Altered Circulating miRNA Expression Profile in Pregestational and Gestational Obesity
Gemma Carreras-Badosa1, Alexandra Bonmatí1, Francisco-Jose Ortega1
1Departments of Pediatrics (G.C.-B., E.P.-G., A.L.-B., J.B.) and Gynecology (A.B.), Dr Josep Trueta Hospital, Department of Diabetes, Endocrinology, and Nutrition (F.-J.O., J.-M.F.-R.), Girona Institute for Biomedical Research (G.C.-B., E.P.-G., A.L.-B., J.B.), and Department of Physical Therapy (A.P.-P.), Escola Universitària de la Salut i l'Esport (EUSES), University of Girona, 17007 Girona, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (F.-J.O., J.-M.F.-R.) and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (F.-J.O., J.-M.F.-R.), Instituto de Salud Carlos III, 28029 Madrid, Spain; Joint program on Computational Biology, Barcelona Supercomputing Center and Institut de Recerca Biomèdica de Barcelona (BSC-IRB) (J.-M.M., M.G.-M., D.T.), Barcelona Supercomputing Center, 08003 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (D.T.), 08916 Barcelona, Spain; Institute of Legal Medicine of Catalonia (J.-M.M.-C.), 17001 Girona, Spain; Department of Development and Regeneration (F.D.Z.), University of Leuven, B-3000 Leuven, Belgium; and Department of Endocrinology (L.I.), Hospital Sant Joan de Déu, University of Barcelona, 08950 Esplugues, Barcelona, Spain.
Context:
MicroRNAs (miRNAs) are valuable circulating biomarkers and therapeutic targets for metabolic diseases.
Objective:
The objective of the study was to define the pattern of circulating miRNAs in pregestational and gestational obesity and to explore their associations with maternal metabolic parameters and with markers for pre- and postnatal growth. design, settings, and main outcome measure: TaqMan low-density arrays were used to profile plasma miRNAs in six women with pregestational obesity (PregestOB), six with gestational obesity (GestOB), and six with normal pregnancies (control) during the second trimester of gestation. The most relevant miRNAs were validated in 70 pregnant women (20 PregestOB, 25 GestOB, and 25 control). Maternal metabolic parameters including glucose, glycated hemoglobin, homeostasis model assessment index of insulin resistance, C-peptide, and lipids were assessed. Placentas were weighed at delivery and newborns also during 6 months of life.
Results:
We identified 13 circulating miRNAs differentially expressed in maternal obesity, including decreased levels of miR-29c, miR-99b, miR-103, miR-221, and miR-340 and increased levels of miR-30a-5p, miR-130a, and miR-150 in GestOB; and decreased levels of miR-122, miR-324-3p, miR-375, and miR-652 and increased levels of miR-625 in both PregestOB and GestOB (P < .05 to P < .0001 vs control). Decreased levels of several of these miRNAs associated with a more adverse maternal metabolic status (more pregnancy weight gain, glucose, glycated hemoglobin, homeostasis model assessment index of insulin resistance, C-peptide, and triacylglycerol and less high density lipoprotein cholesterol), with more placental weight, weight at birth, and weight at 6 months of life (all P < .05 to P < .001).
Conclusions:
This study provides the first identification of altered circulating miRNAs in maternal obesity and suggests a possible role of such miRNAS as markers for pre- and postnatal growth.
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