PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats

KURTZ M, CAPOBIANCO E, MARTINEZ N, ROBERTI S, ARANY E, JAWERBAUM A

JOURNAL OF MOLECULAR ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2014 vol. 53 p. 237 - 246

0952-5041

In maternal diabetes, the fetal heart can be structurally and functionally affected. Maternal diets enriched in certain unsaturated fatty acids can activate the nuclear receptors PPARs and regulate metabolic and anti-inflammatory pathways during development. Our aim was to investigate whether PPARalpha expression, lipid metabolism, lipoperoxidation and nitric oxide production are altered in the fetal hearts of diabetic rats, and analyze putative effects of in vivo PPAR activation on these parameters. We found decreased PPARalpha expression in hearts of male but not female fetuses from diabetic rats when compared to controls. Fetal treatments with the PPARalpha ligand leukotriene B4 up-regulated the expression of PPARalpha and target genes involved in fatty acid oxidation in fetal hearts. Increased concentrations of triglycerides, cholesterol and phospholipids were found in the heart of fetuses from diabetic rats. Maternal treatments with diets supplemented with 6% olive oil or 6% safflower oil, enriched in unsaturated fatty acids that can activate PPARs, led to few changes in lipid concentrations, but up-regulated PPARalpha expression in fetal hearts. Nitric oxide production, which was increased in the heart of male and female fetuses in the diabetic group, and lipoperoxidation, which was increased in the heart of male fetuses in the diabetic group, was reduced by the maternal treatments supplemented with safflower oil. In conclusion, impaired PPARalpha expression, altered lipid metabolism and increased oxidative and nitridergic pathways were evidenced in hearts of fetuses from diabetic rats and were regulated in a gender-dependent manner by dietary treatments enriched in PPAR ligands.