Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
Department of Biochemistry, Juntendo University Graduate School of Medicine, Tokyo, Japan.
FEBS Lett. 2021 Jul;595(14):1920-1932. doi: 10.1002/1873-3468.14134. Epub 2021 Jun 1.
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.
多不饱和脂肪酸 (PUFA) 的缺乏已知会导致肝脂肪变性。然而，哪种类型的 PUFAs 会导致脂肪变性恶化尚不清楚。本研究观察到，在缺乏 C18 和 ≥C20 PUFAs 的脂肪酸去饱和酶 2 敲除 (FADS2) 小鼠中，当给予富含 PUFAs 的饮食时，肝脏三酰基甘油和胆固醇明显积聚。肝三酰基甘油的积聚与固醇调节元件结合蛋白 (SREBP)-1 依赖性脂肪生成增强和通过极低密度脂蛋白 (VLDL) 向血浆中的三酰基甘油分泌减少有关。此外，胆固醇合成的上调导致 FADS2 小鼠肝脏胆固醇含量增加。这些结果表明，FADS2 合成的 ≥C20 PUFAs 在富含 PUFAs 的饮食缺乏时对调节肝脏三酰基甘油和胆固醇的积累很重要。
