RESUMEN
DNA methylation could provide a link between environmental, genetic factors and weight control and can modify gene expression pattern. This study aimed to identify genes, which are differentially expressed and methylated depending on adiposity state by evaluating normal weight women and obese women before and after bariatric surgery (BS). We enrolled 24 normal weight (BMI: 22.5 ± 1.6 kg/m2) and 24 obese women (BMI: 43.3 ± 5.7 kg/m2) submitted to BS. Genome-wide methylation analysis was conducted using Infinium Human Methylation 450 BeadChip (threshold for significant CpG sites based on delta methylation level with a minimum value of 5%, a false discovery rate correction (FDR) of q < 0.05 was applied). Expression levels were measured using HumanHT-12v4 Expression BeadChip (cutoff of p ≤ 0.05 and fold change ≥2.0 was used to detect differentially expressed probes). The integrative analysis of both array data identified four genes (i.e. TPP2, PSMG6, ARL6IP1 and FAM49B) with higher methylation and lower expression level in pre-surgery women compared to normal weight women: and two genes (i.e. ZFP36L1 and USP32) that were differentially methylated after BS. These methylation changes were in promoter region and gene body. All genes are related to MAPK cascade, NIK/NF-kappaB signaling, cellular response to insulin stimulus, proteolysis and others. Integrating analysis of DNA methylation and gene expression evidenced that there is a set of genes relevant to obesity that changed after BS. A gene ontology analysis showed that these genes were enriched in biological functions related to adipogenesis, orexigenic, oxidative stress and insulin metabolism pathways. Also, our results suggest that although methylation plays a role in gene silencing, the majority of effects were not correlated.
Asunto(s)
Adiposidad/genética , Cirugía Bariátrica , Metilación de ADN , Obesidad/genética , Transcriptoma , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Aminopeptidasas/genética , Aminopeptidasas/metabolismo , Factor 1 de Respuesta al Butirato/genética , Factor 1 de Respuesta al Butirato/metabolismo , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/genética , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/metabolismo , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Redes y Vías Metabólicas , Persona de Mediana Edad , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Obesidad/metabolismo , Obesidad/cirugía , Periodo Posoperatorio , Periodo Preoperatorio , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/metabolismoRESUMEN
BACKGROUND/OBJECTIVES: Obesity has been associated with gene methylation regulation. Recent studies have shown that epigenetic signature plays a role in metabolic homeostasis after Roux-en Y gastric bypass (RYGB). To conduct a genome-wide epigenetic analysis in peripheral blood to investigate whether epigenetic changes following RYGB stem from weight loss or the surgical procedure per se. SUBJECTS/METHODS: By means of the Infinium Human Methylation 450 BeadChip array, global methylation was analyzed in blood of 24 severely obese women before and 6 months after RYGB and in 24 normal-weight women (controls). RESULTS: In blood cells, nine DMCpG sites showed low methylation levels before surgery, methylation levels increased after RYGB and neared the levels measured in the controls. Additionally, 44 CpG sites associated with the Wnt and p53 signaling pathways were always differently methylated in the severely obese patients as compared to the controls and were not influenced by RYGB. Finally, 1638 CpG sites related to inflammation, angiogenesis, and apoptosis presented distinct methylation in the post-surgery patients as compared to the controls. CONCLUSION: Bariatric surgery per se acts on CpGs related to inflammation, angiogenesis, and endothelin-signaling. However, the gene cluster associated with obesity remains unchanged, suggesting that weight loss 6 months after RYGB surgery cannot promote this effect.
Asunto(s)
Metilación de ADN , Epigénesis Genética , Derivación Gástrica , Adulto , Peso Corporal/genética , Islas de CpG/genética , Femenino , Humanos , Masculino , Obesidad/genética , Obesidad/cirugía , Fenotipo , Factores de TiempoRESUMEN
BACKGROUND/OBJECTIVES: Although energy restriction contributes to weight loss, it may also reduce energy expenditure, limiting the success of weight loss in the long term. Studies have described how genetics contributes to the development of obesity, and uncoupling proteins 1 and 2 (UCP1 and UCP2) and beta-3-adrenoceptor (ADRB3) have been implicated in the metabolic pathways that culminate in this condition. This study aimed to evaluate how the UCP1, UCP2 and ADRB3 genes influence weight loss in severely obese women submitted to hypocaloric dietary intervention. SUBJECTS/METHODS: This longitudinal study included 21 women divided into two groups: Group 1 (Dietary intervention (G1)) consisted of 11 individuals with severe obesity (body mass index (BMI) ⩾40 kg/m2), selected for dietary intervention and Group 2 (Control (G2)) consisted of 10 normal-weight women (BMI between 18.5 and 24.9 kg/m2). Evaluation included weight (kg), height (m), waist circumference (cm), body composition, resting metabolic rate (RMR, kcal) and abdominal subcutaneous adipose tissue collection. The dietary intervention required that G1 patients remained hospitalized in the university hospital for 6 weeks receiving a hypocaloric diet (1200 kcal per day). The statistical analyses included t-test for paired samples, Spearman correlation and multivariate linear regressions, with the level of significance set at P<0.05. RESULTS: Weight (155.0±31.4-146.5±27.8 kg), BMI (58.5±10.5-55.3±9.2 kg/m2), fat-free mass (65.4±8.6-63.1±7.1 kg), fat mass (89.5±23.0-83.4±21.0 kg) and RMR (2511.6±386.1-2324.0±416.4 kcal per day) decreased significantly after dietary intervention. Multiple regression analyses showed that UCP2 expression contributed to weight loss after dietary intervention (P=0.05). CONCLUSIONS: UCP2 expression is associated with weight loss after hypocaloric diet intervention.
Asunto(s)
Dieta Reductora , Proteína Desacopladora 2/metabolismo , Pérdida de Peso/genética , Adulto , Metabolismo Basal , Composición Corporal , Índice de Masa Corporal , Femenino , Regulación de la Expresión Génica , Humanos , Modelos Lineales , Estudios Longitudinales , Persona de Mediana Edad , Análisis Multivariante , Obesidad/genética , Obesidad Mórbida/genética , Receptores Adrenérgicos beta 3/genética , Receptores Adrenérgicos beta 3/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 2/genética , Circunferencia de la Cintura , Adulto JovenRESUMEN
Uncoupling protein 2 ( UCP2 ) plays an important role in body weight and energy metabolism and may be related to the control of food consumption. This study aimed to investigate the contribution of UCP2 gene variants on the dietary intake on a population after bariatric surgery. This study enrolled 150 obese patients (body mass index ≥ 35kg m(-2) ) who submitted to Roux-en-Y gastric bypass. Weight (kg), BMI (kg m(-2) ), energy (kcal d(-1) ) and macronutrients intake (g d(-1) ) of preoperative and 1-year postoperative period were collected from medical records. Ala55Val and -866G>A polymorphisms in the UCP2 gene were genotyped through allelic discrimination method in real-time polymerase chain reaction using the TaqMan pre-designed SNP Genotyping Assays kits. Hardy-Weinberg equilibrium, t-test and regression models were performed in statistical analysis (P<0.05).We found an allelic frequency of 0.44 for allele Val and 0.41 for allele A. In the postoperative period, patients with at least one rare allele for polymorphisms and with at least one rare allele for both polymorphisms together (haplotype) present a greater energy and carbohydrate intake, even after adjusting for gender, age and weight. Genetic variants in UCP2 gene were associated with the dietary consumption after Roux-En-Y gastric bypass.