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.

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.

Avaliação da Percepção do Paladar de Pacientes Oncológicos: Relação com Variáveis Pessoais e Clínicas e Comparação com um Grupo Controle / Evaluation of Taste Perception of Oncological Patients: Relationship with Personal and Clinical Variables and Comparison with a Control Group / Evaluación de la Percepción del Sabor de Pacientes Oncológicos: Relación con Variables Personales y Clínicas y Comparación con un Grupo de Control

Introdução: O tratamento antineoplásico pode causar efeitos colaterais que prejudicam a ingestão alimentar e o estado nutricional dos pacientes. Objetivo: Avaliar a percepção do paladar de pacientes em tratamento oncológico, relacioná-la com as variáveis pessoais e clínicas e compará-la com a percepção do paladar de indivíduos sadios. Método: Trata-se de um estudo transversal com 50 indivíduos em tratamento oncológico e outros 50 indivíduos do grupo controle. Para avaliar a percepção do paladar, os participantes receberam amostras de alimentos e foram questionados quanto aos sabores doce, amargo, salgado e azedo. A intensidade do sabor foi avaliada por meio de uma escala de 1 a 5. Resultados: Os pacientes em tratamento oncológico perceberam os sabores dos seguintes alimentos de maneira mais acentuada: doce de leite (4,48±1,0 vs. 3,78±0,9; p<0,05), goiabada (4,10±1,0 vs. 3,52±0,9; p<0,05), suco de limão (4,42±0,9 vs. 2,86±1,0; p<0,05), suco de maracujá (3,76±1,2 vs. 2,56±1,0; p<0,05) e café (4,42±0,8 vs. 3,14±0,9; p<0,05). Já os alimentos: biscoito de polvilho, iogurte natural, rúcula e chicória foram percebidos com menor intensidade quando comparados ao grupo controle. Entre as quatro categorias de sabor avaliadas, os alimentos do grupo salgado foram os que menos se diferenciaram quanto à percepção do paladar e os alimentos azedos e amargos foram percebidos de forma mais distinta entre os grupos. Conclusão: O presente estudo é pioneiro em avaliar a percepção do paladar utilizando alimentos, ao invés de soluções padronizadas; e, por meio dessa técnica, identificaram-se diferenças significativas na intensidade da percepção do paladar dos indivíduos em tratamento oncológico.

Introduction: Antineoplastic treatment can cause side effects that impair the patients' food intake and nutritional status. Objective: To evaluate the taste perception in patients undergoing cancer treatment, to relate it to personal and clinical variables and to compare with taste perception in healthy individuals. Method: Cross-sectional study with 50 individuals undergoing cancer treatment and another 50 individuals in the control group. To assess taste perception, participants received food samples and were asked about sweet, bitter, salty and sour flavors. The intensity of the flavor was assessed using a scale from 1 to 5. Results: Patients undergoing cancer treatment perceived the flavors of the following foods more strongly: dulce de leche (4.48±1.0 vs. 3.78±0.9; p<0.05), guava (4.10±1.0 vs. 3.52±0.9; p<0.05), lemon juice (4.42±0.9 vs. 2.86±1.0; p<0.05), passion fruit juice (3.76±1.2 vs. 2.56±1.0; p<0.05) and coffee (4.42±0.8 vs. 3.14±0.9; p<0.05). The foods: cassava starch, natural yogurt, arugula and chicory were perceived with less intensity when compared to the control group. Among the four flavor categories evaluated, the foods in the salty group were the ones that least differed in terms of the taste perception and sour and bitter foods were perceived more distinctly between the groups. Conclusion: The present study is pioneer in evaluating the taste perception using food, instead of standardized solutions, and through this technique, significant differences were identified in the intensity of taste perception of individuals undergoing cancer treatment.

Introducción: El tratamiento antineoplásico puede causar efectos secundarios que perjudican la ingesta de alimentos y el estado nutricional de los pacientes. Objetivo: Evaluar la percepción del gusto en pacientes sometidos a tratamiento contra el cáncer, relacionarlo con variables personales y clínicas y compararlo con la percepción del gusto en individuos sanos. Método: Este es un estudio transversal con 50 individuos en tratamiento contra el cáncer y otros 50 individuos en el grupo de control. Para evaluar la percepción del sabor, los participantes recibieron las muestras de alimentos y se les preguntó sobre los sabores dulces, amargos, salados y agrios. La intensidad del sabor se evaluó usando una escala del 1 al 5. Resultados: Los pacientes en tratamiento contra el cáncer percibieron los sabores de los siguientes alimentos con más fuerza: dulce de leche (4,48±1,0 vs. 3,78±0,9; p<0,05), guayaba (4,10±1,0 vs. 3,52±0,9; p<0,05), jugo de limón (4,42±0,9 vs. 2,86±1,0; p<0,05), jugo de maracuyá (3,76±1,2 vs. 2,56±1,0; p<0,05) y café (4,42±0,8 vs. 3,14±0,9; p<0,05). Los alimentos: galletas de almidón, yogur, rúcula y achicoria se percibieron con menos intensidad en comparación con el grupo de control. Entre los sabores, los alimentos salados fueron los que menos diferían y los alimentos amargos y amargos se percibieron más claramente entre los grupos. Conclusión: El presente estudio es pionero en evaluar la percepción del gusto utilizando alimentos, en lugar de soluciones estandarizadas, y identificó diferencias significativas en la intensidad de la percepción del gusto en individuos en tratamiento contra el cáncer.

IS THERE ANY CHANGE IN PHENOTYPIC CHARACTERISTICS COMPARING 5 TO 10 YEARS OF FOLLOW-UP IN OBESE PATIENTS UNDERGOING ROUX-EN-Y GASTRIC BYPASS?

BACKGROUND: : Bariatric surgery promotes significant weight loss and improvement of associated comorbidities; however, nutrients deficiencies and weight regain may occur in the middle-late postoperative period. AIM: To investigate nutritional status in 10 years follow-up. METHODS: : Longitudinal retrospective study in which anthropometric, biochemical indicators and nutritional intake were assessed before and after one, two, three, four, five and ten years of Roux-en Y gastric bypass through analysis of medical records. RESULTS: : After ten years there was a reduction of 29.2% of initial weight; however, 87.1% of patients had significant weight regain. Moreover, there was an increase of incidence of iron (9.2% to 18.5%), vitamin B12 (4.2% to 11.1%) and magnesium deficiency (14.1% to 14.8%). Folic acid concentrations increased and the percentage of individuals with glucose (40.4% to 3.7%), triglycerides (38% to 7.4%), HDL cholesterol (31 % to 7.4%) and uric acid (70.5% to 11.1%) abnormalities reduced. Also, there is a reduction of food intake at first year postoperative. After 10 years, there was an increase in energy, protein and lipid intake, also a reduction in folid acid intake. CONCLUSIONS: : Roux-en Y gastric bypass is an effective procedure to promote weight loss and improve comorbidities associated with obesity. However, comparison between postoperative period of five and 10 years showed a high prevalence of minerals deficiency and a significant weight regain, evidencing the need for nutritional follow-up in the postoperative period.

Green tea supplementation improves oxidative stress biomarkers and modulates IL-6 circulating levels in obese women.

INTRODUCTION: 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: 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.

Impact of green tea epigallocatechin-3-gallate on HIF1-α and mTORC2 expression in obese women: anti-cancer and anti-obesity effects? / Impacto del té verde epigalocatequina-3-galato en la expresión de HF1-a y mTORC2 en mujeres obesas: ¿efectos anticancerígenos y antiobesidad?

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: 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

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.

Is there any change in phenotypic characteristics comparing 5 to 10 years of follow-up in obese patients undergoing roux-en-y gastric bypass? / Características fenotípicas de pacientes com obesidade submetidos a derivação gástrica em y-de-roux: qual as reais mudanças comparando-se 5 a 10 anos de acompanhamento?

ABSTRACT Background : Bariatric surgery promotes significant weight loss and improvement of associated comorbidities; however, nutrients deficiencies and weight regain may occur in the middle-late postoperative period. Aim: To investigate nutritional status in 10 years follow-up. Methods : Longitudinal retrospective study in which anthropometric, biochemical indicators and nutritional intake were assessed before and after one, two, three, four, five and ten years of Roux-en Y gastric bypass through analysis of medical records. Results : After ten years there was a reduction of 29.2% of initial weight; however, 87.1% of patients had significant weight regain. Moreover, there was an increase of incidence of iron (9.2% to 18.5%), vitamin B12 (4.2% to 11.1%) and magnesium deficiency (14.1% to 14.8%). Folic acid concentrations increased and the percentage of individuals with glucose (40.4% to 3.7%), triglycerides (38% to 7.4%), HDL cholesterol (31 % to 7.4%) and uric acid (70.5% to 11.1%) abnormalities reduced. Also, there is a reduction of food intake at first year postoperative. After 10 years, there was an increase in energy, protein and lipid intake, also a reduction in folid acid intake. Conclusions : Roux-en Y gastric bypass is an effective procedure to promote weight loss and improve comorbidities associated with obesity. However, comparison between postoperative period of five and 10 years showed a high prevalence of minerals deficiency and a significant weight regain, evidencing the need for nutritional follow-up in the postoperative period.

RESUMO Racional: A cirurgia bariátrica promove importante perda ponderal e melhora das comorbidades associadas; entretanto, deficiências nutricionais e reganho de peso podem ocorrer no pós-operatório médio e tardio. Objetivo: Investigar a evolução do estado nutricional de pacientes após cinco e 10 anos de pós-operatório. Método: Estudo retrospectivo longitudinal, no qual indicadores antropométricos, bioquímicos e a ingestão alimentar foram avaliados no período pré-operatório e após um, dois, três, quatro, cinco e dez anos da operação, por meio de revisão de prontuários. Resultados: Após 10 anos observou-se redução de 29,2% do peso inicial; no entanto, 87,1% dos pacientes tiveram reganho significativo de peso. Além disso, houve aumento da incidência de deficiência de ferro (9,2% para 18,5%), vitamina B12 (4,2% para 11,1%) e magnésio (14,1% para 14,8%). As concentrações de ácido fólico aumentaram e a porcentagem de indivíduos com alterações na glicemia (40,4% a 3,7%), triglicérides (38% a 7,4%), colesterol HDL (31% a 7,4%) e ácido úrico (70,5% a 11,1%) diminuiu. Além disso, houve redução na ingestão alimentar no primeiro ano de pós-operatório. Após 10 anos, houve aumento na ingestão de energia, proteína e lipídios, e redução na de ácido fólico. Conclusões: A derivação gástrica em Y-de-Roux é procedimento eficaz para promover perda de peso e melhorar as comorbidades associadas à obesidade. Entretanto, a comparação entre os períodos pós-operatórios de cinco e 10 anos mostrou que uma porcentagem de pacientes apresenta deficiências de vitaminas e minerais e reganho de peso significativo, evidenciando a necessidade do acompanho nutricional no período pós-operatório.

Mammalian target of rapamycin complex 2 signaling in obese women changes after bariatric surgery.

OBJECTIVES: After bariatric surgery, modifications to signaling pathway networks including those of the metabolic regulator called mammalian or mechanistic target of rapamycin (mTOR) may lead to molecular alterations related to energy source availability, systemic nutrients, and catabolic and anabolic cellular processes. This study aimed to identify gene expression changes with regard to the mTOR complex 2 subunit signaling pathway in obese patients before and after bariatric surgery. METHODS: The experimental group included 13 obese women who were examined before (preoperative) and 6 mo after (postoperative) Roux-en-Y gastric bypass (RYGB) surgery. The control group included nine apparently eutrophic women matched by age and without any other metabolic diseases (i.e., no diabetes and no liver or kidney diseases). Peripheral blood mononuclear cell samples were collected for RNA extraction and subsequent microarray analysis. RESULTS: After this methodological procedure, we identified 47 000 differentially expressed genes. A subsequent bioinformatic analysis showed that three diferentially expressed genes (rapamycin-insensitive companion of mTOR [RICTOR], phosphoinositide-3-kinase regulatory subunit 1 [PIK3 R1], and hypoxia inducible factor 1 alpha subunit 1A [HIF1 A]) participated in the mTOR signaling pathway. Real-time quantitative polymerase chain reaction revealed that RICTOR, PIK3 R1, and HIF1 A were upregulated 6 mo after RYGB surgery (P <0.05). In addition, patients in the experimental group lost weight significantly and presented significant improvement in biochemical/metabolic variables. CONCLUSIONS: The weight loss that was induced by RYGB surgery alters the mTOR signaling pathway and specifically the mTOR complex 2 subunit. The increased expression of genes that act in this pathway such as RICTOR, PIK3 R1, and HIF1 A reflects the induced weight loss and improved metabolic indicators (e.g., insulin resistance and lipolysis) that are evidenced in this study.

A new resting metabolic rate equation for women with class III obesity.

OBJECTIVE: Resting metabolic rate (RMR) is an important parameter to guide the nutritional therapy of class III obese patients. The aims of the present study were to develop a predictive equation for RMR estimation in class III obese women using anthropometric indicators and to compare indirect calorimetry with other predictive equations. METHODS: This was a cross-sectional study on women with class III obesity (body mass index >40 kg/m2). Weight, height, fat-free mass, fat mass, and RMR of all individuals were measured. Multiple linear regression was used to determine the new RMR equation and the Bland-Altman plot was used to analyze the agreement between indirect calorimetry and the results of predictive equations. RESULTS: We evaluated 101 women with obesity class III and a mean age of 36.3 ± 10 y. The anthropometric and body composition variables used in the new equation had a coefficient of determination of 0.80, and a significant influence on RMR (P = 0.01). Harris-Benedict and World Health Organization equations showed similar bias and limits (181.6, +2 SD = 765.5, -2 SD = -402.2; 156.4, +2 SD = 799.4, -2 SD = -486.6, respectively). The Mifflin-St Jeor and Owen equations showed large clinical bias (mean, 239.2 and 463.9, respectively), and a tendency to overestimate RMR. CONCLUSION: The prediction equations tested in the study had low accuracy in estimating RMR of women with class III obesity. However, our equation was developed specifically for this population, using variables known to influence their energy expenditure.

Green tea supplementation upregulates uncoupling protein 3 expression in severe obese women adipose tissue but does not promote weight loss.

This study aims (i) to verify expression of the UCPs, PLIN1, PPARG2, and ADRB3 genes in the abdominal subcutaneous adipose tissue of obese women at baseline and after 8 weeks of supplementation with decaffeinated green tea extract, and (ii) to associate findings with clinical parameters. This is a longitudinal study during which 11 women with obesity grade III were submitted to supplementation with 450 mg of (-)-epigallocatechin gallate (EGCG) (intervention group); the control group consisted of 10 eutrophic women. Anthropometric parameters [weight, height, and body mass index (BMI)], resting metabolic rate (RMR, measured by indirect calorimetry), and gene expression (measured by real-time PCR, RT-qPCR) were determined before and after supplementation. After 8 weeks, clinical parameters and UCP1, PLIN1, PPARG2, and ADRB3 expression remained unaltered in the intervention group (p > .05). Genetic analysis also showed that the UCP3 gene was upregulated (p = .026), but its upregulation did not promote weight loss.

Influence of expression of UCP3, PLIN1 and PPARG2 on the oxidation of substrates after hypocaloric dietary intervention.

BACKGROUND & AIMS: In addition to environmental and psychosocial factors, it is known that genetic factors can also influence the regulation of energy metabolism, body composition and determination of excess weight. The objective of this study was to evaluate the influence of UCP3, PLIN1 and PPARG2 genes on the substrates oxidation in women with grade III obesity after hypocaloric dietary intervention. SUBJECTS/METHODS: This is a longitudinal study with 21 women, divided into two groups: Intervention Group (G1): 11 obese women (Body Mass Index (BMI) ≥40 kg/m2), and Control Group (G2): 10 eutrophic women (BMI between 18.5 kg/m2 and 24.9 kg/m2). Weight (kg), height (m), BMI (kg/m2), substrate oxidation (by Indirect Calorimetry) and abdominal subcutaneous adipose tissue were collected before and after the intervention. For the dietary intervention, the patients were hospitalized for 6 weeks receiving 1200 kcal/day. RESULTS: There was a significant weight loss (8.4 ± 4.3 kg - 5.2 ± 1.8%) and reduction of UCP3 expression after hypocaloric dietary intervention. There was a positive correlation between carbohydrate oxidation and UCP3 (r = 0.609; p = 0.04), PLIN1 (r = 0.882; p = 0.00) and PPARG2 (r = 0.791; p = 0.00) expression before dietary intervention and with UCP3 (r = 0.682; p = 0.02) and PLIN1 (r = 0.745; p = 0.00) genes after 6 weeks of intervention. There was a negative correlation between lipid oxidation and PLIN1 (r = -0.755; p = 0.00) and PPARG2 (r = 0.664; p = 0.02) expression before dietary intervention and negative correlation with PLIN1 (r = 0.730; p = 0.02) expression after 6 weeks of hypocaloric diet. CONCLUSION: Hypocaloric diet reduces UCP3 expression in individuals with obesity and the UCP3, PLIN1 and PPARG2 expression correlate positively with carbohydrate oxidation and negatively with lipid oxidation.

Comparison of gene expression profile between blood cells and white adipose tissue of patients with obesity

INTRODUCTION: Gene expression analyses from peripheral blood mononuclear cells (PBMC) and white adipose tissue are conflicting. It seems that results from single tissue are not enough to explain how changes affect humans as a complex biological system. OBJECTIVE: The aim of this study was to compare, from obesity subjects, PBMC and white adipose tissue gene expression that regulates adipogenesis (perilipin 1 [PLIN1], adrenoreceptor beta 3 [ADRB3] and peroxisome proliferator-activated receptor [PPARG2]) and the energy metabolism (uncoupling protein UCP1, UCP2 and UCP3) process. METHODS: This study enrolled 35 obese patients, with a body mass index (BMI) > 40 kg/m2 (obesity group [OG]), and ten eutrophic health subjects, 18 > BMI > 24.9 kg/m2 (control group [CG]). Anthropometric and body composition data were assessed at recruitment using standardized protocols. Samples of peripheral blood and subcutaneous adipose tissue (biopsy) were collected to analyze gene expression by RT-qPCR technique. For statistical analysis, we used the Shapiro-Wilk test and Wilcoxon tests by the SPSS software version 20.0; a p < 0.05 significance level was adopted. RESULTS: There were significant differences of PLIN1, ADRB3, PPARG2 and UCP3 expression between blood against adipose tissue samples, showing that these genes are upregulated in adipose tissue. UCP2 expression was upregulated in PBMC. CONCLUSION: The PLIN1, ADRB3, PPARG2 and UCP3 genes were preferentially expressed in adipose tissue. However, UCP2 was upregulated in PBMC, suggesting that this gene may be assessed in a peripheral blood cell, which is easily accessible, safe and practical.

Comparison of gene expression profile between blood cells and white adipose tissue of patients with obesity / Comparación del perfil de expresión génica entre células de la sangre y el tejido adiposo blanco de pacientes con obesidad

Introduction: Gene expression analyses from peripheral blood mononuclear cells (PBMC) and white adipose tissue are conflicting. It seems that results from single tissue are not enough to explain how changes affect humans as a complex biological system. Objective: The aim of this study was to compare, from obesity subjects, PBMC and white adipose tissue gene expression that regulates adipogenesis (perilipin 1 [PLIN1], adrenoreceptor beta 3 [ADRB3] and peroxisome proliferator-activated receptor [PPARG2]) and the energy metabolism (uncoupling protein UCP1, UCP2 and UCP3) process. Methods: This study enrolled 35 obese patients, with a body mass index (BMI) > 40 kg/m2 (obesity group [OG]), and ten eutrophic health subjects, 18 > BMI > 24.9 kg/m2 (control group [CG]). Anthropometric and body composition data were assessed at recruitment using standardized protocols. Samples of peripheral blood and subcutaneous adipose tissue (biopsy) were collected to analyze gene expression by RT-qPCR technique. For statistical analysis, we used the Shapiro-Wilk test and Wilcoxon tests by the SPSS software version 20.0; a p < 0.05 significance level was adopted. Results: There were significant differences of PLIN1, ADRB3, PPARG2 and UCP3 expression between blood against adipose tissue samples, showing that these genes are upregulated in adipose tissue. UCP2 expression was upregulated in PBMC. Conclusion: The PLIN1, ADRB3, PPARG2 and UCP3 genes were preferentially expressed in adipose tissue. However, UCP2 was upregulated in PBMC, suggesting that this gene may be assessed in a peripheral blood cell, which is easily accessible, safe and practical (AU)

Introducción: la expresión de genes de células mononucleares de sangre periférica y de tejido adiposo blanco es contradictoria. Los resultados del tejido no son suficientes para explicar cómo afectan los cambios al ser humano como un sistema biológico complejo. Objetivo: el objetivo de este estudio fue comparar, en individuos con obesidad, la expresión de genes que regulan los procesos de adipogénesis (PLIN1, ADRB3 y PPARg2) y el metabolismo energético (UCP1, UCP2 y UCP3) en sangre y tejido adiposo blanco. Métodos: este estudio incluyó a 35 pacientes con obesidad e índice de masa corporal (IMC) > 40 kg/m2 en el grupo obesidad (GO) y a diez personas sanas con peso normal (18 > IMC > 24,9 kg/m2) en el grupo control (GC). Los datos antropométricos y de composición corporal fueron obtenidos por protocolos estandarizados. Se recogieron muestras de sangre periférica y tejido adiposo subcutáneo (biopsia) para analizar la expresión génica por la técnica de RT-qPCR. Para el análisis estadístico se utilizaron el test de Shapiro-Wilk y pruebas de Wilcoxon mediante el programa SPSS versión 20.0 (p < 0,05). Resultados: no se encontraron diferencias significativas en la expresión de genes PLIN1, ADRB3, PPARg2 y UCP3 entre la sangre y las muestras de tejido adiposo, mostrando que estos genes son regulados positivamente en el tejido adiposo. La expresión del gen UCP2 fue regulada positivamente en sangre. Conclusión: los genes PLIN1, ADRB3, PPARg2 y UCP3 se expresaron de forma preferente en el tejido adiposo. Sin embargo, el gen UCP2 se reguló positivamente en sangre, lo que sugiere que puede ser evaluado en sangre periférica, que es fácilmente accesible, de forma segura y práctica (AU)

Pregnancy After Roux en Y Gastric Bypass: Nutritional and Biochemical Aspects.

INTRODUCTION: Although pregnancy after bariatric surgery is related to risk reduction, nutritional complications may occur. This study aimed to evaluate nutritional and biochemical indicators of women who became pregnant after Roux en Y gastric bypass (RYGB). MATERIALS AND METHODS: We carried out a retrospective study with women who became pregnant after RYGB. We evaluated anthropometric, biochemical, and dietary intake indicators in the preoperative period and before, during, and after pregnancy by analysis of medical records. Shapiro-Wilk test and ANOVA for repeated measures were performed (p < 0.05). RESULTS: The study included 25 patients (35.7 ± 3.8 years), who became pregnant 31.3 ± 21.7 months after RYGB. Weight loss until the beginning of pregnancy was 32.4%, and the gestational weight gain was 3.8 ± 12 kg. There was a higher frequency of patients with hypertension in the preoperative time when compared to that during the pregnancy period. Total cholesterol (180.9 ± 24.8 versus 148.5 ± 30.4 mg/dL), LDL-cholesterol (103.5 ± 19.2 versus 85.8 ± 23.1 mg/dL), HDL-cholesterol (56.4 ± 8 versus 46.9 ± 8.7 mg/dL), and latent iron-binding capacity (337.6 ± 95.8 versus 277.8 ± 65 µg/dL) were higher during the pregnancy compared to that before the pregnancy, while hemoglobin values (11.2 ± 1 versus 12.3 ± 1.2 g/dL) and sodium (138.8 ± 2.9 versus 141 ± 3 mmol/L) were lower. No differences of food intake were found among times. There is no difference on gestational weight gain between women who became pregnant before or after the first year. CONCLUSION: During pregnancy, there was an expected weight gain and maintenance of the lipid profile within the normal range; however, there was a reduction of hemoglobin levels. These findings show the need for individualized follow-up with adequate nutritional intervention in the event of deficiencies.

UCP2 and PLIN1 Expression Affects the Resting Metabolic Rate and Weight Loss on Obese Patients.

BACKGROUND: Analysis of the expression of genes related to the energy metabolism can elucidate the understanding of physiological and genetic factors that contribute to obesity. This study aimed to evaluate the expression of genes and its influence on resting metabolic rate and weight loss in obese patients before and after bariatric surgery. METHODS: This study was conducted on 23 women, who were divided into two groups: bariatric surgery (preoperative and 6 months after surgery) and control. Abdominal subcutaneous adipose tissue samples were collected to analyze the gene expression, and the resting metabolic rate (RMR) was measured by indirect calorimetry. RESULTS: Significant differences were observed in weight reduction (22 %, p = 0.01), BMI (22.5 %, p = 0.01), and RMR values (10.5 %, p = 0.01) after the bariatric surgery, while the weight-adjusted RMR increased (15.8 %, p = 0.01). Increased UCP2 expression after 6 months of Roux-en-Y gastric bypass (RYGB) as compared to preoperative period (0.764 to 1.268, p = 0.01) was observed. Analysis with weight-adjusted RMR as dependent variable revealed that UCP2 (r 2 = 0.517, p = 0.01) and PLIN1 (r 2 = 0.420, p = 0.04) expression determine the RMR values in preoperative period. Moreover, UCP2 and PLIN1 expression in preoperative period influenced the percentage of weight loss, even when adjusted for age and BMI. CONCLUSIONS: We have demonstrated that after 6 months of bariatric surgery, there is significant increase in the UCP2 expression. Additionally, the expression of UCP2 and PLIN1 genes influences the resting metabolic rate in obese individuals and could predict the weight loss after bariatric surgery.

The Genetic Predisposition Score of Seven Obesity-Related Single Nucleotide Polymorphisms Is Associated with Better Metabolic Outcomes after Roux-en-Y Gastric Bypass.

BACKGROUND/AIMS: Genetic variants associated with obesity have cumulative effects on obesity risk and related phenotypes. This study aimed to estimate the contribution of a genetic predisposition score (GPS) calculated from 7 obesity-related polymorphisms to the improvement of biochemical parameters 1 year after Roux-en-Y gastric bypass (RYGB). METHODS: Obese patients (n = 150; aged 47.2 ± 10.5 years) were enrolled and weight, body mass index (BMI), and biochemical parameters (glycemia and lipid profile) were evaluated preoperatively and 1 year after RYGB. A GPS was calculated with the polymorphisms rs1801282 of PPARG2, rs4994 of ADRB3, rs1800592 of UCP1, rs659366 and rs669339 of UCP2, rs7121 of GNAS1, and rs5443 of GNB3. We observed that 66.3% of the patients has a GPS >5. RESULTS: During the preoperative period, the GPS showed a significant association with weight (ß = -0.163; p = 0.020), BMI (ß = -0.169; p = 0.038), and glucose concentrations (ß = -0.177; p = 0.036). After sex and age adjustment, a higher GPS was associated with a greater reduction in glycemia (ß = -0.158; p = 0.048), triglycerides (ß = -0.256; p = 0.002), and total cholesterol (ß = -0.172; p = 0.038) concentrations 1 year after surgery. CONCLUSION: Our data elucidated that a higher GPS provides a greater metabolic benefit of RYGB.

Comparison between two models of training with regard to resting energy expenditure and body composition in obese adolescents / Comparação entre dois modelos de treinamento sobre o gasto energético de repouso e a composição corporal de adolescentes com obesidade

Abstract Different types of physical activity programs have been used with the purpose of improving body composition and increasing resting energy expenditure (REE) in obese adolescents. The aim of the present study was to compare the effects of two training models on REE and body composition in this population. The study included 20 obese male adolescents, who were randomly assigned to follow two training models: strength training (n=8, age=13,4±1.0) and functional training (n=12, age= 13.0±1.1). Body composition variables were estimated by dual-energy X-ray absorptiometry. REE was assessed by indirect calorimetry using the QUARK-PFT equipment (COSMED, Rome, Italy). The training protocol consisted of 30 minutes of aerobic training followed by 30 minutes of strength training (ST) or functional training (FT), both with a duration of 20 weeks. There were no significant differences between the two training models with regard to body composition (fat mass, FT= -7.6±5.5% vs. ST= -8.9±6.2%; p=0.620), (lean body mass, FT= 9.0±5.3% vs. ST= 6.8±6.7%; p=0.431) and to REE (FT= 19.6±15.3% vs. ST= 10.7±24.5%; p=0.331). Moreover, lean body mass (p=0.01) and fat mass (0.01) had an influence on REE. No differences were observed between the two training models, but both were effective in improving body composition and increasing REE in obese adolescents. Furthermore, the present study showed the importance of systematic physical training, since lean body mass and fat mass contributed to the increase in REE after the training period.

Resumo Diferentes tipos de programas de exercícios físicos têm sido utilizados na tentativa de melhorar a composição corporal e aumentar o gasto energético de repouso (GER) de adolescentes obesos. O objetivo foi comparar os efeitos de dois modelos de treinamento sobre o gasto energético de repouso e a composição corporal de adolescentes com obesidade. Participaram do estudo vinte adolescentes obesos do sexo masculino, foram divididos de forma aleatória em dois modelos de treinamento: treinamento contra resistência (n=8, idade=13,4±1,0) e treinamento funcional (n=12, idade= 13,0±1,1). As variáveis de composição corporal foram estimadas pela densitometria radiológica de dupla energia. O GER foi realizado por meio da calorimetria indireta usando o equipamento QUARK-PFT (COSMED, Roma, Itália). O protocolo de treinamento consistiu de 30 minutos de treino aeróbio seguidos de 30 minutos de treino contra resistência (TC) ou funcional (TF), ambos durante 20 semanas. Não houve diferenças significantes entre os dois modelos de treinamento na composição corporal (massa gorda, TF= -7,6±5,5% x TC= -8,9±6,2%; p=0,620), (massa corporal magra, TF= 9,0±5,3% x TC= 6,8±6,7%; p=0,431) e no GER (TF= 19,6±15,3% x TC= 10,7±24,5%; p=0,331). Além disso, a massa corporal magra (p=0,01) e massa gorda (p=0,01) influenciam o GER. Não há diferença entre os dois modelos de treinamento, porém ambos são eficazes na redução da composição corporal e aumento do GER de adolescentes obesos. Adicionalmente, foi verificada a importância do treinamento físico sistematizado, uma vez que a massa corporal magra e massa gorda contribuíram para o aumento do GER após o treinamento.

DNA Methylation and Hydroxymethylation Levels in Relation to Two Weight Loss Strategies: Energy-Restricted Diet or Bariatric Surgery.

BACKGROUND: Weight loss can be influenced by genetic factors and epigenetic mechanisms that participate in the regulation of body weight. This study aimed to investigate whether the weight loss induced by two different obesity treatments (energy restriction or bariatric surgery) may affect global DNA methylation (LINE-1) and hydroxymethylation profile, as well as the methylation patterns in inflammatory genes. METHODS: This study encompassed women from three differents groups: 1. control group (n = 9), normal weight individuals; 2. energy restriction group (n = 22), obese patients following an energy-restricted Mediterranean-based dietary treatment (RESMENA); and 3. bariatric surgery group (n = 14), obese patients underwent a hypocaloric diet followed by bariatric surgery. Anthropometric measurements and 12-h fasting blood samples were collected before the interventions and after 6 months. Lipid and glucose biomarkers, global hydroxymethylation (by ELISA), LINE-1, SERPINE-1, and IL-6 (by MS-HRM) methylation levels were assessed in all participants. RESULTS: Baseline LINE-1 methylation was associated with serum glucose levels whereas baseline hydroxymethylation was associated with BMI, waist circumference, total cholesterol, and triglycerides. LINE-1 and SERPINE-1 methylation levels did not change after weight loss, whereas IL-6 methylation increased after energy restriction and decreased in the bariatric surgery group. An association between SERPINE-1 methylation and weight loss responses was found. CONCLUSIONS: Global DNA methylation and hydroxymethylation might be biomarkers for obesity and associated comorbidities. Depending on the obesity treatment (diet or surgery), the DNA methylation patterns behave differently. Baseline SERPINE-1 methylation may be a predictor of weight loss values after bariatric surgery.

Red meat intolerance in patients submitted to gastric bypass: a 4-year follow-up study.

BACKGROUND: Bariatric surgery provides significant weight reduction; however, it may result in food intolerance followed by gastrointestinal complications that may lead to nutritional deficiencies. This study evaluated the influence of red meat intolerance on the dietary pattern, biochemical indicators, and clinical symptoms after Roux-en-Y gastric bypass (RYGB). METHODS: This retrospective study evaluated patients 4 years after RYGB. The patients were divided into 2 groups: patients with and without red meat intolerance, and data for the following were collected: food intake, anthropometric data, biochemical data, and presence of nausea, vomiting, weakness, weak nails, and hair loss. The difference between groups in the times postoperative was determined by ANOVA. RESULTS: Of the 72 patients included in the study, 63 were evaluated during the first postoperative year, 45 during the second, 56 during the third, and 41 during the fourth. Red meat intolerance was observed in 49.2%, 42.2%, 46.4%, and 39% of the patients after 1, 2, 3, and 4 years, respectively. After 1 year, the intolerant group showed lower calorie, carbohydrate, and iron intake. After 3 years, tolerant patients showed weight regain (2.9 ± 5.3 kg), while the intolerant ones remained stable. There was no difference in the presence of clinical symptoms or biochemical indicators between groups. CONCLUSION: Red meat intolerance is frequent after bariatric surgery and may alter energy, iron intake, and weight loss; however, it is not associated with the presence of clinical symptoms and biochemical profile.