Association of maternal prepregnancy BMI with metabolomic profile across gestation

Hellmuth, Christian; Lindsay, Karen L.; Uhl, Olaf; Buß, Claudia; Wadhwa, Pathik D.; Koletzko, Berthold; Entringer, Sonja

doi:10.1038/ijo.2016.153

Cited by 75 publications

(87 citation statements)

References 57 publications

(61 reference statements)

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“…Maternal obesity is often characterized by elevated levels of blood triglycerides which are transported across the placenta, thereby increasing fetal fat deposition [6, 45, 46]. While maternal circulating NEFA and triglyceride levels were not affected by HF feeding in the current study, we did observe increased accumulation of triglycerides in placentas from the HFCO versus NFCO dams.…”

Section: Discussioncontrasting

confidence: 73%

Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity

Nam

Greenwald

Jack-Roberts

et al. 2017

The Journal of Nutritional Biochemistry

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Maternal obesity increases placental transport of macronutrients, resulting in fetal overgrowth and obesity later in life. Choline participates in fatty acid metabolism, serves as a methyl donor, and influences growth signaling, which may modify placental macronutrient homeostasis and affect fetal growth. Using a mouse model of maternal obesity, we assessed the effect of maternal choline supplementation on preventing fetal overgrowth and restoring placental macronutrient homeostasis. C57BL/6J mice were fed either a high-fat (HF, 60% kcal from fat) diet or a normal (NF, 10% kcal from fat) diet with a drinking supply of either 25 mM choline chloride or control purified water, respectively, beginning 4 weeks prior to mating until gestational day 12.5. Fetal and placental weight, metabolites, and gene expression were measured. HF feeding significantly (P < 0.05) increased placental and fetal weight in the HF-control (HFCO) versus NF-control (NFCO) animals, whereas the HF choline-supplemented (HFCS) group effectively normalized placental and fetal weight to the levels of the NFCO group. Compared to HFCO, the HFCS group had lower (P < 0.05) glucose transporter 1 (GLUT1) and fatty acid transport protein 1 (FATP1) expression as well as lower accumulation of glycogen in the placenta. The HFCS group also had lower (P < 0.05) placental 4E-binding protein 1 and ribosomal protein s6 phosphorylation, which are indicators of mechanistic target of rapamycin complex 1 (mTORC1) activation favoring macronutrient anabolism. In summary, our results suggest that maternal choline supplementation prevented fetal overgrowth in obese mice at mid-gestation and improved biomarkers of placental macronutrient homeostasis.

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Section: Discussioncontrasting

confidence: 73%

Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity

Nam

Greenwald

Jack-Roberts

et al. 2017

The Journal of Nutritional Biochemistry

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“…On the other hand, a recent study by Hellmuth et al reported no relationship between pre-pregnancy BMI and amino acids, including BCAAs, in serum of 167 pregnant women throughout pregnancy (56); a potential explanation for this discrepancy could be related to the type of fluid used for metabolomics analyses…”

Section: Discussionmentioning

confidence: 98%

Associations of cord blood metabolites with perinatal characteristics, newborn anthropometry, and cord blood hormones in project viva

et al. 2017

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Context Metabolomics has emerged as a powerful tool to characterize biomarkers and elucidate physiological processes underlying adverse health outcomes. Little is known of these relationships during gestation and infancy, which are critical period for development of metabolic disease risk. Objectives To identify cord blood metabolite patterns associated with birth size; and to investigate relations of the birth size-associated metabolite patterns, and a branched chain amino acid (BCAA) metabolite pattern with a range of newborn and perinatal characteristics. Methods Using untargeted mass-spectrometry, we quantified metabolites in cord blood of 126 mother-child pairs. After excluding 103 xenobiotics, we used principal components analysis (PCA) to consolidate the remaining 606 metabolites into principal components (“factors”). Next, we identified factors associated with gestational age-and sex-standardized birthweight z-score (BW/GA) and examined associations of the BW/GA-associated pattern(s) and the BCAA pattern with cord blood insulin, leptin, adiponectin, insulin-like growth factor (IGF)-1, IGF-2, and IGF binding protein 3 (IGFBP-3) using multivariable linear regression. Finally, we examined associations of maternal/perinatal characteristics with the cord blood metabolite patterns Results Mean BW/GA z-score was 0.27 ± 0.98 units. About half of the infants were male (52.4%) and white (57.1%). Of the 6 factors identified from PCA, one was associated with higher BW/GA: Factor 5, which comprised metabolites involved in energy production (malate, succinate, fumarate) and nucleotide turnover (inosine 5-monophosphate, adenosine 5-monophosphate, cytidine 5-monophosphate) pathways. In multivariable analysis, Factor 5 was related to higher cord blood leptin (1.64 [95% CI: 0.42, 2.87] ng/mL) and IGF-1 even after adjusting for IGFBP-3 (3.35 [0.25, 6.44] ng/mL). The BCAA pattern was associated with higher BW/GA (0.20 [0.03, 0.36] z-scores) and IGFBP-3 (106.5 [44.7, 168.2] ng/mL). No maternal characteristics were associated with either metabolite pattern; however, infants born via Cesarean delivery exhibited a higher score for Factor 5, and gestation length was inversely associated with the BCAA pattern. Conclusions Metabolites in energy production and DNA/RNA turnover pathways in cord blood are associated with larger size at birth, and higher leptin and IGF-1. Similarly, the BCAA pattern was associated with larger birth size and IGFBP-3.

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“…Recently, the association of several plasma metabolites with maternal prepregnancy BMI across gestation in a cohort of 167 non-Hispanic and Hispanic ancestry women was reported (10). In the third trimester, associated metabolites included two n-6 long-chain fatty acids and 3-hydroxybutyrate.…”

Section: Discussionmentioning

confidence: 99%

“…Pregnancy-related changes in metabolism, including those accompanying maternal hyperglycemia and obesity, are reflected in the maternal metabolome (10–14), which is determined by both intrinsic (e.g., genetic) and extrinsic (e.g., diet, exercise, etc.) factors (15,16).…”

Section: Introductionmentioning

confidence: 99%

Targeted Metabolomics Demonstrates Distinct and Overlapping Maternal Metabolites Associated With BMI, Glucose, and Insulin Sensitivity During Pregnancy Across Four Ancestry Groups

et al. 2017

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OBJECTIVEWe used targeted metabolomics in pregnant mothers to compare maternal metabolite associations with maternal BMI, glycemia, and insulin sensitivity.RESEARCH DESIGN AND METHODSTargeted metabolomic assays of clinical metabolites, amino acids, and acylcarnitines were performed on fasting and 1-h postglucose serum samples from European ancestry, Afro-Caribbean, Thai, and Mexican American mothers (400 from each ancestry group) who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and underwent an oral glucose tolerance test at ∼28 weeks gestation.RESULTSK-means clustering, which identified patterns of metabolite levels across ancestry groups, demonstrated that, at both fasting and 1-h, levels of the majority of metabolites were similar across ancestry groups. Meta-analyses demonstrated association of a broad array of fasting and 1-h metabolites, including lipids and amino acids and their metabolites, with maternal BMI, glucose levels, and insulin sensitivity before and after adjustment for the different phenotypes. At fasting and 1 h, a mix of metabolites was identified that were common across phenotypes or associated with only one or two phenotypes. Partial correlation estimates, which allowed comparison of the strength of association of different metabolites with maternal phenotypes, demonstrated that metabolites most strongly associated with different phenotypes included some that were common across as well as unique to each phenotype.CONCLUSIONSMaternal BMI and glycemia have metabolic signatures that are both shared and unique to each phenotype. These signatures largely remain consistent across different ancestry groups and may contribute to the common and independent effects of these two phenotypes on adverse pregnancy outcomes.

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Association of maternal prepregnancy BMI with metabolomic profile across gestation

Abstract: 33Background/Objectives: Elevated pre-pregnancy BMI (pBMI) and excess gestational weight gain (GWG) 34

Cited by 75 publications

References 57 publications

Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity

Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity

Associations of cord blood metabolites with perinatal characteristics, newborn anthropometry, and cord blood hormones in project viva

Targeted Metabolomics Demonstrates Distinct and Overlapping Maternal Metabolites Associated With BMI, Glucose, and Insulin Sensitivity During Pregnancy Across Four Ancestry Groups

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