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Dyslipidemia, insulin resistance, and impairment of placental metabolism in the offspring of obese mothers

Published online by Cambridge University Press:  13 November 2020

Matthew Bucher ,
Kim Ramil C. Montaniel ,
Leslie Myatt ,
Susan Weintraub ,
Hagai Tavori  and
Alina Maloyan Open the ORCID record for Alina Maloyan [Opens in a new window]
Matthew Bucher
Affiliation:
Knight Cardiovascular Institute, School of Medicine, Oregon Health & Science University, Portland, OR, USA Department of OB/GYN, Oregon Health & Science University, Portland, OR, USA
Kim Ramil C. Montaniel
Affiliation:
Knight Cardiovascular Institute, School of Medicine, Oregon Health & Science University, Portland, OR, USA The Graduate Program in Biomedical Sciences (PBMS), Oregon Health & Science University, Portland, OR, USA
Leslie Myatt
Affiliation:
Department of OB/GYN, Oregon Health & Science University, Portland, OR, USA
Susan Weintraub
Affiliation:
Department of Biochemistry, The Metabolomics Core Facility, Institutional Mass Spectrometry Laboratory, University of Texas Health, San Antonio, TX, USA
Hagai Tavori
Affiliation:
Knight Cardiovascular Institute, School of Medicine, Oregon Health & Science University, Portland, OR, USA
Alina Maloyan*
Affiliation:
Knight Cardiovascular Institute, School of Medicine, Oregon Health & Science University, Portland, OR, USA The Graduate Program in Biomedical Sciences (PBMS), Oregon Health & Science University, Portland, OR, USA
*
Address for Correspondence: Alina Maloyan, Knight Cardiovascular Institute, School of Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, Oregon97239, USA. Email: maloyan@ohsu.edu
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Abstract

Obesity is a chronic condition associated with dyslipidemia and insulin resistance. Here, we show that the offspring of obese mothers are dyslipidemic and insulin resistant from the outset.

Maternal and cord blood and placental tissues were collected following C-section at term. Patients were grouped as being normal weight (NW, BMI = 18–24.9) or obese (OB, BMI ≥ 30), and separated by fetal sex. We measured plasma lipids, insulin, and glucose in maternal and cord blood. Insulin resistance was quantified using the HOMA-IR. Placental markers of lipid and energy metabolism and relevant metabolites were measured by western blot and metabolomics, respectively.

For OB women, total cholesterol was decreased in both maternal and cord blood, while HDL was decreased only in cord blood, independent of sex. In babies born to OB women, cord blood insulin and insulin resistance were increased. Placental protein expression of the energy and lipid metabolism regulators PGC1α, and SIRT3, ERRα, CPT1α, and CPT2 decreased with maternal obesity in a sex-dependent manner (P < 0.05). Metabolomics showed lower levels of acylcarnitines C16:0, C18:2, and C20:4 in OB women’s placentas, suggesting a decrease in β-oxidation. Glutamine, glutamate, alpha-ketoglutarate (αKG), and 2-hydroxyglutarate (2-HG) were increased, and the glutamine-to-glutamate ratio decreased (P < 0.05), in OB placentas, suggesting induction of glutamate into αKG conversion to maintain a normal metabolic flux.

Newly-born offspring of obese mothers begin their lives dyslipidemic and insulin resistant. If not inherited genetically, such major metabolic perturbations might be explained by abnormal placental metabolism with potential long-term adverse consequences for the offspring’s health and wellbeing.

Keywords

Maternal obesitylipid profileplacental functionmetabolomicsinsulin resistance
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 12 , Issue 5 , October 2021 , pp. 738 - 747
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Copyright
© The Author(s), 2020. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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