Fig. 4
From: Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease
Regulatory factors in ALD. Ethanol is absorbed by villous epithelial cells in the intestine and is mostly transported to the liver for metabolism. Ethanol downregulates AMPK, SIRT1, miR-122, and FXR activity, increases the expression of lipid synthesis genes, and inhibits PPARα-mediated β-oxidation of fatty acids (FAs), leading to ethanol-induced fat accumulation in hepatocytes. The upregulation of miR-155 but suppression of AMPK initiated by ethanol activates apoptosis pathways in the liver. Increased bile acid synthesis due to ethanol-induced inhibition of FXR also accelerates hepatic apoptosis. The upregulation of NF-κB by ethanol stimulates the release of inflammatory factors and chemokines, leading to alcoholic hepatitis (AH). The body develops defences against the toxic effects of ethanol. For example, NRF2 is induced in hepatocytes by ethanol and promotes adaptive resistance to ethanol-initiated oxidative stress. SIRT1 sirtuin 1miR-122, microRNA-122FXRPPARαmiR-155, microRNA-155AMPK, AMP-activated protein kinaseNF-κB, nuclear factor-kappaBNRF2, nuclear factor E2-related factor 2