scholarly journals Longitudinal Metabolomic Profile Trajectories in Healthy Pregnancy and Variation by BMI and Fetal Sex

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1041-1041
Author(s):  
Susanna D Mitro ◽  
Jing Wu ◽  
Mohammad Rahman ◽  
Mengying Li ◽  
Stefanie Hinkle ◽  
...  

Abstract Objectives Maternal plasma metabolites have been linked with pregnancy outcomes, and two studies reported that metabolite levels differ by trimester. However, dynamic metabolite trajectories in normal pregnancy have not been characterized. We examined metabolite trajectories and tested whether trajectories differed by maternal body mass index (BMI) or fetal sex. Methods We quantified 3 panels of targeted metabolites—37 amino acids, 37 phospholipid fatty acids and 28 acylcarnitines—in blood samples collected longitudinally from 214 pregnant women (at 10–14, 15–26, 26–31, and 33–39 weeks, staggered to sample most weeks of pregnancy). Participants were healthy controls in a nested case-control study in the Fetal Growth Studies—Singletons. We used linear mixed models to estimate metabolite trajectories and evaluate if trajectories varied by maternal BMI (<25, 25–29.9, 30) or fetal sex. We used novel methods such as hierarchical clustering to group metabolite trajectories. Results Concentrations of most carnitines, 57% of fatty acids, and 24% of amino acids (e.g., branched chain amino acids) significantly decreased over pregnancy; 22% of fatty acids and 24% of amino acids (e.g., threonine, histidine) significantly increased. Trajectories of 2 carnitines (propionylcarnitine and stearoylcarnitine) and 3 fatty acids (15:0, 17:0, 22:0) significantly differed by sex. Trajectories of dodecenoylcarnitine, 2 fatty acids and 2 fatty acid ratios (17:0, 20:3n6, AA/DHA, AA/(DHA + EPA)) significantly differed by BMI: specifically, 17:0, AA/DHA, and AA/(DHA + EPA) decreased less over pregnancy for women with high BMI. Conclusions Concentrations of most metabolites significantly changed during pregnancy, and trajectories of some carnitines and fatty acids differed significantly by maternal BMI and fetal sex. Future pregnancy metabolomics studies should consider BMI, fetal sex, and multiple samples across pregnancy. Funding Sources Eunice Kennedy Shriver National Institute of Child Health and Human Development.

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Bret Rust ◽  
Aaron Mehus ◽  
Joseph Idso ◽  
Matthew Picklo

Abstract Objectives Obesity and obesity-related disease contribute to health care costs and pose serious health risks. Rodent studies indicate that time-restricted feeding (TRF) may be effective in reducing adiposity and metabolic disease associated with obesity. However, the metabolic pathways impacted by TRF in the context of obesogenic, high-fat (HF) diets need clarity. In the present work we examined the metabolomic changes in plasma induced by TRF of a HF diet in mice compared to a HF diet eaten ad libitum (AL) vs AL intake of a low-fat (LF) control diet. Methods Male mice (12 weeks old) were fed a LF-AL diet (16%en fat), a HF-AL diet (48%en fat) or a HF diet restricted to feeding for 12 hours per day during the dark phase (HF-TRF). In week 9 of the study, energy expenditure data were collected. After 12 weeks, animals were fasted and plasma collected for clinical chemistries and metabolomic analysis. Multivariate analysis was used to discriminate diet treatments in untargeted metabolomic data. Results Energy expenditure measurements throughout the day showed a markedly reduced fasting respiratory exchange ratio (RER) in HF-TRF mice during the inactive (light) phase compared to AL groups. Measures of insulin resistance, while increased with HF-AL intake, were resolved in the HF-TRF group. Partial least squares discriminant analysis revealed plasma non-esterified fatty acids (NEFA) and amino acids (AA) to be important discriminators between diet treatments. TRF resulted in elevated NEFA concentrations of the saturated fatty acids (12:0 to 18:0) and the polyunsaturated fatty acids α-linolenic acid and linoleic acid compared to HF-AL. Conversely, the concentrations of aromatic and branched chain amino acids were reduced in HF-TRF mice compared to HF-AL mice. Conclusions Alterations in plasma metabolites following TRF of a HF diet are consistent with greater lipid utilization during the inactive phase as reflected in the RER. Decreases in the aromatic and branched chain amino acid concentrations are consistent with improved insulin sensitivity in humans. Funding Sources This work was supported by USDA-ARS project 3062-51000-053-00D. Supporting Tables, Images and/or Graphs


1982 ◽  
Vol 152 (1) ◽  
pp. 246-254
Author(s):  
Caroline S. Harwood ◽  
Ercole Canale-Parola

Spirochete MA-2, which is anaerobic, ferments glucose, forming acetate as a major product. The spirochete also ferments (but does not utilize as growth substrates) small amounts of l -leucine, l -isoleucine, and l -valine, forming the branched-chain fatty acids isovalerate, 2-methylbutyrate, and isobutyrate, respectively, as end products. Energy generated through the fermentation of these amino acids is utilized to prolong cell survival under conditions of growth substrate starvation. A branched-chain fatty acid kinase and two acetate kinase isozymes were resolved from spirochete MA-2 cell extracts. Kinase activity was followed by measuring the formation of acyl phosphate from fatty acid and ATP. The branched-chain fatty acid kinase was active with isobutyrate, 2-methylbutyrate, isovalerate, butyrate, valerate, or propionate as a substrate but not with acetate as a substrate. The acetate kinase isozymes were active with acetate and propionate as substrates but not with longer-chain fatty acids as substrates. The acetate kinase isozymes and the branched-chain fatty acid kinase differed in nucleoside triphosphate and cation specificities. Each acetate kinase isozyme had an apparent molecular weight of approximately 125,000, whereas the branched-chain fatty acid kinase had a molecular weight of approximately 76,000. These results show that spirochete MA-2 synthesizes a branched-chain fatty acid kinase specific for leucine, isoleucine, and valine fermentation. It is likely that a phosphate branched-chain amino acids is also synthesized by spirochete MA-2. Thus, in spirochete MA-2, physiological mechanisms have evolved which serve specifically to generate maintenance energy from branched-chain amino acids.


2016 ◽  
Vol 15 (5) ◽  
pp. 1728-1739 ◽  
Author(s):  
David Meierhofer ◽  
Melanie Halbach ◽  
Nesli Ece Şen ◽  
Suzana Gispert ◽  
Georg Auburger

Author(s):  
Madalina Neacsu ◽  
Nicholas J. Vaughan ◽  
Salvatore Multari ◽  
Elisabeth Haljas ◽  
Lorraine Scobbie ◽  
...  

Abstract Purpose This study evaluated the postprandial effects following consumption of buckwheat, fava bean, pea, hemp and lupin compared to meat (beef); focussing on biomarkers of satiety, gut hormones, aminoacids and plant metabolites bioavailability and metabolism. Methods Ten subjects (n = 3 men; n = 7 women; 42 ± 11.8 years of age; BMI 26 ± 5.8 kg/m2) participated in six 1-day independent acute interventions, each meal containing 30 g of protein from buckwheat, fava bean, pea, hemp, lupin and meat (beef). Blood samples were collected during 24-h and VAS questionnaires over 5-h. Results Volunteers consumed significantly higher amounts of most amino acids from the meat meal, and with few exceptions, postprandial composition of plasma amino acids was not significantly different after consuming the plant-based meals. Buckwheat meal was the most satious (300 min hunger scores, p < 0.05).Significant increase in GLP-1 plasma (AUC, iAUC p = 0.01) found after hemp compared with the other plant-based meals. Decreased plasma ghrelin concentrations (iAUC p < 0.05) found on plant (hemp) vs. meat meal. Several plasma metabolites after hemp meal consumption were associated with hormone trends (partial least squares-discriminant analysis (PLS-DA): 4-hydroxyphenylpyruvic acid, indole 3-pyruvic acid, 5-hydoxytryptophan, genistein and biochanin A with GLP-1, PYY and insulin; 3-hydroxymandelic acid and luteolidin with GLP-1 and ghrelin and 4-hydroxymandelic acid, benzoic acid and secoisolariciresinol with insulin and ghrelin. Plasma branched-chain amino acids (BCAAs), (iAUC, p < 0.001); and phenylalanine and tyrosine (iAUC, p < 0.05) were lower after buckwheat comparison with meat meal. Conclusion Plants are valuable sources of amino acids which are promoting satiety. The impact of hemp and buckwheat on GLP-1 and, respectively, BCAAs should be explored further as could be relevant for aid and prevention of chronic diseases such as type 2 diabetes. Study registered with clinicaltrial.gov on 12th July 2013, study ID number: NCT01898351.


1998 ◽  
Vol 275 (3) ◽  
pp. E423-E431 ◽  
Author(s):  
Satish C. Kalhan ◽  
Karen Q. Rossi ◽  
Lourdes L. Gruca ◽  
Dennis M. Super ◽  
Samuel M. Savin

Protein and nitrogen (N) accretion by the mother is a major adaptive response to pregnancy in humans and animals to meet the demands of the growing conceptus. Quantitative changes in whole body N metabolism were examined during normal pregnancy by measuring the rates of leucine N ( QN) and carbon ( QC) kinetics with the use of [1-13C,15N]leucine. Rate of synthesis of urea was measured by [15N2]urea tracer. Pregnancy-related change in total body water was quantified by H2[18O] dilution, and respiratory calorimetry was performed to quantify substrate oxidation. A significant decrease in the rate of urea synthesis was evident in the 1st trimester (nonpregnant 4.69 ± 1.14 vs. pregnant 3.44 ± 1.11 μmol ⋅ kg−1⋅ min−1; means ± SD, P < 0.05). The lower rate of urea synthesis was sustained through the 2nd and 3rd trimesters. QNwas also lower in the 1st trimester during fasting; however, it reached a significant level only in the 3rd trimester (nonpregnant 166 ± 35 vs. 3rd trimester 135 ± 16 μmol ⋅ kg−1⋅ h−1; P < 0.05). There was no significant change in QCduring pregnancy. A significant decrease in the rate of transamination of leucine was evident in the 3rd trimester both during fasting and in response to nutrient administration ( P< 0.05). The rate of deamination of leucine was correlated with the rate of urea synthesis during fasting ( r = 0.59, P = 0.001) and during feeding ( r = 0.407, P = 0.01). These data show that pregnancy-related adaptations in maternal N metabolism are evident early in gestation before any significant increase in fetal N accretion. It is speculated that the lower transamination of branched-chain amino acids may be due to decreased availability of N acceptors such as α-ketoglutarate as a consequence of resistance to insulin action evident in pregnancy.


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