- [ÁREA DE OBESIDAD]
- [CIRUGÍA GENERAL Y DIGESTIVA]
- [ANESTESIA Y CUIDADOS INTENSIVOS]
- [ENDOCRINOLOGÍA Y NUTRICIÓN]
GLP-1 Limits Adipocyte Inflammation and Its Low Circulating Pre-Operative Concentrations Predict Worse Type 2 Diabetes Remission after Bariatric Surgery in Obese Patients
Maitane Izaguirre 1 , Javier Gómez-Ambrosi 2 3 4 , Amaia Rodríguez 5 6 7 , Beatriz Ramírez 8 9 10 , Sara Becerril 11 12 , Víctor Valentí 13 14 15 , Rafael Moncada 16 17 18 , Xabier Unamuno 19 20 , Camilo Silva 21 22 , Magdalena de la Higuera 23 , Javier Salvador 24 25 , Ignacio Monreal 26 , Gema Frühbeck 27 28 29 30 , Victoria Catalán 31 32 33
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.