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

KURTZ M; CAPOBIANCO E; MARTÍNEZ N,; ROBERTIS 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 PPARa expression, lipid metabolism, lipoperoxidation, andnitricoxide(NO) productionare alteredinthe fetal hearts of diabetic rats, and to analyze the putative effects of in vivo PPARactivation on these parameters. We found decreased PPARalfa expression in the hearts ofmale but not female fetuses of diabetic rats when compared with controls. Fetal treatments with the PPARalfa ligand leukotriene B4 upregulated the expression of PPARalfa 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,enrichedinunsaturatedfatty acids that canactivate PPARs, led to few changes in lipid concentrations, but up-regulated PPARalfa 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 ofmale fetuses in the diabetic group,was reduced by thematernal treatments supplementedwithsaffloweroil. In conclusion, impaired PPARalfa expression, altered lipid metabolism, and increased oxidative and nitridergic pathways were evidenced in hearts of fetuses of diabetic rats and were regulated in a genderdependent manner by treatments enriched with PPAR ligands.