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GLP-1 Limits Adipocyte Inflammation and Its Low Circulating Pre-Operative Concentrations Predict Worse Type 2 Diabetes Remission after Bariatric Surgery in Obese Patients

Objective: Glucagon-like peptide (GLP)-1 has been proposed as a key candidate in glucose improvements after bariatric surgery. Our aim was to explore the role of GLP-1 in surgically-induced type 2 diabetes (T2D) improvement and its capacity to regulate human adipocyte inflammation. Methods: Basal ci...

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Autores principales: Izaguirre, Maitane, Gómez-Ambrosi, Javier, Rodríguez, Amaia, Ramírez, Beatriz, Becerril, Sara, Valentí, Víctor, Moncada, Rafael, Unamuno, Xabier, Silva, Camilo, de la Higuera, Magdalena, Salvador, Javier, Monreal, Ignacio, Frühbeck, Gema, Catalán, Victoria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518381/
https://www.ncbi.nlm.nih.gov/pubmed/30970605
http://dx.doi.org/10.3390/jcm8040479
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author Izaguirre, Maitane
Gómez-Ambrosi, Javier
Rodríguez, Amaia
Ramírez, Beatriz
Becerril, Sara
Valentí, Víctor
Moncada, Rafael
Unamuno, Xabier
Silva, Camilo
de la Higuera, Magdalena
Salvador, Javier
Monreal, Ignacio
Frühbeck, Gema
Catalán, Victoria
author_facet Izaguirre, Maitane
Gómez-Ambrosi, Javier
Rodríguez, Amaia
Ramírez, Beatriz
Becerril, Sara
Valentí, Víctor
Moncada, Rafael
Unamuno, Xabier
Silva, Camilo
de la Higuera, Magdalena
Salvador, Javier
Monreal, Ignacio
Frühbeck, Gema
Catalán, Victoria
author_sort Izaguirre, Maitane
collection PubMed
description Objective: Glucagon-like peptide (GLP)-1 has been proposed as a key candidate in glucose improvements after bariatric surgery. Our aim was to explore the role of GLP-1 in surgically-induced type 2 diabetes (T2D) improvement and its capacity to regulate human adipocyte inflammation. Methods: Basal circulating concentrations of GLP-1 as well as during an oral glucose tolerance test (OGTT) were measured in lean and obese volunteers with and without T2D (n = 93). In addition, GLP-1 levels were determined before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 77). The impact of GLP-1 on inflammation signalling pathways was also evaluated. Results: We show that the reduced (p < 0.05) circulating levels of GLP-1 in obese T2D patients increased (p < 0.05) after RYGB. The area under the curve was significantly lower in obese patients with (p < 0.01) and without (p < 0.05) T2D compared to lean volunteers while obese patients with T2D exhibited decreased GLP-1 levels at baseline (p < 0.05) and 120 min (p < 0.01) after the OGTT. Importantly, higher (p < 0.05) pre-operative GLP-1 concentrations were found in patients with T2D remission after RYGB. We also revealed that exendin-4, a GLP-1 agonist, downregulated the expression of inflammation-related genes (IL1B, IL6, IL8, TNF) and, conversely, upregulated the mRNA levels of ADIPOQ in human visceral adipocytes. Furthermore, exendin-4 blocked (p < 0.05) LPS-induced inflammation in human adipocytes via downregulating the expression and secretion of key inflammatory markers. Conclusions: Our data indicate that GLP-1 may contribute to glycemic control and exert a role in T2D remission after RYGB. GLP-1 is also involved in limiting inflammation in human visceral adipocytes.
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spelling pubmed-65183812019-05-31 GLP-1 Limits Adipocyte Inflammation and Its Low Circulating Pre-Operative Concentrations Predict Worse Type 2 Diabetes Remission after Bariatric Surgery in Obese Patients Izaguirre, Maitane Gómez-Ambrosi, Javier Rodríguez, Amaia Ramírez, Beatriz Becerril, Sara Valentí, Víctor Moncada, Rafael Unamuno, Xabier Silva, Camilo de la Higuera, Magdalena Salvador, Javier Monreal, Ignacio Frühbeck, Gema Catalán, Victoria J Clin Med Article Objective: Glucagon-like peptide (GLP)-1 has been proposed as a key candidate in glucose improvements after bariatric surgery. Our aim was to explore the role of GLP-1 in surgically-induced type 2 diabetes (T2D) improvement and its capacity to regulate human adipocyte inflammation. Methods: Basal circulating concentrations of GLP-1 as well as during an oral glucose tolerance test (OGTT) were measured in lean and obese volunteers with and without T2D (n = 93). In addition, GLP-1 levels were determined before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 77). The impact of GLP-1 on inflammation signalling pathways was also evaluated. Results: We show that the reduced (p < 0.05) circulating levels of GLP-1 in obese T2D patients increased (p < 0.05) after RYGB. The area under the curve was significantly lower in obese patients with (p < 0.01) and without (p < 0.05) T2D compared to lean volunteers while obese patients with T2D exhibited decreased GLP-1 levels at baseline (p < 0.05) and 120 min (p < 0.01) after the OGTT. Importantly, higher (p < 0.05) pre-operative GLP-1 concentrations were found in patients with T2D remission after RYGB. We also revealed that exendin-4, a GLP-1 agonist, downregulated the expression of inflammation-related genes (IL1B, IL6, IL8, TNF) and, conversely, upregulated the mRNA levels of ADIPOQ in human visceral adipocytes. Furthermore, exendin-4 blocked (p < 0.05) LPS-induced inflammation in human adipocytes via downregulating the expression and secretion of key inflammatory markers. Conclusions: Our data indicate that GLP-1 may contribute to glycemic control and exert a role in T2D remission after RYGB. GLP-1 is also involved in limiting inflammation in human visceral adipocytes. MDPI 2019-04-09 /pmc/articles/PMC6518381/ /pubmed/30970605 http://dx.doi.org/10.3390/jcm8040479 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Izaguirre, Maitane
Gómez-Ambrosi, Javier
Rodríguez, Amaia
Ramírez, Beatriz
Becerril, Sara
Valentí, Víctor
Moncada, Rafael
Unamuno, Xabier
Silva, Camilo
de la Higuera, Magdalena
Salvador, Javier
Monreal, Ignacio
Frühbeck, Gema
Catalán, Victoria
GLP-1 Limits Adipocyte Inflammation and Its Low Circulating Pre-Operative Concentrations Predict Worse Type 2 Diabetes Remission after Bariatric Surgery in Obese Patients
title GLP-1 Limits Adipocyte Inflammation and Its Low Circulating Pre-Operative Concentrations Predict Worse Type 2 Diabetes Remission after Bariatric Surgery in Obese Patients
title_full GLP-1 Limits Adipocyte Inflammation and Its Low Circulating Pre-Operative Concentrations Predict Worse Type 2 Diabetes Remission after Bariatric Surgery in Obese Patients
title_fullStr GLP-1 Limits Adipocyte Inflammation and Its Low Circulating Pre-Operative Concentrations Predict Worse Type 2 Diabetes Remission after Bariatric Surgery in Obese Patients
title_full_unstemmed GLP-1 Limits Adipocyte Inflammation and Its Low Circulating Pre-Operative Concentrations Predict Worse Type 2 Diabetes Remission after Bariatric Surgery in Obese Patients
title_short GLP-1 Limits Adipocyte Inflammation and Its Low Circulating Pre-Operative Concentrations Predict Worse Type 2 Diabetes Remission after Bariatric Surgery in Obese Patients
title_sort glp-1 limits adipocyte inflammation and its low circulating pre-operative concentrations predict worse type 2 diabetes remission after bariatric surgery in obese patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518381/
https://www.ncbi.nlm.nih.gov/pubmed/30970605
http://dx.doi.org/10.3390/jcm8040479
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