Gender-dependent regulation of lipid metabolizing enzymes in the fetal heart from control and diabetic rats

KURTZ M; WHITE V; HIGA R; MARTÍNEZ N; JAWERBAUM A

Santiago de Chile

Congreso; International Federation of Placental Associations IFPA Meeting 2010; 2010

IFPA

Introduction: In maternal diabetes, the fetal heart is exposed to the increased lipids transferred though the placenta.  PPARa regulates the expression of several enzymes of lipid metabolism such as acylCoA oxidase (ACO) and  carnitine palmtyltransferase-1 (CPT1-1), respective rate limiting enzymes in peroxisomal and mitochondrial fatty acid b-oxidation.  Objective: To evaluate lipid concentrations and PPARa, ACO and CPT-1 expression in the fetal heart from control and diabetic rats on day 21 of pregnancy, and to analyze whether PPARá activation regulates PPARa, ACO and CPT-1 expression in hearts from female and male fetuses from control and diabetic rats. Methods: Diabetes was induced by streptozotocin administration. On day 21 of gestation, fetal hearts were explanted and lipids concentrations (TLC and densitometry) and PPARa, ACO and CPT-1 expression (RT-PCR) were analyzed. Fetuses from control and diabetic rats were injected through the uterine wall with the PPARá agonist leukotriene B4 (LTB4, 0.1ìM) on days 19, 20, and 21 of gestation. On day 21 of gestation, fetal heart expression of PPARa, ACO and CPT-1 were evaluated.  Results: Male and female fetal hearts from diabetic rats showed increased concentrations of triglycerides (p<0.001), cholesterol (p<0.05) and phospholipids (p<0.05) and no changes in cholesteryl ester concentrations. PPARa (p<0.01), ACO (p<0.05) and CPT-1 expression (p<0.001) were reduced in male fetal hearts, while only CPT-1 (p<0.05) was reduced in female fetal hearts. In diabetic animals, fetal treatment with LTB4 increased PPARa in male and female fetal hearts (p<0.05), increased ACO in male and female fetal hearts (p<0.01) and increased CPT-1 only in male fetal hearts (p<0.01). Conclusions: Overaccumulation of lipids in the fetal heart is probably related with reductions in the expression of the studied transcription factor and enzymes that regulate lipid oxidation, expression that can be positively regulated by fetal administration of a natural PPARa agonist in a gender-dependent manner.