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Changes in gene expression in gastric and intestinal tissue of type 2 Diabetes patients submitted to Roux-en-Y gastric bypass

Grant number: 11/09612-3
Support type:Research Projects - Thematic Grants
Duration: January 01, 2013 - June 30, 2017
Field of knowledge:Health Sciences - Nutrition
Principal Investigator:Dan Linetzky Waitzberg
Grantee:Dan Linetzky Waitzberg
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Co-Principal Investigators:Daniel Giannella Neto ; Eduardo Guimarães Hourneaux de Moura ; Ismael Dale Cotrim Guerreiro da Silva ; Marco Aurélio Santo ; Maria Lucia Cardillo Corrêa Giannella
Assoc. researchers:Angela Flávia Logullo Waitzberg ; Camila de Siqueira Cardinelli ; Cesar Isaac ; Danielle Cristina Fonseca ; Flair José Carrilho ; Giliane Belarmino ; Karina Al Assal ; Lívia Samara dos Reis Rodrigues ; Marcus Castro Ferreira ; Natasha Mendonça Machado ; Paulo Sakai ; Priscila Sala Kobal ; Robson Kiyoshi Ishida ; Rogério Kuga ; Rui Curi ; Viviane Lyrio Do Valle de Pardo Blois ; Wilson Cintra Junior
Associated scholarship(s):15/22820-5 - Short and long term evaluation of caloric intake and macro and micronutrients on obese pacients carriers of melittus type 2 after bypass surgery - Y-Roux, BP.IC
14/05220-1 - Metabolomics of fecal water in obese patients with Type 2 Diabetes before and after gastroplasty reduction in Y-Roux (GRYR), BP.DD
13/23355-9 - Metabolomics profile of patients with type 2 diabetes and obesity after Roux en Y gastric bypass, BP.DR
12/23762-0 - Assessment of food intake and comparison of 24h food recall and food record of 7 days applied in obese patients in the preoperative and postoperative of Roux-en-Y gastric bypass, BP.IC
13/03246-0 - Genomic, proteomic and metabolomic study of gastrointestinal tissue for patients with type 2 Diabetes mellitus after Roux-en-Y gastric bypass, BP.DD

Abstract

Severe obese patients with type 2 diabetes mellitus (T2DM) submitted to Roux-en-Y gastric bypass (RYGB) show significant improvement in glucose control after surgery upon discharge from the hospital, even before a considerable weight loss, with suppression of hypoglycemic drugs. Experimentally, the anatomical changes induced by RYGB can change genes expression in gastrointestinal tissue related to glucose control determinants to T2DM reversal. However, there aren't clinical studies that prove these findings in humans. We will study 20 severely obese patients with T2DM candidates for RYGB. Before and 3 months after surgery, biopsies will be collected from the gastric body, gastric fundus, duodenum, jejunum and ileum by double balloon enteroscopy, used to verify changes in mRNA expression by microarray technique. Altered gene expressed will be validated by RT-qPCR and protein expression by mass spectrometry. The plasma glucose, incretins, insulin, C-peptide and glycosylated hemoglobin will also be evaluated before and after surgery. Metabolic pathways involving genes reportedly regulated after RYGB will be identified and proposed as a potential therapeutic target for T2DM. The composition of intestinal microbiota in obese patients with T2DM has been suggested as key element in glucose control. Accordingly, in parallel, we evaluate the preoperative and postoperative changes in the composition of fecal microbiota in our patients. (AU)

Scientific publications (14)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CARDINELLI, CAMILA DE SIQUEIRA; TORRINHAS, RAQUEL SUSANA; SALA, PRISCILA; PUDENZI, MARCOS ALBIERI; ANGOLINI, CELIO FERNANDO F.; DA SILVA, MARIANE MARQUES; MACHADO, NATASHA MENDONCA; RAVACCI, GRAZIELA; EBERLIN, MARCOS N.; WAITZBERG, DAN L. 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. Clinical Nutrition, v. 38, n. 6, p. 2906-2912, DEC 2019. Web of Science Citations: 1.
GARLA, PRISCILA; SALA, PRISCILA; MATOS TORRINHAS, RAQUEL SUSANA; MACHADO, NATASHA MENDONCA; FONSECA, DANIELLE CRISTINA; DA SILVA, MARIANE MARQUES; RAVACCI, GRAZIELA ROSA; BELARMINO, GILIANE; ISHIDA, ROBSON KIYOSHI; MOTA SIQUEIRA GUARDA, ISMAEL FRANCISCO; HOURNEAUX DE MOURA, EDUARDO GUIMARDES; SAKAI, PAULO; SANTO, MARCO AURELIO; COTRIM GUERREIRO DA SILVA, ISMAEL DALE; ALVES PEREIRA, CLAUDIA CRISTINA; HEYMSFIELD, STEVEN; CARDILLO CORREA-GIANNELLA, MARIA LUCIA; CALDER, PHILIP C.; WAITZBERG, DAN LINETZKY. Reduced intestinal FADS1 gene expression and plasma omega-3 fatty acids following Roux-en-Y gastric bypass. Clinical Nutrition, v. 38, n. 3, p. 1280-1288, JUN 2019. Web of Science Citations: 0.
RAVACCI, GRAZIELA ROSA; ISHIDA, ROBSON; TORRINHAS, RAQUEL SUZANA; SALA, PRISCILA; MACHADO, NATASHA MENDONCA; FONSECA, DANIELLE CRISTINA; BAPTISTA CANUTO, GISELE ANDRE; PINTO, ERNANI; NASCIMENTO, VIVIANE; MAGGI TAVARES, MARINA FRANCO; SAKAI, PAULO; FAINTUCH, JOEL; SANTO, MARCO AURELIO; HOURNEAUX MOURA, EDUARDO GUIMARAES; ARTIGIANI NETO, RICARDO; LOGULLO, ANGELA FLAVIA; WAITZBERG, DAN LINETZKY. Potential premalignant status of gastric portion excluded after Roux en-Y gastric bypass in obese women: A pilot study. SCIENTIFIC REPORTS, v. 9, APR 3 2019. Web of Science Citations: 0.
SALA, PRISCILA; CORREA-GIANNELLA, M. L.; WAITZBERG, DAN L. Bariatric surgery and gene expression in the gut. CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE, v. 21, n. 4, p. 246-251, JUL 2018. Web of Science Citations: 0.
FONSECA, DANIELLE CRISTINA; SALA, PRISCILA; SINGER, JOELLE; SINGER, PIERRE; TORRINHAS, RAQUEL SUSANA; WAITZBERG, DAN LINETZKY. Upregulation of Ghrelin Gene Expression in the Excluded Stomach of Obese Women with Type 2 Diabetes After Roux-en-Y Gastric Bypass in the SURMetaGIT Study. OBESITY SURGERY, v. 28, n. 3, p. 877-880, MAR 2018. Web of Science Citations: 3.
SALA, PRISCILA; TORRINHAS, RAQUEL SUSANA; FONSECA, DANIELLE CRISTINA; HEYMSFIELD, STEVEN; GIANNELLA-NETO, DANIEL; WAITZBERG, DAN LINETZKY. 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. OBESITY SURGERY, v. 27, n. 4, p. 1123-1127, APR 2017. Web of Science Citations: 8.
SALA, PRISCILA; MATOS DE MIRANDA TORRINHAS, RAQUEL SUSANA; FONSECA, DANIELLE CRISTINA; RAVACCI, GRAZIELA ROSA; WAITZBERG, DAN LINETZKY; GIANNELLA-NETO, DANIEL. Tissue-specific methylation profile in obese patients with type 2 diabetes before and after Roux-en-Y gastric bypass. DIABETOLOGY & METABOLIC SYNDROME, v. 9, FEB 22 2017. Web of Science Citations: 11.
SALA, PRISCILA; BELARMINO, GILIANE; TORRINHAS, RAQUEL S.; MACHADO, NATASHA M.; FONSECA, DANIELLE C.; RAVACCI, GRAZIELA R.; ISHIDA, ROBSON K.; GUARDA, ISMAEL F. M. S.; DE MOURA, EDUARDO G.; SAKAI, PAULO; SANTO, MARCO A.; DA SILVA, ISMAEL D. C. G.; PEREIRA, CLAUDIA C. A.; LOGULLO, ANGELA F.; HEYMSFIELD, STEVEN; GIANNELLA-NETO, DANIEL; WAITZBERG, DAN L. Gastrointestinal Transcriptomic Response of Metabolic Vitamin B12 Pathways in Roux-en-Y Gastric Bypass. CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY, v. 8, JAN 2017. Web of Science Citations: 5.
SALA, PRISCILA; BELARMINO, GILIANE; MACHADO, NATASHA MENDONCA; CARDINELLI, CAMILA SIQUEIRA; AL ASSAL, KARINA; SILVA, MARIANE MARQUES; FONSECA, DANIELLE CRISTINA; ISHIDA, ROBSON KIYOSHI; SANTO, MARCO AURELIO; HOURNEAUX DE MOURA, EDUARDO GUIMARAES; SAKAI, PAULO; MOTA SIQUEIRA GUARDA, ISMAEL FRANCISCO; COTRIM GUERREIRO DA SILVA, ISMAEL DALE; RODRIGUES, AGATHA SACRAMENTO; DE BRAGANCA PEREIRA, CARLOS ALBERTO; HEYMSFIELD, STEVEN; DORE, JOEL; MATOS DE MIRANDA TORRINHAS, RAQUEL SUSANA; GIANNELLA-NETO, DANIEL; WAITZBERG, DAN LINETZKY. The SURMetaGIT study: Design and rationale for a prospective pan-omics examination of the gastrointestinal response to Roux-en-Y gastric bypass surgery. JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, v. 44, n. 6, p. 1359-1375, DEC 2016. Web of Science Citations: 4.
BELARMINO, GILIANE; HORIE, LILIAN MIKA; SALA, PRISCILA CAMPOS; TORRINHAS, RAQUEL S.; HEYMSFIELD, STEVEN B.; WAITZBERG, DAN L. Body adiposity index performance in estimating body fat in a sample of severely obese Brazilian patients. NUTRITION JOURNAL, v. 14, DEC 30 2015. Web of Science Citations: 3.
CARDINELLI, CAMILA S.; SALA, PRISCILA C.; ALVES, CLAUDIA C.; TORRINHAS, RAQUEL S.; WAITZBERG, DAN L. Influence of Intestinal Microbiota on Body Weight Gain: a Narrative Review of the Literature. OBESITY SURGERY, v. 25, n. 2, p. 346-353, FEB 2015. Web of Science Citations: 8.
DA SILVA, MARIANE MARQUES; SALA, PRISCILLA CAMPOS; MATOS DE MIRANDA TORRINHAS, RAQUEL SUZANA; WAITZBERG, DAN LINETZKY. Efficiency of the 24-hour food recall instrument for assessing nutrient intake before and after Roux-en-Y gastric bypass. NUTRICION HOSPITALARIA, v. 30, n. 6, p. 1240-1247, DEC 2014. Web of Science Citations: 4.
SALA, PRISCILA CAMPOS; TORRINHAS, RAQUEL SUSANA; GIANNELLA-NETO, DANIEL; WAITZBERG, DAN LINETZKY. Relationship between gut hormones and glucose homeostasis after bariatric surgery. DIABETOLOGY & METABOLIC SYNDROME, v. 6, AUG 16 2014. Web of Science Citations: 18.
DA SILVA, MARIANE MARQUES; SALA, PRISCILA CAMPOS; CARDINELLI, CAMILA SIQUEIRA; TORRINHAS, RAQUEL SUZANA; WAITZBERG, DAN LINETZKY. Comparison of Virtual Nutri Plus (R) and Dietpro 5i (R) software systems for the assessment of nutrient intake before and after Roux-en-Y gastric bypass. Clinics, v. 69, n. 11, p. 714-722, 2014. Web of Science Citations: 2.

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