Elsevier

Placenta

Volume 54, June 2017, Pages 59-67
Placenta

Review: Placental transport and metabolism of energy substrates in maternal obesity and diabetes

https://doi.org/10.1016/j.placenta.2016.12.006Get rights and content

Abstract

Maternal obesity is growing in prevalence and is associated with increased morbidity and mortality for both mother and child. Women who are obese during pregnancy have a greater risk of metabolic complications such as gestational diabetes mellitus (GDM) as well as type 2 diabetes after pregnancy. Children of obese and/or GDM mothers have an increased susceptibility to congenital abnormalities and a range of cardio-metabolic disorders. The placenta is at the interface of the maternal and fetal environments and, its function per se, plays a major role in dictating the impact of maternal health on fetal development. Here, we review the literature on how placental function is affected in pregnancies complicated by obesity, and pre-gestational and gestational diabetes. The focus is on the availability of three key substrates in these conditions: glucose, lipids, and amino acids, and their impact on placental metabolic activity. Maternal obesity and diabetes are not always associated with fetal compromise and the adaptation of the placenta may partially determine the outcome. Understanding the differences in metabolic adaptation may open avenues for therapeutic development.

Introduction

The global prevalence of overweight, obesity, and diabetes mellitus is increasing [1]. In developed nations, one third of pregnant women are overweight or obese [2] and 5–10% have diabetes in pregnancy [3]. In these complicated pregnancies, physiological changes are exaggerated, including alterations to lipoprotein levels and enhanced gluconeogenesis [4]. High maternal weight, dyslipidemia, and/or hyperglycemia place mother and child at risk, with the most common adverse outcome being high birth weight (macrosomia) [5], [6], [7], [8], [9], [10], [11], [12]. Large for gestational age infants born to women with GDM have a higher percent body fat when compared to infants from uncomplicated pregnancies [13] and ∼70% of mothers [14] and offspring [15] will develop type 2 diabetes in later life.

The influence of maternal disease on fetal outcomes is governed, to a large extent, by the placenta. In maternal obesity and hyperglycemia, placental size is greater and structural changes including thrombosis may be evident [16], [17], [18], [19]. There are three main mechanisms that regulate fetal exposure to maternal nutrients: direct placental transfer, placental consumption, and placental conversion into alternative sources of fuel [20], [21]. While direct transfer is often regarded as the predominant pathway in regulating maternal-fetal exchange, the placenta has a high metabolic activity, which is affected by an obesogenic and/or diabetogenic environment. Alterations in placental metabolism may serve as a checkpoint to regulate fetal exposure and, ultimately, determine the degree of influence that abnormal maternal metabolism has on fetal growth and development (Fig. 1) [22].

Section snippets

Glucose transport and metabolism

Glucose is the predominant source of energy for the fetus and placenta [23]. There is limited capacity for the fetus to generate its own glucose and almost all of fetal glucose is derived from the mother [24], [25]. Net glucose transfer is determined by placental transporter density, the maternal-fetal concentration gradient, and placental glucose metabolism [26].

Glucose transfer across the placenta occurs via the family of facilitated glucose transporters (GLUTs). In the human

Lipid transport and metabolism

Fetal growth and development is also supported by free fatty acids and the constituent fatty acids and cholesterol that are transported in maternal lipoproteins. Markers of fetal cholesterol synthesis are very low in early pregnancy and increase only after 19 weeks gestation [50]. Placental transfer of lipoproteins is facilitated by lipoprotein receptors, lipases (lipoprotein lipase (LPL), endothelial lipase (EL), hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL)), and fatty

Amino acid transport and metabolism

Amino acids are important substrates for the formation of proteins and nucleic acids in the fetus and placental transport is a tightly regulated process. Maternal amino acids are transported against the concentration gradient with placental intervillous concentrations generally exceeding maternal concentrations by two-fold [85], [86]. The concentrations in the umbilical vein mirror those of the placental intervillous space for most amino acids [85]. The high amino acid concentrations in the

Conclusions

In pregnancies complicated by obesity and/or diabetes, glucose appears to be the preferred energy substrate for placental metabolism - its uptake increasing in both states. Glucose transport and metabolism, however, are not merely modulated by maternal glucose per se, but likely to involve a complex and dynamic interplay with other energy substrates and fetal growth factors. Lipid processing and transfer by the placenta is influenced by maternal BMI, glucose status, and inflammation. Amino acid

Conflict of interest

None.

Acknowledgments

LAG was supported by a fellowship from the National Health and Medical Research Council (NHMRC) (APP1089763) and Heart Foundation (Australia) (100519). HLB is supported by an Australian Diabetes Society – Skip Martin Early Career Research Fellowship. This review was generated as part of the Queensland Perinatal Consortium Inaugural Conference held on July 15th, 2016 in Brisbane, Queensland Australia. The conference was supported by an Intra-Faculty Collaborative Workshop grant from the Faculty

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