Lefkowith J B
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Biochim Biophys Acta. 1990 May 1;1044(1):13-9. doi: 10.1016/0005-2760(90)90212-g.
Essential fatty acid (EFA) deficiency is an important tool in probing the role of arachidonic acid (20:4(n-6] in pathophysiologic processes, but requires stringent and prolonged deprivation of (n-6) fatty acids. The present study investigated whether induction of the delta 9 desaturase, which is responsible for the synthesis of oleate, the precursor of 20:3(n-9) which uniquely accumulates in the deficiency state, might serve to accelerate the biochemical and biological effects of EFA deficiency. By alternately fasting and feeding animals a fat-free diet, it was possible to induce markedly the delta 9 desaturase selectively in liver. This dietary manipulation in consequence led to dramatic and rapid changes in hepatic phospholipid fatty acid composition. Within 2 weeks, 20:3(n-9) to 20:4(n-6) ratios in liver phospholipids were several fold greater than those seen in animals fed a fat-free diet alone. These changes, however, contrasted with those seen in the serum and other tissues. The mol% of 20:3(n-9) in serum was not increased by delta 9 desaturase induction and the 20:3(n-9) to 20:4(n-6) ratio was only modestly increased. The effects of delta 9 desaturase induction were even more attenuated in tissues other than the liver. Desaturase induction led to a doubling in the 20:3(n-9) to 20:4(n-6) ratio in phosphatidylcholine in renal cortex and heart, although the ratio in the other phospholipids was unaffected. The 20:3(n-9) to 20:4(n-6) ratio in peritoneal macrophage phospholipids was unaffected by desaturase induction. Thus, delta 9 desaturase induction greatly augments the synthesis of (n-9) fatty acids within the liver and leads to the rapid and substantial accumulation of the abnormal fatty acid, 20:3(n-9). This markedly augmented synthesis of hepatic 20:3(n-9), however, is not reflected in increased plasma levels of 20:3(n-9), and thus the effects of delta 9 desaturase induction are attenuated in tissues other than the liver. These data underscore the notable ability of the liver to maintain polyunsaturated fatty acid homeostasis.
必需脂肪酸（EFA）缺乏是探究花生四烯酸（20:4(n-6)）在病理生理过程中作用的重要手段，但需要严格且长期剥夺（n-6）脂肪酸。本研究调查了负责合成油酸（20:3(n-9)的前体，在缺乏状态下会独特积累）的δ9去饱和酶的诱导是否可能加速EFA缺乏的生化和生物学效应。通过交替禁食和给动物喂食无脂饮食，能够在肝脏中显著且选择性地诱导δ9去饱和酶。这种饮食操作进而导致肝脏磷脂脂肪酸组成发生显著且快速的变化。在2周内，肝脏磷脂中20:3(n-9)与20:4(n-6)的比值比仅喂食无脂饮食的动物高出数倍。然而，这些变化与血清和其他组织中的变化形成对比。δ9去饱和酶诱导并未使血清中20:3(n-9)的摩尔百分比增加，且20:3(n-9)与20:4(n-6)的比值仅适度增加。在肝脏以外的组织中，δ9去饱和酶诱导的效应甚至更弱。去饱和酶诱导使肾皮质和心脏中磷脂酰胆碱的20:3(n-9)与20:4(n-6)比值翻倍，尽管其他磷脂中的比值未受影响。腹膜巨噬细胞磷脂中的20:3(n-9)与20:4(n-6)比值不受去饱和酶诱导的影响。因此，δ9去饱和酶诱导极大地增强了肝脏内（n-9）脂肪酸的合成，并导致异常脂肪酸20:3(n-9)快速大量积累。然而，肝脏中20:3(n-9)合成的显著增强并未反映在血浆中20:3(n-9)水平的升高上，因此δ9去饱和酶诱导的效应在肝脏以外的组织中减弱。这些数据强调了肝脏维持多不饱和脂肪酸稳态的显著能力。
