Abstract
The aim of this study was to determine the impact of diabetic macrosomia on cholesterol and lipoprotein metabolism. Age-related changes in the activities of serum LCAT, hepatic HMG-CoA reductase, cholesterol 7α-hydroxylase, and ACAT, the major enzymes involved in cholesterol metabolism, were determined in macrosomic offspring of streptozotocin-induced diabetic rats. Hepatic, serum, and lipoprotein cholesterol contents were also examined. Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, macrosomic pups had higher serum, LDL-HDL1, and HDL2-3 cholesterol levels (P < 0.05) associated with increased LCAT activity (+57%) compared with control values. At 1 and 2 months of life, serum and lipoprotein cholesterol concentrations in macrosomic rats were similar to those of controls, whereas LCAT activity remained elevated about 1.5-fold. In addition, there was no change in hepatic cholesterol contents but hepatic HMG-CoA reductase, cholesterol 7α-hydroxylase, and ACAT activities were higher in both macrosomic males and females than in their respective controls (P < 0.01). By 3 months, macrosomic rats had developed hypercholesterolemia with a rise in all lipoproteins. Enzyme activities were still increased in these mature macrosomic rats, and hepatic cholesteryl esters were higher only in macrosomic females.These data demonstrate an overproduction, combined with overutilization, of cholesterol during the phase of rapid growth in macrosomic rats. However, cholesterol oversynthesis exceeded its removal and was a major contributor to hypercholesterolemia in adult macrosomic rats. In conclusion, macrosomia was associated with alterations in cholesterol metabolism through adulthood.—Merzouk, H., S. Madani, A. Boualga, J. Prost, M. Bouchenak, and J. Belleville. Age-related changes in cholesterol metabolism in macrosomic offspring of rats with streptozotocin-induced diabetes. J. Lipid Res. 2001. 42: 1152–1159.
Highlights
The aim of this study was to determine the impact of diabetic macrosomia on cholesterol and lipoprotein metabolism
Serum cholesterol levels increased with age in both control and macrosomic rats (Table 1)
All serum lipid levels were higher in macrosomic than in control newborns. These data show that fat synthesis was increased in the hyperinsulinemic fetus, and are in agreement with earlier reports [3, 5, 26]
Summary
The aim of this study was to determine the impact of diabetic macrosomia on cholesterol and lipoprotein metabolism. Age-related changes in the activities of serum LCAT, hepatic HMG-CoA reductase, cholesterol 7␣-hydroxylase, and ACAT, the major enzymes involved in cholesterol metabolism, were determined in macrosomic offspring of streptozotocin-induced diabetic rats. At 1 and 2 months of life, serum and lipoprotein cholesterol concentrations in macrosomic rats were similar to those of controls, whereas LCAT activity remained elevated about 1.5-fold. We produced a situation in which the fetal environment simulated that of a fetus in a poorly controlled human diabetic mother, which resulted in accelerated fetal growth in conjunction with fetal hyperinsulinemia These macrosomic rats maintained accelerated postnatal growth combined with high adipose tissue weight up to 12 weeks of age [7]. At 3 months of age, compared with controls, macrosomic rats had increased serum cholesterol levels associated with high hepatic cholesterol contents in females [7]. Several alterations in carbohydrate and lipid metabolism are observed in these macrosomic infants and
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
