RESUMO
Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect of in vivo activation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B4 (LTB4, PPARα ligand) or 15deoxyΔ(12,14)prostaglandin J2 (15dPGJ2, PPARγ ligand) and ii) fed during pregnancy with 6% olive oil- or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB4 and partially restored by 15dPGJ2 in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil- and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.
Assuntos
Diabetes Gestacional/metabolismo , Leucotrieno B4/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Pulmão/metabolismo , PPAR alfa/metabolismo , PPAR gama/metabolismo , Prostaglandina D2/análogos & derivados , Animais , Diabetes Gestacional/genética , Feminino , Feto/embriologia , Feto/metabolismo , Ligantes , Pulmão/química , Pulmão/embriologia , Masculino , Azeite de Oliva , PPAR alfa/genética , PPAR gama/genética , Óleos de Plantas/metabolismo , Gravidez , Prostaglandina D2/metabolismo , Ratos , Ratos Wistar , Óleo de Cártamo/metabolismoRESUMO
Correction of essential fatty acid deficiency by transcutaneous absorption of topically applied EFA-rich oil has been reported. We measured serum EFA levels in two groups of neonates receiving fat-free total parenteral nutrition: nine control patients after 16 and 25 days of TPN, and six patients before and 12 days after beginning cutaneous application of 100 mg/kg/day of linoleic acid as sunflower seed oil. Progressive biochemical EFA deficiency occurred in all but one of the control patients. Of the six patients receiving 100 mg/kg/day of linoleic acid, one patient with mild deficiency improved, but progressive EFA deficiency occurred in the other five patients. Serum EFA levels were also measured in four patients following 76 days of TPN and daily application of high doses of topical safflower oil, all of whom had severe biochemical EFA deficiency. The topical application of EFA-rich oil cannot be assumed to be uniformly effective in reversing or preventing EFA deficiency. The transcutaneous absorption of essential fatty acids must be documented by appropriate measurements of EFA in serum lipids.