Immunological and molecular mechanisms in NAFLD

Abstract

Chronic metabolic inflammation, maintained by numerous proinflammatory mediators, links the metabolic syndrome to NASH. Epigeal changes that accelerate the synthesis of proinflammatory mediators in response to nutritional factors and life style are not fully known. Numerous proinflammatory transcription pathways have been described where nuclear factor kappa B plays a critical role in stimulating proinflammatory gene promoter region interdependent with epigenetic machinery. Of the many cytokines, adipokines, myokines involved in the evolution of NAFLD from simple steatosis to NASH and cirrhosis, the most important is the balance between proinflammatory cytokines TNFα and IL 6 on one hand and adiponectin on the other hand, these factors being produced by Kupffer cells, hepatic stellate cells and inflammatory hepatocytes. Starting from the classical "two hit" theory of the pathogenesis of NAFLD, recent studies have revealed the important role of free cholesterol, diacylglycerols and ceramides in the induction of insulin resistance by stimulating sterol-element-binding protein 1c and thus stimulating de novo lipogenesis. The important roles of mitochondrial dysfunction, oxidative stress endoplasmic reticulum, inflammasomes, hepatocyte apoptosis and necrosis have also been highlighted.