The Important Role of Phosphatidylserine, ADAM17, TNF-Alpha, and Soluble MER on Efferocytosis Activity in Central Obesity

Figure 1

Illustrating the mechanism of efferocytosis impairment in central obesity. The cellular mechanism in central obesity continually leads to the damage and death of adipocytes. This is shown by the movement of PS to the outside of the cell membrane and the release of protein S/Gas6 and extracellular vesicles (EVs). Phagocytic cells, primarily macrophages, recognize PS as a “find me” signal. Meanwhile, protein S/Gas6 acts as an “eat-me” signal, binding to MERTK on phagocytic cells to initiate the clearance of damaged or dead cells and their components. PS, once bound to its receptor in phagocytic cells, activates ADAM17, which cleaves various cytokines such as TNF-α, serving as an inflammation marker. This leads to an increase in circulating TNF-α. However, ADAM17 also cleaves MERTK in phagocytic cells, generating sMER in the circulation. When sMER is high, it interferes with efferocytosis because it binds to the protein S/Gas6, which is made by damaged or dead cells. Consequently, competition arises between MERTK and sMER, which interferes with the efferocytosis process.