Priscila Sala1, Raquel Susana Matos de Miranda Torrinhas2, Danielle C Fonseca2, Natasha Mendonça Machado2, Joelle Singer3, Pierre Singer4, Graziela Rosa Ravacci2, Giliane Belarmino2, Beatriz A M Ferreira2, Mariane Marques2, Robson Kiyoshi Ishida5, Ismael Francisco Mota Siqueira Guarda5, Eduardo Guimarães Hourneaux de Moura5, Paulo Sakai5, Marco Aurélio Santo5, Daniele Yumi Sunaga6, Steven B Heymsfield7, Daniele Pereira Dos Santos Bezerra8, Maria Lúcia Corrêa-Giannella9, Dan Linetzky Waitzberg2. 1. Laboratório de Nutrição e Cirurgia Metabólica (LIM-35), Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil; Laboratório de Carboidratos e Radioimunoensaio (LIM-18), Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil; Programa de Pós-graduação em Medicina, Universidade Nove de Julho, São Paulo, Brazil. Electronic address: sala.priscila@gmail.com. 2. Laboratório de Nutrição e Cirurgia Metabólica (LIM-35), Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. 3. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Endocrinology, Diabetes & Metabolism - Beilinson, Rabin Medical Center, Belinson Hospital, Petah Tikva, Israel. 4. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; General Intensive Care Department & Institute for Nutrition Research, Rabin Medical Center, Belinson Hospital, Petah Tikva, Israel. 5. Hospital das Clínicas, University of São Paulo, School of Medicine, São Paulo, Brazil. 6. Max Delbrück Center for Molecular Medicine, Berlin, Germany. 7. Pennington Biomedical Research Center, Baton Rouge, Louisiana. 8. Laboratório de Carboidratos e Radioimunoensaio (LIM-18), Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. 9. Laboratório de Carboidratos e Radioimunoensaio (LIM-18), Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil; Programa de Pós-graduação em Medicina, Universidade Nove de Julho, São Paulo, Brazil.
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.
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 obesewomen (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 obesewomen 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.
Authors: Laia Bertran; Rosa Jorba-Martin; Andrea Barrientos-Riosalido; Marta Portillo-Carrasquer; Carmen Aguilar; David Riesco; Salomé Martínez; Margarita Vives; Fàtima Sabench; Daniel Del Castillo; Cristóbal Richart; Teresa Auguet Journal: Int J Mol Sci Date: 2022-07-04 Impact factor: 6.208