Ackerman, D., Tumanov, S., Qiu, B., Michalopoulou, E., Spata, M., Azzam, A., Xie, H., Simon, M. C. and Kamphorst, J. J. (2018) Triglycerides promote lipid homeostasis during hypoxic stress by balancing fatty acid saturation. Cell Reports, 24(10), 2596-2605.e5. (doi: 10.1016/j.celrep.2018.08.015) (PMID:30184495) (PMCID:PMC6137821)
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Abstract
Lipid droplets, which store triglycerides and cholesterol esters, are a prominent feature of clear cell renal cell carcinoma (ccRCC). Although their presence in ccRCC is critical for sustained tumorigenesis, their contribution to lipid homeostasis and tumor cell viability is incompletely understood. Here we show that disrupting triglyceride synthesis compromises the growth of both ccRCC tumors and ccRCC cells exposed to tumor-like conditions. Functionally, hypoxia leads to increased fatty acid saturation through inhibition of the oxygen-dependent stearoyl-CoA desaturase (SCD) enzyme. Triglycerides counter a toxic buildup of saturated lipids, primarily by releasing the unsaturated fatty acid oleate (the principal product of SCD activity) from lipid droplets into phospholipid pools. Disrupting this process derails lipid homeostasis, causing overproduction of toxic saturated ceramides and acyl-carnitines as well as activation of the NF-κB transcription factor. Our work demonstrates that triglycerides promote homeostasis by “buffering” specific fatty acids.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Kamphorst, Dr Jurre and Michalopoulou, Evdokia and Tumanov, Dr Sergey |
| Creator Roles: | Tumanov, S.Methodology, Investigation Michalopoulou, E.Methodology, Investigation Kamphorst, J. J.Conceptualization, Methodology, Writing – original draft, Writing – review and editing, Funding acquisition, Resources, Supervision |
| Authors: | Ackerman, D., Tumanov, S., Qiu, B., Michalopoulou, E., Spata, M., Azzam, A., Xie, H., Simon, M. C., and Kamphorst, J. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Cell Reports |
| Publisher: | Elsevier (Cell Press) |
| ISSN: | 2211-1247 |
| ISSN (Online): | 2211-1247 |
| Copyright Holders: | Copyright © 2018 The Authors |
| First Published: | First published in Cell Reports 24(10): 2596-2605.e5 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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