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.

Our previous work suggests that stressors that impact placental vascular growth result in a deformed chorionic surface shape, which reflects an abnormal placental three-dimensional shape. We propose to use variability of placental disk thickness as a reflector of deviations in placental vascular growth at the finer level of the fetal stems. We hypothesize that increased variability of thickness is associated with abnormal chorionic surface shape, but will be a predictor of reduced placental functional efficiency (smaller baby for a given placental weight) independent of shape. These measures may shed light on the mechanisms linking placental growth to risk of adult disease. The sample was drawn from the Pregnancy, Infection and Nutrition Study. In all, 94.6% of the cohort consented to placental examination. Of the 1023 delivered at term, those previously sectioned by the Pathology Department were excluded, leaving 587 (57%) cases with intact placentas that were sliced and photographed. The chorionic surface shape and the shape of a central randomly oriented placental slice were analyzed and measures were compared using correlation. Lower mean placental disk thickness and more variable disk thickness were each strongly and significantly correlated with deformed chorionic plate shapes. More variable disk thickness was strongly correlated with reduced placental efficiency independent of abnormal chorionic surface shape. Variability of placental disk thickness, simple to measure in a single randomly oriented central slice, may be an easily acquired measure that is an independent indicator of lowered placental efficiency, which may in turn program the infant and result in increased risk for development of adult diseases.