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Lipid metabolism alterations in U87 glioma cells deficient in very long‐chain acyl‐CoA synthetase 3 are associated with a less malignant phenotype
Author(s) -
Watkins Paul A.,
Pei Zhengtong,
Kolar Elizabeth A.,
Clay Emily M.,
Shi Xiaohai,
Laterra John
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.996.1
Subject(s) - glioma , lipid metabolism , gene knockdown , chemistry , metabolism , phenotype , cell culture , in vitro , in vivo , downregulation and upregulation , biochemistry , microbiology and biotechnology , biology , cancer research , apoptosis , gene , genetics
Expression of ACSVL3, an acyl‐CoA synthetase that activates long‐ to very long‐chain fatty acids (FA), is elevated in malignant gliomas and in glioma cells. Knocking down ACSVL3 expression in U87 glioma cells by RNA interference decreased their in vitro and in vivo malignant properties. To determine whether the beneficial effects of ACSVL3 depletion were mediated by changes in downstream lipid metabolism, we investigated the metabolic fate of FAs in control and ACSVL3 knockdown (KD) U87 cells. Beta‐oxidation of both C16:0 and C24:0 was decreased in KD cells. There was decreased incorporation of radiolabeled FAs (C16:0, C18:0, C18:1, C18:2n‐6, C20:4n‐6, C22:6n‐3) into phospholipids PI, PS, and PE, but not into PC. ACSVL3 KD had little effect on incorporation of several FAs into most neutral lipids. However, increased incorporation of C20:4n‐6 and C22:6n‐ 3 into triacylglycerol and cholesterol esters was seen in KD cells. ACSVL3 KD altered the total FA profile of U87 cells, and KD cells had decreased rates of de novo FA synthesis from acetate. Thus, depletion of ACSVL3 had multiple effects on U87 glioma cell lipid metabolism. Further study is needed to determine whether any of these changes are critical for switching these cells from a malignant to a more normal phenotype. Supported by NS062043.