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 peroxisome proliferator-activated 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 (NO) production are altered in the fetal hearts of diabetic rats, and to analyze the putative effects of in vivo PPAR activation on these parameters. We found decreased PPARalpha expression in the hearts of male but not female fetuses of diabetic rats when compared with controls. Fetal treatments with the PPARalpha ligand leukotriene B4 upregulated the expression of PPARalpha and target genes involved in fatty acid oxidation in the fetal hearts. Increased concentrations of triglycerides, cholesterol, and phospholipids were found in the hearts of fetuses of diabetic rats. Maternal treatments with diets supplemented with6%oliveoil or6%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. NO production, which was increased in the hearts of male and female fetuses in the diabetic group, and lipoperoxidation, which was increased in the hearts 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 of diabetic rats and were regulated in a gender dependent manner by treatments enriched with PPAR ligands.