title: [Palmitic acid induces hepatocellular oxidative stress and activation of inflammasomes].
abstract: OBJECTIVE
  To evaluate the effect of palmitic acid (PA) on oxidative stress and activation of inflammasomes in hepatocytes.
  
  
  METHODS
  To test the dose-dependent effect of PA on normal murine hepatocytes AML12, the cells were treated with 0, 0.15, 0.25 and 0.4 mmol/L of palmitic acid (PA). The cells were also divided into blank control group, 0.25 mmol/L PA group and 0.25 mmol/L PA+N-acetylcysteine (NAC) group to examine the effect of reactive oxygen species (ROS) on the activation of inflammasomes. After 24 h of treatment, lipid accumulation, total ROS, mitochondrial ROS, expression and localization of NOX4, and expressions of inflammasomes and IL-1β were detected in the hepatocytes.
  
  
  RESULTS
  Compared with the control cells, PA treatment of the cells significantly increased cytoplasmic lipid accumulation, concentrations of total ROS (12 463.09±2.72 vs 6691.23±2.45, P=0.00) and mitochondrial ROS (64.98±0.94 vs 45.04±0.92, P=0.00), and the expressions of NOX4, NLRP3, ASC, caspase-1, and IL-1β (1603.52±1.32 vs 2629.33±2.57, P=0.00). The mitochondria and NOX4 were found to be co-localized in the cytoplasm. NAC obviously reduced cellular ROS level stimulated by PA (7782.15±2.87 vs 5445.6±1.17, P=0.00) and suppressed the expressions of NLRP3, ASC and caspase-1.
  
  
  CONCLUSIONS
  PA treatment can stimulate lipid accumulation in hepatocytes and induce oxidative stress through NOX4 and mitochondria pathway to activate inflammasomes and stimulate the secretion of IL-1β.
authors.affiliation: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.E-mail: xuwen217@foxmail.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.forename: Yu-Bin
authors.initials: YB
authors.lastname: Guo
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: He
authors.forename: Si-de
authors.initials: SD
authors.lastname: Liu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress; D019308:Palmitic Acid / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; D019308:Palmitic Acid; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D020170:Caspase 1; D000111:Acetylcysteine