VSIG4 and Insulin resistance: In summary, MAFLD is characterized by compromised intestinal barrier and a significant reduction in the population of Vsig4+ and CRIg+ macrophages, which allows mEVs to transport bacterial DNA or pro-inflammatory cytokines to distant target cells, including hepatocytes, HSCs, adipocytes, pancreatic β cells, and skeletal muscle cells, thereby leading to insulin resistance, liver inflammation and dysfunction.