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Genetic reprogramming of rHemnant duodenum may contribute to type 2 diabetes improvement after Roux-en-Y gastric bypass

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Sala, Priscila ; Machado, Natasha Mendonca ; Torrinhas, Raquel Susana Matos de Miranda ; Fonseca, Danielle C. ; Ferreira, Beatriz A. M. ; Ishida, Robson Kiyoshi ; Guarda, Ismael Francisco Mota Siqueira ; de Moura, Eduardo Guimaraes Hourneaux ; Sakai, Paulo ; Santo, Marco Aurelio ; Heymsfield, Steven B. ; Correa-Giannella, Maria Lucia ; Waitzberg, Dan Linetzky
Total Authors: 13
Document type: Journal article
Source: NUTRITION; v. 99-100, p. 10-pg., 2022-04-28.
Abstract

Objectives: Type 2 diabetes control occurs within a few days after Roux-en-Y gastric bypass (RYGB) and might be related to intestinal adaptation to the new anatomic arrangement. The aim of this study was to evaluate the intestinal transcriptome response to RYGB and its correlation with markers of glycemic homeostasis. Methods: Global transcriptomic analyses performed by microarray technique were conducted in intestinal biopsies collected from adult women with obesity (N = 20) and T2D before and 3 mo after RYGB. Clinical and biochemical markers of glycemic homeostasis were also evaluated. At 1-y postoperative, patients were clas-sified as responsive (R) or non-responsive (NR) to complete T2D remission according to the American Diabe-tes Association criteria. Intestinal differentially expressed genes (DEGs) were analyzed separately in the two groups, validated by reverse transcription quantitative polymerase chain reaction, and applied in functional enrichment and canonical pathway analysis. Spearman correlations between clinical and biochemical varia-bles with DEGs were conducted. Twelve patients were classified as R and displayed 62 (duodenum), 241 (jejunum), and 63 (ileum) DEGs. Results: Eight of the patients with DEGs presented very strong or strong positive correlations with glycemia or glycated hemoglobin. Duodenal changes of genes involved in the LXR/RXR pathway were more likely to be associated with T2D. Conclusion: In obese women, complete remission of T2D after RYGB might include intestinal transcriptomic changes that suggest a potential role of intracellular cholesterol and lipid homeostasis on glucose control.(c) 2022 Elsevier Inc. All rights reserved. (AU)

FAPESP's process: 13/03246-0 - Genomic, proteomic and metabolomic study of gastrointestinal tissue for patients with type 2 Diabetes mellitus after Roux-en-Y gastric bypass
Grantee:Priscila Sala Kobal
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 11/09612-3 - Changes in gene expression in gastric and intestinal tissue of type 2 Diabetes patients submitted to Roux-en-Y gastric bypass
Grantee:Dan Linetzky Waitzberg
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 14/07742-5 - Genomic, proteomic and metabolomic study of gastrointestinal tissue for patients with type 2 diabetes mellitus after Roux-en-Y gastric bypass
Grantee:Priscila Sala Kobal
Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)