Fatty Acid Uptake and Lipid Storage Induced by HIF-1α Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation
Summary: An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both of which are involved in fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1α (H...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714007323 |
| _version_ | 1818336745309077504 |
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| author | Karim Bensaad Elena Favaro Caroline A. Lewis Barrie Peck Simon Lord Jennifer M. Collins Katherine E. Pinnick Simon Wigfield Francesca M. Buffa Ji-Liang Li Qifeng Zhang Michael J.O. Wakelam Fredrik Karpe Almut Schulze Adrian L. Harris |
| author_facet | Karim Bensaad Elena Favaro Caroline A. Lewis Barrie Peck Simon Lord Jennifer M. Collins Katherine E. Pinnick Simon Wigfield Francesca M. Buffa Ji-Liang Li Qifeng Zhang Michael J.O. Wakelam Fredrik Karpe Almut Schulze Adrian L. Harris |
| author_sort | Karim Bensaad |
| collection | DOAJ |
| description | Summary: An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both of which are involved in fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. There was a significant lipid droplet (LD) accumulation in hypoxia that was time and O2 concentration dependent. Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component) significantly impaired LD formation under hypoxia. We showed that LD accumulation is due to FABP3/7-dependent fatty acid uptake while de novo fatty acid synthesis is repressed in hypoxia. We also showed that ATP production occurs via β-oxidation or glycogen degradation in a cell-type-dependent manner in hypoxia-reoxygenation. Finally, inhibition of lipid storage reduced protection against reactive oxygen species toxicity, decreased the survival of cells subjected to hypoxia-reoxygenation in vitro, and strongly impaired tumorigenesis in vivo. : Bensaad et al. now show that FABP3 and FABP7 are induced by HIF-1α and lead to a significant lipid droplet (LD) accumulation in hypoxia. In hypoxia-reoxygenation, ATP production occurs via fatty acid β-oxidation or glycogen degradation in a cell-type-dependent manner, while inhibition of LD formation increases ROS toxicity and decreases cell survival in vitro and strongly impairs tumorigenesis in vivo. |
| first_indexed | 2024-12-13T14:44:12Z |
| format | Article |
| id | doaj.art-e1e264078b5c49b6b6c2525e5f12d70f |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T14:44:12Z |
| publishDate | 2014-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-e1e264078b5c49b6b6c2525e5f12d70f2022-12-21T23:41:32ZengElsevierCell Reports2211-12472014-10-0191349365Fatty Acid Uptake and Lipid Storage Induced by HIF-1α Contribute to Cell Growth and Survival after Hypoxia-ReoxygenationKarim Bensaad0Elena Favaro1Caroline A. Lewis2Barrie Peck3Simon Lord4Jennifer M. Collins5Katherine E. Pinnick6Simon Wigfield7Francesca M. Buffa8Ji-Liang Li9Qifeng Zhang10Michael J.O. Wakelam11Fredrik Karpe12Almut Schulze13Adrian L. Harris14CRUK Hypoxia and Angiogenesis Group, The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK; Corresponding authorCRUK Hypoxia and Angiogenesis Group, The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UKGene Expression Analysis Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UKGene Expression Analysis Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UKCRUK Hypoxia and Angiogenesis Group, The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UKOxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UKOxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UKCRUK Hypoxia and Angiogenesis Group, The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UKCRUK Hypoxia and Angiogenesis Group, The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UKCRUK Hypoxia and Angiogenesis Group, The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UKThe Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UKThe Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UKOxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK; NIHR Oxford Biomedical Research Centre, OUH Trust, Churchill Hospital, Oxford OX3 7LF, UKGene Expression Analysis Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK; Department of Biochemistry and Molecular Biology, Theodor Boveri Institute, Biocenter, Am Hubland, 97074 Würzburg, GermanyCRUK Hypoxia and Angiogenesis Group, The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UKSummary: An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both of which are involved in fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. There was a significant lipid droplet (LD) accumulation in hypoxia that was time and O2 concentration dependent. Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component) significantly impaired LD formation under hypoxia. We showed that LD accumulation is due to FABP3/7-dependent fatty acid uptake while de novo fatty acid synthesis is repressed in hypoxia. We also showed that ATP production occurs via β-oxidation or glycogen degradation in a cell-type-dependent manner in hypoxia-reoxygenation. Finally, inhibition of lipid storage reduced protection against reactive oxygen species toxicity, decreased the survival of cells subjected to hypoxia-reoxygenation in vitro, and strongly impaired tumorigenesis in vivo. : Bensaad et al. now show that FABP3 and FABP7 are induced by HIF-1α and lead to a significant lipid droplet (LD) accumulation in hypoxia. In hypoxia-reoxygenation, ATP production occurs via fatty acid β-oxidation or glycogen degradation in a cell-type-dependent manner, while inhibition of LD formation increases ROS toxicity and decreases cell survival in vitro and strongly impairs tumorigenesis in vivo.http://www.sciencedirect.com/science/article/pii/S2211124714007323 |
| spellingShingle | Karim Bensaad Elena Favaro Caroline A. Lewis Barrie Peck Simon Lord Jennifer M. Collins Katherine E. Pinnick Simon Wigfield Francesca M. Buffa Ji-Liang Li Qifeng Zhang Michael J.O. Wakelam Fredrik Karpe Almut Schulze Adrian L. Harris Fatty Acid Uptake and Lipid Storage Induced by HIF-1α Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation Cell Reports |
| title | Fatty Acid Uptake and Lipid Storage Induced by HIF-1α Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation |
| title_full | Fatty Acid Uptake and Lipid Storage Induced by HIF-1α Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation |
| title_fullStr | Fatty Acid Uptake and Lipid Storage Induced by HIF-1α Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation |
| title_full_unstemmed | Fatty Acid Uptake and Lipid Storage Induced by HIF-1α Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation |
| title_short | Fatty Acid Uptake and Lipid Storage Induced by HIF-1α Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation |
| title_sort | fatty acid uptake and lipid storage induced by hif 1α contribute to cell growth and survival after hypoxia reoxygenation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714007323 |
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