Understanding the Mechanisms of Lipid Metabolism Reprogramming and Ferroptosis in Diabetic Kidney Disease Progression

Diabetic kidney disease (DKD) is a common complication of diabetes. The primary mechanism by which renal damage affects renal cells, including podocytes and renal tubular epithelial cells in DKD patients, is lipid metabolism reprogramming. These changes result in a metabolic stress response, including oxidative stress, energy stress in mitochondria, lysosomal stress, endoplasmic reticulum stress, and other stress reactions. Altered lipid metabolism, including abnormalities in proteins and enzymes related to lipid absorption, synthesis, and breakdown, may result in lipid peroxidation and the generation of reactive oxygen species derived from lipids, ultimately initiating ferroptosis in kidney cells. Ferroptosis is a crucial form of programmed cell death in DKD, marked by the buildup of toxic lipid peroxides dependent on iron. It plays a significant role in the progression of kidney-related tissue damage. The discussion also touches on the potential of reducing ferroptosis treatment in DKD by targeting lipid metabolism reprogramming and the metabolic stress response.