Increased nitric oxide production and gender-dependent changes in PPARa

KURTZ MELISA; MARTINEZ NORA; CAPOBIANCO EVANGELINA; HIGA ROMINA; FORNES DAIANA; WHITE VERONICA; JAWERBAUM ALICIA

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2012 vol. 362 p. 120 - 127

0303-7207

The fetal lung is affected by maternal diabetes. Nuclear receptor PPARalpha regulates nitric oxide (NO) overproduction in different tissues. We aimed to determine whether fetal lung PPARalpha expression is altered by maternal diabetes, and if there are gender-dependent changes in PPARalpha regulation of NO production in the fetal lung. Fetal lungs from control and diabetic rats were explanted on day 21 of gestation and evaluated for PPARá expression and NO production. Fetuses were injected with the PPARalpha ligand LTB(4) on days 19, 20 and 21, and the fetal lung explanted on day 21 to evaluate PPARalpha and the inducible isoform of NO synthase (iNOS). Besides, pregnant rats were fed with olive oil- and safflower oil-supplemented diets, enriched in PPAR ligands, for evaluation of fetal lung NO production and PPARalpha expression. We found reduced PPARalpha concentrations only in the lung from male fetuses from the diabetic group when compared to controls, although maternal diabetes led to NO overproduction in both male and female fetal lungs. Fetal activation of PPARalpha led to changes in lung PPARalpha expression only in female fetuses, although this treatment increased iNOS expression in both male and female fetuses in the diabetic group. Diets supplemented with olive oil and not with safflower oil led to a reduction in NO production in male and female fetal lungs. In conclusion, there are gender-dependent changes in PPARalpha expression and signaling in the fetal lung from diabetic rats, although PPARalpha activation prevents maternal diabetes-induced lung NO overproduction in both male and female fetuses.