3.4.2 Ferroptosis may mediate insulin resistance
ACSL4 is another important factor in the occurrence of ferroptosis, and its increase will enhance lipid peroxidation and promote the production of more lipid peroxides, finally leading to the ferroptosis of cells108. Up-regulation of ACSL4 expression was observed in mice fed a high-fat diet(HD). In the same study, adipocyte-specific ACSL4 knockout mice were found to be protected from HD-induced cell death and insulin resistance109. Another experiment showed that ACSL4 protein is present in human and rat islet β cells, concentrated around insulin secretory granules and mitochondria, and participates in insulin secretion by modifying fatty acids in insulin secretory granules and mitochondria110. These findings suggest that ACSL4 may promote insulin secretion in beta cells, but it may exacerbate peripheral insulin resistance. Therefore, more experiments on the function of ACSL4 are needed to explore whether ACSL4 mediates ferroptosis and plays an important role in the pathogenesis of DM and whether targeting ACSL4 can prevent and treat DM.