Intestinal expression of toll-like receptor gene changes early after gastric bypass surgery and association with type 2 diabetes remission

Author(s):Show less -

Sala, Priscila ^{[1, 2, 3]} ; Matos de Miranda Torrinhas, Raquel Susana ^[2] ; Fonseca, Danielle C. ^[2] ; Machado, Natasha Mendonca ^[2] ; Singer, Joelle ^{[4, 5]} ; Singer, Pierre ^{[4, 6, 7]} ; Ravacci, Graziela Rosa ^[2] ; Belarmino, Giliane ^[2] ; Ferreira, Beatriz A. M. ^[2] ; Marques, Mariane ^[2] ; Ishida, Robson Kiyoshi ^[8] ; Mota Siqueira Guarda, Ismael Francisco ^[8] ; Hourneaux de Moura, Eduardo Guimaraes ^[8] ; Sakai, Paulo ^[8] ; Santo, Marco Aurelio ^[8] ; Sunaga, Daniele Yumi ^[9] ; Heymsfield, Steven B. ^[10] ; dos Santos Bezerra, Daniele Pereira ^[3] ; Correa-Giannella, Maria Lucia ^{[1, 3]} ; Waitzberg, Dan Linetzky ^[2]

Affiliation

^[1] Univ Nove de Julho, Programa Posgrad Med, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Hosp Clin HCFMUSP, Lab Nutr & Cirurgia Metab LIM 35, Fac Med, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Hosp Clin HCFMUSP, Lab Carboidratos & Radioimunoensaio LIM 18, Fac Med, Sao Paulo - Brazil

^[4] Tel Aviv Univ, Sackler Sch Med, Tel Aviv - Israel

^[5] Belinson Hosp, Rabin Med Ctr, Dept Endocrinol Diabet Ea Metab Beilinson, Petah Tiqwa - Israel

^[6] Belinson Hosp, Rabin Med Ctr, Gen Intens Care Dept, Petah Tiqwa - Israel

^[7] Belinson Hosp, Rabin Med Ctr, Inst Nutr Res, Petah Tiqwa - Israel

^[8] Univ Sao Paulo, Hosp Clin, Sch Med, Sao Paulo - Brazil

^[9] Max Delbruck Ctr Mol Med, Berlin - Germany

^[10] Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 - USA

• Document type: Journal article
• Source: NUTRITION; v. 79-80, NOV-DEC 2020.
• Web of Science Citations: 1

Abstract

Objectives: 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. (C) 2020 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 16/19170-1 - Changes in gene expression and identification of gastrointestinal epigenetic signature related to the early resolution and late recurrence of Type 2 Diabetes after 2 years of Roux-in-Y gastric bypass
• Grantee: Priscila Sala Kobal
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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