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

Yuri Hayashi; Hyeon-Cheol Lee-Okada; Eri Nakamura; Norihiro Tada; Takehiko Yokomizo; Yoko Fujiwara; Ikuyo Ichi

doi:10.1002/1873-3468.14134

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.

Authors

Yuri Hayashi¹, Hyeon-Cheol Lee-Okada², Eri Nakamura³, Norihiro Tada³, Takehiko Yokomizo², Yoko Fujiwara^{4

5}, Ikuyo Ichi^{4

5}

Affiliations

¹ Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
² Department of Biochemistry, Juntendo University Graduate School of Medicine, Tokyo, Japan.
³ Laboratory of Genome Research, Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan.
⁴ Institute for Human Life Innovation, Ochanomizu University, Tokyo, Japan.
⁵ Natural Science Division, Faculty of Core Research, Ochanomizu University, Tokyo, Japan.

PMID: 34008174
DOI: 10.1002/1873-3468.14134

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