Placental lipases in pregnancies complicated by gestational diabetes mellitus (GDM).

Helen L Barrett,Kerina J Denny,Trent M Woodruff,Marta H Kubala,Katherin Scholz Romero,Leonie K Callaway,Marloes Dekker Nitert,H David Mcintyre,Cheryl S Rosenfeld

doi:10.1371/journal.pone.0104826

Helen L Barrett, Kerina J Denny + Show 7 more

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https://doi.org/10.1371/journal.pone.0104826

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Abstract

Infants of women with gestational diabetes mellitus (GDM) are more likely to be born large for gestational age with a higher percentage body fat. Elevated maternal lipids may contribute to this. Placental lipases such as lipoprotein lipase (LPL), endothelial lipase (EL) and hormone sensitive lipase (HSL) are involved in transferring lipids from mother to fetus. Previous studies of expression of these lipases in placentae in women with diabetes in pregnancy have reported divergent results. Intracellular lipases such as adipose triglyceride lipase (ATGL), and HSL are central to lipid droplet metabolism. The activities of these lipases are both influenced by Perilipin 1, and ATGL is also activated by a co-factor comparative gene identification-58 (CGI-58) and inhibited by G0/G1 switch gene 2 (GS02). None of these modifying factors or ATGL have been examined previously in placenta. The purpose of this study was therefore to examine the expression of ATGL, HSL, LPL, EL, as well as Perilipin 1, GS02 and CGI-58 in term pregnancies complicated by GDM. mRNA and protein expression of the lipases were measured in placentae from 17 women with GDM and 17 normoglycaemic pregnancies, matched for maternal BMI and gestational age of delivery. ATGL mRNA expression was increased and HSL mRNA expression reduced in placentae from GDM although there was no differences in protein expression of any of the lipases. All lipases were localised to trophoblasts and endothelial cells. The expression of Perilipin 1 and CGI-58 mRNA was increased and GS02 not altered in GDM. These results suggest that there is no difference in expression in these four lipases between GDM and normoglycaemic placentae, and therefore altered lipid transfer via these lipases does not contribute to large for gestational age in infants of women with GDM.

Highlights

In pregnancy, the mother supplies multiple fuel sources for infant growth, including glucose, free fatty acids, ketone bodies and amino acids [1]
The current study examines the placental expression of adipose triglyceride lipase (ATGL) and its activators and inhibitors, hormone sensitive lipase (HSL), endothelial lipase (EL) and lipoprotein lipase (LPL) in placentae from women with Gestational diabetes mellitus (GDM) and uncomplicated pregnancy
ATGL mRNA was increased and HSL mRNA decreased in placentae from women with GDM compared to controls, but no difference in protein expression or localisation between GDM and control placentae

Summary

Introduction

The mother supplies multiple fuel sources for infant growth, including glucose, free fatty acids, ketone bodies and amino acids [1]. Both maternal glucose and maternal lipids have been associated with infant birth weight and rates of large for gestational age infants [2]. Maternal metabolism in the third trimester is altered to ensure an adequate supply of nutrients to the fetus. These alterations include increased maternal lipoprotein concentrations and an increase in the triglyceride content of maternal lipoproteins [1]

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