Liquid Chromatography-Mass Spectrometry Based Lipidomics to Identify Lipids that Play a Role in Fatostatin Treated MCF7 Cells
Sakallioglu, Isin Tuna
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Lipids are essential regulators of many cellular processes. Inhibiting cellular lipid metabolism of cancer cells would be a promising target to stop their proliferation. In this work, we used fatostatin, a recently synthesized anti-lipogenic compound that is proposed to block the growth of tumor tissues by inhibiting lipid synthesis. Fatostatin inhibits activation of endoplasmic reticulum (ER) residing sterol regulatory element binding protein (SREBP). Our results showed inactivation of SREBP on endoplasmic reticulum by fatostatin induces severe ER-stress and causes elevated lipid peroxidation. Liquid chromatography-mass spectrometry (LC-MS) based untargeted and targeted lipidomic approaches were used to identify lipid species that significantly changed during fatostatin treatment. The majority of these changes were the accumulation of triacylglycerols (TAG) containing polyunsaturated fatty acyl chains (PUFAs). The elevated mRNA expression levels and enzymatic activity of key enzymes involved in TAG biosynthesis showed that these could be responsible for the origin of the observed TAG accumulation. Upon the basis of these findings, we suggest that accumulation of PUFA-TAGs in lipid droplets could be linked to induced ER-stress and lipid peroxidation conditions.