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(EX-4)2-Fc, an effective long-acting GLP-1 receptor agonist, reduces obesity-related inflammation by inhibiting leptin expression.
- Source :
-
Biochemical & Biophysical Research Communications . Aug2020, Vol. 529 Issue 3, p562-568. 7p. - 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 X -4) 2 -Fc, which has been shown to reduce body weight and improve glucose tolerance in vivo. In this study, we observed that (E X -4) 2 -Fc also has anti-inflammatory functions in adipose tissue. After the treatment of diet-induced obesity (DIO) mice with (E X -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, (E X -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 (E X -4) 2 -Fc treatment. Leptin has been proven to be closely related to immunity, and we demonstrated that the effect of (E X -4) 2 -Fc on adipocyte inflammation was related to leptin. The data suggested that (E X -4) 2 -Fc could modulate the inflammatory response by inhibiting the expression of leptin in adipose tissue. F0B7 (Ex-4) 2 -Fc could profoundly ameliorate obesity-induced inflammation in the adipose tissues of the DIO mice. F0B7 (Ex-4) 2 -Fc promotes the polarization of M2 macrophages in adipose tissue. F0B7 (Ex-4) 2 -Fc modulates the MAPK and NF-κB signalling pathways in adipose tissue. F0B7 (E X -4) 2 -Fc suppresses obesity-related inflammation by inhibiting leptin secretion. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 529
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 144802049
- Full Text :
- https://doi.org/10.1016/j.bbrc.2020.06.054