Triglycerides Promote Lipid Homeostasis During Hypoxic Stress by Balancing Fatty Acid Saturation

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2018 Sep 6

PMID 30184495

Citations 136

Authors

Daniel Ackerman

Sergey Tumanov

Bo Qiu

Evdokia Michalopoulou

Michelle Spata

Andrew Azzam

Hong Xie

M Celeste Simon

Jurre J Kamphorst

Affiliations

Soon will be listed here.

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.

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