Metabolic abnormalities in the fetal liver of rats with gestational diabetes induced by intrauterine programming

DAIANA FORNES, ROMINA HIGA, IVANA LINENBERG, EVANGELINA CAPOBIANCO, ALICIA JAWERBAUM

Mar del Plata

Congreso; VI SLIMP Latin American Symposium on Maternal Fetal Interaction and Placenta; 2015

SLIMP

Gestational diabetes (GDM) is a prevalent disease with adverse consequences to both mothers and offspring. We have recently described a new GDM model obtained through adverse intrauterine programming in the offspring of diabetic rats. This model allows analyzing the regulation of lipid metabolism in the fetal liver of GDM mothers. Peroxisome proliferator activated receptors (PPARs) are nuclear receptors involved in lipid metabolic pathways, being PPARalpha a major regulator of lipid catabolism, while PPARgamma is highly involved in lipid synthesis and deposition in different tissues. Objective: To evaluate whether lipid concentrations are altered and related to impaired PPAR protein expression in the fetal liver of GDM ratsControl and GDM rats (obtained from intrauterine programming (F1) in the offspring of streptozotocin-induced diabetic rats (F0)) were evaluated on day 21 of pregnancy. Glucose and insulin concentrations were measured in maternal and fetal serum. Lipid concentrations were measured by TLC and PPARalpha and PPARgamma protein expression were evaluated through immunohistochemistry. Results: GDM rats showed increased glycemia and insulinemia only in pregnancy (p 0.01). Male and female fetuses had increased glycemia and insulinemia (p 0.01). Male fetuses from GDM rats showed increased triglycerides (33%) and cholesterol (30%) concentrations in the liver when compared to controls (p 0.05). In these GDM fetal tissues, PPARalpha protein expression was increased (p 0.001) whereas PPARalpha protein expression showed no changes compared to controls. Differently, female fetuses from GDM rats showed reduced triglycerides (34%), cholesterol (26%), phospholipids (29%) and free fatty acids (25%) in the liver, p 0.02, compared to controls. Also, in these GDM fetal tissues, both PPARalpha and PPARgamma levels were reduced (p 0.01). In a GDM model induced by intrauterine programming, the altered lipid deposition in the fetal liver is gender-dependent and possibly related to changes in the concentrations of the different PPAR isotypes in this fetal tissue.