Laura Stirm1,2, Markéta Kovárová3, Sarah Perschbacher4, Renate Michlmaier5, Louise Fritsche1,2, Dorothea Siegel-Axel1,2,3, Erwin Schleicher1,2,3, Andreas Peter1,2,3, Jan Pauluschke-Fröhlich6, Sara Brucker6, Harald Abele6, Diethelm Wallwiener6, Hubert Preissl1,2,3,7,8, Christian Wadsack5, Hans-Ulrich Häring1,2,3, Andreas Fritsche1,2,3, Regina Ensenauer4,9, Gernot Desoye5, Harald Staiger1,2,8. 1. Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at Eberhard Karls University Tübingen, Tübingen, Germany. 2. German Center for Diabetes Research, Tübingen, Germany. 3. Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany. 4. Institute for Social Pediatrics and Adolescent Medicine, Ludwig-Maximilians-Universität München, Munich, Germany. 5. Department of Obstetrics and Gynaecology, Medical University of Graz, Graz, Austria. 6. Department of Obstetrics and Gynaecology, University Hospital Tübingen, Tübingen, Germany. 7. Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, Munich, Germany. 8. Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard Karls University Tübingen, Tübingen, Germany. 9. Division of Experimental Pediatrics and Metabolism, University Children's Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Abstract
Purpose: Recently, alterations in maternal lipid metabolism were associated with gestational diabetes mellitus (GDM). However, detailed plasma lipid profiles and their relevance for placental and fetal metabolism are currently not understood. Methods: Maternal and placental lipid profiles were characterized in women with GDM and women with normal glucose tolerance (NGT). Inflammatory gene expression was compared in placentas and primary term trophoblasts between the groups. In addition, trophoblasts were stimulated with nonesterified fatty acids (NEFAs), and effects on gene expression were quantified. Finally, placental macrophage content and cord blood concentrations of inflammatory parameters and NEFAs were compared between women with GDM and women with NGT with similar body mass index (BMI). Results: Palmitate and stearate levels were elevated in both maternal plasma and placental tissue of women with GDM. Placental GDM-associated elevations of IL6, IL8, and TLR2 expression were reflected in trophoblasts derived from women with GDM. Stimulation of primary trophoblasts with palmitate led to increased mRNA expression and protein release of the cytokine IL6 and the chemokine IL8. In line with this, elevated amounts of CD68-positive cells were quantified in the placental tissue of women with GDM. No GDM-associated elevations in a range of inflammatory parameters and NEFAs in cord blood of NGT vs GDM neonates was found. Conclusions: GDM, independently of BMI, altered maternal plasma NEFAs and the placental lipid profile. GDM was associated with trophoblast and whole-placenta lipoinflammation; however, this was not accompanied by elevated concentrations of inflammatory cytokines or NEFAs in neonatal cord blood.
Purpose: Recently, alterations in maternal lipid metabolism were associated with gestational diabetes mellitus (GDM). However, detailed plasma lipid profiles and their relevance for placental and fetal metabolism are currently not understood. Methods: Maternal and placental lipid profiles were characterized in women with GDM and women with normal glucose tolerance (NGT). Inflammatory gene expression was compared in placentas and primary term trophoblasts between the groups. In addition, trophoblasts were stimulated with nonesterified fatty acids (NEFAs), and effects on gene expression were quantified. Finally, placental macrophage content and cord blood concentrations of inflammatory parameters and NEFAs were compared between women with GDM and women with NGT with similar body mass index (BMI). Results:Palmitate and stearate levels were elevated in both maternal plasma and placental tissue of women with GDM. Placental GDM-associated elevations of IL6, IL8, and TLR2 expression were reflected in trophoblasts derived from women with GDM. Stimulation of primary trophoblasts with palmitate led to increased mRNA expression and protein release of the cytokine IL6 and the chemokine IL8. In line with this, elevated amounts of CD68-positive cells were quantified in the placental tissue of women with GDM. No GDM-associated elevations in a range of inflammatory parameters and NEFAs in cord blood of NGT vs GDM neonates was found. Conclusions: GDM, independently of BMI, altered maternal plasma NEFAs and the placental lipid profile. GDM was associated with trophoblast and whole-placenta lipoinflammation; however, this was not accompanied by elevated concentrations of inflammatory cytokines or NEFAs in neonatal cord blood.
Authors: Chung-Ho E Lau; Victoria Taylor-Bateman; Panagiotis A Vorkas; Gonçalo Graça; Thanh-Huyen T Vu; Lifang Hou; Elena Chekmeneva; Timothy M D Ebbels; Queenie Chan; Linda Van Horn; Elaine Holmes Journal: Metabolites Date: 2020-12-04