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 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 ( = 93). In addition, GLP-1 levels were determined before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) ( = 77). The impact of GLP-1 on inflammation signalling pathways was also evaluated.

Results: We show that the reduced ( < 0.05) circulating levels of GLP-1 in obese T2D patients increased ( < 0.05) after RYGB. The area under the curve was significantly lower in obese patients with ( < 0.01) and without ( < 0.05) T2D compared to lean volunteers while obese patients with T2D exhibited decreased GLP-1 levels at baseline ( < 0.05) and 120 min ( < 0.01) after the OGTT. Importantly, higher ( < 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 (, , , ) and, conversely, upregulated the mRNA levels of in human visceral adipocytes. Furthermore, exendin-4 blocked ( < 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.