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(E X -4) 2 -Fc, an effective long-acting GLP-1 receptor agonist, reduces obesity-related inflammation by inhibiting leptin expression.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2020 Aug 27; Vol. 529 (3), pp. 562-568. Date of Electronic Publication: 2020 Jul 15. - Publication Year :
- 2020
-
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 <subscript>X</subscript> -4) <subscript>2</subscript> -Fc, which has been shown to reduce body weight and improve glucose tolerance in vivo. In this study, we observed that (E <subscript>X</subscript> -4) <subscript>2</subscript> -Fc also has anti-inflammatory functions in adipose tissue. After the treatment of diet-induced obesity (DIO) mice with (E <subscript>X</subscript> -4) <subscript>2</subscript> -Fc, we found that the inflammatory response in adipose tissue was significantly attenuated. (Ex-4) <subscript>2</subscript> -Fc can reduce obesity-associated proinflammatory cytokine levels and macrophage numbers in DIO mice. In addition, (E <subscript>X</subscript> -4) <subscript>2</subscript> -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 (E <subscript>X</subscript> -4) <subscript>2</subscript> -Fc treatment. Leptin has been proven to be closely related to immunity, and we demonstrated that the effect of (E <subscript>X</subscript> -4) <subscript>2</subscript> -Fc on adipocyte inflammation was related to leptin. The data suggested that (E <subscript>X</subscript> -4) <subscript>2</subscript> -Fc could modulate the inflammatory response by inhibiting the expression of leptin in adipose tissue.<br />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.<br /> (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 529
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 32736674
- Full Text :
- https://doi.org/10.1016/j.bbrc.2020.06.054