Hypoxia Induces Dysregulation of Lipid Metabolism in HepG2 Cells via Activation of HIF-2α
Background: Hypoxia is a risk factor for non-alcoholic fatty liver diseases, leading to permanent imbalance of liver lipid homeostasis and steatohepatitis. The current study examined the effect of HIF-2α, an oxygen-sensitive heterodimeric transcription factor, on hypoxia-induced dysregulation of lip...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2014-10-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/366348 |
| _version_ | 1819168506512408576 |
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| author | Risheng Cao Xiaodan Zhao Shuo Li Haiyun Zhou Weixu Chen Lihua Ren Xiqiao Zhou Hongjie Zhang Ruihua Shi |
| author_facet | Risheng Cao Xiaodan Zhao Shuo Li Haiyun Zhou Weixu Chen Lihua Ren Xiqiao Zhou Hongjie Zhang Ruihua Shi |
| author_sort | Risheng Cao |
| collection | DOAJ |
| description | Background: Hypoxia is a risk factor for non-alcoholic fatty liver diseases, leading to permanent imbalance of liver lipid homeostasis and steatohepatitis. The current study examined the effect of HIF-2α, an oxygen-sensitive heterodimeric transcription factor, on hypoxia-induced dysregulation of lipid metabolism in HepG2 cells. Methods: Studies were conducted in C57BL/6 male mice and human HepG2 cells under hypoxic conditions, transfected with HIF-2α-targeted shRNA. The mRNA and protein expressions of key genes relevant to lipid metabolism were determined via RT-qPCR and western blot, respectively. Intracellular lipid accumulation was determined by Nile red, filipin staining and quantitative assay kits. Results: HIF-2α protein was quantified in both HepG2 cells and C57BL/6 mice under hypoxic conditions. Intracellular lipid accumulation and increased lipid levels induced by hypoxia were significantly reduced by silence of HIF-2α expression, associated with reversed expression of ABCA1 and ADRP, key genes in involved cholesterol excretion and fatty acid uptake respectively. However, HIF-2α had no effect on enzymatic activity and expression of key genes involved in fatty acid β-oxidation or cholesterol metabolism. Conclusion: Inhibition of HIF-2α protein reversed lipid metabolism dysregulation induced by acute hypoxia in HepG2 cells, which suggested that HIF-2α signaling may be relevant to oxygen-dependent lipid homeostasis in the liver. |
| first_indexed | 2024-12-22T19:04:41Z |
| format | Article |
| id | doaj.art-c8027754f71a40aab4c01dbeeea27075 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-22T19:04:41Z |
| publishDate | 2014-10-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-c8027754f71a40aab4c01dbeeea270752022-12-21T18:15:51ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782014-10-013451427144110.1159/000366348366348Hypoxia Induces Dysregulation of Lipid Metabolism in HepG2 Cells via Activation of HIF-2αRisheng CaoXiaodan ZhaoShuo LiHaiyun ZhouWeixu ChenLihua RenXiqiao ZhouHongjie ZhangRuihua ShiBackground: Hypoxia is a risk factor for non-alcoholic fatty liver diseases, leading to permanent imbalance of liver lipid homeostasis and steatohepatitis. The current study examined the effect of HIF-2α, an oxygen-sensitive heterodimeric transcription factor, on hypoxia-induced dysregulation of lipid metabolism in HepG2 cells. Methods: Studies were conducted in C57BL/6 male mice and human HepG2 cells under hypoxic conditions, transfected with HIF-2α-targeted shRNA. The mRNA and protein expressions of key genes relevant to lipid metabolism were determined via RT-qPCR and western blot, respectively. Intracellular lipid accumulation was determined by Nile red, filipin staining and quantitative assay kits. Results: HIF-2α protein was quantified in both HepG2 cells and C57BL/6 mice under hypoxic conditions. Intracellular lipid accumulation and increased lipid levels induced by hypoxia were significantly reduced by silence of HIF-2α expression, associated with reversed expression of ABCA1 and ADRP, key genes in involved cholesterol excretion and fatty acid uptake respectively. However, HIF-2α had no effect on enzymatic activity and expression of key genes involved in fatty acid β-oxidation or cholesterol metabolism. Conclusion: Inhibition of HIF-2α protein reversed lipid metabolism dysregulation induced by acute hypoxia in HepG2 cells, which suggested that HIF-2α signaling may be relevant to oxygen-dependent lipid homeostasis in the liver.http://www.karger.com/Article/FullText/366348HIF-2αHepG2Fatty acid metabolismCholesterol metabolism |
| spellingShingle | Risheng Cao Xiaodan Zhao Shuo Li Haiyun Zhou Weixu Chen Lihua Ren Xiqiao Zhou Hongjie Zhang Ruihua Shi Hypoxia Induces Dysregulation of Lipid Metabolism in HepG2 Cells via Activation of HIF-2α Cellular Physiology and Biochemistry HIF-2α HepG2 Fatty acid metabolism Cholesterol metabolism |
| title | Hypoxia Induces Dysregulation of Lipid Metabolism in HepG2 Cells via Activation of HIF-2α |
| title_full | Hypoxia Induces Dysregulation of Lipid Metabolism in HepG2 Cells via Activation of HIF-2α |
| title_fullStr | Hypoxia Induces Dysregulation of Lipid Metabolism in HepG2 Cells via Activation of HIF-2α |
| title_full_unstemmed | Hypoxia Induces Dysregulation of Lipid Metabolism in HepG2 Cells via Activation of HIF-2α |
| title_short | Hypoxia Induces Dysregulation of Lipid Metabolism in HepG2 Cells via Activation of HIF-2α |
| title_sort | hypoxia induces dysregulation of lipid metabolism in hepg2 cells via activation of hif 2α |
| topic | HIF-2α HepG2 Fatty acid metabolism Cholesterol metabolism |
| url | http://www.karger.com/Article/FullText/366348 |
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