Activation of the nuclear receptor PPARalpha regulates lipid metabolism in fetal liver from diabetic rats: Implications in diabetes-induced fetal overgrowth.

MARTÍNEZ NORA; WHITE VERÓNICA; KURTZ MELISA; HIGA ROMINA; CAPOBIANCO EVANGELINA; JAWERBAUM ALICIA

DIABETES/METABOLISM RESEARCH AND REVIEWS.

JOHN WILEY & SONS LTD

Año: 2010 p. 35 - 46

1520-7552

Background PPARalpha is a crucial regulator of liver lipid metabolism. As maternal diabetes impairs fetal lipid metabolism and growth, we aimed to determine whether PPARalpha activation regulates lipid metabolism in the fetal liver from diabetic rats as well as fetal overall and fetal liver weight.   Methods Diabetes was induced by neonatal streptozotocin administration (90 mg/kg). For ex vivo studies, livers from 21-day-old fetuses from control and diabetic rats were explanted and incubated in the presence of PPARa agonists (clofibrate and LTB4) for further evaluation of lipid levels (by TLC and densitometry), de novo lipid synthesis (by 14C-acetate incorporated), and lipid peroxidation (by TBARS). For in vivo studies, fetuses were injected through the uterine wall with LTB4 on days 19, 20, and 21 of gestation. On day 21 of gestation, fetal liver concentrations of lipids and lipoperoxides were evaluated.  Results Fetuses from diabetic rats showed increased weight and liver weight, as well as accumulation of triglycerides and cholesteryl esters, increased de novo lipid synthesis and lipid peroxidation in the liver when compared to controls. Ex vivo studies showed that PPARá ligands reduced the concentrations and synthesis of the lipid species studied and lipid peroxidation in the fetal liver from diabetic rats. In vivo experiments showed that LTB4 reduced the concentrations of triglycerides, cholesteryl esters and phospholipids, as well as lipid peroxidation, fetal weight and fetal liver weight in diabetic rats.   Conclusions PPARalpha activation regulates the impaired fetal liver lipid metabolism, prevents hepatomegaly and reduces fetal overgrowth induced by maternal diabetes.