1. (E X -4) 2 -Fc, an effective long-acting GLP-1 receptor agonist, reduces obesity-related inflammation by inhibiting leptin expression.
- Author
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Zhou B, Dong C, Zhao B, Su X, Luo Y, Xie L, Tian Y, Zhang R, and Yang L
- Subjects
- Adipose Tissue cytology, Adipose Tissue metabolism, Animals, Anti-Inflammatory Agents pharmacology, Cytokines metabolism, Diabetes Mellitus, Type 2 metabolism, Diet, High-Fat adverse effects, Glucagon-Like Peptide 1 chemistry, Inflammation metabolism, Leptin metabolism, Macrophage Activation drug effects, Macrophages classification, Macrophages drug effects, Macrophages metabolism, Male, Mice, Inbred C57BL, Mice, Obese, NF-kappa B metabolism, Obesity etiology, Signal Transduction drug effects, Adipose Tissue drug effects, Glucagon-Like Peptide 1 pharmacology, Glucagon-Like Peptide-1 Receptor agonists, Inflammation prevention & control, Leptin antagonists & inhibitors, Obesity metabolism
- Abstract
Obesity has been recognized as a low-grade, chronic inflammatory disease that leads to an increase in obesity-associated disorders, including type 2 diabetes (T2D), fatty liver diseases and cancer. Glucagon-like peptide-1 (GLP-1) is an effective drug for T2D, and it not only has glucose-regulating effects but also has anti-inflammatory effects in obesity. In our previous study, we designed a novel GLP-1 analogue, (E
X -4)2 -Fc, which has been shown to reduce body weight and improve glucose tolerance in vivo. In this study, we observed that (EX -4)2 -Fc also has anti-inflammatory functions in adipose tissue. After the treatment of diet-induced obesity (DIO) mice with (EX -4)2 -Fc, we found that the inflammatory response in adipose tissue was significantly attenuated. (Ex-4)2 -Fc can reduce obesity-associated proinflammatory cytokine levels and macrophage numbers in DIO mice. In addition, (EX -4)2 -Fc treatment resulted in proinflammatory M1-type macrophages beginning to transform into anti-inflammatory M2-type macrophages. The inflammatory mitogen-activated protein kinase (MAPK) signalling pathway and nuclear factor kappa B (NF-κB) were altered in adipose tissue after (EX -4)2 -Fc treatment. Leptin has been proven to be closely related to immunity, and we demonstrated that the effect of (EX -4)2 -Fc on adipocyte inflammation was related to leptin. The data suggested that (EX -4)2 -Fc could modulate the inflammatory response by inhibiting the expression of leptin in adipose tissue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
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