were combined to yield 90,937 SNPs. R packages were applied to quality control and imputation. We also performed the ancestral proportion analysis. The Search Tool for the Retrieval of Interacting Genes was used to interrogate known protein–protein interaction networks (PPIs). Our ancestral proportion analysis estimated 71% of the genome was from Caucasians, 22% was from Africans, and 8% was from East Asians. We identified the SNP rs1561573 in the TraB domain containing 2B (TRABD2B), rs425664 in MAF bZIP transcription factor (MAF), rs10444656 in spermatogenesis-associated 13 (SPATA13), and rs6592284 in heat shock protein nuclear import factor (HIKESHI) genes. The PPI analysis showed functional associations of Se deficiency, thyroid hormone metabolism, NRF2-ARE and the Wnt pathway, and heat stress. Our findings show evidence of a genetic association between Se deficiency and metabolic pathways indirectly linked to Se regulation, reinforcing the complex relationship between Se intake and the endogenous factors affecting the Se requirements for optimal health.

Obesity is a complex disease with a multifactorial etiology and could be associated with psychiatric disorders, such as Binge Eating Disorder (BED), characterized by recurrent episodes of binge eating in the absence of compensatory behaviors. The present study aimed to analyze anthropometric and body composition changes over five years after bariatric surgery in patients diagnosed or not diagnosed with BED, depression, and anxiety in the preoperative period. One hundred and eighteen patients undergoing bariatric surgery were evaluated and divided into two groups according to the presence or absence of BED. The patients were submitted to anthropometric and body composition evaluation. We also analyzed BED diagnosis, depression, and anxiety according to the DSM-5 and validated questionnaires. The Kolmogorov–Smirnov, t-test, Fisher’s, and chi-square tests were used for statistical analysis. Over five years after bariatric surgery, only the BED group exhibited an increased weight and BMI (p < 0.05). In the preoperative period, patients with BED had severe depression (13,11%, p = 0.0079) and a higher frequency of moderate (22.95%, p < 0.01) or severe (14.75%, p < 0.01) anxiety. In conclusion, patients with BED had more intense symptoms of depression and anxiety in the preoperative period, and this disorder may persist in the postoperative period of bariatric surgery, contributing to weight gain and increased BMI.

Background: Previous studies have suggested that changes in the composition of intestinal microbiota may be influenced by dietary quality. Objective: This study aimed to assess the impact of a hypocaloric diet on the relationship between microbiota and clinical/dietary variables. Methods: This was a longitudinal study. Ten women with obesity (Obese Group, ObG) participated in an 8-week home-based hypocaloric diet intervention. Anthropometric, dietary intake, biochemical, and gut microbiota assessments were conducted before and after the intervention. Microbiota relative abundance was determined using real-time PCR in triplicate. Results: In the ObG, the hypocaloric diet intervention led to significant weight loss (before: 119.5 ± 10.3 kg; after: 114.9 ± 10.2 kg; p = 0.003). Following the intervention, positive correlations were observed between nutrient intake and phyla composition: Actinobacteria phylum with fibers (r = 0.787; p = 0.012), Firmicutes phylum with proteins (r = 0.736; p = 0.024), and Proteobacteria phylum with lipids (r = 0.669; p = 0.049). Conclusions: The hypocaloric diet intervention improved health parameters associated with obesity and its comorbidities, demonstrating associations between nutrient intake and specific phyla.

Background and Objectives: Enzymes involved with acetylation capacity affects the metabolization of several xenobiotics that can be deposited in adipose tissue and hinder weight loss, leading to obesity. Our aim was to identify single nucleotide polymorphisms (SNPs) related to the xenobiotic’s metabolism and to associate such with the serum levels of heavy metals in an individual with excess body weight. Methods: The sample was selected at the Ribeirão Preto Medical School at the University of São Paulo, Brazil. Genotyping arrays were performed with 23 SNPs. Quality control and imputation steps were applied using the functions in the package ‘snpReady’ (CRAN) and ‘imput’ (Bioconductor). Results: This study selected 189 individuals of mixed ethnicity of both sexes, with a mean age of 42.2 ± 12.9 years and a mean BMI of 45.1 ± 11.4 kg/cm². From the cluster of 23 evaluated SNPs, we observed a higher frequency of SNP 1799930 in the NAT2 gene (N-acetyltraferase). The genotypes were correlated to the serum levels of different metals. We observed that individuals homozygous for the mutant allele (AA), called fast metabolizers, had lower levels of aluminum (Al) (51.4 ± 18.9 µg/L) compared to those considered slow metabolizers (GG) (64.0 ± 37.2 µg/L; p = 0.02). No difference was observed when compared with heterozygosity (AG). Furthermore, the BMI of fast metabolizers (48.7 ± 12.8 kg/cm²) was higher than the slow metabolizer individuals (45.9 ± 10.4 kg/cm²; p < 0.05). Discussion: Fast metabolizers seem to have a greater Al metabolization only in homozygosis, that is, the dose-dependent gene, to exert its effect. Interestingly, the presence of the AA genotype is associated with a higher BMI, suggesting that larger studies should be carried out investigating the deposition of metals in adipose tissue.