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

FEBS Letters

article

Yuri Hayashi¹  Hyeon-Cheol Lee-Okada²  Eri Nakamura³  Norihiro Tada³  Takehiko Yokomizo²  Yoko Fujiwara⁴  Ikuyo Ichi⁴ 

[1] Graduate School of Humanities and Sciences, Ochanomizu University;Department of Biochemistry, Juntendo University Graduate School of Medicine;Laboratory of Genome Research, Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine;Institute for Human Life Innovation, Ochanomizu University;Natural Science Division, Faculty of Core Research, Ochanomizu University

关键词: cholesterol;    fatty acid desaturase;    hepatic steatosis;    highly unsaturated fatty acids;    lipogenesis;    polyunsaturated fatty acid;   

DOI  :  10.1002/1873-3468.14134

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown