Title:Critical Role of NFκB in the Pathogenesis of Non-alcoholic Fatty Liver Disease: A Widespread Key Regulator
Volume: 21
Issue: 6
Author(s): Lorenzo Franceschetti, Francesca Bonomini*, Luigi Fabrizio Rodella and Rita Rezzani
Affiliation:
- Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Brescia,Italy
Keywords:
Non-alcoholic fatty liver disease, Nuclear factor kappa b, Non-alcoholic steatohepatitis, Hepatic
steatosis, inflammation, oxidative stress.
Abstract: Non-alcoholic fatty liver disease is a chronic metabolic disorder representing
the most common cause of chronic liver disease in western civilization and one of the
main causes of cirrhosis with a significant impact on all-cause mortality in the most
advanced phases. It is characterized by hepatic fat accumulation in the absence of
significant ethanol consumption, virus infection or other specific causes of liver disease.
Accumulation of fat in liver tissue occurs as a consequence of the imbalance between
overconsumption of high-fat diet and increased de novo lipogenesis and decreased lipid
disposal. Novel dietary and pharmacological therapies for the prevention of fatty liver
disease and the progression to cirrhosis are an actual field of study but still poorly
understood. In this perspective, the current review aims to summarise and clarify the
transcription factor NFκB effects, which may exert among non-alcoholic fatty liver
diseases and their progression. Through extensive previous research, it has become
clear that several signaling pathways are involved: metabolic dysregulation (such as free
fatty acids increase, adipokine alteration, insulin resistance), oxidative stress and
inflammation contribute together in a “vicious circle” to the pathogenesis of non-alcoholic
fatty liver diseases. Within this, NFκB signaling is a primary factor in inflammatory
reactions and diseases, with important molecular connections between metabolic,
oxidative, immune and inflammation systems.
