Abstract
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.
Highlights
Obesity is increasing worldwide, reaching epidemic proportions and becoming an international public health challenge [1]
Exendin-4 Inhibits LPS- and Hypoxia-Induced Inflammation in Human Visceral Adipocytes Given the evidence for the anti-inflammatory properties of exendin-4 in adipocytes and the role of LPS as a potent activator of the immune system and a regulator of gut functions, we investigated its effects on LPS-induced inflammation in human adipocytes
Our results showed that the Glucagon-like peptide (GLP)-1 response to an oral glucose tolerance test (OGTT) is reduced in obese patients with and without type 2 diabetes (T2D)
Summary
Obesity is increasing worldwide, reaching epidemic proportions and becoming an international public health challenge [1]. Since bariatric surgery induces weight loss and T2D remission together with a rise in postprandial GLP-1 secretion, the role of GLP-1 in the response to surgery-associated benefits has been extensively studied [4,11] In this sense, the response to the administration of GLP-1 agonists has been shown to predict the efficacy of Roux-en-Y gastric bypass (RYGB) on glucose tolerance in diet-induced obese rats [12]. Different studies have revealed that GLP-1 agonists reduced the circulating levels of pro-inflammatory C-reactive protein (CRP) [18] and interleukin (IL)-6 [19] in patients with T2D It remains unclear whether GLP-1 modulates inflammation directly by interacting with its receptor expressed in circulating immune cells or indirectly by promoting weight loss and glycaemic improvement [20]. We studied the role of exendin-4 in LPS-mediated inflammation signalling pathways
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