FADS2 inhibition in essential fatty acid deficiency induces hepatic lipid accumulation via impairment of very low-density lipoprotein (VLDL) secretion

Biochem Biophys Res Commun. 2018 Feb 5;496(2):549-555. doi: 10.1016/j.bbrc.2018.01.064. Epub 2018 Jan 17.

Abstract

Fatty acid desaturase 2 (FADS2) is responsible for the first desaturation reaction in the synthesis of highly unsaturated fatty acids (HUFAs), such as arachidonic acid (20:4n-6) and eicosapentaenoic acid (20:5n-3), and is involved in Mead acid (20:3n-9) production during essential fatty acid deficiency (EFAD). In this study, an obvious hepatic lipid accumulation was observed in EFAD mice treated with a FADS2 inhibitor. FADS2 inhibition in the EFAD state reduced secretion of very low-density lipoprotein (VLDL) and markedly diminished Mead acid in phosphatidylcholine (PC) in the liver and plasma. As the results, the amount of C20 HUFAs in hepatic and plasma PC dramatically reduced in the EFAD mice treated with a FADS2 inhibitor, whereas the decrease of C20 HUFA levels of PC in EFAD mice was not observed because of the increased Mead acid in PC. These results supposed that Mead acid in PC is important as a component of VLDL. It is possible that Mead acid plays the role of a substitute of HUFAs in VLDL secretion during EFAD.

Keywords: Essential fatty acid; Fatty liver; Mead acid; Phosphatidylcholine; Unsaturated fatty acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8,11,14-Eicosatrienoic Acid / analogs & derivatives
  • 8,11,14-Eicosatrienoic Acid / metabolism
  • Animals
  • Fatty Acid Desaturases / antagonists & inhibitors
  • Fatty Acid Desaturases / metabolism*
  • Fatty Acids, Unsaturated / metabolism*
  • Fatty Liver / metabolism
  • Lipid Metabolism
  • Lipoproteins, VLDL / metabolism*
  • Liver / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Oxidation-Reduction
  • Phosphatidylcholines / metabolism

Substances

  • Fatty Acids, Unsaturated
  • Lipoproteins, VLDL
  • Phosphatidylcholines
  • Fatty Acid Desaturases
  • FADS2 protein, mouse
  • 8,11,14-Eicosatrienoic Acid
  • mead acid