CEFYBO 02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
artículos
Título:
Activation of nuclear receptor PPARalpha regulates lipid metabolism in foetal liver from diabetic rts: implications in diabetes-induced foetal overgrowth.
Autor/es:
MARTINEZ NORA; WHITE VERÓNICA; KURTZ MELISA; HIGA ROMINA; CAPOBIANCO EVANGELINA; JAWERBAUM ALICIA
Revista:
DIABETES/METABOLISM RESEARCH AND REVIEWS.
Editorial:
JOHN WILEY & SONS LTD
Referencias:
Año: 2011 vol. 27 p. 35 - 46
ISSN:
1520-7552
Resumen:
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 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 (TLC and densitometry), de novo lipid synthesis, and lipid peroxidation (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 PPARalpha ligands reduced the concentrations and synthesis of the lipid species studied and reduced lipid peroxidation in the fetal liver from diabetic rats. In vivo experiments showed that LTB4 reduced the concentrations of triglycerides, cholesteryl esters and phospholipids, lipid peroxidation and weight in fetal livers from diabetic rats, and also reduced overall fetal weight. Conclusions PPARalpha activation regulates the impaired fetal liver lipid metabolism, prevents hepatomegaly and reduces fetal overgrowth induced by maternal diabetes.
