Maternal obesity programs mitochondrial and lipid metabolism gene expression in infant umbilical vein endothelial cells.

BACKGROUND/OBJECTIVES: Maternal obesity increases risk for childhood obesity, but molecular mechanisms are not well understood. We hypothesized that primary umbilical vein endothelial cells (HUVEC) from infants of overweight and obese mothers would harbor transcriptional patterns reflecting offspring obesity risk. SUBJECTS/METHODS: In this observational cohort study, we recruited 13 lean (pre-pregnancy body mass index (BMI) <25.0 kg m-2) and 24 overweight-obese ('ov-ob', BMI⩾25.0 kg m-2) women. We isolated primary HUVEC, and analyzed both gene expression (Primeview, Affymetrix) and cord blood levels of hormones and adipokines. RESULTS: A total of 142 transcripts were differentially expressed in HUVEC from infants of overweight-obese mothers (false discovery rate, FDR<0.05). Pathway analysis revealed that genes involved in mitochondrial and lipid metabolism were negatively correlated with maternal BMI (FDR<0.05). To test whether these transcriptomic patterns were associated with distinct nutrient exposures in the setting of maternal obesity, we analyzed the cord blood lipidome and noted significant increases in the levels of total free fatty acids (lean: 95.5±37.1 µg ml-1, ov-ob: 124.1±46.0 µg ml-1, P=0.049), palmitate (lean: 34.5±12.7 µg ml-1, ov-ob: 46.3±18.4 µg ml-1, P=0.03) and stearate (lean: 20.8±8.2 µg ml-1, ov-ob: 29.7±17.2 µg ml-1, P=0.04), in infants of overweight-obese mothers. CONCLUSIONS: Prenatal exposure to maternal obesity alters HUVEC expression of genes involved in mitochondrial and lipid metabolism, potentially reflecting developmentally programmed differences in oxidative and lipid metabolism.

Associations of cord blood metabolites with early childhood obesity risk.

BACKGROUND/OBJECTIVE: Rapid postnatal weight gain is a potentially modifiable risk factor for obesity and metabolic syndrome. To identify markers of rapid infancy weight gain and childhood obesity, we analyzed the metabolome in cord blood from infants differing in their postnatal weight trajectories. METHODS: We performed a nested case-control study within Project Viva, a longitudinal cohort of mothers and children. We selected cases (n=26) based on top quartile of change in weight-for-age 0-6 months and body mass index (BMI) >85th percentile in mid-childhood (median 7.7 years). Controls (n=26) were age and sex matched, had normal postnatal weight gain (2nd or 3rd quartile of change in weight-for-age 0-6 months) and normal mid-childhood weight (BMI 25th-75th percentile). Cord blood metabolites were measured using untargeted liquid chromatography-mass spectrometry; individual metabolites and pathways differing between cases and controls were compared in categorical analyses. We adjusted metabolites for maternal age, maternal BMI and breastfeeding duration (linear regression), and assessed whether metabolites improved the ability to predict case-control status (logistic regression). RESULTS: Of 415 detected metabolites, 16 were altered in cases versus controls (t-test, nominal P<0.05). Three metabolites were related to tryptophan: serotonin, tryptophan betaine and tryptophyl leucine (46%, 48% and 26% lower in cases, respectively, P<0.05). Mean levels of two methyl donors, dimethylglycine and N-acetylmethionine, were also lower in cases (18% and 16%, respectively, P=0.01). Moreover, the glutamine:glutamate ratio was reduced by 33% (P<0.05) in cases. Levels of serotonin, tryptophyl leucine and N-acetylmethionine remained significantly different after adjustment for maternal BMI, age and breastfeeding. Adding metabolite levels to logistic regression models including only clinical covariates improved the ability to predict case versus control status. CONCLUSIONS: Several cord blood metabolites are associated with rapid postnatal weight gain. Whether these patterns are causally linked to childhood obesity is not clear from this cross-sectional analysis, but will require further study.