title: Hydrogen peroxide impairs autophagic flux in a cell model of nonalcoholic fatty liver disease.
abstract: Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, but the pathogenesis of NAFLD is not fully clear. The aim of this study was to determine whether autophagy plays a role in the pathogenesis of NAFLD. We found that the levels of autophagy were elevated in hepatoma cells upon exposure to free fatty acids, as confirmed by the increase in the number of autophagosomes. However, exposure of hepatoma cells to H2O2 and TNF-α, two typical "second hit" factors, increased the initiation of autophagy but inhibited the autophagic flux. The inhibition of autophagy sensitized cells to pro-apoptotic stimuli. Taken together, our results suggest that autophagy acts as a protective mechanism in the pathogenesis of NAFLD and that impairment of autophagy might induce more severe lesions of the liver. These findings will be a benefit to the understanding of the pathogenesis of NAFLD and might suggest a strategy for the prevention and cure of NAFLD.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, PR China.
authors.forename: Pengtao
authors.initials: P
authors.lastname: Jiang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Taotao
authors.initials: T
authors.lastname: Wei
mesh_terms: D000818:Animals; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog; D002470:Cell Survival; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology*; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008954:Models, Biological; D065626:Non-alcoholic Fatty Liver Disease; D018384:Oxidative Stress; D010588:Phagosomes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D005230:Fatty Acids, Nonesterified; D047908:Intracellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C484754:ULK1 protein, human