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Open AccessFeature PaperArticle

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

1
Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain
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CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 31008 Pamplona, Spain
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Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
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Department of Surgery, Clínica Universidad de Navarra, 31008 Pamplona, Spain
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Department of Anesthesia, Clínica Universidad de Navarra, 31008 Pamplona, Spain
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Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, 31008 Pamplona/Madrid, Spain
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Department of Biochemistry, Clínica Universidad de Navarra, 31008 Pamplona, Spain
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(4), 479; https://doi.org/10.3390/jcm8040479
Received: 18 March 2019 / Revised: 1 April 2019 / Accepted: 8 April 2019 / Published: 9 April 2019
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
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. View Full-Text
Keywords: GLP-1; inflammation; obesity; adipose tissue; bariatric surgery; T2D remission GLP-1; inflammation; obesity; adipose tissue; bariatric surgery; T2D remission
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Izaguirre, M.; Gómez-Ambrosi, J.; Rodríguez, A.; Ramírez, B.; Becerril, S.; Valentí, V.; Moncada, R.; Unamuno, X.; Silva, C.; de la Higuera, M.; Salvador, J.; Monreal, I.; Frühbeck, G.; Catalán, V. GLP-1 Limits Adipocyte Inflammation and Its Low Circulating Pre-Operative Concentrations Predict Worse Type 2 Diabetes Remission after Bariatric Surgery in Obese Patients. J. Clin. Med. 2019, 8, 479.

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