Ozanne S E, Martensz N D, Petry C J, Loizou C L, Hales C N
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, UK.
Diabetologia. 1998 Nov;41(11):1337-42. doi: 10.1007/s001250051074.
Numerous studies show an association between poor fetal growth and adult insulin resistance. Recent studies have shown relation between the long chain polyunsaturated fatty acid composition of skeletal muscle membranes and insulin sensitivity. More detailed analysis has indicated that the activity of delta5 desaturase is inversely correlated to insulin resistance. The amount of docosahexaenoic acid (C22:6n3) is also thought to play a part in determining insulin sensitivity. The purpose of this study was to test the hypothesis that early growth retardation in the rat, as a result of maternal protein restriction, would lead to alterations in desaturase activities similar to those observed in human insulin resistance. There were no differences in phospholipid fatty acid composition in liver or muscle from control and low protein rats. In both muscle and liver the ratio of docosahexaenoic acid to docosapentaenoic acid was, however, reduced in low protein offspring. Direct measurement of delta5 desaturase activity in hepatic microsomes showed a reduction (p < 0.03) in the low protein offspring which was negatively correlated (r = -0.855) with fasting plasma insulin. No correlation was observed in controls. These results show that it is possible to programme the activity of key enzymes involved in the desaturation of long chain polyunsaturated fatty acids. This is possibly a mechanism linking fetal growth retardation to insulin resistance.
大量研究表明胎儿生长发育不良与成人胰岛素抵抗之间存在关联。近期研究显示骨骼肌细胞膜的长链多不饱和脂肪酸组成与胰岛素敏感性之间存在联系。更详细的分析表明,δ5去饱和酶的活性与胰岛素抵抗呈负相关。二十二碳六烯酸(C22:6n3)的含量也被认为在决定胰岛素敏感性方面发挥作用。本研究的目的是检验这样一个假设,即由于母体蛋白质限制导致的大鼠早期生长迟缓会导致去饱和酶活性发生改变,类似于在人类胰岛素抵抗中观察到的情况。对照大鼠和低蛋白大鼠的肝脏或肌肉中的磷脂脂肪酸组成没有差异。然而,在低蛋白后代中,肌肉和肝脏中二十二碳六烯酸与二十二碳五烯酸的比例均降低。对肝微粒体中δ5去饱和酶活性的直接测量显示,低蛋白后代中的该活性降低(p < 0.03),且与空腹血浆胰岛素呈负相关(r = -0.855)。在对照大鼠中未观察到相关性。这些结果表明,有可能对参与长链多不饱和脂肪酸去饱和作用的关键酶的活性进行编程。这可能是一种将胎儿生长迟缓与胰岛素抵抗联系起来的机制。