Age-related changes in fatty acids in obese offspring of streptozotocin-induced diabetic rats.

Abstract

The long-term effects of fetal hyperinsulinemia, time course of changes in liver and very-low-density lipoprotein (VLDL) lipid levels and fatty acid compositions were investigated in obese offspring of streptozotocin-induced mildly diabetic rats. Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin on day 5 of gestation. Control pregnant rats were injected with citrate buffer. Liver and VLDL lipids and fatty acids were analyzed in offspring at different ages. At birth, obese pups had higher VLDL triglyceride levels, saturated fatty acids, and C20:4n-6. They also had lower C18:2n-6 proportions in VLDL triglycerides, phospholipids, and cholesteryl esters than controls pups. In 1-month-old male and female obese rats, VLDL and liver lipid amounts were similar to those in their respective controls; however, high levels of C18:2n-6 and C20:4n-6 were noted in liver and VLDL lipids. At the age of 2 months, liver and VLDL triglyceride levels were higher in obese females than in control females. Fatty acid abnormalities seen in obese rats included low C18:3n-3 and high C22:6n-3 proportions in liver triglycerides and phospholipids. At the age of 3 months, obese rats, both males and females, compared with control animals, had higher VLDL and hepatic lipids with reduced C20:4n-6 levels and polyunsaturated/saturated fatty acids ratios in hepatic and VLDL triglycerides and phospholipids. Fetal obesity, associated with alterations in VLDL lipid fatty acid composition, represents an important risk factor for adult obesity and diabetes.