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Sample records for panorganismal metabolic response

  1. Panorganismal metabolic response modeling of an experimental Echinostoma caproni infection in the mouse.

    PubMed

    Saric, Jasmina; Li, Jia V; Wang, Yulan; Keiser, Jennifer; Veselkov, Kirill; Dirnhofer, Stephan; Yap, Ivan K S; Nicholson, Jeremy K; Holmes, Elaine; Utzinger, Jürg

    2009-08-01

    describes the panorganismal metabolic response of the infection. PMID:19489577

  2. Metabolic response to exercise.

    PubMed

    De Feo, P; Di Loreto, C; Lucidi, P; Murdolo, G; Parlanti, N; De Cicco, A; Piccioni, F; Santeusanio, F

    2003-09-01

    At the beginning, the survival of humans was strictly related to their physical capacity. There was the need to resist predators and to provide food and water for life. Achieving these goals required a prompt and efficient energy system capable of sustaining either high intensity or maintaining prolonged physical activity. Energy for skeletal muscle contraction is supplied by anaerobic and aerobic metabolic pathways. The former can allow short bursts of intense physical activity (60-90 sec) and utilizes as energetic source the phosphocreatine shuttle and anaerobic glycolysis. The aerobic system is the most efficient ATP source for skeletal muscle. The oxidative phosporylation of carbohydrates, fats and, to a minor extent, proteins, can sustain physical activity for many hours. Carbohydrates are the most efficient fuel for working muscle and their contribution to total fuel oxidation is positively related to the intensity of exercise. The first metabolic pathways of carbohydrate metabolism to be involved are skeletal muscle glycogenolysis and glycolysis. Later circulating glucose, formed through activated gluconeogenesis, becomes an important energetic source. Among glucose metabolites, lactate plays a primary role as either direct or indirect (gluconeogenesis) energy source for contracting skeletal muscle. Fat oxidation plays a primary role during either low-moderate intensity exercise or protracted physical activity (over 90-120 min). Severe muscle glycogen depletion results in increased rates of muscle proteolysis and branched chain amino acid oxidation. Endurance training ameliorates physical performance by improving cardiopulmonary efficiency and optimizing skeletal muscle supply and oxidation of substrates. PMID:14964437

  3. Selected Metabolic Responses to Skateboarding

    ERIC Educational Resources Information Center

    Hetzler, Ronald K.; Hunt, Ian; Stickley, Christopher D.; Kimura, Iris F.

    2011-01-01

    Despite the popularity of skateboarding worldwide, the authors believe that no previous studies have investigated the metabolic demands associated with recreational participation in the sport. Although metabolic equivalents (METs) for skateboarding were published in textbooks, the source of these values is unclear. Therefore, the rise in…

  4. [Metabolic response to trauma and stress].

    PubMed

    Omerbegović, Meldijana; Durić, Amira; Muratović, Nusreta; Mulalić, Lejla; Hamzanija, Emina

    2003-01-01

    Trauma, surgery, burns and infection are accompanied with catabolic response which is characterized by enhanced protelysis, enhanced excretion of nitrogen, neoglucogenesis and resistance of peripheral tissues to insulin. This catabolic response is mediated through neural pathways and neuroendocrine axis. The purpose of this response is restoration of adequate perfusion and oxygenation and releasing of energy and substrates for the tissues, organs and systems which functions are essential for the survival. Metabolic response to injury and severe infection leads to decomposition of skeletal muscle proteins to amino acids, intensive liver gluconcogenesis from lactate, glycerol and alanin with enhanced oxidation of aminoacids. These substrates are necessary for synthesis of various mediators of protein or lipid nature, which are important for the defense and tissue regeneration. The changes result in negative balance of nitrogen, loss of body weight, and lower plasma concentration of all aminoacids. Patients who were unable to develop this hypercatabolic response have poor prognosis, and the patients with hypercatabolic response rapidly lose their body cell mass and without metabolic and nutritive support have more complications and higher mortality. Although neoglucogenesis, proteolysis and lipolysis are resistant to exogenous nutrients, metabolic support in critical illness improves the chances for survival until the healing of the disease. Casual therapy in such conditions is elimination of "stressors" which maintain abnormal endocrine and metabolic response. Adequate oxygenation, hemostasis, infection control and control of extracellular compartment expansion and low flows, are essential for the efficacy of nutritive support and that is the only way to convalescence and wound healing. PMID:15017867

  5. Pancreatic Islet Responses to Metabolic Trauma.

    PubMed

    Burke, Susan J; Karlstad, Michael D; Collier, J Jason

    2016-09-01

    Carbohydrate, lipid, and protein metabolism are largely controlled by the interplay of various hormones, which includes those secreted by the pancreatic islets of Langerhans. While typically representing only 1% to 2% of the total pancreatic mass, the islets have a remarkable ability to adapt to disparate situations demanding a change in hormone release, such as peripheral insulin resistance. There are many different routes to the onset of insulin resistance, including obesity, lipodystrophy, glucocorticoid excess, and the chronic usage of atypical antipsychotic drugs. All of these situations are coupled to an increase in pancreatic islet size, often with a corresponding increase in insulin production. These adaptive responses within the islets are ultimately intended to maintain glycemic control and to promote macronutrient homeostasis during times of stress. Herein, we review the consequences of specific metabolic trauma that lead to insulin resistance and the corresponding adaptive alterations within the pancreatic islets. PMID:26974425

  6. Metabolic Responses of Bacterial Cells to Immobilization.

    PubMed

    Żur, Joanna; Wojcieszyńska, Danuta; Guzik, Urszula

    2016-01-01

    In recent years immobilized cells have commonly been used for various biotechnological applications, e.g., antibiotic production, soil bioremediation, biodegradation and biotransformation of xenobiotics in wastewater treatment plants. Although the literature data on the physiological changes and behaviour of cells in the immobilized state remain fragmentary, it is well documented that in natural settings microorganisms are mainly found in association with surfaces, which results in biofilm formation. Biofilms are characterized by genetic and physiological heterogeneity and the occurrence of altered microenvironments within the matrix. Microbial cells in communities display a variety of metabolic differences as compared to their free-living counterparts. Immobilization of bacteria can occur either as a natural phenomenon or as an artificial process. The majority of changes observed in immobilized cells result from protection provided by the supports. Knowledge about the main physiological responses occurring in immobilized cells may contribute to improving the efficiency of immobilization techniques. This paper reviews the main metabolic changes exhibited by immobilized bacterial cells, including growth rate, biodegradation capabilities, biocatalytic efficiency and plasmid stability. PMID:27455220

  7. Precision Metabolic Engineering: the Design of Responsive, Selective, and Controllable Metabolic Systems

    PubMed Central

    McNerney, Monica P.; Watstein, Daniel M.; Styczynski, Mark P.

    2015-01-01

    Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed “precision metabolic engineering,” involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. PMID:26189665

  8. Metabolic and hormonal responses to exercise in partially hepatectomised rats.

    PubMed

    Lavoie, J M; Warren, C; Arcelin, K; Latour, M G; Désy, F; Shinoda, M; Ethier, C; Gascon-Barré, M

    1998-06-01

    To characterise how the liver affects metabolic and hormonal exercise responses, hepatectomised (70%; HX) rats were submitted to a 30- or 50-min treadmill exercise (26 m/min, 0% slope) 48 hr or 7 days after surgery (reduced or normal liver mass, respectively). To determine whether metabolic effects of liver mass reduction during exercise were caused by reduced capacity of the liver to produce glucose, metabolic and hormonal responses to the same exercise protocol were measured in 48-hr HX rats. Euglycemia, maintained by exogenous glucose infusion, produced attenuated lactate, insulin, and glucagon values in 48-hr HX rats but did not affect FFA, glycerol, and plasma catecholamine responses. Results indicate that metabolic and hormonal exercise responses are amplified in 48-hr HX rats. Maintaining euglycemia in 48-hr HX rats during exercise does not reduce all responses. Intrahepatic events, similar to those in a short-term (48-hr) HX liver, may influence metabolic and hormonal exercise responses. PMID:9615872

  9. RELATCH: relative optimality in metabolic networks explains robust metabolic and regulatory responses to perturbations

    PubMed Central

    2012-01-01

    Predicting cellular responses to perturbations is an important task in systems biology. We report a new approach, RELATCH, which uses flux and gene expression data from a reference state to predict metabolic responses in a genetically or environmentally perturbed state. Using the concept of relative optimality, which considers relative flux changes from a reference state, we hypothesize a relative metabolic flux pattern is maintained from one state to another, and that cells adapt to perturbations using metabolic and regulatory reprogramming to preserve this relative flux pattern. This constraint-based approach will have broad utility where predictions of metabolic responses are needed. PMID:23013597

  10. Metabolic host responses to infection by intracellular bacterial pathogens

    PubMed Central

    Eisenreich, Wolfgang; Heesemann, Jürgen; Rudel, Thomas; Goebel, Werner

    2013-01-01

    The interaction of bacterial pathogens with mammalian hosts leads to a variety of physiological responses of the interacting partners aimed at an adaptation to the new situation. These responses include multiple metabolic changes in the affected host cells which are most obvious when the pathogen replicates within host cells as in case of intracellular bacterial pathogens. While the pathogen tries to deprive nutrients from the host cell, the host cell in return takes various metabolic countermeasures against the nutrient theft. During this conflicting interaction, the pathogen triggers metabolic host cell responses by means of common cell envelope components and specific virulence-associated factors. These host reactions generally promote replication of the pathogen. There is growing evidence that pathogen-specific factors may interfere in different ways with the complex regulatory network that controls the carbon and nitrogen metabolism of mammalian cells. The host cell defense answers include general metabolic reactions, like the generation of oxygen- and/or nitrogen-reactive species, and more specific measures aimed to prevent access to essential nutrients for the respective pathogen. Accurate results on metabolic host cell responses are often hampered by the use of cancer cell lines that already exhibit various de-regulated reactions in the primary carbon metabolism. Hence, there is an urgent need for cellular models that more closely reflect the in vivo infection conditions. The exact knowledge of the metabolic host cell responses may provide new interesting concepts for antibacterial therapies. PMID:23847769

  11. Global Metabolic Responses to Salt Stress in Fifteen Species

    PubMed Central

    Pollak, Georg R.; Kuehne, Andreas; Sauer, Uwe

    2016-01-01

    Cells constantly adapt to unpredictably changing extracellular solute concentrations. A cornerstone of the cellular osmotic stress response is the metabolic supply of energy and building blocks to mount appropriate defenses. Yet, the extent to which osmotic stress impinges on the metabolic network remains largely unknown. Moreover, it is mostly unclear which, if any, of the metabolic responses to osmotic stress are conserved among diverse organisms or confined to particular groups of species. Here we investigate the global metabolic responses of twelve bacteria, two yeasts and two human cell lines exposed to sustained hyperosmotic salt stress by measuring semiquantitative levels of hundreds of cellular metabolites using nontargeted metabolomics. Beyond the accumulation of osmoprotectants, we observed significant changes of numerous metabolites in all species. Global metabolic responses were predominantly species-specific, yet individual metabolites were characteristically affected depending on species’ taxonomy, natural habitat, envelope structure or salt tolerance. Exploiting the breadth of our dataset, the correlation of individual metabolite response magnitudes across all species implicated lower glycolysis, tricarboxylic acid cycle, branched-chain amino acid metabolism and heme biosynthesis to be generally important for salt tolerance. Thus, our findings place the global metabolic salt stress response into a phylogenetic context and provide insights into the cellular phenotype associated with salt tolerance. PMID:26848578

  12. Opposite metabolic responses of shoots and roots to drought

    NASA Astrophysics Data System (ADS)

    Gargallo-Garriga, Albert; Sardans, Jordi; Pérez-Trujillo, Míriam; Rivas-Ubach, Albert; Oravec, Michal; Vecerova, Kristyna; Urban, Otmar; Jentsch, Anke; Kreyling, Juergen; Beierkuhnlein, Carl; Parella, Teodor; Peñuelas, Josep

    2014-10-01

    Shoots and roots are autotrophic and heterotrophic organs of plants with different physiological functions. Do they have different metabolomes? Do their metabolisms respond differently to environmental changes such as drought? We used metabolomics and elemental analyses to answer these questions. First, we show that shoots and roots have different metabolomes and nutrient and elemental stoichiometries. Second, we show that the shoot metabolome is much more variable among species and seasons than is the root metabolome. Third, we show that the metabolic response of shoots to drought contrasts with that of roots; shoots decrease their growth metabolism (lower concentrations of sugars, amino acids, nucleosides, N, P, and K), and roots increase it in a mirrored response. Shoots are metabolically deactivated during drought to reduce the consumption of water and nutrients, whereas roots are metabolically activated to enhance the uptake of water and nutrients, together buffering the effects of drought, at least at the short term.

  13. Reproducibility of regional brain metabolic responses to lorazepam

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Overall, J. |

    1996-10-01

    Changes in regional brain glucose metabolism in response to benzodiazepine agonists have been used as indicators of benzodiazepine-GABA receptor function. The purpose of this study was to assess the reproducibility of these responses. Sixteen healthy right-handed men underwent scanning with PET and [{sup 18}F]fluorodeoxyglucose (FDG) twice: before placebo and before lorazepam (30 {mu}g/kg). The same double FDG procedure was repeated 6-8 wk later on the men to assess test-retest reproducibility. The regional absolute brain metabolic values obtained during the second evaluation were significantly lower than those obtained from the first evaluation regardless of condition (p {le} 0.001). Lorazepam significantly and consistently decreased both whole-brain metabolism and the magnitude. The regional pattern of the changes were comparable for both studies (12.3% {plus_minus} 6.9% and 13.7% {plus_minus} 7.4%). Lorazepam effects were the largest in the thalamus (22.2% {plus_minus} 8.6% and 22.4% {plus_minus} 6.9%) and occipital cortex (19% {plus_minus} 8.9% and 21.8% {plus_minus} 8.9%). Relative metabolic measures were highly reproducible both for pharmacolgic and replication condition. This study measured the test-retest reproducibility in regional brain metabolic responses, and although the global and regional metabolic values were significantly lower for the repeated evaluation, the response to lorazepam was highly reproducible. 1613 refs., 3 figs., 3 tabs.

  14. Metabolic Profiling of the Response to an Oral Glucose Tolerance Test Detects Subtle Metabolic Changes

    PubMed Central

    Wopereis, Suzan; Rubingh, Carina M.; van Erk, Marjan J.; Verheij, Elwin R.; van Vliet, Trinette; Cnubben, Nicole H. P.; Smilde, Age K.; van der Greef, Jan; van Ommen, Ben; Hendriks, Henk F. J.

    2009-01-01

    Background The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism. Methodology To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation. Conclusions Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men. PMID:19242536

  15. Biofilm shows spatially stratified metabolic responses to contaminant exposure

    PubMed Central

    Cao, Bin; Majors, Paul D.; Ahmed, Bulbul; Renslow, Ryan S.; Silvia, Crystal P.; Shi, Liang; Kjelleberg, Staffan; Fredrickson, Jim K.; Beyenal, Haluk

    2012-01-01

    Summary Biofilms are core to a range of biological processes, including the bioremediation of environmental contaminants. Within a biofilm population, cells with diverse genotypes and phenotypes coexist, suggesting that distinct metabolic pathways may be expressed based on the local environmental conditions in a biofilm. However, metabolic responses to local environmental conditions in a metabolically active biofilm interacting with environmental contaminants have never been quantitatively elucidated. In this study, we monitored the spatiotemporal metabolic responses of metabolically active Shewanella oneidensis MR-1 biofilms to U(VI) (uranyl, UO22+) and Cr(VI) (chromate, CrO42−) using noninvasive nuclear magnetic resonance imaging (MRI) and spectroscopy (MRS) approaches to obtain insights into adaptation in biofilms during biofilm-contaminant interactions. While overall biomass distribution was not significantly altered upon exposure to U(VI) or Cr(VI), MRI and spatial mapping of the diffusion revealed localized changes in the water diffusion coefficients in the biofilms, suggesting significant contaminant-induced changes in structural or hydrodynamic properties during bioremediation. Finally, we quantitatively demonstrated that the metabolic responses of biofilms to contaminant exposure are spatially stratified, implying that adaptation in biofilms is custom-developed based on local microenvironments. PMID:22925136

  16. Extracellular Adenosine Mediates a Systemic Metabolic Switch during Immune Response

    PubMed Central

    Bajgar, Adam; Kucerova, Katerina; Jonatova, Lucie; Tomcala, Ales; Schneedorferova, Ivana; Okrouhlik, Jan; Dolezal, Tomas

    2015-01-01

    Immune defense is energetically costly, and thus an effective response requires metabolic adaptation of the organism to reallocate energy from storage, growth, and development towards the immune system. We employ the natural infection of Drosophila with a parasitoid wasp to study energy regulation during immune response. To combat the invasion, the host must produce specialized immune cells (lamellocytes) that destroy the parasitoid egg. We show that a significant portion of nutrients are allocated to differentiating lamellocytes when they would otherwise be used for development. This systemic metabolic switch is mediated by extracellular adenosine released from immune cells. The switch is crucial for an effective immune response. Preventing adenosine transport from immune cells or blocking adenosine receptor precludes the metabolic switch and the deceleration of development, dramatically reducing host resistance. Adenosine thus serves as a signal that the “selfish” immune cells send during infection to secure more energy at the expense of other tissues. PMID:25915062

  17. Genetic regulation of warfarin metabolism and response.

    PubMed

    Daly, Ann K; Aithal, Guruprasad P

    2003-08-01

    Genetic factors make an important contribution to the wide interindividual variation in warfarin dose requirement. Several cytochromes P450, each of which shows genetic polymorphism leading to interindividual variation in levels of activity, contribute to oxidative metabolism of warfarin. The most important of these is CYP2C9, which 7-hydroxylates S-warfarin. In clinical studies, possession of the CYP2C9*2 or CYP2C9*3 variant alleles, which result in decreased enzyme activity, has been associated with a significant decrease in mean warfarin dose requirement in at least eight studies. Several studies also suggest that possession of a variant allele is associated with an increased risk of adverse events. Other genetic factors such as polymorphisms affecting CYP3A4 or CYP1A2 may also be relevant to warfarin dose requirement. The molecular basis of warfarin resistance remains unclear but could be due to unusually high CYP2C9 activity (pharmacokinetic resistance) or to abnormal vitamin K epoxide reductase (pharmacodynamic resistance). There is less information available on genetic factors affecting other anticoagulants, but the CYP2C9 genotype is also relevant to acenocoumarol dose. PMID:15199455

  18. Mitochondrial metabolic remodeling in response to genetic and environmental perturbations.

    PubMed

    Hollinshead, Kate E R; Tennant, Daniel A

    2016-07-01

    Mitochondria are metabolic hubs within mammalian cells and demonstrate significant metabolic plasticity. In oxygenated environments with ample carbohydrate, amino acid, and lipid sources, they are able to use the tricarboxylic acid cycle for the production of anabolic metabolites and ATP. However, in conditions where oxygen becomes limiting for oxidative phosphorylation, they can rapidly signal to increase cytosolic glycolytic ATP production, while awaiting hypoxia-induced changes in the proteome mediated by the activity of transcription factors such as hypoxia-inducible factor 1. Hypoxia is a well-described phenotype of most cancers, driving many aspects of malignancy. Improving our understanding of how mitochondria change their metabolism in response to this stimulus may therefore elicit the design of new selective therapies. Many of the recent advances in our understanding of mitochondrial metabolic plasticity have been acquired through investigations of cancer-associated mutations in metabolic enzymes, including succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase. This review will describe how metabolic perturbations induced by hypoxia and mutations in these enzymes have informed our knowledge in the control of mitochondrial metabolism, and will examine what this may mean for the biology of the cancers in which these mutations are observed. WIREs Syst Biol Med 2016, 8:272-285. doi: 10.1002/wsbm.1334 For further resources related to this article, please visit the WIREs website. PMID:27196610

  19. Mitochondrial metabolic remodeling in response to genetic and environmental perturbations

    PubMed Central

    Hollinshead, Kate E.R.

    2016-01-01

    Mitochondria are metabolic hubs within mammalian cells and demonstrate significant metabolic plasticity. In oxygenated environments with ample carbohydrate, amino acid, and lipid sources, they are able to use the tricarboxylic acid cycle for the production of anabolic metabolites and ATP. However, in conditions where oxygen becomes limiting for oxidative phosphorylation, they can rapidly signal to increase cytosolic glycolytic ATP production, while awaiting hypoxia‐induced changes in the proteome mediated by the activity of transcription factors such as hypoxia‐inducible factor 1. Hypoxia is a well‐described phenotype of most cancers, driving many aspects of malignancy. Improving our understanding of how mitochondria change their metabolism in response to this stimulus may therefore elicit the design of new selective therapies. Many of the recent advances in our understanding of mitochondrial metabolic plasticity have been acquired through investigations of cancer‐associated mutations in metabolic enzymes, including succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase. This review will describe how metabolic perturbations induced by hypoxia and mutations in these enzymes have informed our knowledge in the control of mitochondrial metabolism, and will examine what this may mean for the biology of the cancers in which these mutations are observed. WIREs Syst Biol Med 2016, 8:272–285. doi: 10.1002/wsbm.1334 For further resources related to this article, please visit the WIREs website. PMID:27196610

  20. Erythropoietin Action in Stress Response, Tissue Maintenance and Metabolism

    PubMed Central

    Zhang, Yuanyuan; Wang, Li; Dey, Soumyadeep; Alnaeeli, Mawadda; Suresh, Sukanya; Rogers, Heather; Teng, Ruifeng; Noguchi, Constance Tom

    2014-01-01

    Erythropoietin (EPO) regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia for two and half decades and has facilitated studies of EPO action. Reports of animal and cell models of ischemic stress in vitro and injury suggest potential EPO benefit beyond red blood cell production including vascular endothelial response to increase nitric oxide production, which facilitates oxygen delivery to brain, heart and other non-hematopoietic tissues. This review discusses these and other reports of EPO action beyond red blood cell production, including EPO response affecting metabolism and obesity in animal models. Observations of EPO activity in cell and animal model systems, including mice with tissue specific deletion of EPO receptor (EpoR), suggest the potential for EPO response in metabolism and disease. PMID:24918289

  1. Erythropoietin action in stress response, tissue maintenance and metabolism.

    PubMed

    Zhang, Yuanyuan; Wang, Li; Dey, Soumyadeep; Alnaeeli, Mawadda; Suresh, Sukanya; Rogers, Heather; Teng, Ruifeng; Noguchi, Constance Tom

    2014-01-01

    Erythropoietin (EPO) regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia for two and half decades and has facilitated studies of EPO action. Reports of animal and cell models of ischemic stress in vitro and injury suggest potential EPO benefit beyond red blood cell production including vascular endothelial response to increase nitric oxide production, which facilitates oxygen delivery to brain, heart and other non-hematopoietic tissues. This review discusses these and other reports of EPO action beyond red blood cell production, including EPO response affecting metabolism and obesity in animal models. Observations of EPO activity in cell and animal model systems, including mice with tissue specific deletion of EPO receptor (EpoR), suggest the potential for EPO response in metabolism and disease. PMID:24918289

  2. ERK2 Mediates Metabolic Stress Response to Regulate Cell Fate.

    PubMed

    Shin, Sejeong; Buel, Gwen R; Wolgamott, Laura; Plas, David R; Asara, John M; Blenis, John; Yoon, Sang-Oh

    2015-08-01

    Insufficient nutrients disrupt physiological homeostasis, resulting in diseases and even death. Considering the physiological and pathological consequences of this metabolic stress, the adaptive responses that cells utilize under this condition are of great interest. We show that under low-glucose conditions, cells initiate adaptation followed by apoptosis responses using PERK/Akt and MEK1/ERK2 signaling, respectively. For adaptation, cells engage the ER stress-induced unfolded protein response, which results in PERK/Akt activation and cell survival. Sustained and extreme energetic stress promotes a switch to isoform-specific MEK1/ERK2 signaling, induction of GCN2/eIF2α phosphorylation, and ATF4 expression, which overrides PERK/Akt-mediated adaptation and induces apoptosis through ATF4-dependent expression of pro-apoptotic factors including Bid and Trb3. ERK2 activation during metabolic stress contributes to changes in TCA cycle and amino acid metabolism, and cell death, which is suppressed by glutamate and α-ketoglutarate supplementation. Taken together, our results reveal promising targets to protect cells or tissues from metabolic stress. PMID:26190261

  3. Combined hormonal infusion simulates the metabolic response to injury.

    PubMed Central

    Bessey, P Q; Watters, J M; Aoki, T T; Wilmore, D W

    1984-01-01

    To investigate the role of hormones as mediators of the metabolic response to injury, nine normal male volunteers received a continuous 74-hour infusion of the three 'stress' hormones: cortisol, glucagon, and epinephrine. As a control, each subject received a saline infusion during another 4-day period. Diets were constant and matched on both occasions. Hormonal infusion achieved hormone concentrations similar to those seen following mild-moderate injury. With this alteration in the endocrine environment significant hypermetabolism, negative nitrogen and potassium balances, glucose intolerance, hyperinsulinemia, insulin resistance, sodium retention, and peripheral leukocytosis were observed. Additional studies with single hormone infusions indicated that these responses resulted from both additive and synergistic interactions of the hormones. Triple hormone infusion simulated many of the metabolic responses observed following mild-moderate injury and other catabolic illnesses. PMID:6431917

  4. Fetal and maternal metabolic responses to exercise during pregnancy.

    PubMed

    Mottola, Michelle F; Artal, Raul

    2016-03-01

    Pregnancy is characterized by physiological, endocrine and metabolic adaptations creating a pseudo-diabetogenic state of progressive insulin resistance. These adaptations occur to sustain continuous fetal requirements for nutrients and oxygen. Insulin resistance develops at the level of the skeletal muscle, and maternal exercise, especially activity involving large muscle groups improve glucose tolerance and insulin sensitivity. We discuss the maternal hormonal and metabolic changes associated with a normal pregnancy, the metabolic dysregulation that may occur leading to gestational diabetes mellitus (GDM), and the consequences to mother and fetus. We will then examine the acute and chronic (training) responses to exercise in the non-pregnant state and relate these alterations to maternal exercise in a low-risk pregnancy, how exercise can be used to regulate glucose tolerance in women at risk for or diagnosed with GDM. Lastly, we present key exercise guidelines to help maintain maternal glucose regulation and suggest future research directions. PMID:26803360

  5. Optimal Biofilm Featues: metabolic and geometric response to multiple oxidants

    NASA Astrophysics Data System (ADS)

    Kempes, C.; Okegbe, C.; Mears-Clarke, Z.; Follows, M. J.; Dietrich, L.

    2014-12-01

    An important challenge in understanding complex microbial mat communities is determining how groups of a single species balance metabolic requirements with the dynamics of resource supply. We have investigated this problem in the context of redox resources within a single-species bacterial biofilm. We developed a mathematical model of oxidant availability and metabolic response within biofilm features and we show that observed biofilm geometries maximize cellular reproduction and growth efficiency. Our model accurately predicts the measured distribution of two types of electron acceptors: oxygen, which is available from the environment, and phenazines, redox-active small molecules produced by the bacterium. Because our model is based on resource dynamics, we are also able to predict observed shifts in feature geometry based on changes in the availability of redox resources such as variations in the external availability of oxygen or the removal of phenazines. This analysis suggests various avenues for understanding microstructure and the evolution of spatial metabolism in microbial mats.

  6. Disparate metabolic response to fructose feeding between different mouse strains

    PubMed Central

    Montgomery, M. K.; Fiveash, C. E.; Braude, J. P.; Osborne, B.; Brown, S. H. J.; Mitchell, T. W.; Turner, N.

    2015-01-01

    Diets enriched in fructose (FR) increase lipogenesis in the liver, leading to hepatic lipid accumulation and the development of insulin resistance. Previously, we have shown that in contrast to other mouse strains, BALB/c mice are resistant to high fat diet-induced metabolic deterioration, potentially due to a lack of ectopic lipid accumulation in the liver. In this study we have compared the metabolic response of BALB/c and C57BL/6 (BL6) mice to a fructose-enriched diet. Both strains of mice increased adiposity in response to FR-feeding, while only BL6 mice displayed elevated hepatic triglyceride (TAG) accumulation and glucose intolerance. The lack of hepatic TAG accumulation in BALB/c mice appeared to be linked to an altered balance between lipogenic and lipolytic pathways, while the protection from fructose-induced glucose intolerance in this strain was likely related to low levels of ER stress, a slight elevation in insulin levels and an altered profile of diacylglycerol species in the liver. Collectively these findings highlight the multifactorial nature of metabolic defects that develop in response to changes in the intake of specific nutrients and the divergent response of different mouse strains to dietary challenges. PMID:26690387

  7. Metabolic Context Regulates Distinct Hypothalamic Transcriptional Responses to Antiaging Interventions

    PubMed Central

    Stranahan, Alexis M.; Martin, Bronwen; Chadwick, Wayne; Park, Sung-Soo; Wang, Liyun; Becker, Kevin G.; WoodIII, William H.; Zhang, Yongqing; Maudsley, Stuart

    2012-01-01

    The hypothalamus is an essential relay in the neural circuitry underlying energy metabolism that needs to continually adapt to changes in the energetic environment. The neuroendocrine control of food intake and energy expenditure is associated with, and likely dependent upon, hypothalamic plasticity. Severe disturbances in energy metabolism, such as those that occur in obesity, are therefore likely to be associated with disruption of hypothalamic transcriptomic plasticity. In this paper, we investigated the effects of two well-characterized antiaging interventions, caloric restriction and voluntary wheel running, in two distinct physiological paradigms, that is, diabetic (db/db) and nondiabetic wild-type (C57/Bl/6) animals to investigate the contextual sensitivity of hypothalamic transcriptomic responses. We found that, both quantitatively and qualitatively, caloric restriction and physical exercise were associated with distinct transcriptional signatures that differed significantly between diabetic and non-diabetic mice. This suggests that challenges to metabolic homeostasis regulate distinct hypothalamic gene sets in diabetic and non-diabetic animals. A greater understanding of how genetic background contributes to hypothalamic response mechanisms could pave the way for the development of more nuanced therapeutics for the treatment of metabolic disorders that occur in diverse physiological backgrounds. PMID:22934110

  8. Thermoregulatory and metabolic responses of Japanese quail to hypoxia

    PubMed Central

    Atchley, Dylan S.; Foster, Jennifer A.; Bavis, Ryan W.

    2008-01-01

    Common responses to hypoxia include decreased body temperature (Tb) and decreased energy metabolism. In this study, the effects of hypoxia and hypercapnia on Tb and metabolic oxygen consumption (V̇o2) were investigated in Japanese quail (Coturnix japonica). When exposed to hypoxia (15, 13, 11 and 9% O2), Tb decreased only at 11% and 9% O2 compared to normoxia; quail were better able to maintain Tb during acute hypoxia after a one-week acclimation to 10% O2. V̇o2 also decreased during hypoxia, but at 9% O2 this was partially offset by increased anaerobic metabolism. Tb and V̇o2 responses to 9% O2 were exaggerated at lower ambient temperature (Ta), reflecting a decreased lower critical temperature during hypoxia. Conversely, hypoxia had little effect on Tb or V̇o2 at higher Ta (36°C). We conclude that Japanese quail respond to hypoxia in much the same way as mammals, by reducing both Tb and V̇o2. No relationship was found between the magnitudes of decreases in Tb and V̇o2 during 9% O2, however. Since metabolism is the source of heat generation, this suggests that Japanese quail increase thermolysis to reduce Tb. During hypercapnia (3, 6 and 9% CO2), Tb was reduced only at 9% CO2 while V̇o2 was unchanged. PMID:18727957

  9. Metabolic PET Imaging in Cancer Detection and Therapy Response

    PubMed Central

    Zhu, Aizhi; Lee, Daniel; Shim, Hyunsuk

    2010-01-01

    Positron emission tomography (PET) is a noninvasive imaging technique that provides a functional or metabolic assessment of normal tissue or disease conditions. 18F-fluorodeoxyglucose PET imaging (FDG-PET) is widely used clinically for tumor imaging due to increased glucose metabolism in most types of tumors, and has been shown to improve the diagnosis and subsequent treatment of cancers. In this chapter, we review its use in cancer diagnosis, staging, restaging, and assessment of response to treatment. In addition, other metabolic PET imaging agents in research or clinical trial stages are discussed, including amino acid analogs based on increased protein synthesis, and choline, which is based on increased membrane lipid synthesis. Amino acid analogs and choline are more specific to tumor cells than FDG, so they play an important role in differentiating cancers from benign conditions and in the diagnosis of cancers with low FDG uptake or high background FDG uptake. For decades, researchers have shown that tumors have altered metabolic profiles and display elevated uptake of glucose, amino acids, and lipids, which can be used for cancer diagnosis and monitoring of the therapeutic response with excellent signal-to-noise ratios. PMID:21362516

  10. A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate

    PubMed Central

    Wone, B W M; Madsen, P; Donovan, E R; Labocha, M K; Sears, M W; Downs, C J; Sorensen, D A; Hayes, J P

    2015-01-01

    Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR, and BMR was slightly, but not significantly, higher (2.5%). Compared with controls, MMR was significantly higher (5.3%) in antagonistically selected lines, and BMR was slightly, but not significantly, lower (4.2%). Analysis of breeding values revealed no positive genetic trend for elevated BMR in high-MMR lines. A weak positive genetic correlation was detected between MMR and BMR. That weak positive genetic correlation supports the aerobic capacity model for the evolution of endothermy in the sense that it fails to falsify a key model assumption. Overall, the results suggest that at least in these mice there is significant capacity for independent evolution of metabolic traits. Whether that is true in the ancestral animals that evolved endothermy remains an important but unanswered question. PMID:25604947

  11. Vasodilator responses and endothelin-dependent vasoconstriction in metabolically healthy obesity and the metabolic syndrome.

    PubMed

    Schinzari, Francesca; Iantorno, Micaela; Campia, Umberto; Mores, Nadia; Rovella, Valentina; Tesauro, Manfredi; Di Daniele, Nicola; Cardillo, Carmine

    2015-11-01

    Patients with metabolically healthy obesity (MHO) do not present the cluster of metabolic abnormalities that define the metabolic syndrome (MetS). Whether MHO is associated with lower impairment of vasoreactivity than the MetS is unknown. For this purpose, forearm blood flow (FBF) responses were measured by strain-gauge plethysmography during the intra-arterial infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and/or the selective endothelin type A (ETA) receptor blocker BQ-123 in 119 obese individuals with MHO (n = 34) or with the MetS (n = 85) and in healthy lean controls (n = 56). ACh and SNP caused a significant vasodilation in both obese and lean participants (all P < 0.001). However, the response to both agents was significantly lower in the obese than in the control group (both P < 0.001). Among the obese participants, the reactivity to ACh was higher in MHO than in MetS patients, whereas the responsiveness to SNP was equally impaired in both groups (P = 0.45). Infusion of BQ-123 significantly increased FBF in obese patients (P < 0001), but not in the lean participants; hence, FBF following ETA receptor blockade was higher in both obese groups than in controls (both P < 0.001). FBF response to BQ-123 was significantly higher in patients with the MetS than in those with MHO (P = 0.007). In conclusion, patients with MHO have abnormal vascular reactivity, although their endothelial dysfunction is less pronounced than in patients with the MetS. These findings indicate that obesity is associated with vascular damage independent of those metabolic abnormalities underlying the MetS. PMID:26374766

  12. Biofilm Shows Spatially Stratified Metabolic Responses to Contaminant Exposure

    SciTech Connect

    Cao, Bin; Majors, Paul D.; Ahmed, B.; Renslow, Ryan S.; Sylvia, Crystal P.; Shi, Liang; Kjelleberg, Staffan; Fredrickson, Jim K.; Beyenal, Haluk

    2012-11-01

    The objective of this study was to elucidate the spatiotemporal responses of live S. oneidensis MR-1 biofilms to U(VI) (uranyl, UO22+) and Cr(VI) (chromate, CrO42-), important environmental contaminants at DOE contaminated sites. Toward this goal, we applied noninvasive nuclear magnetic resonance (NMR) imaging, diffusion, relaxation and spectroscopy techniques to monitor in situ spatiotemporal responses of S. oneidensis biofilms to U(VI) and Cr(VI) exposure in terms of changes in biofilm structures, diffusion properties, and cellular metabolism. Exposure to U(VI) or Cr(VI) did not appear to change the overall biomass distribution but caused changes in the physicochemical microenvironments inside the biofilm as indicated by diffusion measurements. Changes in the diffusion properties of the biofilms in response to U(VI) and Cr(VI) exposure imply a novel function of the extracellular polymeric substances (EPS) affecting the biotransformation and transport of contaminants in the environment. In the presence of U(VI) or Cr(VI), the anaerobic metabolism of lactate was inhibited significantly, although the biofilms were still capable of reducing U(VI) and Cr(VI). Local concentrations of Cr(III)aq in the biofilm suggested relatively high Cr(VI) reduction activities at the top of the biofilm, near the medium-biofilm interface. The depth-resolved metabolic activities of the biofilm suggested higher diversion effects of gluconeogenesis and C1 metabolism pathways at the bottom of the biofilm and in the presence of U(VI). This study provides a noninvasive means to investigate spatiotemporal responses of biofilms, including surface-associated microbial communities in engineering, natural and medical settings, to various environmental perturbations including exposure to environmental contaminants and antimicrobials.

  13. Thermal sensation and thermophysiological responses to metabolic step-changes

    NASA Astrophysics Data System (ADS)

    Goto, T.; Toftum, J.; de Dear, R.; Fanger, P. O.

    2006-05-01

    This study investigated the effect on thermal perception and thermophysiological variables of controlled metabolic excursions of various intensities and durations. Twenty-four subjects were alternately seated on a chair or exercised by walking on a treadmill at a temperature predicted to be neutral at sedentary activity. In a second experimental series, subjects alternated between rest and exercise as well as between exercise at different intensities at two temperature levels. Measurements comprised skin and oesophageal temperatures, heart rate and subjective responses. Thermal sensation started to rise or decline immediately (within 1 min) after a change of activity, which means that even moderate activity changes of short duration affect thermal perceptions of humans. After approximately 15 20 min under constant activity, subjective thermal responses approximated the steady-state response. The sensitivity of thermal sensation to changes in core temperature was higher for activity down-steps than for up-steps. A model was proposed that estimates transient thermal sensation after metabolic step-changes. Based on predictions by the model, weighting factors were suggested to estimate a representative average metabolic rate with varying activity levels, e.g. for the prediction of thermal sensation by steady-state comfort models. The activity during the most recent 5 min should be weighted 65%, during the prior 10 5 min 25% and during the prior 20 10 min 10%.

  14. Enhanced regional brain metabolic responses to benzodiazepines in cocaine abusers

    SciTech Connect

    Volkow, N.D.; Wang, G.J.; Fowler, J.S.

    1997-05-01

    While dopamine (DA) appears to be crucial for cocaine reinforcement, its involvement in cocaine addiction is much less clear. Using PET we have shown persistent reductions in striatal DA D2 receptors (which arc predominantly located on GABA cells) in cocaine abusers. This finding coupled to GABA`s role as an effector for DA led us to investigate if there were GABAergic abnormalities in cocaine abusers. In this study we measured regional brain metabolic responses to lorazepam, to indirectly assess GABA function (benzodiazepines facilitate GABAergic neurotransmission). Methods: The experimental subjects consisted of 12 active cocaine abusers and 32 age matched controls. Each subject underwent two PET FDG scans obtained within 1 week of each other. The first FDG scan was obtained after administration of placebo (3 cc of saline solution) given 40-50 minutes prior to FDG; and the second after administration of lorazepam (30 {mu}g/kg) given 40-50 minutes prior to FDG. The subjects were blind to the drugs received. Results: Lorazepam-induced sleepiness was significantly greater in abusers than in controls (p<0.001). Lorazepam-induced decreases in brain glucose metabolism were significantly larger in cocaine abusers than in controls. Whereas in controls whole brain metabolism decreased 13{+-}7 %, in cocaine abusers it decreased 21{+-}13 % (p < 0.05). Lorazepam-induced decrements in regional metabolism were significantly larger in striatum (p < 0.0 1), thalamus (p < 0.01) and cerebellum (p < 0.005) of cocaine abusers than of controls (ANOVA diagnosis by condition (placebo versus lorazepam) interaction effect). The only brain region for which the absolute metabolic changes-induced by lorazepam in cocaine abusers were equivalent to those in controls was the orbitofrontal cortex. These results document an accentuated sensitivity to benzodiazepines in cocaine abusers which is compatible with disrupted GABAergic function in these patients.

  15. Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions

    PubMed Central

    Prakash, Chandra; Zuniga, Baltazar; Song, Chung Seog; Jiang, Shoulei; Cropper, Jodie; Park, Sulgi; Chatterjee, Bandana

    2016-01-01

    Orally delivered small-molecule therapeutics are metabolized in the liver and intestine by phase I and phase II drug-metabolizing enzymes (DMEs), and transport proteins coordinate drug influx (phase 0) and drug/drug-metabolite efflux (phase III). Genes involved in drug metabolism and disposition are induced by xenobiotic-activated nuclear receptors (NRs), i.e. PXR (pregnane X receptor) and CAR (constitutive androstane receptor), and by the 1α, 25-dihydroxy vitamin D3-activated vitamin D receptor (VDR), due to transactivation of xenobiotic-response elements (XREs) present in phase 0-III genes. Additional NRs, like HNF4-α, FXR, LXR-α play important roles in drug metabolism in certain settings, such as in relation to cholesterol and bile acid metabolism. The phase I enzymes CYP3A4/A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, CYP1A2, CYP2C8, CYP2A6, CYP2J2, and CYP2E1 metabolize >90% of all prescription drugs, and phase II conjugation of hydrophilic functional groups (with/without phase I modification) facilitates drug clearance. The conjugation step is mediated by broad-specificity transferases like UGTs, SULTs, GSTs. This review delves into our current understanding of PXR/CAR/VDR-mediated regulation of DME and transporter expression, as well as effects of single nucleotide polymorphism (SNP) and epigenome (specified by promoter methylation, histone modification, microRNAs, long non coding RNAs) on the expression of PXR/CAR/VDR and phase 0-III mediators, and their impacts on variable drug response. Therapeutic agents that target epigenetic regulation and the molecular basis and consequences (overdosing, underdosing, or beneficial outcome) of drug-drug/drug-food/drug-herb interactions are also discussed. Precision medicine requires understanding of a drug’s impact on DME and transporter activity and their NR-regulated expression in order to achieve optimal drug efficacy without adverse drug reactions. In future drug screening, new tools such as humanized mouse models and

  16. Metabolomics reveals insect metabolic responses associated with fungal infection.

    PubMed

    Xu, Yong-Jiang; Luo, Feifei; Gao, Qiang; Shang, Yanfang; Wang, Chengshu

    2015-06-01

    The interactions between insects and pathogenic fungi are complex. We employed metabolomic techniques to profile insect metabolic dynamics upon infection by the pathogenic fungus Beauveria bassiana. Silkworm larvae were infected with fungal spores and microscopic observations demonstrated that the exhaustion of insect hemocytes was coupled with fungal propagation in the insect body cavity. Metabolomic analyses revealed that fungal infection could significantly alter insect energy and nutrient metabolisms as well as the immune defense responses, including the upregulation of carbohydrates, amino acids, fatty acids, and lipids, but the downregulation of eicosanoids and amines. The insect antifeedant effect of the fungal infection was evident with the reduced level of maclurin (a component of mulberry leaves) in infected insects but elevated accumulations in control insects. Insecticidal and cytotoxic mycotoxins like oosporein and beauveriolides were also detected in insects at the later stages of infection. Taken together, the metabolomics data suggest that insect immune responses are energy-cost reactions and the strategies of nutrient deprivation, inhibition of host immune responses, and toxin production would be jointly employed by the fungus to kill insects. The data obtained in this study will facilitate future functional studies of genes and pathways associated with insect-fungus interactions. PMID:25895944

  17. Metabolic response of Clostridium ljungdahlii to oxygen exposure.

    PubMed

    Whitham, Jason M; Tirado-Acevedo, Oscar; Chinn, Mari S; Pawlak, Joel J; Grunden, Amy M

    2015-12-01

    Clostridium ljungdahlii is an important synthesis gas-fermenting bacterium used in the biofuels industry, and a preliminary investigation showed that it has some tolerance to oxygen when cultured in rich mixotrophic medium. Batch cultures not only continue to grow and consume H2, CO, and fructose after 8% O2 exposure, but fermentation product analysis revealed an increase in ethanol concentration and decreased acetate concentration compared to non-oxygen-exposed cultures. In this study, the mechanisms for higher ethanol production and oxygen/reactive oxygen species (ROS) detoxification were identified using a combination of fermentation, transcriptome sequencing (RNA-seq) differential expression, and enzyme activity analyses. The results indicate that the higher ethanol and lower acetate concentrations were due to the carboxylic acid reductase activity of a more highly expressed predicted aldehyde oxidoreductase (CLJU_c24130) and that C. ljungdahlii's primary defense upon oxygen exposure is a predicted rubrerythrin (CLJU_c39340). The metabolic responses of higher ethanol production and oxygen/ROS detoxification were found to be linked by cofactor management and substrate and energy metabolism. This study contributes new insights into the physiology and metabolism of C. ljungdahlii and provides new genetic targets to generate C. ljungdahlii strains that produce more ethanol and are more tolerant to syngas contaminants. PMID:26431975

  18. Gut microbiota dictates the metabolic response of Drosophila to diet

    PubMed Central

    Wong, Adam C.-N.; Dobson, Adam J.; Douglas, Angela E.

    2014-01-01

    Animal nutrition is profoundly influenced by the gut microbiota, but knowledge of the scope and core mechanisms of the underlying animal–microbiota interactions is fragmentary. To investigate the nutritional traits shaped by the gut microbiota of Drosophila, we determined the microbiota-dependent response of multiple metabolic and performance indices to systematically varied diet composition. Diet-dependent differences between Drosophila bearing its unmanipulated microbiota (conventional flies) and experimentally deprived of its microbiota (axenic flies) revealed evidence for: microbial sparing of dietary B vitamins, especially riboflavin, on low-yeast diets; microbial promotion of protein nutrition, particularly in females; and microbiota-mediated suppression of lipid/carbohydrate storage, especially on high sugar diets. The microbiota also sets the relationship between energy storage and body mass, indicative of microbial modulation of the host signaling networks that coordinate metabolism with body size. This analysis identifies the multiple impacts of the microbiota on the metabolism of Drosophila, and demonstrates that the significance of these different interactions varies with diet composition and host sex. PMID:24577449

  19. Metabolic Response of Clostridium ljungdahlii to Oxygen Exposure

    PubMed Central

    Whitham, Jason M.; Tirado-Acevedo, Oscar; Chinn, Mari S.; Pawlak, Joel J.

    2015-01-01

    Clostridium ljungdahlii is an important synthesis gas-fermenting bacterium used in the biofuels industry, and a preliminary investigation showed that it has some tolerance to oxygen when cultured in rich mixotrophic medium. Batch cultures not only continue to grow and consume H2, CO, and fructose after 8% O2 exposure, but fermentation product analysis revealed an increase in ethanol concentration and decreased acetate concentration compared to non-oxygen-exposed cultures. In this study, the mechanisms for higher ethanol production and oxygen/reactive oxygen species (ROS) detoxification were identified using a combination of fermentation, transcriptome sequencing (RNA-seq) differential expression, and enzyme activity analyses. The results indicate that the higher ethanol and lower acetate concentrations were due to the carboxylic acid reductase activity of a more highly expressed predicted aldehyde oxidoreductase (CLJU_c24130) and that C. ljungdahlii's primary defense upon oxygen exposure is a predicted rubrerythrin (CLJU_c39340). The metabolic responses of higher ethanol production and oxygen/ROS detoxification were found to be linked by cofactor management and substrate and energy metabolism. This study contributes new insights into the physiology and metabolism of C. ljungdahlii and provides new genetic targets to generate C. ljungdahlii strains that produce more ethanol and are more tolerant to syngas contaminants. PMID:26431975

  20. The Metabolic Responses to Aerial Diffusion of Essential Oils

    PubMed Central

    Xie, Guoxiang; Zhao, Aihua; Pan, Xiaolan; Chen, Tianlu; Hu, Yixue; Liu, Yumin; Cheng, Yu; Chi, Yi; Yao, Lei; Jia, Wei

    2012-01-01

    Anxiety disorders are the most prevalent psychiatric disorders and affect a great number of people worldwide. Essential oils, take effects through inhalation or topical application, are believed to enhance physical, emotional, and spiritual well-being. Although clinical studies suggest that the use of essential oils may have therapeutic potential, evidence for the efficacy of essential oils in treating medical conditions remains poor, with a particular lack of studies employing rigorous analytical methods that capture its identifiable impact on human biology. Here, we report a comprehensive gas chromatography time-of-flight mass spectrometry (GC-TOFMS) based metabonomics study that reveals the aromas-induced metabolic changes and the anxiolytic effect of aromas in elevated plus maze (EPM) induced anxiety model rats. The significant alteration of metabolites in the EPM group was attenuated by aromas treatment, concurrent with the behavioral improvement with significantly increased open arms time and open arms entries. Brain tissue and urinary metabonomic analysis identified a number of altered metabolites in response to aromas intervention. These metabolic changes included the increased carbohydrates and lowered levels of neurotransmitters (tryptophan, serine, glycine, aspartate, tyrosine, cysteine, phenylalanine, hypotaurine, histidine, and asparagine), amino acids, and fatty acids in the brain. Elevated aspartate, carbohydrates (sucrose, maltose, fructose, and glucose), nucleosides and organic acids such as lactate and pyruvate were also observed in the urine. The EPM induced metabolic differences observed in urine or brain tissue was significantly reduced after 10 days of aroma inhalation, as noted with the loss of statistical significance on many of the metabolites in the aroma-EPM group. This study demonstrates, for the first time, that the metabonomics approach can capture the subtle metabolic changes resulting from exposure to essential oils and provide the

  1. Liposoluble vitamins in Crustacean feed: Metabolic and Histological responses.

    PubMed

    Fernández-Gimenez, Analía Verónica

    2016-05-01

    Vitamins are vital for normal growth and survival of living organisms and they are distributed in feedstuffs in small quantities. This review is focused on the liposoluble vitamins (A, D, E and K) in the diets and metabolic responses of the Argentine penaeoid shrimps Pleoticus muelleri and Artemesia longinaris, distributed along the South American coast line. Growth, survival and histological analyses serve as indicators of the nutritional value derived from vitamin deficiency. Liposoluble vitamins are also related to stress, antioxidant defense and immune response of shrimps. Effective diet for shrimp culture that provide not only macronutrients including protein and lipid but also micronutrients such as vitamins for optimal growth is an ever improving subject. This review may help formulating suitable feeds for shrimps. PMID:27319048

  2. Non-invasive in vivo imaging of early metabolic tumor response to therapies targeting choline metabolism.

    PubMed

    Mignion, Lionel; Danhier, Pierre; Magat, Julie; Porporato, Paolo E; Masquelier, Julien; Gregoire, Vincent; Muccioli, Giulio G; Sonveaux, Pierre; Gallez, Bernard; Jordan, Bénédicte F

    2016-04-15

    The cholinic phenotype, characterized by elevated phosphocholine and a high production of total-choline (tCho)-containing metabolites, is a metabolic hallmark of cancer. It can be exploited for targeted therapy. Non-invasive imaging biomarkers are required to evaluate an individual's response to targeted anticancer agents that usually do not rapidly cause tumor shrinkage. Because metabolic changes can manifest at earlier stages of therapy than changes in tumor size, the aim of the current study was to evaluate (1)H-MRS and diffusion-weighted MRI (DW-MRI) as markers of tumor response to the modulation of the choline pathway in mammary tumor xenografts. Inhibition of choline kinase activity was achieved with the direct pharmacological inhibitor H-89, indirect inhibitor sorafenib and down-regulation of choline-kinase α (ChKA) expression using specific short-hairpin RNA (shRNA). While all three strategies significantly decreased tCho tumor content in vivo, only sorafenib and anti-ChKA shRNA significantly repressed tumor growth. The increase of apparent-diffusion-coefficient of water (ADCw) measured by DW-MRI, was predictive of the induced necrosis and inhibition of the tumor growth in sorafenib treated mice, while the absence of change in ADC values in H89 treated mice predicted the absence of effect in terms of tumor necrosis and tumor growth. In conclusion, (1)H-choline spectroscopy can be useful as a pharmacodynamic biomarker for choline targeted agents, while DW-MRI can be used as an early marker of effective tumor response to choline targeted therapies. DW-MRI combined to choline spectroscopy may provide a useful non-invasive marker for the early clinical assessment of tumor response to therapies targeting choline signaling. PMID:26595604

  3. Modular metabolic control analysis of large responses in branched systems--application to aspartate metabolism.

    PubMed

    Ortega, Fernando; Acerenza, Luis

    2011-07-01

    Organisms subject to changing environmental conditions or experimental protocols show complex patterns of responses. The design principles behind these patterns are still poorly understood. Here, modular metabolic control analysis is developed to deal with large changes in branched pathways. Modular aggregation of the system dramatically reduces the number of explicit variables and modulation sites. Thus, the resulting number of control coefficients, which describe system responses, is small. Three properties determine the pattern for large changes in the variables: the values of infinitesimal control coefficients, the effect of large rate changes on the control coefficients and the range of rate changes preserving feasible intermediate concentrations. Importantly, this pattern gives information about the possibility of obtaining large variable changes by changing parameters inside the module, without the need to perform any parameter modulations. The framework is applied to a detailed model of Asp metabolism. The system is aggregated in one supply module, producing Thr from Asp (SM1), and two demand modules, incorporating Thr (DM2) and Ile (DM3) into protein. Their fluxes are: J(1), J(2), and J(3), respectively. The analysis shows similar high infinitesimal control coefficients of J(2) by the rates of SM1 and DM2 (C(v1)(J2) = 0.6 and C(v2)(J2) = 0.7, respectively). In addition, these coefficients present only moderate decreases when the rates of the corresponding modules are increased. However, the range of feasible rate changes in SM1 is narrow. Therefore, for large increases in J(2) to be obtained, DM2 must be modulated. Of the rich network of allosteric interactions present, only two groups of inhibitions generate the control pattern for large responses. PMID:21592306

  4. Stress-responsive hydroxycinnamate glycosyltransferase modulates phenylpropanoid metabolism in Populus

    PubMed Central

    Babst, Benjamin A.; Chen, Han-Yi; Wang, Hong-Qiang; Payyavula, Raja S.; Thomas, Tina P.; Harding, Scott A.; Tsai, Chung-Jui

    2014-01-01

    The diversity of phenylpropanoids offers a rich inventory of bioactive chemicals that can be exploited for plant improvement and human health. Recent evidence suggests that glycosylation may play a role in the partitioning of phenylpropanoid precursors for a variety of downstream uses. This work reports the functional characterization of a stress-responsive glycosyltransferase, GT1-316 in Populus. GT1-316 belongs to the UGT84A subfamily of plant glycosyltransferase family 1 and is designated UGT84A17. Recombinant protein analysis showed that UGT84A17 is a hydroxycinnamate glycosyltransferase and able to accept a range of unsubstituted and substituted cinnamic and benzoic acids as substrates in vitro. Overexpression of GT1-316 in transgenic Populus led to plant-wide increases of hydroxycinnamoyl-glucose esters, which were further elevated under N-limiting conditions. Levels of the two most abundant flavonoid glycosides, rutin and kaempferol-3-O-rutinoside, decreased, while levels of other less abundant flavonoid and phenylpropanoid conjugates increased in leaves of the GT1-316-overexpressing plants. Transcript levels of representative phenylpropanoid pathway genes were unchanged in transgenic plants, supporting a glycosylation-mediated redirection of phenylpropanoid carbon flow as opposed to enhanced phenylpropanoid pathway flux. The metabolic response of N-replete transgenic plants overlapped with that of N-stressed wild types, as the majority of phenylpropanoid derivatives significantly affected by GT1-316 overexpression were also significantly changed by N stress in the wild types. These results suggest that UGT84A17 plays an important role in phenylpropanoid metabolism by modulating biosynthesis of hydroxycinnamoyl-glucose esters and their derivatives in response to developmental and environmental cues. PMID:24803501

  5. Cell Wall Metabolism in Response to Abiotic Stress

    PubMed Central

    Gall, Hyacinthe Le; Philippe, Florian; Domon, Jean-Marc; Gillet, Françoise; Pelloux, Jérôme; Rayon, Catherine

    2015-01-01

    This review focuses on the responses of the plant cell wall to several abiotic stresses including drought, flooding, heat, cold, salt, heavy metals, light, and air pollutants. The effects of stress on cell wall metabolism are discussed at the physiological (morphogenic), transcriptomic, proteomic and biochemical levels. The analysis of a large set of data shows that the plant response is highly complex. The overall effects of most abiotic stress are often dependent on the plant species, the genotype, the age of the plant, the timing of the stress application, and the intensity of this stress. This shows the difficulty of identifying a common pattern of stress response in cell wall architecture that could enable adaptation and/or resistance to abiotic stress. However, in most cases, two main mechanisms can be highlighted: (i) an increased level in xyloglucan endotransglucosylase/hydrolase (XTH) and expansin proteins, associated with an increase in the degree of rhamnogalacturonan I branching that maintains cell wall plasticity and (ii) an increased cell wall thickening by reinforcement of the secondary wall with hemicellulose and lignin deposition. Taken together, these results show the need to undertake large-scale analyses, using multidisciplinary approaches, to unravel the consequences of stress on the cell wall. This will help identify the key components that could be targeted to improve biomass production under stress conditions. PMID:27135320

  6. Cell Wall Metabolism in Response to Abiotic Stress.

    PubMed

    Le Gall, Hyacinthe; Philippe, Florian; Domon, Jean-Marc; Gillet, Françoise; Pelloux, Jérôme; Rayon, Catherine

    2015-01-01

    This review focuses on the responses of the plant cell wall to several abiotic stresses including drought, flooding, heat, cold, salt, heavy metals, light, and air pollutants. The effects of stress on cell wall metabolism are discussed at the physiological (morphogenic), transcriptomic, proteomic and biochemical levels. The analysis of a large set of data shows that the plant response is highly complex. The overall effects of most abiotic stress are often dependent on the plant species, the genotype, the age of the plant, the timing of the stress application, and the intensity of this stress. This shows the difficulty of identifying a common pattern of stress response in cell wall architecture that could enable adaptation and/or resistance to abiotic stress. However, in most cases, two main mechanisms can be highlighted: (i) an increased level in xyloglucan endotransglucosylase/hydrolase (XTH) and expansin proteins, associated with an increase in the degree of rhamnogalacturonan I branching that maintains cell wall plasticity and (ii) an increased cell wall thickening by reinforcement of the secondary wall with hemicellulose and lignin deposition. Taken together, these results show the need to undertake large-scale analyses, using multidisciplinary approaches, to unravel the consequences of stress on the cell wall. This will help identify the key components that could be targeted to improve biomass production under stress conditions. PMID:27135320

  7. Microbial nitrogen metabolism: response to warming and resource supply

    NASA Astrophysics Data System (ADS)

    Buckeridge, K. M.; Min, K.; Lehmeier, C.; Ballantyne, F.; Billings, S. A.

    2013-12-01

    Ecosystem nitrogen (N) dynamics are dependent on microbial metabolic responses to a changing climate. Most studies that investigate soil microbial N dynamics in response to temperature employ measurements reflective of many interacting and confounding phenomena, as altering soil temperature can simultaneously alter moisture regime, substrate availability, and competitive dynamics between microbial populations. As a result, it is difficult to discern how temperature alone can alter patterns of microbial N metabolism using whole soils. Without that knowledge, it is impossible to parse temperature effects on soil N fluxes from other drivers. We address this issue by exploring the sensitivity of microbial partitioning of N between assimilation (growing biomass) and dissimilation (releasing N to the environment) in response to changes in temperature and quality (C:N ratio) of substrate, using a chemostat approach in which a microbial population is maintained at steady state. We perform our experiments using a Gram-negative bacterium (Pseudomonas fluorescens), ubiquitous in soils and dependent on organic compounds to satisfy its resource demand. Individual chemostat runs, all conducted at similar microbial growth rates, generate data describing microbial biomass N, solution N pools and microbial biomass and solution d15N. With these data we can calculate d15N enrichment (d15N microbial biomass - d15N nutrient solution) a proxy for microbial N partitioning. From a recently published model of microbial biomass d15N drivers, fractionation of N occurs with both uptake and excretion of NH3+ so that microbes with a net dissimilation become 15N enriched relative to their source. Because a related study has demonstrated increased microbial C demand with temperature, we predict that in a warming environment microorganisms will become relatively C limited. Accordingly, we hypothesize that warming will enhance microbial dissimilation, and that this N release will be exacerbated as

  8. Metabolic phenotyping reveals a lipid mediator response to ionizing radiation.

    PubMed

    Laiakis, Evagelia C; Strassburg, Katrin; Bogumil, Ralf; Lai, Steven; Vreeken, Rob J; Hankemeier, Thomas; Langridge, James; Plumb, Robert S; Fornace, Albert J; Astarita, Giuseppe

    2014-09-01

    Exposure to ionizing radiation has dramatically increased in modern society, raising serious health concerns. The molecular response to ionizing radiation, however, is still not completely understood. Here, we screened mouse serum for metabolic alterations following an acute exposure to γ radiation using a multiplatform mass-spectrometry-based strategy. A global, molecular profiling revealed that mouse serum undergoes a series of significant molecular alterations following radiation exposure. We identified and quantified bioactive metabolites belonging to key biochemical pathways and low-abundance, oxygenated, polyunsaturated fatty acids (PUFAs) in the two groups of animals. Exposure to γ radiation induced a significant increase in the serum levels of ether phosphatidylcholines (PCs) while decreasing the levels of diacyl PCs carrying PUFAs. In exposed mice, levels of pro-inflammatory, oxygenated metabolites of arachidonic acid increased, whereas levels of anti-inflammatory metabolites of omega-3 PUFAs decreased. Our results indicate a specific serum lipidomic biosignature that could be utilized as an indicator of radiation exposure and as novel target for therapeutic intervention. Monitoring such a molecular response to radiation exposure might have implications not only for radiation pathology but also for countermeasures and personalized medicine. PMID:25126707

  9. Cattle temperament influences metabolism: metabolic response to glucose tolerance and insulin sensitivity tests in beef steers.

    PubMed

    Burdick Sanchez, N C; Carroll, J A; Broadway, P R; Hughes, H D; Roberts, S L; Richeson, J T; Schmidt, T B; Vann, R C

    2016-07-01

    Cattle temperament, defined as the reactivity of cattle to humans or novel environments, can greatly influence several physiological systems in the body, including immunity, stress, and most recently discovered, metabolism. Greater circulating concentrations of nonesterified fatty acids (NEFAs) found in temperamental cattle suggest that temperamental cattle are metabolically different than calm cattle. Further, elevated NEFA concentrations have been reported to influence insulin sensitivity. Therefore, the objective of this study was to determine whether cattle temperament would influence the metabolic response to a glucose tolerance test (GTT) and insulin sensitivity test (IST). Angus-cross steers (16 calm and 15 temperamental; 216 ± 6 kg BW) were selected based on temperament score measured at weaning. On day 1, steers were moved into indoor stanchions to allow measurement of individual ad libitum feed intake. On day 6, steers were fitted with indwelling rectal temperature probes and jugular catheters. At 9 AM on day 7, steers received the GTT (0.5-mL/kg BW of a 50% dextrose solution), and at 2 PM on day 7, steers received the IST (2.5 IU bovine insulin/kg BW). Blood samples were collected and serum isolated at -60, -45, -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, and 150 min relative to each challenge. Serum was stored at -80°C until analyzed for cortisol, glucose, NEFA, and blood urea nitrogen concentrations. All variables changed over time (P < 0.01). For the duration of the study, temperamental steers maintained greater (P < 0.01) serum NEFA and less (P ≤ 0.01) serum blood urea nitrogen and insulin sensitivity (calculated using Revised Quantitative Insulin Sensitivity Check Index) compared with calm steers. During the GTT, temperamental steers had greater (P < 0.01) serum glucose, yet decreased (P = 0.03) serum insulin and (P < 0.01) serum insulin: serum glucose compared to calm cattle. During the IST, temperamental steers had greater (P < 0.01) serum

  10. Acute metabolic and physiologic response of goats to narcosis

    NASA Technical Reports Server (NTRS)

    Schatte, C. L.; Bennett, P. B.

    1973-01-01

    Assessment of the metabolic consequences of exposure to elevated partial pressures of nitrogen and helium under normobaric and hyperbaric conditions in goats. The results include the finding that hyperbaric nitrogen causes and increase in metabolic rate and a general decrease in blood constituent levels which is interpreted as reflecting a shift toward fatty acid metabolism at the expense of carbohydrates. A similar but more pronounced pattern was observed with hyperbaric helium.

  11. Metabolic and Cardiovascular Response to Shallow Water Exercise in Young and Older Women.

    ERIC Educational Resources Information Center

    Campbell, Jennifer A.; D'Acquisto, Leo J.; D'Acquisto, Debra M.; Cline, Michael G.

    2003-01-01

    Compared the metabolic and cardiovascular responses of young and older women while performing shallow water exercise (SWE). Overall, SWE elicited metabolic and cardiovascular responses that met American College of Sports Medicine's guidelines for establishing health benefits. Older females self-selected a greater relative exercise intensity during…

  12. Human Skeletal Muscle Protein Metabolism Responses to Amino Acid Nutrition.

    PubMed

    Mitchell, W Kyle; Wilkinson, Daniel J; Phillips, Bethan E; Lund, Jonathan N; Smith, Kenneth; Atherton, Philip J

    2016-07-01

    Healthy individuals maintain remarkably constant skeletal muscle mass across much of adult life, suggesting the existence of robust homeostatic mechanisms. Muscle exists in dynamic equilibrium whereby the influx of amino acids (AAs) and the resulting increases in muscle protein synthesis (MPS) associated with the intake of dietary proteins cancel out the efflux of AAs from muscle protein breakdown that occurs between meals. Dysregulated proteostasis is evident with aging, especially beyond the sixth decade of life. Women and men aged 75 y lose muscle mass at a rate of ∼0.7% and 1%/y, respectively (sarcopenia), and lose strength 2- to 5-fold faster (dynapenia) as muscle "quality" decreases. Factors contributing to the disruption of an otherwise robust proteostatic system represent targets for potential therapies that promote healthy aging. Understanding age-related impairments in anabolic responses to AAs and identifying strategies to mitigate these factors constitute major areas of interest. Numerous studies have aimed to identify 1) the influence of distinct protein sources on absorption kinetics and muscle anabolism, 2) the latency and time course of MPS responses to protein/AAs, 3) the impacts of protein/AA intake on muscle microvascular recruitment, and 4) the role of certain AAs (e.g., leucine) as signaling molecules, which are able to trigger anabolic pathways in tissues. This review aims to discuss these 4 issues listed, to provide historical and modern perspectives of AAs as modulators of human skeletal muscle protein metabolism, to describe how advances in stable isotope/mass spectrometric approaches and instrumentation have underpinned these advances, and to highlight relevant differences between young adults and older individuals. Whenever possible, observations are based on human studies, with additional consideration of relevant nonhuman studies. PMID:27422520

  13. Metabolic response to dietary fibre composition in horses.

    PubMed

    Brøkner, C; Austbø, D; Næsset, J A; Blache, D; Bach Knudsen, K E; Tauson, A H

    2016-07-01

    The hypothesis for this study was that a higher dietary proportion of soluble fibre would result in stable and constant plasma metabolite and regulatory hormone concentrations. The study was a 4×4 Latin Square design with a sequence of 17 days adaptation to the ration followed by 8 sampling days. The feed rations consisted of only timothy hay (H), hay plus molassed sugar beet pulp combined with either whole oats (OB) or barley (BB) and hay plus a loose chaff-based concentrate (M). Four horses were fitted with permanent caecal cannulas and liquid caecal content was withdrawn manually and blood was drawn from the jugular vein at 0, 3 and 9 h postprandial. The horses were exercised daily at medium level for about 1 h. Samples were analysed for short-chain fatty acids (SCFA) and metabolic traits. Caecal SCFA and propionic acid concentrations increased with increased dietary starch and soluble fibre. The diet highest in soluble fibre (M) resulted in the highest plasma glucose and insulin concentrations in the morning, which then remained stable and constant throughout the day. A strong interaction (P<0.01) between time and diet was measured for plasma urea, glucose, insulin and leptin. The greatest variations in plasma glycaemic and insulinaemic responses were associated with the cereal grain diets (OB and BB). There were indications of a negative energy balance, which was reflected in a significantly higher plasma β-hydroxybutyrate concentration and a numerically higher non-esterified fatty acid concentration. In conclusion, this study found that inclusion of soluble fibre resulted in increased total caecal SCFA and propionic acid concentrations. This consequently resulted in stable and constant plasma glycaemic and insulinaemic responses. Diets with a high content of soluble fibre provided enough energy for horses at medium work level. PMID:26755337

  14. Acute responses of muscle protein metabolism to reduced blood flow reflect metabolic priorities for homeostasis.

    PubMed

    Zhang, Xiao-Jun; Irtun, Oivind; Chinkes, David L; Wolfe, Robert R

    2008-03-01

    The present experiment was designed to measure the synthetic and breakdown rates of muscle protein in the hindlimb of rabbits with or without clamping the femoral artery. l-[ring-(13)C(6)]phenylalanine was infused as a tracer for measurement of muscle protein kinetics by means of an arteriovenous model, tracer incorporation, and tracee release methods. The ultrasonic flowmeter, dye dilution, and microsphere methods were used to determine the flow rates in the femoral artery, in the leg, and in muscle capillary, respectively. The femoral artery flow accounted for 65% of leg flow. A 50% reduction in the femoral artery flow reduced leg flow by 28% and nutritive flow by 26%, which did not change protein synthetic or breakdown rate in leg muscle. Full clamp of the femoral artery reduced leg flow by 42% and nutritive flow by 59%, which decreased (P < 0.05) both the fractional synthetic rate from 0.19 +/- 0.05 to 0.14 +/- 0.03%/day and fractional breakdown rate from 0.28 +/- 0.07 to 0.23 +/- 0.09%/day of muscle protein. Neither the partial nor full clamp reduced (P = 0.27-0.39) the intracellular phenylalanine concentration or net protein balance in leg muscle. We conclude that the flow threshold to cause a fall of protein turnover rate in leg muscle was a reduction of 30-40% of the leg flow. The acute responses of muscle protein kinetics to the reductions in blood flow reflected the metabolic priorities to maintain muscle homeostasis. These findings cannot be extrapolated to more chronic conditions without experimental validation. PMID:18089763

  15. Relationships between hemodynamic, hemorheological and metabolic responses during exercise.

    PubMed

    Connes, Philippe; Tripette, Julien; Mukisi-Mukaza, Martin; Baskurt, Oguz K; Toth, Kalman; Meiselman, Herbert J; Hue, Olivier; Antoine-Jonville, Sophie

    2009-01-01

    Aerobic performance is dependent on both cardio-respiratory and peripheral factors with hemodynamic parameters playing a major role. However, whether blood rheology might affect aerobic performance through an effect on hemodynamic factors is not known. The aim of the present study was to assess the relationships between hemodynamic, hemorheological and metabolic parameters in response to a sub-maximal cycling exercise protocol consisting of three successive levels of nine min duration (50, 100 and 150 W). Ten young sportsmen participated in the present study. Mean arterial pressure (MAP) was measured manually, with thoracic impedance used to monitor cardiac output (Qc): systemic vascular resistance (SVR) was then calculated. Whole blood viscosity (etab) was measured and used to calculate systemic vascular hindrance. Hematocrit (Hct) was determined by micro-centrifugation and red blood cell (RBC) deformability (EI) was determined by ecktacytometry. A breath-by-breath gas analyzer was used to measure oxygen uptake (VO2); the Fick equation was used to calculate arterio-venous oxygen difference [(a-v)O(2)] from VO(2) and Qc. All measurements were performed at rest, during exercise and during recovery. Compared to baseline, Qc, MAP, Hct, EI, VO(2), and (a-v)O(2) increased during exercise. etab increased above baseline only at 150 W and remained elevated during recovery; the increase in etab during the last level of exercise was associated with a decrease of SVR and systemic vascular hindrance. There was a significant negative correlation between EI and SVR (r=-0.35, p<0.01) and a significant positive relationship between EI and (a-v)O(2) (r=0.35, p<0.01) and between EI and VO(2) (r=0.37, p<0.01) across all exercise workloads, thus suggesting a potential role for RBC deformability as a factor affecting aerobic performance via oxygen delivery to tissues. These data lend support to the concept that hemorheological parameters may contribute to hemodynamic and cardio

  16. Cattle temperament influences metabolism: 1. Metabolic response to a glucose tolerance test in beef steers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Temperamental cattle are behaviorally, physiologically, and immunologically different in comparison to calm cattle. Recently, the metabolic differences between temperamental and calm cattle have begun to be explored; temperamental cattle maintain greater circulating concentrations of non-esterified ...

  17. Detecting Functional Groups of Arabidopsis Mutants by Metabolic Profiling and Evaluation of Pleiotropic Responses

    PubMed Central

    Hofmann, Jörg; Börnke, Frederik; Schmiedl, Alfred; Kleine, Tatjana; Sonnewald, Uwe

    2011-01-01

    Metabolic profiles and fingerprints of Arabidopsis thaliana plants with various defects in plastidic sugar metabolism or photosynthesis were analyzed to elucidate if the genetic mutations can be traced by comparing their metabolic status. Using a platform of chromatographic and spectrometric tools data from untargeted full MS scans as well as from selected metabolites including major carbohydrates, phosphorylated intermediates, carboxylates, free amino acids, major antioxidants, and plastidic pigments were evaluated. Our key observations are that by multivariate statistical analysis each mutant can be separated by a unique metabolic signature. Closely related mutants come close. Thus metabolic profiles of sugar mutants are different but more similar than those of photosynthesis mutants. All mutants show pleiotropic responses mirrored in their metabolic status. These pleiotropic responses are typical and can be used for separating and grouping of the mutants. Our findings show that metabolite fingerprints can be taken to classify mutants and hence may be used to sort genes into functional groups. PMID:22639613

  18. Low-dose radiation exposure induces a HIF-1-mediated adaptive and protective metabolic response

    PubMed Central

    Lall, R; Ganapathy, S; Yang, M; Xiao, S; Xu, T; Su, H; Shadfan, M; Asara, J M; Ha, C S; Ben-Sahra, I; Manning, B D; Little, J B; Yuan, Z-M

    2014-01-01

    Because of insufficient understanding of the molecular effects of low levels of radiation exposure, there is a great uncertainty regarding its health risks. We report here that treatment of normal human cells with low-dose radiation induces a metabolic shift from oxidative phosphorylation to aerobic glycolysis resulting in increased radiation resistance. This metabolic change is highlighted by upregulation of genes encoding glucose transporters and enzymes of glycolysis and the oxidative pentose phosphate pathway, concomitant with downregulation of mitochondrial genes, with corresponding changes in metabolic flux through these pathways. Mechanistically, the metabolic reprogramming depends on HIF1α, which is induced specifically by low-dose irradiation linking the metabolic pathway with cellular radiation dose response. Increased glucose flux and radiation resistance from low-dose irradiation are also observed systemically in mice. This highly sensitive metabolic response to low-dose radiation has important implications in understanding and assessing the health risks of radiation exposure. PMID:24583639

  19. A computational model of skeletal muscle metabolism linking cellular adaptations induced by altered loading states to metabolic responses during exercise

    PubMed Central

    Dash, Ranjan K; DiBella, John A; Cabrera, Marco E

    2007-01-01

    Background The alterations in skeletal muscle structure and function after prolonged periods of unloading are initiated by the chronic lack of mechanical stimulus of sufficient intensity, which is the result of a series of biochemical and metabolic interactions spanning from cellular to tissue/organ level. Reduced activation of skeletal muscle alters the gene expression of myosin heavy chain isoforms to meet the functional demands of reduced mechanical load, which results in muscle atrophy and reduced capacity to process fatty acids. In contrast, chronic loading results in the opposite pattern of adaptations. Methods To quantify interactions among cellular and skeletal muscle metabolic adaptations, and to predict metabolic responses to exercise after periods of altered loading states, we develop a computational model of skeletal muscle metabolism. The governing model equations – with parameters characterizing chronic loading/unloading states- were solved numerically to simulate metabolic responses to moderate intensity exercise (WR ≤ 40% VO2 max). Results Model simulations showed that carbohydrate oxidation was 8.5% greater in chronically unloaded muscle compared with the loaded muscle (0.69 vs. 0.63 mmol/min), while fat oxidation was 7% higher in chronically loaded muscle (0.14 vs. 0.13 mmol/min), during exercise. Muscle oxygen uptake (VO2) and blood flow (Q) response times were 29% and 44% shorter in chronically loaded muscle (0.4 vs. 0.56 min for VO2 and 0.25 vs. 0.45 min for Q). Conclusion The present model can be applied to test complex hypotheses during exercise involving the integration and control of metabolic processes at various organizational levels (cellular to tissue) in individuals who have undergone periods of chronic loading or unloading. PMID:17448235

  20. Metabolic profiling reveals altered sugar and secondary metabolism in response to UGPase overexpression in Populus

    DOE PAGESBeta

    Payyavula, Raja S.; Tschaplinski, Timothy J.; Jawdy, Sara; Sykes, Robert; Tuskan, Gerald A.; Kalluri, Udaya C.

    2014-10-07

    Background: UDP-glucose pyrophopharylase (UGPase) is a sugar metabolizing enzyme (E.C. 2.7.7.9) that catalyzes a reversible reaction of UDP-glucose and pyrophosphate from glucose-1-phosphate and uridine triphosphate glucose. UDP-glucose is a key intermediate sugar that is channeled to multiple metabolic pathways. The functional role of UGPase in woody plants such as Populus is poorly understood. Results: We characterized the functional role of UGPase in Populus deltoides by overexpressing a native gene. Overexpression of the native gene resulted in increased leaf area and leaf-to-shoot biomass ratio but decreased shoot and root growth. Metabolomic analyses showed that manipulation of UGPase results in perturbations inmore » primary as well as secondary metabolism resulting in reduced sugar and starch levels and increased phenolics such as caffeoyl- and feruloyl conjugates. While cellulose and lignin levels in the cell walls were not significantly altered, the syringyl-to-guaiacyl ratio was significantly reduced. Conclusions: These results demonstrate that UGPase plays a key role in the tightly coupled primary and secondary metabolic pathways and perturbation in its function results in pronounced effects on growth and metabolism outside of cell wall biosynthesis of Populus.« less

  1. Metabolic profiling reveals altered sugar and secondary metabolism in response to UGPase overexpression in Populus

    SciTech Connect

    Payyavula, Raja S.; Tschaplinski, Timothy J.; Jawdy, Sara; Sykes, Robert; Tuskan, Gerald A.; Kalluri, Udaya C.

    2014-10-07

    Background: UDP-glucose pyrophopharylase (UGPase) is a sugar metabolizing enzyme (E.C. 2.7.7.9) that catalyzes a reversible reaction of UDP-glucose and pyrophosphate from glucose-1-phosphate and uridine triphosphate glucose. UDP-glucose is a key intermediate sugar that is channeled to multiple metabolic pathways. The functional role of UGPase in woody plants such as Populus is poorly understood. Results: We characterized the functional role of UGPase in Populus deltoides by overexpressing a native gene. Overexpression of the native gene resulted in increased leaf area and leaf-to-shoot biomass ratio but decreased shoot and root growth. Metabolomic analyses showed that manipulation of UGPase results in perturbations in primary as well as secondary metabolism resulting in reduced sugar and starch levels and increased phenolics such as caffeoyl- and feruloyl conjugates. While cellulose and lignin levels in the cell walls were not significantly altered, the syringyl-to-guaiacyl ratio was significantly reduced. Conclusions: These results demonstrate that UGPase plays a key role in the tightly coupled primary and secondary metabolic pathways and perturbation in its function results in pronounced effects on growth and metabolism outside of cell wall biosynthesis of Populus.

  2. Socially responsive effects of brain oxidative metabolism on aggression

    PubMed Central

    Li-Byarlay, Hongmei; Rittschof, Clare C.; Massey, Jonathan H.; Pittendrigh, Barry R.; Robinson, Gene E.

    2014-01-01

    Despite ongoing high energetic demands, brains do not always use glucose and oxygen in a ratio that produces maximal ATP through oxidative phosphorylation. In some cases glucose consumption exceeds oxygen use despite adequate oxygen availability, a phenomenon known as aerobic glycolysis. Although metabolic plasticity seems essential for normal cognition, studying its functional significance has been challenging because few experimental systems link brain metabolic patterns to distinct behavioral states. Our recent transcriptomic analysis established a correlation between aggression and decreased whole-brain oxidative phosphorylation activity in the honey bee (Apis mellifera), suggesting that brain metabolic plasticity may modulate this naturally occurring behavior. Here we demonstrate that the relationship between brain metabolism and aggression is causal, conserved over evolutionary time, cell type-specific, and modulated by the social environment. Pharmacologically treating honey bees to inhibit complexes I or V in the oxidative phosphorylation pathway resulted in increased aggression. In addition, transgenic RNAi lines and genetic manipulation to knock down gene expression in complex I in fruit fly (Drosophila melanogaster) neurons resulted in increased aggression, but knockdown in glia had no effect. Finally, honey bee colony-level social manipulations that decrease individual aggression attenuated the effects of oxidative phosphorylation inhibition on aggression, demonstrating a specific effect of the social environment on brain function. Because decreased neuronal oxidative phosphorylation is usually associated with brain disease, these findings provide a powerful context for understanding brain metabolic plasticity and naturally occurring behavioral plasticity. PMID:25092297

  3. Metabolic product response profiles of Cherax quadricarinatus towards white spot syndrome virus infection.

    PubMed

    Fan, Weiwei; Ye, Yangfang; Chen, Zhen; Shao, Yina; Xie, Xiaolu; Zhang, Weiwei; Liu, Hai-Peng; Li, Chenghua

    2016-08-01

    White spot syndrome virus (WSSV) is one of the most devastating viral pathogens in both shrimp and crayfish farms, which often causes disease outbreak and leads to massive moralities with significant economic losses of aquaculture. However, limited research has been carried out on the intrinsic mechanisms toward WSSV challenge at the metabolic level. To gain comprehensive insight into metabolic responses induced by WSSV, we applied an NMR approach to investigate metabolic changes of crayfish gill and hepatopancreas infected by WSSV for 1, 6 and 12 h. In gill, an enhanced energy metabolism was observed in WSSV-challenged crayfish samples at 1 h, as marked by increased glucose, alanine, methionine, glutamate and uracil. Afterwards, energy metabolism, lipid metabolism as well as osmoregulation were markedly increased at 6 hpi, as shown by elevated glucose, alanine, methionine, fumarate, tyrosine, tryptophan, histidine, phosphorylcholine, betaine and uracil, whereas no obvious metabolites change was detected at 12 hpi. As for hepatopancreas, disturbed lipid metabolism and induced osmotic regulation was found at 6 hpi based on the metabolic biomarkers such as branched chain amino acids, threonine, alanine, methionine, glutamate, glutamine, tyrosine, phenylalanine, lactate and lipid. However, no obvious metabolic change was shown in hepatopancreas at both 1 hpi and 12 hpi. Taken together, our present results provided essential metabolic information about host-pathogen interactions in crayfish, which shed new light on our understanding of WSSV infection at metabolic level. PMID:27068762

  4. Whole-body CO2 production as an index of the metabolic response to sepsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Whole-body carbon dioxide (CO2) production (RaCO2) is an index of substrate oxidation and energy expenditure; therefore, it may provide information about the metabolic response to sepsis. Using stable isotope techniques, we determined RaCO2 and its relationship to protein and glucose metabolism in m...

  5. Bioenergetic phenotypes and metabolic stress responses in cells derived from ecologically and commercially important fish species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Various stressors negatively affect wild and cultured fish and can result in metabolic disturbances that first manifest at the level of the cell. In the present study, we sought to further our understanding of cellular metabolism in fish by examining the stress responses of cells derived from three...

  6. 13C metabolic flux analysis shows that resistin impairs the metabolic response to insulin in L6E9 myotubes

    PubMed Central

    2014-01-01

    Background It has been suggested that the adipokine resistin links obesity and insulin resistance, although how resistin acts on muscle metabolism is controversial. We aimed to quantitatively analyse the effects of resistin on the glucose metabolic flux profile and on insulin response in L6E9 myotubes at the metabolic level using a tracer-based metabolomic approach and our in-house developed software, Isodyn. Results Resistin significantly increased glucose uptake and glycolysis, altering pyruvate utilisation by the cell. In the presence of resistin, insulin only slightly increased glucose uptake and glycolysis, and did not alter the flux profile around pyruvate induced by resistin. Resistin prevented the increase in gene expression in pyruvate dehydrogenase-E1 and the sharp decrease in gene expression in cytosolic phosphoenolpyruvate carboxykinase-1 induced by insulin. Conclusions These data suggest that resistin impairs the metabolic activation of insulin. This impairment cannot be explained by the activity of a single enzyme, but instead due to reorganisation of the whole metabolic flux distribution. PMID:25217974

  7. Size matters: plasticity in metabolic scaling shows body-size may modulate responses to climate change.

    PubMed

    Carey, Nicholas; Sigwart, Julia D

    2014-08-01

    Variability in metabolic scaling in animals, the relationship between metabolic rate ( R: ) and body mass ( M: ), has been a source of debate and controversy for decades. R: is proportional to MB: , the precise value of B: much debated, but historically considered equal in all organisms. Recent metabolic theory, however, predicts B: to vary among species with ecology and metabolic level, and may also vary within species under different abiotic conditions. Under climate change, most species will experience increased temperatures, and marine organisms will experience the additional stressor of decreased seawater pH ('ocean acidification'). Responses to these environmental changes are modulated by myriad species-specific factors. Body-size is a fundamental biological parameter, but its modulating role is relatively unexplored. Here, we show that changes to metabolic scaling reveal asymmetric responses to stressors across body-size ranges; B: is systematically decreased under increasing temperature in three grazing molluscs, indicating smaller individuals were more responsive to warming. Larger individuals were, however, more responsive to reduced seawater pH in low temperatures. These alterations to the allometry of metabolism highlight abiotic control of metabolic scaling, and indicate that responses to climate warming and ocean acidification may be modulated by body-size. PMID:25122741

  8. Phosphorus stress in common bean: root transcript and metabolic responses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phosphorus (P) is an essential element for plant growth. Crop production of common bean (Phaseolus vulgaris), the most important legume for human consumption, is often limited by low P in the soil. Functional genomics technologies were used to investigate global gene expression and metabolic respons...

  9. METABOLIC RESPONSES OF AQUATIC ECOSYSTEMS TO CLIMATE WARMING

    EPA Science Inventory

    There is increasing evidence that stream metabolic processes that increase CO2 flux to the atmosphere will be highly sensitive to rising temperatures, changing precipitation patterns and shifts in carbon loading from watersheds. In addition, preliminary data suggest that th...

  10. Metabolic Response of Candida albicans to Phenylethyl Alcohol under Hyphae-Inducing Conditions

    PubMed Central

    Han, Ting-Li; Tumanov, Sergey; Cannon, Richard D.; Villas-Boas, Silas G.

    2013-01-01

    Phenylethyl alcohol was one of the first quorum sensing molecules (QSMs) identified in C. albicans. This extracellular signalling molecule inhibits the hyphal formation of C. albicans at high cell density. Little is known, however, about the underlying mechanisms by which this QSM regulates the morphological switches of C. albicans. Therefore, we have applied metabolomics and isotope labelling experiments to investigate the metabolic changes that occur in C. albicans in response to phenylethyl alcohol under defined hyphae-inducing conditions. Our results showed a global upregulation of central carbon metabolism when hyphal development was suppressed by phenylethyl alcohol. By comparing the metabolic changes in response to phenylethyl alcohol to our previous metabolomic studies, we were able to short-list 7 metabolic pathways from central carbon metabolism that appear to be associated with C. albicans morphogenesis. Furthermore, isotope-labelling data showed that phenylethyl alcohol is indeed taken up and catabolised by yeast cells. Isotope-labelled carbon atoms were found in the majority of amino acids as well as in lactate and glyoxylate. However, isotope-labelled carbon atoms from phenylethyl alcohol accumulated mainly in the pyridine ring of NAD+/NADH and NADP−/NADPH molecules, showing that these nucleotides were the main products of phenylethyl alcohol catabolism. Interestingly, two metabolic pathways where these nucleotides play an important role, nitrogen metabolism and nicotinate/nicotinamide metabolism, were also short-listed through our previous metabolomics works as metabolic pathways likely to be closely associated with C. albicans morphogenesis. PMID:23951145

  11. Metabolism

    MedlinePlus

    Metabolism refers to all the physical and chemical processes in the body that convert or use energy, ... Tortora GJ, Derrickson BH. Metabolism. In: Tortora GJ, Derrickson BH. Principles of Anatomy and Physiology . 14th ed. Hoboken, NJ: John H Wiley and Sons; 2013: ...

  12. Targeting amino acid metabolism in cancer growth and anti-tumor immune response

    PubMed Central

    Ananieva, Elitsa

    2015-01-01

    Recent advances in amino acid metabolism have revealed that targeting amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. There are currently several drugs in clinical trials that specifically target amino acid metabolic pathways in tumor cells. In the context of the tumor microenvironment, however, tumor cells form metabolic relationships with immune cells, and they often compete for common nutrients. Many tumors evolved to escape immune surveillance by taking advantage of their metabolic flexibility and redirecting nutrients for their own advantage. This review outlines the most recent advances in targeting amino acid metabolic pathways in cancer therapy while giving consideration to the impact these pathways may have on the anti-tumor immune response. PMID:26629311

  13. Muscle metabolic remodeling in response to endurance exercise in salmonids

    PubMed Central

    Morash, Andrea J.; Vanderveken, Mark; McClelland, Grant B.

    2014-01-01

    Phenotypic plasticity of skeletal muscle is relevant to swimming performance and metabolism in fishes, especially those that undergo extreme locomotory feats, such as seasonal migration. However, the influence of endurance exercise and the molecular mechanisms coordinating this remodeling are not well understood. The present study examines muscle metabolic remodeling associated with endurance exercise in fed rainbow trout as compared to migrating salmon. Trout were swum for 4 weeks at 1.5 BL/s, a speed similar to that of migrating salmon and red and white muscles were sampled after each week. We quantified changes in key enzymes in aerobic and carbohydrate metabolism [citrate synthase (CS), β-hydroxyacyl-CoA dehydrogenase (HOAD), hexokinase (HK)] and changes in mRNA expression of major regulators of metabolic phenotype (AMPK, PPARs) and lipid (carnitine palmitoyltransferase, CPT I), protein (aspartate aminotransferase, AST) and carbohydrate (HK) oxidation pathways. After 1 week of swimming substantial increases were seen in AMPK and PPARα mRNA expression and of their downstream target genes, CPTI and HK in red muscle. However, significant changes in CS and HK activity occurred only after 4 weeks. In contrast, there were few changes in mRNA expression and enzyme activities in white muscle over the 4-weeks. Red muscle results mimic those found in migrating salmon suggesting a strong influence of exercise on red muscle phenotype. In white muscle, only changes in AMPK and PPAR expression were similar to that seen with migrating salmon. However, in contrast to exercise alone, in natural migration HK decreased while AST increased suggesting that white muscle plays a role in supplying fuel and intermediates possibly through tissue breakdown during prolonged fasting. Dissecting individual and potentially synergistic effects of multiple stressors will enable us to determine major drivers of the metabolic phenotype and their impacts on whole animal performance. PMID

  14. Hepatic autophagy contributes to the metabolic response to dietary protein restriction.

    PubMed

    Henagan, Tara M; Laeger, Thomas; Navard, Alexandra M; Albarado, Diana; Noland, Robert C; Stadler, Krisztian; Elks, Carrie M; Burk, David; Morrison, Christopher D

    2016-06-01

    Autophagy is an essential cellular response which acts to release stored cellular substrates during nutrient restriction, and particularly plays a key role in the cellular response to amino acid restriction. However, there has been limited work testing whether the induction of autophagy is required for adaptive metabolic responses to dietary protein restriction in the whole animal. Here, we found that moderate dietary protein restriction led to a series of metabolic changes in rats, including increases in food intake and energy expenditure, the downregulation of hepatic fatty acid synthesis gene expression and reduced markers of hepatic mitochondrial number. Importantly, these effects were also associated with an induction of hepatic autophagy. To determine if the induction of autophagy contributes to these metabolic effects, we tested the metabolic response to dietary protein restriction in BCL2-AAA mice, which bear a genetic mutation that impairs autophagy induction. Interestingly, BCL2-AAA mice exhibit exaggerated responses in terms of both food intake and energy expenditure, whereas the effects of protein restriction on hepatic metabolism were significantly blunted. These data demonstrate that restriction of dietary protein is sufficient to trigger hepatic autophagy, and that disruption of autophagy significantly alters both hepatic and whole animal metabolic response to dietary protein restriction. PMID:27173459

  15. Test-retest reproducibility for regional brain metabolic responses to lorazepam

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Overall, J. |||

    1996-05-01

    Changes in regional brain glucose metabolism as assessed with PET and FDG in response to acute administration of benzodiazepine agonists have been used as indicators of benzodiazepine-GABA receptor function. The purpose of this study was to assess the reproducibility of these responses. Sixteen healthy right-handed men were scanned with positron emission tomography (PET) and [F-18] fluorodeoxyglucose (FDG) twice: prior to placebo and prior to lorazepam (30 {mu}g/kg). The same double FDG procedure was repeated 6-8 weeks later to assess test-retest reproducibility. The regional absolute brain metabolic values obtained during the second evaluation were significantly lower than those obtained for the first evaluation regardless of condition (p {le} 0.001). Lorazepam significantly and consistently decreased whole brain metabolism and the magnitude as well as the regional pattern of the changes was comparable for both studies (12.3 {plus_minus} 6.9% and 13.7 {plus_minus} 7.4%). Lorazepam effects were largest in thalamus (22.2 {plus_minus} 8.9%). Relative metabolic measures ROI/global were highly reproducible both for drug as well as replication condition. This is the first study to measure test-retest reproducibility in regional brain metabolic response to a pharmacological challenge. While the global and regional absolute metabolic values were significantly lower for the repeated evaluation, the regional brain metabolic response to lorazepam was highly reproducible.

  16. Early hemorrhage triggers metabolic responses that build up during prolonged shock

    PubMed Central

    Moore, Hunter B.; Moore, Ernest E.; Wither, Matthew; Nemkov, Travis; Gonzalez, Eduardo; Slaughter, Anne; Fragoso, Miguel; Hansen, Kirk C.; Silliman, Christopher C.; Banerjee, Anirban

    2015-01-01

    Metabolic staging after trauma/hemorrhagic shock is a key driver of acidosis and directly relates to hypothermia and coagulopathy. Metabolic responses to trauma/hemorrhagic shock have been assayed through classic biochemical approaches or NMR, thereby lacking a comprehensive overview of the dynamic metabolic changes occurring after shock. Sprague-Dawley rats underwent progressive hemorrhage and shock. Baseline and postshock blood was collected, and late hyperfibrinolysis was assessed (LY30 >3%) in all of the tested rats. Extreme and intermediate time points were collected to assay the dynamic changes of the plasma metabolome via ultra-high performance liquid chromatography-mass spectrometry. Sham controls were used to determine whether metabolic changes could be primarily attributable to anesthesia and supine positioning. Early hemorrhage-triggered metabolic changes that built up progressively and became significant during sustained hemorrhagic shock. Metabolic phenotypes either resulted in immediate hypercatabolism, or late hypercatabolism, preceded by metabolic deregulation during early hemorrhage in a subset of rats. Hemorrhagic shock consistently promoted hyperglycemia, glycolysis, Krebs cycle, fatty acid, amino acid, and nitrogen metabolism (urate and polyamines), and impaired redox homeostasis. Early dynamic changes of the plasma metabolome are triggered by hemorrhage in rats. Future studies will determine whether metabolic subphenotypes observed in rats might be consistently observed in humans and pave the way for tailored resuscitative strategies. PMID:25876652

  17. Organogenic nodule development in hop (Humulus lupulus L.): Transcript and metabolic responses

    PubMed Central

    Fortes, Ana M; Santos, Filipa; Choi, Young H; Silva, Marta S; Figueiredo, Andreia; Sousa, Lisete; Pessoa, Fernando; Santos, Bartolomeu A; Sebastiana, Mónica; Palme, Klaus; Malhó, Rui; Verpoorte, Rob; Pais, Maria S

    2008-01-01

    Background Hop (Humulus lupulus L.) is an economically important plant forming organogenic nodules which can be used for genetic transformation and micropropagation. We are interested in the mechanisms underlying reprogramming of cells through stress and hormone treatments. Results An integrated molecular and metabolomic approach was used to investigate global gene expression and metabolic responses during development of hop's organogenic nodules. Transcript profiling using a 3,324-cDNA clone array revealed differential regulation of 133 unigenes, classified into 11 functional categories. Several pathways seem to be determinant in organogenic nodule formation, namely defense and stress response, sugar and lipid metabolism, synthesis of secondary metabolites and hormone signaling. Metabolic profiling using 1H NMR spectroscopy associated to two-dimensional techniques showed the importance of metabolites related to oxidative stress response, lipid and sugar metabolism and secondary metabolism in organogenic nodule formation. Conclusion The expression profile of genes pivotal for energy metabolism, together with metabolites profile, suggested that these morphogenic structures gain energy through a heterotrophic, transport-dependent and sugar-degrading anaerobic metabolism. Polyamines and auxins are likely to be involved in the regulation of expression of many genes related to organogenic nodule formation. These results represent substantial progress toward a better understanding of this complex developmental program and reveal novel information regarding morphogenesis in plants. PMID:18823540

  18. Metabolic profiling of the tissue-specific responses in mussel Mytilus galloprovincialis towards Vibrio harveyi challenge.

    PubMed

    Liu, Xiaoli; Ji, Chenglong; Zhao, Jianmin; Wang, Qing; Li, Fei; Wu, Huifeng

    2014-08-01

    Mussel Mytilus galloprovincialis is a marine aquaculture shellfish distributing widely along the coast in north China. In this work, we studied the differential metabolic responses induced by Vibrio harveyi in digestive gland and gill tissues from M. galloprovincialis using NMR-based metabolomics. The differential metabolic responses in the two tissue types were detected, except the similarly altered taurine and betaine. These metabolic responses suggested that V. harveyi mainly induced osmotic disruption and reduced energy demand via the metabolic pathways of glucose synthesis and ATP/AMP conversion in mussel digestive gland. In mussel gill tissues, V. harveyi basically caused osmotic stress and possible reduced energy demand as shown by the elevated phosphocholine that is involved in one of the metabolic pathways of ATP synthesis from ADP and phosphocholine. The altered mRNA expression levels of related genes (superoxide dismutase with copper and zinc, heat shock protein 90, defensin and lysozyme) suggested that V. harveyi induced clear oxidative and immune stresses in both digestive gland and gill tissues. However, the mRNA expression levels of both lysozyme and defensin in digestive gland were more significantly up-regulated than those in gill from V. harveyi-challenged mussel M. galloprovincialis, meaning that the immune organ, digestive gland, was more sensitive than gill. Overall, our results indicated that V. harveyi could induce tissue-specific metabolic responses in mussel M. galloprovincialis. PMID:24911264

  19. Variation in metabolic responses to meal challenges differing in glycemic index in healthy women: Is it meaningful?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Metabolic phenotyping has potential utility as a diagnostic tool. While clinical parameters are commonly used in disease diagnosis, tools that enhance diagnosis of metabolic dysfunctions are needed. Objective: To identify typical and atypical metabolite temporal patterns in response to ...

  20. Variations in metabolic responses to meal challenges differing in glycemic index in healthy women: Is it meaningful?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Metabolic phenotyping has potential utility as a diagnostic tool. While clinical parameters are commonly used in disease diagnosis, tools that enhance diagnosis of metabolic dysfunctions are needed. Objective: To identify typical and atypical metabolite temporal patterns in response t...

  1. Dynamic metabolic engineering: New strategies for developing responsive cell factories

    PubMed Central

    Brockman, Irene M.; Prather, Kristala L.J.

    2015-01-01

    Metabolic engineering strategies have enabled improvements in yield and titer for a variety of valuable small molecules produced naturally in microorganisms, as well as those produced via heterologous pathways. Typically, the approaches have been focused on up- and downregulation of genes to redistribute steady-state pathway fluxes, but more recently a number of groups have developed strategies for dynamic regulation, which allows rebalancing of fluxes according to changing conditions in the cell or the fermentation medium. This review highlights some of the recently published work related to dynamic metabolic engineering strategies and explores how advances in high-throughput screening and synthetic biology can support development of new dynamic systems. Dynamic gene expression profiles allow trade-offs between growth and production to be better managed and can help avoid build-up of undesired intermediates. The implementation is more complex relative to static control, but advances in screening techniques and DNA synthesis will continue to drive innovation in this field. PMID:25868062

  2. Aluminum induced metabolic responses in two tea cultivars.

    PubMed

    Xu, Qingshan; Wang, Yu; Ding, Zhaotang; Song, Lubin; Li, Yusheng; Ma, Dexin; Wang, Yi; Shen, Jiazhi; Jia, Sisi; Sun, Haiwei; Zhang, Hong

    2016-04-01

    Tea [Camellia sinensis (L.)], is an aluminum (Al(3+)) hyperaccumulator plant and grows well in acid soils. In the present study, roots of two tea cultivars, JHC and YS were treated with different concentrations of Al(3+). After treatments, the root length, dry matter, root activity and chlorophyll content (SPAD value) of JHC had greater increase than that of YS. We also detected metabolic changes of two varieties using GC-MS method. Comparison between two cultivars indicated that shikimic pathway was more enhanced in YS roots by Al(3+) with higher levels of catechine, quinic acid and shikimic acid. While, more active amino acid synthesis was found in JHC roots and JHC leaves remained the higher level contents of metabolites related to cysteine synthesis. The comparison also showed that a large amount of sugar alcohols were accumulated in roots of two varieties, whereas most of them were reduced in YS leaves. Other well-known ligands, such as phosphoric acid and malic acid were observed in two cultivars that showed significantly altered abundances under Al(3+) treatments. The results indicated that Al(3+) adaptation of two cultivars may be correlated with their differential metabolism of amino acids, sugars and shikimic acids. PMID:26895429

  3. Metabolic Regulation and Coordination of the Metabolism in Bacteria in Response to a Variety of Growth Conditions.

    PubMed

    Shimizu, Kazuyuki

    2016-01-01

    Living organisms have sophisticated but well-organized regulation system. It is important to understand the metabolic regulation mechanisms in relation to growth environment for the efficient design of cell factories for biofuels and biochemicals production. Here, an overview is given for carbon catabolite regulation, nitrogen regulation, ion, sulfur, and phosphate regulations, stringent response under nutrient starvation as well as oxidative stress regulation, redox state regulation, acid-shock, heat- and cold-shock regulations, solvent stress regulation, osmoregulation, and biofilm formation, and quorum sensing focusing on Escherichia coli metabolism and others. The coordinated regulation mechanisms are of particular interest in getting insight into the principle which governs the cell metabolism. The metabolism is controlled by both enzyme-level regulation and transcriptional regulation via transcription factors such as cAMP-Crp, Cra, Csr, Fis, P(II)(GlnB), NtrBC, CysB, PhoR/B, SoxR/S, Fur, MarR, ArcA/B, Fnr, NarX/L, RpoS, and (p)ppGpp for stringent response, where the timescales for enzyme-level and gene-level regulations are different. Moreover, multiple regulations are coordinated by the intracellular metabolites, where fructose 1,6-bisphosphate (FBP), phosphoenolpyruvate (PEP), and acetyl-CoA (AcCoA) play important roles for enzyme-level regulation as well as transcriptional control, while α-ketoacids such as α-ketoglutaric acid (αKG), pyruvate (PYR), and oxaloacetate (OAA) play important roles for the coordinated regulation between carbon source uptake rate and other nutrient uptake rate such as nitrogen or sulfur uptake rate by modulation of cAMP via Cya. PMID:25712586

  4. Metabolic response to exogenous ethanol in yeast: an in vivo NMR and mathematical modelling approach.

    PubMed

    Martini, Silvia; Ricci, Maso; Bartolini, Fiora; Bonechi, Claudia; Braconi, Daniela; Millucci, Lia; Santucci, Annalisa; Rossi, Claudio

    2006-03-20

    The understanding of the metabolic behaviour of complex systems such as eukaryotic cells needs the development of new approaches that are able to deal with the complexity due to a large number of interactions within the system. In this paper, we applied an approach based on the combined use of in vivo NMR experiments and mathematical modelling in order to analyze the metabolic response to ethanol stress in a wild-strain of Saccharomyces cerevisiae. Considering the cellular metabolic processes resulting from activation, inhibition, and feed-back activities, we developed a model able to describe the modulation of the whole system induced by an external stress due to increasing concentrations of exogenous ethanol. This approach was able to interpret the experimental results in terms of metabolic response to exogenous ethanol in the yeast. The robustness and flexibility of the model enables it to work correctly at different initial exogenous ethanol concentrations. PMID:16316719

  5. Quantitative H2S-mediated protein sulfhydration reveals metabolic reprogramming during the integrated stress response.

    PubMed

    Gao, Xing-Huang; Krokowski, Dawid; Guan, Bo-Jhih; Bederman, Ilya; Majumder, Mithu; Parisien, Marc; Diatchenko, Luda; Kabil, Omer; Willard, Belinda; Banerjee, Ruma; Wang, Benlian; Bebek, Gurkan; Evans, Charles R; Fox, Paul L; Gerson, Stanton L; Hoppel, Charles L; Liu, Ming; Arvan, Peter; Hatzoglou, Maria

    2015-01-01

    The sulfhydration of cysteine residues in proteins is an important mechanism involved in diverse biological processes. We have developed a proteomics approach to quantitatively profile the changes of sulfhydrated cysteines in biological systems. Bioinformatics analysis revealed that sulfhydrated cysteines are part of a wide range of biological functions. In pancreatic β cells exposed to endoplasmic reticulum (ER) stress, elevated H2S promotes the sulfhydration of enzymes in energy metabolism and stimulates glycolytic flux. We propose that transcriptional and translational reprogramming by the integrated stress response (ISR) in pancreatic β cells is coupled to metabolic alternations triggered by sulfhydration of key enzymes in intermediary metabolism. PMID:26595448

  6. Coupling of metabolism and cardiovascular response represents normal physiology.

    PubMed

    Steinberg, Helmut O

    2003-12-01

    In this issue of Clinical Science, Fugmann and co-workers demonstrate a highly integrated cardiovascular response to changes in plasma concentrations of glucose, triacylglycerols (triglycerides), fatty acids and insulin. Since the different substrates, alone and combined, evoked these changes, this response is likely to be a physiological one and directed towards minimizing the extent and duration of substrate elevations that could cause vascular dysfunction. PMID:12917009

  7. Physiological responses to environmental factors related to space flight. [hemodynamic and metabolic responses to weightlessness

    NASA Technical Reports Server (NTRS)

    Pace, N.

    1973-01-01

    Physiological base line data are established, and physiological procedures and instrumentation necessary for the automatic measurement of hemodynamic and metabolic parameters during prolonged periods of weightlessness are developed.

  8. Probing soil C metabolism in response to temperature: results from experiments and modeling

    NASA Astrophysics Data System (ADS)

    Dijkstra, P.; Dalder, J.; Blankinship, J.; Selmants, P. C.; Schwartz, E.; Koch, G. W.; Hart, S.; Hungate, B. A.

    2010-12-01

    C use efficiency (CUE) is one of the least understood aspects of soil C cycling, has a very large effect on soil respiration and C sequestration, and decreases with elevated temperature. CUE is directly related to substrate partitioning over energy production and biosynthesis. The production of energy and metabolic precursors occurs in well-known processes such as glycolysis and Krebs cycle. We have developed a new stable isotope approach using position-specific 13C-labeled metabolic tracers to measure these fundamental metabolic processes in intact soil communities (1). We use this new approach, combined with models of soil metabolic flux patterns, to analyze the response of microbial energy production, biosynthesis, and CUE to temperature. The method consists of adding small but precise amounts of position-specific 13C -labeled metabolic tracers to parallel soil incubations, in this case 1-13C and 2,3-13C pyruvate and 1-13C and U-13C glucose. The measurement of CO2 released from the labeled tracers is used to calculate the C flux rates through various metabolic pathways. A simplified metabolic model consisting of 23 reactions is iteratively solved using results of the metabolic tracer experiments and information on microbial precursor demand under different temperatures. This new method enables direct study of fundamental aspects of microbial energy production, C use efficiency, and soil organic matter formation in response to temperature. (1) Dijkstra P, Blankinship JC, Selmants PC, Hart SC, Koch GW, Schwarz E and Hungate BA. Probing metabolic flux patterns of soil microbial communities using parallel position-specific tracer labeling. Soil Biology and Biochemistry (accepted)

  9. Fasciola hepatica: motility response to metabolic inhibitors in vitro.

    PubMed

    Holmes, S D; Fairweather, I

    1985-06-01

    The effects of metabolic inhibitors on the in vitro motility of Fasciola hepatica have been determined by means of an isometric transducer system. Sodium fluoride, an inhibitor of glycolysis, causes a long-term suppression of motility; this is also the effect of sodium iodoacetate (another glycolysis inhibitor) at low concentrations (1 X 10(-5) M and below). However, higher concentrations of iodoacetate induce a rapid inhibition of activity leading to a spastic paralysis. Both rotenone and oligomycin, which act as inhibitors of oxidative phosphorylation, produce a long-term suppression of movement. Carbonylcyanide-p-trifluoromethoxyphenylhydrazone and carbonylcyanide-m-chlorophenylhydrazone, which are uncouplers of oxidative phosphorylation, induce a spastic paralysis of the fluke; this is rapid at high concentrations (1 X 10(-4) and 1 X 10(-5) M). A brief stimulation of activity is evident at 1 X 10(-5) M and lasts longer at 1 X 10(-6) and 1 X 10(-7) M, before inhibition sets in. There is no stimulation at low concentrations of carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (1 X 10(-8) and 1 X 10(-9) M), only inhibition leading to a medium-term spastic paralysis. In contrast, a third uncoupler, 2,4-dinitrophenol, causes a flaccid paralysis and the effect is rapid only at high concentrations, being accompanied by an initial increase in muscle tone at 1 X 10(-2) M and a brief stimulation of motility at 1 X 10(-3) M. Stimulation lasts longer at 1 X 10(-4) and 1 X 10(-5) M, but is not evident at concentrations below this. The effects on motility at these lower concentrations are essentially long term in nature. That the rapid effects of the uncouplers on muscle tone and motility are not due primarily to uncoupling is shown by 2,4,6-trinitrophenol and hydroquinone, compounds structurally related to 2,4-dinitrophenol. 2,4,6-Trinitrophenol is a membrane-impermeable compound devoid of uncoupling activity; at 1 X 10(-3) M, it causes an immediate inhibition of activity

  10. Metabolic, immune, and gut microbial signals mount a systems response to Leishmania major infection.

    PubMed

    Lamour, Sabrina D; Veselkov, Kirill A; Posma, Joram M; Giraud, Emilie; Rogers, Matthew E; Croft, Simon; Marchesi, Julian R; Holmes, Elaine; Seifert, Karin; Saric, Jasmina

    2015-01-01

    Parasitic infections such as leishmaniasis induce a cascade of host physiological responses, including metabolic and immunological changes. Infection with Leishmania major parasites causes cutaneous leishmaniasis in humans, a neglected tropical disease that is difficult to manage. To understand the determinants of pathology, we studied L. major infection in two mouse models: the self-healing C57BL/6 strain and the nonhealing BALB/c strain. Metabolic profiling of urine, plasma, and feces via proton NMR spectroscopy was performed to discover parasite-specific imprints on global host metabolism. Plasma cytokine status and fecal microbiome were also characterized as additional metrics of the host response to infection. Results demonstrated differences in glucose and lipid metabolism, distinctive immunological phenotypes, and shifts in microbial composition between the two models. We present a novel approach to integrate such metrics using correlation network analyses, whereby self-healing mice demonstrated an orchestrated interaction between the biological measures shortly after infection. In contrast, the response observed in nonhealing mice was delayed and fragmented. Our study suggests that trans-system communication across host metabolism, the innate immune system, and gut microbiome is key for a successful host response to L. major and provides a new concept, potentially translatable to other diseases. PMID:25369177

  11. Organ-specific metabolic responses to drought in Pinus pinaster Ait.

    PubMed

    de Miguel, Marina; Guevara, M Ángeles; Sánchez-Gómez, David; de María, Nuria; Díaz, Luis Manuel; Mancha, Jose A; Fernández de Simón, Brígida; Cadahía, Estrella; Desai, Nalini; Aranda, Ismael; Cervera, María-Teresa

    2016-05-01

    Drought is an important driver of plant survival, growth, and distribution. Water deficit affects different pathways of metabolism, depending on plant organ. While previous studies have mainly focused on the metabolic drought response of a single organ, analysis of metabolic differences between organs is essential to achieve an integrated understanding of the whole plant response. In this work, untargeted metabolic profiling was used to examine the response of roots, stems, adult and juvenile needles from Pinus pinaster Ait. full-sib individuals, subjected to a moderate and long lasting drought period. Cyclitols content showed a significant alteration, in response to drought in all organs examined, but other metabolites increased or decreased differentially depending on the analyzed organ. While a high number of flavonoids were only detected in aerial organs, an induction of the glutathione pathway was mainly detected in roots. This result may reflect different antioxidant mechanisms activated in aerial organs and roots. Metabolic changes were more remarkable in roots than in the other organs, highlighting its prominent role in the response to water stress. Significant changes in flavonoids and ascorbate metabolism were also observed between adult and juvenile needles, consistent with previously proven differential functional responses between the two developmental stages. Genetic polymorphisms in candidate genes coding for a Myb1 transcription factor and a malate dehydrogenase (EC 1.1.1.37) were associated with different concentration of phenylalanine, phenylpropanoids and malate, respectively. The results obtained will support further research on metabolites and genes potentially involved in functional mechanisms related to drought tolerance in trees. PMID:26897116

  12. Suppression of the HSF1-mediated proteotoxic stress response by the metabolic stress sensor AMPK

    PubMed Central

    Dai, Siyuan; Tang, Zijian; Cao, Junyue; Zhou, Wei; Li, Huawen; Sampson, Stephen; Dai, Chengkai

    2015-01-01

    Numerous extrinsic and intrinsic insults trigger the HSF1-mediated proteotoxic stress response (PSR), an ancient transcriptional program that is essential to proteostasis and survival under such conditions. In contrast to its well-recognized mobilization by proteotoxic stress, little is known about how this powerful adaptive mechanism reacts to other stresses. Surprisingly, we discovered that metabolic stress suppresses the PSR. This suppression is largely mediated through the central metabolic sensor AMPK, which physically interacts with and phosphorylates HSF1 at Ser121. Through AMPK activation, metabolic stress represses HSF1, rendering cells vulnerable to proteotoxic stress. Conversely, proteotoxic stress inactivates AMPK and thereby interferes with the metabolic stress response. Importantly, metformin, a metabolic stressor and popular anti-diabetic drug, inactivates HSF1 and provokes proteotoxic stress within tumor cells, thereby impeding tumor growth. Thus, these findings uncover a novel interplay between the metabolic stress sensor AMPK and the proteotoxic stress sensor HSF1 that profoundly impacts stress resistance, proteostasis, and malignant growth. PMID:25425574

  13. The unfolded protein response mediates reversible tau phosphorylation induced by metabolic stress

    PubMed Central

    van der Harg, J M; Nölle, A; Zwart, R; Boerema, A S; van Haastert, E S; Strijkstra, A M; Hoozemans, J JM; Scheper, W

    2014-01-01

    The unfolded protein response (UPR) is activated in neurodegenerative tauopathies such as Alzheimer's disease (AD) in close connection with early stages of tau pathology. Metabolic disturbances are strongly associated with increased risk for AD and are a potent inducer of the UPR. Here, we demonstrate that metabolic stress induces the phosphorylation of endogenous tau via activation of the UPR. Strikingly, upon restoration of the metabolic homeostasis, not only the levels of the UPR markers pPERK, pIRE1α and BiP, but also tau phosphorylation are reversed both in cell models as well as in torpor, a physiological hypometabolic model in vivo. Intervention in the UPR using the global UPR inhibitor TUDCA or a specific small-molecule inhibitor of the PERK signaling pathway, inhibits the metabolic stress-induced phosphorylation of tau. These data support a role for UPR-mediated tau phosphorylation as part of an adaptive response to metabolic stress. Failure to restore the metabolic homeostasis will lead to prolonged UPR activation and tau phosphorylation, and may thus contribute to AD pathogenesis. We demonstrate that the UPR is functionally involved in the early stages of tau pathology. Our data indicate that targeting of the UPR may be employed for early intervention in tau-related neurodegenerative diseases. PMID:25165879

  14. [Response of arbuscular mycorrhizal fungal lipid metabolism to symbiotic signals in mycorrhiza].

    PubMed

    Tian, Lei; Li, Yuanjing; Tian, Chunjie

    2016-01-01

    Arbuscular mycorrhizal (AM) fungi play an important role in energy flow and nutrient cycling, besides their wide distribution in the cosystem. With a long co-evolution, AM fungi and host plant have formed a symbiotic relationship, and fungal lipid metabolism may be the key point to find the symbiotic mechanism in arbusculart mycorrhiza. Here, we reviewed the most recent progress on the interaction between AM fungal lipid metabolism and symbiotic signaling networks, especially the response of AM fungal lipid metabolism to symbiotic signals. Furthermore, we discussed the response of AM fungal lipid storage and release to symbiotic or non-symbiotic status, and the correlation between fungal lipid metabolism and nutrient transfer in mycorrhiza. In addition, we explored the feedback of the lipolysis process to molecular signals during the establishment of symbiosis, and the corresponding material conversion and energy metabolism besides the crosstalk of fungal lipid metabolism and signaling networks. This review will help understand symbiotic mechanism of arbuscular mycorrhiza fungi and further application in ecosystem. PMID:27305777

  15. Bioenergetic and metabolic response to continuous v intermittent nasoenteric feeding.

    PubMed

    Heymsfield, S B; Casper, K; Grossman, G D

    1987-06-01

    Resting thermal energy losses and metabolic balances of N, K, P, Ca, Na, and Mg were compared during continuous and intermittent nasoenteric formula infusion in four healthy men. Each feeding protocol lasted 1 week in a 4-week double crossover experiment. The initial feeding schedule was established randomly. Continuous nasoenteric formula infusion produced no increase in thermal energy losses above the fasting level; energy expenditure fell with sleep to the same extent as with intermittent feeding. Thermal losses were similar during intermittent feeding with the exception of the thermic effect of food that produced an additional average energy loss of 115.7 kcal/d. The total resting and sleeping 24-hour energy expenditure was significantly lower (P less than .01) during continuous formula infusion (means +/- SD for n = 8 balance periods, 1344 +/- 119 kcal) compared to intermittent feeding (1457 +/- 179 kcal). No significant differences in nutrient absorption or balances of N, Na, Ca, and Mg were detected between the two feeding protocols. In contrast, continuous infusion of formula was accompanied by negative balances of K and the cytosolic portion of P; weight balance was slightly negative. Weight, K, and cytosolic P balances were all positive during intermittent feeding (P = NS, less than 0.01, and P less than .05 compared to respective continuous infusion periods). Hence, 1 week of continuous nasogastric formula infusion is associated with similar nutrient absorption, a significant reduction in thermal energy losses, and equivalent protein (N) balance relative to intermittent feeding. Differences in weight balance between the two feeding protocols can be ascribed largely to fluid and mineral shifts. These results suggest that energy requirements are lower during continuous formula infusion by about 100 kcal/d compared to regular meal ingestion. PMID:3108622

  16. Jasmonate-responsive transcription factors regulating plant secondary metabolism.

    PubMed

    Zhou, Meiliang; Memelink, Johan

    2016-01-01

    Plants produce a large variety of secondary metabolites including alkaloids, glucosinolates, terpenoids and phenylpropanoids. These compounds play key roles in plant-environment interactions and many of them have pharmacological activity in humans. Jasmonates (JAs) are plant hormones which induce biosynthesis of many secondary metabolites. JAs-responsive transcription factors (TFs) that regulate the JAs-induced accumulation of secondary metabolites belong to different families including AP2/ERF, bHLH, MYB and WRKY. Here, we give an overview of the types and functions of TFs that have been identified in JAs-induced secondary metabolite biosynthesis, and highlight their similarities and differences in regulating various biosynthetic pathways. We review major recent developments regarding JAs-responsive TFs mediating secondary metabolite biosynthesis, and provide suggestions for further studies. PMID:26876016

  17. Cephalic phase metabolic responses in normal weight adults.

    PubMed

    Bruce, D G; Storlien, L H; Furler, S M; Chisholm, D J

    1987-08-01

    The presence and physiologic importance of cephalic phase insulin release in humans remains controversial. The aim of these studies was to determine whether cephalic phase insulin release could be demonstrated in normal weight subjects and whether it would be associated with changes in blood glucose, free fatty acid, and pancreatic polypeptide levels. The studies were followed by a hyperglycemic clamp to determine whether cephalic responses would alter overall glucose disposal or glucose-stimulated insulin secretion. In all, 17 subjects were studied on two occasions with and without (control study) presentation of food stimuli. Tease-feeding alone (n = 6), or the administration of a sweet taste alone (aspartame, n = 5) failed to stimulate cephalic responses. However, the presentation of the combined stimuli (tease meals plus sweet taste, n = 7) resulted in a significant fall (P less than .005) in blood glucose levels and a variable rise in serum insulin (% insulin rise 38 +/- 15%, P less than .05) and C-peptide levels (7 +/- 6%, NS) within five minutes of the food presentation when compared with control studies, with no change seen in free fatty acid or pancreatic polypeptide levels. The blood glucose fall correlated strongly (r = .90, P less than .01) with a score of the subjective response to the food and taste.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3298939

  18. Metabolic responses in Candida tropicalis to complex inhibitors during xylitol bioconversion.

    PubMed

    Wang, Shizeng; Li, Hao; Fan, Xiaoguang; Zhang, Jingkun; Tang, Pingwah; Yuan, Qipeng

    2015-09-01

    During xylitol fermentation, Candida tropicalis is often inhibited by inhibitors in hemicellulose hydrolysate. The mechanisms involved in the metabolic responses to inhibitor stress and the resistances to inhibitors are still not clear. To understand the inhibition mechanisms and the metabolic responses to inhibitors, a GC/MS-based metabolomics approach was performed on C. tropicalis treated with and without complex inhibitors (CI, including furfural, phenol and acetic acid). Partial least squares discriminant analysis was used to determine the metabolic variability between CI-treated groups and control groups, and 25 metabolites were identified as possible entities responsible for the discrimination caused by inhibitors. We found that xylose uptake rate and xylitol oxidation rate were promoted by CI treatment. Metabolomics analysis showed that the flux from xylulose to pentose phosphate pathway increased, and tricarboxylic acid cycle was disturbed by CI. Moreover, the changes in levels of 1,3-propanediol, trehalose, saturated fatty acids and amino acids showed different mechanisms involved in metabolic responses to inhibitor stress. The increase of 1,3-propanediol was considered to be correlated with regulating redox balance and osmoregulation. The increase of trehalose might play a role in protein stabilization and cellular membranes protection. Saturated fatty acids could cause the decrease of membrane fluidity and make the plasma membrane rigid to maintain the integrity of plasma membrane. The deeper understanding of the inhibition mechanisms and the metabolic responses to inhibitors will provide us with more information on the metabolism regulation during xylitol bioconversion and the construction of industrial strains with inhibitor tolerance for better utilization of bioresource. PMID:26127015

  19. Metabolic flux ratio analysis and multi-objective optimization revealed a globally conserved and coordinated metabolic response of E. coli to paraquat-induced oxidative stress.

    PubMed

    Shen, Tie; Rui, Bin; Zhou, Hong; Zhang, Ximing; Yi, Yin; Wen, Han; Zheng, Haoran; Wu, Jihui; Shi, Yunyu

    2013-01-27

    The ability of a microorganism to adapt to changes in the environment, such as in nutrient or oxygen availability, is essential for its competitive fitness and survival. The cellular objective and the strategy of the metabolic response to an extreme environment are therefore of tremendous interest and, thus, have been increasingly explored. However, the cellular objective of the complex regulatory structure of the metabolic changes has not yet been fully elucidated and more details regarding the quantitative behaviour of the metabolic flux redistribution are required to understand the systems-wide biological significance of this response. In this study, the intracellular metabolic flux ratios involved in the central carbon metabolism were determined by fractional (13)C-labeling and metabolic flux ratio analysis (MetaFoR) of the wild-type E. coli strain JM101 at an oxidative environment in a chemostat. We observed a significant increase in the flux through phosphoenolpyruvate carboxykinase (PEPCK), phosphoenolpyruvate carboxylase (PEPC), malic enzyme (MEZ) and serine hydroxymethyltransferase (SHMT). We applied an ε-constraint based multi-objective optimization to investigate the trade-off relationships between the biomass yield and the generation of reductive power using the in silico iJR904 genome-scale model of E. coli K-12. The theoretical metabolic redistribution supports that the trans-hydrogenase pathway should not play a direct role in the defence mounted by E. coli against oxidative stress. The agreement between the measured ratio and the theoretical redistribution established the significance of NADPH synthesis as the goal of the metabolic reprogramming that occurs in response to oxidative stress. Our work presents a framework that combines metabolic flux ratio analysis and multi-objective optimization to investigate the metabolic trade-offs that occur under varied environmental conditions. Our results led to the proposal that the metabolic response of E

  20. Fibroblasts from patients with major depressive disorder show distinct transcriptional response to metabolic stressors

    PubMed Central

    Garbett, K A; Vereczkei, A; Kálmán, S; Wang, L; Korade, Ž; Shelton, R C; Mirnics, K

    2015-01-01

    Major depressive disorder (MDD) is increasingly viewed as interplay of environmental stressors and genetic predisposition, and recent data suggest that the disease affects not only the brain, but the entire body. As a result, we aimed at determining whether patients with major depression have aberrant molecular responses to stress in peripheral tissues. We examined the effects of two metabolic stressors, galactose (GAL) or reduced lipids (RL), on the transcriptome and miRNome of human fibroblasts from 16 pairs of patients with MDD and matched healthy controls (CNTR). Our results demonstrate that both MDD and CNTR fibroblasts had a robust molecular response to GAL and RL challenges. Most importantly, a significant part (messenger RNAs (mRNAs): 26–33% microRNAs (miRNAs): 81–90%) of the molecular response was only observed in MDD, but not in CNTR fibroblasts. The applied metabolic challenges uncovered mRNA and miRNA signatures, identifying responses to each stressor characteristic for the MDD fibroblasts. The distinct responses of MDD fibroblasts to GAL and RL revealed an aberrant engagement of molecular pathways, such as apoptosis, regulation of cell cycle, cell migration, metabolic control and energy production. In conclusion, the metabolic challenges evoked by GAL or RL in dermal fibroblasts exposed adaptive dysfunctions on mRNA and miRNA levels that are characteristic for MDD. This finding underscores the need to challenge biological systems to bring out disease-specific deficits, which otherwise might remain hidden under resting conditions. PMID:25756806

  1. Deciphering the metabolic response of M ycobacterium tuberculosis to nitrogen stress

    PubMed Central

    Williams, Kerstin J.; Jenkins, Victoria A.; Barton, Geraint R.; Bryant, William A.; Krishnan, Nitya

    2015-01-01

    Summary A key component to the success of M ycobacterium tuberculosis as a pathogen is the ability to sense and adapt metabolically to the diverse range of conditions encountered in vivo, such as oxygen tension, environmental pH and nutrient availability. Although nitrogen is an essential nutrient for every organism, little is known about the genes and pathways responsible for nitrogen assimilation in M . tuberculosis. In this study we have used transcriptomics and chromatin immunoprecipitation and high‐throughput sequencing to address this. In response to nitrogen starvation, a total of 185 genes were significantly differentially expressed (96 up‐regulated and 89 down regulated; 5% genome) highlighting several significant areas of metabolic change during nitrogen limitation such as nitrate/nitrite metabolism, aspartate metabolism and changes in cell wall biosynthesis. We identify GlnR as a regulator involved in the nitrogen response, controlling the expression of at least 33 genes in response to nitrogen limitation. We identify a consensus GlnR binding site and relate its location to known transcriptional start sites. We also show that the GlnR response regulator plays a very different role in M . tuberculosis to that in non‐pathogenic mycobacteria, controlling genes involved in nitric oxide detoxification and intracellular survival instead of genes involved in nitrogen scavenging. PMID:26077160

  2. Loss of DJ-1 impairs antioxidant response by altered glutamine and serine metabolism.

    PubMed

    Meiser, J; Delcambre, S; Wegner, A; Jäger, C; Ghelfi, J; d'Herouel, A Fouquier; Dong, X; Weindl, D; Stautner, C; Nonnenmacher, Y; Michelucci, A; Popp, O; Giesert, F; Schildknecht, S; Krämer, L; Schneider, J G; Woitalla, D; Wurst, W; Skupin, A; Weisenhorn, D M Vogt; Krüger, R; Leist, M; Hiller, K

    2016-05-01

    The oncogene DJ-1 has been originally identified as a suppressor of PTEN. Further on, loss-of-function mutations have been described as a causative factor in Parkinson's disease (PD). DJ-1 has an important function in cellular antioxidant responses, but its role in central metabolism of neurons is still elusive. We applied stable isotope assisted metabolic profiling to investigate the effect of a functional loss of DJ-1 and show that DJ-1 deficient neuronal cells exhibit decreased glutamine influx and reduced serine biosynthesis. By providing precursors for GSH synthesis, these two metabolic pathways are important contributors to cellular antioxidant response. Down-regulation of these pathways, as a result of loss of DJ-1 leads to an impaired antioxidant response. Furthermore, DJ-1 deficient mouse microglia showed a weak but constitutive pro-inflammatory activation. The combined effects of altered central metabolism and constitutive activation of glia cells raise the susceptibility of dopaminergic neurons towards degeneration in patients harboring mutated DJ-1. Our work reveals metabolic alterations leading to increased cellular instability and identifies potential new intervention points that can further be studied in the light of novel translational medicine approaches. PMID:26836693

  3. Metabolic responses to low temperature in fish muscle.

    PubMed

    Guderley, Helga

    2004-05-01

    For most fish, body temperature is very close to that of the habitat. The diversity of thermal habitats exploited by fish as well as their capacity to adapt to thermal change makes them excellent organisms in which to examine the evolutionary and phenotypic responses to temperature. An extensive literature links cold temperatures with enhanced oxidative capacities in fish tissues, particularly skeletal muscle. Closer examination of inter-species comparisons (i.e. the evolutionary perspective) indicates that the proportion of muscle fibres occupied by mitochondria increases at low temperatures, most clearly in moderately active demersal species. Isolated muscle mitochondria show no compensation of protein-specific rates of substrate oxidation during evolutionary adaptation to cold temperatures. During phenotypic cold acclimation, mitochondrial volume density increases in oxidative muscle of some species (striped bass Morone saxatilis, crucian carp Carassius carassius), but remains stable in others (rainbow trout Oncorhynchus mykiss). A role for the mitochondrial reticulum in distributing oxygen through the complex architecture of skeletal muscle fibres may explain mitochondrial proliferation. In rainbow trout, compensatory increases in the protein-specific rates of mitochondrial substrate oxidation maintain constant capacities except at winter extremes. Changes in mitochondrial properties (membrane phospholipids, enzymatic complement and cristae densities) can enhance the oxidative capacity of muscle in the absence of changes in mitochondrial volume density. Changes in the unsaturation of membrane phospholipids are a direct response to temperature and occur in isolated cells. This fundamental response maintains the dynamic phase behaviour of the membrane and adjusts the rates of membrane processes. However, these adjustments may have deleterious consequences. For fish living at low temperatures, the increased polyunsaturation of mitochondrial membranes should raise

  4. Induction of the Unfolded Protein Response Drives Enhanced Metabolism and Chemoresistance in Glioma Cells

    PubMed Central

    Merz, Andrea L.; Dechkovskaia, Anjelika M.; Herring, Matthew; Winston, Benjamin A.; Lencioni, Alex M.; Russell, Rae L.; Madsen, Helen; Nega, Meheret; Dusto, Nathaniel L.; White, Jason; Bigner, Darell D.; Nicchitta, Christopher V.; Serkova, Natalie J.; Graner, Michael W.

    2013-01-01

    The unfolded protein response (UPR) is an endoplasmic reticulum (ER)-based cytoprotective mechanism acting to prevent pathologies accompanying protein aggregation. It is frequently active in tumors, but relatively unstudied in gliomas. We hypothesized that UPR stress effects on glioma cells might protect tumors from additional exogenous stress (ie, chemotherapeutics), postulating that protection was concurrent with altered tumor cell metabolism. Using human brain tumor cell lines, xenograft tumors, human samples and gene expression databases, we determined molecular features of glioma cell UPR induction/activation, and here report a detailed analysis of UPR transcriptional/translational/metabolic responses. Immunohistochemistry, Western and Northern blots identified elevated levels of UPR transcription factors and downstream ER chaperone targets in gliomas. Microarray profiling revealed distinct regulation of stress responses between xenograft tumors and parent cell lines, with gene ontology and network analyses linking gene expression to cell survival and metabolic processes. Human glioma samples were examined for levels of the ER chaperone GRP94 by immunohistochemistry and for other UPR components by Western blotting. Gene and protein expression data from patient gliomas correlated poor patient prognoses with increased expression of ER chaperones, UPR target genes, and metabolic enzymes (glycolysis and lipogenesis). NMR-based metabolomic studies revealed increased metabolic outputs in glucose uptake with elevated glycolytic activity as well as increased phospholipid turnover. Elevated levels of amino acids, antioxidants, and cholesterol were also evident upon UPR stress; in particular, recurrent tumors had overall higher lipid outputs and elevated specific UPR arms. Clonogenicity studies following temozolomide treatment of stressed or unstressed cells demonstrated UPR-induced chemoresistance. Our data characterize the UPR in glioma cells and human tumors, and

  5. Induction of the unfolded protein response drives enhanced metabolism and chemoresistance in glioma cells.

    PubMed

    Epple, Laura M; Dodd, Rebecca D; Merz, Andrea L; Dechkovskaia, Anjelika M; Herring, Matthew; Winston, Benjamin A; Lencioni, Alex M; Russell, Rae L; Madsen, Helen; Nega, Meheret; Dusto, Nathaniel L; White, Jason; Bigner, Darell D; Nicchitta, Christopher V; Serkova, Natalie J; Graner, Michael W

    2013-01-01

    The unfolded protein response (UPR) is an endoplasmic reticulum (ER)-based cytoprotective mechanism acting to prevent pathologies accompanying protein aggregation. It is frequently active in tumors, but relatively unstudied in gliomas. We hypothesized that UPR stress effects on glioma cells might protect tumors from additional exogenous stress (ie, chemotherapeutics), postulating that protection was concurrent with altered tumor cell metabolism. Using human brain tumor cell lines, xenograft tumors, human samples and gene expression databases, we determined molecular features of glioma cell UPR induction/activation, and here report a detailed analysis of UPR transcriptional/translational/metabolic responses. Immunohistochemistry, Western and Northern blots identified elevated levels of UPR transcription factors and downstream ER chaperone targets in gliomas. Microarray profiling revealed distinct regulation of stress responses between xenograft tumors and parent cell lines, with gene ontology and network analyses linking gene expression to cell survival and metabolic processes. Human glioma samples were examined for levels of the ER chaperone GRP94 by immunohistochemistry and for other UPR components by Western blotting. Gene and protein expression data from patient gliomas correlated poor patient prognoses with increased expression of ER chaperones, UPR target genes, and metabolic enzymes (glycolysis and lipogenesis). NMR-based metabolomic studies revealed increased metabolic outputs in glucose uptake with elevated glycolytic activity as well as increased phospholipid turnover. Elevated levels of amino acids, antioxidants, and cholesterol were also evident upon UPR stress; in particular, recurrent tumors had overall higher lipid outputs and elevated specific UPR arms. Clonogenicity studies following temozolomide treatment of stressed or unstressed cells demonstrated UPR-induced chemoresistance. Our data characterize the UPR in glioma cells and human tumors, and

  6. Reserve carbohydrate metabolism in Saccharomyces cerevisiae: responses to nutrient limitation.

    PubMed Central

    Lillie, S H; Pringle, J R

    1980-01-01

    The amounts of glycogen and trehalose have been measured in cells of a prototrophic diploid yeast strain subjected to a variety of nutrient limitations. Both glycogen and trehalose were accumulated in cells deprived specifically of nirogen, sulfur, or phosphorus, suggesting that reserve carbohydrate accumulation is a general response to nutrient limitation. The patterns of accumulation and utilization of glycogen and trehalose were not identical under these conditions, suggesting that the two carbohydrates may play distinct physiological roles. Glycogen and trehalose were also accumulated by cells undergoing carbon and energy limitation, both during diauxic growth in a relatively poor medium and during the approach to stationary phase in a rich medium. Growth in the rich medium was shown to be carbon or energy limited or both, although the interaction between carbon source limitation and oxygen limitation was complex. In both media, the pattern of glycogen accumulation and utilization was compatible with its serving as a source of energy both during respiratory adaptation and during a subsequent starvation. In contrast, the pattern of trehalose accumulation and utilization seemed compatible only with the latter role. In cultures that were depleting their supplies of exogenous glucose, the accumulation of glycogen began at glucose concentrations well above those sufficient to suppress glycogen accumulation in cultures growing with a constant concentration of exogenous glucose. The mechanism of this effect is not clear, but may involve a response to the rapid rate of change in the glucose concentration. PMID:6997270

  7. Role of Metabolism by Intestinal Bacteria in Arbutin-Induced Suppression of Lymphoproliferative Response in vitro.

    PubMed

    Kang, Mi Jeong; Ha, Hyun Woo; Kim, Ghee Hwan; Lee, Sang Kyu; Ahn, Young Tae; Kim, Dong Hyun; Jeong, Hye Gwang; Jeong, Tae Cheon

    2012-03-01

    Role of metabolism by intestinal bacteria in arbutin-induced immunotoxicity was investigated in splenocyte cultures. Following an incubation of arbutin with 5 different intestinal bacteria for 24 hr, its aglycone hydroquinone could be produced and detected in the bacterial culture media with different amounts. Toxic effects of activated arbutin by intestinal bacteria on lymphoproliferative response were tested in splenocyte cultures from normal mice. Lipopolysaccharide and concanavalin A were used as mitogens for B- and T-cells, respectively. When bacteria cultured medium with arbutin was treated into the splenocytes for 3 days, the medium cultured with bacteria producing large amounts of hydroquinone induced suppression of lymphoproliferative responses, indicating that metabolic activation by intestinal bacteria might be required in arbutin-induced toxicity. The results indicated that the present testing system might be applied for determining the possible role of metabolism by intestinal bacteria in certain chemical-induced immunotoxicity in animal cell cultures. PMID:24116295

  8. The Metabolic Response to Hypocaloric Protein Diets in Obese Man

    PubMed Central

    Marliss, Errol B.; Murray, Frederick T.; Nakhooda, Azima F.

    1978-01-01

    Exogenous protein in the absence of other calories can cause protein-sparing, but the mechanisms involved are controversial. It has been postulated that low insulin and high fat-derived substrate levels are necessary and sufficient conditions for such protein-sparing. We therefore established such conditions with differing protocols of protein input to define the role of protein input in mediating the response. Three groups of obese, nondiabetic subjects received the following diets: (1) 82.5±1.0 g protein/day (400 cal/day) for 21 days, n = 7; (2) the same, but as a refeeding diet for 7 days after 21-28 days of total fasts, n = 7; and (3) commencing with the same input, but with daily stepwise decrements over 14 days to 19.4±2.2 g/day, then maintained an additional 7 days, n = 4. Diet 3 gave approximately the amount and pattern of protein lost during total fasting. The circulating hormone and substrate responses of diets 1 and 3 were comparable and resembled those of total fasts, in that plasma glucose and insulin fell and free fatty acids rose. Blood levels of alanine, pyruvate, and other glucogenic amino acids fell and blood levels of branched-chain amino acids rose transiently. Blood 3-hydroxybutyrate levels and urinary excretion were greater in diet 3 than diet 1, but less than in total fasting. Nitrogen balance in diet 1 was transiently negative, but in equilibrium from 12 to 21 days. In diet 3, it was constantly negative at −6 g/day, the values also observed at 21 days of fasting. Mean 3-methylhistidine excretion decreased by 170 μmol/day in diet 1 and 107 μmol/day in diet 3, reflecting decreased muscle protein catabolism. The refed, protein-depleted subjects, diet 2, showed an increase in plasma glucose without alteration in insulin levels. Free fatty acid and ketone body levels decreased to those of the steady state observed in diet 1. Glucogenic and branched-chain amino acids decreased transiently. Nitrogen balance became positive, and the low 3

  9. Metabolic responses of two contrasting sorghums to water-deficit stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study investigated metabolic responses of the stay-green line BTx642 and the senescent line SC1211-11E to the onset of water-deficit stress in the greenhouse and field. Because of the reported differences in osmotic potential among stay-green and senescent lines we examined whether BTx642 and ...

  10. Chromium supplementation enhances the metabolic response of steers to lipopolysaccharide (LPS) challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of chromium (Cr; KemTRACE®brandChromiumProprionate 0.04%, Kemin Industries) supplementation on the metabolic response to LPS challenge was examined. Steers (n=20; 235±4 kg body weight (BW)) received a premix that added 0 (Con) or 0.2 mg/kg Cr to the total diet (DM (dry matter) basis) for ...

  11. Prenatal transportation alters the metabolic response of Brahman bull calves exposed to a lipopolysaccharide (LPS) challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine if prenatal transportation influences the metabolic response to a postnatal lipopolysaccharide (LPS) challenge. Pregnant Brahman cows (n=96) matched by age and parity were separated into transported (TRANS; n=48; transported for 2 hours on gestational day 60, 80,...

  12. Positron computed tomography studies of cerebral metabolic responses to complex motor tasks

    SciTech Connect

    Phelps, M.E.; Mazziotta, J.C.

    1984-01-01

    Human motor system organization was explored in 8 right-handed male subjects using /sup 18/F-fluorodeoxyglucose and positron computed tomography to measure cerebral glucose metabolism. Five subjects had triple studies (eyes closed) including: control (hold pen in right hand without moving), normal size writing (subject repeatedly writes name) and large (10-15 X normal) name writing. In these studies normal and large size writing had a similar distribution of metabolic responses when compared to control studies. Activations (percent change from control) were in the range of 12-20% and occurred in the striatum bilaterally > contralateral Rolandic cortex > contralateral thalamus. No significant activations were observed in the ipsilateral thalamus, Rolandic cortex or cerebellum (supplementary motor cortex was not examined). The magnitude of the metabolic response in the striatum was greater with the large versus normal sized writing. This differential response may be due to an increased number and topographic distribution of neurons responding with the same average activity between tasks or an increase in the functional activity of the same neuronal population between the two tasks (present spatial resolution inadequate to differentiate). When subjects (N=3) performed novel sequential finger movements, the maximal metabolic response was in the contralateral Rolandic cortex > striatum. Such studies provide a means of exploring human motor system organization, motor learning and provide a basis for examining patients with motor system disorders.

  13. Physiological and metabolic responses of gestating Brahaman cows to repeated transportation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to examine physiological and metabolic responses to repeated transportation of gestating Brahman cows, previously classified as mature cows into temperament groups of Calm, Intermediate, or Temperamental. Brahman cows (n = 48) were subjected to 2 hours of transport (TRA...

  14. Functional significance of metabolic responses to thermal acclimation in fish muscle.

    PubMed

    Guderley, H

    1990-08-01

    Compensatory increases of the aerobic capacity of fish swimming muscle are frequently observed in response to cold acclimation. Such thermal compensation occurs both in fish that remain active in the cold and in fish that become dormant at cold temperatures. For cold-active fish, positive thermal compensation is best explained by conservation of the capacity for aerobic metabolic flux at low temperatures. The compensatory responses of cold-active species can be used to suggest the temperature range over which the activities of glycolytic and tricarboxylic acid cycle enzymes in a muscle, i.e., the muscle's "metabolic profile," can suffice. Analysis of the available data suggests that a 16 degrees C range of temperatures cannot be covered by one metabolic profile, even when the preferred temperatures are centered between the acclimation temperatures. For cold-inactive species that remain normoxic during winter dormancy, the compensatory metabolic modifications may facilitate lipid catabolism. Alternately, an increased aerobic capacity may be adaptive during the relatively cold periods that precede and follow winter dormancy. For goldfish and carp that encounter hypoxia and anoxia during winter dormancy, increased mitochondrial abundance could facilitate ethanol production during anoxia and the diffusion of oxygen to mitochondria during hypoxia. Finally, metabolic modifications during natural acclimatization indicate both thermal compensation and direct thermal effects and suggest that thermal compensation may be masked by reproductive and feeding activities. PMID:2201217

  15. Larval starvation improves metabolic response to adult starvation in honey bees (Apis mellifera L.).

    PubMed

    Wang, Ying; Campbell, Jacob B; Kaftanoglu, Osman; Page, Robert E; Amdam, Gro V; Harrison, Jon F

    2016-04-01

    Environmental changes during development have long-term effects on adult phenotypes in diverse organisms. Some of the effects play important roles in helping organisms adapt to different environments, such as insect polymorphism. Others, especially those resulting from an adverse developmental environment, have a negative effect on adult health and fitness. However, recent studies have shown that those phenotypes influenced by early environmental adversity have adaptive value under certain (anticipatory) conditions that are similar to the developmental environment, though evidence is mostly from morphological and behavioral observations and it is still rare at physiological and molecular levels. In the companion study, we applied a short-term starvation treatment to fifth instar honey bee larvae and measured changes in adult morphology, starvation resistance, hormonal and metabolic physiology and gene expression. Our results suggest that honey bees can adaptively respond to the predicted nutritional stress. In the present study, we further hypothesized that developmental starvation specifically improves the metabolic response of adult bees to starvation instead of globally affecting metabolism under well-fed conditions. Here, we produced adult honey bees that had experienced a short-term larval starvation, then we starved them for 12 h and monitored metabolic rate, blood sugar concentrations and metabolic reserves. We found that the bees that experienced larval starvation were able to shift to other fuels faster and better maintain stable blood sugar levels during starvation. However, developmental nutritional stress did not change metabolic rates or blood sugar levels in adult bees under normal conditions. Overall, our study provides further evidence that early larval starvation specifically improves the metabolic responses to adult starvation in honey bees. PMID:27030776

  16. Odorant Metabolism Catalyzed by Olfactory Mucosal Enzymes Influences Peripheral Olfactory Responses in Rats

    PubMed Central

    Thiebaud, Nicolas; Veloso Da Silva, Stéphanie; Jakob, Ingrid; Sicard, Gilles; Chevalier, Joëlle; Ménétrier, Franck; Berdeaux, Olivier; Artur, Yves; Heydel, Jean-Marie; Le Bon, Anne-Marie

    2013-01-01

    A large set of xenobiotic-metabolizing enzymes (XMEs), such as the cytochrome P450 monooxygenases (CYPs), esterases and transferases, are highly expressed in mammalian olfactory mucosa (OM). These enzymes are known to catalyze the biotransformation of exogenous compounds to facilitate elimination. However, the functions of these enzymes in the olfactory epithelium are not clearly understood. In addition to protecting against inhaled toxic compounds, these enzymes could also metabolize odorant molecules, and thus modify their stimulating properties or inactivate them. In the present study, we investigated the in vitro biotransformation of odorant molecules in the rat OM and assessed the impact of this metabolism on peripheral olfactory responses. Rat OM was found to efficiently metabolize quinoline, coumarin and isoamyl acetate. Quinoline and coumarin are metabolized by CYPs whereas isoamyl acetate is hydrolyzed by carboxylesterases. Electro-olfactogram (EOG) recordings revealed that the hydroxylated metabolites derived from these odorants elicited lower olfactory response amplitudes than the parent molecules. We also observed that glucurono-conjugated derivatives induced no olfactory signal. Furthermore, we demonstrated that the local application of a CYP inhibitor on rat olfactory epithelium increased EOG responses elicited by quinoline and coumarin. Similarly, the application of a carboxylesterase inhibitor increased the EOG response elicited by isoamyl acetate. This increase in EOG amplitude provoked by XME inhibitors is likely due to enhanced olfactory sensory neuron activation in response to odorant accumulation. Taken together, these findings strongly suggest that biotransformation of odorant molecules by enzymes localized to the olfactory mucosa may change the odorant’s stimulating properties and may facilitate the clearance of odorants to avoid receptor saturation. PMID:23555703

  17. HexR Controls Glucose-Responsive Genes and Central Carbon Metabolism in Neisseria meningitidis

    PubMed Central

    Antunes, Ana; Golfieri, Giacomo; Ferlicca, Francesca; Giuliani, Marzia M.; Scarlato, Vincenzo

    2015-01-01

    ABSTRACT Neisseria meningitidis, an exclusively human pathogen and the leading cause of bacterial meningitis, must adapt to different host niches during human infection. N. meningitidis can utilize a restricted range of carbon sources, including lactate, glucose, and pyruvate, whose concentrations vary in host niches. Microarray analysis of N. meningitidis grown in a chemically defined medium in the presence or absence of glucose allowed us to identify genes regulated by carbon source availability. Most such genes are implicated in energy metabolism and transport, and some are implicated in virulence. In particular, genes involved in glucose catabolism were upregulated, whereas genes involved in the tricarboxylic acid cycle were downregulated. Several genes encoding surface-exposed proteins, including the MafA adhesins and Neisseria surface protein A, were upregulated in the presence of glucose. Our microarray analysis led to the identification of a glucose-responsive hexR-like transcriptional regulator that controls genes of the central carbon metabolism of N. meningitidis in response to glucose. We characterized the HexR regulon and showed that the hexR gene is accountable for some of the glucose-responsive regulation; in vitro assays with the purified protein showed that HexR binds to the promoters of the central metabolic operons of the bacterium. Based on DNA sequence alignment of the target sites, we propose a 17-bp pseudopalindromic consensus HexR binding motif. Furthermore, N. meningitidis strains lacking hexR expression were deficient in establishing successful bacteremia in an infant rat model of infection, indicating the importance of this regulator for the survival of this pathogen in vivo. IMPORTANCE Neisseria meningitidis grows on a limited range of nutrients during infection. We analyzed the gene expression of N. meningitidis in response to glucose, the main energy source available in human blood, and we found that glucose regulates many genes

  18. Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses.

    PubMed

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-09-01

    Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle microvascular recruitment. We demonstrated that a high-fat diet induces vascular adiponectin and insulin resistance but globular adiponectin administration can restore vascular insulin responses and improve insulin's metabolic action via an AMPK- and nitric oxide-dependent mechanism. This suggests that globular adiponectin might have a therapeutic potential for improving insulin resistance and preventing cardiovascular complications in patients with diabetes via modulation of microvascular insulin responses. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague-Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by

  19. Macroautophagy and Cell Responses Related to Mitochondrial Dysfunction, Lipid Metabolism and Unconventional Secretion of Proteins

    PubMed Central

    Demine, Stéphane; Michel, Sébastien; Vannuvel, Kayleen; Wanet, Anaïs; Renard, Patricia; Arnould, Thierry

    2012-01-01

    Macroautophagy has important physiological roles and its cytoprotective or detrimental function is compromised in various diseases such as many cancers and metabolic diseases. However, the importance of autophagy for cell responses has also been demonstrated in many other physiological and pathological situations. In this review, we discuss some of the recently discovered mechanisms involved in specific and unspecific autophagy related to mitochondrial dysfunction and organelle degradation, lipid metabolism and lipophagy as well as recent findings and evidence that link autophagy to unconventional protein secretion. PMID:24710422

  20. Metabolic Communication between Astrocytes and Neurons via Bicarbonate-Responsive Soluble Adenylyl Cyclase

    PubMed Central

    Choi, Hyun B.; Gordon, Grant R.J.; Zhou, Ning; Tai, Chao; Rungta, Ravi L.; Martinez, Jennifer; Milner, Teresa A.; Ryu, Jae K.; McLarnon, James G.; Tresguerres, Martin; Levin, Lonny R.; Buck, Jochen; MacVicar, Brian A.

    2013-01-01

    SUMMARY Astrocytes are proposed to participate in brain energy metabolism by supplying substrates to neurons from their glycogen stores and from glycolysis. However, the molecules involved in metabolic sensing and the molecular pathways responsible for metabolic coupling between different cell types in the brain are not fully understood. Here we show that a recently cloned bicarbonate (HCO3−) sensor, soluble adenylyl cyclase (sAC), is highly expressed in astrocytes and becomes activated in response to HCO3− entry via the electrogenic NaHCO3 cotransporter (NBC). Activated sAC increases intracellular cAMP levels, causing glycogen breakdown, enhanced glycolysis, and the release of lactate into the extracellular space, which is subsequently taken up by neurons for use as an energy substrate. This process is recruited over a broad physiological range of [K+]ext and also during aglycemic episodes, helping to maintain synaptic function. These data reveal a molecular pathway in astrocytes that is responsible for brain metabolic coupling to neurons. PMID:22998876

  1. Comparative Proteomics Provides Insights into Metabolic Responses in Rat Liver to Isolated Soy and Meat Proteins.

    PubMed

    Song, Shangxin; Hooiveld, Guido J; Zhang, Wei; Li, Mengjie; Zhao, Fan; Zhu, Jing; Xu, Xinglian; Muller, Michael; Li, Chunbao; Zhou, Guanghong

    2016-04-01

    It has been reported that isolated dietary soy and meat proteins have distinct effects on physiology and liver gene expression, but the impact on protein expression responses are unknown. Because these may differ from gene expression responses, we investigated dietary protein-induced changes in liver proteome. Rats were fed for 1 week semisynthetic diets that differed only regarding protein source; casein (reference) was fully replaced by isolated soy, chicken, fish, or pork protein. Changes in liver proteome were measured by iTRAQ labeling and LC-ESI-MS/MS. A robust set totaling 1437 unique proteins was identified and subjected to differential protein analysis and biological interpretation. Compared with casein, all other protein sources reduced the abundance of proteins involved in fatty acid metabolism and Pparα signaling pathway. All dietary proteins, except chicken, increased oxidoreductive transformation reactions but reduced energy and essential amino acid metabolic pathways. Only soy protein increased the metabolism of sulfur-containing and nonessential amino acids. Soy and fish proteins increased translation and mRNA processing, whereas only chicken protein increased TCA cycle but reduced immune responses. These findings were partially in line with previously reported transcriptome results. This study further shows the distinct effects of soy and meat proteins on liver metabolism in rats. PMID:26886706

  2. Failure of Hyperglycemia and Hyperinsulinemia to Compensate for Impaired Metabolic Response to an Oral Glucose Load

    PubMed Central

    Hussain, M; Janghorbani, M; Schuette, S; Considine, RV; Chisholm, RL; Mather, KJ

    2014-01-01

    Objective To evaluate whether the augmented insulin and glucose response to a glucose challenge is sufficient to compensate for defects in glucose utilization in obesity and type 2 diabetes, using a breath test measurement of integrated glucose metabolism. Methods Non-obese, obese normoglycemic and obese Type 2 diabetic subjects were studied on 2 consecutive days. A 75g oral glucose load spiked with 13C-glucose was administered, measuring exhaled breath 13CO2 as an integrated measure of glucose metabolism and oxidation. A hyperinsulinemic euglycemic clamp was performed, measuring whole body glucose disposal rate. Body composition was measured by DEXA. Multivariable analyses were performed to evaluate the determinants of the breath 13CO2. Results Breath 13CO2 was reduced in obese and type 2 diabetic subjects despite hyperglycemia and hyperinsulinemia. The primary determinants of breath response were lean mass, fat mass, fasting FFA concentrations, and OGTT glucose excursion. Multiple approaches to analysis showed that hyperglycemia and hyperinsulinemia were not sufficient to compensate for the defect in glucose metabolism in obesity and diabetes. Conclusions Augmented insulin and glucose responses during an OGTT are not sufficient to overcome the underlying defects in glucose metabolism in obesity and diabetes. PMID:25511878

  3. Sexually dimorphic myeloid inflammatory and metabolic responses to diet-induced obesity.

    PubMed

    Griffin, C; Lanzetta, N; Eter, L; Singer, K

    2016-08-01

    It is well known in clinical and animal studies that women and men have different disease risk as well as different disease physiology. Women of reproductive age are protected from metabolic and cardiovascular disease compared with postmenopausal women and men. Most murine studies are skewed toward the use of male mice to study obesity-induced metabolic dysfunction because of similar protection in female mice. We have investigated dietary obesity in a mouse model and have directly compared inflammatory responses in males and females. In this review we will summarize what is known about sex differences in diet-induced inflammation and will summarize our data on this topic. It is clear that sex differences in high-fat diet-induced inflammatory activation are due to cell intrinsic differences in hematopoietic responses to obesogenic cues, but further research is needed to understand what leads to sexually dimorphic responses. PMID:27252473

  4. Interplay between cold-responsive gene regulation, metabolism and RNA processing during plant cold acclimation.

    PubMed

    Zhu, Jianhua; Dong, Chun-Hai; Zhu, Jian-Kang

    2007-06-01

    Temperate plants are capable of developing freezing tolerance when they are exposed to low nonfreezing temperatures. Acquired freezing tolerance involves extensive reprogramming of gene expression and metabolism. Recent full-genome transcript profiling studies, in combination with mutational and transgenic plant analyses, have provided a snapshot of the complex transcriptional network that operates under cold stress. Ubiquitination-mediated proteosomal protein degradation has a crucial role in regulating one of the upstream transcription factors, INDUCER OF CBF EXPRESSION 1 (ICE1), and thus in controlling the cold-responsive transcriptome. The changes in expression of hundreds of genes in response to cold temperatures are followed by increases in the levels of hundreds of metabolites, some of which are known to have protective effects against the damaging effects of cold stress. Genetic analysis has revealed important roles for cellular metabolic signals, and for RNA splicing, export and secondary structure unwinding, in regulating cold-responsive gene expression and chilling and freezing tolerance. PMID:17468037

  5. Gender-specific metabolic responses in hepatopancreas of mussel Mytilus galloprovincialis challenged by Vibrio harveyi.

    PubMed

    Liu, Xiaoli; Sun, Hushan; Wang, Yiyan; Ma, Mengwen; Zhang, Yuemei

    2014-10-01

    Mussel Mytilus galloprovincialis is a marine aquaculture shellfish and frequently studied in shellfish immunology. In this work, the gender-specific metabolic responses induced by Vibrio harveyi in hepatopancreas from M. galloprovincialis were characterized using NMR-based metabolomics. In details, V. harveyi challenge increased the levels of amino acids including (valine, leucine, isoleucine, threonine, alanine, arginine and tyrosine) and ATP, and decreased the level of glucose in male mussel hepatopancreas. In V. harveyi-challenged female mussel hepatopancreas, both threonine and AMP were significantly elevated, and choline, phoshphocholine, sn-glycero-3-phosphocholine, taurine, betaine and ATP were depleted. Obviously, only threonine was similarly altered to that in V. harveyi-challenged male mussel hepatopancreas. These findings confirmed the gender-specific metabolic responses in mussels challenged by V. harveyi. Overall, V. harveyi induced an enhanced energy demand through activated glycolysis and immune response indicated by increased BCAAs in male mussel hepatopancreas. In female mussel hepatopancreas, V. harveyi basically caused disturbances in both osmotic regulation and energy metabolism through the metabolic pathways of conversions of phosphocholine and ADP to choline and ATP, and sn-glycero-3-phosphocholine and H2O into choline and sn-glycerol 3-phosphate. The altered mRNA expression levels of related genes (Cu/Zn-SOD, HSP90, lysozyme and defensin) suggested that V. harveyi induced obvious oxidative and immune stresses in both male and female mussel hepatopancreas. This work demonstrated that V. harveyi could induce gender-specific metabolic responses in mussel M. galloprovincialis hepatopancreas using NMR-based metabolomics. PMID:25123832

  6. Metabolic history impacts mammary tumor epithelial hierarchy and early drug response in mice.

    PubMed

    Montales, Maria Theresa E; Melnyk, Stepan B; Liu, Shi J; Simmen, Frank A; Liu, Y Lucy; Simmen, Rosalia C M

    2016-09-01

    The emerging links between breast cancer and metabolic dysfunctions brought forth by the obesity pandemic predict a disproportionate early disease onset in successive generations. Moreover, sensitivity to chemotherapeutic agents may be influenced by the patient's metabolic status that affects the disease outcome. Maternal metabolic stress as a determinant of drug response in progeny is not well defined. Here, we evaluated mammary tumor response to doxorubicin in female mouse mammary tumor virus-Wnt1 transgenic offspring exposed to a metabolically compromised environment imposed by maternal high-fat diet. Control progeny were from dams consuming diets with regular fat content. Maternal high-fat diet exposure increased tumor incidence and reduced tumor latency but did not affect tumor volume response to doxorubicin, compared with control diet exposure. However, doxorubicin-treated tumors from high-fat-diet-exposed offspring demonstrated higher proliferation status (Ki-67), mammary stem cell-associated gene expression (Notch1, Aldh1) and basal stem cell-like (CD29(hi)CD24(+)) epithelial subpopulation frequencies, than tumors from control diet progeny. Notably, all epithelial subpopulations (CD29(hi)CD24(+), CD29(lo)CD24(+), CD29(hi)CD24(+)Thy1(+)) in tumors from high-fat-diet-exposed offspring were refractory to doxorubicin. Further, sera from high-fat-diet-exposed offspring promoted sphere formation of mouse mammary tumor epithelial cells and of human MCF7 cells. Untargeted metabolomics analyses identified higher levels of kynurenine and 2-hydroxyglutarate in plasma of high-fat diet than control diet offspring. Kynurenine/doxorubicin co-treatment of MCF7 cells enhanced the ability to form mammosphere and decreased apoptosis, relative to doxorubicin-only-treated cells. Maternal metabolic dysfunctions during pregnancy and lactation may be targeted to reduce breast cancer risk and improve early drug response in progeny, and may inform clinical management of disease

  7. Quantitative H2S-mediated protein sulfhydration reveals metabolic reprogramming during the integrated stress response

    PubMed Central

    Gao, Xing-Huang; Krokowski, Dawid; Guan, Bo-Jhih; Bederman, Ilya; Majumder, Mithu; Parisien, Marc; Diatchenko, Luda; Kabil, Omer; Willard, Belinda; Banerjee, Ruma; Wang, Benlian; Bebek, Gurkan; Evans, Charles R.; Fox, Paul L.; Gerson, Stanton L.; Hoppel, Charles L.; Liu, Ming; Arvan, Peter; Hatzoglou, Maria

    2015-01-01

    The sulfhydration of cysteine residues in proteins is an important mechanism involved in diverse biological processes. We have developed a proteomics approach to quantitatively profile the changes of sulfhydrated cysteines in biological systems. Bioinformatics analysis revealed that sulfhydrated cysteines are part of a wide range of biological functions. In pancreatic β cells exposed to endoplasmic reticulum (ER) stress, elevated H2S promotes the sulfhydration of enzymes in energy metabolism and stimulates glycolytic flux. We propose that transcriptional and translational reprogramming by the integrated stress response (ISR) in pancreatic β cells is coupled to metabolic alternations triggered by sulfhydration of key enzymes in intermediary metabolism. DOI: http://dx.doi.org/10.7554/eLife.10067.001 PMID:26595448

  8. Role of Glucocorticoids in the Response to Unloading of Muscle Protein and Amino Acid Metabolism

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.; Jaspers, S. R.

    1985-01-01

    Intact control (weight bearing) and suspended rats gained weight at a similar rate during a 6 day period. Adrenaectomized (adx) weight bearing rats gained less weight during this period while adrenalectomized suspended rats showed no significant weight gain. Cortisol treatment of both of these groups of animals caused a loss of body weight. Results from these studies show several important findings: (1) Metabolic changes in the extensor digitorum longus muscle of suspended rats are due primarily to increased circulating gluccorticoids; (2) Metabolic changes in the soleus due to higher steroid levels are probably potentiated by greater numbers of receptors; and (3) Not all metabolic responses in the unloaded soleus muscle are due to direct action of elevated glucocorticoids or increased sensitivity to these hormones.

  9. Quantitative PET imaging of bone marrow glucose metabolic response to hematopoietic cytokines

    SciTech Connect

    Yao, W.J.; Hoh, C.K.; Hawkins, R.A.

    1995-05-01

    To evaluate the effects of hematopoietic cytokines on bone marrow glucose metabolism noninvasively, the authors studied serial quantitative FDG-PET images in 18 patients with metastic melanoma and normal bone marrow who were undergoing granulocyte-macrophage colony-stimulating factor (GMCSF) or macrophage colony-stimulating factor (MCSF) administration as an adjunct to chemotherapy. All patients received 14 days of cytokine therapy in three groups; four patients were treated with GMCSF (5 {mu}g/kg/d SQ), eight patients were treated with GMCSF (5 {mu}g/kg/d SQ) and monoclonal antibody (MAbR24) and six patients were treated with MCSF (80 {mu}g/kg/d IVCI) and MAbR24. Dynamic FDG-PET imaging was performed over the lower thoracic or upper lumbar spine at four time points in each patient. Baseline glucose metabolic rates in the bone marrow of these three groups of patients were similar (5.2 {plus_minus} 0.7, 4.4 {plus_minus} 0.8 and 4.8 {plus_minus} 1.2 {mu}g/min/g as mean value and standard deviations, respectively). In both GMCSF and GMCSF + R24 groups, rapid increases in bone marrow glucose metabolic rates were observed during therapy. After GMCSF was stopped, bone marrow glucose metabolic rates rapdily decreased in both groups. The glucose metabolic response in these two groups was not significantly different by pooled t-statistics (p = 0.105). In the MCSF + R24 group, the increase of glucose metabolic rate on Days 3 and 10 was 35% and 31% above baseline on the average, but was not significant. The results support the use of parametric FDG-PET imaging for noninvasive quantitation of bone marrow glucose metabolic changes to hematopoietic cytokines in vivo. 32 refs., 2 figs., 2 tabs.

  10. CK2 inhibition induced PDK4-AMPK axis regulates metabolic adaptation and survival responses in glioma.

    PubMed

    Dixit, Deobrat; Ahmad, Fahim; Ghildiyal, Ruchi; Joshi, Shanker Datt; Sen, Ellora

    2016-05-15

    Understanding mechanisms that link aberrant metabolic adaptation and pro-survival responses in glioma cells is crucial towards the development of new anti-glioma therapies. As we have previously reported that CK2 is associated with glioma cell survival, we evaluated its involvement in the regulation of glucose metabolism. Inhibition of CK2 increased the expression of metabolic regulators, PDK4 and AMPK along with the key cellular energy sensor CREB. This increase was concomitant with altered metabolic profile as characterized by decreased glucose uptake in a PDK4 and AMPK dependent manner. Increased PDK4 expression was CREB dependent, as exogenous inhibition of CREB functions abrogated CK2 inhibitor mediated increase in PDK4 expression. Interestingly, PDK4 regulated AMPK phosphorylation which in turn affected cell viability in CK2 inhibitor treated glioma cells. CK2 inhibitor 4,5,6,7-Tetrabromobenzotriazole (TBB) significantly retarded the growth of glioma xenografts in athymic nude mouse model. Coherent with the in vitro findings, elevated senescence, pAMPK and PDK4 levels were also observed in TBB-treated xenograft tissue. Taken together, CK2 inhibition in glioma cells drives the PDK4-AMPK axis to affect metabolic profile that has a strong bearing on their survival. PMID:27001465

  11. Metabolic responses to fasting and refeeding in lean and genetically obese rats.

    PubMed

    Rothwell, N J; Saville, M E; Stock, M J

    1983-05-01

    Injection of norepinephrine (NE) (25 micrograms/100 g body wt) caused a similar rise in metabolic rate in lean and obese (fa/fa) Zucker rats, but 3-day fasting suppressed the response in lean rats and enhanced the rise in obese mutants. Triiodothyronine (T3) injection (10 micrograms/100 g body wt) caused a significantly greater rise in oxygen consumption (Vo2) in obese than lean rats, but the response was attenuated by fasting in all animals. The thermic response to a single meal of either mixed composition, carbohydrate, or protein (40 kJ) was much smaller in obese rats than lean, but the response to the mixed nutrient meal was similar for all rats after a 3-day fast. Refeeding 3-day fasted lean rats with a single carbohydrate meal (40 kJ) caused a rise in plasma T3 levels after 3 h and a delayed increase in metabolic rate 24 h later. Injection of NE instead of refeeding caused a similar delayed rise in metabolic rate. Carbohydrate refeeding had no effect on plasma T3 levels or oxygen consumption in 3-day fasted obese Zuckers, but injection of NE did produce a significant increase in metabolic rate after 24 h. Refeeding 3-day fasted rats with protein (40 kJ) caused a rise in oxygen consumption 24 h later in lean animals but had no effect in obese animals. The data from lean Zucker rats confirm previous findings in Sprague-Dawley rats and suggest that the thermic response to refeeding involves a complex interaction between the sympathetic nervous system and thyroid hormones. Obese Zuckers responded normally to NE and T3, indicating that their reduced thermogenesis after food may be due to insensitivity to nutrient availability or an inability to activate the sympathetic nervous system. PMID:6846570

  12. Application of the Key Events Dose-response Framework to Folate Metabolism.

    PubMed

    Hu, Jing; Wang, Bing; Sahyoun, Nadine R

    2016-06-10

    Folate is a vitamin that plays a role as a cofactor and coenzyme in many essential reactions. These reactions are interrelated and any change in folate homeostasis could affect other reactions. With food fortified with folic acid, and use of multivitamin, unmetabolized folic acid (UMFA) has been detected in blood circulation, particularly among older adults. This has raised concern about the potential harmful effect of high folic acid intake and UMFA on health conditions such as cognitive dysfunction and cancer. To examine what is known about folate metabolism and the release of circulating UMFA, the Key Events Dose-Response Framework (KEDRF) was used to review each of the major key events, dose-response characteristics and homeostatic mechanisms of folate metabolism. The intestine, liver and kidneys each play essential roles in regulating body folate homeostasis. But the determining event in folate metabolism leading to the release of UMFA in circulation appears to be the saturation of dihydrofolate reductase in the liver. However, at each of the key events in folate metabolism, limited information is available on threshold, homeostatic regulation and intracellular effects of folic acid. More studies are needed to fill in the knowledge gaps for quantitatively characterizing the dose-effect relationship especially in light of the call for extending folate fortification to other foods. PMID:25674817

  13. Sex differences in metabolic and adipose tissue responses to juvenile-onset obesity in sheep.

    PubMed

    Bloor, Ian D; Sébert, Sylvain P; Saroha, Vivek; Gardner, David S; Keisler, Duane H; Budge, Helen; Symonds, Michael E; Mahajan, Ravi P

    2013-10-01

    Sex is a major factor determining adipose tissue distribution and the subsequent adverse effects of obesity-related disease including type 2 diabetes. The role of gender on juvenile obesity and the accompanying metabolic and inflammatory responses is not well established. Using an ovine model of juvenile onset obesity induced by reduced physical activity, we examined the effect of gender on metabolic, circulatory, and related inflammatory and energy-sensing profiles of the major adipose tissue depots. Despite a similar increase in fat mass with obesity between genders, males demonstrated a higher storage capacity of lipids within perirenal-abdominal adipocytes and exhibited raised insulin. In contrast, obese females became hypercortisolemic, a response that was positively correlated with central fat mass. Analysis of gene expression in perirenal-abdominal adipose tissue demonstrated the stimulation of inflammatory markers in males, but not females, with obesity. Obese females displayed increased expression of genes involved in the glucocorticoid axis and energy sensing in perirenal-abdominal, but not omental, adipose tissue, indicating a depot-specific mechanism that may be protective from the adverse effects of metabolic dysfunction and inflammation. In conclusion, young males are at a greater risk than females to the onset of comorbidities associated with juvenile-onset obesity. These sex-specific differences in cortisol and adipose tissue could explain the earlier onset of the metabolic-related diseases in males compared with females after obesity. PMID:23885012

  14. Divergent metabolic responses of Apostichopus japonicus suffered from skin ulceration syndrome and pathogen challenge.

    PubMed

    Shao, Yina; Li, Chenghua; Ou, Changrong; Zhang, Peng; Lu, Yali; Su, Xiurong; Li, Ye; Li, Taiwu

    2013-11-13

    Skin ulceration syndrome (SUS) is the main limitation in the development of Apostichopus japonicus culture industries, in which Vibrio splendidus has been well documented as one of the major pathogens. However, the intrinsic mechanisms toward pathogen challenge and disease outbreak remain largely unknown at the metabolic level. In this work, the metabolic responses were investigated in muscles of sea cucumber among natural SUS-diseased and V. splendidus-challenged samples. The pathogen did not induce obvious biological effects in A. japonicus samples after infection for the first 24 h. An enhanced energy storage (or reduced energy demand) and immune responses were observed in V. splendidus-challenged A. japonicus samples at 48 h, as marked by increased glucose and branched chain amino acids, respectively. Afterward, infection of V. splendidus induced significant increases in energy demand in A. japonicus samples at both 72 and 96 h, confirmed by decreased glucose and glycogen, and increased ATP. Surprisingly, high levels of glycogen and glucose and low levels of threonine, alanine, arginine, glutamate, glutamine, taurine and ATP were founded in natural SUS-diseased sea cucumber. Our present results provided essential metabolic information about host-pathogen interaction for sea cucumber, and informed that the metabolic biomarkers induced by V. splendidus were not usable for the prediction of SUS disease in practice. PMID:24127639

  15. PTRF/Cavin-1 promotes efficient ribosomal RNA transcription in response to metabolic challenges.

    PubMed

    Liu, Libin; Pilch, Paul F

    2016-01-01

    Ribosomal RNA transcription mediated by RNA polymerase I represents the rate-limiting step in ribosome biogenesis. In eukaryotic cells, nutrients and growth factors regulate ribosomal RNA transcription through various key factors coupled to cell growth. We show here in mature adipocytes, ribosomal transcription can be acutely regulated in response to metabolic challenges. This acute response is mediated by PTRF (polymerase I transcription and release factor, also known as cavin-1), which has previously been shown to play a critical role in caveolae formation. The caveolae-independent rDNA transcriptional role of PTRF not only explains the lipodystrophy phenotype observed in PTRF deficient mice and humans, but also highlights its crucial physiological role in maintaining adipocyte allostasis. Multiple post-translational modifications of PTRF provide mechanistic bases for its regulation. The role of PTRF in ribosomal transcriptional efficiency is likely relevant to many additional physiological situations of cell growth and organismal metabolism. PMID:27528195

  16. Mitochondrial Functional Impairment in Response to Environmental Toxins in the Cardiorenal Metabolic Syndrome

    PubMed Central

    Jia, Guanghong; Aroor, Annayya R.; Martinez-Lemus, Luis A.; Sowers, James R.

    2015-01-01

    Environmental toxins can promote cardiovascular, metabolic and renal abnormalities, which characterize the cardiorenal metabolic syndrome (CRS). Heavy metals, such as mercury and arsenic, represent two of the most toxic pollutants. Exposure to these toxins is increasing due to increased industrialization throughout much of the world. Studies conducted to understand the impact of environmental toxins have shown a major impact on mitochondrial structure and function. The maladaptive adaptive stress products caused by these toxins, including aggregated proteins, damaged organelles, and intracellular pathogens, can be removed through autophagy, which is also known as mitophagy in mitochondria. Although the underlying mechanisms involved in the regulation of mitophagy in response to pollution are not well understood, accumulating evidence supports a role for maladaptive mitochondrial responses to environmental pollution in the pathogenesis of the CRS. In this review, we discuss ongoing research, which explores the mechanisms by which these toxins promote abnormalities in mitophagy and associated mitochondrial dysfunction and the CRS. PMID:25559775

  17. Heat-shock response in Arabidopsis thaliana explored by multiplexed quantitative proteomics using differential metabolic labeling.

    PubMed

    Palmblad, Magnus; Mills, Davinia J; Bindschedler, Laurence V

    2008-02-01

    We have developed a general method for multiplexed quantitative proteomics using differential metabolic stable isotope labeling and mass spectrometry. The method was successfully used to study the dynamics of heat-shock response in Arabidopsis thaliana. A number of known heat-shock proteins were confirmed, and some proteins not previously associated with heat shock were discovered. The method is applicable in stable isotope labeling and allows for high degrees of multiplexing. PMID:18189342

  18. Phosphate-responsive signaling pathway is a novel component of NAD+ metabolism in Saccharomyces cerevisiae.

    PubMed

    Lu, Shu-Ping; Lin, Su-Ju

    2011-04-22

    Nicotinamide adenine dinucleotide (NAD(+)) is an essential cofactor involved in various cellular biochemical reactions. To date the signaling pathways that regulate NAD(+) metabolism remain unclear due to the dynamic nature and complexity of the NAD(+) metabolic pathways and the difficulty of determining the levels of the interconvertible pyridine nucleotides. Nicotinamide riboside (NmR) is a key pyridine metabolite that is excreted and re-assimilated by yeast and plays important roles in the maintenance of NAD(+) pool. In this study we establish a NmR-specific reporter system and use it to identify yeast mutants with altered NmR/NAD(+) metabolism. We show that the phosphate-responsive signaling (PHO) pathway contributes to control NAD(+) metabolism. Yeast strains with activated PHO pathway show increases in both the release rate and internal concentration of NmR. We further identify Pho8, a PHO-regulated vacuolar phosphatase, as a potential NmR production factor. We also demonstrate that Fun26, a homolog of human ENT (equilibrative nucleoside transporter), localizes to the vacuolar membrane and establishes the size of the vacuolar and cytosolic NmR pools. In addition, the PHO pathway responds to depletion of cellular nicotinic acid mononucleotide (NaMN) and mediates nicotinamide mononucleotide (NMN) catabolism, thereby contributing to both NmR salvage and phosphate acquisition. Therefore, NaMN is a putative molecular link connecting the PHO signaling and NAD(+) metabolic pathways. Our findings may contribute to the understanding of the molecular basis and regulation of NAD(+) metabolism in higher eukaryotes. PMID:21349851

  19. Biological and metabolic response in STS-135 space-flown mouse skin.

    PubMed

    Mao, X W; Pecaut, M J; Stodieck, L S; Ferguson, V L; Bateman, T A; Bouxsein, M L; Gridley, D S

    2014-08-01

    There is evidence that space flight condition-induced biological damage is associated with increased oxidative stress and extracellular matrix (ECM) remodeling. To explore possible mechanisms, changes in gene expression profiles implicated in oxidative stress and in ECM remodeling in mouse skin were examined after space flight. The metabolic effects of space flight in skin tissues were also characterized. Space Shuttle Atlantis (STS-135) was launched at the Kennedy Space Center on a 13-day mission. Female C57BL/6 mice were flown in the STS-135 using animal enclosure modules (AEMs). Within 3-5 h after landing, the mice were euthanized and skin samples were harvested for gene array analysis and metabolic biochemical assays. Many genes responsible for regulating production and metabolism of reactive oxygen species (ROS) were significantly (p < 0.05) altered in the flight group, with fold changes >1.5 compared to AEM control. For ECM profile, several genes encoding matrix and metalloproteinases involved in ECM remodeling were significantly up-/down-regulated following space flight. To characterize the metabolic effects of space flight, global biochemical profiles were evaluated. Of 332 named biochemicals, 19 differed significantly (p < 0.05) between space flight skin samples and AEM ground controls, with 12 up-regulated and 7 down-regulated including altered amino acid, carbohydrate metabolism, cell signaling, and transmethylation pathways. Collectively, the data demonstrated that space flight condition leads to a shift in biological and metabolic homeostasis as the consequence of increased regulation in cellular antioxidants, ROS production, and tissue remodeling. This indicates that astronauts may be at increased risk for pathophysiologic damage or carcinogenesis in cutaneous tissue. PMID:24796731

  20. Metabolic Response of the Cerebral Cortex Following Gentle Sleep Deprivation and Modafinil Administration

    PubMed Central

    Petit, Jean-Marie; Tobler, Irene; Kopp, Caroline; Morgenthaler, Florence; Borbély, Alexander A.; Magistretti, Pierre J.

    2010-01-01

    Study Objectives: The main energy reserve of the brain is glycogen, which is almost exclusively localized in astrocytes. We previously reported that cerebral expression of certain genes related to glycogen metabolism changed following instrumental sleep deprivation in mice. Here, we extended our investigations to another set of genes related to glycogen and glucose metabolism. We also compared the effect of instrumentally and pharmacologically induced prolonged wakefulness, followed (or not) by 3 hours of sleep recovery, on the expression of genes related to brain energy metabolism. Design: Sleep deprivation for 6–7 hours. Setting: Animal sleep research laboratory. Participants: Adults OF1 mice. Interventions: Wakefulness was maintained by “gentle sleep deprivation” method (GSD) or by administration of the wakefulness-promoting drug modafinil (MOD) (200 mg/kg i.p.). Measurements and Results: Levels of mRNAs encoding proteins related to energy metabolism were measured by quantitative real-time PCR in the cerebral cortex. The mRNAs encoding protein targeting to glycogen (PTG) and the glial glucose transporter were significantly increased following both procedures used to prolong wakefulness. Glycogenin mRNA levels were increased only after GSD, while neuronal glucose transporter mRNA only after MOD. These effects were reversed after sleep recovery. A significant enhancement of glycogen synthase activity without any changes in glycogen levels was observed in both conditions. Conclusions: These results indicate the existence of a metabolic adaptation of astrocytes aimed at maintaining brain energy homeostasis during the sleep-wake cycle. Citation: Petit, JM; Tobler I; Kopp C; Morgenthaler F; Borbély AA; Magistretti PJ. Metabolic response of the cerebral cortex following gentle sleep deprivation and modafinil administration. SLEEP 2010;33(7):901–908. PMID:20614850

  1. Effect of carbon on whole-biofilm metabolic response to high doses of streptomycin.

    PubMed

    Jackson, Lindsay M D; Kroukamp, Otini; Wolfaardt, Gideon M

    2015-01-01

    Biofilms typically exist as complex communities comprising multiple species with the ability to adapt to a variety of harsh conditions. In clinical settings, antibiotic treatments based on planktonic susceptibility tests are often ineffective against biofilm infections. Using a CO2 evolution measurement system we delineated the real-time metabolic response in continuous flow biofilms to streptomycin doses much greater than their planktonic susceptibilities. Stable biofilms from a multispecies culture (containing mainly Pseudomonas aeruginosa and Stenotrophomonas maltophilia), Gram-negative environmental isolates, and biofilms formed by pure culture P. aeruginosa strains PAO1 and PAO1 ΔMexXY (minimum planktonic inhibitory concentrations between 1.5 and 3.5 mg/l), were exposed in separate experiments to 4000 mg/l streptomycin for 4 h after which growth medium resumed. In complex medium, early steady state multispecies biofilms were susceptible to streptomycin exposure, inferred by a cessation of CO2 production. However, multispecies biofilms survived high dose exposures when there was extra carbon in the antibiotic medium, or when they were grown in defined citrate medium. The environmental isolates and PAO1 biofilms showed similar metabolic profiles in response to streptomycin; ceasing CO2 production after initial exposure, with CO2 levels dropping toward baseline levels prior to recovery back to steady state levels, while subsequent antibiotic exposure elicited increased CO2 output. Monitoring biofilm metabolic response in real-time allowed exploration of conditions resulting in vulnerability after antibiotic exposure compared to the resistance displayed following subsequent exposures. PMID:26441887

  2. Effect of carbon on whole-biofilm metabolic response to high doses of streptomycin

    PubMed Central

    Jackson, Lindsay M. D.; Kroukamp, Otini; Wolfaardt, Gideon M.

    2015-01-01

    Biofilms typically exist as complex communities comprising multiple species with the ability to adapt to a variety of harsh conditions. In clinical settings, antibiotic treatments based on planktonic susceptibility tests are often ineffective against biofilm infections. Using a CO2 evolution measurement system we delineated the real-time metabolic response in continuous flow biofilms to streptomycin doses much greater than their planktonic susceptibilities. Stable biofilms from a multispecies culture (containing mainly Pseudomonas aeruginosa and Stenotrophomonas maltophilia), Gram-negative environmental isolates, and biofilms formed by pure culture P. aeruginosa strains PAO1 and PAO1 ΔMexXY (minimum planktonic inhibitory concentrations between 1.5 and 3.5 mg/l), were exposed in separate experiments to 4000 mg/l streptomycin for 4 h after which growth medium resumed. In complex medium, early steady state multispecies biofilms were susceptible to streptomycin exposure, inferred by a cessation of CO2 production. However, multispecies biofilms survived high dose exposures when there was extra carbon in the antibiotic medium, or when they were grown in defined citrate medium. The environmental isolates and PAO1 biofilms showed similar metabolic profiles in response to streptomycin; ceasing CO2 production after initial exposure, with CO2 levels dropping toward baseline levels prior to recovery back to steady state levels, while subsequent antibiotic exposure elicited increased CO2 output. Monitoring biofilm metabolic response in real-time allowed exploration of conditions resulting in vulnerability after antibiotic exposure compared to the resistance displayed following subsequent exposures. PMID:26441887

  3. Delicate Metabolic Control and Coordinated Stress Response Critically Determine Antifungal Tolerance of Candida albicans Biofilm Persisters

    PubMed Central

    Li, Peng; Alpi, Emanuele; Vizcaino, Juan A.

    2015-01-01

    Candida infection has emerged as a critical health care burden worldwide, owing to the formation of robust biofilms against common antifungals. Recent evidence shows that multidrug-tolerant persisters critically account for biofilm recalcitrance, but their underlying biological mechanisms are poorly understood. Here, we first investigated the phenotypic characteristics of Candida biofilm persisters under consecutive harsh treatments of amphotericin B. The prolonged treatments effectively killed the majority of the cells of biofilms derived from representative strains of Candida albicans, Candida glabrata, and Candida tropicalis but failed to eradicate a small fraction of persisters. Next, we explored the tolerance mechanisms of the persisters through an investigation of the proteomic profiles of C. albicans biofilm persister fractions by liquid chromatography-tandem mass spectrometry. The C. albicans biofilm persisters displayed a specific proteomic signature, with an array of 205 differentially expressed proteins. The crucial enzymes involved in glycolysis, the tricarboxylic acid cycle, and protein synthesis were markedly downregulated, indicating that major metabolic activities are subdued in the persisters. It is noteworthy that certain metabolic pathways, such as the glyoxylate cycle, were able to be activated with significantly increased levels of isocitrate lyase and malate synthase. Moreover, a number of important proteins responsible for Candida growth, virulence, and the stress response were greatly upregulated. Interestingly, the persisters were tolerant to oxidative stress, despite highly induced intracellular superoxide. The current findings suggest that delicate metabolic control and a coordinated stress response may play a crucial role in mediating the survival and antifungal tolerance of Candida biofilm persisters. PMID:26195524

  4. Examination of metabolic responses to phosphorus limitation via proteomic analyses in the marine diatom Phaeodactylum tricornutum.

    PubMed

    Feng, Tian-Ya; Yang, Zhi-Kai; Zheng, Jian-Wei; Xie, Ying; Li, Da-Wei; Murugan, Shanmugaraj Bala; Yang, Wei-Dong; Liu, Jie-Sheng; Li, Hong-Ye

    2015-01-01

    Phosphorus (P) is an essential macronutrient for the survival of marine phytoplankton. In the present study, phytoplankton response to phosphorus limitation was studied by proteomic profiling in diatom Phaeodactylum tricornutum in both cellular and molecular levels. A total of 42 non-redundant proteins were identified, among which 8 proteins were found to be upregulated and 34 proteins were downregulated. The results also showed that the proteins associated with inorganic phosphate uptake were downregulated, whereas the proteins involved in organic phosphorus uptake such as alkaline phosphatase were upregulated. The proteins involved in metabolic responses such as protein degradation, lipid accumulation and photorespiration were upregulated whereas energy metabolism, photosynthesis, amino acid and nucleic acid metabolism tend to be downregulated. Overall our results showed the changes in protein levels of P. tricornutum during phosphorus stress. This study preludes for understanding the role of phosphorous in marine biogeochemical cycles and phytoplankton response to phosphorous scarcity in ocean. It also provides insight into the succession of phytoplankton community, providing scientific basis for elucidating the mechanism of algal blooms. PMID:26020491

  5. Examination of metabolic responses to phosphorus limitation via proteomic analyses in the marine diatom Phaeodactylum tricornutum

    PubMed Central

    Feng, Tian-Ya; Yang, Zhi-Kai; Zheng, Jian-Wei; Xie, Ying; Li, Da-Wei; Murugan, Shanmugaraj Bala; Yang, Wei-Dong; Liu, Jie-Sheng; Li, Hong-Ye

    2015-01-01

    Phosphorus (P) is an essential macronutrient for the survival of marine phytoplankton. In the present study, phytoplankton response to phosphorus limitation was studied by proteomic profiling in diatom Phaeodactylum tricornutum in both cellular and molecular levels. A total of 42 non-redundant proteins were identified, among which 8 proteins were found to be upregulated and 34 proteins were downregulated. The results also showed that the proteins associated with inorganic phosphate uptake were downregulated, whereas the proteins involved in organic phosphorus uptake such as alkaline phosphatase were upregulated. The proteins involved in metabolic responses such as protein degradation, lipid accumulation and photorespiration were upregulated whereas energy metabolism, photosynthesis, amino acid and nucleic acid metabolism tend to be downregulated. Overall our results showed the changes in protein levels of P. tricornutum during phosphorus stress. This study preludes for understanding the role of phosphorous in marine biogeochemical cycles and phytoplankton response to phosphorous scarcity in ocean. It also provides insight into the succession of phytoplankton community, providing scientific basis for elucidating the mechanism of algal blooms. PMID:26020491

  6. Zinc oxide induces the stringent response and major reorientations in the central metabolism of Bacillus subtilis.

    PubMed

    Luche, Sylvie; Eymard-Vernain, Elise; Diemer, Hélène; Van Dorsselaer, Alain; Rabilloud, Thierry; Lelong, Cécile

    2016-03-01

    Microorganisms, such as bacteria, are one of the first targets of nanoparticles in the environment. In this study, we tested the effect of two nanoparticles, ZnO and TiO2, with the salt ZnSO4 as the control, on the Gram-positive bacterium Bacillus subtilis by 2D gel electrophoresis-based proteomics. Despite a significant effect on viability (LD50), TiO2 NPs had no detectable effect on the proteomic pattern, while ZnO NPs and ZnSO4 significantly modified B. subtilis metabolism. These results allowed us to conclude that the effects of ZnO observed in this work were mainly attributable to Zn dissolution in the culture media. Proteomic analysis highlighted twelve modulated proteins related to central metabolism: MetE and MccB (cysteine metabolism), OdhA, AspB, IolD, AnsB, PdhB and YtsJ (Krebs cycle) and XylA, YqjI, Drm and Tal (pentose phosphate pathway). Biochemical assays, such as free sulfhydryl, CoA-SH and malate dehydrogenase assays corroborated the observed central metabolism reorientation and showed that Zn stress induced oxidative stress, probably as a consequence of thiol chelation stress by Zn ions. The other patterns affected by ZnO and ZnSO4 were the stringent response and the general stress response. Nine proteins involved in or controlled by the stringent response showed a modified expression profile in the presence of ZnO NPs or ZnSO4: YwaC, SigH, YtxH, YtzB, TufA, RplJ, RpsB, PdhB and Mbl. An increase in the ppGpp concentration confirmed the involvement of the stringent response during a Zn stress. All these metabolic reorientations in response to Zn stress were probably the result of complex regulatory mechanisms including at least the stringent response via YwaC. PMID:26211718

  7. Dynamics of ceramide generation and metabolism in response to fenretinide--Diversity within and among leukemia.

    PubMed

    Morad, Samy A F; Davis, Traci S; Kester, Mark; Loughran, Thomas P; Cabot, Myles C

    2015-10-01

    Fenretinide, N-(4-hydroxyphenyl)retinamide, (4-HPR), a synthetic retinoid, owes its cancer-toxic effects in part to the generation of ceramide, a potent tumor-suppressing sphingolipid. As such, 4-HPR has garnered considerable interest as a chemotherapeutic. Cancer cells, however, via various metabolic routes, inactivate ceramide, and this can limit 4-HPR efficacy. As relatively little is known regarding 4-HPR-induced ceramide management in acute myelogeneous leukemia (AML), we undertook the present study to evaluate the impact of 4-HPR on ceramide production, metabolism, and cytotoxicity. In KG-1, HL-60, and HL-60/VCR (multidrug resistant) human leukemia cells, 4-HPR induced 15-, 2-, and 20-fold increases in ceramide (measured using [3H]palmitic acid), respectively. By use of specific inhibitors we show that ceramide was produced by sphingomyelinase and de novo pathways in response to 4-HPR exposure. HL-60/VCR cells metabolized ceramide to glucosylceramide (GC). 4-HPR exposure (1.25-10 μM) reduced viability in all cell lines, with approximate IC50's ranging from 1 to 8.0 μM. Reactive oxygen species (ROS) were generated in response to 4-HPR treatment, and the concomitant cytotoxicity was reversed by addition of vitamin E. 4-HPR was not cytotoxic nor did it elicit ceramide formation in K562, a chronic myeloid leukemia cell line; however, K562 cells were sensitive to a cell-deliverable form of ceramide, C6-ceramide. Treatment of Molt-3, an acute lymphoblastic leukemia cell line, with 4-HPR revealed moderate ceramide production (5-fold over control), robust conversion of ceramide to GC and sphingomyelin, and resistance to 4-HPR and C6-ceramide. In conclusion, this work demonstrates diversity within and among leukemia in 4-HPR sensitivity and ceramide generation and subsequent metabolism. As such, knowledge of these metabolic pathways can provide guidance for enhancing ceramide-driven effects of 4-HPR in treatment of leukemia. PMID:26220867

  8. Fight-flight or freeze-hide? Personality and metabolic phenotype mediate physiological defence responses in flatfish.

    PubMed

    Rupia, Emmanuel J; Binning, Sandra A; Roche, Dominique G; Lu, Weiqun

    2016-07-01

    Survival depends on appropriate behavioural and physiological responses to danger. In addition to active 'fight-flight' defence responses, a passive 'freeze-hide' response is adaptive in some contexts. However, the physiological mechanisms determining which individuals choose a given defence response remain poorly understood. We examined the relationships among personality, metabolic performance and physiological stress responses across an environmental gradient in the olive flounder, Paralichthys olivaceus. We employed four behavioural assays to document the existence of two distinct behavioural types ('bold' and 'shy') in this species. We found consistent metabolic differences between individuals of a given behavioural type across an environmental gradient: shy individuals had overall lower aerobic scope, maximum metabolic rate and standard metabolic rate than bold individuals in both high (25 ppt) and low (3 ppt) salinity. These behavioural and metabolic differences translated into divergent physiological responses during acute stress: shy individuals adopted a passive 'freeze-hide' response by reducing their oxygen consumption rates (akin to shallow breathing) whereas bold individuals adopted an active 'fight-flight' response by increasing their rates of respiration. These distinct defence strategies were repeatable within individuals between salinity treatments. Although it has been suggested theoretically, this is the first empirical evidence that the metabolic response to stressful situations differs between bold and shy individuals. Our results emphasize the importance of incorporating physiological measures to understand the mechanisms driving persistent inter-individual differences in animals. PMID:27044558

  9. Metabolic and vasomotor responses of rhesus monkeys exposed to 225-MHz radiofrequency energy. [Macaca mulatta

    SciTech Connect

    Lotz, W.G.; Saxton, J.L.

    1987-01-01

    A previous study showed a substantial increase in the colonic temperature of rhesus monkeys (Macaca mulatta) exposed to radiofrequency (RF) fields at a frequency near whole-body resonance and specific absorption rates (SAR) of 2-3 W/kg. The present experiments were conducted to determine the metabolic and vasomotor responses during exposures to similar RF fields. We exposed five adult male rhesus monkeys to 225 MHz radiation (E orientation) in an anechoic chamber. Oxygen consumption and carbon dioxide production were measured before, during, and after RF exposure. Colonic, tail and leg skin temperatures were continuously monitored with RF-nonperturbing probes. The monkeys were irradiated at two carefully-controlled ambient temperatures, either cool (20 degrees C) or thermoneutral (26 degrees C). Power densities ranged from 0 (sham) to 10.0 mW/cm2 with an average whole-body SAR of 0.285 (W/kg)/(mW/cm2). We used two experimental protocols, each of which began with a 120-min pre-exposure equilibration period. One protocol involved repetitive 10-min RF exposures at successively higher power densities with a recovery period between exposures. In the second protocol, a 120-min RF exposure permitted the measurement of steady-state thermoregulatory responses. Metabolic and vasomotor adjustments in the rhesus monkey exposed to 225 MHz occurred during brief or sustained exposures at SARs at or above 1.4 W/kg. The SAR required to produce a given response varied with ambient temperature. Metabolic and vasomotor responses were coordinated effectively to produce a stable deep body temperature. The results show that the thermoregulatory response of the rhesus monkey to an RF exposure at a resonant frequency limits storage of heat in the body. However, substantial increases in colonic temperature were not prevented by such responses, even in a cool environment.

  10. Importance of understanding the main metabolic regulation in response to the specific pathway mutation for metabolic engineering of Escherichia coli

    PubMed Central

    Matsuoka, Yu; Shimizu, Kazuyuki

    2013-01-01

    Recent metabolic engineering practice was briefly reviewed in particular for the useful metabolite production such as natural products and biofuel productions. With the emphasis on systems biology approach, the metabolic regulation of the main metabolic pathways in E. coli was discussed from the points of view of enzyme level (allosteric and phosphorylation/ dephosphorylation) regulation, and gene level (transcriptional) regulation. Then the effects of the specific pathway gene knockout such as pts, pgi, zwf, gnd, pyk, ppc, pckA, lpdA, pfl gene knockout on the metabolism in E. coli were overviewed from the systems biology point of view with possible application for strain improvement point. PMID:24688678

  11. Dynamic responses of reserve carbohydrate metabolism under carbon and nitrogen limitations in Saccharomyces cerevisiae.

    PubMed

    Parrou, J L; Enjalbert, B; Plourde, L; Bauche, A; Gonzalez, B; François, J

    1999-02-01

    The dynamic responses of reserve carbohydrates with respect to shortage of either carbon or nitrogen source was studied to obtain a sound basis for further investigations devoted to the characterization of mechanisms by which the yeast Saccharomyces cerevisiae can cope with nutrient limitation during growth. This study was carried out in well-controlled bioreactors which allow accurate monitoring of growth and frequent sampling without disturbing the culture. Under glucose limitation, genes involved in glycogen and trehalose biosynthesis (GLG1, GSY1, GSY2, GAC1, GLC3, TPS1), in their degradation (GPH1, NTHI), and the typical stress-responsive CTT1 gene were coordinately induced in parallel with glycogen, when the growth has left the pure exponential phase and while glucose was still plentiful in the medium. Trehalose accumulation was delayed until the diauxic shift, although TPS1 was induced much earlier, due to hydrolysis of trehalose by high trehalase activity. In contrast, under nitrogen limitation, both glycogen and trehalose began to accumulate at the precise time when the nitrogen source was exhausted from the medium, coincidentally with the transcriptional activation of genes involved in their metabolism. While this response to nitrogen starvation was likely mediated by the stress-responsive elements (STREs) in the promoter of these genes, we found that these elements were not responsible for the co-induction of genes involved in reserve carbohydrate metabolism during glucose limitation, since GLG1, which does not contain any STRE, was coordinately induced with GSY2 and TPS1. PMID:10077186

  12. Sugar metabolism, redox balance and oxidative stress response in the respiratory yeast Kluyveromyces lactis

    PubMed Central

    González-Siso, M Isabel; García-Leiro, Ana; Tarrío, Nuria; Cerdán, M Esperanza

    2009-01-01

    A lot of studies have been carried out on Saccharomyces cerevisiae, an yeast with a predominant fermentative metabolism under aerobic conditions, which allows exploring the complex response induced by oxidative stress. S. cerevisiae is considered a eukaryote model for these studies. We propose Kluyveromyces lactis as a good alternative model to analyse variants in the oxidative stress response, since the respiratory metabolism in this yeast is predominant under aerobic conditions and it shows other important differences with S. cerevisiae in catabolic repression and carbohydrate utilization. The knowledge of oxidative stress response in K. lactis is still a developing field. In this article, we summarize the state of the art derived from experimental approaches and we provide a global vision on the characteristics of the putative K. lactis components of the oxidative stress response pathway, inferred from their sequence homology with the S. cerevisiae counterparts. Since K. lactis is also a well-established alternative host for industrial production of native enzymes and heterologous proteins, relevant differences in the oxidative stress response pathway and their potential in biotechnological uses of this yeast are also reviewed. PMID:19715615

  13. [Response to aggression: evaluation and therapeutic implications. Work Group on Metabolism and Nutrition of the SEMIUC].

    PubMed

    García de Lorenzo, A; Ortiz Leyba, C

    1997-01-01

    The metabolic response to stress/aggression is a complex process which is mainly mediated by the interaction between the neuro-endocrine system and the circulating cytokines. This interaction brings about physiological and metabolic alterations--severe metabolic-nutritional deficits--of the hypermetabolic type, muscular proteolysis, lipolysis, glycogenolysis, and gluconeogenesis among others, which should be studied and understood prior to initiating or not a nutritional support. The parenteral or enteral nutritional support is usually indicated to prevent a worsening of these situations of altered metabolism frequently associated with inanition, although one should not attempt to revert to normal preexisting deficit situations. On the other hand, and is this special context, we should not forget the advances in nutrients with pharmacological effects, and in pharmacological nutrition. At this II Consensus Conference of the SEMIUC (Sociedad Española de Medicine Intensiva y Unidades Coronarias = Spanish Society of Intensive Medicine and Coronary Units), we have proposed four objectives: i) To make recommendation, based both on the scientific evidence, as on the experience of the components. ii) Define the scientific terminology to be used in this specific context. iii) Give an answer to the different and assorted clinical problems which are secondary to a situation of stress which has a multiple etiology. iv) Provide new ideas for the development of clinical trails and studies of this specific context. PMID:9617181

  14. {sup 18}-F-Fluorodeoxyglucose-Positron Emission Tomography Evaluation of Early Metabolic Response During Radiation Therapy for Cervical Cancer

    SciTech Connect

    Schwarz, Julie K.; Lin, Lillie L.; Siegel, Barry A.; Miller, Tom R.; Grigsby, Perry W.

    2008-12-01

    Purpose: To document changes in cervical tumor {sup 18}-F-fluorodeoxyglocose (FDG) uptake during radiation therapy and to correlate those changes with post-treatment tumor response and survival outcome. Methods and Materials: A total of 36 patients with Stage Ib1 to IIIb cervical cancer were enrolled in an institutional protocol examining the use of fluorodeoxyglucose-positron emission tomography (FDG-PET) for brachytherapy treatment planning. As part of this study, FDG-PET or PET/computed tomograpy (CT) images were obtained before, during, and after the completion of radiation therapy. Tumor metabolic responses were assessed qualitatively and semi-quantitatively by measurement of the maximal standardized uptake value (SUV{sub max}). Results: Post-treatment FDG-PET images were obtained for 36 patients in this study. Of the patients, 29 patients had a complete metabolic response on the post-treatment PET, 4 had a partial metabolic response, and 3 had new sites of FDG uptake. Six patients had a complete metabolic response observed during radiation therapy, 26 had a partial metabolic response and 4 had stable or increased tumor metabolic activity. For patients with complete metabolic response during radiation therapy, median time to complete response was 29.5 days (range, 18-43 days). The mean cervical tumor SUV{sub max} decreased from 11.2 (SD, 6.3; range, 2.1-38.0) pretreatment to 2.4 (SD, 2.7; range, 0-8.8) mid treatment, and 0.5 (SD, 1.7; range, 0-8.3) post-treatment. Conclusions: During radiation therapy for cervical cancer, FDG-PET can be used to monitor treatment response. Complete metabolic response during radiation therapy was observed for a subset of patients. Recommendations regarding the optimal timing of FDG-PET during treatment for cervical cancer will require further systematic study.

  15. Metabolic Imaging to Assess Treatment Response to Cytotoxic and Cytostatic Agents

    PubMed Central

    Serkova, Natalie J.; Eckhardt, S. Gail

    2016-01-01

    For several decades, cytotoxic chemotherapeutic agents were considered the basis of anticancer treatment for patients with metastatic tumors. A decrease in tumor burden, assessed by volumetric computed tomography and magnetic resonance imaging, according to the response evaluation criteria in solid tumors (RECIST), was considered as a radiological response to cytotoxic chemotherapies. In addition to RECIST-based dimensional measurements, a metabolic response to cytotoxic drugs can be assessed by positron emission tomography (PET) using 18F-fluoro-thymidine (FLT) as a radioactive tracer for drug-disrupted DNA synthesis. The decreased 18FLT-PET uptake is often seen concurrently with increased apparent diffusion coefficients by diffusion-weighted imaging due to chemotherapy-induced changes in tumor cellularity. Recently, the discovery of molecular origins of tumorogenesis led to the introduction of novel signal transduction inhibitors (STIs). STIs are targeted cytostatic agents; their effect is based on a specific biological inhibition with no immediate cell death. As such, tumor size is not anymore a sensitive end point for a treatment response to STIs; novel physiological imaging end points are desirable. For receptor tyrosine kinase inhibitors as well as modulators of the downstream signaling pathways, an almost immediate inhibition in glycolytic activity (the Warburg effect) and phospholipid turnover (the Kennedy pathway) has been seen by metabolic imaging in the first 24 h of treatment. The quantitative imaging end points by magnetic resonance spectroscopy and metabolic PET (including 18F-fluoro-deoxy-glucose, FDG, and total choline) provide an early treatment response to targeted STIs, before a reduction in tumor burden can be seen. PMID:27471678

  16. Metabolic and vasomotor responses of rhesus monkeys exposed to 225-MHz radiofrequency energy

    SciTech Connect

    Lotz, W.G.; Saxton, J.L.

    1987-01-01

    A previous study showed a substantial increase in the colonic temperature of rhesus monkeys (Macaca mulatta) exposed to radio-frequency (RF) fields at a frequency near whole-body resonance and specific absorption rates (SAR) of 2 to 3 W/kg. The present experiments were conducted to determine the metabolic and vasomotor responses during exposures to similar RF fields. Five adult male rhesus monkeys were exposed to 225-MHz radiation (E orientation) in an anechoic chamber. The monkeys were irradiated at two carefully-controlled ambient temperatures, either cool (20 C) or thermoneutral (26 C). Power densities ranged from 0 (sham) to 10.0 mW/sq cm with an average whole-body SAR of 0.285 (W/kg)/(mW/sq cm). Two experimental protocols were used, each of which began with a 120-min preexposure equilibration period. Then, one protocol involved repetitive 10-min RF exposures at successively higher power densities with a recovery period between exposures. In the second protocol, a 120-min RF exposure permitted the measurement of steady-state thermoregulatory responses. Metabolic and vasomotor adjustments in the rhesus monkey exposed to 225 MHz occurred during brief or sustained exposures at SARs at or above 1.4 W/kg. Metabolic and vasomotor responses were coordinated effectively to produce a stable deep-body temperature. The results show that the thermoregulatory response of the rhesus monkey to an RF exposure at a resonant frequency limits storage of heat in the body. However, substantial increases in colonic temperature were not prevented by such responses, even in a cool environment.

  17. Metabolomics Analysis of Hormone-Responsive and Triple-Negative Breast Cancer Cell Responses to Paclitaxel Identify Key Metabolic Differences.

    PubMed

    Stewart, Delisha A; Winnike, Jason H; McRitchie, Susan L; Clark, Robert F; Pathmasiri, Wimal W; Sumner, Susan J

    2016-09-01

    To date, no targeted therapies are available to treat triple negative breast cancer (TNBC), while other breast cancer subtypes are responsive to current therapeutic treatment. Metabolomics was conducted to reveal differences in two hormone receptor-negative TNBC cell lines and two hormone receptor-positive Luminal A cell lines. Studies were conducted in the presence and absence of paclitaxel (Taxol). TNBC cell lines had higher levels of amino acids, branched-chain amino acids, nucleotides, and nucleotide sugars and lower levels of proliferation-related metabolites like choline compared with Luminal A cell lines. In the presence of paclitaxel, each cell line showed unique metabolic responses, with some similarities by type. For example, in the Luminal A cell lines, levels of lactate and creatine decreased while certain choline metabolites and myo-inositol increased with paclitaxel. In the TNBC cell lines levels of glutamine, glutamate, and glutathione increased, whereas lysine, proline, and valine decreased in the presence of drug. Profiling secreted inflammatory cytokines in the conditioned media demonstrated a greater response to paclitaxel in the hormone-positive Luminal cells compared with a secretion profile that suggested greater drug resistance in the TNBC cells. The most significant differences distinguishing the cell types based on pathway enrichment analyses were related to amino acid, lipid and carbohydrate metabolism pathways, whereas several biological pathways were differentiated between the cell lines following treatment. PMID:27447733

  18. Intramolecular stable isotope distributions detect plant metabolic responses on century time scales

    NASA Astrophysics Data System (ADS)

    Schleucher, Jürgen; Ehlers, Ina; Augusti, Angela; Betson, Tatiana

    2014-05-01

    Plants respond to environmental changes on a vast range of time scales, and plant gas exchanges constitute important feedback mechanisms in the global C cycle. Responses on time scales of decades to centuries are most important for climate models, for prediction of crop productivity, and for adaptation to climate change. Unfortunately, responses on these timescale are least understood. We argue that the knowledge gap on intermediate time scales is due to a lack of adequate methods that can bridge between short-term manipulative experiments (e.g. FACE) and paleo research. Manipulative experiments in plant ecophysiology give information on metabolism on time scales up to years. However, this information cannot be linked to results from retrospective studies in paleo research, because little metabolic information can be derived from paleo archives. Stable isotopes are prominent tools in plant ecophysiology, biogeochemistry and in paleo research, but in all applications to date, isotope ratios of whole molecules are measured. However, it is well established that stable isotope abundance varies among intramolecular groups of biochemical metabolites, that is each so-called "isotopomer" has a distinct abundance. This intramolecular variation carries information on metabolic regulation, which can even be traced to individual enzymes (Schleucher et al., Plant, Cell Environ 1999). Here, we apply intramolecular isotope distributions to study the metabolic response of plants to increasing atmospheric [CO2] during the past century. Greenhouse experiments show that the deuterium abundance among the two positions in the C6H2 group of photosynthetic glucose depends on [CO2] during growth. This is observed for all plants using C3 photosynthesis, and reflects the metabolic flux ratio between photorespiration and photosynthesis. Photorespiration is a major C flux that limits assimilation in C3 plants, which encompass the overwhelming fraction of terrestrial photosynthesis and the

  19. Ventilatory, cardiovascular and metabolic responses to hypoxia and hypercapnia in the armadillo.

    PubMed

    Boggs, D F; Frappell, P B; Kilgore, D L

    1998-08-01

    Armadillos have a low resting metabolic rate and high hemoglobin affinity for their size, a rigid carapace and a semi-fossorial life style. These characteristics could contribute to unusual respiratory responses to hypoxia and hypercapnia which were investigated in this study. Ventilatory and oxygen consumption responses of six adult unanesthetized armadillos to 15, 12, 10 and 8% O2 and 1.5, 3, 5 and 7% CO2 were measured by barometric plethysmography and flow-through respirometry. A significant increase in ventilation occurred in response to 10 and 8% O2 but a decline in oxygen consumption only occurred at 8% inspired O2. The convection requirement response has a threshold at a PaO2 of approximately = 28 Torr which corresponds to a Hb saturation of approximately 70%. Ventilation increased in response to 3% and higher levels of CO2, with no change in oxygen consumption. The magnitude of the ventilatory response to CO2 was similar to other semi-fossorial mammals and less than that of nonburrowing species. However, the pattern of the response was unique in being largely a frequency response with little change in tidal volume, contrary to the tidal volume dominated response to hypercapnia typical of mammals. This feature, not shared by another Xenarthran, the sloth, who lacks a carapace, is likely attributable to the low respiratory system compliance and increased airway resistance resulting from the rigid carapace and small lungs of armadillos and emphasizes the importance of respiratory mechanics in determining breathing pattern. PMID:9832229

  20. Osmotic and metabolic responses to dehydration and urea-loading in a dormant, terrestrially hibernating frog.

    PubMed

    Muir, Timothy J; Costanzo, Jon P; Lee, Richard E

    2007-11-01

    Physiological responses to dehydration in amphibians are reasonably well documented, although little work has addressed this problem in hibernating animals. We investigated osmotic and metabolic responses to experimental manipulation of hydration state in the wood frog (Rana sylvatica), a terrestrial hibernator that encounters low environmental water potential during autumn and winter. In winter-conditioned frogs, plasma osmolality varied inversely with body water content (range 69-79%, fresh mass) primarily due to increases in sodium and chloride concentrations, as well as accumulation of glucose and urea. Decreased hydration was accompanied by a marked reduction in the resting rate of oxygen consumption, which was inversely correlated with plasma osmolality and urea concentration. In a separate experiment, resting rates of oxygen consumption in fully hydrated frogs receiving injections of saline or saline containing urea did not differ initially; however, upon dehydration, metabolic rates decreased sooner in the urea-loaded frogs than in control frogs. Our findings suggest an important role for urea, acting in concert with dehydration, in the metabolic regulation and energy conservation of hibernating R. sylvatica. PMID:17661060

  1. Voxelwise single-subject analysis of imaging metabolic response to therapy in neuro-oncology.

    PubMed

    Guo, Mengye; Yap, Jeffrey T; Van den Abbeele, Annick D; Lin, Nancy U; Schwartzman, Armin

    2014-01-01

    F-18-Fluorodeoxyglucose positron emission tomography (FDG-PET) has been used to evaluate the metabolic response of metastatic brain tumors to treatment by comparing their tumor glucose metabolism before and after treatment. The standard analysis based on regions-of-interest has the advantage of simplicity. However, it is by definition restricted to those regions and is subject to observer variability. In addition, the observed changes in tumor metabolism are often confounded by normal changes in the tissue background, which can be heterogenous. We propose an analysis pipeline for automatically detecting the change at each voxel in the entire brain of a single subject, while adjusting for changes in the background. The complete analysis includes image registration, segmentation, a hierarchical model for background adjustment and voxelwise statistical comparisons. We demonstrate the method's ability to identify areas of tumor response and/or progression in two subjects enrolled in a clinical trial using FDG-PET to evaluate lapatinib for the treatment of brain metastases in breast cancer patients. PMID:24999285

  2. Functional and metabolic properties of alveolar macrophages in response to the gas phase of tobacco smoke.

    PubMed Central

    Drath, D B; Shorey, J M; Huber, G L

    1981-01-01

    The effect of whole tobacco smoke and the gas phase of tobacco smoke on the metabolism and phagocytic ability of alveolar macrophages was monitored over a 30-day exposure period. It was demonstrated that both the gas phase and whole tobacco smoke induced a weight loss in exposed rats. Alveolar macrophage oxygen consumption was markedly increased by both exposure regimens. Superoxide generation was not affected by whole tobacco smoke exposure but was increased in response to the filtered gas phase. Hexose monophosphate shunt activity was not altered by either treatment. When metabolic alterations were seen in response to the separate exposures, they were seen only after a phagocytic challenge to the macrophage and not when the cell was unchallenged. Neither whole tobacco smoke nor the gas phase had any significant effect on the ability of alveolar macrophages to phagocytize a viable challenge of Staphylococcus aureus. Our results suggest that many of the metabolic and functional effects of tobacco smoke on alveolar macrophages can be attributed to the gas-phase component of whole tobacco smoke. PMID:6271676

  3. Functional and metabolic properties of alveolar macrophages in response to the gas phase of tobacco smoke.

    PubMed

    Drath, D B; Shorey, J M; Huber, G L

    1981-10-01

    The effect of whole tobacco smoke and the gas phase of tobacco smoke on the metabolism and phagocytic ability of alveolar macrophages was monitored over a 30-day exposure period. It was demonstrated that both the gas phase and whole tobacco smoke induced a weight loss in exposed rats. Alveolar macrophage oxygen consumption was markedly increased by both exposure regimens. Superoxide generation was not affected by whole tobacco smoke exposure but was increased in response to the filtered gas phase. Hexose monophosphate shunt activity was not altered by either treatment. When metabolic alterations were seen in response to the separate exposures, they were seen only after a phagocytic challenge to the macrophage and not when the cell was unchallenged. Neither whole tobacco smoke nor the gas phase had any significant effect on the ability of alveolar macrophages to phagocytize a viable challenge of Staphylococcus aureus. Our results suggest that many of the metabolic and functional effects of tobacco smoke on alveolar macrophages can be attributed to the gas-phase component of whole tobacco smoke. PMID:6271676

  4. Responses of the Metabolism of the Larvae of Pocillopora damicornis to Ocean Acidification and Warming

    PubMed Central

    Rivest, Emily B.; Hofmann, Gretchen E.

    2014-01-01

    Ocean acidification and warming are expected to threaten the persistence of tropical coral reef ecosystems. As coral reefs face multiple stressors, the distribution and abundance of corals will depend on the successful dispersal and settlement of coral larvae under changing environmental conditions. To explore this scenario, we used metabolic rate, at holobiont and molecular levels, as an index for assessing the physiological plasticity of Pocillopora damicornis larvae from this site to conditions of ocean acidity and warming. Larvae were incubated for 6 hours in seawater containing combinations of CO2 concentration (450 and 950 µatm) and temperature (28 and 30°C). Rates of larval oxygen consumption were higher at elevated temperatures. In contrast, high CO2 levels elicited depressed metabolic rates, especially for larvae released later in the spawning period. Rates of citrate synthase, a rate-limiting enzyme in aerobic metabolism, suggested a biochemical limit for increasing oxidative capacity in coral larvae in a warming, acidifying ocean. Biological responses were also compared between larvae released from adult colonies on the same day (cohorts). The metabolic physiology of Pocillopora damicornis larvae varied significantly by day of release. Additionally, we used environmental data collected on a reef in Moorea, French Polynesia to provide information about what adult corals and larvae may currently experience in the field. An autonomous pH sensor provided a continuous time series of pH on the natal fringing reef. In February/March, 2011, pH values averaged 8.075±0.023. Our results suggest that without adaptation or acclimatization, only a portion of naïve Pocillopora damicornis larvae may have suitable metabolic phenotypes for maintaining function and fitness in an end-of-the century ocean. PMID:24769774

  5. Development of the Poplar-Laccaria bicolor Ectomycorrhiza Modifies Root Auxin Metabolism, Signaling, and Response.

    PubMed

    Vayssières, Alice; Pěnčík, Ales; Felten, Judith; Kohler, Annegret; Ljung, Karin; Martin, Francis; Legué, Valérie

    2015-09-01

    Root systems of host trees are known to establish ectomycorrhizae (ECM) interactions with rhizospheric fungi. This mutualistic association leads to dramatic developmental modifications in root architecture, with the formation of numerous short and swollen lateral roots ensheathed by a fungal mantle. Knowing that auxin plays a crucial role in root development, we investigated how auxin metabolism, signaling, and response are affected in poplar (Populus spp.)-Laccaria bicolor ECM roots. The plant-fungus interaction leads to the arrest of lateral root growth with simultaneous attenuation of the synthetic auxin response element DR5. Measurement of auxin-related metabolites in the free-living partners revealed that the mycelium of L. bicolor produces high concentrations of the auxin indole-3-acetic acid (IAA). Metabolic profiling showed an accumulation of IAA and changes in the indol-3-pyruvic acid-dependent IAA biosynthesis and IAA conjugation and degradation pathways during ECM formation. The global analysis of auxin response gene expression and the regulation of AUXIN SIGNALING F-BOX PROTEIN5, AUXIN/IAA, and AUXIN RESPONSE FACTOR expression in ECM roots suggested that symbiosis-dependent auxin signaling is activated during the colonization by L. bicolor. Taking all this evidence into account, we propose a model in which auxin signaling plays a crucial role in the modification of root growth during ECM formation. PMID:26084921

  6. The Role of the Renal Ammonia Transporter Rhcg in Metabolic Responses to Dietary Protein

    PubMed Central

    Bounoure, Lisa; Ruffoni, Davide; Müller, Ralph; Kuhn, Gisela Anna; Devuyst, Olivier

    2014-01-01

    High dietary protein imposes a metabolic acid load requiring excretion and buffering by the kidney. Impaired acid excretion in CKD, with potential metabolic acidosis, may contribute to the progression of CKD. Here, we investigated the renal adaptive response of acid excretory pathways in mice to high-protein diets containing normal or low amounts of acid-producing sulfur amino acids (SAA) and examined how this adaption requires the RhCG ammonia transporter. Diets rich in SAA stimulated expression of enzymes and transporters involved in mediating NH4+ reabsorption in the thick ascending limb of the loop of Henle. The SAA-rich diet increased diuresis paralleled by downregulation of aquaporin-2 (AQP2) water channels. The absence of Rhcg transiently reduced NH4+ excretion, stimulated the ammoniagenic pathway more strongly, and further enhanced diuresis by exacerbating the downregulation of the Na+/K+/2Cl− cotransporter (NKCC2) and AQP2, with less phosphorylation of AQP2 at serine 256. The high protein acid load affected bone turnover, as indicated by higher Ca2+ and deoxypyridinoline excretion, phenomena exaggerated in the absence of Rhcg. In animals receiving a high-protein diet with low SAA content, the kidney excreted alkaline urine, with low levels of NH4+ and no change in bone metabolism. Thus, the acid load associated with high-protein diets causes a concerted response of various nephron segments to excrete acid, mostly in the form of NH4+, that requires Rhcg. Furthermore, bone metabolism is altered by a high-protein acidogenic diet, presumably to buffer the acid load. PMID:24652796

  7. Optical Metabolic Imaging of Treatment Response in Human Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Shah, Amy T.; Demory Beckler, Michelle; Walsh, Alex J.; Jones, William P.; Pohlmann, Paula R.; Skala, Melissa C.

    2014-01-01

    Optical metabolic imaging measures fluorescence intensity and lifetimes from metabolic cofactors nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD). These molecular level measurements provide unique biomarkers for early cellular responses to cancer treatments. Head and neck squamous cell carcinoma (HNSCC) is an attractive target for optical imaging because of easy access to the site using fiber optic probes. Two HNSCC cell lines, SCC25 and SCC61, were treated with Cetuximab (anti-EGFR antibody), BGT226 (PI3K/mTOR inhibitor), or cisplatin (chemotherapy) for 24 hours. Results show increased redox ratio, NADH α1 (contribution from free NADH), and FAD α1 (contribution from protein-bound FAD) for malignant cells compared with the nonmalignant cell line OKF6 (p<0.05). In SCC25 and SCC61 cells, the redox ratio is unaffected by cetuximab treatment and decreases with BGT226 and cisplatin treatment (p<0.05), and these results agree with standard measurements of proliferation rates after treatment. For SCC25, NADH α1 is reduced with BGT226 and cisplatin treatment. For SCC61, NADH α1 is reduced with cetuximab, BGT226, and cisplatin treatment. Trends in NADH α1 are statistically similar to changes in standard measurements of glycolytic rates after treatment. FAD α1 is reduced with cisplatin treatment (p<0.05). These shifts in optical endpoints reflect early metabolic changes induced by drug treatment. Overall, these results indicate that optical metabolic imaging has potential to detect early response to cancer treatment in HNSCC, enabling optimal treatment regimens and improved patient outcomes. PMID:24595244

  8. Interneurons contribute to the hemodynamic/metabolic response to epileptiform discharges.

    PubMed

    Saillet, Sandrine; Quilichini, Pascale P; Ghestem, Antoine; Giusiano, Bernard; Ivanov, Anton I; Hitziger, Sebastian; Vanzetta, Ivo; Bernard, Christophe; Bénar, Christian-G

    2016-03-01

    Interpretation of hemodynamic responses in epilepsy is hampered by an incomplete understanding of the underlying neurovascular coupling, especially the contributions of excitation and inhibition. We made simultaneous multimodal recordings of local field potentials (LFPs), firing of individual neurons, blood flow, and oxygen level in the somatosensory cortex of anesthetized rats. Epileptiform discharges induced by bicuculline injections were used to trigger large local events. LFP and blood flow were robustly coupled, as were LFP and tissue oxygen. In a parametric linear model, LFP and the baseline activities of cerebral blood flow and tissue partial oxygen tension contributed significantly to blood flow and oxygen responses. In an analysis of recordings from 402 neurons, blood flow/tissue oxygen correlated with the discharge of putative interneurons but not of principal cells. Our results show that interneuron activity is important in the vascular and metabolic responses during epileptiform discharges. PMID:26745250

  9. Cortico-limbic-striatal contribution after response and reversal learning: a metabolic mapping study.

    PubMed

    Fidalgo, Camino; Conejo, N M; González-Pardo, Héctor; Arias, J L

    2011-01-12

    Learning of arbitrary stimulus-response associations is an adaptive behavior essential for species survival in an ever-changing environment. Particular subdivisions of the striatum have been shown to be critical for both motor-response learning and reversal learning. However, recent evidence suggests that different cortical and subcortical brain regions may be involved in response learning, a kind of learning more complex than previously thought. In fact, many brain regions subserving response learning seem to be also related to reversal learning, traditionally ascribed to the prefrontal cortex. The present study examined the role of different subdivisions of the rat prefrontal cortex, striatum, amygdala and the ventral tegmental area on both response and reversal learning evaluated in the water T-maze. Increased neuronal metabolic activity, as measured by cytochrome oxidase (CO) histochemistry, was found in most brain regions after training rats in a response learning task as compared to yoked controls. Reversal learning was associated with a return to baseline CO activity levels except for the orbitofrontal cortex and the ventral tegmental area. Analysis of functional connectivity among brain regions showed significant correlations in CO activity between particular cortical and striatal subdivisions in the reversal learning group. These findings suggest that the interaction of specific frontal and subcortical regions is required for reversal but not for response learning. However, our findings support the involvement of a cortico-limbic-striatal circuit in both types of learning. PMID:21036158

  10. Metabolic profiling of Lolium perenne shows functional integration of metabolic responses to diverse subtoxic conditions of chemical stress.

    PubMed

    Serra, Anne-Antonella; Couée, Ivan; Renault, David; Gouesbet, Gwenola; Sulmon, Cécile

    2015-04-01

    Plant communities are confronted with a great variety of environmental chemical stresses. Characterization of chemical stress in higher plants has often been focused on single or closely related stressors under acute exposure, or restricted to a selective number of molecular targets. In order to understand plant functioning under chemical stress conditions close to environmental pollution conditions, the C3 grass Lolium perenne was subjected to a panel of different chemical stressors (pesticide, pesticide degradation compound, polycyclic aromatic hydrocarbon, and heavy metal) under conditions of seed-level or root-level subtoxic exposure. Physiological and metabolic profiling analysis on roots and shoots revealed that all of these subtoxic chemical stresses resulted in discrete physiological perturbations and complex metabolic shifts. These metabolic shifts involved stressor-specific effects, indicating multilevel mechanisms of action, such as the effects of glyphosate and its degradation product aminomethylphosphonic acid on quinate levels. They also involved major generic effects that linked all of the subtoxic chemical stresses with major modifications of nitrogen metabolism, especially affecting asparagine, and of photorespiration, especially affecting alanine and glycerate. Stress-related physiological effects and metabolic adjustments were shown to be integrated through a complex network of metabolic correlations converging on Asn, Leu, Ser, and glucose-6-phosphate, which could potentially be modulated by differential dynamics and interconversion of soluble sugars (sucrose, trehalose, fructose, and glucose). Underlying metabolic, regulatory, and signalling mechanisms linking these subtoxic chemical stresses with a generic impact on nitrogen metabolism and photorespiration are discussed in relation to carbohydrate and low-energy sensing. PMID:25618145

  11. Metabolic profiling of Lolium perenne shows functional integration of metabolic responses to diverse subtoxic conditions of chemical stress

    PubMed Central

    Serra, Anne-Antonella; Couée, Ivan; Renault, David; Gouesbet, Gwenola; Sulmon, Cécile

    2015-01-01

    Plant communities are confronted with a great variety of environmental chemical stresses. Characterization of chemical stress in higher plants has often been focused on single or closely related stressors under acute exposure, or restricted to a selective number of molecular targets. In order to understand plant functioning under chemical stress conditions close to environmental pollution conditions, the C3 grass Lolium perenne was subjected to a panel of different chemical stressors (pesticide, pesticide degradation compound, polycyclic aromatic hydrocarbon, and heavy metal) under conditions of seed-level or root-level subtoxic exposure. Physiological and metabolic profiling analysis on roots and shoots revealed that all of these subtoxic chemical stresses resulted in discrete physiological perturbations and complex metabolic shifts. These metabolic shifts involved stressor-specific effects, indicating multilevel mechanisms of action, such as the effects of glyphosate and its degradation product aminomethylphosphonic acid on quinate levels. They also involved major generic effects that linked all of the subtoxic chemical stresses with major modifications of nitrogen metabolism, especially affecting asparagine, and of photorespiration, especially affecting alanine and glycerate. Stress-related physiological effects and metabolic adjustments were shown to be integrated through a complex network of metabolic correlations converging on Asn, Leu, Ser, and glucose-6-phosphate, which could potentially be modulated by differential dynamics and interconversion of soluble sugars (sucrose, trehalose, fructose, and glucose). Underlying metabolic, regulatory, and signalling mechanisms linking these subtoxic chemical stresses with a generic impact on nitrogen metabolism and photorespiration are discussed in relation to carbohydrate and low-energy sensing. PMID:25618145

  12. A clickable glutathione approach for identification of protein glutathionylation in response to glucose metabolism.

    PubMed

    Samarasinghe, Kusal T G; Munkanatta Godage, Dhanushka N P; Zhou, Yani; Ndombera, Fidelis T; Weerapana, Eranthie; Ahn, Young-Hoon

    2016-07-19

    Glucose metabolism and mitochondrial function are closely interconnected with cellular redox-homeostasis. Although glucose starvation, which mimics ischemic conditions or insufficient vascularization, is known to perturb redox-homeostasis, global and individual protein glutathionylation in response to glucose metabolism or mitochondrial activity remains largely unknown. In this report, we use our clickable glutathione approach, which forms clickable glutathione (azido-glutathione) by using a mutant of glutathione synthetase (GS M4), for detection and identification of protein glutathionylation in response to glucose starvation. We found that protein glutathionylation is readily induced in HEK293 cells in response to low glucose concentrations when mitochondrial reactive oxygen species (ROS) are elevated in cells, and glucose is the major determinant for inducing reversible glutathionylation. Proteomic and biochemical analysis identified over 1300 proteins, including SMYD2, PP2Cα, and catalase. We further showed that PP2Cα is glutathionylated at C314 in a C-terminal domain, and PP2Cα C314 glutathionylation disrupts the interaction with mGluR3, an important glutamate receptor associated with synaptic plasticity. PMID:27216279

  13. Increased response to insulin of glucose metabolism in the 6-day unloaded rat soleus muscle

    NASA Technical Reports Server (NTRS)

    Henriksen, Erik J.; Tischler, Marc E.; Johnson, David G.

    1986-01-01

    Hind leg muscles of female rats were unloaded by tail cast suspension for 6 days. In the fresh-frozen unloaded soleus, the significantly greater concentration of glycogen correlated with a lower activity ratio of glycogen phosphorylase (p less than 0.02). The activity ratio of glycogen synthase also was lower (p less than 0.001), possibly due to the higher concentration of glycogen. In isolated unloaded soleus, insulin (0.1 milliunit/ml) increased the oxidation of D(U-C-14) glucose, release of lactate and pyruvate, incorporation of D-(U-C-14) glucose into glycogen, and the concentration of glucose 6-phosphate more (p less than 0.05) than in the weight-bearing soleus. At physiological doses of insulin, the percent of maximal uptake of 2-deoxy-D-(1,2-H-3) glucose/muscle also was greater in the unloaded soleus. Unloading of the soleus increased, by 50 percent the concentration of insuling receptors, due to no decrease in total receptor number during muscle atrophy. This increase may account for the greater response of glucose metabolism to insulin in this muscle. The extensor digitorum longus, which generally shows little response to unloading, displayed no differential response of glucose metabolism to insulin.

  14. Poly(ADP-ribose) metabolism in young and old cells: response to cellular stresses

    SciTech Connect

    Gracy, R.W.; Sims, J.L.; Cini, J.

    1986-05-01

    The authors have examined the effect of several cellular stresses on poly(ADP-ribose) metabolism in human fibroblasts of low passage number derived from young and old donors. Poly(ADP-ribose) was synthesized in response to alkylation of DNA caused by N-methyl-N'-nitro-N-nitroguanidine and by hyperthermic treatment at 43 /sup 0/C or 45 /sup 0/C. Ethanol is able to potentiate poly(ADP-ribose) accumulation following these treatments. There was little if any difference in the response of young and old cells to these stresses. Amino acid analogs are thought to induce a response in mammalian cells similar to that caused by hyperthermia and ethanol. However, amino acid analogs such as L-azetidine did not produce effects on poly(ADP-ribose) metabolism like those produced by ethanol or hyperthermia. The authors have also examined the poly(ADP-ribose) content of bovine eye lens. Each eye lens contains populations of young and old cells that are distributed in a fixed graduated manner. Thus, the eye lens allows the study of aging cells with identical genetic backgrounds without the complications of serial passage of young cultures in in vitro aging systems.

  15. Botanical and biological pesticides elicit a similar Induced Systemic Response in tomato (Solanum lycopersicum) secondary metabolism.

    PubMed

    Pretali, Luca; Bernardo, Letizia; Butterfield, Timothy S; Trevisan, Marco; Lucini, Luigi

    2016-10-01

    Natural pesticides have attracted substantial interest due to the increase in organic agriculture and enhanced attention to environmental pollution. Plant Growth Promoting Bacteria (PGPB) are applied for both disease control and growth enhancement; PGPBs are known to elicit Induced Systemic Response (ISR) in plants. However, less is known about the effect of botanical pesticides, such as the azadirachtin-containing neem extracts, on plant metabolism. This study aimed to investigate the effects of foliar application of the above-mentioned natural pesticides on the metabolic profiling of tomato. Leaf application of Bacillus subtilis fostered Induced Systemic Resistance (ISR) in treated plants via the Jasmonic acid pathway, and enhanced production of secondary metabolites such as flavonoids, phytoalexins and auxins. Changes in sterols and terpenes, as well as an increase in glucosinolates were also observed. Interestingly, azadirachtin-treated tomatoes also showed an increase in ISR and our results revealed that most of the enriched metabolites are shared with a B. subtilis treatment, suggesting conserved biochemical responses. These (un)expected findings indicate that plants are not insensitive to application of natural pesticide and while Azadirachtin is applied as a direct pesticide, it also stimulates a defense response in tomatoes very similar to B. subtilis induced ISR. PMID:27251587

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

    PubMed

    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. PMID:27297969

  17. Metabolic responses of clam Ruditapes philippinarum exposed to its pathogen Vibrio tapetis in relation to diet.

    PubMed

    Richard, Gaëlle; Guérard, Fabienne; Corporeau, Charlotte; Lambert, Christophe; Paillard, Christine; Pernet, Fabrice

    2016-07-01

    We investigated the effect of brown ring disease (BRD) development and algal diet on energy reserves and activity of enzymes related to energy metabolism, antioxidant system and immunity in Manila clam, Ruditapes philippinarum. We found that algal diet did not impact the metabolic response of clams exposed to Vibrio tapetis. At two days post-injection (dpi), activities of superoxide dismutase and glutathione peroxidase (GPx) decreased whereas activities of nitric oxide synthase (iNOS) and catalase increased in infected clams, although no clinical signs were visible (BRD-). At 7 dpi, activities of several antioxidant and immune-related enzymes were markedly increased in BRD-likely indicating an efficient reactive oxygen species (ROS) scavenging compared to animals which developed clinical signs of BRD (BRD+). Therefore, resistance to BRD clinical signs appearance was associated with higher detoxification of ROS and enhancement of immune response. This study provides new biochemical indicators of disease resistance and a more comprehensive view of the global antioxidant response of clam to BRD development. PMID:26921670

  18. Rain influences the physiological and metabolic responses to exercise in hot conditions.

    PubMed

    Ito, Ryo; Yamashita, Naoyuki; Suzuki, Eiko; Matsumoto, Takaaki

    2015-01-01

    Outdoor exercise often proceeds in rainy conditions. However, the cooling effects of rain on human physiological responses have not been systematically studied in hot conditions. The present study determined physiological and metabolic responses using a climatic chamber that can precisely simulate hot, rainy conditions. Eleven healthy men ran on a treadmill at an intensity of 70% VO2max for 30 min in the climatic chamber at an ambient temperature of 33°C in the presence (RAIN) or absence (CON) of 30 mm · h(-1) of precipitation and a headwind equal to the running velocity of 3.15 ± 0.19 m · s(-1). Oesophageal temperature, mean skin temperature, heart rate, rating of perceived exertion, blood parameters, volume of expired air and sweat loss were measured. Oesophageal and mean skin temperatures were significantly lower from 5 to 30 min, and heart rate was significantly lower from 20 to 30 min in RAIN than in CON (P < 0.05 for all). Plasma lactate and epinephrine concentrations (30 min) and sweat loss were significantly lower (P < 0.05) in RAIN compared with CON. Rain appears to influence physiological and metabolic responses to exercise in heat such that heat-induced strain might be reduced. PMID:25555077

  19. The response of the metabolic network of the red blood cell to pyruvate kinase deficiency.

    PubMed

    Sun, Xiaoliang; Lu, Zuhong

    2005-01-01

    The response of the metabolic network of human red blood cell is investigated using the E-Cell simulation system when pyruvate kinase (PK) is deficient. The results that several downstream metabolites of the glycolysis pathway accumulate are in a good agreement with experimental data reported in literatures. This accumulation results in the reaction that phosphoglycerate kinase (PGK) catalyzes reversing its direction. Mathematical analysis to the simulation results shows that the PGK-catalyzing reaction reversing its direction happens simultaneously with an abrupt change of the second derivative of the ATP quantity. PMID:17282332

  20. Visible light optical coherence tomography measures retinal oxygen metabolic response to systemic oxygenation

    PubMed Central

    Yi, Ji; Liu, Wenzhong; Chen, Siyu; Backman, Vadim; Sheibani, Nader; Sorenson, Christine M.; Fawzi, Amani A.; Linsenmeier, Robert A.; Zhang, Hao F.

    2015-01-01

    The lack of capability to quantify oxygen metabolism noninvasively impedes both fundamental investigation and clinical diagnosis of a wide spectrum of diseases including all the major blinding diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Using visible light optical coherence tomography (vis-OCT), we demonstrated accurate and robust measurement of retinal oxygen metabolic rate (rMRO2) noninvasively in rat eyes. We continuously monitored the regulatory response of oxygen consumption to a progressive hypoxic challenge. We found that both oxygen delivery, and rMRO2 increased from the highly regulated retinal circulation (RC) under hypoxia, by 0.28 ± 0.08 μL min−1 (p < 0.001), and 0.20 ± 0.04 μL min−1 (p < 0.001) per 100 mmHg systemic pO2 reduction, respectively. The increased oxygen extraction compensated for the deficient oxygen supply from the poorly regulated choroidal circulation. Results from an oxygen diffusion model based on previous oxygen electrode measurements corroborated our in vivo observations. We believe that vis-OCT has the potential to reveal the fundamental role of oxygen metabolism in various retinal diseases. PMID:26658555

  1. In silico analysis of Clostridium acetobutylicum ATCC 824 metabolic response to an external electron supply.

    PubMed

    Gallardo, Roberto; Acevedo, Alejandro; Quintero, Julián; Paredes, Ivan; Conejeros, Raúl; Aroca, Germán

    2016-02-01

    The biological production of butanol has become an important research field and thanks to genome sequencing and annotation; genome-scale metabolic reconstructions have been developed for several Clostridium species. This work makes use of the iCAC490 model of Clostridium acetobutylicum ATCC 824 to analyze its metabolic capabilities and response to an external electron supply through a constraint-based approach using the Constraint-Based Reconstruction Analysis Toolbox. Several analyses were conducted, which included sensitivity, production envelope, and phenotypic phase planes. The model showed that the use of an external electron supply, which acts as co-reducing agent along with glucose-derived reducing power (electrofermentation), results in an increase in the butanol-specific productivity. However, a proportional increase in the butyrate uptake flux is required. Besides, the uptake of external butyrate leads to the coupling of butanol production and growth, which coincides with results reported in literature. Phenotypic phase planes showed that the reducing capacity becomes more limiting for growth at high butyrate uptake fluxes. An electron uptake flux allows the metabolism to reach the growth optimality line. Although the maximum butanol flux does not coincide with the growth optimality line, a butyrate uptake combined with an electron uptake flux would result in an increased butanol volumetric productivity, being a potential strategy to optimize the production of butanol by C. acetobutylicum ATCC 824. PMID:26650720

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

    NASA Astrophysics Data System (ADS)

    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.

  3. Differential response of high-elevation planktonic bacterial community structure and metabolism to experimental nutrient enrichment.

    PubMed

    Nelson, Craig E; Carlson, Craig A

    2011-01-01

    Nutrient enrichment of high-elevation freshwater ecosystems by atmospheric deposition is increasing worldwide, and bacteria are a key conduit for the metabolism of organic matter in these oligotrophic environments. We conducted two distinct in situ microcosm experiments in a high-elevation lake (Emerald Lake, Sierra Nevada, California, USA) to evaluate responses in bacterioplankton growth, carbon utilization, and community structure to short-term enrichment by nitrate and phosphate. The first experiment, conducted just following ice-off, employed dark dilution culture to directly assess the impact of nutrients on bacterioplankton growth and consumption of terrigenous dissolved organic matter during snowmelt. The second experiment, conducted in transparent microcosms during autumn overturn, examined how bacterioplankton in unmanipulated microbial communities responded to nutrients concomitant with increasing phytoplankton-derived organic matter. In both experiments, phosphate enrichment (but not nitrate) caused significant increases in bacterioplankton growth, changed particulate organic stoichiometry, and induced shifts in bacterial community composition, including consistent declines in the relative abundance of Actinobacteria. The dark dilution culture showed a significant increase in dissolved organic carbon removal in response to phosphate enrichment. In transparent microcosms nutrient enrichment had no effect on concentrations of chlorophyll, carbon, or the fluorescence characteristics of dissolved organic matter, suggesting that bacterioplankton responses were independent of phytoplankton responses. These results demonstrate that bacterioplankton communities in unproductive high-elevation habitats can rapidly alter their taxonomic composition and metabolism in response to short-term phosphate enrichment. Our results reinforce the key role that phosphorus plays in oligotrophic lake ecosystems, clarify the nature of bacterioplankton nutrient limitation, and

  4. Metabolic Response of Dungeness Crab Larvae Exposed to Elevated CO2 and Hypoxia

    NASA Astrophysics Data System (ADS)

    Nichols, Z.; Busch, S.; McElhany, P.

    2015-12-01

    Ocean acidification (OA) and deoxygenation, both resulting from rising atmospheric CO2 levels, are lowering the pH and oxygen levels of global oceans. Assessing the impacts of OA and deoxygenation on harvested species is crucial for guiding resource management with the aim of maintaining healthy and sustainable populations. The Dungeness crab, Cancer magister, is an important species ecologically and economically for the US West Coast. Crabs transition through four main stages: zoea, megalopa, juvenile, and adult. Each stage results in a different morphology and behavior, and as a result, is exposed to various environmental parameters, such as pH and dissolved oxygen (DO). The first two stages exhibit diel vertical migration while the final stages are benthic. Our study focused on the megalopae stage and their metabolic response to OA and hypoxia. We exposed wild-caught megalopae to a pH x DO cross, producing treatment waters with combinations of low or high pH and O2, all maintained at 12˚C. Closed-chamber respirometry was used to compare standard metabolic rates in a common garden setting with high pH/high DO conditions. We predict that the megalopae exposed to the low pH/high DO treatment will have a higher metabolic rate than those exposed to the high pH/high DO treatment. This may be a result of homeostatic processes increasing to return the megalopae's internal pH back to equilibrium. We predict that the high pH/low DO treatment will cause a decrease in metabolism when compared to the high pH/high DO treatment due to the megalopae conserving oxygen in a limiting environment. If results support our hypothesis, they would suggest that OA and hypoxia affects Dungeness crabs in sublethal ways.

  5. Metabolic and Genomic Response to Dietary Isocaloric Protein Restriction in the Rat*

    PubMed Central

    Kalhan, Satish C.; Uppal, Sonal O.; Moorman, Jillian L.; Bennett, Carole; Gruca, Lourdes L.; Parimi, Prabhu S.; Dasarathy, Srinivasan; Serre, David; Hanson, Richard W.

    2011-01-01

    We have examined hepatic, genomic, and metabolic responses to dietary protein restriction in the non-pregnant Sprague-Dawley rat. Animals were pair-fed either a 6 or 24% casein-based diet for 7–10 days. At the end of the dietary period, a microarray analysis of the liver was performed, followed by validation of the genes of interest. The rates of appearance of phenylalanine, methionine, serine, and glucose and the contribution of pyruvate to serine and glucose were quantified using tracer methods. Plasma and tissue amino acid levels, enzyme activities, and metabolic intermediates were measured. Protein restriction resulted in significant differential expression of a number of genes involved in cell cycle, cell differentiation, transport, transcription, and metabolic processes. RT-PCR showed that the expression of genes involved in serine biosynthesis and fatty acid oxidation was higher, and those involved in fatty acid synthesis and urea synthesis were lower in the liver of protein-restricted animals. Free serine and glycine levels were higher and taurine levels lower in all tissues examined. Tracer isotope studies showed an ∼50% increase in serine de novo synthesis. Pyruvate was the primary (∼90%) source of serine in both groups. Transmethylation of methionine was significantly higher in the protein-restricted group. This was associated with a higher S-adenosylmethionine/S-adenosylhomocysteine ratio and lower cystathione β-synthase and cystathionine γ-lyase activity. Dietary isocaloric protein restriction results in profound changes in hepatic one-carbon metabolism within a short period. These may be related to high methylation demands placed on the organism and caused by possible changes in cellular osmolarity as a result of the efflux of the intracellular taurine. PMID:21147771

  6. Acute metabolic, hormonal, and psychological responses to different endurance training protocols.

    PubMed

    Wahl, P; Mathes, S; Köhler, K; Achtzehn, S; Bloch, W; Mester, J

    2013-10-01

    In the last years, mainly 2 high-intensity-training (HIT) protocols became common: first, a Wingate-based "all-out" protocol and second, a 4×4 min protocol. However, no direct comparison between these protocols exists, and also a comparison with high-volume-training (HVT) is missing. Therefore, the aim of the present study was to compare these 3 endurance training protocols on metabolic, hormonal, and psychological responses. Twelve subjects performed: 1) HVT [130 min at 55% peak power output (PPO)]; 2) 4×4 min at 95% PPO; 3) 4×30 s all-out. Human growth hormone (hGH), testosterone, and cortisol were determined before (pre) and 0', 30', 60', 180' after each intervention. Metabolic stimuli and perturbations were characterized by lactate, blood gas (pH, BE, HCO₃⁻, pO₂, PCO₂), and spirometric analysis. Furthermore, changes of the person's perceived physical state were determined. The 4×30 s training caused the highest increases in cortisol and hGH, followed by 4 × 4 min and HVT. Testosterone levels were significantly increased by all 3 exercise protocols. Metabolic stress was highest during and after 4×30 s, followed by 4×4 min and HVT. The 4×30 s training was also the most demanding intervention from an athlete's point of view. In conclusion, the results suggest that 4×30 s and 4×4 min promote anabolic processes more than HVT, due to higher increases of hGH, testosterone, and the T/C ratio. It can be speculated that the acute hormonal increase and the metabolic perturbations might play a positive role in optimizing training adaptation and in eliciting health benefits as it has been shown by previous long term training studies using similar exercise protocols. PMID:23794400

  7. Metabolic response to a glucagon challenge varies with adiposity and life-history stage in fasting northern elephant seals.

    PubMed

    Crocker, Daniel E; Fowler, Melinda A; Champagne, Cory D; Vanderlugt, Anna L; Houser, Dorian S

    2014-01-01

    Metabolic adaptations for extended fasting in wildlife prioritize beta-oxidation of lipids and reduced glucose utilization to support energy metabolism. The pancreatic hormone glucagon plays key roles in regulating glycemia and lipid metabolism during fasting in model species but its function in wildlife species adapted for extended fasting is not well understood. Northern elephant seals (NES) undergo natural fasts of 1-3months while under constraints of high nutrient demands including lactation and development. We performed a glucagon challenge on lactating, molting and developing NES, early and late in their natural fasts, to examine the impact of this important regulatory hormone on metabolism. Glucagon caused increases in plasma glucose, insulin, fatty acids, ketones and urea, but the magnitude of these effects varied widely with adiposity and life-history stage. The strong impact of adiposity on glucose and insulin responses suggest a potential role for adipose derived factors in regulating hepatic metabolism and pancreatic sensitivity. Elevations in plasma glucose in response to glucagon were strongly associated with increases in protein catabolism, suggesting negative impacts of elevated glucagon on protein sparing. Glucagon promoted rapid ketone accumulation suggesting that low ketoacid levels in NES reflect low rates of production. These results demonstrate strong metabolic impacts of glucagon and support the idea that glucagon levels are downregulated in the context of metabolic adaptation to extended fasting. These results suggest that the regulation of carbohydrate and lipid metabolism in NES changes with adiposity, fasting duration and under various constraints of nutrient demands. PMID:24239794

  8. A forage-only diet alters the metabolic response of horses in training.

    PubMed

    Jansson, A; Lindberg, J E

    2012-12-01

    Most athletic horses are fed a high-starch diet despite the risk of health problems. Replacing starch concentrate with high-energy forage would alleviate these health problems, but could result in a shift in major substrates for muscle energy supply from glucose to short-chain fatty acids (SCFA) due to more hindgut fermentation of fibre. Dietary fat inclusion has previously been shown to promote aerobic energy supply during exercise, but the contribution of SCFA to exercise metabolism has received little attention. This study compared metabolic response with exercise and lactate threshold (VLa4) in horses fed a forage-only diet (F) and a more traditional high-starch, low-energy forage diet (forage-concentrate diet - FC). The hypothesis was that diet F would increase plasma acetate concentration and increase VLa4 compared with diet FC. Six Standardbred geldings in race training were used in a 29-day change-over experiment. Plasma acetate, non-esterified fatty acids (NEFA), lactate, glucose and insulin concentrations and venous pH were measured in samples collected before, during and after a treadmill exercise test (ET, day 25) and muscle glycogen concentrations before and after ET. Plasma acetate concentration was higher before and after exercise in horses on diet F compared with diet FC, and there was a tendency (P = 0.09) for increased VLa4 on diet F. Venous pH and plasma glucose concentrations during exercise were higher in horses on diet F than diet FC, as was plasma NEFA on the day after ET. Plasma insulin and muscle glycogen concentrations were lower for diet F, but glycogen utilisation was similar for the two diets. The results show that a high-energy, forage-only diet alters the metabolic response to exercise and, with the exception of lowered glycogen stores, appears to have positive rather than negative effects on performance traits. PMID:22717208

  9. The metabolic response to postnatal leptin in rats varies with age and may be litter dependent.

    PubMed

    Granado, M; Diaz, F; Fuente-Martín, E; García-Cáceres, C; Argente, J; Chowen, J A

    2014-06-01

    Hyperleptinemia during postnatal life induces long-term effects on metabolism. However, these effects are controversial as both increased and decreased propensity towards obesity has been reported. To further analyze the effects of chronic neonatal hyperleptinemia on the subsequent metabolic profile, male Wistar rats proceeding from 18 different litters (8 pups/litter) received a daily subcutaneous injection of either saline (10 ml/kg, n=36) or leptin (3 μg/g, n=36) from postnatal day (PND) 2 to PND9. Rats were sacrificed at 10, 40, or 150 days of age. At 10 days of age, leptin treated rats had decreased body weight (p<0.001) and body fat (p<0.05). Leptin levels and glycemia were increased (p<0.01), whereas insulin, total lipids, triglycerides and glycerol levels were decreased (p<0.05). At PND40 rats receiving leptin had increased glycemia (p<0.01) and plasma HDL and LDL levels, but decreased total lipids (p<0.05). At PND150 neonatal leptin treatment induced different effects in rats raised in different litters. Rats from litter 1 had increased body weight (p<0.05), body fat (p<0.01), and plasma leptin (p<0.001), cholesterol (p<0.001), triglyceride (p<0.001), total lipid (p<0.001), LDL (p<0.05), and glycerol (p<0.001) levels. In rats from litter 2 these parameters did not differ from controls. Rats from litter 3 had decreased body weight (p<0.05), visceral fat (p<0.01) and plasma leptin (p<0.001), cholesterol (p<0.001), triglyceride (p<0.001), glycerol (p<0.001), and HDL (p<0.001) levels. In conclusion, the metabolic response to postnatal leptin varies with age, with the response in adulthood being variable and most likely influenced by other factors, including the genetic make-up. PMID:24446159

  10. The Hsp72 response in peri-parturient dairy cows: relationships with metabolic and immunological parameters

    PubMed Central

    Catalani, Elisabetta; Amadori, Massimo; Vitali, Andrea; Bernabucci, Umberto; Nardone, Alessandro

    2010-01-01

    The study was aimed at assessing whether the peri-parturient period is associated with changes of intracellular and plasma inducible heat shock proteins (Hsp) 72 kDa molecular weight in dairy cows, and to establish possible relationships between Hsp72, metabolic, and immunological parameters subjected to changes around calving. The study was carried out on 35 healthy peri-parturient Holstein cows. Three, two, and one week before the expected calving, and 1, 2, 3, 4, and 5 weeks after calving, body conditions score (BCS) was measured and blood samples were collected to separate plasma and peripheral blood mononuclear cells (PBMC). Concentrations of Hsp72 in PBMC and plasma increased sharply after calving. In the post-calving period, BCS and plasma glucose declined, whereas plasma nonesterified fatty acids (NEFA) and tumor necrosis factor-alpha increased. The proliferative responses of PBMC to lipopolysaccharide (LPS) declined progressively after calving. The percentage of PBMC expressing CD14 receptors and Toll-like receptors (TLR)-4 increased and decreased in the early postpartum period, respectively. Correlation analysis revealed significant positive relationships between Hsp72 and NEFA, and between PBMC proliferation in response to LPS and the percentage of PBMC expressing TLR-4. Conversely, significant negative relationships were found between LPS-triggered proliferation of PBMC and both intracellular and plasma Hsp72. Literature data and changes of metabolic and immunological parameters reported herein authorize a few interpretative hypotheses and encourage further studies aimed at assessing possible cause and effect relationships between changes of PBMC and circulating Hsp72, metabolic, and immune parameters in dairy cows. PMID:20349286

  11. Oxidative stress and metabolic responses to copper in freshwater- and seawater-acclimated killifish, Fundulus heteroclitus.

    PubMed

    Ransberry, Victoria E; Morash, Andrea J; Blewett, Tamzin A; Wood, Chris M; McClelland, Grant B

    2015-04-01

    In freshwater (FW), many of the main mechanisms of copper (Cu) toxicity have been characterized; however, toxicity mechanisms in seawater (SW) are less well understood. We investigated the effects of salinity on Cu-induced oxidative stress and metabolic responses in adult killifish, Fundulus heteroclitus. We exposed FW and SW-acclimated killifish to either low Cu (LC, 50 μg/L) or high Cu (HC, 200 μg/L) for 96 h and compared them to controls (CTRL) under the same salinities without added Cu. Cu exerted minimal influence on tissue ion levels in either FW or SW. Salinity generally protected against Cu bioaccumulation in the gills and liver, but not in the carcass. Hematocrit (Hct) and hemoglobin (Hb) levels were increased by LC and HC in both FW and SW, and blood lactate was reduced in FW-killifish exposed to LC and HC. Rates of oxygen consumption were similar across treatments. Salinity reduced Cu load in gill, liver and intestine at LC but only in the gills at HC. In general, Cu increased gill, liver, and intestine catalase (CAT) activity, while superoxide dismutase (SOD) either decreased or remained unchanged depending on tissue-type. These changes did not directly correlate with levels of protein carbonyls, used as an index of oxidative stress. Cu-induced changes in carbohydrate metabolic enzymes were low across tissues and the effect of salinity was variable. Thus, while salinity clearly protects against Cu bioaccumulation in some tissues, it is unclear whether salinity protects against Cu-induced oxidative stress and metabolic responses. PMID:25731683

  12. Time course of the response of carbohydrate metabolism to unloading of the soleus

    NASA Technical Reports Server (NTRS)

    Henriksen, Erik J.; Tischler, Marc E.

    1988-01-01

    The time course of the response of carbohydrate metabolism to unloading was studied in the soleus muscle of rats subjected to tail-cast suspension. In the fresh soleus, 12 hours of unloading led to higher concentrations of glycogen and lower activity ratios of both glycogen synthase and glycogen phosphorylase. These changes were still evident on day three. Thereafter, the increased glycogen concentration apparently diminished the activity ratio of glycogen synthase, leading to a subsequent fall in the total glycogen content after day one. After 24 hours of unloading, when no significant atrophy was detectable, there was no differential response to insulin for in vitro glucose metabolism. On day three, the soleus atrophied significantly and displayed a greater sensitivity to insulin for most of these parameters compared to the weight-bearing control muscle. However, insulin sensitivity for glycogen synthesis was unchanged. These results showed that the increased sensitivity to insulin of the unloaded soleus is associated with the degree of muscle atrophy, likely due to an increased insulin binding capacity relative to muscle mass. This study also showed that insulin regulation of glucose uptake and of glycogen synthesis is affected differentially in the unloaded soleus muscle.

  13. Sulfation of 25-hydroxycholesterol regulates lipid metabolism, inflammatory responses, and cell proliferation

    PubMed Central

    Ning, Yanxia

    2013-01-01

    Intracellular lipid accumulation, inflammatory responses, and subsequent apoptosis are the major pathogenic events of metabolic disorders, including atherosclerosis and nonalcoholic fatty liver diseases. Recently, a novel regulatory oxysterol, 5-cholesten-3b, 25-diol 3-sulfate (25HC3S), has been identified, and hydroxysterol sulfotransferase 2B1b (SULT2B1b) has been elucidated as the key enzyme for its biosynthesis from 25-hydroxycholesterol (25HC) via oxysterol sulfation. The product 25HC3S and the substrate 25HC have been shown to coordinately regulate lipid metabolism, inflammatory responses, and cell proliferation in vitro and in vivo. 25HC3S decreases levels of the nuclear liver oxysterol receptor (LXR) and sterol regulatory element-binding proteins (SREBPs), inhibits SREBP processing, subsequently downregulates key enzymes in lipid biosynthesis, decreases intracellular lipid levels in hepatocytes and THP-1-derived macrophages, prevents apoptosis, and promotes cell proliferation in liver tissues. Furthermore, 25HC3S increases nuclear PPARγ and cytosolic IκBα and decreases nuclear NF-κB levels and proinflammatory cytokine expression and secretion when cells are challenged with LPS and TNFα. In contrast to 25HC3S, 25HC, a known LXR ligand, increases nuclear LXR and decreases nuclear PPARs and cytosol IκBα levels. In this review, we summarize our recent findings, including the discovery of the regulatory oxysterol sulfate, its biosynthetic pathway, and its functional mechanism. We also propose that oxysterol sulfation functions as a regulatory signaling pathway. PMID:24302009

  14. Medicago truncatula Mtha1-2 mutants loose metabolic responses to mycorrhizal colonization.

    PubMed

    Hubberten, Hans-Michael; Sieh, Daniela; Zöller, Daniela; Hoefgen, Rainer; Krajinski, Franziska

    2015-01-01

    Bidirectional nutrient transfer is one of the key features of the arbuscular mycorrhizal symbiosis. Recently we were able to identify a Medicago truncatula mutant (mtha1-2) that is defective in the uptake of phosphate from the periarbuscular space due to a lack of the energy providing proton gradient provided by the symbiosis specific proton ATPase MtHA1 In order to further characterize the impact of fungal colonization on the plant metabolic status, without the beneficial aspect of improved mineral nutrition, we performed leaf ion analyses in mutant and wildtype plants with and without fungal colonization. Although frequency of fungal colonization was unaltered, the mutant did not show a positive growth response to mycorrhizal colonization. This indicates that nutrient transfer into the plant cell fails in the truncated arbuscules due to lacking expression of a functional MtHA1 protein. The leaves of wildtype plants showed clear metabolic responses to root mycorrhizal colonization, whereas no changes of leaf metabolite levels of mycorrhizal mtha1-2 plants were detected, even though they were colonized. These results show that MtHa1 is indispensable for a functional mycorrhizal symbiosis and, moreover, suggest that fungal root colonization per se does not depend on nutrient transfer to the plant host. PMID:25751449

  15. Polyamine metabolic canalization in response to drought stress in Arabidopsis and the resurrection plant Craterostigma plantagineum

    PubMed Central

    Bartels, Dorothea; Koncz, Csaba; Altabella, Teresa

    2011-01-01

    In this work, we have studied the transcriptional profiles of polyamine biosynthetic genes and analyzed polyamine metabolic fluxes during a gradual drought acclimation response in Arabidopsis thaliana and the resurrection plant Craterostigma plantagineum. The analysis of free putrescine, spermidine and spermine titers in Arabidopsis arginine decarboxylase (adc1–3, adc2–3), spermidine synthase (spds1–2, spds2–3) and spermine synthase (spms-2) mutants during drought stress, combined with the quantitative expression of the entire polyamine biosynthetic pathway in the wild-type, has revealed a strong metabolic canalization of putrescine to spermine induced by drought. Such canalization requires spermidine synthase 1 (SPDS1) and spermine synthase (SPMS) activities and, intriguingly, does not lead to spermine accumulation but to a progressive reduction in spermidine and spermine pools in the wild-type. Our results suggest the participation of the polyamine back-conversion pathway during the drought stress response rather than the terminal catabolism of spermine. The putrescine to spermine canalization coupled to the spermine to putrescine back-conversion confers an effective polyamine recycling-loop during drought acclimation. Putrescine to spermine canalization has also been revealed in the desiccation tolerant plant C. plantagineum, which conversely to Arabidopsis, accumulates high spermine levels which associate with drought tolerance. Our results provide a new insight to the polyamine homeostasis mechanisms during drought stress acclimation in Arabidopsis and resurrection plants. PMID:21330782

  16. Systems-level analysis of the metabolic responses of the diatom Phaeodactylum tricornutum to phosphorus stress.

    PubMed

    Yang, Zhi-Kai; Zheng, Jian-Wei; Niu, Ying-Fang; Yang, Wei-Dong; Liu, Jie-Sheng; Li, Hong-Ye

    2014-06-01

    Phosphorus is an important macronutrient. To understand the molecular and cellular responses to phosphorus stress better, transcriptome profiling in combination with biochemical investigations was conducted in the model diatom Phaeodactylum tricornutum. Out of 10 402 predicted genes, 2491 and 405 genes were significantly upregulated or downregulated respectively. Unsurprisingly, genes associated with phosphate uptake were upregulated, such as the phosphate transporters and alkaline phosphatases. Genes encoding stress-shock proteins were accordingly upregulated, including genes associated with stress-responsive proteins, signal transduction and secondary metabolism. Additionally, genes related to protein translation, carbon fixation, glycolysis and the citric acid cycle were also upregulated. Genes associated with gene transcription were downregulated, thereby resulting in the upregulation of translation to compensate for the limited supply of messenger RNA. The downregulation of genes related to β-oxidation could contribute to the accumulation of fatty acids. Accordingly, triacylglycerols, which are important for energy storage, were determined to increase by 1.65-fold. Intracellular membranes, other than chloroplast membranes, tended to be dispersed; this finding was in accordance with the increased transcription of a total of 11 genes encoding putative phospholipases. Taken together, this work revealed the coordination of multiple metabolic pathways and certain key genes in the adaptation of P. tricornutum to phosphorus stress. PMID:24467511

  17. PTRF/Cavin-1 promotes efficient ribosomal RNA transcription in response to metabolic challenges

    PubMed Central

    Liu, Libin; Pilch, Paul F

    2016-01-01

    Ribosomal RNA transcription mediated by RNA polymerase I represents the rate-limiting step in ribosome biogenesis. In eukaryotic cells, nutrients and growth factors regulate ribosomal RNA transcription through various key factors coupled to cell growth. We show here in mature adipocytes, ribosomal transcription can be acutely regulated in response to metabolic challenges. This acute response is mediated by PTRF (polymerase I transcription and release factor, also known as cavin-1), which has previously been shown to play a critical role in caveolae formation. The caveolae–independent rDNA transcriptional role of PTRF not only explains the lipodystrophy phenotype observed in PTRF deficient mice and humans, but also highlights its crucial physiological role in maintaining adipocyte allostasis. Multiple post-translational modifications of PTRF provide mechanistic bases for its regulation. The role of PTRF in ribosomal transcriptional efficiency is likely relevant to many additional physiological situations of cell growth and organismal metabolism. DOI: http://dx.doi.org/10.7554/eLife.17508.001 PMID:27528195

  18. Growth, metabolism and physiological response of the sea cucumber, Apostichopus japonicus Selenka during periods of inactivity

    NASA Astrophysics Data System (ADS)

    Du, Rongbin; Zang, Yuanqi; Tian, Xiangli; Dong, Shuanglin

    2013-03-01

    The growth, metabolism and physiological response of the sea cucumber, Apostichopus japonicus, were investigated during periods of inactivity. The body weight, oxygen consumption rate (OCR), activities of acidic phosphatase (ACP), alkaline phosphatase (AKP), catalase (CAT) and superoxide dismutase (SOD), and content of heat shock protein 70 (Hsp70) in the body wall and coelomic fluid of A. japonicus were measured during starvation, experimental aestivation and aestivation. The results showed that the body weight of sea cucumber in the three treatments decreased significantly during the experimental period ( P < 0.05). The OCR of sea cucumber reduced in starvation and experimental aestivation treatments, but increased gradually in natural aestivation treatment. The activities of ACP and AKP of sea cucumber decreased gradually in all treatments, whereas those of SOD and CAT as well as Hsp70 content decreased in the starvation and experimental aestivation treatments and increased in natural aestivation treatment. The sea cucumber entered a state of aestivation at 24°C. To some extent, the animals in experimental aestivation were different from those in natural aestivation in metabolism and physiological response. These findings suggested that the aestivation mechanism of A. japonicus is complex and may not be attributed to the elevated temperature only.

  19. Calcium-dependent physiologic and pathologic stimulus-metabolic response coupling in hepatocytes.

    PubMed

    Gaspers, Lawrence D; Mémin, Elisabeth; Thomas, Andrew P

    2012-07-01

    A recurrent paradigm in calcium signaling is the coordination of the target response of the calcium signal with activation of metabolic energy production to support that response. This occurs in many tissues, including cardiac and skeletal muscle where contractile activity and ATP production are coordinately regulated by the frequency and amplitude of calcium transients, endocrine and exocrine cells that use calcium to drive the secretory process, and hepatocytes where the downstream targets of calcium include both catabolic and anabolic processes. The primary mechanism by which calcium enhances the capacity for energy production is through calcium-dependent stimulation of mitochondrial oxidative metabolism, achieved by increasing NADH production and respiratory chain flux. Although this enhances energy supply, it also has the potential for deleterious consequences resulting from increased generation of reactive oxygen species (ROS). The negative consequences of calcium-dependent mitochondrial activation can be ameliorated when the underlying cytosolic calcium signals occur as brief calcium spikes or oscillations, with signal strength encoded through the spike frequency (frequency modulation). Frequency modulation increases signal fidelity, and reduces pathological effects of calcium, including excess mitochondrial ROS production and apoptotic or necrotic outcomes. The present article reviews these issues using data obtained in hepatocytes under physiologic and pathologic conditions. PMID:22564906

  20. Calcium-Dependent Physiologic and Pathologic Stimulus-Metabolic Response Coupling in Hepatocytes

    PubMed Central

    Gaspers, Lawrence D.; Mémin, Elisabeth; Thomas, Andrew P.

    2012-01-01

    A recurrent paradigm in calcium signaling is the coordination of the target response of the calcium signal with activation of metabolic energy production to support that response. This occurs in many tissues, including cardiac and skeletal muscle where contractile activity and ATP production are coordinately regulated by the frequency and amplitude of calcium transients, endocrine and exocrine cells that use calcium to drive the secretory process, and hepatocytes where the downstream targets of calcium include both catabolic and anabolic processes. The primary mechanism by which calcium enhances the capacity for energy production is through calcium-dependent stimulation of mitochondrial oxidative metabolism, achieved by increasing NADH production and respiratory chain flux. Although this enhances energy supply, it also has the potential for deleterious consequences resulting from increased generation of reactive oxygen species (ROS). The negative consequences of calcium-dependent mitochondrial activation can be ameliorated when the underlying cytosolic calcium signals occur as brief calcium spikes or oscillations, with signal strength encoded through the spike frequency (frequency modulation). Frequency modulation increases signal fidelity, and reduces pathological effects of calcium, including excess mitochondrial ROS production and apoptotic or necrotic outcomes. The present article reviews these issues using data obtained in hepatocytes under physiologic and pathologic conditions. PMID:22564906

  1. Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress

    PubMed Central

    Picard, Martin; McManus, Meagan J.; Gray, Jason D.; Nasca, Carla; Moffat, Cynthia; Kopinski, Piotr K.; Seifert, Erin L.; McEwen, Bruce S.; Wallace, Douglas C.

    2015-01-01

    The experience of psychological stress triggers neuroendocrine, inflammatory, metabolic, and transcriptional perturbations that ultimately predispose to disease. However, the subcellular determinants of this integrated, multisystemic stress response have not been defined. Central to stress adaptation is cellular energetics, involving mitochondrial energy production and oxidative stress. We therefore hypothesized that abnormal mitochondrial functions would differentially modulate the organism’s multisystemic response to psychological stress. By mutating or deleting mitochondrial genes encoded in the mtDNA [NADH dehydrogenase 6 (ND6) and cytochrome c oxidase subunit I (COI)] or nuclear DNA [adenine nucleotide translocator 1 (ANT1) and nicotinamide nucleotide transhydrogenase (NNT)], we selectively impaired mitochondrial respiratory chain function, energy exchange, and mitochondrial redox balance in mice. The resulting impact on physiological reactivity and recovery from restraint stress were then characterized. We show that mitochondrial dysfunctions altered the hypothalamic–pituitary–adrenal axis, sympathetic adrenal–medullary activation and catecholamine levels, the inflammatory cytokine IL-6, circulating metabolites, and hippocampal gene expression responses to stress. Each mitochondrial defect generated a distinct whole-body stress-response signature. These results demonstrate the role of mitochondrial energetics and redox balance as modulators of key pathophysiological perturbations previously linked to disease. This work establishes mitochondria as stress-response modulators, with implications for understanding the mechanisms of stress pathophysiology and mitochondrial diseases. PMID:26627253

  2. Effects of tempol on altered metabolism and renal vascular responsiveness in fructose-fed rats.

    PubMed

    Abdulla, Mohammed H; Sattar, Munavvar A; Johns, Edward J

    2016-02-01

    This study investigated the effect of tempol (a superoxide dismutase mimetic) on renal vasoconstrictor responses to angiotensin II (Ang II) and adrenergic agonists in fructose-fed Sprague-Dawley rats (a model of metabolic syndrome). Rats were fed 20% fructose in drinking water (F) for 8 weeks. One fructose-fed group received tempol (FT) at 1 mmol·L(-1) in drinking water for 8 weeks or as an infusion (1.5 mg·kg(-1)·min(-1)) intrarenally. At the end of the treatment regimen, the renal responses to noradrenaline, phenylephrine, methoxamine, and Ang II were determined. F rats exhibited hyperinsulinemia, hyperuricemia, hypertriglyceridemia, and hypertension. Tempol reduced blood glucose and insulin levels (all p < 0.05) in FT rats compared with their untreated counterparts. The vasoconstriction response to all agonists was lower in F rats than in control rats by about 35%-65% (all p < 0.05). Vasoconstrictor responses to noradrenaline, phenylephrine, and methoxamine but not Ang II were about 41%-75% higher in FT rats compared with F rats (all p < 0.05). Acute tempol infusion blunted responses to noradrenaline, methoxamine, and Ang II in control rats by 32%, 33%, and 62%, while it blunted responses to noradrenaline and Ang II in F rats by 26% and 32%, respectively (all p < 0.05), compared with their untreated counterparts. Superoxide radicals play a crucial role in controlling renal vascular responses to adrenergic agonists in insulin-resistant rats. Chronic but not acute tempol treatment enhances renal vascular responsiveness in fructose-fed rats. PMID:26789093

  3. Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions

    PubMed Central

    Klevenhusen, Fenja; Humer, Elke; Metzler-Zebeli, Barbara; Podstatzky-Lichtenstein, Leopold; Wittek, Thomas; Zebeli, Qendrim

    2015-01-01

    Simple Summary This research established an association between lactation number and milk production and metabolic and inflammatory responses in high-producing dairy cows affected by left abomasal displacement in small-scaled dairy farms. The study showed metabolic alterations, liver damage, and inflammation in the sick cows, which were further exacerbated with increasing lactation number and milk yield of the cows. Abstract Left displaced abomasum (LDA) is a severe metabolic disease of cattle with a strong negative impact on production efficiency of dairy farms. Metabolic and inflammatory alterations associated with this disease have been reported in earlier studies, conducted mostly in large dairy farms. This research aimed to: (1) evaluate metabolic and inflammatory responses in dairy cows affected by LDA in small-scaled dairy farms; and (2) establish an association between lactation number and milk production with the outcome of metabolic variables. The cows with LDA had lower serum calcium (Ca), but greater concentrations of non-esterified fatty acids (NEFA) and beta-hydroxy-butyrate (BHBA), in particular when lactation number was >2. Cows with LDA showed elevated levels of aspartate aminotransferase, glutamate dehydrogenase, and serum amyloid A (SAA), regardless of lactation number. In addition, this study revealed strong associations between milk yield and the alteration of metabolic profile but not with inflammation in the sick cows. Results indicate metabolic alterations, liver damage, and inflammation in LDA cows kept under small-scale farm conditions. Furthermore, the data suggest exacerbation of metabolic profile and Ca metabolism but not of inflammation and liver health with increasing lactation number and milk yield in cows affected by LDA. PMID:26479481

  4. Effects of Chronic Environmental Cold on Growth, Health and Select Metabolic and Immunologic Responses of Preruminant Calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The physiological response of the preruminant calf to sustained exposure to cold has not been studied extensively. Effects of cold on growth performance and health of preruminant calves as well as functional measures of energy metabolism, fat-soluble vitamin, and immune responsiveness were evaluate...

  5. TRPA1 mediates amplified sympathetic responsiveness to activation of metabolically sensitive muscle afferents in rats with femoral artery occlusion

    PubMed Central

    Xing, Jihong; Lu, Jian; Li, Jianhua

    2015-01-01

    Autonomic responses to activation of mechanically and metabolically sensitive muscle afferent nerves during static contraction are augmented in rats with femoral artery occlusion. Moreover, metabolically sensitive transient receptor potential cation channel subfamily A, member 1 (TRPA1) has been reported to contribute to sympathetic nerve activity (SNA) and arterial blood pressure (BP) responses evoked by static muscle contraction. Thus, in the present study, we examined the mechanisms by which afferent nerves' TRPA1 plays a role in regulating amplified sympathetic responsiveness due to a restriction of blood flow directed to the hindlimb muscles. Our data show that 24–72 h of femoral artery occlusion (1) upregulates the protein levels of TRPA1 in dorsal root ganglion (DRG) tissues; (2) selectively increases expression of TRPA1 in DRG neurons supplying metabolically sensitive afferent nerves of C-fiber (group IV); and (3) enhances renal SNA and BP responses to AITC (a TRPA1 agonist) injected into the hindlimb muscles. In addition, our data demonstrate that blocking TRPA1 attenuates SNA and BP responses during muscle contraction to a greater degree in ligated rats than those responses in control rats. In contrast, blocking TRPA1 fails to attenuate SNA and BP responses during passive tendon stretch in both groups. Overall, results of this study indicate that alternations in muscle afferent nerves' TRPA1 likely contribute to enhanced sympathetically mediated autonomic responses via the metabolic component of the muscle reflex under circumstances of chronic muscle ischemia. PMID:26441669

  6. Juvenile roach (Rutilus rutilus) increase their anaerobic metabolism in response to copper exposure in laboratory conditions.

    PubMed

    Maes, Virginie; Betoulle, Stéphane; Jaffal, Ali; Dedourge-Geffard, Odile; Delahaut, Laurence; Geffard, Alain; Palluel, Olivier; Sanchez, Wilfried; Paris-Palacios, Séverine; Vettier, Aurélie; David, Elise

    2016-07-01

    This study aims to determine the potential impairment of cell energy synthesis processes (glycolysis and respiratory chain pathways) by copper in juvenile roach at different regulation levels by using a multi-marker approach. Juvenile roach were exposed to 0, 10, 50, and 100 µg/L of copper for 7 days in laboratory conditions. The glycolysis pathway was assessed by measuring the relative expression levels of 4 genes encoding glycolysis enzymes. The respiratory chain was studied by assessing the electron transport system and cytochrome c oxidase gene expression. Muscle mitochondria ultrastructure was studied, and antioxidant responses were measured. Furthermore, the main energy reserves-carbohydrates, lipids, and proteins-were measured, and cellular energy was evaluated by measuring ATP, ADP, AMP and IMP concentrations. This study revealed a disturbance of the cell energy metabolism due to copper exposure, with a significant decrease in adenylate energy charge in roach exposed to 10 μg/L of copper after 1 day. Moreover, ATP concentrations significantly decreased in roach exposed to 10 μg/L of copper after 1 day. This significant decrease persisted in roach exposed to 50 µg/L of copper after 7 days. AMP concentrations increased in all contaminated fish after 1 day of exposure. In parallel, the relative expression of 3 genes encoding for glycolysis enzymes increased in all contaminated fish after 1 day of copper exposure. Focusing on the respiratory chain, cytochrome c oxidase gene expression also increased in all contaminated fish at the two time-points. The activity of the electron transport system was not disturbed by copper, except in roach exposed to 100 µg/L of copper after 1 day. Copper induced a metabolic stress. Juvenile roach seemed to respond to the ensuing high energy demand by increasing their anaerobic metabolism, but the energy produced by the anaerobic metabolism is unable to compensate for the stress induced by copper after 7

  7. The Prognostic Significance of Metabolic Response Heterogeneity in Metastatic Colorectal Cancer

    PubMed Central

    Hendlisz, Alain; Deleporte, Amelie; Delaunoit, Thierry; Maréchal, Raphaël; Peeters, Marc; Holbrechts, Stéphane; Van den Eynde, Marc; Houbiers, Ghislain; Filleul, Bertrand; Van Laethem, Jean-Luc; Ceyssens, Sarah; Barbuto, Anna-Maria; Lhommel, Renaud; Demolin, Gauthier; Garcia, Camilo; El Mansy, Hazem; Ameye, Lieveke; Moreau, Michel; Guiot, Thomas; Paesmans, Marianne; Piccart, Martine; Flamen, Patrick

    2015-01-01

    Background Tumoral heterogeneity is a major determinant of resistance in solid tumors. FDG-PET/CT can identify early during chemotherapy non-responsive lesions within the whole body tumor load. This prospective multicentric proof-of-concept study explores intra-individual metabolic response (mR) heterogeneity as a treatment efficacy biomarker in chemorefractory metastatic colorectal cancer (mCRC). Methods Standardized FDG-PET/CT was performed at baseline and after the first cycle of combined sorafenib (600mg/day for 21 days, then 800mg/day) and capecitabine (1700 mg/m²/day administered D1-14 every 21 days). MR assessment was categorized according to the proportion of metabolically non-responding (non-mR) lesions (stable FDG uptake with SUVmax decrease <15%) among all measurable lesions. Results Ninety-two patients were included. The median overall survival (OS) and progression-free survival (PFS) were 8.2 months (95% CI: 6.8–10.5) and 4.2 months (95% CI: 3.4–4.8) respectively. In the 79 assessable patients, early PET-CT showed no metabolically refractory lesion in 47%, a heterogeneous mR with at least one non-mR lesion in 32%, and a consistent non-mR or early disease progression in 21%. On exploratory analysis, patients without any non-mR lesion showed a significantly longer PFS (HR 0.34; 95% CI: 0.21–0.56, P-value <0.001) and OS (HR 0.58; 95% CI: 0.36–0.92, P-value 0.02) compared to the other patients. The proportion of non-mR lesions within the tumor load did not impact PFS/OS. Conclusion The presence of at least one metabolically refractory lesion is associated with a poorer outcome in advanced mCRC patients treated with combined sorafenib-capecitabine. Early detection of treatment-induced mR heterogeneity may represent an important predictive efficacy biomarker in mCRC. Trial Registration ClinicalTrials.gov NCT01290926 PMID:26421426

  8. Intra-myocellular fatty acid metabolism plays a critical role in mediating responses to dietary restriction in Drosophila melanogaster

    PubMed Central

    Katewa, Subhash D.; Demontis, Fabio; Kolipinski, Marysia; Hubbard, Allan; Gill, Matthew S.; Perrimon, Norbert; Melov, Simon; Kapahi, Pankaj

    2012-01-01

    Summary Changes in fat content have been associated with dietary restriction (DR), but whether they play a causal role in mediating various responses to DR remains unknown. We demonstrate that upon DR, Drosophila melanogaster shift their metabolism towards increasing both fatty acid synthesis and breakdown, which is required for various responses to DR. Inhibition of fatty acid synthesis or oxidation genes specifically in the muscle tissue inhibited lifespan extension upon DR. Furthermore, DR enhances spontaneous activity of flies which was found to be dependent on the enhanced fatty acid metabolism. This increase in activity was found to be at least partially required for the lifespan extension upon DR. Over-expression of adipokinetic hormone (dAKH), the functional ortholog of glucagon, enhances fat metabolism, spontaneous activity and lifespan. Together, these results suggest that enhanced fat metabolism in the muscle and physical activity play a key role in the protective effects of DR. PMID:22768842

  9. Impact of Ocean Acidification on Energy Metabolism of Oyster, Crassostrea gigas—Changes in Metabolic Pathways and Thermal Response

    PubMed Central

    Lannig, Gisela; Eilers, Silke; Pörtner, Hans O.; Sokolova, Inna M.; Bock, Christian

    2010-01-01

    Climate change with increasing temperature and ocean acidification (OA) poses risks for marine ecosystems. According to Pörtner and Farrell [1], synergistic effects of elevated temperature and CO2-induced OA on energy metabolism will narrow the thermal tolerance window of marine ectothermal animals. To test this hypothesis, we investigated the effect of an acute temperature rise on energy metabolism of the oyster, Crassostrea gigas chronically exposed to elevated CO2 levels (partial pressure of CO2 in the seawater ~0.15 kPa, seawater pH ~ 7.7). Within one month of incubation at elevated Pco2 and 15 °C hemolymph pH fell (pHe = 7.1 ± 0.2 (CO2-group) vs. 7.6 ± 0.1 (control)) and Peco2 values in hemolymph increased (0.5 ± 0.2 kPa (CO2-group) vs. 0.2 ± 0.04 kPa (control)). Slightly but significantly elevated bicarbonate concentrations in the hemolymph of CO2-incubated oysters ([HCO− 3]e = 1.8 ± 0.3 mM (CO2-group) vs. 1.3 ± 0.1 mM (control)) indicate only minimal regulation of extracellular acid-base status. At the acclimation temperature of 15 °C the OA-induced decrease in pHe did not lead to metabolic depression in oysters as standard metabolism rates (SMR) of CO2-exposed oysters were similar to controls. Upon acute warming SMR rose in both groups, but displayed a stronger increase in the CO2-incubated group. Investigation in isolated gill cells revealed a similar temperaturedependence of respiration between groups. Furthermore, the fraction of cellular energy demand for ion regulation via Na+/K+-ATPase was not affected by chronic hypercapnia or temperature. Metabolic profiling using 1H-NMR spectroscopy revealed substantial changes in some tissues following OA exposure at 15 °C. In mantle tissue alanine and ATP levels decreased significantly whereas an increase in succinate levels was observed in gill tissue. These findings suggest shifts in metabolic pathways following OA-exposure. Our study confirms that OA affects energy metabolism in oysters and

  10. Impact of ocean acidification on energy metabolism of oyster, Crassostrea gigas--changes in metabolic pathways and thermal response.

    PubMed

    Lannig, Gisela; Eilers, Silke; Pörtner, Hans O; Sokolova, Inna M; Bock, Christian

    2010-01-01

    Climate change with increasing temperature and ocean acidification (OA) poses risks for marine ecosystems. According to Pörtner and Farrell, synergistic effects of elevated temperature and CO₂-induced OA on energy metabolism will narrow the thermal tolerance window of marine ectothermal animals. To test this hypothesis, we investigated the effect of an acute temperature rise on energy metabolism of the oyster, Crassostrea gigas chronically exposed to elevated CO₂ levels (partial pressure of CO₂ in the seawater ~0.15 kPa, seawater pH ~ 7.7). Within one month of incubation at elevated PCo₂ and 15 °C hemolymph pH fell (pH(e) = 7.1 ± 0.2 (CO₂-group) vs. 7.6 ± 0.1 (control)) and P(e)CO₂ values in hemolymph increased (0.5 ± 0.2 kPa (CO₂-group) vs. 0.2 ± 0.04 kPa (control)). Slightly but significantly elevated bicarbonate concentrations in the hemolymph of CO₂-incubated oysters ([HCO₃⁻](e) = 1.8 ± 0.3 mM (CO₂-group) vs. 1.3 ± 0.1 mM (control)) indicate only minimal regulation of extracellular acid-base status. At the acclimation temperature of 15 °C the OA-induced decrease in pH(e) did not lead to metabolic depression in oysters as standard metabolism rates (SMR) of CO₂-exposed oysters were similar to controls. Upon acute warming SMR rose in both groups, but displayed a stronger increase in the CO₂-incubated group. Investigation in isolated gill cells revealed a similar temperature dependence of respiration between groups. Furthermore, the fraction of cellular energy demand for ion regulation via Na+/K+-ATPase was not affected by chronic hypercapnia or temperature. Metabolic profiling using ¹H-NMR spectroscopy revealed substantial changes in some tissues following OA exposure at 15 °C. In mantle tissue alanine and ATP levels decreased significantly whereas an increase in succinate levels was observed in gill tissue. These findings suggest shifts in metabolic pathways following OA-exposure. Our study confirms that OA affects energy

  11. SU-C-303-02: Correlating Metabolic Response to Radiation Therapy with HIF-1alpha Expression

    SciTech Connect

    Campos, D; Peeters, W; Nickel, K; Eliceiri, K; Kimple, R; Van Der Kogel, A; Kissick, M

    2015-06-15

    Purpose: To understand radiation induced alterations in cellular metabolism which could be used to assess treatment or normal tissue response to aid in patient-specific adaptive radiotherapy. This work aims to compare the metabolic response of two head and neck cell lines, one malignant (UM-SCC-22B) and one benign (Normal Oral Keratinocyte), to ionizing radiation. Responses are compared to alterations in HIF-1alpha expression. These dynamics can potentially serve as biomarkers in assessing treatment response allowing for patient-specific adaptive radiotherapy. Methods: Measurements of metabolism and HIF-1alpha expression were taken before and X minutes after a 10 Gy dose of radiation delivered via an orthovoltage x-ray source. In vitro changes in metabolic activity were measured via fluorescence lifetime imaging (FLIM) to assess the mean lifetime of NADH autofluorescence following a dose of 10 Gy. HIF-1alpha expression was measured via immunohistochemical staining of in vitro treated cells and expression was quantified using the FIJI software package. Results: FLIM demonstrated a decrease in the mean fluorescence lifetime of NADH by 100 ps following 10 Gy indicating a shift towards glycolytic pathways for malignant cells; whereas this benign cell line showed little change in metabolic signature. Immunohistochemical analysis showed significant changes in HIF-1alpha expression in response to 10 Gy of radiation that correlate to metabolic profiles. Conclusion: Radiation induces significant changes in metabolic activity and HIF-1alpha expression. These alterations occur on time scales approximating the duration of common radiation treatments (approximately tens of minutes). Further understanding these dynamics has important implications with regard to improvement of therapy and biomarkers of treatment response.

  12. Metabolic, anabolic, and mitogenic insulin responses: A tissue-specific perspective for insulin receptor activators

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insulin acts as the major regulator of the fasting-to-fed metabolic transition by altering substrate metabolism, promoting energy storage, and helping activate protein synthesis. In addition to its glucoregulatory and other metabolic properties, insulin can also act as a growth factor. The metabolic...

  13. Effects of gender on neuroendocrine and metabolic counterregulatory responses to exercise in normal man.

    PubMed

    Davis, S N; Galassetti, P; Wasserman, D H; Tate, D

    2000-01-01

    Significant, sexual dimorphisms exist in counterregulatory responses to commonly occurring stresses, such as hypoglycemia, fasting, and cognitive testing. The question of whether counterregulatory responses differ during exercise in healthy men and women remains controversial. The aim of this study was to determine whether a sexual dimorphism exists in neuroendocrine, metabolic, or cardiovascular responses to prolonged moderate exercise. Sixteen healthy (eight men and eight women) subjects matched for age (28+/-2 yr), body mass index (22+/-1 kg/m2), nutrient intake, and spectrum of physical fitness were studied in a randomized fashion during 90 min of exercise on a cycle ergometer at 80% of their anaerobic threshold (approximately 50% VO2 max). Respiratory quotient and oxygen consumption relative to body weight were identical in men and women. Glycemia was equated (5.3+/-0.2 mmol/L) during exercise via an exogenous glucose infusion. Gender had significant effects on counterregulatory responses during exercise. Arterialized epinephrine (1.05+/-0.2 vs. 0.45+/-0.04 nmol/L), norepinephrine (9.2+/-1.1 vs. 5.8+/-1.1 nmol/L), and pancreatic polypeptide (52+/-6 vs. 37+/-6 pmol/L) were significantly (P<0.01) increased in men compared to women, respectively. Plasma glucagon, cortisol, and GH levels responded similarly in men and women. Insulin values were higher at baseline in men and fell by a greater amount to reach similar levels during exercise compared to those in women. Endogenous glucose production, measured with [3-3H]glucose was similar in men and women. Carbohydrate oxidation was significantly increased in men relative to women (21.2+/-2 vs. 15.6+/-2 mg/kg fat free mass x min; P<0.05). Despite reduced sympathetic nervous system (SNS) drive, lipolytic responses were increased in women. Arterialized blood glycerol (215+/-30 vs. 140+/-20 micromol/L), beta-hydroxybutyrate (54+/-9 vs. 25+/-10 micromol/L), and plasma nonesterified fatty acids (720+/-56 vs. 469

  14. Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions.

    PubMed

    Klevenhusen, Fenja; Humer, Elke; Metzler-Zebeli, Barbara; Podstatzky-Lichtenstein, Leopold; Wittek, Thomas; Zebeli, Qendrim

    2015-01-01

    Left displaced abomasum (LDA) is a severe metabolic disease of cattle with a strong negative impact on production efficiency of dairy farms. Metabolic and inflammatory alterations associated with this disease have been reported in earlier studies, conducted mostly in large dairy farms. This research aimed to: (1) evaluate metabolic and inflammatory responses in dairy cows affected by LDA in small-scaled dairy farms; and (2) establish an Animals 2015, 5 1022 association between lactation number and milk production with the outcome of metabolic variables. The cows with LDA had lower serum calcium (Ca), but greater concentrations of non-esterified fatty acids (NEFA) and beta-hydroxy-butyrate (BHBA), in particular when lactation number was >2. Cows with LDA showed elevated levels of aspartate aminotransferase, glutamate dehydrogenase, and serum amyloid A (SAA), regardless of lactation number. In addition, this study revealed strong associations between milk yield and the alteration of metabolic profile but not with inflammation in the sick cows. Results indicate metabolic alterations, liver damage, and inflammation in LDA cows kept under small-scale farm conditions. Furthermore, the data suggest exacerbation of metabolic profile and Ca metabolism but not of inflammation and liver health with increasing lactation number and milk yield in cows affected by LDA. PMID:26479481

  15. Regulation of Primary Metabolism in Response to Low Oxygen Availability as Revealed by Carbon and Nitrogen Isotope Redistribution1[OPEN

    PubMed Central

    Päpke, Carola; Diab, Houssein; Fernie, Alisdair R.

    2016-01-01

    Based on enzyme activity assays and metabolic responses to waterlogging of the legume Lotus japonicus, it was previously suggested that, during hypoxia, the tricarboxylic acid cycle switches to a noncyclic operation mode. Hypotheses were postulated to explain the alternative metabolic pathways involved, but as yet, a direct analysis of the relative redistribution of label through the corresponding pathways was not made. Here, we describe the use of stable isotope-labeling experiments for studying metabolism under hypoxia using wild-type roots of the crop legume soybean (Glycine max). [13C]Pyruvate labeling was performed to compare metabolism through the tricarboxylic acid cycle, fermentation, alanine metabolism, and the γ-aminobutyric acid shunt, while [13C]glutamate and [15N]ammonium labeling were performed to address the metabolism via glutamate to succinate. Following these labelings, the time course for the redistribution of the 13C/15N label throughout the metabolic network was evaluated with gas chromatography-time of flight-mass spectrometry. Our combined labeling data suggest the inhibition of the tricarboxylic acid cycle enzyme succinate dehydrogenase, also known as complex II of the mitochondrial electron transport chain, providing support for the bifurcation of the cycle and the down-regulation of the rate of respiration measured during hypoxic stress. Moreover, up-regulation of the γ-aminobutyric acid shunt and alanine metabolism explained the accumulation of succinate and alanine during hypoxia. PMID:26553649

  16. Altered response to neuroendocrine challenge linked to indices of the metabolic syndrome in healthy adults.

    PubMed

    Tyrka, A R; Walters, O C; Price, L H; Anderson, G M; Carpenter, L L

    2012-06-01

    Metabolic syndrome (MetS) is characterized by central obesity, hypertension, insulin resistance, and hypercholesterolemia. Hypothalamic-pituitary-adrenal (HPA) axis activity is frequently abnormal in MetS, and excessive cortisol exposure may be implicated in metabolic derangements. We investigated the hypothesis that cortisol and adrenocorticotropic hormone (ACTH) responses to a standardized neuroendocrine challenge test would be associated with indices of MetS in a community sample of healthy adults. Healthy adults, 125 men and 170 women, without significant medical problems or chronic medications were recruited from the community. Participants completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, and anthropometric measurements, blood pressure, glycosylated hemoglobin (HbA1c), and cholesterol were measured. Participants reported on their history of early life stress and recent stress, as well as mood and anxiety symptoms. Cortisol and ACTH responses to the Dex/CRH test were negatively associated with measures of central adiposity (p<0.001) and blood pressure (p<0.01), and positively associated with HDL cholesterol (p<0.01). These findings remained significant after controlling for body mass index (BMI). Measures of stress and anxiety and depressive symptoms were negatively correlated with cortisol and ACTH responses in the Dex/CRH test but were not related to MetS indices. That altered HPA axis function is linked to MetS components even in a healthy community sample suggests that these processes may be involved in the pathogenesis of MetS. Identification of premorbid risk processes might allow for detection and intervention prior to the development of disease. PMID:22549400

  17. Metabolomic analysis of wild and transgenic Nicotiana langsdorffii plants exposed to abiotic stresses: unraveling metabolic responses.

    PubMed

    Scalabrin, Elisa; Radaelli, Marta; Rizzato, Giovanni; Bogani, Patrizia; Buiatti, Marcello; Gambaro, Andrea; Capodaglio, Gabriele

    2015-08-01

    Nicotiana langsdorffii plants, wild and transgenic for the Agrobacterium rhizogenes rol C gene and the rat glucocorticoid receptor (GR) gene, were exposed to different abiotic stresses (high temperature, water deficit, and high chromium concentrations). An untargeted metabolomic analysis was carried out in order to investigate the metabolic effects of the inserted genes in response to the applied stresses and to obtain a comprehensive profiling of metabolites induced during abiotic stresses. High-performance liquid chromatography separation (HPLC) coupled to high-resolution mass spectrometry (HRMS) enabled the identification of more than 200 metabolites, and statistical analysis highlighted the most relevant compounds for each plant treatment. The plants exposed to heat stress showed a unique set of induced secondary metabolites, some of which were known while others were not previously reported for this kind of stress; significant changes were observed especially in lipid composition. The role of trichome, as a protection against heat stress, is here suggested by the induction of both acylsugars and glykoalkaloids. Water deficit and Cr(VI) stresses resulted mainly in enhanced antioxidant (HCAs, polyamine) levels and in the damage of lipids, probably as a consequence of reactive oxygen species (ROS) production. Moreover, the ability of rol C expression to prevent oxidative burst was confirmed. The results highlighted a clear influence of GR modification on plant stress response, especially to water deficiency-a phenomenon whose applications should be further investigated. This study provides new insights into the field of system biology and demonstrates the importance of metabolomics in the study of plant functioning. Graphical Abstract Untargeted metabolomic analysis was applied to wild type, GR and RolC modified Nicotiana Langsdorffii plants exposed to heat, water and Cr(VI) stresses. The key metabolites, highly affected by stress application, were identified

  18. Moderate stress responses and specific changes in polyamine metabolism characterize Scots pine somatic embryogenesis.

    PubMed

    Salo, Heikki M; Sarjala, Tytti; Jokela, Anne; Häggman, Hely; Vuosku, Jaana

    2016-03-01

    Somatic embryogenesis (SE) is one of the methods with the highest potential for the vegetative propagation of commercially important coniferous species. However, many conifers, including Scots pine (Pinus sylvestris L.), are recalcitrant to SE and a better understanding of the mechanisms behind the SE process is needed. In Scots pine SE cultures, embryo production is commonly induced by the removal of auxin, addition of abscisic acid (ABA) and the desiccation of cell masses by polyethylene glycol (PEG). In the present study, we focus on the possible link between the induction of somatic embryo formation and cellular stress responses such as hydrogen peroxide protection, DNA repair, changes in polyamine (PA) metabolism and autophagy. Cellular PA contents and the expression of the PA metabolism genes arginine decarboxylase (ADC), spermidine synthase (SPDS), thermospermine synthase (ACL5) and diamine oxidase (DAO) were analyzed, as well as the expression of catalase (CAT), DNA repair genes (RAD51, KU80) and autophagy-related genes (ATG5, ATG8) throughout the induction of somatic embryo formation in Scots pine SE cultures. Among the embryo-producing SE lines, the expression of ADC, SPDS, ACL5, DAO, CAT, RAD51, KU80 and ATG8 showed consistent profiles. Furthermore, the overall low expression of the stress-related genes suggests that cells in those SE lines were not stressed but recognized the ABA+PEG treatment as a signal to trigger the embryogenic pathway. In those SE lines that were unable to produce embryos, cells seemed to experience the ABA+PEG treatment mostly as osmotic stress and activated a wide range of stress defense mechanisms. Altogether, our results suggest that the direction to the embryogenic pathway is connected with cellular stress responses in Scots pine SE cultures. Thus, the manipulation of stress response pathways may provide a way to enhance somatic embryo production in recalcitrant Scots pine SE lines. PMID:26786537

  19. Polyamine metabolism in flax in response to treatment with pathogenic and non–pathogenic Fusarium strains

    PubMed Central

    Wojtasik, Wioleta; Kulma, Anna; Namysł, Katarzyna; Preisner, Marta; Szopa, Jan

    2015-01-01

    Flax crop yield is limited by various environmental stress factors, but the largest crop losses worldwide are caused by Fusarium infection. Polyamines are one of the many plant metabolites possibly involved in the plant response to infection. However, in flax plants the polyamine composition, genes involved in polyamine synthesis, and in particular their regulation, were previously unknown. The aim of this study was to investigate the polyamine synthesis pathway in flax and its involvement in response to pathogen infection. It is well established that polyamines are essential for the growth and development of both plants and fungi, but their role in pathogen infection still remains unknown. In our study we correlated the expression of genes involved in polyamine metabolism with the polyamine levels in plant tissues and compared the results for flax seedlings treated with two pathogenic and one non-pathogenic strains of Fusarium. We observed an increase in the expression of genes participating in polyamine synthesis after fungal infection, and it was reflected in an increase of polyamine content in the plant tissues. The highest level of mRNA was characteristic for ornithine decarboxylase during infection with all tested, pathogenic and non-pathogenic, Fusarium strains and the arginine decarboxylase gene during infection with the pathogenic strain of Fusarium culmorum. The main polyamine identified in the flax seedlings was putrescine, and its level changed the most during infection. Moreover, the considerable increase in the contents of cell wall-bound polyamines compared to the levels of free and conjugated polyamines may indicate that their main role during pathogen infection lies in strengthening of the cell wall. In vitro experiments showed that the polyamines inhibit Fusarium growth, which suggests that they play an important role in plant defense mechanisms. Furthermore, changes in metabolism and content of polyamines indicate different defense mechanisms

  20. Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response.

    PubMed

    Yogev, Ohad; Yogev, Orli; Singer, Esti; Shaulian, Eitan; Goldberg, Michal; Fox, Thomas D; Pines, Ophry

    2010-03-01

    In eukaryotes, fumarase (FH in human) is a well-known tricarboxylic-acid-cycle enzyme in the mitochondrial matrix. However, conserved from yeast to humans is a cytosolic isoenzyme of fumarase whose function in this compartment remains obscure. A few years ago, FH was surprisingly shown to underlie a tumor susceptibility syndrome, Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). A biallelic inactivation of FH has been detected in almost all HLRCC tumors, and therefore FH was suggested to function as a tumor suppressor. Recently it was suggested that FH inhibition leads to elevated intracellular fumarate, which in turn acts as a competitive inhibitor of HPH (HIF prolyl hydroxylase), thereby causing stabilization of HIF (Hypoxia-inducible factor) by preventing proteasomal degradation. The transcription factor HIF increases the expression of angiogenesis regulated genes, such as VEGF, which can lead to high microvessel density and tumorigenesis. Yet this mechanism does not fully explain the large cytosolic population of fumarase molecules. We constructed a yeast strain in which fumarase is localized exclusively to mitochondria. This led to the discovery that the yeast cytosolic fumarase plays a key role in the protection of cells from DNA damage, particularly from DNA double-strand breaks. We show that the cytosolic fumarase is a member of the DNA damage response that is recruited from the cytosol to the nucleus upon DNA damage induction. This function of fumarase depends on its enzymatic activity, and its absence in cells can be complemented by high concentrations of fumaric acid. Our findings suggest that fumarase and fumaric acid are critical elements of the DNA damage response, which underlies the tumor suppressor role of fumarase in human cells and which is most probably HIF independent. This study shows an exciting crosstalk between primary metabolism and the DNA damage response, thereby providing a scenario for metabolic control of tumor propagation

  1. Interdependence of tetrapyrrole metabolism, the generation of oxidative stress and the mitigative oxidative stress response.

    PubMed

    Busch, Andrea W U; Montgomery, Beronda L

    2015-01-01

    Tetrapyrroles are involved in light harvesting and light perception, electron-transfer reactions, and as co-factors for key enzymes and sensory proteins. Under conditions in which cells exhibit stress-induced imbalances of photosynthetic reactions, or light absorption exceeds the ability of the cell to use photoexcitation energy in synthesis reactions, redox imbalance can occur in photosynthetic cells. Such conditions can lead to the generation of reactive oxygen species (ROS) associated with alterations in tetrapyrrole homeostasis. ROS accumulation can result in cellular damage and detrimental effects on organismal fitness, or ROS molecules can serve as signals to induce a protective or damage-mitigating oxidative stress signaling response in cells. Induced oxidative stress responses include tetrapyrrole-dependent and -independent mechanisms for mitigating ROS generation and/or accumulation. Thus, tetrapyrroles can be contributors to oxidative stress, but are also essential in the oxidative stress response to protect cells by contributing to detoxification of ROS. In this review, we highlight the interconnection and interdependence of tetrapyrrole metabolism with the occurrence of oxidative stress and protective oxidative stress signaling responses in photosynthetic organisms. PMID:25618582

  2. Interdependence of tetrapyrrole metabolism, the generation of oxidative stress and the mitigative oxidative stress response

    PubMed Central

    Busch, Andrea W.U.; Montgomery, Beronda L.

    2015-01-01

    Tetrapyrroles are involved in light harvesting and light perception, electron-transfer reactions, and as co-factors for key enzymes and sensory proteins. Under conditions in which cells exhibit stress-induced imbalances of photosynthetic reactions, or light absorption exceeds the ability of the cell to use photoexcitation energy in synthesis reactions, redox imbalance can occur in photosynthetic cells. Such conditions can lead to the generation of reactive oxygen species (ROS) associated with alterations in tetrapyrrole homeostasis. ROS accumulation can result in cellular damage and detrimental effects on organismal fitness, or ROS molecules can serve as signals to induce a protective or damage-mitigating oxidative stress signaling response in cells. Induced oxidative stress responses include tetrapyrrole-dependent and -independent mechanisms for mitigating ROS generation and/or accumulation. Thus, tetrapyrroles can be contributors to oxidative stress, but are also essential in the oxidative stress response to protect cells by contributing to detoxification of ROS. In this review, we highlight the interconnection and interdependence of tetrapyrrole metabolism with the occurrence of oxidative stress and protective oxidative stress signaling responses in photosynthetic organisms. PMID:25618582

  3. Sex differences in renal and metabolic responses to a high-fructose diet in mice

    PubMed Central

    Sharma, Nikhil; Li, Lijun

    2014-01-01

    High fructose intake has been associated with increased incidences of renal disease and hypertension, among other pathologies. Most fructose is cleared by the portal system and metabolized in the liver; however, systemic levels of fructose can rise with increased consumption. We tested whether there were sex differences in the renal responses to a high-fructose diet in mice. Two-month-old male and female C57BL6/129/SV mice (n = 6 mice per sex per treatment) were randomized to receive control or high-fructose (65% by weight) diets as pelleted chow ad libitum for 3 mo. Fructose feeding did not significantly affect body weight but led to a 19% and 10% increase in kidney weight in male and female mice, respectively. In male mice, fructose increased the expression (∼50%) of renal cortical proteins involved in metabolism, including glucose transporter 5 (facilitative fructose transporter), ketohexokinase, and the insulin receptor (β-subunit). Female mice had lower basal levels of glucose transporter 5, which were unresponsive to fructose. However, female mice had increased urine volume and plasma K+ and decreased plasma Na+ with fructose, whereas male mice were less affected. Likewise, female mice showed a two- to threefold reduction in the expression Na+-K+-2Cl− cotransporter 2 in the thick ascending limb and aquaporin-2 in the collecting duct with fructose relative to female control mice, whereas male mice had no change. Overall, our results support greater proximal metabolism of fructose in male animals and greater distal tubule/collecting duct (electrolyte homeostasis) alterations in female animals. These sex differences may be important determinants of the specific nature of pathologies that develop in association with high fructose consumption. PMID:25537743

  4. Effects of metabolic rate on thermal responses at different air velocities in -10 degrees C.

    PubMed

    Mäkinen, T T; Gavhed, D; Holmér, I; Rintamäki, H

    2001-04-01

    The effects of exercise intensity on thermoregulatory responses in cold (-10 degrees C) in a 0.2 (still air, NoWi), 1.0 (Wi1), and 5.0 (Wi5) m x s(-1) wind were studied. Eight young and healthy men, preconditioned in thermoneutral (+20 degrees C) environment for 60 min, walked for 60 min on the treadmill at 2.8 km/h with different combinations of wind and exercise intensity. Exercise level was adjusted by changing the inclination of the treadmill between 0 degrees (lower exercise intensity, metabolic rate 124 W x m(-2), LE) and 6 degrees (higher exercise intensity, metabolic rate 195 W x m(-2), HE). Due to exercise increased heat production and circulatory adjustments, the rectal temperature (T(re)), mean skin temperature (Tsk) and mean body temperature (Tb) were significantly higher at the end of HE in comparison to LE in NoWi and Wi1, and T(re) and Tb also in Wi5. Tsk and Tb were significantly decreased by 5.0 m x s(-1) wind in comparison to NoWi and Wi1. The higher exercise intensity was intense enough to diminish peripheral vasoconstriction and consequently the finger skin temperature was significantly higher at the end of HE in comparison to LE in NoWi and Wi1. Mean heat flux from the skin was unaffected by the exercise intensity. At LE oxygen consumption (VO2) was significantly higher in Wi5 than NoWi and Wi1. Heart rate was unaffected by the wind speed. The results suggest that, with studied exercise intensities, produced without changes in walking speed, the metabolic rate is not so important that it should be taken into consideration in the calculation of wind chill index. PMID:11282319

  5. Visible light optical coherence tomography measure retinal oxygen metabolic response to systemic oxygenation (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Yi, Ji; Liu, Wenzhong; Chen, Siyu; Backman, Vadim; Sheibani, Nader; Sorenson, Christine M.; Fawzi, Amani A.; Linsenmeier, Robert A.; Zhang, Hao F.

    2016-03-01

    The lack of capability to quantify oxygen metabolism noninvasively impedes both fundamental investigation and clinical diagnosis of a wide spectrum of diseases including all the major blinding diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Using visible light optical coherence tomography (vis-OCT), we demonstrated accurate and robust measurement of retinal oxygen metabolic rate (rMRO2) noninvasively in rat eyes. The rMRO2 was calculated by concurrent measurement of blood flow and blood oxygen saturation (sO2). Blood flow was calculated by the principle of Doppler optical coherence tomography, where the phase shift between two closely spaced A-lines measures the axial velocity. The distinct optical absorption spectra of oxy- and deoxy-hemoglobin provided the contrast for sO2 measurement, combined with the spectroscopic analysis of vis-OCT signal within the blood vessels. We continuously monitored the regulatory response of oxygen consumption to a progressive hypoxic challenge. We found that both oxygen delivery, and rMRO2 increased from the highly regulated retinal circulation (RC) under hypoxia, by 0.28+/-0.08 μL/min (p<0.001), and 0.20+/-0.04 μL/min (p<0.001) per 100 mmHg systemic pO2 reduction, respectively. The increased oxygen extraction compensated for the deficient oxygen supply from the poorly regulated choroidal circulation (CC).

  6. Food odors trigger an endocrine response that affects food ingestion and metabolism.

    PubMed

    Lushchak, Oleh V; Carlsson, Mikael A; Nässel, Dick R

    2015-08-01

    Food odors stimulate appetite and innate food-seeking behavior in hungry animals. The smell of food also induces salivation and release of gastric acid and insulin. Conversely, sustained odor exposure may induce satiation. We demonstrate novel effects of food odors on food ingestion, metabolism and endocrine signaling in Drosophila melanogaster. Acute exposure to attractive vinegar odor triggers a rapid and transient increase in circulating glucose, and a rapid upregulation of genes encoding the glucagon-like hormone adipokinetic hormone (AKH), four insulin-like peptides (DILPs) and some target genes in peripheral tissues. Sustained exposure to food odors, however, decreases food intake. Hunger-induced strengthening of synaptic signaling from olfactory sensory neurons (OSNs) to brain neurons increases food-seeking behavior, and conversely fed flies display reduced food odor sensitivity and feeding. We show that increasing the strength of OSN signaling chronically by genetic manipulation of local peptide neuromodulation reduces feeding, elevates carbohydrates and diminishes lipids. Furthermore, constitutively strengthened odor sensitivity altered gene transcripts for AKH, DILPs and some of their targets. Thus, we show that food odor can induce a transient anticipatory endocrine response, and that boosted sensitivity to this odor affects food intake, as well as metabolism and hormonal signaling. PMID:25782410

  7. Metabolic responses of Rhodococcus erythropolis PR4 grown on diesel oil and various hydrocarbons.

    PubMed

    Laczi, Krisztián; Kis, Ágnes; Horváth, Balázs; Maróti, Gergely; Hegedüs, Botond; Perei, Katalin; Rákhely, Gábor

    2015-11-01

    Rhodococcus erythropolis PR4 is able to degrade diesel oil, normal-, iso- and cycloparaffins and aromatic compounds. The complete DNA content of the strain was previously sequenced and numerous oxygenase genes were identified. In order to identify the key elements participating in biodegradation of various hydrocarbons, we performed a comparative whole transcriptome analysis of cells grown on hexadecane, diesel oil and acetate. The transcriptomic data for the most prominent genes were validated by RT-qPCR. The expression of two genes coding for alkane-1-monooxygenase enzymes was highly upregulated in the presence of hydrocarbon substrates. The transcription of eight phylogenetically diverse cytochrome P450 (cyp) genes was upregulated in the presence of diesel oil. The transcript levels of various oxygenase genes were determined in cells grown in an artificial mixture, containing hexadecane, cycloparaffin and aromatic compounds and six cyp genes were induced by this hydrocarbon mixture. Five of them were not upregulated by linear and branched hydrocarbons. The expression of fatty acid synthase I genes was downregulated by hydrocarbon substrates, indicating the utilization of external alkanes for fatty acid synthesis. Moreover, the transcription of genes involved in siderophore synthesis, iron transport and exopolysaccharide biosynthesis was also upregulated, indicating their important role in hydrocarbon metabolism. Based on the results, complex metabolic response profiles were established for cells grown on various hydrocarbons. Our results represent a functional annotation of a rhodococcal genome, provide deeper insight into molecular events in diesel/hydrocarbon utilization and suggest novel target genes for environmental monitoring projects. PMID:26346267

  8. Metabolic responses to sulfur dioxide in grapevine (Vitis vinifera L.): photosynthetic tissues and berries

    PubMed Central

    Considine, Michael J.; Foyer, Christine H.

    2015-01-01

    Research on sulfur metabolism in plants has historically been undertaken within the context of industrial pollution. Resolution of the problem of sulfur pollution has led to sulfur deficiency in many soils. Key questions remain concerning how different plant organs deal with reactive and potentially toxic sulfur metabolites. In this review, we discuss sulfur dioxide/sulfite assimilation in grape berries in relation to gene expression and quality traits, features that remain significant to the food industry. We consider the intrinsic metabolism of sulfite and its consequences for fruit biology and postharvest physiology, comparing the different responses in fruit and leaves. We also highlight inconsistencies in what is considered the “ambient” environmental or industrial exposures to SO2. We discuss these findings in relation to the persistent threat to the table grape industry that intergovernmental agencies will revoke the industry’s exemption to the worldwide ban on the use of SO2 for preservation of fresh foods. Transcriptome profiling studies on fruit suggest that added value may accrue from effects of SO2 fumigation on the expression of genes encoding components involved in processes that underpin traits related to customer satisfaction, particularly in table grapes, where SO2 fumigation may extend for several months. PMID:25750643

  9. Interactions between negative energy balance, metabolic diseases, uterine health and immune response in transition dairy cows.

    PubMed

    Esposito, Giulia; Irons, Pete C; Webb, Edward C; Chapwanya, Aspinas

    2014-01-30

    The biological cycles of milk production and reproduction determine dairying profitability thus making management decisions dynamic and time-dependent. Diseases also negatively impact on net earnings of a dairy enterprise. Transition cows in particular face the challenge of negative energy balance (NEB) and/or disproportional energy metabolism (fatty liver, ketosis, subacute, acute ruminal acidosis); disturbed mineral utilization (milk fever, sub-clinical hypocalcemia); and perturbed immune function (retained placenta, metritis, mastitis). Consequently NEB and reduced dry matter intake are aggravated. The combined effects of all these challenges are reduced fertility and milk production resulting in diminishing profits. Risk factors such as NEB, inflammation and impairment of the immune response are highly cause-and-effect related. Thus, managing cows during the transition period should be geared toward reducing NEB or feeding specially formulated diets to improve immunity. Given that all cows experience a reduced feed intake and body condition, infection and inflammation of the uterus after calving, there is a need for further research on the immunology of transition dairy cows. Integrative approaches at the molecular, cellular and animal level may unravel the complex interactions between disturbed metabolism and immune function that predispose cows to periparturient diseases. PMID:24378117

  10. Yeast cell wall supplementation alters the metabolic responses of crossbred heifers to an endotoxin challenge.

    PubMed

    Sanchez, Nicole C Burdick; Young, Tanner R; Carroll, Jeffery A; Corley, Jimmie R; Rathmann, Ryan J; Johnson, Bradley J

    2014-01-01

    This study examined the effect of feeding yeast cell wall (YCW) products on the metabolic responses of newly-received feedlot cattle to an endotoxin challenge. Heifers were separated into treatment groups receiving either a Control diet, YCW-A or YCW-C, and were fed for 52 d. Heifers were weighed on d 0, 14, 36, 38 and 52. On d 37 heifers were challenged i.v. with LPS [0.5 µg/kg body weight (BW)] and blood samples were collected relative to LPS challenge. Heifer BW increased from d 0 to 36 and from d 38 to 52, but was not affected by treatment. Post-LPS, glucose concentrations increased and were less in YCW-A than Control and YCW-C heifers. Pre-LPS, insulin concentrations were greater in YCW-A and YCW-C than Control heifers. Post-LPS, insulin concentrations increased with YCW-C having greater insulin than Control heifers. Pre-LPS, NEFA concentrations tended to be less in YCW-C than Control heifers. Post-LPS non-esterified fatty acids (NEFA) concentrations were less in YCW-C than Control and YCW-A heifers. Post-LPS, blood urea nitrogen (BUN) concentrations were greater in YCW-A than Control and YCW-C. These data indicate, based on NEFA and BUN data, that certain YCW products can enhance energy metabolism during an immune challenge without causing lipolysis or muscle catabolism. PMID:23606515

  11. Effect of a straw-derived xylooligosaccharide on broiler growth performance, endocrine metabolism, and immune response

    PubMed Central

    Zhenping, Sun; Wenting, Lv; Ruikui, Yu; Jia, Li; Honghong, Liu; Wei, Sun; Zhongmie, Wang; Jingpan, Li; Zhe, Shan; Yuling, Qin

    2013-01-01

    The aim of this work was to evaluate the effect of 3 levels of supplemental xylooligosaccharides (XOS) from straw on the growth performance, endocrine metabolism, and immune response of broiler chickens. Day-old, healthy Arbor Acres broilers (n = 192) received a basal diet of maize–soybean meal and, depending on the group to which they were allocated, no additive (control group) or the following experimental treatments for 59 d: treatment 1: 5 g XOS/kg; treatment 2: 10 g XOS/kg; and treatment 3: 20 g XOS/kg. By day 59 the body weight gain of the chickens receiving treatment 2 had increased by 9.44% (P < 0.01) over the gain of the control group. The levels of serum triiodothyronine, thyroxine, and insulin on day 44 were significantly higher in the treatment groups than in the control group. The titers of antibody to the avian influenza H5N1 virus on day 24 were also significantly higher in the treatment groups than in the control group, and on day 59 the titer of the chickens receiving treatment 2 were still significantly increased (P < 0.05). Thus, the addition of XOS to feed can increase growth performance, enhance endocrine metabolism, and improve immune function in broiler chickens. PMID:24082401

  12. Metabolic responses to sulfur dioxide in grapevine (Vitis vinifera L.): photosynthetic tissues and berries.

    PubMed

    Considine, Michael J; Foyer, Christine H

    2015-01-01

    Research on sulfur metabolism in plants has historically been undertaken within the context of industrial pollution. Resolution of the problem of sulfur pollution has led to sulfur deficiency in many soils. Key questions remain concerning how different plant organs deal with reactive and potentially toxic sulfur metabolites. In this review, we discuss sulfur dioxide/sulfite assimilation in grape berries in relation to gene expression and quality traits, features that remain significant to the food industry. We consider the intrinsic metabolism of sulfite and its consequences for fruit biology and postharvest physiology, comparing the different responses in fruit and leaves. We also highlight inconsistencies in what is considered the "ambient" environmental or industrial exposures to SO2. We discuss these findings in relation to the persistent threat to the table grape industry that intergovernmental agencies will revoke the industry's exemption to the worldwide ban on the use of SO2 for preservation of fresh foods. Transcriptome profiling studies on fruit suggest that added value may accrue from effects of SO2 fumigation on the expression of genes encoding components involved in processes that underpin traits related to customer satisfaction, particularly in table grapes, where SO2 fumigation may extend for several months. PMID:25750643

  13. Metabolic and transcriptional response of central metabolism affected by root endophytic fungus Piriformospora indica under salinity in barley.

    PubMed

    Ghaffari, Mohammad Reza; Ghabooli, Mehdi; Khatabi, Behnam; Hajirezaei, Mohammad Reza; Schweizer, Patrick; Salekdeh, Ghasem Hosseini

    2016-04-01

    The root endophytic fungus Piriformospora indica enhances plant adaptation to environmental stress based on general and non-specific plant species mechanisms. In the present study, we integrated the ionomics, metabolomics, and transcriptomics data to identify the genes and metabolic regulatory networks conferring salt tolerance in P. indica-colonized barley plants. To this end, leaf samples were harvested at control (0 mM NaCl) and severe salt stress (300 mM NaCl) in P. indica-colonized and non-inoculated barley plants 4 weeks after fungal inoculation. The metabolome analysis resulted in an identification of a signature containing 14 metabolites and ions conferring tolerance to salt stress. Gene expression analysis has led to the identification of 254 differentially expressed genes at 0 mM NaCl and 391 genes at 300 mM NaCl in P. indica-colonized compared to non-inoculated samples. The integration of metabolome and transcriptome analysis indicated that the major and minor carbohydrate metabolism, nitrogen metabolism, and ethylene biosynthesis pathway might play a role in systemic salt-tolerance in leaf tissue induced by the root-colonized fungus. PMID:26951140

  14. Genome-wide screen for inositol auxotrophy in Saccharomyces cerevisiae implicates lipid metabolism in stress response signaling

    PubMed Central

    Villa-García, Manuel J.; Choi, Myung Sun; Hinz, Flora I.; Gaspar, María L.; Jesch, Stephen A.

    2011-01-01

    Inositol auxotrophy (Ino− phenotype) in budding yeast has classically been associated with misregulation of INO1 and other genes involved in lipid metabolism. To identify all non-essential yeast genes that are necessary for growth in the absence of inositol, we carried out a genome-wide phenotypic screening for deletion mutants exhibiting Ino− phenotypes under one or more growth conditions. We report the identification of 419 genes, including 385 genes not previously reported, which exhibit this phenotype when deleted. The identified genes are involved in a wide range of cellular processes, but are particularly enriched in those affecting transcription, protein modification, membrane trafficking, diverse stress responses, and lipid metabolism. Among the Ino− mutants involved in stress response, many exhibited phenotypes that are strengthened at elevated temperature and/or when choline is present in the medium. The role of inositol in regulation of lipid metabolism and stress response signaling is discussed. PMID:21136082

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

    NASA Astrophysics Data System (ADS)

    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 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

  16. Root metabolic responses to short term anaerobiosis in the temperate sea grass Zostera marina L

    SciTech Connect

    Smith, R.D.; Pregnall, A.M.; Alberte, R.S.

    1986-04-01

    The submerged angiosperm Z. marina grows in highly reducing marine sediments. The roots experience periods of oxygen deprivation at night when photosynthesis-mediated oxygen transport from the shoot ceases. Despite this apparently inhospitable environment, Z. marina is extremely productive. This study sought to determine root metabolic responses to short term anaerobiosis. Roots were incubated for 4 h in the presence of /sup 14/C-sucrose. Amino acids and Krebs cycle intermediates were then extracted and label was quantified. Ethanol and lactate were the most heavily labeled metabolites following short term anaerobiosis. Despite increased synthesis of ethanol during anaerobiosis, endogenous levels do not increase significantly. Instead over 90% of newly synthesized ethanol is released by roots into the incubation medium. The authors conclude that release of ethanol by roots occurs naturally and prevents excessive accumulation of a potentially toxic product.

  17. Methods of Assessing Human Tendon Metabolism and Tissue Properties in Response to Changes in Mechanical Loading.

    PubMed

    Heinemeier, Katja M; Kjaer, Michael; Magnusson, S Peter

    2016-01-01

    In recent years a number of methodological developments have improved the opportunities to study human tendon. Microdialysis enables sampling of interstitial fluid in the peritendon tissue, while sampling of human tendon biopsies allows direct analysis of tendon tissue for gene- and protein expression as well as protein synthesis rate. Further the (14)C bomb-pulse method has provided data on long-term tissue turnover in human tendon. Non-invasive techniques allow measurement of tendon metabolism (positron emission tomography (PET)), tendon morphology (magnetic resonance imaging (MRI)), and tendon mechanical properties (ultrasonography combined with force measurement during movement). Finally, 3D cell cultures of human tendon cells provide the opportunity to investigate cell-matrix interactions in response to various interventions. PMID:27535251

  18. Metabolic responses to adrenaline and muscle glycogen content in dogs treated with thyroxine.

    PubMed

    Brzezińska, Z; Kaciuba-Uściłko, H

    1978-01-01

    Lipolytic, hyperglycaemic and lactacidaemic responses to 1h adrenaline infusion (0.1 microgram/kg/min) were compared in resting dogs before (control) and after prolonged thyroxine (T4) treatment. Besides, the effect of 2-week thyroxine administration on muscle glycogen content, and its changes following adrenaline infusion were examined. Prolonged T4-treatment of dogs resulted in considerable alterations of the metabolic actions of adrenaline. A marked difference between the control and T4-treated dogs was also found in the muscle glycogen content, which was significantly lower in the latter. Both in the control and T4-injected dogs adrenaline infusion caused similar depletion of the muscle glycogen store. However, in all the control animals examined supercompensation of muscle glycogen was noted 1 h following termination of adrenaline infusion, whereas T4-treated dogs were unable of incurring any significant muscle glycogen deposition. PMID:742367

  19. Black and white with some shades of grey: the diverse responses of inducible metabolic pathways in Escherichia coli.

    PubMed

    Rao, Christopher V; Koirala, Santosh

    2014-09-01

    The metabolic pathways for many sugars are inducible. This process has been extensively studied in the case of Escherichia coli lactose metabolism. It has long been known that gratuitous induction of the lac operon with non-metabolizable lactose analogues generates an all-or-nothing response, where some cells express the lac genes at a maximal rate and others not at all. However, the response to lactose itself is graded, where all cells express the lac genes in proportion to lactose concentrations. The mechanisms generating these distinct behaviours in lactose metabolism have been a topic of many studies. Despite this large body of work, little is known about how other pathways respond to their cognate sugars. An article of Molecular Microbiology investigated the response of eight metabolic pathways in E. coli to their cognate sugars at single-cell resolution. The authors demonstrate that these pathways exhibit diverse responses, ranging from graded to all-or-nothing responses and combinations thereof. Remarkably, they were able to interpret these responses using a simple mathematical model and identify the mechanisms likely giving rise to each. PMID:25069377

  20. Survival Response to Increased Ceramide Involves Metabolic Adaptation through Novel Regulators of Glycolysis and Lipolysis

    PubMed Central

    Walls, Stanley M.; Singh, Alka; Zhu, Lihua Julie; Bamba, Takeshi; Fukusaki, Eiichiro; Srideshikan, Sargur M.; Harris, Greg L.; Ip, Y. Tony; Bodmer, Rolf; Acharya, Usha R.

    2013-01-01

    The sphingolipid ceramide elicits several stress responses, however, organisms survive despite increased ceramide but how they do so is poorly understood. We demonstrate here that the AKT/FOXO pathway regulates survival in increased ceramide environment by metabolic adaptation involving changes in glycolysis and lipolysis through novel downstream targets. We show that ceramide kinase mutants accumulate ceramide and this leads to reduction in energy levels due to compromised oxidative phosphorylation. Mutants show increased activation of Akt and a consequent decrease in FOXO levels. These changes lead to enhanced glycolysis by upregulating the activity of phosphoglyceromutase, enolase, pyruvate kinase, and lactate dehydrogenase to provide energy. A second major consequence of AKT/FOXO reprogramming in the mutants is the increased mobilization of lipid from the gut through novel lipase targets, CG8093 and CG6277 for energy contribution. Ubiquitous reduction of these targets by knockdown experiments results in semi or total lethality of the mutants, demonstrating the importance of activating them. The efficiency of these adaptive mechanisms decreases with age and leads to reduction in adult life span of the mutants. In particular, mutants develop cardiac dysfunction with age, likely reflecting the high energy requirement of a well-functioning heart. The lipases also regulate physiological triacylglycerol homeostasis and are important for energy metabolism since midgut specific reduction of them in wild type flies results in increased sensitivity to starvation and accumulation of triglycerides leading to cardiac defects. The central findings of increased AKT activation, decreased FOXO level and activation of phosphoglyceromutase and pyruvate kinase are also observed in mice heterozygous for ceramide transfer protein suggesting a conserved role of this pathway in mammals. These data reveal novel glycolytic and non-autonomous lipolytic pathways in response to increased

  1. Inflammatory and metabolic responses to high-fat meals with and without dairy products in men.

    PubMed

    Schmid, Alexandra; Petry, Nicolai; Walther, Barbara; Bütikofer, Ueli; Luginbühl, Werner; Gille, Doreen; Chollet, Magali; McTernan, Philip G; Gijs, Martin A M; Vionnet, Nathalie; Pralong, François P; Laederach, Kurt; Vergères, Guy

    2015-06-28

    Postprandial inflammation is an important factor for human health since chronic low-grade inflammation is associated with chronic diseases. Dairy products have a weak but significant anti-inflammatory effect on postprandial inflammation. The objective of the present study was to compare the effect of a high-fat dairy meal (HFD meal), a high-fat non-dairy meal supplemented with milk (HFM meal) and a high-fat non-dairy control meal (HFC meal) on postprandial inflammatory and metabolic responses in healthy men. A cross-over study was conducted in nineteen male subjects. Blood samples were collected before and 1, 2, 4 and 6 h after consumption of the test meals. Plasma concentrations of insulin, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and C-reactive protein (CRP) were measured at each time point. IL-6, TNF-α and endotoxin concentrations were assessed at baseline and endpoint (6 h). Time-dependent curves of these metabolic parameters were plotted, and the net incremental AUC were found to be significantly higher for TAG and lower for CRP after consumption of the HFM meal compared with the HFD meal; however, the HFM and HFD meals were not different from the HFC meal. Alterations in IL-6, TNF-α and endotoxin concentrations were not significantly different between the test meals. The results suggest that full-fat milk and dairy products (cheese and butter) have no significant impact on the inflammatory response to a high-fat meal. PMID:25990454

  2. Endocrine-metabolic responses to military field operations: Effects of cold and moderate altitude exposure

    SciTech Connect

    Floyd, E.; Hackney, A.C.; Hodgdon, J.A.; Coyne, J.T.; Kelleher, D.L. Univ. of North Carolina, Chapel Hill )

    1991-03-11

    Select endocrine-metabolic responses of US Marines to 4.5 day field operations (FOPS) in different environments were examined. Blood and urine samples were collected in the field immediately before and after FOPS at: (1) sea level, neutral temperatures (Ts) (SLN; n = 14), (2) sea level, cold Ts (SLC; n = 16), (3) 2,500 M altitude, neutral Ts (ALN; n = 16), and (4) 2,500 M altitude, cold Ts (ALC; n = 45). Measures examined were testosterone (T), cortisol (C), glucose (Glu), triglycerides (Tg), and urinary ketones (Uket). T decreased pre-post the FOPS in the cold conditions ({bar X}; 6.7 to 5.5 hg/ml; n = 61) but did not change in neutral conditions. C increased pre-post FOPS at SLC (12.1 to 19.8 ug/dl, p < 0.01), ALN (9.3 to 13.9 ug/dl, p < 0.01), and ALC (16.7 to 19.0 ug/dl, p = 0.08). Normoglycemia was maintained under each condition. Tg decreased (p < 0.01) at SLC, ALN, and ALC ({bar X}{triangle}: {minus}59.1, {minus}102.2, {minus}93.3 mg/dl, respectively), but increased at SLN (+74.0 mg/dl). Uket increased post FOPS only at ALN and ALC ({bar X}{triangle}: 3.4 mg/dl and +11.3 mg/dl). The Uket increases were correlated to Tg decreases. Results suggest FOPS induces a slight endocrine stress response, which is augmented with moderate altitude or cold exposure. Furthermore FOPS at altitude, especially in the cold, seems to shift the body towards fat metabolism.

  3. Thermal and metabolic responses of temperature-acclimated rats during cold and heat exposures.

    PubMed

    Kuroshima, A; Yahata, T; Doi, K; Ohno, T

    1982-01-01

    Some endocrine and metabolic responses to acute cold and heat exposures were observed in rats acclimated to cold, heat, or both cold and heat. Rats exposed to both cold (12 hr, 5 degrees C) and heat (12 hr, 34 degrees C) for 4 to 5 weeks (CHA) showed less fall of colonic temperature (Tc) in the cold (-5 degrees C) than heat-acclimated rats (34 degrees C, 4 to 5 weeks) (HA) and warm controls (WC), but a greater fall than cold-acclimated rats (5 degrees C, 4 to 5 weeks) (CA). CHA possessed a larger quantity of interscapular brown adipose tissue and showed greater cold-induced oxygen consumption (VO2) than WC and HA but less than CA. Blood glycerol levels rose similarly in all groups in the cold, while the increase in blood free fatty acids (FFA) levels was significantly greater in HA and smaller in CA than in WC and CHA. Acute cold exposure caused the elevation of plasma glucagon level in WC and HA, but not in CA and CHA. It lowered plasma insulin levels in HA, and the insulin/glucagon molar ratio (I/G) in WC, HA, and CHA. All groups showed the same increases in Tc during acute heat exposure (34 degrees C). However, the heat-induced increase in VO2 was greater in WC than in HA, CA, and CHA. Blood metabolite levels were not affected by acute heat exposure in all groups. Plasma glucagon levels decreased in CHA, while plasma insulin levels increased in WC and CA. I/G increased in WC and CHA. These results indicate that thermal and metabolic responses would be modified by previous exposures to cold, heat, and cold-heat. PMID:6757502

  4. Regional Differences of Metabolic Response During Dynamic Incremental Exercise by (31)P-CSI.

    PubMed

    Kaneko, Yasuhisa; Kime, Ryotaro; Hongo, Yoshinori; Ohno, Yusuke; Sakamoto, Ayumi; Katsumura, Toshihito

    2016-01-01

    The aim of this study was to detect the differences in muscle metabolic response of the quadriceps during incremental dynamic knee exercise using regional (31)Phosphorus Chemical Shift Imaging ((31)P-CSI). Sixteen healthy men participated in this study (age 28 ± 5 years, height 171.4 ± 3.9 cm, weight 67.1 ± 9.8 kg). The experiments were carried out with a 1.5-T superconducting magnet with a 5-in. diameter circular surface coil. The subjects performed isometric unilateral knee extension exercise to detect their maximum voluntary contraction (MVC) in prone position. Then they performed dynamic unilateral knee extension exercise in the magnet at 10, 20, 30 and 40 % of their MVC with the transmit-receive coil placed under the right quadriceps. The subjects pulled down a rope with the adjusted weight attached to the ankle at a frequency of 0.5 Hz for 380 s. Intracellular pH (pHi) was calculated from the median chemical shift of the inorganic phosphate (Pi) peak relative to phosphocreatine (PCr). The quadriceps were divided into three regions, (1) medial, (2) anterior, (3) lateral, and in comparison, there was no significant difference in Pi/PCr nor in pHi between regions, except Pi/PCr of the medial region was significantly higher than the anterior region at maximum intensity (p < 0.05). These results suggest that regional muscle metabolic response is similar in the quadriceps except at maximum intensity. PMID:27526153

  5. Heritability of metabolic response to the intravenous glucose tolerance test in German Holstein Friesian bulls.

    PubMed

    Pieper, Laura; Staufenbiel, Rudolf; Christ, Jana; Panicke, Lothar; Müller, Uwe; Brockmann, Gudrun A

    2016-09-01

    Selection for improved health and welfare in farm animals is of increasing interest worldwide. Peripartum energy balance is a key factor for pathogenesis of diseases in dairy cows. The intravenous glucose tolerance test (ivGTT) can be used to study the metabolic response to a glucose stimulus. The aim of this study was to estimate heritability of ivGTT traits in German Holstein bulls. A total of 541 Holstein bulls aged 7 to 17 mo from 2 breeding stations were subjected to the ivGTT. Serum glucose concentrations were measured at 0, 7, 14, 21, 28, 35, 42, 49, 56, and 63 min relative to glucose infusion. The maximum increase in blood glucose concentration, glucose area equivalent, and blood glucose half-life period were calculated. Heritabilities were estimated using a univariate animal model including station-year-season and age as fixed effects, and animal additive genetic and residual as random effects. The estimated heritabilities were 0.19 for fasting glucose concentration, 0.43 for glucose area equivalent, 0.40 for glucose half-life period, 0.14 for the peak glucose concentration, and 0.12 for the maximum increase of blood glucose concentration. Correlations between ivGTT traits and breeding values for milk yield and composition were not found. The results indicate that heritability for response to glucose is high, which warrants further investigation of this trait for genetic improvement of metabolic disorders. Research is necessary to determine the target levels of ivGTT traits and potential associations between ivGTT traits in breeding bulls and periparturient diseases in their offspring. PMID:27394937

  6. Structural adaptation of microvessel diameters in response to metabolic stimuli: where are the oxygen sensors?

    PubMed

    Reglin, Bettina; Secomb, Timothy W; Pries, Axel R

    2009-12-01

    Maintenance of functional vascular networks requires structural adaptation of vessel diameters in response to hemodynamic and metabolic conditions. The mechanisms by which diameters respond to the metabolic state are not known, but may involve the release of vasoactive substances in response to low oxygen by tissue ("tissue signaling", e.g., CO2, adenosine), by vessel walls ("wall signaling", e.g., prostaglandins, adenosine), and/or by red blood cells (RBCs) ("RBC signaling", e.g., ATP and nitric oxide). Here, the goal was to test the potential of each of these locations of oxygen-dependent signaling to control steady-state vascular diameters and tissue oxygenation. A previously developed theoretical model of structural diameter adaptation based on experimental data on microvascular network morphology and hemodynamics was used. Resulting network characteristics were analyzed with regard to tissue oxygenation (Oxdef; percentage of tissue volume with PO2<1 Torr) and the difference between estimated blood flow velocities and corresponding experimental data [velocity error (Verr); root mean square deviation of estimated vs. measured velocity]. Wall signaling led to Oxdef<1% and to the closest hemodynamic similarity (Verr: 0.60). Tissue signaling also resulted in a low oxygen deficit, but a higher Verr (0.73) and systematic diameter deviations. RBC signaling led to widespread hypoxia (Oxdef: 4.7%), unrealistic velocity distributions (Verr: 0.81), and shrinkage of small vessels. The results suggest that wall signaling plays a central role in structural control of vessel diameters in microvascular networks of given angioarchitecture. Tissue-derived and RBC-derived signaling of oxygen levels may be more relevant for the regulation of angiogenesis and/or smooth muscle tone. PMID:19783778

  7. Structural adaptation of microvessel diameters in response to metabolic stimuli: where are the oxygen sensors?

    PubMed Central

    Reglin, Bettina; Secomb, Timothy W.

    2009-01-01

    Maintenance of functional vascular networks requires structural adaptation of vessel diameters in response to hemodynamic and metabolic conditions. The mechanisms by which diameters respond to the metabolic state are not known, but may involve the release of vasoactive substances in response to low oxygen by tissue (“tissue signaling”, e.g., CO2, adenosine), by vessel walls (“wall signaling”, e.g., prostaglandins, adenosine), and/or by red blood cells (RBCs) (“RBC signaling”, e.g., ATP and nitric oxide). Here, the goal was to test the potential of each of these locations of oxygen-dependent signaling to control steady-state vascular diameters and tissue oxygenation. A previously developed theoretical model of structural diameter adaptation based on experimental data on microvascular network morphology and hemodynamics was used. Resulting network characteristics were analyzed with regard to tissue oxygenation (Oxdef; percentage of tissue volume with Po2 < 1 Torr) and the difference between estimated blood flow velocities and corresponding experimental data [velocity error (Verr); root mean square deviation of estimated vs. measured velocity]. Wall signaling led to Oxdef < 1% and to the closest hemodynamic similarity (Verr: 0.60). Tissue signaling also resulted in a low oxygen deficit, but a higher Verr (0.73) and systematic diameter deviations. RBC signaling led to widespread hypoxia (Oxdef: 4.7%), unrealistic velocity distributions (Verr: 0.81), and shrinkage of small vessels. The results suggest that wall signaling plays a central role in structural control of vessel diameters in microvascular networks of given angioarchitecture. Tissue-derived and RBC-derived signaling of oxygen levels may be more relevant for the regulation of angiogenesis and/or smooth muscle tone. PMID:19783778

  8. Metabolic and hormonal responses during exercise at 20°, 0° and -20°C

    NASA Astrophysics Data System (ADS)

    Quirion, A.; Laurencelle, L.; Paulin, L.; Therminarias, A.; Brisson, G. R.; Audet, A.; Dulac, S.; Vogelaere, P.

    1989-12-01

    This study was designed to clarify the effects of cold air exposure on metabolic and hormonal responses during progressive incremental exercise. Eight healthy males volunteered for the study. Informed consent was obtained from every participant. The following protocol was administered to each subject on three occasions in a climatic chamber in which the temperature was 20°, 0° or -20°C with relative humidity at 60%±1%. Exercise tests were conducted on an electrically braked ergocycle, and consisted of a propressive incremental maximal exercise. Respiratory parameters were continuously monitored by an automated open-circuit sampling system Exercise blood lactate (LA), free fatty acids (FFA), glucose levels, bicarbonate concentration (HCO{3/-}), acidbase balance, plasma epinephrine (E) and norepinephrine (NE) were determined from venous blood samples obtained through an indwelling brachial catheter. Maximal oxygen uptake was significantly different between conditions: 72.0±5.4 ml kg-1 min-1 at 20°C; 68.9±5.1 ml kg-1 min-1 at 0°C and 68.5±4.6 ml kg-1 min-1 at -20°C. Workload, time to exhaustion, glucose levels and rectal Catecholamines and lactate values were not significantly altered by thermal conditions after maximal exercise but the catecholamines were decreased during rest. Bicarbonate, respiratory quotient, lactate and ventilatory thresholds increased significantly at -20°C. The data support the contention that metabolic and hormonal responses following progressive incremental exercise are altered by cold exposure and they indicate a marked decrease in maximal oxygen uptake, time to exhaustion and workload.

  9. The phosphotransferase system of Lactobacillus casei: regulation of carbon metabolism and connection to cold shock response.

    PubMed

    Monedero, Vicente; Mazé, Alain; Boël, Grégory; Zúñiga, Manuel; Beaufils, Sophie; Hartke, Axel; Deutscher, Josef

    2007-01-01

    Genome sequencing of two different Lactobacillus casei strains (ATCC334 and BL23) is presently going on and preliminary data revealed that this lactic acid bacterium possesses numerous carbohydrate transport systems probably reflecting its capacity to proliferate under varying environmental conditions. Many carbohydrate transporters belong to the phosphoenolpyruvate:sugar phosphotransferase system (PTS), but all different kinds of non-PTS transporters are present as well and their substrates are known in a few cases. In L. casei regulation of carbohydrate transport and carbon metabolism is mainly achieved by PTS proteins. Carbon catabolite repression (CCR) is mediated via several mechanisms, including the major P-Ser-HPr/catabolite control protein A (CcpA)-dependent mechanism. Catabolite response elements, the target sites for the P-Ser-HPr/CcpA complex, precede numerous genes and operons. PTS regulation domain-containing antiterminators and transcription activators are also present in both L. casei strains. Their activity is usually controlled by two PTS-mediated phosphorylation reactions exerting antagonistic effects on the transcription regulators: P~EIIB-dependent phosphorylation regulates induction of the corresponding genes and P~His-HPr-mediated phosphorylation plays a role in CCR. Carbohydrate transport of L. casei is also regulated via inducer exclusion and inducer expulsion. The presence of glucose, fructose, etc. leads to inhibition of the transport or metabolism of less favorable carbon sources (inducer exclusion) or to the export of accumulated non-metabolizable carbon sources (inducer expulsion). While P-Ser-HPr is essential for inducer exclusion of maltose, it is not necessary for the expulsion of accumulated thio-methyl-beta-D-galactopyranoside. Surprisingly, recent evidence suggests that the PTS of L. casei also plays a role in cold shock response. PMID:17183208

  10. Impact of clock-associated Arabidopsis pseudo-response regulators in metabolic coordination

    PubMed Central

    Fukushima, Atsushi; Kusano, Miyako; Nakamichi, Norihito; Kobayashi, Makoto; Hayashi, Naomi; Sakakibara, Hitoshi; Mizuno, Takeshi; Saito, Kazuki

    2009-01-01

    In higher plants, the circadian clock controls a wide range of cellular processes such as photosynthesis and stress responses. Understanding metabolic changes in arrhythmic plants and determining output-related function of clock genes would help in elucidating circadian-clock mechanisms underlying plant growth and development. In this work, we investigated physiological relevance of PSEUDO-RESPONSE REGULATORS (PRR 9, 7, and 5) in Arabidopsis thaliana by transcriptomic and metabolomic analyses. Metabolite profiling using gas chromatography–time-of-flight mass spectrometry demonstrated well-differentiated metabolite phenotypes of seven mutants, including two arrhythmic plants with similar morphology, a PRR 9, 7, and 5 triple mutant and a CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1)-overexpressor line. Despite different light and time conditions, the triple mutant exhibited a dramatic increase in intermediates in the tricarboxylic acid cycle. This suggests that proteins PRR 9, 7, and 5 are involved in maintaining mitochondrial homeostasis. Integrated analysis of transcriptomics and metabolomics revealed that PRR 9, 7, and 5 negatively regulate the biosynthetic pathways of chlorophyll, carotenoid and abscisic acid, and α-tocopherol, highlighting them as additional outputs of pseudo-response regulators. These findings indicated that mitochondrial functions are coupled with the circadian system in plants. PMID:19359492