Long-term streptozotocin diabetes impairs arachidonic and docosahexaenoic acid metabolism and Δ5 desaturation indices in aged rats

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 Delta 6 desaturase (D6D), Delta 5 desaturase (Delta 6D), Delta 9 desaturase (Delta 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 Delta 9D and Delta 5D indices in tested tissues, while indices for Delta 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. (C) 2014 Elsevier Inc. All rights reserved.