ATTENUATION OF PLACENTAL LIPID DEPOSITION BY GLUTAMINE SUPPLEMENTATION IMPROVES FETAL OUTCOME IN INSULIN-RESISTANT PREGNANT RATS

Abstract

Objective: Maternal metabolic adaptation is critical for placental and fetal development, growth and survival. However, evidence exists that indiscriminate consumption of fructose-enrich drink (FRD) during pregnancy disrupts maternal-fetal metabolic tolerance and/or glucose homeostasis with consequent adverse pregnancy outcomes. Glutamine supplementation (GLN) has been shown to exert a modulatory effect in metabolic pathologies. Nevertheless, the effects of GLN on FRD-induced placental lipotoxicity during pregnancy are unknown. The present study was conducted to investigate the protective effects of GLN on pregnancy outcomes of female rats exposed to gestational FRD. Design and method: Pregnant Wistar rats weighing 160–180 g were randomly allotted into control, GLN, FRD and FRD+GLU groups (6 rats per group). The groups received vehicle (p.o.), glutamine (1 g/kg), fructose (10%; w/v) and fructose plus glutamine respectively throughout the period of gestation. Insulin resistance (IR) and insulin sensitivity were estimated by homeostatic model of assessment (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) respectively. Plasma and tissue biochemical analysis were determined using enzyme-linked immunosorbent assay kits or fluorescence assay as appropriate. Results: Data showed that FRD increased placental weight and decreased fetal length and weight. It also caused maternal insulin resistance with correspondent increase in blood glucose, plasma insulin and decreased insulin sensitivity. In addition, FRD increased placental triglyceride, total cholesterol, low density lipoprotein-cholesterol, free fatty acid, atherogenic lipid, lipid peroxidation (malondialdehyde), lactate and uric acid synthesis, and decreased nitric oxide, adenosine and glucose-6-phosphate dehydrogenase-dependent antioxidant defense. Conclusions: The present study demonstrates that high FRD consumption during pregnancy causes placental lipotoxicity-driven defects with consequent fetal growth restriction. The findings also suggest that glutamine supplementation improves fetal outcome by ameliorating placental defects through suppression of uric acid synthesis and lipid peroxidation, as well as enhancement of NO-dependent endothelial function and antioxidant defense (Figure 1). Similarly, the study also suggests that glutamine supplementation in pregnancy could be useful as a reprogramming intervention to prevent impaired placental-fetal development and subsequent newborn and adulthood metabolic-related syndromes (Figure 1).