Mašek Tomislav, Filipović Natalija, Hamzić Lejla Ferhatović, Puljak Livia, Starčević Kristina
Department of Animal Nutrition and Dietetics, University of Zagreb Faculty of Veterinary Medicine, Heinzelova 55, 10000 Zagreb, Croatia.
Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia.
Exp Gerontol. 2014 Dec;60:140-6. doi: 10.1016/j.exger.2014.10.015. Epub 2014 Oct 30.
We have investigated the long term effects of insulin dependent diabetes mellitus (IDDM) on the fatty acid profile of tissues in aging rats. For this purpose, a rat model for IDDM was established by streptozotocin application. The rats were randomly divided into four groups of 8 animals each: CON 6 (control group sacrificed after 6 months of the experiment), CON 12 (control group sacrificed after 12 months of the experiment), DM 6 (streptozotocin treated and sacrificed after 6 months of diabetes) and DM 12 (streptozotocin treated and sacrificed after 12 months of diabetes). The periods of 6 and 12 months were taken to observe the changes in lipid metabolism for chronic, long-term diabetes. Fatty acid profiles of the liver and skeletal muscle total lipids and phospholipids as well as desaturation indices for ∆6 desaturase (D6D), ∆5 desaturase (∆6D), ∆9 desaturase (∆9D) and de novo lipogenesis index (DNL) were estimated. Additionally the long-term effects (12 months) were tested in the brain, perirenal fat and bone marrow. The fatty acid composition of lipids was altered in IDDM rats in all tested tissues. The desaturation indices revealed the expected significant decrease in ∆9D and ∆5D indices in tested tissues, while indices for ∆6D were not influenced by diabetes. DNL revealed the strong inhibition of de novo lipogenesis in the liver tissue. Values for arachidonic C20:4n6 (arachidonic acid) significantly decreased in liver total lipids in DM 6 and DM 12 groups and in phospholipids in the DM 12 group. Surprisingly, values for C20:4n6 were also significantly lower in the brain tissue in the DM 12 group. Accumulation of C20:4n6 precursors (C18:2n6 and C20:3n6) was visible in all tissues. Docosahexaenoic acid (C22:6n3) significantly decreased in liver total lipids, liver phospholipids and in the brain phospholipids of the DM 12 group. The present results show that age could exacerbate the expected decrease in the liver synthesis of C20:4n6 in IDDM. Moreover, long-term diabetes could impair C22:6n3 synthesis in the liver and muscle, and incorporation of both important fatty acids into brain phospholipids. In conclusion, numerous changes in fatty acid composition are caused by long-term diabetes in aged rats. These changes could be involved in the pathogenesis of senile and diabetes-induced damage. The results could have clinical significance due to the increasing age of diabetic patients.
我们研究了胰岛素依赖型糖尿病（IDDM）对衰老大鼠组织脂肪酸谱的长期影响。为此，通过腹腔注射链脲佐菌素建立了IDDM大鼠模型。大鼠被随机分为四组，每组8只：CON 6（实验6个月后处死的对照组）、CON 12（实验12个月后处死的对照组）、DM 6（链脲佐菌素处理且糖尿病6个月后处死）和DM 12（链脲佐菌素处理且糖尿病12个月后处死）。选取6个月和12个月的时间段来观察慢性长期糖尿病脂质代谢的变化。测定了肝脏和骨骼肌总脂质及磷脂的脂肪酸谱，以及Δ6去饱和酶（D6D）、Δ5去饱和酶（Δ5D）、Δ9去饱和酶（Δ9D）的去饱和指数和从头脂肪生成指数（DNL）。此外，还在脑、肾周脂肪和骨髓中测试了长期（12个月）影响。在所有测试组织中，IDDM大鼠脂质的脂肪酸组成均发生了改变。去饱和指数显示，测试组织中Δ9D和Δ5D指数出现预期的显著下降，而Δ6D指数不受糖尿病影响。DNL显示肝脏组织中从头脂肪生成受到强烈抑制。在DM 6组和DM 12组的肝脏总脂质中以及DM 12组的磷脂中，花生四烯酸C20:4n6（花生四烯酸）的值显著降低。令人惊讶的是，在DM 12组的脑组织中，C20:4n6的值也显著较低。在所有组织中均可见C20:4n6前体（C18:2n6和C20:3n6）的积累。在DM 12组的肝脏总脂质、肝脏磷脂和脑磷脂中，二十二碳六烯酸（C22:6n3）显著降低。目前的结果表明，年龄可能会加剧IDDM患者肝脏中C20:4n6合成预期的下降。此外，长期糖尿病可能会损害肝脏和肌肉中C22:6n3的合成，以及这两种重要脂肪酸掺入脑磷脂的过程。总之，长期糖尿病会导致老年大鼠脂肪酸组成发生诸多变化。这些变化可能参与了衰老和糖尿病诱导损伤的发病机制。由于糖尿病患者年龄不断增加，这些结果可能具有临床意义。
