PATHOPHYSIOLOGY OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD): CELLULAR MECHANISMS AND THERAPEUTIC TARGETS
Keywords:
Non-Alcoholic Fatty Liver Disease, oxidative stress, mitochondrial dysfunction, NF-κB, autophagy, therapeutic targets, liver inflammation, lipid accumulationAbstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is a major global health concern characterized by hepatic lipid accumulation, oxidative stress, and inflammation. This study aimed to investigate the cellular mechanisms involved in the progression of NAFLD and evaluate potential therapeutic strategies targeting oxidative stress, mitochondrial dysfunction, and inflammatory pathways. Using in vitro human hepatocyte cell models exposed to varying concentrations of free fatty acids (FFAs), we observed a significant increase in triglyceride accumulation, reactive oxygen species (ROS) levels, and a decline in mitochondrial membrane potential, indicating the critical role of oxidative stress and mitochondrial dysfunction in the pathogenesis of NAFLD. Analysis of gene expression revealed elevated levels of inflammation-related genes together with metabolic genes PPAR-α, NF-κB, and IL-6 that validated the metabolic dysregulation as well as inflammation found in this condition. The NAFLD mice underwent dietary intervention tests yielding liver tissue results indicating severe steatosis together with widespread fibrotic areas. A reduction in NF-κB signaling while activating autophagy functioned as therapeutic targets because this combination resulted in significant decreases of NAFLD-related tissue inflammation and fatty accumulations and fibrosis within the subject model. The findings show that NAFLD treatment becomes possible when medical professionals manage oxidative stress together with NF-κB and autophagy control systems to enhance NAFLD molecular pathway knowledge.
