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

Journal of Clinical Medicine

Javier Salvador¹  Camilo Silva²  Rafael Moncada²  Víctor Valentí²  Ignacio Monreal²  Gema Frühbeck³  Magdalena de la Higuera⁴  Maitane Izaguirre⁵  Victoria Catalán⁵  Javier Gómez-Ambrosi⁵  Beatriz Ramírez⁵  Amaia Rodríguez⁵  Sara Becerril⁵  Xabier Unamuno⁵ 

[1] Nutrition, Clínica Universidad de Navarra, 31008 Pamplona/Madrid, Spain;CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 31008 Pamplona, Spain;Department of Biochemistry, Clínica Universidad de Navarra, 31008 Pamplona, Spain;;Department of Endocrinology &Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain;

关键词: GLP-1;    inflammation;    obesity;    adipose tissue;    bariatric surgery;    T2D remission;   

DOI  :  10.3390/jcm8040479

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown