DANIELLE CRISTINA FONSECA CANDIAN
Projetos de Pesquisa
Unidades Organizacionais
LIM/35 - Laboratório de Nutrição e Cirurgia Metabólica do Aparelho Digestivo, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
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- Gastrointestinal Transcriptomic Response of Metabolic Vitamin B12 Pathways in Roux-en-Y Gastric Bypass(2017) SALA, Priscila; BELARMINO, Giliane; TORRINHAS, Raquel S.; MACHADO, Natasha M.; FONSECA, Danielle C.; RAVACCI, Graziela R.; ISHIDA, Robson K.; GUARDA, Ismael F. M. S.; MOURA, Eduardo G. de; SAKAI, Paulo; SANTO, Marco A.; SILVA, Ismael D. C. G. da; PEREIRA, Claudia C. A.; LOGULLO, Angela F.; HEYMSFIELD, Steven; GIANNELLA-NETO, Daniel; WAITZBERG, Dan L.OBJECTIVES: Vitamin B12 (B12) deficiency after Roux-en-Y gastric bypass (RYGB) is highly prevalent and may contribute to postoperative complications. Decreased production of intrinsic factor owing to gastric fundus removal is thought to have a major role, but other components of B12 metabolism may also be affected. We evaluated changes in the expression levels of multiple B12 pathway-encoding genes in gastrointestinal (GI) tissues to evaluate the potential roles in contributing to post-RYGB B12 deficiency. METHODS: During double-balloon enteroscopy, serial GI biopsies were collected from 20 obese women (age, 46.9 +/- 6.2 years; body mass index, 46.5 +/- 5.3 kg/m(2)) with adult-onset type 2 diabetes (fasting plasma glucose >= 126 mg/dl; hemoglobin A1c >= 6.5%) before and, at the same site, 3 months after RYGB. Gene expression levels were assessed by the Affymetrix Human GeneChip 1.0 ST microarray. Findings were validated by real-time quantitative PCR (RT-qPCR). RESULTS: Gene expression levels with significant changes (P <= 0.05) included: transcobalamin I (TCN1) in remnant (-1.914-fold) and excluded (-1.985-fold) gastric regions; gastric intrinsic factor (GIF) in duodenum (-0.725-fold); and cubilin (CUBN) in duodenum (+0.982-fold), jejunum (+1.311-fold), and ileum (+0.685-fold). Validation by RT-qPCR confirmed (P <= 0.05) observed changes for TCN1 in the remnant gastric region (-0.132-fold) and CUBN in jejunum (+2.833-fold). CONCLUSIONS: RYGB affects multiple pathway-encoding genes that may be associated with postoperative B12 deficiency. Decreased TCN1 levels seem to be the main contributing factor. Increased CUBN levels suggest an adaptive genetic reprogramming of intestinal tissue aiming to compensate for impaired intestinal B12 delivery.
- Type 2 Diabetes Remission After Roux-en-Y Gastric Bypass: Evidence for Increased Expression of Jejunal Genes Encoding Regenerating Pancreatic Islet-Derived Proteins as a Potential Mechanism(2017) SALA, Priscila; TORRINHAS, Raquel Susana; FONSECA, Danielle Cristina; HEYMSFIELD, Steven; GIANNELLA-NETO, Daniel; WAITZBERG, Dan LinetzkyBackground Intestinal expression of regenerating pancreatic islet-derived protein-encoding genes (REG) would be enhanced after Roux-en-Y gastric bypass (RYGB) and would affect postoperative type 2 diabetes remission (T2Dr). Methods Intestinal biopsy samples were collected from 20 adult obese women with T2D before and 3 months after RYGB. Levels of REG expression and the gene encoding its putative receptor (EXTL3) were assessed by microarray and validated by quantitative RT-PCR. T2Dr was assessed according to ADA criteria 1 year after RYGB. Results After RYGB, only patients with T2Dr had significantly increased REG1 alpha and REG3 gamma expression in the jejunum, as validated by quantitative RT-PCR. Conclusions Our data provide support for the hypothesis that increased jejunal expression of REG genes after RYGB affects T2Dr, possibly by playing an endocrine function.
- Tissue-specific methylation profile in obese patients with type 2 diabetes before and after Roux-en-Y gastric bypass(2017) SALA, Priscila; TORRINHAS, Raquel Susana Matos de Miranda; FONSECA, Danielle Cristina; RAVACCI, Graziela Rosa; WAITZBERG, Dan Linetzky; GIANNELLA-NETO, DanielEating habits, lifestyles, and exposure to specific environmental factors can greatly impact the risk of developing type 2 diabetes (T2D), influence the genome epigenetically, and affect the expression of genes, including genes related to glycemic control, at any stage of life. The epigenetic mechanism underlying obesity and T2D pathogenesis remains poorly understood. Conventional strategies for the treatment of obesity and its comorbidities often have poor longterm adherence, and pharmacological interventions are limited. Bariatric surgery is the most effective current option to treat severe obesity, and Roux-en-Y gastric bypass (RYGB) is the most applied technique worldwide. Epigenetic changes differ depending on the approach used to treat obesity and its associated comorbidities (clinical or surgical). Compared to primary clinical care, bariatric surgery leads to much greater loss of body weight and higher remission rates of T2D and metabolic syndrome, with methylation profiles in promoter regions of genes in obese individuals becoming similar to those of normal-weight individuals. Bariatric surgery can influence DNA methylation in parallel with changes in gene expression pattern. Changes in clinical biomarkers that reflect improvements in glucose and lipid metabolism after RYGB often occur before major weight loss and are coordinated by surgery-induced changes in intestinal hormones. Therefore, the intestine methylation profile would assist in understanding the mechanisms involved in improved glycemic control after bariatric surgery. The main objectives in this area for the future are to identify epigenetic marks that could be used as early indicators of metabolic risk, and to develop treatments able to delay or even reverse these epigenetic changes. Studies that provide the ""human epigenetic profile"" will be of considerable value to identify tissue-specific epigenetic signatures and their role in the development of chronic diseases. Further studies should apply methods based on global analysis of the genome to identify methylated sites associated with disease and epigenetic marks associated with the remodeling response to bariatric surgery. This review describes the main epigenetic alterations associated with obesity and T2D and the potential role of RYGB in remodeling these changes.