Activation of the nuclear receptor PPARalfa 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

Lugar: Londres; Año: 2011

1520-7552

BACKGROUND: peroxisome proliferator-activated receptor alpha (PPARalpha) is a crucial regulator of liver lipid metabolism. As maternal diabetes impairs foetal lipid metabolism and growth, we aimed to determine whether PPARalpha activation regulates lipid metabolism in the foetal liver from diabetic rats as well as foetal weight and foetal liver weight. METHODS: diabetes was induced by neonatal streptozotocin administration (90 mg/kg). For ex vivo studies, livers from 21-day-old foetuses from control and diabetic rats were explanted and incubated in the presence of PPARalpha agonists (clofibrate and leukotriene B 4 (LTB4) for further evaluation of lipid levels (by thin layer chromatography and densitometry), de novo lipid synthesis by (14) C-acetate incorporation) and lipid peroxidation (by thiobarbituric reactive substances evaluation). For in vivo studies, foetuses were injected through the uterine wall with leukotriene B4 on days 19, 20 and 21 of gestation. On day 21 of gestation, foetal liver concentrations of lipids and lipoperoxides were evaluated. RESULTS: foetuses from diabetic rats showed increased body 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 both the concentrations and synthesis of the lipid species studied and lipid peroxidation in the foetal liver from diabetic rats. In vivo experiments showed that leukotriene B4 reduced the concentrations of triglycerides, cholesteryl esters and phospholipids, as well as lipid peroxidation, foetal weight and foetal liver weight in diabetic rats. CONCLUSIONS: PPARalpha activation regulates the impaired foetal liver lipid metabolism, prevents hepatomegaly and reduces foetal overgrowth induced by maternal diabetes.