In mice with obesity, the drug semaglutide is linked to lower activity of certain genes in heart tissue that are related to neutrophils, a type of immune cell.
Mechanism
Synthesis from 1 study
Semaglutide helps protect the hearts of obese mice by quieting down a type of immune cell that causes inflammation. It does this by lowering the production of three specific chemicals these cells release, which in turn reduces damage and stress in the heart tissue.
Most probable mechanism
In obese mice, semaglutide helps calm down a type of immune cell called neutrophils in the heart. These cells normally release chemicals that attract more immune cells and cause damage. Semaglutide turns down the production of three specific chemicals (Cxcl2, S100a8, S100a9) made by these neutrophils. With less of these chemicals, fewer immune cells enter the heart, and less harmful stress builds up, which helps protect the heart tissue.
Semaglutide activates GLP-1 receptors on immune cells or induces systemic metabolic changes that alter neutrophil gene expression
Expression of the neutrophil-specific genes Cxcl2, S100a8, and S100a9 is reduced in cardiac tissue
Reduced Cxcl2 decreases chemotactic signaling that recruits additional neutrophils and monocytes into cardiac tissue
Reduced S100a8 and S100a9 diminishes formation of the calprotectin complex, lowering activation of TLR4/NF-κB signaling and reactive oxygen species production
Lower neutrophil-derived inflammatory signals reduce activation of cardiac macrophages and endothelial cells, decreasing cytokine and oxidative stress marker release
Reduced inflammation and oxidative stress in cardiac tissue attenuates myocardial damage
Evidence from Studies
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