TY - JOUR
T1 - Dyslipidemia, insulin resistance, and impairment of placental metabolism in the offspring of obese mothers
AU - Bucher, Matthew
AU - Montaniel, Kim Ramil C.
AU - Myatt, Leslie
AU - Weintraub, Susan
AU - Tavori, Hagai
AU - Maloyan, Alina
N1 - Publisher Copyright:
© 2021 Cambridge University Press. All rights reserved.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
KW - Maternal obesity
KW - insulin resistance
KW - lipid profile
KW - metabolomics
KW - placental function
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UR - http://www.scopus.com/inward/citedby.url?scp=85096199515&partnerID=8YFLogxK
U2 - 10.1017/S2040174420001026
DO - 10.1017/S2040174420001026
M3 - Article
C2 - 33185172
AN - SCOPUS:85096199515
SN - 2040-1744
VL - 12
SP - 738
EP - 747
JO - Journal of developmental origins of health and disease
JF - Journal of developmental origins of health and disease
IS - 5
ER -