Olive oil diet in mild pre-gestational diabetes impacts offspring β-cell development.

Maternal diabetes impairs fetal development and increases the risk of metabolic diseases in the offspring. Previously, we showed maternal dietary supplementation with 6% of olive oil prevents diabetes-induced embryo and fetal defects, in part, through the activation of peroxisome proliferator-activated receptors (PPARs). In this study we examined the effects of this diet on neonatal and adult pancreatic development in both male and female offspring. A mild diabetic model was developed by injecting neonatal rats with streptozotocin (90 mg/kg). During pregnancy these dams were fed a chow diet supplemented or not with 6% olive oil. Dual immunohistochemistry was performed to detect α and β cells in islets at post-natal day 2 and at 5 months of age. Morphometric analysis was carried out to determine the number of islets, α and β cell clusters and β-cell mass. At 5 months, male offspring of diabetic mothers had reduced β-cell mass. Moreover, this β-cell pancreatic deficit was prevented by the maternal supplementation with olive oil. While no changes in PPARα expression was detected in the pancreas, both PPARβ/δ and PPARγ expression were reduced in 5-month-old male offspring of diabetic rats. Interestingly, the reduction in PPAR β/δ expression was prevented by maternal olive-oil supplementation. To further explore the direct effects on PPARs, INS-1E (β) and αTC1-6 (α) cell lines were treated with oleic acid. Interestingly PPARβ/δ expression is highly expressed in INS-1E. Collectively, these findings suggest that olive oil supplementation in utero may prevent diabetes-induced β cell loss in postnatal life by modulating pancreatic PPARs.