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

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 7 ␣ -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-HDL 1 , and HDL 2-3 cholesterol levels ( P Ͻ 0.05) associated with increased LCAT activity ( ϩ 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 7 ␣ -hydroxylase, and ACAT activities were higher in both macrosomic males and females than in their respective controls ( P Ͻ 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.

Altered Distribution of Unesterified Cholesterol among Lipoprotein Subfractions of Patients with Diabetes Mellitus Type 2

“…The enrichment of VLDL in free cholesterol may be caused by reduced ACAT activity in diabetes. However, the data from animal experiments are controversial and showed decreased [ 17 , 18 ], increased [ 19 , 20 , 21 ], or unchanged ACAT activity [ 18 , 22 ] in the liver of diabetic rats or rabbits compared to control animals.…”

Efeitos da leptina na ingestão alimentar de descendentes de ratas com alterações metabólicas e nutricionais

“…No entanto, os estudos experimentais divergem, com alguns obtendo um quadro semelhante aos estudos clínicos (Merzouk, H., 2000(Merzouk, H., , 2001Merzouk, Hafida, 2002), e outros nos quais não há aumento expressivo de recém-nascidos grandes para a idade de prenhez (Kervran et al, 1978;Kiss, 2012). Esses achados evidenciam a relevância do estudo de modelos experimentais de diabete no período gestacional, para conhecer os pontos de semelhança e divergência com os achados da clínica, além de possibilitar a melhor compreensão dos seus impactos sobre a prole e possíveis translações para a população humana.…”