Molecular mechanisms in the pathogenesis of metabolically associated fatty liver disease.

Inflammation is a common feature of all chronic liver diseases and atherosclerosis. The article discusses the participation of cytokines and inflammasomes in the process of development of metabolically associated fatty liver disease (MAFLD) and the ways of their activation under the influence of inductive stimuli (toxins, alcohol, fat, viruses, etc.), most often in the case of disruption of intestinal permeability through toll-like receptors with an imbalance in the composition of intestinal microflora and bile acids. Inflammasomes and cytokines are the sources of sterile inflammation in the liver in obesity and metabolic syndrome with subsequent lipotoxicity which is followed by fibrogenesis. The prospects for therapeutic modulation of diseases with the participation of inflammasomes are therefore sought precisely at the level of influencing the mentioned molecular mechanisms. The article emphasizes the importance of the liver-intestinal axis and modulation of microbiome, as well as calls attention to the influence of the circadian rhythm of the 12-hour pacemaker on gene production in NASH (non-alcoholic steatohepatitis) developing (Fig. 4, Ref. 56). Keywords: NASH, MAFLD, microbiome, lipotoxicity, bile acids, inflammasomes.