Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications

Figure 3 Dysregulated triglyceride catabolism in the liver enhances lipid toxicity. Dysregulated hepatic triglyceride catabolism (adipose triglyceride lipase/carnitine palmitoyltransferase 1A dysfunction) causes free fatty acid/ceramide accumulation, triggering oxidative stress and organelle damage. Impaired autophagy and peroxisome proliferator-activated receptor α dysregulation exacerbate lipotoxicity, synergistically driving metabolic dysfunction-associated steatotic disease progression. TG: Triglyceride; FFA: Free fatty acid; CPT1A: Carnitine palmitoyltransferase 1A; TCA: Tricarboxylic acid cycle; ACOX1: Acyl-CoA oxidase 1; ROS: Reactive oxygen species; ETC: Electron transport chain; ER: Endoplasmic reticulum; ATGL: Adipose triglyceride lipase; Cer: Ceramide; SERCA: Sarcoplasmic endoplasmic reticulum calcium ATPase; MASLD: Metabolic dysfunction-associated steatotic disease; mTORC1: Mechanistic target of rapamycin complex 1.