Intrauterine programming of metabolic and heart alterations in a diabetic rat model.

CAPOBIANCO E, PELESSON M, KURTZ M, MAZZUCCO MB, JAWERBAUM A.

St Julians

Congreso; 45th Annual Meeting, Diabetes and Pregnancy Study Group (DPSG), EASD.; 2013

DPSG

Maternal diabetes can program metabolic diseases and affect cardiovascular functions in the offspring, although whether this can be observed in mild experimental diabetic models is still unknown. The aim of this work was to evaluate whether a mild model of diabetes and pregnancy leads to intrauterine programming of metabolic diseases and affects lipid accumulation, lipoperoxidation and nitric oxide production in the fetal heart of adult offspring. Methods: Diabetes was induced by neonatal streptozotocin administration (90 mg/kg), leading to adult diabetic animals with fasting glycemia values between 130 and 230 mg/dl. Control and diabetic adult females were mated. In the offspring, glycemia, triglyceridemia and cholesterolemia were analysed at day 2, day 14, day 21 and 4 month of age. Concentrations of triglyceride, cholesterol, free fatty acids and phospholipids (by TLC), lipoperoxidation (by TBARS) and nitric oxide production (evaluation of nitrates/nitrites concentrations) were analysed in the heart of 4 month offspring. Results: We found that seric triglyceride concentrations were elevated in the offspring from diabetic rats on days 14 (males 117%, p lower than 0.05, females NS), 21 (males 70% and females 67%, p lower than 0.05) and 4 month of age (males 28% and females 19%, p lower than 0.05) when compared to controls, serum cholesterol was only increased in the offspring of diabetic rats on day 14 (males 16%, p lower than 0.05, females NS), and glycemia was increased in the offspring from diabetic rats only in offspring of 4 month of age (males 20% and females 23%, p lower than 0.05). When we analyzed the adult offspring from diabetic rats we found that in the females, the heart showed overaccumulation of free fatty acids (69%, p lower than 0.01) and phospholipids (36%, p lower than 0.05), whereas in the males, the heart showed overacummulation of triglycerides (52%, p lower than 0.05). Lipoperoxidation was increased (20%, p lower than 0.05) in the heart of both male and female offspring of diabetic rats when compared to controls. Also nitric oxide was overproduced in the heart of both male (39%, p lower than 0.01) and female (31%, p lower than 0.001) offspring of diabetic rats when related to controls. Conclusion: Maternal mild diabetes induces intrauterine programming of metabolic disease. In the offspring, lipid alterations precede glucose metabolic alterations. Even in mild maternal diabetes, the heart of the offspring was profoundly altered, showing metabolic alterations, as indicated by the overaccumulation of lipids, increased lipoperoxidation, a marker of oxidative stress, and nitric oxide overproduction, a marker of a pro-inflammatory environment.