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Activation of the nuclear receptor PPARα regulates lipid metabolism in foetal liver from diabetic rats: implications in diabetes‐induced foetal overgrowth
Author(s) -
Martínez Nora,
White Verónica,
Kurtz Melisa,
Higa Romina,
Capobianco Evangelina,
Jawerbaum Alicia
Publication year - 2011
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1151
Subject(s) - endocrinology , medicine , lipid metabolism , lipid peroxidation , chemistry , ex vivo , fatty liver , biology , biochemistry , in vitro , oxidative stress , disease
Background Peroxisome proliferator‐activated receptor α (PPARα) is a crucial regulator of liver lipid metabolism. As maternal diabetes impairs foetal lipid metabolism and growth, we aimed to determine whether PPARα 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 PPARα agonists (clofibrate and leukotriene B 4 ) 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 B 4 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 PPARα 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 B 4 reduced the concentrations of triglycerides, cholesteryl esters and phospholipids, as well as lipid peroxidation, foetal weight and foetal liver weight in diabetic rats. Conclusions PPARα activation regulates the impaired foetal liver lipid metabolism, prevents hepatomegaly and reduces foetal overgrowth induced by maternal diabetes. Copyright © 2010 John Wiley & Sons, Ltd.