Review Article

Autophagy and Non-Alcoholic Fatty Liver Disease

Figure 2

NAFLD. The spectrum of non-alcoholic fatty liver diseases (NAFLD) extends from isolated steatosis (triglyceride accumulation) to steatohepatitis (steatosis with inflammation) (non-alcoholic steatohepatitis [NASH]), steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. Peripheral insulin resistance may represent the “first hit” in the pathogenesis of NAFLD, which leads to hepatic steatosis. Combined hyperglycemia and hyperinsulinemia promote de novo lipid synthesis and structural defects in mitochondria within hepatocytes. Moreover, insulin resistance of adipose tissue leads to an enhanced free fatty acid flux to the liver that contributes to steatosis. Steatotic hepatocytes may be vulnerable to a “second hit” induced by cytokines (such as TNFα) and oxidative/ER stresses, which lead to the development of steatohepatitis and fibrosis. Apoptotic hepatocytes are engulfed by kupffer cells, which results in their activation and inflammation. The activation of stellate cells by apoptotic bodies or by TGFβ from activated kupffer cells then leads to liver fibrosis [22].
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