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Associations among amino acid, lipid, and glucose metabolic profiles in childhood obesity.

ABSTRACT: BACKGROUND:Plasma-free amino acid profiles have been reported to correlate with obesity and glucose metabolism, and have been studied as potentially useful biomarkers of lifestyle-related diseases affecting metabolism in adulthood. However, knowledge of these relationships is lacking in children, despite the growing public health problem posed by childhood obesity. The aim of this study was to assess whether plasma-free amino acid profiles can serve as useful biomarkers of lifestyle-related diseases in children with obesity. METHODS:This retrospective study used the medical records of 26 patients (15 male, 11 female) aged 9 or 10?years presenting with moderate to severe obesity and hyperlipidemia between April 2015 and March 2017. A degree of obesity of 30% or more was defined as moderate or severe. Amino acid levels were compared between obese children with and without impaired glucose tolerance using a t-test or Mann-Whitney U test. In addition, the influence of factors such as intima media thickness, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, amino acids, and homeostasis model assessment-insulin resistance (HOMA-IR) were analyzed pairwise using Pearson's correlation or Spearman's rank correlation. RESULTS:HOMA-IR was positively correlated with valine, leucine (Leu), isoleucine, phenylalanine, tryptophan, methionine, threonine, lysine, alanine, tyrosine, glutamate (Glu), proline, arginine, ornithine, total free amino acids (all P?

SUBMITTER: Suzuki Y

PROVIDER: S-EPMC6683574 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Associations among amino acid, lipid, and glucose metabolic profiles in childhood obesity.

Suzuki Yosuke Y Kido Jun J Matsumoto Shirou S Shimizu Kie K Nakamura Kimitoshi K

BMC pediatrics 20190806 1

<h4>Background</h4>Plasma-free amino acid profiles have been reported to correlate with obesity and glucose metabolism, and have been studied as potentially useful biomarkers of lifestyle-related diseases affecting metabolism in adulthood. However, knowledge of these relationships is lacking in children, despite the growing public health problem posed by childhood obesity. The aim of this study was to assess whether plasma-free amino acid profiles can serve as useful biomarkers of lifestyle-rela ...[more]

PMID: 31387549

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Project description:Childhood obesity is associated with chronic low-grade inflammation considered as a precursor to metabolic disease; however, the underlying mechanisms for this remain unclear. Studies in adults have implicated gut derived gram-negative bacterial fragments known as lipopolysaccharide or endotoxin, activating the inflammatory response, whilst the importance in childhood obesity is unclear. The aim of this research is to understand the relationship between circulating endotoxin in childhood obesity, and its' association with inflammatory and cardiovascular (CV) injury biomarkers.Fasted blood was obtained from children with varying degrees of obesity (age: 13.9 ± 2.3Yr; BMI: 35.1 ± 5.2 Kg/m(2); n = 60). Multiplex CVD biomarker immunoassays were used to determine systemic levels of inflammatory and vascular injury biomarkers, such as tumour necrosis factor-α (TNF-α), interleukin (IL-) 1β, 6, 8 and 10, plasminogen activator inhibitor-1 (PAI-1), soluble intercellular adhesion molecule type-1 (sICAM-1), matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO) and vascular endothelial growth factor (VEGF) as well as endotoxin levels.Endotoxin levels demonstrated a significant and positive correlation with the markers for inflammation, vascular injury and atherogenesis (TNF-α: r(2) = 0.077, p < 0.05; PAI-1: r(2) = 0.215, p < 0.01; sICAM-1: r(2) = 0.159, p < 0.01; MMP-9: r(2) = 0.159, p < 0.01; MPO: r(2) = 0.07, p < 0.05; VEGF: r(2) = 0.161, p < 0.01). Males demonstrated significantly higher circulating endotoxin than females (Males: 9.63 ± 5.34 EU/ml; p = 0.004; Females: 5.56 ± 4.06 EU/ml; n = 60) in these BMI and age-matched cohorts.The present study demonstrates for the first time a significant association between circulating endotoxin and biomarkers of metabolic risk in children as young as 11 years. Thus, endotoxin-mediated sub-clinical inflammation during childhood obesity may be a key contributor to T2DM and CVD development later in life.

Project description:ObjectiveThis prospective cohort study was aimed at investigating the associations between cord blood metabolic factors and early-childhood growth, further elucidating the relationships between cord blood metabolites and overweight and obesity in early life.MethodsA total of 2,267 pairs of mothers and offspring were recruited in our study. Cord blood plasma was assayed for triglycerides (TGs), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), C-peptide, insulin, and glycosylated hemoglobin type A1C (HbA1c) levels. Data of anthropometric measurements were collected from offspring at birth, 6 months, 12 months, and 18 months. Multiple linear regression models were used to evaluate the correlations between cord blood metabolic factors and weight Z-scores, body mass index (BMI) Z-scores, and weight gains at the early stage of life. Forward stepwise logistic regression analyses were applied to explore the associations between cord blood metabolic factors and early-childhood overweight and obesity. Receiver operating characteristic (ROC) curve analyses were applied to determine the optimal cutoff points for cord blood metabolic factors in predicting early-childhood overweight and obesity.ResultsAfter adjustments for covariates, cord blood TG concentrations and TG/TC ratios were negatively associated with weight Z-scores from birth to 18 months. Cord blood C-peptide and HbA1c levels were inversely associated with weight Z-scores at 6 months and 18 months. Cord blood TG concentrations and TG/TC ratios were negatively correlated with BMI Z-scores up to 18 months. Cord blood C-peptide levels and HbA1c levels were inversely correlated with BMI Z-scores at 18 months. Cord blood TG, TG/TC ratios, C-peptide, and HbA1c had negative correlations with weight gains from birth to 6 months, but the correlations attenuated as time went on. Increase in cord blood TG and HbA1c levels and TG/TC ratios were significantly associated with decreased risks of overweight and obesity at 6 months, 12 months, and 18 months.ConclusionsCord blood metabolic factors were significantly associated with early-childhood growth patterns.

Project description:BACKGROUND AND OBJECTIVES:Metabolomics is instrumental in identifying novel biomarkers of kidney function to aid in the prevention and management of CKD. However, data linking the metabolome to incident eGFR are sparse, particularly in Asian populations with different genetic backgrounds and environmental exposures. Therefore, we aimed to investigate the associations of amino acid and acylcarnitine profiles with change in eGFR in a Chinese cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:This study included 1765 community-living Chinese adults aged 50-70 years with baseline eGFR?60 ml/min per 1.73 m2. At baseline, 22 amino acids and 34 acylcarnitines in plasma were quantified by gas or liquid chromatography coupled with mass spectrometry. Annual rate of change in eGFR was calculated, and incident eGFR decline was defined as eGFR<60 ml/min per 1.73 m2 by the end of 6 years of follow-up. RESULTS:The mean (SD) unadjusted annual change in eGFR was 2.2±2.0 ml/min per 1.73 m2 and the incidence of reduced eGFR was 16%. After Bonferroni correction, 13 of 56 metabolites were significantly associated with annual eGFR change. After multivariable adjustment of baseline covariates, including baseline eGFR, seven of the 13 metabolites, including cysteine, long-chain acylcarnitines (C14:1OH, C18, C18:2, and C20:4), and other acylcarnitines (C3DC and C10), were significantly associated with incident reduced eGFR (relative risks ranged from 1.16 to 1.25 per SD increment of metabolites; P<3.8E-03 after Bonferroni correction of multiple testing of the 13 metabolites). Moreover, principal component analysis identified two factors, consisting of cysteine and long-chain acylcarnitines, respectively, that were associated with incident reduced eGFR. CONCLUSIONS:Elevated plasma levels of cysteine and a panel of acylcarnitines were associated with a higher incidence of reduced eGFR in Chinese adults, independent of baseline eGFR and other conventional risk factors.

Project description:ObjectivePrenatal metabolomics profiles, providing measures of in utero nutritional and environmental exposures, may improve the prediction of childhood outcomes. We aimed to identify prenatal plasma metabolites associated with early childhood body mass index (BMI) trajectories and overweight/obesity risk in offspring.MethodsThis study included 450 African American mother-child pairs from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study. An untargeted metabolomics analysis was performed on the mothers' plasma samples collected during the second trimester. The children's BMI-z-score trajectories from birth to age 4 [rising-high- (9.8%), moderate- (68.2%), and low-BMI (22.0%)] and overweight/obesity status at age 4 were the main outcomes. The least absolute shrinkage and selection operator (LASSO) was used to select the prenatal metabolites associated with childhood outcomes.ResultsThe mothers were 24.5 years old on average at recruitment, 76.4% having education less than 12 years and 80.0% with Medicaid or Medicare. In LASSO, seven and five prenatal metabolites were associated with the BMI-z-score trajectories and overweight/obese at age 4, respectively. These metabolites are mainly from/relevant to the pathways of steroid biosynthesis, amino acid metabolism, vitamin B complex, and xenobiotics metabolism (e.g., caffeine and nicotine). The odds ratios (95% CI) associated with a one SD increase in the prenatal metabolite risk scores (MRSs) constructed from the LASSO-selected metabolites were 2.97 (1.95-4.54) and 2.03 (1.54-2.67) for children being in the rising-high-BMI trajectory group and overweight/obesity at age 4, respectively. The MRSs significantly improved the risk prediction for childhood outcomes beyond traditional prenatal risk factors. The increase (95% CI) in the area under the receiver operating characteristic curves were 0.10 (0.03-0.18) and 0.07 (0.02-0.12) for the rising-high-BMI trajectory (P = 0.005) and overweight/obesity at age 4 (P = 0.007), respectively.ConclusionsPrenatal metabolomics profiles advanced prediction of early childhood growth trajectories and obesity risk in offspring.

Dataset Information

Associations among amino acid, lipid, and glucose metabolic profiles in childhood obesity.

Publications

Associations among amino acid, lipid, and glucose metabolic profiles in childhood obesity.

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