Genetic Factors in the Pathogenesis of Nonalcoholic Fatty Liver and Steatohepatitis

Figure 1

Molecular genetics of NASH. (a) NAFLD is characterized by the hepatic fat accumulation in lipid droplets resulting from an unbalance between triglycerides acquisition and secretion. FFA stored as triglycerides during hepatic steatosis derive from peripheral lipolysis related to adipose tissue insulin resistance, followed by de novo lipogenesis induced by hyperinsulinemia, and excessive food intake. In the liver, FFA can be catabolized through β-oxidation and reesterification to triglycerides and stored as lipid droplets or exported as VLDL. (b) PNPLA3 I148M variant is attached on the surface of lipid droplets reducing triglyceride breakdown leading to lipid retention in the hepatocyte lipid droplet. (c) TM6SF2 E167K variant reduces triglycerides secretion through VLDL, leading to hepatocellular retention of lipids.

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