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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Authors: Izaguirre, M. (Maitane)|||/items/b1ef9430-ad86-441d-8789-a92f881a166a, Gomez-Ambrosi, J. (Javier)|||/items/21d09997-940a-45f7-9b4b-0a9f64b2ed8e, Rodriguez, A. (Amaia)|||/items/50976a5f-9842-47f1-8a9c-508e59996427, Ramirez-Sola, B. (Beatriz)|||/items/95970833-a061-4e49-b5d8-e6ecc6ec59c4, Becerril-Mañas, S. (Sara)|||/items/5edb25ec-0edd-44eb-8ef1-c81d0ebd7300, Valenti-Azcarate, V. (Víctor)|||/items/43ffa5b1-000e-4670-8fa2-4ab80d1960d7, Moncada, R. (Rafael)|||/items/2675adbe-8b28-4af8-b1d6-baa3319591bc, Unamuno, X. (Xabier)|||/items/15dc60c5-74df-4a3f-a0c0-7410321a8d3b, Silva-Frojan, C. (Camilo)|||/items/4037daf2-cf27-42c3-b76c-2ad9aa9465ef, Higuera-López-Frías, M. (Magdalena) de la|||/items/515ec706-13aa-4d3f-91a8-25a4af30e5a2, Salvador-Rodríguez, F.J. (Francisco Javier)|||/items/1175815b-412b-41a6-b91f-6dbfa349f9c8, Monreal, J.I. (José Ignacio)|||/items/54707c2a-e68a-4e73-9141-0276a5bc7a2b, Frühbeck, G. (Gema)|||/items/7f0b1f72-bc91-4ab0-a3fd-21e9a3fb663b, Catalán-Goñi, V. (Victoria)|||/items/9a5a055c-323a-4b41-800f-65abf7f22c79
Format: article
Publication Date:2019
Country:España
Institution:Universidad de Navarra
Repository:Dadun. Depósito Académico Digital de la Universidad de Navarra
Language:English
OAI Identifier:oai:dadun.unav.edu:10171/111539
Online Access:https://hdl.handle.net/10171/111539
Access Level:Open access
Keyword:GLP-1
inflammation
obesity
adipose tissue
bariatric surgery
T2D remission
Description
Summary: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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