title: [Hypoxia-induced alterations of lipid metabolism in the normal human hepatic L02 cell line].
abstract: OBJECTIVE
  To investigate the effects of hypoxia on lipid metabolism in the normal human hepatic cell line L02 and to investigate the underlying molecular mechanisms.
  
  
  METHODS
  L02 cells were exposed to hypoxic conditions (experimental groups: at 1% O2, 5% CO2, 94% N2 for 3, 6, 12, 24, or 48 hours) or normoxic conditions (control group: at 21% O2). Lipid droplet accumulation and triglyceride content were measured in each group by oil red O staining and biochemical assay, respectively. The mRNA expression levels of hypoxia-inducible factor (HIF)-2a and sterol regulatory element binding protein (SREBP)-1c were detected by reverse transcription-polymerase chain reaction. Protein expression levels of HIF-2a, adipose differentiation-related protein (ADRP), and Fas were tested by Western blot analysis.
  
  
  RESULTS
  Lipid droplet accumulation and the triglyceride content were significantly higher in the hypoxia group than the normoxia group. In addition, the hypoxia groups had significantly down-regulated mRNA expression of SREBP-1c (12h: 0.236+/-0.043, 24 h: 0.287+/-0.044, 48 h: 0.342+/-0.049 vs. normoxia: 0.503+/-0.037; F = 28.37, P less than 0.01) and FAS protein (12 h: 0.562+/-0.054, 24 h: 0.674+/-0.062, 48 h: 0.682+/-0.057 vs normoxia: 0.857+/-0.069; F = 16.08, P less than 0.01). In normoxic cells, little or no expression of HIF-2a protein was detected by Western blot. In hypoxic cells, HIF-2a protein expression peaked at 6h (0.973+/-0.067). ADRP protein expression was significantly higher in hypoxia groups than in the normoxia group (12 h: 0.319+/-0.043, 24 h: 0.732+/-0.056 and 48 h: 0.873+/-0.066 vs. 0.211+/-0.019; all, P less than 0.05.
  
  
  CONCLUSIONS
  Exposure to hypoxic conditions might induce lipidosis in normal human hepatic cells by stimulating HIF-2a and ADRP expression.
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital, Chongqing Medical University, China.
authors.forename: Wen-hui
authors.initials: WH
authors.lastname: Cheng
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015687:Cell Hypoxia; D002460:Cell Line; D015536:Down-Regulation; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D000070780:Perilipin-2; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D008565:Membrane Proteins; D010100:Oxygen; D000070780:Perilipin-2; D051780:Sterol Regulatory Element Binding Protein 1; D000099162:Endothelial PAS Domain-Containing Protein 1; C000602982:PLIN2 protein, human