Supplementation with polyunsaturated fatty acids in pregnant rats with mild diabetes normalizes placental PPARγ and mTOR signaling in female offspring developing gestational diabetes

Abstract

Maternal diabetes impairs fetoplacental development and programs metabolic diseases in the offspring. We have previously reported that female offspring of pregnant rats with mild diabetes develop gestational diabetes mellitus (GDM) when they become pregnant. Here, we studied the effects of supplementation with polyunsaturated fatty acids (PUFAs) in pregnant mild diabetic rats (F0) by feeding a 6% safflower-oil-enriched diet from day 1 to 14 followed by a 6% chia-oil-enriched diet from day 14 of pregnancy to term. We analyzed maternal metabolic parameters and placental signaling at term in pregnant offspring (F1). The offspring of both PUFAs-treated and untreated mild diabetic rats developed GDM. Although gestational hyperglycemia was not prevented by dietary PUFAs treatment in F0, triglyceridemia and cholesterolemia in F1 mothers were normalized by F0 PUFAs dietary treatment. In the placenta of F1 GDM rats, PPARγ levels were reduced and lipoperoxidation was increased, changes that were prevented by the maternal diets enriched in PUFAs in the F0 generation. Moreover, fetal overgrowth and placental activation of mTOR signaling pathways were reduced in F1 GDM rats whose mothers were treated with PUFAs diets. These results suggest that F0 PUFAs dietary treatment in pregnancies with mild diabetes improves maternal dyslipidemia, fetal overgrowth and placental signaling in female offspring when they become pregnant. We speculate that an increased PUFAs intake in pregnancies complicated by diabetes may prove effective to ameliorate metabolic programming in the offspring, thereby improving the health of future generations.