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.

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.

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.

Optimising blood glucose control with portioned meal box in type 2 diabetes mellitus patients: a randomised control trial.

Background: The impact of dietary factors on glycaemic control in type 2 diabetes mellitus (T2DM) is well established. However, the effectiveness of transforming portion control into a practical innovation for glycaemic control in T2DM has not yet been established for counselling in nutrition. The aim of this study was to compare the effect of general counselling in nutrition (GCN) and a portioned meal box (PMB) on fasting blood glucose, glycated haemoglobin (HbA1c) and body composition. Methods: A randomised, parallel intervention trial was conducted over 12 weeks, with GCN: carbohydrate portion control concept by using food exchange lists (n = 25) and PMB: portioned meal box was set by energy requirements (n = 25). Results: Both GCN and PMB demonstrated reductions in HbA1c levels at the 6th and 12th weeks compared to baseline. However, no significant difference in HbA1c was observed between GCN and PMB at either the 6th or 12th week. Using PMB at least four times a week significantly decreased HbA1c during the intervention period (p = 0.021 and p < 0.001 for weeks 6 and 12 when compared with baseline, respectively). Changes in body composition were observed: body weight decrease in PMB only, body fat decrease and constant muscle mass in both groups. Both methods tended to relieve hunger and increased satiety in both groups. The satisfaction evaluation showed that participants preferred to use PMB over GCN (p = 0.001). Additionally, participants consumed less energy, carbohydrate and fat in PMB (p = 0.001, p = 0.019, and p = 0.001, respectively) and less energy and fat in GCN (p = 0.006 and p = 0.001, respectively). Conclusion: A better diet, either through GCN or PMB, can play an important role in improving dietary intake compliance and controlling blood glucose.

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.

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.

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.

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.

Bariatric surgery can acutely modulate ER-stress and inflammation on subcutaneous adipose tissue in non-diabetic patients with obesity.

BACKGROUND: Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the most effective and durable treatment option for severe obesity. The mechanisms involving adipose tissue may be important to explain the effects of surgery. METHODS: We aimed to identify the genetic signatures of adipose tissue in patients undergoing RYGB. We evaluated 13 obese, non-diabetic patients (mean age 37 years, 100% women, Body mass index (BMI) 42.2 kg/m2) one day before surgery, 3 and 6 months (M) after RYGB. RESULTS: Analysis of gene expression in adipose tissue collected at surgery compared with samples collected at 3 M and 6 M Post-RYGB showed that interleukins [Interleukin 6, Tumor necrosis factor-α (TNF-α), and Monocyte chemoattractant protein-1(MCP1)] and endoplasmic reticulum stress (ERS) genes [Eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) and Calreticulin (CALR)] decreased during the follow-up (P ≤ 0.01 for all). Otherwise, genes involved in energy homeostasis [Adiponectin and AMP-activated protein kinase (AMPK)], cellular response to oxidative stress [Sirtuin 1, Sirtuin 3, and Nuclear factor erythroid 2-related factor 2 (NRF2)], mitochondrial biogenesis [Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)] and amino acids metabolism [General control nonderepressible 2 (GCN2)] increased from baseline to all other time points evaluated (P ≤ 0.01 for all). Also, expression of Peroxisome proliferator-activated receptor gamma (PPARϒ) (adipogenesis regulation) was significantly decreased after RYGB (P < 0.05). Additionally, we observed that PGC1α, SIRT1 and AMPK strongly correlated to BMI at 3 M (P ≤ 0.01 for all), as well as ADIPOQ and SIRT1 to BMI at 6 M (P ≤ 0.01 for all). CONCLUSIONS: Our findings demonstrate that weight loss is associated with amelioration of inflammation and ERS and increased protection against oxidative stress in adipose tissue. These observations are strongly correlated with a decrease in BMI and essential genes that control cellular energy homeostasis, suggesting an adaptive process on a gene expression level during the caloric restriction and weight loss period after RYGB. Trial registration CAAE: 73,585,317.0.0000.5440.

Analysis of Body Composition and Pain Intensity in Women with Chronic Pelvic Pain Secondary to Endometriosis.

OBJECTIVE: To determine the average body composition (percentage of body fat), the anthropometric markers, and the intensity of clinical pain in women with a clinical diagnosis of chronic pelvic pain (CPP) secondary to endometriosis. METHODS: A case-control study performed with 91 women, 46 of whom with CPP secondary to endometriosis and 45 of whom with CPP secondary to other causes. They underwent an evaluation of the anthropometric parameters by means of the body mass index (BMI), the perimeters (waist, abdomen, hip), and the percentage of body fat (%BF), which were assessed on a body composition monitor by bioimpedance; the intensity of the clinical pain was evaluated using the visual analog scale (VAS), and the symptoms of anxiety and depression, using the hospital's anxiety and depression scale (HAD). RESULTS: The groups did not differ in terms of mean age, BMI, %BF or regarding the available waist-to-hip ratio (WHR). The mean intensity of the clinical pain by the VAS was of 7.2 ± 2.06 in the group with CPP secondary to endometriosis, and of 5.93 ± 2.64 in the group with CPP secondary to other causes (p = 0.03), revealing significant differences between the groups. CONCLUSION: We concluded that, despite the difference in the pain score assessed between the two groups, there was no difference regarding body composition and anthropometry.

OBJETIVO: Determinar a composição corporal média (porcentagem de gordura corporal), os marcadores antropométricos, e a intensidade de dor clínica em mulheres com diagnóstico clínico de dor pélvica crônica (DPC) secundária a endometriose. MéTODOS: Um estudo de caso-controle realizado com 91 mulheres, 46 das quais com DPC secundária a endometriose, e 45 das quais com DPC secundária a outras causas. As pacientes foram submetidas à avaliação dos parâmetros antropométricos por meio do índice de massa corporal (IMC), dos perímetros (cintura, abdômen, quadril), e do percentual de gordura corporal (%GC), que foram avaliados em monitor de composição corporal por bioimpedância; a intensidade clínica da dor foi avaliada usando-se a escala visual analógica (EVA), e os sintomas de ansiedade e depressão, usando a escala de ansiedade e depressão do hospital (EADH). RESULTADOS: Os grupos não diferiram quanto à idade média, ao IMC, ao %GC, nem quanto à relação da cintura­quadril (RCQ) disponível. A média da intensidade clínica da dor pela EVA foi de 7,2 ± 2,06 no grupo com DPC secundária a endometriose, e de 5,93 ± 2,64 no grupo com DPC secundária a outras causas (p = 0,03), revelando diferenças significativas entre os grupos. Em relação à EADH, ambos os grupos estavam acima da média de corte. CONCLUSãO: Concluímos que, apesar da diferença no escore de dor avaliado entre os dois grupos, não houve diferença com relação à composição corporal e à antropometria.

Nutritional genomics, inflammation and obesity.

The Human Genome Project has significantly broadened our understanding of the molecular aspects regulating the homeostasis and the pathophysiology of different clinical conditions. Consequently, the field of nutrition has been strongly influenced by such improvements in knowledge - especially for determining how nutrients act at the molecular level in different conditions, such as obesity, type 2 diabetes, cardiovascular disease, and cancer. In this manner, characterizing how the genome influences the diet and vice-versa provides insights about the molecular mechanisms involved in chronic inflammation-related diseases. Therefore, the present review aims to discuss the potential application of Nutritional Genomics to modulate obesity-related inflammatory responses. Arch Endocrinol Metab. 2020;64(3):205-22.

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.

Association of MFSD3 promoter methylation level and weight regain after gastric bypass: Assessment for 3 y after surgery.

OBJECTIVES: Genetic predisposition and epigenetic signatures could explain why some individuals regain the weight lost after different obesity treatments. Major facilitator superfamily domain 3 (MFSD3) is a family of membrane-bound solute carriers whose expression has been recently associated with nutrient intake and adipose tissue homeostasis. This study aimed to evaluate a possible association between MFSD3 preoperative methylation pattern and weight regain after bariatric surgery. METHODS: This is a longitudinal study comprising 24 obese (body mass index > 35 m/kg2) women submitted to gastric bypass. Anthropometric measurements were evaluated at preoperative time and 1, 2, and 3 y after surgery, and then weight regain was calculated. Genomic DNA was extracted from leukocytes and was bisulfite modified by specific kits, according manufacturer's instructions. Methylation analysis was performed with the Infinium Human Methylation 450 K bead chip technology, and methylation level was expressed as a ß value ranging from 0 (unmethylated) to 1 (fully methylated). Shapiro-Wilk, repeated-means analysis of variance, Spearman correlation, Mann-Whitney, and independent t tests were used in statistical analysis (P < 0.05). RESULTS: A total of 25% of patients regained significant weight. Weight regain after bariatric surgery was positively correlated with cg00010266 MFSD3 preoperative methylation levels (r = 0.6804, P = 0.0126). Moreover, cg00010266 MFSD3 baseline methylation levels were significantly higher in regainer patients than non-regainers (6.2 ± 1.5 versus 3.9 ± 1.2%, P = 0.026). Patients allocated in the higher cg00010266 MFSD3 preoperative methylation group had higher weight regain (4.1 ± 1.8 versus 6.7 ± 2.2 kg, P = 0.037). CONCLUSIONS: Preoperative hypermethylation of MFSD3 gene is significantly associated with weight regain and a worse response to gastric bypass.