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Sample records for altered iron metabolism

  1. Altered erythropoiesis and iron metabolism in carriers of thalassemia

    Science.gov (United States)

    Guimarães, Jacqueline S.; Cominal, Juçara G.; Silva-Pinto, Ana Cristina; Olbina, Gordana; Ginzburg, Yelena Z.; Nandi, Vijay; Westerman, Mark; Rivella, Stefano; de Souza, Ana Maria

    2014-01-01

    The thalassemia syndromes (α- and β-thalassemia) are the most common and frequent disorders associated with ineffective erythropoiesis. Imbalance of α- or β-globin chain production results in impaired red blood cell synthesis, anemia and more erythroid progenitors in the blood stream. While patients affected by these disorders show definitive altered parameters related to erythropoiesis, the relationship between the degree of anemia, altered erythropoiesis and dysfunctional iron metabolism have not been investigated in both α-thalassemia carriers (ATC) and β-thalassemia carriers (BTC). Here we demonstrate that ATC have a significantly reduced hepcidin and increased soluble transferrin receptor levels but relatively normal hematological findings. In contrast, BTC have several hematological parameters significantly different from controls, including increased soluble transferrin receptor and erythropoietin levels. These changings in both groups suggest an altered balance between erythropoiesis and iron metabolism. The index sTfR/log ferrin and (hepcidin/ferritin)/sTfR are respectively increased and reduced relative to controls, proportional to the severity of each thalassemia group. In conclusion, we showed in this study, for the first time in the literature, that thalassemia carriers have altered iron metabolism and erythropoiesis. PMID:25307880

  2. Testosterone alters iron metabolism and stimulates red blood cell production independently of dihydrotestosterone.

    Science.gov (United States)

    Beggs, Luke A; Yarrow, Joshua F; Conover, Christine F; Meuleman, John R; Beck, Darren T; Morrow, Matthew; Zou, Baiming; Shuster, Jonathan J; Borst, Stephen E

    2014-09-01

    Testosterone (T) stimulates erythropoiesis and regulates iron homeostasis. However, it remains unknown whether the (type II) 5α-reduction of T to dihydrotestosterone (DHT) mediates these androgenic effects, as it does in some other tissues. Our purpose was to determine whether inhibition of type II 5α-reductase (via finasteride) alters red blood cell (RBC) production and serum markers of iron homeostasis subsequent to testosterone-enanthate (TE) administration in older hypogonadal men. Sixty men aged ≥60 yr with serum T <300 ng/dl or bioavailable T <70 ng/dl received treatment with TE (125 mg/wk) vs. vehicle paired with finasteride (5 mg/day) vs. placebo using a 2 × 2 factorial design. Over the course of 12 mo, TE increased RBC count 9%, hematocrit 4%, and hemoglobin 8% while suppressing serum hepcidin 57% (P < 0.001 for all measurements). Most of the aforementioned changes occurred in the first 3 mo of treatment, and finasteride coadministration did not significantly alter any of these effects. TE also reduced serum ferritin 32% (P = 0.002) within 3 mo of treatment initiation without altering iron, transferrin, or transferrin saturation. We conclude that TE stimulates erythropoiesis and alters iron homeostasis independently of the type II 5α-reductase enzyme. These results demonstrate that elevated DHT is not required for androgen-mediated erythropoiesis or for alterations in iron homeostasis that would appear to support iron incorporation into RBCs.

  3. Proteomic analysis reveals that iron availability alters the metabolic status of the pathogenic fungus Paracoccidioides brasiliensis.

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    Ana F A Parente

    Full Text Available Paracoccidioides brasiliensis is a thermodimorphic fungus and the causative agent of paracoccidioidomycosis (PCM. The ability of P. brasiliensis to uptake nutrients is fundamental for growth, but a reduction in the availability of iron and other nutrients is a host defense mechanism many pathogenic fungi must overcome. Thus, fungal mechanisms that scavenge iron from host may contribute to P. brasiliensis virulence. In order to better understand how P. brasiliensis adapts to iron starvation in the host we compared the two-dimensional (2D gel protein profile of yeast cells during iron starvation to that of iron rich condition. Protein spots were selected for comparative analysis based on the protein staining intensity as determined by image analysis. A total of 1752 protein spots were selected for comparison, and a total of 274 out of the 1752 protein spots were determined to have changed significantly in abundance due to iron depletion. Ninety six of the 274 proteins were grouped into the following functional categories; energy, metabolism, cell rescue, virulence, cell cycle, protein synthesis, protein fate, transcription, cellular communication, and cell fate. A correlation between protein and transcript levels was also discovered using quantitative RT-PCR analysis from RNA obtained from P. brasiliensis under iron restricting conditions and from yeast cells isolated from infected mouse spleens. In addition, western blot analysis and enzyme activity assays validated the differential regulation of proteins identified by 2-D gel analysis. We observed an increase in glycolytic pathway protein regulation while tricarboxylic acid cycle, glyoxylate and methylcitrate cycles, and electron transport chain proteins decreased in abundance under iron limiting conditions. These data suggest a remodeling of P. brasiliensis metabolism by prioritizing iron independent pathways.

  4. Iron metabolism in man.

    Science.gov (United States)

    von Drygalski, Annette; Adamson, John W

    2013-09-01

    Iron metabolism in man is a highly regulated process designed to provide iron for erythropoiesis, mitochondrial energy production, electron transport, and cell proliferation. The mechanisms of iron handling also protect cells from the deleterious effects of free iron, which can produce oxidative damage of membranes, proteins, and lipids. Over the past decade, several important molecules involved in iron homeostasis have been discovered, and their function has expanded our understanding of iron trafficking under normal and pathological conditions. Physiologic iron metabolism is strongly influenced by inflammation, which clinically leads to anemia. Although hepcidin, a small circulating peptide produced by the liver, has been found to be the key regulator of iron trafficking, molecular pathways of iron sensing that control iron metabolism and hepcidin production are still incompletely understood. With this review, we provide an overview of the current understanding of iron metabolism, the recently discovered regulators of iron trafficking, and a focus on the effects of inflammation on the process.

  5. Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin

    DEFF Research Database (Denmark)

    Robach, Paul; Recalcati, Stefania; Girelli, Domenico

    2009-01-01

    The high iron demand associated with enhanced erythropoiesis during high-altitude hypoxia leads to skeletal muscle iron mobilization and decrease in myoglobin protein levels. To investigate the effect of enhanced erythropoiesis on systemic and muscle iron metabolism under nonhypoxic conditions, 8...

  6. Iron Dextran Increases Hepatic Oxidative Stress and Alters Expression of Genes Related to Lipid Metabolism Contributing to Hyperlipidaemia in Murine Model

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    Maísa Silva

    2015-01-01

    Full Text Available The objective of this study was to investigate the effects of iron dextran on lipid metabolism and to determine the involvement of oxidative stress. Fischer rats were divided into two groups: the standard group (S, which was fed the AIN-93M diet, and the standard plus iron group (SI, which was fed the same diet but also received iron dextran injections. Serum cholesterol and triacylglycerol levels were higher in the SI group than in the S group. Iron dextran was associated with decreased mRNA levels of pparα, and its downstream gene cpt1a, which is involved in lipid oxidation. Iron dextran also increased mRNA levels of apoB-100, MTP, and L-FABP indicating alterations in lipid secretion. Carbonyl protein and TBARS were consistently higher in the liver of the iron-treated rats. Moreover, a significant positive correlation was found between oxidative stress products, lfabp expression, and iron stores. In addition, a negative correlation was found between pparα expression, TBARS, carbonyl protein, and iron stores. In conclusion, our results suggest that the increase observed in the transport of lipids in the bloodstream and the decreased fatty acid oxidation in rats, which was promoted by iron dextran, might be attributed to increased oxidative stress.

  7. Altered metabolism in cancer

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    Locasale Jason W

    2010-06-01

    Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

  8. Obesity Promotes Alterations in Iron Recycling

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    Marta Citelli

    2015-01-01

    Full Text Available Hepcidin is a key hormone that induces the degradation of ferroportin (FPN, a protein that exports iron from reticuloendothelial macrophages and enterocytes. The aim of the present study was to experimentally evaluate if the obesity induced by a high-fat diet (HFD modifies the expression of FPN in macrophages and enterocytes, thus altering the iron bioavailability. In order to directly examine changes associated with iron metabolism in vivo, C57BL/6J mice were fed either a control or a HFD. Serum leptin levels were evaluated. The hepcidin, divalent metal transporter-1 (DMT1, FPN and ferritin genes were analyzed by real-time polymerase chain reaction. The amount of iron present in both the liver and spleen was determined by flame atomic absorption spectrometry. Ferroportin localization within reticuloendothelial macrophages was observed by immunofluorescence microscopy. Obese animals were found to exhibit increased hepcidin gene expression, while iron accumulated in the spleen and liver. They also exhibited changes in the sublocation of splenic cellular FPN and a reduction in the FPN expression in the liver and the spleen, while no changes were observed in enterocytes. Possible explanations for the increased hepcidin expression observed in HFD animals may include: increased leptin levels, the liver iron accumulation or endoplasmic reticulum (ER stress. Together, the results indicated that obesity promotes changes in iron bioavailability, since it altered the iron recycling function.

  9. Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism

    Czech Academy of Sciences Publication Activity Database

    Rychtarčíková, Zuzana; Lettlová, Sandra; Tomkova, Veronika; Korenková, Vlasta; Langerová, Lucie; Simonova, Ekaterina; Zjablovskaja, Polina; Alberich-Jorda, Meritxell; Neužil, Jiří; Truksa, Jaroslav

    2017-01-01

    Roč. 8, č. 4 (2017), s. 6376-6398 ISSN 1949-2553 R&D Projects: GA ČR GA13-28830S; GA ČR GA15-03796S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 ; RVO:68378050 Keywords : tumor-initiating cells * breast cancer * iron metabolism Subject RIV: FD - Oncology ; Hematology; EB - Genetics ; Molecular Biology (UMG-J) OBOR OECD: Cell biology; Cell biology (UMG-J) Impact factor: 5.168, year: 2016

  10. Iron metabolism and toxicity

    International Nuclear Information System (INIS)

    Papanikolaou, G.; Pantopoulos, K.

    2005-01-01

    Iron is an essential nutrient with limited bioavailability. When present in excess, iron poses a threat to cells and tissues, and therefore iron homeostasis has to be tightly controlled. Iron's toxicity is largely based on its ability to catalyze the generation of radicals, which attack and damage cellular macromolecules and promote cell death and tissue injury. This is lucidly illustrated in diseases of iron overload, such as hereditary hemochromatosis or transfusional siderosis, where excessive iron accumulation results in tissue damage and organ failure. Pathological iron accumulation in the liver has also been linked to the development of hepatocellular cancer. Here we provide a background on the biology and toxicity of iron and the basic concepts of iron homeostasis at the cellular and systemic level. In addition, we provide an overview of the various disorders of iron overload, which are directly linked to iron's toxicity. Finally, we discuss the potential role of iron in malignant transformation and cancer

  11. A computational model of liver iron metabolism.

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    Simon Mitchell

    Full Text Available Iron is essential for all known life due to its redox properties; however, these same properties can also lead to its toxicity in overload through the production of reactive oxygen species. Robust systemic and cellular control are required to maintain safe levels of iron, and the liver seems to be where this regulation is mainly located. Iron misregulation is implicated in many diseases, and as our understanding of iron metabolism improves, the list of iron-related disorders grows. Recent developments have resulted in greater knowledge of the fate of iron in the body and have led to a detailed map of its metabolism; however, a quantitative understanding at the systems level of how its components interact to produce tight regulation remains elusive. A mechanistic computational model of human liver iron metabolism, which includes the core regulatory components, is presented here. It was constructed based on known mechanisms of regulation and on their kinetic properties, obtained from several publications. The model was then quantitatively validated by comparing its results with previously published physiological data, and it is able to reproduce multiple experimental findings. A time course simulation following an oral dose of iron was compared to a clinical time course study and the simulation was found to recreate the dynamics and time scale of the systems response to iron challenge. A disease state simulation of haemochromatosis was created by altering a single reaction parameter that mimics a human haemochromatosis gene (HFE mutation. The simulation provides a quantitative understanding of the liver iron overload that arises in this disease. This model supports and supplements understanding of the role of the liver as an iron sensor and provides a framework for further modelling, including simulations to identify valuable drug targets and design of experiments to improve further our knowledge of this system.

  12. Genetic/metabolic effect of iron metabolism and rare anemias

    OpenAIRE

    Clara Camaschella

    2013-01-01

    Advances in iron metabolism have allowed a novel classification of iron disorders and to identify previously unknown diseases. These disorders include genetic iron overload (hemochromatosis) and inherited iron-related anemias, in some cases accompanied by iron overload. Rare inherited anemias may affect the hepcidin pathway, iron absorption, transport, utilization and recycling. Among the genetic iron-related anemias the most common form is likely the iron-refractory iron-deficiency anemia (I...

  13. Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism

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    Camilla Ceccatelli Berti

    2015-04-01

    Full Text Available Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA, namely PKAN and CoPAN. PKAN are defined by mutations in PANK2, encoding the pantothenate kinase 2 enzyme, that account for about 50% of cases of NBIA, whereas mutations in CoA synthase COASY have been recently reported as the second inborn error of CoA synthesis leading to CoPAN. As reported previously, yeast cells expressing the pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.

  14. Iron metabolism: microbes, mouse, and man.

    Science.gov (United States)

    Latunde-Dada, Gladys O

    2009-12-01

    Recent advances in research on iron metabolism have revealed the identity of a number of genes, signal transduction pathways, and proteins involved in iron regulation in mammals. The emerging paradigm is a coordination of homeostasis within a network of classical iron metabolic pathways and other cellular processes such as cell differentiation, growth, inflammation, immunity, and a host of physiologic and pathologic conditions. Iron, immunity, and infection are intricately linked and their regulation is fundamental to the survival of mammals. The mutual dependence on iron by the host and invading pathogenic organisms elicits competition for the element during infection. While the host maintains mechanisms to utilize iron for its own metabolism exclusively, pathogenic organisms are armed with a myriad of strategies to circumvent these measures. This review explores iron metabolism in mammalian host, defense mechanisms against pathogenic microbes and the competitive devices of microbes for access to iron.

  15. Specific hemosiderin deposition in spleen induced by a low dose of cisplatin: altered iron metabolism and its implication as an acute hemosiderin formation model.

    Science.gov (United States)

    Wang, Yingze; Juan, L V; Ma, Xiaowei; Wang, Dongliang; Ma, Huili; Chang, Yanzhong; Nie, Guangjun; Jia, Lee; Duan, Xianglin; Liang, Xing-Jie

    2010-07-01

    cisplatin and hemosiderin accumulation and iron metabolism in vivo.

  16. In male rats with concurrent iron and (n-3) fatty acid deficiency, provision of either iron or (n-3) fatty acids alone alters monoamine metabolism and exacerbates the cognitive deficits associated with combined deficiency

    NARCIS (Netherlands)

    Baumgartner, J.; Smuts, C.M.; Malan, L.; Arnold, M.; Yee, B.K.; Bianco, L.E.; Boekschoten, M.V.; Muller, M.R.; Langhans, W.; Hurrell, R.F.; Zimmermann, M.B.

    2012-01-01

    Concurrent deficiencies of iron (Fe) (ID) and (n-3) fatty acids [(n-3)FAD)] in rats can alter brain monoamine pathways and impair learning and memory. We examined whether repletion with Fe and DHA/EPA, alone and in combination, corrects the deficits in brain monoamine activity (by measuring

  17. Mammalian iron metabolism and its control by iron regulatory proteins☆

    Science.gov (United States)

    Anderson, Cole P.; Shen, Lacy; Eisenstein, Richard S.; Leibold, Elizabeth A.

    2013-01-01

    Cellular iron homeostasis is maintained by iron regulatory proteins 1 and 2 (IRP1 and IRP2). IRPs bind to iron-responsive elements (IREs) located in the untranslated regions of mRNAs encoding protein involved in iron uptake, storage, utilization and export. Over the past decade, significant progress has been made in understanding how IRPs are regulated by iron-dependent and iron-independent mechanisms and the pathological consequences of IRP2 deficiency in mice. The identification of novel IREs involved in diverse cellular pathways has revealed that the IRP–IRE network extends to processes other than iron homeostasis. A mechanistic understanding of IRP regulation will likely yield important insights into the basis of disorders of iron metabolism. This article is part of a Special Issue entitled: Cell Biology of Metals. PMID:22610083

  18. Iron metabolism and maternal-fetal iron circulation 

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    Artur Słomka

    2012-11-01

    Full Text Available Iron is an essential micronutrient for the proper functioning of most organisms. This element is used in oxygen transport, myelin and neurotransmitters synthesis, cell cycle and synthesis of nucleic acids. The importance of iron in the maturation of lymphocytes and proper functioning of the eye is also stressed. Newborns are particularly sensitive to imbalances in iron metabolism. Iron deficiency during pregnancy carries serious clinical consequences. It seems that a key role in the transport of iron between mother and fetus is plays by hepcidin and, described in 2010 zyklopen. The physiological role of proteins involved in iron metabolism and transport of this metal by the placenta are described in this paper. 

  19. Staphylococcus aureus redirects central metabolism to increase iron availability.

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    David B Friedman

    2006-08-01

    Full Text Available Staphylococcus aureus pathogenesis is significantly influenced by the iron status of the host. However, the regulatory impact of host iron sources on S. aureus gene expression remains unknown. In this study, we combine multivariable difference gel electrophoresis and mass spectrometry with multivariate statistical analyses to systematically cluster cellular protein response across distinct iron-exposure conditions. Quadruplicate samples were simultaneously analyzed for alterations in protein abundance and/or post-translational modification state in response to environmental (iron chelation, hemin treatment or genetic (Deltafur alterations in bacterial iron exposure. We identified 120 proteins representing several coordinated biochemical pathways that are affected by changes in iron-exposure status. Highlighted in these experiments is the identification of the heme-regulated transport system (HrtAB, a novel transport system which plays a critical role in staphylococcal heme metabolism. Further, we show that regulated overproduction of acidic end-products brought on by iron starvation decreases local pH resulting in the release of iron from the host iron-sequestering protein transferrin. These findings reveal novel strategies used by S. aureus to acquire scarce nutrients in the hostile host environment and begin to define the iron and heme-dependent regulons of S. aureus.

  20. Smectite alteration by anaerobic iron corrosion

    International Nuclear Information System (INIS)

    Sanders, D.; Kaufhold, S.; Hassel, A.W.; Dohrmann, R.

    2010-01-01

    Document available in extended abstract form only. The interaction of smectites with corroding steel/iron represents a crucial topic in the estimation of the long term confinement properties of clay barriers for the encasement of steel/iron containers. Especially in case of engineered clay barriers a possible deterioration of favourable smectite properties as response to corrosion could reduce the barrier capacity. The extent of this reduction is unknown, yet. The essential properties of bentonite clays in this context are on the one hand the relatively high swelling pressure together with low hydraulic conductivity, which results from the well known expandability of smectite interlayers in aqueous environments. On the other hand smectites are cation exchangers being able to long term encase radioactive cations in a way that negative charges of silicate layers are compensated by easily exchangeable hydrated cations. Both properties are directly related to the crystal and chemical composition of smectites. The nature of the corrosion of steel canisters in clay barriers will - after a first short aerobic phase - predominantly be anaerobic resulting in the formation of Fe(II) and two equivalents of hydroxide ions. In a set of exposition experiments anaerobic corroding iron in bentonite gels was studied in order to determine alteration of the smectite fraction. During the exposition a green coloration of the bentonite neighbouring to corroding iron was observed. Upon contact to oxygen in a humid state the bentonite turned reddish indicating the oxidation of Fe(II) to Fe(III). This observation is in accordance with reported results indicating the formation of an iron rich smectite. Chemical analysis of the 'green bentonite' reveals an increase of iron fraction e.g. from 3.4% mass to 9.3% mass . The adsorbed iron is predominantly Fe(II) which was proven by chromato-metric titration. The estimated ratio between silicon to increased iron content is Si: Fe ≅ 2

  1. Genetic/metabolic effect of iron metabolism and rare anemias

    Directory of Open Access Journals (Sweden)

    Clara Camaschella

    2013-03-01

    Full Text Available Advances in iron metabolism have allowed a novel classification of iron disorders and to identify previously unknown diseases. These disorders include genetic iron overload (hemochromatosis and inherited iron-related anemias, in some cases accompanied by iron overload. Rare inherited anemias may affect the hepcidin pathway, iron absorption, transport, utilization and recycling. Among the genetic iron-related anemias the most common form is likely the iron-refractory iron-deficiency anemia (IRIDA, due to mutations of the hepcidin inhibitor TMPRSS6 encoding the serine protease matriptase-2. IRIDA is characterized by hepcidin up-regulation, decrease iron absorption and macrophage recycling and by microcytic- hypochromic anemia, unresponsive to oral iron. High serum hepcidin levels may suggest the diagnosis, which requires demonstrating the causal TMPRSS6 mutations by gene sequencing. Other rare microcytic hypochromic anemias associated with defects of iron transport-uptake are the rare hypotransferrinemia, and DMT1 and STEAP3 mutations. The degree of anemia is variable and accompanied by secondary iron overload even in the absence of blood transfusions. This is due to the iron-deficient or expanded erythropoiesis that inhibits hepcidin transcription, increases iron absorption, through the erythroid regulator, as in untransfused beta-thalassemia. Sideroblastic anemias are due to decreased mitochondrial iron utilization for heme or sulfur cluster synthesis. Their diagnosis requires demonstrating ringed sideroblasts by Perl’s staining of the bone marrow smears. The commonest X-linked form is due to deltaamino- levulinic-synthase-2-acid (ALAS2 mutations. The recessive, more severe form, affects SLC25A38, which encodes a potential mitochondrial importer of glycine, an amino acid essential for ALA synthesis and thus results in heme deficiency. Two disorders affect iron/sulfur cluster biogenesis: deficiency of the ATP-binding cassette B7 (ABCB7 causes X

  2. Exploring the iron metabolism in multidrug resistant tuberculosis ...

    African Journals Online (AJOL)

    The iron metabolism plays a key role in the progression of active Tuberculosis. Several studies have shown a link between iron metabolism disorders an active tuberculosis. The aim of this study was to explore the iron metabolism of 100 patients with multidrug-resistant tuberculosis (MDR-TB) treated with second generation ...

  3. Exploring the iron metabolism in multidrug resistant tuberculosis ...

    African Journals Online (AJOL)

    The iron metabolism plays a key role in the progression of active Tuberculosis. Several studies have shown a link between iron metabolism disorders an active tuberculosis. The aim of this study was to explore the iron metabolism of 100 patients with multidrug-resistant tuberculosis. (MDR-TB) treated with second ...

  4. In male rats with concurrent iron and (n-3) fatty acid deficiency, provision of either iron or (n-3) fatty acids alone alters monoamine metabolism and exacerbates the cognitive deficits associated with combined deficiency.

    Science.gov (United States)

    Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K; Bianco, Laura E; Boekschoten, Mark V; Müller, Michael; Langhans, Wolfgang; Hurrell, Richard F; Zimmermann, Michael B

    2012-08-01

    Concurrent deficiencies of iron (Fe) (ID) and (n-3) fatty acids [(n-3)FAD)] in rats can alter brain monoamine pathways and impair learning and memory. We examined whether repletion with Fe and DHA/EPA, alone and in combination, corrects the deficits in brain monoamine activity (by measuring monoamines and related gene expression) and spatial working and reference memory [by Morris water maze (MWM) testing] associated with deficiency. Using a 2 × 2 design, male rats with concurrent ID and (n-3)FAD [ID+(n-3)FAD] were fed an Fe+DHA/EPA, Fe+(n-3)FAD, ID+DHA/EPA, or ID+(n-3)FAD diet for 5 wk [postnatal d 56-91]. Biochemical measures and MWM performance after repletion were compared to age-matched control rats. The provision of Fe in combination with DHA/EPA synergistically increased Fe concentrations in the olfactory bulb (OB) (Fe x DHA/EPA interaction). Similarly, provision of DHA/EPA in combination with Fe resulted in higher brain DHA concentrations than provision of DHA alone in the frontal cortex (FC) and OB (P FAD affects the DA and 5-HT pathways differently than combined repletion and exacerbates the cognitive deficits associated with combined deficiency.

  5. Dietary iron controls circadian hepatic glucose metabolism through heme synthesis.

    Science.gov (United States)

    Simcox, Judith A; Mitchell, Thomas Creighton; Gao, Yan; Just, Steven F; Cooksey, Robert; Cox, James; Ajioka, Richard; Jones, Deborah; Lee, Soh-Hyun; King, Daniel; Huang, Jingyu; McClain, Donald A

    2015-04-01

    The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  6. Oncometabolites: linking altered metabolism with cancer

    Science.gov (United States)

    Yang, Ming; Soga, Tomoyoshi; Pollard, Patrick J.

    2013-01-01

    The discovery of cancer-associated mutations in genes encoding key metabolic enzymes has provided a direct link between altered metabolism and cancer. Advances in mass spectrometry and nuclear magnetic resonance technologies have facilitated high-resolution metabolite profiling of cells and tumors and identified the accumulation of metabolites associated with specific gene defects. Here we review the potential roles of such “oncometabolites” in tumor evolution and as clinical biomarkers for the detection of cancers characterized by metabolic dysregulation. PMID:23999438

  7. Iron status alters murine systemic lupus erythematosus.

    Science.gov (United States)

    Leiter, L M; Reuhl, K R; Racis, S P; Sherman, A R

    1995-03-01

    /MPJ-lpr/lpr mice is altered by dietary iron.

  8. Metabolic alterations in renal cell carcinoma.

    Science.gov (United States)

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Brunelli, Matteo; Piva, Francesco; Modena, Alessandra; Bimbatti, Davide; Fantinel, Emanuela; Santini, Daniele; Cheng, Liang; Cascinu, Stefano; Montironi, Rodolfo; Tortora, Giampaolo

    2015-11-01

    Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways). We analyzed the key metabolic abnormalities underlying RCC carcinogenesis, highlighting those altered pathways that may represent potential targets for the development of more effective therapeutic strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Effect of chronic ethanol administration on iron metabolism in the rat

    International Nuclear Information System (INIS)

    Sanchez, J.; Casas, M.; Rama, R.

    1988-01-01

    This study shows that the ingestion of ethanol provokes alterations in iron metabolism which may lead to iron overload. Impaired release of reticuloendothelial iron was shown by a decrease of the maximum red blood cell utilization when radioactive iron was supplied as colloidal iron. An impairment in the erythropoietic activity of ethanoltreated animals was also observed, as can be seen from the reduced plasma iron turnover and red blood cell utilization within 24 h of iron administration. A rise in marrow transit time was also observed. In ethanol-treated rats there was an increase in the amount of iron retained both in the liver and the spleen. This was observed in both sexes and also in the offspring from ethanol-treated mothers. (author)

  10. Dysregulation of Iron Metabolism in Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Satoru Oshiro

    2011-01-01

    Full Text Available Dysregulation of iron metabolism has been observed in patients with neurodegenerative diseases (NDs. Utilization of several importers and exporters for iron transport in brain cells helps maintain iron homeostasis. Dysregulation of iron homeostasis leads to the production of neurotoxic substances and reactive oxygen species, resulting in iron-induced oxidative stress. In Alzheimer's disease (AD and Parkinson's disease (PD, circumstantial evidence has shown that dysregulation of brain iron homeostasis leads to abnormal iron accumulation. Several genetic studies have revealed mutations in genes associated with increased iron uptake, increased oxidative stress, and an altered inflammatory response in amyotrophic lateral sclerosis (ALS. Here, we review the recent findings on brain iron metabolism in common NDs, such as AD, PD, and ALS. We also summarize the conventional and novel types of iron chelators, which can successfully decrease excess iron accumulation in brain lesions. For example, iron-chelating drugs have neuroprotective effects, preventing neural apoptosis, and activate cellular protective pathways against oxidative stress. Glial cells also protect neurons by secreting antioxidants and antiapoptotic substances. These new findings of experimental and clinical studies may provide a scientific foundation for advances in drug development for NDs.

  11. Obesogenic diets alter metabolism in mice.

    Science.gov (United States)

    Showalter, Megan R; Nonnecke, Eric B; Linderholm, A L; Cajka, Tomas; Sa, Michael R; Lönnerdal, Bo; Kenyon, Nicholas J; Fiehn, Oliver

    2018-01-01

    Obesity and accompanying metabolic disease is negatively correlated with lung health yet the exact mechanisms by which obesity affects the lung are not well characterized. Since obesity is associated with lung diseases as chronic bronchitis and asthma, we designed a series of experiments to measure changes in lung metabolism in mice fed obesogenic diets. Mice were fed either control or high fat/sugar diet (45%kcal fat/17%kcal sucrose), or very high fat diet (60%kcal fat/7% sucrose) for 150 days. We performed untargeted metabolomics by GC-TOFMS and HILIC-QTOFMS and lipidomics by RPLC-QTOFMS to reveal global changes in lung metabolism resulting from obesity and diet composition. From a total of 447 detected metabolites, we found 91 metabolite and lipid species significantly altered in mouse lung tissues upon dietary treatments. Significantly altered metabolites included complex lipids, free fatty acids, energy metabolites, amino acids and adenosine and NAD pathway members. While some metabolites were altered in both obese groups compared to control, others were different between obesogenic diet groups. Furthermore, a comparison of changes between lung, kidney and liver tissues indicated few metabolic changes were shared across organs, suggesting the lung is an independent metabolic organ. These results indicate obesity and diet composition have direct mechanistic effects on composition of the lung metabolome, which may contribute to disease progression by lung-specific pathways.

  12. Profile of altered brain iron acquisition in restless legs syndrome

    Science.gov (United States)

    Ponnuru, Padmavathi; Wang, Xin-Sheng; Patton, Stephanie M.; Allen, Richard P.; Earley, Christopher J.

    2011-01-01

    nigra of restless legs syndrome brains. This study reveals that there are alterations in the iron management protein profile in restless legs syndrome compared with controls at the site of blood–brain interface suggesting fundamental differences in brain iron acquisition in individuals with restless legs syndrome. Furthermore, the decrease in transferrin receptor expression in the microvasculature in the presence of relative brain iron deficiency reported in restless legs syndrome brains may underlie the problems associated with brain iron acquisition in restless legs syndrome. The consistent finding of loss of iron regulatory protein activity in restless legs syndrome brain tissue further implicates this protein as a factor in the underlying cause of the iron deficiency in the restless legs syndrome brain. The data herein provide evidence for regulation of iron uptake and storage within brain microvessels that challenge the existing paradigm that the blood–brain barrier is merely a transport system. PMID:21398376

  13. Serum Visfatin in Relation to Some Parameters of Iron Metabolism in ...

    African Journals Online (AJOL)

    1Visfatin is an adipokine mainly synthesized and secreted in visceral fat. Visfatin was found to have important proinflammatory and immunomodulating properties. The aim of the present work was to clarify the relation between plasma visfatin, some parameters of iron metabolism and insulin resistance in altered glucose ...

  14. Iron metabolism study in humans by means of stable tracers

    International Nuclear Information System (INIS)

    Cantone, M.C.; Molho, N.; Pirola, L.; Gambarini, G.; Hansen, C.; Roth, P.; Werner, E.

    1988-01-01

    An investigation of iron metabolism in a female patient volunteer by administration of stable iron isotopes as tracers was performed. The applied methodology had already been tested in rabbits in comparison with radioactive tracer technique. The subject under study was given 58 Fe solution intravenously and about 45 min later 57 Fe solution orally. Ten blood samples were drawn at different times within 522 min from injection. Single iron isotopes content in plasma samples was determined by proton nuclear activation. A Compton suppressor system was utilized to improve the detector limits. The characteristic parameters of iron plasma clearance and of iron intestinal absorption were determined

  15. Iron overload alters glucose homeostasis, causes liver steatosis, and increases serum triacylglycerols in rats.

    Science.gov (United States)

    Silva, Maísa; Silva, Marcelo E; de Paula, Heberth; Carneiro, Cláudia Martins; Pedrosa, Maria Lucia

    2008-06-01

    The objective of this study was to investigate the effect of iron overload with a hyperlipidemic diet on the histologic feature of hepatic tissue, the lipid and glycemic serum profiles, and the markers of oxidative damage and stress in a rat model. Twenty-four male Fischer rats, purchased from Experimental Nutrition Laboratory, Federal University of Ouro Preto, were assigned to 4 equal groups, 2 were fed a standard cholesterol-free diet (group C or control and CI or control with iron) containing 8.0% soybean oil and 2 were fed a hyperlipidemic diet (group H or hyperlipidemic and HI or hyperlipidemic with iron) containing 1.0% cholesterol and 25.0% soybean oil. A total of 50 mg of iron was administered to rats in groups CI and HI in 5 equal doses (1 every 3 weeks for a 16-week period) by intraperitoneal injections of 0.1 mL of iron dextran solution (100 g Fe(2+)/L; Sigma, St Louis, Mo). The other rats in groups C and H were treated in a similar manner but with sterile saline (0.1 mL). Irrespective of the diet, iron excess enhanced serum triacylglycerols (P .05) were observed in paraoxonase activities or in serum levels of free or total sulfhydryl radicals, malondialdehyde, or total antioxidants. The findings suggest that iron excess in the rat probably modifies lipid metabolism and, as a consequence, alters glucose homeostasis and increases the level of serum triacylglycerols but not of cholesterol.

  16. Current status of iron metabolism: Clinical and therapeutic implications.

    Science.gov (United States)

    Conde Diez, Susana; de Las Cuevas Allende, Ricardo; Conde García, Eulogio

    2017-03-03

    Hepcidin is the main regulator of iron metabolism and a pathogenic factor in iron disorders. Hepcidin deficiency causes iron overload, whereas hepcidin excess causes or contributes to the development of iron-restricted anaemia in chronic inflammatory diseases. We know the mechanisms involved in the synthesis of hepcidin and, under physiological conditions, there is a balance between activating signals and inhibitory signals that regulate its synthesis. The former include those related to plasmatic iron level and also those related to chronic inflammatory diseases. The most important inhibitory signals are related to active erythropoiesis and to matriptase-2. Knowing how hepcidin is synthesised has helped design new pharmacological treatments whose main target is the hepcidin. In the near future, there will be effective treatments aimed at correcting the defect of many of these iron metabolism disorders. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  17. [Effect of copper deficiency on iron metabolism in rats].

    Science.gov (United States)

    Wang, Kebo; Wang, Chaoxu; Liu, Baosheng; Jiang, Shan

    2010-07-01

    To study the effect of copper deficiency on the nutritional status of iron, the expression of hepcidin mRNA and transferrin receptor mRNA in rats. Forty eight clean male SD rats were randomly divided into four groups according to body weight; and there were 12 rats in each group. The groups are normal iron and copper control group (group I), normal iron and copper deficiency group (group II), normal iron and copper slightly deficient group (group III), both iron and copper slightly deficient group (group IV). Serum, liver and spleen of rats were collected by the end of 8th week. Serum copper, serum iron, hemoglobin, serum transferrin receptor, serum ferritin, liver iron and liver copper, spleen iron and spleen copper were determined. The expression of liver transferring receptor mRNA and hepcidin mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR) method. Compared with the controls, the contents of serum iron and serum ferritin decreased (P copper deficiency. The expression of transferrin receptor mRNA in liver increased but the expression of hepcidin mRNA in liver decreased significantly under copper deficiency (P copper deficiency through influencing the absorption, storage and transportation of iron. Under the condition of copper deficiency, the expression of hepcidin mRNA in liver was lowered and the expression of transferrin receptor mRNA was enhanced through the way of iron response element-iron regulatory protein (IRE-IRP) to regulate iron metabolism.

  18. Biochemical and biophysical methods for studying mitochondrial iron metabolism.

    Science.gov (United States)

    Holmes-Hampton, Gregory P; Tong, Wing-Hang; Rouault, Tracey A

    2014-01-01

    Iron is a heavily utilized element in organisms and numerous mechanisms accordingly regulate the trafficking, metabolism, and storage of iron. Despite the high regulation of iron homeostasis, several diseases and mutations can lead to the misregulation and often accumulation of iron in the cytosol or mitochondria of tissues. To understand the genesis of iron overload, it is necessary to employ various techniques to quantify iron in organisms and mitochondria. This chapter discusses techniques for determining the total iron content of tissue samples, ranging from colorimetric determination of iron concentrations, atomic absorption spectroscopy, inductively coupled plasma-optical emission spectroscopy, and inductively coupled plasma-mass spectrometry. In addition, we discuss in situ techniques for analyzing iron including electron microscopic nonheme iron histochemistry, electron energy loss spectroscopy, synchrotron X-ray fluorescence imaging, and confocal Raman microscopy. Finally, we discuss biophysical methods for studying iron in isolated mitochondria, including ultraviolet-visible, electron paramagnetic resonance, X-ray absorbance, and Mössbauer spectroscopies. This chapter should aid researchers to select and interpret mitochondrial iron quantifications.

  19. Divergence of iron metabolism in wild Malaysian yeast.

    Science.gov (United States)

    Lee, Hana N; Mostovoy, Yulia; Hsu, Tiffany Y; Chang, Amanda H; Brem, Rachel B

    2013-12-09

    Comparative genomic studies have reported widespread variation in levels of gene expression within and between species. Using these data to infer organism-level trait divergence has proven to be a key challenge in the field. We have used a wild Malaysian population of S. cerevisiae as a test bed in the search to predict and validate trait differences based on observations of regulatory variation. Malaysian yeast, when cultured in standard medium, activated regulatory programs that protect cells from the toxic effects of high iron. Malaysian yeast also showed a hyperactive regulatory response during culture in the presence of excess iron and had a unique growth defect in conditions of high iron. Molecular validation experiments pinpointed the iron metabolism factors AFT1, CCC1, and YAP5 as contributors to these molecular and cellular phenotypes; in genome-scale sequence analyses, a suite of iron toxicity response genes showed evidence for rapid protein evolution in Malaysian yeast. Our findings support a model in which iron metabolism has diverged in Malaysian yeast as a consequence of a change in selective pressure, with Malaysian alleles shifting the dynamic range of iron response to low-iron concentrations and weakening resistance to extreme iron toxicity. By dissecting the iron scarcity specialist behavior of Malaysian yeast, our work highlights the power of expression divergence as a signpost for biologically and evolutionarily relevant variation at the organismal level. Interpreting the phenotypic relevance of gene expression variation is one of the primary challenges of modern genomics.

  20. [The characteristics of iron metabolism under iron-deficiency anemia and chronic disorders anemia].

    Science.gov (United States)

    Smorkalova, E V; Aznabaeva, L F; Nikulicheva, V I; Safuanova, G Sh; Chepurnaia, A N

    2011-07-01

    The study investigated the issues of iron metabolism under iron-deficiency anemia and chronic disorders anemia and dependencies of production of IL-1? and sICAM-1 immunoinflammatory markers from degree of severity and duration of anemia. The study data indicates that under iron-deficiency anemia lactoferrin and sICAM-1 are the negative regulators of hemopoiesis. The inhibition of transferrin expression by the proinflammatory cytokines is one of the causes of inefficient hemopoiesis under chronic disorders anemia.

  1. The role of mitochondria in cellular iron-sulfur protein biogenesis and iron metabolism.

    Science.gov (United States)

    Lill, Roland; Hoffmann, Bastian; Molik, Sabine; Pierik, Antonio J; Rietzschel, Nicole; Stehling, Oliver; Uzarska, Marta A; Webert, Holger; Wilbrecht, Claudia; Mühlenhoff, Ulrich

    2012-09-01

    Mitochondria play a key role in iron metabolism in that they synthesize heme, assemble iron-sulfur (Fe/S) proteins, and participate in cellular iron regulation. Here, we review the latter two topics and their intimate connection. The mitochondrial Fe/S cluster (ISC) assembly machinery consists of 17 proteins that operate in three major steps of the maturation process. First, the cysteine desulfurase complex Nfs1-Isd11 as the sulfur donor cooperates with ferredoxin-ferredoxin reductase acting as an electron transfer chain, and frataxin to synthesize an [2Fe-2S] cluster on the scaffold protein Isu1. Second, the cluster is released from Isu1 and transferred toward apoproteins with the help of a dedicated Hsp70 chaperone system and the glutaredoxin Grx5. Finally, various specialized ISC components assist in the generation of [4Fe-4S] clusters and cluster insertion into specific target apoproteins. Functional defects of the core ISC assembly machinery are signaled to cytosolic or nuclear iron regulatory systems resulting in increased cellular iron acquisition and mitochondrial iron accumulation. In fungi, regulation is achieved by iron-responsive transcription factors controlling the expression of genes involved in iron uptake and intracellular distribution. They are assisted by cytosolic multidomain glutaredoxins which use a bound Fe/S cluster as iron sensor and additionally perform an essential role in intracellular iron delivery to target metalloproteins. In mammalian cells, the iron regulatory proteins IRP1, an Fe/S protein, and IRP2 act in a post-transcriptional fashion to adjust the cellular needs for iron. Thus, Fe/S protein biogenesis and cellular iron metabolism are tightly linked to coordinate iron supply and utilization. This article is part of a Special Issue entitled: Cell Biology of Metals. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Proteomic analysis of iron acquisition, metabolic and regulatory responses of Yersinia pestis to iron starvation

    Directory of Open Access Journals (Sweden)

    Fleischmann Robert D

    2010-01-01

    Full Text Available Abstract Background The Gram-negative bacterium Yersinia pestis is the causative agent of the bubonic plague. Efficient iron acquisition systems are critical to the ability of Y. pestis to infect, spread and grow in mammalian hosts, because iron is sequestered and is considered part of the innate host immune defence against invading pathogens. We used a proteomic approach to determine expression changes of iron uptake systems and intracellular consequences of iron deficiency in the Y. pestis strain KIM6+ at two physiologically relevant temperatures (26°C and 37°C. Results Differential protein display was performed for three Y. pestis subcellular fractions. Five characterized Y. pestis iron/siderophore acquisition systems (Ybt, Yfe, Yfu, Yiu and Hmu and a putative iron/chelate outer membrane receptor (Y0850 were increased in abundance in iron-starved cells. The iron-sulfur (Fe-S cluster assembly system Suf, adapted to oxidative stress and iron starvation in E. coli, was also more abundant, suggesting functional activity of Suf in Y. pestis under iron-limiting conditions. Metabolic and reactive oxygen-deactivating enzymes dependent on Fe-S clusters or other iron cofactors were decreased in abundance in iron-depleted cells. This data was consistent with lower activities of aconitase and catalase in iron-starved vs. iron-rich cells. In contrast, pyruvate oxidase B which metabolizes pyruvate via electron transfer to ubiquinone-8 for direct utilization in the respiratory chain was strongly increased in abundance and activity in iron-depleted cells. Conclusions Many protein abundance differences were indicative of the important regulatory role of the ferric uptake regulator Fur. Iron deficiency seems to result in a coordinated shift from iron-utilizing to iron-independent biochemical pathways in the cytoplasm of Y. pestis. With growth temperature as an additional variable in proteomic comparisons of the Y. pestis fractions (26°C and 37°C, there was

  3. Petrography, alteration and genesis of iron mineralization in Roshtkhar

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    Habib Biabangard

    2017-07-01

    Full Text Available Introduction Iron mineralization in Roshtkhar is located in 48 Km east of the city of Roshtkhar and south of the Khorasan Razavi province. It is geologically located in the north east of the Lut block and the Khaf-Bardeskan volcano-plutonic belt. The Khaf-Bardeskan belt is an important metallogenic province since it is a host of valuable ore deposits such as the Kuh-e-Zar Au-Spicularite, the Tanourcheh and the Khaf Iron ore deposits (Karimpour and Malekzadeh Shafaroudi, 2007. Iron and Copper mineralization in this belt are known as the hydrothermal, skarn and IOCG types (Karimpour and Malekzadeh Shafaroudi, 2007. IOCG deposits are a new type of magmatic to hydrothermal mineralization in the continental crust (Hitzman et al., 1992. Precambrian marble, Lower Paleozoic schist and metavolcanics are the oldest rocks of the area. The younger units are Oligocene conglomerate, shale and sandstone, Miocene marl and Quaternary deposits. Iron oxides and Cu sulfides are associated with igneous rocks. Fe and Cu mineralization in Roshtkhar has been subject of a few studies such as Yousefi Surani (2006. This study describes the petrography of the host rocks, ore paragenesis, alteration types, geochemistry, genesis and other features of the Fe and Cu mineralization in the Roshtkhar iron. Methods After detailed field studies and sampling, 30 thin sections and 20 polished sections that were prepared from host rocks and ores were studied by conventional petrographic and mineraloghraphic methods in the geology department of the University of Sistan and Baluchestan. 5 samples from the alteration zones were examined by XRD in the Yamagata University in Japan, and 8 samples from the less altered ones were analyzed by XRF and ICP-OES in the Kharazmi University and the Iranian mineral processing research center (IMPRC in Karaj, respectively. The XRF and ICP-OES data are presented in Table 1. Result and discussion The host rocks of the Roshtkhar Iron deposit are diorite

  4. A role for heme in Alzheimer's disease: Heme binds amyloid β and has altered metabolism

    OpenAIRE

    Atamna, Hani; Frey, William H.

    2004-01-01

    Heme is a common factor linking several metabolic perturbations in Alzheimer's disease (AD), including iron metabolism, mitochondrial complex IV, heme oxygenase, and bilirubin. Therefore, we determined whether heme metabolism was altered in temporal lobes obtained at autopsy from AD patients and age-matched nondemented subjects. AD brain demonstrated 2.5-fold more heme-b (P < 0.01) and 26% less heme-a (P = 0.16) compared with controls, resulting in a highly significant 2.9-fold decrease in he...

  5. Altered calcium metabolism: the probable major biochemical lesion ...

    African Journals Online (AJOL)

    These data are suggestive of altered calcium metabolism impairing cell membrane stabilization, the vasorelaxing effect of calcium and cell signaling. Altered calcium metabolism may be the major biochemical lesion underlying many pathological and clinical states of lead toxicity. Journal of Biomedical Investigation Vol.

  6. Diversity and Evolutionary History of Iron Metabolism Genes in Diatoms.

    Directory of Open Access Journals (Sweden)

    Ryan D Groussman

    Full Text Available Ferroproteins arose early in Earth's history, prior to the emergence of oxygenic photosynthesis and the subsequent reduction of bioavailable iron. Today, iron availability limits primary productivity in about 30% of the world's oceans. Diatoms, responsible for nearly half of oceanic primary production, have evolved molecular strategies for coping with variable iron concentrations. Our understanding of the evolutionary breadth of these strategies has been restricted by the limited number of species for which molecular sequence data is available. To uncover the diversity of strategies marine diatoms employ to meet cellular iron demands, we analyzed 367 newly released marine microbial eukaryotic transcriptomes, which include 47 diatom species. We focused on genes encoding proteins previously identified as having a role in iron management: iron uptake (high-affinity ferric reductase, multi-copper oxidase, and Fe(III permease; iron storage (ferritin; iron-induced protein substitutions (flavodoxin/ferredoxin, and plastocyanin/cytochrome c6 and defense against reactive oxygen species (superoxide dismutases. Homologs encoding the high-affinity iron uptake system components were detected across the four diatom Classes suggesting an ancient origin for this pathway. Ferritin transcripts were also detected in all Classes, revealing a more widespread utilization of ferritin throughout diatoms than previously recognized. Flavodoxin and plastocyanin transcripts indicate possible alternative redox metal strategies. Predicted localization signals for ferredoxin identify multiple examples of gene transfer from the plastid to the nuclear genome. Transcripts encoding four superoxide dismutase metalloforms were detected, including a putative nickel-coordinating isozyme. Taken together, our results suggest that the majority of iron metabolism genes in diatoms appear to be vertically inherited with functional diversity achieved via possible neofunctionalization of

  7. Diversity and Evolutionary History of Iron Metabolism Genes in Diatoms.

    Science.gov (United States)

    Groussman, Ryan D; Parker, Micaela S; Armbrust, E Virginia

    2015-01-01

    Ferroproteins arose early in Earth's history, prior to the emergence of oxygenic photosynthesis and the subsequent reduction of bioavailable iron. Today, iron availability limits primary productivity in about 30% of the world's oceans. Diatoms, responsible for nearly half of oceanic primary production, have evolved molecular strategies for coping with variable iron concentrations. Our understanding of the evolutionary breadth of these strategies has been restricted by the limited number of species for which molecular sequence data is available. To uncover the diversity of strategies marine diatoms employ to meet cellular iron demands, we analyzed 367 newly released marine microbial eukaryotic transcriptomes, which include 47 diatom species. We focused on genes encoding proteins previously identified as having a role in iron management: iron uptake (high-affinity ferric reductase, multi-copper oxidase, and Fe(III) permease); iron storage (ferritin); iron-induced protein substitutions (flavodoxin/ferredoxin, and plastocyanin/cytochrome c6) and defense against reactive oxygen species (superoxide dismutases). Homologs encoding the high-affinity iron uptake system components were detected across the four diatom Classes suggesting an ancient origin for this pathway. Ferritin transcripts were also detected in all Classes, revealing a more widespread utilization of ferritin throughout diatoms than previously recognized. Flavodoxin and plastocyanin transcripts indicate possible alternative redox metal strategies. Predicted localization signals for ferredoxin identify multiple examples of gene transfer from the plastid to the nuclear genome. Transcripts encoding four superoxide dismutase metalloforms were detected, including a putative nickel-coordinating isozyme. Taken together, our results suggest that the majority of iron metabolism genes in diatoms appear to be vertically inherited with functional diversity achieved via possible neofunctionalization of paralogs. This

  8. Metabolic alterations in experimental models of depression

    Directory of Open Access Journals (Sweden)

    Maria G. Puiu

    2016-10-01

    Full Text Available Introduction: Major depressive disorder is one of the most prevalent psychiatric disorders and is associated with a severe impact on the personal functioning, thus with incurring significant direct and indirect costs. The presence of depression in patients with medical comorbidities increases the risks of myocardial infarction and decreases diabetes control, and adherence to treatment. The mechanism through which these effects are produced is still uncertain. Objectives of this study were to evaluate the metabolic alterations in female Wistar rats with induced depression, with and without administration of Agomelatine. The methods included two experiments. All data were analyzed by comparison with group I (control, and with each other. In the first experiment we induced depression by: exposure to chronic mild stress-group II; olfactory bulbectomy-group III; and exposure to chronic mild stress and hyperlipidic/ hyper caloric dietgroup IV. The second experiment was similar with the first but the rats received Agomelatine (0.16mg/ animal: group V (depression induced through exposure to chronic mild stress, VI (depression induced through olfactory bulbectomy and VII (depression induced through exposure to chronic mild stressing hyperlipidic/ hypercaloric diet. Weight, cholesterol, triglycerides and glycaemia were measured at day 0 and 28, and leptin value was measured at day 28. The results in the 1st experiment revealed significant differences (p<0.01 for weight and cholesterol in Group IV, for triglycerides in groups III and IV (p<0.001, and for glycaemia in group II. The 2nd experiment revealed significant differences (p<0.001 in group VII for weight and triglycerides, and in groups V and VI for triglycerides (p<0.01. In conclusion, significant correlations were found between high level of triglycerides and depression induced by chronic stress and olfactory bulbectomy. Agomelatine groups had a lower increase of triglycerides levels.

  9. Heme metabolism as an integral part of iron homeostasis

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    Paweł Lipiński

    2014-01-01

    Full Text Available Heme, a ferrous iron protoporphyrin IX complex, is employed as a prosthetic group in a number of diverse heme proteins that participate in important cellular and systemic physiological processes. Provision of an adequate amount of iron for heme biosynthesis is one of the elemental hallmarks of intracellular iron homeostasis. In the cell the bioavailability of iron for the two main iron biological pathways – heme synthesis and the biogenesis of iron-sulfur clusters ([Fe-S] – is mainly regulated by the IRP/IRE posttranscriptional system. The biogenesis of [Fe-S] centers is crucial for heme synthesis because these co-factors determine the activity of IRP1 and that of ferrochelatase, an enzyme responsible for the insertion of an iron into protoporphyrin IX to produce heme. On the other hand, delivery of iron for heme and hemoglobin synthesis in erythroblasts, precursors of erythrocytes in bone marrow, is an indispensable element of body iron homeostasis. This process relies on the recovery of iron from senescent red blood cells through the enzymatic degradation of heme molecules and recycling of iron to the circulation. Molecular coordination of these processes involves the activity of heme oxygenase 1, IRP1 and IRP2 as well as the functioning of the hepcidin-ferroportin regulatory axis. Recent studies show in mammals the existence of an expanded system of proteins involved in the transport of intact heme molecules at the cellular and systemic levels. The biological role of this system is of particular importance when the concentration of free heme reaches a toxic level in the body (intravascular hemolysis as well as locally in cells having intensive heme metabolism such as erythroblasts and macrophages.

  10. [Heme metabolism as an integral part of iron homeostasis].

    Science.gov (United States)

    Lipiński, Paweł; Starzyński, Rafał R; Styś, Agnieszka; Gajowiak, Anna; Staroń, Robert

    2014-01-02

    Heme, a ferrous iron protoporphyrin IX complex, is employed as a prosthetic group in a number of diverse heme proteins that participate in important cellular and systemic physiological processes. Provision of an adequate amount of iron for heme biosynthesis is one of the elemental hallmarks of intracellular iron homeostasis. In the cell the bioavailability of iron for the two main iron biological pathways--heme synthesis and the biogenesis of iron-sulfur clusters ([Fe-S])--is mainly regulated by the IRP/IRE posttranscriptional system. The biogenesis of [Fe-S] centers is crucial for heme synthesis because these co-factors determine the activity of IRP1 and that of ferrochelatase, an enzyme responsible for the insertion of an iron into protoporphyrin IX to produce heme. On the other hand, delivery of iron for heme and hemoglobin synthesis in erythroblasts, precursors of erythrocytes in bone marrow, is an indispensable element of body iron homeostasis. This process relies on the recovery of iron from senescent red blood cells through the enzymatic degradation of heme molecules and recycling of iron to the circulation. Molecular coordination of these processes involves the activity of heme oxygenase 1, IRP1 and IRP2 as well as the functioning of the hepcidin-ferroportin regulatory axis. Recent studies show in mammals the existence of an expanded system of proteins involved in the transport of intact heme molecules at the cellular and systemic levels. The biological role of this system is of particular importance when the concentration of free heme reaches a toxic level in the body (intravascular hemolysis) as well as locally in cells having intensive heme metabolism such as erythroblasts and macrophages.

  11. Novel insights into iron metabolism by integrating deletome and transcriptome analysis in an iron deficiency model of the yeast Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Arkin Adam P

    2009-03-01

    Full Text Available Abstract Background Iron-deficiency anemia is the most prevalent form of anemia world-wide. The yeast Saccharomyces cerevisiae has been used as a model of cellular iron deficiency, in part because many of its cellular pathways are conserved. To better understand how cells respond to changes in iron availability, we profiled the yeast genome with a parallel analysis of homozygous deletion mutants to identify essential components and cellular processes required for optimal growth under iron-limited conditions. To complement this analysis, we compared those genes identified as important for fitness to those that were differentially-expressed in the same conditions. The resulting analysis provides a global perspective on the cellular processes involved in iron metabolism. Results Using functional profiling, we identified several genes known to be involved in high affinity iron uptake, in addition to novel genes that may play a role in iron metabolism. Our results provide support for the primary involvement in iron homeostasis of vacuolar and endosomal compartments, as well as vesicular transport to and from these compartments. We also observed an unexpected importance of the peroxisome for growth in iron-limited media. Although these components were essential for growth in low-iron conditions, most of them were not differentially-expressed. Genes with altered expression in iron deficiency were mainly associated with iron uptake and transport mechanisms, with little overlap with those that were functionally required. To better understand this relationship, we used expression-profiling of selected mutants that exhibited slow growth in iron-deficient conditions, and as a result, obtained additional insight into the roles of CTI6, DAP1, MRS4 and YHR045W in iron metabolism. Conclusion Comparison between functional and gene expression data in iron deficiency highlighted the complementary utility of these two approaches to identify important functional

  12. Regulation of iron metabolism during Neisseria meningitidis infection in mice

    Energy Technology Data Exchange (ETDEWEB)

    Letendre, E.D.

    1984-01-01

    Bacterial invasion of vertebrates triggers a marked reduction in the levels of iron associated with the plasma transferrin (Tf) pool. This hypoferremic response has been regarded as a host attempt to withhold essential iron from the invading pathogen. The exact nature of the mechanisms involved remains obscure. The kinetics of iron processing by the RE system were studied by labeling the RE compartments with /sup 59/Fe-labeled denatured red blood cells. Uptake and redistribution of the label indicated the RE-processed iron was not returned to the plasma Tf pool during the hypoferremia. Fractionation of hepatic cellular compartments showed that this impaired release of iron resulted from a preferential incorporation of home-derived iron into the intracellular ferritin pool and this produces the hypoferremia. The role of ceruloplasmin (ferroxidase I,EC.1.16.3.1) (Cp) in iron metabolism during meningococcal infection was investigated. Plasma Cp ferroxidase activity was found to increase greatly in mice during the convalescence phase.

  13. Severe postnatal iron deficiency alters emotional behavior and dopamine levels in the prefrontal cortex of young male rats.

    Science.gov (United States)

    Li, Yuan; Kim, Jonghan; Buckett, Peter D; Böhlke, Mark; Maher, Timothy J; Wessling-Resnick, Marianne

    2011-12-01

    Iron deficiency in early human life is associated with abnormal neurological development. The objective of this study was to evaluate the effect of postnatal iron deficiency on emotional behavior and dopaminergic metabolism in the prefrontal cortex in a young male rodent model. Weanling, male, Sprague-Dawley rats were fed standard nonpurified diet (220 mg/kg iron) or an iron-deficient diet (2-6 mg/kg iron). After 1 mo, hematocrits were 0.42 ± 0.0043 and 0.16 ± 0.0068 (mean ± SEM; P emotional behavior. Iron-deficient rats displayed anxious behavior with fewer entries and less time spent in open arms compared to control rats (0.25 ± 0.25 vs. 1.8 ± 0.62 entries; 0.88 ± 0.88 vs. 13 ± 4.6 s; P effects were associated with reduced concentrations of extracellular dopamine in the prefrontal cortex of the iron-deficient rats (79 ± 7.0 vs. 110 ± 14 ng/L; P < 0.05; n = 4). Altered dopaminergic signaling in the prefrontal cortex most likely contributes to the anxious behavior observed in young male rats with severe iron deficiency.

  14. Metabolic disorders with typical alterations in MRI

    International Nuclear Information System (INIS)

    Warmuth-Metz, M.

    2010-01-01

    The classification of metabolic disorders according to the etiology is not practical for neuroradiological purposes because the underlying defect does not uniformly transform into morphological characteristics. Therefore typical MR and clinical features of some easily identifiable metabolic disorders are presented. Canavan disease, Pelizaeus-Merzbacher disease, Alexander disease, X-chromosomal adrenoleukodystrophy and adrenomyeloneuropathy, mitochondrial disorders, such as MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) and Leigh syndrome as well as L-2-hydroxyglutaric aciduria are presented. (orig.) [de

  15. Altered expression of iron regulatory proteins with aging is associated with transient hepatic iron accumulation after environmental heat stress.

    Science.gov (United States)

    Bloomer, Steven A; Han, Okhee; Kregel, Kevin C; Brown, Kyle E

    2014-01-01

    An increasing body of evidence suggests that dysregulation of iron metabolism contributes to age-related pathologies. We have previously observed increased hepatic iron with aging, and that environmental heat stress stimulates a further increase in iron and oxidative liver injury in old rats. The purpose of this study was to determine a mechanism for the increase in hepatic iron in old rats after heat stress. Young (6 mo) and old (24 mo) Fischer 344 rats were exposed to two heating bouts separated by 24 h. Livers were harvested after the second heat stress, and protein levels of the iron import protein, transferrin receptor-1 (TFR1), and the iron export protein, ferroportin (Fpn) were determined by immunoblot. In the nonheated condition, old rats had lower TFR1 expression, and higher Fpn expression. After heat stress, TFR1 declined in the old rats, and iron chelation studies demonstrated that this decline was dependent on a hyperthermia-induced increase in iron. TFR1 did not change in the young rats after heat stress. Since TFR1 is inversely regulated by iron, our results suggest that the increase in intracellular iron with aging and heat stress lower TFR1 expression. Fpn expression increased in both age groups after heat stress, but this response was delayed in old rats. This delay in the induction of an iron exporter suggests a mechanism for the increase in hepatic iron and oxidative injury after heat stress in aged organisms. © 2013.

  16. [Effects of copper deficiency on iron metabolism in rats].

    Science.gov (United States)

    Xiao, Fei; Wang, Chaoxu; Yang, Li

    2013-07-01

    To study the effects of copper deficiency on iron metabolism, the expression of IRP mRNA and Fn mRNA and transferrin receptor mRNA in rats. Forty clean male SD rats were randomly divided into four groups according to body weight and there were 10 rats in each group. The groups are normal iron and copper control group (group I), copper deficiency group (group II), normal iron and copper slightly deficient group (group III), both iron and copper slightly deficient group (group IV). After 8 weeks, all the rats were killed by sodium pentobarbital anesthesia and all samples were collected and detected for gene expression. Compared with the controls, the contents of serum iron and serum ferritin in completely copper deficiency group decreased (P copper deficiency (P copper deficiency group was significantly increased (P copper deficiency group was significantly decreased (P copper deficiency through influencing the absorption, the results indicate that copper deficiency influences iron homeostasis in cells through affecting the expression of IRP2 and the activity of IRP-RNA combination which change the expressions of ferritin and transferrin mRNA.

  17. Haemodialysis and peritoneal dialysis: metabolic alterations and nutritional status.

    Science.gov (United States)

    Cano, N

    1999-07-01

    In dialysis patients, malnutrition is an independent factor causing morbidity and mortality. Both inadequate alimentation and metabolic alterations, which involve nitrogen and energy metabolism, contribute to malnutrition. Future research must address the treatment of anorexia and inflammation-induced catabolism, as well as the evaluation of nutritional supplementation techniques and anabolic drugs.

  18. The Impair Iron Metabolism in Acute Pancreatitis

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    Yu. P. Orlov

    2010-01-01

    Full Text Available Objective: to develop a method for preventing hepatic failure. Subjects and methods: Sixty-three patients with a complicated course of acute pancreatitis, admitted to the intensive care unit, were examined and treated. Thirty-one patients received standard intensive therapy and 32 patients had an intensive treatment program comprising deferoxamine in a dose of 6—12 mg/kg without octreotide. The activities of AsAT and AlAT and the levels of total bilirubin and its fractions, ferritin, and free hemoglobin were determined in plasma three times (on admission, 1 and 3 days later; the activities of superoxide dismutase and catalase were also examined. The severity of endotoxemia was assessed by the levels of low- and medium-molecular-weight substances in plasma and on red blood cells. Results. Incorporation of deferoxamine into the intensive therapy program for severe acute pancreatitis could reduce the incidence of hepatopathy and decrease that of pancreatogenic sepsis and retroperitoneal phlegmon by 3 times and mortality rate by 19.6%. Conclusion. The use of deferoxamine in the intensive therapy program is pathogenetically warranted because, by binding excess iron ions in plasma, the agent prevents the development of occasionally fatal complications of acute pancreatitis.

  19. Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner

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    Jessica M. V. Pino

    2017-05-01

    Full Text Available Iron is an essential micronutrient for several physiological functions, including the regulation of dopaminergic neurotransmission. On the other hand, both iron, and dopamine can affect the folding and aggregation of proteins related with neurodegenerative diseases, such as cellular prion protein (PrPC and α-synuclein, suggesting that deregulation of iron homeostasis and the consequential disturbance of dopamine metabolism can be a risk factor for conformational diseases. These proteins, in turn, are known to participate in the regulation of iron and dopamine metabolism. In this study, we evaluated the effects of dietary iron restriction on brain ferritin levels, dopamine metabolism, and the expression levels of PrPC and α-synuclein. To achieve this goal, C57BL/6 mice were fed with iron restricted diet (IR or with normal diet (CTL for 1 month. IR reduced iron and ferritin levels in liver. Ferritin reduction was also observed in the hippocampus. However, in the striatum of IR group, ferritin level was increased, suggesting that under iron-deficient condition, each brain area might acquire distinct capacity to store iron. Increased lipid peroxidation was observed only in hippocampus of IR group, where ferritin level was reduced. IR also generated discrete results regarding dopamine metabolism of distinct brain regions: in striatum, the level of dopamine metabolites (DOPAC and HVA was reduced; in prefrontal cortex, only HVA was increased along with the enhanced MAO-A activity; in hippocampus, no alterations were observed. PrPC levels were increased only in the striatum of IR group, where ferritin level was also increased. PrPC is known to play roles in iron uptake. Thus, the increase of PrPC in striatum of IR group might be related to the increased ferritin level. α-synuclein was not altered in any regions. Abnormal accumulation of ferritin, increased MAO-A activity or lipid peroxidation are molecular features observed in several neurological

  20. Human macrophage hemoglobin-iron metabolism in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Custer, G.; Balcerzak, S.; Rinehart, J.

    1982-01-01

    An entirely in vitro technique was employed to characterize hemoglobin-iron metabolism by human macrophages obtained by culture of blood monocytes and pulmonary alveolar macrophages. Macrophages phagocytized about three times as many erythrocytes as monocytes and six times as many erythrocytes as pulmonary alveolar macrophages. The rate of subsequent release of /sup 59/Fe to the extracellular transferrin pool was two- to fourfold greater for macrophages as compared to the other two cell types. The kinetics of /sup 59/Fe-transferrin release were characterized by a relatively rapid early phase (hours 1-4) followed by a slow phase (hours 4-72) for all three cell types. Intracellular movement of iron was characterized by a rapid shift from hemoglobin to ferritin that was complete with the onset of the slow phase of extracellular release. A transient increase in /sup 59/Fe associated with an intracellular protein eluting with transferrin was also observed within 1 hour after phagocytosis. The process of hemoglobin-iron release to extracellular transferrin was inhibited at 4 degrees C but was unaffected by inhibitory of protein synthesis, glycolysis, microtubule function, and microfilament function. These data emphasize the rapidity of macrophage hemoglobin iron metabolism, provide a model for characterization of this process in vitro, and in general confirm data obtained utilizing in vivo animal models.

  1. Human macrophage hemoglobin-iron metabolism in vitro

    International Nuclear Information System (INIS)

    Custer, G.; Balcerzak, S.; Rinehart, J.

    1982-01-01

    An entirely in vitro technique was employed to characterize hemoglobin-iron metabolism by human macrophages obtained by culture of blood monocytes and pulmonary alveolar macrophages. Macrophages phagocytized about three times as many erythrocytes as monocytes and six times as many erythrocytes as pulmonary alveolar macrophages. The rate of subsequent release of 59 Fe to the extracellular transferrin pool was two- to fourfold greater for macrophages as compared to the other two cell types. The kinetics of 59 Fe-transferrin release were characterized by a relatively rapid early phase (hours 1-4) followed by a slow phase (hours 4-72) for all three cell types. Intracellular movement of iron was characterized by a rapid shift from hemoglobin to ferritin that was complete with the onset of the slow phase of extracellular release. A transient increase in 59 Fe associated with an intracellular protein eluting with transferrin was also observed within 1 hour after phagocytosis. The process of hemoglobin-iron release to extracellular transferrin was inhibited at 4 degrees C but was unaffected by inhibitory of protein synthesis, glycolysis, microtubule function, and microfilament function. These data emphasize the rapidity of macrophage hemoglobin iron metabolism, provide a model for characterization of this process in vitro, and in general confirm data obtained utilizing in vivo animal models

  2. Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments.

    Directory of Open Access Journals (Sweden)

    Kimberly B Zumbrennen-Bullough

    Full Text Available Iron Regulatory Protein 2 (Irp2, Ireb2 is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2-/- mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc, expression are increased and decreased, respectively, in the brain from Irp2-/- mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments.

  3. Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects

    KAUST Repository

    Papsdorf, Katharina

    2015-09-03

    Background Protein aggregation and its pathological effects are the major cause of several neurodegenerative diseases. In Huntington’s disease an elongated stretch of polyglutamines within the protein Huntingtin leads to increased aggregation propensity. This induces cellular defects, culminating in neuronal loss, but the connection between aggregation and toxicity remains to be established. Results To uncover cellular pathways relevant for intoxication we used genome-wide analyses in a yeast model system and identify fourteen genes that, if deleted, result in higher polyglutamine toxicity. Several of these genes, like UGO1, ATP15 and NFU1 encode mitochondrial proteins, implying that a challenged mitochondrial system may become dysfunctional during polyglutamine intoxication. We further employed microarrays to decipher the transcriptional response upon polyglutamine intoxication, which exposes an upregulation of genes involved in sulfur and iron metabolism and mitochondrial Fe-S cluster formation. Indeed, we find that in vivo iron concentrations are misbalanced and observe a reduction in the activity of the prominent Fe-S cluster containing protein aconitase. Like in other yeast strains with impaired mitochondria, non-fermentative growth is impossible after intoxication with the polyglutamine protein. NMR-based metabolic analyses reveal that mitochondrial metabolism is reduced, leading to accumulation of metabolic intermediates in polyglutamine-intoxicated cells. Conclusion These data show that damages to the mitochondrial system occur in polyglutamine intoxicated yeast cells and suggest an intricate connection between polyglutamine-induced toxicity, mitochondrial functionality and iron homeostasis in this model system.

  4. Metabolic changes of iron uptake in N(2)-fixing common bean nodules during iron deficiency.

    Science.gov (United States)

    Slatni, Tarek; Vigani, Gianpiero; Salah, Imen Ben; Kouas, Saber; Dell'Orto, Marta; Gouia, Houda; Zocchi, Graziano; Abdelly, Chedly

    2011-08-01

    Iron is an important nutrient in N(2)-fixing legume nodules. The demand for this micronutrient increases during the symbiosis establishment, where the metal is utilized for the synthesis of various iron-containing proteins in both the plant and the bacteroid. Unfortunately, in spite of its importance, iron is poorly available to plant uptake since its solubility is very low when in its oxidized form Fe(III). In the present study, the effect of iron deficiency on the activity of some proteins involved in Strategy I response, such as Fe-chelate reductase (FC-R), H(+)-ATPase, and phosphoenolpyruvate carboxylase (PEPC) and the protein level of iron regulated transporter (IRT1) and H(+)-ATPase proteins has been investigated in both roots and nodules of a tolerant (Flamingo) and a susceptible (Coco blanc) cultivar of common bean plants. The main results of this study show that the symbiotic tolerance of Flamingo can be ascribed to a greater increase in the FC-R and H(+)-ATPase activities in both roots and nodules, leading to a more efficient Fe supply to nodulating tissues. The strong increase in PEPC activity and organic acid content, in the Flamingo root nodules, suggests that under iron deficiency nodules can modify their metabolism in order to sustain those activities necessary to acquire Fe directly from the soil solution. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Iron

    DEFF Research Database (Denmark)

    Hansen, Jakob Bondo; Moen, I W; Mandrup-Poulsen, T

    2014-01-01

    The interest in the role of ferrous iron in diabetes pathophysiology has been revived by recent evidence of iron as an important determinant of pancreatic islet inflammation and as a biomarker of diabetes risk and mortality. The iron metabolism in the β-cell is complex. Excess free iron is toxic......, but at the same time, iron is required for normal β-cell function and thereby glucose homeostasis. In the pathogenesis of diabetes, iron generates reactive oxygen species (ROS) by participating in the Fenton chemistry, which can induce oxidative damage and apoptosis. The aim of this review is to present...... and discuss recent evidence, suggesting that iron is a key pathogenic factor in both type 1 and type 2 diabetes with a focus on inflammatory pathways. Pro-inflammatory cytokine-induced β-cell death is not fully understood, but may include iron-induced ROS formation resulting in dedifferentiation by activation...

  6. Effects of Protein-Iron Complex Concentrate Supplementation on Iron Metabolism, Oxidative and Immune Status in Preweaning Calves

    Directory of Open Access Journals (Sweden)

    Robert Kupczyński

    2017-07-01

    Full Text Available The objective of this study was to determine the effects of feeding protein-iron complex (PIC on productive performance and indicators of iron metabolism, hematology parameters, antioxidant and immune status during first 35 days of a calf’s life. Preparation of the complex involved enzymatic hydrolysis of milk casein (serine protease from Yarrowia lipolytica yeast. Iron chloride was then added to the hydrolyzate and lyophilizate. Calves were divided into treated groups: LFe (low iron dose 10 g/day calf of protein-iron complex, HFe (height iron dose 20 g/day calf, and control group. Dietary supplements containing the lower dose of concentrate had a significant positive effect on iron metabolism, while the higher dose of concentrate resulted in increase of total iron binding capacity (TIBC, saturation of transferrin and decrease of and unsaturated iron binding capacity (UIBC, which suggest iron overload. Additionally, treatment with the lower dose of iron remarkably increased the antioxidant parameters, mainly total antioxidant (TAS and glutathione peroxidase activity (GPx. Higher doses of PIC were related to lower total antioxidant status. IgG, IgM, insulin, glucose, TNFα and IGF-1 concentration did not change significantly in either group after supplementation. In practice, the use of protein-iron complex concentrate requires taking into account the iron content in milk replacers and other feedstuffs.

  7. Metabolic alterations triggered by silicon nutrition

    Science.gov (United States)

    Detmann, Kelly C.; Araújo, Wagner L.; Martins, Samuel C.V.; Fernie, Alisdair R.; DaMatta, Fábio M.

    2013-01-01

    Although the beneficial role of silicon (Si) in stimulating the growth and development of many plants is generally accepted, our knowledge concerning the physiological and molecular mechanisms underlying this response remains far from comprehensive. Considerable effort has been invested in understanding the role of Si on plant disease, which has led to several new and compelling hypotheses; in unstressed plants, however, Si is believed to have no molecular or metabolic effects. Recently, we have demonstrated that Si nutrition can modulate the carbon/nitrogen balance in unstressed rice plants. Our findings point to an important role of Si as a signaling metabolite able to promote amino acid remobilization. In this article we additionally discuss the agronomic significance of these novel observations and suggest Si nutrition as an important target in future attempts to improve yields of agronomic crops. PMID:23104113

  8. Epileptic Focus and Alteration of Metabolism

    Czech Academy of Sciences Publication Activity Database

    Otáhal, Jakub; Folbergrová, Jaroslava; Kovacs, R.; Kunz, W.S.; Maggio, N.

    2014-01-01

    Roč. 114, č. 2014 (2014), s. 209-243 ISSN 0074-7742 R&D Projects: GA ČR(CZ) GAP303/10/0999; GA ČR(CZ) GA309/05/2015; GA ČR(CZ) GA309/08/0292; GA ČR(CZ) GAP302/10/0971; GA MŠk(CZ) LL1204; GA MZd(CZ) NT14489; GA ČR(CZ) GA14-02634S Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : epilepsy * epileptogenesis * cerebral blood flow * blood brain barrier * reactive oxygen species * energy metabolism * mitochondria * oxidative posttranslational modifications * mtDNA mutations * pharmacoresistance Subject RIV: FH - Neurology Impact factor: 1.921, year: 2014

  9. Behavioral, biochemical, and genetic analysis of iron metabolism in high-intensity blood donors.

    Science.gov (United States)

    Mast, Alan E; Foster, Tisha M; Pinder, Holly L; Beczkiewicz, Craig A; Bellissimo, Daniel B; Murphy, Anthony T; Kovacevic, Steve; Wroblewski, Victor J; Witcher, Derrick R

    2008-10-01

    Individuals donating whole blood 13 times in a 2-year period without development of iron deficiency anemia (superdonors) are a self-selected population that is deferred for low hematocrit (Hct) level less frequently than other donors. Iron metabolism was assessed in 138 superdonors through a questionnaire and measurement of Hct, serum ferritin, serum hepcidin, and serum growth differentiation factor 15 (GDF15). Genetic testing for HFE and JAK-2 mutations was also performed. Iron deficiency (ferritin level, <30 microg/L) is present in more than 60 percent of superdonors. Behaviors altering iron status included casual use of iron supplements in males, but not in females, and cigarette smoking that produced increased Hct associated with decreased ferritin. The striking biochemical characteristic of superdonors is greatly decreased serum hepcidin, consistent with their need to absorb maximal amounts of dietary iron to replace that lost from blood donation. GDF15 is normal in most superdonors, indicating that GDF15 overexpression arising from the expanded erythroid pool necessary to replace donated red cells is not the biochemical mechanism for the decreased serum hepcidin. Mutations in JAK-2 were not found, indicating that undiagnosed polycythemia vera is not a common cause for successful repeated blood donation by superdonors. Mutations in HFE associated with hemochromatosis were present in superdonors at the same frequency as the normal population. However, superdonors heterozygous for the H63D mutation in HFE had significantly decreased hepcidin : ferritin ratios demonstrating for the first time that the heterozygous state for HFE mutations is associated with alterations in hepcidin expression.

  10. Zonulin and iron metabolism in heart transplant recipients.

    Science.gov (United States)

    Przybyłowski, P; Nowak, E; Janik, L; Wasilewski, G; Kozlowska, S; Małyszko, J

    2014-10-01

    In patients after heart transplantation, anemia is relatively common and is associated with impaired kidney function, subclinical inflammatory state, and immunosuppressive treatment. Zonulin-prehaptoglibin-2 is newly discovered protein with poorly defined function. Hemoglobin binds haptoglobin, and this stable complex prevents oxidative stress caused by hemoglobin. Zonulin is necessary for integrity of intracellular tight junction in the gut. Taking into consideration iron metabolism, including its absorption in the gut, the aim of this study was to assess zonulin levels in heart transplant recipients and their possible correlations with iron status, immunosuppressive therapy, and kidney function. The study was performed with 80 stable heart transplant recipients and 22 healthy volunteers. Zonulin, iron status, and inflammatory markers were assessed with the use of commercially available kits. Zonulin correlated with intraventricular diameter (r = 0.30; P zonulin and iron status. Zonulin was significantly lower in heart transplant recipients than in healthy volunteers (P zonulin level. Zonulin, despite its effect on the absorption of different nutrients and other substances and hypothethic role in oxidative stress, seems not to play a role in the pathogenesis of anemia in heart transplant recipients. Its physiologic role remains obscure.

  11. Metabolismo do ferro em equinos atletas Iron metabolism in athletics horses

    Directory of Open Access Journals (Sweden)

    Luciana Pereira Machado

    2010-03-01

    Full Text Available O ferro participa de várias funções vitais do organismo, como o transporte de oxigênio e de elétrons e a síntese do DNA. Desequilíbrios do metabolismo do ferro podem estar relacionados a sua deficiência ou sobrecarga, porém a deficiência é rara em equinos adultos. Apesar disso, criadores e veterinários de cavalos de esporte utilizam frequentemente suplementos contendo ferro com o objetivo de melhorar o desempenho atlético. Até o momento, nenhum estudo comprovou que o exercício induz deficiência de ferro nessa espécie ou que a suplementação de ferro melhora o seu desempenho. O diagnóstico de deficiência ou sobrecarga de ferro depende de uma avaliação laboratorial criteriosa. A suplementação em equinos não deficientes pode induzir o acúmulo excessivo de ferro, com graves consequências para o animal. Este trabalho revisa as alterações do metabolismo do ferro em equinos submetidos ao exercício, os métodos laboratoriais de avaliação dos estoques de ferro e as consequências da suplementação indevida.Iron participates in many vital functions, e.g. oxygen and electron transport, and DNA synthesis. Iron metabolism imbalances can be related to deficiency or overload; however, the deficiency is rare in adult horses. Despite this, breeders and veterinarians usually supplement horses with iron, aiming to improve athletic performance. Until now, no study proved that exercise induces iron deficiency in this species or that iron supplementation improves its performance. Diagnosis of iron deficiency or overload depends on a comprehensive laboratorial evaluation. Supplementation in horses without disabilities can induce excessive iron storage, with serious consequences for the animal. This study reviews the iron metabolism alterations in equine submitted to exercise, laboratorial methods for the evaluation of iron storage, and consequences of improper supplementation.

  12. Hepcidin: an important iron metabolism regulator in chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Sandra Azevedo Antunes

    Full Text Available Abstract Anemia is a common complication and its impact on morbimortality in patients with chronic kidney disease (CKD is well known. The discovery of hepcidin and its functions has contributed to a better understanding of iron metabolism disorders in CKD anemia. Hepcidin is a peptide mainly produced by hepatocytes and, through a connection with ferroportin, it regulates iron absorption in the duodenum and its release of stock cells. High hepcidin concentrations described in patients with CKD, especially in more advanced stages are attributed to decreased renal excretion and increased production. The elevation of hepcidin has been associated with infection, inflammation, atherosclerosis, insulin resistance and oxidative stress. Some strategies were tested to reduce the effects of hepcidin in patients with CKD, however more studies are necessary to assess the impact of its modulation in the management of anemia in this population.

  13. Altered carbon dioxide metabolism and creatine abnormalities in rett syndrome

    NARCIS (Netherlands)

    Halbach, Nicky S J; Smeets, Eric E J; Bierau, Jörgen; Keularts, Irene M L W; Plasqui, Guy; Julu, Peter O O; Engerström, Ingegerd Witt; Bakker, Jaap A.; Curfs, Leopold M G

    2012-01-01

    Despite their good appetite, many females with Rett syndrome (RTT) meet the criteria for moderate to severe malnutrition. Although feeding difficulties may play a part in this, other constitutional factors such as altered metabolic processes are suspected. Irregular breathing is a common clinical

  14. Altered metabolic signature in pre-diabetic NOD mice.

    Directory of Open Access Journals (Sweden)

    Rasmus Madsen

    Full Text Available Altered metabolism proceeding seroconversion in children progressing to Type 1 diabetes has previously been demonstrated. We tested the hypothesis that non-obese diabetic (NOD mice show a similarly altered metabolic profile compared to C57BL/6 mice. Blood samples from NOD and C57BL/6 female mice was collected at 0, 1, 2, 3, 4, 5, 6, 7, 9, 11, 13 and 15 weeks and the metabolite content was analyzed using GC-MS. Based on the data of 89 identified metabolites OPLS-DA analysis was employed to determine the most discriminative metabolites. In silico analysis of potential involved metabolic enzymes was performed using the dbSNP data base. Already at 0 weeks NOD mice displayed a unique metabolic signature compared to C57BL/6. A shift in the metabolism was observed for both strains the first weeks of life, a pattern that stabilized after 5 weeks of age. Multivariate analysis revealed the most discriminative metabolites, which included inosine and glutamic acid. In silico analysis of the genes in the involved metabolic pathways revealed several SNPs in either regulatory or coding regions, some in previously defined insulin dependent diabetes (Idd regions. Our result shows that NOD mice display an altered metabolic profile that is partly resembling the previously observation made in children progressing to Type 1 diabetes. The level of glutamic acid was one of the most discriminative metabolites in addition to several metabolites in the TCA cycle and nucleic acid components. The in silico analysis indicated that the genes responsible for this reside within previously defined Idd regions.

  15. Catecholamines promote Actinobacillus pleuropneumoniae growth by regulating iron metabolism.

    Science.gov (United States)

    Li, Lu; Chen, Zhaohui; Bei, Weicheng; Su, Zhipeng; Huang, Qi; Zhang, Liang; Chen, Huanchun; Zhou, Rui

    2015-01-01

    Catecholamines are host stress hormones that can induce the growth of many bacteria by facilitating iron utilization and/or regulate the expression of virulence genes through specific hormone receptors. Whether these two responsive pathways are interconnected is unknown. In our previous study, it was found that catecholamines can regulate the expression of a great number of genes of Actinobacillus pleuropneumoniae, an important swine respiratory pathogen. However, bacterial growth was not affected by catecholamines in rich medium. In this study, it was discovered that catecholamines affected A. pleuropneumoniae growth in chemically defined medium (CDM). We found that serum inhibited A. pleuropneumoniae growth in CDM, while epinephrine, norepinephrine and dopamine promoted A. pleuropneumoniae growth in the CDM containing serum. The known bacterial hormone receptor QseC didn't play roles in this process. Ion-supplementation and transcriptome analysis indicated that serum addition resulted in iron-restricted conditions which were alleviated by the addition of catecholamines. Transferrin, one of the components in serum, inhibited the growth of A. pleuropneumoniae in CDM, an effect reversed by addition of catecholamines in a TonB2-dependent manner. Our data demonstrate that catecholamines promote A. pleuropneumoniae growth by regulating iron-acquisition and metabolism, which is independent of the adrenergic receptor QseC.

  16. Catecholamines promote Actinobacillus pleuropneumoniae growth by regulating iron metabolism.

    Directory of Open Access Journals (Sweden)

    Lu Li

    Full Text Available Catecholamines are host stress hormones that can induce the growth of many bacteria by facilitating iron utilization and/or regulate the expression of virulence genes through specific hormone receptors. Whether these two responsive pathways are interconnected is unknown. In our previous study, it was found that catecholamines can regulate the expression of a great number of genes of Actinobacillus pleuropneumoniae, an important swine respiratory pathogen. However, bacterial growth was not affected by catecholamines in rich medium. In this study, it was discovered that catecholamines affected A. pleuropneumoniae growth in chemically defined medium (CDM. We found that serum inhibited A. pleuropneumoniae growth in CDM, while epinephrine, norepinephrine and dopamine promoted A. pleuropneumoniae growth in the CDM containing serum. The known bacterial hormone receptor QseC didn't play roles in this process. Ion-supplementation and transcriptome analysis indicated that serum addition resulted in iron-restricted conditions which were alleviated by the addition of catecholamines. Transferrin, one of the components in serum, inhibited the growth of A. pleuropneumoniae in CDM, an effect reversed by addition of catecholamines in a TonB2-dependent manner. Our data demonstrate that catecholamines promote A. pleuropneumoniae growth by regulating iron-acquisition and metabolism, which is independent of the adrenergic receptor QseC.

  17. Fisiologia e metabolismo do ferro Iron physiology and metabolism

    Directory of Open Access Journals (Sweden)

    Helena Z. W. Grotto

    2010-06-01

    Full Text Available O conhecimento sobre a fisiologia e metabolismo do ferro foi bastante incrementado nos últimos anos. A identificação de alguns genes e as repercussões quando de suas mutações, principalmente as relacionadas ao acúmulo de ferro, auxiliaram no entendimento dos mecanismos regulatórios responsáveis pela manutenção da homeostase desse nutriente essencial para numerosos processos bioquímicos. A função de diversas moléculas já está bem estabelecida, como da transferrina e seu receptor e, nas últimas décadas, novas moléculas têm sido identificadas, como a ferroportina, o transportador de metal divalente e hemojuvelina. Um elegante mecanismo de controle mantém o equilíbrio entre os processos de absorção do ferro, reciclagem, mobilização, utilização e estoque. Alterações no sincronismo desses processos podem causar tanto a deficiência como a sobrecarga de ferro, ambos com importantes repercussões clínicas para o paciente. Nessa minirrevisão serão abordados aspectos relacionados ao metabolismo do ferro e à participação de várias proteínas e mediadores envolvidos. Serão também apresentados os mecanismos regulatórios celular e sistêmico responsáveis pela disponibilidade do ferro em concentrações ideais para a manutenção de sua homeostase.Knowledge of the iron physiology and metabolism has increased greatly over the last few years. The identification of genes and the consequences of mutations, especially those related to the accumulation of iron, have improved the understanding of the regulatory mechanisms responsible for maintaining homeostasis of this essential nutrient in many biochemical processes. The function of several molecules is well established, as in the case of transferrin and its receptor and, in recent decades, new molecules have been identified such as ferroportin, divalent metal transporter, hemojuvelin and hepcidin. An elegant control mechanism maintains the balance between the processes of

  18. Nitrate-Dependent Iron Oxidation: A Potential Mars Metabolism

    Science.gov (United States)

    Price, Alex; Pearson, Victoria K.; Schwenzer, Susanne P.; Miot, Jennyfer; Olsson-Francis, Karen

    2018-01-01

    This work considers the hypothetical viability of microbial nitrate-dependent Fe2+ oxidation (NDFO) for supporting simple life in the context of the early Mars environment. This draws on knowledge built up over several decades of remote and in situ observation, as well as recent discoveries that have shaped current understanding of early Mars. Our current understanding is that certain early martian environments fulfill several of the key requirements for microbes with NDFO metabolism. First, abundant Fe2+ has been identified on Mars and provides evidence of an accessible electron donor; evidence of anoxia suggests that abiotic Fe2+ oxidation by molecular oxygen would not have interfered and competed with microbial iron metabolism in these environments. Second, nitrate, which can be used by some iron oxidizing microorganisms as an electron acceptor, has also been confirmed in modern aeolian and ancient sediment deposits on Mars. In addition to redox substrates, reservoirs of both organic and inorganic carbon are available for biosynthesis, and geochemical evidence suggests that lacustrine systems during the hydrologically active Noachian period (4.1–3.7 Ga) match the circumneutral pH requirements of nitrate-dependent iron-oxidizing microorganisms. As well as potentially acting as a primary producer in early martian lakes and fluvial systems, the light-independent nature of NDFO suggests that such microbes could have persisted in sub-surface aquifers long after the desiccation of the surface, provided that adequate carbon and nitrates sources were prevalent. Traces of NDFO microorganisms may be preserved in the rock record by biomineralization and cellular encrustation in zones of high Fe2+ concentrations. These processes could produce morphological biosignatures, preserve distinctive Fe-isotope variation patterns, and enhance preservation of biological organic compounds. Such biosignatures could be detectable by future missions to Mars with appropriate

  19. Nitrate-Dependent Iron Oxidation: A Potential Mars Metabolism

    Directory of Open Access Journals (Sweden)

    Alex Price

    2018-03-01

    Full Text Available This work considers the hypothetical viability of microbial nitrate-dependent Fe2+ oxidation (NDFO for supporting simple life in the context of the early Mars environment. This draws on knowledge built up over several decades of remote and in situ observation, as well as recent discoveries that have shaped current understanding of early Mars. Our current understanding is that certain early martian environments fulfill several of the key requirements for microbes with NDFO metabolism. First, abundant Fe2+ has been identified on Mars and provides evidence of an accessible electron donor; evidence of anoxia suggests that abiotic Fe2+ oxidation by molecular oxygen would not have interfered and competed with microbial iron metabolism in these environments. Second, nitrate, which can be used by some iron oxidizing microorganisms as an electron acceptor, has also been confirmed in modern aeolian and ancient sediment deposits on Mars. In addition to redox substrates, reservoirs of both organic and inorganic carbon are available for biosynthesis, and geochemical evidence suggests that lacustrine systems during the hydrologically active Noachian period (4.1–3.7 Ga match the circumneutral pH requirements of nitrate-dependent iron-oxidizing microorganisms. As well as potentially acting as a primary producer in early martian lakes and fluvial systems, the light-independent nature of NDFO suggests that such microbes could have persisted in sub-surface aquifers long after the desiccation of the surface, provided that adequate carbon and nitrates sources were prevalent. Traces of NDFO microorganisms may be preserved in the rock record by biomineralization and cellular encrustation in zones of high Fe2+ concentrations. These processes could produce morphological biosignatures, preserve distinctive Fe-isotope variation patterns, and enhance preservation of biological organic compounds. Such biosignatures could be detectable by future missions to Mars with

  20. Insights into the Structure and Metabolic Function of Microbes That Shape Pelagic Iron-Rich Aggregates (“Iron Snow”)

    Science.gov (United States)

    Lu, Shipeng; Chourey, Karuna; Reiche, Marco; Nietzsche, Sandor; Shah, Manesh B.; Neu, Thomas R.; Hettich, Robert L.

    2013-01-01

    Microbial ferrous iron [Fe(II)] oxidation leads to the formation of iron-rich macroscopic aggregates (“iron snow”) at the redoxcline in a stratified lignite mine lake in east-central Germany. We aimed to identify the abundant Fe-oxidizing and Fe-reducing microorganisms likely to be involved in the formation and transformation of iron snow present in the redoxcline in two basins of the lake that differ in their pH values. Nucleic acid- and lipid-stained microbial cells of various morphologies detected by confocal laser scanning microscopy were homogeneously distributed in all iron snow samples. The dominant iron mineral appeared to be schwertmannite, with shorter needles in the northern than in the central basin samples. Total bacterial 16S rRNA gene copies ranged from 5.0 × 108 copies g (dry weight)−1 in the acidic central lake basin (pH 3.3) to 4.0 × 1010 copies g (dry weight)−1 in the less acidic (pH 5.9) northern basin. Total RNA-based quantitative PCR assigned up to 61% of metabolically active microbial communities to Fe-oxidizing- and Fe-reducing-related bacteria, indicating that iron metabolism was an important metabolic strategy. Molecular identification of abundant groups suggested that iron snow surfaces were formed by chemoautotrophic iron oxidizers, such as Acidimicrobium, Ferrovum, Acidithiobacillus, Thiobacillus, and Chlorobium, in the redoxcline and were rapidly colonized by heterotrophic iron reducers, such as Acidiphilium, Albidiferax-like, and Geobacter-like groups. Metaproteomics yielded 283 different proteins from northern basin iron snow samples, and protein identification provided a glimpse into some of their in situ metabolic processes, such as primary production (CO2 fixation), respiration, motility, and survival strategies. PMID:23645202

  1. Insights into the structure and metabolic function of microbes that shape pelagic iron-rich aggregates ("iron snow").

    Science.gov (United States)

    Lu, Shipeng; Chourey, Karuna; Reiche, Marco; Nietzsche, Sandor; Shah, Manesh B; Neu, Thomas R; Hettich, Robert L; Küsel, Kirsten

    2013-07-01

    Microbial ferrous iron [Fe(II)] oxidation leads to the formation of iron-rich macroscopic aggregates ("iron snow") at the redoxcline in a stratified lignite mine lake in east-central Germany. We aimed to identify the abundant Fe-oxidizing and Fe-reducing microorganisms likely to be involved in the formation and transformation of iron snow present in the redoxcline in two basins of the lake that differ in their pH values. Nucleic acid- and lipid-stained microbial cells of various morphologies detected by confocal laser scanning microscopy were homogeneously distributed in all iron snow samples. The dominant iron mineral appeared to be schwertmannite, with shorter needles in the northern than in the central basin samples. Total bacterial 16S rRNA gene copies ranged from 5.0 × 10(8) copies g (dry weight)(-1) in the acidic central lake basin (pH 3.3) to 4.0 × 10(10) copies g (dry weight)(-1) in the less acidic (pH 5.9) northern basin. Total RNA-based quantitative PCR assigned up to 61% of metabolically active microbial communities to Fe-oxidizing- and Fe-reducing-related bacteria, indicating that iron metabolism was an important metabolic strategy. Molecular identification of abundant groups suggested that iron snow surfaces were formed by chemoautotrophic iron oxidizers, such as Acidimicrobium, Ferrovum, Acidithiobacillus, Thiobacillus, and Chlorobium, in the redoxcline and were rapidly colonized by heterotrophic iron reducers, such as Acidiphilium, Albidiferax-like, and Geobacter-like groups. Metaproteomics yielded 283 different proteins from northern basin iron snow samples, and protein identification provided a glimpse into some of their in situ metabolic processes, such as primary production (CO2 fixation), respiration, motility, and survival strategies.

  2. Sleep disorders: A review of the interface between restless legs syndrome and iron metabolism

    Directory of Open Access Journals (Sweden)

    Paulo Daubian-Nosé

    2014-12-01

    Full Text Available Restless legs syndrome (RLS is characterized by unpleasant sensations mainly in the legs. 43% of RLS-associated conditions have also been associated with systemic iron deficiency. The objective of this study was to review in the literature the relationship between iron metabolism and RLS. With an initial search using the keywords combination “Iron Metabolism OR Iron Deficiency AND Restless Legs Syndrome,” 145 articles were screened, and 20 articles were selected. Few studies were found for this review in the period of 2001–2014, however, the correlation between RLS and iron was evident.

  3. Radiation Exposure Alters Expression of Metabolic Enzyme Genes In Mice

    Science.gov (United States)

    Wotring, Virginia E.; Mangala, L. S.; Zhang, Y.; Wu, H.

    2010-01-01

    Most pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Because of the importance of the liver in drug metabolism it is important to understand the effects of spaceflight on the enzymes of the liver. Exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. This study is an effort to examine the effects of adaptive mechanisms that may be triggered by early exposure to low radiation doses. Using procedures approved by the JSC Animal Care & Use Committee, C57 male mice were exposed to Cs-137 in groups: controls, low dose (50 mGy), high dose (6Gy) and a fourth group that received both radiation doses separated by 24 hours. Animals were anesthetized and sacrificed 4 hours after their last radiation exposure. Livers were removed immediately and flash-frozen in liquid nitrogen. Tissue was homogenized, RNA extracted and purified (Absolutely RNA, Agilent). Quality of RNA samples was evaluated (Agilent Bioanalyzer 2100). Complementary DNA was prepared from high-quality RNA samples, and used to run RT-qPCR screening arrays for DNA Repair and Drug Metabolism (SuperArray, SABiosciences/Qiagen; BioRad Cfx96 qPCR System). Of 91 drug metabolism genes examined, expression of 7 was altered by at least one treatment condition. Genes that had elevated expression include those that metabolize promethazine and steroids (4-8-fold), many that reduce oxidation products, and one that reduces heavy metal exposure (greater than 200-fold). Of the 91 DNA repair and general metabolism genes examined, expression of 14 was altered by at least one treatment condition. These gene expression changes are likely homeostatic and could lead to development of new radioprotective countermeasures.

  4. THE IRON METABOLISM IN CHILDREN IS NORMAL ALSO AT INFECTIOUS DISEASES

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    A. M. Aliyeva

    2017-01-01

    Full Text Available The authors consistently consider various aspects of iron metabolism in children and in pediatric patients with accompanying infectious process. Special attention is attributed to the problem of combined infections with anemia/iron-deficiency states, non-infectious factors of iron deficiency and anemia in childhood,  as well as to novel approaches to diagnostics of iron metabolism disorders (including the studies of markers such as hepcidin, ferroportin, soluble transferrin receptor, hypoxia inducible factor, divalent metals transporter, etc. Foreign investigations incorporating novel iron metabolism markers in pediatric patients of various ages with infectious/inflammatory disorders are concisely described. The ambiguity and disputability of iron metabolism in pediatric patients against the background of infections and conditions, accompanied with inflammation are stressed.

  5. Iron metabolism is associated with adipocyte insulin resistance and plasma adiponectin

    NARCIS (Netherlands)

    Wlazlo, N.; Greevenbroek, van M.M.J.; Ferreira, I.; Jansen, E.H.J.M.; Feskens, E.J.M.; Kallen, van der C.J.H.; Schalkwijk, C.G.; Bravenboer, B.; Stehouwer, C.D.A.

    2013-01-01

    OBJECTIVE-Adipocyte insulin resistance (IR) is a key feature early in the pathogenesis of type 2 diabetes mellitus (T2DM), and although scarce, data in the literature suggest a direct role for iron and iron metabolism-related factors in adipose tissue function and metabolism. Serum ferritin and

  6. Visible light alters yeast metabolic rhythms by inhibiting respiration

    OpenAIRE

    Robertson, James Brian; Davis, Chris R.; Johnson, Carl Hirschie

    2013-01-01

    In some organisms, respiration fluctuates cyclically, and these rhythms can be a sensitive gauge of metabolism. Constant or pulsatile exposure of yeast to visible wavelengths of light significantly alters and/or initiates these respiratory oscillations, revealing a further dimension of the challenges to yeast living in natural environments. Our results also have implications for the use of light as research tools—e.g., for excitation of fluorescence microscopically—even in organisms such as y...

  7. Evidence for an altered tryptophan metabolism in fibromyalgia.

    Science.gov (United States)

    Schwarz, M J; Offenbaecher, M; Neumeister, A; Ewert, T; Willeit, M; Praschak-Rieder, N; Zach, J; Zacherl, M; Lossau, K; Weisser, R; Stucki, G; Ackenheil, M

    2002-12-01

    Fibromyalgia (FM) is a prevalent syndrome with chronic pain and a hypothesized underlying disturbance of the tryptophan (TRP) metabolism. We performed a tryptophan depletion (TD) test in 17 FM patients and 17 controls. TRP, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and interleukin-6 (IL-6) were measured. Additionally pain perception was monitored in the FM patients. FM patients and controls exhibited a decrease of TRP and KYN during TD. 5-HIAA levels also decreased in all controls and in 11 FM patients, but showed a marked increase in 6 FM patients. IL-6 significantly increased during TD in the patients, but not in the controls. Pain perception was not affected in the FM patients. These data demonstrate an altered TRP metabolism in a subgroup of FM patients, where the TD seems to activate 5-HT metabolism. Our findings may have diagnostic as well as therapeutic implications in the field of fibromyalgia.

  8. Experimental evaluation of an altered tryptophan metabolism in fibromyalgia.

    Science.gov (United States)

    Schwarz, Markus J; Offenbaecher, Martin; Neumeister, Alexander; Ackenheil, Manfred

    2003-01-01

    Fibromyalgia (FM) is a prevalent syndrome with chronic pain and a hypothesised underlying disturbance of the tryptophan (TRP) metabolism. We performed a tryptophan depletion (TD) test in 17 FM patients and 17 controls. TRP, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and Interleukin-6 (IL-6) were measured. Additionally pain perception was monitored in the FM patients. FM patients and controls exhibited a decrease of TRP and KYN during TD. 5-HIAA levels also decreased in all controls and in 11 FM patients, but showed a marked increase in 6 FM patients. IL-6 significantly increased during TD in the patients, but not in the controls. Pain perception was not affected in the FM patients. These data demonstrate an altered TRP metabolism in a subgroup of FM patients, where the TD seems to activate 5-HT metabolism and IL-6 production. Our findings may have diagnostic as well as therapeutic implications in the field of fibromyalgia.

  9. Altered oxidative stress and carbohydrate metabolism in canine mammary tumors

    Directory of Open Access Journals (Sweden)

    K. Jayasri

    2016-12-01

    Full Text Available Aim: Mammary tumors are the most prevalent type of neoplasms in canines. Even though cancer induced metabolic alterations are well established, the clinical data describing the metabolic profiles of animal tumors is not available. Hence, our present investigation was carried out with the aim of studying changes in carbohydrate metabolism along with the level of oxidative stress in canine mammary tumors. Materials and Methods: Fresh mammary tumor tissues along with the adjacent healthy tissues were collected from the college surgical ward. The levels of thiobarbituric acid reactive substances (TBARS, glutathione, protein, hexose, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and glucose-6-phosphate dehydrogenase (G6PD were analyzed in all the tissues. The results were analyzed statistically. Results: More than two-fold increase in TBARS and three-fold increase in glutathione levels were observed in neoplastic tissues. Hexokinase activity and hexose concentration (175% was found to be increased, whereas glucose-6-phosphatase (33%, fructose-1, 6-bisphosphatase (42%, and G6PD (5 fold activities were reduced in tumor mass compared to control. Conclusion: Finally, it was revealed that lipid peroxidation was increased with differentially altered carbohydrate metabolism in canine mammary tumors.

  10. Co-regulation of Iron Metabolism and Virulence Associated Functions by Iron and XibR, a Novel Iron Binding Transcription Factor, in the Plant Pathogen Xanthomonas

    Science.gov (United States)

    Pandey, Sheo Shankar; Patnana, Pradeep Kumar; Lomada, Santosh Kumar; Tomar, Archana; Chatterjee, Subhadeep

    2016-01-01

    Abilities of bacterial pathogens to adapt to the iron limitation present in hosts is critical to their virulence. Bacterial pathogens have evolved diverse strategies to coordinately regulate iron metabolism and virulence associated functions to maintain iron homeostasis in response to changing iron availability in the environment. In many bacteria the ferric uptake regulator (Fur) functions as transcription factor that utilize ferrous form of iron as cofactor to regulate transcription of iron metabolism and many cellular functions. However, mechanisms of fine-tuning and coordinated regulation of virulence associated function beyond iron and Fur-Fe2+ remain undefined. In this study, we show that a novel transcriptional regulator XibR (named X anthomonas iron binding regulator) of the NtrC family, is required for fine-tuning and co-coordinately regulating the expression of several iron regulated genes and virulence associated functions in phytopathogen Xanthomonas campestris pv. campestris (Xcc). Genome wide expression analysis of iron-starvation stimulon and XibR regulon, GUS assays, genetic and functional studies of xibR mutant revealed that XibR positively regulates functions involved in iron storage and uptake, chemotaxis, motility and negatively regulates siderophore production, in response to iron. Furthermore, chromatin immunoprecipitation followed by quantitative real-time PCR indicated that iron promoted binding of the XibR to the upstream regulatory sequence of operon’s involved in chemotaxis and motility. Circular dichroism spectroscopy showed that purified XibR bound ferric form of iron. Electrophoretic mobility shift assay revealed that iron positively affected the binding of XibR to the upstream regulatory sequences of the target virulence genes, an effect that was reversed by ferric iron chelator deferoxamine. Taken together, these data revealed that how XibR coordinately regulates virulence associated and iron metabolism functions in Xanthomonads in

  11. Knocking down mitochondrial iron transporter (MIT) reprograms primary and secondary metabolism in rice plants.

    Science.gov (United States)

    Vigani, Gianpiero; Bashir, Khurram; Ishimaru, Yasuhiro; Lehmann, Martin; Casiraghi, Fabio Marco; Nakanishi, Hiromi; Seki, Motoaki; Geigenberger, Peter; Zocchi, Graziano; Nishizawa, Naoko K

    2016-03-01

    Iron (Fe) is an essential micronutrient for plant growth and development, and its reduced bioavailability strongly impairs mitochondrial functionality. In this work, the metabolic adjustment in the rice (Oryza sativa) mitochondrial Fe transporter knockdown mutant (mit-2) was analysed. Biochemical characterization of purified mitochondria from rice roots showed alteration in the respiratory chain of mit-2 compared with wild-type (WT) plants. In particular, proteins belonging to the type II alternative NAD(P)H dehydrogenases accumulated strongly in mit-2 plants, indicating that alternative pathways were activated to keep the respiratory chain working. Additionally, large-scale changes in the transcriptome and metabolome were observed in mit-2 rice plants. In particular, a strong alteration (up-/down-regulation) in the expression of genes encoding enzymes of both primary and secondary metabolism was found in mutant plants. This was reflected by changes in the metabolic profiles in both roots and shoots of mit-2 plants. Significant alterations in the levels of amino acids belonging to the aspartic acid-related pathways (aspartic acid, lysine, and threonine in roots, and aspartic acid and ornithine in shoots) were found that are strictly connected to the Krebs cycle. Furthermore, some metabolites (e.g. pyruvic acid, fumaric acid, ornithine, and oligosaccharides of the raffinose family) accumulated only in the shoot of mit-2 plants, indicating possible hypoxic responses. These findings suggest that the induction of local Fe deficiency in the mitochondrial compartment of mit-2 plants differentially affects the transcript as well as the metabolic profiles in root and shoot tissues. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  12. Metabolic state alters economic decision making under risk in humans.

    Directory of Open Access Journals (Sweden)

    Mkael Symmonds

    2010-06-01

    Full Text Available Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores. Specifically, animals often express a preference for risky (more variable food sources when below a metabolic reference point (hungry, and safe (less variable food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans.We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake, and circulating leptin levels (providing an assay of energy reserves. We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively.We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has

  13. Duodenal Cytochrome b (DCYTB in Iron Metabolism: An Update on Function and Regulation

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    Darius J. R. Lane

    2015-03-01

    Full Text Available Iron and ascorbate are vital cellular constituents in mammalian systems. The bulk-requirement for iron is during erythropoiesis leading to the generation of hemoglobin-containing erythrocytes. Additionally; both iron and ascorbate are required as co-factors in numerous metabolic reactions. Iron homeostasis is controlled at the level of uptake; rather than excretion. Accumulating evidence strongly suggests that in addition to the known ability of dietary ascorbate to enhance non-heme iron absorption in the gut; ascorbate regulates iron homeostasis. The involvement of ascorbate in dietary iron absorption extends beyond the direct chemical reduction of non-heme iron by dietary ascorbate. Among other activities; intra-enterocyte ascorbate appears to be involved in the provision of electrons to a family of trans-membrane redox enzymes; namely those of the cytochrome b561 class. These hemoproteins oxidize a pool of ascorbate on one side of the membrane in order to reduce an electron acceptor (e.g., non-heme iron on the opposite side of the membrane. One member of this family; duodenal cytochrome b (DCYTB; may play an important role in ascorbate-dependent reduction of non-heme iron in the gut prior to uptake by ferrous-iron transporters. This review discusses the emerging relationship between cellular iron homeostasis; the emergent “IRP1-HIF2α axis”; DCYTB and ascorbate in relation to iron metabolism.

  14. Ferrokinetic Parameters and Regulation of Iron Metabolism in Patients with Chronic Inflammatory Bowel Diseases

    Directory of Open Access Journals (Sweden)

    T.Y. Boiko

    2014-11-01

    Full Text Available Article presents parameters of iron metabolism and cytokines (IL-6 and TNF-α in patients with chronic inflammatory bowel diseases (CIBD. The material for the study was the blood of 69 patients with CIBD and anemia and 26 — without anemia. We have studied the features of main ferrokinetic parameters — iron, total iron-binding capacity of serum, transferrin saturation, ferritin, transferrin receptor, erythropoietin, hepcidin depending on hemoglobin level and the type of anemia. The relationship of iron metabolism disorders with the level of proinflammatory cytokines (IL-6 and TNF-α is shown.

  15. Tumor-induced disorder of iron metabolism in major organs: a new insight from chemical speciation of iron.

    Science.gov (United States)

    Chen, Rujie; Chen, Guangcun

    2018-01-01

    Objective To investigate the evolution of iron speciation in major organs of tumor-bearing mice and its role in cancer formation and cancer-associated complications. Methods The concentration and chemical speciation of iron in the spleen, liver, lung, kidney, heart, blood, muscle, and tumor tissue of healthy mice and tumor-bearing mice were studied by synchrotron radiation-based total reflection X-ray fluorescence spectrometry (SR-TXRF) coupled with X-ray absorption spectroscopy (XAS). Results The TXRF and XAS results showed that the iron content, especially the ferritin content, significantly decreased in the blood and spleen but significantly increased in the liver, lung, and muscle of mice after tumor implantation. The chemical speciation of iron in the tumor mainly comprised ferrous-sulfide-like iron and ferritin. Conclusion The tumors disturbed the iron metabolism in major organs, and the evolution of iron may be involved in iron deficiency anemia, cancer growth, and immunity. Additionally, iron speciation-based markers may be further developed as clinical indicators for cancer and cancer-associated complications.

  16. Metabolic flux prediction in cancer cells with altered substrate uptake.

    Science.gov (United States)

    Schwartz, Jean-Marc; Barber, Michael; Soons, Zita

    2015-12-01

    Proliferating cells, such as cancer cells, are known to have an unusual metabolism, characterized by an increased rate of glycolysis and amino acid metabolism. Our understanding of this phenomenon is limited but could potentially be used in order to develop new therapies. Computational modelling techniques, such as flux balance analysis (FBA), have been used to predict fluxes in various cell types, but remain of limited use to explain the unusual metabolic shifts and altered substrate uptake in human cancer cells. We implemented a new flux prediction method based on elementary modes (EMs) and structural flux (StruF) analysis and tested them against experimentally measured flux data obtained from (13)C-labelling in a cancer cell line. We assessed the quality of predictions using different objective functions along with different techniques in normalizing a metabolic network with more than one substrate input. Results show a good correlation between predicted and experimental values and indicate that the choice of cellular objective critically affects the quality of predictions. In particular, lactate gives an excellent correlation and correctly predicts the high flux through glycolysis, matching the observed characteristics of cancer cells. In contrast with FBA, which requires a priori definition of all uptake rates, often hard to measure, atomic StruFs (aStruFs) are able to predict uptake rates of multiple substrates. © 2015 Authors; published by Portland Press Limited.

  17. Does caffeine alter muscle carbohydrate and fat metabolism during exercise?

    DEFF Research Database (Denmark)

    Graham, Terry E; Battram, Danielle S; Dela, Flemming

    2008-01-01

    Caffeine, an adenosine receptor antagonist, has been studied for decades as a putative ergogenic aid. In the past 2 decades, the information has overwhelmingly demonstrated that it indeed is a powerful ergogenic aid, and frequently theories have been proposed that this is due to alterations in fat...... and carbohydrate metabolism. While caffeine certainly mobilizes fatty acids from adipose tissue, rarely have measures of the respiratory exchange ratio indicated an increase in fat oxidation. However, this is a difficult measure to perform accurately during exercise, and small changes could be physiologically...... and increased (p caffeine were to increase (p caffeine has ergogenic effects as a result of enhanced fat oxidation...

  18. Thrombolytic therapy of acute myocardial infarction alters collagen metabolism

    DEFF Research Database (Denmark)

    Høst, N B; Hansen, S S; Jensen, L T

    1994-01-01

    infarction and receiving thrombolytic therapy. Regardless of whether acute myocardial infarction was confirmed or not, S-PIIINP increased (94-120%) 4 h after streptokinase therapy (p ....02). With confirmed acute myocardial infarction, S-PIIINP increased from 24 h towards a plateau reached at day 2-3 (p acute myocardial infarction had S-PICP above baseline at 1, 2, and 6 months (p ....05). A less pronounced S-PIIINP increase was noted with tissue-plasminogen activator than with streptokinase. Thrombolytic therapy induces collagen breakdown regardless of whether acute myocardial infarction is confirmed or not. With confirmed acute myocardial infarction collagen metabolism is altered...

  19. Iron oxides alter methanogenic pathways of acetate in production water of high-temperature petroleum reservoir.

    Science.gov (United States)

    Pan, Pan; Hong, Bo; Mbadinga, Serge Maurice; Wang, Li-Ying; Liu, Jin-Feng; Yang, Shi-Zhong; Gu, Ji-Dong; Mu, Bo-Zhong

    2017-09-01

    Acetate is a key intermediate in anaerobic crude oil biodegradation and also a precursor for methanogenesis in petroleum reservoirs. The impact of iron oxides, viz. β-FeOOH (akaganéite) and magnetite (Fe 3 O 4 ), on the methanogenic acetate metabolism in production water of a high-temperature petroleum reservoir was investigated. Methane production was observed in all the treatments amended with acetate. In the microcosms amended with acetate solely about 30% of the acetate utilized was converted to methane, whereas methane production was stimulated in the presence of magnetite (Fe 3 O 4 ) resulting in a 48.34% conversion to methane. Methane production in acetate-amended, β-FeOOH (akaganéite)-supplemented microcosms was much faster and acetate consumption was greatly improved compared to the other conditions in which the stoichiometric expected amounts of methane were not produced. Microbial community analysis showed that Thermacetogenium spp. (known syntrophic acetate oxidizers) and hydrogenotrophic methanogens closely related to Methanothermobacter spp. were enriched in acetate and acetate/magnetite (Fe 3 O 4 ) microcosms suggesting that methanogenic acetate metabolism was through hydrogenotrophic methanogenesis fueled by syntrophic acetate oxidizers. The acetate/β-FeOOH (akaganéite) microcosms, however, differed by the dominance of archaea closely related to the acetoclastic Methanosaeta thermophila. These observations suggest that supplementation of β-FeOOH (akaganéite) accelerated the production of methane further, driven the alteration of the methanogenic community, and changed the pathway of acetate methanogenesis from hydrogenotrophic methanogenesis fueled by syntrophic acetate oxidizers to acetoclastic.

  20. Is metabolic flexibility altered in multiple sclerosis patients?

    Directory of Open Access Journals (Sweden)

    Anja Mähler

    Full Text Available OBJECTIVES: Metabolic flexibility is defined as ability to adjust fuel oxidation to fuel availability. Multiple sclerosis (MS results in reduced muscle strength and exercise intolerance. We tested the hypothesis that altered metabolic flexibility contributes to exercise intolerance in MS patients. METHODS: We studied 16 patients (all on glatiramer and 16 matched healthy controls. Energy expenditure (EE, and carbohydrate (COX and lipid oxidation (LOX rates were determined by calorimetry, before and after an oral glucose load. We made measurements either at rest (canopy device or during 40 min low-grade (0.5 W/kg exercise (metabolic chamber. We also obtained plasma, and adipose tissue and skeletal muscle dialysate samples by microdialysis to study tissue-level metabolism under resting conditions. RESULTS: At rest, fasting and postprandial plasma glucose, insulin, and free fatty acid levels did not differ between patients and controls. Fasting and postprandial COX was higher and LOX lower in patients. In adipose, fasting and postprandial dialysate glucose, lactate, and glycerol levels were higher in patients vs. controls. In muscle, fasting and postprandial dialysate metabolite levels did not differ significantly between the groups. During exercise, EE did not differ between the groups. However, COX increased sharply over 20 min in patients, without reaching a steady state, followed by an immediate decrease within the next 20 min and fell even below basal levels after exercise in patients, compared to controls. CONCLUSIONS: Glucose tolerance is not impaired in MS patients. At rest, there is no indication for metabolic inflexibility or mitochondrial dysfunction in skeletal muscle. The increased adipose tissue lipolytic activity might result from glatiramer treatment. Autonomic dysfunction might cause dysregulation of postprandial thermogenesis at rest and lipid mobilization during exercise.

  1. Bile Acid Alters Male Mouse Fertility in Metabolic Syndrome Context.

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    Aurélie Vega

    Full Text Available Bile acids have recently been demonstrated as molecules with endocrine activities controlling several physiological functions such as immunity and glucose homeostases. They act mainly through two receptors, the nuclear receptor Farnesol-X-Receptor alpha (FXRα and the G-protein coupled receptor (TGR5. These recent studies have led to the idea that molecules derived from bile acids (BAs and targeting their receptors must be good targets for treatment of metabolic diseases such as obesity or diabetes. Thus it might be important to decipher the potential long term impact of such treatment on different physiological functions. Indeed, BAs have recently been demonstrated to alter male fertility. Here we demonstrate that in mice with overweight induced by high fat diet, BA exposure leads to increased rate of male infertility. This is associated with the altered germ cell proliferation, default of testicular endocrine function and abnormalities in cell-cell interaction within the seminiferous epithelium. Even if the identification of the exact molecular mechanisms will need more studies, the present results suggest that both FXRα and TGR5 might be involved. We believed that this work is of particular interest regarding the potential consequences on future approaches for the treatment of metabolic diseases.

  2. Bile Acid Alters Male Mouse Fertility in Metabolic Syndrome Context

    Science.gov (United States)

    Baptissart, Marine; De Haze, Angélique; Vaz, Frederic; Kulik, Wim; Damon-Soubeyrand, Christelle; Baron, Silvère; Caira, Françoise; Volle, David H.

    2015-01-01

    Bile acids have recently been demonstrated as molecules with endocrine activities controlling several physiological functions such as immunity and glucose homeostases. They act mainly through two receptors, the nuclear receptor Farnesol-X-Receptor alpha (FXRα) and the G-protein coupled receptor (TGR5). These recent studies have led to the idea that molecules derived from bile acids (BAs) and targeting their receptors must be good targets for treatment of metabolic diseases such as obesity or diabetes. Thus it might be important to decipher the potential long term impact of such treatment on different physiological functions. Indeed, BAs have recently been demonstrated to alter male fertility. Here we demonstrate that in mice with overweight induced by high fat diet, BA exposure leads to increased rate of male infertility. This is associated with the altered germ cell proliferation, default of testicular endocrine function and abnormalities in cell-cell interaction within the seminiferous epithelium. Even if the identification of the exact molecular mechanisms will need more studies, the present results suggest that both FXRα and TGR5 might be involved. We believed that this work is of particular interest regarding the potential consequences on future approaches for the treatment of metabolic diseases. PMID:26439743

  3. Traumatic brain injury alters methionine metabolism: implications for pathophysiology

    Directory of Open Access Journals (Sweden)

    Pramod K Dash

    2016-04-01

    Full Text Available Methionine is an essential proteinogenic amino acid that is obtained from the diet. In addition to its requirement for protein biosynthesis, methionine is metabolized to generate metabolites that play key roles in a number of cellular functions. Metabolism of methionine via the transmethylation pathway generates S-adenosylmethionine (SAM that serves as the principal methyl (-CH3 donor for DNA and histone methyltransferases to regulate epigenetic changes in gene expression. SAM is also required for methylation of other cellular proteins that serve various functions and phosphatidylcholine synthesis that participate in cellular signaling.. Under conditions of oxidative stress, homocysteine (which is derived from SAM enters the transsulfuration pathway to generate glutathione, an important cytoprotective molecule against oxidative damage. As both experimental and clinical studies have shown that traumatic brain injury (TBI alters DNA and histone methylation and causes oxidative stress, we examined if TBI alters the plasma levels of methionine and its metabolites in human patients. Blood samples were collected from healthy volunteers (n = 20 and patients with mild TBI (GCS > 12; n = 20 or severe TBI (GCS < 8; n = 20 within the first 24 hours of injury. The levels of methionine and its metabolites in the plasma samples were analyzed by either liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry (LC-MS or GC-MS. Severe TBI decreased the levels of methionine, SAM, betaine and 2-methylglycine as compared to healthy volunteers, indicating a decrease in metabolism through the transmethylation cycle. In addition, precursors for the generation of glutathione, cysteine and glycine were also found to be decreased as were intermediate metabolites of the gamma-glutamyl cycle (gamma-glutamyl amino acids and 5-oxoproline. Mild TBI also decreased the levels of methionine, α-ketobutyrate, 2 hydroxybutyrate and glycine, albeit to lesser

  4. Effects of an iron or iron and vitamin D-fortified flavored skim milk on iron metabolism: a randomized controlled double-blind trial in iron-deficient women.

    Science.gov (United States)

    Toxqui, Laura; Pérez-Granados, Ana M; Blanco-Rojo, Ruth; Wright, Ione; González-Vizcayno, Carmen; Vaquero, M Pilar

    2013-01-01

    Iron deficiency anemia and vitamin D deficiency are considered global pandemics. The aim of this study was to determine whether the consumption of a dairy product fortified with iron and vitamin D, compared to the equivalent with only added iron, exerts an additional effect on iron metabolism in iron-deficient menstruating women. The design was a randomized, placebo-controlled, double-blind, parallel-group trial of 16 weeks' duration. Subjects were randomized into 2 groups that consumed, as part of their usual diet, 500 mL/day of an iron (n = 54) or iron- and vitamin D-fortified (n = 55) flavored skim milk. At baseline and monthly, dietary intake, body weight, and hematological and iron metabolism biomarkers were determined. Serum 25-hydroxyvitamin D was analyzed at baseline and weeks 8 and 16. Data were analyzed by analysis of variance (ANOVA) of repeated measures for time and Time × Group interaction effects. A total of 109 volunteers completed the study. Calcium and iron intakes increased during the intervention (p Iron-fortified flavored skim milk does not improve iron status in iron-deficient menstruating women. However, vitamin D fortification slightly enhances erythropoiesis and iron status.

  5. Alteration In Bones Metabolism In Active Rheumatoid Arthritis

    International Nuclear Information System (INIS)

    Salem, E.S.

    2013-01-01

    The strength and integrity of the human skeleton depends on a delicate equilibrium between bone resorption and bone formation. Osteocalcin (OC) is synthesized by osteoblasts and is considered to be a marker of bone formation and helps in corporating calcium into bone tissue. Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease characterized by bone complication including bone pain, erosion and osteoporosis. The aim of the present study is to evaluate some factors responsible in bone metabolism termed OC, vitamin D (vit. D), oncostatin M (OSM), ionized calcium and alkaline phosphatase. Fifty pre-menopausal female patients with active RA and twenty healthy controls of the same age were included in the present study. Radioimmunoassay (RIA) was used to estimate serum OC and active vitamin D. The quantitative determination of ionized calcium and alkaline phosphatase were carried out colorimetrically. OSM was measured by ELISA and serum levels of OC and active vitamin D were significantly decreased in RA patients as compared to those of the control group. On the other hand, the levels of serum OSM, ionized calcium and alkaline phosphatase were significantly increased in the RA patients as compared to their healthy control subjects. The results of this study indicated that early investigation and therapy of disturbances of bone metabolism in active RA are necessary for better prognosis and exhibited the importance of OC as a diagnostic tool of alterations of bone metabolism in RA patients.

  6. New insights into uremia-induced alterations in metabolic pathways.

    Science.gov (United States)

    Rhee, Eugene P; Thadhani, Ravi

    2011-11-01

    This article summarizes recent studies on uremia-induced alterations in metabolism, with particular emphasis on the application of emerging metabolomics technologies. The plasma metabolome is estimated to include more than 4000 distinct metabolites. Because these metabolites can vary dramatically in size and polarity and are distributed across several orders of magnitude in relative abundance, no single analytical method is capable of comprehensive metabolomic profiling. Instead, a variety of analytical techniques, including targeted and nontargeted liquid chromatography-mass spectrometry, have been employed for metabolomic analysis of human plasma. Recent efforts to apply this technology to study uremia have reinforced the common view that end-stage renal disease is a state of generalized small molecule excess. However, the identification of precursor depletion and downstream metabolite excess - for example, with tryptophan and downstream kynurenine metabolites, with low molecular weight triglycerides and dicarboxylic acids, and with phosphatidylcholines, choline, and trimethylamine-N-oxide - suggest that uremia may directly modulate these metabolic pathways. Metabolomic studies have also begun to expand some of these findings to individuals with chronic kidney disease and in model systems. Uremia is associated with diverse, but incompletely understood metabolic disturbances. Metabolomic approaches permit higher resolution phenotyping of these disturbances, but significant efforts will be required to understand the functional significance of select findings.

  7. Dealing with iron metabolism in rice: from breeding for stress tolerance to biofortification

    OpenAIRE

    dos Santos, Railson Schreinert; de Araujo, Artur Teixeira; Pegoraro, Camila; de Oliveira, Antonio Costa

    2017-01-01

    Abstract Iron is a well-known metal. Used by humankind since ancient times in many different ways, this element is present in all living organisms, where, unfortunately, it represents a two-way problem. Being an essential block in the composition of different proteins and metabolic pathways, iron is a vital component for animals and plants. That is why iron deficiency has a severe impact on the lives of different organisms, including humans, becoming a major concern, especially in developing ...

  8. REPEATED ACUTE STRESS INDUCED ALTERATIONS IN CARBOHYDRATE METABOLISM IN RAT

    Directory of Open Access Journals (Sweden)

    Nirupama R.

    2010-09-01

    Full Text Available Acute stress induced alterations in the activity levels of rate limiting enzymes and concentration of intermediates of different pathways of carbohydrate metabolism have been studied. Adult male Wistar rats were restrained (RS for 1 h and after an interval of 4 h they were subjected to forced swimming (FS exercise and appropriate controls were maintained. Five rats were killed before the commencement of the experiment (initial controls, 5 control and equal number of stressed rats were killed 2 h after RS and remaining 5 rats in each group were killed 4 h after FS. There was a significant increase in the adrenal 3β- hydroxy steroid dehydrogenase activity following RS, which showed further increase after FS compared to controls and thereby indicated stress response of rats. There was a significant increase in the blood glucose levels following RS which showed further increase and reached hyperglycemic condition after FS. The hyperglycemic condition due to stress was accompanied by significant increases in the activities of glutamate- pyruvate transaminase, glutamate- oxaloacetate transaminase, glucose -6- phosphatase and lactate dehydrogenase and significant decrease in the glucose -6- phosphate dehydrogenase and pyruvate dehydrogenase activities, whereas pyruvate kinase activity did not show any alteration compared to controls. Further, the glycogen and total protein contents of the liver were decreased whereas those of pyruvate and lactate showed significant increase compared to controls after RS as well as FS.The results put together indicate that acute stress induced hyperglycemia results due to increased gluconeogenesis and glycogenolysis without alteration in glycolysis. The study first time reveals that after first acute stress exposure, the subsequent stressful experience augments metabolic stress response leading to hyperglycemia. The results have relevance to human health as human beings are exposed to several stressors in a day and

  9. Immunochemical and mass-spectrometry-based serum hepcidin assays for iron metabolism disorders.

    NARCIS (Netherlands)

    Kroot, J.J.C.; Laarakkers, J.M.M.; Geurts-Moespot, A.; Grebenchtchikov, N.J.; Pickkers, P.; Ede, A.E. van; Peters, H.P.E.; Dongen-Lases, E. van; Wetzels, J.F.M.; Sweep, F.C.; Tjalsma, H.; Swinkels, D.W.

    2010-01-01

    BACKGROUND: Hepcidin is an iron-regulatory peptide hormone that consists of 3 isoforms: bioactive hepcidin-25, and inactive hepcidin-22 and hepcidin-20. Hepcidin is instrumental in the diagnosis and monitoring of iron metabolism disorders, but reliable methods for its quantification in serum are

  10. Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

    Directory of Open Access Journals (Sweden)

    Lars Stechemesser

    2017-01-01

    Conclusions: Our data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism.

  11. Multi-Copper Oxidases and Human Iron Metabolism

    Science.gov (United States)

    Vashchenko, Ganna; MacGillivray, Ross T. A.

    2013-01-01

    Multi-copper oxidases (MCOs) are a small group of enzymes that oxidize their substrate with the concomitant reduction of dioxygen to two water molecules. Generally, multi-copper oxidases are promiscuous with regards to their reducing substrates and are capable of performing various functions in different species. To date, three multi-copper oxidases have been detected in humans—ceruloplasmin, hephaestin and zyklopen. Each of these enzymes has a high specificity towards iron with the resulting ferroxidase activity being associated with ferroportin, the only known iron exporter protein in humans. Ferroportin exports iron as Fe2+, but transferrin, the major iron transporter protein of blood, can bind only Fe3+ effectively. Iron oxidation in enterocytes is mediated mainly by hephaestin thus allowing dietary iron to enter the bloodstream. Zyklopen is involved in iron efflux from placental trophoblasts during iron transfer from mother to fetus. Release of iron from the liver relies on ferroportin and the ferroxidase activity of ceruloplasmin which is found in blood in a soluble form. Ceruloplasmin, hephaestin and zyklopen show distinctive expression patterns and have unique mechanisms for regulating their expression. These features of human multi-copper ferroxidases can serve as a basis for the precise control of iron efflux in different tissues. In this manuscript, we review the biochemical and biological properties of the three human MCOs and discuss their potential roles in human iron homeostasis. PMID:23807651

  12. Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders.

    Directory of Open Access Journals (Sweden)

    Eva C Schulte

    Full Text Available Serum metabolite profiling can be used to identify pathways involved in the pathogenesis of and potential biomarkers for a given disease. Both restless legs syndrome (RLS and Parkinson`s disease (PD represent movement disorders for which currently no blood-based biomarkers are available and whose pathogenesis has not been uncovered conclusively. We performed unbiased serum metabolite profiling in search of signature metabolic changes for both diseases.456 metabolites were quantified in serum samples of 1272 general population controls belonging to the KORA cohort, 82 PD cases and 95 RLS cases by liquid-phase chromatography and gas chromatography separation coupled with tandem mass spectrometry. Genetically determined metabotypes were calculated using genome-wide genotyping data for the 1272 general population controls.After stringent quality control, we identified decreased levels of long-chain (polyunsaturated fatty acids of individuals with PD compared to both RLS (PD vs. RLS: p = 0.0001 to 5.80x10-9 and general population controls (PD vs. KORA: p = 6.09x10-5 to 3.45x10-32. In RLS, inositol metabolites were increased specifically (RLS vs. KORA: p = 1.35x10-6 to 3.96x10-7. The impact of dopaminergic drugs was reflected in changes in the phenylalanine/tyrosine/dopamine metabolism observed in both individuals with RLS and PD.A first discovery approach using serum metabolite profiling in two dopamine-related movement disorders compared to a large general population sample identified significant alterations in the polyunsaturated fatty acid metabolism in PD and implicated the inositol metabolism in RLS. These results provide a starting point for further studies investigating new perspectives on factors involved in the pathogenesis of the two diseases as well as possible points of therapeutic intervention.

  13. Hepcidin: an important iron metabolism regulator in chronic kidney disease.

    Science.gov (United States)

    Antunes, Sandra Azevedo; Canziani, Maria Eugênia Fernandes

    2016-01-01

    Anemia is a common complication and its impact on morbimortality in patients with chronic kidney disease (CKD) is well known. The discovery of hepcidin and its functions has contributed to a better understanding of iron metabolism disorders in CKD anemia. Hepcidin is a peptide mainly produced by hepatocytes and, through a connection with ferroportin, it regulates iron absorption in the duodenum and its release of stock cells. High hepcidin concentrations described in patients with CKD, especially in more advanced stages are attributed to decreased renal excretion and increased production. The elevation of hepcidin has been associated with infection, inflammation, atherosclerosis, insulin resistance and oxidative stress. Some strategies were tested to reduce the effects of hepcidin in patients with CKD, however more studies are necessary to assess the impact of its modulation in the management of anemia in this population. Resumo Anemia é uma complicação frequente e seu impacto na morbimortalidade é bem conhecido em pacientes com doença renal crônica (DRC). A descoberta da hepcidina e de suas funções contribuíram para melhor compreensão dos distúrbios do metabolismo de ferro na anemia da DRC. Hepcidina é um peptídeo produzido principalmente pelos hepatócitos, e através de sua ligação com a ferroportina, regula a absorção de ferro no duodeno e sua liberação das células de estoque. Altas concentrações de hepcidina descritas em pacientes com DRC, principalmente em estádios mais avançados, são atribuídas à diminuição da excreção renal e ao aumento de sua produção. Elevação de hepcidina tem sido associada à ocorrência de infecção, inflamação, aterosclerose, resistência à insulina e estresse oxidativo. Algumas estratégias foram testadas para diminuir os efeitos da hepcidina em pacientes com DRC, entretanto, serão necessários mais estudos para avaliar o impacto de sua modulação no manejo da anemia nessa população.

  14. Gene expression profiling in Entamoeba histolytica identifies key components in iron uptake and metabolism.

    Directory of Open Access Journals (Sweden)

    Nora Adriana Hernández-Cuevas

    Full Text Available Entamoeba histolytica is an ameboid parasite that causes colonic dysentery and liver abscesses in humans. The parasite encounters dramatic changes in iron concentration during its invasion of the host, with relatively low levels in the intestinal lumen and then relatively high levels in the blood and liver. The liver notably contains sources of iron; therefore, the parasite's ability to use these sources might be relevant to its survival in the liver and thus the pathogenesis of liver abscesses. The objective of the present study was to identify factors involved in iron uptake, use and storage in E. histolytica. We compared the respective transcriptomes of E. histolytica trophozoites grown in normal medium (containing around 169 µM iron, low-iron medium (around 123 µM iron, iron-deficient medium (around 91 µM iron, and iron-deficient medium replenished with hemoglobin. The differentially expressed genes included those coding for the ATP-binding cassette transporters and major facilitator transporters (which share homology with bacterial siderophores and heme transporters and genes involved in heme biosynthesis and degradation. Iron deficiency was associated with increased transcription of genes encoding a subset of cell signaling molecules, some of which have previously been linked to adaptation to the intestinal environment and virulence. The present study is the first to have assessed the transcriptome of E. histolytica grown under various iron concentrations. Our results provide insights into the pathways involved in iron uptake and metabolism in this parasite.

  15. Gene Expression Profiling in Entamoeba histolytica Identifies Key Components in Iron Uptake and Metabolism

    Science.gov (United States)

    Hernández-Cuevas, Nora Adriana; Weber, Christian; Hon, Chung-Chau; Guillen, Nancy

    2014-01-01

    Entamoeba histolytica is an ameboid parasite that causes colonic dysentery and liver abscesses in humans. The parasite encounters dramatic changes in iron concentration during its invasion of the host, with relatively low levels in the intestinal lumen and then relatively high levels in the blood and liver. The liver notably contains sources of iron; therefore, the parasite's ability to use these sources might be relevant to its survival in the liver and thus the pathogenesis of liver abscesses. The objective of the present study was to identify factors involved in iron uptake, use and storage in E. histolytica. We compared the respective transcriptomes of E. histolytica trophozoites grown in normal medium (containing around 169 µM iron), low-iron medium (around 123 µM iron), iron-deficient medium (around 91 µM iron), and iron-deficient medium replenished with hemoglobin. The differentially expressed genes included those coding for the ATP-binding cassette transporters and major facilitator transporters (which share homology with bacterial siderophores and heme transporters) and genes involved in heme biosynthesis and degradation. Iron deficiency was associated with increased transcription of genes encoding a subset of cell signaling molecules, some of which have previously been linked to adaptation to the intestinal environment and virulence. The present study is the first to have assessed the transcriptome of E. histolytica grown under various iron concentrations. Our results provide insights into the pathways involved in iron uptake and metabolism in this parasite. PMID:25210888

  16. Evaluation of bentonite alteration due to interactions with iron. Sensitivity analyses to identify the important factors for the bentonite alteration

    International Nuclear Information System (INIS)

    Sasamoto, Hiroshi; Wilson, James; Sato, Tsutomu

    2013-01-01

    Performance assessment of geological disposal systems for high-level radioactive waste requires a consideration of long-term systems behaviour. It is possible that the alteration of swelling clay present in bentonite buffers might have an impact on buffer functions. In the present study, iron (as a candidate overpack material)-bentonite (I-B) interactions were evaluated as the main buffer alteration scenario. Existing knowledge on alteration of bentonite during I-B interactions was first reviewed, then the evaluation methodology was developed considering modeling techniques previously used overseas. A conceptual model for smectite alteration during I-B interactions was produced. The following reactions and processes were selected: 1) release of Fe 2+ due to overpack corrosion; 2) diffusion of Fe 2+ in compacted bentonite; 3) sorption of Fe 2+ on smectite edge and ion exchange in interlayers; 4) dissolution of primary phases and formation of alteration products. Sensitivity analyses were performed to identify the most important factors for the alteration of bentonite by I-B interactions. (author)

  17. Estrogen-induced disruption of intracellular iron metabolism leads to oxidative stress, membrane damage, and cell cycle arrest in MCF-7 cells.

    Science.gov (United States)

    Bajbouj, Khuloud; Shafarin, Jasmin; Abdalla, Maher Y; Ahmad, Iman M; Hamad, Mawieh

    2017-10-01

    It is well established that several forms of cancer associate with significant iron overload. Recent studies have suggested that estrogen (E2) disrupts intracellular iron homeostasis by reducing hepcidin synthesis and maintaining ferroportin integrity. Here, the ability of E2 to alter intracellular iron status and cell growth potential was investigated in MCF-7 cells treated with increasing concentrations of E2. Treated cells were assessed for intracellular iron status, the expression of key proteins involved in iron metabolism, oxidative stress, cell survival, growth, and apoptosis. E2 treatment resulted in a significant reduction in hepcidin expression and a significant increase in hypoxia-inducible factor 1 alpha, ferroportin, transferrin receptor, and ferritin expression; a transient decrease in labile iron pool; and a significant increase in total intracellular iron content mainly at 20 nM/48 h E2 dose. Treated cells also showed increased total glutathione and oxidized glutathione levels, increased superoxide dismutase activity, and increased hemoxygenase 1 expression. Treatment with E2 at 20 nM for 48 h resulted in a significant reduction in cell growth (0.35/1 migration rate) and decreased cell survival (iron metabolism and precipitates adverse effects concerning cell viability, membrane integrity, and growth potential.

  18. The effect of iron and/or lactose on strontium metabolism in neonatal and weanling rats

    International Nuclear Information System (INIS)

    Gruden, N.; Mataushicj, S.

    1988-01-01

    Iron-fortified cow's milk increased strontium-85 retention in the femur and brain of neonatal rats by 16-44%, irrespective of the presence or absence of lactose. A similar effect was observed in the brain of weaning rats if milk was enriched with lactose and was not altered by simultaneous addition of iron. (author). 18 refs.; 1 tab

  19. Hepcidin and iron metabolism disorders in patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Jelić Marija

    2013-01-01

    Full Text Available Bacground/Aim. Hepcidin may play a pathogenetic role in iron metobolism disorders. The aim of this study was to determine the correlation between hepcidin concentration and parameters of iron metabolism in patients with different stage of chronic kidney disease (CKD. Methods. The study involved 104 patients with CKD: 64 on hemodialysis (HD and 40 patients in pre-dialysis stadium (pre-HD with adequate erythropoetin therapy and iron supplementation. The HD group was divided in four subgroups according to the level of serum ferritin (up to 100; 100-199; 200-499 and over 500 ng/mL. Parameters of anemia, iron status, inflamation and hepcidin level were evaluated. Results. The HD patients had a significantly lower eritrocyte count, erythrocytes indexes, hemoglobin and transferrin saturation and significantly higher iron, ferritin, hepcidin and total iron binding capacity (TIBC. The HD subgroups up to 199 ng/mL of serum feritin had lower high-sensitivity Creactive protein (hsCRP, iron and higher unbuffered iron binding capacity (UIBC, transferrin saturation and TIBC compared to the HD subgroups over 200 ng/mL. The lowest and the highest ferritin subgroups had the highest hepcidin level and it showed significant correlation with ferritin. Conclusion. Hepcidin may serve as a marker for better diagnosing and monitoring anemia and iron metabolism disorders in CKD.

  20. Dysregulation of Iron Metabolism in Cholangiocarcinoma Stem-like Cells

    DEFF Research Database (Denmark)

    Raggi, Chiara; Gammella, Elena; Correnti, Margherita

    2017-01-01

    conditions, CSC form 3D spheres (SPH), which retain stem-like tumour-initiating features. Here, we found different expression of iron proteins indicating increased iron content, oxidative stress and higher expression of CSC markers in CCA-SPH compared to tumour cells growing as monolayers. Exposure...

  1. Insights into the Structure and Metabolic Function of Microbes That Shape Pelagic Iron-Rich Aggregates ( Iron Snow )

    Energy Technology Data Exchange (ETDEWEB)

    Lu, S [Friedrich Schiller University Jena, Jena Germany; Chourey, Karuna [ORNL; REICHE, M [Friedrich Schiller University Jena, Jena Germany; Nietzsche, S [Friedrich Schiller University Jena, Jena Germany; Shah, Manesh B [ORNL; Hettich, Robert {Bob} L [ORNL; Kusel, K [Friedrich Schiller University Jena, Jena Germany

    2013-01-01

    Metaproteomics combined with total nucleic acid-based methods aided in deciphering the roles of microorganisms in the formation and transformation of iron-rich macroscopic aggregates (iron snow) formed in the redoxcline of an acidic lignite mine lake. Iron snow had high total bacterial 16S rRNA gene copies, with 2 x 109 copies g (dry wt)-1 in the acidic (pH 3.5) central lake basin and 4 x 1010 copies g (dry wt)-1 in the less acidic (pH 5.5) northern lake basin. Active microbial communities in the central basin were dominated by Alphaproteobacteria (36.6%) and Actinobacteria (21.4%), and by Betaproteobacteria (36.2%) in the northern basin. Microbial Fe-cycling appeared to be the dominant metabolism in the schwertmannite-rich iron snow, because cloning and qPCR assigned up to 61% of active bacteria as Fe-cycling bacteria (FeB). Metaproteomics revealed 70 unique proteins from central basin iron snow and 283 unique proteins from 43 genera from northern basin. Protein identification provided a glimpse into in situ processes, such as primary production, motility, metabolism of acidophilic FeB, and survival strategies of neutrophilic FeB. Expression of carboxysome shell proteins and RubisCO indicated active CO2 fixation by Fe(II) oxidizers. Flagellar proteins from heterotrophs indicated their activity to reach and attach surfaces. Gas vesicle proteins related to CO2-fixing Chlorobium suggested that microbes could influence iron snow sinking. We suggest that iron snow formed by autotrophs in the redoxcline acts as a microbial parachute, since it is colonized by motile heterotrophs during sinking which start to dissolve schwertmannite.

  2. Relationship between indices of iron status and metabolic syndrome in an Iranian population

    Directory of Open Access Journals (Sweden)

    Niloofar Tavakoli-Hoseini

    2014-11-01

    Full Text Available Introduction: Iron overload may contribute to the pathogenesis of metabolic syndrome (MS. A growing body of evidence indicates that the oxidative stress that results from excess tissue iron can leads to insulin resistance, tissue damage, and other complications observed in MS. The objective of this study was to investigate indices of iron status including serum ferritin, iron, total iron binding capacity (TIBC levels, and full blood cell count, together with demographic and anthropometric characteristics, lipid profile components, and other biochemical parameters in subjects with and with-out MS. Methods: A total of, 385 individuals (176 with and 209 subjects without MS according to the International Diabetes Federation’s (IDF criteria were recruited. Indices of iron status and other clinical and biochemical parameters were determined in MS patients and healthy controls using standard methods. Results: Higher serum iron and ferritin values were observed in subjects with MS in compared to healthy controls (P 0.050. Among the other indices, only red blood cell (RBC was associated considerably with the presence of MS (P < 0.050. Conclusion: Our data indicate that even in a country with a comparatively high prevalence of iron deficiency, serum iron and ferritin values in MS patients are higher than healthy controls. The reason why ferritin and iron are higher in MS patient may be related to dietary factors.

  3. Genomic Organization and Expression of Iron Metabolism Genes in the Emerging Pathogenic Mold Scedosporium apiospermum

    Directory of Open Access Journals (Sweden)

    Yohann Le Govic

    2018-04-01

    Full Text Available The ubiquitous mold Scedosporium apiospermum is increasingly recognized as an emerging pathogen, especially among patients with underlying disorders such as immunodeficiency or cystic fibrosis (CF. Indeed, it ranks the second among the filamentous fungi colonizing the respiratory tract of CF patients. However, our knowledge about virulence factors of this fungus is still limited. The role of iron-uptake systems may be critical for establishment of Scedosporium infections, notably in the iron-rich environment of the CF lung. Two main strategies are employed by fungi to efficiently acquire iron from their host or from their ecological niche: siderophore production and reductive iron assimilation (RIA systems. The aim of this study was to assess the existence of orthologous genes involved in iron metabolism in the recently sequenced genome of S. apiospermum. At first, a tBLASTn analysis using A. fumigatus iron-related proteins as query revealed orthologs of almost all relevant loci in the S. apiospermum genome. Whereas the genes putatively involved in RIA were randomly distributed, siderophore biosynthesis and transport genes were organized in two clusters, each containing a non-ribosomal peptide synthetase (NRPS whose orthologs in A. fumigatus have been described to catalyze hydroxamate siderophore synthesis. Nevertheless, comparative genomic analysis of siderophore-related clusters showed greater similarity between S. apiospermum and phylogenetically close molds than with Aspergillus species. The expression level of these genes was then evaluated by exposing conidia to iron starvation and iron excess. The expression of several orthologs of A. fumigatus genes involved in siderophore-based iron uptake or RIA was significantly induced during iron starvation, and conversely repressed in iron excess conditions. Altogether, these results indicate that S. apiospermum possesses the genetic information required for efficient and competitive iron uptake

  4. Studying disorders of vertebrate iron and heme metabolism using zebrafish.

    Science.gov (United States)

    van der Vorm, Lisa N; Paw, Barry H

    2017-01-01

    Iron is a crucial component of heme- and iron-sulfur clusters, involved in vital cellular functions such as oxygen transport, DNA synthesis, and respiration. Both excess and insufficient levels of iron and heme-precursors cause human disease, such as iron-deficiency anemia, hemochromatosis, and porphyrias. Hence, their levels must be tightly regulated, requiring a complex network of transporters and feedback mechanisms. The use of zebrafish to study these pathways and the underlying genetics offers many advantages, among others their optical transparency, ex-vivo development and high genetic and physiological conservations. This chapter first reviews well-established methods, such as large-scale mutagenesis screens that have led to the initial identification of a series of iron and heme transporters and the generation of a variety of mutant lines. Other widely used techniques are based on injection of RNA, including complementary morpholino knockdown and gene overexpression. In addition, we highlight several recently developed approaches, most notably endonuclease-based gene knockouts such as TALENs or the CRISPR/Cas9 system that have been used to study how loss of function can induce human disease phenocopies in zebrafish. Rescue by chemical complementation with iron-based compounds or small molecules can subsequently be used to confirm causality of the genetic defect for the observed phenotype. All together, zebrafish have proven to be - and will continue to serve as an ideal model to advance our understanding of the pathogenesis of human iron and heme-related diseases and to develop novel therapies to treat these conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Oncogene-directed alterations in cancer cell metabolism.

    Science.gov (United States)

    Nagarajan, Arvindhan; Malvi, Parmanand; Wajapeyee, Narendra

    2016-07-01

    Oncogenes are key drivers of tumor growth. Although several cancer-driving mechanisms have been identified, the role of oncogenes in shaping metabolic patterns in cancer cells is only beginning to be appreciated. Recent studies show that oncogenes directly regulate critical metabolic enzymes and metabolic signaling pathways. Here, we present evidence for oncogene-directed cancer metabolic regulation and discuss the importance of identifying underlying mechanisms that can be targeted for developing precision cancer therapies.

  6. Determination of oxidation state of iron in normal and pathologically altered human aortic valves

    Energy Technology Data Exchange (ETDEWEB)

    Czapla-Masztafiak, J. [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Kraków (Poland); Lis, G.J.; Gajda, M.; Jasek, E. [Department of Histology, Jagiellonian University Medical College, Kopernika 7, 31-034 Kraków (Poland); Czubek, U. [Department of Coronary Disease, Jagiellonian University Medical College, John Paul II Hospital, Prądnicka 80, 31-202 Kraków (Poland); Bolechała, F. [Department of Forensic Medicine, Jagiellonian University Medical College, Grzegórzecka 16, 31-531 Kraków (Poland); Borca, C. [Swiss Light Source, Paul Scherrer Institute, 5232 Villigen PSI (Switzerland); Kwiatek, W.M. [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Kraków (Poland)

    2015-12-01

    In order to investigate changes in chemical state of iron in normal and pathologically altered human aortic valves X-ray absorption spectroscopy was applied. Since Fe is suspected to play detrimental role in aortic valve stenosis pathogenesis the oxidation state of this element has been determined. The experimental material consisted of 10 μm sections of valves excised during routine surgery and from autopsies. The experiment was performed at the MicroXAS beamline of the SLS synchrotron facility in Villigen (Switzerland). The Fe K-edge XANES spectra obtained from tissue samples were carefully analyzed and compared with the spectra of reference compounds containing iron in various chemical structures. The analysis of absorption edge position and shape of the spectra revealed that both chemical forms of iron are presented in valve tissue but Fe{sup 3+} is the predominant form. Small shift of the absorption edge toward higher energy in the spectra from stenotic valve samples indicates higher content of the Fe{sup 3+} form in pathological tissue. Such a phenomenon suggests the role of Fenton reaction and reactive oxygen species in the etiology of aortic valve stenosis. The comparison of pre-edge regions of XANES spectra for control and stenotic valve tissue confirmed no differences in local symmetry or spin state of iron in analyzed samples.

  7. Iron deficiency differently affects metabolic responses in soybean roots.

    Science.gov (United States)

    Zocchi, Graziano; De Nisi, Patrizia; Dell'Orto, Marta; Espen, Luca; Gallina, Pietro Marino

    2007-01-01

    Iron deficiency responses were investigated in roots of soybean, a Strategy I plant species. Soybean responds to iron deficiency by decreasing growth, both at the root and shoot level. Chlorotic symptoms in younger leaves were evident after a few days of iron deficiency, with chlorophyll content being dramatically decreased. Moreover, several important differences were found as compared with other species belonging to the same Strategy I. The main differences are (i) a lower capacity to acidify the hydroponic culture medium, that was also reflected by a lower H(+)-ATPase activity as determined in a plasma membrane-enriched fraction isolated from the roots; (ii) a drastically reduced activity of the phosphoenolpyruvate carboxylase enzyme; (iii) a decrease in both cytosolic and vacuolar pHs; (iv) an increase in the vacuolar phosphate concentration, and (v) an increased exudation of organic carbon, particularly citrate, phenolics, and amino acids. Apparently, in soybean roots, some of the responses to iron deficiency, such as the acidification of the rhizosphere and other related processes, do not occur or occur only at a lower degree. These results suggest that the biochemical mechanisms induced by this nutritional disorder are differently regulated in this plant. A possible role of inorganic phosphate in the balance of intracellular pHs is also discussed.

  8. A report on the metabolism of iron in goats artificially infected with Haemonchus contortus

    International Nuclear Information System (INIS)

    Perpuse, W.G.; Yumul, B.Y.; Anden, A.

    1976-03-01

    The determination of iron metabolism in goats artificially infected with N. contortus using tracer method has been conducted. Radioferric chloride ( 59 Fe) was given orally and intravenously and the distribution and utilization in goats were determined. Results showed that anemic goats have a higher absorption rate compared to non-anemic goats. Of all the organs examined the bone marrow showed the highest activity

  9. Toll- like receptors expressed on embryonic macrophages couple inflammatory signals to iron metabolism during early ontogenesis

    Czech Academy of Sciences Publication Activity Database

    Balounová, Jana; Vavrochová, Tereza; Benešová, Martina; Ballek, Ondřej; Kolář, Michal; Filipp, Dominik

    2014-01-01

    Roč. 44, č. 5 (2014), s. 1491-1502 ISSN 0014-2980 R&D Projects: GA AV ČR IAA500520707 Institutional support: RVO:68378050 Keywords : Embryonic macrophages * Ferroportin * Gene expression microarray * Iron metabolism * TLR stimulation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.034, year: 2014

  10. Toll- like receptors expressed on embryonic macrophages couple inflammatory signals to iron metabolism during early ontogenesis

    Czech Academy of Sciences Publication Activity Database

    Balounová, Jana; Vavrochová, Tereza; Benešová, Martina; Ballek, Ondřej; Kolář, Michal; Filipp, Dominik

    2014-01-01

    Roč. 44, č. 5 (2014), s. 1491-1502 ISSN 0014-2980 R&D Projects: GA AV ČR IAA500520707 Institutional support: RVO:68378050 Keywords : Embryo nic macrophages * Ferroportin * Gene expression microarray * Iron metabolism * TLR stimulation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.034, year: 2014

  11. Deciphering Fur transcriptional regulatory network highlights its complex role beyond iron metabolism in Escherichia coli

    DEFF Research Database (Denmark)

    Seo, Sang Woo; Kim, Donghyuk; Latif, Haythem

    2014-01-01

    The ferric uptake regulator (Fur) plays a critical role in the transcriptional regulation of iron metabolism. However, the full regulatory potential of Fur remains undefined. Here we comprehensively reconstruct the Fur transcriptional regulatory network in Escherichia coli K-12 MG1655 in response...

  12. Copper metabolism and its interactions with dietary iron, zinc, tin and selenium in rats

    NARCIS (Netherlands)

    Yu, S.

    1993-01-01

    This thesis describes various studies on copper metabolism and its interactions with selected dietary trace elements in rats. The rats were fed purified diets throughout. High intakes of iron or tin reduced copper concentrations in plasma, liver and kidneys. The dietary treatments also

  13. Cadmium Toxicity Induced Alterations in the Root Proteome of Green Gram in Contrasting Response towards Iron Supplement

    Directory of Open Access Journals (Sweden)

    Sowbiya Muneer

    2014-04-01

    Full Text Available Cadmium signifies a severe threat to crop productivity and green gram is a notably iron sensitive plant which shows considerable variation towards cadmium stress. A gel-based proteomics analysis was performed with the roots of green gram exposed to iron and cadmium combined treatments. The resulting data show that twenty three proteins were down-regulated in iron-deprived roots either in the absence (−Fe/−Cd or presence (−Fe/+Cd of cadmium. These down-regulated proteins were however well expressed in roots under iron sufficient conditions, even in the presence of cadmium (+Fe/+Cd. The functional classification of these proteins determined that 21% of the proteins are associated with nutrient metabolism. The other proteins in higher quantities are involved in either transcription or translation regulation, and the rest are involved in biosynthesis metabolism, antioxidant pathways, molecular chaperones and stress response. On the other hand, several protein spots were also absent in roots in response to iron deprivation either in absence (−Fe/−Cd or presence (−Fe/+Cd of cadmium but were well expressed in the presence of iron (+Fe/+Cd. Results suggest that green gram plants exposed to cadmium stress are able to change the nutrient metabolic balance in roots, but in the mean time regulate cadmium toxicity through iron supplements.

  14. Assessment of (patho)physiologic alterations in equine muscle metabolism

    NARCIS (Netherlands)

    Westermann, C.M.

    2008-01-01

    This thesis focussed on the diagnostic use of metabolic products and enzymes found in plasma, urine and muscle of the horse, the identification of which can reveal physiological or pathological changes in muscle metabolism. In this thesis analyses of carbohydrate-, lipid- and protein metabolites

  15. The Causes and Consequences of Altered Glucose Metabolism in Cancer

    Science.gov (United States)

    2007-10-05

    result in scurvy when ascorbate is deficient from the diet . The iron and 2-oxoglutarate dependant dioxygenase family is known to contain several...to the disulfide, resulting in the reduction of FAD to FADH2 which is reoxidized by electron transfer to NAD+, to yield NADH and H+. B. Pyruvate

  16. Alteration of plasma membrane-bound redox systems of iron deficient pea roots by chitosan.

    Science.gov (United States)

    Meisrimler, Claudia-Nicole; Planchon, Sebastien; Renaut, Jenny; Sergeant, Kjell; Lüthje, Sabine

    2011-08-12

    Iron is essential for all living organisms and plays a crucial role in pathogenicity. This study presents the first proteome analysis of plasma membranes isolated from pea roots. Protein profiles of four different samples (+Fe, +Fe/Chitosan, -Fe, and -Fe/Chitosan) were compared by native IEF-PAGE combined with in-gel activity stains and DIGE. Using DIGE, 89 proteins of interest were detected in plasma membrane fractions. Data revealed a differential abundance of several spots in all samples investigated. In comparison to the control and -FeCh the abundance of six protein spots increased whereas 56 spots decreased in +FeCh. Altered protein spots were analyzed by MALDI-TOF-TOF mass spectrometry. Besides stress-related proteins, transport proteins and redox enzymes were identified. Activity stains after native PAGE and spectrophotometric measurements demonstrated induction of a ferric-chelate reductase (-Fe) and a putative respiratory burst oxidase homolog (-FeCh). However, the activity of the ferric-chelate reductase decreased in -Fe plants after elicitor treatment. The activity of plasma membrane-bound class III peroxidases increased after elicitor treatment and decreased under iron-deficiency, whereas activity of quinone reductases decreased mostly after elicitor treatment. Possible functions of proteins identified and reasons for a weakened pathogen response of iron-deficient plants were discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Identification of the Consistently Altered Metabolic Targets in Human Hepatocellular CarcinomaSummary

    Directory of Open Access Journals (Sweden)

    Zeribe Chike Nwosu

    2017-09-01

    Full Text Available Background & Aims: Cancer cells rely on metabolic alterations to enhance proliferation and survival. Metabolic gene alterations that repeatedly occur in liver cancer are largely unknown. We aimed to identify metabolic genes that are consistently deregulated, and are of potential clinical significance in human hepatocellular carcinoma (HCC. Methods: We studied the expression of 2,761 metabolic genes in 8 microarray datasets comprising 521 human HCC tissues. Genes exclusively up-regulated or down-regulated in 6 or more datasets were defined as consistently deregulated. The consistent genes that correlated with tumor progression markers (ECM2 and MMP9 (Pearson correlation P < .05 were used for Kaplan-Meier overall survival analysis in a patient cohort. We further compared proteomic expression of metabolic genes in 19 tumors vs adjacent normal liver tissues. Results: We identified 634 consistent metabolic genes, ∼60% of which are not yet described in HCC. The down-regulated genes (n = 350 are mostly involved in physiologic hepatocyte metabolic functions (eg, xenobiotic, fatty acid, and amino acid metabolism. In contrast, among consistently up-regulated metabolic genes (n = 284 are those involved in glycolysis, pentose phosphate pathway, nucleotide biosynthesis, tricarboxylic acid cycle, oxidative phosphorylation, proton transport, membrane lipid, and glycan metabolism. Several metabolic genes (n = 434 correlated with progression markers, and of these, 201 predicted overall survival outcome in the patient cohort analyzed. Over 90% of the metabolic targets significantly altered at the protein level were similarly up- or down-regulated as in genomic profile. Conclusions: We provide the first exposition of the consistently altered metabolic genes in HCC and show that these genes are potentially relevant targets for onward studies in preclinical and clinical contexts. Keywords: Liver Cancer, HCC, Tumor Metabolism

  18. Associations of iron metabolism genes with blood manganese levels: a population-based study with validation data from animal models

    Directory of Open Access Journals (Sweden)

    Claus Henn Birgit

    2011-11-01

    Full Text Available Abstract Background Given mounting evidence for adverse effects from excess manganese exposure, it is critical to understand host factors, such as genetics, that affect manganese metabolism. Methods Archived blood samples, collected from 332 Mexican women at delivery, were analyzed for manganese. We evaluated associations of manganese with functional variants in three candidate iron metabolism genes: HFE [hemochromatosis], TF [transferrin], and ALAD [δ-aminolevulinic acid dehydratase]. We used a knockout mouse model to parallel our significant results as a novel method of validating the observed associations between genotype and blood manganese in our epidemiologic data. Results Percentage of participants carrying at least one copy of HFE C282Y, HFE H63D, TF P570S, and ALAD K59N variant alleles was 2.4%, 17.7%, 20.1%, and 6.4%, respectively. Percentage carrying at least one copy of either C282Y or H63D allele in HFE gene was 19.6%. Geometric mean (geometric standard deviation manganese concentrations were 17.0 (1.5 μg/l. Women with any HFE variant allele had 12% lower blood manganese concentrations than women with no variant alleles (β = -0.12 [95% CI = -0.23 to -0.01]. TF and ALAD variants were not significant predictors of blood manganese. In animal models, Hfe-/- mice displayed a significant reduction in blood manganese compared with Hfe+/+ mice, replicating the altered manganese metabolism found in our human research. Conclusions Our study suggests that genetic variants in iron metabolism genes may contribute to variability in manganese exposure by affecting manganese absorption, distribution, or excretion. Genetic background may be critical to consider in studies that rely on environmental manganese measurements.

  19. Iron

    Science.gov (United States)

    Iron is a mineral that our bodies need for many functions. For example, iron is part of hemoglobin, a protein which carries ... It helps our muscles store and use oxygen. Iron is also part of many other proteins and ...

  20. Copper and ectopic expression of the Arabidopsis transport protein COPT1 alter iron homeostasis in rice (Oryza sativa L.).

    Science.gov (United States)

    Andrés-Bordería, Amparo; Andrés, Fernando; Garcia-Molina, Antoni; Perea-García, Ana; Domingo, Concha; Puig, Sergi; Peñarrubia, Lola

    2017-09-01

    Copper deficiency and excess differentially affect iron homeostasis in rice and overexpression of the Arabidopsis high-affinity copper transporter COPT1 slightly increases endogenous iron concentration in rice grains. Higher plants have developed sophisticated mechanisms to efficiently acquire and use micronutrients such as copper and iron. However, the molecular mechanisms underlying the interaction between both metals remain poorly understood. In the present work, we study the effects produced on iron homeostasis by a wide range of copper concentrations in the growth media and by altered copper transport in Oryza sativa plants. Gene expression profiles in rice seedlings grown under copper excess show an altered expression of genes involved in iron homeostasis compared to standard control conditions. Thus, ferritin OsFER2 and ferredoxin OsFd1 mRNAs are down-regulated whereas the transcriptional iron regulator OsIRO2 and the nicotianamine synthase OsNAS2 mRNAs rise under copper excess. As expected, the expression of OsCOPT1, which encodes a high-affinity copper transport protein, as well as other copper-deficiency markers are down-regulated by copper. Furthermore, we show that Arabidopsis COPT1 overexpression (C1 OE ) in rice causes root shortening in high copper conditions and under iron deficiency. C1 OE rice plants modify the expression of the putative iron-sensing factors OsHRZ1 and OsHRZ2 and enhance the expression of OsIRO2 under copper excess, which suggests a role of copper transport in iron signaling. Importantly, the C1 OE rice plants grown on soil contain higher endogenous iron concentration than wild-type plants in both brown and white grains. Collectively, these results highlight the effects of rice copper status on iron homeostasis, which should be considered to obtain crops with optimized nutrient concentrations in edible parts.

  1. Qualitative Alterations of Bacterial Metabolome after Exposure to Metal Nanoparticles with Bactericidal Properties: A Comprehensive Workflow Based on (1)H NMR, UHPLC-HRMS, and Metabolic Databases.

    Science.gov (United States)

    Chatzimitakos, Theodoros G; Stalikas, Constantine D

    2016-09-02

    Metal nanoparticles (NPs) have proven to be more toxic than bulk analogues of the same chemical composition due to their unique physical properties. The NPs, lately, have drawn the attention of researchers because of their antibacterial and biocidal properties. In an effort to shed light on the mechanism through which the bacteria elimination is achieved and the metabolic changes they undergo, an untargeted metabolomic fingerprint study was carried out on Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria species. The (1)H NMR spectroscopy, in conjunction with high resolution mass-spectrometry (HRMS) and an unsophisticated data processing workflow were implemented. The combined NMR/HRMS data, supported by an open-access metabolomic database, proved to be efficacious in the process of assigning a putative annotation to a wide range of metabolite signals and is a useful tool to appraise the metabolome alterations, as a consequence of bacterial response to NPs. Interestingly, not all the NPs diminished the intracellular metabolites; bacteria treated with iron NPs produced metabolites not present in the nonexposed bacteria sample, implying the activation of previously inactive metabolic pathways. In contrast, copper and iron-copper NPs reduced the annotated metabolites, alluding to the conclusion that the metabolic pathways (mainly alanine, aspartate, and glutamate metabolism, beta-alanine metabolism, glutathione metabolism, and arginine and proline metabolism) were hindered by the interactions of NPs with the intracellular metabolites.

  2. A Corn Tissue Culture Cell Line with Altered Lipid Metabolism

    OpenAIRE

    Yue-ie C, Hsing; Jack M, Widholm; Robert W, Rinne; Institute of Botany, Academia Sinica; Department of Agronomy, University of Illinois at Urbana; Plant Physiology and Genetics Research Unit, Department of Agriculture, Agricultural Research Service and Department of Agronomy, University of Illinois at Urbana

    1991-01-01

    A variant corn callus line derived from callus which originated from etiolated leaves of Illinois High Oil corn (Zea mays L.) has been identified. The variant corn callus line had increased lipid content concomitant with increased acetyl-CoA carboxylase activity and altered biotin-containing protein patterns relative to the wild type callus. The variant callus line also had altered fatty acid composition concomitant with decreased oleate desaturase activity compared to the wild type callus. T...

  3. Investigation on Abnormal Iron Metabolism and Related Inflammation in Parkinson Disease Patients with Probable RBD

    Science.gov (United States)

    Hu, Yang; Yu, Shu-Yang; Zuo, Li-Jun; Piao, Ying-Shan; Cao, Chen-Jie; Wang, Fang; Chen, Ze-Jie; Du, Yang; Lian, Teng-Hong; Liu, Gai-Fen; Wang, Ya-Jie; Chan, Piu; Chen, Sheng-Di; Wang, Xiao-Min; Zhang, Wei

    2015-01-01

    Objective To investigate potential mechanisms involving abnormal iron metabolism and related inflammation in Parkinson disease (PD) patients with probable rapid eye movement sleep behavior disorder (PRBD). Methods Total 210 PD patients and 31 controls were consecutively recruited. PD patients were evaluated by RBD Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD (NPRBD) groups. Demographics information were recorded and clinical symptoms were evaluated by series of rating scales. Levels of iron and related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were detected. Comparisons among control, NPRBD and PRBD groups and correlation analyses between RBDSQ score and levels of above factors were performed. Results (1)The frequency of PRBD in PD patients is 31.90%. (2)PRBD group has longer disease duration, more advanced disease stage, severer motor symptoms and more non-motor symptoms than NPRBD group. (3)In CSF, levels of iron, transferrin, NO and IL–1β in PRBD group are prominently increased. RBDSQ score is positively correlated with the levels of iron, transferrin, NO and IL–1β in PD group. Iron level is positively correlated with the levels of NO and IL–1β in PD group. (4)In serum, transferrin level is prominently decreased in PRBD group. PGE2 level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive correlation with PGE2 level in PD group. Conclusions PRBD is common in PD patients. PRBD group has severer motor symptoms and more non-motor symptoms. Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with PRBD through neuroinflammation. PMID:26431210

  4. Radiation Exposure Alters Expression of Metabolic Enzyme Genes in Mice

    Science.gov (United States)

    Wotring, V. E.; Mangala, L. S.; Zhang, Y.; Wu, H.

    2011-01-01

    Most administered pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand the effects of spaceflight on the enzymes of the liver and exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. Additionally, it has been previous noted that pre-exposure to small radiation doses seems to confer protection against later and larger radiation doses. This protective power of pre-exposure has been called a priming effect or radioadaptation. This study is an effort to examine the drug metabolizing effects of radioadaptation mechanisms that may be triggered by early exposure to low radiation doses.

  5. Short-term fasting alters cytochrome P450-mediated drug metabolism in humans

    NARCIS (Netherlands)

    Lammers, Laureen A.; Achterbergh, Roos; de Vries, Emmely M.; van Nierop, F. Samuel; Klümpen, Heinz-Josef; Soeters, Maarten R.; Boelen, Anita; Romijn, Johannes A.; Mathôt, Ron A. A.

    2015-01-01

    Experimental studies indicate that short-term fasting alters drug metabolism. However, the effects of short-term fasting on drug metabolism in humans need further investigation. Therefore, the aim of this study was to evaluate the effects of short-term fasting (36 h) on P450-mediated drug

  6. Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function

    DEFF Research Database (Denmark)

    Yang, Jason H.; Bhargava, Prerna; McCloskey, Douglas

    2017-01-01

    Bactericidal antibiotics alter microbial metabolism as part of their lethality and can damage mitochondria in mammalian cells. In addition, antibiotic susceptibility is sensitive to extracellular metabolites, but it remains unknown whether metabolites present at an infection site can affect eithe...... the immunomodulatory potential of antibiotics and reveal the local metabolic microenvironment to be an important determinant of infection resolution....

  7. Ironing Out the Wrinkles in Host Defense: Interactions between Iron Homeostasis and Innate Immunity

    Science.gov (United States)

    Wang, Lijian; Cherayil, Bobby J.

    2009-01-01

    Iron is an essential micronutrient for both microbial pathogens and their mammalian hosts. Changes in iron availability and distribution have significant effects on pathogen virulence and on the immune response to infection. Recent advances in our understanding of the molecular regulation of iron metabolism have shed new light on how alterations in iron homeostasis both contribute to and influence innate immunity. In this article, we review what is currently known about the role of iron in the response to infection. PMID:20375603

  8. Effects of long-distance running on iron metabolism and hematological parameters.

    Science.gov (United States)

    Seiler, D; Nagel, D; Franz, H; Hellstern, P; Leitzmann, C; Jung, K

    1989-10-01

    In 110 well-trained participants of a 1000-km running competition lasting for 20 days hematological parameters, iron metabolism, and their respective changes during the race were investigated. Thirty-nine men and 11 women were accustomed to wholesome vegetarian food (lacto-ovovegetarian), 52 men and 8 women consumed a conventional western diet. In each group 50% of the runners finished the race. Before the competition started red blood cell count, hematocrit, and hemoglobin were on average below the values observed in the normal population in all groups. Both male and female runners consuming the wholesome diet showed significantly lower ferritin values than those on a western diet. During the first days of the competition hemolysis occurred leading to increased serum concentrations of bilirubin and iron and decreased haptoglobin levels. Hb concentrations showed a constant decrease during the race. Serum ferritin concentration rose about twofold within the first days and then decreased again without reaching pre-race levels. Serum iron concentrations showed a significant decrease between days 3 and 6. Iron loss was caused by hematuria (25% of all urines tested), gastrointestinal blood loss (10% of all stool specimens tested), and by sweating (4.5 micrograms iron/dl sweat). Our results suggest that especially in female long-distance runners it may be difficult to supply sufficient quantities of iron with the diet.

  9. PEDF-induced alteration of metabolism leading to insulin resistance.

    Science.gov (United States)

    Carnagarin, Revathy; Dharmarajan, Arunasalam M; Dass, Crispin R

    2015-02-05

    Pigment epithelium-derived factor (PEDF) is an anti-angiogenic, immunomodulatory, and neurotrophic serine protease inhibitor protein. PEDF is evolving as a novel metabolic regulatory protein that plays a causal role in insulin resistance. Insulin resistance is the central pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, polycystic ovarian disease, and metabolic syndrome, and PEDF is associated with them. The current evidence suggests that PEDF administration to animals induces insulin resistance, whereas neutralisation improves insulin sensitivity. Inflammation, lipolytic free fatty acid mobilisation, and mitochondrial dysfunction are the proposed mechanism of PEDF-mediated insulin resistance. This review summarises the probable mechanisms adopted by PEDF to induce insulin resistance, and identifies PEDF as a potential therapeutic target in ameliorating insulin resistance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer

    OpenAIRE

    Roy, Debarshi; Mondal, Susmita; Wang, Chen; He, Xiaoping; Khurana, Ashwani; Giri, Shailendra; Hoffmann, Robert; Jung, Deok-Beom; Kim, Sung H; Chini, Eduardo N; Periera, Juliana Camacho; Folmes, Clifford D; Mariani, Andrea; Dowdy, Sean C; Bakkum-Gamez, Jamie N

    2014-01-01

    Background Loss of the endosulfatase HSulf-1 is common in ovarian cancer, upregulates heparin binding growth factor signaling and potentiates tumorigenesis and angiogenesis. However, metabolic differences between isogenic cells with and without HSulf-1 have not been characterized upon HSulf-1 suppression in vitro. Since growth factor signaling is closely tied to metabolic alterations, we determined the extent to which HSulf-1 loss affects cancer cell metabolism. Results Ingenuity pathway anal...

  11. Antidepressants Alter Cerebrovascular Permeability and Metabolic Rate in Primates

    Science.gov (United States)

    Preskorn, Sheldon H.; Raichle, Marcus E.; Hartman, Boyd K.

    1982-07-01

    External detection of the annihilation radiation produced by water labeled with oxygen-15 was used to measure cerebrovascular permeability and cerebral blood flow in six rhesus monkeys. Use of oxygen-15 also permitted assessment of cerebral metabolic rate in two of the monkeys. Amitriptyline produced a dose-dependent, reversible increase in permeability at plasma drug concentrations which are therapeutic for depressed patients. At the same concentrations the drug also produced a 20 to 30 percent reduction in cerebral metabolic rate. At higher doses normal autoregulation of cerebral blood flow was suspended, but responsivity to arterial carbon dioxide was normal.

  12. Thrombolytic therapy of acute myocardial infarction alters collagen metabolism

    DEFF Research Database (Denmark)

    Høst, N B; Hansen, S S; Jensen, L T

    1994-01-01

    The objective of the study was to monitor collagen metabolism after thrombolytic therapy. Sequential measurements of serum aminoterminal type-III procollagen propeptide (S-PIIINP) and carboxyterminal type-I procollagen propeptide (S-PICP) were made in 62 patients suspected of acute myocardial...

  13. Visible light alters yeast metabolic rhythms by inhibiting respiration.

    Science.gov (United States)

    Robertson, James Brian; Davis, Chris R; Johnson, Carl Hirschie

    2013-12-24

    Exposure of cells to visible light in nature or in fluorescence microscopy often is considered to be relatively innocuous. However, using the yeast respiratory oscillation (YRO) as a sensitive measurement of metabolism, we find that non-UV visible light has a significant impact on yeast metabolism. Blue/green wavelengths of visible light shorten the period and dampen the amplitude of the YRO, which is an ultradian rhythm of cell metabolism and transcription. The wavelengths of light that have the greatest effect coincide with the peak absorption regions of cytochromes. Moreover, treating yeast with the electron transport inhibitor sodium azide has similar effects on the YRO as visible light. Because impairment of respiration by light would change several state variables believed to play vital roles in the YRO (e.g., oxygen tension and ATP levels), we tested oxygen's role in YRO stability and found that externally induced oxygen depletion can reset the phase of the oscillation, demonstrating that respiratory capacity plays a role in the oscillation's period and phase. Light-induced damage to the cytochromes also produces reactive oxygen species that up-regulate the oxidative stress response gene TRX2 that is involved in pathways that enable sustained growth in bright visible light. Therefore, visible light can modulate cellular rhythmicity and metabolism through unexpectedly photosensitive pathways.

  14. Stress transgenerationally programs metabolic pathways linked to altered mental health.

    Science.gov (United States)

    Kiss, Douglas; Ambeskovic, Mirela; Montina, Tony; Metz, Gerlinde A S

    2016-12-01

    Stress is among the primary causes of mental health disorders, which are the most common reason for disability worldwide. The ubiquity of these disorders, and the costs associated with them, lends a sense of urgency to the efforts to improve prediction and prevention. Down-stream metabolic changes are highly feasible and accessible indicators of pathophysiological processes underlying mental health disorders. Here, we show that remote and cumulative ancestral stress programs central metabolic pathways linked to mental health disorders. The studies used a rat model consisting of a multigenerational stress lineage (the great-great-grandmother and each subsequent generation experienced stress during pregnancy) and a transgenerational stress lineage (only the great-great-grandmother was stressed during pregnancy). Urine samples were collected from adult male F4 offspring and analyzed using 1 H NMR spectroscopy. The results of variable importance analysis based on random variable combination were used for unsupervised multivariate principal component analysis and hierarchical clustering analysis, as well as metabolite set enrichment analysis (MSEA) and pathway analysis. We identified distinct metabolic profiles associated with the multigenerational and transgenerational stress phenotype, with consistent upregulation of hippurate and downregulation of tyrosine, threonine, and histamine. MSEA and pathway analysis showed that these metabolites are involved in catecholamine biosynthesis, immune responses, and microbial host interactions. The identification of metabolic signatures linked to ancestral programming assists in the discovery of gene targets for future studies of epigenetic regulation in pathogenic processes. Ultimately, this research can lead to biomarker discovery for better prediction and prevention of mental health disorders.

  15. Salicylic Acid Alters Antioxidant and Phenolics Metabolism in ...

    African Journals Online (AJOL)

    Key words: Antioxidant enzymes; Catharanthus roseus; indole alkaloids; phenolic metabolism; salicylic acid; salinity stress. Abbreviations: CAT - catalase; Chl - chlorophyll; Car - carotenoids; DTNB - 5,5-dithiobis-2-nitrobenzoic acid; GR - glutathione reductase; GST - Glutathione-S-transferase; H2O2 - hydrogen peroxide; ...

  16. General geology, alteration, and iron deposits in the Palaeoproterozoic Misi region, northern Finland

    Directory of Open Access Journals (Sweden)

    Tero Niiranen

    2003-01-01

    Full Text Available The Paleoproterozoic Misi region forms the northeastern part of the Peräpohja Schist Belt in northern Finland. The area comprises mafic volcanic and sedimentary rocks, differentiated gabbros, and late-orogenic granitoids. Three geochemically different mafic volcanic units were recognised: LREE-depleted amygdaloidal lavas, slightly LREE-enriched lavas, and mafic tuffs that have a flat REE pattern. Sedimentary rocks include arkosites, mica gneisses, dolomitic marbles, quartzites, tuffites, mica schists, calc-silicate rocks and graphite-bearing schists. Two types of gabbros wereidentified: one with a LREE-enriched pattern and another with flat REE pattern. The age of the former is according to Perttunen and Vaasjoki (2001 2117±4 Ma, whereas there is no age determination for the latter. The granitoid intrusions belong to the ca. 1800 Malate-orogenic group of the Central Lapland Granitoid Complex. The geochemistry and the stable isotope data on mafic lavas and dolomitic marbles show similarities with the mafic volcanic rocks and marbles of the lower part of the Kivalo group in the western part of Peräpohja Schist Belt. Peak metamorphic conditions in the region vary from upper-greenschist to upper-amphibolite facies. Three major stages of deformation were distinguished: N-S compressional D1 with ductile deformation, NE-SW compressional D2 with ductile to brittle-ductile deformation, and E-W compressional D3 with brittle deformation. Several magnetite occurrences are known in the region and four of those have been mined for iron. The ores are mainly composed of magnetite with minor haematite, pyrite, chalcopyrite and bornite. Besides iron, the ores contain small amounts of P, S and V aswell as trace amounts of Cu, Co, Te and Au. The magnetite bodies are hosted by skarnoids within the ca. 2220–2120 Ma dolomitic marble-quartzite sequence, and highly differentiated, intensely albitised, LREE-enriched gabbro. Multistage and -type alteration is

  17. Doxycycline alters metabolism and proliferation of human cell lines.

    Directory of Open Access Journals (Sweden)

    Ethan Ahler

    Full Text Available The tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells-including inhibition of the mitochondrial ribosome-there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism.

  18. Recombinant bacterial hemoglobin alters metabolism of Aspergillus niger

    DEFF Research Database (Denmark)

    Hofmann, Gerald; Diano, Audrey; Nielsen, Jens

    2009-01-01

    The filamentous fungus Aspergillus niger is used extensively for the production of enzymes and organic acids. A major problem in industrial fermentations with this fungus is to ensure sufficient supply of oxygen required for respiratory metabolism of the fungus. In case of oxygen limitation......, the fungus will produce various by-products like organic acids and polyols. In order to circumvent this problem we here study the effects of the expression of a bacterial hemoglobin protein on the metabolism of A. niger. We integrated the vgb gene from Vitreoscilla sp. into the genome at the pyrA locus...... behind the strong gpdA promoter from Aspergillus nidulans. Analysis of secreted metabolites, oxygen uptake, CO2 evolution and biomass formation points towards a relief of stress in the mutant expressing VHB when it is exposed to oxygen limitation. Our findings therefore point to an interesting strategy...

  19. Metabolic alterations in patients with self-inflicted aggressive behaviour

    OpenAIRE

    Westling, Sofie

    2009-01-01

    Self-inflicted aggressive behaviour is a cross diagnostic phenomenon of major clinical relevance in psychiatric setting. Accumulating evidence speaks for a role of metabolic and immunological factors in aggressive behaviour. The aim of this thesis is to enlighten the role of leptin, insulin, glucagon, glucose and IL-1beta in the context of self-inflicted aggressive behaviour. We used cerebrospinal fluid (CSF-) samples from patients with a recent suicide attempt and plasma samples from a five-...

  20. Iron Sulfur and Molybdenum Cofactor Enzymes Regulate the Drosophila Life Cycle by Controlling Cell Metabolism

    Science.gov (United States)

    Marelja, Zvonimir; Leimkühler, Silke; Missirlis, Fanis

    2018-01-01

    Iron sulfur (Fe-S) clusters and the molybdenum cofactor (Moco) are present at enzyme sites, where the active metal facilitates electron transfer. Such enzyme systems are soluble in the mitochondrial matrix, cytosol and nucleus, or embedded in the inner mitochondrial membrane, but virtually absent from the cell secretory pathway. They are of ancient evolutionary origin supporting respiration, DNA replication, transcription, translation, the biosynthesis of steroids, heme, catabolism of purines, hydroxylation of xenobiotics, and cellular sulfur metabolism. Here, Fe-S cluster and Moco biosynthesis in Drosophila melanogaster is reviewed and the multiple biochemical and physiological functions of known Fe-S and Moco enzymes are described. We show that RNA interference of Mocs3 disrupts Moco biosynthesis and the circadian clock. Fe-S-dependent mitochondrial respiration is discussed in the context of germ line and somatic development, stem cell differentiation and aging. The subcellular compartmentalization of the Fe-S and Moco assembly machinery components and their connections to iron sensing mechanisms and intermediary metabolism are emphasized. A biochemically active Fe-S core complex of heterologously expressed fly Nfs1, Isd11, IscU, and human frataxin is presented. Based on the recent demonstration that copper displaces the Fe-S cluster of yeast and human ferredoxin, an explanation for why high dietary copper leads to cytoplasmic iron deficiency in flies is proposed. Another proposal that exosomes contribute to the transport of xanthine dehydrogenase from peripheral tissues to the eye pigment cells is put forward, where the Vps16a subunit of the HOPS complex may have a specialized role in concentrating this enzyme within pigment granules. Finally, we formulate a hypothesis that (i) mitochondrial superoxide mobilizes iron from the Fe-S clusters in aconitase and succinate dehydrogenase; (ii) increased iron transiently displaces manganese on superoxide dismutase, which

  1. Iron Sulfur and Molybdenum Cofactor Enzymes Regulate the Drosophila Life Cycle by Controlling Cell Metabolism

    Directory of Open Access Journals (Sweden)

    Zvonimir Marelja

    2018-02-01

    Full Text Available Iron sulfur (Fe-S clusters and the molybdenum cofactor (Moco are present at enzyme sites, where the active metal facilitates electron transfer. Such enzyme systems are soluble in the mitochondrial matrix, cytosol and nucleus, or embedded in the inner mitochondrial membrane, but virtually absent from the cell secretory pathway. They are of ancient evolutionary origin supporting respiration, DNA replication, transcription, translation, the biosynthesis of steroids, heme, catabolism of purines, hydroxylation of xenobiotics, and cellular sulfur metabolism. Here, Fe-S cluster and Moco biosynthesis in Drosophila melanogaster is reviewed and the multiple biochemical and physiological functions of known Fe-S and Moco enzymes are described. We show that RNA interference of Mocs3 disrupts Moco biosynthesis and the circadian clock. Fe-S-dependent mitochondrial respiration is discussed in the context of germ line and somatic development, stem cell differentiation and aging. The subcellular compartmentalization of the Fe-S and Moco assembly machinery components and their connections to iron sensing mechanisms and intermediary metabolism are emphasized. A biochemically active Fe-S core complex of heterologously expressed fly Nfs1, Isd11, IscU, and human frataxin is presented. Based on the recent demonstration that copper displaces the Fe-S cluster of yeast and human ferredoxin, an explanation for why high dietary copper leads to cytoplasmic iron deficiency in flies is proposed. Another proposal that exosomes contribute to the transport of xanthine dehydrogenase from peripheral tissues to the eye pigment cells is put forward, where the Vps16a subunit of the HOPS complex may have a specialized role in concentrating this enzyme within pigment granules. Finally, we formulate a hypothesis that (i mitochondrial superoxide mobilizes iron from the Fe-S clusters in aconitase and succinate dehydrogenase; (ii increased iron transiently displaces manganese on superoxide

  2. Altered circadian rhythm and metabolic gene profile in rats subjected to advanced light phase shifts.

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    Laura Herrero

    Full Text Available The circadian clock regulates metabolic homeostasis and its disruption predisposes to obesity and other metabolic diseases. However, the effect of phase shifts on metabolism is not completely understood. We examined whether alterations in the circadian rhythm caused by phase shifts induce metabolic changes in crucial genes that would predispose to obesity. Three-month-old rats were maintained on a standard diet under lighting conditions with chronic phase shifts consisting of advances, delays or advances plus delays. Serum leptin, insulin and glucose levels decreased only in rats subjected to advances. The expression of the clock gene Bmal 1 increased in the hypothalamus, white adipose tissue (WAT, brown adipose tissue (BAT and liver of the advanced group compared to control rats. The advanced group showed an increase in hypothalamic AgRP and NPY mRNA, and their lipid metabolism gene profile was altered in liver, WAT and BAT. WAT showed an increase in inflammation and ER stress and brown adipocytes suffered a brown-to-white transformation and decreased UCP-1 expression. Our results indicate that chronic phase advances lead to significant changes in neuropeptides, lipid metabolism, inflammation and ER stress gene profile in metabolically relevant tissues such as the hypothalamus, liver, WAT and BAT. This highlights a link between alteration of the circadian rhythm and metabolism at the transcriptional level.

  3. Supplementary Material for: Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects

    KAUST Repository

    Papsdorf, Katharina

    2015-01-01

    Abstract Background Protein aggregation and its pathological effects are the major cause of several neurodegenerative diseases. In Huntingtonâ s disease an elongated stretch of polyglutamines within the protein Huntingtin leads to increased aggregation propensity. This induces cellular defects, culminating in neuronal loss, but the connection between aggregation and toxicity remains to be established. Results To uncover cellular pathways relevant for intoxication we used genome-wide analyses in a yeast model system and identify fourteen genes that, if deleted, result in higher polyglutamine toxicity. Several of these genes, like UGO1, ATP15 and NFU1 encode mitochondrial proteins, implying that a challenged mitochondrial system may become dysfunctional during polyglutamine intoxication. We further employed microarrays to decipher the transcriptional response upon polyglutamine intoxication, which exposes an upregulation of genes involved in sulfur and iron metabolism and mitochondrial Fe-S cluster formation. Indeed, we find that in vivo iron concentrations are misbalanced and observe a reduction in the activity of the prominent Fe-S cluster containing protein aconitase. Like in other yeast strains with impaired mitochondria, non-fermentative growth is impossible after intoxication with the polyglutamine protein. NMR-based metabolic analyses reveal that mitochondrial metabolism is reduced, leading to accumulation of metabolic intermediates in polyglutamine-intoxicated cells. Conclusion These data show that damages to the mitochondrial system occur in polyglutamine intoxicated yeast cells and suggest an intricate connection between polyglutamine-induced toxicity, mitochondrial functionality and iron homeostasis in this model system.

  4. Knockdown of proteins involved in iron metabolism limits tick reproduction and development

    Czech Academy of Sciences Publication Activity Database

    Hajdušek, O.; Sojka, Daniel; Kopáček, Petr; Burešová, Veronika; Franta, Zdeněk; Šauman, Ivo; Winzerling, J.; Grubhoffer, L.

    2009-01-01

    Roč. 106, č. 4 (2009), s. 1033-1038 ISSN 0027-8424 R&D Projects: GA MŠk(CZ) LC06009; GA MŠk LC07032; GA AV ČR IAA600220603 Institutional research plan: CEZ:AV0Z60220518; CEZ:AV0Z50070508 Keywords : tick ferritin * iron metabolism * RNA interference Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.432, year: 2009

  5. Zebrafish in the sea of mineral (iron, zinc, and copper) metabolism

    Science.gov (United States)

    Zhao, Lu; Xia, Zhidan; Wang, Fudi

    2014-01-01

    Iron, copper, zinc, and eight other minerals are classified as essential trace elements because they present in minute in vivo quantities and are essential for life. Because either excess or insufficient levels of trace elements can be detrimental to life (causing human diseases such as iron-deficiency anemia, hemochromatosis, Menkes syndrome and Wilson's disease), the endogenous levels of trace minerals must be tightly regulated. Many studies have demonstrated the existence of systems that maintain trace element homeostasis, and these systems are highly conserved in multiple species ranging from yeast to mice. As a model for studying trace mineral metabolism, the zebrafish is indispensable to researchers. Several large-scale mutagenesis screens have been performed in zebrafish, and these screens led to the identification of a series of metal transporters and the generation of several mutagenesis lines, providing an in-depth functional analysis at the system level. Moreover, because of their developmental advantages, zebrafish have also been used in mineral metabolism-related chemical screens and toxicology studies. Here, we systematically review the major findings of trace element homeostasis studies using the zebrafish model, with a focus on iron, zinc, copper, selenium, manganese, and iodine. We also provide a homology analysis of trace mineral transporters in fish, mice and humans. Finally, we discuss the evidence that zebrafish is an ideal experimental tool for uncovering novel mechanisms of trace mineral metabolism and for improving approaches to treat mineral imbalance-related diseases. PMID:24639652

  6. [Asbestos-stimulated changes in nitric oxide and iron metabolism in rats].

    Science.gov (United States)

    Shandarenko, S H; Kishko, T O; Chumachenko, I M; Dmytrenko, M P

    2011-01-01

    Under intratracheal asbestos fibers installation it has been investigated NO synthesis in the lung and liver tissues of Wistar rats by EPR method. Asbestos A6-45, sifted through the sieve with size 0.1 mm, has been administrated in a dose of 5 mg/kg. To evaluate the NO synthesis EPR and NO-trap methods have been used. The amplitude of EPR signal "trap-NO" in the lung samples was 12, 16 and 14 times greater than in controls on the 3th, 6th and 10th days after asbestos installation and was corresponding to NO rate of about 2 mkmol/(g x h). In the liver samples of asbestos-stimulated animals the NO level contained in the non-heme iron nitrosyl complexes was about 2 mkmol/g. Thus, the asbestos fibers stimulate NO synthesis not only in the lung tissue, but also in other organs. The obtained data shows that under NO hyperproduction certain changes in iron metabolism take place, such as: the decrease of transferrin iron and the accumulation of ferric iron not bound with transferrin. The accumulation of ferric iron not shielded by proteins is one of the oxidative stress triggers.

  7. Dealing with iron metabolism in rice: from breeding for stress tolerance to biofortification

    Directory of Open Access Journals (Sweden)

    Railson Schreinert dos Santos

    2017-03-01

    Full Text Available Abstract Iron is a well-known metal. Used by humankind since ancient times in many different ways, this element is present in all living organisms, where, unfortunately, it represents a two-way problem. Being an essential block in the composition of different proteins and metabolic pathways, iron is a vital component for animals and plants. That is why iron deficiency has a severe impact on the lives of different organisms, including humans, becoming a major concern, especially in developing countries where access to adequate nutrition is still difficult. On the other hand, this metal is also capable of causing damage when present in excess, becoming toxic to cells and affecting the whole organism. Because of its importance, iron absorption, transport and storage mechanisms have been extensively investigated in order to design alternatives that may solve this problem. As the understanding of the strategies that plants use to control iron homeostasis is an important step in the generation of improved plants that meet both human agricultural and nutritional needs, here we discuss some of the most important points about this topic.

  8. Hemoglobin, iron metabolism and angiographic coronary artery disease (The Ludwigshafen Risk and Cardiovascular Health Study).

    Science.gov (United States)

    Grammer, Tanja B; Kleber, Marcus E; Silbernagel, Günther; Pilz, Stefan; Scharnagl, Hubert; Tomaschitz, Andreas; König, Wolfgang; März, Winfried

    2014-10-01

    Anemia has been shown to be a risk factor for coronary artery disease and mortality. The involvement of body iron stores in the development of CAD remains controversial. So far, studies that examined hemoglobin and parameters of iron metabolism simultaneously do not exist. Hemoglobin and iron status were determined in 1480 patients with stable angiographic coronary artery disease (CAD) and in 682 individuals in whom CAD had been ruled out by angiography. The multivariate adjusted odds ratios (OR) for CAD in the lowest quartiles of hemoglobin and iron were 1.62 (95%CI: 1.22-2.16), and 2.05 (95%CI: 1.51-2.78), respectively compared to their highest gender-specific quartiles. The fully adjusted ORs for CAD in the lowest quartiles of transferrin saturation, ferritin (F) and soluble transferrin receptor (sTfR)/log10F index were 1.69 (95%CI: 1.25-2.27), 1.98 (95%CI: 1.48-2.65), and 1.64 (95%CI: 1.23-2.18), respectively compared to their highest gender-specific quartiles. When adjusting in addition for iron and ferritin the OR for CAD in the lowest quartiles of hemoglobin was still 1.40 (95%CI: 1.04-1.90) compared to the highest gender-specific quartiles. Thus, the associations between either iron status or low hemoglobin and CAD appeared independent from each other. The sTfR was only marginally associated with angiographic CAD. Both low hemoglobin and iron depletion are independently associated with angiographic CAD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. The Role of Iron Metabolism as a Mediator of Macrophage Inflammation and Lipid Handling in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Anwer Khaled Habib

    2014-08-01

    Full Text Available Iron is an essential mineral needed for normal physiologic processes. While its function in oxygen transport and other important physiologic processes is well known, less is understood about its role in inflammatory diseases such as atherosclerosis. Existing paradigms suggest iron as a driver of atherosclerosis through its actions as a pro-oxidant capable of causing lipid oxidation and tissue damage. Recently we and others have identified hemoglobin derived iron as an important factor in determining macrophage differentiation and function in areas of intraplaque hemorrhage within human atherosclerosis. Hemoglobin associated macrophages, M(Hb, are distinct from traditional macrophage foam cells because they do not contain large amounts of lipid or inflammatory cytokines, are characterized by high levels of expression of mannose receptor (CD206 and CD163 in addition to producing anti-inflammatory cytokines such as IL-10. Despite the well-known role of iron as an catalyst capable of producing lipid peroxidation through generation of reactive oxygen species such as hydroxyl radical, we and others have shown that macrophages in areas of intraplaque hemorrhage demonstrate reduced intracellular iron and reactive oxygen species (ROS which triggers production of anti-inflammatory cytokines as well as genes involved in cholesterol efflux. These data suggest that manipulation of macrophage iron itself may be a promising pharmacologic target for atherosclerosis prevention through its effects on macrophage inflammation and lipid metabolism. In this review we will summarize the current understanding of iron as it relates to plaque inflammation and discuss how further exploration of this subject may lead to new therapies for atherosclerosis.

  10. Experimental ocean acidification alters the allocation of metabolic energy.

    Science.gov (United States)

    Pan, T-C Francis; Applebaum, Scott L; Manahan, Donal T

    2015-04-14

    Energy is required to maintain physiological homeostasis in response to environmental change. Although responses to environmental stressors frequently are assumed to involve high metabolic costs, the biochemical bases of actual energy demands are rarely quantified. We studied the impact of a near-future scenario of ocean acidification [800 µatm partial pressure of CO2 (pCO2)] during the development and growth of an important model organism in developmental and environmental biology, the sea urchin Strongylocentrotus purpuratus. Size, metabolic rate, biochemical content, and gene expression were not different in larvae growing under control and seawater acidification treatments. Measurements limited to those levels of biological analysis did not reveal the biochemical mechanisms of response to ocean acidification that occurred at the cellular level. In vivo rates of protein synthesis and ion transport increased ∼50% under acidification. Importantly, the in vivo physiological increases in ion transport were not predicted from total enzyme activity or gene expression. Under acidification, the increased rates of protein synthesis and ion transport that were sustained in growing larvae collectively accounted for the majority of available ATP (84%). In contrast, embryos and prefeeding and unfed larvae in control treatments allocated on average only 40% of ATP to these same two processes. Understanding the biochemical strategies for accommodating increases in metabolic energy demand and their biological limitations can serve as a quantitative basis for assessing sublethal effects of global change. Variation in the ability to allocate ATP differentially among essential functions may be a key basis of resilience to ocean acidification and other compounding environmental stressors.

  11. Plant interactions alter the predictions of metabolic scaling theory.

    Directory of Open Access Journals (Sweden)

    Yue Lin

    Full Text Available Metabolic scaling theory (MST is an attempt to link physiological processes of individual organisms with macroecology. It predicts a power law relationship with an exponent of -4/3 between mean individual biomass and density during density-dependent mortality (self-thinning. Empirical tests have produced variable results, and the validity of MST is intensely debated. MST focuses on organisms' internal physiological mechanisms but we hypothesize that ecological interactions can be more important in determining plant mass-density relationships induced by density. We employ an individual-based model of plant stand development that includes three elements: a model of individual plant growth based on MST, different modes of local competition (size-symmetric vs. -asymmetric, and different resource levels. Our model is consistent with the observed variation in the slopes of self-thinning trajectories. Slopes were significantly shallower than -4/3 if competition was size-symmetric. We conclude that when the size of survivors is influenced by strong ecological interactions, these can override predictions of MST, whereas when surviving plants are less affected by interactions, individual-level metabolic processes can scale up to the population level. MST, like thermodynamics or biomechanics, sets limits within which organisms can live and function, but there may be stronger limits determined by ecological interactions. In such cases MST will not be predictive.

  12. Altered biodistribution of gallium-67 in a patient with multiple factors influencing iron-transport protein saturation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jeon Young; Kim, Sang Eun; Lee, Kyung Han; Kim, Byung Tae [College of Medicine, Samsung Medical Center, Seoul (Korea, Republic of)

    1998-01-01

    We present a case of a young female patient with fulminant hepatitis who showed an altered biodistribution of Ga-67, after being scanned twice at 10 month intervals. On initial scan, uptake of Ga-67 was increased in the liver, kidneys, and skeletons. Increased hepatic Ga-67 uptake may be explained by increased transferrin unbound Ga-67 that was taken up by the inflamed liver. The saturation of iron-binding proteins due to multiple transfusions may lead to increased renal and skeletal Ga-67 uptake. On follow-up scan hepatic Ga-67 uptake was markedly increased. Also increased Ga-67 uptake in the axial skeleton and normalized renal uptake were shown. The findings were consistent with iron deficiency anemia. This case demonstrates altered Ga-67 biodistribution associated with multiple transfusions, fulminant hepatitis, and iron deficiency anemia.

  13. Directed Evolution Reveals Unexpected Epistatic Interactions That Alter Metabolic Regulation and Enable Anaerobic Xylose Use by Saccharomyces cerevisiae.

    Science.gov (United States)

    Sato, Trey K; Tremaine, Mary; Parreiras, Lucas S; Hebert, Alexander S; Myers, Kevin S; Higbee, Alan J; Sardi, Maria; McIlwain, Sean J; Ong, Irene M; Breuer, Rebecca J; Avanasi Narasimhan, Ragothaman; McGee, Mick A; Dickinson, Quinn; La Reau, Alex; Xie, Dan; Tian, Mingyuan; Reed, Jennifer L; Zhang, Yaoping; Coon, Joshua J; Hittinger, Chris Todd; Gasch, Audrey P; Landick, Robert

    2016-10-01

    The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically. We report that rapid xylose conversion by engineered and evolved S. cerevisiae strains depends upon epistatic interactions among genes encoding a xylose reductase (GRE3), a component of MAP Kinase (MAPK) signaling (HOG1), a regulator of Protein Kinase A (PKA) signaling (IRA2), and a scaffolding protein for mitochondrial iron-sulfur (Fe-S) cluster biogenesis (ISU1). Interestingly, the mutation in IRA2 only impacted anaerobic xylose consumption and required the loss of ISU1 function, indicating a previously unknown connection between PKA signaling, Fe-S cluster biogenesis, and anaerobiosis. Proteomic and metabolomic comparisons revealed that the xylose-metabolizing mutant strains exhibit altered metabolic pathways relative to the parental strain when grown in xylose. Further analyses revealed that interacting mutations in HOG1 and ISU1 unexpectedly elevated mitochondrial respiratory proteins and enabled rapid aerobic respiration of xylose and other non-fermentable carbon substrates. Our findings suggest a surprising connection between Fe-S cluster biogenesis and signaling that facilitates aerobic respiration and anaerobic fermentation of xylose, underscoring how much remains unknown about the eukaryotic signaling systems that regulate carbon metabolism.

  14. Directed Evolution Reveals Unexpected Epistatic Interactions That Alter Metabolic Regulation and Enable Anaerobic Xylose Use by Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Trey K Sato

    2016-10-01

    Full Text Available The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically. We report that rapid xylose conversion by engineered and evolved S. cerevisiae strains depends upon epistatic interactions among genes encoding a xylose reductase (GRE3, a component of MAP Kinase (MAPK signaling (HOG1, a regulator of Protein Kinase A (PKA signaling (IRA2, and a scaffolding protein for mitochondrial iron-sulfur (Fe-S cluster biogenesis (ISU1. Interestingly, the mutation in IRA2 only impacted anaerobic xylose consumption and required the loss of ISU1 function, indicating a previously unknown connection between PKA signaling, Fe-S cluster biogenesis, and anaerobiosis. Proteomic and metabolomic comparisons revealed that the xylose-metabolizing mutant strains exhibit altered metabolic pathways relative to the parental strain when grown in xylose. Further analyses revealed that interacting mutations in HOG1 and ISU1 unexpectedly elevated mitochondrial respiratory proteins and enabled rapid aerobic respiration of xylose and other non-fermentable carbon substrates. Our findings suggest a surprising connection between Fe-S cluster biogenesis and signaling that facilitates aerobic respiration and anaerobic fermentation of xylose, underscoring how much remains unknown about the eukaryotic signaling systems that regulate carbon metabolism.

  15. Plant interactions alter the predictions of metabolic scaling theory

    DEFF Research Database (Denmark)

    Lin, Yue; Berger, Uta; Grimm, Volker

    2013-01-01

    produced variable results, and the validity of MST is intensely debated. MST focuses on organisms’ internal physiological mechanisms but we hypothesize that ecological interactions can be more important in determining plant mass-density relationships induced by density. We employ an individual-based model....... Slopes were significantly shallower than 24/3 if competition was size-symmetric. We conclude that when the size of survivors is influenced by strong ecological interactions, these can override predictions of MST, whereas when surviving plants are less affected by interactions, individual-level metabolic...... processes can scale up to the population level. MST, like thermodynamics or biomechanics, sets limits within which organisms can live and function, but there may be stronger limits determined by ecological interactions. In such cases MST will not be predictive....

  16. Hexachlorophene induced alterations in brain carbohydrate metabolism of Wistar rat.

    Science.gov (United States)

    Rajendra, W; Rao, P V; Suhasini, N; Sailaja, P

    1992-12-01

    Effect of repeated oral administration of hexachlorophene (HCP) on glycolytic and oxidative pathways was studied in the rat brain. The rats were divided into three batches of six in each batch. The first batch was treated with paralytic dose (60 mg.kg-1.day-1) of HCP for 7 days. The second batch of animals was treated with sublethal dose (18 mg.kg-1.day-1) for 7 days. The third batch of animals was served as the age matched controls which received vehicle (corn oil) only. The glycolytic and oxidative metabolism of carbohydrates was significantly inhibited in the brain of rat during HCP treatment and the inhibition was more pronounced in paralytic dose treatment as compared to sublethal dose treatment. The inhibition of NADP-isocitrate dehydrogenase coupled with glucose 6-phosphate dehydrogenase indicates reduced generation of NADPH2 and pentoses for the synthesis of fatty acids and nucleotides.

  17. Copy Number Alterations in Enzyme-Coding and Cancer-Causing Genes Reprogram Tumor Metabolism.

    Science.gov (United States)

    Sharma, Ashwini Kumar; Eils, Roland; König, Rainer

    2016-07-15

    Somatic copy number alterations frequently occur in the cancer genome affecting not only oncogenic or tumor suppressive genes, but also passenger and potential codriver genes. An intrinsic feature resulting from such genomic perturbations is the deregulation in the metabolism of tumor cells. In this study, we have shown that metabolic and cancer-causing genes are unexpectedly often proximally positioned in the chromosome and share loci with coaltered copy numbers across multiple cancers (19 cancer types from The Cancer Genome Atlas). We have developed an analysis pipeline, Identification of Metabolic Cancer Genes (iMetCG), to infer the functional impact on metabolic remodeling from such coamplifications and codeletions and delineate genes driving cancer metabolism from those that are neutral. Using our identified metabolic genes, we were able to classify tumors based on their tissue and developmental origins. These metabolic genes were similar to known cancer genes in terms of their network connectivity, isoform frequency, and evolutionary features. We further validated these identified metabolic genes by (i) using gene essentiality data from several tumor cell lines, (ii) showing that these identified metabolic genes are strong indicators for patient survival, and (iii) observing a significant overlap between our identified metabolic genes and known cancer-metabolic genes. Our analyses revealed a hitherto unknown generic mechanism for large-scale metabolic reprogramming in cancer cells based on linear gene proximities between cancer-causing and -metabolic genes. We have identified 119 new metabolic cancer genes likely to be involved in rewiring cancer cell metabolism. Cancer Res; 76(14); 4058-67. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. Is a 50 Hz magnetic field susceptible to change the iron metabolism and to induce an anemia?; Un champ magnetique de 50 Hz est-il susceptible d'alterer le metabolisme du fer et d'induire une anemie?

    Energy Technology Data Exchange (ETDEWEB)

    Nafziger, J. [Universite Rene Descartes, Lab. d' Hematologie Cellulaire et Moleculaire, UPRES EA-2509, UFR des Sciences Pharmaceutiques et Biologiques de Paris, 75 - Paris (France)

    2001-07-01

    Significant difference have been observed between the exposed and the reference persons for the iron by storage in the spleen and for the percentage of red line cells in the bone marrow, but the observed changes have not been associated to an anemia during the fifteen exposure weeks. however, given the change in iron storage and the reduction of red line cells in the bone marrow, the possibility of delayed effects is not out of the question. (N.C.)

  19. Altered metabolism of growth hormone receptor mutant mice: a combined NMR metabonomics and microarray study.

    Directory of Open Access Journals (Sweden)

    Horst Joachim Schirra

    Full Text Available BACKGROUND: Growth hormone is an important regulator of post-natal growth and metabolism. We have investigated the metabolic consequences of altered growth hormone signalling in mutant mice that have truncations at position 569 and 391 of the intracellular domain of the growth hormone receptor, and thus exhibit either low (around 30% maximum or no growth hormone-dependent STAT5 signalling respectively. These mutations result in altered liver metabolism, obesity and insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: The analysis of metabolic changes was performed using microarray analysis of liver tissue and NMR metabonomics of urine and liver tissue. Data were analyzed using multivariate statistics and Gene Ontology tools. The metabolic profiles characteristic for each of the two mutant groups and wild-type mice were identified with NMR metabonomics. We found decreased urinary levels of taurine, citrate and 2-oxoglutarate, and increased levels of trimethylamine, creatine and creatinine when compared to wild-type mice. These results indicate significant changes in lipid and choline metabolism, and were coupled with increased fat deposition, leading to obesity. The microarray analysis identified changes in expression of metabolic enzymes correlating with alterations in metabolite concentration both in urine and liver. Similarity of mutant 569 to the wild-type was seen in young mice, but the pattern of metabolites shifted to that of the 391 mutant as the 569 mice became obese after six months age. CONCLUSIONS/SIGNIFICANCE: The metabonomic observations were consistent with the parallel analysis of gene expression and pathway mapping using microarray data, identifying metabolites and gene transcripts involved in hepatic metabolism, especially for taurine, choline and creatinine metabolism. The systems biology approach applied in this study provides a coherent picture of metabolic changes resulting from impaired STAT5 signalling by the growth hormone

  20. Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations

    Directory of Open Access Journals (Sweden)

    Ariel B. Ganz

    2017-01-01

    Full Text Available Single nucleotide polymorphisms (SNPs in choline metabolizing genes are associated with disease risk and greater susceptibility to organ dysfunction under conditions of dietary choline restriction. However, the underlying metabolic signatures of these variants are not well characterized and it is unknown whether genotypic differences persist at recommended choline intakes. Thus, we sought to determine if common genetic risk factors alter choline dynamics in pregnant, lactating, and non-pregnant women consuming choline intakes meeting and exceeding current recommendations. Women (n = 75 consumed 480 or 930 mg choline/day (22% as a metabolic tracer, choline-d9 for 10–12 weeks in a controlled feeding study. Genotyping was performed for eight variant SNPs and genetic differences in metabolic flux and partitioning of plasma choline metabolites were evaluated using stable isotope methodology. CHKA rs10791957, CHDH rs9001, CHDH rs12676, PEMT rs4646343, PEMT rs7946, FMO3 rs2266782, SLC44A1 rs7873937, and SLC44A1 rs3199966 altered the use of choline as a methyl donor; CHDH rs9001 and BHMT rs3733890 altered the partitioning of dietary choline between betaine and phosphatidylcholine synthesis via the cytidine diphosphate (CDP-choline pathway; and CHKA rs10791957, CHDH rs12676, PEMT rs4646343, PEMT rs7946 and SLC44A1 rs7873937 altered the distribution of dietary choline between the CDP-choline and phosphatidylethanolamine N-methyltransferase (PEMT denovo pathway. Such metabolic differences may contribute to disease pathogenesis and prognosis over the long-term.

  1. Metabolic Alterations in Cancer Cells and the Emerging Role of Oncometabolites as Drivers of Neoplastic Change.

    Science.gov (United States)

    Zhou, Zhengqiu; Ibekwe, Elochukwu; Chornenkyy, Yevgen

    2018-01-17

    The mitochondrion is an important organelle and provides energy for a plethora of intracellular reactions. Metabolic dysregulation has dire consequences for the cell, and alteration in metabolism has been identified in multiple disease states-cancer being one. Otto Warburg demonstrated that cancer cells, in the presence of oxygen, undergo glycolysis by reprogramming their metabolism-termed "aerobic glycolysis". Alterations in metabolism enable cancer cells to gain a growth advantage by obtaining precursors for macromolecule biosynthesis, such as nucleic acids and lipids. To date, several molecules, termed "oncometabolites", have been identified to be elevated in cancer cells and arise from mutations in nuclear encoded mitochondrial enzymes. Furthermore, there is evidence that oncometabolites can affect mitochondrial dynamics. It is believed that oncometabolites can assist in reprogramming enzymatic pathways and providing cancer cells with selective advantages. In this review, we will touch upon the effects of normal and aberrant mitochondrial metabolism in normal and cancer cells, the advantages of metabolic reprogramming, effects of oncometabolites on metabolism and mitochondrial dynamics and therapies aimed at targeting oncometabolites and metabolic aberrations.

  2. Searching iron sensors in plants by exploring the link among 2’-OG-dependent dioxygenases, the iron deficiency response and metabolic adjustments occurring under iron deficiency

    Directory of Open Access Journals (Sweden)

    GIANPIERO eVIGANI

    2013-05-01

    Full Text Available Knowledge accumulated on the regulation of iron (Fe homeostasis, its intracellular trafficking and transport across various cellular compartments and organs in plants; storage proteins, transporters and transcription factors involved in Fe metabolism have been analysed in detail in recent years. However, the key sensor(s of cellular plant Fe status triggering the long-distance shoot-root signalling and leading to the root Fe-deficiency responses is (are still unknown. Local Fe sensing is also a major task for roots, for adjusting the internal Fe requirements to external Fe availability: how such sensing is achieved and how it leads to metabolic adjustments in case of nutrient shortage, is mostly unknown. Two proteins belonging to the 2′-OG dependent dioxygenases family accumulate several folds in Fe-deficient Arabidopsis roots. Such proteins require Fe(II as enzymatic cofactor; one of their subgroups, the HIF-P4H (Hypoxia Inducible Factor- Prolyl 4-Hydroxylase, is an effective oxygen sensor in animal cells. We envisage here the possibility that some members of the 2′-OG dioxygenase family may be involved in the Fe-deficiency response and in the metabolic adjustments to Fe deficiency or even in sensing Fe, in plant cells.

  3. Long term alteration of glass/iron systems in anoxic conditions: contribution of archaeological analogues to the study of mechanisms

    International Nuclear Information System (INIS)

    Michelin, A.

    2011-01-01

    The knowledge of glass alteration mechanisms arouses a great interest over the last decades, particularly in the nuclear field, since vitrification is used to stabilize high-level radioactive wastes in many countries. In the French concept, these nuclear glasses would be stored in geological repositories. This multi-barrier system (glass matrix, stainless steel container, low carbon steel over-container, geological barrier) must ensure the durable confinement of radionuclides. But laboratory experiments do not permit to predict directly the behaviour of these materials over typically a million-year timescale and the extrapolation of short-term laboratory data to long time periods remains problematic. Part of the validation of the predictive models relies on natural and archaeological analogues. Here, the analogues considered are vitreous slags produced as wastes by a blast furnace working during the 16. century in the iron making site of Glinet (Normandy, France). The choice of these specific artefacts is due to the presence of particular interface between corrosion products and glass matrix inside the blocks. Thus, they can help us to understand the influence of iron corrosion products from the steel containers on the glass alteration mechanisms and kinetics. A first part of this work concerns the characterization of the archaeological artefacts especially the interfacial area between glass and corrosion products inside cracks using micro and nano-beam techniques (μRaman spectroscopy, FEG-SEM, TEM, STXM...). This study has enabled to suggest an alteration process with different geochemical steps that leads to alteration profile observed. One of these steps is the precipitation of an iron silicate phase. In a second time, leaching experiments were set up on a synthetic glass of similar composition than the archaeological one to understand the first stages of alteration with and without iron. Two phenomena can be observed: silicon sorption and precipitation of iron

  4. Weight loss is associated with plasma free amino acid alterations in subjects with metabolic syndrome

    OpenAIRE

    Tochikubo, O; Nakamura, H; Jinzu, H; Nagao, K; Yoshida, H; Kageyama, N; Miyano, H

    2016-01-01

    Objectives: The prevalence of metabolic syndrome is increasing worldwide, especially in Asian populations. Early detection and effective intervention are vital. Plasma free amino acid profile is a potential biomarker for the early detection for lifestyle-related diseases. However, little is known about whether the altered plasma free amino acid profiles in subjects with metabolic syndrome are related to the effectiveness of dietary and exercise interventions. Methods: Eighty-five Japanese sub...

  5. Difference and alteration in pharmacokinetic and metabolic characteristics of low-solubility natural medicines.

    Science.gov (United States)

    Yan, Shenglei; Liu, Yuying; Feng, Jianfang; Zhao, Hua; Yu, Zhongshu; Zhao, Jing; Li, Yao; Zhang, Jingqing

    2018-02-01

    Drug metabolism plays vital roles in the absorption and pharmacological activity of poorly soluble natural medicines. It is important to choose suitable delivery systems to increase the bioavailability and bioactivity of natural medicines with low solubility by regulating their metabolism and pharmacokinetics. This review investigates recent developments about the metabolic and pharmacokinetic behavior of poorly soluble natural medicines and their delivery systems. Delivery systems, dosage, administration route and drug-drug interactions alter the metabolic pathway, and bioavailability of low-solubility natural medicines to different degrees. Influencing factors such as formulation, dosage, and administration route are discussed. The metabolic reactions, metabolic enzymes, metabolites and pharmacokinetic behaviors of low-solubility natural medicines, and their delivery systems are systematically reviewed. There are various metabolic situations in the case of low-solubility natural medicines. CYP3A4 and CYP2C are the most common metabolic enzymes, and hydroxylation is the most common metabolic reaction of low solubility natural medicines. The stereo isomeric configuration can have a large influence on metabolism. This review will be useful for physicians and pharmacists to guide more accurate treatment with low-solubility natural medicines by increasing drug efficacies and protecting patients from toxic side effects.

  6. Alterations in cancer cell metabolism: the Warburg effect and metabolic adaptation.

    Science.gov (United States)

    Asgari, Yazdan; Zabihinpour, Zahra; Salehzadeh-Yazdi, Ali; Schreiber, Falk; Masoudi-Nejad, Ali

    2015-05-01

    The Warburg effect means higher glucose uptake of cancer cells compared to normal tissues, whereas a smaller fraction of this glucose is employed for oxidative phosphorylation. With the advent of high throughput technologies and computational systems biology, cancer cell metabolism has been reinvestigated over the last decades toward identifying various events underlying "how" and "why" a cancer cell employs aerobic glycolysis. Significant progress has been shaped to revise the Warburg effect. In this study, we have integrated the gene expression of 13 different cancer cells with the genome-scale metabolic network of human (Recon1) based on the E-Flux method, and analyzed them based on constraint-based modeling. Results show that regardless of significant up- and down-regulated metabolic genes, the distribution of metabolic changes is similar in different cancer types. These findings support the theory that the Warburg effect is a consequence of metabolic adaptation in cancer cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Altered Activities of Antioxidant Enzymes in Patients with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Lucie Vávrová

    2013-02-01

    Full Text Available Objective: In the pathogenesis of the metabolic syndrome (MetS, an increase of oxidative stress could play an important role which is closely linked with insulin resistance, endothelial dysfunction, and chronic inflammation. The aim of our study was to assess several parameters of the antioxidant status in MetS. Methods: 40 subjects with MetS and 40 age- and sex-matched volunteers without MetS were examined for activities of superoxide dismutase (CuZnSOD, catalase (CAT, glutathione peroxidase 1 (GPX1, glutathione reductase (GR, paraoxonase1 (PON1, concentrations of reduced glutathione (GSH, and conjugated dienes in low-density lipoprotein (CD-LDL. Results: Subjects with MetS had higher activities of CuZnSOD (p Conclusions: Our results implicated an increased oxidative stress in MetS and a decreased antioxidative defense that correlated with some laboratory (triglycerides, high-density lipoprotein cholesterol (HDL-C and clinical (waist circumference, blood pressure components of MetS.

  8. Altered placental tryptophan metabolic pathway in human fetal growth restriction.

    Science.gov (United States)

    Murthi, Padma; Wallace, Euan M; Walker, David W

    2017-04-01

    Tryptophan is a substrate for kynurenine pathway metabolism in the placenta. We investigated if kynurenine metabolites change over gestation, if they are different between pregnancies with normal and fetal growth restriction (FGR), and if the oxygen environment modulated kynurenine pathway activity in the human placenta. Tryptophan, kynurenine, and downstream kynurenine metabolites were determined in maternal venous blood, umbilical cord blood, and placental samples obtained in 1st and 3rd trimester pregnancies including FGR, and in the media of placental explants incubated with 20% or 5-8% O 2 for 24, 48 or 72 h. All the major kynurenine metabolites were present in cord blood, and in general were higher than in maternal blood. IDO and TDO mRNA and protein expression, responsible for kynurenine production from tryptophan, were significantly lower in placentas from FGR pregnancies compared with control. Explants prepared from 1st and 3rd trimester placentas actively produced all the major kynurenine pathway metabolites which, together with expression of IDO, TDO, KYN-OHase and 3HAO mRNAs, were significantly lower after 24 h exposure to 5-8% O 2 compared to 20% O 2 CONCLUSIONS: Expression and activity of the kynurenine pathway is present in the placenta from early gestation, and is down-regulated by hypoxia and in FGR pregnancies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Hormonal alterations in PCOS and its influence on bone metabolism.

    Science.gov (United States)

    Krishnan, Abhaya; Muthusami, Sridhar

    2017-02-01

    According to the World Health Organization (WHO) polycystic ovary syndrome (PCOS) occurs in 4-8% of women worldwide. The prevalence of PCOS in Indian adolescents is 12.2% according to the Indian Council of Medical Research (ICMR). The National Institute of Health has documented that it affects approximately 5 million women of reproductive age in the United States. Hormonal imbalance is the characteristic of many women with polycystic ovarian syndrome (PCOS). The influence of various endocrine changes in PCOS women and their relevance to bone remains to be documented. Hormones, which include gonadotrophin-releasing hormone (GnRH), insulin, the leutinizing/follicle-stimulating hormone (LH/FSH) ratio, androgens, estrogens, growth hormones (GH), cortisol, parathyroid hormone (PTH) and calcitonin are disturbed in PCOS women. These hormones influence bone metabolism in human subjects directly as well as indirectly. The imbalance in these hormones results in increased prevalence of osteoporosis in PCOS women. Limited evidence suggests that the drugs taken during the treatment of PCOS increase the risk of bone fracture in PCOS patients through endocrine disruption. This review is aimed at the identification of the relationship between bone mineral density and hormonal changes in PCOS subjects and identifies potential areas to study bone-related disorders in PCOS women. © 2017 Society for Endocrinology.

  10. Impaired Iron Metabolism in the Pathogenesis of Critical Conditions (an Experimental Study

    Directory of Open Access Journals (Sweden)

    Yu. P. Orlov

    2011-01-01

    Full Text Available Objective: to study the pathogenetic value of iron metabolic disturbances in microcirculatory disorders and in the development of endotoxemia in the critical conditions caused by abdominal sepsis and bone injury. Material and methods: Abdominal sepsis was simulated in the first series of experiments on 40 male Wistar rats; hip fracture of both hind limbs was done in 40 rats in the second series. In each series of experiments, deferoxamine was injected at a dose of 80 mg/kg in 10 animals for preventive purposes 2 hours before simulating the critical condition. The viscosity of blood and the levels of serum transferrin, ferritin, iron, oligopeptides, and low and medium molecular weight substances (LMMWS were studied. Results. In severe bone injury and abdominal sepsis, there was a reduction in serum transferrin by more than 50%, impaired blood rheology, and increases in LMMWS and oligopeptides. Pre-administration of deferoxamine led to the normalization of transferrin concentrations and blood rheology, which was associated with lower serum Fe2+ concentrations. Conclusion. Thus, pre-administration of deferoxamine reduces impaired blood rheology and the intensity of endotoxemia in different critical conditions. Key words: critical conditions, iron metabolism, transferrin, microcirculatory disorders, endotoxemia, deferoxamine.

  11. Maternal iron deficiency alters circulating thyroid hormone levels in developing neonatal rats

    Science.gov (United States)

    Thyroid hormone insufficiency and iron deficiency (FeD) during fetal and neonatal life are both similarly deleterious to mammalian development suggesting a possible linkage between iron and thyroid hormone insufficiencies. Recent published data from our laboratory demonstrate a r...

  12. Alterations in lipid metabolism and antioxidant status in lichen planus

    Directory of Open Access Journals (Sweden)

    Falguni H Panchal

    2015-01-01

    Full Text Available Background: Lichen planus (LP, a T-cell-mediated inflammatory disorder, wherein inflammation produces lipid metabolism disturbances, is linked to increase in cardiovascular (CV risk with dyslipidemia. Increased reactive oxygen species and lipid peroxides have also been implicated in its pathogenesis. Aim and Objective: The aim of the study was to evaluate the status on lipid disturbances, oxidative stress, and inflammation in LP patients. Materials and Methods: The study was initiated after obtaining Institutional Ethics Committee permission and written informed consent from participants. The study included 125 patients (74 LP patients and 51 age and sex-matched controls visiting the outpatient clinic in the dermatology department of our hospital. Variables analyzed included lipid profile, C-reactive protein (CRP, malondialdehyde (MDA, and catalase (CAT activity. Results: Analysis of lipid parameters revealed significantly higher levels of total cholesterol (TC, triglycerides, and low-density lipoprotein cholesterol (LDL-C along with decreased levels of high-density lipoprotein cholesterol (HDL-C in LP patients as compared to their respective controls. LP patients also presented with a significantly higher atherogenic index that is, (TC/HDL-C and LDL-C/HDL-C ratios than the controls. A significant increase in CRP levels was observed among the LP patients. There was a statistically significant increase in the serum levels of the lipid peroxidation product, MDA and a statistically significant decrease in CAT activity in LP patients as compared to their respective controls. A statistically significant positive correlation (r = 0.96 was observed between serum MDA levels and duration of LP whereas a significantly negative correlation (r = −0.76 was seen between CAT activity and LP duration. Conclusion: Chronic inflammation in patients with LP may explain the association with dyslipidemia and CV risk. Our findings also suggest that an increase in

  13. Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism

    DEFF Research Database (Denmark)

    Jansen, S W; Akintola, A A; Roelfsema, F

    2015-01-01

    of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis...... hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring...... may favour longevity without altering energy metabolism....

  14. Biochemical aspects of overtraining in endurance sports : the metabolism alteration process syndrome.

    Science.gov (United States)

    Petibois, Cyril; Cazorla, Georges; Poortmans, Jacques-Rémi; Déléris, Gérard

    2003-01-01

    Recent studies have shown that endurance overtraining could result from successive and cumulative alterations in metabolism, which become chronic during training. The onset of this process is a biochemical alteration in carbohydrate (saccharide) metabolism. During endurance exercises, the amount of saccharide chains from two blood glycoproteins (alpha(2)-macroglobulin and alpha(1)-acid glycoprotein) was found to have decreased, i.e. concentrations of these proteins remained unchanged but their quality changed. These saccharide chains were probably used for burning liver glycogen stores during exercise. This step was followed by alterations in lipid metabolism. The most relevant aspect of this step was that the mean chain length of blood fatty acids decreased, i.e. the same amount of fatty acids were found within the blood, but overtrained individuals presented shorter fatty acids than well-trained individuals. This suggests that alterations appeared in the liver synthesis of long-chain fatty acids or that higher peroxidation of blood lipoparticles occurred. For the final step of this overtraining process, it was found that these dysfunctions in carbohydrate/lipid metabolism led to the higher use of amino acids, which probably resulted from protein catabolism. The evolution of three protein concentrations (alpha(1)-acid glycoprotein, alpha(2)-macroglobulin and IgG(3)) correlated with this amino acid concentration increase, suggesting a specific catabolism of these proteins. At this time only, overtraining was clinically diagnosed through conventional symptoms. Therefore, this process described successive alterations in exercise metabolism that shifted from the main energetic stores of exercise (carbohydrates and lipids) towards molecular pools (proteins) normally not substantially used for the energetic supply of skeletal muscles. Now, a general biochemical model of the overtraining process may be proposed which includes most of the previously identified metabolic

  15. Saharan dust inputs and high UVR levels jointly alter the metabolic balance of marine oligotrophic ecosystems

    Science.gov (United States)

    Cabrerizo, Marco J.; Medina-Sánchez, Juan Manuel; González-Olalla, Juan Manuel; Villar-Argaiz, Manuel; Carrillo, Presentación

    2016-10-01

    The metabolic balance of the most extensive bioma on the Earth is a controversial topic of the global-change research. High ultraviolet radiation (UVR) levels by the shoaling of upper mixed layers and increasing atmospheric dust deposition from arid regions may unpredictably alter the metabolic state of marine oligotrophic ecosystems. We performed an observational study across the south-western (SW) Mediterranean Sea to assess the planktonic metabolic balance and a microcosm experiment in two contrasting areas, heterotrophic nearshore and autotrophic open sea, to test whether a combined UVR × dust impact could alter their metabolic balance at mid-term scales. We show that the metabolic state of oligotrophic areas geographically varies and that the joint impact of UVR and dust inputs prompted a strong change towards autotrophic metabolism. We propose that this metabolic response could be accentuated with the global change as remote-sensing evidence shows increasing intensities, frequencies and number of dust events together with variations in the surface UVR fluxes on SW Mediterranean Sea. Overall, these findings suggest that the enhancement of the net carbon budget under a combined UVR and dust inputs impact could contribute to boost the biological pump, reinforcing the role of the oligotrophic marine ecosystems as CO2 sinks.

  16. Metabolic Alterations in Cancer Cells and the Emerging Role of Oncometabolites as Drivers of Neoplastic Change

    Directory of Open Access Journals (Sweden)

    Zhengqiu Zhou

    2018-01-01

    Full Text Available The mitochondrion is an important organelle and provides energy for a plethora of intracellular reactions. Metabolic dysregulation has dire consequences for the cell, and alteration in metabolism has been identified in multiple disease states—cancer being one. Otto Warburg demonstrated that cancer cells, in the presence of oxygen, undergo glycolysis by reprogramming their metabolism—termed “aerobic glycolysis”. Alterations in metabolism enable cancer cells to gain a growth advantage by obtaining precursors for macromolecule biosynthesis, such as nucleic acids and lipids. To date, several molecules, termed “oncometabolites”, have been identified to be elevated in cancer cells and arise from mutations in nuclear encoded mitochondrial enzymes. Furthermore, there is evidence that oncometabolites can affect mitochondrial dynamics. It is believed that oncometabolites can assist in reprogramming enzymatic pathways and providing cancer cells with selective advantages. In this review, we will touch upon the effects of normal and aberrant mitochondrial metabolism in normal and cancer cells, the advantages of metabolic reprogramming, effects of oncometabolites on metabolism and mitochondrial dynamics and therapies aimed at targeting oncometabolites and metabolic aberrations.

  17. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

    International Nuclear Information System (INIS)

    Luo, Hanwen; Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng; Ping, Jie; Xu, Dan; Ma, Lu; Chen, Liaobin; Wang, Hui

    2014-01-01

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

  18. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, Jie; Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology and Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2014-02-01

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

  19. Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice.

    Directory of Open Access Journals (Sweden)

    Monika Burns

    Full Text Available Iron deficiency anemia (IDA affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world's population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group were dosed with H. pylori (Hp strain SS1 or sham dosed at 6-9 weeks of age, and were necropsied at 27-29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p < 0.0001. Infected mice had a lower red blood cell count (p<0.0001, hematocrit (p < 0.001, and hemoglobin concentration (p <0.0001 than uninfected mice. Relative expression of gastric hepcidin antimicrobial peptide (Hamp was downregulated in mice infected with Hp SS1 compared to sham-dosed controls (p<0.001. Expression of bone morphogenic protein 4 (Bmp4, a growth factor upstream of hepcidin, was downregulated in gastric tissue of Hp SS1-infected mice (p<0.001. Hp SS1-infected mice had downregulated brain expression of tyrosine hydroxylase (Th (p = 0.02. Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp and proteolipid protein 2 (Plp2 was downregulated in infected mice (p = 0.001 and p = 0.02. Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3, Psd95 (a membrane associated guanylate kinase, and insulin-like growth factor 1 (Igf1 was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively. Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use of Hp SS

  20. Dietary patterns in men and women are simultaneously determinants of altered glucose metabolism and bone metabolism.

    Science.gov (United States)

    Langsetmo, Lisa; Barr, Susan I; Dasgupta, Kaberi; Berger, Claudie; Kovacs, Christopher S; Josse, Robert G; Adachi, Jonathan D; Hanley, David A; Prior, Jerilynn C; Brown, Jacques P; Morin, Suzanne N; Davison, Kenneth S; Goltzman, David; Kreiger, Nancy

    2016-04-01

    We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone-specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Improved metabolic health alters host metabolism in parallel with changes in systemic xeno-metabolites of gut origin.

    Directory of Open Access Journals (Sweden)

    Caitlin Campbell

    Full Text Available Novel plasma metabolite patterns reflective of improved metabolic health (insulin sensitivity, fitness, reduced body weight were identified before and after a 14-17 wk weight loss and exercise intervention in sedentary, obese insulin-resistant women. To control for potential confounding effects of diet- or microbiome-derived molecules on the systemic metabolome, sampling was during a tightly-controlled feeding test week paradigm. Pairwise and multivariate analysis revealed intervention- and insulin-sensitivity associated: (1 Changes in plasma xeno-metabolites ("non-self" metabolites of dietary or gut microbial origin following an oral glucose tolerance test (e.g. higher post-OGTT propane-1,2,3-tricarboxylate [tricarballylic acid] or in the overnight-fasted state (e.g., lower γ-tocopherol; (2 Increased indices of saturated very long chain fatty acid elongation capacity; (3 Increased post-OGTT α-ketoglutaric acid (α-KG, fasting α-KG inversely correlated with Matsuda index, and altered patterns of malate, pyruvate and glutamine hypothesized to stem from improved mitochondrial efficiency and more robust oxidation of glucose. The results support a working model in which improved metabolic health modifies host metabolism in parallel with altering systemic exposure to xeno-metabolites. This highlights that interpretations regarding the origins of peripheral blood or urinary "signatures" of insulin resistance and metabolic health must consider the potentially important contribution of gut-derived metabolites toward the host's metabolome.

  2. Progressive alterations in lipid and glucose metabolism during short-term fasting in young adult men

    NARCIS (Netherlands)

    Klein, S.; Sakurai, Y.; Romijn, J. A.; Carroll, R. M.

    1993-01-01

    Stable isotope tracers and indirect calorimetry were used to evaluate the progressive alterations in lipid and glucose metabolism after 12, 18, 24, 30, 42, 54, and 72 h of fasting in six healthy male volunteers. The rates of appearance (Ra) of glycerol and palmitic acid in plasma doubled from 2.08

  3. Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals.

    Science.gov (United States)

    Vázquez-Castellanos, J F; Serrano-Villar, S; Latorre, A; Artacho, A; Ferrús, M L; Madrid, N; Vallejo, A; Sainz, T; Martínez-Botas, J; Ferrando-Martínez, S; Vera, M; Dronda, F; Leal, M; Del Romero, J; Moreno, S; Estrada, V; Gosalbes, M J; Moya, A

    2015-07-01

    Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+ individuals, the metagenome gene pool associated with HIV infection remains unknown. The aim of this study is to characterize the functional gene content of gut microbiota in HIV+ patients and to define the metabolic pathways of this bacterial community, which is potentially associated with immune dysfunction. We determined systemic markers of innate and adaptive immunity in a cohort of HIV-infected individuals on successful antiretroviral therapy without comorbidities and in healthy non-HIV-infected subjects. Metagenome sequencing revealed an altered functional profile, with enrichment of the genes involved in various pathogenic processes, lipopolysaccharide biosynthesis, bacterial translocation, and other inflammatory pathways. In contrast, we observed depletion of genes involved in amino acid metabolism and energy processes. Bayesian networks showed significant interactions between the bacterial community, their altered metabolic pathways, and systemic markers of immune dysfunction. This study reveals altered metabolic activity of microbiota and provides novel insight into the potential host-microbiota interactions driving the sustained inflammatory state in successfully treated HIV-infected patients.

  4. Maternal nutrition during the first 50 days of gestation alters bovine fetal hepatic metabolic transcriptome

    Science.gov (United States)

    We hypothesized that maternal nutrition during the first 50 d of gestation would alter the metabolic transcriptome of the bovine fetal liver. Fourteen beef heifers were estrus synchronized and assigned to 2 treatments at breeding (CON, 100% of requirements to gain 0.45kg/d; RES, 60% of CON). Heifers...

  5. Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

    Science.gov (United States)

    Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

  6. Chromium supplementation alters both glucose and lipid metabolism in feedlot cattle during the receiving period

    Science.gov (United States)

    Crossbred steers (n = 20; 235 +/- 4 kg) were fed 53 days during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brandChromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0...

  7. Chromium supplementation alters the glucose and lipid metabolism of feedlot cattle during the receiving period

    Science.gov (United States)

    Crossbreed steers (n = 20; 235 ± 4 kg) were fed 53 d during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brand Chromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0 (C...

  8. Metabolic alterations derived from absence of Two-Pore Channel 1 ...

    Indian Academy of Sciences (India)

    2016-11-23

    Nov 23, 2016 ... To explore the cardiac function of TPCN1, we developed proteomic approaches as 2-DE-MALDI-MS and LC-MALDI-MS in the cardiac left ventricle of TPCN1 KO and WT mice, and found alterations in several proteins implicated in glucose and fatty acid metabolism in TPCN1 KO vs. WT mice. The results.

  9. Iron in Child Obesity. Relationships with Inflammation and Metabolic Risk Factors

    Directory of Open Access Journals (Sweden)

    Dominique Bouglé

    2013-06-01

    Full Text Available Iron (Fe sequestration is described in overweight and in its associated metabolic complications, i.e., metabolic syndrome (MetS and non-alcoholic liver fatty disease (NAFLD; however, the interactions between Fe, obesity and inflammation make it difficult to recognize the specific role of each of them in the risk of obesity-induced metabolic diseases. Even the usual surrogate marker of Fe stores, ferritin, is influenced by inflammation; therefore, in obese subjects inflammation parameters must be measured together with those of Fe metabolism. This cross-sectional study in obese youth (502 patients; 57% girls: 11.4 ± 3.0 years old (x ± SD; BMI z score 5.5 ± 2.3, multivariate regression analysis showed associations between Fe storage assessed by serum ferritin with risk factors for MetS and NAFLD, assessed by transaminase levels, which were independent of overweight and the acute phase protein fibrinogen. Further studies incorporating the measurement of complementary parameters of Fe metabolism could improve the comprehension of mechanisms involved.

  10. Metabolic alterations and neurodevelopmental outcome of infants with transposition of the great arteries.

    Science.gov (United States)

    Park, I Sook; Yoon, S Young; Min, J Yeon; Kim, Y Hwue; Ko, J Kok; Kim, K Soo; Seo, D Man; Lee, J Hee

    2006-01-01

    Abnormal neurodevelopment has been reported for infants who were born with transposition of the great arteries (TGA) and underwent arterial switch operation (ASO). This study evaluates the cerebral metabolism of TGA infants at birth and before ASO and neurodevelopment 1 year after ASO. Proton magnetic resonance spectroscopy (1H-MRS) was performed on 16 full-term TGA brains before ASO within 3-6 days after birth. The brain metabolite ratios of [NAA/Cr], [Cho/Cr], and [mI/Cr] evaluated measured. Ten infants were evaluated at 1 year using the Bayley Scales of Infants Development II (BSED II). Cerebral metabolism of infants with TGA was altered in parietal white matter (PWM) and occipital gray matter (OGM) at birth before ASO. One year after ASO, [Cho/Cr] in PWM remained altered, but all metabolic ratios in OGM were normal. The results of BSID II at 1 year showed delayed mental and psychomotor development. This delayed neurodevelopmental outcome may reflect consequences of the altered cerebral metabolism in PWM measured by 1H-MRS. It is speculated that the abnormal hemodynamics due to TGA in utero may be responsible for the impaired cerebral metabolism and the subsequent neurodevelopmental deficit.

  11. Does measurement site for visceral and abdominal subcutaneous adipose tissue alter associations with the metabolic syndrome?

    Science.gov (United States)

    Kuk, Jennifer L; Church, Timothy S; Blair, Steven N; Ross, Robert

    2006-03-01

    To determine whether the associations between visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), and the metabolic syndrome are altered depending on measurement site for VAT and ASAT and the definition used to identify the metabolic syndrome. Total VAT and ASAT volume was derived using approximately 37 contiguous computed tomography (CT) images from T10-T11 to L5-S1 in 85 men. CT images obtained at eight intervertebral locations (e.g., L4-L5, L3-L4, etc.) were used to determine the associations between partial volumes (single images) and metabolic syndrome. Metabolic syndrome was defined using the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. Logistic regression was used to calculate the odds ratio (OR) per SD increase in adipose tissue. For total and all partial volumes, VAT was more strongly associated with metabolic syndrome than ASAT independent of metabolic syndrome criteria. The OR (per SD) for NCEP metabolic syndrome was higher for total VAT volume (OR = 7.26) and for the partial volumes at T12-L1 (7.46) and L1-L2 (8.77) than those at the L4-L5 level (3.94). The OR for metabolic syndrome ( approximately 2.6) was not substantially different among the ASAT measures. A similar pattern of association was observed using the IDF metabolic syndrome criteria. The measurement site for VAT, but not for ASAT, has a substantial influence on the magnitude of the association with both metabolic syndrome definitions. However, because VAT remained significantly associated with metabolic syndrome regardless of measurement site, the clinical interpretation was unaltered by measurement protocol or metabolic syndrome definition.

  12. Helicobacter pylori infection and low dietary iron alter behavior, induce iron deficiency anemia, and modulate hippocampal gene expression in female C57BL/6 mice.

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    Monika Burns

    Full Text Available Helicobacter pylori (H.pylori, a bacterial pathogen, is a causative agent of gastritis and peptic ulcer disease and is a strong risk factor for development of gastric cancer. Environmental conditions, such as poor dietary iron resulting in iron deficiency anemia (IDA, enhance H.pylori virulence and increases risk for gastric cancer. IDA affects billions of people worldwide, and there is considerable overlap between regions of high IDA and high H.pylori prevalence. The primary aims of our study were to evaluate the effect of H.pylori infection on behavior, iron metabolism, red blood cell indices, and behavioral outcomes following comorbid H. pylori infection and dietary iron deficiency in a mouse model. C57BL/6 female mice (n = 40 were used; half were placed on a moderately iron deficient (ID diet immediately post-weaning, and the other half were maintained on an iron replete (IR diet. Half were dosed with H.pylori SS1 at 5 weeks of age, and the remaining mice were sham-dosed. There were 4 study groups: a control group (-Hp, IR diet as well as 3 experimental groups (-Hp, ID diet; +Hp, IR diet; +Hp,ID diet. All mice were tested in an open field apparatus at 8 weeks postinfection. Independent of dietary iron status, H.pylori -infected mice performed fewer exploratory behaviors in the open field chamber than uninfected mice (p<0.001. Hippocampal gene expression of myelination markers and dopamine receptor 1 was significantly downregulated in mice on an ID diet (both p<0.05, independent of infection status. At 12 months postinfection, hematocrit (Hct and hemoglobin (Hgb concentration were significantly lower in +Hp, ID diet mice compared to all other study groups. H.pylori infection caused IDA in mice maintained on a marginal iron diet. The mouse model developed in this study is a useful model to study the neurologic, behavioral, and hematologic impact of the common human co-morbidity of H. pylori infection and IDA.

  13. Western diet-induced anxiolytic effects in mice are associated with alterations in tryptophan metabolism.

    Science.gov (United States)

    Ohland, Christina L; Pankiv, Evelina; Baker, Glen; Madsen, Karen L

    2016-10-01

    Western-style diets high in saturated fat and refined carbohydrate have been shown to alter gut microbiota as well as being associated with altered behaviour and learning ability. The objective of this study was to determine the effects of short-term intake of a Western-style diet on intestinal cytokine expression, tryptophan metabolism, and levels of neurotransmitters in the brain. At 7 weeks of age, 129S1/SvImJ mice were placed on a standard chow or Western-style diet (fat 33%, refined carbohydrates 49%) for 3 weeks. Anxiety-like behaviour was assessed by the latency to step-down test and exploration assessed in a Barnes maze. Neurotransmitter levels in forebrains were analysed by high-pressure liquid chromatography. Liver metabolism was examined by 1 H nuclear magnetic resonance (NMR). Cytokine expression in the intestine was measured using MesoScale discovery platform. mRNA levels of tryptophan hydroxylase (Tph) and indoleamine 2,3-dioxygenase (IDO) in the brain and intestine were measured using qPCR. Results showed that mice fed the Western diet displayed reduced exploratory and anxiety-like behaviour. Anxiolytic effects correlated with increased hippocampal brain-derived neurotrophic factor (BDNF) and tryptophan levels. Brain serotonin was not altered. These changes were associated with reduced expression of small intestinal indoleamine 2,3-dioxygenase, a tryptophan-processing enzyme. Western diet-fed mice exhibited low-grade systemic and intestinal inflammation along with altered liver metabolic profiles. In conclusion, diets high in fat and refined sugar are associated with increased levels of brain BDNF and tryptophan and decreased exploratory and anxiety-like behaviour. These behavioural changes correlated with altered intestinal tryptophan metabolism and liver metabolic profiles.

  14. Iron metabolism in BeWo chorion carcinoma cells. Transferrin-mediated uptake and release of iron

    NARCIS (Netherlands)

    van der Ende, A.; du Maine, A.; Simmons, C. F.; Schwartz, A. L.; Strous, G. J.

    1987-01-01

    Growing human choriocarcinoma BeWo b24 cells contain 1.5 X 10(6) functional cell surface transferrin binding sites and 2.0 X 10(6) intracellular binding sites. These cells rapidly accumulate iron at a rate of 360,000 iron atoms/min/cell. During iron uptake the transferrin and its receptor recycle at

  15. Diurnal variations in iron concentrations and expression of genes involved in iron absorption and metabolism in pigs.

    Science.gov (United States)

    Zhang, Yiming; Wan, Dan; Zhou, Xihong; Long, Ciming; Wu, Xin; Li, Lan; He, Liuqin; Huang, Pan; Chen, Shuai; Tan, Bie; Yin, Yulong

    2017-09-02

    Diurnal variations in serum iron levels have been well documented in clinical studies, and serum iron is an important diagnostic index for iron-deficiency anemia. However, the underlying mechanism of dynamic iron regulation in response to the circadian rhythm is still unclear. In this study, we investigated daily variations in iron status in the plasma and liver of pigs. The transcripts encoding key factors involved in iron uptake and homeostasis were evaluated. The results showed that iron levels in the plasma and liver exhibited diurnal rhythms. Diurnal variations were also observed in transcript levels of divalent metal transporter 1 (DMT1), membrane-associated ferric reductase 1 (DCYTB), and transferrin receptor (TfR) in the duodenum and jejunum, as well as hepcidin (HAMP) and TfR in the liver. Moreover, the results showed a network in which diurnal variations in systemic iron levels were tightly regulated by hepcidin and Tf/TfR via DCYTB and DMT1. These findings provide new insights into circadian iron homeostasis regulation. The diurnal variations in serum iron levels may also have pathophysiological implications for clinical diagnostics related to iron deficiency anemia in pigs. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Metabolic syndrome in HD patients: association with body composition, nutritional status, inflammation and serum iron.

    Science.gov (United States)

    Rasic-Milutinovic, Zorica; Perunicic, Gordana; Pljesa, Steva; Gluvic, Zoran; Ilic, Mirka; Stokić, Edith

    2007-01-01

    Insulin resistance and metabolic syndrome (MeS) are common in end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD). Such metabolic and clinical abnormalities may lead to an increased risk for cardiovascular disease. The study group included 22 well-nourished and 20 middle- to moderate-malnourished, stable ESRD patients, with median dialysis duration of 48 months (IQR 24.5-82.0). To determine nutritional status, body composition, inflammatory biomarkers and the presence of MeS subjective global assessment (SGA), anthropometrical measurements (BMI and waist circumference), bioelectrical impedance analysis (BIA), and biochemical parameters [the levels of serum albumin, cholesterol, HDL-cholesterol, triglyceride, hematocrit, hemoglobin, iron, TIBC, transferrin saturation (TSAT), ferritin, calcium, phosphorus, intact parathormone (i-PTH), TNF-alpha, IL-6 and high sensitivity C-reactive protein (hs-CRP)] were used. All parameters were evaluated by comparisons between two groups, with MeS (Group 2) and without it (Group 1). Logistical regression analysis was used to evaluate the correlation between measured variables and the presence of MeS in HD patients. Independent variables for MeS were identified by backward multivariate regression analysis. To identify the independent predictors for insulin resistance index (HOMA-IR) multivariate regression analysis was conducted, after linear regression analysis. After adjustment for confounding variables, a model consisting of serum levels of iron, transferrin saturation (TSAT), and BMI which accounted for 62% of the variance in MeS, determined only BMI as an independent marker (according to ATP-III criteria). But, serum glucose level, iron, waist and total fat mass accounted for 68% of the variance in MeS, according to IDF criteria. Glucose level was an independent predictor. BMI and iron, as independent variables, contributed to 29% of the variance in IR HOMA, the sensitive marker of MeS. The present study

  17. Exercise training dose differentially alters muscle and heart capillary density and metabolic functions in an obese rat with metabolic syndrome.

    Science.gov (United States)

    Machado, Marcus Vinicius; Vieira, Aline Bomfim; da Conceição, Fabiana Gomes; Nascimento, Alessandro Rodrigues; da Nóbrega, Antonio Claudio Lucas; Tibirica, Eduardo

    2017-12-01

    What is the central question of this study? Regular exercise is recommended as a non-pharmacological approach for the prevention and treatment of metabolic syndrome. However, the impact of different combinations of intensity, duration and frequency of exercise on metabolic syndrome and microvascular density has not been reported. What is the main finding and its importance? We provide evidence on the impact of aerobic exercise dose on metabolic and microvascular alterations in an experimental model of metabolic syndrome induced by high-fat diet. We found that the exercise frequency and duration were the main factors affecting anthropometric and metabolic parameters and microvascular density in the skeletal muscle. Exercise intensity was related only to microvascular density in the heart. We evaluated the effect of the frequency, duration and intensity of exercise training on metabolic parameters and structural capillary density in obese rats with metabolic syndrome. Wistar-Kyoto rats were fed either a standard commercial diet (CON) or a high-fat diet (HFD). Animals that received the HFD were randomly separated into either a sedentary (SED) group or eight different exercise groups that varied according to the frequency, duration and intensity of training. After 12 weeks of aerobic exercise training, the body composition, aerobic capacity, haemodynamic variables, metabolic parameters and capillary density in the heart and skeletal muscle were evaluated. All the exercise training groups showed reduced resting systolic blood pressure and heart rate and normalized fasting glucose. The minimal amount of exercise (90 min per week) produced little effect on metabolic syndrome parameters. A moderate amount of exercise (150 min per week) was required to reduce body weight and improve capillary density. However, only the high amount of exercise (300 min per week) significantly reduced the amount of body fat depots. The three-way ANOVA showed a main effect of exercise

  18. Bypasses in intracellular glucose metabolism in iron-limited Pseudomonas putida.

    Science.gov (United States)

    Sasnow, Samantha S; Wei, Hua; Aristilde, Ludmilla

    2016-02-01

    Decreased biomass growth in iron (Fe)-limited Pseudomonas is generally attributed to downregulated expression of Fe-requiring proteins accompanied by an increase in siderophore biosynthesis. Here, we applied a stable isotope-assisted metabolomics approach to explore the underlying carbon metabolism in glucose-grown Pseudomonas putida KT2440. Compared to Fe-replete cells, Fe-limited cells exhibited a sixfold reduction in growth rate but the glucose uptake rate was only halved, implying an imbalance between glucose uptake and biomass growth. This imbalance could not be explained by carbon loss via siderophore production, which accounted for only 10% of the carbon-equivalent glucose uptake. In lieu of the classic glycolytic pathway, the Entner-Doudoroff (ED) pathway in Pseudomonas is the principal route for glucose catabolism following glucose oxidation to gluconate. Remarkably, gluconate secretion represented 44% of the glucose uptake in Fe-limited cells but only 2% in Fe-replete cells. Metabolic (13) C flux analysis and intracellular metabolite levels under Fe limitation indicated a decrease in carbon fluxes through the ED pathway and through Fe-containing metabolic enzymes. The secreted siderophore was found to promote dissolution of Fe-bearing minerals to a greater extent than the high extracellular gluconate. In sum, bypasses in the Fe-limited glucose metabolism were achieved to promote Fe availability via siderophore secretion and to reroute excess carbon influx via enhanced gluconate secretion. © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  19. Zebrafish in the Sea of Mineral (Iron, Zinc and Copper Metabolism

    Directory of Open Access Journals (Sweden)

    Lu eZhao

    2014-03-01

    Full Text Available Iron, copper, zinc and eight other minerals are classified as essential trace elements because they present in minute in vivo quantities and are essential for life. Because either excess or insufficient levels of trace elements can be detrimental to life (causing human diseases such as iron-deficiency anemia, hemochromatosis, Menkes syndrome and Wilson’s disease, the endogenous levels of trace minerals must be tightly regulated. Many studies have demonstrated the existence of systems that maintain trace element homeostasis, and these systems are highly conserved in multiple species ranging from yeast to mice. As a model for studying trace mineral metabolism, the zebrafish is indispensable to researchers. Several large-scale mutagenesis screens have been performed in zebrafish, and these screens led to the identification of a series of metal transporters and the generation of several mutagenesis lines, providing an in-depth functional analysis at the system level. Moreover, because of their developmental advantages, zebrafish have also been used in mineral metabolism‒related chemical screens and toxicology studies. Here, we systematically review the major findings of trace element homeostasis studies using the zebrafish model. We also provide a homology analysis of trace mineral transporters in fish, mice and humans. Finally, we discuss the evidence that zebrafish are an ideal experimental tool for uncovering novel mechanisms of trace mineral metabolism and for improving approaches to treat mineral imbalance‒related diseases.

  20. Iron effect on the fermentative metabolism of Clostridium acetobutylicum ATCC 824 using cheese whey as substrate

    Directory of Open Access Journals (Sweden)

    Victoria Rosalía Durán-Padilla

    2014-12-01

    Full Text Available Butanol is considered a superior liquid fuel that can replace gasoline in internal combustion engines. It is produced by acetone-butanol-ethanol (ABE fermentation using various species of solventogenic clostridia. Performance of ABE fermentation process is severely limited mostly by high cost of substrate, substrate inhibition and low solvent tolerance; leading to low product concentrations, low productivity, low yield, and difficulty in controlling culture metabolism. In order to decrease the cost per substrate and exploit a waste generated by dairy industry, this study proposes using cheese whey as substrate for ABE fermentation. It was observed that the addition of an iron source was strictly necessary for the cheese whey to be a viable substrate because this metal is needed to produce ferredoxin, a key protein in the fermentative metabolism of Clostridium acetobutylicum serving as a temporary electron acceptor. Lack of iron in the cheese whey impedes ferredoxin synthesis and therefore, restricts pyruvate-ferredoxin oxidoreductase activity leading to the production of lactic acid instead of acetone, butanol and ethanol. Moreover, the addition of FeSO4 notably improved ABE production performance by increasing butanol content (7.13 ± 1.53 g/L by 65% compared to that of FeCl3 (4.32 ± 0.94 g/L under the same fermentation conditions.

  1. Combined metabolomic and correlation networks analyses reveal fumarase insufficiency altered amino acid metabolism.

    Science.gov (United States)

    Hou, Entai; Li, Xian; Liu, Zerong; Zhang, Fuchang; Tian, Zhongmin

    2018-04-01

    Fumarase catalyzes the interconversion of fumarate and l-malate in the tricarboxylic acid cycle. Fumarase insufficiencies were associated with increased levels of fumarate, decreased levels of malate and exacerbated salt-induced hypertension. To gain insights into the metabolism profiles induced by fumarase insufficiency and identify key regulatory metabolites, we applied a GC-MS based metabolomics platform coupled with a network approach to analyze fumarase insufficient human umbilical vein endothelial cells (HUVEC) and negative controls. A total of 24 altered metabolites involved in seven metabolic pathways were identified as significantly altered, and enriched for the biological module of amino acids metabolism. In addition, Pearson correlation network analysis revealed that fumaric acid, l-malic acid, l-aspartic acid, glycine and l-glutamic acid were hub metabolites according to Pagerank based on their three centrality indices. Alanine aminotransferase and glutamate dehydrogenase activities increased significantly in fumarase deficiency HUVEC. These results confirmed that fumarase insufficiency altered amino acid metabolism. The combination of metabolomics and network methods would provide another perspective on expounding the molecular mechanism at metabolomics level. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Effect of Nordic Walking training on iron metabolism in elderly women

    Directory of Open Access Journals (Sweden)

    Kortas J

    2015-11-01

    Full Text Available Jakub Kortas,1 Katarzyna Prusik,2 Damian Flis,3 Krzysztof Prusik,1 Ewa Ziemann,4 Neil Leaver,5 Jedrzej Antosiewicz6 1Department of Recreation and Tourism, Gdansk University of Physical Education and Sport, Gdansk, Poland; 2Department of Biomedical Basis of Health, Gdansk University of Physical Education and Sport, Gdansk, Poland; 3Department of Bioenergetics and Physiology of Exercise, Medical University of Gdansk, Gdansk, Poland; 4Department of Physiology and Pharmacology, Gdansk University of Physical Education and Sport, Gdansk, Poland; 5The Immunosuppression monitoring service (IMS Laboratory, Royal Brompton & Harefield NHS Foundation Trust, Heart Science Centre, Harefield Hospital, Harefield, UK; 6Department of Biochemistry, Gdansk University of Physical Education and Sport, Gdansk, Poland Background: Despite several, well-documented pro-healthy effects of regular physical training, its influence on body iron stores in elderly people remains unknown. At the same time, body iron accumulation is associated with high risk of different morbidities.Purpose: We hypothesized that Nordic Walking training would result in pro-healthy changes in an elderly group of subjects by reducing body iron stores via shifts in iron metabolism-regulating proteins.Methods: Thirty-seven women aged 67.7±5.3 years participated in this study. They underwent 32 weeks of training, 1-hour sessions three times a week, between October 2012 and May 2013. Fitness level, blood morphology, CRP, vitamin D, ferritin, hepcidin, and soluble Hjv were assessed before and after the training.Results: The training program caused a significant decrease in ferritin, which serves as a good marker of body iron stores. Simultaneously, the physical cardiorespiratory fitness had improved. Furthermore, blood hepcidin was positively correlated with the ferritin concentration after the training. The concentration of blood CRP dropped, but the change was nonsignificant. The applied training

  3. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

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    Zhu Zhu

    2016-01-01

    Full Text Available Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice by altering exposure to light. C57 BL/6J mice (C57 mice and ApoE-KO mice (ApoE-KO mice exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1 levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

  4. Abnormal iron metabolism and oxidative stress in mice expressing a mutant form of the ferritin light polypeptide gene

    Science.gov (United States)

    Barbeito, Ana G.; Garringer, Holly J.; Baraibar, Martin A.; Gao, Xiaoying; Arredondo, Miguel; Núñez, Marco T.; Smith, Mark A.; Ghetti, Bernardino; Vidal, Ruben

    2009-01-01

    Insertional mutations in exon 4 of the ferritin light chain (FTL) gene are associated with hereditary ferritinopathy (HF) or neuroferritinopathy, an autosomal dominant neurodegenerative disease characterized by progressive impairment of motor and cognitive functions. To determine the pathogenic mechanisms by which mutations in FTL lead to neurodegeneration, we investigated iron metabolism and markers of oxidative stress in the brain of transgenic (Tg) mice that express the mutant human FTL498-499InsTC cDNA. Compared with wild-type mice, brain extracts from Tg (FTL-Tg) mice showed an increase in the cytoplasmic levels of both FTL and ferritin heavy chain polypeptides, a decrease in the protein and mRNA levels of transferrin receptor-1, and a significant increase in iron levels. Transgenic mice also showed the presence of markers for lipid peroxidation, protein carbonyls, and nitrone–protein adducts in the brain. However, gene expression analysis of iron management proteins in the liver of Tg mice indicates that the FTL-Tg mouse liver is iron deficient. Our data suggest that disruption of iron metabolism in the brain has a primary role in the process of neurodegeneration in HF and that the pathogenesis of HF is likely to result from a combination of reduction in iron storage function and enhanced toxicity associated with iron-induced ferritin aggregates in the brain. PMID:19519778

  5. Iron

    Science.gov (United States)

    ... Share: Search the ODS website Submit Search NIH Office of Dietary Supplements Consumer Datos en español Health ... eating a variety of foods, including the following: Lean meat, seafood, and poultry. Iron-fortified breakfast cereals ...

  6. Metabolic alterations in broiler chickens experimentally infected with sporulated oocysts of Eimeria maxima

    OpenAIRE

    Freitas,Fagner Luiz da Costa

    2014-01-01

    Metabolic and morphometric alterations of the duodenal villi caused by parasitism of chickens by Eimeria maxima were evaluated, using 100 male Cobb birds, randomly distributed into two groups (control and infected). The infected group was inoculated with 0.5 ml of a solution containing 5×103 sporulated oocysts of Eimeria maxima. Ten birds per sample were sacrificed on the 6th, 11th, 22nd and 41st days post-infection (dpi). In order to evaluate the alterations, samples of duodenum, jejunum and...

  7. Rethinking Iron Regulation and Assessment in Iron Deficiency, Anemia of Chronic Disease, and Obesity: Introducing Hepcidin

    Science.gov (United States)

    Tussing-Humphreys, Lisa; Pustacioglu, Cenk; Nemeth, Elizabeta; Braunschweig, Carol

    2012-01-01

    Adequate iron availability is essential to human development and overall health. Iron is a key component of oxygen-carrying proteins, has a pivotal role in cellular metabolism, and is essential to cell growth and differentiation. Inadequate dietary iron intake, chronic and acute inflammatory conditions, and obesity are each associated with alterations in iron homeostasis. Tight regulation of iron is necessary because iron is highly toxic and human beings can only excrete small amounts through sweat, skin and enterocyte sloughing, and fecal and menstrual blood loss. Hepcidin, a small peptide hormone produced mainly by the liver, acts as the key regulator of systemic iron homeostasis. Hepcidin controls movement of iron into plasma by regulating the activity of the sole known iron exporter ferroportin-1. Downregulation of the ferroportin-1 exporter results in sequestration of iron within intestinal enterocytes, hepatocytes, and iron-storing macrophages reducing iron bioavailability. Hepcidin expression is increased by higher body iron levels and inflammation and decreased by anemia and hypoxia. Importantly, existing data illustrate that hepcidin may play a significant role in the development of several iron-related disorders, including the anemia of chronic disease and the iron dysregulation observed in obesity. Therefore, the purpose of this article is to discuss iron regulation, with specific emphasis on systemic regulation by hepcidin, and examine the role of hepcidin within several disease states, including iron deficiency, anemia of chronic disease, and obesity. The relationship between obesity and iron depletion and the clinical assessment of iron status will also be reviewed. PMID:22717199

  8. Membrane lipid alterations in the metabolic syndrome and the role of dietary oils.

    Science.gov (United States)

    Perona, Javier S

    2017-09-01

    The metabolic syndrome is a cluster of pathological conditions, including hypertension, hyperglycemia, hypertriglyceridemia, obesity and low HDL levels that is of great concern worldwide, as individuals with metabolic syndrome have an increased risk of type-2 diabetes and cardiovascular disease. Insulin resistance, the key feature of the metabolic syndrome, might be at the same time cause and consequence of impaired lipid composition in plasma membranes of insulin-sensitive tissues like liver, muscle and adipose tissue. Diet intervention has been proposed as a powerful tool to prevent the development of the metabolic syndrome, since healthy diets have been shown to have a protective role against the components of the metabolic syndrome. Particularly, dietary fatty acids are capable of modulating the deleterious effects of these conditions, among other mechanisms, by modifications of the lipid composition of the membranes in insulin-sensitive tissues. However, there is still scarce data based of high-level evidence on the effects of dietary oils on the effects of the metabolic syndrome and its components. This review summarizes the current knowledge on the effects of dietary oils on improving alterations of the components of the metabolic syndrome. It also examines their influence in the modulation of plasma membrane lipid composition and in the functionality of membrane proteins involved in insulin activity, like the insulin receptor, GLUT-4, CD36/FAT and ABCA-1, and their effect in the metabolism of glucose, fatty acids and cholesterol, and, in turn, the key features of the metabolic syndrome. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The effect of the hemochromatosis (HFE genotype on lead load and iron metabolism among lead smelter workers.

    Directory of Open Access Journals (Sweden)

    Guangqin Fan

    Full Text Available Both an excess of toxic lead (Pb and an essential iron disorder have been implicated in many diseases and public health problems. Iron metabolism genes, such as the hemochromatosis (HFE gene, have been reported to be modifiers for lead absorption and storage. However, the HFE gene studies among the Asian population with occupationally high lead exposure are lacking.To explore the modifying effects of the HFE genotype (wild-type, H63D variant and C282Y variant on the Pb load and iron metabolism among Asian Pb-workers with high occupational exposure.Seven hundred and seventy-one employees from a lead smelter manufacturing company were tested to determine their Pb intoxication parameters, iron metabolic indexes and identify the HFE genotype. Descriptive and multivariate analyses were conducted.Forty-five H63D variant carriers and no C282Y variant carrier were found among the 771 subjects. Compared with subjects with the wild-type genotype, H63D variant carriers had higher blood lead levels, even after controlling for factors such as age, sex, marriage, education, smoking and lead exposure levels. Multivariate analyses also showed that the H63D genotype modifies the associations between the blood lead levels and the body iron burden/transferrin.No C282Y variant was found in this Asian population. The H63D genotype modified the association between the lead and iron metabolism such that increased blood lead is associated with a higher body iron content or a lower transferrin in the H63D variant. It is indicated that H63D variant carriers may be a potentially highly vulnerable sub-population if they are exposed to high lead levels occupationally.

  10. Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders

    Science.gov (United States)

    2016-09-01

    trophic factor for the fetal brain before it acts as a neurotransmitter . 5-HT signaling modulates fetal brain wiring mechanisms and its disruption at...metabolism in the placenta, and consequently placental 5-HT synthesis , may directly affect fetal brain development and constitute a new molecular...Aim I: To determine whether maternal inflammation alters placental synthesis and fetal exposure to 5-HT and kynurenine-pathway compounds. This

  11. Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways

    OpenAIRE

    Pérez-Plasencia, Carlos; Vázquez-Ortiz, Guelaguetza; López-Romero, Ricardo; Piña-Sanchez, Patricia; Moreno, José; Salcedo, Mauricio

    2007-01-01

    Abstract Background Cervical carcinoma (CC) is a leading cause of death among women worldwide. Human papilloma virus (HPV) is a major etiological factor in CC and HPV 16 is the more frequent viral type present. Our aim was to characterize metabolic pathways altered in HPV 16 tumor samples by means of transcriptome wide analysis and bioinformatics tools for visualizing expression data in the context of KEGG biological pathways. Results We found 2,067 genes significantly up or down-modulated (a...

  12. Catalytic function of the mycobacterial binuclear iron monooxygenase in acetone metabolism.

    Science.gov (United States)

    Furuya, Toshiki; Nakao, Tomomi; Kino, Kuniki

    2015-10-01

    Mycobacteria such as Mycobacterium smegmatis strain mc(2)155 and Mycobacterium goodii strain 12523 are able to grow on acetone and use it as a source of carbon and energy. We previously demonstrated by gene deletion analysis that the mimABCD gene cluster, which encodes a binuclear iron monooxygenase, plays an essential role in acetone metabolism in these mycobacteria. In the present study, we determined the catalytic function of MimABCD in acetone metabolism. Whole-cell assays were performed using Escherichia coli cells expressing the MimABCD complex. When the recombinant E. coli cells were incubated with acetone, a product was detected by gas chromatography (GC) analysis. Based on the retention time and the gas chromatography-mass spectrometry (GC-MS) spectrum, the reaction product was identified as acetol (hydroxyacetone). The recombinant E. coli cells produced 1.02 mM of acetol from acetone within 24 h. Furthermore, we demonstrated that MimABCD also was able to convert methylethylketone (2-butanone) to 1-hydroxy-2-butanone. Although it has long been known that microorganisms such as mycobacteria metabolize acetone via acetol, this study provides the first biochemical evidence for the existence of a microbial enzyme that catalyses the conversion of acetone to acetol. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Rescue of Metabolic Alterations in AR113Q Skeletal Muscle by Peripheral Androgen Receptor Gene Silencing

    Directory of Open Access Journals (Sweden)

    Elisa Giorgetti

    2016-09-01

    Full Text Available Spinal and bulbar muscular atrophy (SBMA, a progressive degenerative disorder, is caused by a CAG/glutamine expansion in the androgen receptor (polyQ AR. Recent studies demonstrate that skeletal muscle is an important site of toxicity that contributes to the SBMA phenotype. Here, we sought to identify critical pathways altered in muscle that underlie disease manifestations in AR113Q mice. This led to the unanticipated identification of gene expression changes affecting regulators of carbohydrate metabolism, similar to those triggered by denervation. AR113Q muscle exhibits diminished glycolysis, altered mitochondria, and an impaired response to exercise. Strikingly, the expression of genes regulating muscle energy metabolism is rescued following peripheral polyQ AR gene silencing by antisense oligonucleotides (ASO, a therapeutic strategy that alleviates disease. Our data establish the occurrence of a metabolic imbalance in SBMA muscle triggered by peripheral expression of the polyQ AR and indicate that alterations in energy utilization contribute to non-neuronal disease manifestations.

  14. HIV lipodystrophy diagnosis and management. Body composition and metabolic alterations: diagnosis and management.

    Science.gov (United States)

    Engelson, Ellen S

    2003-04-01

    Body composition alterations are common in HIV infection and include AIDS wasting and lipodystrophy. Both are associated with metabolic alterations, including hypertriglyceridemia and reduced high-density lipoprotein cholesterol levels; insulin resistance and elevated low-density lipoprotein cholesterol levels are also associated with lipodystrophy. However, there is no accepted case definition for HIV-associated lipodystrophy, and patients may have one or all aspects at any given time. The inability of cross-sectional studies to capture the dynamic process of these alterations has hindered the search for a case definition. In the meantime, there are several approaches to treatment of the resulting abnormalities. Switching antiretrovirals has been most successful for improving metabolism, with little or not effect on fat distribution. Growth hormone treatment has successfully reduced visceral fat and buffalo humps but is not FDA-approved for this indication. Metformin and rosiglitazone have produced some improvement in fat distribution as well as glucose metabolism. Other methods that have been tried with varying degrees of success (and little published data) include treatment with testosterone and its derivatives, weight reduction through diet and exercise, and plastic surgery.

  15. Application of Circuit Simulation Method for Differential Modeling of TIM-2 Iron Uptake and Metabolism in Mouse Kidney Cells

    Directory of Open Access Journals (Sweden)

    Zhijian eXie

    2013-06-01

    Full Text Available Circuit simulation is a powerful methodology to generate differential mathematical models. Due to its highly accurate modelling capability, circuit simulation can be used to investigate interactions between the parts and processes of a cellular system. Circuit simulation has become a core technology for the field of electrical engineering, but its application in biology has not yet been fully realized. As a case study for evaluating the more advanced features of a circuit simulation tool called Advanced Design System (ADS, we collected and modeled laboratory data for iron metabolism in mouse kidney cells for a H ferritin (HFt receptor, T cell immunoglobulin and mucin domain-2 (TIM-2. The internal controlling parameters of TIM-2 associated iron metabolism were extracted and the ratios of iron movement among cellular compartments were quantified by ADS. The differential model processed by circuit simulation demonstrated a capability to identify variables and predict outcomes that could not be readily measured by in vitro experiments. For example, an initial rate of uptake of iron-loaded HFt was 2.17 pmol per million cells. TIM-2 binding probability with iron-loaded HFt was 16.6%. An average of 8.5 minutes was required for the complex of TIM-2 and iron-loaded HFt to form an endosome. The endosome containing HFt lasted roughly 2 hours. At the end of endocytosis, about 28% HFt remained intact and the rest was degraded. Iron released from degraded HFt was in the labile iron pool (LIP and stimulated the generation of endogenous HFt for new storage. Both experimental data and the model showed that TIM-2 was not involved in the process of iron export. The extracted internal controlling parameters successfully captured the complexity of TIM-2 pathway and the use of circuit simulation-based modeling across a wider range of cellular systems is the next step for validating the significance and utility of this method.

  16. NF-Y activates genes of metabolic pathways altered in cancer cells.

    Science.gov (United States)

    Benatti, Paolo; Chiaramonte, Maria Luisa; Lorenzo, Mariangela; Hartley, John A; Hochhauser, Daniel; Gnesutta, Nerina; Mantovani, Roberto; Imbriano, Carol; Dolfini, Diletta

    2016-01-12

    The trimeric transcription factor NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types. NF-Y controls de novo biosynthetic pathways of lipids, teaming up with the master SREBPs regulators. It activates glycolytic genes, but, surprisingly, is neutral or represses mitochondrial respiratory genes. NF-Y targets the SOCG (Serine, One Carbon, Glycine) and Glutamine pathways, as well as genes involved in the biosynthesis of polyamines and purines. Specific cancer-driving nodes are generally under NF-Y control. Altogether, these data delineate a coherent strategy to promote expression of metabolic genes fuelling anaerobic energy production and other anabolic pathways commonly altered in cancer cells.

  17. Deficiency of the GPR39 receptor is associated with obesity and altered adipocyte metabolism

    DEFF Research Database (Denmark)

    Petersen, Pia Steen; Jin, Chunyu; Madsen, Andreas Nygaard

    2011-01-01

    on body weight and adipocyte metabolism. GPR39-deficient mice were subjected to a high-fat diet and body composition, glucose tolerance, insulin secretion, food intake, and energy expenditure were evaluated. The cell biology of adipocyte metabolism was studied on both mRNA and protein levels......-induced thermogenesis, measured by the oxygen consumption rate (Vo(2)) on change from normal to high-fat diet. Analysis of the adipose tissue for lipolytic enzymes demonstrated decreased level of phosphorylated hormone-sensitive lipase (HSL) and a decreased level of adipose triglyceride lipase (ATGL) by 35 and 60......, conceivably due to decreased energy expenditure and adipocyte lipolytic activity.-Petersen, P. S., Jin, C., Madsen, A. N., Rasmussen, M., Kuhre, R., L. Egerod, K. L., Nielsen, L. B., Schwartz. T. W., Holst, B. Deficiency of the GPR39 receptor is associated with obesity and altered adipocyte metabolism....

  18. Fluorescence lifetime microscopy of NADH distinguishes alterations in cerebral metabolism in vivo.

    Science.gov (United States)

    Yaseen, Mohammad A; Sutin, Jason; Wu, Weicheng; Fu, Buyin; Uhlirova, Hana; Devor, Anna; Boas, David A; Sakadžić, Sava

    2017-05-01

    Evaluating cerebral energy metabolism at microscopic resolution is important for comprehensively understanding healthy brain function and its pathological alterations. Here, we resolve specific alterations in cerebral metabolism in vivo in Sprague Dawley rats utilizing minimally-invasive 2-photon fluorescence lifetime imaging (2P-FLIM) measurements of reduced nicotinamide adenine dinucleotide (NADH) fluorescence. Time-resolved fluorescence lifetime measurements enable distinction of different components contributing to NADH autofluorescence. Ostensibly, these components indicate different enzyme-bound formulations of NADH. We observed distinct variations in the relative proportions of these components before and after pharmacological-induced impairments to several reactions involved in glycolytic and oxidative metabolism. Classification models were developed with the experimental data and used to predict the metabolic impairments induced during separate experiments involving bicuculline-induced seizures. The models consistently predicted that prolonged focal seizure activity results in impaired activity in the electron transport chain, likely the consequence of inadequate oxygen supply. 2P-FLIM observations of cerebral NADH will help advance our understanding of cerebral energetics at a microscopic scale. Such knowledge will aid in our evaluation of healthy and diseased cerebral physiology and guide diagnostic and therapeutic strategies that target cerebral energetics.

  19. [Metabolic syndrome and ageing: cognitive impairment and structural alterations of the central nervous system].

    Science.gov (United States)

    Segura, B; Jurado, M A

    The metabolic syndrome is a cluster of vascular risk factors, including: hypertension, insulin resistance, low levels of high density lipoproteins, high levels of triglycerides and obesity. Nowadays the prevalence of the syndrome in the developmental societies increases and it is related to aging. To review the relation of metabolic syndrome to the cognitive impairment and cerebrovascular alterations during the aging. The syndrome involves higher risk of vascular pathologies and recently has been related to the pathological aging, including cognitive impairment and structural damage in the central nervous system. Specifically the studies about metabolic syndrome have described a profile of higher general cognitive impairment and higher risk of dementia, as well as concrete neuropsychological deficits probably related to white matter alterations. The independent effects of vascular risk factors in cognition have been studied before as well as their influences in structural integrity of the brain. Nowadays further research is necessary to know if the metabolic syndrome effects on cognition and brain are greater than the sum of the effect of his components. In the future the knowledge about the cognitive and structural damage due to the syndrome could be useful to design prevention programs and promote the healthy aging.

  20. Effect of short-term food restriction on iron metabolism, relative well-being and depression symptoms in healthy women.

    Science.gov (United States)

    Wojciak, Rafal W

    2014-01-01

    The idea that iron deficiency anemia can be recognized in depressive patients has been around for a few years, as well as negative association between ferritin levels and depression. Iron deficiency anemia, associated with low iron intake, has been observed in women using restriction diets, for example in vegetarians or anorexics. There are no data on the influence of the short-term food restrictions, observed for example in slimming women, on iron management and its connection with behavior expressed via changes in the subject's emotional state. This study describes the effect of one- and two-day food restrictions (every 8 days for a period of 48 days) on selected iron management parameters in the serum and blood of 46 healthy volunteer women (23 in each group), aged 25.5 ± 3.0 years, in association with the subjects' self-described emotional status and depression symptoms. The association between iron parameters and depression was also analyzed. Results show that short-term (2 days) fasting significantly decreases iron concentrations in serum and hair, as well as levels of ferritin, hemoglobin, hematocrit, red blood cells, and total iron binding capacity, but the short-term fasting did not influence the other iron management parameters. Each model of food restrictions also increased negative feelings towards depression. A significant negative correlation between serum ferritin levels and depression was found in women who starved for 2 days. The study shows that, through an impact on mineral levels, even short-term food restrictions, as observed in many slimming women and girls, can be a reason for iron deficiency and also can alter the emotional status of healthy women. Maybe depression symptoms in anorexia or other eating disorders patients can be associated with iron deficiencies.

  1. Alteration of tricarboxylic acid cycle metabolism in rat brain slices by halothane

    International Nuclear Information System (INIS)

    Cheng, S.C.; Brunner, E.A.

    1978-01-01

    Metabolism of [2- 14 C] pyruvate, [1- 14 C] acetate and [5- 14 C] citrate in rat cerebral cortex slices was studied in the presence of halothane. Metabolites assayed include acetylcholine (ACh), citrate, glutamate, glutamineγ-aminobutyrate (GABA) and aspartate. The trichloroacetic acid soluble extract, the trichloracetic acid insoluble precipitate and its lipid extract were also studied. In control experiments, pyruvate preferentially labelled ACh, citrate, glutamate, GABA and aspartate. Acetate labelled ACh, but to a lesser extent than pyruvate. Acetate also labelled lipids and glutamine. Citrate labelled lipids but not ACh and served as a preferential precursor for glutamine. These data support a three-compartment model for cerebral tricarboxylic acid cycle metabolism. Halothane caused increases in GABA and aspartate contents and a decrease in ACh content. It has no effect on the contents of citrate, glutamate and glutamine. Halothane preferentially inhibited the metabolic transfer of radioactivity from pyruvate into almost all metabolites, an effect probably not related to pyruvate permeability. This is interpreted as halothane depression of the large metabolic compartment which includes the nerve endings. Halothane increased the metabolic transfer of radioactivity from acetate into lipids but did not alter such a transfer into the trichloroacetic acid extract. Halothane increased the metabolic transfer of radioactivity from citrate into the trichloroacetic acid precipitate, lipids and especially glutamine. Transfer of citrate radioactivity into GABA was somewhat decreased. The differential effects of halothane on acetate and citrate utilization suggest that the small metabolic compartment should be subdivided. Therefore, at least three metabolic compartments are demonstrated. Halothane did not interfere with the dicarboxylic acid portion of the tricarboxylic acid cycle. (author)

  2. A high fat diet does not affect the iron bioavailability in Wistar rats fed with chia and increases gene expression of iron metabolism proteins.

    Science.gov (United States)

    da Silva, Bárbara Pereira; Matyelka, Jéssika Camila da Silva; Moreira, Maria Eliza de Castro; Toledo, Renata Celi Lopes; Della Lucia, Ceres Mattos; Pinheiro-Sant'Ana, Helena Maria; Martino, Hércia Stampini Duarte

    2016-12-07

    This study evaluated the effect of chia on the iron bioavailability and gene expression of proteins involved in iron metabolism in animals fed with a high fat diet and a standard diet. Four experimental groups were tested (n = 8): standard diet + ferrous sulfate (SD + FS), standard diet + chia (SD + C), high fat diet + ferrous sulfate (HFD + FS), high fat diet + chia (HFD + C). The hemoglobin gain, hemoglobin regeneration efficiency, biological relative value of HRE, serum ferritin and transferrin, liver iron concentration and gene expression of proteins were evaluated. The SD + C group showed lower transferrin expression when compared to the control group. The control group showed serum transferrin concentration higher than the other groups. Serum ferritin and liver iron concentration did not differ among the animals that received chia ferritin and hephaestin expression was lower in experimental groups when compared with the control group. The peroxisome proliferator activated receptor expression was higher in animals fed with SD + C than in the control group. The expression of duodenal cytochrome B and divalent metal transporter 1 in the HFD + C group was higher and ferroportin was lower in the groups containing chia. Animals fed with chia showed similar iron bioavailability compared to animals fed with ferrous sulfate.

  3. Practice guidelines for the diagnosis and management of microcytic anemias due to genetic disorders of iron metabolism or heme synthesis

    NARCIS (Netherlands)

    Donker, A.E.; Raymakers, R.A.P.; Vlasveld, L.T.; Barneveld, T. van; Terink, R.; Dors, N.; Brons, P.P.T.; Knoers, N.V.A.M.; Swinkels, D.W.

    2014-01-01

    During recent years, our understanding of the pathogenesis of inherited microcytic anemias has gained from the identification of several genes and proteins involved in systemic and cellular iron metabolism and heme syntheses. Numerous case reports illustrate that the implementation of these novel

  4. Altered glucose metabolism in Harvey-ras transformed MCF10A cells.

    Science.gov (United States)

    Zheng, Wei; Tayyari, Fariba; Gowda, G A Nagana; Raftery, Daniel; McLamore, Eric S; Porterfield, D Marshall; Donkin, Shawn S; Bequette, Brian; Teegarden, Dorothy

    2015-02-01

    Metabolic reprogramming that alters the utilization of glucose including the "Warburg effect" is critical in the development of a tumorigenic phenotype. However, the effects of the Harvey-ras (H-ras) oncogene on cellular energy metabolism during mammary carcinogenesis are not known. The purpose of this study was to determine the effect of H-ras transformation on glucose metabolism using the untransformed MCF10A and H-ras oncogene transfected (MCF10A-ras) human breast epithelial cells, a model for early breast cancer progression. We measured the metabolite fluxes at the cell membrane by a selective micro-biosensor, [(13)C6 ]glucose flux by (13)C-mass isotopomer distribution analysis of media metabolites, intracellular metabolite levels by NMR, and gene expression of glucose metabolism enzymes by quantitative PCR. Results from these studies indicated that MCF10A-ras cells exhibited enhanced glycolytic activity and lactate production, decreased glucose flux through the tricarboxylic acid (TCA) cycle, as well as an increase in the utilization of glucose in the pentose phosphate pathway (PPP). These results provide evidence for a role of H-ras oncogene in the metabolic reprogramming of MCF10A cells during early mammary carcinogenesis. © 2013 Wiley Periodicals, Inc.

  5. Maternal obesity and increased neonatal adiposity correspond with altered infant mesenchymal stem cell metabolism.

    Science.gov (United States)

    Baker, Peter R; Patinkin, Zachary; Shapiro, Allison Lb; De La Houssaye, Becky A; Woontner, Michael; Boyle, Kristen E; Vanderlinden, Lauren; Dabelea, Dana; Friedman, Jacob E

    2017-11-02

    Maternal obesity is a global health problem that increases offspring obesity risk. The metabolic pathways underlying early developmental programming in human infants at risk for obesity remain poorly understood, largely due to barriers in fetal/infant tissue sampling. Utilizing umbilical cord-derived mesenchymal stem cells (uMSC) from offspring of normal weight and obese mothers, we tested whether energy metabolism and gene expression differ in differentiating uMSC myocytes and adipocytes, in relation to maternal obesity exposures and/or neonatal adiposity. Biomarkers of incomplete β-oxidation were uniquely positively correlated with infant adiposity and maternal lipid levels in uMSC myocytes from offspring of obese mothers only. Metabolic and biosynthetic processes were enriched in differential gene expression analysis related to maternal obesity. In uMSC adipocytes, maternal obesity and lipids were associated with downregulation in multiple insulin-dependent energy-sensing pathways including PI3K and AMPK. Maternal lipids correlated with uMSC adipocyte upregulation of the mitochondrial respiratory chain but downregulation of mitochondrial biogenesis. Overall, our data revealed cell-specific alterations in metabolism and gene expression that correlated with maternal obesity and adiposity of their offspring, suggesting tissue-specific metabolic and regulatory changes in these newborn cells. We provide important insight into potential developmental programming mechanisms of increased obesity risk in offspring of obese mothers.

  6. Fatty acid metabolism is altered in non-alcoholic steatohepatitis independent of obesity.

    Science.gov (United States)

    Walle, Paula; Takkunen, Markus; Männistö, Ville; Vaittinen, Maija; Lankinen, Maria; Kärjä, Vesa; Käkelä, Pirjo; Ågren, Jyrki; Tiainen, Mika; Schwab, Ursula; Kuusisto, Johanna; Laakso, Markku; Pihlajamäki, Jussi

    2016-05-01

    Non-alcoholic steatohepatitis (NASH) is associated with changes in fatty acid (FA) metabolism. However, specific changes in metabolism and hepatic mRNA expression related to NASH independent of simple steatosis, obesity and diet are unknown. Liver histology, serum and liver FA composition and estimated enzyme activities based on the FA ratios in cholesteryl esters and triglycerides were assessed in 92 obese participants of the Kuopio Obesity Surgery Study (KOBS) divided to those with normal liver, steatosis or NASH (30 men and 62 women, age 46.8±9.5years (mean±SD), BMI 44.2±6.2kg/m(2)). Plasma FA composition was also investigated in the Metabolic Syndrome in Men (METSIM) Study (n=769), in which serum alanine aminotransferase (ALT) was used as a marker of liver disease. Obese individuals with NASH had higher activity of estimated activities of delta-6 desaturase (D6D, pliver. Estimated activities of D5D, D6D and SCD1 correlated positively between liver and serum indicating that serum estimates reflected liver metabolism. Accordingly, NASH was associated with higher hepatic mRNA expression of corresponding genes FADS1, FADS2 and SCD. Finally, differences in FA metabolism that associated with NASH in obese individuals were also associated with high ALT in the METSIM Study. We demonstrated alterations in FA metabolism and endogenous desaturase activities that associate with NASH, independent of obesity and diet. This suggests that changes in endogenous FA metabolism are related to NASH and that they may contribute to the progression of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Preschool-Aged Children with Iron Deficiency Anemia Show Altered Affect and Behavior1,2

    Science.gov (United States)

    Lozoff, Betsy; Corapci, Feyza; Burden, Matthew J.; Kaciroti, Niko; Angulo-Barroso, Rosa; Sazawal, Sunil; Black, Maureen

    2012-01-01

    This study compared social looking and response to novelty in preschool-aged children (47–68 mo) with or without iron deficiency anemia (IDA). Iron status of the participants from a low-income community in New Delhi, India, was based on venous hemoglobin, mean corpuscular volume, and red cell distribution width. Children’s social looking toward adults, affect, and wary or hesitant behavior in response to novelty were assessed in a semistructured paradigm during an in-home play observation. Affect and behavior were compared as a function of iron status: IDA (n = 74) vs. nonanemic (n = 164). Compared with nonanemic preschoolers, preschoolers with IDA displayed less social looking toward their mothers, moved close to their mothers more quickly, and were slower to display positive affect and touch novel toys for the first time. These results indicate that IDA in the preschool period has affective and behavioral effects similar to those reported for IDA in infancy. PMID:17311960

  8. Danazol alters mitochondria metabolism of fibrocystic breast Mcf10A cells.

    Science.gov (United States)

    Irgebay, Zhazira; Yeszhan, Banu; Sen, Bhaswati; Tuleukhanov, Sultan; Brooks, Ari D; Sensenig, Richard; Orynbayeva, Zulfiya

    2017-10-01

    Fibrocystic Breast Disease (FBD) or Fibrocystic change (FC) affects about 60% of women at some time during their life. Although usually benign, it is often associated with pain and tenderness (mastalgia). The synthetic steroid danazol has been shown to be effective in reducing the pain associated with FBD, but the cellular and molecular mechanisms for its action have not been elucidated. We investigated the hypothesis that danazol acts by affecting energy metabolism. Effects of danazol on Mcf10A cells homeostasis, including mechanisms of oxidative phosphorylation, cytosolic calcium signaling and oxidative stress, were assessed by high-resolution respirometry and flow cytometry. In addition to fast physiological responses the associated genomic modulations were evaluated by Affimetrix microarray analysis. The alterations of mitochondria membrane potential and respiratory activity, downregulation of energy metabolism transcripts result in suppression of energy homeostasis and arrest of Mcf10A cells growth. The data obtained in this study impacts the recognition of direct control of mitochondria by cellular mechanisms associated with altered energy metabolism genes governing the breast tissue susceptibility and response to medication by danazol. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Dietary Fatty Acids Alter Lipid Profiles and Induce Myocardial Dysfunction without Causing Metabolic Disorders in Mice.

    Science.gov (United States)

    Chen, Bainian; Huang, Yifan; Zheng, Dong; Ni, Rui; Bernards, Mark A

    2018-01-19

    Oversupply of bulk saturated fatty acids (SFA) induces metabolic disorders and myocardial dysfunction. We investigated whether, without causing metabolic disorders, the uptake of individual dietary SFA species alters lipid profiles and induces myocardial dysfunction. C57BL/6 mice were fed various customized long-chain SFA diets (40% caloric intake from SFA), including a beef tallow (HBD), cocoa butter (HCD), milk fat (HMD) and palm oil diet (HPD), for 6 months. An isocaloric fat diet, containing medium-chain triglycerides, served as a control (CHD). Long-term intake of dietary long-chain SFA differentially affected the fatty acid composition in cardiac phospholipids. All long-chain SFA diets increased the levels of arachidonic acid and total SFA in cardiac phospholipids. The preferential incorporation of individual SFA into the cardiac phospholipid fraction was dependent on the dietary SFA species. Cardiac ceramide content was elevated in all mice fed long-chain SFA diets, while cardiac hypertrophy was only presented in mice fed HMD or HPD. We have demonstrated that the intake of long-chain SFA species differentially alters cardiac lipid profiles and induces cardiac dysfunction, without causing remarkable metabolic disorders.

  10. Metabolic syndrome alters expression of insulin signaling-related genes in swine mesenchymal stem cells.

    Science.gov (United States)

    Conley, Sabena M; Zhu, Xiang-Yang; Eirin, Alfonso; Tang, Hui; Lerman, Amir; van Wijnen, Andre J; Lerman, Lilach O

    2018-02-20

    Metabolic syndrome (MetS) is associated with insulin resistance (IR) and impaired glucose metabolism in muscle, fat, and other cells, and may induce inflammation and vascular remodeling. Endogenous reparative systems, including adipose tissue-derived mesenchymal stem/stromal cells (MSC), are responsible for repair of damaged tissue. MSC have also been proposed as an exogenous therapeutic intervention in patients with cardiovascular and chronic kidney disease (CKD). The feasibility of using autologous cells depends on their integrity, but whether in MetS IR involves adipose tissue-derived MSC remains unknown. The aim of this study was to examine the expression of mRNA involved in insulin signaling in MSC from subjects with MetS. Domestic pigs consumed a lean or obese diet (n=6 each) for 16weeks. MSC were collected from subcutaneous abdominal fat and analyzed using high-throughput RNA-sequencing for expression of genes involved in insulin signaling. Expression profiles for enriched (fold change>1.4, pinsulin signaling. Enriched mRNAs were implicated in biological pathways including hepatic glucose metabolism, adipocyte differentiation, and transcription regulation, and down-regulated mRNAs in intracellular calcium signaling and cleaving peptides. Functional analysis suggested that overall these alterations could increase IR. MetS alters mRNA expression related to insulin signaling in adipose tissue-derived MSC. These observations mandate caution during administration of autologous MSC in subjects with MetS. Copyright © 2017. Published by Elsevier B.V.

  11. Gene expression of sphingolipid metabolism pathways is altered in hidradenitis suppurativa.

    Science.gov (United States)

    Dany, Mohammed; Elston, Dirk

    2017-08-01

    Hidradenitis suppurativa (HS) is a debilitating skin disease characterized by painful recurrent nodules and abscesses caused by chronic inflammation. Early events in the development of HS are believed to occur in the folliculopilosebaceous unit; however, the signaling pathways behind this mechanism are unknown. Sphingolipids, such as ceramide, are essential components of the skin and appendages and have important structural and signaling roles. We sought to explore whether the gene expression of enzymes involved in sphingolipid metabolic pathways is altered in HS. A microarray data set including 30 samples was used to compare the expression of sphingolipid-related enzymes in inflammatory skin lesions from HS patients (n = 17) with the expression in clinically healthy skin tissue (n = 13). Differential expression of sphingolipid metabolism-related genes was analyzed using Gene Expression Omnibus 2R. HS lesional skin samples have significantly decreased expression of enzymes generating ceramide and sphingomyelin, increased expression of enzymes catabolizing ceramide to sphingosine, and increased expression of enzymes converting ceramide to galactosylceramide and gangliosides. Limitations of this study include assessing the expression of sphingolipid-related enzymes without assessing the levels of the related sphingolipids. Our study suggests that sphingolipid metabolism is altered in HS lesional skin compared with normal skin. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  12. The alteration of lipid metabolism in Burkitt lymphoma identifies a novel marker: adipophilin.

    Directory of Open Access Journals (Sweden)

    Maria R Ambrosio

    Full Text Available BACKGROUND: Recent evidence suggests that lipid pathway is altered in many human tumours. In Burkitt lymphoma this is reflected by the presence of lipid droplets which are visible in the cytoplasm of neoplastic cells in cytological preparations. These vacuoles are not identifiable in biopsy section as lipids are "lost" during tissue processing. METHODS AND RESULTS: In this study we investigated the expression of genes involved in lipid metabolism, at both RNA and protein level in Burkitt lymphoma and in other B-cell aggressive lymphoma cases. Gene expression profile indicated a significant over-expression of the adipophilin gene and marked up-regulation of other genes involved in lipid metabolism in Burkitt lymphoma. These findings were confirmed by immunohistochemistry on a series od additional histological samples: 45 out of 47 BL cases showed strong adipophilin expression, while only 3 cases of the 33 of the not-Burkitt lymphoma category showed weak adipophilin expression (p<0.05. CONCLUSIONS: Our preliminary results suggest that lipid metabolism is altered in BL, and this leads to the accumulation of lipid vacuoles. These vacuoles may be specifically recognized by a monoclonal antibody against adipophilin, which may therefore be a useful marker for Burkitt lymphoma because of its peculiar expression pattern. Moreover this peptide might represent an interesting candidate for interventional strategies.

  13. Does exposure to testosterone significantly alter endogenous metabolism in the marine mussel Mytilus galloprovincialis?

    Science.gov (United States)

    Fernandes, Denise; Navarro, Juan Carlos; Riva, Consuelo; Bordonali, Silvia; Porte, Cinta

    2010-11-15

    Mussels (Mytilus galloprovincialis) were exposed to different concentrations of testosterone (T: 20, 200 and 2000ng/L) in a semi-static water regime (1-day dosing intervals) for up to 5 days in an attempt to see whether endogenous steroid levels and steroid metabolism were altered by exogenous exposure to testosterone. Whole tissue levels of total testosterone (free+esterified) sharply increased in a concentration-dependent manner, from 2ng/g in controls to 290ng/g in organisms exposed to the highest concentration. In contrast, levels of free testosterone were only significantly elevated at the high-exposure group (5-fold increase with respect to controls). Increased activity of palmitoyl-CoA:testosterone acyltransferase (ATAT) was detected in organisms exposed to the highest concentration of testosterone, while those exposed to low and medium concentrations showed significant alterations in their polyunsaturated fatty acid profiles. The obtained results suggest that esterification of the excess of T with fatty acids might act as a homeostatic mechanism to maintain endogenous levels of free T stable. Interestingly, a decrease in CYP3A-like activity was detected in T-exposed mussels together with a significant decrease in the metabolism of the androgen precursor androstenedione to dihydrotestosterone (5α-DHT). Overall, the work contributes to the better knowledge of androgen metabolism in mussels. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Does altered protein metabolism interfere with postmortem degradation analysis for PMI estimation?

    Science.gov (United States)

    Zissler, A; Ehrenfellner, B; Foditsch, E E; Monticelli, F C; Pittner, S

    2018-03-02

    An accurate estimation of the postmortem interval (PMI) is a central aspect in forensic routine. Recently, a novel approach based on the analysis of postmortem muscle protein degradation has been proposed. However, a number of questions remain to be answered until sensible application of this method to a broad variety of forensic cases is possible. To evaluate whether altered in vivo protein metabolism interferes with postmortem degradation patterns, we conducted a comparative study. We developed a standardized animal degradation model in rats, and collected additional muscle samples from animals recovering from muscle injury and from rats with developed disuse muscle atrophy after induced spinal cord injury. All samples were analyzed by SDS-PAGE and Western blot, labeling well-characterized muscle proteins. Tropomyosin was found to be stable throughout the investigated PMI and no alterations were detected in regenerating and atrophic muscles. In contrast, significant predictable postmortem changes occurred in desmin and vinculin protein band patterns. While no significant deviations from native patterns were detected in at-death samples of disuse muscle atrophy, interestingly, samples of rats recovering from muscle injury revealed additional desmin and vinculin degradation bands that did not occur in this form in any of the examined postmortem samples regardless of PMI. It remains to be investigated whether in vivo-altered metabolism influences postmortem degradation kinetics or if such muscle samples undergo postmortem degradation in a regular fashion.

  15. Effects of Radiation and Dietary Iron on Expression of Genes and Proteins Involved in Drug Metabolism

    Science.gov (United States)

    Faust, K. M.; Wotring, V. E.

    2014-01-01

    Liver function, especially the rate of metabolic enzyme activities, determines the concentration of circulating drugs and the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand any effects of spaceflight on the enzymes of the liver. Dietary factors and exposure to radiation are aspects of spaceflight that are potential oxidative stressors and both can be modeled in ground experiments. In this experiment, we examined the effects of high dietary iron and low dose gamma radiation (individually and combined) on the gene expression of enzymes involved in drug metabolism, redox homeostasis, and DNA repair. METHODS All procedures were approved by the JSC Animal Care and Use Committee. Male Sprague-Dawley rats were divided into 4 groups (n=8); control, high Fe diet (650 mg iron/kg), radiation (fractionated 3 Gy exposure from a Cs- 137 source) and combined high Fe diet + radiation exposure. Animals were euthanized 24h after the last treatment of radiation; livers were removed immediately and flash -frozen in liquid nitrogen. Expression of genes thought to be involved in redox homeostasis, drug metabolism and DNA damage repair was measured by RT-qPCR. Where possible, protein expression of the same genes was measured by western blotting. All data are expressed as % change in expression normalized to reference gene expression; comparisons were then made of each treatment group to the sham exposed/ normal diet control group. Data was considered significant at pprotein

  16. Energy metabolism, leptin, and biochemical parameters are altered in rats subjected to the chronic administration of olanzapine

    OpenAIRE

    Zugno,Alexandra I.; Barcelos,Mariely; Oliveira,Larissa de; Canever,Leila; Luca,Renata D. de; Fraga,Daiane B.; Matos,Maria Paula; Rezin,Gislaine T.; Scaini,Giselli; Búrigo,Márcio; Streck,Emilio L.; Quevedo,João

    2012-01-01

    OBJECTIVES: Olanzapine, an atypical antipsychotic drug with affinities for dopamine, serotonin, and histamine binding sites appears to be associated with substantial weight gain and metabolic alterations. The aim of this study was to evaluate weight gain and metabolic alterations in rats treated with olanzapine on a hypercaloric diet. METHODS: We used 40 rats divided into 4 groups: Group 1, standard food and water conditions (control); Group 2, standard diet plus olanzapine; Group 3, cafeteri...

  17. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    International Nuclear Information System (INIS)

    Liu, Yansong; Xu, Dan; Feng, Jianghua; Kou, Hao; Liang, Gai; Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

    2012-01-01

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by 1 H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine ingestion

  18. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yansong [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Feng, Jianghua, E-mail: jianghua.feng@xmu.edu.cn [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071 (China); Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, 361005 (China); Kou, Hao; Liang, Gai [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin [Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China)

    2012-07-15

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine

  19. Induction of autophagy by ARHI (DIRAS3) alters fundamental metabolic pathways in ovarian cancer models.

    Science.gov (United States)

    Ornelas, Argentina; McCullough, Christopher R; Lu, Zhen; Zacharias, Niki M; Kelderhouse, Lindsay E; Gray, Joshua; Yang, Hailing; Engel, Brian J; Wang, Yan; Mao, Weiqun; Sutton, Margie N; Bhattacharya, Pratip K; Bast, Robert C; Millward, Steven W

    2016-10-26

    Autophagy is a bulk catabolic process that modulates tumorigenesis, therapeutic resistance, and dormancy. The tumor suppressor ARHI (DIRAS3) is a potent inducer of autophagy and its expression results in necroptotic cell death in vitro and tumor dormancy in vivo. ARHI is down-regulated or lost in over 60 % of primary ovarian tumors yet is dramatically up-regulated in metastatic disease. The metabolic changes that occur during ARHI induction and their role in modulating death and dormancy are unknown. We employed Nuclear Magnetic Resonance (NMR)-based metabolomic strategies to characterize changes in key metabolic pathways in both cell culture and xenograft models of ARHI expression and autophagy. These pathways were further interrogated by cell-based immunofluorescence imaging, tracer uptake studies, targeted metabolic inhibition, and in vivo PET/CT imaging. Induction of ARHI in cell culture models resulted in an autophagy-dependent increase in lactate production along with increased glucose uptake and enhanced sensitivity to glycolytic inhibitors. Increased uptake of glutamine was also dependent on autophagy and dramatically sensitized cultured ARHI-expressing ovarian cancer cell lines to glutaminase inhibition. Induction of ARHI resulted in a reduction in mitochondrial respiration, decreased mitochondrial membrane potential, and decreased Tom20 staining suggesting an ARHI-dependent loss of mitochondrial function. ARHI induction in mouse xenograft models resulted in an increase in free amino acids, a transient increase in [ 18 F]-FDG uptake, and significantly altered choline metabolism. ARHI expression has previously been shown to trigger autophagy-associated necroptosis in cell culture. In this study, we have demonstrated that ARHI expression results in decreased cellular ATP/ADP, increased oxidative stress, and decreased mitochondrial function. While this bioenergetic shock is consistent with programmed necrosis, our data indicates that the accompanying up

  20. Iron deficiency affects nitrogen metabolism in cucumber (Cucumis sativus L. plants

    Directory of Open Access Journals (Sweden)

    Borlotti Andrea

    2012-10-01

    Full Text Available Abstract Background Nitrogen is a principal limiting nutrient in plant growth and development. Among factors that may limit NO3- assimilation, Fe potentially plays a crucial role being a metal cofactor of enzymes of the reductive assimilatory pathway. Very few information is available about the changes of nitrogen metabolism occurring under Fe deficiency in Strategy I plants. The aim of this work was to study how cucumber (Cucumis sativus L. plants modify their nitrogen metabolism when grown under iron deficiency. Results The activity of enzymes involved in the reductive assimilation of nitrate and the reactions that produce the substrates for the ammonium assimilation both at root and at leaf levels in Fe-deficient cucumber plants were investigated. Under Fe deficiency, only nitrate reductase (EC 1.7.1.1 activity decreased both at the root and leaf level, whilst for glutamine synthetase (EC 6.3.1.2 and glutamate synthase (EC 1.4.1.14 an increase was found. Accordingly, the transcript analysis for these enzymes showed the same behaviour except for root nitrate reductase which increased. Furthermore, it was found that amino acid concentration greatly decreased in Fe-deficient roots, whilst it increased in the corresponding leaves. Moreover, amino acids increased in the xylem sap of Fe-deficient plants. Conclusions The data obtained in this work provided new insights on the responses of plants to Fe deficiency, suggesting that this nutritional disorder differentially affected N metabolism in root and in leaf. Indeed under Fe deficiency, roots respond more efficiently, sustaining the whole plant by furnishing metabolites (i.e. aa, organic acids to the leaves.

  1. Altered protein and iron levels of patients with active tuberculosis in ...

    African Journals Online (AJOL)

    Backgound: Tuberculosis as a state of chronic inflammation impacts on haematologic functions of the body. Objectives: This study aimed at assessing iron parameters and serum protein levels of ninety tuberculosis patients aged fifteen to sixty years, enrolled from Dr Lawrence Henshaw Memorial Hospital, Calabar, Nigeria.

  2. Inflammatory and metabolic alterations of Kager's fat pad in chronic achilles tendinopathy

    DEFF Research Database (Denmark)

    Pingel, Jessica; Petersen, Marie Christine Helby; Fredberg, Ulrich

    2015-01-01

    of inflammatory markers and metabolic enzymes in Kager's fat pad. METHODS: A biopsy was taken from Kager's fat pad from 31 patients with chronic Achilles tendinopathy and from 13 healthy individuals. Gene expression was measured by reverse transcription-quantitative PCR. Focus was on genes related to inflammation...... inflamed than in the healthy control group. Additionally, the results indicate an altered lipid metabolism in Kager's fat pad of Achilles tendinopathy patients.......BACKGROUND: Achilles tendinopathy is a painful inflammatory condition characterized by swelling, stiffness and reduced function of the Achilles tendon. Kager's fat pad is an adipose tissue located in the area anterior to the Achilles tendon. Observations reveal a close physical interplay between...

  3. Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.

    Directory of Open Access Journals (Sweden)

    Erwin van Vliet

    Full Text Available Intrauterine Growth Restriction (IUGR due to placental insufficiency occurs in 5-10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development.At gestation day 25, IUGR was induced in two New Zealand rabbits by 40-50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR.IUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino acid levels, fatty acid profiles and oxidative stress

  4. Editor's Highlight: Pregnancy Alters Aflatoxin B1 Metabolism and Increases DNA Damage in Mouse Liver.

    Science.gov (United States)

    Sriwattanapong, Kanokwan; Slocum, Stephen L; Chawanthayatham, Supawadee; Fedeles, Bogdan I; Egner, Patricia A; Groopman, John D; Satayavivad, Jutamaad; Croy, Robert G; Essigmann, John M

    2017-11-01

    Pregnancy is a complex physiological state, in which the metabolism of endogenous as well as exogenous agents is ostensibly altered. One exogenous agent of concern is the hepatocarcinogen aflatoxin B1 (AFB1), a foodborne fungal toxin, that requires phase I metabolic oxidation for conversion to its toxic and carcinogenic form, the AFB1-8,9-exo-epoxide. The epoxide interacts with cellular targets causing toxicity and cell death; these targets include the covalent modification of DNA leading to mutations that can initiate malignant transformation. The main detoxification pathway of the AFB1-epoxide involves phase II metabolic enzymes including the glutathione-S-transferase (GST) family. Pregnancy can modulate both phase I and II metabolism and alter the biological potency of AFB1. The present work investigated the impact of pregnancy on AFB1 exposure in mice. A single IP dose of 6 mg/kg AFB1 was administered to pregnant C57BL/6 J mice at gestation day 14 and matched non-pregnant controls. Pregnant mice accumulated 2-fold higher AFB1-N7-guanine DNA adducts in the liver when compared with nonpregnant controls 6 h post-exposure. Enhanced DNA adduct formation in pregnant animals paralleled elevated hepatic protein expression of mouse CYP1A2 and mouse homologs of human CYP3A4, phase I enzymes capable of bioactivating AFB1. Although phase II enzymes GSTA1/2 showed decreased protein expression, GSTA3, the primary enzymatic protection against the AFB1-epoxide, was unaffected at the protein level. Taken together, our results reveal that pregnancy may constitute a critical window of susceptibility for maternal health, and provide insight into the biochemical factors that could explain the underlying risks. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology.

  5. Altered Metabolism and Lipodystrophy in the Early B-Cell Factor 1-Deficient Mouse

    OpenAIRE

    Fretz, Jackie A.; Nelson, Tracy; Xi, Yougen; Adams, Douglas J.; Rosen, Clifford J.; Horowitz, Mark C.

    2010-01-01

    We previously reported that mice deficient for the transcription factor early B-cell factor (Ebf1) exhibit markedly increased numbers of osteoblasts, bone formation rate, and serum osteocalcin, but the bone marrow of Ebf1−/− mice is also striking in its increased marrow adiposity. The purpose of this work was to analyze the metabolic phenotype that accompanies the altered bone morphology of Ebf1−/− mice. Whereas marrow adiposity was increased, deposition of white adipose tissue in other regio...

  6. Aquatic metabolism response to the hydrologic alteration in the Yellow River estuary, China

    Science.gov (United States)

    Shen, Xiaomei; Sun, Tao; Liu, Fangfang; Xu, Jing; Pang, Aiping

    2015-06-01

    Successful artificial hydrologic regulation and environmental flow assessments for the ecosystem protection require an accurate understanding of the linkages between flow events and biotic responses. To explore an ecosystem's functional responses to hydrologic alterations, we analysed spatial and temporal variations in aquatic metabolism and the main factors influenced by artificial hydrologic alterations based on the data collected from 2009 to 2012 in the Yellow River estuary, China. Gross primary production (GPP) ranged from 0.002 to 8.488 mg O2 L-1 d-1. Ecosystem respiration (ER) ranged from 0.382 to 8.968 mg O2 L-1 d-1. Net ecosystem production (NEP) ranged from -5.792 to 7.293 mg O2 L-1 d-1 and the mean of NEP was -0.506 mg O2 L-1 d-1, which means that the trophic status of entire estuary was near to balance. The results showed that seasonal variations in the aquatic metabolism are influenced by the hydrologic alteration in the estuary. High water temperature and solar radiation in summer are associated with low turbidity and consequently high rates of GPP and ER, making the estuary net autotrophic in summer, and that also occurred after water-sediment regulation in August. Turbidity and water temperature were identified as two particularly important factors that influenced the variation in the metabolic balance. As a result, metabolism rate did not decrease but increased after the regulation. ER increased significantly in summer and autumn and reached a maximum after the water-sediment regulation in September. GPP and NEP reached a maximum value after the water-sediment regulation in August, and then decreased in autumn. Estuarine ecosystem shifted from net heterotrophy in spring to net autotrophy in summer, and then to net heterotrophy in autumn. Our study indicated that estuarine metabolism may recover to a high level faster in summer than that in other seasons after the short-term water-sediment regulation due to higher water temperature and nutrients.

  7. Impact of surfactant-induced wettability alterations on DNAPL invasion in quartz and iron oxide-coated sand systems

    Science.gov (United States)

    Molnar, Ian L.; O'Carroll, Denis M.; Gerhard, Jason I.

    2011-01-01

    Dense non-aqueous phase liquids (DNAPLs) present in the subsurface may contain surface active compounds that impact DNAPL migration and distribution. While a number of studies have revealed the role surface active compounds play in altering the wettability of quartz sand, few have considered the implications for other minerals common to contaminated sites. This study extends understanding of DNAPL/surfactant wettability to iron oxide surfaces. Specifically, quartz and iron oxide-coated sands in a tetrachloroethene (PCE)/water system containing the organic base (an organic molecule that acts as a base) dodecylamine (DDA) were compared at a variety of scales. Wettability of the minerals' surfaces, and the impact of wettability on capillary resistance to DNAPL entry, were assessed as a function of pH through: (i) advancing and receding contact angles, (ii) primary drainage capillary pressure-saturation experiments, and (iii) small, two-dimensional, flow cell experiments. The work revealed that, at neutral pH and under identical boundary capillary pressures, DNAPL invaded quartz sand but not iron oxide-coated sand; however, at low pH, DNAPL invaded both sands equally. These differences were demonstrated to be due to wettability alterations associated with the strength of attractive forces between DDA and the mineral surface, dictated by the isolectric point of the minerals and system pH. Observed differences in DNAPL invasion behavior were consistent with measured intrinsic contact angles and P c-S relationships, the latter requiring scaling by the operative contact angle inside the porous medium for a meaningful comparison. This study suggests that the distribution of minerals (and, more specifically, their isoelectric points), as well as the aqueous phase pH at a given site, may have a significant impact on the DNAPL source zone architecture.

  8. Cytochrome P450-mediated metabolic alterations in preeclampsia evaluated by quantitative steroid signatures.

    Science.gov (United States)

    Moon, Ju-Yeon; Moon, Myeong Hee; Kim, Ki Tae; Jeong, Dae Hoon; Kim, Young Nam; Chung, Bong Chul; Choi, Man Ho

    2014-01-01

    Although preeclampsia has been suggested potential risk factors including placental and systemic inflammation, oxidative stress, and abnormal steroid metabolism during pregnancy, the pathogenesis of preeclampsia has not fully been elucidated, particularly in steroid metabolism. The association between various cytochrome P450 (CYP)-mediated steroid metabolic markers and preeclampsia risk was therefore investigated. The serum levels of 54 CYP-mediated regioselective hydroxysteroids and their substrates were quantitatively evaluated from both pregnant women with preeclampsia (n=30; age, 30.8±4.5 years) and normotensive controls (n=30; age, 31.0±3.5 years), who were similar with respect to maternal age, gestational age, and body mass index. The levels of 6ß-, 7a-, and 11ß-hydroxymetabolites of androgens and corticoids were significantly increased in women with preeclampsia. In addition, the levels of oxysterols, including 7a-, 7ß-, 4ß-, 20a-, 24S-, and 27-hydroxycholesterol, were markedly higher, while the levels of 16a-OH-DHEA, 16a-OH-androstenedione, and cholesterol were significantly decreased in patients. The 6ß-hydroxylation of androgens and corticoids by CYP3A4 (P2.0-fold) were positively correlated with the conditions of preeclampsia. Our metabolic profiling suggests the CYP-mediated alterations in steroid metabolism and hydroxylation in pregnancy-induced hypertension. These multiple markers could serve as background information for improved clinical diagnosis and management during pregnancy. This article is part of a Special Issue entitled "Pregnancy and Steroids". Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. The effect of alterations in total coenzyme A on metabolic pathways in the liver and heart

    Energy Technology Data Exchange (ETDEWEB)

    Schlosser, C.A.S.

    1989-01-01

    The first set of experiments involved in vitro experiments using primary cultures of rat hepatocytes. A range of conditions were developed which resulted in cell cultures with variations in total CoA over a range of 1.3 to 2.9 nmol/mg protein with identical hormonal activation which simulated metabolic stress. Elevations of total CoA levels above that of controls due to preincubation with cyanamide plus pantothenate were correlated with diminished rates of total ketone body production, 3-hydroxybutyrate production and ratios of 3 hydroxybutyrate/acetoactetate with palmitate as substrate. In contrast, cells with elevated total CoA levels had higher rates of ({sup 14}C) CO{sub 2} production from radioactive palmitate which implied greater flux of acetyl CoA units into the TCA cycle and less to the pathway of ketogenesis. The second set of experiments were designed to alter total CoA levels in vivo by maintaining rats on a chronic ethanol diet with or without pantothenate-supplementation. The effect of alterations of CoA on mitochondrial metabolism was evaluated by measuring substrate oxidation rates in liver and heat mitochondria as well as ketone body production with palmitoyl-1-carnitine as substrate.

  10. Altered dopamine and serotonin metabolism in motorically asymptomatic R6/2 mice.

    Directory of Open Access Journals (Sweden)

    Fanny Mochel

    Full Text Available The pattern of cerebral dopamine (DA abnormalities in Huntington disease (HD is complex, as reflected by the variable clinical benefit of both DA antagonists and agonists in treating HD symptoms. In addition, little is known about serotonin metabolism despite the early occurrence of anxiety and depression in HD. Post-mortem enzymatic changes are likely to interfere with the in vivo profile of biogenic amines. Hence, in order to reliably characterize the regional and chronological profile of brain neurotransmitters in a HD mouse model, we used a microwave fixation system that preserves in vivo concentrations of dopaminergic and serotoninergic amines. DA was decreased in the striatum of R6/2 mice at 8 and 12 weeks of age while DA metabolites, 3-methoxytyramine and homovanillic acid, were already significantly reduced in 4-week-old motorically asymptomatic R6/2 mice. In the striatum, hippocampus and frontal cortex of 4, 8 and 12-week-old R6/2 mice, serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly decreased in association with a decreased turnover of serotonin. In addition, automated high-resolution behavioural analyses displayed stress-like behaviours such as jumping and grooming and altered spatial learning in R6/2 mice at age 4 and 6 weeks respectively. Therefore, we describe the earliest alterations of DA and serotonin metabolism in a HD murine model. Our findings likely underpin the neuropsychological symptoms at time of disease onset in HD.

  11. Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses.

    Science.gov (United States)

    Webb, Tonya J; Carey, Gregory B; East, James E; Sun, Wenji; Bollino, Dominique R; Kimball, Amy S; Brutkiewicz, Randy R

    2016-08-01

    Natural killer T (NKT) cells play a critical role in the host's innate immune response. CD1d-mediated presentation of glycolipid antigens to NKT cells has been established; however, the mechanisms by which NKT cells recognize infected or cancerous cells remain unclear. 5(')-AMP activated protein kinase (AMPK) is a master regulator of lipogenic pathways. We hypothesized that activation of AMPK during infection and malignancy could alter the repertoire of antigens presented by CD1d and serve as a danger signal to NKT cells. In this study, we examined the effect of alterations in metabolism on CD1d-mediated antigen presentation to NKT cells and found that an infection with lymphocytic choriomeningitis virus rapidly increased CD1d-mediated antigen presentation. Hypoxia inducible factors (HIF) enhance T-cell effector functions during infection, therefore antigen presenting cells pretreated with pharmacological agents that inhibit glycolysis, induce HIF and activate AMPK were assessed for their ability to induce NKT-cell responses. Pretreatment with 2-deoxyglucose, cobalt chloride, AICAR and metformin significantly enhanced CD1d-mediated NKT-cell activation. In addition, NKT cells preferentially respond to malignant B cells and B-cell lymphomas express HIF-1α. These data suggest that targeting cellular metabolism may serve as a novel means of inducing innate immune responses. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Acute dim light at night increases body mass, alters metabolism, and shifts core body temperature circadian rhythms.

    Science.gov (United States)

    Borniger, Jeremy C; Maurya, Santosh K; Periasamy, Muthu; Nelson, Randy J

    2014-10-01

    The circadian system is primarily entrained by the ambient light environment and is fundamentally linked to metabolism. Mounting evidence suggests a causal relationship among aberrant light exposure, shift work, and metabolic disease. Previous research has demonstrated deleterious metabolic phenotypes elicited by chronic (>4 weeks) exposure to dim light at night (DLAN) (∼ 5 lux). However, the metabolic effects of short-term (body mass, alter whole body metabolism, and display altered body temperature (Tb) and activity rhythms compared to mice maintained in dark nights. Our data largely support these predictions; DLAN mice gained significantly more mass, reduced whole body energy expenditure, increased carbohydrate over fat oxidation, and altered temperature circadian rhythms. Importantly, these alterations occurred despite similar activity locomotor levels (and rhythms) and total food intake between groups. Peripheral clocks are potently entrained by body temperature rhythms, and the deregulation of body temperature we observed may contribute to metabolic problems due to "internal desynchrony" between the central circadian oscillator and temperature sensitive peripheral clocks. We conclude that even relatively short-term exposure to low levels of nighttime light can influence metabolism to increase mass gain.

  13. Long-term alteration of bentonite in the presence of metallic iron

    International Nuclear Information System (INIS)

    Kumpulainen, Sirpa; Kiviranta, Leena; Carlsson, Torbjoern; Muurinen, Arto; Svensson, Daniel; Sasamoto, Hiroshi; Yui, Mikatzu; Wersin, Paul; Rosch, Dominic

    2010-05-01

    According to the KBS-3H concept, each copper canister containing spent nuclear fuel will be surrounded by a bentonite buffer and a perforated steel cylinder. Since steel is unstable in wet bentonite, it will corrode and the corrosion products will interact with the surrounding bentonite in ways that are not fully understood. Such interaction may seriously impair the bentonite's functioning as a buffer material, e.g. by lowering its CEC or decreasing its swelling capacity. This report presents results from two iron-bentonite experiments carried out under quite different conditions at VTT (Finland) and JAEA (Japan). Both studies focused on long-term iron-bentonite interactions under anaerobic conditions. The study at VTT comprised eight years long experiments focused on diffusive based interactions between solid cast-iron and compacted MX-80 bentonite (dry density 1.5-1.6 g/cm 3 ) in contact with an aqueous 0.5 M NaCl solution. The study at JAEA comprised ten years long batch experiments, each involving a mixture of metallic iron powder (25 g), an industrially refined Na bentonite, Kunipia F, which contains more than 99% montmorillonite (25 g), and an aqueous solution (250 mL). Samples were sent to B+Tech in airtight steel vessels filled with N 2 and subsequently analyzed at various laboratories in Finland and Sweden. The JAEA samples differed with regard to the initial solution chemistry, which was either distilled water, 0.3 M NaCl, 0.6 M NaCl, 0.1 M NaHCO 3 , or 0.05 M Na 2 SO 4 . The analyses of the MX-80 bentonite samples were carried out on samples containing a cast iron cylinder and also on corresponding background samples with no cast iron. In addition, the external solution and gas phase in contact with the bentonite were analyzed. Briefly, the gas contained H 2 , most possibly caused by corrosion of the cast iron, and CO 2 , mainly as a result of carbonate dissolution. The eight years old external solution exhibited, inter alia, reducing conditions, a pH of

  14. Long-term alteration of bentonite in the presence of metallic iron

    Energy Technology Data Exchange (ETDEWEB)

    Kumpulainen, Sirpa; Kiviranta, Leena (BandTech Oy (Finland)); Carlsson, Torbjoern; Muurinen, Arto (VTT (Finland)); Svensson, Daniel (Svensk Kaernbraenslehantering AB (Sweden)); Sasamoto, Hiroshi; Yui, Mikatzu (JAEA (Japan)); Wersin, Paul; Rosch, Dominic (Gruner Ltd (Switzerland))

    2010-05-15

    According to the KBS-3H concept, each copper canister containing spent nuclear fuel will be surrounded by a bentonite buffer and a perforated steel cylinder. Since steel is unstable in wet bentonite, it will corrode and the corrosion products will interact with the surrounding bentonite in ways that are not fully understood. Such interaction may seriously impair the bentonite's functioning as a buffer material, e.g. by lowering its CEC or decreasing its swelling capacity. This report presents results from two iron-bentonite experiments carried out under quite different conditions at VTT (Finland) and JAEA (Japan). Both studies focused on long-term iron-bentonite interactions under anaerobic conditions. The study at VTT comprised eight years long experiments focused on diffusive based interactions between solid cast-iron and compacted MX-80 bentonite (dry density 1.5-1.6 g/cm3) in contact with an aqueous 0.5 M NaCl solution. The study at JAEA comprised ten years long batch experiments, each involving a mixture of metallic iron powder (25 g), an industrially refined Na bentonite, Kunipia F, which contains more than 99% montmorillonite (25 g), and an aqueous solution (250 mL). Samples were sent to B+Tech in airtight steel vessels filled with N{sub 2} and subsequently analyzed at various laboratories in Finland and Sweden. The JAEA samples differed with regard to the initial solution chemistry, which was either distilled water, 0.3 M NaCl, 0.6 M NaCl, 0.1 M NaHCO{sub 3}, or 0.05 M Na{sub 2}SO{sub 4}. The analyses of the MX-80 bentonite samples were carried out on samples containing a cast iron cylinder and also on corresponding background samples with no cast iron. In addition, the external solution and gas phase in contact with the bentonite were analyzed. Briefly, the gas contained H{sub 2}, most possibly caused by corrosion of the cast iron, and CO{sub 2}, mainly as a result of carbonate dissolution. The eight years old external solution exhibited, inter alia

  15. What the Erythrocytic Nuclear Alteration Frequencies Could Tell Us about Genotoxicity and Macrophage Iron Storage?

    Directory of Open Access Journals (Sweden)

    Juliana M M Gomes

    Full Text Available Erythrocytic nuclear alterations have been considered as an indicative of organism's exposure to genotoxic agents. Due to their close relationship among their frequencies and DNA damages, they are considered excellent markers of exposure in eukaryotes. However, poor data has been found in literature concerning their genesis, differential occurrence and their life span. In this study, we use markers of cell viability; genotoxicity and cellular turn over in order to shed light to these events. Tilapia and their blood were exposed to cadmium in acute exposure and in vitro assays. They were analyzed using flow cytometry for oxidative stress and membrane disruption, optical microscopy for erythrocytic nuclear alteration, graphite furnace atomic absorption spectrometry for cadmium content in aquaria water, blood and cytochemical and analytical electron microscopy techniques for the hemocateretic aspects. The results showed a close relationship among the total nuclear alterations and cadmium content in the total blood and melanomacrophage centres area, mismatching reactive oxygen species and membrane damages. Moreover, nuclear alterations frequencies (vacuolated, condensed and blebbed showed to be associated to cadmium exposure whereas others (lobed and bud were associated to depuration period. Decrease on nuclear alterations frequencies was also associated with hemosiderin increase inside spleen and head kidney macrophages mainly during depurative processes. These data disclosure in temporal fashion the main processes that drive the nuclear alterations frequencies and their relationship with some cellular and systemic biomarkers.

  16. Altered metabolism in the melatonin-related receptor (GPR50) knockout mouse.

    Science.gov (United States)

    Ivanova, Elena A; Bechtold, David A; Dupré, Sandrine M; Brennand, John; Barrett, Perry; Luckman, Simon M; Loudon, Andrew S I

    2008-01-01

    The X-linked orphan receptor GPR50 shares 45% homology with the melatonin receptors, yet its ligand and physiological function remain unknown. Here we report that mice lacking functional GPR50 through insertion of a lacZ gene into the coding sequence of GPR50 exhibit an altered metabolic phenotype. GPR50 knockout mice maintained on normal chow exhibit lower body weight than age-matched wild-type littermates by 10 wk of age. Furthermore, knockout mice were partially resistant to diet-induced obesity. When placed on a high-energy diet (HED) for 5 wk, knockout mice consumed significantly more food per unit body weight yet exhibited an attenuated weight gain and reduced body fat content compared with wild-type mice. Wheel-running activity records revealed that, although GPR50 knockout mice showed no alteration of circadian period, the overall levels of activity were significantly increased over wild types in both nocturnal and diurnal phases. In line with this, basal metabolic rate (O2 consumption, CO2 production, and respiratory quotient) was found to be elevated in knockout mice. Using in situ hybridization (wild-type mice) and beta-galactosidase activity (from LacZ insertion element in knockout mice), brain expression of GPR50 was found to be restricted to the ependymal layer of the third ventricle and dorsomedial nucleus of the hypothalamus. GPR50 expression was highly responsive to energy status, showing a significantly reduced expression following both fasting and 5 wk of HED. These data implicate GPR50 as an important regulator of energy metabolism.

  17. Is age a risk factor for liver disease and metabolic alterations in ataxia Telangiectasia patients?

    Science.gov (United States)

    Paulino, Talita Lemos; Rafael, Marina Neto; Hix, Sonia; Shigueoka, David Carlos; Ajzen, Sergio Aron; Kochi, Cristiane; Suano-Souza, Fabíola Isabel; da Silva, Rosangela; Costa-Carvalho, Beatriz T; Sarni, Roseli O S

    2017-08-04

    Ataxia telangiectasia (A-T) is a neurodegenerative disease that leads to mitochondrial dysfunction and oxidative stress. Insulin resistance (IR), type 2 diabetes and the risk for development of cardiovascular disease was recently associated as an extended phenotype of the disease. We aimed to assess IR; liver involvement; carotid intima-media thickness (cIMT) and metabolic alterations associated to cardiovascular risk in A-T patients, and relate them with age. Glucose metabolism alterations were found in 54.6% of the patients. Hepatic steatosis was diagnosed in 11/17 (64.7%) A-T patients. AST/ALT ratio > 1 was observed in 10/17 (58.8%). A strong positive correlation was observed between insulin sum concentrations with ALT (r = 0.782, p < 0.004) and age (r = 0.818, p = 0.002). Dyslipidemia was observed in 55.5% of the patients. The apolipoprotein (Apo-B)/ApoA-I ratio (r = 0.619; p < 0.01), LDL/HDL-c (r = 0.490; p < 0.05) and the Apo-B levels (r = 0.545; p < 0.05) were positively correlated to cIMT. Metabolic disorders implicated in cardiovascular and liver diseases are frequently observed in adolescent A-T patients and those tend to get worse as they become older. Therefore, nutritional intervention and the use of drugs may be necessary.

  18. Alterations in the placental methylome with maternal obesity and evidence for metabolic regulation.

    Science.gov (United States)

    Mitsuya, Kohzoh; Parker, Ashley N; Liu, Lu; Ruan, Jianhua; Vissers, Margreet C M; Myatt, Leslie

    2017-01-01

    The inflammatory and metabolic derangements of obesity in pregnant women generate an adverse intrauterine environment, increase pregnancy complications and adverse fetal outcomes and program the fetus for obesity and metabolic syndrome in later life. We hypothesized that epigenetic modifications in placenta including altered DNA methylation/hydroxymethylation may mediate these effects. Term placental villous tissue was collected following cesarean section from lean (prepregnancy BMI30) women. Genomic DNA was isolated, methylated and hydroxymethylated DNA immunoprecipitated and hybridized to the NimbleGen 2.1M human DNA methylation array. Intermediate metabolites in placental tissues were measured by HPLC-ESI-MS, ascorbate levels by reverse phase HPLC and gene expression by RT-PCR. Differentially methylated and hydroxymethylated regions occurred across the genome, with a 21% increase in methylated but a 31% decrease in hydroxymethylated regions in obese vs lean groups. Whereas increased methylation and decreased methylation was evident around transcription start sites of multiple genes in the GH/CSH and PSG gene clusters on chromosomes 17 and 19 in other areas there was no relationship. Increased methylation was associated with decreased expression only for some genes in these clusters. Biological pathway analysis revealed the 262 genes which showed reciprocal differential methylation/ hydroxymethylation were enriched for pregnancy, immune response and cell adhesion-linked processes. We found a negative relationship for maternal BMI but a positive relationship for ascorbate with α-ketoglutarate a metabolite that regulates ten eleven translocase (TET) which mediates DNA methylation. We provide evidence for the obese maternal metabolic milieu being linked to an altered DNA methylome that may affect placental gene expression in relation to adverse outcomes.

  19. Alterations in the placental methylome with maternal obesity and evidence for metabolic regulation.

    Directory of Open Access Journals (Sweden)

    Kohzoh Mitsuya

    Full Text Available The inflammatory and metabolic derangements of obesity in pregnant women generate an adverse intrauterine environment, increase pregnancy complications and adverse fetal outcomes and program the fetus for obesity and metabolic syndrome in later life. We hypothesized that epigenetic modifications in placenta including altered DNA methylation/hydroxymethylation may mediate these effects. Term placental villous tissue was collected following cesarean section from lean (prepregnancy BMI30 women. Genomic DNA was isolated, methylated and hydroxymethylated DNA immunoprecipitated and hybridized to the NimbleGen 2.1M human DNA methylation array. Intermediate metabolites in placental tissues were measured by HPLC-ESI-MS, ascorbate levels by reverse phase HPLC and gene expression by RT-PCR. Differentially methylated and hydroxymethylated regions occurred across the genome, with a 21% increase in methylated but a 31% decrease in hydroxymethylated regions in obese vs lean groups. Whereas increased methylation and decreased methylation was evident around transcription start sites of multiple genes in the GH/CSH and PSG gene clusters on chromosomes 17 and 19 in other areas there was no relationship. Increased methylation was associated with decreased expression only for some genes in these clusters. Biological pathway analysis revealed the 262 genes which showed reciprocal differential methylation/ hydroxymethylation were enriched for pregnancy, immune response and cell adhesion-linked processes. We found a negative relationship for maternal BMI but a positive relationship for ascorbate with α-ketoglutarate a metabolite that regulates ten eleven translocase (TET which mediates DNA methylation. We provide evidence for the obese maternal metabolic milieu being linked to an altered DNA methylome that may affect placental gene expression in relation to adverse outcomes.

  20. Aluminum stress inhibits root growth and alters physiological and metabolic responses in chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Choudhury, Shuvasish; Sharma, Parul

    2014-12-01

    Chickpea (Cicer arietinum L.) roots were treated with aluminum (Al3+) in calcium chloride (CaCl2) solution (pH 4.7) and growth responses along with physiological and metabolic changes were investigated. Al3+ treatment for 7d resulted in a dose dependent decline of seed germination and inhibition of root growth. A significant (p ≤ 0.05) decline in fresh and dry biomass were observed after 7d of Al3+ stress.The root growth (length) was inhibited after 24 and 48 h of stress imposition. The hydrogen peroxide (H2O2) levels increased significantly (p ≤ 0.05) with respect to control in Al3+ treated roots. The hematoxylin and Evans blue assay indicated significant (p ≤ 0.05) accumulation of Al3+ in the roots and loss of plasma membrane integrity respectively. The time-course evaluation of lipid peroxidation showed increase in malondialdehyde (MDA) after 12, 24 and 48 h of stress imposition. Al3+ treatment did not alter the MDA levels after 2 or 4 h of stress, however, a minor increase was observed after 6 and 10 h of treatment. The proton (1H) nuclear magnetic resonance (NMR) spectrum of the perchloric acid extracts showed variation in the abundance of metabolites and suggested a major metabolic shift in chickpea root during Al3+ stress. The key differences that were observed include changes in energy metabolites. Accumulation of phenolic compounds suggested its possible role in Al3+ exclusion in roots during stress. The results suggested that Al3+ alters growth pattern in chickpea and induces reactive oxygen species (ROS) production that causes physiological and metabolic changes.

  1. High fructose corn syrup induces metabolic dysregulation and altered dopamine signaling in the absence of obesity

    Science.gov (United States)

    2017-01-01

    The contribution of high fructose corn syrup (HFCS) to metabolic disorder and obesity, independent of high fat, energy-rich diets, is controversial. While high-fat diets are widely accepted as a rodent model of diet-induced obesity (DIO) and metabolic disorder, the value of HFCS alone as a rodent model of DIO is unclear. Impaired dopamine function is associated with obesity and high fat diet, but the effect of HFCS on the dopamine system has not been investigated. The objective of this study was to test the effect of HFCS on weight gain, glucose regulation, and evoked dopamine release using fast-scan cyclic voltammetry. Mice (C57BL/6) received either water or 10% HFCS solution in combination with ad libitum chow for 15 weeks. HFCS consumption with chow diet did not induce weight gain compared to water, chow-only controls but did induce glucose dysregulation and reduced evoked dopamine release in the dorsolateral striatum. These data show that HFCS can contribute to metabolic disorder and altered dopamine function independent of weight gain and high-fat diets. PMID:29287121

  2. Kalpaamruthaa ameliorates mitochondrial and metabolic alterations in diabetes mellitus induced cardiovascular damage.

    Science.gov (United States)

    Latha, Raja; Shanthi, Palanivelu; Sachdanandam, Panchanadham

    2014-12-01

    Efficacy of Kalpaamruthaa on the activities of lipid and carbohydrate metabolic enzymes, electron transport chain complexes and mitochondrial ATPases were studied in heart and liver of experimental rats. Cardiovascular damage (CVD) was developed in 8 weeks after type 2 diabetes mellitus induction with high fat diet (2 weeks) and low dose of streptozotocin (2 × 35 mg/kg b.w. i.p. in 24 hr interval). In CVD-induced rats, the activities of total lipase, cholesterol ester hydrolase and cholesterol ester synthetase were increased, while lipoprotein lipase and lecithin-cholesterol acyltransferase activities were decreased. The activities of lipid-metabolizing enzymes were altered by Kalpaamruthaa in CVD-induced rats towards normal. Kalpaamruthaa modulated the activities of glycolytic enzymes (hexokinase, phosphogluco-isomerase, aldolase and glucose-6-phosphate dehydrogenase), gluconeogenic enzymes (glucose-6-phosphatase and fructose-1, 6-bisphosphatase) and glycogenolytic enzyme (glycogen phosphorylase) along with increased glycogen content in the liver of CVD-induced rats. The activities of isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, α-ketoglutarate dehydrogenase, Complexes and ATPases (Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase) were decreased in CVD-induced rats, which were ameliorated by the treatment with Kalpaamruthaa. This study ascertained the efficacy of Kalpaamruthaa for the treatment of CVD in diabetes through the modulation of metabolizing enzymes and mitochondrial dysfunction.

  3. Inflammatory and Metabolic Alterations of Kager's Fat Pad in Chronic Achilles Tendinopathy.

    Science.gov (United States)

    Pingel, Jessica; Petersen, M Christine H; Fredberg, Ulrich; Kjær, Søren G; Quistorff, Bjørn; Langberg, Henning; Hansen, Jacob B

    2015-01-01

    Achilles tendinopathy is a painful inflammatory condition characterized by swelling, stiffness and reduced function of the Achilles tendon. Kager's fat pad is an adipose tissue located in the area anterior to the Achilles tendon. Observations reveal a close physical interplay between Kager's fat pad and its surrounding structures during movement of the ankle, suggesting that Kager's fat pad may stabilize and protect the mechanical function of the ankle joint. The aim of this study was to characterize whether Achilles tendinopathy was accompanied by changes in expression of inflammatory markers and metabolic enzymes in Kager's fat pad. A biopsy was taken from Kager's fat pad from 31 patients with chronic Achilles tendinopathy and from 13 healthy individuals. Gene expression was measured by reverse transcription-quantitative PCR. Focus was on genes related to inflammation and lipid metabolism. Expression of the majority of analyzed inflammatory marker genes was increased in patients with Achilles tendinopathy compared to that in healthy controls. Expression patterns of the patient group were consistent with reduced lipolysis and increased fatty acid β-oxidation. In the fat pad, the pain-signaling neuropeptide substance P was found to be present in one third of the subjects in the Achilles tendinopathy group but in none of the healthy controls. Gene expression changes in Achilles tendinopathy patient samples were consistent with Kager's fat pad being more inflamed than in the healthy control group. Additionally, the results indicate an altered lipid metabolism in Kager's fat pad of Achilles tendinopathy patients.

  4. Taurine alters respiratory gas exchange and nutrient metabolism in type 2 diabetic rats.

    Science.gov (United States)

    Harada, Nagakatsu; Ninomiya, Chika; Osako, Yoshie; Morishima, Masaki; Mawatari, Kazuaki; Takahashi, Akira; Nakaya, Yutaka

    2004-07-01

    To assess the effect of taurine supplementation on respiratory gas exchange, which might reflect the improved metabolism of glucose and/or lipid in the type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Male OLETF rats (16 weeks of age) were randomly divided into two groups: unsupplemented group and taurine-supplemented (3% in drinking water) group. After 9 weeks of treatment, indirect calorimetry and insulin tolerance tests were conducted. The amounts of visceral fat pads, tissue glycogen, the blood concentrations of glucose, triacylglycerol, taurine, and electrolytes, and the level of hematocrit were compared between groups. A nondiabetic rat strain (Long-Evans Tokushima Otsuka) was used as the age-matched normal control. The indirect calorimetry showed that the treatment of OLETF rats with taurine could reduce a part of postprandial glucose oxidation possibly responsible for the increase of triacylglycerol synthesis in the body. Taurine supplementation also improved hyperglycemia and insulin resistance and increased muscle glycogen content in the OLETF rats. Supplementation with taurine increased the blood concentration of taurine and electrolyte and fluid volume, all of which were considered to be related to the improvement of metabolic disturbance in OLETF rats. Taurine supplementation may be an effective treatment for glucose intolerance and fat/lipid accumulation observed in type 2 diabetes associated with obesity. These metabolic changes might be ascribed, in part, to the alteration of circulating blood profiles, where the improved hyperglycemia and/or the blood accumulation of taurine itself would play roles. Copyright 2004 NAASO

  5. Fluvoxamine alters the activity of energy metabolism enzymes in the brain.

    Science.gov (United States)

    Ferreira, Gabriela K; Cardoso, Mariane R; Jeremias, Isabela C; Gonçalves, Cinara L; Freitas, Karolina V; Antonini, Rafaela; Scaini, Giselli; Rezin, Gislaine T; Quevedo, João; Streck, Emilio L

    2014-09-01

    Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg) for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent.

  6. Exposure to 2,4-dichlorophenoxyacetic acid alters glucose metabolism in immature rat Sertoli cells.

    Science.gov (United States)

    Alves, M G; Neuhaus-Oliveira, A; Moreira, P I; Socorro, S; Oliveira, P F

    2013-07-01

    The purpose of this study was to determine the effects of 2,4-D, an herbicide used worldwide also known as endocrine disruptor, in Sertoli cell (SC) metabolism. Immature rat SCs were maintained 50h under basal conditions or exposed to 2,4-D (100nM, 10μM and 1mM). SCs exposed to 10μM and 1mM of 2,4-D presented lower intracellular glucose and lactate content. Exposure to 10μM of 2,4-D induced a significant decrease in glucose transporter-3 mRNA levels and phosphofructokinase-1 mRNA levels decreased in cells exposed to 100nM and 10μM of 2,4-D. Exposure to 100nM and 10μM also induced a decrease in lactate dehydrogenase (LDH) mRNA levels while the LDH protein levels were only decreased in cells exposed to 1mM of 2,4-D. Exposure to 2,4-D altered glucose uptake and metabolization in SCs, as well as lactate metabolism and export that may result in impaired spermatogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Fluvoxamine alters the activity of energy metabolism enzymes in the brain

    Directory of Open Access Journals (Sweden)

    Gabriela K. Ferreira

    2014-09-01

    Full Text Available Objective: Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Methods: Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. Results: The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Conclusions: Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent.

  8. Long-term alteration of bentonite in the presence of metallic iron

    International Nuclear Information System (INIS)

    Kumpulainen, S.; Kiviranta, L.; Carlsson, T.; Muurinen, A.; Svensson, D.; Sasamoto, Hiroshi; Yui, Mikatzu; Wersin, P.; Rosch, D.

    2011-12-01

    According to the KBS-3H concept, each copper canister containing spent nuclear fuel will be surrounded by a bentonite buffer and a perforated steel cylinder. Since steel is unstable in wet bentonite, it will corrode and the corrosion products will interact with the surrounding bentonite in ways that are not fully understood. Such interaction may seriously impair the bentonite's functioning as a buffer material, e.g. by lowering its CEC or decreasing its swelling capacity. This report presents results from two ironbentonite experiments carried out under quite different conditions at VTT (Finland) and JAEA (Japan). Both studies focused on long-term iron-bentonite interactions under anaerobic conditions. The study at VTT comprised eight years long experiments focused on diffusive based interactions between solid cast-iron and compacted MX-80 bentonite (dry density 1.5- 1.6 g/cm 3 ) in contact with an aqueous 0.5 M NaCl solution. The study at JAEA comprised ten years long batch experiments, each involving a mixture of metallic iron powder (25 g), an industrially refined Na bentonite, Kunipia F, which contains more than 99% montmorillonite (25 g), and an aqueous solution (250 mL). Samples were sent to B and Tech in airtight steel vessels filled with N 2 and subsequently analyzed at various laboratories in Finland and Sweden. The JAEA samples differed with regard to the initial solution chemistry, which was either distilled water, 0.3 M NaCl, 0.6 M NaCl, 0.1 M NaHCO 3 , or 0.05 M Na 2 SO 4 . The analyses of the MX-80 bentonite samples were carried out on samples containing a cast iron cylinder and also on corresponding background samples with no cast iron. In addition, the external solution and gas phase in contact with the bentonite were analyzed. Briefly, the gas contained H 2 , most possibly caused by corrosion of the cast iron, and CO 2 , mainly as a result of carbonate dissolution. The eight years old external solution exhibited, inter alia, reducing conditions, a p

  9. Long-term alteration of bentonite in the presence of metallic iron

    Energy Technology Data Exchange (ETDEWEB)

    Kumpulainen, S.; Kiviranta, L. [B and Tech Oy, Helsinki (Finland); Carlsson, T.; Muurinen, A. [VTT Technical Research Centre of Finland, Espoo (Finland); Svensson, D. [Svensk Kaernbraenslehantering AB (SKB), Stockholm (Sweden); Sasamoto, Hiroshi; Yui, Mikatzu [Japan Atomic Energy Agency (JAEA) (Japan); Wersin, P.; Rosch, D. [Gruner Ltd, Basel (Switzerland)

    2011-12-15

    According to the KBS-3H concept, each copper canister containing spent nuclear fuel will be surrounded by a bentonite buffer and a perforated steel cylinder. Since steel is unstable in wet bentonite, it will corrode and the corrosion products will interact with the surrounding bentonite in ways that are not fully understood. Such interaction may seriously impair the bentonite's functioning as a buffer material, e.g. by lowering its CEC or decreasing its swelling capacity. This report presents results from two ironbentonite experiments carried out under quite different conditions at VTT (Finland) and JAEA (Japan). Both studies focused on long-term iron-bentonite interactions under anaerobic conditions. The study at VTT comprised eight years long experiments focused on diffusive based interactions between solid cast-iron and compacted MX-80 bentonite (dry density 1.5- 1.6 g/cm{sup 3}) in contact with an aqueous 0.5 M NaCl solution. The study at JAEA comprised ten years long batch experiments, each involving a mixture of metallic iron powder (25 g), an industrially refined Na bentonite, Kunipia F, which contains more than 99% montmorillonite (25 g), and an aqueous solution (250 mL). Samples were sent to B and Tech in airtight steel vessels filled with N{sub 2} and subsequently analyzed at various laboratories in Finland and Sweden. The JAEA samples differed with regard to the initial solution chemistry, which was either distilled water, 0.3 M NaCl, 0.6 M NaCl, 0.1 M NaHCO{sub 3}, or 0.05 M Na{sub 2}SO{sub 4}. The analyses of the MX-80 bentonite samples were carried out on samples containing a cast iron cylinder and also on corresponding background samples with no cast iron. In addition, the external solution and gas phase in contact with the bentonite were analyzed. Briefly, the gas contained H{sub 2}, most possibly caused by corrosion of the cast iron, and CO{sub 2}, mainly as a result of carbonate dissolution. The eight years old external solution exhibited

  10. Metabolic alterations in broiler chickens experimentally infected with sporulated oocysts of Eimeria maxima

    Directory of Open Access Journals (Sweden)

    Fagner Luiz da Costa Freitas

    Full Text Available Metabolic and morphometric alterations of the duodenal villi caused by parasitism of chickens by Eimeria maxima were evaluated, using 100 male Cobb birds, randomly distributed into two groups (control and infected. The infected group was inoculated with 0.5 ml of a solution containing 5×103 sporulated oocysts of Eimeria maxima. Ten birds per sample were sacrificed on the 6th, 11th, 22nd and 41st days post-infection (dpi. In order to evaluate the alterations, samples of duodenum, jejunum and ileum fragments were collected after necropsy for histological analysis. Villus biometry was determined by means of a slide graduated in microns that was attached to a binocular microscope. To evaluate the biochemical data, 5 ml of blood were sampled from the birds before sacrifice. The statistical analyses were performed using the GraphPad 5 statistical software for Windows. Tukey's multiple comparison test (p <0.05 was performed for the different dpi's and the unpaired t test for the difference between the groups. Infection by E. maxima causes both qualitative and quantitative alterations to the structure of the intestinal villi, thereby interfering with the absorption of nutrients such as calcium, phosphorus, magnesium, protein and lipids, with consequent reductions in the birds' weights.

  11. Metabolic alterations in broiler chickens experimentally infected with sporulated oocysts of Eimeria maxima.

    Science.gov (United States)

    Freitas, Fagner Luiz da Costa

    2014-01-01

    Metabolic and morphometric alterations of the duodenal villi caused by parasitism of chickens by Eimeria maxima were evaluated, using 100 male Cobb birds, randomly distributed into two groups (control and infected). The infected group was inoculated with 0.5 ml of a solution containing 5 × 10³ sporulated oocysts of Eimeria maxima. Ten birds per sample were sacrificed on the 6th, 11th, 22nd and 41st days post-infection (dpi). In order to evaluate the alterations, samples of duodenum, jejunum and ileum fragments were collected after necropsy for histological analysis. Villus biometry was determined by means of a slide graduated in microns that was attached to a binocular microscope. To evaluate the biochemical data, 5 ml of blood were sampled from the birds before sacrifice. The statistical analyses were performed using the GraphPad 5 statistical software for Windows. Tukey's multiple comparison test (p <0.05) was performed for the different dpi's and the unpaired t test for the difference between the groups. Infection by E. maxima causes both qualitative and quantitative alterations to the structure of the intestinal villi, thereby interfering with the absorption of nutrients such as calcium, phosphorus, magnesium, protein and lipids, with consequent reductions in the birds' weights.

  12. [Markers for early detection of alterations in carbohydrate metabolism after acute myocardial infarction].

    Science.gov (United States)

    de Gea-García, J H; Benali, L; Galcerá-Tomás, J; Padilla-Serrano, A; Andreu-Soler, E; Melgarejo-Moreno, A; Alonso-Fernández, N

    2014-03-01

    Undiagnosed abnormal glucose metabolism is often seen in patients admitted with acute myocardial infarction, although there is no consensus on which patients should be studied with a view to establishing an early diagnosis. The present study examines the potential of certain variables obtained upon admission to diagnose abnormal glucose metabolism. A prospective cohort study was carried out. The Intensive Care Unit of Arrixaca University Hospital (Murcia), Spain. A total of 138 patients admitted to the Intensive Care Unit with acute myocardial infarction and without known or de novo diabetes mellitus. After one year, oral glucose tolerance testing was performed. Clinical and laboratory test parameters were recorded upon admission and one year after discharge. Additionally, after one year, oral glucose tolerance tests were made, and a study was made of the capacity of the variables obtained at admission to diagnose diabetes, based on the ROC curves and multivariate analysis. Of the 138 patients, 112 (72.5%) had glucose metabolic alteration, including 16.7% with diabetes. HbA1c was independently associated with a diagnosis of diabetes (RR: 7.28, 95%CI 1.65 to 32.05, P = .009), and showed the largest area under the ROC curve for diabetes (0.81, 95%CI 0.69 to 0.92, P = .001). In patients with acute myocardial infarction, HbA1c helps identify those individuals with abnormal glucose metabolism after one year. Thus, its determination in this group of patients could be used to identify those subjects requiring a more exhaustive study in order to establish an early diagnosis. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  13. Untargeted Metabolomics Reveals Predominant Alterations in Lipid Metabolism Following Light Exposure in Broccoli Sprouts

    Directory of Open Access Journals (Sweden)

    Mariateresa Maldini

    2015-06-01

    Full Text Available The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics approach to investigate the effect of light and dark exposure on the metabolome of broccoli sprouts and we applied such an approach to provide a bird’s-eye view of the overall metabolic response after light exposure. Broccoli seeds were germinated and grown hydroponically for five days in total darkness or with a light/dark photoperiod (16 h light/8 h dark cycle. We used an ultra-performance liquid-chromatography system coupled to an ion-mobility, time-of-flight mass spectrometer to profile the large array of metabolites present in the sprouts. Differences at the metabolite level between groups were analyzed using multivariate statistical analyses, including principal component analysis and correlation analysis. Altered metabolites were identified by searching publicly available and in-house databases. Metabolite pathway analyses were used to support the identification of subtle but significant changes among groups of related metabolites that may have gone unnoticed with conventional approaches. Besides the chlorophyll pathway, light exposure activated the biosynthesis and metabolism of sterol lipids, prenol lipids, and polyunsaturated lipids, which are essential for the photosynthetic machinery. Our results also revealed that light exposure increased the levels of polyketides, including flavonoids, and oxylipins, which play essential roles in the plant’s developmental processes and defense mechanism against herbivores. This study highlights the significant contribution of light exposure to the ultimate metabolic phenotype, which might affect the cellular physiology and nutritional value of broccoli sprouts. Furthermore, this study highlights the

  14. Nighttime feeding likely alters morning metabolism but not exercise performance in female athletes.

    Science.gov (United States)

    Ormsbee, Michael J; Gorman, Katherine A; Miller, Elizabeth A; Baur, Daniel A; Eckel, Lisa A; Contreras, Robert J; Panton, Lynn B; Spicer, Maria T

    2016-07-01

    The timing of morning endurance competition may limit proper pre-race fueling and resulting performance. A nighttime, pre-sleep nutritional strategy could be an alternative method to target the metabolic and hydrating needs of the early morning athlete without compromising sleep or gastrointestinal comfort during exercise. Therefore, the purpose of this investigation was to examine the acute effects of pre-sleep chocolate milk (CM) ingestion on next-morning running performance, metabolism, and hydration status. Twelve competitive female runners and triathletes (age, 30 ± 7 years; peak oxygen consumption, 53 ± 4 mL·kg(-1)·min(-1)) randomly ingested either pre-sleep CM or non-nutritive placebo (PL) ∼30 min before sleep and 7-9 h before a morning exercise trial. Resting metabolic rate (RMR) was assessed prior to exercise. The exercise trial included a warm-up, three 5-min incremental workloads at 55%, 65%, and 75% peak oxygen consumption, and a 10-km treadmill time trial (TT). Physiological responses were assessed prior, during (incremental and TT), and postexercise. Paired t tests and magnitude-based inferences were used to determine treatment differences. TT performances were not different ("most likely trivial" improvement with CM) between conditions (PL: 52.8 ± 8.4 min vs CM: 52.8 ± 8.0 min). RMR was "likely" increased (4.8%) and total carbohydrate oxidation (g·min(-1)) during exercise was "possibly" or likely increased (18.8%, 10.1%, 9.1% for stage 1-3, respectively) with CM versus PL. There were no consistent changes to hydration indices. In conclusion, pre-sleep CM may alter next-morning resting and exercise metabolism to favor carbohydrate oxidation, but effects did not translate to 10-km running performance improvements.

  15. Morning and Evening Blue-Enriched Light Exposure Alters Metabolic Function in Normal Weight Adults

    Science.gov (United States)

    Cheung, Ivy N.; Zee, Phyllis C.; Shalman, Dov; Malkani, Roneil G.; Kang, Joseph; Reid, Kathryn J.

    2016-01-01

    Increasing evidence points to associations between light-dark exposure patterns, feeding behavior, and metabolism. This study aimed to determine the acute effects of 3 hours of morning versus evening blue-enriched light exposure compared to dim light on hunger, metabolic function, and physiological arousal. Nineteen healthy adults completed this 4-day inpatient protocol under dim light conditions (morning group) or 10.5 hours after wake (n = 10; evening group). All participants remained in dim light on Day 2 to serve as their baseline. Subjective hunger and sleepiness scales were collected hourly. Blood was sampled at 30-minute intervals for 4 hours in association with the light exposure period for glucose, insulin, cortisol, leptin, and ghrelin. Homeostatic model assessment of insulin resistance (HOMA-IR) and area under the curve (AUC) for insulin, glucose, HOMA-IR and cortisol were calculated. Comparisons relative to baseline were done using t-tests and repeated measures ANOVAs. In both the morning and evening groups, insulin total area, HOMA-IR, and HOMA-IR AUC were increased and subjective sleepiness was reduced with blue-enriched light compared to dim light. The evening group, but not the morning group, had significantly higher glucose peak value during blue-enriched light exposure compared to dim light. There were no other significant differences between the morning or the evening groups in response to blue-enriched light exposure. Blue-enriched light exposure acutely alters glucose metabolism and sleepiness, however the mechanisms behind this relationship and its impacts on hunger and appetite regulation remain unclear. These results provide further support for a role of environmental light exposure in the regulation of metabolism. PMID:27191727

  16. Targeted mutation of the MLN64 START domain causes only modest alterations in cellular sterol metabolism.

    Science.gov (United States)

    Kishida, Tatsuro; Kostetskii, Igor; Zhang, Zhibing; Martinez, Federico; Liu, Pei; Walkley, Steven U; Dwyer, Nancy K; Blanchette-Mackie, E Joan; Radice, Glenn L; Strauss, Jerome F

    2004-04-30

    The StAR-related lipid transfer (START) domain, first identified in the steroidogenic acute regulatory protein (StAR), is involved in the intracellular trafficking of lipids. Sixteen mammalian START domain-containing proteins have been identified to date. StAR, a protein targeted to mitochondria, stimulates the movement of cholesterol from the outer to the inner mitochondrial membranes, where it is metabolized into pregnenolone in steroidogenic cells. MLN64, the START domain protein most closely related to StAR, is localized to late endosomes along with other proteins involved in sterol trafficking, including NPC1 and NPC2, where it has been postulated to participate in sterol distribution to intracellular membranes. To investigate the role of MLN64 in sterol metabolism, we created mice with a targeted mutation in the Mln64 START domain, expecting to find a phenotype similar to that in humans and mice lacking NPC1 or NPC2 (progressive neurodegenerative symptoms, free cholesterol accumulation in lysosomes). Unexpectedly, mice homozygous for the Mln64 mutant allele were viable, neurologically intact, and fertile. No significant alterations in plasma lipid levels, liver lipid content and distribution, and expression of genes involved in sterol metabolism were observed, except for an increase in sterol ester storage in mutant mice fed a high fat diet. Embryonic fibroblast cells transfected with the cholesterol side-chain cleavage system and primary cultures of granulosa cells from Mln64 mutant mice showed defects in sterol trafficking as reflected in reduced conversion of endogenous cholesterol to steroid hormones. These observations suggest that the Mln64 START domain is largely dispensable for sterol metabolism in mice.

  17. Morning and Evening Blue-Enriched Light Exposure Alters Metabolic Function in Normal Weight Adults.

    Science.gov (United States)

    Cheung, Ivy N; Zee, Phyllis C; Shalman, Dov; Malkani, Roneil G; Kang, Joseph; Reid, Kathryn J

    2016-01-01

    Increasing evidence points to associations between light-dark exposure patterns, feeding behavior, and metabolism. This study aimed to determine the acute effects of 3 hours of morning versus evening blue-enriched light exposure compared to dim light on hunger, metabolic function, and physiological arousal. Nineteen healthy adults completed this 4-day inpatient protocol under dim light conditions (blue-enriched light exposure on Day 3 starting either 0.5 hours after wake (n = 9; morning group) or 10.5 hours after wake (n = 10; evening group). All participants remained in dim light on Day 2 to serve as their baseline. Subjective hunger and sleepiness scales were collected hourly. Blood was sampled at 30-minute intervals for 4 hours in association with the light exposure period for glucose, insulin, cortisol, leptin, and ghrelin. Homeostatic model assessment of insulin resistance (HOMA-IR) and area under the curve (AUC) for insulin, glucose, HOMA-IR and cortisol were calculated. Comparisons relative to baseline were done using t-tests and repeated measures ANOVAs. In both the morning and evening groups, insulin total area, HOMA-IR, and HOMA-IR AUC were increased and subjective sleepiness was reduced with blue-enriched light compared to dim light. The evening group, but not the morning group, had significantly higher glucose peak value during blue-enriched light exposure compared to dim light. There were no other significant differences between the morning or the evening groups in response to blue-enriched light exposure. Blue-enriched light exposure acutely alters glucose metabolism and sleepiness, however the mechanisms behind this relationship and its impacts on hunger and appetite regulation remain unclear. These results provide further support for a role of environmental light exposure in the regulation of metabolism.

  18. Meal time shift disturbs circadian rhythmicity along with metabolic and behavioral alterations in mice.

    Directory of Open Access Journals (Sweden)

    Ji-Ae Yoon

    Full Text Available In modern society, growing numbers of people are engaged in various forms of shift works or trans-meridian travels. Such circadian misalignment is known to disturb endogenous diurnal rhythms, which may lead to harmful physiological consequences including metabolic syndrome, obesity, cancer, cardiovascular disorders, and gastric disorders as well as other physical and mental disorders. However, the precise mechanism(s underlying these changes are yet unclear. The present work, therefore examined the effects of 6 h advance or delay of usual meal time on diurnal rhythmicities in home cage activity (HCA, body temperature (BT, blood metabolic markers, glucose homeostasis, and expression of genes that are involved in cholesterol homeostasis by feeding young adult male mice in a time-restrictive manner. Delay of meal time caused locomotive hyperactivity in a significant portion (42% of subjects, while 6 h advance caused a torpor-like symptom during the late scotophase. Accordingly, daily rhythms of blood glucose and triglyceride were differentially affected by time-restrictive feeding regimen with concurrent metabolic alterations. Along with these physiological changes, time-restrictive feeding also influenced the circadian expression patterns of low density lipoprotein receptor (LDLR as well as most LDLR regulatory factors. Strikingly, chronic advance of meal time induced insulin resistance, while chronic delay significantly elevated blood glucose levels. Taken together, our findings indicate that persistent shifts in usual meal time impact the diurnal rhythms of carbohydrate and lipid metabolisms in addition to HCA and BT, thereby posing critical implications for the health and diseases of shift workers.

  19. Study on iron metabolism in children using double labelling of 51Cr and 59Fe

    International Nuclear Information System (INIS)

    Kobayashi, Masatsura

    1974-01-01

    In the children before and after treatment for iron deficiency anemia and those on ingesting a long-term low caloric and iron diet, life span of Ashby Technique 1/2(AST) red cells, circulatory blood volume (CBV), plasma iron disappearance(PID), red cell-iron utility(RCIU), plasma-iron turnover rate(PITR), and red cell-ironturnover rate(RCITR) were respectively determined using double labeling of 51 Cr and 59 Fe, and the following results and conclusions were obtained: In the patients with iron deficiency anemia, the rate of RCIU was highly increased, and simultaneously the shortening in AST was observed. Among the children with the iron deficiency anemia, five patients were examined immediately after the improvement on the anemia by iron drugs; the serum iron (SFe) averaged 74μg/ml. So the erthropiesis appeared to recover to normal, yet AST has hardly changed, still more has it shortened. In five children with celebral palsy associated with disturbance of physical development, who had ingested a long-term liquid low iron diet no evident increase of RCIU was found except for high calues of RCITR. The shortening in AST was not entirely seen in contrast with that of the simple alimentary iron deficiency anemia. Besides the CBV measured par kg of weight showed the remarkable increase. (Oyama, S.)

  20. Iron transformations during low temperature alteration of variably serpentinized rocks from the Samail ophiolite, Oman

    Science.gov (United States)

    Mayhew, Lisa E.; Ellison, Eric T.; Miller, Hannah M.; Kelemen, Peter B.; Templeton, Alexis S.

    2018-02-01

    Partially serpentinized peridotites in the Samail ophiolite in the Sultanate of Oman currently undergo low temperature alteration and hydration both at shallow levels, with water recently in contact with the atmosphere, and at depth, with anoxic, reducing fluids. However, it is unclear how changes in the distribution and oxidation state of Fe are driving the production of energy-rich gases such as hydrogen and methane detected in peridotite catchments. We track the Fe transformations in a suite of outcrop samples representing a subset of the spectrum of least to most altered end-members of the Oman peridotites. We use microscale mineralogical and geochemical analyses including QEMSCAN, Raman spectroscopy, synchrotron radiation X-ray fluorescence (XRF) mapping, and electron microprobe wavelength dispersive spectroscopy. The less-altered peridotites possess a diversity of Fe-bearing phases including relict primary minerals (e.g. olivine, pyroxene, chromite) and secondary phases (e.g. serpentine and brucite). Raman spectroscopy and electron microprobe data (Si/(Mg + Fe)) indicate that much of the serpentine is significantly intergrown with brucite on the sub-micron scale. These data also indicate that the Fe content of the brucite ranges from 10 to 20 wt% FeO. The mineral assemblage of the highly reacted rocks is less diverse, dominated by serpentine and carbonate while olivine and brucite are absent. Magnetite is relatively rare and mainly associated with chromite. Goethite and hematite, both Fe(III)-hydroxides, were also identified in the highly altered rocks. Whole rock chemical analyses reflect these mineralogical differences and show that Fe in the partially serpentinized samples is on average more reduced (∼0.40-0.55 Fe3+/FeTotal) than Fe in the highly reacted rocks (∼0.85-0.90 Fe3+/FeTotal). We propose that olivine, brucite, chromite and, perhaps, serpentine in the less-altered peridotites act as reactive phases during low temperature alteration of the Oman

  1. Replicatively senescent human fibroblasts reveal a distinct intracellular metabolic profile with alterations in NAD+ and nicotinamide metabolism.

    Science.gov (United States)

    James, Emma L; Lane, James A E; Michalek, Ryan D; Karoly, Edward D; Parkinson, E Kenneth

    2016-12-07

    Cellular senescence occurs by proliferative exhaustion (PEsen) or following multiple cellular stresses but had not previously been subject to detailed metabolomic analysis. Therefore, we compared PEsen fibroblasts with proliferating and transiently growth arrested controls using a combination of different mass spectroscopy techniques. PEsen cells showed many specific alterations in both the NAD+ de novo and salvage pathways including striking accumulations of nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) in the amidated salvage pathway despite no increase in nicotinamide phosphoribosyl transferase or in the NR transport protein, CD73. Extracellular nicotinate was depleted and metabolites of the deamidated salvage pathway were reduced but intracellular NAD+ and nicotinamide were nevertheless maintained. However, sirtuin 1 was downregulated and so the accumulation of NMN and NR was best explained by reduced flux through the amidated arm of the NAD+ salvage pathway due to reduced sirtuin activity. PEsen cells also showed evidence of increased redox homeostasis and upregulated pathways used to generate energy and cellular membranes; these included nucleotide catabolism, membrane lipid breakdown and increased creatine metabolism. Thus PEsen cells upregulate several different pathways to sustain their survival which may serve as pharmacological targets for the elimination of senescent cells in age-related disease.

  2. Metabolic fingerprints of altered brain growth, osmoregulation and neurotransmission in a Rett syndrome model.

    Directory of Open Access Journals (Sweden)

    Angèle Viola

    Full Text Available BACKGROUND: Rett syndrome (RS is the leading cause of profound mental retardation of genetic origin in girls. Since RS is mostly caused by mutations in the MECP2 gene, transgenic animal models such as the Mecp2-deleted ("Mecp2-null" mouse have been employed to study neurological symptoms and brain function. However, an interdisciplinary approach drawing from chemistry, biology and neuroscience is needed to elucidate the mechanistic links between the genotype and phenotype of this genetic disorder. METHODOLOGY/PRINCIPAL FINDINGS: We performed, for the first time, a metabolomic study of brain extracts from Mecp2-null mice by using high-resolution magnetic resonance spectroscopy. A large number of individual water-soluble metabolites and phospholipids were quantified without prior selection for specific metabolic pathways. Results were interpreted in terms of Mecp2 gene deletion, brain cell function and brain morphology. This approach provided a "metabolic window" to brain characteristics in Mecp2-null mice (n = 4, revealing (i the first metabolic evidence of astrocyte involvement in RS (decreased levels of the astrocyte marker, myo-inositol, vs. wild-type mice; p = 0.034; (ii reduced choline phospholipid turnover in Mecp2-null vs. wild-type mice, implying a diminished potential of cells to grow, paralleled by globally reduced brain size and perturbed osmoregulation; (iii alterations of the platelet activating factor (PAF cycle in Mecp2-null mouse brains, where PAF is a bioactive lipid acting on neuronal growth, glutamate exocytosis and other processes; and (iv changes in glutamine/glutamate ratios (p = 0.034 in Mecp2-null mouse brains potentially indicating altered neurotransmitter recycling. CONCLUSIONS/SIGNIFICANCE: This study establishes, for the first time, detailed metabolic fingerprints of perturbed brain growth, osmoregulation and neurotransmission in a mouse model of Rett syndrome. Combined with morphological and neurological findings

  3. The regulation of iron metabolism by hepcidin contributes to unloading-induced bone loss.

    Science.gov (United States)

    Xu, Zi; Sun, Weijia; Li, Yuheng; Ling, Shukuan; Zhao, Chenyang; Zhong, Guohui; Zhao, Dingsheng; Song, Jinping; Song, Hailin; Li, Jinqiao; You, Linhao; Nie, Guangjun; Chang, Yanzhong; Li, Yingxian

    2017-01-01

    Iron overload inhibits osteoblast function and promotes osteoclastogenesis. Hepcidin plays an important role in this process. The changes in iron content and the regulation of hepcidin under unloading-induced bone loss remain unknown. A hindlimb suspension model was adopted to simulate unloading-induced bone loss in mice. The results showed that iron deposition in both liver and bone was markedly increased in hindlimb unloaded mice, and was accompanied by the upregulation of osteoclast activity and downregulation of osteoblast activity. The iron chelator deferoxamine mesylate (DFO) reduced the iron content in bone and alleviated unloading-induced bone loss. The increased iron content in bone was mainly a result of the upregulation of transferrin receptor 1 (TfR1) and divalent metal transporter 1 with iron response element (DMT1+IRE), rather than changes in the iron transporter ferroportin 1 (FPN1). The hepcidin level in the liver was significantly higher, while the FPN1 level in the duodenum was substantially reduced. However, there were no changes in the FPN1 level in bone tissue. During hindlimb unloading, downregulation of hepcidin by siRNA increased iron uptake in bone and liver, which aggravated unloading-induced bone loss. In summary, these data show that unloading-induced bone loss was orchestrated by iron overload and coupled with the regulation of hepcidin by the liver. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Alteration of proteins and pigments influence the function of photosystem I under iron deficiency from Chlamydomonas reinhardtii.

    Directory of Open Access Journals (Sweden)

    Venkateswarlu Yadavalli

    Full Text Available BACKGROUND: Iron is an essential micronutrient for all organisms because it is a component of enzyme cofactors that catalyze redox reactions in fundamental metabolic processes. Even though iron is abundant on earth, it is often present in the insoluble ferric [Fe (III] state, leaving many surface environments Fe-limited. The haploid green alga Chlamydomonas reinhardtii is used as a model organism for studying eukaryotic photosynthesis. This study explores structural and functional changes in PSI-LHCI supercomplexes under Fe deficiency as the eukaryotic photosynthetic apparatus adapts to Fe deficiency. RESULTS: 77K emission spectra and sucrose density gradient data show that PSI and LHCI subunits are affected under iron deficiency conditions. The visible circular dichroism (CD spectra associated with strongly-coupled chlorophyll dimers increases in intensity. The change in CD signals of pigments originates from the modification of interactions between pigment molecules. Evidence from sucrose gradients and non-denaturing (green gels indicates that PSI-LHCI levels were reduced after cells were grown for 72 h in Fe-deficient medium. Ultrafast fluorescence spectroscopy suggests that red-shifted pigments in the PSI-LHCI antenna were lost during Fe stress. Further, denaturing gel electrophoresis and immunoblot analysis reveals that levels of the PSI subunits PsaC and PsaD decreased, while PsaE was completely absent after Fe stress. The light harvesting complexes were also susceptible to iron deficiency, with Lhca1 and Lhca9 showing the most dramatic decreases. These changes in the number and composition of PSI-LHCI supercomplexes may be caused by reactive oxygen species, which increase under Fe deficiency conditions. CONCLUSIONS: Fe deficiency induces rapid reduction of the levels of photosynthetic pigments due to a decrease in chlorophyll synthesis. Chlorophyll is important not only as a light-harvesting pigment, but also has a structural role

  5. Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887

    Science.gov (United States)

    Merrill, A. H. Jr; Hoel, M.; Wang, E.; Mullins, R. E.; Hargrove, J. L.; Jones, D. P.; Popova, I. A.; Merrill AH, J. r. (Principal Investigator)

    1990-01-01

    To determine the possible biochemical effects of prolonged weightlessness on liver function, samples of liver from rats that had flown aboard Cosmos 1887 were analyzed for protein, glycogen, and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. Among the parameters measured, the major differences were elevations in the glycogen content and hydroxymethylglutaryl-CoA (HMG-CoA) reductase activities for the rats flown on Cosmos 1887 and decreases in the amount of microsomal cytochrome P-450 and the activities of aniline hydroxylase and ethylmorphine N-demethylase, cytochrome P-450-dependent enzymes. These results support the earlier finding of differences in these parameters and suggest that altered hepatic function could be important during spaceflight and/or the postflight recovery period.

  6. MicroRNAs mir-184 and let-7 alter Drosophila metabolism and longevity.

    Science.gov (United States)

    Gendron, Christi M; Pletcher, Scott D

    2017-12-01

    MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression associated with many complex biological processes. By comparing miRNA expression between long-lived cohorts of Drosophila melanogaster that were fed a low-nutrient diet with normal-lived control animals fed a high-nutrient diet, we identified miR-184, let-7, miR-125, and miR-100 as candidate miRNAs involved in modulating aging. We found that ubiquitous, adult-specific overexpression of these individual miRNAs led to significant changes in fat metabolism and/or lifespan. Most impressively, adult-specific overexpression of let-7 in female nervous tissue increased median fly lifespan by ~22%. We provide evidence that this lifespan extension is not due to alterations in nutrient intake or to decreased insulin signaling. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  7. Aluminum, copper, iron and zinc differentially alter amyloid-Aβ(1-42) aggregation and toxicity.

    Science.gov (United States)

    Bolognin, Silvia; Messori, Luigi; Drago, Denise; Gabbiani, Chiara; Cendron, Laura; Zatta, Paolo

    2011-06-01

    Amyloid-β(1-42) (Aβ) is believed to play a crucial role in the ethiopathogenesis of Alzheimer's Disease (AD). In particular, its interactions with biologically relevant metal ions may lead to the formation of highly neurotoxic complexes. Here we describe the species that are formed upon reacting Aβ with several biometals, namely copper, zinc, iron, and with non-physiological aluminum to assess whether different metal ions are able to differently drive Aβ aggregation. The nature of the resulting Aβ-metal complexes and of the respective aggregates was ascertained through a number of biophysical techniques, including electrospray ionization mass spectrometry, dynamic light scattering, fluorescence, transmission electron microscopy and by the use of conformation-sensitive antibodies (OC, αAPF). Metal binding to Aβ is shown to confer highly different chemical properties to the resulting complexes; accordingly, their overall aggregation behaviour was deeply modified. Both aluminum(III) and iron(III) ions were found to induce peculiar aggregation properties, ultimately leading to the formation of annular protofibrils and of fibrillar oligomers. Notably, only Aβ-aluminum was characterized by the presence of a relevant percentage of aggregates with a mean radius slightly smaller than 30 nm. In contrast, both zinc(II) and copper(II) ions completely prevented the formation of soluble fibrillary aggregates. The biological effects of the various Aβ-metal complexes were studied in neuroblastoma cell cultures: Aβ-aluminum turned out to be the only species capable of triggering amyloid precursor and tau181 protein overproduction. Our results point out that Al can effectively interact with Aβ, forming "structured" aggregates with peculiar biophysical properties which are associated with a high neurotoxicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Injury timing alters metabolic, inflammatory and functional outcomes following repeated mild traumatic brain injury.

    Science.gov (United States)

    Weil, Zachary M; Gaier, Kristopher R; Karelina, Kate

    2014-10-01

    Repeated head injuries are a major public health concern both for athletes, and members of the police and armed forces. There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma. Injuries that occur close together in time produce greater cognitive, histological, and behavioral impairments than do injuries separated by a longer period. Traumatic brain injuries alter cerebral glucose metabolism and the resolution of altered glucose metabolism may signal the end of the period of greater vulnerability. Here, we injured mice either once or twice separated by three or 20days. Repeated injuries that were separated by three days were associated with greater axonal degeneration, enhanced inflammatory responses, and poorer performance in a spatial learning and memory task. A single injury induced a transient but marked increase in local cerebral glucose utilization in the injured hippocampus and sensorimotor cortex, whereas a second injury, three days after the first, failed to induce an increase in glucose utilization at the same time point. In contrast, when the second injury occurred substantially later (20days after the first injury), an increase in glucose utilization occurred that paralleled the increase observed following a single injury. The increased glucose utilization observed after a single injury appears to be an adaptive component of recovery, while mice with 2 injuries separated by three days were not able to mount this response, thus this second injury may have produced a significant energetic crisis such that energetic demands outstripped the ability of the damaged cells to utilize energy. These data strongly reinforce the idea that too rapid return to activity after a traumatic brain injury can induce permanent damage and disability, and that monitoring cerebral energy utilization may be a tool to determine when it is safe to return to the activity that caused the initial

  9. L-arginine Availability and Metabolism Is Altered in Ulcerative Colitis

    Science.gov (United States)

    Coburn, Lori A.; Horst, Sara N.; Allaman, Margaret M.; Brown, Caroline T.; Williams, Christopher S.; Hodges, Mallary E.; Druce, Jennifer P.; Beaulieu, Dawn B.; Schwartz, David A.; Wilson, Keith T.

    2016-01-01

    Background L-arginine (L-Arg) is the substrate for both inducible nitric oxide (NO) synthase (NOS2) and arginase (ARG) enzymes. L-Arg is actively transported into cells via cationic amino acid transporter (SLC7) proteins. We have linked L-Arg and arginase 1 activity to epithelial restitution. Our aim was to determine if L-Arg, related amino acids, and metabolic enzymes are altered in ulcerative colitis (UC). Methods Serum and colonic tissues were prospectively collected from 38 controls and 137 UC patients. Dietary intake, histologic injury, and clinical disease activity were assessed. Amino acid levels were measured by HPLC. mRNA levels were measured by real-time PCR. Colon tissue samples from 12 Crohn’s disease (CD) patients were obtained for comparison. Results Dietary intake of arginine and serum L-Arg levels were not different in UC patients versus controls. In active UC, tissue L-Arg was decreased, while L-citrulline (L-Cit) and the L-Cit/L-Arg ratio were increased. This pattern was also seen when paired involved (left) versus uninvolved (right) colon tissues in UC were assessed. In active UC, SLC7A2 and ARG1 mRNA levels were decreased, while ARG2 and NOS2 were increased. Similar alterations in mRNA expression occurred in tissues from CD patients. In involved UC, SLC7A2 and ARG1 mRNA levels were decreased, and NOS2 and ARG2 increased, when compared to uninvolved tissues. Conclusions UC patients exhibit diminished tissue L-Arg, likely attributable to decreased cellular uptake and increased consumption by NOS2. These findings combined with decreased ARG1 expression, indicate a pattern of dysregulated L-Arg availability and metabolism in UC. PMID:27104830

  10. Serum prohepcidin and other iron metabolism parameters in elderly patients with anemia of chronic disease and with iron deficiency anemia.

    Science.gov (United States)

    Przybyszewska, Justyna; Żekanowska, Ewa; Kędziora-Kornatowska, Kornelia; Boinska, Joanna; Cichon, Roman; Porzych, Katarzyna

    2013-01-01

    The diagnosis of iron deficiency anemia (IDA) in the context of the anemia of chronic disease (ACD) in elderly patients is often difficult due to the existence of many disorders. Recent studies have shown that hepcidin measurement (combined with the existing diagnostic methods) may possibly help in the differential diagnosis of IDA and ACD. The aim of the study was to evaluate the differential diagnostic value of serum prohepcidin in elderly patients with IDA and ACD. The study included 65 individuals aged 65 years or more: 26 patients with ACD, 13 patients with IDA, and 26 age-matched controls. Prohepcidin, ferritin, soluble transferrin receptor, erythropoietin, and interleukin 6 (IL-6) were measured using the commercially available enzyme-linked immunosorbent assay kits. Complete blood count, total iron-binding capacity (TIBC), and iron, transferrin, and C-reactive protein (CRP) levels were assayed using the standard laboratory methods. Prohepcidin concentrations were similar in patients with ACD (196.59 ng/ml) compared with those with IDA (230.16 ng/ml) (P = 0.35). Patients with ACD had significantly lower levels of TIBC compared with those with IDA (P <0.0001). Serum ferritin concentration in patients with ACD was almost 20-fold higher compared with those observed in patients with IDA (P <0.0001). CRP and IL-6 concentrations in patients with ACD were significantly higher compared with those with IDA. The results of the study indicate that serum prohepcidin has limited value in the differential diagnosis of IDA and ACD in elderly patients.

  11. Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women

    Science.gov (United States)

    Wiklund, Petri; Zhang, Xiaobo; Pekkala, Satu; Autio, Reija; Kong, Lingjia; Yang, Yifan; Keinänen-Kiukaanniemi, Sirkka; Alen, Markku; Cheng, Sulin

    2016-01-01

    Insulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectroscopy, serum metabolites by nuclear magnetic resonance spectroscopy and adipose tissue and skeletal muscle gene expression by microarrays. High HOMA-IR subjects had higher serum branched-chain amino acid concentrations (BCAA) (p HOMA-IR subjects (p < 0.05 for all), but no differentially expressed genes in skeletal muscle were found. In conclusion, in normoglycemic women insulin resistance was associated with increased serum BCAA concentrations, down-regulation of mitochondrial energy metabolism and increased expression of inflammation-related genes in the adipose tissue. PMID:27080554

  12. Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery

    International Nuclear Information System (INIS)

    Clow, D.W.; Hammer, R.P. Jr.

    1991-01-01

    2-[14C]deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine

  13. Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions.

    Science.gov (United States)

    Bian, Xiaoming; Tu, Pengcheng; Chi, Liang; Gao, Bei; Ru, Hongyu; Lu, Kun

    2017-09-01

    Maintaining the balance of the gut microbiota and its metabolic functions is vital for human health, however, this balance can be disrupted by various external factors including food additives. A range of food and beverages are sweetened by saccharin, which is generally considered to be safe despite controversial debates. However, recent studies indicated that saccharin perturbed the gut microbiota. Inflammation is frequently associated with disruptions of the gut microbiota. The aim of this study is to investigate the relationship between host inflammation and perturbed gut microbiome by saccharin. C57BL/6J male mice were treated with saccharin in drinking water for six months. Q-PCR was used to detect inflammatory markers in mouse liver, while 16S rRNA gene sequencing and metabolomics were used to reveal changes of the gut microbiota and its metabolomic profiles. Elevated expression of pro-inflammatory iNOS and TNF-α in liver indicated that saccharin induced inflammation in mice. The altered gut bacterial genera, enriched orthologs of pathogen-associated molecular patterns, such as LPS and bacterial toxins, in concert with increased pro-inflammatory metabolites suggested that the saccharin-induced liver inflammation could be associated with the perturbation of the gut microbiota and its metabolic functions. Copyright © 2017. Published by Elsevier Ltd.

  14. Downregulation of SREBP inhibits tumor growth and initiation by altering cellular metabolism in colon cancer.

    Science.gov (United States)

    Wen, Yang-An; Xiong, Xiaopeng; Zaytseva, Yekaterina Y; Napier, Dana L; Vallee, Emma; Li, Austin T; Wang, Chi; Weiss, Heidi L; Evers, B Mark; Gao, Tianyan

    2018-02-15

    Sterol regulatory element-binding proteins (SREBPs) belong to a family of transcription factors that regulate the expression of genes required for the synthesis of fatty acids and cholesterol. Three SREBP isoforms, SREBP1a, SREBP1c, and SREBP2, have been identified in mammalian cells. SREBP1a and SREBP1c are derived from a single gene through the use of alternative transcription start sites. Here we investigated the role of SREBP-mediated lipogenesis in regulating tumor growth and initiation in colon cancer. Knockdown of either SREBP1 or SREBP2 decreased levels of fatty acids as a result of decreased expression of SREBP target genes required for lipid biosynthesis in colon cancer cells. Bioenergetic analysis revealed that silencing SREBP1 or SREBP2 expression reduced the mitochondrial respiration, glycolysis, as well as fatty acid oxidation indicating an alteration in cellular metabolism. Consequently, the rate of cell proliferation and the ability of cancer cells to form tumor spheroids in suspension culture were significantly decreased. Similar results were obtained in colon cancer cells in which the proteolytic activation of SREBP was blocked. Importantly, knockdown of either SREBP1 or SREBP2 inhibited xenograft tumor growth in vivo and decreased the expression of genes associated with cancer stem cells. Taken together, our findings establish the molecular basis of SREBP-dependent metabolic regulation and provide a rationale for targeting lipid biosynthesis as a promising approach in colon cancer treatment.

  15. Alterations in tryptophan and purine metabolism in cocaine addiction: a metabolomic study.

    Science.gov (United States)

    Patkar, Ashwin A; Rozen, Steve; Mannelli, Paolo; Matson, Wayne; Pae, Chi-Un; Krishnan, K Ranga; Kaddurah-Daouk, Rima

    2009-10-01

    Mapping metabolic "signatures" can provide new insights into addictive mechanisms and potentially identify biomarkers and therapeutic targets. We examined the differences in metabolites related to the tyrosine, tryptophan, purine, and oxidative stress pathways between cocaine-dependent subjects and healthy controls. Several of these metabolites serve as biological indices underlying the mechanisms of reinforcement, toxicity, and oxidative stress. Metabolomic analysis was performed in 18 DSM-IV-diagnosed cocaine-dependent individuals with at least 2 weeks of abstinence and ten drug-free controls. Plasma concentrations of 37 known metabolites were analyzed and compared using a liquid chromatography electrochemical array platform. Multivariate analyses were used to study the relationship between severity of drug use [Addiction Severity Index (ASI) scores] and biological measures. Cocaine subjects showed significantly higher levels of n-methylserotonin (p cocaine and control groups with no overlap. Alterations in the methylation processes in the serotonin pathways and purine metabolism seem to be associated with chronic exposure to cocaine. Given the preliminary nature and cross-sectional design of the study, the findings need to be confirmed in larger samples of cocaine-dependent subjects, preferably in a longitudinal design.

  16. Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways

    Science.gov (United States)

    Pérez-Plasencia, Carlos; Vázquez-Ortiz, Guelaguetza; López-Romero, Ricardo; Piña-Sanchez, Patricia; Moreno, José; Salcedo, Mauricio

    2007-01-01

    Background Cervical carcinoma (CC) is a leading cause of death among women worldwide. Human papilloma virus (HPV) is a major etiological factor in CC and HPV 16 is the more frequent viral type present. Our aim was to characterize metabolic pathways altered in HPV 16 tumor samples by means of transcriptome wide analysis and bioinformatics tools for visualizing expression data in the context of KEGG biological pathways. Results We found 2,067 genes significantly up or down-modulated (at least 2-fold) in tumor clinical samples compared to normal tissues, representing ~3.7% of analyzed genes. Cervical carcinoma was associated with an important up-regulation of Wnt signaling pathway, which was validated by in situ hybridization in clinical samples. Other up-regulated pathways were those of calcium signaling and MAPK signaling, as well as cell cycle-related genes. There was down-regulation of focal adhesion, TGF-β signaling, among other metabolic pathways. Conclusion This analysis of HPV 16 tumors transcriptome could be useful for the identification of genes and molecular pathways involved in the pathogenesis of cervical carcinoma. Understanding the possible role of these proteins in the pathogenesis of CC deserves further studies. PMID:17822553

  17. Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways

    Directory of Open Access Journals (Sweden)

    Salcedo Mauricio

    2007-09-01

    Full Text Available Abstract Background Cervical carcinoma (CC is a leading cause of death among women worldwide. Human papilloma virus (HPV is a major etiological factor in CC and HPV 16 is the more frequent viral type present. Our aim was to characterize metabolic pathways altered in HPV 16 tumor samples by means of transcriptome wide analysis and bioinformatics tools for visualizing expression data in the context of KEGG biological pathways. Results We found 2,067 genes significantly up or down-modulated (at least 2-fold in tumor clinical samples compared to normal tissues, representing ~3.7% of analyzed genes. Cervical carcinoma was associated with an important up-regulation of Wnt signaling pathway, which was validated by in situ hybridization in clinical samples. Other up-regulated pathways were those of calcium signaling and MAPK signaling, as well as cell cycle-related genes. There was down-regulation of focal adhesion, TGF-β signaling, among other metabolic pathways. Conclusion This analysis of HPV 16 tumors transcriptome could be useful for the identification of genes and molecular pathways involved in the pathogenesis of cervical carcinoma. Understanding the possible role of these proteins in the pathogenesis of CC deserves further studies.

  18. Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency.

    Science.gov (United States)

    Collantes, María; Serrano-Mendioroz, Irantzu; Benito, Marina; Molinet-Dronda, Francisco; Delgado, Mercedes; Vinaixa, María; Sampedro, Ana; Enríquez de Salamanca, Rafael; Prieto, Elena; Pozo, Miguel A; Peñuelas, Iván; Corrales, Fernando J; Barajas, Miguel; Fontanellas, Antonio

    2016-04-01

    Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Alterations of specific biomarkers of metabolic pathways in vascular tree from patients with Type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Rosa Bernal-Lopez M

    2012-07-01

    Full Text Available Abstract The aims of this study were to check whether different biomarkers of inflammatory, apoptotic, immunological or lipid pathways had altered their expression in the occluded popliteal artery (OPA compared with the internal mammary artery (IMA and femoral vein (FV and to examine whether glycemic control influenced the expression of these genes. The study included 20 patients with advanced atherosclerosis and type 2 diabetes mellitus, 15 of whom had peripheral arterial occlusive disease (PAOD, from whom samples of OPA and FV were collected. PAOD patients were classified based on their HbA1c as well (HbA1c ≤ 6.5 or poorly (HbA1c > 6.5 controlled patients. Controls for arteries without atherosclerosis comprised 5 IMA from patients with ischemic cardiomyopathy (ICM. mRNA, protein expression and histological studies were analyzed in IMA, OPA and FV. After analyzing 46 genes, OPA showed higher expression levels than IMA or FV for genes involved in thrombosis (F3, apoptosis (MMP2, MMP9, TIMP1 and TIM3, lipid metabolism (LRP1 and NDUFA, immune response (TLR2 and monocytes adhesion (CD83. Remarkably, MMP-9 expression was lower in OPA from well-controlled patients. In FV from diabetic patients with HbA1c ≤6.5, gene expression levels of BCL2, CDKN1A, COX2, NDUFA and SREBP2 were higher than in FV from those with HbA1c >6.5. The atherosclerotic process in OPA from diabetic patients was associated with high expression levels of inflammatory, lipid metabolism and apoptotic biomarkers. The degree of glycemic control was associated with gene expression markers of apoptosis, lipid metabolism and antioxidants in FV. However, the effect of glycemic control on pro-atherosclerotic gene expression was very low in arteries with established atherosclerosis.

  20. Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome.

    Science.gov (United States)

    Dinel, Anne-Laure; André, Caroline; Aubert, Agnès; Ferreira, Guillaume; Layé, Sophie; Castanon, Nathalie

    2011-01-01

    Converging clinical data suggest that peripheral inflammation is likely involved in the pathogenesis of the neuropsychiatric symptoms associated with metabolic syndrome (MetS). However, the question arises as to whether the increased prevalence of behavioral alterations in MetS is also associated with central inflammation, i.e. cytokine activation, in brain areas particularly involved in controlling behavior. To answer this question, we measured in a mouse model of MetS, namely the diabetic and obese db/db mice, and in their healthy db/+ littermates emotional behaviors and memory performances, as well as plasma levels and brain expression (hippocampus; hypothalamus) of inflammatory cytokines. Our results shows that db/db mice displayed increased anxiety-like behaviors in the open-field and the elevated plus-maze (i.e. reduced percent of time spent in anxiogenic areas of each device), but not depressive-like behaviors as assessed by immobility time in the forced swim and tail suspension tests. Moreover, db/db mice displayed impaired spatial recognition memory (hippocampus-dependent task), but unaltered object recognition memory (hippocampus-independent task). In agreement with the well-established role of the hippocampus in anxiety-like behavior and spatial memory, behavioral alterations of db/db mice were associated with increased inflammatory cytokines (interleukin-1β, tumor necrosis factor-α and interleukin-6) and reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus but not the hypothalamus. These results strongly point to interactions between cytokines and central processes involving the hippocampus as important contributing factor to the behavioral alterations of db/db mice. These findings may prove valuable for introducing novel approaches to treat neuropsychiatric complications associated with MetS.

  1. Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Anne-Laure Dinel

    Full Text Available Converging clinical data suggest that peripheral inflammation is likely involved in the pathogenesis of the neuropsychiatric symptoms associated with metabolic syndrome (MetS. However, the question arises as to whether the increased prevalence of behavioral alterations in MetS is also associated with central inflammation, i.e. cytokine activation, in brain areas particularly involved in controlling behavior. To answer this question, we measured in a mouse model of MetS, namely the diabetic and obese db/db mice, and in their healthy db/+ littermates emotional behaviors and memory performances, as well as plasma levels and brain expression (hippocampus; hypothalamus of inflammatory cytokines. Our results shows that db/db mice displayed increased anxiety-like behaviors in the open-field and the elevated plus-maze (i.e. reduced percent of time spent in anxiogenic areas of each device, but not depressive-like behaviors as assessed by immobility time in the forced swim and tail suspension tests. Moreover, db/db mice displayed impaired spatial recognition memory (hippocampus-dependent task, but unaltered object recognition memory (hippocampus-independent task. In agreement with the well-established role of the hippocampus in anxiety-like behavior and spatial memory, behavioral alterations of db/db mice were associated with increased inflammatory cytokines (interleukin-1β, tumor necrosis factor-α and interleukin-6 and reduced expression of brain-derived neurotrophic factor (BDNF in the hippocampus but not the hypothalamus. These results strongly point to interactions between cytokines and central processes involving the hippocampus as important contributing factor to the behavioral alterations of db/db mice. These findings may prove valuable for introducing novel approaches to treat neuropsychiatric complications associated with MetS.

  2. Iron chelation: an adjuvant therapy to target metabolism, growth and survival of murine PTEN-deficient T lymphoma and human T lymphoblastic leukemia/lymphoma.

    Science.gov (United States)

    Benadiba, Joy; Rosilio, Celia; Nebout, Marielle; Heimeroth, Vera; Neffati, Zouhour; Popa, Alexandra; Mary, Didier; Griessinger, Emmanuel; Imbert, Véronique; Sirvent, Nicolas; Peyron, Jean-François

    2017-06-01

    Iron is an essential nutrient, acting as a catalyst for metabolic reactions that are fundamental to cell survival and proliferation. Iron complexed to transferrin is delivered to the metabolism after endocytosis via the CD71 surface receptor. We found that transformed cells from a murine PTEN-deficient T-cell lymphoma model and from T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LL) cell lines overexpress CD71. As a consequence, the cells developed an addiction toward iron whose chelation by deferoxamine (DFO) dramatically affected their survival to induce apoptosis. Interestingly, DFO displayed synergistic activity with three ALL-specific drugs: dexamethasone, doxorubicin, and L-asparaginase. DFO appeared to act through a reactive oxygen species-dependent DNA damage response and potentiated the action of an inhibitor of the PARP pathway of DNA repair. Our results demonstrate that targeting iron metabolism could be an interesting adjuvant therapy for acute lymphoblastic leukemia.

  3. Wearing red for signaling: the heme-bach axis in heme metabolism, oxidative stress response and iron immunology.

    Science.gov (United States)

    Igarashi, Kazuhiko; Watanabe-Matsui, Miki

    2014-04-01

    The connection between gene regulation and metabolism is an old issue that warrants revisiting in order to understand both normal as well as pathogenic processes in higher eukaryotes. Metabolites affect the gene expression by either binding to transcription factors or serving as donors for post-translational modification, such as that involving acetylation and methylation. The focus of this review is heme, a prosthetic group of proteins that includes hemoglobin and cytochromes. Heme has been shown to bind to several transcription factors, including Bach1 and Bach2, in higher eukaryotes. Heme inhibits the transcriptional repressor activity of Bach1, resulting in the derepression of its target genes, such as globin in erythroid cells and heme oxygenase-1 in diverse cell types. Since Bach2 is important for class switch recombination and somatic hypermutation of immunoglobulin genes as well as regulatory and effector T cell differentiation and the macrophage function, the heme-Bach2 axis may regulate the immune response as a signaling cascade. We discuss future issues regarding the topic of the iron/heme-gene regulation network based on current understanding of the heme-Bach axis, including the concept of "iron immunology" as the synthesis of the iron metabolism and the immune response.

  4. Iron metabolism in mynah birds (Gracula religiosa) resembles human hereditary haemochromatosis

    NARCIS (Netherlands)

    Mete, A; Hendriks, HG; Klaren, PHM; Dorrestein, GM; van Dijk, JE; Marx, JJM

    2003-01-01

    Iron overload is a very frequent finding in several animal species and a genetic predisposition is suggested. In one of the most commonly reported species with susceptibility for iron overload ( mynah bird), it was recently shown that the cause of this pathophysiology is high uptake and retention of

  5. The Aging of Iron Man.

    Science.gov (United States)

    Ashraf, Azhaar; Clark, Maryam; So, Po-Wah

    2018-01-01

    Brain iron is tightly regulated by a multitude of proteins to ensure homeostasis. Iron dyshomeostasis has become a molecular signature associated with aging which is accompanied by progressive decline in cognitive processes. A common theme in neurodegenerative diseases where age is the major risk factor, iron dyshomeostasis coincides with neuroinflammation, abnormal protein aggregation, neurodegeneration, and neurobehavioral deficits. There is a great need to determine the mechanisms governing perturbations in iron metabolism, in particular to distinguish between physiological and pathological aging to generate fruitful therapeutic targets for neurodegenerative diseases. The aim of the present review is to focus on the age-related alterations in brain iron metabolism from a cellular and molecular biology perspective, alongside genetics, and neuroimaging aspects in man and rodent models, with respect to normal aging and neurodegeneration. In particular, the relationship between iron dyshomeostasis and neuroinflammation will be evaluated, as well as the effects of systemic iron overload on the brain. Based on the evidence discussed here, we suggest a synergistic use of iron-chelators and anti-inflammatories as putative anti-brain aging therapies to counteract pathological aging in neurodegenerative diseases.

  6. Dietary isoflavones alter regulatory behaviors, metabolic hormones and neuroendocrine function in Long-Evans male rats

    Directory of Open Access Journals (Sweden)

    Bu Lihong

    2004-12-01

    protein (UCP-1 mRNA levels in brown adipose tissue (BAT were seen in Phyto-600 fed males. However, decreased core body temperature was recorded in these same animals compared to Phyto-free fed animals. Conclusions This study demonstrates that consumption of a soy-based (isoflavone-rich diet, significantly alters several parameters involved in maintaining body homeostatic balance, energy expenditure, feeding behavior, hormonal, metabolic and neuroendocrine function in male rats.

  7. Use of radioisotopes in studying iron metabolism in humans in Sri Lanka

    International Nuclear Information System (INIS)

    Liyanage, C.E.; Thabrew, M.I.

    1994-01-01

    Anaemia due to iron deficiency is the commonest haematological problem found in Sri Lankan pregnant women and pre-school children. The reported prevalence rates amongst pregnant and lactating women ranged from 60-80%. The present study revealed that 3% of pregnant women had satisfactory iron stores and 57% had virtually no iron stores. Routine iron supplementation is justified not only to correct the anaemia but also to build up the maternal iron stores. In a longitudinal study of 100 pregnant women a very high prevalence was observed in spite of the fact that the population studied was on iron supplementation. A very poor compliance on iron therapy was seen. The incidence of low birth weight observed was 32%, quite similar to that has been reported previously for Sri Lanka. Therefore, further longitudinal studies have been designed to find out the efficacy of the present supplementary programme. In Galle District 54.5% of the pre-school children were found clearly anaemic and another 20% had evidence of iron depletion. As the dietary intake of iron was marginal, the weaning foods that are in practice were tested for iron availability. Iron absorption/availability studies by in-vivo (extrinsic tag method) and in-vitro (using radioiron 59 Fe tracer) methods have shown a very poor (less than 5%) availability in many of the commonly used weaning foods. A statistically significant decrease in iron availability was seen with increase in amount of polyphenols mainly in some of the preparations made with green leaves. Addition of ascorbic acid rich food items showed an increase in iron availability (by 2-6 times). Dietary zinc intake of 46 children (2-5 yrs) was found 2-4 mg/1000 kcal, relating to total energy intake. Mean plasma zinc concentration of these children was 13.8±0.8 μmol/L. Therefore further studies on the improvement of zinc and iron availability in weaning foods have been designed to be done in future. (author). 3 refs, 1 fig

  8. Role of iron metabolism genetic determinants in response to chelation therapy in a cohort of β-thalassemia and sickle cell syndromes Italian patients

    Directory of Open Access Journals (Sweden)

    Maria Concetta Renda

    2014-09-01

    Full Text Available In patients with β-thalassemia and sickle cell syndromes there is an important secondary iron overload due to regular blood transfusions and increased duodenal iron absorption. As in genetic hemochromatosis, also the secondary iron storage leads to tissue injury that involves all the major organs: liver, heart, kidney, endocrine glands. At present, in patients with β-thalassemia and sickle cell syndrome, iron chelation therapy is widely used for the treatment of secondary hemochromatosis, to limit the toxic effects of iron overload. In order to maintain the correct homeostasis, several genes are involved in the metabolic pathways of iron, including HFE, FPN (ferroportin and TF (transferrin. In this study we analyzed the genes HFE, FPN and TF, to assess their possible effects on response to therapy with deferasirox and deferiprone, either as monotherapy or in combination therapy in a cohort of patients with β-thalassemia and sickle cell syndromes.

  9. Sodium ascorbate kills Candida albicans in vitro via iron-catalyzed Fenton reaction: importance of oxygenation and metabolism.

    Science.gov (United States)

    Avci, Pinar; Freire, Fernanda; Banvolgyi, Andras; Mylonakis, Eleftherios; Wikonkal, Norbert M; Hamblin, Michael R

    2016-12-01

    Ascorbate can inhibit growth and even decrease viability of various microbial species including Candida albicans. However the optimum conditions and the mechanism of action are unclear. Materials/methodology: Candida albicans shaken for 90 min in a buffered solution of ascorbate (90 mM) gave a 5-log reduction of cell viability, while there was no killing without shaking, in growth media with different carbon sources or at 4°C. Killing was inhibited by the iron chelator 2,2'-bipyridyl. Hydroxyphenyl fluorescein probe showed the intracellular generation of hydroxyl radicals. Ascorbate-mediated killing of C. albicans depends on oxygenation and metabolism, involves iron-catalyzed generation of hydroxyl radicals via Fenton reaction and depletion of intracellular NADH. Ascorbate could serve as a component of a topical antifungal therapy.

  10. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    International Nuclear Information System (INIS)

    Feng Jianghua; Liu Huili; Zhang Limin; Bhakoo, Kishore; Lu Lehui

    2010-01-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

  11. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    Energy Technology Data Exchange (ETDEWEB)

    Feng Jianghua [Department of Physics, Fujian Key Laboratory of Plasma and Magnetic Resonance, State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen, 361005 (China); Liu Huili; Zhang Limin [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); Bhakoo, Kishore [Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A-STAR) 138667 (Singapore); Lu Lehui, E-mail: jianghua.feng@hotmail.com, E-mail: jianghua.feng@wipm.ac.cn [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022 (China)

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary {alpha}-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary {alpha}-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies ({beta}-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of

  12. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids.

    Science.gov (United States)

    Feng, Jianghua; Liu, Huili; Zhang, Limin; Bhakoo, Kishore; Lu, Lehui

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary alpha-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary alpha-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (beta-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

  13. Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease

    NARCIS (Netherlands)

    Cheng, Sulin; Wiklund, Petri; Autio, Reija; Borra, Ronald; Ojanen, Xiaowei; Xu, Leiting; Törmäkangas, Timo; Alen, Markku

    2015-01-01

    BACKGROUND: Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49) and women (n = 52) with and without NAFLD. METHODS: Hepatic fat content was

  14. Delineating the role of alterations in lipid metabolism to the pathogenesis of inherited skeletal and cardiac muscle disorders

    NARCIS (Netherlands)

    Saini-Chohan, Harjot K.; Mitchell, Ryan W.; Vaz, Frédéric M.; Zelinski, Teresa; Hatch, Grant M.

    2012-01-01

    As the specific composition of lipids is essential for the maintenance of membrane integrity, enzyme function, ion channels, and membrane receptors, an alteration in lipid composition or metabolism may be one of the crucial changes occurring during skeletal and cardiac myopathies. Although the

  15. Supplementation with a Lactobacillus acidophilus fermentation product alters the metabolic response following a lipopolysaccharide challenge in weaned pigs

    Science.gov (United States)

    This study was designed to determine if feeding a Lactobacillus acidophilus fermentation product to weaned pigs would alter the metabolic response following a lipopolysaccharide (LPS) challenge. Pigs (n=30; 6.4+/-0.1 kg BW) were housed individually with ad libitum access to feed and water. Pigs were...

  16. Cpt1a gene expression in peripheral blood mononuclear cells as an early biomarker of diet-related metabolic alterations

    KAUST Repository

    Diaz-Rua, Ruben

    2016-11-23

    Background: Research on biomarkers that provide early information about the development of future metabolic alterations is an emerging discipline. Gene expression analysis in peripheral blood mononuclear cells (PBMC) is a promising tool to identify subjects at risk of developing diet-related diseases.

  17. The role of hepcidin in iron metabolism in inflammatory bowel diseases

    Directory of Open Access Journals (Sweden)

    Paulina Krawiec

    2014-07-01

    Full Text Available Hepcidin is a 25-amino-acid peptide synthesized predominantly in hepatocytes, which plays an essential role in the regulation of systemic iron homeostasis. As a result of inflammation, hepcidin binds to ferroportin resulting in its internalization and degradation in enterocytes and macrophages. Thus iron is trapped in both enterocytes and macrophages, leading to functional hypoferremia. In iron deficiency or enhanced erythropoiesis, hepcidin expression is reduced. That fact results in increase of iron absorption and releasing iron storage from macrophages. The discovery of the biological properties of hepcidin clarified the relationship between iron homeostasis, immune response, and anaemia of chronic disease. Anaemia is the most common extra intestinal manifestation of inflammatory bowel disease. Anaemia significantly reduces the quality-of-life among patients and can lead to a number of serious complications, even life-threatening. The main types of anaemia in inflammatory bowel diseases are iron deficiency anaemia and anaemia of chronic disease. These two types of anaemia coexist commonly. The key issue is differentiation these types of anaemia to implement a proper management. Commonly used parameters as iron concentration, ferritin and transferrin, are rather unreliable indices for the evaluation of anaemia in inflammatory bowel diseases. In recent studies the important role of hepcidin as a potential alternative marker of anemia and iron status has been shown. Moreover, there are data that antihepcidin treatment may be an effective treatment of anaemia of chronic disease in inflammatory bowel disease. This paper presents hepcidin structure, mechanism of action and regulation, and highlights hepcidin function in anaemia in inflammatory bowel disease.

  18. Binding of hepatitis B virus to its cellular receptor alters the expression profile of genes of bile acid metabolism.

    Science.gov (United States)

    Oehler, Nicola; Volz, Tassilo; Bhadra, Oliver D; Kah, Janine; Allweiss, Lena; Giersch, Katja; Bierwolf, Jeanette; Riecken, Kristoffer; Pollok, Jörg M; Lohse, Ansgar W; Fehse, Boris; Petersen, Joerg; Urban, Stephan; Lütgehetmann, Marc; Heeren, Joerg; Dandri, Maura

    2014-11-01

    Chronic hepatitis B virus (HBV) infection has been associated with alterations in lipid metabolism. Moreover, the Na+-taurocholate cotransporting polypeptide (NTCP), responsible for bile acid (BA) uptake into hepatocytes, was identified as the functional cellular receptor mediating HBV entry. The aim of the study was to determine whether HBV alters the liver metabolic profile by employing HBV-infected and uninfected human liver chimeric mice. Humanized urokinase plasminogen activator/severe combined immunodeficiency mice were used to establish chronic HBV infection. Gene expression profiles were determined by real-time polymerase chain reaction using primers specifically recognizing transcripts of either human or murine origin. Liver biopsy samples obtained from HBV-chronic individuals were used to validate changes determined in mice. Besides modest changes in lipid metabolism, HBV-infected mice displayed a significant enhancement of human cholesterol 7α-hydroxylase (human [h]CYP7A1; median 12-fold induction; Pmetabolic alterations. Binding of HBV to NTCP limits its function, thus promoting compensatory BA synthesis and cholesterol provision. The intimate link determined between HBV and liver metabolism underlines the importance to exploit further metabolic pathways, as well as possible NTCP-related viral-drug interactions. © 2014 by the American Association for the Study of Liver Diseases.

  19. ATAD3 gene cluster deletions cause cerebellar dysfunction associated with altered mitochondrial DNA and cholesterol metabolism.

    Science.gov (United States)

    Desai, Radha; Frazier, Ann E; Durigon, Romina; Patel, Harshil; Jones, Aleck W; Dalla Rosa, Ilaria; Lake, Nicole J; Compton, Alison G; Mountford, Hayley S; Tucker, Elena J; Mitchell, Alice L R; Jackson, Deborah; Sesay, Abdul; Di Re, Miriam; van den Heuvel, Lambert P; Burke, Derek; Francis, David; Lunke, Sebastian; McGillivray, George; Mandelstam, Simone; Mochel, Fanny; Keren, Boris; Jardel, Claude; Turner, Anne M; Ian Andrews, P; Smeitink, Jan; Spelbrink, Johannes N; Heales, Simon J; Kohda, Masakazu; Ohtake, Akira; Murayama, Kei; Okazaki, Yasushi; Lombès, Anne; Holt, Ian J; Thorburn, David R; Spinazzola, Antonella

    2017-06-01

    Although mitochondrial disorders are clinically heterogeneous, they frequently involve the central nervous system and are among the most common neurogenetic disorders. Identifying the causal genes has benefited enormously from advances in high-throughput sequencing technologies; however, once the defect is known, researchers face the challenge of deciphering the underlying disease mechanism. Here we characterize large biallelic deletions in the region encoding the ATAD3C, ATAD3B and ATAD3A genes. Although high homology complicates genomic analysis of the ATAD3 defects, they can be identified by targeted analysis of standard single nucleotide polymorphism array and whole exome sequencing data. We report deletions that generate chimeric ATAD3B/ATAD3A fusion genes in individuals from four unrelated families with fatal congenital pontocerebellar hypoplasia, whereas a case with genomic rearrangements affecting the ATAD3C/ATAD3B genes on one allele and ATAD3B/ATAD3A genes on the other displays later-onset encephalopathy with cerebellar atrophy, ataxia and dystonia. Fibroblasts from affected individuals display mitochondrial DNA abnormalities, associated with multiple indicators of altered cholesterol metabolism. Moreover, drug-induced perturbations of cholesterol homeostasis cause mitochondrial DNA disorganization in control cells, while mitochondrial DNA aggregation in the genetic cholesterol trafficking disorder Niemann-Pick type C disease further corroborates the interdependence of mitochondrial DNA organization and cholesterol. These data demonstrate the integration of mitochondria in cellular cholesterol homeostasis, in which ATAD3 plays a critical role. The dual problem of perturbed cholesterol metabolism and mitochondrial dysfunction could be widespread in neurological and neurodegenerative diseases. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  20. Altered metabolism and lipodystrophy in the early B-cell factor 1-deficient mouse.

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    Fretz, Jackie A; Nelson, Tracy; Xi, Yougen; Adams, Douglas J; Rosen, Clifford J; Horowitz, Mark C

    2010-04-01

    We previously reported that mice deficient for the transcription factor early B-cell factor (Ebf1) exhibit markedly increased numbers of osteoblasts, bone formation rate, and serum osteocalcin, but the bone marrow of Ebf1(-/-) mice is also striking in its increased marrow adiposity. The purpose of this work was to analyze the metabolic phenotype that accompanies the altered bone morphology of Ebf1(-/-) mice. Whereas marrow adiposity was increased, deposition of white adipose tissue in other regions of the body was severely reduced (sc 40-50%, abdominally 80-85%). Brown adipose exhibited decreased lipid deposition. Subcutaneous and perigonadal white adipose tissue showed a decrease in mRNA transcripts for peroxisomal proliferator-activated receptor-gamma2 and CCAAT/enhancer-binding protein-beta in Ebf1(-/-) tissue compared with wild type. Circulating levels of leptin were decreased in Ebf1(-/-) animals compared with their littermate controls (down 65-95%), whereas adiponectin remained comparable after 2 wk of age. Serum analysis also found the Ebf1(-/-) animals were hypoglycemic and hypotriglyceridemic. After ip injection of insulin, the serum glucose levels in Ebf1(-/-) mice took longer to recover, and after a glucose challenge the Ebf1(-/-) animals reached serum glucose levels almost twice that of their wild-type counterparts. Measurement of circulating pancreatic hormones revealed normal or reduced insulin levels in the Ebf1(-/-) mice, whereas glucagon was significantly increased (up 1.7- to 8.5-fold). Metabolically the Ebf1(-/-) mice had increased O(2) consumption, CO(2) production, food and water intake, and activity. Markers for gluconeogenesis, however, were decreased in the Ebf1(-/-) mice compared with controls. In conclusion, the Ebf1-deficient animals exhibit defects in adipose tissue deposition with increased marrow adiposity and impaired glucose mobilization.

  1. Heme oxygenase 1 improves glucoses metabolism and kidney histological alterations in diabetic rats

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    Ptilovanciv Ellen ON

    2013-01-01

    Full Text Available Abstract One important concern in the treatment of diabetes is the maintenance of glycemic levels and the prevention of diabetic nephropathy. Inducible heme oxygenase 1 (HO-1 is a rate-limiting enzyme thought to have antioxidant and cytoprotective roles. The goal of the present study was to analyze the effect of HO-1 induction in chronically hyperglycemic rats. The hyperglycemic rats were divided into two groups: one group, called STZ, was given a single injection of streptozotocin; and the other group was given a single streptozotocin injection as well as daily injections of hemin, an HO-1 inducer, over 60 days (STZ + HEME. A group of normoglycemic, untreated rats was used as the control (CTL. Body weight, diuresis, serum glucose levels, microalbuminuria, creatinine clearance rate, urea levels, sodium excretion, and lipid peroxidation were analyzed. Histological alterations and immunohistochemistry for HO-1 and inducible nitric oxide synthase (iNOS were assessed. After 60 days, the STZ group exhibited an increase in blood glucose, diuresis, urea, microalbuminuria, and sodium excretion. There was no weight gain, and there was a decrease in creatinine clearance in comparison to the CTL group. In the STZ + HEME group there was an improvement in the metabolic parameters and kidney function, a decrease in blood glucose, serum urea, and microalbuminuria, and an increase of creatinine clearance, in comparison to the STZ group. There was glomerulosclerosis, collagen deposition in the STZ rats and increase in iNOS and HO-1 expression. In the STZ + HEME group, the glomerulosclerosis and fibrosis was prevented and there was an increase in the expression of HO-1, but decrease in iNOS expression and lipid peroxidation. In conclusion, our data suggest that chronic induction of HO-1 reduces hyperglycemia, improves glucose metabolism and, at least in part, protects the renal tissue from hyperglycemic injury, possibly through the antioxidant

  2. Altered glutamatergic metabolism associated with punctate white matter lesions in preterm infants.

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    Jessica L Wisnowski

    Full Text Available Preterm infants (∼10% of all births are at high-risk for long-term neurodevelopmental disabilities, most often resulting from white matter injury sustained during the neonatal period. Glutamate excitotoxicity is hypothesized to be a key mechanism in the pathogenesis of white matter injury; however, there has been no in vivo demonstration of glutamate excitotoxicity in preterm infants. Using magnetic resonance spectroscopy (MRS, we tested the hypothesis that glutamate and glutamine, i.e., markers of glutamatergic metabolism, are altered in association with punctate white matter lesions and "diffuse excessive high signal intensity" (DEHSI, the predominant patterns of preterm white matter injury. We reviewed all clinically-indicated MRS studies conducted on preterm infants at a single institution during a six-year period and determined the absolute concentration of glutamate, glutamine, and four other key metabolites in the parietal white matter in 108 of those infants after two investigators independently evaluated the studies for punctate white matter lesions and DEHSI. Punctate white matter lesions were associated with a 29% increase in glutamine concentration (p = 0.002. In contrast, there were no differences in glutamatergic metabolism in association with DEHSI. Severe DEHSI, however, was associated with increased lactate concentration (p = 0.001, a marker of tissue acidosis. Findings from this study support glutamate excitotoxicity in the pathogenesis of punctate white matter lesions, but not necessarily in DEHSI, and suggest that MRS provides a useful biomarker for determining the pathogenesis of white matter injury in preterm infants during a period when neuroprotective agents may be especially effective.

  3. Interaction of metabolic stress with chronic mild stress in altering brain cytokines and sucrose preference.

    Science.gov (United States)

    Remus, Jennifer L; Stewart, Luke T; Camp, Robert M; Novak, Colleen M; Johnson, John D

    2015-06-01

    There is growing evidence that metabolic stressors increase an organism's risk of depression. Chronic mild stress is a popular animal model of depression and several serendipitous findings have suggested that food deprivation prior to sucrose testing in this model is necessary to observe anhedonic behaviors. Here, we directly tested this hypothesis by exposing animals to chronic mild stress and used an overnight 2-bottle sucrose test (food ad libitum) on Day 5 and 10, then food and water deprive animals overnight and tested their sucrose consumption and preference in a 1-hr sucrose test the following morning. Approximately 65% of stressed animals consumed sucrose and showed a sucrose preference similar to nonstressed controls in an overnight sucrose test, and 35% showed a decrease in sucrose intake and preference. Following overnight food and water deprivation the previously "resilient" animals showed a significant decrease in sucrose preference and greatly reduced sucrose intake. In addition, we evaluated whether the onset of anhedonia following food and water deprivation corresponds to alterations in corticosterone, epinephrine, circulating glucose, or interleukin-1 beta (IL-1β) expression in limbic brain areas. Although all stressed animals showed adrenal hypertrophy and elevated circulating epinephrine, only stressed animals that were food deprived were hypoglycemic compared with food-deprived controls. Additionally, food and water deprivation significantly increased hippocampus IL-1β while food and water deprivation only increased hypothalamus IL-1β in stress-susceptible animals. These data demonstrate that metabolic stress of food and water deprivation interacts with chronic stressor exposure to induce physiological and anhedonic responses. (c) 2015 APA, all rights reserved).

  4. DEPRESSIVE BEHAVIOR AND METABOLIC ALTERATIONS IN MICE ARE MUSICAL STYLE-DEPENDENT

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    V. S. Lima

    2015-10-01

    Full Text Available Nowadays, the world population has been affected by two serious psychological disorders, anxiety and depression, but there are few discoveries for new therapies to combat them. Studies have shown that music therapy has its beneficial behavioral effects. Therefore, the aim of the present study it was to investigate the possible effects of two music styles in some lipids and carbohydrate metabolism parameters resulting from behavioral changes related to anxiety and depression. So, mice were used with 30 days of age, divided into 6 groups: G1: saline, G2: Diazepam (DZP, G3: Fluoxetine (FLX, G4: control (no treatment, G5: Rock, and G6: Mozart Sonata. The animals from groups G1, G2 and G3 received treatments by oral route (gavage for 15 days. The music therapy sessions (2x/day 4 hours/day occurred in the same period of time at a 65dB frequency for G5 and G6 groups. After being evaluated in spontaneous locomotion, elevated plus maze and forced swimming tests, the animals were euthanized. The lactate, total cholesterol and plasma glucose levels were measured from the blood. No change was observed in spontaneous locomotion test and elevated plus maze. In the forced swimming test animals exposed to Rock showed an increase in immobility time. Furthermore, it was observed an increase in glucose and a reduction in cholesterol levels in the groups exposed to Rock and Mozart, while a decrease of lactate was observed only in group Rock. It was concluded that the auditory stimulus caused by music in mice was able to encourage depressive behavior and alter some lipids and carbohydrate metabolism parameters dependently of the musical style.

  5. Choline and methionine differentially alter methyl carbon metabolism in bovine neonatal hepatocytes.

    Science.gov (United States)

    Chandler, Tawny L; White, Heather M

    2017-01-01

    Intersections in hepatic methyl group metabolism pathways highlights potential competition or compensation of methyl donors. The objective of this experiment was to examine the expression of genes related to methyl group transfer and lipid metabolism in response to increasing concentrations of choline chloride (CC) and DL-methionine (DLM) in primary neonatal hepatocytes that were or were not exposed to fatty acids (FA). Primary hepatocytes isolated from 4 neonatal Holstein calves were maintained as monolayer cultures for 24 h before treatment with CC (61, 128, 2028, and 4528 μmol/L) and DLM (16, 30, 100, 300 μmol/L), with or without a 1 mmol/L FA cocktail in a factorial arrangement. After 24 h of treatment, media was collected for quantification of reactive oxygen species (ROS) and very low-density lipoprotein (VLDL), and cell lysates were collected for quantification of gene expression. No interactions were detected between CC, DLM, or FA. Both CC and DLM decreased the expression of methionine adenosyltransferase 1A (MAT1A). Increasing CC did not alter betaine-homocysteine S-methyltranferase (BHMT) but did increase 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) and methylenetetrahydrofolate reductase (MTHFR) expression. Increasing DLM decreased expression of BHMT and MTR, but did not affect MTHFR. Expression of both phosphatidylethanolamine N-methyltransferase (PEMT) and microsomal triglyceride transfer protein (MTTP) were decreased by increasing CC and DLM, while carnitine palmitoyltransferase 1A (CPT1A) was unaffected by either. Treatment with FA decreased the expression of MAT1A, MTR, MTHFR and tended to decrease PEMT but did not affect BHMT and MTTP. Treatment with FA increased CPT1A expression. Increasing CC increased secretion of VLDL and decreased the accumulation of ROS in media. Within neonatal bovine hepatocytes, choline and methionine differentially regulate methyl carbon pathways and suggest that choline may play a critical role in

  6. Hereditary kidney cancer syndromes: Genetic disorders driven by alterations in metabolism and epigenome regulation.

    Science.gov (United States)

    Hasumi, Hisashi; Yao, Masahiro

    2018-03-01

    Although hereditary kidney cancer syndrome accounts for approximately five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, USA and the first kidney cancer-associated gene, VHL, was identified through kindred analysis of von Hippel-Lindau (VHL) syndrome in 1993. Subsequent molecular studies on VHL function have elucidated that the VHL protein is a component of E3 ubiquitin ligase complex for hypoxia-inducible factor (HIF), which provided the basis for the development of tyrosine kinase inhibitors targeting the HIF-VEGF/PDGF pathway. Recent whole-exome sequencing analysis of sporadic kidney cancer exhibited the recurrent mutations in chromatin remodeling genes and the later study has revealed that several chromatin remodeling genes are altered in kidney cancer kindred at the germline level. To date, more than 10 hereditary kidney cancer syndromes together with each responsible gene have been characterized and most of the causative genes for these genetic disorders are associated with either metabolism or epigenome regulation. In this review article, we describe the molecular mechanisms of how an alteration of each kidney cancer-associated gene leads to renal tumorigenesis as well as denote therapeutic targets elicited by studies on hereditary kidney cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  7. Gallium Maltolate Disrupts Tumor Iron Metabolism and Retards the Growth of Glioblastoma by Inhibiting Mitochondrial Function and Ribonucleotide Reductase.

    Science.gov (United States)

    Chitambar, Christopher R; Al-Gizawiy, Mona M; Alhajala, Hisham S; Pechman, Kimberly R; Wereley, Janine P; Wujek, Robert; Clark, Paul A; Kuo, John S; Antholine, William E; Schmainda, Kathleen M

    2018-03-28

    Gallium, a metal with antineoplastic activity, binds transferrin (Tf) and enters tumor cells via Tf receptor1 (TfR1); it disrupts iron homeostasis leading to cell death. We hypothesized that TfR1 on brain microvascular endothelial cells (BMECs) would facilitate Tf-Ga transport into the brain enabling it to target TfR-bearing glioblastoma. We show that U-87 MG and D54 glioblastoma cell lines and multiple glioblastoma stem cell (GSCs) lines express TfRs and that their growth is inhibited by gallium maltolate (GaM) in vitro. After 24-h of incubation with GaM, cells displayed a loss of mitochondrial reserve capacity followed by a dose-dependent decrease in oxygen consumption and a decrease in the activity of the iron-dependent M2 subunit of ribonucleotide reductase (RRM2). Immunohistochemical staining of rat and human tumor-bearing brains showed that glioblastoma, but not normal glial cells, expressed TfR1 and RRM2 and that glioblastoma expressed greater levels of H- and L-ferritin than normal brain. In an orthotopic U-87 MG glioblastoma xenograft rat model, GaM retarded the growth of brain tumors relative to untreated control (p=0.0159) and reduced tumor mitotic figures (p=0.045). Tumors in GaM-treated animals displayed an upregulation of TfR1 expression relative to control animals thus indicating that gallium produced tumor iron deprivation. GaM also inhibited iron uptake and upregulated TfR1 expression in U-87 MG and D54 cells in vitro. We conclude that GaM enters the brain via TfR1 on BMECs and targets iron metabolism in glioblastoma in vivo, thus inhibiting tumor growth. Further development of novel gallium compounds for brain tumor treatment is warranted. Copyright ©2018, American Association for Cancer Research.

  8. Alteration of mammalian-cell toxicity of pesticides by structural iron(II) in ferruginous smectite.

    Science.gov (United States)

    Sorensen, Kara C; Stucki, Joseph W; Warner, Richard E; Plewa, Michael J

    2004-08-15

    The ultimate concern over pesticides in the environment is their toxic impact on nontarget organisms, including humans. Soil clays are known to interact with pesticides in ways that decrease the concentration of the parent compound in the soil solution (adsorption, sequestration, degradation). These phenomena are generally regarded as beneficial, but toxicological verification is lacking. In this study, mammalian-cell cytotoxicity of four commonly used agricultural chemicals (2,4-D, alachlor, dicamba, and oxamyl) was assessed after exposure to either reduced or oxidized ferruginous smectite (SWa-1). Results revealed that treatment with reduced smectite produced differential effects on mammalian-cell viability, depending on the pesticide. Oxamyl and alachlor reacted with reduced SWa-1 showed a significant decrease in their overall cytotoxic potential. Dicamba reacted with the reduced-clay treatment and generated products that were more toxic than the parent pesticide. Finally, no differences were observed between redox treatments for 2,4-D. The significance of these results is that oxidized smectites have virtually no influence on the toxicity of pesticides, whereas reduced-Fe smectite plays an important role in altering the cytotoxic potential of agricultural pesticides. The Fe oxidation state of clay minerals should, therefore, be taken into account in pesticide management programs.

  9. Alterations in cholesterol metabolism restrict HIV-1 trans infection in nonprogressors.

    Science.gov (United States)

    Rappocciolo, Giovanna; Jais, Mariel; Piazza, Paolo; Reinhart, Todd A; Berendam, Stella J; Garcia-Exposito, Laura; Gupta, Phalguni; Rinaldo, Charles R

    2014-04-29

    ABSTRACT HIV-1-infected nonprogressors (NP) inhibit disease progression for years without antiretroviral therapy. Defining the mechanisms for this resistance to disease progression could be important in determining strategies for controlling HIV-1 infection. Here we show that two types of professional antigen-presenting cells (APC), i.e., dendritic cells (DC) and B lymphocytes, from NP lacked the ability to mediate HIV-1 trans infection of CD4(+) T cells. In contrast, APC from HIV-1-infected progressors (PR) and HIV-1-seronegative donors (SN) were highly effective in mediating HIV-1 trans infection. Direct cis infection of T cells with HIV-1 was comparably efficient among NP, PR, and SN. Lack of HIV-1 trans infection in NP was linked to lower cholesterol levels and an increase in the levels of the reverse cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) in APC but not in T cells. Moreover, trans infection mediated by APC from NP could be restored by reconstitution of cholesterol and by inhibiting ABCA1 by mRNA interference. Importantly, this appears to be an inherited trait, as it was evident in APC obtained from NP prior to their primary HIV-1 infection. The present study demonstrates a new mechanism wherein enhanced lipid metabolism in APC results in remarkable control of HIV-1 trans infection that directly relates to lack of HIV-1 disease progression. IMPORTANCE HIV-1 can be captured by antigen-presenting cells (APC) such as dendritic cells and transferred to CD4 helper T cells, which results in greatly enhanced viral replication by a mechanism termed trans infection. A small percentage of HIV-1-infected persons are able to control disease progression for many years without antiretroviral therapy. In our study, we linked this lack of disease progression to a profound inability of APC from these individuals to trans infect T cells. This effect was due to altered lipid metabolism in their APC, which appears to be an inherited trait. These

  10. The Relation between Fructose-Induced Metabolic Syndrome and Altered Renal Haemodynamic and Excretory Function in the Rat

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    Mohammed H. Abdulla

    2011-01-01

    Full Text Available This paper explores the possible relationships between dietary fructose and altered neurohumoral regulation of renal haemodynamic and excretory function in this model of metabolic syndrome. Fructose consumption induces hyperinsulinemia, hypertriglyceridaemia, insulin resistance, and hypertension. The pathogenesis of fructose-induced hypertension is dubious and involves numerous pathways acting both singly and together. In addition, hyperinsulinemia and hypertension contribute significantly to progressive renal disease in fructose-fed rats. Moreover, increased activity of the renin-angiotensin and sympathetic nervous systems leading to downregulation of receptors may be responsible for the blunted vascular sensitivity to angiotensin II and catecholamines, respectively. Various approaches have been suggested to prevent the development of fructose-induced hypertension and/or metabolic alteration. In this paper, we address the role played by the renin-angiotensin and sympathetic nervous systems in the haemodynamic alterations that occur due to prolonged consumption of fructose.

  11. Evidence of Insulin Resistance and Other Metabolic Alterations in Boys with Duchenne or Becker Muscular Dystrophy

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    Maricela Rodríguez-Cruz

    2015-01-01

    Full Text Available Aim. Our aim was (1 to determine the frequency of insulin resistance (IR in patients with Duchenne/Becker muscular dystrophy (DMD/BMD, (2 to identify deleted exons of DMD gene associated with obesity and IR, and (3 to explore some likely molecular mechanisms leading to IR. Materials and Methods. In 66 patients with DMD/BMD without corticosteroids treatment, IR, obesity, and body fat mass were evaluated. Molecules involved in glucose metabolism were analyzed in muscle biopsies. Results show that 18.3%, 22.7%, and 68% were underweight, overweight, or obese, and with high adiposity, respectively; 48.5% and 36.4% presented hyperinsulinemia and IR, respectively. Underweight patients (27.3% exhibited hyperinsulinemia and IR. Carriers of deletions in exons 45 (OR = 9.32; 95% CI = 1.16–74.69 and 50 (OR = 8.73; 95% CI = 1.17–65.10 from DMD gene presented higher risk for IR than noncarriers. We observed a greater staining of cytoplasmic aggregates for GLUT4 in muscle biopsies than healthy muscle tissue. Conclusion. Obesity, hyperinsulinemia, and IR were observed in DMD/BMD patients and are independent of corticosteroids treatment. Carriers of deletion in exons 45 or 50 from DMD gene are at risk for developing IR. It is suggested that alteration in GLUT4 in muscle fibers from DMD patients could be involved in IR.

  12. Alterations in glucose and protein metabolism in animals subjected to simulated microgravity

    Science.gov (United States)

    Mondon, C. E.; Rodnick, K. J.; Azhar, S.; Reaven, G. M.; Dolkas, C. B.

    1992-01-01

    Reduction of physical activity due to disease or environmental restraints, such as total bed rest or exposure to spaceflight, leads to atrophy of skeletal muscle and is frequently accompanied by alterations in food intake and the concentration of metabolic regulatory hormones such as insulin. Hindlimb suspension of laboratory rats, as a model for microgravity, also shows marked atrophy of gravity-dependent muscles along with a reduced gain in body weight. Suspended rats exhibit enhanced sensitivity to insulin-induced glucose uptake when compared with normal control rats and resistance to insulin action when compared with control rats matched similarly for reduced body weight gain. These changes are accompanied by decreased insulin binding and tyrosine kinase activity in soleus but not plantaris muscle, unchanged glucose uptake by perfused hindlimb and decreased sensitivity but not responsiveness to insulin-induced suppression of net proteolysis in hindlimb skeletal muscle. These findings suggest that loss of insulin sensitivity during muscle atrophy is associated with decreased insulin binding and tyrosine kinase activity in atrophied soleus muscle along with decreased sensitivity to the effects of insulin on suppressing net protein breakdown but not on enhancing glucose uptake by perfused hindlimb.

  13. Aerobic training does not alter blood pressure in menopausal women with metabolic syndrome.

    Science.gov (United States)

    Lima, Aluísio Henrique Rodrigues de Andrade; Couto, Henrique Eduardo; Cardoso, Glêbia Alexa; Toscano, Lidiane Tavares; Silva, Alexandre Sérgio; Mota, Maria Paula Gonçalves

    2012-11-01

    Arterial Hypertension (AH) is an aggravating condition for Metabolic Syndrome (MS), as well as being aggravated by it. Menopause can make hypertension treatment more difficult, as it favors the worsening of MS components. Although there is evidence that exercise training reduces blood pressure, whether menopause and SM affect the exercise-induced benefits is yet to be elucidated. To compare the effects of aerobic training on blood pressure in non-menopausal and menopausal women with MS METHODS: A total of 44 women were recruited and divided into four groups: non-menopausal control (NMC: 39.5 ± 3.6 years, n = 11); menopausal control (MC: 54.9 ± 5.9 years, n = 12), non-menopausal aerobics (NMA: 43.1 ± 6.8 years, n = 11) and menopausal aerobics (MA: 52.1 ± 5 years, n = 10). The exercise groups performed aerobic training for three months, five times a week, at an intensity between 60% and 70% of heart rate reserve. The resting blood pressure and blood pressure response after 60 minutes of exercise were measured before and after the training period. The two-way ANOVA test was used, considering a p value 0.05). Three months of aerobic training improved MS components, but did not alter resting blood pressure or the BP response after an acute exercise session in women with MS.

  14. Evidence of Insulin Resistance and Other Metabolic Alterations in Boys with Duchenne or Becker Muscular Dystrophy

    Science.gov (United States)

    Rodríguez-Cruz, Maricela; Sanchez, Raúl; Escobar, Rosa E.; Cruz-Guzmán, Oriana del Rocío; López-Alarcón, Mardia; Bernabe García, Mariela; Coral-Vázquez, Ramón; Matute, Guadalupe; Velázquez Wong, Ana Claudia

    2015-01-01

    Aim. Our aim was (1) to determine the frequency of insulin resistance (IR) in patients with Duchenne/Becker muscular dystrophy (DMD/BMD), (2) to identify deleted exons of DMD gene associated with obesity and IR, and (3) to explore some likely molecular mechanisms leading to IR. Materials and Methods. In 66 patients with DMD/BMD without corticosteroids treatment, IR, obesity, and body fat mass were evaluated. Molecules involved in glucose metabolism were analyzed in muscle biopsies. Results show that 18.3%, 22.7%, and 68% were underweight, overweight, or obese, and with high adiposity, respectively; 48.5% and 36.4% presented hyperinsulinemia and IR, respectively. Underweight patients (27.3%) exhibited hyperinsulinemia and IR. Carriers of deletions in exons 45 (OR = 9.32; 95% CI = 1.16–74.69) and 50 (OR = 8.73; 95% CI = 1.17–65.10) from DMD gene presented higher risk for IR than noncarriers. We observed a greater staining of cytoplasmic aggregates for GLUT4 in muscle biopsies than healthy muscle tissue. Conclusion. Obesity, hyperinsulinemia, and IR were observed in DMD/BMD patients and are independent of corticosteroids treatment. Carriers of deletion in exons 45 or 50 from DMD gene are at risk for developing IR. It is suggested that alteration in GLUT4 in muscle fibers from DMD patients could be involved in IR. PMID:26089900

  15. Association between the pattern of IGFBP-1 alteration and the glucose/insulin metabolic control.

    Science.gov (United States)

    Nedić, O; Masnikosa, R; Lagundžin, D

    2011-05-01

    Little is known on the possible association between impaired glucose/insulin metabolism, the pattern of IGFBP-1 phosphorylation and the complex formation with other serum proteins. In this study, the concentration, isoform, multimer and complex pattern of IGFBP-1 was compared in healthy persons and patients with type 2 diabetes mellitus or with hypoglycemia. Concentrations of insulin and IGFBP-1 were determined by radioimmunoassay. Metal affinity and immunoaffinity chromatography were used for the separation of molecular forms of IGFBP-1, which were detected by immunoblotting and SELDI. The counter directional change in insulin and IGFBP-1 concentrations, expressed as a factor that takes into consideration the rate of insulin increase and IGFBP-1 decrease after glucose intake was approximately twice more pronounced in patients with diabetes than in healthy and hypoglycemic persons. The alteration in the phosphorylation pattern of IGFBP-1 due to diabetes or hypoglycemia was not observed. IGFBP-1 multimers found in the circulation of patients with diabetes type 2 differed from those detected in the circulation of others: there were 3 molecular forms between 90 and 100 kDa (compared to one in patients with hypoglycemia or 2 in healthy persons), 2 of which were α (2)M-reactive and one not. These results suggest a possible greater involvement of IGF system in glucose regulation in patients with diabetes type 2. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  16. Downstream targets of altered sphingolipid metabolism in response to inhibition of ENOX2 by phenoxodiol.

    Science.gov (United States)

    De Luca, Thomas; Bosneaga, Elena; Morré, Dorothy M; Morré, D James

    2008-01-01

    Phenoxodiol, an ENOX2 inhibitor, alters cytosolic NADH levels to initiate a regulatory cascade linking sphingolipid metabolism and the PI3K/Akt pathway to programmed cell death. Specifically, the pyridine nucleotide products of plasma membrane redox, NAD+ and NADH, directly modulate in a recriprocal manner two key plasma membrane enzymes. NADH stimulation of sphingomyelinase and NADH inhibition of sphingosine kinase potentially lead to G1 arrest (increase in ceramide) and apoptosis (loss of sphingosine-1-phosphate). The findings link plasma membrane electron transport and the anticancer action of several clinically-relevant anticancer agents targeted to ENOX2 such as phenoxodiol. Growth inhibition by phenoxodiol is unaffected by inhibitors of protein or mRNA synthesis. Findings with okadiaic acid, an inhibitor of serine/threonine phosphatases, suggest that hyperphosphorylation of intracellular substrates does not affect the action of phenoxodiol on ENOX2. Our findings and those of others are consistent with operation of the FAS signaling pathway of apoptosis and its suppression by sphingosine-1-phosphate. The prevailing hypothesis is that products of Akt activation, c-FLIP and XIAP, which exhibit anticaspase activities to block FAS signaling when sphingosine-1-phospate is elevated, are down regulated to permit apoptosis when sphingosine-1-phosphate is decreased by inhibition of sphingosine kinase under conditions of elevated cytosolic NADH associated with anticancer drug inhibition of ENOX2.

  17. 3'-Azido-3'-deoxythymidine (AZT) induces apoptosis and alters metabolic enzyme activity in human placenta

    International Nuclear Information System (INIS)

    Collier, Abby C.; Helliwell, Rachel J.A.; Keelan, Jeffrey A.; Paxton, James W.; Mitchell, Murray D.; Tingle, Malcolm D.

    2003-01-01

    The anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) is the drug of choice for preventing maternal-fetal HIV transmission during pregnancy. Our aim was to assess the cytotoxic effects of AZT on human placenta in vitro. The mechanisms of AZT-induced effects were investigated using JEG-3 choriocarcinoma cells and primary explant cultures from term and first-trimester human placentas. Cytotoxicity measures included trypan blue exclusion, MTT, and reactive oxygen species (ROS) assays. Apoptosis was measured with an antibody specific to cleaved caspase-3 and by rescue of cells by the general caspase inhibitor Boc-D-FMK. The effect of AZT on the activities of glutathione-S-transferase, β-glucuronidase, UDP-glucuronosyl transferase, cytochrome P450 (CYP) 1A, and CYP reductase (CYPR) in the placenta was assessed using biochemical assays and immunoblotting. AZT increased ROS levels, decreased cellular proliferation rates, was toxic to mitochondria, and initiated cell death by a caspase-dependent mechanism in the human placenta in vitro. In the absence of serum, the effects of AZT were amplified in all the models used. AZT also increased the amounts of activity of GST, β-glucuronidase, and CYP1A, whereas UGT and CYPR were decreased. We conclude that AZT causes apoptosis in the placenta and alters metabolizing enzymes in human placental cells. These findings have implications for the safe administration of AZT in pregnancy with respect to the maintenance of integrity of the maternal-fetal barrier

  18. Alterations in glucose and protein metabolism in animals subjected to simulated microgravity

    Science.gov (United States)

    Mondon, C. E.; Rodnick, K. J.; Dolkas, C. B.; Azhar, S.; Reaven, G. M.

    1992-09-01

    Reduction of physical activity due to disease or environmental restraints, such as total bed rest or exposure to spaceflight, leads to atrophy of skeletal muscle and is frequently accompanied by alterations in food intake and the concentration of metabolic regulatory hormones such as insulin. Hindlimb suspension of laboratory rats, as a model for microgravity, also shows marked atrophy of gravity dependent muscles along with a reduced gain in body weight. Suspended rats exhibit enhanced sensitivity to insulin-induced glucose uptake when compared with normal control rats and resistance to insulin action when compared with control rats matched similarly for reduced body weight gain. These changes are accompanied by decreased insulin binding and tyrosine kinase activity in soleus but not plantaris muscle, unchanged glucose uptake by perfused hindlimb and decreased sensitivity but not responsiveness to insulin-induced suppression of net proteolysis in hindlimb skeletal muscle. These findings suggest that loss of insulin sensitivity during muscle atrophy is associated with decreased insulin binding and tyrosine kinase activity in atrophied soleus muscle along with decreased sensitivity to the effects of insulin on suppressing net protein breakdown but not on enhancing glucose uptake by perfused hindlimb.

  19. Proteomic Characterization of Armillaria mellea Reveals Oxidative Stress Response Mechanisms and Altered Secondary Metabolism Profiles

    Directory of Open Access Journals (Sweden)

    Cassandra Collins

    2017-09-01

    Full Text Available Armillaria mellea is a major plant pathogen. Yet, the strategies the organism uses to infect susceptible species, degrade lignocellulose and other plant material and protect itself against plant defences and its own glycodegradative arsenal are largely unknown. Here, we use a combination of gel and MS-based proteomics to profile A. mellea under conditions of oxidative stress and changes in growth matrix. 2-DE and LC-MS/MS were used to investigate the response of A. mellea to H2O2 and menadione/FeCl3 exposure, respectively. Several proteins were detected with altered abundance in response to H2O2, but not menadione/FeCl3 (i.e., valosin-containing protein, indicating distinct responses to these different forms of oxidative stress. One protein, cobalamin-independent methionine synthase, demonstrated a common response in both conditions, which may be a marker for a more general stress response mechanism. Further changes to the A. mellea proteome were investigated using MS-based proteomics, which identified changes to putative secondary metabolism (SM enzymes upon growth in agar compared to liquid cultures. Metabolomic analyses revealed distinct profiles, highlighting the effect of growth matrix on SM production. This establishes robust methods by which to utilize comparative proteomics to characterize this important phytopathogen.

  20. Proteomic Characterization of Armillaria mellea Reveals Oxidative Stress Response Mechanisms and Altered Secondary Metabolism Profiles.

    Science.gov (United States)

    Collins, Cassandra; Hurley, Rachel; Almutlaqah, Nada; O'Keeffe, Grainne; Keane, Thomas M; Fitzpatrick, David A; Owens, Rebecca A

    2017-09-17

    Armillaria mellea is a major plant pathogen. Yet, the strategies the organism uses to infect susceptible species, degrade lignocellulose and other plant material and protect itself against plant defences and its own glycodegradative arsenal are largely unknown. Here, we use a combination of gel and MS-based proteomics to profile A. mellea under conditions of oxidative stress and changes in growth matrix. 2-DE and LC-MS/MS were used to investigate the response of A. mellea to H₂O₂ and menadione/FeCl₃ exposure, respectively. Several proteins were detected with altered abundance in response to H₂O₂, but not menadione/FeCl₃ (i.e., valosin-containing protein), indicating distinct responses to these different forms of oxidative stress. One protein, cobalamin-independent methionine synthase, demonstrated a common response in both conditions, which may be a marker for a more general stress response mechanism. Further changes to the A. mellea proteome were investigated using MS-based proteomics, which identified changes to putative secondary metabolism (SM) enzymes upon growth in agar compared to liquid cultures. Metabolomic analyses revealed distinct profiles, highlighting the effect of growth matrix on SM production. This establishes robust methods by which to utilize comparative proteomics to characterize this important phytopathogen.

  1. Cpt1a gene expression in peripheral blood mononuclear cells as an early biomarker of diet-related metabolic alterations

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    Rubén Díaz-Rúa

    2016-11-01

    Full Text Available Background: Research on biomarkers that provide early information about the development of future metabolic alterations is an emerging discipline. Gene expression analysis in peripheral blood mononuclear cells (PBMC is a promising tool to identify subjects at risk of developing diet-related diseases. Objective: We analysed PBMC expression of key energy homeostasis-related genes in a time-course analysis in order to find out early markers of metabolic alterations due to sustained intake of high-fat (HF and high-protein (HP diets. Design: We administered HF and HP diets (4 months to adult Wistar rats in isocaloric conditions to a control diet, mainly to avoid overweight associated with the intake of hyperlipidic diets and, thus, to be able to characterise markers of metabolically obese normal-weight (MONW syndrome. PBMC samples were collected at different time points of dietary treatment and expression of relevant energy homeostatic genes analysed by real-time reverse transcription-polymerase chain reaction. Serum parameters related with metabolic syndrome, as well as fat deposition in liver, were also analysed. Results: The most outstanding results were those obtained for the expression of the lipolytic gene carnitine palmitoyltransferase 1a (Cpt1a. Cpt1a expression in PBMC increased after only 1 month of exposure to both unbalanced diets, and this increased expression was maintained thereafter. Interestingly, in the case of the HF diet, Cpt1a expression was altered even in the absence of increased body weight but correlated with alterations such as higher insulin resistance, alteration of serum lipid profile and, particularly, increased fat deposition in liver, a feature characteristic of metabolic syndrome, which was even observed in animals fed with HP diet. Conclusions: We propose Cpt1a gene expression analysis in PBMC as an early biomarker of metabolic alterations associated with MONW phenotype due to the intake of isocaloric HF diets, as

  2. Iron oxide nanoparticles induced alterations in haematological, biochemical and ionoregulatory responses of an Indian major carp Labeo rohita

    Energy Technology Data Exchange (ETDEWEB)

    Saravanan, M.; Suganya, R.; Ramesh, M., E-mail: mathanramesh@yahoo.com; Poopal, R. K. [Bharathiar University, Unit of Toxicology, Department of Zoology, School of Life Sciences (India); Gopalan, N. [Bharathiar University, DRDO-BU (India); Ponpandian, N. [Bharathiar University, Department of Nanoscience and Technology (India)

    2015-06-15

    The wide use of iron oxide nanoparticles (Fe{sub 2}O{sub 3} NPs) in various applications has raised great concerns worldwide. In this work, we measured the potential harmful effects of Fe{sub 2}O{sub 3} NP (<50 nm) at concentrations of 1 and 25 mg/L on haematological, biochemical, and ionoregulatory responses in an Indian major carp, Labeo rohita for a short-term period of 96 h. The results revealed significant (P < 0.05) decreases in haemoglobin, haematocrit, mean cellular volume, mean cellular haemoglobin, protein, sodium (Na{sup +}), potassium (K{sup +}), chloride (Cl{sup −}) and gill Na{sup +}/K{sup +}-ATPase levels in both the concentrations. White blood cell, mean cellular haemoglobin concentration and glucose levels were significantly (P < 0.05) increased in response to both concentrations during the study period. However, no significant changes in red blood cell count and gill Na{sup +}/K{sup +}-ATPase (25 mg/L) activity were noticed compared to those of the respective control groups. Based on this study, it was found that the Fe{sub 2}O{sub 3} NPs do have prominent effects on freshwater fish L. rohita. Our data suggest that the alterations of these parameters can be used as nonspecific biomarkers to monitor the environmental risks arising from nanoparticles in aquatic ecosystem and also regulate the use, production and release of nanoparticles.

  3. The presence of serum alters the properties of iron oxide nanoparticles and lowers their accumulation by cultured brain astrocytes

    Science.gov (United States)

    Geppert, Mark; Petters, Charlotte; Thiel, Karsten; Dringen, Ralf

    2013-01-01

    Iron oxide nanoparticles (IONPs) are considered for various diagnostic and therapeutic applications. Such particles are able to cross the blood-brain barrier and are taken up into brain cells. To test whether serum components affect the properties of IONPs and/or their uptake into brain cells, we have incubated dimercaptosuccinate-coated magnetic IONPs without and with fetal calf serum (FCS) and have exposed cultured brain astrocytes with IONPs in the absence or presence of FCS. Incubation with FCS caused a concentration-dependent increase in the average hydrodynamic diameter of the particles and of their zeta-potential. In the presence of 10 % FCS, the diameter of the IONPs increased from 57 ± 2 to 107 ± 6 nm and the zeta-potential of the particles from -22 ± 5 to -9 ± 1 mV. FCS affected also strongly the uptake of IONPs by cultured astrocytes. The efficient time- and temperature-dependent cellular accumulation of IONPs was lowered with increasing concentration of FCS by up to 90 %. In addition, in the absence of serum, endocytosis inhibitors did not alter the IONP accumulation by astrocytes, while chlorpromazine or wortmannin lowered significantly the accumulation of IONPs in the presence of FCS, suggesting that clathrin-mediated endocytosis and macropinocytosis are involved in astrocytic IONP uptake from serum-containing medium. These data demonstrate that the presence of FCS strongly affects the properties of IONPs as well as their accumulation by cultured brain cells.

  4. The presence of serum alters the properties of iron oxide nanoparticles and lowers their accumulation by cultured brain astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Geppert, Mark; Petters, Charlotte [University of Bremen, Centre for Biomolecular Interactions Bremen (Germany); Thiel, Karsten [Fraunhofer Institute for Manufacturing Technology and Advanced Materials (Germany); Dringen, Ralf, E-mail: ralf.dringen@uni-bremen.de [University of Bremen, Centre for Biomolecular Interactions Bremen (Germany)

    2013-01-15

    Iron oxide nanoparticles (IONPs) are considered for various diagnostic and therapeutic applications. Such particles are able to cross the blood-brain barrier and are taken up into brain cells. To test whether serum components affect the properties of IONPs and/or their uptake into brain cells, we have incubated dimercaptosuccinate-coated magnetic IONPs without and with fetal calf serum (FCS) and have exposed cultured brain astrocytes with IONPs in the absence or presence of FCS. Incubation with FCS caused a concentration-dependent increase in the average hydrodynamic diameter of the particles and of their zeta-potential. In the presence of 10 % FCS, the diameter of the IONPs increased from 57 {+-} 2 to 107 {+-} 6 nm and the zeta-potential of the particles from -22 {+-} 5 to -9 {+-} 1 mV. FCS affected also strongly the uptake of IONPs by cultured astrocytes. The efficient time- and temperature-dependent cellular accumulation of IONPs was lowered with increasing concentration of FCS by up to 90 %. In addition, in the absence of serum, endocytosis inhibitors did not alter the IONP accumulation by astrocytes, while chlorpromazine or wortmannin lowered significantly the accumulation of IONPs in the presence of FCS, suggesting that clathrin-mediated endocytosis and macropinocytosis are involved in astrocytic IONP uptake from serum-containing medium. These data demonstrate that the presence of FCS strongly affects the properties of IONPs as well as their accumulation by cultured brain cells.

  5. Dysmetabolic iron overload syndrome (DIOS).

    Science.gov (United States)

    Deugnier, Yves; Bardou-Jacquet, Édouard; Lainé, Fabrice

    2017-12-01

    Dysmetabolic iron overload syndrome (DIOS) corresponds to mild increase in both liver and body iron stores associated with various components of metabolic syndrome in the absence of any identifiable cause of iron excess. It is characterized by hyperferritinemia with normal or moderately increased transferrin saturation, one or several metabolic abnormalities (increased body mass index with android distribution of fat, elevated blood pressure, dyslipidaemia, abnormal glucose metabolism, steatohepatitis), and mild hepatic iron excess at magnetic resonance imaging or liver biopsy. Alteration of iron metabolism in DIOS likely results from a multifactorial and dynamic process triggered by an excessively rich diet, facilitated by environmental and genetic cofactors and implying a cross-talk between the liver and visceral adipose tissue. Phlebotomy therapy cannot be currently considered as a valuable option in DIOS patients. Sustained modification of diet and life-style habits remains the first therapeutic intervention in these patients together with drug control of increased blood pressure, abnormal blood glucose and dyslipidaemia when necessary. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Altered Mycobacterium tuberculosis Cell Wall Metabolism and Physiology Associated With RpoB Mutation H526D

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    Victoria L. Campodónico

    2018-03-01

    Full Text Available Background:Mycobacterium tuberculosis (Mtb rpoB mutations are associated with global metabolic remodeling. However, the net effects of rpoB mutations on Mtb physiology, metabolism and function are not completely understood. Based on previous work, we hypothesized that changes in the expression of cell wall molecules in Mtb mutant RpoB 526D lead to changes in cell wall permeability and to altered resistance to environmental stresses and drugs.Methods: The phenotypes of a fully drug-susceptible clinical strain of Mtb and its paired rifampin-monoresistant, RpoB H526D mutant progeny strain were compared.Results: The rpoB mutant showed altered colony morphology, bacillary length and cell wall thickness, which were associated with increased cell wall permeability and susceptibility to the cell wall detergent sodium dodecyl sulfate (SDS after exposure to nutrient starvation. Relative to the isogenic rifampin-susceptible strain, the RpoB H526D mutant showed altered bacterial cellular metabolic activity and an eightfold increase in susceptibility to the cell-wall acting drug vancomycin.Conclusion: Our data suggest that RpoB mutation H526D is associated with altered cell wall physiology and resistance to cell wall-related stress. These findings are expected to contribute to an improved understanding of the pathogenesis of drug-resistant M. tuberculosis infections.

  7. Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study.

    Science.gov (United States)

    Karwowski, Mateusz P; Just, Allan C; Bellinger, David C; Jim, Rebecca; Hatley, Earl L; Ettinger, Adrienne S; Hu, Howard; Wright, Robert O

    2014-10-06

    Given the relationship between iron metabolism and lead toxicokinetics, we hypothesized that polymorphisms in iron metabolism genes might modify maternal-fetal lead transfer. The objective of this study was to determine whether maternal and/or infant transferrin (TF) and hemochromatosis (HFE) gene missense variants modify the association between maternal blood lead (MBL) and umbilical cord blood lead (UCBL). We studied 476 mother-infant pairs whose archived blood specimens were genotyped for TF P570S, HFE H63D and HFE C282Y. MBL and UCBL were collected within 12 hours of delivery. Linear regression models were used to examine the association between log-transformed MBL and UCBL, examine for confounding and collinearity, and explore gene-environment interactions. The geometric mean MBL was 0.61 μg/dL (range 0.03, 3.2) and UCBL 0.42 (lead transfer among women with MBL 5 μg/dL. Maternal HFE C282Y gene variant status is associated with greater reductions in placental transfer of lead as MBL increases. The inclusion of gene-environment interaction in risk assessment models may improve efforts to safeguard vulnerable populations.

  8. Practice guidelines for the diagnosis and management of microcytic anemias due to genetic disorders of iron metabolism or heme synthesis.

    Science.gov (United States)

    Donker, Albertine E; Raymakers, Reinier A P; Vlasveld, L Thom; van Barneveld, Teus; Terink, Rieneke; Dors, Natasja; Brons, Paul P T; Knoers, Nine V A M; Swinkels, Dorine W

    2014-06-19

    During recent years, our understanding of the pathogenesis of inherited microcytic anemias has gained from the identification of several genes and proteins involved in systemic and cellular iron metabolism and heme syntheses. Numerous case reports illustrate that the implementation of these novel molecular discoveries in clinical practice has increased our understanding of the presentation, diagnosis, and management of these diseases. Integration of these insights into daily clinical practice will reduce delays in establishing a proper diagnosis, invasive and/or costly diagnostic tests, and unnecessary or even detrimental treatments. To assist the clinician, we developed evidence-based multidisciplinary guidelines on the management of rare microcytic anemias due to genetic disorders of iron metabolism and heme synthesis. These genetic disorders may present at all ages, and therefore these guidelines are relevant for pediatricians as well as clinicians who treat adults. This article summarizes these clinical practice guidelines and includes background on pathogenesis, conclusions, and recommendations and a diagnostic flowchart to facilitate using these guidelines in the clinical setting. © 2014 by The American Society of Hematology.

  9. Glycogen metabolism in brain and neurons - astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure.

    Science.gov (United States)

    Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Gąssowska, Magdalena; Kolasa-Wołosiuk, Agnieszka; Tarnowski, Maciej; Chibowska, Karina; Goschorska, Marta; Lubkowska, Anna; Chlubek, Dariusz

    2017-09-01

    Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase β (PHKB). Moreover, the expression of connexin 43 (Cx43) was evaluated to analyze whether Pb poisoning during the early phase of life may affect the neuron-astrocytes' metabolic cooperation. This work shows for the first time that exposure to Pb in early life can impair brain energy metabolism by reducing the amount of glycogen and decreasing the rate of its metabolism. This reduction in brain glycogen level was accompanied by a decrease in Gys1 expression. We noted a reduction in the immunoreactivity and the gene expression of both PYGB and PYGM isoform, as well as an increase in the expression of PHKB in Pb-treated rats. Moreover, exposure to Pb induced decrease in connexin 43 immunoexpression in all the brain structures analyzed, both in astrocytes as well as in neurons. Our data suggests that exposure to Pb in the pre- and neonatal periods results in a decrease in the level of brain glycogen and a reduction in the rate of its metabolism, thereby reducing glucose availability, which as a further consequence may lead to the impairment of brain energy metabolism and the metabolic cooperation between neurons and astrocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Alterations in lipid metabolism mediate inflammation, fibrosis, and proliferation in a mouse model of chronic cholestatic liver injury.

    Science.gov (United States)

    Moustafa, Tarek; Fickert, Peter; Magnes, Christoph; Guelly, Christian; Thueringer, Andrea; Frank, Sasa; Kratky, Dagmar; Sattler, Wolfgang; Reicher, Helga; Sinner, Frank; Gumhold, Judith; Silbert, Dagmar; Fauler, Günter; Höfler, Gerald; Lass, Achim; Zechner, Rudolf; Trauner, Michael

    2012-01-01

    The liver controls central processes of lipid and bile acid homeostasis. We aimed to investigate whether alterations in lipid metabolism contribute to the pathogenesis of chronic cholestatic liver disease in mice. We used microarray and metabolic profiling analyses to identify alterations in systemic and hepatic lipid metabolism in mice with disruption of the gene ATP-binding cassette sub-family B member 4 (Abcb4(-/-) mice), a model of inflammation-induced cholestatic liver injury, fibrosis, and cancer. Alterations in Abcb4(-/-) mice, compared with wild-type mice, included deregulation of genes that control lipid synthesis, storage, and oxidation; decreased serum levels of cholesterol and phospholipids; and reduced hepatic long-chain fatty acyl-CoAs (LCA-CoA). Feeding Abcb4(-/-) mice the side chain-modified bile acid 24-norursodeoxycholic acid (norUDCA) reversed their liver injury and fibrosis, increased serum levels of lipids, lowered phospholipase and triglyceride hydrolase activities, and restored hepatic LCA-CoA and triglyceride levels. Additional genetic and nutritional studies indicated that lipid metabolism contributed to chronic cholestatic liver injury; crossing peroxisome proliferator-activated receptor (PPAR)-α-deficient mice with Abcb4(-/-) mice (to create double knockouts) or placing Abcb4(-/-) mice on a high-fat diet protected against liver injury, with features similar to those involved in the response to norUDCA. Placing pregnant Abcb4(-/-) mice on high-fat diets prevented liver injury in their offspring. However, fenofibrate, an activator of PPARα, aggravated liver injury in Abcb4(-/-) mice. Alterations in lipid metabolism contribute to the pathogenesis and progression of cholestatic liver disease in mice. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Anaerobic sulfur metabolism coupled to dissimilatory iron reduction in the extremophile Acidithiobacillus ferrooxidans.

    Science.gov (United States)

    Osorio, Héctor; Mangold, Stefanie; Denis, Yann; Ñancucheo, Ivan; Esparza, Mario; Johnson, D Barrie; Bonnefoy, Violaine; Dopson, Mark; Holmes, David S

    2013-04-01

    Gene transcription (microarrays) and protein levels (proteomics) were compared in cultures of the acidophilic chemolithotroph Acidithiobacillus ferrooxidans grown on elemental sulfur as the electron donor under aerobic and anaerobic conditions, using either molecular oxygen or ferric iron as the electron acceptor, respectively. No evidence supporting the role of either tetrathionate hydrolase or arsenic reductase in mediating the transfer of electrons to ferric iron (as suggested by previous studies) was obtained. In addition, no novel ferric iron reductase was identified. However, data suggested that sulfur was disproportionated under anaerobic conditions, forming hydrogen sulfide via sulfur reductase and sulfate via heterodisulfide reductase and ATP sulfurylase. Supporting physiological evidence for H2S production came from the observation that soluble Cu(2+) included in anaerobically incubated cultures was precipitated (seemingly as CuS). Since H(2)S reduces ferric iron to ferrous in acidic medium, its production under anaerobic conditions indicates that anaerobic iron reduction is mediated, at least in part, by an indirect mechanism. Evidence was obtained for an alternative model implicating the transfer of electrons from S(0) to Fe(3+) via a respiratory chain that includes a bc(1) complex and a cytochrome c. Central carbon pathways were upregulated under aerobic conditions, correlating with higher growth rates, while many Calvin-Benson-Bassham cycle components were upregulated during anaerobic growth, probably as a result of more limited access to carbon dioxide. These results are important for understanding the role of A. ferrooxidans in environmental biogeochemical metal cycling and in industrial bioleaching operations.

  12. Genetic and metabolic signals during acute enteric bacterial infection alter the microbiota and drive progression to chronic inflammatory disease

    Energy Technology Data Exchange (ETDEWEB)

    Kamdar, Karishma; Khakpour, Samira; Chen, Jingyu; Leone, Vanessa; Brulc, Jennifer; Mangatu, Thomas; Antonopoulos, Dionysios A.; Chang, Eugene B; Kahn, Stacy A.; Kirschner, Barbara S; Young, Glenn; DePaolo, R. William

    2016-01-13

    Chronic inflammatory disorders are thought to arise due to an interplay between predisposing host genetics and environmental factors. For example, the onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear. We have shown previously that genetic defiency in TLR1 promotes acute enteric infection by the proteobacteria Yersinia enterocolitica. Examining that model further, we uncovered an altered cellular immune response that promotes the recruitment of neutrophils which in turn increases metabolism of the respiratory electron acceptor tetrathionate by Yersinia. These events drive permanent alterations in anti-commensal immunity, microbiota composition, and chronic inflammation, which persist long after Yersinia clearence. Deletion of the bacterial genes involved in tetrathionate respiration or treatment using targeted probiotics could prevent microbiota alterations and inflammation. Thus, acute infection can drive long term immune and microbiota alterations leading to chronic inflammatory disease in genetically predisposed individuals.

  13. Methylphenidate treatment causes oxidative stress and alters energetic metabolism in an animal model of attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Comim, Clarissa M; Gomes, Karin M; Réus, Gislaine Z; Petronilho, Fabrícia; Ferreira, Gabriela K; Streck, Emílio L; Dal-Pizzol, Felipe; Quevedo, João

    2014-04-01

    To evaluate oxidative damage through the thiobarbituric acid-reactive species (TBARS) and protein carbonyl groups; antioxidant enzymatic system - superoxide dismutase (SOD) and catalase (CAT); and energetic metabolism in the brain of spontaneously hypertensive adult rats (SHR) after both acute and chronic treatment with methylphenidate hydrochloride (MPH). Adult (60 days old) SHRs were treated during 28 days (chronic treatment), or 1 day (acute treatment). The rats received one i.p. injection per day of either saline or MPH (2 mg/kg). Two hours after the last injection, oxidative damage parameters and energetic metabolism in the cerebellum, prefrontal cortex, hippocampus, striatum and cortex were evaluated. We observed that both acute and/or chronic treatment increased TBARS and carbonyl groups, and decreased SOD and CAT activities in many of the brain structures evaluated. Regarding the energetic metabolism evaluation, the acute and chronic treatment altered the energetic metabolism in many of the brain structures evaluated. We observed that both acute and chronic use of methylphenidate hydrochloride (MPH) in adult spontaneously hypertensive rats (SHRs) was associated with increased oxidative stress and energetic metabolism alterations. These data also reinforce the importance of the SHR animal model in further studies regarding MPH.

  14. Metabolic dysfunction and altered mitochondrial dynamics in the utrophin-dystrophin deficient mouse model of duchenne muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Meghna Pant

    Full Text Available The utrophin-dystrophin deficient (DKO mouse model has been widely used to understand the progression of Duchenne muscular dystrophy (DMD. However, it is unclear as to what extent muscle pathology affects metabolism. Therefore, the present study was focused on understanding energy expenditure in the whole animal and in isolated extensor digitorum longus (EDL muscle and to determine changes in metabolic enzymes. Our results show that the 8 week-old DKO mice consume higher oxygen relative to activity levels. Interestingly the EDL muscle from DKO mouse consumes higher oxygen per unit integral force, generates less force and performs better in the presence of pyruvate thus mimicking a slow twitch muscle. We also found that the expression of hexokinase 1 and pyruvate kinase M2 was upregulated several fold suggesting increased glycolytic flux. Additionally, there is a dramatic increase in dynamin-related protein 1 (Drp 1 and mitofusin 2 protein levels suggesting increased mitochondrial fission and fusion, a feature associated with increased energy demand and altered mitochondrial dynamics. Collectively our studies point out that the dystrophic disease has caused significant changes in muscle metabolism. To meet the increased energetic demand, upregulation of metabolic enzymes and regulators of mitochondrial fusion and fission is observed in the dystrophic muscle. A better understanding of the metabolic demands and the accompanied alterations in the dystrophic muscle can help us design improved intervention therapies along with existing drug treatments for the DMD patients.

  15. Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity

    Directory of Open Access Journals (Sweden)

    Mette J. Jacobsen

    2016-01-01

    Full Text Available Obesity is associated with immunological perturbations that contribute to insulin resistance. Epigenetic mechanisms can control immune functions and have been linked to metabolic complications, although their contribution to insulin resistance still remains unclear. In this study, we investigated the link between metabolic dysfunction and immune alterations with the epigenetic signature in leukocytes in a porcine model of obesity. Global DNA methylation of circulating leukocytes, adipose tissue leukocyte trafficking, and macrophage polarisation were established by flow cytometry. Adipose tissue inflammation and metabolic function were further characterised by quantification of metabolites and expression levels of genes associated with obesity and inflammation. Here we show that obese pigs showed bigger visceral fat pads, higher levels of circulating LDL cholesterol, and impaired glucose tolerance. These changes coincided with impaired metabolism, sustained macrophages infiltration, and increased inflammation in the adipose tissue. Those immune alterations were linked to global DNA hypermethylation in both B-cells and T-cells. Our results provide novel insight into the possible contribution of immune cell epigenetics into the immunological disturbances observed in obesity. The dramatic changes in the transcriptomic and epigenetic signature of circulating lymphocytes reinforce the concept that epigenetic processes participate in the increased immune cell activation and impaired metabolic functions in obesity.

  16. Effect of diet composition and mixture of selected food additives on the erythrocytic system and iron metabolism in peripheral blood of male rats.

    Science.gov (United States)

    Sadowska, Joanna; Kuchlewska, Magdalena

    2011-01-01

    Metabolic processes of food additives which are "exogenous xenobiotics" are catalysed, primarily, by enzymes located in microsomes of hepatocytes affiliated to P-450 cytochrome superfamily, containing iron. The aim of the study was to investigate the effect of diet composition and selected food additives on the erythrocyte system and iron metabolism in peripheral blood of male rats. The experiment was carried out on 30 male rats sorted into three equinumerous groups. For drinking animals received pure, settled tap water, animals from group III were receiving additionally an aqueous solution of sodium (nitrate), potassium nitrite, benzoic acid, sorbic acid and monosodium glutamate. Ascertained a significant effect of changes in diet composition on the increase in hematocrit marker value and the count of red blood cells in blood of animals examined. Used food additives diminished hemoglobin concentration, hematocrit value and red blood cell count, diminishing also iron concentration in serum, the total iron binding capacity and transferrin saturation with iron. Analysis of the results allowed ascertain adverse changes in values of the erythrocytic system markers, occurring under the influence of the applied mixture of food additives. Used food additives change the iron metabolism, most likely from the necessity of applied xenobiotics biotransformation by heme-containing monoxygenases of P-450 cytochrome.

  17. Pregnancy and lactation alter biomarkers of biotin metabolism in women consuming a controlled diet.

    Science.gov (United States)

    Perry, Cydne A; West, Allyson A; Gayle, Antoinette; Lucas, Lauren K; Yan, Jian; Jiang, Xinyin; Malysheva, Olga; Caudill, Marie A

    2014-12-01

    Biotin functions as a cofactor for several carboxylase enzymes with key roles in metabolism. At present, the dietary requirement for biotin is unknown and intake recommendations are provided as Adequate Intakes (AIs). The biotin AI for adults and pregnant women is 30 μg/d, whereas 35 μg/d is recommended for lactating women. However, pregnant and lactating women may require more biotin to meet the demands of these reproductive states. The current study sought to quantify the impact of reproductive state on biotin status response to a known dietary intake of biotin. To achieve this aim, we measured a panel of biotin biomarkers among pregnant (gestational week 27 at study entry; n = 26), lactating (postnatal week 5 at study entry; n = 28), and control (n = 21) women who participated in a 10- to 12-wk feeding study providing 57 μg of dietary biotin/d as part of a mixed diet. Over the course of the study, pregnant women excreted 69% more (vs. control; P biotin-dependent methylcrotonyl-coenzyme A carboxylase is impaired. Interestingly, urinary excretion of 3-hydroxyisovaleryl-carnitine (3-HIA-carnitine), a downstream metabolite of 3-HIA, was 27% lower (P = 0.05) among pregnant (vs. control) women, a finding that may arise from carnitine inadequacy during gestation. No differences (P > 0.05) were detected in plasma biotin, urinary biotin, or urinary bisnorbiotin between pregnant and control women. Lactating women excreted 76% more (vs. control; P = 0.001) of the biotin catabolite bisnorbiotin, indicating that lactation accelerates biotin turnover and loss. Notably, with respect to control women, lactating women excreted 23% less (P = 0.04) urinary 3-HIA and 26% less (P = 0.05) urinary 3-HIA-carnitine, suggesting that lactation reduces leucine catabolism and that these metabolites may not be useful indicators of biotin status during lactation. Overall, these data demonstrate significant alterations in markers of biotin metabolism during pregnancy and lactation and

  18. Pregnancy and Lactation Alter Biomarkers of Biotin Metabolism in Women Consuming a Controlled Diet123

    Science.gov (United States)

    Perry, Cydne A; West, Allyson A; Gayle, Antoinette; Lucas, Lauren K; Yan, Jian; Jiang, Xinyin; Malysheva, Olga; Caudill, Marie A

    2014-01-01

    Background: Biotin functions as a cofactor for several carboxylase enzymes with key roles in metabolism. At present, the dietary requirement for biotin is unknown and intake recommendations are provided as Adequate Intakes (AIs). The biotin AI for adults and pregnant women is 30 μg/d, whereas 35 μg/d is recommended for lactating women. However, pregnant and lactating women may require more biotin to meet the demands of these reproductive states. Objective: The current study sought to quantify the impact of reproductive state on biotin status response to a known dietary intake of biotin. Methods: To achieve this aim, we measured a panel of biotin biomarkers among pregnant (gestational week 27 at study entry; n = 26), lactating (postnatal week 5 at study entry; n = 28), and control (n = 21) women who participated in a 10- to 12-wk feeding study providing 57 μg of dietary biotin/d as part of a mixed diet. Results: Over the course of the study, pregnant women excreted 69% more (vs. control; P biotin-dependent methylcrotonyl–coenzyme A carboxylase is impaired. Interestingly, urinary excretion of 3-hydroxyisovaleryl-carnitine (3-HIA-carnitine), a downstream metabolite of 3-HIA, was 27% lower (P = 0.05) among pregnant (vs. control) women, a finding that may arise from carnitine inadequacy during gestation. No differences (P > 0.05) were detected in plasma biotin, urinary biotin, or urinary bisnorbiotin between pregnant and control women. Lactating women excreted 76% more (vs. control; P = 0.001) of the biotin catabolite bisnorbiotin, indicating that lactation accelerates biotin turnover and loss. Notably, with respect to control women, lactating women excreted 23% less (P = 0.04) urinary 3-HIA and 26% less (P = 0.05) urinary 3-HIA-carnitine, suggesting that lactation reduces leucine catabolism and that these metabolites may not be useful indicators of biotin status during lactation. Conclusions: Overall, these data demonstrate significant alterations in markers of

  19. Serum Hepcidin and Soluble Transferrin Receptor in the Assessment of Iron Metabolism in Children on a Vegetarian Diet.

    Science.gov (United States)

    Ambroszkiewicz, Jadwiga; Klemarczyk, Witold; Mazur, Joanna; Gajewska, Joanna; Rowicka, Grażyna; Strucińska, Małgorzata; Chełchowska, Magdalena

    2017-12-01

    The aim of this study was to assess the effect of vegetarian diet on iron metabolism parameters paying special attention to serum hepcidin and soluble transferrin receptor (sTfR) concentrations in 43 prepubertal children (age range 4.5-9.0 years) on vegetarian and in 46 children on omnivorous diets. There were no significant differences according to age, weight, height, and body mass index (BMI) between vegetarian and omnivorous children. Vegetarians had similar intake of iron and vitamin B 12 and a significantly higher intake of vitamin C (p children. Serum transferrin levels were similar in all subjects; however, ferritin concentrations were significantly (p children on a vegetarian diet, median hepcidin levels were lower (p children. In the multivariate regression model, we observed associations between hepcidin level and ferritin concentration (β = 0.241, p = 0.05) in the whole group of children as well as between hepcidin concentration and CRP level (β = 0.419, p = 0.047) in vegetarians. We did not find significant associations with concentration of sTfR and selected biochemical, anthropometric, and dietary parameters in any of the studied groups of children. As hematologic parameters and iron concentrations in vegetarians and omnivores were comparable and ferritin level was lower in vegetarians, we suggest that inclusion of novel markers, in particular sTfR (not cofounded by inflammation) and hepcidin, can better detect subclinical iron deficiency in children following vegetarian diets.

  20. Radioisotope techniques in studies on the metabolism of calcium, iodine and iron in ruminants

    International Nuclear Information System (INIS)

    Lengemann, F.W.

    1984-01-01

    A short review is presented of radioisotopic procedures useful in research on calcium, iodine and iron studies with tropical ruminants. The procedures discussed can be useful in determining the availability of the mineral from feedstuffs, the faecal endogenous losses by the animal, detection of deficiency states, and responses to physiological and environmental stress. Methods that entail the use of radioisotopes in the laboratory or the use of stable isotopes in the animal are mentioned as alternatives to the administration of radioisotopes to the animal. While the review focuses on calcium, iodine and iron, the principles of the methods presented can be employed in the study of many other trace minerals. (author)

  1. Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids.

    Science.gov (United States)

    Das, Undurti N

    2013-10-01

    Autism has a strong genetic and environmental basis in which inflammatory markers and factors concerned with synapse formation, nerve transmission, and information processing such as brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs): arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acids (DHA) and their products and neurotransmitters: dopamine, serotonin, acetylcholine, γ-aminobutyric acid, and catecholamines and cytokines are altered. Antioxidants, vitamins, minerals, and trace elements are needed for the normal metabolism of neurotrophic factors, eicosanoids, and neurotransmitters, supporting reports of their alterations in autism. But, the exact relationship among these factors and their interaction with genes and proteins concerned with brain development and growth is not clear. It is suggested that maternal infections and inflammation and adverse events during intrauterine growth of the fetus could lead to alterations in the gene expression profile and proteomics that results in dysfunction of the neuronal function and neurotransmitters, alteration(s) in the metabolism of PUFAs and their metabolites resulting in excess production of proinflammatory eicosanoids and cytokines and a deficiency of anti-inflammatory cytokines and bioactive lipids that ultimately results in the development of autism. Based on these evidences, it is proposed that selective delivery of BDNF and methods designed to augment the production of anti-inflammatory cytokines and eicosanoids and PUFAs may prevent, arrest, or reverse the autism disease process. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Polyamine Metabolism Is Altered in Unpollinated Parthenocarpic pat-2 Tomato Ovaries1

    Science.gov (United States)

    Fos, Mariano; Proaño, Karina; Alabadí, David; Nuez, Fernando; Carbonell, Juan; García-Martínez, José L.

    2003-01-01

    Facultative parthenocarpy induced by the recessive mutation pat-2 in tomato (Lycopersicon esculentum Mill.) depends on gibberellins (GAs) and is associated with changes in GA content in unpollinated ovaries. Polyamines (PAs) have also been proposed to play a role in early tomato fruit development. We therefore investigated whether PAs are able to induce parthenocarpy and whether the pat-2 mutation alters the content and metabolism of PAs in unpollinated ovaries. Application of putrescine, spermidine, and spermine to wild-type unpollinated tomato ovaries (cv Madrigal [MA/wt]) induced partial parthenocarpy. Parthenocarpic growth of MA/pat-2 (a parthenocarpic near-isogenic line to MA/wt) ovaries was negated by paclobutrazol (GA biosynthesis inhibitor), and this inhibition was counteracted by spermidine. Application of α-difluoromethyl-ornithine (-Orn) and/or α-difluoromethyl-arginine (-Arg), irreversible inhibitors of the putrescine biosynthesis enzymes Orn decarboxylase (ODC) and Arg decarboxylase, respectively, prevented growth of unpollinated MA/pat-2 ovaries. α-Difluoromethyl-Arg inhibition was counteracted by putrescine and GA3, whereas that of α-difluoromethyl-Orn was counteracted by GA3 but not by putrescine or spermidine. In unpollinated MA/pat-2 ovaries, the content of free spermine was significantly higher than in MA/wt ovaries. ODC activity was higher in pat-2 ovaries than in MA/wt. Transcript levels of genes encoding ODC and spermidine synthase were also higher in MA/pat-2. All together, these results strongly suggest that the parthenocarpic ability of pat-2 mutants depends on elevated PAs levels in unpollinated mutant ovaries, which correlate with an activation of the ODC pathway, probably as a consequence of elevated GA content in unpollinated pat-2 tomato ovaries. PMID:12529543

  3. Altered clock gene expression in obese visceral adipose tissue is associated with metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Elaine Vieira

    Full Text Available Clock gene expression was associated with different components of metabolic syndrome (MS in human adipose tissue. However, no study has been done to compare the expression of clock genes in visceral adipose tissue (VAT from lean and obese subjects and its clinical implications. Therefore, we studied in lean and obese women the endogenous 24 h expression of clock genes in isolated adipocytes and its association with MS components. VAT was obtained from lean (BMI 21-25 kg/m2; n = 21 and morbidly obese women (BMI >40 kg/m2; n = 28. The 24 h pattern of clock genes was analyzed every 6 hours using RT-PCR. Correlation of clinical data was studied by Spearman analysis. The 24 h pattern of clock genes showed that obesity alters the expression of CLOCK, BMAL1, PER1, CRY2 and REV-ERB ALPHA in adipocytes with changes found in CRY2 and REV-ERB ALPHA throughout the 24 h period. The same results were confirmed in VAT and stromal cells (SC showing an upregulation of CRY2 and REV-ERB ALPHA from obese women. A positive correlation was observed for REV-ERB ALPHA gene expression with BMI and waist circumference in the obese population. Expression of ROR ALPHA was correlated with HDL levels and CLOCK with LDL. Obese subjects with MS exhibited positive correlation in the PER2 gene with LDL cholesterol, whereas REV-ERB ALPHA was correlated with waist circumference. We identified CRY2 and REV-ERB ALPHA as the clock genes upregulated in obesity during the 24 h period and that REV-ERB ALPHA is an important gene associated with MS.

  4. Thalamic metabolic alterations with cognitive dysfunction in idiopathic trigeminal neuralgia: a multivoxel spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuan; Bao, Faxiu; Ma, Shaohui; Guo, Chenguang; Jin, Chenwang; Zhang, Ming [First Affiliated Hospital of Xi' an Jiaotong University, Department of Medical Imaging, Xi' an, Shaanxi (China); Li, Dan [First Affiliated Hospital of Xi' an Jiaotong University, Department of Respiratory and Critical Care Medicine, Xi' an, Shaanxi (China)

    2014-08-15

    Although abnormalities in metabolite compositions in the thalamus are well described in patients with idiopathic trigeminal neuralgia (ITN), differences in distinct thalamic subregions have not been measured with proton magnetic resonance spectroscopy ({sup 1}H-MRS), and whether there are correlations between thalamic metabolites and cognitive function still remain unknown. Multivoxel MRS was recorded to investigate the metabolic alterations in the thalamic subregions of patients with ITN. The regions of interest were localized in the anterior thalamus (A-Th), intralaminar portion of the thalamus (IL-Th), posterior lateral thalamus (PL-Th), posterior medial thalamus (PM-Th), and medial and lateral pulvinar of the thalamus (PuM-Th and PuL-Th). The N-acetylaspartate to creatine (NAA/Cr) and choline to creatine (Cho/Cr) ratios were measured in the ITN and control groups. Scores of the visual analogue scale (VAS) and the Montreal Cognitive Assessment (MoCA) were analyzed to correlate with the neuroradiological findings. The NAA/Cr ratio in the affected side of PM-Th and PL-Th in ITN patients was statistically lower than that in the corresponding regions of the thalamus in controls. The NAA/Cr ratio in the affected PM-Th was negatively associated with VAS and disease duration. Furthermore, decreases of NAA/Cr and Cho/Cr were detected in the affected side of IL-Th, and lower Cho/Cr was positively correlated with MoCA values in the ITN group. Our result of low level of NAA/Cr in the affected PM-Th probably serves as a marker of the pain-rating index, and decreased Cho/Cr in IL-Th may be an indicator of cognitive disorder in patients with ITN. (orig.)

  5. Altered Concentrations in Dyslipidemia Evidence a Role for ANGPTL8/Betatrophin in Lipid Metabolism in Humans.

    Science.gov (United States)

    Gómez-Ambrosi, Javier; Pascual-Corrales, Eider; Catalán, Victoria; Rodríguez, Amaia; Ramírez, Beatriz; Romero, Sonia; Vila, Neus; Ibáñez, Patricia; Margall, María A; Silva, Camilo; Gil, María J; Salvador, Javier; Frühbeck, Gema

    2016-10-01

    Angiopoietin-like protein 8 (ANGPTL8)/betatrophin is a secreted protein initially involved in β-cell replication. Recent data in humans and mice models suggest that ANGPTL8/betatrophin is more related to lipid metabolism. The aim of the present study was to compare the circulating concentrations of ANGPTL8/betatrophin in individuals with dyslipidemia defined as having high or low levels of high-density lipoprotein (HDL)-cholesterol or triglycerides, respectively. Serum concentrations of ANGPTL8/betatrophin were measured by an ELISA in 177 subjects. We studied two different selected case-control dyslipidemic cohorts including individuals with high (n = 43) or low (n = 46) circulating concentrations of HDL-cholesterol or with low (n = 48) or high (n = 40) levels of triglycerides. Circulating concentrations of ANGPTL8/betatrophin were significantly lower in individuals with dyslipidemia (P < .001) in both males (controls 27.8 ± 15.2 vs dyslipidemic 17.0 ± 11.2 ng/mL) and females (controls 50.0 ± 22.2 vs dyslipidemic 27.0 ± 16.5 ng/mL). The magnitude of the differences was higher in dyslipidemic patients with low HDL-cholesterol than in those with high triglyceride concentrations. ANGPTL8/betatrophin levels were lower in subjects with type 2 diabetes (P < .001), but the impact of type 2 diabetes vanished (P = .257) when the effect of dyslipidemia was included in the analysis. We conclude that serum ANGPTL8/betatrophin concentrations are altered in human dyslipidemia. ANGPTL8/betatrophin emerges as a potential player in dyslipidemia with a strong association with HDL-cholesterol and a potential therapeutic tool for the treatment of dyslipidemia.

  6. Altered glucose metabolism in juvenile myoclonic epilepsy: a PET study with statistical parametric mapping

    Energy Technology Data Exchange (ETDEWEB)

    Lim, G. C.; Kim, J. H.; Kang, J. G.; Kim, J. S.; Yeo, J. S.; Lee, S. A.; Moon, D. H [Asan Medical Center, Seoul (Korea, Republic of)

    2004-07-01

    Juvenile myoclonic epilepsy (JME) is a hereditary, age-dependent epilepsy syndrome, characterized by myoclonic jerks on awakening and generalized tonic-clonic seizures. Although there have been considerable studies on the mechanism to elucidate pathogenesis of JME, the accurate pathogenesis of JME remains obscure. The aim of this study was to investigate alterations of cerebral glucose metabolism in patients with JME. We studied 16 JME patients (Mean age: 22 yrs, M/F: 9/7) with brain FDG-PET and simultaneous EEG recording. On the basis of the number of generalized spike-and-wave (GSW) discharges on the 30 min EEG recording after the injection of FDG (370MBq), we classified patients into two groups (patients in group A had 10 or more GSW and group B. 9 or less). We applied the automated and objective technique of statistical parametric mapping (SPM) to the analysis of FDG-PET to determine the significant hyper- and hypometabolic regions compared with those of 19 age matched normal control subjects. We found significant hypermetabolic regions in bilateral thalamus and central portion of upper brainstem in 16 patients with JME at a statistical threshold of uncorrected P < 0.05. These changes were also shown in group A (n=8), but not in group B (n=8). Additionally, we found significant hypometabolism in bilateral, widespread cortical regions in 16 patients with JME at a threshold of uncorrected P < 0.01. Similar hypometabolic patterns were also observed in both group A and group B, being more prominent in group A. This study provides evidence for the key role of the thalamus and brainstem reticular activating system in generating spontaneous GSW discharge, which is considered as a fundamental pathogenesis underlying JME. This study also suggests that patients with JME might suffer from subtle abnormalities of cognitive and executive cortical functions.

  7. Polyamine metabolism is altered in unpollinated parthenocarpic pat-2 tomato ovaries.

    Science.gov (United States)

    Fos, Mariano; Proaño, Karina; Alabadí, David; Nuez, Fernando; Carbonell, Juan; García-Martínez, José L

    2003-01-01

    Facultative parthenocarpy induced by the recessive mutation pat-2 in tomato (Lycopersicon esculentum Mill.) depends on gibberellins (GAs) and is associated with changes in GA content in unpollinated ovaries. Polyamines (PAs) have also been proposed to play a role in early tomato fruit development. We therefore investigated whether PAs are able to induce parthenocarpy and whether the pat-2 mutation alters the content and metabolism of PAs in unpollinated ovaries. Application of putrescine, spermidine, and spermine to wild-type unpollinated tomato ovaries (cv Madrigal [MA/wt]) induced partial parthenocarpy. Parthenocarpic growth of MA/pat-2 (a parthenocarpic near-isogenic line to MA/wt) ovaries was negated by paclobutrazol (GA biosynthesis inhibitor), and this inhibition was counteracted by spermidine. Application of alpha-difluoromethyl-ornithine (-Orn) and/or alpha-difluoromethyl-arginine (-Arg), irreversible inhibitors of the putrescine biosynthesis enzymes Orn decarboxylase (ODC) and Arg decarboxylase, respectively, prevented growth of unpollinated MA/pat-2 ovaries. Alpha-difluoromethyl-Arg inhibition was counteracted by putrescine and GA(3), whereas that of alpha-difluoromethyl-Orn was counteracted by GA(3) but not by putrescine or spermidine. In unpollinated MA/pat-2 ovaries, the content of free spermine was significantly higher than in MA/wt ovaries. ODC activity was higher in pat-2 ovaries than in MA/wt. Transcript levels of genes encoding ODC and spermidine synthase were also higher in MA/pat-2. All together, these results strongly suggest that the parthenocarpic ability of pat-2 mutants depends on elevated PAs levels in unpollinated mutant ovaries, which correlate with an activation of the ODC pathway, probably as a consequence of elevated GA content in unpollinated pat-2 tomato ovaries.

  8. Alterations in Multiple Lifestyle Factors in Subjects with the Metabolic Syndrome Independently of Obesity.

    Science.gov (United States)

    Roos, Vendela; Elmståhl, Sölve; Ingelsson, Erik; Sundström, Johan; Ärnlöv, Johan; Lind, Lars

    2017-04-01

    Many lifestyle factors have been associated with the metabolic syndrome (MetS). However, most of these studies have not considered the potential impact of obesity and have often only investigated one lifestyle factor at the time. We aimed to investigate the interplay between body mass index (BMI) and MetS with respect to multiple lifestyle factors. BMI and MetS [National Cholesterol Education Program (NCEP)/Adult Treatment Panel III criteria] were assessed in a sample of 18,880 subjects aged 45-75 years from the population-based EpiHealth study. Participants were categorized into six groups according to BMI category (normal weight/BMI obesity/BMI >30 kg/m 2 ) and MetS status (+/-, NCEP criteria). A wide range of lifestyle factors related to physical activity, smoking, alcohol, sleep quality, working conditions, quality of life and stress, and eating patterns were assessed using a questionnaire. Prevalent MetS (23% in the sample) was associated with less physical activity (P TV watching (P < 0.0001), more years of smoking (P < 0.0001), lower education level (P = 0.007), and experiencing a poor general quality of life (P < 0.0001). These lifestyle factors were all associated with MetS, independently of each other and independently of BMI. Similar results were generated when number of MetS components and presence/absence of individual MetS components were used as outcomes. This cross-sectional study identified alterations in a number of lifestyle factors associated with MetS independently of each other and independently of BMI. Future longitudinal studies are needed to assess causal and temporal relationships between lifestyle factors and MetS development.

  9. Loss of FTO in adipose tissue decreases Angptl4 translation and alters triglyceride metabolism.

    Science.gov (United States)

    Wang, Chao-Yung; Shie, Shian-Sen; Wen, Ming-Shien; Hung, Kuo-Chun; Hsieh, I-Chang; Yeh, Ta-Sen; Wu, Delon

    2015-12-15

    A common variant of the FTO (fat mass- and obesity-associated) gene is a risk factor for obesity. We found that mice with an adipocyte-specific deletion of FTO gained more weight than control mice on a high-fat diet. Analysis of mice lacking FTO in adipocytes fed a normal diet or adipocytes from these mice revealed alterations in triglyceride metabolism that would be expected to favor increased fatty acid storage by adipose tissue. Mice lacking FTO in adipocytes showed increased serum triglyceride breakdown and clearance, which was associated with lower serum triglyceride concentrations. In addition, lipolysis in response to β-adrenergic stimulation was decreased in adipocytes and ex vivo adipose explants from the mutant mice. FTO is a nucleic acid demethylase that removes N(6)-methyladenosine (m(6)A) from mRNAs. We found that FTO bound to Angptl4, which encodes an adipokine that stimulates intracellular lipolysis in adipocytes. Unexpectedly, the adipose tissue of fasted or fed mice lacking FTO in adipocytes had greater Angptl4 mRNA abundance. However, after high-fat feeding, the mutant mice had less Angptl4 protein and more m(6)A-modified Angptl4 than control mice, suggesting that lack of FTO prevented the translation of Angptl4. Injection of Angptl4-encoding adenovirus into mice lacking FTO in adipocytes restored serum triglyceride concentrations and lipolysis to values similar to those in control mice and abolished excessive weight gain from a high-fat diet. These results reveal that FTO regulates fatty acid mobilization in adipocytes and thus body weight in part through posttranscriptional regulation of Angptl4. Copyright © 2015, American Association for the Advancement of Science.

  10. Metabolic system alterations in pancreatic cancer patient serum: potential for early detection

    International Nuclear Information System (INIS)

    Ritchie, Shawn A; Jin, Wei; Sajobi, Tolulope T; Jayasinghe, Dushmanthi; Chitou, Bassirou; Yamazaki, Yasuyo; White, Thayer; Goodenowe, Dayan B; Akita, Hirofumi; Takemasa, Ichiro; Eguchi, Hidetoshi; Pastural, Elodie; Nagano, Hiroaki; Monden, Morito; Doki, Yuichiro; Mori, Masaki

    2013-01-01

    The prognosis of pancreatic cancer (PC) is one of the poorest among all cancers, due largely to the lack of methods for screening and early detection. New biomarkers for identifying high-risk or early-stage subjects could significantly impact PC mortality. The goal of this study was to find metabolic biomarkers associated with PC by using a comprehensive metabolomics technology to compare serum profiles of PC patients to healthy control subjects. A non-targeted metabolomics approach based on high-resolution, flow-injection Fourier transform ion cyclotron resonance mass spectrometry (FI-FTICR-MS) was used to generate comprehensive metabolomic profiles containing 2478 accurate mass measurements from the serum of Japanese PC patients (n=40) and disease-free subjects (n=50). Targeted flow-injection tandem mass spectrometry (FI-MS/MS) assays for specific metabolic systems were developed and used to validate the FI-FTICR-MS results. A FI-MS/MS assay for the most discriminating metabolite discovered by FI-FTICR-MS (PC-594) was further validated in two USA Caucasian populations; one comprised 14 PCs, six intraductal papillary mucinous neoplasims (IPMN) and 40 controls, and a second comprised 1000 reference subjects aged 30 to 80, which was used to create a distribution of PC-594 levels among the general population. FI-FTICR-MS metabolomic analysis showed significant reductions in the serum levels of metabolites belonging to five systems in PC patients compared to controls (all p<0.000025). The metabolic systems included 36-carbon ultra long-chain fatty acids, multiple choline-related systems including phosphatidylcholines, lysophosphatidylcholines and sphingomyelins, as well as vinyl ether-containing plasmalogen ethanolamines. ROC-AUCs based on FI-MS/MS of selected markers from each system ranged between 0.93 ±0.03 and 0.97 ±0.02. No significant correlations between any of the systems and disease-stage, gender, or treatment were observed. Biomarker PC-594 (an ultra long

  11. Oral administration of iron-saturated bovine lactoferrin–loaded ceramic nanocapsules for breast cancer therapy and influence on iron and calcium metabolism

    Directory of Open Access Journals (Sweden)

    Mahidhara G

    2015-06-01

    Full Text Available Ganesh Mahidhara, Rupinder K Kanwar, Kislay Roy, Jagat R Kanwar Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research, School of Medicine, Molecular and Medical Research Strategic Research Centre, Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia Abstract: We determined the anticancer efficacy and internalization mechanism of our polymeric–ceramic nanoparticle system (calcium phosphate nanocores, enclosed in biodegradable polymers chitosan and alginate nanocapsules/nanocarriers [ACSC NCs] loaded with iron-saturated bovine lactoferrin (Fe-bLf in a breast cancer xenograft model. ACSC-Fe-bLf NCs with an overall size of 322±27.2 nm were synthesized. In vitro internalization and anticancer efficacy were evaluated in the MDA-MB-231 cells using multicellular tumor spheroids, CyQUANT and MTT assays. These NCs were orally delivered in a breast cancer xenograft mice model, and their internalization, cytotoxicity, biodistribution, and anticancer efficacy were evaluated. Chitosan-coated calcium phosphate Fe-bLf NCs effectively (59%, P≤0.005 internalized in a 1-hour period using clathrin-mediated endocytosis (P≤0.05 and energy-mediated pathways (P≤0.05 for internalization; 3.3 mg/mL of ACSC-Fe-bLf NCs completely disintegrated (~130-fold reduction, P≤0.0005 the tumor spheroids in 72 hours and 96 hours. The IC50 values determined for ACSC-Fe-bLf NCs were 1.69 mg/mL at 10 hours and 1.62 mg/mL after 20 hours. We found that Fe-bLf-NCs effectively (P≤0.05 decreased the tumor size (4.8-fold compared to the void NCs diet and prevented tumor recurrence when compared to intraperitoneal injection of Taxol and Doxorubicin. Receptor gene expression and micro-RNA analysis confirmed upregulation of low-density lipoprotein receptor and transferrin receptor (liver, intestine, and brain. Several micro-RNAs responsible for iron metabolism upregulated with NCs were identified. Taken together, orally delivered Fe-bLf NCs

  12. Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins

    Directory of Open Access Journals (Sweden)

    Khanichi N. Charles

    2017-10-01

    Full Text Available Deterioration of metabolic health is a hallmark of aging and generally assumed to be detrimental to longevity. Exposure to a high-calorie diet impairs metabolism and accelerates aging; conversely, calorie restriction (CR prevents age-related metabolic diseases and extends lifespan. However, it is unclear whether preservation of metabolic health is sufficient to extend lifespan. We utilized a genetic mouse model lacking Fabp4/5 that confers protection against metabolic diseases and shares molecular and lipidomic features with CR to address this question. Fabp-deficient mice exhibit extended metabolic healthspan, with protection against insulin resistance and glucose intolerance, inflammation, deterioration of adipose tissue integrity, and fatty liver disease. Surprisingly, however, Fabp-deficient mice did not exhibit any extension of lifespan. These data indicate that extension of metabolic healthspan in the absence of CR can be uncoupled from lifespan, indicating the potential for independent drivers of these pathways, at least in laboratory mice.

  13. Hepcidin as a biomarker for the diagnosis of iron metabolism disorders: a review.

    Science.gov (United States)

    Vermeulen, E; Vermeersch, P

    2012-01-01

    Hepcidin plays a key role in the regulation of plasma iron levels through inhibition of iron export from enterocytes and macrophages. Hepcidin is considered a promising marker in the investigation of iron status, especially in patients that still pose a diagnostic challenge, such as infants and patients with chronic (kidney) disease. To critically review the current evidence for the diagnostic utility of hepcidin, including the (pre) analytical aspects in hepcidin determination. (Pre)analytical aspects--Since it is doubtful that the prohormone prohepcidin is a relevant biomarker, only the mature peptide hepcidin should be measured. Determinations of serum hepcidin are preferable, as the value of urine concentrations is still unclear. Method harmonization is needed since hepcidin values vary widely between methods. Several (pre-) analytical issues remain unanswered. These barriers hamper the investigation into the diagnostic value of hepcidin. Diagnostic utility--Hepcidin is an acute-phase reactant. The diagnostic potential of hepcidin is controversial in the different settings of iron deficiency as evidence is contradictory (anaemia of chronic disease) or limited (infants). In the setting of haemochromatosis, it has been suggested that hepcidin could be useful to stratify molecular testing, or to optimize the frequency of phlebotomies, but this remains to be investigated.

  14. Effects of iron limitation on photosynthesis and carbohydrate metabolism in the Antarctic diatom Chaetoceros brevis (Bacillariophyceae)

    NARCIS (Netherlands)

    van Oijen, T; van Leeuwe, MA; Gieskes, WWC; de Baar, HJW

    Iron, one of the structural elements of organic components that play an essential role in photosynthesis and nitrogen assimilation of plants, is available at extremely low concentrations in large parts of the Southern Ocean's surface waters. We tested the hypothesis that photosynthesis is the

  15. Interactions between iron and titanium metabolism in spinach: A chlorophyll fluorescence study in hydropony

    Czech Academy of Sciences Publication Activity Database

    Cígler, Petr; Olejníčková, Julie; Hrubý, Martin; Cséfalvay, Ladislav; Peterka, J.; Kužel, S.

    2010-01-01

    Roč. 167, č. 18 (2010), s. 1592-1597 ISSN 0176-1617 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z40500505; CEZ:AV0Z60870520 Keywords : chlorophyll fluorescence * iron * photosynthetic apparatus * spinach * titanium Subject RIV: CC - Organic Chemistry Impact factor: 2.677, year: 2010

  16. Integration of Concentration-Area Fractal Modeling and Spectral Angle Mapper for Ferric Iron Alteration Mapping and Uranium Exploration in the Xiemisitan Area, NW China

    Directory of Open Access Journals (Sweden)

    Jun-Ting Qiu

    2015-10-01

    Full Text Available The high-grade uranium deposits in the Xiemisitan area, northwestern China, are genetically associated with the faulting of felsic volcanic or sub-volcanic rocks. Ferric iron alteration indicates that oxidizing hydrothermal fluids percolated through the rocks. In this study, we measured the gamma-ray intensities of rocks in the Xiemisitan area and we propose a hybrid method for the mapping of ferric iron alteration using concentration-area fractal modeling and spectral angle mapper. The method enables ferric iron alteration to be distinguished from potash-feldspar granitic rocks. The mapping results were integrated with structural data to assist with exploration for uranium in the study area. Using this approach, six prospective areas of mineralization were proposed. Of these areas, two anomalies with high gamma-ray intensities of 104 and 650 Uγ were identified and verified by field inspection. These observations suggest that Enhanced Thematic Mapper Plus images are a valuable tool that can improve the efficiency of uranium exploration.

  17. A High-Fat Diet Causes Impairment in Hippocampal Memory and Sex-Dependent Alterations in Peripheral Metabolism

    Directory of Open Access Journals (Sweden)

    Erica L. Underwood

    2016-01-01

    Full Text Available While high-fat diets are associated with rising incidence of obesity/type-2 diabetes and can induce metabolic and cognitive deficits, sex-dependent comparisons are rarely systematically made. Effects of exclusive consumption of a high-fat diet (HFD on systemic metabolism and on behavioral measures of hippocampal-dependent memory were compared in young male and female LE rats. Littermates were fed from weaning either a HFD or a control diet (CD for 12 wk prior to testing. Sex-different effects of the HFD were observed in classic metabolic signs associated with type-2 diabetes. Males fed the HFD became obese, and had elevated fasted blood glucose levels, elevated corticosterone, and impaired glucose-tolerance, while females on the HFD exhibited only elevated corticosterone. Regardless of peripheral metabolism alteration, rats of both sexes fed the HFD were equally impaired in a spatial object recognition memory task associated with impaired hippocampal function. While the metabolic changes reported here have been characterized previously in males, the set of diet-induced effects observed here in females are novel. Impaired memory can have significant cognitive consequences, over the short-term and over the lifespan. A significant need exists for comparative research into sex-dependent differences underlying obesity and metabolic syndromes relating systemic, cognitive, and neural plasticity mechanisms.

  18. Cardiac energy metabolic alterations in pressure overload–induced left and right heart failure (2013 Grover Conference Series)

    Science.gov (United States)

    Lopaschuk, Gary D.

    2015-01-01

    Abstract Pressure overload of the heart, such as seen with pulmonary hypertension and/or systemic hypertension, can result in cardiac hypertrophy and the eventual development of heart failure. The development of hypertrophy and heart failure is accompanied by numerous molecular changes in the heart, including alterations in cardiac energy metabolism. Under normal conditions, the high energy (adenosine triphosphate [ATP]) demands of the heart are primarily provided by the mitochondrial oxidation of fatty acids, carbohydrates (glucose and lactate), and ketones. In contrast, the hypertrophied failing heart is energy deficient because of its inability to produce adequate amounts of ATP. This can be attributed to a reduction in mitochondrial oxidative metabolism, with the heart becoming more reliant on glycolysis as a source of ATP production. If glycolysis is uncoupled from glucose oxidation, a decrease in cardiac efficiency can occur, which can contribute to the severity of heart failure due to pressure-overload hypertrophy. These metabolic changes are accompanied by alterations in the enzymes that are involved in the regulation of fatty acid and carbohydrate metabolism. It is now becoming clear that optimizing both energy production and the source of energy production are potential targets for pharmacological intervention aimed at improving cardiac function in the hypertrophied failing heart. In this review, we will focus on what alterations in energy metabolism occur in pressure overload induced left and right heart failure. We will also discuss potential targets and pharmacological approaches that can be used to treat heart failure occurring secondary to pulmonary hypertension and/or systemic hypertension. PMID:25992268

  19. Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming.

    Science.gov (United States)

    Xu, Dan; Xia, Li-ping; Shen, Lang; Lei, You-ying; Liu, Lian; Zhang, Li; Magdalou, Jacques; Wang, Hui

    2013-12-01

    Prenatal nicotine exposure (PNE) alters the hypothalamic-pituitary-adrenocortical (HPA) axis-associated neuroendocrine metabolic programming in intrauterine growth retardation offspring rats. In this study we aimed to clarify the susceptibility to metabolic diseases of PNE offspring rats fed a high-fat diet. Maternal Wistar rats were injected with nicotine (1.0 mg/kg, sc) twice per day from gestational day 11 until full-term delivery, and all pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress (UCS) during postnatal weeks 18-20. Blood samples were collected before and after chronic stress, and serum ACTH, corticosterone, glucose, insulin, total cholesterol, triglyceride and free fatty acids levels were measured. The hypothalamus, pituitary gland and liver were dissected for histological studies. UCS significantly increased the serum ACTH, corticosterone and insulin levels as well as the insulin resistant index without changing the serum glucose, total cholesterol, triglyceride and free fatty acids levels in adult offspring rats without PNE. The body weight of PNE offspring rats presented a typical "catch-up" growth pattern. PNE not only aggravated the UCS-induced changes in the HPA axis programmed alteration (caused further increases in the serum ACTH and corticosterone levels), but also significantly changed the glucose and lipid metabolism after UCS (caused further increases in the serum glucose level and insulin resistant index, and decrease in the serum free fatty acids). The effects of PNE on the above indexes after UCS showed gender differences. Pathological studies revealed that PNE led to plenty of lipid droplets in multiple organs. PNE enhances not only the HPA axis, but also the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet after UCS in a gender-specific manner and enhances the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet.

  20. Hyperchloraemic metabolic acidosis induced by the iron chelator deferasirox: a case report and review of the literature.

    Science.gov (United States)

    Dell'Orto, V G; Bianchetti, M G; Brazzola, P

    2013-12-01

    Deferasirox is a new treatment of iron overload that is administered orally once-a-day, resulting in better acceptance in patients. Deferasirox-induced renal tubular dysfunction has been reported on very rare occasions. A 17-year-old adolescent with β-thalassaemia on deferasirox 30 mg/kg daily presented with isolated hyperchloraemic metabolic acidosis (bicarbonate 12·9 mM, sodium 137 mM, chloride 111 mM, potassium 3·6 mM). Acidosis resolved after withdrawing deferasirox. Naranjo adverse drug reaction scale suggested that the likelihood that deferasirox was responsible for acidosis was probable. Eight cases of metabolic acidosis have been reported in patients treated with deferasirox. In most cases, acidosis was associated with further features of renal tubular dysfunction. We describe herein a case of metabolic acidosis in the setting of treatment with the deferasirox. Our case and the literature indicate a potential risk of kidney toxicity on this agent. © 2013 John Wiley & Sons Ltd.

  1. Metabolic flexibility of the Fe(II)-oxidizing phototropic strain Rhodopseudomonas palustris TIE1 and its potential role in microbial iron cycling

    Science.gov (United States)

    Schmidt, C.; Oswald, K.; Melton, E. D.; Kappler, A.

    2012-04-01

    The biogeochemical conversion of iron(II) and iron(III) is widespread in many aquatic and terrestrial environments. In the anoxic regime of soils and sediments the conversion and alternation of the iron redox state is predominantly run by microorganisms that are thought to gain life-sustaining energy by the oxidation and/or reduction of ferrous/ferric components. The spatial arrangement of microbial iron(II) oxidation and iron(III) reduction is largely controlled by the availability of the required electron acceptor and electron donor, as well as the essential source of energy (i.e. light or chemical energy). The physico-chemical patterns of many microbial environments undergo dynamic variations (i.e. diurnal and seasonal changes) as a function of natural external forces (i.e. seasonality, storm events, algae blooms) which strongly affects the local budget of organic carbon and nutrients, as well as the day light penetration. Such fluctuations force microorganisms either to follow the flow of substrate or to switch their metabolism to alternative electron acceptors and/or donors. Different photoferrotrophic bacteria have been shown to be able to grow either on organic (heterotrophic) or inorganic (autotrophic) substrates while exploiting light as their energy source. Within the frame of this study the preference for organic substrates (lactate and acetate) and/or ferrous iron (in simultaneous presence) for photo(ferro)trophic growth of Rhodopseudomonas palustris TIE1 has been investigated in detail. Rates of iron oxidation, acetate/lactate consumption and growth have been followed over time as a function of different lactate to acetate to iron(II) ratios. Additional experiments have been designed to evaluate the potential of Rhodopseudomonas palustris TIE1 to contribute to the redox cycling of iron. TIE1 has been grown in a batch set-up in which the iron(III)-reducing strain Shewanella oneidensis MR1 has been incubated at different ferrihydrite concentrations in

  2. Added value of SPECT / CT fusion to evaluate outbreaks with pathologically altered bone metabolism in patients with oncological diseases

    International Nuclear Information System (INIS)

    Nikolova, K.; Chavdarova, L.; Hristov, A.; Piperkova, E.

    2017-01-01

    Over the past 10 years, SPECT / CT imaging has added a new dimension to the routine whole-body bone scintigraphy. The hybrid chambers combining SPECT and CT provide the ability to obtain diagnostic quality CT imaging of scintigraphically defined outbreaks that directly correlate with the SPECT image. The addition of targeted SPECT / CT after whole-body scanning facilitates the oncological diagnosis in inconclusive scintigraphic planar images. The purpose of this work is to determine the significance and contribution of 3D-SPECT / CT in assessing of outbreaks with increased bone metabolism with a vague (malignant / benign) characteristic of planar whole-body bone scintigraphy in patients with oncological diseases. Our study included 269 patients with a variety of oncology patients who underwent whole-body bone scintigraphy followed by SPECT / CT to assess outbreaks with increased bone metabolism. In 59% of the studied patients the unclear pathological characteristic of pathologically altered bone metabolism in whole-body scintigraphy correlated with benign bone changes in SPECT / CT, 24% correlated with osteosclerotic and osytic metastases and 17% remain undefined. In conclusion, SPECT / CT fusion significantly increases the sensitivity and specificity of SPECT for evaluating outbreaks with pathologically altered bone metabolism. [bg

  3. Modulation of the pentose phosphate pathway alters phase I metabolism of testosterone and dextromethorphan in HepG2 cells.

    Science.gov (United States)

    Xiao, Wen-jing; Ma, Ting; Ge, Chun; Xia, Wen-juan; Mao, Yong; Sun, Run-bin; Yu, Xiao-yi; Aa, Ji-ye; Wang, Guang-ji

    2015-02-01

    The pentose phosphate pathway (PPP) is involved in the activity of glucose-6-phosphate dehydrogenase (G6PD) and generation of NADPH, which plays a key role in drug metabolism. The aim of this study was to investigate the effects of modulation of the PPP on drug metabolism capacity in vitro. A pair of hepatic cell lines, ie, the cancerous HepG2 cells and normal L02 cells, was used. The expression of CYP450 enzymes, p53 and G6PD in the cells were analyzed. The metabolism of testosterone (TEST, 10 μmol/L) and dextromethorphan (DEM, 1 μmol/L), the two typical substrates for CYP3A4 and CYP2D6, in the cells was examined in the presence of different agents. Both the expression and metabolic activities of CYP3A4 and CYP2D6 were considerably higher in HepG2 cells than in L02 cells. The metabolism of TEST and DEM in HepG2 cells was dose-dependently inhibited by the specific CYP3A4 inhibitor ketoconazole and CYP2D6 inhibitor quinidine. Addition of the p53 inhibitor cyclic PFT-α (5, 25 μmol/L) in HepG2 cells dose-dependently enhanced the metabolism of DEM and TEST, whereas addition of the p53 activator NSC 66811 (3, 10, 25 μmol/L) dose-dependently inhibited the metabolism. Furthermore, addition of the G6PD inhibitor 6-aminonicotinamide (5, 15 μmol/L) in HepG2 cells dose-dependently inhibited the metabolism of DEM and TEST, whereas addition of the PPP activity stimulator menadione (1, 5, 15 μmol/L) dose-dependently enhanced the metabolism. Modulation of p53 and the PPP alters the metabolism of DEM and TEST, suggesting that the metabolic flux pattern of PPP may be closely involved in drug metabolism and the individual variance.

  4. Microbial Community Composition Impacts Pathogen Iron Availability during Polymicrobial Infection.

    Directory of Open Access Journals (Sweden)

    Apollo Stacy

    2016-12-01

    Full Text Available Iron is an essential nutrient for bacterial pathogenesis, but in the host, iron is tightly sequestered, limiting its availability for bacterial growth. Although this is an important arm of host immunity, most studies examine how bacteria respond to iron restriction in laboratory rather than host settings, where the microbiome can potentially alter pathogen strategies for acquiring iron. One of the most important transcriptional regulators controlling bacterial iron homeostasis is Fur. Here we used a combination of RNA-seq and chromatin immunoprecipitation (ChIP-seq to characterize the iron-restricted and Fur regulons of the biofilm-forming opportunistic pathogen Aggregatibacter actinomycetemcomitans. We discovered that iron restriction and Fur regulate 4% and 3.5% of the genome, respectively. While most genes in these regulons were related to iron uptake and metabolism, we found that Fur also directly regulates the biofilm-dispersing enzyme Dispersin B, allowing A. actinomycetemcomitans to escape from iron-scarce environments. We then leveraged these datasets to assess the availability of iron to A. actinomycetemcomitans in its primary infection sites, abscesses and the oral cavity. We found that A. actinomycetemcomitans is not restricted for iron in a murine abscess mono-infection, but becomes restricted for iron upon co-infection with the oral commensal Streptococcus gordonii. Furthermore, in the transition from health to disease in human gum infection, A. actinomycetemcomitans also becomes restricted for iron. These results suggest that host iron availability is heterogeneous and dependent on the infecting bacterial community.

  5. The effect of maternal glucose metabolism, iron, vitamin B 12 and ...

    African Journals Online (AJOL)

    nutritional, sociodemographic and glucose metabolism) on pregnancy outcome of women recruited during the third trimester. Design. A longitudinal analytical study. Setting. Villages in the central region of the Limpopo province. Subjects.

  6. Tick iron and heme metabolism – New target for an anti-tick intervention

    Czech Academy of Sciences Publication Activity Database

    Hajdušek, Ondřej; Šíma, Radek; Perner, Jan; Loosová, Gabriela; Harcubová, Adéla; Kopáček, Petr

    2016-01-01

    Roč. 7, č. 4 (2016), s. 565-572 ISSN 1877-959X R&D Projects: GA ČR GA13-11043S; GA ČR GP13-27630P; GA ČR GP13-12816P EU Projects: European Commission(XE) 316304 - MODBIOLIN Institutional support: RVO:60077344 Keywords : tick * iron * heme * RNAi * vaccine Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.230, year: 2016

  7. Changes in serum markers of iron metabolism and their clinical significance in patients with nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    OU Qiang

    2016-12-01

    Full Text Available ObjectiveTo investigate the changes in the serum markers of iron metabolism and their clinical significance in patients with nonalcoholic fatty liver disease (NAFLD. MethodsA total of 68 NAFLD patients who were admitted to The Eighth People′s Hospital of Shanghai from July 2014 to April 2016 were enrolled as NAFLD group, and 70 healthy persons who underwent physical examination were enrolled as healthy control group. Among the 68 patients in the NAFLD group, 24 had NAFLD alone and 44 were complicated by abnormal alanine aminotransferase (ALT level. The levels of aspartate aminotransferase (AST, ALT, total cholesterol (TC, triglyceride (TG, and serum markers of iron metabolism [serum iron (SI, serum ferritin (SF, and serum hepcidin (HEPC] were measured for all patients, and the correlations between abnormal ALT level and serum markers of iron metabolism were analyzed. The independent samples t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, and the Pearson correlation coefficient was used to investigate the correlation between two variables. ResultsThe NAFLD group had significantly higher body mass index and serum levels of ALT, AST, TC, and TG than the healthy control group (t=9.8, 8.6, 8.5, 9.2, and 2.7, all P<0.05. Compared with the healthy control group, the NAFLD group had significantly higher levels of SI (21.7±7.1 μmol/L vs 187±6.9 μmol/L, t=2.3, P=0.02 and SF (340.2±257.6 μg/L vs 119.1±81.2 μg/L, t=6.7, P<0.01 and a significantly lower level of HEPC (12.2±5.3 μg/L vs 22.2±6.5 μg/L, t=9.9, P<0.01. Compared with those with NAFLD alone, the patients complicated by abnormal ALT level had significantly higher serum levels of ALT (89±58 U/L vs 26±8 U/L, t=7.1, P<0.01, SI (23.4±6.2 μmol/L vs 19.6±7.9 μmol/L, t=2.2, P=0.03, and SF (406.2±290.0 μg/L vs 219.4±112.0 μg/L, t=3.7, P<0.01, as well as a significantly

  8. Clinical features and dysfunctions of iron metabolism in Parkinson disease patients with hyper echogenicity in substantia nigra: a cross-sectional study.

    Science.gov (United States)

    Yu, Shu-Yang; Cao, Chen-Jie; Zuo, Li-Jun; Chen, Ze-Jie; Lian, Teng-Hong; Wang, Fang; Hu, Yang; Piao, Ying-Shan; Li, Li-Xia; Guo, Peng; Liu, Li; Yu, Qiu-Jin; Wang, Rui-Dan; Chan, Piu; Chen, Sheng-di; Wang, Xiao-Min; Zhang, Wei

    2018-01-17

    Transcranial ultrasound is a useful tool for providing the evidences for the early diagnosis and differential diagnosis of Parkinson disease (PD). However, the relationship between hyper echogenicity in substantia nigra (SN) and clinical symptoms of PD patients remains unknown, and the role of dysfunction of iron metabolism on the pathogenesis of SN hyper echogenicity is unclear. PD patients was detected by transcranial sonography and divided into with no hyper echogenicity (PDSN-) group and with hyper echogenicity (PDSN+) group. Motor symptoms (MS) and non-motor symptoms (NMS) were evaluated, and the levels of iron and related proteins in serum and cerebrospinal fluid (CSF) were detected for PD patients. Data comparison between the two groups and correlation analyses were performed. PDSN+ group was significantly older, and had significantly older age of onset, more advanced Hohen-Yahr stage, higher SCOPA-AUT score and lower MoCA score than PDSN- group (P hyper echogenicity in SN are older, at more advanced disease stage, have severer motor symptoms, and non-motor symptoms of cognitive impairment and autonomic dysfunction. Hyper echogenicity of SN in PD patients is related to dysfunction of iron metabolism, involving increased iron transport from peripheral system to central nervous system, reduction of intracellular iron release and excessive iron deposition in brain.

  9. Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery.

    Science.gov (United States)

    Hansen, Jakob S; Zhao, Xinjie; Irmler, Martin; Liu, Xinyu; Hoene, Miriam; Scheler, Mika; Li, Yanjie; Beckers, Johannes; Hrabĕ de Angelis, Martin; Häring, Hans-Ulrich; Pedersen, Bente K; Lehmann, Rainer; Xu, Guowang; Plomgaard, Peter; Weigert, Cora

    2015-08-01

    The therapeutic benefit of physical activity to prevent and treat type 2 diabetes is commonly accepted. However, the impact of the disease on the acute metabolic response is less clear. To this end, we investigated the effect of type 2 diabetes on exercise-induced plasma metabolite changes and the muscular transcriptional response using a complementary metabolomics/transcriptomics approach. We analysed 139 plasma metabolites and hormones at nine time points, and whole genome expression in skeletal muscle at three time points, during a 60 min bicycle ergometer exercise and a 180 min recovery phase in type 2 diabetic patients and healthy controls matched for age, percentage body fat and maximal oxygen consumption (VO2). Pathway analysis of differentially regulated genes upon exercise revealed upregulation of regulators of GLUT4 (SLC2A4RG, FLOT1, EXOC7, RAB13, RABGAP1 and CBLB), glycolysis (HK2, PFKFB1, PFKFB3, PFKM, FBP2 and LDHA) and insulin signal mediators in diabetic participants compared with controls. Notably, diabetic participants had normalised rates of lactate and insulin levels, and of glucose appearance and disappearance, after exercise. They also showed an exercise-induced compensatory regulation of genes involved in biosynthesis and metabolism of amino acids (PSPH, GATM, NOS1 and GLDC), which responded to differences in the amino acid profile (consistently lower plasma levels of glycine, cysteine and arginine). Markers of fat oxidation (acylcarnitines) and lipolysis (glycerol) did not indicate impaired metabolic flexibility during exercise in diabetic participants. Type 2 diabetic individuals showed specific exercise-regulated gene expression. These data provide novel insight into potential mechanisms to ameliorate the disturbed glucose and amino acid metabolism associated with type 2 diabetes.

  10. Plasma lipids, lipoprotein metabolism and HDL lipid transfers are equally altered in metabolic syndrome and in type 2 diabetes.

    Science.gov (United States)

    Silva, Vanessa M; Vinagre, Carmen G C; Dallan, Luis A O; Chacra, Ana P M; Maranhão, Raul C

    2014-07-01

    Metabolic syndrome (MetS) refers to states of insulin resistance that predispose to development of cardiovascular disease and type 2 diabetes (T2DM). The aim was to investigate whether plasma lipids and lipid metabolism differ in MetS patients compared to those with T2DM with poor glycemic control (glycated hemoglobin > 7.0). Eighteen patients with T2DM, 18 with MetS and 14 controls, paired for age (40-70 years) and body mass index (BMI), were studied. Plasma lipids and the kinetics of a triacylglycerol-rich emulsion labeled with [(3)H]-triolein ([(3)H]-TAG) and [(14)C]-cholesteryl esters ([(14)C]-CE) injected intravenously followed by one-hour blood sampling were determined. Lipid transfers from an artificial nanoemulsion donor to high-density lipoprotien (HDL) were assayed in vitro. Low-density lipoprotein (LDL) and HDL cholesterol (mg/dl) were not different in T2DM (128 ± 7; 42 ± 7) and MetS (142 ± 6; 39 ± 3), but triacylglycerols were even higher in MetS (215 ± 13) than in T2DM (161 ±11, p lipid metabolism examined here, and suggest that there are different thresholds for the insulin action on glucose and lipids. These findings highlight the magnitude of the lipid disturbances in MetS, and may have implications in the prevention of cardiovascular diseases.

  11. Geology of the Riacho do Pontal iron oxide copper-gold (IOCG prospect, Bahia, Brazil: hydrothermal alteration approached via hierarchical cluster analysis

    Directory of Open Access Journals (Sweden)

    Sérgio Roberto Bacelar Huhn

    Full Text Available The Riacho do Pontal prospect is situated on the border between the Borborema Province and the São Francisco Craton, in Bahia state. It comprises rocks polydeformed during the Neoproterozoic. The prospect area includes migmatites and gneissic rocks intruded by several sin- to post-tectonic granites. Structural analysis indicates a strong relationship between the development of ductile to brittle-ductile shear zones and associated hydrothermalism. The main tracts of high-strain rate are represented by the Riacho do Pontal (north and Macururé (south shear zones. Several copper occurrences have been mapped within the Riacho do Pontal prospect along secondary shear zones. In these areas, the gneissic rocks were affected by intense hydrothermal alteration. Hierarchical cluster analysis permitted the identification of the main hydrothermal mineral associations present in these rocks, which resulted from potassic (biotite and sodic-calcic (amphibole-albite alteration, in addition to silicification and iron alteration (hematite. These hydrothermal alteration types are similar to those typically found in iron oxide copper-gold deposits developed at intermediate crustal levels. Hematite-quartz-albite-chalcopyrite-pyrite hydrothermal breccias host the highest-grade copper ore (chalcopyrite-pyrite-chalcocite zones. The spatial relationship between copper deposits and shear zones improves the metallogenic potential for copper of the Borborema Province and has important implications for mineral exploration in the region.

  12. Thyroid Hormone Receptor beta Mediates Acute Illness-Induced Alterations in Central Thyroid Hormone Metabolism

    NARCIS (Netherlands)

    Boelen, Anita; Kwakkel, Joan; Chassande, Olivier; Fliers, Eric

    2009-01-01

    Acute illness in mice profoundly affects thyroid hormone metabolism in the hypothalamus and pituitary gland. It remains unknown whether the thyroid hormone receptor (TR)-beta is involved in these changes. In the present study, we investigated central thyroid hormone metabolism during

  13. Controlled atmosphere storage, temperature conditioning, and antioxidant treatment alter postharvest 'Honeycrisp' metabolism

    Science.gov (United States)

    The physiology and metabolism characterizing postharvest chilling and CO2 injury in apple has important implications for postharvest management of soft scald and soggy breakdown. This research assessed differences of primary metabolism related to soggy breakdown (cortex chilling injury) and CO2 cor...

  14. Effects of independently altering body weight and body mass on the metabolic cost of running

    NARCIS (Netherlands)

    Teunissen, L.P.J.; Grabowski, A.; Kram, R.

    2011-01-01

    The metabolic cost of running is substantial, despite the savings from elastic energy storage and return. Previous studies suggest that generating vertical force to support body weight and horizontal forces to brake and propel body mass are the major determinants of the metabolic cost of running. In

  15. Regulatory mechanisms for iron transport across the blood-brain barrier.

    Science.gov (United States)

    Duck, Kari A; Simpson, Ian A; Connor, James R

    2017-12-09

    Many critical metabolic functions in the brain require adequate and timely delivery of iron. However, most studies when considering brain iron uptake have ignored the iron requirements of the endothelial cells that form the blood-brain barrier (BBB). Moreover, current models of BBB iron transport do not address regional regulation of brain iron uptake or how neurons, when adapting to metabolic demands, can acquire more iron. In this study, we demonstrate that both iron-poor transferrin (apo-Tf) and the iron chelator, deferoxamine, stimulate release of iron from iron-loaded endothelial cells in an in vitro BBB model. The role of the endosomal divalent metal transporter 1 (DMT1) in BBB iron acquisition and transport has been questioned. Here, we show that inhibition of DMT1 alters the transport of iron and Tf across the endothelial cells. These data support an endosome-mediated model of Tf-bound iron uptake into the brain and identifies mechanisms for local regional regulation of brain iron uptake. Moreover, our data provide an explanation for the disparity in the ratio of Tf to iron transport into the brain that has confounded the field. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Redox Balance in Lactobacillus reuteri DSM20016: Roles of Iron-Dependent Alcohol Dehydrogenases in Glucose/ Glycerol Metabolism.

    Science.gov (United States)

    Chen, Lu; Bromberger, Paul David; Nieuwenhuiys, Gavin; Hatti-Kaul, Rajni

    2016-01-01

    Lactobacillus reuteri, a heterofermentative bacterium, metabolizes glycerol via a Pdu (propanediol-utilization) pathway involving dehydration to 3-hydroxypropionaldehyde (3-HPA) followed by reduction to 1,3-propandiol (1,3-PDO) with concomitant generation of an oxidized cofactor, NAD+ that is utilized to maintain cofactor balance required for glucose metabolism and even for oxidation of 3-HPA by a Pdu oxidative branch to 3-hydroxypropionic acid (3-HP). The Pdu pathway is operative inside Pdu microcompartment that encapsulates different enzymes and cofactors involved in metabolizing glycerol or 1,2-propanediol, and protects the cells from the toxic effect of the aldehyde intermediate. Since L. reuteri excretes high amounts of 3-HPA outside the microcompartment, the organism is likely to have alternative alcohol dehydrogenase(s) in the cytoplasm for transformation of the aldehyde. In this study, diversity of alcohol dehydrogenases in Lactobacillus species was investigated with a focus on L. reuteri. Nine ADH enzymes were found in L. reuteri DSM20016, out of which 3 (PduQ, ADH6 and ADH7) belong to the group of iron-dependent enzymes that are known to transform aldehydes/ketones to alcohols. L. reuteri mutants were generated in which the three ADHs were deleted individually. The lagging growth phenotype of these deletion mutants revealed that limited NAD+/NADH recycling could be restricting their growth in the absence of ADHs. Notably, it was demonstrated that PduQ is more active in generating NAD+ during glycerol metabolism within the microcompartment by resting cells, while ADH7 functions to balance NAD+/NADH by converting 3-HPA to 1,3-PDO outside the microcompartment in the growing cells. Moreover, evaluation of ADH6 deletion mutant showed strong decrease in ethanol level, supporting the role of this bifuctional alcohol/aldehyde dehydrogenase in ethanol production. To the best of our knowledge, this is the first report revealing both internal and external recycling

  17. Alterations in carbohydrate and lipid metabolism induced by a diet rich in coconut oil and cholesterol in a rat model.

    Science.gov (United States)

    Zulet, M A; Barber, A; Garcin, H; Higueret, P; Martínez, J A

    1999-02-01

    The type of dietary fat as well as the amount of cholesterol occurring in the diet have been associated with several metabolic disorders. Thus, the aim of the present study was to investigate the influence of a hypercholesterolemic diet enriched with coconut oil and cholesterol on carbohydrate and lipid metabolism in a rat model. Twenty male Wistar rats weighing about 190 g were assigned to two dietary groups. One group received a semipurified control diet and the other was given a diet enriched in coconut oil (25% by weight) and cholesterol (1% by weight) for 26 days. Our results indicated a significant increase in serum total cholesterol (+285%; pcholesterol (+1509%; pcholesterol acyltransferase activity (-66%; p<0.001) was found. The situation of hypoglycemia (-18%; p<0.05) was accompanied by lower levels of serum insulin (-45%; p<0.01) and liver glycogen (-30%; p<0.05) in the hypercholesterolemic rats. Furthermore, glucose utilization was altered since lower glucose-6-Pase (-33%; p<0.05) and increased glucokinase (+212%; p<0.001) activities in the liver were found in the rat model of hypercholesterolemia. These results provide new evidence that a diet-induced hypercholesterolemia in rats is associated with several adaptative changes in carbohydrate metabolism. These findings may be of importance not only considering the role of western diets on cholesterogenesis, but also in other metabolic disturbances involving lipid and carbohydrate metabolism.

  18. Quantitative metabolomics by H-NMR and LC-MS/MS confirms altered metabolic pathways in diabetes.

    Directory of Open Access Journals (Sweden)

    Ian R Lanza

    2010-05-01

    Full Text Available Insulin is as a major postprandial hormone with profound effects on carbohydrate, fat, and protein metabolism. In the absence of exogenous insulin, patients with type 1 diabetes exhibit a variety of metabolic abnormalities including hyperglycemia, glycosurea, accelerated ketogenesis, and muscle wasting due to increased proteolysis. We analyzed plasma from type 1 diabetic (T1D humans during insulin treatment (I+ and acute insulin deprivation (I- and non-diabetic participants (ND by (1H nuclear magnetic resonance spectroscopy and liquid chromatography-tandem mass spectrometry. The aim was to determine if this combination of analytical methods could provide information on metabolic pathways known to be altered by insulin deficiency. Multivariate statistics differentiated proton spectra from I- and I+ based on several derived plasma metabolites that were elevated during insulin deprivation (lactate, acetate, allantoin, ketones. Mass spectrometry revealed significant perturbations in levels of plasma amino acids and amino acid metabolites during insulin deprivation. Further analysis of metabolite levels measured by the two analytical techniques indicates several known metabolic pathways that are perturbed in T1D (I- (protein synthesis and breakdown, gluconeogenesis, ketogenesis, amino acid oxidation, mitochondrial bioenergetics, and oxidative stress. This work demonstrates the promise of combining multiple analytical methods with advanced statistical methods in quantitative metabolomics research, which we have applied to the clinical situation of acute insulin deprivation in T1D to reflect the numerous metabolic pathways known to be affected by insulin deficiency.

  19. Genetic deletion of Rheb1 in the brain reduces food intake and causes hypoglycemia with altered peripheral metabolism.

    Science.gov (United States)

    Yang, Wanchun; Jiang, Wanxiang; Luo, Liping; Bu, Jicheng; Pang, Dejiang; Wei, Jing; Du, Chongyangzi; Xia, Xiaoqiang; Cui, Yiyuan; Liu, Shuang; Mao, Qing; Chen, Mina

    2014-01-21

    Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral metabolism need to be better understood for developing pharmacological interventions to manage eating behavior and obesity. Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a master regulator of cellular metabolism in different cell types. Pharmacological manipulations of mTOR complex 1 (mTORC1) activity in hypothalamic neurons alter food intake and body weight. Our previous study identified Rheb1 (Ras homolog enriched in brain 1) as an essential activator of mTORC1 activity in the brain. Here we examine whether central Rheb1 regulates food intake and peripheral metabolism through mTORC1 signaling. We find that genetic deletion of Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid mobilization in adipose tissue and ketogenesis in the liver. Our work highlights the importance of central Rheb1 signaling in euglycemia and energy homeostasis in animals.

  20. Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism

    Science.gov (United States)

    Yang, Wanchun; Jiang, Wanxiang; Luo, Liping; Bu, Jicheng; Pang, Dejiang; Wei, Jing; Du, Chongyangzi; Xia, Xiaoqiang; Cui, Yiyuan; Liu, Shuang; Mao, Qing; Chen, Mina

    2014-01-01

    Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral metabolism need to be better understood for developing pharmacological interventions to manage eating behavior and obesity. Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a master regulator of cellular metabolism in different cell types. Pharmacological manipulations of mTOR complex 1 (mTORC1) activity in hypothalamic neurons alter food intake and body weight. Our previous study identified Rheb1 (Ras homolog enriched in brain 1) as an essential activator of mTORC1 activity in the brain. Here we examine whether central Rheb1 regulates food intake and peripheral metabolism through mTORC1 signaling. We find that genetic deletion of Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid mobilization in adipose tissue and ketogenesis in the liver. Our work highlights the importance of central Rheb1 signaling in euglycemia and energy homeostasis in animals. PMID:24451134

  1. Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism

    Directory of Open Access Journals (Sweden)

    Wanchun Yang

    2014-01-01

    Full Text Available Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral metabolism need to be better understood for developing pharmacological interventions to manage eating behavior and obesity. Mammalian target of rapamycin (mTOR, a serine/threonine kinase, is a master regulator of cellular metabolism in different cell types. Pharmacological manipulations of mTOR complex 1 (mTORC1 activity in hypothalamic neurons alter food intake and body weight. Our previous study identified Rheb1 (Ras homolog enriched in brain 1 as an essential activator of mTORC1 activity in the brain. Here we examine whether central Rheb1 regulates food intake and peripheral metabolism through mTORC1 signaling. We find that genetic deletion of Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid mobilization in adipose tissue and ketogenesis in the liver. Our work highlights the importance of central Rheb1 signaling in euglycemia and energy homeostasis in animals.

  2. Excessive fluoride consumption increases haematological alteration in subjects with iron deficiency, thalassaemia, and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

    Science.gov (United States)

    Pornprasert, Sakorn; Wanachantararak, Phenphichar; Kantawong, Fahsai; Chamnanprai, Supoj; Kongpan, Chatpat; Pienthai, Nattasit; Yanola, Jintana; Duangmano, Suwit; Prasannarong, Mujalin

    2017-08-01

    Excessive fluoride consumption leads to accelerated red blood cell death and anaemia. Whether that increases the haematological alteration in subjects with haematological disorders (iron deficiency, thalassaemia, and G-6-PD deficiency) is still unclear. The fluoride in serum and urine and haematological parameters of students at Mae Tuen School (fluoride endemic area) were analysed and compared to those of students at Baan Yang Poa and Baan Mai Schools (control areas). Iron deficiency, thalassaemia, and G-6-PD deficiency were also diagnosed in these students. The students at Mae Tuen School had significantly (P fluoride in the serum and urine than those in control areas. In both control and fluoride endemic areas, students with haematological disorders had significantly lower levels of Hb, Hct, MCV, MCH, and MCHC than those without haematological disorders. Moreover, the lowest levels of Hb, MCH, and MCHC were observed in the students with haematological disorders who live in the fluoride endemic area. Thus, the excessive fluoride consumption increased haematological alteration in subjects with iron deficiency, thalassaemia, and G-6-PD deficiency and that may increase the risk of anaemia in these subjects.

  3. Red blotch disease alters grape berry development and metabolism by interfering with the transcriptional and hormonal regulation of ripening

    Science.gov (United States)

    Blanco-Ulate, Barbara; Hopfer, Helene; Figueroa-Balderas, Rosa; Ye, Zirou; Rivero, Rosa M.; Albacete, Alfonso; Pérez-Alfocea, Francisco; Koyama, Renata; Anderson, Michael M.; Smith, Rhonda J.; Ebeler, Susan E.

    2017-01-01

    Abstract Grapevine red blotch-associated virus (GRBaV) is a major threat to the wine industry in the USA. GRBaV infections (aka red blotch disease) compromise crop yield and berry chemical composition, affecting the flavor and aroma properties of must and wine. In this study, we combined genome-wide transcriptional profiling with targeted metabolite analyses and biochemical assays to characterize the impact of the disease on red-skinned berry ripening and metabolism. Using naturally infected berries collected from two vineyards, we were able to identify consistent berry responses to GRBaV across different environmental and cultural conditions. Specific alterations of both primary and secondary metabolism occurred in GRBaV-infected berries during ripening. Notably, GRBaV infections of post-véraison berries resulted in the induction of primary metabolic pathways normally associated with early berry development (e.g. thylakoid electron transfer and the Calvin cycle), while inhibiting ripening-associated pathways, such as a reduced metabolic flux in the central and peripheral phenylpropanoid pathways. We show that this metabolic reprogramming correlates with perturbations at multiple regulatory levels of berry development. Red blotch caused the abnormal expression of transcription factors (e.g. NACs, MYBs, and AP2-ERFs) and elements of the post-transcriptional machinery that function during red-skinned berry ripening. Abscisic acid, ethylene, and auxin pathways, which control both the initiation of ripening and stress responses, were also compromised. We conclude that GRBaV infections disrupt normal berry development and stress responses by altering transcription factors and hormone networks, which result in the inhibition of ripening pathways involved in the generation of color, flavor, and aroma compounds. PMID:28338755

  4. [Iron dysregulation and anemias].

    Science.gov (United States)

    Ikuta, Katsuya

    2015-10-01

    Most iron in the body is utilized as a component of hemoglobin that delivers oxygen to the entire body. Under normal conditions, the iron balance is tightly regulated. However, iron dysregulation does occasionally occur; total iron content reductions cause iron deficiency anemia and overexpression of the iron regulatory peptide hepcidin disturbs iron utilization resulting in anemia of chronic disease. Conversely, the presence of anemia may ultimately lead to iron overload; for example, thalassemia, a common hereditary anemia worldwide, often requires transfusion, but long-term transfusions cause iron accumulation that leads to organ damage and other poor outcomes. On the other hand, there is a possibility that iron overload itself can cause anemia; iron chelation therapy for the post-transfusion iron overload observed in myelodysplastic syndrome or aplastic anemia improves dependency on transfusions in some cases. These observations reflect the extremely close relationship between anemias and iron metabolism.

  5. Trend overtime of total haemoglobin, iron metabolism and trace minerals in veal calves fed high amounts of two different solid feeds

    Directory of Open Access Journals (Sweden)

    Anna-Lisa Stefani

    2010-01-01

    Full Text Available Fifty Polish Friesian veal calves were administrated high amounts of two different solid feeds (maize grain and a mix diet containing 10% of straw and 8% of soy in addition to the traditional milk replacer diet. Compared to the mix diet, maize grain had a lower content of iron, copper and zinc and a minor fibre level. Effects of the two diets on calves’ blood haemoglobin, iron, iron metabolism parameters, copper and zinc concentrations were studied. Haemoglobin concentration resulted higher at the end of the fattening for calves fed the mix diet, as expected. Values remained, however, within ranges that allowed acceptable carcass paleness. Haematic iron, unsaturated iron binding capacity (UIBC and total iron binding capacity (TIBC levels were not significantly different between the two solid feeds. Lower copper and zinc blood concentrations resulted for calves fed the mix diet were likely due to the feed fibre interfering with the bioavailability of the two minerals, according to what happens for iron.

  6. Changes in the proteomic and metabolic profiles of Beta vulgaris root tips in response to iron deficiency and resupply

    Directory of Open Access Journals (Sweden)

    Álvarez-Fernández Ana

    2010-06-01

    Full Text Available Abstract Background Plants grown under iron deficiency show different morphological, biochemical and physiological changes. These changes include, among others, the elicitation of different strategies to improve the acquisition of Fe from the rhizosphere, the adjustment of Fe homeostasis processes and a reorganization of carbohydrate metabolism. The application of modern techniques that allow the simultaneous and untargeted analysis of multiple proteins and metabolites can provide insight into multiple processes taking place in plants under Fe deficiency. The objective of this study was to characterize the changes induced in the root tip proteome and metabolome of sugar beet plants in response to Fe deficiency and resupply. Results Root tip extract proteome maps were obtained by 2-D isoelectric focusing polyacrylamide gel electrophoresis, and approximately 140 spots were detected. Iron deficiency resulted in changes in the relative amounts of 61 polypeptides, and 22 of them were identified by mass spectrometry (MS. Metabolites in root tip extracts were analyzed by gas chromatography-MS, and more than 300 metabolites were resolved. Out of 77 identified metabolites, 26 changed significantly with Fe deficiency. Iron deficiency induced increases in the relative amounts of proteins and metabolites associated to glycolysis, tri-carboxylic acid cycle and anaerobic respiration, confirming previous studies. Furthermore, a protein not present in Fe-sufficient roots, dimethyl-8-ribityllumazine (DMRL synthase, was present in high amounts in root tips from Fe-deficient sugar beet plants and gene transcript levels were higher in Fe-deficient root tips. Also, a marked increase in the relative amounts of the raffinose family of oligosaccharides (RFOs was observed in Fe-deficient plants, and a further increase in these compounds occurred upon short term Fe resupply. Conclusions The increases in DMRL synthase and in RFO sugars were the major changes induced by Fe

  7. Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally

    International Nuclear Information System (INIS)

    Blossom, Sarah J.; Cooney, Craig A.; Melnyk, Stepan B.; Rau, Jenny L.; Swearingen, Christopher J.; Wessinger, William D.

    2013-01-01

    Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL +/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28 mg/kg/day) postnatally from birth until 6 weeks of age on redox homeostasis and biomarkers of oxidative stress in the cerebellum. In addition, pathway intermediates involved in methyl metabolism and global DNA methylation patterns were examined in cerebellar tissue. Because the cerebellum is functionally important for coordinating motor activity, including exploratory and social approach behaviors, these parameters were evaluated in the present study. Mice exposed to 28 mg/kg/day TCE exhibited increased locomotor activity over time as compared with control mice. In the novel object exploration test, these mice were more likely to enter the zone with the novel object as compared to control mice. Similar results were obtained in a second test when an unfamiliar mouse was introduced into the testing arena. The results show for the first time that postnatal exposure to TCE causes key metabolic changes in the cerebellum that may contribute to global DNA methylation deficits and behavioral alterations in TCE-exposed mice. - Highlights: • We exposed male mice to low-level trichloroethylene from postnatal days 1 through 42. • This exposure altered redox potential and increased oxidative stress in cerebellum. • This exposure altered metabolites important in cellular methylation in cerebellum. • This exposure promoted DNA hypomethylation in cerebellum. • This exposure enhanced locomotor

  8. Dietary trans-10, cis-12-conjugated linoleic acid alters fatty acid metabolism and microbiota composition in mice.

    Science.gov (United States)

    Marques, Tatiana M; Wall, Rebecca; O'Sullivan, Orla; Fitzgerald, Gerald F; Shanahan, Fergus; Quigley, Eamonn M; Cotter, Paul D; Cryan, John F; Dinan, Timothy G; Ross, R Paul; Stanton, Catherine

    2015-03-14

    The main aim of the present study was to investigate the effects of dietary trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) on intestinal microbiota composition and SCFA production. C57BL/6 mice (n 8 per group) were fed a standard diet either supplemented with t10c12-CLA (0·5 %, w/w) (intervention) or with no supplementation (control), daily for 8 weeks. Metabolic markers (serum glucose, leptin, insulin and TAG, and liver TAG) were assessed by ELISA commercial kits, tissue long-chain fatty acids and caecal SCFA by GC, and microbial composition by 16S rRNA pyrosequencing. Dietary t10c12-CLA significantly decreased visceral fat mass (Pcomposition were affected by t10c12-CLA intake. Caecal acetate, propionate and isobutyrate concentrations were higher (Pmicrobiota composition following 8 weeks of t10c12-CLA supplementation revealed lower proportions of Firmicutes (P= 0·003) and higher proportions of Bacteroidetes (P= 0·027) compared with no supplementation. Furthermore, t10c12-CLA supplementation for 8 weeks significantly altered the gut microbiota composition, harbouring higher proportions of Bacteroidetes, including Porphyromonadaceae bacteria previously linked with negative effects on lipid metabolism and induction of hepatic steatosis. These results indicate that the mechanism of dietary t10c12-CLA on lipid metabolism in mice may be, at least, partially mediated by alterations in gut microbiota composition and functionality.

  9. Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa.

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    Abdelali Agouni

    Full Text Available BACKGROUND: Obesity is associated with increased risks for development of cardiovascular diseases. Epidemiological studies report an inverse association between dietary flavonoid consumption and mortality from cardiovascular diseases. We studied the potential beneficial effects of dietary supplementation of red wine polyphenol extract, Provinols, on obesity-associated alterations with respect to metabolic disturbances and cardiovascular functions in Zucker fatty (ZF rats. METHODOLOGY/PRINCIPAL FINDINGS: ZF rats or their lean littermates received normal diet or supplemented with Provinols for 8 weeks. Provinols improved glucose metabolism by reducing plasma glucose and fructosamine in ZF rats. Moreover, it reduced circulating triglycerides and total cholesterol as well as LDL-cholesterol in ZF rats. Echocardiography measurements demonstrated that Provinols improved cardiac performance as evidenced by an increase in left ventricular fractional shortening and cardiac output associated with decreased peripheral arterial resistances in ZF rats. Regarding vascular function, Provinols corrected endothelial dysfunction in aortas from ZF rats by improving endothelium-dependent relaxation in response to acetylcholine (Ach. Provinols enhanced NO bioavailability resulting from increased nitric oxide (NO production through enhanced endothelial NO-synthase (eNOS activity and reduced superoxide anion release via decreased expression of NADPH oxidase membrane sub-unit, Nox-1. In small mesenteric arteries, although Provinols did not affect the endothelium-dependent response to Ach; it enhanced the endothelial-derived hyperpolarizing factor component of the response. CONCLUSIONS/SIGNIFICANCE: Use of red wine polyphenols may be a potential mechanism for prevention of cardiovascular and metabolic alterations associated with obesity.

  10. Protective effect of Psidium guajava leaf extract on altered carbohydrate metabolism in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Khan, Haseena Banu Hedayathullah; Shanmugavalli, R; Rajendran, Deepa; Bai, Mookambikai Ramya; Sorimuthu, Subramanian

    2013-12-01

    Psidium guajava is an important plant of high medicinal value and has been used in traditional systems of medicine against various ailments. The antidiabetic effect of the ethanolic extract of Psidium guajava leaves and also its protective effect on altered glucose metabolism was evaluated in streptozotocin (stz)-induced diabetic rat model. Diabetes was induced in rats by means of intraperitoneal injection of 50-mg/kg body weight (b.wt.) of stz. Diabetes-induced rats were randomly divided into two groups. One group of rats was treated with Psidium guajava leaf extract at a dosage of 300-mg/kg b.wt. and the other group of rats was treated with the standard drug glyclazide at a dosage of 5-mg/kg b.wt. for 30 days. The blood glucose levels, plasma insulin, Hb, HbA1c were measured. The effect on the drug on altered glucose metabolizing enzymes were also studied. Treatment with Psidium guajava extract showed a significant reduction in blood glucose and HbA1c levels and a significant increase in plasma insulin levels. The drug also significantly restored the activities of carbohydrate metabolizing enzymes. This suggests that the potential antidiabetic effect of the ethanolic extract of the Psidium guajava leaves may be due to the presence of flavonoids and other phenolic components present in the drug.

  11. Profiling of Plasma Metabolites Suggests Altered Mitochondrial Fuel Usage and Remodeling of Sphingolipid Metabolism in Individuals With Type 2 Diabetes and Kidney Disease

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    Jian-Jun Liu

    2017-05-01

    Discussion: DKD is associated with altered fuel substrate use and remodeling of sphingolipid metabolism in T2DM with DKD. Associations of albuminuria and impaired filtration function with distinct metabolomic signatures suggest different pathophysiology underlying these 2 manifestations of DKD.

  12. Soluble Fms-Like Tyrosine Kinase-1 Alters Cellular Metabolism and Mitochondrial Bioenergetics in Preeclampsia

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    Lissette C. Sánchez-Aranguren

    2018-03-01

    Full Text Available Preeclampsia is a maternal hypertensive disorder that affects up to 1 out of 12 pregnancies worldwide. It is characterized by proteinuria, endothelial dysfunction, and elevated levels of the soluble form of the vascular endothelial growth factor receptor-1 (VEGFR-1, known as sFlt-1. sFlt-1 effects are mediated in part by decreasing VEGF signaling. The direct effects of sFlt-1 on cellular metabolism and bioenergetics in preeclampsia, have not been established. The goal of this study was to evaluate whether sFlt-1 causes mitochondrial dysfunction leading to disruption of normal functioning in endothelial and placental cells in preeclampsia. Endothelial cells (ECs and first-trimester trophoblast (HTR-8/SVneo were treated with serum from preeclamptic women rich in sFlt-1 or with the recombinant protein. sFlt-1, dose-dependently inhibited ECs respiration and acidification rates indicating a metabolic phenotype switch enhancing glycolytic flux. HTR-8/SVneo displayed a strong basal glycolytic metabolism, remaining less sensitive to sFlt-1-induced mitochondrial impairment. Moreover, results obtained in ECs exposed to serum from preeclamptic subjects demonstrated that increased sFlt-1 leads to metabolic perturbations accountable for mitochondrial dysfunction observed in preeclampsia. sFlt-1 exacerbated mitochondrial reactive oxygen species (ROS formation and mitochondrial membrane potential dissipation in ECs and trophoblasts exposed to serum from preeclamptic women. Forcing oxidative metabolism by culturing cells in galactose media, further sensitized cells to sFlt-1. This approach let us establish that sFlt-1 targets mitochondrial function in ECs. Effects of sFlt-1 on HTR-8/SVneo cells metabolism were amplified in galactose, demonstrating that sFlt-1 only target cells that rely mainly on oxidative metabolism. Together, our results establish the early metabolic perturbations induced by sFlt-1 and the resulting endothelial and mitochondrial dysfunction

  13. Fructose increases corticosterone production in association with NADPH metabolism alterations in rat epididymal white adipose tissue.

    Science.gov (United States)

    Prince, Paula D; Santander, Yanina A; Gerez, Estefania M; Höcht, Christian; Polizio, Ariel H; Mayer, Marcos A; Taira, Carlos A; Fraga, Cesar G; Galleano, Monica; Carranza, Andrea

    2017-08-01

    Metabolic syndrome is an array of closely metabolic disorders that includes glucose intolerance/insulin resistance, central obesity, dyslipidemia, and hypertension. Fructose, a highly lipogenic sugar, has profound metabolic effects in adipose tissue, and has been associated with the etiopathology of many components of the metabolic syndrome. In adipocytes, the enzyme 11 β-HSD1 amplifies local glucocorticoid production, being a key player in the pathogenesis of central obesity and metabolic syndrome. 11 β-HSD1 reductase activity is dependent on NADPH, a cofactor generated by H6PD inside the endoplasmic reticulum. Our focus was to explore the effect of fructose overload on epididymal white adipose tissue (EWAT) machinery involved in glucocorticoid production and NADPH and oxidants metabolism. Male Sprague-Dawley rats fed with a fructose solution (10% (w/v) in tap water) during 9 weeks developed some characteristic features of metabolic syndrome, such as hypertriglyceridemia, and hypertension. In addition, high levels of plasma and EWAT corticosterone were detected. Activities and expressions of H6PD and 11 β-HSD1, NAPDH content, superoxide anion production, expression of NADPH oxidase 2 subunits, and indicators of oxidative metabolism were measured. Fructose overloaded rats showed an increased potential in oxidant production respect to control rats. In parallel, in EWAT from fructose overloaded rats we found higher expression/activity of H6PD and 11 β-HSD1, and NADPH/NADP + ratio. Our in vivo results support that fructose overload installs in EWAT conditions favoring glucocorticoid production through higher H6PD expression/activity supplying NADPH for enhanced 11 β-HSD1 expression/activity, becoming this tissue a potential extra-adrenal source of corticosterone under these experimental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery

    DEFF Research Database (Denmark)

    Hansen, Jakob S; Zhao, Xinjie; Irmler, Martin

    2015-01-01

    AIMS/HYPOTHESIS: The therapeutic benefit of physical activity to prevent and treat type 2 diabetes is commonly accepted. However, the impact of the disease on the acute metabolic response is less clear. To this end, we investigated the effect of type 2 diabetes on exercise-induced plasma metabolite...... changes and the muscular transcriptional response using a complementary metabolomics/transcriptomics approach. METHODS: We analysed 139 plasma metabolites and hormones at nine time points, and whole genome expression in skeletal muscle at three time points, during a 60 min bicycle ergometer exercise...... and a 180 min recovery phase in type 2 diabetic patients and healthy controls matched for age, percentage body fat and maximal oxygen consumption (VO2). RESULTS: Pathway analysis of differentially regulated genes upon exercise revealed upregulation of regulators of GLUT4 (SLC2A4RG, FLOT1, EXOC7, RAB13...

  15. Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial: the Sysdimet study.

    Directory of Open Access Journals (Sweden)

    Maria Lankinen

    Full Text Available Due to the growing prevalence of type 2 diabetes, new dietary solutions are needed to help improve glucose and lipid metabolism in persons at high risk of developing the disease. Herein we investigated the effects of low-insulin-response grain products, fatty fish, and berries on glucose metabolism and plasma lipidomic profiles in persons with impaired glucose metabolism.Altogether 106 men and women with impaired glucose metabolism and with at least two other features of the metabolic syndrome were included in a 12-week parallel dietary intervention. The participants were randomized into three diet intervention groups: (1 whole grain and low postprandial insulin response grain products, fatty fish three times a week, and bilberries three portions per day (HealthyDiet group, (2 Whole grain enriched diet (WGED group, which includes principally the same grain products as group (1, but with no change in fish or berry consumption, and (3 refined wheat breads (Control. Oral glucose tolerance, plasma fatty acids and lipidomic profiles were measured before and after the intervention. Self-reported compliance with the diets was good and the body weight remained constant. Within the HealthyDiet group two hour glucose concentration and area-under-the-curve for glucose decreased and plasma proportion of (n-3 long-chain PUFAs increased (False Discovery Rate p-values <0.05. Increases in eicosapentaenoic acid and docosahexaenoic acid associated curvilinearly with the improved insulin secretion and glucose disposal. Among the 364 characterized lipids, 25 changed significantly in the HealthyDiet group, including multiple triglycerides incorporating the long chain (n-3 PUFA.The results suggest that the diet rich in whole grain and low insulin response grain products, bilberries, and fatty fish improve glucose metabolism and alter the lipidomic profile. Therefore, such a diet may have a beneficial effect in the efforts to prevent type 2 diabetes in high risk

  16. Ectopic lipid accumulation: A potential cause for metabolic disturbances and a contributor to the alteration of kidney function.

    Science.gov (United States)

    Guebre-Egziabher, Fitsum; Alix, Pascaline M; Koppe, Laetitia; Pelletier, Caroline C; Kalbacher, Emilie; Fouque, Denis; Soulage, Christophe O

    2013-11-01

    Ectopic lipid accumulation is now known to be a mechanism that contributes to organ injury in the context of metabolic diseases. In muscle and liver, accumulation of lipids impairs insulin signaling. This hypothesis accounts for the mechanism of insulin resistance in obesity, type 2 diabetes, aging and lipodystrophy. Increasing data suggest that lipid accumulation in the kidneys could also contribute to the alteration of kidney function in the context of metabolic syndrome and obesity. Furthermore and more unexpectedly, animal models of kidney disease exhibit a decreased adiposity and ectopic lipid redistribution suggesting that kidney disease may be a state of lipodystrophy. However, whether this abnormal lipid partitioning during chronic kidney disease (CKD) may have any functional impact in these tissues needs to be investigated. Here, we provide a perspective by defining the problem and analyzing the possible causes and consequences. Further human studies are required to strengthen these observations, and provide novel therapeutic approaches. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  17. Vaccinium virgatum fruit extract as an important adjuvant in biochemical and behavioral alterations observed in animal model of metabolic syndrome.

    Science.gov (United States)

    Oliveira, Pathise Souto; Gazal, Marta; Flores, Natália Porto; Zimmer, Aline Rigon; Chaves, Vitor Clasen; Reginatto, Flávio Henrique; Kaster, Manuella Pinto; Tavares, Rejane Giacomelli; Spanevello, Roselia Maria; Lencina, Claiton Leoneti; Stefanello, Francieli Moro

    2017-04-01

    The aim of this study was to investigate the effect of blueberry (Vaccinium virgatum) fruit extract on metabolic, behavioral and oxidative stress parameters in the hippocampus and cerebral cortex of mice submitted to an experimental model of metabolic syndrome induced by a highly palatable diet (HPD). Mice C57BL/6 were divided into 4 experimental groups: (1) received standard chow and saline orally, (2) received standard chow and blueberry hydroalcoholic extract, (3) received HPD and saline orally, (4) received HPD and blueberry hydroalcoholic extract. The animals were treated for 150days. Our results showed that the animals fed with HPD presented insulin resistance, increased body weight, visceral fat, glucose, triglycerides, and total cholesterol when compared to the control group. The blueberry extract prevented the increase of these metabolic parameters. Also, the extract was able to reduce the levels of thiobarbituric acid reactive substances in the cerebral cortex and hippocampus of animals submitted to HPD. In contrast, no differences were observed in the total thiol content, activity of the antioxidant enzymes catalase and superoxide dismutase. In addition, the HPD fed animals showed a significant increase in immobility time in the forced swimming test and blueberry prevented this alteration, although no changes were observed in the ambulatory behavior, as well as in the anxiolytic profile of these animals. Overall, our findings suggest that chronic consumption of blueberry extract exhibits hypoglycemic, hypolipidemic, antidepressant-like and antiperoxidative effects in an animal model of metabolic syndrome. Copyright © 2017. Published by Elsevier Masson SAS.

  18. Metabonomic Analysis Reveals Efficient Ameliorating Effects of Acupoint Stimulations on the Menopause-caused Alterations in Mammalian Metabolism

    Science.gov (United States)

    Zhang, Limin; Wang, Yulan; Xu, Yunxiang; Lei, Hehua; Zhao, Ying; Li, Huihui; Lin, Xiaosheng; Chen, Guizhen; Tang, Huiru

    2014-01-01

    Acupoint stimulations are effective in ameliorating symptoms of menopause which is an unavoidable ageing consequence for women. To understand the mechanistic aspects of such treatments, we systematically analyzed the effects of acupoint laser-irradiation and catgut-embedding on the ovariectomy-induced rat metabolic changes using NMR and GC-FID/MS methods. Results showed that ovariectomization (OVX) caused comprehensive metabolic changes in lipid peroxidation, glycolysis, TCA cycle, choline and amino acid metabolisms. Both acupoint laser-irradiation and catgut-embedding ameliorated the OVX-caused metabonomic changes more effectively than hormone replacement therapy (HRT) with nilestriol. Such effects of acupoint stimulations were highlighted in alleviating lipid peroxidation, restoring glucose homeostasis and partial reversion of the OVX-altered amino acid metabolism. These findings provided new insights into the menopause effects on mammalian biochemistry and beneficial effects of acupoint stimulations in comparison with HRT, demonstrating metabonomics as a powerful approach for potential applications in disease prognosis and developments of effective therapies.

  19. Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice[S

    Science.gov (United States)

    Palmisano, Brian T.; Le, Thao D.; Zhu, Lin; Lee, Yoon Kwang; Stafford, John M.

    2016-01-01

    Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. PMID:27354419

  20. Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice.

    Science.gov (United States)

    Palmisano, Brian T; Le, Thao D; Zhu, Lin; Lee, Yoon Kwang; Stafford, John M

    2016-08-01

    Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  1. Alteration of metabolomic markers of amino-acid metabolism in piglets with in-feed antibiotics.

    Science.gov (United States)

    Mu, Chunlong; Yang, Yuxiang; Yu, Kaifan; Yu, Miao; Zhang, Chuanjian; Su, Yong; Zhu, Weiyun

    2017-04-01

    In-feed antibiotics have been used to promote growth in piglets, but its impact on metabolomics profiles associated with host metabolism is largely unknown. In this study, to test the hypothesis that antibiotic treatment may affect metabolite composition both in the gut and host biofluids, metabolomics profiles were analyzed in antibiotic-treated piglets. Piglets were fed a corn-soy basal diet with or without in-feed antibiotics from postnatal day 7 to day 42. The serum biochemical parameters, metabolomics profiles of the serum, urine, and jejunal digesta, and indicators of microbial metabolism (short-chain fatty acids and biogenic amines) were analyzed. Compared to the control group, antibiotics treatment did not have significant effects on serum biochemical parameters except that it increased (P Antibiotics treatment increased the relative concentrations of metabolites involved in amino-acid metabolism in the serum, while decreased the relative concentrations of most amino acids in the jejunal content. Antibiotics reduced urinary 2-ketoisocaproate and hippurate. Furthermore, antibiotics decreased (P Antibiotics significantly affected the concentrations of biogenic amines, which are derived from microbial amino-acid metabolism. The three major amines, putrescine, cadaverine, and spermidine, were all increased (P antibiotics-treated piglets. These results identified the phenomena that in-feed antibiotics may have significant impact on the metabolomic markers of amino-acid metabolism in piglets.

  2. Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism

    Science.gov (United States)

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Lamers, Wouter H.; Chaudhry, Farrukh A.; Verlander, Jill W.

    2016-01-01

    Glutamine synthetase (GS) catalyzes the recycling of NH4+ with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na+-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression. PMID:27009341

  3. Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism.

    Science.gov (United States)

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E; Lamers, Wouter H; Chaudhry, Farrukh A; Verlander, Jill W; Weiner, I David

    2016-06-01

    Glutamine synthetase (GS) catalyzes the recycling of NH4 (+) with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na(+)-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression.

  4. 5-HT2Areceptor deficiency alters the metabolic and transcriptional, but not the behavioral, consequences of chronic unpredictable stress.

    Science.gov (United States)

    Jaggar, Minal; Weisstaub, Noelia; Gingrich, Jay A; Vaidya, Vidita A

    2017-12-01

    Chronic stress enhances risk for psychiatric disorders, and in animal models is known to evoke depression-like behavior accompanied by perturbed neurohormonal, metabolic, neuroarchitectural and transcriptional changes. Serotonergic neurotransmission, including serotonin 2A (5-HT 2A ) receptors, have been implicated in mediating specific aspects of stress-induced responses. Here we investigated the influence of chronic unpredictable stress (CUS) on depression-like behavior, serum metabolic measures, and gene expression in stress-associated neurocircuitry of the prefrontal cortex (PFC) and hippocampus in 5-HT 2A receptor knockout (5-[Formula: see text]) and wild-type mice of both sexes. While 5-[Formula: see text] male and female mice exhibited a baseline reduced anxiety-like state, this did not alter the onset or severity of behavioral despair during and at the cessation of CUS, indicating that these mice can develop stress-evoked depressive behavior. Analysis of metabolic parameters in serum revealed a CUS-evoked dyslipidemia, which was abrogated in 5-[Formula: see text] female mice with a hyperlipidemic baseline phenotype. 5-[Formula: see text] male mice in contrast did not exhibit such a baseline shift in their serum lipid profile. Specific stress-responsive genes ( Crh , Crhr1 , Nr3c1, and Nr3c2 ), trophic factors ( Bdnf , Igf1 ) and immediate early genes (IEGs) ( Arc , Fos , Fosb , Egr1-4 ) in the PFC and hippocampus were altered in 5-[Formula: see text] mice both under baseline and CUS conditions. Our results support a role for the 5-HT 2A receptor in specific metabolic and transcriptional, but not behavioral, consequences of CUS, and highlight that the contribution of the 5-HT 2A receptor to stress-evoked changes is sexually dimorphic.

  5. Altered behavior, physiology, and metabolism in fish exposed to polystyrene nanoparticles.

    Science.gov (United States)

    Mattsson, Karin; Ekvall, Mikael T; Hansson, Lars-Anders; Linse, Sara; Malmendal, Anders; Cedervall, Tommy

    2015-01-06

    The use of nanoparticles in consumer products, for example, cosmetics, sunscreens, and electrical devices, has increased tremendously over the past decade despite insufficient knowledge about their effects on human health and ecosystem function. Moreover, the amount of plastic waste products that enter natural ecosystems, such as oceans and lakes, is increasing, and degradation of the disposed plastics produces smaller particles toward the nano scale. Therefore, it is of utmost importance to gain knowledge about how plastic nanoparticles enter and affect living organisms. Here we have administered 24 and 27 nm polystyrene nanoparticles to fish through an aquatic food chain, from algae through Daphnia, and studied the effects on behavior and metabolism. We found severe effects on feeding and shoaling behavior as well as metabolism of the fish; hence, we conclude that polystyrene nanoparticles have severe effects on both behavior and metabolism in fish and that commonly used nanosized particles may have considerable effects on natural systems and ecosystem services derived from them.

  6. Helicobacter pylori seropositivity's association with markers of iron, 1-carbon metabolism, and antioxidant status among US adults: a structural equations modeling approach.

    Directory of Open Access Journals (Sweden)

    May A Beydoun

    Full Text Available We tested a model in which Helicobacter pylori seropositivity (Hps predicted iron status, which in turn acted as a predictor for markers of 1-C metabolism that were then allowed to predict antioxidant status.National Health and Nutrition Examination Surveys (NHANES 1999-2000 cross-sectional data among adults aged 20-85 y were analyzed (n = 3,055. Markers of Hps, iron status (serum ferritin and transferrin saturation (TS; 1-C metabolism (serum folate (FOLserum, B-12, total homocysteine (tHcy, methylmalonic acid (MMA and antioxidant status (vitamins A and E were entered into a structural equations model (SEM.Predictors of Hps included older age, lower education and income, racial/ethnic groups (lowest among Non-Hispanic Whites, and lifetime cigarette smoking. SEM modeling indicated that Hps had a direct inverse relationship with iron status (combining serum ferritin and TS which in turn was positively related to 1-C metabolites (higher serum folate, B-12 or lower tHcy/MMA that were positively associated with antioxidant status (combining serum vitamins A and E. Another pathway that was found bypassed 1-C metabolites (Hps → Iron_st → Antiox. The sum of all indirect effects from Hps combining both pathways and the other indirect pathways in the model (Hps → Iron_st → OneCarbon; Hps →OneCarbon →Antiox was estimated at β = -0.006±0.003, p<0.05.In sum, of the total effect of H. pylori seropositivity on antioxidant status, two significant indirect pathways through Iron status and 1-Carbon metabolites were found. Randomized controlled trials should be conducted to uncover the concomitant causal effect of H. pylori eradication on improving iron status, folate, B-12 and antioxidant status among H. pylori seropositive individuals.

  7. Sorafenib metabolism is significantly altered in the liver tumor tissue of hepatocellular carcinoma patient.

    Directory of Open Access Journals (Sweden)

    Ling Ye

    Full Text Available BACKGROUND: Sorafenib, the drug used as first line treatment for hepatocellular carcinoma (HCC, is metabolized by cytochrome P450 (CYP 3A4-mediated oxidation and uridine diphosphate glucuronosyl transferase (UGT 1A9-mediated glucuronidation. Liver diseases are associated with reduced CYP and UGT activities, which can considerably affect drug metabolism, leading to drug toxicity. Thus, understanding the metabolism of therapeutic compounds in patients with liver diseases is necessary. However, the metabolism characteristic of sorafenib has not been systematically determined in HCC patients. METHODS: Sorafenib metabolism was tested in the pooled and individual tumor hepatic microsomes (THLMs and adjacent normal hepatic microsomes (NHLMs of HCC patients (n = 18. Commercial hepatic microsomes (CHLMs were used as a control. In addition, CYP3A4 and UGT1A9 protein expression in different tissues were measured by Western blotting. RESULTS: The mean rates of oxidation and glucuronidation of sorafenib were significantly decreased in the pooled THLMs compared with those in NHLMs and CHLMs. The maximal velocity (Vmax of sorafenib oxidation and glucuronidation were approximately 25-fold and 2-fold decreased in the pooled THLMs, respectively, with unchanged Km values. The oxidation of sorafenib in individual THLMs sample was significantly decreased (ranging from 7 to 67-fold than that in corresponding NHLMs sample. The reduction of glucuronidation in THLMs was observed in 15 out of 18 patients' samples. Additionally, the level of CYP3A4 and UGT1A9 expression were both notably decreased in the pooled THLMs. CONCLUSIONS: Sorafenib metabolism was remarkably decreased in THLMs. This result was associated with the down regulation of the protein expression of CYP3A4 and UGT1A9.

  8. Altered behavior, physiology, and metabolism in fish exposed to polystyrene nanoparticles

    DEFF Research Database (Denmark)

    Mattsson, Karin; Ekvall, Mikael T; Hansson, Lars-Anders

    2015-01-01

    The use of nanoparticles in consumer products, for example, cosmetics, sunscreens, and electrical devices, has increased tremendously over the past decade despite insufficient knowledge about their effects on human health and ecosystem function. Moreover, the amount of plastic waste products...... administered 24 and 27 nm polystyrene nanoparticles to fish through an aquatic food chain, from algae through Daphnia, and studied the effects on behavior and metabolism. We found severe effects on feeding and shoaling behavior as well as metabolism of the fish; hence, we conclude that polystyrene...

  9. Genome-wide transcriptional response of a Saccharomyces cerevisiae strain with an altered redox metabolism

    DEFF Research Database (Denmark)

    Bro, Christoffer; Regenberg, Birgitte; Nielsen, Jens

    2004-01-01

    The genome-wide transcriptional response of a Saccharomyces cerevisiae strain deleted in GDH1 that encodes a NADP(+)-dependent glutamate dehydrogenase was compared to a wild-type strain under anaerobic steady-state conditions. The GDH1-deleted strain has a significantly reduced NADPH requirement...... the only one with a direct link to redox metabolism was GND1, encoding phosphogluconate dehydrogenase. To extract additional information we analyzed the transcription data for a gene subset consisting of all known genes encoding metabolic enzymes that use NA