bims-polyam 2021-11-28 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2021–11–28
thirteen papers selected by
Sebastian J. Hofer, University of Graz

Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice.
Spermidine Suppressed the Inhibitory Effects of Polyamines Inhibitors Combination in Maize (Zea mays L.) Seedlings under Chilling Stress.
miR27a, a fine-tuning molecule, interacts with growth hormone (GH) signaling and ornithine decarboxylase (ODC) via targeting STAT5.
Polyamines Involved in Regulating Self-Incompatibility in Apple.
Differences in Polyamine Content between Human Milk and Infant Formulas.
The citrus plant pathogen Xanthomonas citri has a dual polyamine-binding protein.
Spermine-Mediated Tolerance to Selenium Toxicity in Wheat (Triticum aestivum L.) Depends on Endogenous Nitric Oxide Synthesis.
Arginase 2 and Polyamines in Human Pancreatic Beta Cells: Possible Role in the Pathogenesis of Type 2 Diabetes.
Fine-tuning spermidine binding modes in the putrescine binding protein PotF.
Alleviating Chilling Injury in Stored Pomegranate Using a Single Intermittent Warming Cycle: Fatty Acid and Polyamine Modifications.
Acupuncture Synergized With Bortezomib Improves Survival of Multiple Myeloma Mice via Decreasing Metabolic Ornithine.
Non-targeted metabolomics identify polyamine metabolite acisoga as novel biomarker for reduced left ventricular function.
Urinary Metabolomic Profile of Neonates Born to Women with Gestational Diabetes Mellitus.

Nutrients. 2021 Oct 21. pii: 3700. [Epub ahead of print]13(11):

Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice.

Genís Campreciós, Maria Ruart, Aina Anton, Nuria Suárez-Herrera, Carla Montironi, Celia Martínez, Natalia Jiménez, Erica Lafoz, Héctor García-Calderó, Marina Vilaseca, Marta Magaz, Mar Coll, Isabel Graupera, Scott L Friedman, Joan Carles García-Pagán, Virginia Hernández-Gea.

  Chronic liver diseases are multifactorial and the need to develop effective therapies is high. Recent studies have shown the potential of ameliorating liver disease progression through protection of the liver endothelium. Polyamine spermidine (SPD) is a caloric restriction mimetic with autophagy-enhancing properties capable of prolonging lifespan and with a proven beneficial effect in cardiovascular disease in mice and humans. We evaluated the use of dietary supplementation with SPD in two models of liver disease (CCl4 and CDAAH diet). We analyzed the effect of SPD on endothelial dysfunction in vitro and in vivo. C57BL/6J mice were supplemented with SPD in the drinking water prior and concomitantly with CCl4 and CDAAH treatments. Endothelial autophagy deficient (Atg7endo) mice were also evaluated. Liver tissue was used to evaluate the impact of SPD prophylaxis on liver damage, endothelial dysfunction, oxidative stress, mitochondrial status, inflammation and liver fibrosis. SPD improved the endothelial response to oxidative injury in vitro and improved the liver endothelial phenotype and protected against liver injury in vivo. SPD reduced the overall liver oxidative stress and improved mitochondrial fitness. The absence of benefits in the Atg7endo mice suggests an autophagy-dependent effect of SPD. This study suggests SPD diet supplementation in early phases of disease protects the liver endothelium from oxidative stress and may be an attractive approach to modify the chronic liver disease course and halt fibrosis progression.

Keywords:  LSEC; autophagy; endothelial dysfunction; liver fibrosis; mitophagy

DOI:  https://doi.org/10.3390/nu13113700
Plants (Basel). 2021 Nov 10. pii: 2421. [Epub ahead of print]10(11):

Spermidine Suppressed the Inhibitory Effects of Polyamines Inhibitors Combination in Maize (Zea mays L.) Seedlings under Chilling Stress.

Canhong Gao, Mohamed S Sheteiwy, Chen Lin, Yajing Guan, Zaid Ulhassan, Jin Hu.

  Chilling stress greatly inhibited the seed germination, plant growth, development and productivity in this study. The current research aimed to study the effects of different polyamine (PA) inhibitor combinations (Co), e.g., D-arginine (D-Arg), difluoromethylormithine (DFMO), aminoguanidine (Ag) and methylglyoxyl-bis-(guanyhydrazone) (MGBG) at different doses, i.e., 10 µM Co, 100 µM Co, 500 µM Co, 1000 µM Co and 1000 µM Co + 1 mM Spd (Spermidine) in two inbred lines of maize (Zea mays L.), i.e., Mo17 and Huang C, a sensitive and tolerant chilling stress, respectively. The combination treatments of PA inhibitors reduced the biosynthesis of putrescine (Put) in the tissues of both studied inbred lines. Application with 500 µM Co and 1000 µM Co did not result in a significant difference in Put concentrations, except in the coleoptile of Mo17. However, combining Spd to 1000 μM of PA inhibitors enhanced the Put, Spd, spermine (Spm) and total PAs in the roots, coleoptile and mesocotyls. Put and total PAs were increased by 39.7% and 30.54%, respectively, when Spd + 1000 µM Co were applied relative to their controls. Chilling stress and PA inhibitors treatments affected both inbred lines and resulted in differences in the PA contents. Results showed that enzymes involved in the biosynthesis of PAs (ornithine decarboxylase as ODC and S-adenosylmethionine decarboxylase as SAMDC) were significantly downregulated by 1000 µM Co in the tissues of both inbred lines. In contrast, the activity of PAO, a Pas degradation enzyme, was significantly improved by 1000 µM Co under chilling stress. However, Spd + 1000 µM Co significantly improved the activities of ODC and SAMDC and their transcript levels (ODC and SAMDC2). While it significantly downregulated the PAO activity and their relative genes (PAO1, PAO2 and PAO3) under chilling stress. Overall, this study elucidates the specific roles of Spd on the pathway of PA inhibitors and PA biosynthesis metabolism in maize seed development in response to chilling stress. Moreover, the Huang C inbred line was more tolerant than Mo17, which was reflected by higher activities of PA biosynthesis-related enzymes and lower activities of PAs' degradative-related enzymes in Huang C.

Keywords:  chilling stress; gene expression; maize; polyamines; spermidine

DOI:  https://doi.org/10.3390/plants10112421
Amino Acids. 2021 Nov 26.

miR27a, a fine-tuning molecule, interacts with growth hormone (GH) signaling and ornithine decarboxylase (ODC) via targeting STAT5.

Ajda Coker-Gurkan, Kadriye Koyuncu, Pinar Obakan Yerlikaya, Elif Damla Arisan.

  Autocrine growth hormone (GH) expression triggers cell proliferation, invasion-metastasis in vitro and in vivo models, but GH gene mutations inhibit postnatal growth. Natural polyamines (PA); putrescine, spermidine, spermine trigger cell growth and differentiation. The importance of miR27a has shown to exert a suppressive effect on ornithine decarboxylase (ODC) expression in dwarf mice models. We aimed to modulate the role of A13S, F166Δ, T24 GH gene mutations' impact on PA metabolism and epithelial-mesencyhmal transition (EMT) pathway through miR27a. Biologically active GH signaling triggered cell viability, growth, and colony formation, but T24A alteration significantly decreases aggressive profiles due to inactive GH signaling through a decline in STAT5 activity and expressions of STAT5, c-myc and ODC. Although statistically significant increase in intracellular PA levels in wt GH signaling HEK293 cells compared to HEK293 cells with a lack of GH signaling, a sharp decline in PA levels measured in each mutant GH expressing HEK293 cells. When we inhibited miR27a, proliferation and colony formation accelerated through a significant increase in putrescine levels and upregulation of ODC, STAT5 expression. In contrast, a substantial decline in GH-mediated colony enlargement observed via ODC, STAT5 downregulation, and PA depletion in both wt and mutant GH expressing HEK293 cell lines by miR27a mimic transfection. In conclusion, T24A mutant GH expression declines the GH signaling through STAT5 activity, and mutant GH signaling decreased cell proliferation, division, and colony formation via EMT inhibition. The autocrine GH-mediated proliferative profiles were under the control of miR27a that depletes intracellular putrescine levels via targeting ODC.

Keywords:  EMT pathway; Growth hormone; ODC; Polyamine; miRNA27a

DOI:  https://doi.org/10.1007/s00726-021-03101-9
Genes (Basel). 2021 Nov 15. pii: 1797. [Epub ahead of print]12(11):

Polyamines Involved in Regulating Self-Incompatibility in Apple.

Jie Yu, Baoan Wang, Wenqi Fan, Songbo Fan, Ya Xu, Chunsheng Liu, Tianxing Lv, Wanda Liu, Ling Wu, Linfeng Xian, Tianzhong Li.

  Apple exhibits typical gametophytic self-incompatibility, in which self-S-RNase can arrest pollen tube growth, leading to failure of fertilization. To date, there have been few studies on how to resist the toxicity of self-S-RNase. In this study, pollen tube polyamines were found to respond to self-S-RNase and help pollen tubes defend against self-S-RNase. In particular, the contents of putrescine, spermidine, and spermine in the pollen tube treated with self-S-RNase were substantially lower than those treated with non-self-S-RNase. Further analysis of gene expression of key enzymes in the synthesis and degradation pathways of polyamines found that the expression of DIAMINE OXIDASE 4 (MdDAO4) as well as several polyamine oxidases such as POLYAMINE OXIDASES 3 (MdPAO3), POLYAMINE OXIDASES 4 (MdPAO4), and POLYAMINE OXIDASES 6 (MdPAO6) were significantly up-regulated under self-S-RNase treatment, resulting in the reduction of polyamines. Silencing MdPAO6 in pollen tubes alleviates the inhibitory effect of self-S-RNase on pollen tube growth. In addition, exogenous polyamines also enhance pollen tube resistance to self-S-RNase. Transcriptome sequencing data found that polyamines may communicate with S-RNase through the calcium signal pathway, thereby regulating the growth of the pollen tubes. To summarize, our results suggested that polyamines responded to the self-incompatibility reaction and could enhance pollen tube tolerance to S-RNase, thus providing a potential way to break self-incompatibility in apple.

Keywords:  S-RNase; apple; pollen tube; polyamines; self-incompatibility

DOI:  https://doi.org/10.3390/genes12111797
Foods. 2021 Nov 19. pii: 2866. [Epub ahead of print]10(11):

Differences in Polyamine Content between Human Milk and Infant Formulas.

Nelly C Muñoz-Esparza, Oriol Comas-Basté, M Luz Latorre-Moratalla, M Teresa Veciana-Nogués, M Carmen Vidal-Carou.

  Human milk is the gold standard for nutrition during the first months of life, but when breastfeeding is not possible, it may be replaced by infant formulas, either partially or totally. Polyamines, which play an important role in intestinal maturation and the development of the immune system, are found both in human milk and infant formulas, the first exogenous source of these compounds for the newborn. The aim of this study was to evaluate the occurrence and evolution of polyamines in human milk during the first semester of lactation and to compare the polyamine content with that of infant formulas. In total, 30 samples of human milk provided by six mothers during the first five months of lactation as well as 15 different types of infant formulas were analyzed using UHPLC-FL. Polyamines were detected in all human milk samples but with great variation among mothers. Spermidine and spermine levels tended to decrease during the lactation period, while putrescine remained practically unchanged. Considerable differences were observed in the polyamine contents and profiles between human milk and infant formulas, with concentrations being up to 30 times lower in the latter. The predominant polyamines in human milk were spermidine and spermine, and putrescine in infant formulas.

Keywords:  breastfeeding; human milk; infant formulas; polyamines; putrescine; spermidine; spermine

DOI:  https://doi.org/10.3390/foods10112866
Biochem Biophys Rep. 2021 Dec;28 101171

The citrus plant pathogen Xanthomonas citri has a dual polyamine-binding protein.

Aline Sampaio Cremonesi, Lilia I De la Torre, Maximillia Frazão de Souza, Gabriel S Vignoli Muniz, M Teresa Lamy, Cristiano Luis Pinto Oliveira, Andrea Balan.

  ATP-Binding Cassette transporters (ABC transporters) are protein complexes involved in the import and export of different molecules, including ions, sugars, peptides, drugs, and others. Due to the diversity of substrates, they have large relevance in physiological processes such as virulence, pathogenesis, and antimicrobial resistance. In Xanthomonas citri subsp. citri, the phytopathogen responsible for the citrus canker disease, 20% of ABC transporters components are expressed under infection conditions, including the putative putrescine/polyamine ABC transporter, PotFGHI. Polyamines are ubiquitous molecules that mediate cell growth and proliferation and play important role in bacterial infections. In this work, we characterized the X. citri periplasmic-binding protein PotF (XAC2476) using bioinformatics, biophysical and structural methods. PotF is highly conserved in Xanthomonas sp. genus, and we showed it is part of a set of proteins related to the import and assimilation of polyamines in X. citri. The interaction of PotF with putrescine and spermidine was direct and indirectly shown through fluorescence spectroscopy analyses, and experiments of circular dichroism (CD) and small-angle X-ray scattering (SAXS), respectively. The protein showed higher affinity for spermidine than putrescine, but both ligands induced structural changes that coincided with the closing of the domains and increasing of thermal stability.

Keywords:  Ligand-induced conformational changes; Polyamine binding; PotF; Putrescine; Spermidine; Substrate-binding protein; Xanthomonas citri

DOI:  https://doi.org/10.1016/j.bbrep.2021.101171
Antioxidants (Basel). 2021 Nov 19. pii: 1835. [Epub ahead of print]10(11):

Spermine-Mediated Tolerance to Selenium Toxicity in Wheat (Triticum aestivum L.) Depends on Endogenous Nitric Oxide Synthesis.

Md Mahadi Hasan, Basmah M Alharbi, Haifa Abdulaziz Sakit Alhaithloul, Awatif M Abdulmajeed, Suliman Mohammed Alghanem, Amina A M Al-Mushhin, Mohammad Shah Jahan, Francisco J Corpas, Xiang-Wen Fang, Mona H Soliman.

  Excess selenium (Se) causes toxicity, and nitric oxide (NO)'s function in spermine (Spm)-induced tolerance to Se stress is unknown. Using wheat plants exposed to 1 mM sodium selenate-alone or in combination with either 1 mM Spm, 0.1 mM NO donor sodium nitroprusside (SNP) or 0.1 mM NO scavenger cPTIO-the potential beneficial effects of these compounds to palliate Se-induced stress were evaluated at physiological, biochemical and molecular levels. Se-treated plants accumulated Se in their roots (92%) and leaves (95%) more than control plants. Furthermore, Se diminished plant growth, photosynthetic traits and the relative water content and increased the levels of malondialdehyde, H2O2, osmolyte and endogenous NO. Exogenous Spm significantly decreased the levels of malondialdehyde by 28%, H2O2 by 37% and electrolyte leakage by 42%. Combined Spm/NO treatment reduced the Se content and triggered plant growth, photosynthetic traits, antioxidant enzymes and glyoxalase systems. Spm/NO also upregulated MTP1, MTPC3 and HSP70 and downregulated TaPCS1 and NRAMP1 (metal stress-related genes involved in selenium uptake, translocation and detoxification). However, the positive effects of Spm on Se-stressed plants were eliminated by the NO scavenger. Accordingly, data support the notion that Spm palliates selenium-induced oxidative stress since the induced NO elicits antioxidant defence upregulation but downregulates Se uptake and translocation. These findings pave the way for potential biotechnological approaches to supporting sustainable wheat crop production in selenium-contaminated areas.

Keywords:  antioxidant enzymes; gene expression; glyoxalase systems; oxidative stress; reactive oxygen species (ROS)

DOI:  https://doi.org/10.3390/antiox10111835
Int J Mol Sci. 2021 Nov 09. pii: 12099. [Epub ahead of print]22(22):

Arginase 2 and Polyamines in Human Pancreatic Beta Cells: Possible Role in the Pathogenesis of Type 2 Diabetes.

Lorella Marselli, Emanuele Bosi, Carmela De Luca, Silvia Del Guerra, Marta Tesi, Mara Suleiman, Piero Marchetti.

  Arginase 2 (ARG2) is a manganese metalloenzyme involved in several tissue specific processes, from physiology to pathophysiology. It is variably expressed in extra-hepatic tissues and is located in the mitochondria. In human pancreatic beta cells, ARG2 is downregulated in type 2 diabetes. The enzyme regulates the synthesis of polyamines, that are involved in pancreas development and regulation of beta cell function. Here, we discuss several features of ARG2 and polyamines, which can be relevant to the pathophysiology of type 2 diabetes.

Keywords:  arginase 2; beta cells; pancreatic islets; polyamines; type 2 diabetes

DOI:  https://doi.org/10.3390/ijms222212099
J Biol Chem. 2021 Nov 18. pii: S0021-9258(21)01228-X. [Epub ahead of print] 101419

Fine-tuning spermidine binding modes in the putrescine binding protein PotF.

Pascal Kröger, Sooruban Shanmugaratnam, Ulrike Scheib, Birte Höcker.

A profound understanding of the molecular interactions between receptors and ligands is important throughout diverse research such as protein design, drug discovery, or neuroscience. What determines specificity and how do proteins discriminate against similar ligands? In this study we analyzed factors that determine binding in two homologs belonging to the well-known superfamily of periplasmic binding proteins (PBPs), PotF and PotD. Building on a previously designed construct modes of polyamine binding were swapped. This change of specificity was approached by analyzing local differences in the binding pocket as well as overall conformational changes in the protein. Throughout the study, protein variants were generated and characterized structurally and thermodynamically, leading to a specificity swap and improvement in affinity. This dataset not only enriches our knowledge applicable to rational protein design, but our results can further lay groundwork for engineering of specific biosensors as well as help to explain the adaptability of pathogenic bacteria.

DOI: https://doi.org/10.1016/j.jbc.2021.101419
Int J Food Sci. 2021 ;2021 2931353

Alleviating Chilling Injury in Stored Pomegranate Using a Single Intermittent Warming Cycle: Fatty Acid and Polyamine Modifications.

Leila Taghipour, Majid Rahemi, Pedram Assar, Asghar Ramezanian, Seyed Hossein Mirdehghan.

Pomegranate is a perishable superfruit with important human health-promoting phytochemicals. The use of cold storage is inevitable for its long-term preservation. As pomegranate is sensitive to temperatures below 5°C, it is therefore necessary and worthwhile to introduce a postharvest technique that is safe, applicable, and commercially acceptable to maintain the fruit quality under a cold storage condition. The efficacy of intermittent warming (IW) in the form of a single warming period (1 day at 20°C with 70% relative humidity (RH) before returning the treated fruit to storage) during the cold storage of 'Rabab-e-Neyriz' pomegranate (70 days at 2 ± 0.5°C and 90 ± 5% RH) was evaluated. To find the best treatment time, warming was performed at 4 temporary interruption points in storage (after 15, 25, 35, or 45 days of storage). For each interruption date, the treated fruit were compared to the controls twice, once immediately after treatment and once at the end of the storage period. It was founded that a single warming period at the right time during cold storage (before irreversible damage occurs) activated multiple mechanisms and physiological responses in pomegranate fruit peel that are significantly responsible for alleviating the severity of chilling damage to this commodity. In other words, warming on the 15th day was the most efficient treatment, resulting in better preservation of unsaturated fatty acids from peroxidation, lower malondialdehyde (MDA) production, and preservation of the unsaturated/saturated fatty acids (UFAs/SFAs) ratio (membrane integrity index) in the peel during storage and lower chilling injury symptoms. Moreover, the content of spermine (Spm) and putrescine (Put) (as important antioxidants acting as membrane safety agents) was significantly increased immediately after treatment, followed by a continuous increase in Spm and a higher level of Put compared to control until the end of storage.

DOI: https://doi.org/10.1155/2021/2931353
Front Oncol. 2021 ;11 779562

Acupuncture Synergized With Bortezomib Improves Survival of Multiple Myeloma Mice via Decreasing Metabolic Ornithine.

Mengying Ke, Jinjun Qian, Feng Hao, Xinying Li, Hongjie Wu, Xian Luo, Bin Xu, Chunyan Gu, Ye Yang.

  Multiple myeloma (MM) is a hematological malignancy worldwide in urgent need for novel therapeutic strategies. Since Velcade (bortezomib) was approved for the treatment of relapsed/refractory MM in 2003, we have seen considerable improvement in extending MM patient survival. However, most patients are fraught with high recurrence rate and incurability. Acupuncture is known for alleviating patient symptoms and improving the quality of life, but it is not well investigated in MM, especially in combination with bortezomib. In this study, we employed LC-MS and UHPLC-MS together with bioinformatics methods to test serum samples from 5TMM3VT MM murine model mice with four different treatments [control (C) group, bortezomib (V) treatment group, acupuncture (A) group, and combined (VA) group]. MM mice in group VA had longer survival time than mice in group A or group V. Joint pathway analysis indicated the underlying arginine and proline metabolism pathway among the 32 significantly decreased metabolites in group VA. CCK-8 assay and in vivo experiments validated that ornithine, the metabolite of arginine, promoted MM cell proliferation. In addition, gene expression omnibus (GEO) database analysis suggested that MM patients with higher ornithine decarboxylase 1 (ODC1) expression were evidently associated with poor overall survival. In summary, this study demonstrates the synergistic effects of acupuncture and bortezomib on extending the survival of MM model mice and provides potential therapeutic targets in the treatment of MM.

Keywords:  ODC1; acupuncture; metabolomics; multiple myeloma; ornithine

DOI:  https://doi.org/10.3389/fonc.2021.779562
ESC Heart Fail. 2021 Nov 22.

Non-targeted metabolomics identify polyamine metabolite acisoga as novel biomarker for reduced left ventricular function.

Andreas Puetz, Anna Artati, Jerzy Adamski, Katharina Schuett, Francesco Romeo, Robert Stoehr, Nikolaus Marx, Massimo Federici, Michael Lehrke, Ben A Kappel.

   AIMS: Chronic heart failure with reduced ejection fraction remains a major health issue. To date, no reliable biomarker is available to predict reduced left ventricular ejection fraction (LV-EF). We aimed to identify novel circulating biomarkers for reduced left ventricular function using untargeted serum metabolomics in two independent patient cohorts.
METHODS AND RESULTS: Echocardiography and non-targeted serum metabolomics were conducted in two patient cohorts with varying left ventricular function: (1) 25 patients with type 2 diabetes with established cardiovascular disease or high cardiovascular risk (LV-EF range 20-66%) (discovery cohort) and (2) 37 patients hospitalized for myocardial infarction (LV-EF range 25-60%) (validation cohort). In the discovery cohort, untargeted metabolomics revealed seven metabolites performing better than N-terminal pro-B-type natriuretic peptide in the prediction of impaired left ventricular function shown by LV-EF. For only one of the metabolites, acisoga, the predictive value for LV-EF could be confirmed in the validation cohort (r = -0.37, P = 0.02). In the discovery cohort, acisoga did not only correlate with LV-EF (r = -60, P = 0.0016), but also with global circumferential strain (r = 0.67, P = 0.0003) and global longitudinal strain (r = 0.68, P = 0.0002). Similar results could be detected in the discovery cohort in a 6 month follow-up proofing stability of these results over time. With an area under the curve of 0.86 in the receiver operating characteristic analysis, acisoga discriminated between patients with normal EF and LV-EF < 40%. Multivariate analysis exposed acisoga as independent marker for impairment of LV-EF (Beta = -0.71, P = 0.004).
CONCLUSIONS: We found the polyamine metabolite acisoga to be elevated in patients with impaired LV-EF in two independent cohorts. Our analyses suggest that acisoga may be a valuable biomarker to detect patients with heart failure with reduced ejection fraction.

Keywords:  Biomarker; Ejection fraction; HFrEF; Heart failure; Metabolomics; Polyamine metabolism

DOI:  https://doi.org/10.1002/ehf2.13713
Metabolites. 2021 Oct 22. pii: 723. [Epub ahead of print]11(11):

Urinary Metabolomic Profile of Neonates Born to Women with Gestational Diabetes Mellitus.

Ana Sofía Herrera-Van Oostdam, Mariana Salgado-Bustamante, Victoria Lima-Rogel, Juan José Oropeza-Valdez, Jesús Adrián López, Iván Daniel Román Rodríguez, Juan Carlos Toro-Ortiz, David Alejandro Herrera-Van Oostdam, Yamilé López-Hernández, Joel Monárez-Espino.

  Gestational diabetes mellitus (GDM) is one of the most frequent pregnancy complications with potential adverse outcomes for mothers and newborns. Its effects on the newborn appear during the neonatal period or early childhood. Therefore, an early diagnosis is crucial to prevent the development of chronic diseases later in adult life. In this study, the urinary metabolome of babies born to GDM mothers was characterized. In total, 144 neonatal and maternal (second and third trimesters of pregnancy) urinary samples were analyzed using targeted metabolomics, combining liquid chromatographic mass spectrometry (LC-MS/MS) and flow injection analysis mass spectrometry (FIA-MS/MS) techniques. We provide here the neonatal urinary concentration values of 101 metabolites for 26 newborns born to GDM mothers and 22 newborns born to healthy mothers. The univariate analysis of these metabolites revealed statistical differences in 11 metabolites. Multivariate analyses revealed a differential metabolic profile in newborns of GDM mothers characterized by dysregulation of acylcarnitines, amino acids, and polyamine metabolism. Levels of hexadecenoylcarnitine (C16:1) and spermine were also higher in newborns of GDM mothers. The maternal urinary metabolome revealed significant differences in butyric, isobutyric, and uric acid in the second and third trimesters of pregnancy. These metabolic alterations point to the impact of GDM in the neonatal period.

Keywords:  gestational diabetes; metabolomics; newborns; pregnancy

DOI:  https://doi.org/10.3390/metabo11110723