Premium
Ablation of fatty acid desaturase 2 (FADS2) exacerbates hepatic triacylglycerol and cholesterol accumulation in polyunsaturated fatty acid‐depleted mice
Author(s) -
Hayashi Yuri,
LeeOkada HyeonCheol,
Nakamura Eri,
Tada Norihiro,
Yokomizo Takehiko,
Fujiwara Yoko,
Ichi Ikuyo
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14134
Subject(s) - fads2 , polyunsaturated fatty acid , lipogenesis , steatosis , medicine , endocrinology , cholesterol , chemistry , fatty acid , very low density lipoprotein , sterol regulatory element binding protein , sterol , biology , biochemistry , lipoprotein , lipid metabolism , docosahexaenoic acid
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.