fig1

Figure 1. Schematic representation of lipotoxicity signaling pathways in podocytes in DKD. Schematic representation of integrated signaling networks mediating podocyte lipotoxicity in DKD. Dysregulated lipid metabolism (cholesterol accumulation, impaired fatty acid oxidation, ceramide overproduction) triggers mitochondrial dysfunction, ER stress, and oxidative stress, which converge to activate inflammatory pathways and apoptotic cascades, ultimately leading to podocyte loss and disruption of the glomerular filtration barrier. Red arrow: Upregulation; green arrow: downregulation. ABCA1: ATP-binding cassette transporter A1; ACC: acetyl-CoA carboxylase; JAML: junctional adhesion molecule-like protein; AMPK: AMP-activated protein kinase; CCDC92: coiled-coil domain-containing protein 92; C1P: ceramide-1-phosphate; CPT1: carnitine palmitoyltransferase 1; DDR1: discoidin domain receptor 1; ER: endoplasmic reticulum; FTO: fat mass and obesity-associated protein; GSK3β: glycogen synthase kinase 3 beta; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; NLRP3: NOD-like receptor family pyrin domain containing 3; PLC: phospholipase C; PP2A: protein phosphatase 2A; PPARγ: peroxisome proliferator-activated receptor gamma; RhoA: Ras homolog family member A; ROS: reactive oxygen species; S1P: sphingosine-1-phosphate; SD: slit diaphragm; SIRT3: sirtuin 3; SMPDL3b: sphingomyelin phosphodiesterase acid-like 3b; SOAT1: sterol O-acyltransferase 1; STK25: serine/threonine kinase 25; TLR4: toll-like receptor 4; TNF: tumor necrosis factor.