fig2

Figure 2. Key pathogenic processes and therapeutic interventions in podocyte lipotoxicity in DKD. Schematic overview of the hierarchical pathogenic cascade from lipid dysregulation to podocyte injury in DKD. Lipid dysregulation (cholesterol accumulation, impaired FAO, ceramide overproduction triggers cellular stress responses (mitochondrial dysfunction, ER stress/autophagy defect, inflammation), leading to podocyte damage (apoptosis, FP effacement, SD disruption). Corresponding therapeutic interventions are annotated at each stage, including statins, SGLT2i, AdipoRon, STK25 depletion, FTO inhibitors, GSK3β inhibition, ipragliflozin, MCC950, flavonoids, NRG4, and CHILKBP restoration. Bold arrows: Activation or promotion; upward small arrows: upregulation; downward small arrows: downregulation. CHILKBP: CH-ILK-binding protein; DKD: diabetic kidney disease; ER: endoplasmic reticulum; FAO: fatty acid oxidation; FP: foot process; FTO: fat mass and obesity-associated protein; GSK3β: glycogen synthase kinase 3 beta; MCC950: NLRP3 inflammasome inhibitor; NRG4: neuregulin 4; SD: slit diaphragm; SGLT2i: sodium-glucose cotransporter 2 inhibitors; STK25: serine/threonine kinase 25; ZO-1: zonula occludens-1.