Peroxisome proliferator-activated receptor alpha activation regulates lipid metabolism in the feto-placental unit from diabetic rats.
Maternal diabetes promotes an overaccumulation of lipids in the feto-placental unit and impairs feto-placental development and growth. Here, we investigated the role played by the nuclear receptor peroxisome proliferator-activated receptor (PPAR)alpha in lipid metabolism in fetuses and placentas from control and neonatal streptozotocin-induced diabetic rats. Placentas and fetuses were studied on day 13.5 of gestation. The concentrations of PPARalpha (by Western blot) and its endogenous agonist leukotriene B(4) (LTB(4)) (by enzyme immunoassay) were analysed. Placental explants and fetuses were cultured with LTB(4) or clofibrate, and then lipid metabolism analysed (concentrations and synthesis from (14)C-acetate of triglycerides, phospholipids, cholesterol and cholesteryl esters; release of glycerol and free fatty acids (FFAs)). We found that maternal diabetes led to increases in placental concentrations of triglycerides and cholesteryl esters, and fetal concentrations of phospholipids. PPARalpha agonists downregulated fetal and placental lipid concentrations in control and diabetic rats. The synthesis of lipids was reduced in the diabetic placenta but increased in fetuses from diabetic animals. PPARalpha agonists reduced the synthesis of lipids in control placenta and in the fetuses from control and diabetic rats. Glycerol and FFA release was enhanced in the diabetic placenta and in control placenta cultured with PPARalpha agonists. Maternal diabetes led to reductions in fetal and placental LTB(4) concentrations and to increases in placental PPARalpha concentrations. Overall, these data support a novel role of PPARalpha as a regulator of lipid metabolism in the feto-placental unit, relevant in maternal diabetes where fetal and placental PPARalpha, LTB(4) and lipid concentrations are altered.
Martínez
N
N
Laboratory of Reproduction and Metabolism, CEFYBO-CONICET-UBA, School of Medicine, University of Buenos Aires, Paraguay 2155, Buenos Aires, Argentina.
Capobianco
E
E
White
V
V
Pustovrh
M C
MC
Higa
R
R
Jawerbaum
A
A
D000818:Animals; D016640:Diabetes, Gestational / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005990:Glycerol / Q000032:analysis; D007975:Leukotriene B4 / Q000032:analysis / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis / Q000096:biosynthesis; D047493:PPAR alpha / Q000032:analysis / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D005230:Fatty Acids, Nonesterified; D008055:Lipids; D047493:PPAR alpha; D007975:Leukotriene B4; D005990:Glycerol