CD36 deletion ameliorates diabetic kidney disease by restoring fatty acid oxidation and improving mitochondrial function

Renal tubular epithelial cells (TECs) are vulnerable to mitochondrial dysregulation, which is an integral part of diabetic kidney disease (DKD). We found that CD36 knockout ameliorated mitochondrial dysfunction and diabetic kidney injury in mice, improved renal function, glomerular hypertrophy, tubular injury, tubulointerstitial fibrosis, and kidney cell apoptosis. Furthermore, CD36 knockout conferred protection against diabetes-induced mitochondrial dysfunction and restored renal tubular cells and mitochondrial morphology. CD36 knockout also restored mitochondrial fatty acid oxidation (FAO) and enhanced FAO-associated respiration in diabetic TECs. CD36 was found to alter cellular metabolic pathways in diabetic kidneys partly <i>via</i> PDK4 the –AMPK axis inactivation. Because CD36 protects against DKD by improving mitochondrial function and restoring FAO, it can serve as a potential therapeutic target.