NATASHA MENDONCA MACHADO
Projetos de Pesquisa
Unidades Organizacionais
LIM/35 - Laboratório de Nutrição e Cirurgia Metabólica do Aparelho Digestivo, Hospital das Clínicas, Faculdade de Medicina
17 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 17
conferenceObject Reduced Transcobalamin I Gene Expression Following Roux-en-Y Gastric Bypass Surgery Can Contribute to B12 Deficiency(2015) SALA, Priscila; MACHADO, Natasha; BELARMINO, Giliane; ISHIDA, Robson; GUARDA, Ismael; GIANNELLA-NETO, Daniel; SANTO, Marco Aurelio; MOURA, Eduardo; SAKAI, Paulo; SILVA, Ismael; YE, Jianping; HEYMSFIELD, Steven; WAITZBERG, Dan- Potential premalignant status of gastric portion excluded after Roux en-Y gastric bypass in obese women: A pilot study(2019) RAVACCI, Graziela Rosa; ISHIDA, Robson; TORRINHAS, Raquel Suzana; SALA, Priscila; MACHADO, Natasha Mendonca; FONSECA, Danielle Cristina; CANUTO, Gisele Andre Baptista; PINTO, Ernani; NASCIMENTO, Viviane; TAVARES, Marina Franco Maggi; SAKAI, Paulo; FAINTUCH, Joel; SANTO, Marco Aurelio; MOURA, Eduardo Guimaraes Hourneaux; ARTIGIANI NETO, Ricardo; LOGULLO, Angela Flavia; WAITZBERG, Dan LinetzkyWe evaluated whether the excluded stomach (ES) after Roux-en-Y gastric bypass (RYGB) can represent a premalignant environment. Twenty obese women were prospectively submitted to double-balloon enteroscopy (DBE) with gastric juice and biopsy collection, before and 3 months after RYGB. We then evaluated morphological and molecular changes by combining endoscopic and histopathological analyses with an integrated untargeted metabolomics and transcriptomics multiplatform. Preoperatively, 16 women already presented with gastric histopathological alterations and an increased pH (>= 4.0). These gastric abnormalities worsened after RYGB. A 90-fold increase in the concentration of bile acids was found in ES fluid, which also contained other metabolites commonly found in the intestinal environment, urine, and faeces. In addition, 135 genes were differentially expressed in ES tissue. Combined analysis of metabolic and gene expression data suggested that RYGB promoted activation of biological processes involved in local inflammation, bacteria overgrowth, and cell proliferation sustained by genes involved in carcinogenesis. Accumulated fluid in the ES appears to behave as a potential premalignant environment due to worsening inflammation and changing gene expression patterns that are favorable to the development of cancer. Considering that ES may remain for the rest of the patient's life, long-term ES monitoring is therefore recommended for patients undergoing RYGB.
- 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.
- Fecal bile acid profile after Roux-en-Y gastric bypass and its association with the remission of type 2 diabetes in obese women: A preliminary study(2019) CARDINELLI, Camila de Siqueira; TORRINHAS, Raquel Susana; SALA, Priscila; PUDENZI, Marcos Albieri; ANGOLINI, Celio Fernando F.; SILVA, Mariane Marques da; MACHADO, Natasha Mendonca; RAVACCI, Graziela; EBERLIN, Marcos N.; WAITZBERG, Dan L.Objective: To assess the influence of Roux-en-Y gastric by-pass (RYGB) on fecal bile acid (BA) profile and its relationship with postoperative remission of type 2 diabetes (T2D). Methods: Fecal samples were collected 3 and 12 months after RYGB from diabetic obese women who were responsive (n = 12) and non-responsive (n = 8) to postoperative remission of T2D. Fecal BA profile was accessed by liquid chromatography coupled to tandem mass spectrometry in a targeted approach. Results: Relative to pre-operative levels, a total of 10 fecal BA profiles decreased after RYGB (ANOVA, p <= 0.05) with significant fold-changes for glycochenodeoxycholic, glycocholic, taurocholic, and taurochenodeoxycholic acids at 3-months postoperatively, and for glycochenodeoxycholic, glycocholic and taurocholic acids at 12 months postoperatively (Benjamini-Hochberg, p < 0.05). Postoperative changes in fecal BA were different between responsive and non-responsive women, with a significant reduction in more sub-fractions of BA in responsive women than in non-responsive women, and a marked difference in the temporal behavior of cholic acid (CA) and chenodeoxycholic acid (CDCA), thus reflecting changes in CA/CDCA ratio, and tauroursodeoxycolic (TUDCA) levels between these responsiveness groups (ANOVA, p <= 0.05). Conclusion: RYGB induces a marked reduction in the concentration of fecal BA, which is heterogeneous according to T2D responsiveness.
- Type 2 Diabetes Metabolic Improvement After Roux-en-Y Gastric Bypass May Include a Compensatory Mechanism That Balances Fatty Acid beta and omega Oxidation(2020) MACHADO, Natasha Mendonca; TORRINHAS, Raquel Susana; SALA, Priscila; ISHIDA, Robson Kiyoshi; GUARDA, Ismael Francisco Mota Siqueira; MOURA, Eduardo Guimaraes Hourneaux de; SAKAI, Paulo; SANTO, Marco Aurelio; WAITZBERG, Dan LinetzkyBackground More than half of patients who undergo Roux-en-Y gastric bypass (RYGB) can experience type 2 diabetes (T2D) remission, but the systemic and gastrointestinal (GI) metabolic mechanisms of this improvement are still elusive. Methods Paired samples collected before and 3 months after RYGB from 28 women with obesity and T2D were analyzed by metabolomics with gas chromatography coupled to mass spectrometry. Samples include plasma (n = 56) and biopsies of gastric pouch (n = 18), gastric remnant (n = 10), duodenum (n = 16), jejunum (n = 18), and ileum (n = 18), collected by double-balloon enteroscopy. Results After RYGB, improvements in body composition and weight-related and glucose homeostasis parameters were observed. Plasma-enriched metabolic pathways included arginine and proline metabolism, urea and tricarboxylic acid (TCA) cycles, gluconeogenesis, malate-aspartate shuttle, and carnitine synthesis. In GI tissue, we observed alterations of ammonia recycling and carnitine synthesis in gastric pouch, phenylacetate metabolism and trehalose degradation in duodenum and jejunum, ketone bodies in jejunum, and lactose degradation in ileum. Intermediates molecules of the TCA cycle were enriched, particularly in plasma, jejunum, and ileum. Fluctuations of dicarboxylic acids (DCAs) were relevant in several metabolomic tests, and metabolite alterations included aminomalonate and fumaric, malic, oxalic, and succinic acids. The product/substrate relationship between these molecules and its pathways may reflect a compensatory mechanism to balance metabolism. Conclusions RYGB was associated with systemic and GI metabolic reprogramming. DCA alterations link omega and beta fatty acid oxidation to homeostatic mechanisms, including TCA cycle improvement.
- Roux-en-Y gastric bypass affects the expression of genes related to the intestinal folate metabolism pathway in obese women(2023) FERREIRA, Beatriz de Azevedo Muner; FONSECA, Danielle Cristina; SALA, Priscila; ALVES, Juliana Tepedino Martins; PRUDENCIO, Ana Paula Aguiar; MACHADO, Natasha Mendonca; MARQUES, Mariane; BARCELOS, Samira; ISHIDA, Robson Kiyoshi; GUARDA, Ismael Francisco Mota Siqueira; MOURA, Eduardo Guimaraes Hourneaux De; SAKAI, Paulo; SANTE, Marco Aurelio; TORRINHAS, Raquel Susana Matos de Miranda; WAITZBERG, Dan LinetzkyObjectives: Roux-en-Y gastric bypass (RYGB) promotes sustained weight loss, and the resulting new gastroin-testinal anatomy can contribute to nutritional depletions. Folate deficiency is one of the most frequently observed nutritional deficiencies after RYGB. The aim of this study was to assess whether RYGB affects the expression of genes related to the intestinal folate metabolism pathway as an additional molecular mecha-nism contributing to its postoperative deficiency. Methods: Biopsies from the duodenum, jejunum, and ileum of 20 obese women were collected before and 3 mo after RYGB. The expression of genes involved in intestinal folate metabolism was assessed by microarray and reverse transcriptase polymerase chain reaction (RT-qPCR). Folate intake (7-d food record) and plasma levels (electrochemiluminescence) also were measured. Results: Compared with the preoperative phase, transcriptomic alterations were observed in all intestinal segments studied after RYBG, mainly marked by decreased expression of genes encoding folate transporters/ receptors and increased expression of genes involved in folate biosynthesis (P < 0.05). Reduced folate intake and plasma folate levels were also observed simultaneously (P < 0.05). Plasma folate concentrations corre-lated inversely with intestinal FOLR2 and SHMT2 genes (P < 0.001). Conclusion: The present findings suggested that impaired expression of genes related to intestinal folate metabolism may contribute to the early systemic deficiency after RYGB and highlight a potential transcrip-tomic reprogramming of the intestine in response to RYGB to compensate for folate depletion induced by this surgical technique.(c) 2023 Elsevier Inc. All rights reserved.
conferenceObject CHANGES IN INTESTINAL GENE EXPRESSION AFTER ROUX-EN-Y GASTRIC BYPASS COULD CONTRIBUTE TO ALZHEIMER DISEASE (AD) RISK REDUCTION.(2016) SALA, P.; BELARMINO, G.; MACHADO, N. M.; FONSECA, D. C.; ISHIDA, R. K.; TORRINHAS, R. S. M. M.; GIANNELLA-NETO, D.; WAITZBERG, D. L.- Intestinal expression of toll-like receptor gene changes early after gastric bypass surgery and association with type 2 diabetes remission(2020) SALA, Priscila; TORRINHAS, Raquel Susana Matos de Miranda; FONSECA, Danielle C.; MACHADO, Natasha Mendonca; SINGER, Joelle; SINGER, Pierre; RAVACCI, Graziela Rosa; BELARMINO, Giliane; FERREIRA, Beatriz A. M.; MARQUES, Mariane; ISHIDA, Robson Kiyoshi; GUARDA, Ismael Francisco Mota Siqueira; MOURA, Eduardo Guimaraes Hourneaux de; SAKAI, Paulo; SANTO, Marco Aurelio; SUNAGA, Daniele Yumi; HEYMSFIELD, Steven B.; BEZERRA, Daniele Pereira dos Santos; CORREA-GIANNELLA, Maria Lucia; WAITZBERG, Dan LinetzkyObjectives: Abnormal activation of toll-like receptors (TLRs) is observed in obese rodents and is correlated with local dysbiosis and increased gut permeability. These purported changes trigger systemic inflammation associated with obesity-related comorbidities, including type 2 diabetes (T2D). Roux-en-Y gastric bypass (RYGB) surgery is an effective treatment for severe obesity and known to induce changes in the gut microbiota and decrease systemic inflammation in humans. This study examined the intestinal expression of TLR-encoding genes in obese women (n = 20) treated with RYGB surgery and the relationship of these genes with T2D remission (T2Dr Methods: Intestinal biopsies were performed before and 3 months after RYGB surgery. Partial and complete T2Dr after 1 year was assessed using the American Diabetes Association criteria. Affymetrix Human GeneChip 1.0 ST array (microarray) and TaqMan assay (real-time quantitative polymerase chain reaction) were used to analyze intestinal gene expression, and associations with systemic markers of energy homeostasis were examined. Results: Patients experienced significant weight loss (P < 0.001) and altered gut TLR gene expression 3 months after surgery. The main effects were a reduction in jejunal TLR4 expression in patients with complete and partial T2Dr (P < 0.05). There was a postoperative decrease in jejunal TLR7 expression in patients with complete T2Dr that correlated inversely with high-density lipoprotein cholesterol and positively with triglyceride concentrations, but not with weight loss. Conclusions: RYGB-induced weight loss-independent changes in the expression of intestinal TLR-encoding genes in obese women and complete T2Dr that was correlated with systemic markers of energy homeostasis. The modulation of intestinal TLRs may mediate inflammatory mechanisms linked to T2Dr after RYGB surgery.
conferenceObject INCREASED GHRELIN LEVELS AFTER ROUX-EN-Y GASTRIC BYPASS (RYGB) IS ASSOCIATED WITH AN UPREGULATION OF GHRELIN (GHRL) GENE EXPRESSION IN EXCLUDED STOMACH IN HUMANS(2016) FONSECA, D. C.; SALA, P.; BELARMINO, G.; MACHADO, N. M.; ISHIDA, R. K.; TORRINHAS, R. S. M. M.; GIANNELLA-NETO, D.; WAITZBERG, D. L.- The SURMetaGIT study: Design and rationale for a prospective pan-omics examination of the gastrointestinal response to Roux-en-Y gastric bypass surgery(2016) SALA, Priscila; BELARMINO, Giliane; MACHADO, Natasha Mendonca; CARDINELLI, Camila Siqueira; ASSAL, Karina Al; SILVA, Mariane Marques; FONSECA, Danielle Cristina; ISHIDA, Robson Kiyoshi; SANTO, Marco Aurelio; MOURA, Eduardo Guimaraes Hourneaux de; SAKAI, Paulo; GUARDA, Ismael Francisco Mota Siqueira; SILVA, Ismael Dale Cotrim Guerreiro da; RODRIGUES, Agatha Sacramento; PEREIRA, Carlos Alberto de Braganca; HEYMSFIELD, Steven; DORE, Joel; TORRINHAS, Raquel Susana Matos de Miranda; GIANNELLA-NETO, Daniel; WAITZBERG, Dan LinetzkyObjective: To describe the protocol of the SURgically induced Metabolic effects on the Human GastroIntestinal Tract (SURMetaGIT) study, a clinical pan-omics study exploring the gastrointestinal tract as a central organ driving remission of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGB). The main points considered in the study's design and challenges faced in its application are detailed. Methods: This observational, longitudinal, prospective study involved collection of gastrointestinal biopsy specimens, faeces, urine, and blood from 25 obese women with T2DM who were candidates for RYGB (20 patients for omics assessment and 5 for omics validation). These collections were performed preoperatively and 3 and 24 months postoperatively. Gastrointestinal transcriptomics; faecal metagenomics and metabolomics; plasma proteomics, lipidomics, and metabolomics; and biochemical, nutritional, and metabolic data were assessed to identify their short- and long-term correlations with T2DM remission. Results: Data were collected from 20 patients before and 3 months after RYGB. These patients have nearly completed the 2-year follow-up assessments. The five additional patients are currently being selected for omics data validation. Conclusion: The multi-integrated pan-omics approach of the SURMetaGIT study enables integrated analysis of data that will contribute to the understanding of molecular mechanisms involved in T2DM remission after RYGB.