Age-related changes in cholesterol metabolism in macrosomic offspring of rats with streptozotocin-induced diabetes

The aim of this study was to determine the impact of diabetic macrosomia on cholesterol and lipoprotein metabolism. Age-related changes in the activit ies of serum LCAT, hepatic HMG-CoA reductase, cholesterol 7 alpha -hydroxyl ase, and ACAT, the major enzymes involved in cholesterol metabolism, were d etermined in macrosomic offspring of streptozotocin-induced diabetic rats. Hepatic, serum, and lipoprotein cholesterol contents were also examined. Mi ld hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) on day 5 of gestation, Control pre gnant rats were injected with citrate buffer. At birth, macrosomic pups had higher serum, LDLHDL1, and HDL2-3 cholesterol levels (P < 0.05) associated with increased LCAT activity (+ 57%) compared with control values. At 1 an d 2 months of life, serum and lipoprotein cholesterol concentrations in mac rosomic rats were similar to those of controls, whereas LCAT activity remai ned elevated about 1.5-fold. In addition, there was no change in hepatic ch olesterol contents but hepatic HMG-CoA reductase, cholesterol 7 alpha -hydr oxylase, and ACAT activities were higher in both macrosomic males and femal es than in their respective controls (P < 0.01). By 3 months, macrosomic ra ts had developed hypercholesterolemia with a rise in all lipoproteins, Enzy me activities were still increased in these mature macrosomic rats, and hep atic cholesteryl esters were higher only in macrosomic females.jlr These da ta demonstrate an overproduction combined with overutilization, of choleste rol during the phase of rapid growth in macrosomic rats. However, cholester ol oversynthesis exceeded its removal and was a major contributor to hyperc holesterolemia in adult macrosomic rats, In conclusion, macrosomia was asso ciated with alterations in cholesterol metabolism through adulthood.