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.

中文翻译：

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脂肪酸去饱和酶 2 (FADS2) 的消融会加剧多不饱和脂肪酸耗尽小鼠的肝脏三酰甘油和胆固醇积累

已知缺乏多不饱和脂肪酸 (PUFA) 会导致肝脂肪变性。然而，目前尚不清楚哪种类型的 PUFA 是导致脂肪变性恶化的原因。该研究观察到，在缺乏 C18 和≥ C20 PUFA 的脂肪酸去饱和酶 2 敲除 (FADS2 ^-/- ) 小鼠中，肝脏三酰基甘油和胆固醇显着积聚，而这些小鼠喂食了 PUFA 耗尽的饮食。肝三酰甘油积累与增强的甾醇调节元件结合蛋白 (SREBP)-1 依赖性脂肪生成和减少通过极低密度脂蛋白 (VLDL) 分泌到血浆中的三酰甘油有关。此外，胆固醇合成的上调导致 FADS2 ^{-/- 中}肝脏胆固醇含量的增加老鼠。这些结果表明 FADS2 合成的 ≥ C20 PUFAs 在调节 PUFA 缺乏期间肝脏三酰甘油和胆固醇积累方面很重要。