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

Priscila Sala*, Raquel Susana Matos de Miranda Torrinhas, Danielle C. Fonseca, Natasha Mendonça Machado, Joelle Singer, Pierre Singer, Graziela Rosa Ravacci, Giliane Belarmino, Beatriz A.M. Ferreira, Mariane Marques, Robson Kiyoshi Ishida, Ismael Francisco Mota Siqueira Guarda, Eduardo Guimarães Hourneaux de Moura, Paulo Sakai, Marco Aurélio Santo, Daniele Yumi Sunaga, Steven B. Heymsfield, Daniele Pereira dos Santos Bezerra, Maria Lúcia Corrêa-Giannella, Dan Linetzky Waitzberg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number110885
JournalNutrition
Volume79-80
DOIs
StatePublished - 1 Nov 2020

Keywords

  • Bariatric surgery
  • Toll-like receptors
  • Type 2 diabetes

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