scholarly journals Early Life Iron Excess Enhances Hippocampal Purine Catabolism Through Activation of Xanthine Oxidase in a Nursing Piglet Model (P11-072-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Peng Ji ◽  
Eric Nonnecke ◽  
Nicole Doan ◽  
Bo Lonnerdal ◽  
Bie Tan
Keyword(s):  
Iron Overload ◽  
Xanthine Oxidase ◽  
Early Life ◽  
Redox Balance ◽  
Gas Chromatography Mass Spectrometry ◽  
Purine Salvage ◽  
Atp Production ◽  
Beta Alanine ◽  
Funding Sources ◽  
Purine Degradation

Abstract Objectives Our prior work demonstrated that dietary iron excess in early life results in iron overload in both liver and hippocampus in pre-weanling piglets. Herein, we aimed to identify metabolic processes altered by iron overload in liver and hippocampus. Methods Liver and hippocampal tissues collected from 21-day old nursing piglets receiving high (HI; 50 mg iron/d ${\cdot}$ kg body weight), n = 5) or no oral iron supplementation (NI, n = 5) from birth to PD 21 were analyzed for non-targeted metabolomics, using gas chromatography mass spectrometry. Based on profiled changes in hippocampal metabolites, we further analyzed xanthine oxidase (XO), a rate limiting enzyme for purine degradation, for its mRNA, protein and enzyme activity by RT-qPCR, western blot, and ELISA. Results 108 and 126 metabolites were identified in hippocampus and liver, respectively. In comparison with NI, HI altered abundance of 15 metabolites in hippocampus (P < 0.05, q < 0.2). Myo-inositol and N-acetylaspartic acid, two abundant metabolites in the CNS with broad implications in neuronal function and myelination, were decreased in response to hippocampal iron overload. Seven metabolites involved in purine and pyrimidine metabolism (e.g., hypoxanthine, xanthine and beta-alanine) in hippocampus were modulated in a coordinated pattern by HI, implicating a shift from purine salvage towards degradation, governed by XO. In support of these findings, up-regulation of XO mRNA expression (2.3-fold, P < 0.05) and activity (fold/stats? ) was found in hippocampus but not in liver (P > 0.05). Despite overt iron loading, the hepatic metabolome remained stable (q > 0.2). Conclusions Our findings suggest that iron overload increases hippocampal purine degradation via enhanced XO expression and activity, deleteriously altering tissue redox balance and ROS production. Purine salvage contributes to ATP production in the CNS, where a global shift from purine salvage to degradation due to HI may compromise energetics in the developing hippocampus. Funding Sources UC Davis; NIFA.

scholarly journals Excess Iron Enhances Purine Catabolism Through Activation of Xanthine Oxidase and Impairs Myelination in the Hippocampus of Nursing Piglets

2019 ◽  
Vol 149 (11) ◽  
pp. 1911-1919 ◽  
Author(s):  
Peng Ji ◽  
Eric B Nonnecke ◽  
Nicole Doan ◽  
Bo Lönnerdal ◽  
Bie Tan
Keyword(s):  
Body Weight ◽  
Iron Overload ◽  
Xanthine Oxidase ◽  
Neuronal Function ◽  
Novelty Preference ◽  
Purine Catabolism ◽  
Excess Iron ◽  
Mrna And Protein Expression ◽  
Rate Limiting ◽  
Purine Degradation

Abstract Background Few studies have addressed the risk of nutritional iron overexposure in infancy. We previously found that excess dietary iron in nursing piglets resulted in iron overload in the liver and hippocampus and diminished socialization with novel conspecifics in a test for social novelty preference. Objectives This experiment aimed to identify metabolites and metabolic pathways affected by iron overload in the liver and hippocampus of nursing piglets. Methods Liver and hippocampal tissues collected from 22-d-old piglets (Hampshire × Yorkshire crossbreed; 5.28 ± 0.53 kg body weight; 50% male) that received orally 0 (NI group) or 50 mg iron/(d · kg body weight) (HI group) from postnatal day (PD) 2 to PD21 were analyzed for mRNA and protein expression and enzyme activity of xanthine oxidase (XO). Untargeted metabolomics was performed using GC-MS. Expression of myelin basic protein (MBP) in the hippocampus was determined using western blot. Results There were 108 and 126 metabolites identified in the hippocampus and liver, respectively. Compared with NI, HI altered 15 metabolites (P < 0.05, q < 0.2) in the hippocampus, including a reduction in myo-inositol (0.86-fold) and N-acetylaspartic acid (0.84-fold), 2 metabolites important for neuronal function and myelination. Seven metabolites involved in purine and pyrimidine metabolism (e.g., hypoxanthine, xanthine, and β-alanine) were coordinately changed in the hippocampus (P < 0.05, q < 0.2), suggesting that iron excess enhanced purine catabolism. The mRNA expression (2.3-fold) (P < 0.05) and activity of XO, a rate-limiting enzyme in purine degradation, was increased. Excess iron increased hippocampal lipid peroxidation by 74% (P < 0.05) and decreased MBP by 44% (P = 0.053). The hepatic metabolome was unaffected. Conclusions In nursing piglets, excess iron enhances hippocampal purine degradation through activation of XO, which may induce oxidative stress and alter energy metabolism in the developing brain.

scholarly journals The Stool Volatile Metabolome of Pre-Term Babies

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3341
Author(s):  
Alessandra Frau ◽  
Lauren Lett ◽  
Rachael Slater ◽  
Gregory R. Young ◽  
Christopher J. Stewart ◽  
...  
Keyword(s):  
Early Life ◽  
Solid Phase ◽  
Mass Spectrometry Data ◽  
Gas Chromatography Mass Spectrometry ◽  
Mass Spectral ◽  
Branched Chain Fatty Acids ◽  
Volatile Organic ◽  
Stool Samples ◽  
Branched Chain ◽  
Mixed Modelling

The fecal metabolome in early life has seldom been studied. We investigated its evolution in pre-term babies during their first weeks of life. Multiple (n = 152) stool samples were studied from 51 babies, all <32 weeks gestation. Volatile organic compounds (VOCs) were analyzed by headspace solid phase microextraction gas chromatography mass spectrometry. Data were interpreted using Automated Mass Spectral Deconvolution System (AMDIS) with the National Institute of Standards and Technology (NIST) reference library. Statistical analysis was based on linear mixed modelling, the number of VOCs increased over time; a rise was mainly observed between day 5 and day 10. The shift at day 5 was associated with products of branched-chain fatty acids. Prior to this, the metabolome was dominated by aldehydes and acetic acid. Caesarean delivery showed a modest association with molecules of fungal origin. This study shows how the metabolome changes in early life in pre-term babies. The shift in the metabolome 5 days after delivery coincides with the establishment of enteral feeding and the transition from meconium to feces. Great diversity of metabolites was associated with being fed greater volumes of milk.

scholarly journals Acid Stress-Mediated Metabolic Shift in Lactobacillus sanfranciscensis LSCE1

2011 ◽  
Vol 77 (8) ◽  
pp. 2656-2666 ◽  
Author(s):  
Diana I. Serrazanetti ◽  
Maurice Ndagijimana ◽  
Sylvain L. Sado-Kamdem ◽  
Aldo Corsetti ◽  
Rudi F. Vogel ◽  
...  
Keyword(s):  
Amino Acid ◽  
Solid Phase ◽  
Acid Stress ◽  
Redox Balance ◽  
Gas Chromatography Mass Spectrometry ◽  
Metabolic Shift ◽  
Content Type ◽  
Lactobacillus Sanfranciscensis ◽  
Branched Chain Amino Acid ◽  
Branched Chain

ABSTRACTLactobacillus sanfranciscensisLSCE1 was selected as a target organism originating from recurrently refreshed sourdough to study the metabolic rerouting associated with the acid stress exposure during sourdough fermentation. In particular, the acid stress induced a metabolic shift toward overproduction of 3-methylbutanoic and 2-methylbutanoic acids accompanied by reduced sugar consumption and primary carbohydrate metabolite production. The fate of labeled leucine, the role of different nutrients and precursors, and the expression of the genes involved in branched-chain amino acid (BCAA) catabolism were evaluated at pH 3.6 and 5.8. The novel application of the program XCMS to the solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) data allowed accurate separation and quantification of 2-methylbutanoic and 3-methylbutanoic acids, generally reported as a cumulative datum. The metabolites coming from BCAA catabolism increased up to seven times under acid stress. The gene expression analysis confirmed that some genes associated with BCAA catabolism were overexpressed under acid conditions. The experiment with labeled leucine showed that 2-methylbutanoic acid originated also from leucine. While the overproduction of 3-methylbutanoic acid under acid stress can be attributed to the need to maintain redox balance, the rationale for the production of 2-methylbutanoic acid from leucine can be found in a newly proposed biosynthesis pathway leading to 2-methylbutanoic acid and 3 mol of ATP per mol of leucine. Leucine catabolism to 3-methylbutanoic and 2-methylbutanoic acids suggests that the switch from sugar to amino acid catabolism supports growth inL. sanfranciscensisin restricted environments such as sourdough characterized by acid stress and recurrent carbon starvation.

scholarly journals In silico-guided engineering of Pseudomonas putida towards growth under micro-oxic conditions

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Linde F. C. Kampers ◽  
Ruben G. A. van Heck ◽  
Stefano Donati ◽  
Edoardo Saccenti ◽  
Rita J. M. Volkers ◽  
...  
Keyword(s):  
Pseudomonas Putida ◽  
In Silico ◽  
Redox Balance ◽  
Industrial Applications ◽  
Strictly Aerobic ◽  
Class Iii ◽  
Adaptive Laboratory Evolution ◽  
Laboratory Evolution ◽  
Atp Production ◽  
Lactobacillus Lactis

Abstract Background Pseudomonas putida is a metabolically versatile, genetically accessible, and stress-robust species with outstanding potential to be used as a workhorse for industrial applications. While industry recognises the importance of robustness under micro-oxic conditions for a stable production process, the obligate aerobic nature of P. putida, attributed to its inability to produce sufficient ATP and maintain its redox balance without molecular oxygen, severely limits its use for biotechnology applications. Results Here, a combination of genome-scale metabolic modelling and comparative genomics is used to pinpoint essential $$\text {O}_{2}$$ O 2 -dependent processes. These explain the inability of the strain to grow under anoxic conditions: a deficient ATP generation and an inability to synthesize essential metabolites. Based on this, several P. putida recombinant strains were constructed harbouring acetate kinase from Escherichia coli for ATP production, and a class I dihydroorotate dehydrogenase and a class III anaerobic ribonucleotide triphosphate reductase from Lactobacillus lactis for the synthesis of essential metabolites. Initial computational designs were fine-tuned by means of adaptive laboratory evolution. Conclusions We demonstrated the value of combining in silico approaches, experimental validation and adaptive laboratory evolution for microbial design by making the strictly aerobic Pseudomonas putida able to grow under micro-oxic conditions.

scholarly journals Investigating Relationships Between Breastfeeding Status and Infant Vegetable Experience on Infants’ Acceptance of Novel Vegetables

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 967-967
Author(s):  
Kathryn Davis ◽  
Kameron Moding ◽  
Abigail Flesher ◽  
Rebecca Boenig ◽  
Susan Johnson
Keyword(s):  
Early Life ◽  
Eating Habits ◽  
Descriptive Statistics ◽  
The Novel ◽  
Regression Analyses ◽  
Infants And Toddlers ◽  
Older Children ◽  
Funding Sources ◽  
Child Age

Abstract Objectives Early life flavor exposure is important in shaping lifelong eating habits. We examined relationships among maternal current breastfeeding status, infant vegetable experience and acceptance of a novel vegetable. Methods Caregivers (n = 106, 82% White) and children (n = 106, 54% male) aged 6–12 months (n = 46; infants), 12–18 months (n = 40; younger toddlers) and 18–24 months (n = 20; older toddlers), participated in a videotaped laboratory visit during which infants tasted up to 8 offers of a novel vegetable (pureed kale). Caregivers completed questionnaires on breastfeeding (BF) status (currently BF or pumping milk, 0 = no; 1 = yes), and infant vegetable experience (21 items, 0 = no; 1 = yes). Infant vegetable experience (VE) was scored as the sum of vegetables tasted by the infant to date (range 0–21). Acceptance of the novel vegetable was coded (0 = refusal; 1 = enforced; 2 = acceptance; 3 = anticipation) by trained coders using feeding videos. Descriptive statistics (mean ± s.d.) were calculated and regression analyses were conducted for models predicting VE and acceptance using current BF status and child age (months) as predictors. T-tests were conducted to ascertain differences in VE by current BF status. Significance was set at P &lt; .05. Results Half (50%) of children were currently receiving breastmilk (77% for infants, 47.5% for younger toddlers, 21% for older toddlers). Children had been exposed to an average of 13.6 ± 5.3 vegetables and this differed by age of child (10.1 ± 5.2 for infants, 15.8 ± 3.5 for younger toddlers, 17.4 ± 2.9 for older toddlers). Child age (F = 10.8, P = .000, R2 = .426) was associated with acceptance of kale (1.5 ± 0.7); older children were less accepting (β = –.381). BF status was not significantly associated with acceptance. Child age was predictive of VE (F = 28.6, P = .000, R2 = .376; β = .638). Follow up analyses comparing infants’ and toddlers’ VE by current BF status revealed that older toddlers who were breastfed had greater VE than those not currently breastfed (t = 2.3, P = .036; 20.0 ± 1.1 vs 16.7 ± 2.9). Conclusions Despite introduction to a greater variety of vegetables with age, acceptance of a novel vegetables declined during toddlerhood. Infants and toddlers continued to consume breastmilk, and older toddlers had greater VE; these factors were not associated with greater novel vegetable acceptance. Funding Sources The Sugar Association.

scholarly journals Myocardial native T1 mapping and cardiac outcomes in thalassemia major

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
A Meloni ◽  
N Martini ◽  
A De Luca ◽  
V Positano ◽  
L Pistoia ◽  
...  
Keyword(s):  
Iron Overload ◽  
T1 Mapping ◽  
Thalassemia Major ◽  
Clinical Impact ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Private Company ◽  
Native T1 ◽  
Funding Sources ◽  
History Of

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The E-MIOT project receives “no-profit support” from industrial sponsorships (Chiesi Farmaceutici S.p.A. and ApoPharma Inc. and Bayer). Background. The T2* cardiovascular magnetic resonance (CMR) is the gold standard for the non invasive detection of myocardial iron overload (MIO). The native myocardial T1 mapping has been proposed as a complementary tool, thanks to its higher sensitivity in presence of small amounts of iron, but no data are available in literature about its clinical impact. Objective To explore the clinical impact of T1 mapping for detecting cardiac complications in thalassemia major (TM). Methods. We considered 146 TM patients (87 females, 38.7 ± 11.1 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Three parallel short-axis slices of the left ventricle (LV) were acquired with the Modified Look-Locker Inversion recovery (MOLLI) sequence. The native T1 values in all 16 myocardial segments were obtained and the global value was the mean. Results. Twenty-one patients had an history of cardiac complications: 11 heart failure,  8 arrhythmias (7 supraventricular and 1 ventricular), and 2 pulmonary hyperthension. Patients with cardiac complications had significantly lower global heart T1 values (879.3 ± 121.9 ms vs 963.2 ± 98.5 ms; P &lt; 0.0001) (Figure) but comparable T2* values (33.32 ± 11.66 ms vs 37.17 ± 9.15 ms; P = 0.116). Cardiac complications were more frequent in the group of patients with reduced global heart T1 value (&lt;928 ms for males and &lt;989 ms for females) compared to the group with normal global heart T1 value (71.4% vs 39.5%; P = 0.009). Odds ratio (OR) for cardiac complications was 3.8 (95%CI = 1.3-10.9) for patients with reduced global heart T1 value versus patients with normal global heart T1 value. Conclusion We found out a significant association between decreased native global heart T1 values and a history of cardiac complications, suggesting that an early detection of myocardial iron  burden by  native T1 can support the clinicians in modifing chelation therapy earlier. Abstract Figure.

scholarly journals In Vitro and In Vivo Studies on Quercus acuta Thunb. (Fagaceae) Extract: Active Constituents, Serum Uric Acid Suppression, and Xanthine Oxidase Inhibitory Activity

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
In-Soo Yoon ◽  
Dae-Hun Park ◽  
Min-Suk Bae ◽  
Deuk-Sil Oh ◽  
Nan-Hui Kwon ◽  
...  
Keyword(s):  
South Korea ◽  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
In Vivo Studies ◽  
Gas Chromatography Mass Spectrometry ◽  
Similar Extent ◽  
Active Constituents ◽  
Quercus Acuta

Quercus acuta Thunb. (Fagaceae) (QA) is cultivated as a dietary and ornamental plant in China, Japan, South Korea, and Taiwan. It has been widely used as the main ingredient of acorn tofu, a traditional food in China and South Korea. The aim of this study was to determine in vitro and in vivo xanthine oxidase (XO) inhibitory and antihyperuricemic activities of an ethyl acetate extract of QA leaf (QALE) and identify its active phytochemicals using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC) systems. The QALE was found to possess potent in vitro antioxidant and XO inhibitory activities. In vivo study using hyperuricemic mice induced with potassium oxonate demonstrated that the QALE could inhibit hepatic XO activity at a relatively low oral dose (50 mg/kg) and significantly alleviate hyperuricemia to a similar extent as allopurinol. Several active compounds including vitamin E known to possess XO inhibitory activity were identified from the QALE. To the best of our knowledge, this is the first study that reports the active constituents and antihyperuricemic effect of QA, suggesting that it is feasible to use QALE as a food therapy or alternative medicine for alleviating hyperuricemia and gout.

Xanthine Oxidase Does Not Produce Reactive Oxygen Species in Early Life-Threatening Trauma

2013 ◽  
Vol 179 (2) ◽  
pp. 199
Author(s):  
J.R. Stringham ◽  
E.E. Moore ◽  
T.L. Chin ◽  
A. Ghasabyan ◽  
C.R. Ramos ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Xanthine Oxidase ◽  
Early Life ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Life Threatening

scholarly journals Cytochrome c Oxidase at Full Thrust: Regulation and Biological Consequences to Flying Insects

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 470
Author(s):  
Rafael Mesquita ◽  
Alessandro Gaviraghi ◽  
Renata Gonçalves ◽  
Marcos Vannier-Santos ◽  
Julio Mignaco ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Energy Demand ◽  
Redox Balance ◽  
Mitochondrial Enzymes ◽  
Mitochondrial Energy Metabolism ◽  
Atp Production ◽  
Insect Biology ◽  
Oxidant Production ◽  
Atp Supply

Flight dispersal represents a key aspect of the evolutionary and ecological success of insects, allowing escape from predators, mating, and colonization of new niches. The huge energy demand posed by flight activity is essentially met by oxidative phosphorylation (OXPHOS) in flight muscle mitochondria. In insects, mitochondrial ATP supply and oxidant production are regulated by several factors, including the energy demand exerted by changes in adenylate balance. Indeed, adenylate directly regulates OXPHOS by targeting both chemiosmotic ATP production and the activities of specific mitochondrial enzymes. In several organisms, cytochrome c oxidase (COX) is regulated at transcriptional, post-translational, and allosteric levels, impacting mitochondrial energy metabolism, and redox balance. This review will present the concepts on how COX function contributes to flying insect biology, focusing on the existing examples in the literature where its structure and activity are regulated not only by physiological and environmental factors but also how changes in its activity impacts insect biology. We also performed in silico sequence analyses and determined the structure models of three COX subunits (IV, VIa, and VIc) from different insect species to compare with mammalian orthologs. We observed that the sequences and structure models of COXIV, COXVIa, and COXVIc were quite similar to their mammalian counterparts. Remarkably, specific substitutions to phosphomimetic amino acids at critical phosphorylation sites emerge as hallmarks on insect COX sequences, suggesting a new regulatory mechanism of COX activity. Therefore, by providing a physiological and bioenergetic framework of COX regulation in such metabolically extreme models, we hope to expand the knowledge of this critical enzyme complex and the potential consequences for insect dispersal.

scholarly journals Maternal Soybean Diet on Prevention of Offspring Obesity and Metabolic Disorders

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 345-345
Author(s):  
Yuanyuan (Rose) Li
Keyword(s):  
Lipid Metabolism ◽  
Gut Microbiome ◽  
Early Life ◽  
Developmental Stages ◽  
Control Diet ◽  
Gene Expressions ◽  
Funding Sources ◽  
Safe Level ◽  
Metabolite Profiles ◽  
Prevention Potential

Abstract Objectives Our studies focus on elucidation of the potential mechanisms-mediated early-life gut microbiome development linking maternal dietary genistein (GE) intervention to its obesity prevention potential later in life through regulation of host metabolome and epigenome. Methods C57BL/6 (BL6) dams were provided GE diet during prenatal and postnatal periods. Weaned offspring were exposed to either control diet or a commercially available high-fat diet (HFD) for 20 wks to induce obesity. We evaluated various metabolic parameters, gut microbiome taxonomy, fecal/serum metabolomes (especially microbially-produced metabolites) and epigenetic changes in key glucose/lipid metabolism-related genes in adipose tissues during different developmental stages in BL6 offspring. Results Our studies found that maternal dietary GE a safe level significantly reduced the risk of HFD-induced body fat accumulation and glucose intolerance in mouse offspring. We also found that maternal GE consumption significantly affected the diversity and composition of childhood gut microbiota, the fecal metabolome as well as gene expressions of key glucose/lipid metabolism-related genes in offspring mice. Conclusions Our studies suggest that maternal GE consumption may shape early-life gut microbiome and the signature of bacterial metabolite profiles in the offspring, which may in turn alter the host epigenome and health outcomes. Funding Sources NIH/NCI, NIH/NCCIH.

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