Changes in DNA Methylation and Gene Expression of Insulin and Obesity-Related Gene PIK3R1 after Roux-en-Y Gastric Bypass.

Weight regulation and the magnitude of weight loss after a Roux-en-Y gastric bypass (RYGB) can be genetically determined. DNA methylation patterns and the expression of some genes can be altered after weight loss interventions, including RYGB. The present study aimed to evaluate how the gene expression and DNA methylation of PIK3R1, an obesity and insulin-related gene, change after RYGB. Blood samples were obtained from 13 women (35.9 ± 9.2 years) with severe obesity before and six months after surgical procedure. Whole blood transcriptome and epigenomic patterns were assessed by microarray-based, genome-wide technologies. A total of 1966 differentially expressed genes were identified in the pre- and postoperative periods of RYGB. From these, we observed that genes involved in obesity and insulin pathways were upregulated after surgery. Then, the PIK3R1 gene was selected for further RT-qPCR analysis and cytosine-guanine nucleotide (CpG) sites methylation evaluation. We observed that the PI3KR1 gene was upregulated, and six DNA methylation CpG sites were differently methylated after bariatric surgery. In conclusion, we found that RYGB upregulates genes involved in obesity and insulin pathways.

Exercise training and DNA methylation profile in post-bariatric women: Results from an exploratory study.

Exercise training and bariatric surgery have been shown to independently modulate DNA methylation profile in clusters of genes related to metabolic and inflammatory pathways. This study aimed to investigate the effects of a 6-month exercise training program on DNA methylation profile in women who underwent bariatric surgery. In this exploratory, quasi-experimental study, we analyzed DNA methylation levels by array technology in eleven women who underwent Roux-en-Y Gastric Bypass and a 6-month, three-times-a-week, supervised exercise training program. Epigenome Wide Association Analysis showed 722 CpG sites with different methylation level equal to or greater than 5% (P < 0.01) after exercise training. Some of these CpGs sites were related to pathophysiological mechanisms of inflammation, specially Th17 cell differentiation (FDR value < 0.05 and P < 0.001). Our data showed epigenetic modification in specific CpG sites related to Th17 cell differentiation pathway in post-bariatric women following a 6-months exercise training program.

Exercise training modifies the whole blood DNA methylation profile in middle-aged and older women.

This is a longitudinal single-arm clinical trial aimed to investigate whether exercise training would modify the whole blood methylation profile in healthy women. A total of 45 subjects were engaged in an exercise training protocol during a 14-wk follow up, consisting of aerobic cardiorespiratory and muscle strength exercises. Subjects were evaluated at baseline (PRE), after 7 wk of exercise training (POST 7), and after 14 wk of exercise training (POST 14). Functional primary outcomes included anthropometric, blood pressure, biochemical measurements, physical tests, and global health assessments. Blood samples were collected at each time point to determine the methylation profile using a DNA methylation array technique screening up to 850k different sites. Exercise training decreased blood pressure and triglyceride levels and enhanced physical performance, including upper- and lower-body maximum strength. Moreover, exercise training improved markers of quality of life. In the array analysis, 14 wk of exercise training changed the methylation of more than 800 sites. Across these differentially methylated sites, we found that differentially methylated sites in the promoter region were more hypermethylated after exercise training, suggesting that this hypermethylation process may affect the transcription process. When inputting the differentially methylated sites in pathway analysis, we found several metabolic pathways, including AMPK signaling, TGF-ß signaling, and insulin signaling. This study demonstrates that exercise training promotes a robust change in the whole blood methylation profile and provides new insights into the key regulators of exercise-induced benefits.NEW & NOTEWORTHY We have shown that exercise training lowers blood pressure and triglyceride levels, improves physical performance, and improves quality of life in middle-aged and elderly women. Regarding epigenetic data, we noticed that more than 800 sites are differentially methylated in whole blood after physical training. We emphasize that the differentially methylated sites in the promoter region are more hypermethylated after physical training. In addition, this study shows that key members of metabolic pathways, including AMPK signaling, TGF-ß signaling, and insulin signaling, are among the genes hypermethylated after physical exercise in older women.

The intersection between COVID-19 and obesity in the context of an emerging country.

BACKGROUND & AIMS: The worldwide outbreak of the coronavirus disease 2019 (COVID-19) has already caused a substantial public health burden. Increasing number of studies linked obesity to more severe COVID-19 consequence and mortality, challenging health systems worldwide, especially in emerging countries like Brazil. Herein, we aimed to search the literature and present the current intersection between obesity and COVID-19 in the Brazilian population. METHODS: One hundred twenty-five articles were initially searched after duplicate removal, and nine were finally included in our analysis. RESULTS: Our findings emphasized the magnitude of COVID-19 infection in Brazil and the impact of obesity as a risk factor that aggravates the prognosis of outpatients or hospitalized patients. We also demonstrated social aspects of COVID-19 that could act enhancing the obesity condition in Latin American countries. CONCLUSIONS: A more careful look at the available data could help to understand better the dynamic between obesity and COVID-19, focusing on the Brazilian population and could eventually guide management strategies and therapies for COVID-19 in the future.

Beta-alanine fails to improve on 5000 m running time despite increasing PAT1 expression in long-distance runners.

BACKGROUND: Beta-alanine has become a dietary supplement widely used by athletes due to its ergogenic effect. However, there is still no consensus on the performance benefit of beta-alanine on exercise lasting longer than ten minutes. The present study aimed to evaluate the effect of beta-alanine supplementation on running performance and the expression of TauT and PAT1. METHODS: This double-blind, randomized study enrolled 16 long-distance runners (37±8 years) who were randomly allocated to two groups: placebo (PLA) and beta-alanine (BA) (4.8 g/day 1) for four weeks. Maximal oxygen consumption, anthropometry, body composition, and food intake were determined. Before and after the intervention, the athletes undertook a 5000 m running time trial. Venous blood (TauT and PAT1 expressions) and ear lobe capillary blood (lactate) collected before and after exercise. Between tests, we monitored the training variables. RESULTS: The results were analyzed by t-tests and an ANOVA of repeated measures, with Sidak's post hoc (P<0.05). PLA exhibited lower body fat than BA (8.7±2.2 vs. 11.5±2.8%, P=0.04). After supplementation, there was an increase in PAT1 expression in BA when compared to PLA (1.17±0.47 vs. 0.77±0.18, P=0.04). No significant differences were shown for the 5000 m running time in PLA (PRE: 1128±72; POST: 1123±72s) and BA (PRE: 1107±95; POST: 1093±86s). CONCLUSIONS: Although beta-alanine supplementation increased PAT1 expression, there was no statistically significant improvement in 5000 m running performance. However, individual responses should be considered as the BA showed a higher delta than the PLA.

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.

Impact of green tea epigallocatechin-3-gallate on HIF1-α and mTORC2 expression in obese women: anti-cancer and anti-obesity effects?

INTRODUCTION: Introduction: epigallocatechin-3-gallate (EGCG) is the most abundant catechin contained in green tea (Camellia sinensis) and has been associated with anti-obesity and anti-cancer effects, but the exact molecular mechanisms remain elusive. In this context, this study was designed to improve the understanding of the EGCG anti-obesity and anti-cancer action. Objectives: this study was designed to examine the effects of EGCG on the expression of genes involved in obesity and cancer pathways in the peripheral blood mononuclear cells of obese women. Material and methods: this longitudinal interventional study enrolled eleven women with severe obesity that were submitted to eight weeks of green tea (decaffeinated green tea capsules with 450.7 mg of EGCG, two capsules/day) supplementation (intervention group) and ten eutrophic women as a control group. Weight (kg), body mass index (BMI, kg/m2), fat mass (kg) and gene expression (qPCR method) were assessed before and after supplementation. HIF1-alpha (HIF1-α), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) and rapamycin-insensitive companion of mTOR (RICTOR) were selected as potential targets. Results: after supplementation, body weight (114.9 ± 14.3 versus 115 ± 13.8 kg), body mass index (44.1 ± 3.7 versus 44.1 ± 3.9 kg/m2) and fat mass (47.6 ± 3.3 versus 47.3 ± 3.4 kg) did not change. EGCG upregulated the RICTOR and HIF1-α expression, however, did not modify PI3K expression. Conclusion: this study demonstrated that EGCG has a potential role to obesity and cancer related to obesity control and can be used not only for the purpose of weight loss, but also for the improvement of obesity-related comorbidities.

INTRODUCCIÓN: Introducción: la obesidad se asocia con altos niveles de estrés oxidativo (EO) e inflamación. Existe mucha evidencia de que algunos polifenoles, como el té verde, tienen un impacto positivo en el estado del sistema operativo y consecutivamente en la inflamación. Objetivos: los propósitos de este estudio fueron: a) acceso a biomarcadores de EO en mujeres obesas y de peso normal; y b) evaluar si la suplementación con té verde tiene impacto en los biomarcadores de citoquinas inflamatorias y de EO de mujeres obesas. Métodos: evaluamos mujeres obesas (índice de masa corporal - IMC ≥ 40 kg/m²) y peso normal (IMC entre 18,5 y 24,9 kg/m²). Se utilizaron muestras de sangre para acceder al malondialdehído (MDA), la capacidad antioxidante equivalente de Trolox (TEAC) y las citoquinas inflamatorias. Elegimos al azar pacientes obesos (18 individuos) y luego les dimos suplementos de té verde durante 8 semanas. El análisis estadístico incluyó las pruebas de Shapiro-Wilk, Wilcoxon, t pareadas e independientes, p < 0,05 se consideraron significativas. Resultados: se reclutaron 42 mujeres obesas (IMC: 48,2 ± 9,3 kg/m2) y 21 de peso normal (IMC: 22,5 ± 2 kg/m2) con una edad promedio de 36,2 ± 9,1 años. Los niveles séricos de MDA fueron más altos en las personas obesas (2,52 ± 0,31 µmol/L) que en las mujeres eutróficas (2,13 ± 0,26 µmol/L; p = 0.000). Por otro lado, se observaron valores de TEAC más bajos en obesos (0,75 ± 0,06 mM) que en el grupo eutrófico (0,78 ± 0,04 mM; p = 0,009). Después de la intervención del té verde, la MDA disminuyó 4,7% y el TEAC aumentó 10%. Los niveles séricos de interleucina-6 (IL-6) disminuyeron 12,7% después del tratamiento (p = 0,03). Conclusiones: el grupo obeso tenía menor capacidad antioxidante que el eutrófico. La suplementación con té verde mejoró TEAC y MDA y redujo los niveles séricos de IL-6 en mujeres obesas.

Green tea supplementation promotes leukocyte telomere length elongation in obese women.

INTRODUCTION: inflammation and oxidative stress are factors that may play a substantial role in telomere attrition. In line of this, obesity is associated with telomere shortening. Green tea had anti-inflammatory and antioxidant effects and may alter telomere length (TL). OBJECTIVES: we evaluated the effect of decaffeinated green tea supplementation in obese women on TL. METHODS: we conducted a cross-sectional interventional study with ten obese (body mass index [BMI] > 40 kg/m²) and eight normal weight (BMI > 18.5 and < 24.9 kg/m²) women (age between 27 and 48 years). The supplementation was carried out with capsules (each contained 450.7 mg of epigallocatechin-3-gallate) during eight weeks. Anthropometric and dietary intake assessment, and blood collection (for biochemical and TL analysis by quantitative PCR) were performed before and after supplementation. Normal weight patients were evaluated at a single moment. RESULTS: we observed a significant increase on TL after supplementation (1.57 ± 1.1 to 3.2 ± 2.1 T/Sratio; p < 0.05). Moreover, we found shorter TL in obese patients (day 0) when compared to normal weight individuals (3.2 ± 1.9 T/Sratio; p < 0.05) and an inverse association between TL and BMI, even after age adjustment (beta = -0.527; r² = 0.286; IC = -0.129, -0.009). CONCLUSION: obesity is related to shorter telomeres. Green tea supplementation during eight weeks promotes telomere elongation in obese women.

UCP1 and UCP3 Expression Is Associated with Lipid and Carbohydrate Oxidation and Body Composition.

BACKGROUND/OBJECTIVE: Uncoupling proteins (UCPs) are located in the inner membrane of mitochondria. These proteins participate in thermogenesis and energy expenditure. This study aimed to evaluate how UCP1 and UCP3 expression influences substrate oxidation and elicits possible changes in body composition in patients submitted to bariatric surgery. SUBJECTS/METHODS: This is a longitudinal study comprising 13 women with obesity grade III that underwent bariatric surgery and 10 healthy weight individuals (control group). Body composition was assessed by bioelectrical impedance. Carbohydrate and fat oxidation was determined by indirect calorimetry. Subcutaneous adipose tissue was collected for gene expression analysis. QPCR was used to evaluate UCP1 and UCP3 expression. RESULTS: Obese patients and the control group differed significantly in terms of lipid and carbohydrate oxidation. Six months after bariatric surgery, the differences disappeared. Lipid oxidation correlated with the percentage of fat mass in the postoperative period. Multiple linear regression analysis showed that the UCP1 and UCP3 genes contributed to lipid and carbohydrate oxidation. Additionally, UCP3 expression was associated with BMI, percentage of lean body mass, and percentage of mass in the postoperative period. CONCLUSIONS: UCP1 and UCP3 expression is associated with lipid and carbohydrate oxidation in patients submitted to bariatric surgery. In addition, UCP3 participates in body composition modulation six months postoperatively.

Green tea supplementation improves oxidative stress biomarkers and modulates IL-6 circulating levels in obese women / La suplementación con té verde mejora los biomarcadores del estrés oxidativo y modula los niveles de IL-6 de la circulación en mujeres obesas

Introduction: obesity is associated with high levels of oxidative stress (OS) and inflammation. There is a lot of evidence that some polyphenols, such as green tea, have a positive impact on the OS state and consecutively, on inflammation. Objectives: the purposes of this study were: a) evaluate OS biomarkers in both obese and normal weight women; and b) evaluate if green tea supplementation has an impact on OS and inflammatory cytokine biomarkers of obese women. Methods: we evaluated obese (body mass index [BMI] = 40 kg/m²) and normal weight (BMI between 18.5 and 24.9 kg/m²) women. Blood samples were used to access malondialdehyde (MDA), trolox equivalent antioxidant capacity (TEAC) and inflammatory cytokines. We randomly chose obese patients (18 individuals) and then gave them green tea supplementation for eight weeks. Statistical analysis included the Shapiro-Wilk, Wilcoxon, independent and paired t tests; p < 0.05 were considered as significant. Results: we enrolled 42 obese (BMI: 48.2 ± 9.3kg/m2) and 21 normal weight (BMI: 22.5 ± 2 kg/m2) women with an average age of 36.2 ± 9.1 years old. The serum levels of MDA were higher in obese (2.52 ± 0.31 µmol/l) than in eutrophic women (2.13 ± 0.26 µmol/l; p = 0.000). On the other hand, lower TEAC values were observed in the obese (0.75 ± 0.06 mM/l) than in the eutrophic group (0.78 ± 0.04 mM/l; p = 0.009). After the green tea intervention, MDA decreased 4.7% and TEAC increased 10%. Interleukin-6 (IL-6) serum levels decreased 12.7% after treatment (p = 0.03). Conclusions: a) the obese group had lower antioxidant capacity than eutrophic; and b) green tea supplementation ameliorated TEAC and MDA and reduced serum levels of IL-6 in obese women

Introducción: la obesidad se asocia con altos niveles de estrés oxidativo (EO) e inflamación. Existe mucha evidencia de que algunos polifenoles, como el té verde, tienen un impacto positivo en el estado del EO y, consecutivamente, en la inflamación. Objetivos: los propósitos de este estudio fueron: a) evaluar los biomarcadores de EO en mujeres obesas y de peso normal; y b) evaluar si la suplementación con té verde tiene un impacto en el EO y biomarcadores de citoquinas inflamatorias de las mujeres obesas. Métodos: evaluamos mujeres obesas (índice de masa corporal [IMC] = 40 kg/m²) y con peso normal (IMC entre 18,5 y 24,9 kg/m²). Se utilizaron muestras de sangre para determinar el malondialdehído (MDA), la capacidad antioxidante equivalente de trolox (TEAC) y las citoquinas inflamatorias. Elegimos al azar pacientes obesas (18 individuos) y luego les dimos suplementos de té verde durante ocho semanas. El análisis estadístico incluyó las pruebas de Shapiro-Wilk, Wilcoxon, t pareadas e independientes; p < 0,05 fueron considerados como significativos. Resultados: se reclutaron 42 mujeres obesas (IMC: 48,2 ± 9,3 kg/m2) y 21 de peso normal (IMC: 22,5 ± 2 kg/m2) con un promedio de edad de 36,2 ± 9,1 años. Los niveles séricos de MDA fueron más altos en las personas obesas (2,52 ± 0,31 µmol/L) que en las mujeres eutróficas (2,13 ± 0,26 µmol/L; p = 0,000). Por otro lado, se observaron valores TEAC más bajos en los obesos (0,75 ± 0,06 mM/L) que en el grupo eutrófico (0,78 ± 0,04 mM/L; p = 0,009). Después de la intervención con té verde, la MDA disminuyó 4.7% y el TEAC aumentó 10%. Los niveles séricos de interleucina-6 (IL-6) disminuyeron 12.7% después del tratamiento (p = 0,03). Conclusiones: a) mujeres obesas tienen menor capacidad antioxidante que las eutrófica; y b) la suplementación con té verde mejora TEAC y MDA y redujo los niveles séricos de IL-6 en mujeres obesas

Green tea supplementation promotes leukocyte telomere length elongation in obese women / La suplementación con té verde promueve la elongación de los telómeros de leucocitos en mujeres obesas

Introduction: inflammation and oxidative stress are factors that may play a substantial role in telomere attrition. In line of this, obesity is associated with telomere shortening. Green tea had anti-inflammatory and antioxidant effects and may alter telomere length (TL).Objectives: we evaluated the effect of decaffeinated green tea supplementation in obese women on TL. Methods: we conducted a cross-sectional interventional study with ten obese (body mass index [BMI] > 40 kg/m²) and eight normal weight (BMI > 18.5 and < 24.9 kg/m²) women (age between 27 and 48 years). The supplementation was carried out with capsules (each contained 450.7 mg of epigallocatechin-3-gallate) during eight weeks. Anthropometric and dietary intake assessment, and blood collection (for biochemical and TL analysis by quantitative PCR) were performed before and after supplementation. Normal weight patients were evaluated at a single moment. Results: we observed a significant increase on TL after supplementation (1.57 ± 1.1 to 3.2 ± 2.1 T/Sratio; p < 0.05). Moreover, we found shorter TL in obese patients (day 0) when compared to normal weight individuals (3.2 ± 1.9 T/Sratio; p < 0.05) and an inverse association between TL and BMI, even after age adjustment (beta = -0.527; r² = 0.286; IC = -0.129, -0.009).Conclusion: obesity is related to shorter telomeres. Green tea supplementation during eight weeks promotes telomere elongation in obese women

Introducción: la inflamación y el estrés oxidativo son factores que pueden jugar un papel importante en el desgaste de los telómeros. En línea con esto, la obesidad está asociada con el acortamiento de los telómeros. El té verde tiene efectos antiinflamatorios y antioxidantes y puede alterar la longitud de los telómeros (LT). Objetivos: evaluamos el efecto de la suplementación de té verde descafeinado en la LT en mujeres obesas. Métodos: realizamos un estudio intervencionista de corte transversal con 10 mujeres obesas (IMC > 40 kg/m²) y 8 con peso normal (IMC > 18,5 y < 24,9 kg/m²) (edad entre 27 y 48 años). La suplementación se llevó a cabo con cápsulas (cada una contenía 450,7 mg de epigalocatequina- 3-galato) durante 8 semanas. La evaluación de la ingesta antropométrica y dietética y la recolección de sangre (para análisis bioquímicos y LT por PCR cuantitativa) se realizaron antes y después de la administración de suplementos. Los pacientes de peso normal fueron evaluados en un solo momento. Resultados: observamos un aumento significativo en LT después de la suplementación (1,57 ± 1,1 a 3,2 ± 2,1 T/S ratio; p < 0,05). Además, encontramos LT más corta en pacientes obesos (día 0) en comparación con individuos de peso normal (3,2 ± 1,9 T/S ratio; p < 0,05) y una asociación inversa entre LT e IMC, incluso después del ajuste de edad (beta = -0,527; r² = 0,286; IC = -0,129, -0,009). Conclusión: la obesidad está relacionada con los telómeros más cortos. La administración de suplementos de té verde durante 8 semanas promueve la elongación de los telómeros en mujeres obesas