Age‐Related Changes in Fatty Acids in Obese Offspring of Streptozotocin‐Induced Diabetic Rats

Abstract

MERZOUK, HAFIDA, SIHEM MADANI, AZIZ HICHAMI, JOSIANE PROST, JACQUES BELLEVILLE, AND NAIM A. KHAN. Age-related changes in fatty acids in obese offspring of streptozotocin-induced diabetic rats. Obes Res. 2002;10:703-714. Objective: 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. Research Methods and Procedures: 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. Results: 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. Discussion: Fetal obesity, associated with alterations in VLDL lipid fatty acid composition, represents an important risk factor for adult obesity and diabetes.

N-3 Fatty acids modulate antioxidant status in diabetic rats and their macrosomic offspring

“…42,43 Maternal diabetes mellitus also induced hypercholesterolemia and hypertriglyceridemia in obese offspring, and this observation corroborated our previous studies. 22,24,39 In the present study, we observed a high level of cholesterol in the offspring of the control group at day 60; however, this level remained significantly lower than that of macrosomic offspring. In fact, a significant age-related change in serum cholesterol concentration has been evoked, 44 and this can be explained by the existence of a compensatory mechanism for maintenance of hepatic cholesterol homeostasis with age.…”

“…22 Feeding the n-3 PUFA diet significantly reduced the incidence of gestational diabetes on macrosomia by decreasing the rate of macrosomic pups at birth from 64 to 48%. However, n-3 PUFA diet had no effect on hyperglycemia of macrosomic offspring.…”

“…The protocol of selection of macrosomic offspring has been well described elsewhere. 22 A total of 125 pups from the 15 streptozotocintreated dams and 91 pups from the 10 control dams were delivered at day 21. Pups, from the streptozotocin-treated dams, whose birth weights were 1.7 s.d.…”

Modulations physiologiques et immunologiques du diabète gestationnel et de la macrosomie : implication de la programmation in utero

“…La surproduction de VLDL, une caractéristique commune à l'obésité humaine et aux différentes obésités expérimentales, a été une conséquence directe de l'hyperinsulinémie et de l'hyperlipogenèse hépatique (Bioletto et al, 2000). La première observation importante apparente à l'âge de 3 mois, c'est-à-dire à l'âge adulte, est que ces rats avaient pris progressivement du poids et leur gain pondéral a été significativement plus élevé que celui des rats contrôles (Merzouk et al, 2002). En outre, ils ont été hyperglycémiques et hyperinsulinémiques, avec des concentrations élevées en lipide et lipoprotéine.…”

“…En fait, cette programmation in utero semble créer une sorte de ''mémoire métabolique'' puisque les anomalies observées dans le système physiologique pendant la période gestationnelle sont responsables, à l'âge adulte, de ''l'apparition'' de maladies comme le diabète de type 2 et l'obésité, associées au syndrome métabolique. Il existe, chez la mère et le foetus âgé de 6 mois, une bonne corrélation entre les taux plasmatiques en cholestérol et, certaines altérations telles que les taux élevés de triacylglycérol (TAG), apoB100, VLDL, LDL ont souvent persisté chez les nouveau-nés macrosomiques après un mois de vie (Merzouk et al, 2002). Nous avons montré, chez les rats macrosomiques nés de mères GDM, que la plupart des paramètres lipidiques se sont normalisés vers l'âge de 2 mois et ont réapparu à l'âge adulte.…”