Oral L-glutamine rescues fructose-induced poor fetal outcome by preventing placental triglyceride and uric acid accumulation in Wistar rats

Abstract

Background: Metabolic adaptation of pregnant mothers is crucial for placental development and fetal growth/ survival. However, evidence exists that indiscriminate consumption of fructose-enriched drink (FED) during pregnancy disrupts maternal-fetal metabolic tolerance with attendant adverse fetal outcomes. Glutamine supplementation (GLN) has been shown to exert a modulatory effect in metabolic disorders. Nevertheless, the effects of GLN on FED-induced poor fetal outcome, and in particular the impacts on placental uric acid/lipid accumulation are unknown. The present study was conducted to test the hypothesis that oral GLN improves fetal outcome by attenuating placental lipid accumulation and uric acid synthesis in pregnant rats exposed to FED. Materials and methods: Pregnant Wistar rats (160-180 g) were randomly allotted to control, GLN, FED and FED þ GLN groups (6 rats/group). The groups received vehicle by oral gavage, glutamine (1 g/kg) by oral gavage, fructose (10%; w/v) and fructose þ glutamine, respectively, through gestation. Results: Data showed that FED during pregnancy caused placental inefficiency, reduced fetal growth, and caused insulin resistance with correspondent increase in fasting blood glucose and plasma insulin. FED also resulted in an increased placental triglyceride, total cholesterol and de novo uric acid synthesis by activating adenosine deaminase and xanthine oxidase activities. Moreover, FED during pregnancy led to increased lipid peroxidation, lactate production with correspondent decreased adenosine and glucose-6-phosphate dehydrogenase-dependent antioxidant defense. These alterations were abrogated by GLN supplementation. Conclusion: These findings implicate that high FED intake during pregnancy causes poor fetal outcome via defective placental uric acid/triglyceride-dependent mechanism. The findings also suggest that oral GLN improves fetal outcome by ameliorating placental defects through suppression of uric acid/triglyceride accumulation.

Maternal Fructose Diet-Induced Developmental Programming

“…Furthermore, serum levels of fructose significantly correlate with uric acid levels in the villous tree of human placenta [ 12 ]. Similar to allopurinol, maternal glutamine supplementation in rats decreased placental uric acid levels induced by fructose consumption and abrogated the decrease in fetal weight and length [ 13 ]. Further understanding of how fructose-induced increases in placental uric acid production developmentally program phenotypes in offspring will be essential to define the potential for urate production as a target pathway for preventive therapy.…”

Pregnancy Is Enough to Provoke Deleterious Effects in Descendants of Fructose-Fed Mothers and Their Fetuses

“…As previously described, fructose intake in drinking water during pregnancy led to an increase in liquid consumption along with a diminution in solid food intake in order to compensate the total calorie intake [ 23 , 40 ]. Curiously, in the present study, although total calories ingested by FF dams during gestation were higher than the calorie intake by CC or FC groups, body weight at day 21 of pregnancy and body weight increase during gestation did not show changes between the three experimental groups.…”

“…Surprisingly, levels of adiponectin, another adipokine, were increased in pregnant rats from fructose-fed mothers regardless of the treatment that they had received during pregnancy. Although reductions in adiponectinemia have been related to insulin resistance in rats receiving fructose or high-fat diets [ 40 , 41 ], we have previously reported increments in adiponectin levels both in fructose-fed pregnant rats [ 26 ] and in non-pregnant descendants from fructose-fed mothers with and without re-exposure to fructose [ 29 , 30 ]. Since it is known that adiponectin is able to improve insulin sensitivity [ 39 ], we attributed these increments in adiponectinemia to an attempt to preserve the insulin sensitivity in the livers of these animals.…”