Polyunsaturated fatty acid elongation and desaturation in activated human T-cells: ELOVL5 is the key elongase

J Lipid Res. 2018 Dec;59(12):2383-2396. doi: 10.1194/jlr.M090050. Epub 2018 Oct 6.

Abstract

PUFAs are important constituents of membrane glycerophospholipids. However, changes in the capacities to incorporate and metabolize PUFAs when cells enter the cell cycle have not been thoroughly studied. In this study, differences in the incorporation and metabolism of exogenous PUFAs in resting and proliferating primary human T-cells and in the Jurkat cell line were measured. Overall, proliferating T-cells and Jurkat cells had a greater capacity to incorporate and elongate exogenous 18- and 20-carbon PUFAs compared with resting T-cells. Proliferating T-cells and Jurkat cells also showed a greater capacity to desaturate 18-carbon PUFA substrates. Consistent with these observations, a significant increase in the expression of fatty acid desaturase (FADS) 1, FADS2, and elongation of very long chain fatty acids protein (ELOVL) 5 was measured in proliferating T-cells compared with resting T-cells. No quantifiable ELOVL2 was measured. Knockdown of ELOVL5 in T-cells and Jurkat cells significantly affected cellular monounsaturated and PUFA profiles and strongly impaired the elongation of 18- and 20-carbon PUFAs. In conclusion, the induction of proliferation in human T-cells is associated with a significant increase in the capacity to take up and metabolize exogenous PUFAs, and ELOVL5 is responsible for the elongation of 18- and 20-carbon PUFAs in these cells.

Keywords: arachidonic acid; desaturases; elongation of very long chain fatty acids protein 5; lipids; metabolism; ω-3.

MeSH terms

  • Acetyltransferases / metabolism*
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Arachidonic Acid / metabolism
  • Blotting, Western
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Fatty Acid Elongases
  • Fatty Acids, Unsaturated / metabolism*
  • Female
  • Humans
  • Jurkat Cells / metabolism*
  • Male
  • T-Lymphocytes / metabolism*

Substances

  • ELOVL2 protein, human
  • ELOVL5 protein, human
  • Fatty Acids, Unsaturated
  • Arachidonic Acid
  • Acetyltransferases
  • Fatty Acid Elongases