Hypoxia-induced alterations of lipid metabolism in the normal human hepatic L02 cell line / 中华肝脏病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of hypoxia on lipid metabolism in the normal human hepatic cell line L02 and to investigate the underlying molecular mechanisms.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Exposure to hypoxic conditions might induce lipidosis in normal human hepatic cells by stimulating HIF-2a and ADRP expression.</p>