Extracellular Vesicles in Non-alcoholic Fatty Liver Disease and Alcoholic Liver Disease

Figures

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  Figure 1. The biogenesis of extracellular vesicles (EVs). Exosomes and ectosomes are two types of EVs secreted by cells. Exosomes (~30–200 nm in diameter) originate from the endosomal pathway and are secreted by the fusion of multivesicular bodies (MVBs) with the plasma membrane. Ectosomes (size range ~50–500 nm) are generated by the direct outward budding of the plasma membrane. The budding of EVs involves a variety of mechanisms, and is a combination of one or more of the following mechanisms: endosomal sorting complexes required for transport (ESCRT) complex, neutral sphingomyelinase 2 (nSMase2) generating ceramide, GTPase Ral, and the Rho family. However, specific biogenesis mechanisms are not yet clearly known. EVs are highly heterogeneous population. The cargos of EVs contain different types of cell surface proteins, intracellular protein, genetic materials [such as DNAs, messenger RNAs (mRNAs), and miRNAs], and lipid.

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  Figure 2. Extracellular vesicles in the development of alcoholic liver disease (ALD). Alcohol exposure in the liver can increase the number of circulating EVs. Some biomolecules loaded by EVs are upregulated, acting on target cells [such as macrophages, endothelial cells, and hepatic stellate cells (HSCs)] and promoting inflammation and fibrosis. The release of circulating EVs containing a high level of these biomolecules is related to the progression of ALD to their inflammatory and more aggressive forms alcoholic steatohepatitis (ASH).

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  Figure 3. Extracellular vesicles in the development of non-alcoholic fatty liver disease (NAFLD). During the process of lipotoxicity, a large number of EVs released from liver carry inflammatory molecules to liver non-parenchymal cells (macrophages, HSCs, and endothelial cell), which can promote liver inflammation, angiogenesis, and fibrosis.