Leptin and Nutrition in Gestational Diabetes

Abstract

Leptin is highly expressed in the placenta, mainly by trophoblastic cells, where it has an important autocrine trophic effect. Moreover, increased leptin levels are found in the most frequent pathology of pregnancy: gestational diabetes, where leptin may mediate the increased size of the placenta and the fetus, which becomes macrosomic. In fact, leptin mediates the increased protein synthesis, as observed in trophoblasts from gestational diabetic subjects. In addition, leptin seems to facilitate nutrients transport to the fetus in gestational diabetes by increasing the expression of the glycerol transporter aquaporin-9. The high plasma leptin levels found in gestational diabetes may be potentiated by leptin resistance at a central level, and obesity-associated inflammation plays a role in this leptin resistance. Therefore, the importance of anti-inflammatory nutrients to modify the pathology of pregnancy is clear. In fact, nutritional intervention is the first-line approach for the treatment of gestational diabetes mellitus. However, more nutritional intervention studies with nutraceuticals, such as polyphenols or polyunsaturated fatty acids, or nutritional supplementation with micronutrients or probiotics in pregnant women, are needed in order to achieve a high level of evidence. In this context, the Mediterranean diet has been recently found to reduce the risk of gestational diabetes in a multicenter randomized trial. This review will focus on the impact of maternal obesity on placental inflammation and nutrients transport, considering the mechanisms by which leptin may influence maternal and fetal health in this setting, as well as its role in pregnancy pathologies.

Keywords: Mediterranean diet; bioactive compounds; gestational diabetes mellitus; inflammation; leptin resistance; nutrition; obesity; polyphenolic compounds.

Figure 1

Effects of bioactive food compounds on the leptin resistance associated with obesity and gestational diabetes.

Figure 2

Effects of the Mediterranean diet on the oxidative stress and inflammation associated with obesity and gestational diabetes. Obesity and GDM are linked with higher susceptibility to oxidative stress and inflammation. Adipocyte hypertrophy results in elevated circulation of free fatty acids (FFAs) and increased secretion of leptin, which drives T cells toward a pro-inflammatory phenotype (Th1). These in turn result in immune cell infiltration and the activation of pro-inflammatory signaling pathways. Bioactive food compounds in the Mediterranean diet such as polyphenols exert their anti-inflammatory activity by inhibiting ROS production and inhibiting multiple central kinases that are involved in multiple signaling pathways related to inflammation, such as NF-κB, MAPKs and PI3/Akt signaling pathways.