Association between the relative abundance of phyla actinobacteria, vitamin C consumption, and DNA methylation of genes linked to immune response pathways.

Introduction: There is an emerging body of evidence that vitamin C consumption can modulate microbiota abundance and can also impact DNA methylation in the host, and this could be a link between diet, microbiota, and immune response. The objective of this study was to evaluate common CpG sites associated with both vitamin C and microbiota phyla abundance. Methods: Six healthy women participated in this cohort study. They were divided into two groups, according to the amount of vitamin C they ingested. Ingestion was evaluated using the 24-h recall method. The Illumina 450 k BeadChip was used to evaluate DNA methylation. Singular value decomposition analyses were used to evaluate the principal components of this dataset. Associations were evaluated using the differentially methylated position function from the Champ package for R Studio. Results and discussion: The group with higher vitamin C (HVC) ingestion also had a higher relative abundance of Actinobacteria. There was a positive correlation between those variables (r = 0.84, p = 0.01). The HVC group also had higher granulocytes, and regarding DNA methylation, there were 207 CpG sites commonly related to vitamin C ingestion and the relative abundance of Actinobacteria. From these sites, there were 13 sites hypomethylated and 103 hypermethylated. The hypomethylated targets involved the respective processes: immune function, glucose homeostasis, and general cellular metabolism. The hypermethylated sites were also enriched in immune function-related processes, and interestingly, more immune responses against pathogens were detected. These findings contribute to understanding the interaction between nutrients, microbiota, DNA methylation, and the immune response.

14-Week exercise training modifies the DNA methylation levels at gene sites in non-Alzheimer's disease women aged 50 to 70 years.

Exercise training emerges as a key strategy in lifestyle modification, capable of reducing the risk of developing Alzheimer's disease (AD) due to risk factors such as age, family history, genetics and low level of education associated with AD. We aim to analyze the effect of a 14-week combined exercise training (CT) on the methylation of genes associated with AD in non-alzheimer's disease women. CT sessions lasted 60 min, occurring three times a week for 14 weeks. Forty non-Alzheimer's disease women aged 50 to 70 years (60.7 ± 4.1 years) with a mean height of 1.6 ± 0.1 m, mean weight of 73.12 ± 9.0 kg and a mean body mass index of 29.69 ± 3.5 kg/m2, underwent two physical assessments: pre and post the 14 weeks. DNA methylation assays utilized the EPIC Infinium Methylation BeadChip from Illumina. We observed that 14 weeks of CT led to reductions in systolic (p = 0.001) and diastolic (p = 0.017) blood pressure and improved motor skills post-intervention. Among 25 genes linked to AD, CT induced differentially methylated sites in 12 genes, predominantly showing hypomethylated sites (negative ß values). Interestingly, despite hypomethylated sites, some genes exhibited hypermethylated sites (positive ß values), such as ABCA7, BDNF, and WWOX. A 14-week CT regimen was adequate to induce differential methylation in 12 CE-related genes in healthy older women, alongside improvements in motor skills and blood pressure. In conclusion, this study suggest that combined training can be a strategy to improve physical fitness in older individuals, especially able to induce methylation alterations in genes sites related to development of AD. It is important to highlight that training should act as protective factor in older adults.

The influence of serum selenium in differential epigenetic and transcriptional regulation of CPT1B gene in women with obesity.

INTRODUCTION: The increasing prevalence of obesity has become a major health problem worldwide. The causes of obesity are multifactorial and could be influenced by dietary patterns and genetic factors. Obesity has been associated with a decrease in micronutrient intake and consequently decreased blood concentrations. Selenium is an essential micronutrient for human health, and its metabolism could be affected by obesity, especially severe obesity. This study aimed to identify differential methylation genes associated with serum selenium concentration in women with and without obesity. METHODOLOGY: Thirty-four patients were enrolled in the study and divided into two groups: Obese (Ob) n = 20 and Non-Obese (NOb) n = 14, according to the Body Mass Index (BMI). Anthropometry, body composition, serum selenium, selenium intake, and biochemical parameters were evaluated. DNA extraction and bisulfite conversion were performed to hybridize the samples on the 450k Methylation Chip Infinium Beadchip (Illumina). Bioinformatics analysis was performed using the R program and the Champ package. The differentially methylated regions (DMRs) were identified using the Bumphunter method. In addition, logarithmic conversion was performed for the analysis of serum selenium and methylation. RESULTS: In the Ob group, the body weight, BMI, fat mass, and free fat mass were higher than in the NOb group, as expected. Interestingly, the serum selenium was lower in the Ob than in the NOb group without differences in selenium intake. One DMR corresponding to the CPT1B gene, involved in lipid oxidation, was related to selenium levels. This region was hypermethylated in the Ob group, indicating that the intersection between selenium deficiency and hypermethylation could influence the expression of the CPT1B gene. The transcriptional analysis confirmed the lower expression of the CPT1B gene in the Ob group. CONCLUSION: Studies connecting epigenetics to environmental factors could offer insights into the mechanisms involving the expression of genes related to obesity and its comorbidities. Here we demonstrated that the mineral selenium might play an essential role in lipid oxidation via epigenetic and transcriptional regulation of the CPT1B gene in obesity.

Eight Weeks of Physical Training Decreases 2 Years of DNA Methylation Age of Sedentary Women.

Purpose: The acceleration of epigenetic age is a predictor of mortality and contributes to the increase in chronic diseases. Adherence to a healthy lifestyle is a strategy to reduce epigenetic age. The present study aimed to determine whether eight weeks of combined (aerobic and strength) training (CT) can influence the epigenetic age of women between 50 and 70 years old and the differences in sites and methylated regions. Methods: Eighteen women (AARLow: lower age acceleration residual, n = 10; AARHigh: higher age acceleration residual, n = 8) participated in a combined exercise training program (60 minutes, 3× a week) for eight weeks. DNA was extracted from whole blood using the salting out technique. DNA methylation was performed using the array technique (Illumina's Infinium Methylation BeadChip 850k). We used the DNA Methylation Age Calculator platform to calculate the biological epigenetic age. Two-way ANOVA followed by FISHER LSD posthoc was Applied, adopting p < .05. Results: After eight weeks of CT, there were no changes to the epigenetic age acceleration for the AARLow group (PRE: -2.3 ± 3.2 to POST: -2.3 ± 3.6). However, the AARHigh group significantly decreased the age acceleration (PRE: 3.6 ± 2.6 to POST: 2.2 ± 2.7) (group effect, p = .01; time effect, p = .31; group vs. time effect, p = .005). Conclusion: CT for eight weeks benefits the epigenetic clock of women with the most accelerated age.

Older postmenopausal women with lower lean mass have hypermethylated sites in the PI3K-Akt pathway.

Introduction: The decrease in lean mass is directly related to the loss of independence, muscle strength, and worse quality of life over the years. Although the genetic determinants of muscle mass were well recognized, recent literature has been uncovering new epigenetic factors affecting the state of muscular tissue. This study aimed to verify differences in the DNA methylation profile among Brazilian postmenopausal women aged 50-70 years according to the lean mass evaluation. Methods: A cross-sectional study comprised 40 women aged 50-70 years. After K-means cluster analysis the 40 participants were divided into two groups, the Lower Lean Mass group with 20 participants (61.1 ± 4.6 years) and the Higher Lean Mass group with 20 participants (60.7 ± 3.2 years). Lean mass was measured by dual-energy X-ray emission densitometry (DEXA). The participants' DNA was extracted using the Salting Out technique and subsequently, the Illumina 850k EPIC Infinium Methylation BeadChip was performed to obtain methylation data. Results: We obtained 1,913 differentially methylated sites (p ≤ 0.005 of ß > 5% and ß < -5%) in a total of 979 genes between groups (p ≤ 0.005; -5% > ß > 5%). In addition, the PI3K-Akt pathway had the greatest power of significance with an FDR of 4.6 × 10-3. Conclusion: Our results demonstrate a differentiation between specific sites of different genes, which have essential functions in body composition and energy metabolism, supporting future studies that aim to relate lean mass with epigenetics.

Comparing Fourteen Weeks of Multicomponent Training Versus Combined Training in Physically Inactive Older Women: A Randomized Trial.

BACKGROUND: Combined (CT) and multicomponent training (MT) presents several benefits for aging individuals. However, the literature does not provide evidence on which of the two physical training models can better enhance improvements in physical capacity and health parameters in middle-aged and older women. OBJECTIVE: The aim of this study was to compare the effects of MT and CT on physical capacity, cognitive, behavioral, and psychosocial assessment, and biochemical profile of physically inactive women aged between 50 and 70 years. METHODS: Participants were randomized into two groups: MT (32 women, 64.2 ± 6.4 years) and CT (39 women, 61.4 ± 4.3 years). Both training sessions had a weekly volume of 180 min, for 14 weeks, with assessments at baseline and after the training period. RESULTS: CT showed better results when compared to MT. In the four evaluation blocks, we noticed differences in the effect size (L = large, M = moderate, S = small, and T = trivial) between the groups in 26 variables in total, highlighting the CT group (L = 11, M = 5, S = 2, and T = 8) compared to the MT group (L = 8, M = 7, S = 7, and T = 4). Our findings showed group-time differences for strength variables using the maximum dynamic repetition test in upper and lower limbs and for agility. The multicomponent training showed improvement in the functional strength of the upper limbs evaluated through the elbow flexion and extension test (p = 0.037), and HDL (p = 0.022). CONCLUSIONS: Fourteen weeks of CT showed better benefits when compared to MT.

Efficacy of the argon plasma coagulation in patients with weight regain after gastric bypass: a randomized control trial.

Background and study aims Endoscopic procedure using argon plasma coagulation (APC) promotes a progressive reduction in gastrojejunal anastomosis diameter. The present study aimed to evaluate the efficacy of the APC in patients with weight regain in the postoperative periods of gastric bypass. Patients and methods This was a randomized controlled trial conducted with 66 patients who were randomly assigned selected (using lottery method) and divided into two groups: study group (SG), 38 patients (APC treatment); and control group (CG), 28 patients (only endoscopy procedure). We considered 30 days,180 days, and one year as short-term, medium-term, and long-term, respectively. The parameters analyzed were total weight loss (TWL), excess weight loss (%EWL), total weight loss (%TWL), and reduction of weight regain (%RWR). Furthermore, a biopsy for neoplastic histological changes was carried out for the APC group. For statistical analysis, values of P  < 0.05 were considered significant. Results The %TWL and %RWR were higher in the SG in short, medium, and long terms, when compared to the same periods in the CG ( P  < 0.001). One year after follow-up, the final weight did not reach the statistical difference between groups. Biopsy performed in SG 1 year after APC did not reveal neoplastic histological changes. Conclusions APC effectively treats weight regain after bariatric surgery in the short and medium-term. An important "new" weight gain was observed in the long-term, showing that obesity is a chronic disease that requires multidisciplinary and family care for life. Also, APC is a safe procedure with low adverse event rates.

Can the Brazilian Caffeine Expectancy Questionnaires Differentiate the CYP1A2 and ADORA2A Gene Polymorphisms?-An Exploratory Study with Brazilian Athletes.

This study investigated the ability of the Brazilian Caffeine Expectancy Questionnaire (CaffEQ-BR), full and brief versions, to differentiate genetic profiles regarding the polymorphisms of the CYP1A2 (rs 762551) and ADORA2A (rs 5751876) genes in a cohort of Brazilian athletes. One-hundred and fifty participants were genotyped for CYP1A2 and ADORA2A. After the recruitment and selection phase, 71 (90% male and 10% female, regular caffeine consumers) completed the CaffEQ-BR questionnaires and a self-report online questionnaire concerning sociodemographic data, general health status, and frequency of caffeine consumption. The order of completion of the CaffEQ-BR questionnaires was counterbalanced. The concordance between the full and brief versions of the CaffEQ-BR was analyzed using the intraclass correlation coefficient (ICC). To determine the discriminatory capacity of the questionnaires for genotype, the receiver operating characteristic (ROC) curve was applied for sensitivity and specificity (significance level of 5%). Mean caffeine intake was 244 ± 161 mg·day−1. The frequency of AA genotypes for CYP1A2 was 47.9% (n = 34) and 52.1% (n = 37) for C-allele carriers (AC and CC). The frequencies of TT genotypes for ADORA2A were 22.7% (n = 15) and 77.3% (n = 51) for C-allele carriers (TC and CC). All CaffEQ-BR factors, for the full and brief versions, were ICCs > 0.75, except for factor 6 (anxiety/negative effects; ICC = 0.60), and presented ROC curve values from 0.464 to 0.624 and 0.443 to 0.575 for CYP1A2 and ADORA2A. Overall, the CaffEQ-BR (full and brief versions) did not show discriminatory capacity for CYP1A2 and ADORA2A gene polymorphisms. In conclusion, the CaffEQ-BR was not able to differentiate genotypes for the CYP1A2 or ADORA2A genes in this group of Brazilian athletes.

Food and Nutrition Public Policies in Brazil: From Malnutrition to Obesity.

"Nutrition transition" describes the shifts in dietary consumption and energy expenditure influenced by economic, demographic, and epidemiological changes at a population level. This phenomenon has been associated with rising obesity rates worldwide, especially in developed countries. In Brazil, the historical analysis of temporal trends between malnutrition and obesity characterized the nutrition transition in the country and interweaved it with the formulation and implementation of public food and nutrition policies. Such analysis is crucial for understanding certain principles in each context. Thus, this review contextualized the consolidation of obesity as a critical health and public policy issue in Brazil. Our review suggested that the country may still be at the initial stage of care for obesity, and more efforts are needed to contain the advance of the disease in Brazil.

Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies.

Obesity is directly connected to lifestyle and has been associated with DNA methylation changes that may cause alterations in the adipogenesis and lipid storage processes contributing to the development of the disease. We demonstrate a complete protocol from selection to epigenetic data analysis of patients with and without obesity. All steps from the protocol were tested and validated in a pilot study. 32 women participated in the study, in which 15 individuals were classified with obesity according to Body Mass Index (BMI) (45.1 ± 5.4 kg/m2); and 17 individuals were classified without obesity according to BMI (22.6 ± 1.8 kg/m2). In the group with obesity, 564 CpG sites related to fat mass were identified by linear regression analysis. The CpG sites were in the promoter regions. The differential analysis found 470 CpGs hypomethylated and 94 hypermethylated sites in individuals with obesity. The most hypomethylated enriched pathwayswere in the RUNX, WNT signaling, and response to hypoxia. The hypermethylated pathways were related to insulin secretion, glucagon signaling, and Ca2+. We conclude that the protocol effectively identified DNA methylation patterns and trait-related DNA methylation. These patterns could be associated with altered gene expression, affecting adipogenesis and lipid storage. Our results confirmed that an obesogenic lifestyle could promote epigenetic changes in human DNA.

Corrigendum: Novel Zinc-Related Differentially Methylated Regions in Leukocytes of Women With and Without Obesity.

[This corrects the article DOI: 10.3389/fnut.2022.785281.].

Novel Zinc-Related Differentially Methylated Regions in Leukocytes of Women With and Without Obesity.

Introduction: Nutriepigenetic markers are predictive responses associated with changes in "surrounding" environmental conditions of humans, which may influence metabolic diseases. Although rich in calories, Western diets could be linked with the deficiency of micronutrients, resulting in the downstream of epigenetic and metabolic effects and consequently in obesity. Zinc (Zn) is an essential nutrient associated with distinct biological roles in human health. Despite the importance of Zn in metabolic processes, little is known about the relationship between Zn and epigenetic. Thus, the present study aimed to identify the epigenetic variables associated with Zn daily ingestion (ZnDI) and serum Zinc (ZnS) levels in women with and without obesity. Materials and Methods: This is a case-control, non-randomized, single-center study conducted with 21 women allocated into two groups: control group (CG), composed of 11 women without obesity, and study group (SG), composed of 10 women with obesity. Anthropometric measurements, ZnDI, and ZnS levels were evaluated. Also, leukocyte DNA was extracted for DNA methylation analysis using 450 k Illumina BeadChips. The epigenetic clock was calculated by Horvath method. The chip analysis methylation pipeline (ChAMP) package selected the differentially methylated regions (DMRs). Results: The SG had lower ZnS levels than the CG. Moreover, in SG, the ZnS levels were negatively associated with the epigenetic age acceleration. The DMR analysis revealed 37 DMRs associated with ZnDI and ZnS levels. The DMR of PM20D1 gene was commonly associated with ZnDI and ZnS levels and was hypomethylated in the SG. Conclusion: Our findings provide new information on Zn's modulation of DNA methylation patterns and bring new perspectives for understanding the nutriepigenetic mechanisms in obesity.

DRD2 and BDNF polymorphisms are associated with binge eating disorder in patients with weight regain after bariatric surgery.

AIM: The aim of this study was to analyze the association and susceptibility of Single Nucleotide Polymorphisms (SNPs) in the DRD2 and BDNF genes with BED in patients with weight regain in the postoperative period of bariatric surgery. METHODS: One hundred and seventy-seven individuals who underwent bariatric surgery with weight regain were evaluated and divided into two groups according to the BED diagnostic. The individuals were submitted to an anthropometric evaluation, analysis of the presence of BED using a validated questionnaire, and blood collection for genotyping of the polymorphisms rs6265 (BDNF) and rs1800497 (DRD2) by real-time polymerase chain reaction (RT-PCR). RESULTS: The presence of wild-type alleles for rs1800497 (CC) and rs6265 (GG) was more frequent in patients without BED. Nevertheless, the presence of one or two variant alleles for rs1800497 (CT + TT) and rs6265 (GA + AA) was more frequent in patients with BED. The combination of the two studied SNPs prevailed in patients with BED. CONCLUSIONS: The presence of allele frequency of rs1800497 SNP in the DRD2 gene and rs6265 SNP in the BDNF gene, isolated and/or combined, indicated an additional risk for the development of BED in patients with obesity, especially in the context of weight regain. LEVEL OF EVIDENCE: III (evidence obtained from the case-control analytic study).

Differential Expression of MMP2 and TIMP2 in Peripheral Blood Mononuclear Cells After Roux-en-Y Gastric Bypass.

Matrix metalloproteinases (MMP) and their endogenous inhibitor, the tissue inhibitor of metalloproteinases (TIMP), are expressed in many different cell types and play an important role in physiologic and pathological degradation of extracellular matrix (ECM). Starting from these observations and considering the activation state of peripheral blood mononuclear cells (PBMCs) in obesity, we investigated the gene expression of metalloproteinases before and after Roux-en-Y gastric bypass (RYBG). The study was performed in the Ribeirão Preto Medical School University Hospital. Seventy-three women were divided into a study group (SG), composed of 53 individuals with severe obesity before and after 6 months of RYGB, and a control group (CG), composed of 20 normal-weight individuals. Anthropometric and body composition data were collected, and peripheral blood for ribonucleic acid (RNA) extraction. The biological samples were submitted to a quantitative real-time polymerase chain reaction to evaluate the expression of MMP2 and TIMP2 genes. Alterations in weight loss, body mass index (BMI), and fat mass (FM) were observed after 6 months of RYGB (p < 0.05). A reduction of gene expression of TIMP2 was observed after 6 months of RYGB, contributing positively to the weight loss (R 2 = 0.33 p = 0.04). The enrichment analyses highlighted the interaction between TIMP2 and MMP2 genes and the molecular pathways involving the ECM remodeling in the obesity condition. RYGB contributes significantly to weight loss, improved BMI, reduced FM, and reduced TIMP2 expression in PBMCs, which might contribute to the ECM remodeling in the obesity and could be useful as a circulating biomarker.

Gene signatures of autopsy lungs from obese patients with COVID-19.

BACKGROUND & AIMS: Obesity is associated with low grade systemic inflammation and insulin resistance. Although metabolic and immunological changes may contribute to the increased risk for COVID-19 mortality in obese, little is known about the impact of obesity in the lungs of patients with COVID-19. METHODS: We analyzed gene expression profiles of autopsy lungs of a cohort of 14 COVID-19 patients and 4 control individuals. Patients were divided into 3 groups according to their comorbidities: hypertension, type 2 diabetes (T2D) and obesity. We then identified the molecular alterations associated with these comorbidities in COVID-19 patients. RESULTS: Patients with only hypertension showed higher levels of inflammatory genes and B-cell related genes when compared to those with T2D and obesity. However, the levels of IFN-gamma, IL22, and CD274 (a ligand that binds to receptor PD1) were higher in COVID-19 patients with T2D and obesity. Several metabolic- and immune-associated genes such as G6PD, LCK and IL10 were significantly induced in the lungs of the obese group. CONCLUSION: Our findings suggest that SARS-CoV-2 infection in the lungs may exacerbate the immune response and chronic condition in obese COVID-19 patients.

The Impact of Gastric Bypass on Telomere Length and Shelterin Complex Gene Expression: 6 Months Prospective Study.

BACKGROUND: Telomeres are structures located at the ends of chromosomes associated with a protein complex, known as the shelterin complex. In individuals with obesity, excess adipose tissue plays a key role in inducing a chronic and systemic inflammatory state, which can cause TL shortening. In this context, bariatric surgery is one of the most effective treatment modalities in improving metabolic control. AIM: Therefore, the present study aimed to evaluate how a short postoperative period of gastric bypass affects TL and expression of POT1, TRF1 and TRF2 genes. METHODS: Forty-eight women submitted to RYGB were evaluated before and after 6 months of the surgical procedure. Anthropometric measures of body weight and height (BMI), abdominal circumference (AC), body composition, food intake and blood collection for biochemical evaluation, TL analysis (DNA), and gene expression (RNA) were collected at each moment. RESULTS: There was a reduction of weight, BMI, AC, FM and FFM as well as of glycemia, total cholesterol, LDL-cholesterol, and triglycerides after gastric bypass. No difference in energy intake and macronutrients consumption was observed. There was no significant change in TL, but there was a significant increase of POT1 and TRF1 gene expression after surgery, while TRF2 expression did not change. CONCLUSIONS: Despite bariatric surgery is not capable of increasing telomere length in a short-term period, no reduction is observed; additionally, we found a correlation between serum triglycerides concentration and TL. The increase of POT1 and TRF1 gene expression may explain the maintenance of the TL after 6 months postoperative period.

The effects of short-term combined exercise training on telomere length in obese women: a prospective, interventional study.

BACKGROUND: Telomere length is inversely associated with the senescence and aging process. Parallelly, obesity can promote telomere shortening. Evidence suggests that physical activity may promote telomere elongation. OBJECTIVE: This study's objective is to evaluate the effects of combined exercise training on telomere length in obese women. DESIGN AND METHODS: Twenty pre-menopausal women (BMI 30-40 kg/m2, 20-40 years) submitted to combined training (strength and aerobic exercises), but only 13 finished the protocol. Each exercise session lasted 55 min/day, three times a week, throughout 8 weeks. Anthropometric data, body composition, physical performance (Vo2max), and 8-h fasting blood samples were taken before and after 8 weeks of training. Leukocyte DNA was extracted for telomere length by RT-qPCR reaction, using the 2-ΔΔCt methodology. RESULTS: After the training intervention, significant differences (p < 0.05) were observed in telomere length (respectively before and after, 1.03 ± 0.04 to 1.07 ± 0.04 T/S ratio), fat-free mass (46 ± 7 to 48 ± 5 kg), Vo2max (35 ± 3 to 38 ± 3 ml/kg/min), and waist circumference (96 ± 8 to 90 ± 6 cm). In addition, an inverse correlation between waist circumference and telomere length was found, before (r = - 0.536, p = 0.017) and after (r = - 0.655, p = 0.015) exercise training. CONCLUSION: Combined exercise promoted leukocyte telomere elongation in obese women. Besides, the data suggested that greater waist circumference may predict shorter telomere length. CLINICAL TRIAL REGISTRATION: ClinicalTrails.gov, NCT03119350. Retrospectively registered on 18 April 2017.

Obesity, weight loss, and influence on telomere length: New insights for personalized nutrition.

Telomeres are structures located at the ends of chromosomes associated with proteins, from the shelterin complex, which are responsible for the protection and preservation of the genetic material. The telomere length (TL) progressively decreases with each cell division, and recent evidence suggests that lifestyle can lead to telomere shortening. In individuals with obesity, excess adipose tissue plays a key role in inducing a chronic and systemic inflammatory state, which can cause TL shortening. Thus, the aim of the present review was to show the relationship between obesity and TL in addition to the possible risk factors for its shortening and how the different strategies for weight loss can modulate TL. As the crucial result, we can consider the association between TL and weight loss, and adiposity changes after different interventions, showing that TL may be used as a biomarker of responses to obesity treatment.