Ablation of fatty acid desaturase 2 (FADS2) exacerbates hepatic triacylglycerol and cholesterol accumulation in polyunsaturated fatty acid-depleted mice

FEBS Lett. 2021 Jul;595(14):1920-1932. doi: 10.1002/1873-3468.14134. Epub 2021 Jun 1.

Abstract

Deficiency of polyunsaturated fatty acids (PUFAs) is known to induce hepatic steatosis. However, it is not clearly understood which type of PUFA is responsible for the worsening of steatosis. This study observed a marked accumulation of hepatic triacylglycerol and cholesterol in fatty acid desaturase 2 knockout (FADS2-/- ) mice lacking both C18 and ≥ C20 PUFAs that were fed a PUFA-depleted diet. Hepatic triacylglycerol accumulation was associated with enhanced sterol regulatory element-binding protein (SREBP)-1-dependent lipogenesis and decreased triacylglycerol secretion into the plasma via very-low-density lipoprotein (VLDL). Furthermore, upregulation of cholesterol synthesis contributed to increased hepatic cholesterol content in FADS2-/- mice. These results suggest that ≥ C20 PUFAs synthesized by FADS2 are important in regulating hepatic triacylglycerol and cholesterol accumulation during PUFA deficiency.

Keywords: cholesterol; fatty acid desaturase; hepatic steatosis; highly unsaturated fatty acids; lipogenesis; polyunsaturated fatty acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism
  • Cholesterol / biosynthesis*
  • Diet / adverse effects
  • Disease Models, Animal
  • Fatty Acid Desaturases / deficiency
  • Fatty Acid Desaturases / genetics*
  • Fatty Acid Synthase, Type I / genetics
  • Fatty Acid Synthase, Type I / metabolism
  • Fatty Acids, Unsaturated / deficiency*
  • Fatty Liver / enzymology
  • Fatty Liver / etiology
  • Fatty Liver / genetics*
  • Fatty Liver / pathology
  • Gene Expression
  • Gene Expression Profiling
  • Lipogenesis / genetics
  • Lipoproteins, VLDL / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Stearoyl-CoA Desaturase / genetics
  • Stearoyl-CoA Desaturase / metabolism
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Triglycerides / biosynthesis*

Substances

  • Fatty Acids, Unsaturated
  • Insig1 protein, mouse
  • Lipoproteins, VLDL
  • Membrane Proteins
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • Cholesterol
  • Fatty Acid Desaturases
  • Scd1 protein, mouse
  • Stearoyl-CoA Desaturase
  • FADS2 protein, mouse
  • CPT1B protein, mouse
  • Carnitine O-Palmitoyltransferase
  • Fasn protein, mouse
  • Fatty Acid Synthase, Type I