(E X -4) 2 -Fc, an effective long-acting GLP-1 receptor agonist, reduces obesity-related inflammation by inhibiting leptin expression.

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.
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.
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