Metabolomic signatures of low and high adiposity neonates differ based on maternal BMI

Authors: AYDOGAN MATHYK, BEGUM - University Of South Florida; PICCOLO, BRIAN - Arkansas Children'S Nutrition Research Center (ACNC); ALVARADO, FERNANDA - Tufts Medical Center; SHANKAR, KARTIK - University Of Colorado; O’TIERNEY- GINN, PERRIE - Tufts Medical Center

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/21/2022
Publication Date: 4/25/2022
Citation: Aydogan Mathyk, B., Piccolo, B.D., Alvarado, F., Shankar, K., O’Tierney- Ginn, P. 2022. Metabolomic signatures of low and high adiposity neonates differ based on maternal BMI. American Journal of Physiology - Endocrinology and Metabolism. https://doi.org/10.1152/ajpendo.00356.2021.
DOI: https://doi.org/10.1152/ajpendo.00356.2021

Interpretive Summary: Obesity in the mother can lead to greater fat accumulation in offspring, higher cord blood insulin levels, and inflammation at birth. These outcomes may contribute to future risk of metabolic disease as the child ages. In addition, different total fat levels at birth may also have similar risk for metabolic diseases. Thus, understanding whether disease risk is a function of maternal obesity, total fat at birth, or a combination is important health objective. We looked at an array of small molecules in umbilical blood in babies with high or low fat levels from mothers with or without obesity. Our questions were whether 1) we could identify whether the overall make up of these molecules, or a handful of molecules, could identify if a baby was born with high or low fat and from either a lean or obese mother, and 2) whether any of these molecules have a relationship with clinical markers of metabolic health in either the baby or mother. We found that babies born with less total fat and obese mothers (OBLA) had a unique molecule profile. Lauric acid, a 12 carbon saturated fatty acid, was the most predictive molecule of OBLA offspring and 82-118% in OBLA babies compared to the other groups. Other fatty acids, like palmitate, stearate, and linoleate were also higher in OBLA babies compared to babies born with higher total fat and obese mothers (OBHA). Looking at obese mothers, cord blood lauric acid had a negative relationship with neonatal markers of body composition (total fat mass, lean body mass, percent fat, ponderal index, birth weight), but these relationships were not observed in lean mothers. The results in this study show that molecules related to the baby's metabolism found in cord blood associate with neonatal adiposity and this is further modified by the obesity status of the mother.

Technical Abstract: Maternal obesity (body mass index, BMI>30 kg/m2) is associated with greater neonatal adiposity, cord blood (CB) insulin levels, and a pro-inflammatory phenotype at birth, contributing to risk of future cardiometabolic disease in the offspring. Variation in neonatal adiposity within maternal BMI groups is underappreciated, and it remains unclear whether the metabolic impairments at birth are an outcome of maternal obesity or excess fetal fat accrual. We examined the hypothesis that CB metabolites associated with fetal fat accrual differ between offspring of normal weight and obese women. Umbilical venous blood was collected at the time of scheduled cesarean delivery from 50 normal weight women (LE; pre-gravid BMI=22.3+/-1.7 kg/m2), and 50 (OB; BMI=34.5+/-3.0 kg/m2) women with obesity. Neonatal adiposity was estimated from flank skinfold thickness. The first (low adiposity, LA) and third (high adiposity, HA) tertiles of neonatal %body fat were used to create four groups: OBLA, OBHA, LELA, LEHA. CB metabolites were measured via untargeted metabolomics. Broadly, the LA offspring of OB women (OBLA) metabolite signature differed from other groups. Lauric acid (C12:0) was 82-118% higher in OBLA vs all other groups (FDR <0.01). Several other fatty acids, including palmitate, stearate, and linoleate, were higher in OBLA vs OBHA group. CB metabolites, such as lauric acid, a medium chain FA which may improve insulin sensitivity, were associated with neonatal adiposity differently between offspring of women with and without obesity. Changes in metabolically active lipids at birth may have long-term consequences for offspring metabolism.