Urinary metabolomics (GC-MS) reveals that low and high birth weight infants share elevated inositol concentrations at birth

Barberini, Luigi; Noto, Antonio; Fattuoni, Claudia; Grapov, Dmitry; Casanova, Andrea; Fenu, Gianni; Gaviano, Mauro; Carboni, Roberta; Ottonello, Giovanni; Crisafulli, M.; Fanos, Vassilios; Dessì, Angelica

doi:10.3109/14767058.2014.954786

Cited by 37 publications

(33 citation statements)

References 21 publications

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“…Myoinositol is a cyclitol essential for proper cellular function and has been implicated in glucose homeostasis. Altered fetal levels of myoinositol have been shown in ass o c i a t i o nw i t hI U G Ri nh u m a n sa n da n i m a lm o d e l s (60)(61)(62)(63). Aberrations of myoinositol metabolism are associated with insulin resistance and diabetic complications [reviewed in ref.…”

Section: Discussionmentioning

confidence: 99%

“…There are numerous metabolomic analyses of the immediate effects of IUGR, and on later metabolism, however, fewer studies have examined metabolomic changes in concert with interventions that modify the onset of adult MetS. Specific studies have examined the effects of IUGR in cord blood or urine immediately following birth (60,62,(92)(93)(94)(95). Others, by use of animal models, have examined the effects of IUGR (96)(97)(98)(99), as well as developing MetS (60,97,100), in the F1 generation.…”

Section: Discussionmentioning

confidence: 99%

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Heritable IUGR and adult metabolic syndrome are reversible and associated with alterations in the metabolome following dietary supplementation of 1‐carbon intermediates

et al. 2015

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Metabolic syndrome (MetS), following intrauterine growth restriction (IUGR), is epigenetically heritable. Recently, we abrogated the F2 adult phenotype with essential nutrient supplementation (ENS) of intermediates along the 1-carbon pathway. With the use of the same grandparental uterine artery ligation model, we profiled the F2 serum metabolome at weaning [postnatal day (d)21; n = 76] and adulthood (d160; n = 12) to test if MetS is preceded by alterations in the metabolome. Indicative of developmentally programmed MetS, adult F2, formerly IUGR rats, were obese (621 vs. 461 g; P < 0.0001), dyslipidemic (133 vs. 67 mg/dl; P < 0.001), and glucose intolerant (26 vs. 15 mg/kg/min; P < 0.01). Unbiased gas chromatography-mass spectrometry (GC-MS) profiling revealed 34 peaks corresponding to 12 nonredundant metabolites and 9 unknowns to be changing at weaning [false discovery rate (FDR) < 0.05]. Markers of later-inlife MetS included citric acid, glucosamine, myoinositol, and proline (P < 0.03). Hierarchical clustering revealed grouping by IUGR lineage and supplementation at d21 and d160. Weanlings grouped distinctly for ENS and IUGR by partial least-squares discriminate analysis (PLS-DA; P < 0.01), whereas paternal and maternal IUGR (IUGR pat / IUGR mat , respectively) control-fed rats, destined for MetS, had a distinct metabolome at weaning (randomForest analysis; class error < 0.1) and adulthood (PLS-DA; P < 0.05). In sum, we have found that alterations in the metabolome accompany heritable IUGR, precede adult-onset MetS, and are partially amenable to dietary intervention.-

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Heritable IUGR and adult metabolic syndrome are reversible and associated with alterations in the metabolome following dietary supplementation of 1‐carbon intermediates

et al. 2015

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“…14−16 The noninvasive collection of newborn urine and subsequent ease to address large cohorts, compared to newborn blood, makes it a particularly interesting biofluid in the present context. This has indeed been recognized in reports on the newborn urinary impact of prematurity, 17−20 IUGR, 21−23 large for gestational age (LGA), 22,23 GDM, 3 asphyxia, 11,24,25 respiratory distress syndrome (RDS), 24 meconium aspiration syndrome (MAS), 24 bronchopulmonary dysplasia, 26 IEM, 27 neonatal sepsis, 28 postnatal bacterial, 19 cytomegalovirus, 29 and fungal 30 infections. Most of these studies have considered relatively small cohorts (up to ca.…”

Section: ■ Introductionmentioning

confidence: 99%

Newborn Urinary Metabolic Signatures of Prematurity and Other Disorders: A Case Control Study

et al. 2015

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This work assesses the urinary metabolite signature of prematurity in newborns by nuclear magnetic resonance (NMR) spectroscopy, while establishing the role of possible confounders and signature specificity, through comparison to other disorders. Gender and delivery mode are shown to impact importantly on newborn urine composition, their analysis pointing out at specific metabolite variations requiring consideration in unmatched subject groups. Premature newborns are, however, characterized by a stronger signature of varying metabolites, suggestive of disturbances in nucleotide metabolism, lung surfactants biosynthesis and renal function, along with enhancement of tricarboxylic acid (TCA) cycle activity, fatty acids oxidation, and oxidative stress. Comparison with other abnormal conditions (respiratory depression episode, large for gestational age, malformations, jaundice and premature rupture of membranes) reveals that such signature seems to be largely specific of preterm newborns, showing that NMR metabolomics can retrieve particular disorder effects, as well as general stress effects. These results provide valuable novel information on the metabolic impact of prematurity, contributing to the better understanding of its effects on the newborn's state of health.

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“…Among the metabolites identified in the "galactose metabolism" pathway, the myo-inositol concentration had already been proposed as a marker of development of obesity and type 2 diabetes in human adults [14,26] and also as a marker of IUGR in humans [1,15] and pigs [40]. In these previous studies, a higher plasma or urine concentration of myo-inositol was associated with a higher risk of IUGR and, thus, with a lower maturity.…”

Section: Discussionmentioning

confidence: 99%

The maturity in fetal pigs using a multi-fluid metabolomic approach

Lefort

Servien

Quesnel

et al. 2020

Preprint

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In mammalian species, the first days after birth are an important period for survival and the rates of mortality before weaning are high. In pigs, the perinatal deaths average 20% of the litter, with important economic and societal consequences. Among the factors influencing piglet survival at birth, the maturity is likely to be one of the most important. Maturity can be defined as the outcome of complex mechanisms of intra-uterine development and maturation occurring during the last month of gestation. Here, we provide new insights on maturity by studying the end of gestation at two different stages (three weeks before term and close to term) in two breeds of pigs that strongly differ in terms of neonatal survival. Since metabolomics is a promising approach for phenotype characterization or biomarker discovery, we provide a complete understanding of the metabolome of the fetuses in late gestation in three fluids (plasma, urine, and amniotic fluid). We found that biological processes related to amino acid and carbohydrate metabolisms are critical for piglet maturity. We also confirmed some previously described metabolites associated with delayed growth (e.g., proline and myo-inositol). Altogether, our study proposes new routes for a better characterization of piglet maturity at birth.

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Urinary metabolomics (GC-MS) reveals that low and high birth weight infants share elevated inositol concentrations at birth

Abstract: We postulate that the increase in plasma and consequently urinary inositol may constitute a marker of altered glucose metabolism during fetal development in both IUGR and LGA newborns.

Cited by 37 publications

References 21 publications

Heritable IUGR and adult metabolic syndrome are reversible and associated with alterations in the metabolome following dietary supplementation of 1‐carbon intermediates

Heritable IUGR and adult metabolic syndrome are reversible and associated with alterations in the metabolome following dietary supplementation of 1‐carbon intermediates

Newborn Urinary Metabolic Signatures of Prematurity and Other Disorders: A Case Control Study

The maturity in fetal pigs using a multi-fluid metabolomic approach

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