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Sample records for panorganismal metabolic response

  1. Selected Metabolic Responses to Skateboarding

    Science.gov (United States)

    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…

  2. Substrate metabolism in the metabolic response to injury

    NARCIS (Netherlands)

    Romijn, J. A.

    2000-01-01

    In healthy subjects the metabolic response to starvation invokes regulatory mechanisms aimed at conservation of protein mass. This response is characterized by a decrease in energy expenditure and a progressive decrease in urinary N excretion. Many non-endocrine diseases induce anorexia and a

  3. Metabolic Responses to Weight Lifting

    Directory of Open Access Journals (Sweden)

    Arnold Nelson

    2017-04-01

    Full Text Available Editor's Note, The ability to lift heavy loads while performing multiple repetitions is not only highly correlated with muscle mass or the total number actomyosin interactions, but also metabolic functions that includes substrate concentrations and by-product removal.  Muscles use adenosine triphosphate (ATP in at least three locations during exercise; to run the actomyosin interaction, operate sarcoplasmic reticulum calcium pumps, and operate sarcolemma sodium and potassium pumps.  Weight lifting sessions are considered to be an intermittent activity that includes only a few second bursts of high force and/or velocity movements followed by rest periods of up to several minutes. Therefore, the anaerobic pathways such as the phosphagen and glycolytic systems are the initial pathways to respond due in part to the ability to match the increased rates of ATP depletion by increasing ATP production. After the initial resting ATP stores are used up, the phosphagen system starts contributing to ATP replenishment.  This system consists of reactions from the creatine kinase (CK pathway and the adenylate kinase (AK pathway.  However, the CK pathway can only work at max capacity for a short period for resting phosphocreatine (PCr concentrations are only about 4-6 times the amount of resting ATP stores.  Once the PCr concentrations are depleted, the AK reaction will begin by using two adenosine diphosphate (ADP to form one ATP and one adenosine monophosphate (AMP. Although ATP is produced in this pathway, this production of ATP does coincide with an increased concentration of AMP. This is problematic because increased AMP levels will in turn stimulate the adenylate deaminase reaction, which will produce ammonia (NH3. This conversion of AMP into NH3 will result in the muscle cell having a net loss of total adenine nucleotides available to resynthesize ATP.  Glycolysis is the next reaction in line, which increases its role in ATP replenishment as PCr

  4. Metabolic features of the cell danger response.

    Science.gov (United States)

    Naviaux, Robert K

    2014-05-01

    The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental

  5. Precision metabolic engineering: The design of responsive, selective, and controllable metabolic systems.

    Science.gov (United States)

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

    2015-09-01

    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. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  6. Metabolic and adaptive immune responses induced in mice infected ...

    African Journals Online (AJOL)

    This study investigated metabolic and immuno-inflammatory responses of mice infected with tissue-dwelling larvae of Trichinella zimbabwensis and explored the relationship between infection, metabolic parameters and Th1/Th17 immune responses. Sixty (60) female BALB/c mice aged between 6 to 8 weeks old were ...

  7. Manipulation of the metabolic response in clinical practice

    DEFF Research Database (Denmark)

    Kehlet, H

    2000-01-01

    morbidity. Effective afferent neural blockade with continuous epidural local anesthetic techniques inhibits a major part of the endocrine metabolic response, leading to improved protein economy but without important effects on inflammatory or immunologic responses. In contrast, pain treatment with other...... modalities such as nonsteroidal antiinflammatory drugs (NSAIDs) and opioids has only a small inhibitory effect on endocrine metabolic responses. Preoperative high-dose glucocorticoid therapy provides additional pain relief and improves pulmonary function, but it reduces the inflammatory response (acute......-phase proteins, cytokines, hyperthermia) and immune function. Minimally invasive surgery leaves the endocrine metabolic responses largely unaltered but reduces the inflammatory response and immune suppression. Thus several techniques are available to modify the stress responses in elective surgery patients...

  8. Metabolic response to exogenous ethanol in yeast

    Indian Academy of Sciences (India)

    In this study, we applied this approach to evaluate the effects of increasing concentration of exogenous ethanol on the Saccharomyces cerevisiae fermentative metabolism. We show that the STOCSY analysis correctly identifies the different types of correlations among the enriched metabolites involved in the fermentation, ...

  9. Possible stimuli for strength and power adaptation : acute metabolic responses.

    Science.gov (United States)

    Crewther, Blair; Cronin, John; Keogh, Justin

    2006-01-01

    The metabolic response to resistance exercise, in particular lactic acid or lactate, has a marked influence upon the muscular environment, which may enhance the training stimulus (e.g. motor unit activation, hormones or muscle damage) and thereby contribute to strength and power adaptation. Hypertrophy schemes have resulted in greater lactate responses (%) than neuronal and dynamic power schemes, suggesting possible metabolic-mediated changes in muscle growth. Factors such as age, sex, training experience and nutrition may also influence the lactate responses to resistance exercise and thereafter, muscular adaptation. Although the importance of the mechanical and hormonal stimulus to strength and power adaptation is well recognised, the contribution of the metabolic stimulus is largely unknown. Relatively few studies for example, have examined metabolic change across neuronal and dynamic power schemes, and not withstanding the fact that those mechanisms underpinning muscular adaptation, in relation to the metabolic stimulus, remain highly speculative. Inconsistent findings and methodological limitations within research (e.g. programme design, sampling period, number of samples) make interpretation further difficult. We contend that strength and power research needs to investigate those metabolic mechanisms likely to contribute to weight-training adaptation. Further research is also needed to examine the metabolic responses to different loading schemes, as well as interactions across age, sex and training status, so our understanding of how to optimise strength and power development is improved.

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

    DEFF Research Database (Denmark)

    Wone, B W M; Madsen, Per; Donovan, E R

    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...

  11. Metabolic responses of Haliotis diversicolor to Vibrio parahaemolyticus infection.

    Science.gov (United States)

    Lu, Jie; Shi, Yanyan; Cai, Shuhui; Feng, Jianghua

    2017-01-01

    Vibrio parahemolyticus is a devastating bacterial pathogen that often causes outbreak of vibriosis in abalone Haliotis diversicolor. Elucidation of metabolic mechanisms of abalones in responding to V. parahemolyticus infection is essential for controlling the epidemic. In this work, 1 H NMR-based metabolomic techniques along with correlation and network analyses are used to investigate characteristic metabolites, as well as corresponding disturbed pathways in hepatopancreas and gill of H. diversicolor after V. parahemolyticus infection for 48 h. Results indicate that obvious gender- and tissue-specific metabolic responses are induced. Metabolic responses in female abalones are more clearly observed than those in males, which are primarily manifested in the accumulation of branched-chain amino acids and the depletion of organic osmolytes (homarine, betaine and taurine) in the infected gills of female abalones, as well as in the depletion of glutamate, branched-chain and aromatic amino acids in the infected hepatopancreases of female abalones. Moreover, based on major metabolic functions of the characteristic metabolites, we have found that V. parahemolyticus infection not only cause the disturbance in energy metabolism, nucleotide metabolism and osmotic balance, but also induce oxidative stress, immune stress and neurotoxic effect in different tissues with various mechanisms. Our study provides details of metabolic responses of abalones to V. parahemolyticus infection and will shed light on biochemical defence mechanisms of male and female hosts against pathogen infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Metabolic response to surgery in the cancer patient

    International Nuclear Information System (INIS)

    Brennan, M.F.

    1979-01-01

    The metabolic response to uncomplicated surgery in the patient undergoing primary therapy for malignancy is no different than the response to surgery of similar magnitude for benign disease. Hemodynamic, nutritional-endocrine, and convalescent changes are similar. However, with current aggressive approaches to the management of cancer, the patient often comes to surgery with evidence of major debilitating side effects from his progressive malignancy or from aggressive multimodality therapy. The surgeon must be aware of the consequences of the use of combination therapies on the expected metabolic response to surgery. Awareness of such problems such as the nutritional deficit will allow preventive methods to supercede mtabolic salvage procedures

  13. Metabolic Response to Four Weeks of Muscular Endurance Resistance Training

    Directory of Open Access Journals (Sweden)

    John W. Farrell III

    2017-10-01

    Full Text Available Background: Previous investigations have shown that muscular endurance resistance training (MERT is conducive in improving the onset of blood lactate accumulation (OBLA. However, the metabolic response and time course for adaption is still unclear. Objective: The aims of the current study were to evaluate and track the metabolic response to an individual session of MERT as well as to assess performance adaptations of supplementing an aerobic exercise training program with four weeks of MERT. Methods: Seventeen aerobically active men were randomly assigned to either the experimental (EX or control group (CON, 9 EX and 8 CON. Baseline measures included a graded exercise test (GXT and 1-repetition maximum (1RM testing for leg press (LP, leg curl (LC, and leg extension (LE. CON continued their regular aerobic activity while the EX supplemented their regular aerobic exercise with 4 weeks of MERT. Results: No significant group differences were observed for all pre-training variables. Following four weeks of training no significant differences in cardiorespiratory or metabolic variables were observed for either group. However, significant improvements in LC and LE 1-RM were observed in EX compared to CON. Substantial accumulations in blood lactate were observed following each MERT session. Conclusion: Four weeks of MERT did not improve cardiorespiratory or metabolic variables, but did significantly improve LC and LE. MERT was also observed to induce a blood lactate response similar to that of HIIT. These findings suggest greater than four weeks is need to see metabolic adaptations conducive for improved aerobic performance using MERT.

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

    Directory of Open Access Journals (Sweden)

    Yuanyuan Zhang

    2014-06-01

    Full Text Available 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.

  15. Structural and metabolic responses of Ceratophyllum demersum to ...

    African Journals Online (AJOL)

    Eutrophication in water bodies affects the growth of aquatic plants. In this study, we conducted static experiments to better understand the structural and metabolic responses of Ceratophyllum demersum under eutrophication conditions. The anatomical structure, nitrogen (N) and phosphorous (P) levels in tissue, ...

  16. Modeling metabolic response to changes of enzyme amount in ...

    African Journals Online (AJOL)

    Based on the work of Hynne et al. (2001), in an in silico model of glycolysis, Saccharomyces cerevisiae is established by introducing an enzyme amount multiple factor (.) into the kinetic equations. The model is aimed to predict the metabolic response to the change of enzyme amount. With the help of .α, the amounts of ...

  17. Long-term salt stress responsive growth, carbohydrate metabolism ...

    African Journals Online (AJOL)

    We investigated the long-term responses of tobacco tissues to salt stress, with a particular interest for growth parameters, proline (Pro) accumulation, and carbohydrate metabolism. Exposure of 17-day-old tobacco plants to 0.2 M NaCl was followed by a higher decrease in dry matter in roots than shoots with a decrease of ...

  18. Metabolic changes in serum metabolome in response to a meal.

    Science.gov (United States)

    Shrestha, Aahana; Müllner, Elisabeth; Poutanen, Kaisa; Mykkänen, Hannu; Moazzami, Ali A

    2017-03-01

    The change in serum metabolic response from fasting state to postprandial state provides novel insights into the impact of a single meal on human metabolism. Therefore, this study explored changes in serum metabolite profile after a single meal. Nineteen healthy postmenopausal women with normal glucose tolerance participated in the study. They received a meal consisting of refined wheat bread (50 g carbohydrates, 9 g protein, 4.2 g fat and 2.7 g dietary fibre), 40 g cucumber and 300 mL noncaloric orange drink. Blood samples were collected at fasting and five postprandial time points. Metabolic profile was measured by nuclear magnetic resonance and targeted liquid chromatography-mass spectrometry. Changes over time were assessed with multivariate models and ANOVA, with baseline as control. The metabolomic analyses demonstrated alterations in phospholipids, amino acids and their breakdown products, glycolytic products, acylcarnitines and ketone bodies after a single meal. More specifically, phosphatidylcholines, lysophosphatidylcholines and citrate displayed an overall declining pattern, while leucine, isoleucine, methionine and succinate increased initially but declined thereafter. A sharp decline in acylcarnitines and ketone bodies and increase in glycolytic products postprandially suggest a switch in the body's energy source from β-oxidation to glycolysis. Moreover, individuals with relatively high postprandial insulin responses generated a higher postprandial leucine responses compared to participants with lower insulin responses. The study demonstrated complex changes from catabolic to anabolic metabolism after a meal and indicated that the extent of postprandial responses is different between individuals with high and low insulin response.

  19. LKB1 promotes metabolic flexibility in response to energy stress.

    Science.gov (United States)

    Parker, Seth J; Svensson, Robert U; Divakaruni, Ajit S; Lefebvre, Austin E; Murphy, Anne N; Shaw, Reuben J; Metallo, Christian M

    2017-09-01

    The Liver Kinase B1 (LKB1) tumor suppressor acts as a metabolic energy sensor to regulate AMP-activated protein kinase (AMPK) signaling and is commonly mutated in various cancers, including non-small cell lung cancer (NSCLC). Tumor cells deficient in LKB1 may be uniquely sensitized to metabolic stresses, which may offer a therapeutic window in oncology. To address this question we have explored how functional LKB1 impacts the metabolism of NSCLC cells using 13 C metabolic flux analysis. Isogenic NSCLC cells expressing functional LKB1 exhibited higher flux through oxidative mitochondrial pathways compared to those deficient in LKB1. Re-expression of LKB1 also increased the capacity of cells to oxidize major mitochondrial substrates, including pyruvate, fatty acids, and glutamine. Furthermore, LKB1 expression promoted an adaptive response to energy stress induced by anchorage-independent growth. Finally, this diminished adaptability sensitized LKB1-deficient cells to combinatorial inhibition of mitochondrial complex I and glutaminase. Together, our data implicate LKB1 as a major regulator of adaptive metabolic reprogramming and suggest synergistic pharmacological strategies for mitigating LKB1-deficient NSCLC tumor growth. Copyright © 2016. Published by Elsevier Inc.

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

    Science.gov (United States)

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

    2015-04-01

    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.

  1. Metabolic Response of Maize Roots to Hyperosmotic Shock 1

    Science.gov (United States)

    Spickett, Corinne M.; Smirnoff, Nicholas; Ratcliffe, R. George

    1992-01-01

    31P nuclear magnetic resonance spectroscopy was used to study the response of maize (Zea mays L.) root tips to hyperosmotic shock. The aim was to identify changes in metabolism that might be relevant to the perception of low soil water potential and the subsequent adaptation of the tissue to these conditions. Osmotic shock was found to result in two different types of response: changes in metabolite levels and changes in intracellular pH. The most notable metabolic changes, which were produced by all the osmotica tested, were increases in phosphocholine and vacuolar phosphate, with a transient increase in cytoplasmic phosphate. It was observed that treatment with ionic and nonionic osmotica produced different effects on the concentrations of bioenergetically important metabolites. It is postulated that these changes are the result of hydrolysis of phosphatidylcholine and other membrane phospholipids, due to differential activation of specific membrane-associated phospholipases by changes in the surface tension of the plasmalemma. These events may be important in the detection of osmotic shock and subsequent acclimatization. A cytoplasmic alkalinization was also observed during hyperosmotic treatment, and this response, which is consistent with the activation of the plasmalemma H+-ATPase, together with the other metabolic changes, may suggest the existence of a complex and integrated mechanism of osmoregulation. PMID:16669012

  2. AMPK regulates metabolism and survival in response to ionizing radiation

    International Nuclear Information System (INIS)

    Zannella, Vanessa E.; Cojocari, Dan; Hilgendorf, Susan; Vellanki, Ravi N.; Chung, Stephen; Wouters, Bradly G.; Koritzinsky, Marianne

    2011-01-01

    Background and purpose: AMPK is a metabolic sensor and an upstream inhibitor of mTOR activity. AMPK is phosphorylated by ionizing radiation (IR) in an ATM dependent manner, but the cellular consequences of this phosphorylation event have remained unclear. The objective of this study was to assess whether AMPK plays a functional role in regulating cellular responses to IR. Methods: The importance of AMPK expression for radiation responses was investigated using both MEFs (mouse embryo fibroblasts) double knockout for AMPK α1/α2 subunits and human colorectal carcinoma cells (HCT 116) with AMPK α1/α2 shRNA mediated knockdown. Results: We demonstrate here that IR results in phosphorylation of both AMPK and its substrate, ACC. IR moderately stimulated mTOR activity, and this was substantially exacerbated in the absence of AMPK. AMPK was required for IR induced expression of the mTOR inhibitor REDD1, indicating that AMPK restrains mTOR activity through multiple mechanisms. Likewise, cellular metabolism was deregulated following irradiation in the absence of AMPK, as evidenced by a substantial increase in oxygen consumption rates and lactate production. AMPK deficient cells showed impairment of the G1/S cell cycle checkpoint, and were unable to support long-term proliferation during starvation following radiation. Lastly, we show that AMPK proficiency is important for clonogenic survival after radiation during starvation. Conclusions: These data reveal novel functional roles for AMPK in regulating mTOR signaling, cell cycle, survival and metabolic responses to IR.

  3. Do diabetes and obesity affect the metabolic response to exercise?

    Science.gov (United States)

    Plomgaard, Peter; Weigert, Cora

    2017-07-01

    Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. Poor glycemic control before an intervention can be a risk factor of reduced therapeutic benefit from exercise. But the acute metabolic response to exercise and the transcriptional profile of the working muscle is similar in healthy controls and type 2 diabetic patients, including but not limited to intact activation of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent on the glucagon/insulin ratio and the exercise-induced increase in hepatokines such as fibroblast growth factor 21 and follistatin is impaired in type 2 diabetes and obesity, but consequences for the benefit from exercise are unknown yet. Severe metabolic dysregulation can reduce the benefit from exercise, but the intact response of key metabolic regulators in exercising skeletal muscle of diabetic patients demonstrates the effectiveness of exercise programs to treat the disease.

  4. Deciphering hepatocellular responses to metabolic and oncogenic stress

    Directory of Open Access Journals (Sweden)

    Kathrina L. Marcelo

    2015-08-01

    Full Text Available Each cell type responds uniquely to stress and fractionally contributes to global and tissue-specific stress responses. Hepatocytes, liver macrophages (MΦ, and sinusoidal endothelial cells (SEC play functionally important and interdependent roles in adaptive processes such as obesity and tumor growth. Although these cell types demonstrate significant phenotypic and functional heterogeneity, their distinctions enabling disease-specific responses remain understudied. We developed a strategy for the simultaneous isolation and quantification of these liver cell types based on antigenic cell surface marker expression. To demonstrate the utility and applicability of this technique, we quantified liver cell-specific responses to high-fat diet (HFD or diethylnitrosamine (DEN, a liver-specific carcinogen, and found that while there was only a marginal increase in hepatocyte number, MΦ and SEC populations were quantitatively increased. Global gene expression profiling of hepatocytes, MΦ and SEC identified characteristic gene signatures that define each cell type in their distinct physiological or pathological states. Integration of hepatic gene signatures with available human obesity and liver cancer microarray data provides further insight into the cell-specific responses to metabolic or oncogenic stress. Our data reveal unique gene expression patterns that serve as molecular “fingerprints” for the cell-centric responses to pathologic stimuli in the distinct microenvironment of the liver. The technical advance highlighted in this study provides an essential resource for assessing hepatic cell-specific contributions to metabolic and oncogenic stress, information that could unveil previously unappreciated molecular mechanisms for the cellular crosstalk that underlies the continuum from metabolic disruption to obesity and ultimately hepatic cancer.

  5. Thermal sensation and thermophysiological responses with metabolic step-changes

    DEFF Research Database (Denmark)

    Goto, Tomonobu; Toftum, Jørn; deDear, Richard

    2006-01-01

    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....... 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%....

  6. Effect of radiographic contrast agents on leukocyte metabolic response

    Energy Technology Data Exchange (ETDEWEB)

    Hernanz-Schulman, M. [Dept. of Pediatric Radiology, Vanderbilt Children' s Hospital, Nashville, TN (United States); Vanholder, R.; Waterloos, M.A. [Dept. of Internal Medicine, Nephrology Section, University Hospital, Gent (Belgium); Hakim, R.; Schulman, G. [Department of Nephrology, Vanderbilt University Medical Center, Nashville, TN (United States)

    2000-06-01

    Barium, at clinical dilutions, causes a significant increase of baseline ''resting state'' phagocytic activity, which in turn leads to significant blunting of subsequent response to phagocytic challenge and adversely affects the response to all bacteria tested. There is no baseline activation of leukocytes by the water-soluble media, although there was some inhibition (rather than activation) of leukocyte metabolic activity. The effect of the water-soluble media in bacteria was more complex (although inhibition is minor compared to barium). Our data demonstrate that barium is a significat activator of phagocytic cells, which results in deactivation of phagocytic response when challenged; these dsata serve to explain the enhanced adverse effect of barium in cased of fecal peritonitis. (orig.)

  7. Effect of radiographic contrast agents on leukocyte metabolic response

    International Nuclear Information System (INIS)

    Hernanz-Schulman, M.; Vanholder, R.; Waterloos, M.A.; Hakim, R.; Schulman, G.

    2000-01-01

    Barium, at clinical dilutions, causes a significant increase of baseline ''resting state'' phagocytic activity, which in turn leads to significant blunting of subsequent response to phagocytic challenge and adversely affects the response to all bacteria tested. There is no baseline activation of leukocytes by the water-soluble media, although there was some inhibition (rather than activation) of leukocyte metabolic activity. The effect of the water-soluble media in bacteria was more complex (although inhibition is minor compared to barium). Our data demonstrate that barium is a significant activator of phagocytic cells, which results in deactivation of phagocytic response when challenged; these data serve to explain the enhanced adverse effect of barium in cased of fecal peritonitis. (orig.)

  8. Citric Acid Metabolism in Resistant Hypertension: Underlying Mechanisms and Metabolic Prediction of Treatment Response.

    Science.gov (United States)

    Martin-Lorenzo, Marta; Martinez, Paula J; Baldan-Martin, Montserrat; Ruiz-Hurtado, Gema; Prado, Jose Carlos; Segura, Julian; de la Cuesta, Fernando; Barderas, Maria G; Vivanco, Fernando; Ruilope, Luis Miguel; Alvarez-Llamas, Gloria

    2017-11-01

    Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure to suboptimal blood pressure control results in end-organ damage and cardiovascular risk. Spironolactone is the most effective drug for treatment, but not all patients respond and side effects are not negligible. Little is known on the mechanisms responsible for RH. We aimed to identify metabolic alterations in urine. In addition, a potential capacity of metabolites to predict response to spironolactone was investigated. Urine was collected from 29 patients with RH and from a group of 13 subjects with pseudo-RH. For patients, samples were collected before and after spironolactone administration and were classified in responders (n=19) and nonresponders (n=10). Nuclear magnetic resonance was applied to identify altered metabolites and pathways. Metabolites were confirmed by liquid chromatography-mass spectrometry. Citric acid cycle was the pathway most significantly altered ( P citric acid cycle and deregulation of reactive oxygen species homeostasis control continue its activation after hypertension was developed. A metabolic panel showing alteration before spironolactone treatment and predicting future response of patients is shown. These molecular indicators will contribute optimizing the rate of control of RH patients with spironolactone. © 2017 American Heart Association, Inc.

  9. The metabolic responses to aerial diffusion of essential oils.

    Directory of Open Access Journals (Sweden)

    Yani Wu

    Full Text Available 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

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

    Science.gov (United States)

    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.

  11. Do diabetes and obesity affect the metabolic response to exercise?

    DEFF Research Database (Denmark)

    Plomgaard, Peter; Weigert, Cora

    2017-01-01

    control before an intervention can be a risk factor of reduced therapeutic benefit from exercise. But the acute metabolic response to exercise and the transcriptional profile of the working muscle is similar in healthy controls and type 2 diabetic patients, including but not limited to intact activation...... of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent......PURPOSE OF REVIEW: Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. RECENT FINDINGS: Poor glycemic...

  12. Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J; Richter, E; Madsbad, S

    1987-01-01

    with autonomic neuropathy (P less than 0.01) but was unchanged in the other groups. Since cardiac output increased to a similar extent in the three groups, the decrease in blood pressure was due to a significantly larger decrease (P less than 0.01) in total peripheral vascular resistance in the patients......Norepinephrine-induced vasoconstriction, which is mediated by alpha-adrenergic receptors, is accentuated in patients with autonomic neuropathy. In contrast, responses mediated by beta-adrenergic receptors, including vasodilatation and metabolic changes, have not been evaluated in these patients....... To study these responses, we administered epinephrine in a graded intravenous infusion (0.5 to 5 micrograms per minute) to seven diabetic patients without neuropathy, seven diabetic patients with autonomic neuropathy, and seven normal subjects. Mean arterial pressure decreased significantly in the patients...

  13. Metabolic response to glatiramer acetate therapy in multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    Lidia De Riccardis

    2016-12-01

    Full Text Available Glatiramer acetate (GA; Copaxone is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS. Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4+, the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4+ T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4+ T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4+ T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

  14. Metabolic response to glatiramer acetate therapy in multiple sclerosis patients.

    Science.gov (United States)

    De Riccardis, Lidia; Ferramosca, Alessandra; Danieli, Antonio; Trianni, Giorgio; Zara, Vincenzo; De Robertis, Francesca; Maffia, Michele

    2016-12-01

    Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4 + , the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4 + T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs) and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4 + T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4 + T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

  15. Discriminating response groups in metabolic and regulatory pathway networks.

    Science.gov (United States)

    Van Hemert, John L; Dickerson, Julie A

    2012-04-01

    Analysis of omics experiments generates lists of entities (genes, metabolites, etc.) selected based on specific behavior, such as changes in response to stress or other signals. Functional interpretation of these lists often uses category enrichment tests using functional annotations like Gene Ontology terms and pathway membership. This approach does not consider the connected structure of biochemical pathways or the causal directionality of events. The Omics Response Group (ORG) method, described in this work, interprets omics lists in the context of metabolic pathway and regulatory networks using a statistical model for flow within the networks. Statistical results for all response groups are visualized in a novel Pathway Flow plot. The statistical tests are based on the Erlang distribution model under the assumption of independent and identically Exponential-distributed random walk flows through pathways. As a proof of concept, we applied our method to an Escherichia coli transcriptomics dataset where we confirmed common knowledge of the E.coli transcriptional response to Lipid A deprivation. The main response is related to osmotic stress, and we were also able to detect novel responses that are supported by the literature. We also applied our method to an Arabidopsis thaliana expression dataset from an abscisic acid study. In both cases, conventional pathway enrichment tests detected nothing, while our approach discovered biological processes beyond the original studies. We created a prototype for an interactive ORG web tool at http://ecoserver.vrac.iastate.edu/pathwayflow (source code is available from https://subversion.vrac.iastate.edu/Subversion/jlv/public/jlv/pathwayflow). The prototype is described along with additional figures and tables in Supplementary Material. julied@iastate.edu Supplementary data are available at Bioinformatics online.

  16. Cell Wall Metabolism in Response to Abiotic Stress

    Science.gov (United States)

    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

  17. Metabolic and Transcriptional Response to Cofactor Perturbations in Escherichia coli

    DEFF Research Database (Denmark)

    Holm, Anders Koefoed; Blank, L.M.; Oldiges, M.

    2010-01-01

    Metabolic cofactors such as NADH and ATP play important roles in a large number of cellular reactions, and it is of great interest to dissect the role of these cofactors in different aspects of metabolism. Toward this goal, we overexpressed NADH oxidase and the soluble F1-ATPase in Escherichia coli...... of redox and energy metabolism and should help in developing metabolic engineering strategies in E. coli....

  18. Uptake, accumulation and metabolic response of ferricyanide in weeping willows.

    Science.gov (United States)

    Yu, Xiao-Zhang; Gu, Ji-Dong

    2009-01-01

    The remediation potential and metabolic responses of plants to ferricyanide were investigated using pre-rooted weeping willows (Salix babylonica L.) grown hydroponically in growth chambers and treated with potassium ferricyanide. Positive responses were observed for the plants exposed to cyanide recovered in plant biomass was constant in all treatments, indicating that transport is a major limiting step for the uptake of ferricyanide by plants. The majority of the ferricyanide taken up from the growth media was possibly assimilated during transport through plants. The velocity of the removal processes can be described by Michaelis-Menten kinetics, and the half-saturation constant (K(M)) and the maximum removal capacity (v(max)) were estimated to be 228.1 mg CN L(-1) and 36.43 mg CN kg(-1) d(-1), respectively, using non-linear regression methods. These results suggest that weeping willows can take up, transport and assimilate ferricyanide; and phytoremediation is an option for cleaning up the environmental sites contaminated with cyanide complexes.

  19. Renal responses of trout to chronic respiratory and metabolic acidoses and metabolic alkalosis.

    Science.gov (United States)

    Wood, C M; Milligan, C L; Walsh, P J

    1999-08-01

    Exposure to hyperoxia (500-600 torr) or low pH (4.5) for 72 h or NaHCO(3) infusion for 48 h were used to create chronic respiratory (RA) or metabolic acidosis (MA) or metabolic alkalosis in freshwater rainbow trout. During alkalosis, urine pH increased, and [titratable acidity (TA) - HCO(-)(3)] and net H(+) excretion became negative (net base excretion) with unchanged NH(+)(4) efflux. During RA, urine pH did not change, but net H(+) excretion increased as a result of a modest rise in NH(+)(4) and substantial elevation in [TA - HCO(-)(3)] efflux accompanied by a large increase in inorganic phosphate excretion. However, during MA, urine pH fell, and net H(+) excretion was 3.3-fold greater than during RA, reflecting a similar increase in [TA - HCO(-)(3)] and a smaller elevation in phosphate but a sevenfold greater increase in NH(+)(4) efflux. In urine samples of the same pH, [TA - HCO(-)(3)] was greater during RA (reflecting phosphate secretion), and [NH(+)(4)] was greater during MA (reflecting renal ammoniagenesis). Renal activities of potential ammoniagenic enzymes (phosphate-dependent glutaminase, glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, alanine aminotransferase, phosphoenolpyruvate carboxykinase) and plasma levels of cortisol, phosphate, ammonia, and most amino acids (including glutamine and alanine) increased during MA but not during RA, when only alanine aminotransferase increased. The differential responses to RA vs. MA parallel those in mammals; in fish they may be keyed to activation of phosphate secretion by RA and cortisol mobilization by MA.

  20. Acute metabolic and physiologic response of goats to narcosis

    Science.gov (United States)

    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.

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

    OpenAIRE

    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.

    2012-01-01

    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 t...

  2. Systematic analysis of rice (Oryza sativa) metabolic responses to herbivory.

    Science.gov (United States)

    Alamgir, Kabir Md; Hojo, Yuko; Christeller, John T; Fukumoto, Kaori; Isshiki, Ryutaro; Shinya, Tomonori; Baldwin, Ian T; Galis, Ivan

    2016-02-01

    Plants defend against attack from herbivores by direct and indirect defence mechanisms mediated by the accumulation of phytoalexins and release of volatile signals, respectively. While the defensive arsenals of some plants, such as tobacco and Arabidopsis are well known, most of rice's (Oryza sativa) defence metabolites and their effectiveness against herbivores remain uncharacterized. Here, we used a non-biassed metabolomics approach to identify many novel herbivory-regulated metabolic signatures in rice. Most were up-regulated by herbivore attack while only a few were suppressed. Two of the most prominent up-regulated signatures were characterized as phenolamides (PAs), p-coumaroylputrescine and feruloylputrescine. PAs accumulated in response to attack by both chewing insects, i.e. feeding of the lawn armyworm (Spodoptera mauritia) and the rice skipper (Parnara guttata) larvae, and the attack of the sucking insect, the brown planthopper (Nilaparvata lugens, BPH). In bioassays, BPH insects feeding on 15% sugar solution containing p-coumaroylputrescine or feruloylputrescine, at concentrations similar to those elicited by heavy BPH attack in rice, had a higher mortality compared to those feeding on sugar diet alone. Our results highlight PAs as a rapidly expanding new group of plant defence metabolites that are elicited by herbivore attack, and deter herbivores in rice and other plants. © 2015 John Wiley & Sons Ltd.

  3. Diabetogenic action of streptozotocin: relationship of dose to metabolic response

    Science.gov (United States)

    Junod, Alain; Lambert, André E.; Stauffacher, Werner; Renold, Albert E.

    1969-01-01

    The relationship between the dose of intravenously administered streptozotocin (a N-nitroso derivative of glucosamine) and the diabetogenic response has been explored by use of the following indices of diabetogenic action: serum glucose, urine volume, and glycosuria, ketonuria, serum immunoreactive insulin (IRI), and pancreatic IRI content. Diabetogenic activity could be demonstrated between the doses of 25 and 100 mg/kg, all indices used showing some degree of correlation with the dose administered. Ketonuria was only seen with the largest dose, 100 mg/kg. The most striking and precise correlation was that between the dose and the pancreatic IRI content 24 hr after administration of the drug, and it is suggested that this represents a convenient test system either for both related and unrelated beta cytotoxic compounds or for screening for modifying agents or antidiabetic substances of a novel type. Ability to produce graded depletion of pancreatic IRI storage capacity led to an analysis of the relationship between pancreatic IRI content and deranged carbohydrate metabolism. Abnormal glucose tolerance and insulin response were seen when pancreatic IRI was depleted by about one-third, while fasting hyperglycemia and gross glycosuria occurred when the depletion had reached two-thirds and three-quarters, respectively. The mild yet persistent anomaly produced by the lowest effective streptozotocin dose, 25 mg/kg, exhibits characteristics resembling the state of chemical diabetes in humans and might thus warrant further study as a possible model. Finally, the loss of the diabetogenic action of streptozotocin by pretreatment with nicotinamide was confirmed and was shown to be a function of the relative doses of nicotinamide and streptozotocin and of the interval between injections. PMID:4241908

  4. [Dissociation of antihypertensive and metabolic response to losartan and spironolactone in experimental rats with metabolic sindrome].

    Science.gov (United States)

    Machado, Hussen; Pinheiro, Helady Sanders; Terra, Marcella Martins; Guerra, Martha de Oliveira; de Paula, Rogerio Baumgratz; Peters, Vera Maria

    2012-01-01

    The treatment of arterial hypertension (AH) in patients with metabolic syndrome (MS) is a challenge, since non drug therapies are difficult to implement and optimal pharmacological treatment is not fully established. To assess the blockade of the rennin angiotensin aldosterone system (RAAS) in blood pressure (BP) in renal function and morphology in an experimental model of MS induced by high fat diet. Wistar rats were fed on high fat diet from the fourth week of life, for 20 weeks. The groups received Losartan or Spironolactone from the eighth week of life. We weekly evaluated the body weight and BP by tail plethysmography. At the end of the experiment oral glucose tolerance, lipid profile, creatinine clearance tests, and the direct measurement of BP were performed. A morphometric kidney analysis was performed. The administration of high-fat diet was associated with the development of MS, characterized by central fat accumulation, hypertension, hyperglycemia and hypertriglyceridemia. In this model there were no changes in renal histomorphometry. The blockade of angiotensin II (Ang II) receptor AT1 prevented the development of hypertension. The mineralocorticoid blockage did not have antihypertensive efficacy but was associated with reduction of abdominal fat. The dissociation of the antihypertensive response to the blockades of Ang II receptors and mineralocorticoid indicates the involvement of Ang II in the pathogenesis of hypertension associated with obesity. Reduction of central obesity with Spironolactone suggests the presence of mineralocorticoid adipogenic effect.

  5. Supplementation of Saccharomyces cerevisiae modulates the metabolic response to lipopolysaccharide challenge in feedlot steers

    Science.gov (United States)

    Live yeast has the potential to serve as an alternative to the use of low-dose supplementation of antibiotics in cattle due to the ability to alter ruminant metabolism; which in turn may influence the immune response. Therefore, the objective of this study was to determine the metabolic response to ...

  6. Acute metabolic response to fasted and postprandial exercise

    Directory of Open Access Journals (Sweden)

    Lima FD

    2015-08-01

    Full Text Available Filipe Dinato de Lima,1,2 Ana Luiza Matias Correia,1 Denilson da Silva Teixeira,2 Domingos Vasco da Silva Neto,2 Ítalo Sávio Gonçalves Fernandes,2 Mário Boratto Xavier Viana,2 Mateus Petitto,2 Rodney Antônio da Silva Sampaio,2 Sandro Nobre Chaves,2 Simone Teixeira Alves,2 Renata Aparecida Elias Dantas,2 Márcio Rabelo Mota2 1University of Brasília, Brasília, DF, Brazil; 2Universitary Center of Brasília (UniCEUB, Brasília, DF, BrazilAbstract: The aim of this study was to analyze the acute metabolic response to exercise in fasting and postprandial. For this, ten individuals were submitted to an incremental treadmill test, with an initial speed of 5 and 1 km/h increments every minute, with no inclination, and a body composition assessment. After this 1st day, all volunteers were submitted to two experimental procedures (fasting and postprandial, with an aerobic exercise performed for 36 minutes at 65% of maximal oxygen consumption. At postprandial procedure, all subjects ingested a breakfast containing 59.3 g of carbohydrate (76.73%, 9.97 g of protein (12.90%, 8.01 g of lipids (10.37%, with a total energy intake of 349.17 kcal. An analysis of plasma concentration of triglycerides, lactate, and glucose was performed in two stages: before and after exercise. The Shapiro–Wilk test was used to verify the normality of the data. For analysis of glucose concentration, plasma lactate, and triglycerides, we used a repeated measures analysis of variance factorial 2×2, with Bonferroni multiple comparison test. The significance level of P<0.05 was adopted. The results indicated a maintenance level of glucose at fasting and a decrease in glucose concentration at postprandial exercise. Both conditions increase plasma lactate. Triglycerides also increased in the two experimental conditions; however, after exercise fasting, the increase was significantly higher than in the postprandial exercise. These data suggest that both exercises could increase

  7. Basal metabolic regulatory responses and rhythmic activity of ...

    African Journals Online (AJOL)

    ... Rattus sp. Low concentrations of kola nut extract stimulated the heart by increasing rate and force of contraction as well as metabolic rate. Higher concentrations reduced rate and amplitude of beat resulting, at still higher concentrations in heart failure. Keywords: Kolanut, extract, basal metabolic rate, mammalian heart ...

  8. Global patterns in lake ecosystem responses to warming based on the temperature dependence of metabolism.

    Science.gov (United States)

    Kraemer, Benjamin M; Chandra, Sudeep; Dell, Anthony I; Dix, Margaret; Kuusisto, Esko; Livingstone, David M; Schladow, S Geoffrey; Silow, Eugene; Sitoki, Lewis M; Tamatamah, Rashid; McIntyre, Peter B

    2017-05-01

    Climate warming is expected to have large effects on ecosystems in part due to the temperature dependence of metabolism. The responses of metabolic rates to climate warming may be greatest in the tropics and at low elevations because mean temperatures are warmer there and metabolic rates respond exponentially to temperature (with exponents >1). However, if warming rates are sufficiently fast in higher latitude/elevation lakes, metabolic rate responses to warming may still be greater there even though metabolic rates respond exponentially to temperature. Thus, a wide range of global patterns in the magnitude of metabolic rate responses to warming could emerge depending on global patterns of temperature and warming rates. Here we use the Boltzmann-Arrhenius equation, published estimates of activation energy, and time series of temperature from 271 lakes to estimate long-term (1970-2010) changes in 64 metabolic processes in lakes. The estimated responses of metabolic processes to warming were usually greatest in tropical/low-elevation lakes even though surface temperatures in higher latitude/elevation lakes are warming faster. However, when the thermal sensitivity of a metabolic process is especially weak, higher latitude/elevation lakes had larger responses to warming in parallel with warming rates. Our results show that the sensitivity of a given response to temperature (as described by its activation energy) provides a simple heuristic for predicting whether tropical/low-elevation lakes will have larger or smaller metabolic responses to warming than higher latitude/elevation lakes. Overall, we conclude that the direct metabolic consequences of lake warming are likely to be felt most strongly at low latitudes and low elevations where metabolism-linked ecosystem services may be most affected. © 2016 John Wiley & Sons Ltd.

  9. Induction of a stringent metabolic response in intracellular stages of Leishmania mexicana leads to increased dependence on mitochondrial metabolism.

    Directory of Open Access Journals (Sweden)

    Eleanor C Saunders

    2014-01-01

    Full Text Available Leishmania parasites alternate between extracellular promastigote stages in the insect vector and an obligate intracellular amastigote stage that proliferates within the phagolysosomal compartment of macrophages in the mammalian host. Most enzymes involved in Leishmania central carbon metabolism are constitutively expressed and stage-specific changes in energy metabolism remain poorly defined. Using (13C-stable isotope resolved metabolomics and (2H2O labelling, we show that amastigote differentiation is associated with reduction in growth rate and induction of a distinct stringent metabolic state. This state is characterized by a global decrease in the uptake and utilization of glucose and amino acids, a reduced secretion of organic acids and increased fatty acid β-oxidation. Isotopomer analysis showed that catabolism of hexose and fatty acids provide C4 dicarboxylic acids (succinate/malate and acetyl-CoA for the synthesis of glutamate via a compartmentalized mitochondrial tricarboxylic acid (TCA cycle. In vitro cultivated and intracellular amastigotes are acutely sensitive to inhibitors of mitochondrial aconitase and glutamine synthetase, indicating that these anabolic pathways are essential for intracellular growth and virulence. Lesion-derived amastigotes exhibit a similar metabolism to in vitro differentiated amastigotes, indicating that this stringent response is coupled to differentiation signals rather than exogenous nutrient levels. Induction of a stringent metabolic response may facilitate amastigote survival in a nutrient-poor intracellular niche and underlie the increased dependence of this stage on hexose and mitochondrial metabolism.

  10. Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response

    Directory of Open Access Journals (Sweden)

    Hong Zhong

    2018-01-01

    Full Text Available In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

  11. Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response.

    Science.gov (United States)

    Zhong, Hong; Ma, Minjuan; Liang, Tingming; Guo, Li

    2018-01-01

    In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

  12. Integration of metabolic and gene regulatory networks modulates the C. elegans dietary response.

    Science.gov (United States)

    Watson, Emma; MacNeil, Lesley T; Arda, H Efsun; Zhu, Lihua Julie; Walhout, Albertha J M

    2013-03-28

    Expression profiles are tailored according to dietary input. However, the networks that control dietary responses remain largely uncharacterized. Here, we combine forward and reverse genetic screens to delineate a network of 184 genes that affect the C. elegans dietary response to Comamonas DA1877 bacteria. We find that perturbation of a mitochondrial network composed of enzymes involved in amino acid metabolism and the TCA cycle affects the dietary response. In humans, mutations in the corresponding genes cause inborn diseases of amino acid metabolism, most of which are treated by dietary intervention. We identify several transcription factors (TFs) that mediate the changes in gene expression upon metabolic network perturbations. Altogether, our findings unveil a transcriptional response system that is poised to sense dietary cues and metabolic imbalances, illustrating extensive communication between metabolic networks in the mitochondria and gene regulatory networks in the nucleus. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Bone metabolism and hand grip strength response to aerobic versus ...

    African Journals Online (AJOL)

    porosis is incomplete and has prompted our interest to identify the type of effective osteogenic exercise. ... between aerobic and resistance exercise training in non-insulin dependent ... paired glucose metabolism on bone health as well as to.

  14. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  15. Metabolic and inflammatory responses to the common sweetener stevioside and a glycemic challenge in horses with equine metabolic syndrome.

    Science.gov (United States)

    Elzinga, S E; Rohleder, B; Schanbacher, B; McQuerry, K; Barker, V D; Adams, A A

    2017-07-01

    Extracts derived from the leaves of the stevia plant (stevioside) are commonly used as sweeteners for humans and horses. Stevioside appears to be safe for human consumption, including for individuals with insulin dysregulation. In the horse, the safety or metabolic effects of stevioside on normal animals or on those with metabolic dysfunction are unknown. Furthermore, the inflammatory response to a glycemic challenge or to stevioside in horses is not well defined. Therefore, the objective of this study was to measure the effects of stevioside and a glycemic challenge on insulin, glucose, and inflammatory responses in horses with a common metabolic dysfunction (equine metabolic syndrome or EMS) compared with non-EMS controls. To accomplish this, 15 horses were selected; 8 EMS and 7 age-matched controls. An oral sugar test was performed using Karo corn syrup (karo) or stevioside in a random crossover design. Horses were given 0.15 mL/kg body weight of karo or its equivalent grams of sugar in stevia dissolved in water. Blood samples were collected by jugular venipuncture before administration of either stevia or karo and at 60 and 240 min after administration. Serum was used for glucose and insulin determination and plasma for isolation of peripheral blood mononuclear cells (PBMCs) for inflammatory cytokine analysis via flow cytometry and reverse transcription PCR (RT-PCR). Stevia appeared to stimulate lower glycemic and insulinemic responses when compared to karo, in particular in EMS horses. EMS and control horses had inverse inflammatory responses to administration of either stevia or karo with EMS horses having a proinflammatory response (P ≤ 0.05). These data provide evidence as to why horses with EMS may be predisposed to developing laminitis, potentially as a result of an exaggerated inflammatory response to glycemic and insulinemic responses. Furthermore, the data provide new avenues for exploring mechanisms behind the syndrome, in particular when using a

  16. Climate Coping: Investigating Metabolic Responses in Crocosphaera watsonii

    Science.gov (United States)

    Harris, K.

    2016-02-01

    Climate change causes chemical alterations in the open oceans, such as warming which leads to stratification, affecting nutrient ratios. Changes in nutrient ratios result in species shifts and a change in phytoplankton physiology, affecting all marine life. Unicellular diazotrophic microorganisms play a vital role in our open ocean ecosystems. These organisms do so by implementing metabolic processes that contribute to various availability of nutrients including; nitrogen and carbon. The open ocean diazotrophs are represented by multiple strains of Crocosphaera watsonii. The specific aim of this study was to determine whether the phenotype in small and large strain C. watsonii differs, in response to exposure to altered temperature gradients, measured as changes in cell density, photosynthetic efficiency, and EPS production. Triplicate cultures of C. watsonii WH8501 and C. watsonii WH0003 were inoculated into 60 ml of sterile Vineyard Sound SO media at a 1:10 ratio. Each culture was grown under; warm light levels (˜63 µ E m-2 s-1) on a 14:10 day/night cycle at temperatures of 27oC or 29oC. C. watsonii WH8501 cultures were harvested on Day 11, and C. watsonii WH0003 cultures were harvested on Day 9. To evaluate cell growth, fluorescence measurements were taken daily. Aliquots of experimental cultures were evaluated for cell density using flow-cytrometry, photosynthetic efficiency using FIRe fluorescence, and EPS production using a TEP determination assay. Proteins were extracted and analyzed by LC-MS-MS mass spectrometry. There was a correlation between temperature and EPS production for the two strains, C. watsonii WH8501 had a significantly higher growth rate when grown at 29oC, and a lower growth rate at 27oC compared to C. watsonii WH0003. Cultures grown at 27oC produced more EPS than those grown at 29oC. However, overall C. watsonii WH0003 produced more EPS than C. watsonii WH8501. We an increase in the yield of photosystem II (Fv/Fm) in C. watsonii WH0003 vs

  17. The metabolic response of Candida albicans to farnesol under hyphae-inducing conditions.

    Science.gov (United States)

    Han, Ting-Li; Cannon, Richard D; Villas-Bôas, Silas G

    2012-12-01

    Farnesol is a quorum-sensing molecule (QSM) produced, and sensed, by the polymorphic fungus, Candida albicans. This cell-to-cell communication molecule is known to suppress the hyphal formation of C. albicans at high cell density. Despite many studies investigating the signalling mechanisms by which QSMs influence the morphogenesis of C. albicans, the downstream metabolic effect of these signalling pathways in response to farnesol-mediated morphogenesis remains obscure. Here, we have used metabolomics to investigate the metabolic response of C. albicans upon exposure to farnesol under hyphae-inducing conditions. We have found a general up-regulation of central carbon metabolic pathways when hyphal formation was suppressed by farnesol evidenced by a considerably larger number of central carbon metabolic intermediates detected under this condition at an overall lower intracellular level. By combining the metabolic profiles from farnesol-exposed cells with previous metabolomics data for C. albicans undergoing morphogenesis, we have identified several metabolic pathways that are likely to be associated with the morphogenetic process of C. albicans, as well as metabolic pathways such as those involved in lipid metabolism that appeared to be specifically affected by farnesol. Therefore, our results provide important new insights into the metabolic role of farnesol in C. albicans metabolism. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

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

    Science.gov (United States)

    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...

  19. Metabolic imaging of tumor for diagnosis and response for therapy

    Science.gov (United States)

    Zagaynova, Elena; Shirmanova, Marina; Lukina, Maria; Dudenkova, Varvara; Ignatova, Nadezgda; Elagin, Vadim; Shlivko, Irena; Scheslavsky, Vladislav; Orlinskay, Natalia

    2018-02-01

    Nonlinear optical microscopy combined with fluorescence lifetime imaging is a non-invasive imaging technique, based on the study of fluorescence decay times of naturally occurring fluorescent molecules, enabling a noninvasive investigation of the biological tissue with subcellular resolution. Cancer exhibits altered cellular metabolism, which affects the autofluorescence of metabolic cofactors NAD(P)H and FAD. In this study features of tumor metabolism in different systems of organization (from cell culture to patient lesion) was showed. The observed differences in the relative contributions of free NAD(P)H and FAD testify to an increased a glycolytic metabolism in cancer cells compare to fibroblasts. In 3D spheroids, the cells of the proliferating zone had greater a1 and lower tm values than the cells of the quiescent zone, which likely is a consequence of their higher glycolytic rate. During the growth of colorectal cancer in the experimental mouse model, the contribution of the free component of NAD(P)H was increased. Dysplastic nevus and melanoma is characterized by raised contribution of free NADH compare to healthy skin. Therefore, melanoma cells had very short value of τ1.

  20. Opposite metabolic responses of shoots and roots to drought

    Czech Academy of Sciences Publication Activity Database

    Gargallo-Garriga, A.; Sardans, J.; Pérez-Trujillo, M.; Rivas-Ubach, A.; Oravec, Michal; Večeřová, Kristýna; Urban, Otmar; Jentsch, A.; Kreyling, J.; Beierkuhnlein, C.; Parella, T.; Penuelas, J.

    2014-01-01

    Roč. 4, č. 6829 (2014), s. 1-7 ISSN 2045-2322 Grant - others:AV ČR(CZ) M200871201 Institutional support: RVO:67179843 Keywords : shoot and roots * autotrophic and heterotrophic organs * environmental change * growth metabolism * water and nutirens Subject RIV: EH - Ecology, Behaviour Impact factor: 5.578, year: 2014

  1. Metabolic mapping of the brain's response to visual stimulation: studies in humans

    International Nuclear Information System (INIS)

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

    1981-01-01

    These studies demonstrated increasing glucose metabolic rates in the human primary (PVC) and associative (AVC) visual cortex as the complexity of visual scenes increased. The metabolic response of the AVC increased more rapidly with scene complexity than that of the PVC, indicating the greater involvement of the higher order AVC for complex visual interpretations. Increases in local metabolic activity by as much as a factor of 2 above that of control subjects with eyes closed indicate the wide range and metabolic reserve of the visual cortex

  2. Genetic response to metabolic fluctuations: correlation between central carbon metabolism and DNA replication in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Szalewska-Pałasz Agnieszka

    2011-03-01

    Full Text Available Abstract Background Until now, the direct link between central carbon metabolism and DNA replication has been demonstrated only in Bacillus. subtilis. Therefore, we asked if this is a specific phenomenon, characteristic for this bacterium and perhaps for its close relatives, or a more general biological rule. Results We found that temperature-sensitivity of mutants in particular genes coding for replication proteins could be suppressed by deletions of certain genes coding for enzymes of the central carbon metabolism. Namely, the effects of dnaA46(ts mutation could be suppressed by dysfunction of pta or ackA, effects of dnaB(ts by dysfunction of pgi or pta, effects of dnaE486(ts by dysfunction of tktB, effects of dnaG(ts by dysfunction of gpmA, pta or ackA, and effects of dnaN159(ts by dysfunction of pta or ackA. The observed suppression effects were not caused by a decrease in bacterial growth rate. Conclusions The genetic correlation exists between central carbon metabolism and DNA replication in the model Gram-negative bacterium, E. coli. This link exists at the steps of initiation and elongation of DNA replication, indicating the important global correlation between metabolic status of the cell and the events leading to cell reproduction.

  3. Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes.

    NARCIS (Netherlands)

    Wopereis, S.; Rubingh, C.M. de; Erk, M.J. van; Verheij, E.R.; Vliet, T. van; Cnubben, N.H.; Smilde, A.K.; Greef, J. van der; Ommen, B. van; Hendriks, H.F.

    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

  4. Metabolic Response to Food Restriction in Military-Eligible Women, with a Gender Comparison

    National Research Council Canada - National Science Library

    Young, Vernon

    1998-01-01

    Two major series of investigations are being undertaken to explore the metabolic responses of women who meet military standards for body-weight and percent body-fat to the nutritional stressors of food restriction...

  5. Metabolic Response to Food Restriction in Military-Eligible Women, With a Gender Comparison

    National Research Council Canada - National Science Library

    Young, Vernon

    1996-01-01

    Two major series of investigations will be undertaken to explore the metabolic responses of women, who meet military standards of body-weight and percent body-fat to the nutritional stressors of food restriction...

  6. Metabolic Response to Food Restriction in Military-Eligible Women, with a Gender Comparison

    National Research Council Canada - National Science Library

    Young, Vernon

    1997-01-01

    Two major series of investigations are being undertaken to explore the metabolic responses of women who meet military standards for body-weight and percent body-fat to the nutritional stressors of food restriction...

  7. Metabolic response of Candida albicans to phenylethyl alcohol under hyphae-inducing conditions.

    Science.gov (United States)

    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.

  8. Cardiovascular, hormonal and metabolic responses to graded exercise in juvenile diabetics with and without autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J; Galbo, H; Christensen, N J

    1980-01-01

    Thirteen juvenile diabetics were studied in order to determine if decreased beat-to-beat variation during deep respiration, indicating abnormal autonomic nerve function, imply that cardiovascular, hormonal and metabolic responses are impaired. Patients with decreased beat-to-beat variation had to...... to be more heavily stressed during exercise to reach a certain heart rate or catecholamine level. The relation between other metabolic and hormonal response is discussed....

  9. Metabolic response to feeding in Tupinambis merianae: circadian rhythm and a possible respiratory constraint.

    Science.gov (United States)

    Klein, Wilfried; Perry, Steven F; Abe, Augusto S; Andrade, Denis V

    2006-01-01

    The diurnal tegu lizard Tupinambis merianae exhibits a marked circadian variation in metabolism that is characterized by the significant increase in metabolism during part of the day. These increases in metabolic rate, found in the fasting animal, are absent during the first 2 d after meal ingestion but reappear subsequently, and the daily increase in metabolic rate is added to the increase in metabolic rate caused by digestion. During the first 2 d after feeding, priority is given to digestion, while on the third and following days, the metabolic demands are clearly added to each other. This response seems to be a regulated response of the animal, which becomes less active after food ingestion, rather than an inability of the respiratory system to support simultaneous demands at the beginning of digestion. The body cavity of Tupinambis is divided into two compartments by a posthepatic septum (PHS). Animals that had their PHS surgically removed showed no significant alteration in the postprandial metabolic response compared to tegus with intact PHS. The maximal metabolic increment during digestion, the relative cost of meal digestion, and the duration of the process were virtually unaffected by the removal of the PHS.

  10. MR imaging of metabolic white matter diseases: Therapeutic response

    International Nuclear Information System (INIS)

    Gebarski, S.S.; Allen, R.

    1987-01-01

    In metabolic diseases affecting the brain, MR imaging abnormalities include white-matter signal aberrations suggesting myelination delay, dysmyelination and demyelination, pathologic iron storage, and finally, loss of substance usually in a nonspecific pattern. The authors suggest that MR imaging may have therapeutic implications: (1) classic galactosemia - white-matter signal aberration became normal after dietary therapy; (2) phenylketonuria - age- and sex-matched treated and nontreated adolescents showed marked differences in brain volume, with the treated patient's volume nearly normal; (3) maple syrup urine disease - gross white-matter signal aberration became nearly normal after dietary therapy; and (4) hyperglycinemia - relentless progression of white-matter signal aberration and loss of brain substance despite therapy. These data suggest that brain MR imaging may provide a therapeutic index in certain metabolic diseases

  11. Regulation of longevity by FGF21: Interaction between energy metabolism and stress responses.

    Science.gov (United States)

    Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

    2017-08-01

    Fibroblast growth factor 21 (FGF21) is a hormone-like member of FGF family which controls metabolic multiorgan crosstalk enhancing energy expenditure through glucose and lipid metabolism. In addition, FGF21 acts as a stress hormone induced by endoplasmic reticulum stress and dysfunctions of mitochondria and autophagy in several tissues. FGF21 also controls stress responses and metabolism by modulating the functions of somatotropic axis and hypothalamic-pituitary-adrenal (HPA) pathway. FGF21 is a potent longevity factor coordinating interactions between energy metabolism and stress responses. Recent studies have revealed that FGF21 treatment can alleviate many age-related metabolic disorders, e.g. atherosclerosis, obesity, type 2 diabetes, and some cardiovascular diseases. In addition, transgenic mice overexpressing FGF21 have an extended lifespan. However, chronic metabolic and stress-related disorders involving inflammatory responses can provoke FGF21 resistance and thus disturb healthy aging process. First, we will describe the role of FGF21 in interorgan energy metabolism and explain how its functions as a stress hormone can improve healthspan. Next, we will examine both the induction of FGF21 expression via the integrated stress response and the molecular mechanism through which FGF21 enhances healthy aging. Finally, we postulate that FGF21 resistance, similarly to insulin resistance, jeopardizes human healthspan and accelerates the aging process. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Chronic myeloid leukemia patients sensitive and resistant to imatinib treatment show different metabolic responses.

    Directory of Open Access Journals (Sweden)

    Jiye A

    Full Text Available The BCR-ABL tyrosine kinase inhibitor imatinib is highly effective for chronic myeloid leukemia (CML. However, some patients gradually develop resistance to imatinib, resulting in therapeutic failure. Metabonomic and genomic profiling of patients' responses to drug interventions can provide novel information about the in vivo metabolism of low-molecular-weight compounds and extend our insight into the mechanism of drug resistance. Based on a multi-platform of high-throughput metabonomics, SNP array analysis, karyotype and mutation, the metabolic phenotypes and genomic polymorphisms of CML patients and their diverse responses to imatinib were characterized. The untreated CML patients (UCML showed different metabolic patterns from those of healthy controls, and the discriminatory metabolites suggested the perturbed metabolism of the urea cycle, tricarboxylic acid cycle, lipid metabolism, and amino acid turnover in UCML. After imatinib treatment, patients sensitive to imatinib (SCML and patients resistant to imatinib (RCML had similar metabolic phenotypes to those of healthy controls and UCML, respectively. SCML showed a significant metabolic response to imatinib, with marked restoration of the perturbed metabolism. Most of the metabolites characterizing CML were adjusted to normal levels, including the intermediates of the urea cycle and tricarboxylic acid cycle (TCA. In contrast, neither cytogenetic nor metabonomic analysis indicated any positive response to imatinib in RCML. We report for the first time the associated genetic and metabonomic responses of CML patients to imatinib and show that the perturbed in vivo metabolism of UCML is independent of imatinib treatment in resistant patients. Thus, metabonomics can potentially characterize patients' sensitivity or resistance to drug intervention.

  13. Metabolism

    Science.gov (United States)

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  14. Dealing with hunger: Metabolic stress responses in tumors

    Directory of Open Access Journals (Sweden)

    Michael A Reid

    2013-01-01

    Full Text Available Increased nutrient uptake and usage is a hallmark of many human malignancies. During the course of tumorigenesis, cancer cells often outstrip their local nutrient supply leading to periods of nutrient deprivation. Interestingly, cancer cells often develop strategies to adapt and survive these challenging conditions. Accordingly, understanding these processes is critical for developing therapies that target cancer metabolism. Exciting new progress has been made in elucidating the mechanisms used by cancer cells under nutrient restricted conditions. In this review, we highlight recent studies that have brought insight into how cancer cells deal with low nutrient environments.

  15. Metabolic development of the porcine placenta in response to alterations in maternal or fetal homeostasis

    International Nuclear Information System (INIS)

    Namsey, T.G.; kasser, T.R.; Hausman, G.J.; Martin, R.J.

    1986-01-01

    Porcine placenta has been utilized as a model for elucidating contributions of both fetal and maternal tissues to metabolic activity of the placenta in response to a variety of stresses. Alloxan diabetes, food restriction and genetic obesity all produced alterations in placental metablolism with differences in responses of fetal and maternal placentas. Further analysis of nutrient untilization by the placenta produced dramatic differences in the partitioning of substrates by fetal and maternal tissues during placental development. Metabolic activity of maternal tissue contributed to overall placental metabolic activity to a greater degree than fetal tissue. However, experiments with in utero fetal decapitation indicated that some of differences between fetal and maternal placental metabolic activity may be due to the influence of fetal regulatory mechanisms. Maternal endometrium plays a critical role in metabolic response of uteroplacenta and thus availability of nutrients to the fetus and fetal placenta. Differences in metabolic development of fetal and maternal tissues suggested that regulation of placental metabolism may originate from fetal as well as maternal sources

  16. Corticosterone-responsive and -unresponsive metabolic characteristics of adrenalectomized rats.

    Science.gov (United States)

    Hamelink, C R; Currie, P J; Chambers, J W; Castonguay, T W; Coscina, D V

    1994-09-01

    Glucocorticoids are important in influencing substrate flux through the metabolic pathways. This study was designed to answer the question "Does adrenalectomy (ADX) cause a shift toward fat metabolism as measured by a decrease in respiratory quotient (RQ)?" Male Sprague-Dawley rats were divided into four groups, ADX, ADX + 20% corticosterone (Cort) (ADX-20%), ADX + 40% Cort (ADX-40%), or sham-operated controls (Sham). ADX-20% received 50 mg and ADX-40% 100 mg Cort dissolved in 250-mg cholesterol pellets and placed subcutaneously. Each rat was monitored for 90 min four times both during a preoperative period and again after a 1-wk postsurgical recovery period in an indirect calorimeter. Cort prevented ADX-induced suppression of weight gain and food intake. ADX decreased motoric activity in both the light and dark periods. Cort restored activity to Sham levels. ADX decreased RQ only in the dark (0.858 ADX vs. 0.891 Sham) and was reversed only in the ADX-40% group. Energy expenditure (EE) was depressed in both the light and dark by ADX; Cort partially restored EE to Sham values in the light period.

  17. Maternal high-fat diet intensifies the metabolic response to stress in male rat offspring

    OpenAIRE

    Karbaschi, Roxana; Zardooz, Homeira; Khodagholi, Fariba; Dargahi, Leila; Salimi, Mina; Rashidi, FatemehSadat

    2017-01-01

    Background The mother?s consumption of high-fat food can affect glucose metabolism and the hypothalamic?pituitary?adrenal axis responsiveness in the offspring and potentially affect the metabolic responses to stress as well. This study examines the effect of maternal high-fat diet on the expression of pancreatic glucose transporter 2 and the secretion of insulin in response to stress in offspring. Methods Female rats were randomly divided into normal and high-fat diet groups and were fed in a...

  18. Dietary fatty acids linking postprandial metabolic response and chronic diseases.

    Science.gov (United States)

    Ortega, Almudena; Varela, Lourdes M; Bermudez, Beatriz; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

    2012-01-01

    Chronic diseases are by far one of the main causes of mortality in the world. One of the current global recommendations to counteract disability and premature death resulting from chronic diseases is to decrease the consumption of energy-dense high-fat diets, particularly those rich in saturated fatty acids (SFA). The most effective replacement for SFA in terms of risk factor outcomes for chronic disease are polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA). The biochemical basis for healthy benefits of such a dietary pattern has been widely evaluated under fasting conditions. However, the increasing amount of data available from multiple studies suggest that the postprandial state, i.e., "the period that comprises and follows a meal", plays an important, yet underappreciated, role in the genesis of numerous pathological conditions. In this review, the potential of MUFA, PUFA, and SFA to postprandially affect selected metabolic abnormalities related to chronic diseases is discussed.

  19. Response to Cardiac Resynchronization Therapy: The Muscular Metabolic Pathway

    Directory of Open Access Journals (Sweden)

    Jérémie Jaussaud

    2011-01-01

    245±140 seconds (=.01. Peak VO2, VE/VCO2, peak circulatory power and NYHA were improved after CRT (13±4 to16±5 ml/kg/min (<.05, 45±16 to 39±13 (<.01, 1805±844 to 2225±1171 mmHg.ml/kg/min (<.01 and 3±0.35 to 1.88±0.4 (=.01. In addition, left ventricular ejection fraction and end-systolic volumes were improved from 24±8 to 29±7% (<.01 and from 157±69 to 122±55 ml (<.01. Conclusion. We suggest that CRT leads to an increase in oxidative muscular metabolism and postponed anaerobic threshold reducing exaggerated hyperventilation during exercise.

  20. Metabolic responses to high protein diet in Korean elite bodybuilders with high-intensity resistance exercise

    OpenAIRE

    Kim, Hyerang; Lee, Saningun; Choue, Ryowon

    2011-01-01

    Abstract Background High protein diet has been known to cause metabolic acidosis, which is manifested by increased urinary excretion of nitrogen and calcium. Bodybuilders habitually consumed excessive dietary protein over the amounts recommended for them to promote muscle mass accretion. This study investigated the metabolic response to high protein consumption in the elite bodybuilders. Methods Eight elite Korean bodybuilders within the age from 18 to 25, mean age 21.5 ± 2.6. For data collec...

  1. Endocrine, metabolic and cardiovascular responses to adrenaline after abdominal surgery

    DEFF Research Database (Denmark)

    Hilsted, J; Wilken-Jensen, Charlotte; Birch, K

    1990-01-01

    Adrenaline-induced changes in heart rate, blood pressure, plasma adrenaline and noradrenaline, cortisol, glucagon, insulin, cAMP, glucose lactate, glycerol and beta-hydroxybutyrate were studied preoperatively and 4 and 24 h after skin incision in 8 patients undergoing elective cholecystectomy. Late...... postoperative responses of blood glucose, plasma cAMP, lactate and glycerol to adrenaline infusion were reduced, whereas other responses were unaffected. Blood glucose appearance and disappearance rate as assessed by [3H]3-glucose infusion was unchanged pre- and postoperatively. The increase in glucose...... appearance rate following adrenaline was similar pre- and postoperatively. These findings suggest that several beta-receptor-mediated responses to adrenaline are reduced after abdominal surgery....

  2. The cross-tissue metabolic response of abalone (Haliotis midae) to functional hypoxia.

    Science.gov (United States)

    Venter, Leonie; Loots, Du Toit; Mienie, Lodewyk J; Jansen van Rensburg, Peet J; Mason, Shayne; Vosloo, Andre; Lindeque, Jeremie Z

    2018-03-23

    Functional hypoxia is a stress condition caused by the abalone itself as a result of increased muscle activity, which generally necessitates the employment of anaerobic metabolism if the activity is sustained for prolonged periods. With that being said, abalone are highly reliant on anaerobic metabolism to provide partial compensation for energy production during oxygen-deprived episodes. However, current knowledge on the holistic metabolic response for energy metabolism during functional hypoxia, and the contribution of different metabolic pathways and various abalone tissues towards the overall accumulation of anaerobic end-products in abalone are scarce. Metabolomics analysis of adductor muscle, foot muscle, left gill, right gill, haemolymph and epipodial tissue samples indicated that South African abalone ( Haliotis midae) subjected to functional hypoxia utilises predominantly anaerobic metabolism, and depends on all of the main metabolite classes (proteins, carbohydrates and lipids) for energy supply. Functional hypoxia caused increased levels of anaerobic end-products: lactate, alanopine, tauropine, succinate and alanine. Also, elevation in arginine levels was detected, confirming that abalone use phosphoarginine to generate energy during functional hypoxia. Different tissues showed varied metabolic responses to hypoxia, with functional hypoxia showing excessive changes in the adductor muscle and gills. From this metabolomics investigation, it becomes evident that abalone are metabolically able to produce sufficient amounts of energy when functional hypoxia is experienced. Also, tissue interplay enables the adjustment of H. midae energy requirements as their metabolism shifts from aerobic to anaerobic respiration during functional hypoxia.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

  3. The cross-tissue metabolic response of abalone (Haliotis midae to functional hypoxia

    Directory of Open Access Journals (Sweden)

    Leonie Venter

    2018-03-01

    Full Text Available Functional hypoxia is a stress condition caused by the abalone itself as a result of increased muscle activity, which generally necessitates the employment of anaerobic metabolism if the activity is sustained for prolonged periods. With that being said, abalone are highly reliant on anaerobic metabolism to provide partial compensation for energy production during oxygen-deprived episodes. However, current knowledge on the holistic metabolic response for energy metabolism during functional hypoxia, and the contribution of different metabolic pathways and various abalone tissues towards the overall accumulation of anaerobic end-products in abalone are scarce. Metabolomics analysis of adductor muscle, foot muscle, left gill, right gill, haemolymph and epipodial tissue samples indicated that South African abalone (Haliotis midae subjected to functional hypoxia utilises predominantly anaerobic metabolism, and depends on all of the main metabolite classes (proteins, carbohydrates and lipids for energy supply. Functional hypoxia caused increased levels of anaerobic end-products: lactate, alanopine, tauropine, succinate and alanine. Also, elevation in arginine levels was detected, confirming that abalone use phosphoarginine to generate energy during functional hypoxia. Different tissues showed varied metabolic responses to hypoxia, with functional hypoxia showing excessive changes in the adductor muscle and gills. From this metabolomics investigation, it becomes evident that abalone are metabolically able to produce sufficient amounts of energy when functional hypoxia is experienced. Also, tissue interplay enables the adjustment of H. midae energy requirements as their metabolism shifts from aerobic to anaerobic respiration during functional hypoxia. This article has an associated First Person interview with the first author of the paper.

  4. Redox signalling and mitochondrial stress responses; lessons from inborn errors of metabolism

    DEFF Research Database (Denmark)

    Olsen, Rikke K J; Cornelius, Nanna; Gregersen, Niels

    2015-01-01

    Mitochondria play a key role in overall cell physiology and health by integrating cellular metabolism with cellular defense and repair mechanisms in response to physiological or environmental changes or stresses. In fact, dysregulation of mitochondrial stress responses and its consequences...... in the form of oxidative stress, has been linked to a wide variety of diseases including inborn errors of metabolism. In this review we will summarize how the functional state of mitochondria -- and especially the concentration of reactive oxygen species (ROS), produced in connection with the respiratory...... chain -- regulates cellular stress responses by redox regulation of nuclear gene networks involved in repair systems to maintain cellular homeostasis and health. Based on our own and other's studies we re-introduce the ROS triangle model and discuss how inborn errors of mitochondrial metabolism...

  5. Irisin in response to exercise in humans with and without metabolic syndrome.

    Science.gov (United States)

    Huh, Joo Young; Siopi, Aikaterina; Mougios, Vassilis; Park, Kyung Hee; Mantzoros, Christos S

    2015-03-01

    Irisin is a recently identified exercise-induced myokine. However, the circulating levels of irisin in response to different types of exercise in subjects with metabolic syndrome are unknown. This study aimed to study the levels of irisin in healthy males and subjects with metabolic syndrome at baseline and in response to exercise. Each individual completed high-intensity interval exercise (HIIE), continuous moderate-intensity exercise (CME), and resistance exercise (RE) sessions in a random, crossover design. Percentage change in circulating irisin levels was examined. Two different irisin assays were used to compare the results of the RE study. Circulating irisin increased immediately after HIIE, CME, and RE and declined 1 hour later. The increase was greater in response to resistance compared with either high-intensity intermittent exercise or CME. Change in irisin in response to exercise did not differ between individuals with and without metabolic syndrome. Exercise is able to increase circulating irisin levels in individuals with the metabolic syndrome as well as healthy individuals. Whether this increase may contribute to the beneficial effects of exercise on patients with the metabolic syndrome remains to be studied further.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Tian, Lei; Li, Yuanjing; Tian, Chunjie

    2016-01-04

    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.

  9. Cytolytic T lymphocyte responses to metabolically inactivated stimulator cells. I. Metabolic inactivation impairs both CD and LD antigen signals

    International Nuclear Information System (INIS)

    Kelso, A.; Boyle, W.

    1982-01-01

    The effects of metabolic inactivation of spleen cells on antigen presentation to precursors of alloreactive cytolytic T lymphocytes (T/sub c/) were examined. By serological methods, populations inactivated by ultraviolet irradiation, glutaraldehyde fixation or plasma membrane isolation were found to retain normal levels of H-2K/D and Ia antigens. However, comparison of the antigen doses required to stimulate secondary T/sub c/ responses in mixed leukocyte culture showed that the inactivated preparations were approximately 10-fold less immunogenic than X-irradiated spleen cells. Their total inability to stimulate primary cytolytic responses pointed to at least a 100-fold impairment of immunogenicity for unprimed T/sub c/ precursors in the case of uv-irradiated and glutaraldehyde-treated stimulator cells, and at least a 10-fold impairment for membrane fragments. Experiments showing that the capacity of cell monolayers to absorb precursor T/sub c/ from unprimed spleen populations was reduced following uv-irradiation or glutaraldehyde treatment provided direct evidence that this loss of immunogenicity was due in part to suboptimal antigen presentation to precursor T/sub c/. It is concluded that, in addition to the traditional view that these treatments damage the ''LD'' signal to helper T lymphocytes, metabolic inactivation also impairs recognition of ''CD'' determinants by precursor T/sub c/

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Role of the Mixed-Lineage Protein Kinase Pathway in the Metabolic Stress Response to Obesity

    Directory of Open Access Journals (Sweden)

    Shashi Kant

    2013-08-01

    Full Text Available Saturated free fatty acid (FFA is implicated in the metabolic response to obesity. In vitro studies indicate that FFA signaling may be mediated by the mixed-lineage protein kinase (MLK pathway that activates cJun NH2-terminal kinase (JNK. Here, we examined the role of the MLK pathway in vivo using a mouse model of diet-induced obesity. The ubiquitously expressed MLK2 and MLK3 protein kinases have partially redundant functions. We therefore compared wild-type and compound mutant mice that lack expression of MLK2 and MLK3. MLK deficiency protected mice against high-fat-diet-induced insulin resistance and obesity. Reduced JNK activation and increased energy expenditure contribute to the metabolic effects of MLK deficiency. These data confirm that the MLK pathway plays a critical role in the metabolic response to obesity.

  12. SirT1 regulates energy metabolism and response to caloric restriction in mice.

    Directory of Open Access Journals (Sweden)

    Gino Boily

    Full Text Available The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well-established roles in lifespan determination and response to caloric restriction. We have studied mice carrying two null alleles for SirT1, the mammalian orthologue of sir2, and found that these animals inefficiently utilize ingested food. These mice are hypermetabolic, contain inefficient liver mitochondria, and have elevated rates of lipid oxidation. When challenged with a 40% reduction in caloric intake, normal mice maintained their metabolic rate and increased their physical activity while the metabolic rate of SirT1-null mice dropped and their activity did not increase. Moreover, CR did not extend lifespan of SirT1-null mice. Thus, SirT1 is an important regulator of energy metabolism and, like its orthologues from simpler eukaryotes, the SirT1 protein appears to be required for a normal response to caloric restriction.

  13. Radiographic and metabolic response rates following image-guided stereotactic radiotherapy for lung tumors

    International Nuclear Information System (INIS)

    Mohammed, Nasiruddin; Grills, Inga S.; Wong, Ching-Yee Oliver; Galerani, Ana Paula; Chao, Kenneth; Welsh, Robert; Chmielewski, Gary; Yan Di; Kestin, Larry L.

    2011-01-01

    Purpose: To evaluate radiographic and metabolic response after stereotactic body radiotherapy (SBRT) for early lung tumors. Materials and methods: Thirty-nine tumors were treated prospectively with SBRT (dose = 48-60 Gy, 4-5 Fx). Thirty-six cases were primary NSCLC (T1N0 = 67%; T2N0 = 25%); three cases were solitary metastases. Patients were followed using CT and PET at 6, 16, and 52 weeks post-SBRT, with CT follow-up thereafter. RECIST and EORTC criteria were used to evaluate CT and PET responses. Results: At median follow-up of 9 months (0.4-26), RECIST complete response (CR), partial response (PR), and stable disease (SD) rates were 3%, 43%, 54% at 6 weeks; 15%, 38%, 46% at 16 weeks; 27%, 64%, 9% at 52 weeks. Mean baseline tumor volume was reduced by 46%, 70%, 87%, and 96%, respectively at 6, 16, 52, and 72 weeks. Mean baseline maximum standardized uptake value (SUV) was 8.3 (1.1-20.3) and reduced to 3.4, 3.0, and 3.7 at 6, 16, and 52 weeks after SBRT. EORTC metabolic CR/PR, SD, and progressive disease rates were 67%, 22%, 11% at 6 weeks; 86%, 10%, 3% at 16 weeks; 95%, 5%, 0% at 52 weeks. Conclusions: SBRT yields excellent RECIST and EORTC based response. Metabolic response is rapid however radiographic response occurs even after 1-year post treatment.

  14. Adipose tissue and metabolic and inflammatory responses to stroke are altered in obese mice

    Directory of Open Access Journals (Sweden)

    Michael J. Haley

    2017-10-01

    Full Text Available Obesity is an independent risk factor for stroke, although several clinical studies have reported that obesity improves stroke outcome. Obesity is hypothesised to aid recovery by protecting against post-stroke catabolism. We therefore assessed whether obese mice had an altered metabolic and inflammatory response to stroke. Obese ob/ob mice underwent a 20-min middle cerebral artery occlusion and 24-h reperfusion. Lipid metabolism and expression of inflammatory cytokines were assessed in the plasma, liver and adipose tissue. The obese-specific metabolic response to stroke was assessed in plasma using non-targeted ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS metabolomics coupled with univariate and multivariate analysis. Obesity had no effect on the extent of weight loss 24 h after stroke but affected the metabolic and inflammatory responses to stroke, predominantly affecting lipid metabolism. Specifically, obese mice had increases in plasma free fatty acids and expression of adipose lipolytic enzymes. Metabolomics identified several classes of metabolites affected by stroke in obese mice, including fatty acids and membrane lipids (glycerophospholipids, lysophospholipids and sphingolipids. Obesity also featured increases in inflammatory cytokines in the plasma and adipose tissue. Overall, these results demonstrate that obesity affected the acute metabolic and inflammatory response to stroke and suggest a potential role for adipose tissue in this effect. These findings could have implications for longer-term recovery and also further highlight the importance of considering comorbidities in preclinical stroke research, especially when identifying biomarkers for stroke. However, further work is required to assess whether these changes translate into long-term effects on recovery.

  15. Metabolic Responses in Endothelial Cells Following Exposure to Ketone Bodies

    Directory of Open Access Journals (Sweden)

    Erika Meroni

    2018-02-01

    Full Text Available The ketogenic diet (KD is a high-fat, low-carbohydrate diet based on the induction of the synthesis of ketone bodies (KB. Despite its widespread use, the systemic impact of KD is not completely understood. The purpose of this study was to evaluate the effects of physiological levels of KB on HMEC-1 endothelial cells. To this aim, DNA oxidative damage and the activation of Nrf2, a known transcriptional factor involved in cell responses to oxidative stress, were assessed. The exposure of cells to KB exerted a moderate genotoxic effect, measured by a significant increase in DNA oxidative damage. However, cells pre-treated with KB for 48 h and subjected to a secondary oxidative insult (H2O2, significantly decreased DNA damage compared to control oxidized cells. This protection occurred by the activation of Nrf2 pathway. In KB-treated cells, we found increased levels of Nrf2 in nuclear extracts and higher gene expression of HO-1, a target gene of Nrf2, compared to control cells. These results suggest that KB, by inducing moderate oxidative stress, activate the transcription factor Nrf2, which induces the transcription of target genes involved in the cellular antioxidant defense system.

  16. RNA metabolism in Xylella fastidiosa during cold adaptation and survival responses

    Science.gov (United States)

    Fastidious plant pathogen Xylella fastidiosa has a reduced ability to adapt to cold temperatures, limiting persistence in perennial hosts, such as grapevine, growing in colder regions. RNA metabolism is an essential part of bacterial response to low temperature, including inducible expression of RNA...

  17. The effect of environmental temperature on immune response and metabolism of the young chicken

    NARCIS (Netherlands)

    Henken, A.M.

    1982-01-01

    The effect of environmental temperature on immune response and metabolism was studied in young chickens. Immunization was performed by injecting intramuscularly 0.5 ml packed SRBC (sheep red blood cells) in both thighs of 32 days old pullets ( WarrenSSL ). The

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

    Science.gov (United States)

    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 ...

  19. The structure of wheat bread influences the postprandial metabolic response in healthy men

    NARCIS (Netherlands)

    Eelderink, Coby; Noort, Martijn W. J.; Sozer, Nesli; Koehorst, Martijn; Holst, Jens J.; Deacon, Carolyn F.; Rehfeld, Jens F.; Poutanen, Kaisa; Vonk, Roel J.; Oudhuis, Lizette; Priebe, Marion G.

    2015-01-01

    Postprandial high glucose and insulin responses after starchy food consumption, associated with an increased risk of developing several metabolic diseases, could possibly be improved by altering food structure. We investigated the influence of a compact food structure; different wheat products with

  20. Effects of energy restriction on acute adrenoceptor and metabolic responses to exercise in obese subjects

    NARCIS (Netherlands)

    Kempen, K.P.G.; Saris, W.H.M.; Senden, J.M.G.; Menheere, P.P.C.A.; Blaak, E.E.; van Baak, M.A.

    1994-01-01

    Effects of energy restriction on acute adrenoceptor and metabolic responses to exercise in obese subjects. Kempen KP, Saris WH, Senden JM, Menheere PP, Blaak EE, van Baak MA. Department of Human Biology, University of Limburg, Maastricht, The Netherlands. This study was intended to investigate the

  1. Liquid scintillation vial for radiometric assay of lymphocyte carbohydrate metabolism in response to mitogens

    International Nuclear Information System (INIS)

    Tran, N.; Wagner, H.N. Jr.

    1978-01-01

    We have demonstrated that mitogens--i.e., PHA and Con.A--stimulate lymphocyte carbohydrate metabolism using a liquid-scintillation vial with conventional liquid-scintillation detectors. The results showed that this enclosed system can be useful for development of rapid in vitro tests of lymphocytes immune responsiveness, as well as for radiometric detection of bacterial growth in various gaseous atmospheres

  2. Origin of endotoxemia influences the metabolic response to endotoxin in dogs

    NARCIS (Netherlands)

    Moeniralam, H. S.; Bemelman, W. A.; Romijn, J. A.; Endert, E.; Ackermans, M. T.; van Lanschot, J. J.; Hermsen, R. C.; Sauerwein, H. P.

    1997-01-01

    Different routes of endotoxin administration have been used to mimic inflammatory and metabolic responses observed during sepsis. Because the origin of endotoxemia may affect the reactions to endotoxin, we compared the induction of tumor necrosis factor (TNF), interleukin-6 (IL-6), hormones, and

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    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. © 2016. Published by The Company of Biologists Ltd.

  5. The metabolic cost of mounting an immune response in male brown anoles (Anolis sagrei).

    Science.gov (United States)

    Cox, Christian L; Peaden, Robert T; Cox, Robert M

    2015-09-09

    The tradeoff between reproduction and survival is central to life-history theory and is thought to reflect underlying energetic tradeoffs between reproduction and self-maintenance. Immune responses to parasites and pathogens are important components of self-maintenance in many species, but whether these defenses impose significant energetic costs has only been tested in a handful of organisms. We tested for a metabolic cost of mounting an immune response in the male brown anole (Anolis sagrei), a lizard in which we have previously shown that reproduction causes a marked reduction in immune response to the novel antigen phytohaemagglutinin (PHA). We treated captive male anoles with a subcutaneous injection of either PHA, which induces an immune response that manifests as localized swelling, or saline vehicle as a control. Prior to injection and at 24, 48, and 72 hr post-injection, we measured swelling at the site of injection and whole-animal resting metabolic rate (RMR) using stop-flow respirometry. Although we detected a robust swelling response to PHA at 24, 48, and 72 hr post-injection, mean RMR did not differ between treatments at any of these time points. However, within the PHA treatment group, RMR increased with the extent of swelling, suggesting a variable metabolic cost that scales with the magnitude of the induced immune response. Although individual anoles varied considerably in the extent to which they responded to PHA challenge, our results suggest that an immune response can impose a substantial metabolic cost (potentially as much as 63% above baseline RMR) for individuals that do respond maximally. J. Exp. Zool. 9999A:XX-XX, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2015-01-01

    Abstract 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 ∼60%. However, supplementing gAd fully rescued insulin’s microvascular action and significantly improved the metabolic responses to insulin in HFD male rats and these actions were abolished by inhibition of either AMPK or nitric oxide production. We conclude that HFD induces vascular adiponectin and insulin resistance but gAd administration can restore vascular insulin responses and improve insulin’s metabolic action via an AMPK- and nitric oxide-dependent mechanism in male rats. Key points 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

  7. Metabolic communication between astrocytes and neurons via bicarbonate-responsive soluble adenylyl cyclase.

    Science.gov (United States)

    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

    2012-09-20

    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. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Muscular and metabolic responses to different Nordic walking techniques, when style matters.

    Science.gov (United States)

    Pellegrini, Barbara; Boccia, Gennaro; Zoppirolli, Chiara; Rosa, Raffaela; Stella, Federico; Bortolan, Lorenzo; Rainoldi, Alberto; Schena, Federico

    2018-01-01

    Due to poling action and upper body engagement, Nordic walking (NW) has additional health benefits with respect to conventional walking. The aim of this study was to evaluate the differences in muscle activation and metabolic responses between NW, performed with the technique suggested by NW instructors, and with some modifications in the way to move upper limb and poles. Ten NW instructors volunteered to walk on a treadmill at 5.5 km•h-1 in five conditions: walking (W), Nordic walking (NW), NW with a weak poling action (NWweak), with straight-upper limbs moving the shoulders (NWshoulder) and with elbow flexion-extension pattern and shoulder freezed (NWelbow). Poling forces, body segments and poles movement, upper and lower body muscle activation, as well as metabolic parameters were measured.All modified NW techniques elicited lower muscular activation and metabolic responses with respect to the suggested NW technique (P walking instructors, sport technicians and practitioners should be aware that any deviation from the technique usually suggested might lead to lower benefits. However it is worth to note that any walking technique with poles elicits higher metabolic responses and muscular activation than walking.

  9. Changes in energy metabolism in response to 48 h of overfeeding and fasting in Caucasians and Pima Indians

    DEFF Research Database (Denmark)

    Weyer, C; Vozarova, B; Ravussin, E

    2001-01-01

    Differences in the metabolic response to overfeeding and starvation may confer susceptibility or resistance to obesity in humans. To further examine this hypothesis, we assessed the changes in 24 h energy metabolism in response to short-term overfeeding and fasting in Caucasians (C) and Pima...... Indians (I), a population with a very high propensity for obesity....

  10. Investigating the Cellular and Metabolic Responses of World-Class Canoeists Training: A Sportomics Approach

    Directory of Open Access Journals (Sweden)

    Wagner Santos Coelho

    2016-11-01

    Full Text Available (1 Background: We have been using the Sportomics approach to evaluate biochemical and hematological changes in response to exercise. The aim of this study was to evaluate the metabolic and hematologic responses of world-class canoeists during a training session; (2 Methods: Blood samples were taken at different points and analyzed for their hematological properties, activities of selected enzymes, hormones, and metabolites; (3 Results: Muscle stress biomarkers were elevated in response to exercise which correlated with modifications in the profile of white blood cells, where a leukocyte rise was observed after the canoe session. These results were accompanied by an increase in other exercise intensity parameters such as lactatemia and ammonemia. Adrenocorticotropic hormone and cortisol increased during the exercise sessions. The acute rise in both erythrocytes and white blood profile were probably due to muscle cell damage, rather than hepatocyte integrity impairment; (4 Conclusion: The cellular and metabolic responses found here, together with effective nutrition support, are crucial to understanding the effects of exercise in order to assist in the creation of new training and recovery planning. Also we show that Sportomics is a primal tool for training management and performance improvement, as well as to the understanding of metabolic response to exercise.

  11. Metabolic response to optic centers to visual stimuli in the albino rat: anatomical and physiological considerations

    International Nuclear Information System (INIS)

    Toga, A.W.; Collins, R.C.

    1981-01-01

    The functional organization of the visual system was studied in the albino rat. Metabolic differences were measured using the 14 C-2-deoxyglucose (DG) autoradiographic technique during visual stimulation of one entire retina in unrestrained animals. All optic centers responded to changes in light intensity but to different degrees. The greatest change occurred in the superior colliculus, less in the lateral geniculate, and considerably less in second-order sites such as layer IV of visual cortex. These optic centers responded in particular to on/off stimuli, but showed no incremental change during pattern reversal or movement of orientation stimuli. Both the superior colliculus and lateral geniculate increased their metabolic rate as the frequency of stimulation increased, but the magnitude was twice as great in the colliculus. The histological pattern of metabolic change in the visual system was not homogenous. In the superior colliculus glucose utilization increased only in stratum griseum superficiale and was greatest in visuotopic regions representing the peripheral portions of the visual field. Similarly, in the lateral geniculate, only the dorsal nucleus showed an increased response to greater stimulus frequencies. Second-order regions of the visual system showed changes in metabolism in response to visual stimulation, but no incremental response specific for type or frequency of stimuli. To label proteins of axoplasmic transport to study the terminal fields of retinal projections 14 C-amino acids were used. This was done to study how the differences in the magnitude of the metabolic response among optic centers were related to the relative quantity of retinofugal projections to these centers

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

    Science.gov (United States)

    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.

  13. Response of melanoma tumor phospholipid metabolism to chloroethyle nitrosourea: a high resolution proton NMR spectroscopy study.

    Science.gov (United States)

    Morvan, Daniel; Demidem, Aïcha; Madelmont, Jean-Claude

    2003-07-01

    Phospholipid metabolism is tightly involved in tumor growth regulation and tumor cell survival. The response of phospholipid metabolism to chloroethyle nitrosourea treatment is investigated in a murine B16 melanoma model. Measurements of phospholipid derivatives are performed on intact tumor tissue samples using one- and two-dimensional proton NMR spectroscopy. During the tumor growth inhibition phase under treatment, tumors overexpress phosphocholine, phosphoethanolamine, glycerophosphocholine and glycerophosphoethanolamine, whereas phosphatidylcholine and phosphatidylethanolamine levels are maintained to control levels. During re-growth, which remained quantitatively much below control growth, chloroethyle nitrosourea-treated melanoma tumors overexpress phosphocholine and phosphoethanolamine only. In treated melanoma, phosphatidylcholine levels show an inverse relationship with tumor growth rates. In conclusion, chloroethyle nitrosourea-treated melanoma tumors maintain their phosphatidylcholine levels and exhibit transformed phospholipid metabolism phenotype, by mechanisms that could participate in tumor cell survival.

  14. The Role of Carbohydrate Response Element Binding Protein in Intestinal and Hepatic Fructose Metabolism

    Directory of Open Access Journals (Sweden)

    Katsumi Iizuka

    2017-02-01

    Full Text Available Many articles have discussed the relationship between fructose consumption and the incidence of obesity and related diseases. Fructose is absorbed in the intestine and metabolized in the liver to glucose, lactate, glycogen, and, to a lesser extent, lipids. Unabsorbed fructose causes bacterial fermentation, resulting in irritable bowl syndrome. Therefore, understanding the mechanisms underlying intestinal and hepatic fructose metabolism is important for the treatment of metabolic syndrome and fructose malabsorption. Carbohydrate response element binding protein (ChREBP is a glucose-activated transcription factor that controls approximately 50% of de novo lipogenesis in the liver. ChREBP target genes are involved in glycolysis (Glut2, liver pyruvate kinase, fructolysis (Glut5, ketohexokinase, and lipogenesis (acetyl CoA carboxylase, fatty acid synthase. ChREBP gene deletion protects against high sucrose diet-induced and leptin-deficient obesity, because Chrebp−/− mice cannot consume fructose or sucrose. Moreover, ChREBP contributes to some of the physiological effects of fructose on sweet taste preference and glucose production through regulation of ChREBP target genes, such as fibroblast growth factor-21 and glucose-6-phosphatase catalytic subunits. Thus, ChREBP might play roles in fructose metabolism. Restriction of excess fructose intake will be beneficial for preventing not only metabolic syndrome but also irritable bowl syndrome.

  15. Dynamic Responses of Phosphorus Metabolism to Acute and Chronic Dietary Phosphorus-Limitation in Daphnia

    Directory of Open Access Journals (Sweden)

    Nicole D. Wagner

    2017-06-01

    Full Text Available Food quality is highly dynamic within lake ecosystems and varies spatially and temporally over the growing season. Consumers may need to continuously adjust their metabolism in response to this variation in dietary nutrient content. However, the rates of metabolic responses to changes in food nutrient content has received little direct study. Here, we examine responses in two metabolic phosphorus (P pools, ribonucleic acids (RNA and adenosine triphosphate (ATP, along with body mass and body P content in Daphnia magna exposed to chronic and acute dietary P-limitation. First, we examined food quality effects on animals consuming different food carbon (C:P quality over a 14 day period. Then, we raised daphnids on one food quality for 4 days, switched them to contrasting dietary treatments, and measured changes in their metabolic responses at shorter time-scales (over 48 h. Animal P, RNA, and ATP content all changed through ontogeny with adults containing relatively less of these pools with increasing body mass. Irrespective of age, Daphnia consuming high C:P diets had lower body %P, %RNA, %ATP, and mass compared to animals eating low C:P diets. Diet switching experiments revealed diet dependent changes in body %P, %RNA, %ATP, and animal mass within 48 h. We found that Daphnia switched from low to high C:P diets had some metabolic buffering capacity with decreases in body %P occurring after 24 h but mass remaining similar to initial diet conditions for 36 h after the diet switch. Switching Daphnia from low to high C:P diets caused a decrease in the RNA:P ratio after 48 h. Daphnia switched from high to low C:P diets increased their body P, RNA, and ATP content within 8–24 h. This switch from high to low C:P diets also led to increased RNA:P ratios in animal bodies. Overall, our study revealed that consumer P metabolism reflects both current and past diet due to more dynamic and rapid changes in P biochemistry than total body mass. This metabolic

  16. Ruminant Nutrition Symposium: ruminant production and metabolic responses to heat stress.

    Science.gov (United States)

    Baumgard, L H; Rhoads, R P

    2012-06-01

    Heat stress compromises efficient animal production by marginalizing nutrition, management, and genetic selection efforts to maximize performance endpoints. Modifying farm infrastructure has yielded modest success in mitigating heat stress-related losses, yet poor production during the summer remains arguably the costliest issue facing livestock producers. Reduced output (e.g., milk yield and muscle growth) during heat stress was traditionally thought to result from decreased nutrient intake (i.e., a classic biological response shared by all animals during environmental-induced hyperthermia). Our recent observations have begun to challenge this belief and indicate heat-stressed animals employ novel homeorhetic strategies to direct metabolic and fuel selection priorities independently of nutrient intake or energy balance. Alterations in systemic physiology support a shift in carbohydrate metabolism, evident by increased basal and stimulated circulating insulin concentrations. Perhaps most intriguing given the energetic shortfall of the heat-stressed animal is the apparent lack of basal adipose tissue mobilization coupled with a reduced responsiveness to lipolytic stimuli. Thus, the heat stress response markedly alters postabsorptive carbohydrate, lipid, and protein metabolism independently of reduced feed intake through coordinated changes in fuel supply and utilization by multiple tissues. Interestingly, the systemic, cellular, and molecular changes appear conserved amongst different species and physiological states. Ultimately, these changes result in the reprioritization of fuel selection during heat stress, which appears to be primarily responsible for reduced ruminant animal productivity during the warm summer months.

  17. Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure.

    Science.gov (United States)

    Baud, Maxime O; Parafita, Julia; Nguyen, Audrey; Magistretti, Pierre J; Petit, Jean-Marie

    2016-10-01

    Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment. © 2016 European Sleep Research Society.

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

    Science.gov (United States)

    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.

  19. Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure

    KAUST Repository

    Baud, Maxime O.

    2016-05-03

    © 2016 European Sleep Research Society. Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment.

  20. Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction.

    Science.gov (United States)

    Volek, Jeff S; Feinman, Richard D

    2005-11-16

    surprising but has not been explicitly stated before. The known effects of CHO-induced hypertriglyceridemia, the HDL-lowering effect of low fat, high CHO interventions and the obvious improvement in glucose and insulin from CHO restriction should have made this evident. In addition, recent studies suggest that a subset of MetS, the ratio of TAG/HDL, is a good marker for insulin resistance and risk of CVD, and this indicator is reliably reduced by CHO restriction and exacerbated by high CHO intake. Inability to make this connection in the past has probably been due to the fact that individual responses have been studied in isolation as well as to the emphasis of traditional therapeutic approaches on low fat rather than low CHO. We emphasize that MetS is not a disease but a collection of markers. Individual physicians must decide whether high LDL, or other risk factors are more important than the features of MetS in any individual case but if MetS is to be considered it should be recognized that reducing CHO will bring improvement. Response of symptoms to CHO restriction might thus provide a new experimental criterion for MetS in the face of on-going controversy about a useful definition. As a guide to future research, the idea that control of insulin metabolism by CHO intake is, to a first approximation, the underlying mechanism in MetS is a testable hypothesis.

  1. Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction

    Directory of Open Access Journals (Sweden)

    Feinman Richard D

    2005-11-01

    conclusion is probably not surprising but has not been explicitly stated before. The known effects of CHO-induced hypertriglyceridemia, the HDL-lowering effect of low fat, high CHO interventions and the obvious improvement in glucose and insulin from CHO restriction should have made this evident. In addition, recent studies suggest that a subset of MetS, the ratio of TAG/HDL, is a good marker for insulin resistance and risk of CVD, and this indicator is reliably reduced by CHO restriction and exacerbated by high CHO intake. Inability to make this connection in the past has probably been due to the fact that individual responses have been studied in isolation as well as to the emphasis of traditional therapeutic approaches on low fat rather than low CHO. We emphasize that MetS is not a disease but a collection of markers. Individual physicians must decide whether high LDL, or other risk factors are more important than the features of MetS in any individual case but if MetS is to be considered it should be recognized that reducing CHO will bring improvement. Response of symptoms to CHO restriction might thus provide a new experimental criterion for MetS in the face of on-going controversy about a useful definition. As a guide to future research, the idea that control of insulin metabolism by CHO intake is, to a first approximation, the underlying mechanism in MetS is a testable hypothesis.

  2. The effect of temperature and body weight on the routine metabolic rate and postprandial metabolic response in mulloway, Argyrosomus japonicus.

    Science.gov (United States)

    Pirozzi, Igor; Booth, Mark A

    2009-09-01

    Specific dynamic action (SDA) is the energy expended on the physiological processes associated with meal digestion and is strongly influenced by the characteristics of the meal and the body weight (BW) and temperature of the organism. This study assessed the effects of temperature and body weight on the routine metabolic rate (RMR) and postprandial metabolic response in mulloway, Argyrosomus japonicus. RMR and SDA were established at 3 temperatures (14, 20 and 26 degrees C). 5 size classes of mulloway ranging from 60 g to 1.14 kg were used to establish RMR with 3 of the 5 size classes (60, 120 and 240 g) used to establish SDA. The effect of body size on the mass-specific RMR (mg O(2) kg(-1) h(-1)) varied significantly depending on the temperature; there was a greater relative increase in the mass-specific RMR for smaller mulloway with increasing temperature. No statistical differences were found between the mass exponent (b) values at each temperature when tested against H(0): b=0.8. The gross RMR of mulloway (mg O(2) fish(-1) h(-1)) can be described as function of temperature (T; 14-26 degrees C) as: (0.0195T-0.0454)BW(g)(0.8) and the mass-specific RMR (mg O(2) kg(-1) h(-1)) can be described as: (21.042T-74.867)BW(g)(-0.2). Both SDA duration and time to peak SDA were influenced by temperature and body weight; SDA duration occurred within 41-89 h and peak time occurred within 17-38 h of feeding. The effect of body size on peak metabolic rate varied significantly depending on temperature, generally increasing with temperature and decreasing with increasing body size. Peak gross oxygen consumption (MO(2): mg O(2) fish(-1) h(-1)) scaled allometrically with BW. Temperature, but not body size, significantly affected SDA scope, although the difference was numerically small. There was a trend for MO(2) above RMR over the SDA period to increase with temperature; however, this was not statistically significant. The average proportion of energy expended over the SDA period

  3. Metabolic responses to pyruvate kinase deletion in lysine producing Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Wittmann Christoph

    2008-03-01

    Full Text Available Abstract Background Pyruvate kinase is an important element in flux control of the intermediate metabolism. It catalyzes the irreversible conversion of phosphoenolpyruvate into pyruvate and is under allosteric control. In Corynebacterium glutamicum, this enzyme was regarded as promising target for improved production of lysine, one of the major amino acids in animal nutrition. In pyruvate kinase deficient strains the required equimolar ratio of the two lysine precursors oxaloacetate and pyruvate can be achieved through concerted action of the phosphotransferase system (PTS and phosphoenolpyruvate carboxylase (PEPC, whereby a reduced amount of carbon may be lost as CO2 due to reduced flux into the tricarboxylic acid (TCA cycle. In previous studies, deletion of pyruvate kinase in lysine-producing C. glutamicum, however, did not yield a clear picture and the exact metabolic consequences are not fully understood. Results In this work, deletion of the pyk gene, encoding pyruvate kinase, was carried out in the lysine-producing strain C. glutamicum lysCfbr, expressing a feedback resistant aspartokinase, to investigate the cellular response to deletion of this central glycolytic enzyme. Pyk deletion was achieved by allelic replacement, verified by PCR analysis and the lack of in vitro enzyme activity. The deletion mutant showed an overall growth behavior (specific growth rate, glucose uptake rate, biomass yield which was very similar to that of the parent strain, but differed in slightly reduced lysine formation, increased formation of the overflow metabolites dihydroxyacetone and glycerol and in metabolic fluxes around the pyruvate node. The latter involved a flux shift from pyruvate carboxylase (PC to PEPC, by which the cell maintained anaplerotic supply of the TCA cycle. This created a metabolic by-pass from PEP to pyruvate via malic enzyme demonstrating its contribution to metabolic flexibility of C. glutamicum on glucose. Conclusion The metabolic

  4. Metabolic responses to high protein diet in Korean elite bodybuilders with high-intensity resistance exercise

    Directory of Open Access Journals (Sweden)

    Choue Ryowon

    2011-07-01

    Full Text Available Abstract Background High protein diet has been known to cause metabolic acidosis, which is manifested by increased urinary excretion of nitrogen and calcium. Bodybuilders habitually consumed excessive dietary protein over the amounts recommended for them to promote muscle mass accretion. This study investigated the metabolic response to high protein consumption in the elite bodybuilders. Methods Eight elite Korean bodybuilders within the age from 18 to 25, mean age 21.5 ± 2.6. For data collection, anthropometry, blood and urinary analysis, and dietary assessment were conducted. Results They consumed large amounts of protein (4.3 ± 1.2 g/kg BW/day and calories (5,621.7 ± 1,354.7 kcal/day, as well as more than the recommended amounts of vitamins and minerals, including potassium and calcium. Serum creatinine (1.3 ± 0.1 mg/dl and potassium (5.9 ± 0.8 mmol/L, and urinary urea nitrogen (24.7 ± 9.5 mg/dl and creatinine (2.3 ± 0.7 mg/dl were observed to be higher than the normal reference ranges. Urinary calcium (0.3 ± 0.1 mg/dl, and phosphorus (1.3 ± 0.4 mg/dl were on the border of upper limit of the reference range and the urine pH was in normal range. Conclusions Increased urinary excretion of urea nitrogen and creatinine might be due to the high rates of protein metabolism that follow high protein intake and muscle turnover. The obvious evidence of metabolic acidosis in response to high protein diet in the subjects with high potassium intake and intensive resistance exercise were not shown in this study results. However, this study implied that resistance exercise with adequate mineral supplementation, such as potassium and calcium, could reduce or offset the negative effects of protein-generated metabolic changes. This study provides preliminary information of metabolic response to high protein intake in bodybuilders who engaged in high-intensity resistance exercise. Further studies will be needed to determine the effects of the intensity

  5. Deciphering the mechanisms involved in Portulaca oleracea (C4) response to drought: metabolic changes including crassulacean acid-like metabolism induction and reversal upon re-watering.

    Science.gov (United States)

    D'Andrea, Rodrigo Matías; Andreo, Carlos Santiago; Lara, María Valeria

    2014-11-01

    Portulaca oleracea is a C(4) plant; however, under drought it can change its carbon fixation metabolism into a crassulacean acid metabolism (CAM)-like one. While the C(3) -CAM shift is well known, the C(4) -CAM transition has only been described in Portulaca. Here, a CAM-like metabolism was induced in P. oleracea by drought and then reversed by re-watering. Physiological and biochemical approaches were undertaken to evaluate the drought and recovery responses. In CAM-like plants, chlorophyll fluorescence parameters were transitory affected and non-radiative energy dissipation mechanisms were induced. Induction of flavonoids, betalains and antioxidant machinery may be involved in photosynthetic machinery protection. Metabolic analysis highlights a clear metabolic shift, when a CAM-like metabolism is induced and then reversed. Increases in nitrogenous compounds like free amino acids and urea, and of pinitol could contribute to withstand drought. Reciprocal variations in arginase and urease in drought-stressed and in re-watered plants suggest urea synthesis is strictly regulated. Recovery of C(4) metabolism was accounted by CO(2) assimilation pattern and malate levels. Increases in glycerol and in polyamines would be of importance of re-watered plants. Collectively, in P. oleracea multiple strategies, from induction of several metabolites to the transitory development of a CAM-like metabolism, participate to enhance its adaptation to drought. © 2014 Scandinavian Plant Physiology Society.

  6. Effect of dietary restriction on immune response of laboratory mice divergently selected for basal metabolic rate.

    Science.gov (United States)

    Książek, Aneta; Konarzewski, Marek

    2012-01-01

    To study whether dietary restriction (DR; 70% of ad lib. feeding)-elicited immunosuppression results from the trade-off between the costs of mounting an immune response and the metabolic costs of maintenance, we subjected mice from two divergent lines selected for high basal metabolic rate (H-BMR) and low BMR (L-BMR) to 4 wk of DR and then challenged them with keyhole limpet hemocyanin (KLH) antigen. Those line types differ genetically with respect to BMR and to the mass of metabolically expensive internal organs, which are larger in H-BMR mice. In mice of both line types, DR resulted in a significant reduction of body mass, an immune response, and the downsizing of spleen, lymph nodes, thymus, heart, and kidneys but not small intestines. DR resulted in a greater reduction of the spleen and lymph nodes in mice of the H-BMR line type, whereas the thymus was more affected in L-BMR line type. In contrast, immunization resulted in an increase of liver mass in DR mice of both line types. A comparison of the results of current and earlier studies on the same mouse line types suggests that metabolic trade-offs involving the costs of an immune response are more apparent when animals are forced to increase energy demands (e.g., by cold exposure) compared to when energy demands are decreased through DR. Our findings also suggest that divelrgent selection on BMR resulted in between-line-type differences in T-cell- and B-cell-mediated types of an immune response. More generally, our results indicate that production of a wide repertoire of antibodies is not correlated with high BMR.

  7. Metabolic Response to NAD Depletion across Cell Lines Is Highly Variable.

    Science.gov (United States)

    Xiao, Yang; Kwong, Mandy; Daemen, Anneleen; Belvin, Marcia; Liang, Xiaorong; Hatzivassiliou, Georgia; O'Brien, Thomas

    2016-01-01

    Nicotinamide adenine dinucleotide (NAD) is a cofactor involved in a wide range of cellular metabolic processes and is a key metabolite required for tumor growth. NAMPT, nicotinamide phosphoribosyltransferase, which converts nicotinamide (NAM) to nicotinamide mononucleotide (NMN), the immediate precursor of NAD, is an attractive therapeutic target as inhibition of NAMPT reduces cellular NAD levels and inhibits tumor growth in vivo. However, there is limited understanding of the metabolic response to NAD depletion across cancer cell lines and whether all cell lines respond in a uniform manner. To explore this we selected two non-small cell lung carcinoma cell lines that are sensitive to the NAMPT inhibitor GNE-617 (A549, NCI-H1334), one that shows intermediate sensitivity (NCI-H441), and one that is insensitive (LC-KJ). Even though NAD was reduced in all cell lines there was surprising heterogeneity in their metabolic response. Both sensitive cell lines reduced glycolysis and levels of di- and tri-nucleotides and modestly increased oxidative phosphorylation, but they differed in their ability to combat oxidative stress. H1334 cells activated the stress kinase AMPK, whereas A549 cells were unable to activate AMPK as they contain a mutation in LKB1, which prevents activation of AMPK. However, A549 cells increased utilization of the Pentose Phosphate pathway (PPP) and had lower reactive oxygen species (ROS) levels than H1334 cells, indicating that A549 cells are better able to modulate an increase in oxidative stress. Inherent resistance of LC-KJ cells is associated with higher baseline levels of NADPH and a delayed reduction of NAD upon NAMPT inhibition. Our data reveals that cell lines show heterogeneous response to NAD depletion and that the underlying molecular and genetic framework in cells can influence the metabolic response to NAMPT inhibition.

  8. Metabolic Response to NAD Depletion across Cell Lines Is Highly Variable.

    Directory of Open Access Journals (Sweden)

    Yang Xiao

    Full Text Available Nicotinamide adenine dinucleotide (NAD is a cofactor involved in a wide range of cellular metabolic processes and is a key metabolite required for tumor growth. NAMPT, nicotinamide phosphoribosyltransferase, which converts nicotinamide (NAM to nicotinamide mononucleotide (NMN, the immediate precursor of NAD, is an attractive therapeutic target as inhibition of NAMPT reduces cellular NAD levels and inhibits tumor growth in vivo. However, there is limited understanding of the metabolic response to NAD depletion across cancer cell lines and whether all cell lines respond in a uniform manner. To explore this we selected two non-small cell lung carcinoma cell lines that are sensitive to the NAMPT inhibitor GNE-617 (A549, NCI-H1334, one that shows intermediate sensitivity (NCI-H441, and one that is insensitive (LC-KJ. Even though NAD was reduced in all cell lines there was surprising heterogeneity in their metabolic response. Both sensitive cell lines reduced glycolysis and levels of di- and tri-nucleotides and modestly increased oxidative phosphorylation, but they differed in their ability to combat oxidative stress. H1334 cells activated the stress kinase AMPK, whereas A549 cells were unable to activate AMPK as they contain a mutation in LKB1, which prevents activation of AMPK. However, A549 cells increased utilization of the Pentose Phosphate pathway (PPP and had lower reactive oxygen species (ROS levels than H1334 cells, indicating that A549 cells are better able to modulate an increase in oxidative stress. Inherent resistance of LC-KJ cells is associated with higher baseline levels of NADPH and a delayed reduction of NAD upon NAMPT inhibition. Our data reveals that cell lines show heterogeneous response to NAD depletion and that the underlying molecular and genetic framework in cells can influence the metabolic response to NAMPT inhibition.

  9. Metabolic cost of neuronal information in an empirical stimulus-response model

    Czech Academy of Sciences Publication Activity Database

    Košťál, Lubomír; Lánský, Petr; McDonnell, M.D.

    2013-01-01

    Roč. 107, č. 3 (2013), s. 355-365 ISSN 0340-1200 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GAP103/11/0282; GA ČR(CZ) GPP103/12/P558 Institutional support: RVO:67985823 Keywords : information capacity * metabolic cost * stimulus-response curve Subject RIV: FH - Neurology Impact factor: 1.933, year: 2013

  10. Exercise electrocardiographic responses and serum cystatin C levels among metabolic syndrome patients without overt diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Tanindi A

    2011-02-01

    Full Text Available Asli Tanindi1 Hilal Olgun1 Ayse Tuncel2 Bulent Celik3 Hatice Pasaoglu2 Bulent Boyaci11Department of Cardiology, 2Department of Medical Biochemistry, Faculty of Medicine, 3Department of Statistics, Faculty of Health Sciences, Gazi University, Ankara, TurkeyObjectives: An impaired heart rate response during exercise (chronotropic incompetence and an impaired heart rate recovery (HRR after exercise are predictors of cardiovascular risk and mortality. Cystatin C is a novel marker for cardiovascular disease. We aimed to investigate exercise electrocardiographic responses in patients with metabolic syndrome who were without overt diabetes mellitus, in addition to the association of serum cystatin C levels with the exercise electrocardiographic test results.Method: Forty-three consecutive patients admitted to a cardiology outpatient clinic without angina pectoris were recruited if they met criteria for metabolic syndrome but did not have overt diabetes mellitus. Serum cystatin C levels were measured, and all participants underwent exercise electrocardiographic testing. Patients who were found to have ischemia had a coronary angiography procedure.Results: The mean cystatin C level of patients was higher in metabolic syndrome group than healthy controls (610.1 ± 334.02 vs 337.3 ± 111.01 µg/L; P < 0.001. The percentage of patients with ischemia confirmed by coronary angiography was 13.9% in the metabolic syndrome group. Cystatin C levels in the ischemic patients of the metabolic syndrome group were higher than that in nonischemic patients (957.00 ± 375.6 vs 553.8 ± 295.3 µg /L; P = 0.005. Chronotropic incompetence was observed in 30.2% of the patients with metabolic syndrome compared with 16.7% in the control group (P = 0.186. Chronotropic response indices were 0.8 ± 0.18 versus 0.9 ± 0.10 for the two groups, respectively (P = 0.259. HRR was significantly lower in the metabolic syndrome patients compared with the controls (20.1 ± 8.01 vs 25.2

  11. Metabolomics Reveals Metabolically Healthy and Unhealthy Obese Individuals Differ in their Response to a Caloric Challenge.

    Directory of Open Access Journals (Sweden)

    Flavia Badoud

    Full Text Available To determine if metabolically healthy obese (MHO individuals have a different metabolic response to a standardized diet compared to lean healthy (LH and metabolically unhealthy obese (MUO individuals.Thirty adults (35-70 yrs were classified as LH, MHO, and MUO according to anthropometric and clinical measurements. Participants consumed a standardized high calorie meal (~1330 kcal. Blood glucose and insulin were measured at fasting, and 15, 30, 60, 90 and 120 min postprandially. Additional blood samples were collected for the targeted analysis of amino acids (AAs and derivatives, and fatty acids (FAs.The postprandial response (i.e., area under the curve, AUC for serum glucose and insulin were similar between MHO and LH individuals, and significantly lower than MUO individuals (p < 0.05. Minor differences were found in postprandial responses for AAs between MHO and MUO individuals, while three polyunsaturated FAs (linoleic acid, γ-linolenic acid, arachidonic acid showed smaller changes in serum after the meal in MHO individuals compared to MUO. Fasting levels for various AAs (notably branched-chain AA and FAs (e.g., saturated myristic and palmitic acids were found to correlate with glucose and insulin AUC.MHO individuals show preserved insulin sensitivity and a greater ability to adapt to a caloric challenge compared to MUO individuals.

  12. Cardiovascular and metabolic responses to fasting and thermoneutrality are conserved in obese Zucker rats.

    Science.gov (United States)

    Overton, J M; Williams, T D; Chambers, J B; Rashotte, M E

    2001-04-01

    The primary purpose of the study was to test the hypothesis that reduced leptin signaling is necessary to elicit the cardiovascular and metabolic responses to fasting. Lean (Fa/?; normal leptin receptor; n = 7) and obese (fa/fa; mutated leptin receptor; n = 8) Zucker rats were instrumented with telemetry transmitters and housed in metabolic chambers at 23 degrees C (12:12-h light-dark cycle) for continuous (24 h) measurement of metabolic and cardiovascular variables. Before fasting, mean arterial pressure (MAP) was higher (MAP: obese = 103 +/- 3; lean = 94 +/- 1 mmHg), whereas oxygen consumption (VO(2): obese = 16.5 +/- 0.3; lean = 18.6 +/- 0.2 ml. min(-1). kg(-0.75)) was lower in obese Zucker rats compared with their lean controls. Two days of fasting had no effect on MAP in either lean or obese Zucker rats, whereas VO(2) (obese = -3.1 +/- 0.3; lean = -2.9 +/- 0.1 ml. min(-1). kg(-0.75)) and heart rate (HR: obese = -56 +/- 4; lean = -42 +/- 4 beats/min) were decreased markedly in both groups. Fasting increased HR variability both in lean (+1.8 +/- 0.4 ms) and obese (+2.6 +/- 0.3 ms) Zucker rats. After a 6-day period of ad libitum refeeding, when all parameters had returned to near baseline levels, the cardiovascular and metabolic responses to 2 days of thermoneutrality (ambient temperature 29 degrees C) were determined. Thermoneutrality reduced VO(2) (obese = -2.4 +/- 0.2; lean = -3.3 +/- 0.2 ml. min(-1). kg(-0.75)), HR (obese = -46 +/- 5; lean = -55 +/- 4 beats/min), and MAP (obese = -13 +/- 6; lean = -10 +/- 1 mmHg) similarly in lean and obese Zucker rats. The results indicate that the cardiovascular and metabolic responses to fasting and thermoneutrality are conserved in Zucker rats and suggest that intact leptin signaling may not be requisite for the metabolic and cardiovascular responses to reduced energy intake.

  13. The structure of wheat bread influences the postprandial metabolic response in healthy men.

    Science.gov (United States)

    Eelderink, Coby; Noort, Martijn W J; Sozer, Nesli; Koehorst, Martijn; Holst, Jens J; Deacon, Carolyn F; Rehfeld, Jens F; Poutanen, Kaisa; Vonk, Roel J; Oudhuis, Lizette; Priebe, Marion G

    2015-10-01

    Postprandial high glucose and insulin responses after starchy food consumption, associated with an increased risk of developing several metabolic diseases, could possibly be improved by altering food structure. We investigated the influence of a compact food structure; different wheat products with a similar composition were created using different processing conditions. The postprandial glucose kinetics and metabolic response to bread with a compact structure (flat bread, FB) was compared to bread with a porous structure (control bread, CB) in a randomized, crossover study with ten healthy male volunteers. Pasta (PA), with a very compact structure, was used as the control. The rate of appearance of exogenous glucose (RaE), endogenous glucose production, and glucose clearance rate (GCR) was calculated using stable isotopes. Furthermore, postprandial plasma concentrations of glucose, insulin, several intestinal hormones and bile acids were analyzed. The structure of FB was considerably more compact compared to CB, as confirmed by microscopy, XRT analysis (porosity) and density measurements. Consumption of FB resulted in lower peak glucose, insulin and glucose-dependent insulinotropic polypeptide (ns) responses and a slower initial RaE compared to CB. These variables were similar to the PA response, except for RaE which remained slower over a longer period after PA consumption. Interestingly, the GCR after FB was higher than expected based on the insulin response, indicating increased insulin sensitivity or insulin-independent glucose disposal. These results demonstrate that the structure of wheat bread can influence the postprandial metabolic response, with a more compact structure being more beneficial for health. Bread-making technology should be further explored to create healthier products.

  14. L-carnitine: a partner between immune response and lipid metabolism ?

    Directory of Open Access Journals (Sweden)

    Giuseppe Famularo

    1993-01-01

    Full Text Available The authors demonstrated that in vivo administered L-carnitine strongly ameliorated the immune response in both healthy individuals receiving Intralipid and ageing subjects with cardiovascular diseases, as shown by the enhancement of mixed lymphocyte reaction. Notably, in the latter group L-carnitine treatment also resulted in a significant reduction of serum levels of both cholesterol and triglycerides. Therefore, the hypothesis is that L-carnitine supplementation could ameliorate both the dysregulated immune response and the abnormal lipid metabolism in several conditions.

  15. Humoral and cell-mediated immune responses to influenza vaccination in equine metabolic syndrome (EMS) horses.

    Science.gov (United States)

    Elzinga, Sarah; Reedy, Stephanie; Barker, Virginia D; Chambers, Thomas M; Adams, Amanda A

    2018-05-01

    Obesity is an increasing problem in the equine population with recent reports indicating that the percentage of overweight horses may range anywhere from 20.6-51%. Obesity in horses has been linked to more serious health concerns such as equine metabolic syndrome (EMS). EMS is a serious problem in the equine industry given its defining characteristics of insulin dysregualtion and obesity, as well as the involvement of laminitis. Little research however has been conducted to determine the effects of EMS on routine healthcare of these horses, in particular how they respond to vaccination. It has been shown that obese humans and mice have decreased immune responses to vaccination. EMS may have similar effects on vaccine responses in horses. If this is the case, these animals may be more susceptible to disease, acting as unknown disease reservoirs. Therefore, we investigated the effects of EMS on immune responses to routine influenza vaccination. Twenty-five adult horses of mixed-sex and mixed-breed (8-21 years old) horses; 13 EMS and 12 non-EMS were selected. Within each group, 4 horses served as non-vaccinate saline controls and the remaining horses were vaccinated with a commercially available equine influenza vaccine. Vaccination (influenza or saline) was administered on weeks 0 and 3, and peripheral blood samples taken on week 0 prior to vaccination and on weeks 1, 2, 3, 4, and 5 post vaccination. Blood samples were used to measure hemagglutination inhibition (HI) titers and equine influenza specific IgGa, IgGb, and IgGT levels. Blood samples were also used to isolate peripheral blood mononuclear cells (PBMCs) for analysis of cell mediated immune (CMI) responses via real-time polymerase chain reaction (RT-PCR). All horses receiving influenza vaccination responded with significant increases (P equine influenza specific antibodies following vaccination compared to saline controls. EMS did not significantly affect (P > 0.05) humoral immune responses as measured

  16. Type 2 responses at the interface between immunity and fat metabolism.

    Science.gov (United States)

    Odegaard, Justin I; Chawla, Ajay

    2015-10-01

    Adipose tissue resident leukocytes are often cast solely as the effectors of obesity and its attendant pathologies; however, recent observations have demonstrated that these cells support and effect 'healthy' physiologic function as well as pathologic dysfunction. Importantly, these two disparate outcomes are underpinned by similarly disparate immune programs; type 2 responses instruct and promote metabolic normalcy, while type 1 responses drive tissue dysfunction. In this Review, we summarize the literature regarding type 2 immunity's role in adipose tissue physiology and allude to its potential therapeutic implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Metabolic responses of primary and transformed cells to intracellular Listeria monocytogenes.

    Directory of Open Access Journals (Sweden)

    Nadine Gillmaier

    Full Text Available The metabolic response of host cells, in particular of primary mammalian cells, to bacterial infections is poorly understood. Here, we compare the carbon metabolism of primary mouse macrophages and of established J774A.1 cells upon Listeria monocytogenes infection using (13C-labelled glucose or glutamine as carbon tracers. The (13C-profiles of protein-derived amino acids from labelled host cells and intracellular L. monocytogenes identified active metabolic pathways in the different cell types. In the primary cells, infection with live L. monocytogenes increased glycolytic activity and enhanced flux of pyruvate into the TCA cycle via pyruvate dehydrogenase and pyruvate carboxylase, while in J774A.1 cells the already high glycolytic and glutaminolytic activities hardly changed upon infection. The carbon metabolism of intracellular L. monocytogenes was similar in both host cells. Taken together, the data suggest that efficient listerial replication in the cytosol of the host cells mainly depends on the glycolytic activity of the hosts.

  18. Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses.

    Science.gov (United States)

    Ou, Yang; Wang, Shang-Jui; Li, Dawei; Chu, Bo; Gu, Wei

    2016-11-01

    Although p53-mediated cell-cycle arrest, senescence, and apoptosis remain critical barriers to cancer development, the emerging role of p53 in cell metabolism, oxidative responses, and ferroptotic cell death has been a topic of great interest. Nevertheless, it is unclear how p53 orchestrates its activities in multiple metabolic pathways into tumor suppressive effects. Here, we identified the SAT1 (spermidine/spermine N 1 -acetyltransferase 1) gene as a transcription target of p53. SAT1 is a rate-limiting enzyme in polyamine catabolism critically involved in the conversion of spermidine and spermine back to putrescine. Surprisingly, we found that activation of SAT1 expression induces lipid peroxidation and sensitizes cells to undergo ferroptosis upon reactive oxygen species (ROS)-induced stress, which also leads to suppression of tumor growth in xenograft tumor models. Notably, SAT1 expression is down-regulated in human tumors, and CRISPR-cas9-mediated knockout of SAT1 expression partially abrogates p53-mediated ferroptosis. Moreover, SAT1 induction is correlated with the expression levels of arachidonate 15-lipoxygenase (ALOX15), and SAT1-induced ferroptosis is significantly abrogated in the presence of PD146176, a specific inhibitor of ALOX15. Thus, our findings uncover a metabolic target of p53 involved in ferroptotic cell death and provide insight into the regulation of polyamine metabolism and ferroptosis-mediated tumor suppression.

  19. Photoacoustic microscopy of cerebral hemodynamic and oxygen-metabolic responses to anesthetics

    Science.gov (United States)

    Cao, Rui; Li, Jun; Ning, Bo; Sun, Naidi; Wang, Tianxiong; Zuo, Zhiyi; Hu, Song

    2017-02-01

    General anesthetics are known to have profound effects on cerebral hemodynamics and neuronal activities. However, it remains a challenge to directly assess anesthetics-induced hemodynamic and oxygen-metabolic changes from the true baseline under wakefulness at the microscopic level, due to the lack of an enabling technology for high-resolution functional imaging of the awake mouse brain. To address this challenge, we have developed head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin (CHb and sO2), and blood flow in awake mice. From these hemodynamic measurements, two important metabolic parameters, oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2), can be derived. Side-by-side comparison of the mouse brain under wakefulness and anesthesia revealed multifaceted cerebral responses to isoflurane, a volatile anesthetic widely used in preclinical research and clinical practice. Key observations include elevated cerebral blood flow (CBF) and reduced oxygen extraction and metabolism.

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

    Science.gov (United States)

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

    2016-09-02

    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.

  1. Cardiovascular and Metabolic Responses to the Ingestion of Caffeinated Herbal Tea: Drink It Hot or Cold?

    Science.gov (United States)

    Maufrais, Claire; Sarafian, Delphine; Dulloo, Abdul; Montani, Jean-Pierre

    2018-01-01

    Aim: Tea is usually consumed at two temperatures (as hot tea or as iced tea). However, the importance of drink temperature on the cardiovascular system and on metabolism has not been thoroughly investigated. The purpose of this study was to compare the cardiovascular, metabolic and cutaneous responses to the ingestion of caffeinated herbal tea (Yerba Mate) at cold or hot temperature in healthy young subjects. We hypothesized that ingestion of cold tea induces a higher increase in energy expenditure than hot tea without eliciting any negative effects on the cardiovascular system. Methods: Cardiovascular, metabolic and cutaneous responses were analyzed in 23 healthy subjects (12 men and 11 women) sitting comfortably during a 30-min baseline and 90 min following the ingestion of 500 mL of an unsweetened Yerba Mate tea ingested over 5 min either at cold (~3°C) or hot (~55°C) temperature, according to a randomized cross-over design. Results: Averaged over the 90 min post-drink ingestion and compared to hot tea, cold tea induced (1) a decrease in heart rate (cold tea: -5 ± 1 beats.min -1 ; hot tea: -1 ± 1 beats.min -1 , p hot tea: +3.7%, p hot tea while decreasing cardiac load as suggested by the decrease in the double product. Further experiments are needed to evaluate the clinical impact of unsweetened caffeinated herbal tea at a cold temperature for weight control.

  2. Diurnal changes in CN metabolism and response of rice seedlings to UV-B radiation.

    Science.gov (United States)

    Yun, Hyejin; Lim, Sunhyung; Kim, Yangmin X; Lee, Yejin; Lee, Seulbi; Lee, Deogbae; Park, Keewoong; Sung, Jwakyung

    2018-03-13

    Plants regulate a number of primary metabolites, including carbohydrates, organic acids, and amino acids, in response to UV-B radiation. Therefore, it is essential to understand the time-dependent response of rice plants to UV-B stress. This study focused on the response of plants to UV-B at different leaf developmental phases (emerging, growing, and maturing) in an attempt to fully comprehend the metabolic shift. We analyzed the expression levels of genes related to starch/sucrose metabolism in the leaf blades of rice seedlings (Oryza sativa L. "Saechuchenog") exposed to UV-B irradiation for short (1 day) and long terms (5 days) using quantitative real-time polymerase chain reaction. We also examined the diurnal variations in the contents of primary metabolites using an established GCTOF-MS (gas chromatography time of flight-mass spectrometry) method. The results showed that the levels of primary metabolites were largely dependent upon the diurnal rhythm and leaf developmental phase. The young leaves (sink) produced and accumulated starch rather than sucrose. The short-term (4 h, 1 day) UV-B exposure inhibited sucrose synthesis, which could be the first target of UV-B radiation. Following short- and long-term (5 days) exposure to UV-B radiation, the dynamic response of primary metabolites was evaluated. It was found that the content of carbohydrates decreased throughout the period of exposure to UV-B stress, especially in terms of sucrose concentration. However, the content of the majority of amino acids increased after an early decrease. Our data revealed that the metabolic response, as well as the gene expression, differed with the period (intensity) of exposure to UV-B radiation and with the phase of leaf development. These findings provide new insights for a better understanding of the metabolic response of a variety of plant species exposed to a wide range of UV-B radiation. Copyright © 2018. Published by Elsevier GmbH.

  3. Responses of the metabolism of the larvae of Pocillopora damicornis to ocean acidification and warming.

    Directory of Open Access Journals (Sweden)

    Emily B Rivest

    Full Text Available 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.

  4. Metabolic response of Geobacter sulfurreducens towards electron donor/acceptor variation

    Directory of Open Access Journals (Sweden)

    Lovley Derek R

    2010-11-01

    Full Text Available Abstract Background Geobacter sulfurreducens is capable of coupling the complete oxidation of organic compounds to iron reduction. The metabolic response of G. sulfurreducens towards variations in electron donors (acetate, hydrogen and acceptors (Fe(III, fumarate was investigated via 13C-based metabolic flux analysis. We examined the 13C-labeling patterns of proteinogenic amino acids obtained from G. sulfurreducens cultured with 13C-acetate. Results Using 13C-based metabolic flux analysis, we observed that donor and acceptor variations gave rise to differences in gluconeogenetic initiation, tricarboxylic acid cycle activity, and amino acid biosynthesis pathways. Culturing G. sulfurreducens cells with Fe(III as the electron acceptor and acetate as the electron donor resulted in pyruvate as the primary carbon source for gluconeogenesis. When fumarate was provided as the electron acceptor and acetate as the electron donor, the flux analysis suggested that fumarate served as both an electron acceptor and, in conjunction with acetate, a carbon source. Growth on fumarate and acetate resulted in the initiation of gluconeogenesis by phosphoenolpyruvate carboxykinase and a slightly elevated flux through the oxidative tricarboxylic acid cycle as compared to growth with Fe(III as the electron acceptor. In addition, the direction of net flux between acetyl-CoA and pyruvate was reversed during growth on fumarate relative to Fe(III, while growth in the presence of Fe(III and acetate which provided hydrogen as an electron donor, resulted in decreased flux through the tricarboxylic acid cycle. Conclusions We gained detailed insight into the metabolism of G. sulfurreducens cells under various electron donor/acceptor conditions using 13C-based metabolic flux analysis. Our results can be used for the development of G. sulfurreducens as a chassis for a variety of applications including bioremediation and renewable biofuel production.

  5. Metabolic Responses and Pacing Strategies during Successive Sprint Skiing Time Trials

    DEFF Research Database (Denmark)

    Andersson, Erik; Holmberg, Hans-Christer; Ørtenblad, Niels

    2016-01-01

    PURPOSE: To examine the metabolic responses and pacing strategies during the performance of successive sprint time trials (STTs) in cross-country skiing. METHODS: Ten well-trained male cross-country skiers performed four self-paced 1300-m STTs on a treadmill, each separated by 45 min of recovery...... to estimate the anaerobic energy supply. RESULTS: The individual trial-to-trial variability in STT performance time was 1.3%, where variations in O2 deficit and V˙O2 explained 69% (P 0.05) of the variation in performance. The first and last STTs were equally fast (228 ± 10 s), and ~ 1...... on the first than second course half. In addition, metabolic rates were substantially higher (~_30%) for uphill than for flat skiing, indicating that pacing was regulated to the terrain. CONCLUSIONS: The fastest STTs were characterized primarily by a greater anaerobic energy production, which also explained 69...

  6. Metabolic syndrome is associated with poor treatment response to antiviral therapy in chronic hepatitis C genotype 3 patients.

    Science.gov (United States)

    Aziz, Hafsa; Gill, Uzma; Raza, Abida; Gill, Muzaffar L

    2014-05-01

    Hepatitis C viral (HCV) infection is caused by an RNA virus. HCV infection is considered to induce systemic disease that causes steatosis, alters lipid metabolism, and results in metabolic syndrome. This study aimed to investigate the therapeutic outcome in HCV genotype 3 patients with metabolic syndrome. A total of 621 HCV-positive patients who visited the hospital for treatment were screened. Among these, 441 patients were enrolled for antiviral therapy. These enrolled patients were assessed for metabolic syndrome according to the International Diabetes Federation criteria. Group A included patients with metabolic syndrome and group B included patients without metabolic syndrome. All patients received peginterferon-α2a (180 μg/week) and ribavirin (10 mg/kg/day) for 6 months. The prevalence of metabolic syndrome in chronic HCV patients was 37.9%. We observed that metabolic syndrome was more common among female compared with male participants (43.9 vs. 28.8%, P=0.005). It was found that sustained virologic response (SVR) rates were significantly higher in the patients in group B (without metabolic syndrome) compared with the patients in group A who had metabolic syndrome (72.2 vs. 43.7%, Pmetabolic syndrome and a correlation of metabolic syndrome with nonresponse to antiviral therapy was observed. An interesting correlation among metabolic syndrome, age, and SVR was found: with age, SVR decreases, while metabolic syndrome increases. Metabolic syndrome has an influence on therapeutic outcomes in terms of SVR. Moreover, this information can identify patients who might have a low chance of attaining an SVR and a timely decision may protect the patients from the adverse effects of therapy.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2016-08-01

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

  9. The effect of metabolic alkalosis on the ventilatory response in healthy subjects.

    Science.gov (United States)

    Oppersma, E; Doorduin, J; van der Hoeven, J G; Veltink, P H; van Hees, H W H; Heunks, L M A

    2018-02-01

    Patients with acute respiratory failure may develop respiratory acidosis. Metabolic compensation by bicarbonate production or retention results in posthypercapnic alkalosis with an increased arterial bicarbonate concentration. The hypothesis of this study was that elevated plasma bicarbonate levels decrease respiratory drive and minute ventilation. In an intervention study in 10 healthy subjects the ventilatory response using a hypercapnic ventilatory response (HCVR) test was assessed, before and after administration of high dose sodium bicarbonate. Total dose of sodiumbicarbonate was 1000 ml 8.4% in 3 days. Plasma bicarbonate increased from 25.2 ± 2.2 to 29.2 ± 1.9 mmol/L. With increasing inspiratory CO 2 pressure during the HCVR test, RR, V t , Pdi, EAdi and V E increased. The clinical ratio ΔV E /ΔP et CO 2 remained unchanged, but Pdi, EAdi and V E were significantly lower after bicarbonate administration for similar levels of inspired CO 2 . This study demonstrates that in healthy subjects metabolic alkalosis decreases the neural respiratory drive and minute ventilation, as a response to inspiratory CO 2 . Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Global host metabolic response to Plasmodium vivax infection: a 1H NMR based urinary metabonomic study

    Directory of Open Access Journals (Sweden)

    Sengupta Arjun

    2011-12-01

    Full Text Available Abstract Background Plasmodium vivax is responsible for the majority of malarial infection in the Indian subcontinent. This species of the parasite is generally believed to cause a relatively benign form of the disease. However, recent reports from different parts of the world indicate that vivax malaria can also have severe manifestation. Host response to the parasite invasion is thought to be an important factor in determining the severity of manifestation. In this paper, attempt was made to determine the host metabolic response associated with P. vivax infection by means of NMR spectroscopy-based metabonomic techniques in an attempt to better understand the disease pathology. Methods NMR spectroscopy of urine samples from P. vivax-infected patients, healthy individuals and non-malarial fever patients were carried out followed by multivariate statistical analysis. Two data analysis techniques were employed, namely, Principal Component Analysis [PCA] and Orthogonal Projection to Latent Structure Discriminant Analysis [OPLS-DA]. Several NMR signals from the urinary metabolites were further selected for univariate comparison among the classes. Results The urine metabolic profiles of P. vivax-infected patients were distinct from those of healthy individuals as well as of non-malarial fever patients. A highly predictive model was constructed from urine profile of malarial and non-malarial fever patients. Several metabolites were found to be varying significantly across these cohorts. Urinary ornithine seems to have the potential to be used as biomarkers of vivax malaria. An increasing trend in pipecolic acid was also observed. The results suggest impairment in the functioning of liver as well as impairment in urea cycle. Conclusions The results open up a possibility of non-invasive analysis and diagnosis of P. vivax using urine metabolic profile. Distinct variations in certain metabolites were recorded, and amongst these, ornithine may have the

  11. Role of the mixed-lineage protein kinase pathway in the metabolic stress response to obesity

    OpenAIRE

    Kant, Shashi; Barrett, Tamera; Vertii, Anastassiia; Noh, Yun Hee; Jung, Dae Young; Kim, Jason K.; Davis, Roger J.

    2013-01-01

    Saturated free fatty acid (FFA) is implicated in the metabolic response to obesity. In vitro studies indicate that FFA signaling may be mediated by the mixed-lineage protein kinase (MLK) pathway that activates cJun NH2-terminal kinase (JNK). Here, we examined the role of the MLK pathway in vivo using a mouse model of diet-induced obesity. The ubiquitously expressed MLK2 and MLK3 protein kinases have partially redundant functions. We therefore compared wild-type and compound mutant mice that l...

  12. Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism

    Science.gov (United States)

    Yates, D. T.; Macko, A. R.; Nearing, M.; Chen, X.; Rhoads, R. P.; Limesand, S. W.

    2012-01-01

    Fetal adaptations to placental insufficiency alter postnatal metabolic homeostasis in skeletal muscle by reducing glucose oxidation rates, impairing insulin action, and lowering the proportion of oxidative fibers. In animal models of intrauterine growth restriction (IUGR), skeletal muscle fibers have less myonuclei at birth. This means that myoblasts, the sole source for myonuclei accumulation in fibers, are compromised. Fetal hypoglycemia and hypoxemia are complications that result from placental insufficiency. Hypoxemia elevates circulating catecholamines, and chronic hypercatecholaminemia has been shown to reduce fetal muscle development and growth. We have found evidence for adaptations in adrenergic receptor expression profiles in myoblasts and skeletal muscle of IUGR sheep fetuses with placental insufficiency. The relationship of β-adrenergic receptors shifts in IUGR fetuses because Adrβ2 expression levels decline and Adrβ1 expression levels are unaffected in myofibers and increased in myoblasts. This adaptive response would suppress insulin signaling, myoblast incorporation, fiber hypertrophy, and glucose oxidation. Furthermore, this β-adrenergic receptor expression profile persists for at least the first month in IUGR lambs and lowers their fatty acid mobilization. Developmental programming of skeletal muscle adrenergic receptors partially explains metabolic and endocrine differences in IUGR offspring, and the impact on metabolism may result in differential nutrient utilization. PMID:22900186

  13. Energetic and metabolic transient response of Saccharomyces cerevisiae to benzoic acid.

    Science.gov (United States)

    Kresnowati, M T A P; van Winden, W A; van Gulik, W M; Heijnen, J J

    2008-11-01

    Saccharomyces cerevisiae is known to be able to adapt to the presence of the commonly used food preservative benzoic acid with a large energy expenditure. Some mechanisms for the adaptation process have been suggested, but its quantitative energetic and metabolic aspects have rarely been discussed. This study discusses use of the stimulus response approach to quantitatively study the energetic and metabolic aspects of the transient adaptation of S. cerevisiae to a shift in benzoic acid concentration, from 0 to 0.8 mM. The information obtained also serves as the basis for further utilization of benzoic acid as a tool for targeted perturbation of the energy system, which is important in studying the kinetics and regulation of central carbon metabolism in S. cerevisiae. Using this experimental set-up, we found significant fast-transient (< 3000 s) increases in O(2) consumption and CO(2) production rates, of approximately 50%, which reflect a high energy requirement for the adaptation process. We also found that with a longer exposure time to benzoic acid, S. cerevisiae decreases the cell membrane permeability for this weak acid by a factor of 10 and decreases the cell size to approximately 80% of the initial value. The intracellular metabolite profile in the new steady-state indicates increases in the glycolytic and tricarboxylic acid cycle fluxes, which are in agreement with the observed increases in specific glucose and O(2) uptake rates.

  14. Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism

    Directory of Open Access Journals (Sweden)

    D. T. Yates

    2012-01-01

    Full Text Available Fetal adaptations to placental insufficiency alter postnatal metabolic homeostasis in skeletal muscle by reducing glucose oxidation rates, impairing insulin action, and lowering the proportion of oxidative fibers. In animal models of intrauterine growth restriction (IUGR, skeletal muscle fibers have less myonuclei at birth. This means that myoblasts, the sole source for myonuclei accumulation in fibers, are compromised. Fetal hypoglycemia and hypoxemia are complications that result from placental insufficiency. Hypoxemia elevates circulating catecholamines, and chronic hypercatecholaminemia has been shown to reduce fetal muscle development and growth. We have found evidence for adaptations in adrenergic receptor expression profiles in myoblasts and skeletal muscle of IUGR sheep fetuses with placental insufficiency. The relationship of β-adrenergic receptors shifts in IUGR fetuses because Adrβ2 expression levels decline and Adrβ1 expression levels are unaffected in myofibers and increased in myoblasts. This adaptive response would suppress insulin signaling, myoblast incorporation, fiber hypertrophy, and glucose oxidation. Furthermore, this β-adrenergic receptor expression profile persists for at least the first month in IUGR lambs and lowers their fatty acid mobilization. Developmental programming of skeletal muscle adrenergic receptors partially explains metabolic and endocrine differences in IUGR offspring, and the impact on metabolism may result in differential nutrient utilization.

  15. Tributyltin toxicity in abalone (Haliotis diversicolor supertexta) assessed by antioxidant enzyme activity, metabolic response, and histopathology.

    Science.gov (United States)

    Zhou, Jin; Zhu, Xiao-shan; Cai, Zhong-hua

    2010-11-15

    A toxicity test was performed to investigate the possible harmful effects of tributyltin (TBT) on abalone (Haliotis diversicolor supertexta). Animals were exposed to TBT in a range of environmentally relevant concentrations (2, 10 and 50 ng/L) for 30 days under laboratory conditions. TBT-free conditions were used as control treatments. The activity of antioxidant enzymes superoxide dismutase (SOD) and peroxidase (POD), and malondialdehyde (MDA), along with levels of haemolymph metabolites, and hepatopancreas histopathology were analyzed. The results showed that TBT decreased SOD activity, and increased POD level and MDA production in a dose-dependent way, indicating that oxidative injury was induced by TBT. Haemolymph metabolite measurements showed that TBT increased alanine and glutamate levels, and decreased glucose content, which suggested perturbation of energy metabolism. Elevated levels of acetate and pyruvate in the haemolymph indicated partial alteration of lipid metabolism. A decrease in lactate and an increase in succinate, an intermediate of the tricarboxylic acid (TCA) cycle, indicated disturbance of amino acid metabolism. Hepatopancreas tissues also exhibited inflammatory responses characterized by histopathological changes such as cell swelling, granular degeneration, and inflammation. Taken together, these results demonstrated that TBT was a potential toxin with a variety of deleterious effects on abalone. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Responsive eLearning exercises to enhance student interaction with metabolic pathways.

    Science.gov (United States)

    Roesler, William J; Dreaver-Charles, Kristine

    2018-05-01

    Successful learning of biochemistry requires students to engage with the material. In the past this often involved students writing out pathways by hand, and more recently directing students to online resources such as videos, songs, and animated slide presentations. However, even these latter resources do not really provide students an opportunity to engage with the material in an active fashion. As part of an online introductory metabolism course that was developed at our university, we created a series of twelve online interactive activities using Adobe Captivate 9. These activities targeted glycolysis, gluconeogenesis, the pentose phosphate pathway, glycogen metabolism, the citric acid cycle, and fatty acid oxidation. The interactive exercises consisted of two types. One involved dragging objects such as names of enzymes or allosteric modifiers to their correct drop locations such as a particular point in a metabolic pathway, a specific enzyme, and so forth. A second type involved clicking on objects, locations within a pathway, and so forth, in response to a particular question. In both types of exercises, students received feedback on their decisions in order to enhance learning. The student feedback received on these activities was very positive, and indicated that they found them to increase their confidence in the material and that they had learned the key principles of each pathway. © 2018 by The International Union of Biochemistry and Molecular Biology, 46(3):223-229, 2018. © 2018 The International Union of Biochemistry and Molecular Biology.

  17. Metabolic Profiling of Dendrobium officinale in Response to Precursors and Methyl Jasmonate

    Directory of Open Access Journals (Sweden)

    Chunyan Jiao

    2018-03-01

    Full Text Available Alkaloids are the main active ingredients in the medicinal plant Dendrobium officinale. Based on the published genomic and transcriptomic data, a proposed terpenoid indole alkaloid (TIA biosynthesis pathway may be present in D. officinale. In this study, protocorm-like bodies (PLBs with a high-yielding production of alkaloids were obtained by the optimization of tryptophan, secologanin and methyl jasmonate (MeJA treatment. The results showed that the total alkaloid content was 2.05 times greater than that of the control group when the PLBs were fed with 9 µM tryptophan, 6 µM secologanin and 100 µM MeJA after 36 days. HPLC analysis showed that strictosidine synthase (STR activity also increased in the treated plants. A total of 78 metabolites were identified using gas chromatography-mass spectrometry (GC-MS in combination with liquid chromatography-mass spectrometry (LC-MS methods; 29 differential metabolites were identified according to the multivariate statistical analysis. Among them, carapanaubine, a kind of TIA, exhibited dramatically increased levels. In addition, a possible underlying process of the metabolic flux from related metabolism to the TIA biosynthetic pathway was enhanced. These results provide a comprehensive view of the metabolic changes related to alkaloid biosynthesis, especially TIA biosynthesis, in response to tryptophan, secologanin and MeJA treatment.

  18. Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk.

    Directory of Open Access Journals (Sweden)

    Cathy Slack

    2010-03-01

    Full Text Available Drosophila Lnk is the single ancestral orthologue of a highly conserved family of structurally-related intracellular adaptor proteins, the SH2B proteins. As adaptors, they lack catalytic activity but contain several protein-protein interaction domains, thus playing a critical role in signal transduction from receptor tyrosine kinases to form protein networks. Physiological studies of SH2B function in mammals have produced conflicting data. However, a recent study in Drosophila has shown that Lnk is an important regulator of the insulin/insulin-like growth factor (IGF-1 signaling (IIS pathway during growth, functioning in parallel to the insulin receptor substrate, Chico. As this pathway also has an evolutionary conserved role in the determination of organism lifespan, we investigated whether Lnk is required for normal lifespan in Drosophila. Phenotypic analysis of mutants for Lnk revealed that loss of Lnk function results in increased lifespan and improved survival under conditions of oxidative stress and starvation. Starvation resistance was found to be associated with increased metabolic stores of carbohydrates and lipids indicative of impaired metabolism. Biochemical and genetic data suggest that Lnk functions in both the IIS and Ras/Mitogen activated protein Kinase (MapK signaling pathways. Microarray studies support this model, showing transcriptional feedback onto genes in both pathways as well as indicating global changes in both lipid and carbohydrate metabolism. Finally, our data also suggest that Lnk itself may be a direct target of the IIS responsive transcription factor, dFoxo, and that dFoxo may repress Lnk expression. We therefore describe novel functions for a member of the SH2B protein family and provide the first evidence for potential mechanisms of SH2B regulation. Our findings suggest that IIS signaling in Drosophila may require the activity of a second intracellular adaptor, thereby yielding fundamental new insights into the

  19. Hypothalamic miR-219 regulates individual metabolic differences in response to diet-induced weight cycling

    Directory of Open Access Journals (Sweden)

    Mariana Schroeder

    2018-03-01

    Full Text Available Consumption of a low calorie diet is the most common approach to lose weight. While generally effective at first, it is frequently followed by a relapse where the pre-diet weight is regained, and often exceeded. This pattern of repeated weight loss/regain is referred to as weight cycling and the resulting metabolic response varies greatly between individuals. Objective: We attempted to address the issue of individual differences in the response to weight cycling in male mice. Methods: We first exposed adult wild type mice to repeated cycles of high/low fat food. Next, using a lentiviral approach, we knocked-down or over-expressed miR-219 in the ventromedial hypothalamus (VMH of an additional mouse cohort and performed a full metabolic assessment. Results: Exposure of wild type males to weight cycling resulted in the division of the cohort into subsets of resistant versus metabolic-syndrome-prone (MS animals, which differed in their metabolic profile and hypothalamic miR-219 levels. Lentiviral knock-down of miR-219 in the VMH led to exacerbation of metabolic syndrome. In contrast, over-expression of miR-219 resulted in moderation of the metabolic syndrome phenotype. Conclusions: Our results suggest a role for miR-219 in the mediation of the metabolic phenotype resulting from repeated weight cycling. Keywords: Weight cycling, Metabolic syndrome, miRNAs, Ventromedial hypothalamus, High fat diet, Diabetes

  20. Mechanical and Metabolic Responses to Traditional and Cluster Set Configurations in the Bench Press Exercise.

    Science.gov (United States)

    García-Ramos, Amador; González-Hernández, Jorge M; Baños-Pelegrín, Ezequiel; Castaño-Zambudio, Adrián; Capelo-Ramírez, Fernando; Boullosa, Daniel; Haff, Guy G; Jiménez-Reyes, Pedro

    2017-10-20

    García-Ramos, A, González-Hernández, JM, Baños-Pelegrín, E, Castaño-Zambudio, A, Capelo-Ramírez, F, Boullosa, D, Haff, GG, and Jiménez-Reyes, P. Mechanical and metabolic responses to traditional and cluster set configurations in the bench press exercise. J Strength Cond Res XX(X): 000-000, 2017-This study aimed to compare mechanical and metabolic responses between traditional (TR) and cluster (CL) set configurations in the bench press exercise. In a counterbalanced randomized order, 10 men were tested with the following protocols (sets × repetitions [inter-repetition rest]): TR1: 3 × 10 (0-second), TR2: 6 × 5 (0-second), CL5: 3 × 10 (5-second), CL10: 3 × 10 (10-second), and CL15: 3 × 10 (15-second). The number of repetitions (30), interset rest (5 minutes), and resistance applied (10 repetition maximum) were the same for all set configurations. Movement velocity and blood lactate concentration were used to assess the mechanical and metabolic responses, respectively. The comparison of the first and last set of the training session revealed a significant decrease in movement velocity for TR1 (Effect size [ES]: -0.92), CL10 (ES: -0.85), and CL15 (ES: -1.08) (but not for TR2 [ES: -0.38] and CL5 [ES: -0.37]); while blood lactate concentration was significantly increased for TR1 (ES: 1.11), TR2 (ES: 0.90), and CL5 (ES: 1.12) (but not for CL10 [ES: 0.03] and CL15 [ES: -0.43]). Based on velocity loss, set configurations were ranked as follows: TR1 (-39.3 ± 7.3%) > CL5 (-20.2 ± 14.7%) > CL10 (-12.9 ± 4.9%), TR2 (-10.3 ± 5.3%), and CL15 (-10.0 ± 2.3%). The set configurations were ranked as follows based on the lactate concentration: TR1 (7.9 ± 1.1 mmol·L) > CL5 (5.8 ± 0.9 mmol·L) > TR2 (4.2 ± 0.7 mmol·L) > CL10 (3.5 ± 0.4 mmol·L) and CL15 (3.4 ± 0.7 mmol·L). These results support the use of TR2, CL10, and CL15 for the maintenance of high mechanical outputs, while CL10 and CL15 produce less metabolic stress than TR2.

  1. A single night light exposure acutely alters hormonal and metabolic responses in healthy participants

    Directory of Open Access Journals (Sweden)

    Mohammed S Albreiki

    2017-01-01

    Full Text Available Many animal studies have reported an association between melatonin suppression and the disturbance of metabolic responses; yet, few human studies have investigated bright light effects on metabolic and hormonal responses at night. This study investigated the impact of light on plasma hormones and metabolites prior to, and after, an evening meal in healthy participants. Seventeen healthy participants, 8 females (22.2 ± 2.59 years, mean ± s.d. and 9 males (22.8 ± 3.5 years were randomised to a two-way cross-over design protocol; dim light (DL (500 lux sessions, separated by at least seven days. Saliva and plasma samples were collected prior to and after a standard evening meal at specific intervals. Plasma non-esterified fatty acid (NEFA levels were significantly higher pre-meal in DL compared to BL (P < 0.01. Plasma glucose and insulin levels were significantly greater post-meal in the BL compared to DL session (P = 0.02, P = 0.001, respectively. Salivary melatonin levels were significantly higher in the DL compared to those in BL session (P = 0.005. BL at night was associated with significant increases in plasma glucose and insulin suggestive of glucose intolerance and insulin insensitivity. Raised pre-prandial NEFA levels may be due to changes in insulin sensitivity or the presence of melatonin and/or light at night. Plasma triglyceride (TAG levels were the same in both sessions. These results may explain some of the health issues reported in shift workers; however, further studies are needed to elucidate the cause of these metabolic changes.

  2. Metabolic responses of the Antarctic fishes Notothenia rossii and Notothenia coriiceps to sewage pollution.

    Science.gov (United States)

    Rodrigues, Edson; Feijó-Oliveira, Mariana; Suda, Cecília Nohome Kawagoe; Vani, Gannabathula Sree; Donatti, Lucélia; Rodrigues, Edson; Lavrado, Helena Passeri

    2015-10-01

    The present study aimed to assess the sewage effects of the Brazilian Antarctic Station Comandante Ferraz, Admiralty Bay, King George Island, on the hepatic metabolism (energetic, antioxidant, and arginase levels) and levels of plasma constituents of two Antarctic fish species Notothenia rossii and N. coriiceps. The bioassays were conducted under controlled temperature (0 °C) and salinity (35 psu), exposing the fish for 96 h, to sewage effluent diluted in seawater to 0.5 % (v/v). Liver homogenates were tested for the specific activities of the enzymes glucose-6-phosphatase (G6Pase), glycogen phosphorylase (GPase), hexokinase, citrate synthase, lactate dehydrogenase, malate dehydrogenase, glucose-6-phosphate dehydrogenase, superoxide dismutase, glutathione reductase, catalase, and arginase. Plasma levels of glucose, triacylglycerides, cholesterol, total protein, albumin, chloride, magnesium, calcium, and inorganic phosphate were also determined. In N. rossii, the decrease in citrate synthase and the increase in G6Pase and GPase suggested that the sewage effluent activated glycogenolysis and hepatic gluconeogenesis, whereas is N. coriiceps, only G6Pase levels were increased. In N. rossii, sewage effluent induced hypertriglyceridemia without modulating glucose plasma levels, in contrast to N. coriiceps, which developed hypoglycemia without elevating plasma triglyceride levels. The decrease in glutathione reductase levels in N. coriiceps and in superoxide dismutase and catalase in N. rossii suggest that these two species are susceptible to oxidative stress stemming from the production of reactive oxygen species. An increase in magnesium in N. rossii and a decrease in N. coriiceps showed that sewage effluent compromised the control of plasma levels of this cation. Although phylogenetically close, both species of Antarctic fish exhibited different metabolic responses to the sewage effluent, with N. coriiceps showing greater susceptibility to the toxic effects of the

  3. Transcriptional, proteomic, and metabolic responses to lithium in galactose-grown yeast cells

    DEFF Research Database (Denmark)

    Bro, Christoffer; Regenberg, Birgitte; Lagniel, G.

    2003-01-01

    Lithium is highly toxic to yeast when grown in galactose medium mainly because phosphoglucomutase, a key enzyme of galactose metabolism, is inhibited. We studied the global protein and gene expression profiles of Saccharomyces cerevisiae grown in galactose in different time intervals after addition...... of lithium. These results were related to physiological studies where both secreted and intracellular metabolites were determined. Microarray analysis showed that 664 open reading frames were down-regulated and 725 up-regulated in response to addition of lithium. Genes involved in transcription, translation......-regulated proteins were also identified as being changed on the mRNA level. Functional clusters obtained from proteome data were coincident with transcriptional clusters. Physiological studies showed that acetate, glycerol, and glycogen accumulate in response to lithium, as reflected in expression data, whereas...

  4. Proteomic Analysis of Metabolic Responses to Biofuels and Chemicals in Photosynthetic Cyanobacteria.

    Science.gov (United States)

    Sun, T; Chen, L; Zhang, W

    2017-01-01

    Recent progresses in various "omics" technologies have enabled quantitative measurements of biological molecules in a high-throughput manner. Among them, high-throughput proteomics is a rapidly advancing field that offers a new means to quantify metabolic changes at protein level, which has significantly facilitated our understanding of cellular process, such as protein synthesis, posttranslational modifications, and degradation in responding to environmental perturbations. Cyanobacteria are autotrophic prokaryotes that can perform oxygenic photosynthesis and have recently attracted significant attentions as one promising alternative to traditionally biomass-based "microbial cell factories" to produce green fuels and chemicals. However, early studies have shown that the low tolerance to toxic biofuels and chemicals represented one major hurdle for further improving productivity of the cyanobacterial production systems. To address the issue, metabolic responses and their regulation of cyanobacterial cells to toxic end-products need to be defined. In this chapter, we discuss recent progresses in interpreting cyanobacterial responses to biofuels and chemicals using high-throughput proteomics approach, aiming to provide insights and guidelines on how to enhance tolerance and productivity of biofuels or chemicals in the renewable cyanobacteria systems in the future. © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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 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.

  6. Correlations of Eisenia fetida metabolic responses to extractable phenanthrene concentrations through time

    Energy Technology Data Exchange (ETDEWEB)

    McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda; Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail, Toronto, Ontario, M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.c [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail, Toronto, Ontario, M1C 1A4 (Canada)

    2010-06-15

    Eisenia fetida earthworms were exposed to phenanthrene for thirty days to compare hydroxypropyl-beta-cyclodextrin (HPCD) extraction of soil and {sup 1}H NMR earthworm metabolomics as indicators of bioavailability. The phenanthrene 28-d LC{sub 50} value was 750 mg/kg (632-891, 95% confidence intervals) for the peat soil tested. The initial phenanthrene concentration was 319 mg/kg, which biodegraded to 16 mg/kg within 15 days, at which time HPCD extraction suggested that phenanthrene was no longer bioavailable. Multivariate statistical analysis of {sup 1}H NMR spectra for E. fetida tissue extracts indicated that phenanthrene exposed and control earthworms differed throughout the 30 day experiment despite the low phenanthrene concentrations present after 15 days. This metabolic response was better correlated to total phenanthrene concentrations (Q{sup 2} = 0.59) than HPCD-extractable phenanthrene concentrations (Q{sup 2} = 0.46) suggesting that {sup 1}H NMR metabolomics offers considerable promise as a novel, molecular-level method to directly monitor the bioavailability of contaminants to earthworms in the environment. - Metabolic responses of Eisenia fetida earthworms to phenanthrene exposure are better correlated to total phenanthrene concentrations than to cyclodextrin-extractable concentrations through time.

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

    Science.gov (United States)

    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.

  8. Noninvasive presymptomatic detection of Cercospora beticola infection and identification of early metabolic responses in sugar beet

    Directory of Open Access Journals (Sweden)

    Hans-Peter Mock

    2016-09-01

    Full Text Available Cercospora beticola is an economically significant fungal pathogen of sugar beet, and is the causative pathogen of Cercospora leaf spot. Selected host genotypes with contrasting degree of susceptibility to the disease have been exploited to characterize the patterns of metabolite responses to fungal infection, and to devise a pre-symptomatic, non-invasive method of detecting the presence of the pathogen. Sugar beet genotypes were analyzed for metabolite profiles and hyperspectral signatures. Correlation of data matrices from both approaches facilitated identification of candidates for metabolic markers. Hyperspectral imaging was highly predictive with a classification accuracy of 98.5-99.9 % in detecting C. beticola. Metabolite analysis revealed metabolites altered by the host as part of a successful defence response: these were L-DOPA, 12-hydroxyjasmonic acid 12-O-β-D-glucoside, pantothenic acid and 5-O-feruloylquinic acid. The accumulation of glucosylvitexin in the resistant cultivar suggests it acts as a constitutively-produced protectant. The study establishes a proof-of-concept for an unbiased, presymptomatic and non-invasive detection system for the presence of C. beticola. The test needs to be validated with a larger set of genotypes, to be scalable to the level of a crop improvement program, aiming to speed up the selection for resistant cultivars of sugar beet. Untargeted metabolic profiling is a valuable tool to identify metabolites which correlate with hyperspectral data.

  9. Correlations of Eisenia fetida metabolic responses to extractable phenanthrene concentrations through time

    International Nuclear Information System (INIS)

    McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda; Simpson, Andre J.; Simpson, Myrna J.

    2010-01-01

    Eisenia fetida earthworms were exposed to phenanthrene for thirty days to compare hydroxypropyl-β-cyclodextrin (HPCD) extraction of soil and 1 H NMR earthworm metabolomics as indicators of bioavailability. The phenanthrene 28-d LC 50 value was 750 mg/kg (632-891, 95% confidence intervals) for the peat soil tested. The initial phenanthrene concentration was 319 mg/kg, which biodegraded to 16 mg/kg within 15 days, at which time HPCD extraction suggested that phenanthrene was no longer bioavailable. Multivariate statistical analysis of 1 H NMR spectra for E. fetida tissue extracts indicated that phenanthrene exposed and control earthworms differed throughout the 30 day experiment despite the low phenanthrene concentrations present after 15 days. This metabolic response was better correlated to total phenanthrene concentrations (Q 2 = 0.59) than HPCD-extractable phenanthrene concentrations (Q 2 = 0.46) suggesting that 1 H NMR metabolomics offers considerable promise as a novel, molecular-level method to directly monitor the bioavailability of contaminants to earthworms in the environment. - Metabolic responses of Eisenia fetida earthworms to phenanthrene exposure are better correlated to total phenanthrene concentrations than to cyclodextrin-extractable concentrations through time.

  10. Maternal high-fat diet intensifies the metabolic response to stress in male rat offspring.

    Science.gov (United States)

    Karbaschi, Roxana; Zardooz, Homeira; Khodagholi, Fariba; Dargahi, Leila; Salimi, Mina; Rashidi, FatemehSadat

    2017-01-01

    The mother's consumption of high-fat food can affect glucose metabolism and the hypothalamic-pituitary-adrenal axis responsiveness in the offspring and potentially affect the metabolic responses to stress as well. This study examines the effect of maternal high-fat diet on the expression of pancreatic glucose transporter 2 and the secretion of insulin in response to stress in offspring. Female rats were randomly divided into normal and high-fat diet groups and were fed in accordance with their given diets from pre-pregnancy to the end of lactation. The offspring were divided into control (NC and HFC) and stress (NS and HFS) groups based on their mothers' diet and exposure to stress in adulthood. After the two-week stress induction period was over, an intraperitoneal glucose tolerance test (IPGTT) was performed and plasma glucose and insulin levels were assessed. The pancreas was then removed for measuring insulin secretion from the isolated islets as well as glucose transporter 2 mRNA expression and protein levels. According to the results obtained, plasma corticosterone concentrations increased significantly on days 1 and 14 of the stress induction period and were lower on the last day compared to on the first day. In both the NS and HFS groups, stress reduced plasma insulin concentration in the IPGTT without changing the plasma glucose concentration, suggesting an increased insulin sensitivity in the NS and HFS groups, although more markedly in the latter. Stress reduced insulin secretion (at high glucose concentrations) and increased glucose transporter 2 mRNA and protein expression, especially in the HFS group. Mothers' high-fat diet appears to intensify the stress response by changing the programming of the neuroendocrine system in the offspring.

  11. Gender comparison of psychophysical forces, cardiopulmonary, and muscle metabolic responses during a simulated cart pushing task.

    Science.gov (United States)

    Maikala, Rammohan V; Ciriello, Vincent M; Dempsey, Patrick G; O'Brien, Niall V

    2010-10-01

    The purpose was to compare psychophysiological responses between healthy male and female workers during dynamic pushing. Using a psychophysical approach, 27 participants chose an acceptable force that they could push over a 7.6m distance at a frequency of 1 push per min on a treadmill. On a separate day, cardiopulmonary (e.g., whole-body oxygen uptake, heart rate, ventilation volume) and muscle metabolic measurements (change in muscle blood volume [ΔtHb] and Tissue Oxygenation Index [TOI]) from the right and left gastrocnemius muscles were collected simultaneously while participants pushed the previously chosen acceptable force on the treadmill at a similar frequency and distance for 2h. Results showed no significant difference between men and women for integrated force exerted on the instrumented treadmill handle and cardiopulmonary responses. In contrast, women demonstrated 45.7% lower ΔtHb but 3.6% higher TOI in the gastrocnemius region as compared to men, suggesting a lower hemoglobin concentration in women and high venous oxygen saturation during pushing. When ΔtHb and TOI were corrected for both body mass and pushing force, the disparity in gender was retained, implying an increased muscle oxygen saturation per force development in women than men during pushing. In the left gastrocnemius region, ΔtHb was 60% lower and TOI was 5.7% higher in women than men, suggesting an uneven muscle loading during pushing. Overall, the gender similarity in cardiopulmonary responses versus disparity in muscle metabolic responses suggest the importance of evaluating human performance during physical work at both whole-body and localized muscle levels. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Proteomic Characterization of Armillaria mellea Reveals Oxidative Stress Response Mechanisms and Altered Secondary Metabolism Profiles

    Directory of Open Access Journals (Sweden)

    Cassandra Collins

    2017-09-01

    Full Text Available Armillaria mellea is a major plant pathogen. Yet, the strategies the organism uses to infect susceptible species, degrade lignocellulose and other plant material and protect itself against plant defences and its own glycodegradative arsenal are largely unknown. Here, we use a combination of gel and MS-based proteomics to profile A. mellea under conditions of oxidative stress and changes in growth matrix. 2-DE and LC-MS/MS were used to investigate the response of A. mellea to H2O2 and menadione/FeCl3 exposure, respectively. Several proteins were detected with altered abundance in response to H2O2, but not menadione/FeCl3 (i.e., valosin-containing protein, indicating distinct responses to these different forms of oxidative stress. One protein, cobalamin-independent methionine synthase, demonstrated a common response in both conditions, which may be a marker for a more general stress response mechanism. Further changes to the A. mellea proteome were investigated using MS-based proteomics, which identified changes to putative secondary metabolism (SM enzymes upon growth in agar compared to liquid cultures. Metabolomic analyses revealed distinct profiles, highlighting the effect of growth matrix on SM production. This establishes robust methods by which to utilize comparative proteomics to characterize this important phytopathogen.

  13. Magnetic resonance metabolic profiling of breast cancer tissue obtained with core needle biopsy for predicting pathologic response to neoadjuvant chemotherapy.

    Directory of Open Access Journals (Sweden)

    Ji Soo Choi

    Full Text Available The purpose of this study was to determine whether metabolic profiling of core needle biopsy (CNB samples using high-resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS could be used for predicting pathologic response to neoadjuvant chemotherapy (NAC in patients with locally advanced breast cancer. After institutional review board approval and informed consent were obtained, CNB tissue samples were collected from 37 malignant lesions in 37 patients before NAC treatment. The metabolic profiling of CNB samples were performed by HR-MAS MRS. Metabolic profiles were compared according to pathologic response to NAC using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA. Various metabolites including choline-containing compounds were identified and quantified by HR-MAS MRS in all 37 breast cancer tissue samples obtained by CNB. In univariate analysis, the metabolite concentrations and metabolic ratios of CNB samples obtained with HR-MAS MRS were not significantly different between different pathologic response groups. However, there was a trend of lower levels of phosphocholine/creatine ratio and choline-containing metabolite concentrations in the pathologic complete response group compared to the non-pathologic complete response group. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the pathologic response groups. This study showed OPLS-DA multivariate analysis using metabolic profiles of pretreatment CNB samples assessed by HR- MAS MRS may be used to predict pathologic response before NAC, although we did not identify the metabolite showing statistical significance in univariate analysis. Therefore, our preliminary results raise the necessity of further study on HR-MAS MR metabolic profiling of CNB samples for a large number of cancers.

  14. Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

    International Nuclear Information System (INIS)

    Defo, Michel A.; Bernatchez, Louis; Campbell, Peter G.C.; Couture, Patrice

    2014-01-01

    Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

  15. Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

    Energy Technology Data Exchange (ETDEWEB)

    Defo, Michel A. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Bernatchez, Louis [Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Québec, Québec G1V 0A6 (Canada); Campbell, Peter G.C. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Couture, Patrice, E-mail: patrice.couture@ete.inrs.ca [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada)

    2014-09-15

    Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Campos, D [University of Wisconsin Madison, Madison, WI (United States); Peeters, W [Radboud University Medical Center, Nijmegen, GA (United States); Nickel, K [University of Wisconsin, Madison, WI (United States); Eliceiri, K; Kimple, R; Van Der Kogel, A; Kissick, M [University of Wisconsin, Madison, Wisconsin (United States)

    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.

  18. Responses to high-fat challenges varying in fat type in subjects with different metabolic risk phenotypes: a randomized trial.

    Directory of Open Access Journals (Sweden)

    Susan J van Dijk

    Full Text Available The ability of subjects to respond to nutritional challenges can reflect the flexibility of their biological system. Nutritional challenge tests could be used as an indicator of health status but more knowledge on metabolic and immune responses of different subjects to nutritional challenges is needed. The aim of this study was to compare the responses to high-fat challenges varying in fat type in subjects with different metabolic risk phenotypes.In a cross-over design 42 men (age 50-70 y consumed three high-fat shakes containing saturated fat (SFA, monounsaturated fat (MUFA or n-3 polyunsaturated (PUFA. Men were selected on BMI and health status (lean, obese or obese diabetic and phenotyped with MRI for adipose tissue distribution. Before and 2 and 4 h after shake consumption blood was drawn for measurement of expression of metabolic and inflammation-related genes in peripheral blood mononuclear cells (PBMCs, plasma triglycerides (TAG, glucose, insulin, cytokines and ex vivo PBMC immune response capacity. The MUFA and n-3 PUFA challenge, compared to the SFA challenge, induced higher changes in expression of inflammation genes MCP1 and IL1β in PBMCs. Obese and obese diabetic subjects had different PBMC gene expression and metabolic responses to high-fat challenges compared to lean subjects. The MUFA challenge induced the most pronounced TAG response, mainly in obese and obese diabetic subjects.The PBMC gene expression response and metabolic response to high-fat challenges were affected by fat type and metabolic risk phenotype. Based on our results we suggest using a MUFA challenge to reveal differences in response capacity of subjects.ClinicalTrials.gov NCT00977262.

  19. Proprietary tomato extract improves metabolic response to high-fat meal in healthy normal weight subjects

    Directory of Open Access Journals (Sweden)

    Xavier Deplanque

    2016-10-01

    Full Text Available Background: Low-density lipoprotein (LDL oxidation is a risk factor for atherosclerosis. Lycopene and tomato-based products have been described as potent inhibitors of LDL oxidation. Objectives: To evaluate the effect of a 2-week supplementation with a carotenoid-rich tomato extract (CRTE standardized for a 1:1 ratio of lycopene and phytosterols, on post-prandial LDL oxidation after a high-fat meal. Design: In a randomized, double-blind, parallel-groups, placebo-controlled study, 146 healthy normal weight individuals were randomly assigned to a daily dose of CRTE standardized for tomato phytonutrients or placebo during 2 weeks. Oxidized LDL (OxLDL, glucose, insulin, and triglyceride (TG responses were measured for 8 h after ingestion of a high-fat meal before and at the end of intervention. Results: Plasma lycopene, phytofluene, and phytoene were increased throughout the study period in the CRTE group compared to placebo. CRTE ingestion significantly improved changes in OxLDL response to high-fat meal compared to placebo after 2 weeks (p<0.0001. Changes observed in glucose, insulin, and TG responses were not statistically significant after 2 weeks of supplementation, although together they may suggest a trend of favorable effect on metabolic outcomes after a high-fat meal. Conclusions: Two-week supplementation with CRTE increased carotenoids levels in plasma and improved oxidized LDL response to a high-fat meal in healthy normal weight individuals.

  20. Modification of nucleotide metabolism in relationship with differentiation and in response to irradiation in human tumour cells

    International Nuclear Information System (INIS)

    Wei, Shuang

    1998-01-01

    This research thesis reports the study of the metabolism of nucleotides in human tumour cells. The first part addresses the modifications of nucleotide (more specifically purine) metabolism in relationship with human melanoma cell proliferation and differentiation. The second part addresses the modifications of this metabolism in response to an irradiation in human colon tumour cells. For each part, the author proposes a bibliographic synthesis, and a presentation of studied cells and of methods used to grow cells, and respectively to proliferate and differentiate them or to irradiate them, and then discusses the obtained results [fr

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

    Directory of Open Access Journals (Sweden)

    Fenja Klevenhusen

    2015-10-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2015-10-13

    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.

  3. Energy metabolism and metabolomics response of Pacific white shrimp Litopenaeus vannamei to sulfide toxicity.

    Science.gov (United States)

    Li, Tongyu; Li, Erchao; Suo, Yantong; Xu, Zhixin; Jia, Yongyi; Qin, Jian G; Chen, Liqiao; Gu, Zhimin

    2017-02-01

    The toxicity and poisoning mechanisms of sulfide were studied in Litopenaeus vannamei from the perspective of energy metabolism and metabolomics. The lethal concentrations of sulfide in L. vannamei (LC50) at 24h, 48h, 72h, and 96h were determined. Sulfide at a concentration of 0, 1/10 (425.5μg/L), and 1/5 (851μg/L) of the LC 50 at 96h was used to test the metabolic responses of L. vannamei for 21days. The chronic exposure of shrimp to a higher sulfide concentration of 851μg/L decreased shrimp survival but did not affect weight gain or the hepatopancreas index. The glycogen content in the hepatopancreas and muscle and the activity of hepatopancreas cytochrome C oxidase of the shrimp exposed to all sulfide concentrations were significantly lower, and the serum glucose and lactic acid levels and lactic acid dehydrogenase activity were significantly lower than those in the control. Metabolomics assays showed that shrimp exposed to sulfide had lower amounts of serum pyruvic acid, succinic acid, glycine, alanine, and proline in the 425.5μg/L group and phosphate, succinic acid, beta-alanine, serine, and l-histidine in the 851μg/L group than in the control. Chronic sulfide exposure could disturb protein synthesis in shrimp but enhance gluconeogenesis and substrate absorption for ATP synthesis and tricarboxylic acid cycles to provide extra energy to cope with sulfide stress. Chronic sulfide exposure could adversely affect the health status of L. vannamei, as indicated by the high amounts of serum n-ethylmaleamic acid, pyroglutamic acid, aspartic acid and phenylalanine relative to the control. This study indicates that chronic exposure of shrimp to sulfide can decrease health and lower survival through functional changes in gluconeogenesis, protein synthesis and energy metabolism. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Assessment of chitosan-affected metabolic response by peroxisome proliferator-activated receptor bioluminescent imaging-guided transcriptomic analysis.

    Directory of Open Access Journals (Sweden)

    Chia-Hung Kao

    Full Text Available Chitosan has been widely used in food industry as a weight-loss aid and a cholesterol-lowering agent. Previous studies have shown that chitosan affects metabolic responses and contributes to anti-diabetic, hypocholesteremic, and blood glucose-lowering effects; however, the in vivo targeting sites and mechanisms of chitosan remain to be clarified. In this study, we constructed transgenic mice, which carried the luciferase genes driven by peroxisome proliferator-activated receptor (PPAR, a key regulator of fatty acid and glucose metabolism. Bioluminescent imaging of PPAR transgenic mice was applied to report the organs that chitosan acted on, and gene expression profiles of chitosan-targeted organs were further analyzed to elucidate the mechanisms of chitosan. Bioluminescent imaging showed that constitutive PPAR activities were detected in brain and gastrointestinal tract. Administration of chitosan significantly activated the PPAR activities in brain and stomach. Microarray analysis of brain and stomach showed that several pathways involved in lipid and glucose metabolism were regulated by chitosan. Moreover, the expression levels of metabolism-associated genes like apolipoprotein B (apoB and ghrelin genes were down-regulated by chitosan. In conclusion, these findings suggested the feasibility of PPAR bioluminescent imaging-guided transcriptomic analysis on the evaluation of chitosan-affected metabolic responses in vivo. Moreover, we newly identified that downregulated expression of apoB and ghrelin genes were novel mechanisms for chitosan-affected metabolic responses in vivo.

  5. Muscle Damage and Metabolic Responses to Repeated-Sprint Running With and Without Deceleration.

    Science.gov (United States)

    Minahan, Clare L; Poke, Daniel P; Morrison, Jaime; Bellinger, Phillip M

    2018-04-04

    Minahan, CL, Poke, DP, Morrison, J, and Bellinger, PM. Muscle damage and metabolic responses to repeated-sprint running with and without deceleration. J Strength Cond Res XX(X): 000-000, 2017-This study aimed to determine whether repeated-sprint running with deceleration aggravates markers of muscle damage or delays the recovery of performance compared with repeated-sprint running without deceleration. Fourteen male team-sport athletes performed 2 randomly ordered testing sessions on a nonmotorized treadmill with one session requiring participants to decelerate (TMd) within 4 seconds before stopping or immediately step to the side of the treadmill belt at the completion of each sprint (TMa). Peak and mean velocities, speed decrement, blood lactate concentrations, and oxygen uptake were monitored during the repeated-sprint running protocols. Countermovement vertical jump (CMJ) performance, perceived muscle soreness, sit-and-reach flexibility, plasma creatine kinase (CK), lactate dehydrogenase (LDH), and myoglobin (Mb) concentrations were quantified immediately before and after and 45 minutes, 24 and 48 hours after repeated-sprint running protocols. Although muscle damage was indicated by increases in CK, LDH, and Mb (p ≤ 0.05) in both groups, there was no significant effect of condition (TMa vs. TMd) on any of the measured performance or physiological variables (p > 0.05). The present study indicated that the removal of deceleration from repeated-sprint running on a nonmotorized treadmill has no effect on metabolism or performance during or after repeated-sprint running or markers of muscle damage.

  6. Transcriptomic Changes in Response to Putrescine Production in Metabolically Engineered Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Zhen Li

    2017-10-01

    Full Text Available Putrescine is widely used in industrial production of bioplastics, pharmaceuticals, agrochemicals, and surfactants. Although engineered Corynebacterium glutamicum has been successfully used to produce high levels of putrescine, the overall cellular physiological and metabolic changes caused by overproduction of putrescine remains unclear. To reveal the transcriptional changes that occur in response to putrescine production in an engineered C. glutamicum strain, a comparative transcriptomic analysis was carried out. Overproduction of putrescine resulted in transcriptional downregulation of genes involved in glycolysis; the TCA cycle, pyruvate degradation, biosynthesis of some amino acids, oxidative phosphorylation; vitamin biosynthesis (thiamine and vitamin 6, metabolism of purine, pyrimidine and sulfur, and ATP-, NAD-, and NADPH-consuming enzymes. The transcriptional levels of genes involved in ornithine biosynthesis and NADPH-forming related enzymes were significantly upregulated in the putrescine producing C. glutamicum strain PUT-ALE. Comparative transcriptomic analysis provided some genetic modification strategies to further improve putrescine production. Repressing ATP- and NADPH-consuming enzyme coding gene expression via CRISPRi enhanced putrescine production.

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Transcriptomic Changes in Response to Putrescine Production in Metabolically Engineered Corynebacterium glutamicum

    Science.gov (United States)

    Li, Zhen; Liu, Jian-Zhong

    2017-01-01

    Putrescine is widely used in industrial production of bioplastics, pharmaceuticals, agrochemicals, and surfactants. Although engineered Corynebacterium glutamicum has been successfully used to produce high levels of putrescine, the overall cellular physiological and metabolic changes caused by overproduction of putrescine remains unclear. To reveal the transcriptional changes that occur in response to putrescine production in an engineered C. glutamicum strain, a comparative transcriptomic analysis was carried out. Overproduction of putrescine resulted in transcriptional downregulation of genes involved in glycolysis; the TCA cycle, pyruvate degradation, biosynthesis of some amino acids, oxidative phosphorylation; vitamin biosynthesis (thiamine and vitamin 6), metabolism of purine, pyrimidine and sulfur, and ATP-, NAD-, and NADPH-consuming enzymes. The transcriptional levels of genes involved in ornithine biosynthesis and NADPH-forming related enzymes were significantly upregulated in the putrescine producing C. glutamicum strain PUT-ALE. Comparative transcriptomic analysis provided some genetic modification strategies to further improve putrescine production. Repressing ATP- and NADPH-consuming enzyme coding gene expression via CRISPRi enhanced putrescine production. PMID:29089930

  9. Metabolic and cardiorespiratory response in swimmers during head-out immersion: a prospective study.

    Science.gov (United States)

    Mesfar, Mohamed A; Zendah, Ines; Gharsalli, Houda; Ben Hassen, Chokri; Ghedira, Habib

    2012-11-01

    Sport represents a stress for the body. Many metabolic and cardiorespiratory changes are known during physical activity.However, litte is known in swimmers particularly during head-out immersion. To determine the metabolic and cardiorespiratory response in swimmers during head-out immersion. The energetic, cardiovascular function and ventilatory requirements of a 10 min steady state arm exercise performed by 13 healthy subjects in air and during immersion up to the hip in 26°C water were compared. The same ergometric work load was achieved with an average maximum oxygen uptake of 3.9 ± 2.63 l/min in air versus 3.55 ± 2.48 l/min in water (p=0.953). During exercise, the average values of minute ventilation, ventilation equivalent for oxygen, ventilation equivalent for CO2, peak expiratory flow, respiratory exchange ratio and heart rate were not different in water and in air. However, first ventilatory threshold was significantly higher in water than in air. The mean value of the first ventilatory threshold was 0.89 ± 0.23 l/min in air, and 1.08 ± 0.23 l/min in water immersion; (p=0.016). These results suggest that training swimmers favoring immersion (weight belts) may improve their aerobic capacity.

  10. Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer

    Directory of Open Access Journals (Sweden)

    John Wikswo

    2009-03-01

    Full Text Available Harnessing the potential of cells as complex biosensors promises the potential to create sensitive and selective detectors for discrimination of biodefense agents. Here we present toxin detection and suggest discrimination using cells in a multianalyte microphysiometer (MMP that is capable of simultaneously measuring flux changes in four extracellular analytes (acidification rate, glucose uptake, oxygen uptake, and lactate production in real-time. Differential short-term cellular responses were observed between botulinum neurotoxin A and ricin toxin with neuroblastoma cells, alamethicin and anthrax protective antigen with RAW macrophages, and cholera toxin, muscarine, 2,4-dinitro-phenol, and NaF with CHO cells. These results and the post exposure dynamics and metabolic recovery observed in each case suggest the usefulness of cell-based detectors to discriminate between specific analytes and classes of compounds in a complex matrix, and furthermore to make metabolic inferences on the cellular effects of the agents. This may be particularly valuable for classifying unknown toxins.

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

    Directory of Open Access Journals (Sweden)

    Michael James Considine

    2015-02-01

    Full Text Available Research on sulfite 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 and 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 SO¬2 fumigation may extend for several months.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  14. Metabolic response of Danaüs archippus and Saccharomyces cerevisiae to weak oscillatory magnetic fields

    Science.gov (United States)

    Russell, D. N.; Webb, S. J.

    1981-09-01

    Respiration of the insect larva, Danaüs archippus, and the yeast, Saccharomyces cerevisiae, in log phase has been monitored before and after an oscillatory magnetic insult of 0.005 Gauss rms amplitude and 40 50 min duration. Frequencies used were 10 16 Hz for the insect and 100 200 Hz for the yeast. Depression of as much as 30% in metabolic rate has been found to occur immediately after the field is both imposed and eliminated with a general recovery over the 30-min period thereafter both in and out of the imposed field, although complete recovery to original levels may take much longer. Evidence is given that the response may depend on the frequency pattern used. This data is used to formulate an hypothesis whereby changes in the geomagnetic field variability pattern may act as a biochronometric zeitgeber.

  15. Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.

    Science.gov (United States)

    Tamboli, Robyn A; Antoun, Joseph; Sidani, Reem M; Clements, Austin; Harmata, Emily E; Marks-Shulman, Pam; Gaylinn, Bruce D; Williams, Brandon; Clements, Ronald H; Albaugh, Vance L; Abumrad, Naji N

    2017-09-01

    Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg -1  min -1 ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp. Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion. These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB. © 2017 John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-10-01

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  19. Fagus sylvatica L. provenances maintain different leaf metabolic profiles and functional response

    Science.gov (United States)

    Aranda, Ismael; Sánchez-Gómez, David; de Miguel, Marina; Mancha, Jose Antonio; Guevara, María Angeles; Cadahía, Estrella; Fernández de Simón, María Brígida

    2017-07-01

    Most temperate forest tree species will suffer important environmental changes as result of the climate change. Adaptiveness to local conditions could change at different sites in the future. In this context, the study of intra-specific variability is important to clarify the singularity of different local populations. Phenotypic differentiation between three beech provenances covering a wide latitudinal range (Spain/ES, Germany/DE and Sweden/SE), was studied in a greenhouse experiment. Non-target leaf metabolite profiles and ecophysiological response was analyzed in well-watered and water stressed seedlings. There was a provenance-specific pattern in the relative concentrations of some leaf metabolites regardless watering treatment. The DE and SE from the center and north of the distribution area of the species showed a clear differentiation from the ES provenance in the relative concentration of some metabolites. Thus the ES provenance from the south maintained larger relative concentration of some organic and amino acids (e.g. fumaric and succinic acids or valine and isoleucine), and in some secondary metabolites (e.g. kaempferol, caffeic and ferulic acids). The ecophysiological response to mild water stress was similar among the three provenances as a consequence of the moderate water stress applied to seedlings, although leaf N isotope composition (δ15N) and leaf C:N ratio were higher and lower respectively in DE than in the other two provenances. This would suggest potential differences in the capacity to uptake and post-process nitrogen according to provenance. An important focus of the study was to address for the first time inter-provenance leaf metabolic diversity in beech from a non-targeted metabolic profiling approach that allowed differentiation of the three studied provenances.

  20. Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis

    Directory of Open Access Journals (Sweden)

    Fumiaki Obata

    2014-05-01

    Full Text Available Sterile inflammation triggered by endogenous factors is thought to contribute to the pathogenesis of acute and chronic inflammatory diseases. Here, we demonstrate that apoptosis-deficient mutants spontaneously develop a necrosis-driven systemic immune response in Drosophila and provide an in vivo model for studying the organismal response to sterile inflammation. Metabolomic analysis of hemolymph from apoptosis-deficient mutants revealed increased sarcosine and reduced S-adenosyl-methionine (SAM levels due to glycine N-methyltransferase (Gnmt upregulation. We showed that Gnmt was elevated in response to Toll activation induced by the local necrosis of wing epidermal cells. Necrosis-driven inflammatory conditions induced dFoxO hyperactivation, leading to an energy-wasting phenotype. Gnmt was cell-autonomously upregulated by dFoxO in the fat body as a possible rheostat for controlling energy loss, which functioned during fasting as well as inflammatory conditions. We propose that the dFoxO-Gnmt axis is essential for the maintenance of organismal SAM metabolism and energy homeostasis.

  1. Greater impairment of postprandial triacylglycerol than glucose response in metabolic syndrome subjects with fasting hyperglycaemia.

    Science.gov (United States)

    Jackson, Kim G; Walden, Charlotte M; Murray, Peter; Smith, Adrian M; Minihane, Anne M; Lovegrove, Julie A; Williams, Christine M

    2013-08-01

    Studies have started to question whether a specific component or combinations of metabolic syndrome (MetS) components may be more important in relation to cardiovascular disease risk. Our aim was to examine the impact of the presence of raised fasting glucose as a MetS component on postprandial lipaemia. Men classified with the MetS underwent a sequential test meal investigation, in which blood samples were taken at regular intervals after a test breakfast (t=0 min) and lunch (t=330 min). Lipids, glucose and insulin were measured in the fasting and postprandial samples. MetS subjects with 3 or 4 components were subdivided into those without (n=34) and with (n=23) fasting hyperglycaemia (≥5.6 mmol/l), irrespective of the combination of components. Fasting lipids and insulin were similar in the two groups, with glucose significantly higher in the men with glucose as a MetS component (Pcurve (AUC) and incremental AUC (P ≤0.016) for the postprandial triacylglycerol (TAG) response in men with fasting hyperglycaemia. Greater glucose AUC (Pglucose to be an important predictor of the postprandial TAG and glucose response. Our data analysis has revealed a greater impairment of postprandial TAG than glucose response in MetS subjects with raised fasting glucose. The worsening of postprandial lipaemic control may contribute to the greater CVD risk reported in individuals with MetS component combinations which include hyperglycaemia. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. The Metabolic Response to Stress and Infection in Critically Ill Children: The Opportunity of an Individualized Approach

    Directory of Open Access Journals (Sweden)

    Valentina De Cosmi

    2017-09-01

    Full Text Available The metabolic response to stress and infection is closely related to the corresponding requirements of energy and nutrients. On a general level, the response is driven by a complex endocrine network and related to the nature and severity of the insult. On an individual level, the effects of nutritional interventions are highly variable and a possible source of complications. This narrative review aims to discuss the metabolic changes in critically-ill children and the potential of developing personalized nutritional interventions. Through a literature search strategy, we have investigated the importance of blood glucose levels, the nutritional aspects of the different phases of acute stress response, and the reliability of the available tools to assess the energy expenditure. The dynamics of metabolism during stressful events reveals the difficult balance between risk of hypo- or hyperglycemia and under- or overfeeding. Within this context, individualized and accurate measurement of energy expenditure may help in defining the metabolic needs of patients. Given the variability of the metabolic response in critical conditions, randomized clinical studies in ill children are needed to evaluate the effect of individualized nutritional intervention on health outcomes.

  3. Maximal exercise electrocardiographic responses and coronary heart disease mortality among men with metabolic syndrome.

    Science.gov (United States)

    Lyerly, G William; Sui, Xuemei; Church, Timothy S; Lavie, Carl J; Hand, Gregory A; Blair, Steven N

    2010-03-01

    To examine the association between abnormal exercise electrocardiographic (E-ECG) test results and mortality (all-cause and that resulting from coronary heart disease [CHD] or cardiovascular disease [CVD]) in a large population of asymptomatic men with metabolic syndrome (MetS). A total of 9191 men (mean age, 46.9 years) met the criteria of having MetS. All completed a maximal E-ECG treadmill test (May 14, 1979, through April 9, 2001) and were without a previous CVD event or diabetes at baseline. Main outcomes were all-cause mortality, mortality due to CHD, and mortality due to CVD. Cox regression analysis was used to quantify the mortality risk according to E-ECG responses. During a follow-up of 14 years, 633 deaths (242 CVD and 150 CHD) were identified. Mortality rates and hazard ratios (HRs) across E-ECG responses were the following: for all-cause mortality: HR, 1.36; 95% confidence interval (CI), 1.09-1.70 for equivocal responses and HR, 1.41; 95% CI, 1.12-1.77 for abnormal responses (P(trend)<.001); for mortality due to CVD: HR, 1.29; 95% CI, 0.88-1.88 for equivocal responses and HR, 2.04; 95% CI, 1.46-2.84 for abnormal responses (P(trend)<.001); and for mortality due to CHD: HR, 1.62; 95% CI, 1.02-2.56 for equivocal responses and HR, 2.45; 95% CI, 1.62-3.69 for abnormal responses (P(trend)<.001). A positive gradient for CHD, CVD, and all-cause mortality rates across E-ECG categories within 3, 4, or 5 MetS components was observed (P<.001 for all). Among men with MetS, an abnormal E-ECG response was associated with higher risk of all-cause, CVD, and CHD mortality. These findings underscore the importance of E-ECG tests to identify men with MetS who are at risk of dying.

  4. Pharmacogenetic landscape of Metabolic Syndrome components drug response in Tunisia and comparison with worldwide populations.

    Science.gov (United States)

    Jmel, Haifa; Romdhane, Lilia; Ben Halima, Yosra; Hechmi, Meriem; Naouali, Chokri; Dallali, Hamza; Hamdi, Yosr; Shan, Jingxuan; Abid, Abdelmajid; Jamoussi, Henda; Trabelsi, Sameh; Chouchane, Lotfi; Luiselli, Donata; Abdelhak, Sonia; Kefi, Rym

    2018-01-01

    Genetic variation is an important determinant affecting either drug response or susceptibility to adverse drug reactions. Several studies have highlighted the importance of ethnicity in influencing drug response variability that should be considered during drug development. Our objective is to characterize the genetic variability of some pharmacogenes involved in the response to drugs used for the treatment of Metabolic Syndrome (MetS) in Tunisia and to compare our results to the worldwide populations. A set of 135 Tunisians was genotyped using the Affymetrix Chip 6.0 genotyping array. Variants located in 24 Very Important Pharmacogenes (VIP) involved in MetS drug response were extracted from the genotyping data. Analysis of variant distribution in Tunisian population compared to 20 worldwide populations publicly available was performed using R software packages. Common variants between Tunisians and the 20 investigated populations were extracted from genotyping data. Multidimensional screening showed that Tunisian population is clustered with North African and European populations. The greatest divergence was observed with the African and Asian population. In addition, we performed Inter-ethnic comparison based on the genotype frequencies of five VIP biomarkers. The genotype frequencies of the biomarkers rs3846662, rs1045642, rs7294 and rs12255372 located respectively in HMGCR, ABCB1, VKORC1 and TCF7L2 are similar between Tunisian, Tuscan (TSI) and European (CEU). The genotype frequency of the variant rs776746 located in CYP3A5 gene is similar between Tunisian and African populations and different from CEU and TSI. The present study shows that the genetic make up of the Tunisian population is relatively complex in regard to pharmacogenes and reflects previous historical events. It is important to consider this ethnic difference in drug prescription in order to optimize drug response to avoid serious adverse drug reactions. Taking into account similarities with

  5. Pharmacogenetic landscape of Metabolic Syndrome components drug response in Tunisia and comparison with worldwide populations

    Science.gov (United States)

    Jmel, Haifa; Romdhane, Lilia; Ben Halima, Yosra; Hechmi, Meriem; Naouali, Chokri; Dallali, Hamza; Hamdi, Yosr; Shan, Jingxuan; Abid, Abdelmajid; Jamoussi, Henda; Trabelsi, Sameh; Chouchane, Lotfi; Luiselli, Donata; Abdelhak, Sonia

    2018-01-01

    Genetic variation is an important determinant affecting either drug response or susceptibility to adverse drug reactions. Several studies have highlighted the importance of ethnicity in influencing drug response variability that should be considered during drug development. Our objective is to characterize the genetic variability of some pharmacogenes involved in the response to drugs used for the treatment of Metabolic Syndrome (MetS) in Tunisia and to compare our results to the worldwide populations. A set of 135 Tunisians was genotyped using the Affymetrix Chip 6.0 genotyping array. Variants located in 24 Very Important Pharmacogenes (VIP) involved in MetS drug response were extracted from the genotyping data. Analysis of variant distribution in Tunisian population compared to 20 worldwide populations publicly available was performed using R software packages. Common variants between Tunisians and the 20 investigated populations were extracted from genotyping data. Multidimensional screening showed that Tunisian population is clustered with North African and European populations. The greatest divergence was observed with the African and Asian population. In addition, we performed Inter-ethnic comparison based on the genotype frequencies of five VIP biomarkers. The genotype frequencies of the biomarkers rs3846662, rs1045642, rs7294 and rs12255372 located respectively in HMGCR, ABCB1, VKORC1 and TCF7L2 are similar between Tunisian, Tuscan (TSI) and European (CEU). The genotype frequency of the variant rs776746 located in CYP3A5 gene is similar between Tunisian and African populations and different from CEU and TSI. The present study shows that the genetic make up of the Tunisian population is relatively complex in regard to pharmacogenes and reflects previous historical events. It is important to consider this ethnic difference in drug prescription in order to optimize drug response to avoid serious adverse drug reactions. Taking into account similarities with

  6. Lipid metabolic dose response to dietary alpha-linolenic acid in monk parrot (Myiopsitta monachus).

    Science.gov (United States)

    Petzinger, Christina; Heatley, J J; Bailey, Christopher A; Bauer, John E

    2014-03-01

    Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert α-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Δ7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA.

  7. Stress hormone release is a key component of the metabolic response to lipopolysaccharide (LPS): studies in hypopituitary and healthy subjects

    DEFF Research Database (Denmark)

    Bach, Ermina; Møller, Andreas Buch; Jørgensen, Jens Otto Lunde

    2016-01-01

    OBJECTIVE: Lipopolysaccharide (LPS) generates acute and chronic inflammatory and metabolic responses during acute illness and in the pathogenesis of the metabolic syndrome, type 2 diabetes and cardiovascular disease, but it is unclear whether these responses depend on intact pituitary release...... but not in HP. LPS increased whole body palmitate fluxes (3-fold) and decreased palmitate specific activity 40-50 % in CTR, but not in HP. G(0)/G(1) Switch Gene 2 (G0S2 - an inhibitor of lipolysis) adipose tissue mRNA was decreased in CTR. LPS increased phenylalanine fluxes significantly more in CTR, whereas...

  8. Physiological and Metabolic Changes of Purslane (Portulaca oleracea L.) in Response to Drought, Heat, and Combined Stresses

    Science.gov (United States)

    Jin, Rui; Wang, Yanping; Liu, Ruijie; Gou, Junbo; Chan, Zhulong

    2016-01-01

    Purslane (Portulaca oleracea L.) is a fleshy herbaceous plant. So far, little information is available on the response of this plant to combined drought and heat stress. In this study, changes in physiological and metabolic levels were characterized after treatments with drought, heat and combined stresses. Both individual and combined stress treatments increased malondialdehyde (MDA), electrolyte leakage (EL), O2•− and activities of superoxide dismutase (SOD), peroxidase (POD), while declined chlorophyll content. No significant differences were found between control and treatments in leaf water content (LWC) and catalase (CAT) activity. Additionally, 37 metabolic compounds were detected in purslane. Through pathway analysis, 17 metabolites were directly involved in the glycolysis metabolic pathway. The present study indicated that combined drought and heat stress caused more serious damage in purslane than individual stress. To survive, purslane has a high capability to cope with environmental stress conditions through activation of physiological and metabolic pathways. PMID:26779204

  9. Physiological and metabolic changes of purslane (Portulaca oleracea L. in response to drought, heat and combined stresses

    Directory of Open Access Journals (Sweden)

    Rui eJin

    2016-01-01

    Full Text Available Purslane (Portulaca oleracea L. is a fleshy herbaceous plant. So far, little information is available on the response of this plant to combined drought and heat stress. In this study, changes in physiological and metabolic levels were characterized after treatments with drought, heat and combined stresses. Both individual and combined stress treatments increased malondialdehyde (MDA, electrolyte leakage (EL, O2•− and activities of superoxide dismutase (SOD, peroxidase (POD, while declined chlorophyll content. No significant differences were found between control and treatments in leaf water content (LWC and catalase (CAT activity. Additionally, 37 metabolic compounds were detected in purslane. Through pathway analysis, 17 metabolites were directly involved in the glycolysis metabolic pathway. The present study indicated that combined drought and heat stress caused more serious damage in purslane than individual stress. To survive, purslane has a high capability to cope with environmental stress conditions through activation of physiological and metabolic pathways.

  10. Assessment of therapeutic response and treatment planning for brain tumors using metabolic and physiological MRI.

    Science.gov (United States)

    Nelson, Sarah J

    2011-07-01

    MRI is routinely used for diagnosis, treatment planning and assessment of response to therapy for patients with glioma. Gliomas are spatially heterogeneous and infiltrative lesions that are quite variable in terms of their response to therapy. Patients classified as having low-grade histology have a median overall survival of 7 years or more, but need to be monitored carefully to make sure that their tumor does not upgrade to a more malignant phenotype. Patients with the most aggressive grade IV histology have a median overall survival of 12-15 months and often undergo multiple surgeries and adjuvant therapies in an attempt to control their disease. Despite improvements in the spatial resolution and sensitivity of anatomic images, there remain considerable ambiguities in the interpretation of changes in the size of the gadolinium-enhancing lesion on T(1) -weighted images as a measure of treatment response, and in differentiating between treatment effects and infiltrating tumor within the larger T(2) lesion. The planning of focal therapies, such as surgery, radiation and targeted drug delivery, as well as a more reliable assessment of the response to therapy, would benefit considerably from the integration of metabolic and physiological imaging techniques into routine clinical MR examinations. Advanced methods that have been shown to provide valuable data for patients with glioma are diffusion, perfusion and spectroscopic imaging. Multiparametric examinations that include the acquisition of such data are able to assess tumor cellularity, hypoxia, disruption of normal tissue architecture, changes in vascular density and vessel permeability, in addition to the standard measures of changes in the volume of enhancing and nonenhancing anatomic lesions. This is particularly critical for the interpretation of the results of Phase I and Phase II clinical trials of novel therapies, which are increasingly including agents that are designed to have anti-angiogenic and anti

  11. Antarctic fish in a changing world: metabolic, osmoregulatory and endocrine stress response

    Directory of Open Access Journals (Sweden)

    Pedro Miguel Guerreiro

    2015-10-01

    Full Text Available Fish around Antarctic Peninsula are exposed to the fastest climate change rate in the planet, up to ten times higher than the global average. The evolution in extreme stenothermal isolation was a strong selective pressure for the development of a highly endemic fish fauna, with likely structural and functional constraints. To which extent can coastal notothenioid fish adjust to the conditions forecasted by the models of climate change? Experiments were run in the Arctowski (PL station at Admiralty Bay, King George Island, in 2012/13. Fish, Notothenia rossii and N. coriiceps, were collected by boat at 5-25 meter deep using fishing poles and were transferred to experimental tanks in cold rooms acclimated to natural temperatures (0-2°C. Fish were exposed to rapid/ gradual changes in water temperature or/and salinity (to 6-8°C using thermostat-controlled heaters, to 20-10‰ by addition of freshwater to recirculating tanks, over a period of up to 10 days to evaluate the response of several physiological processes. The stress endocrine axis was tested by injecting known blockers/ agonists of cortisol release and receptors. Exposure to altered conditions had no effect in immediate mortality. Increased temperature reduced overall activity and behavioral response to stimuli, although it had no clear effect on mobilization of energetic substrate. Both cortisol and gene expression of metabolic-related proteins and glucocorticoid- and mineralocorticoid receptors were modified after heat shock, but that the cortisol response to handling was reduced. The rise in temperature induced a dependent decrease in plasma osmolality while increasing branchial Na+/K+-ATPase activity, thus decreasing osmoregulatory efficiency. In conclusion, Antarctic fish are reactive to environmental change, but that their ability to accommodate rapid or adaptive responses may be compromised.

  12. Insulin response of the glucose and fatty acid metabolism in dry dairy cows across a range of body condition scores.

    Science.gov (United States)

    De Koster, J; Hostens, M; Van Eetvelde, M; Hermans, K; Moerman, S; Bogaert, H; Depreester, E; Van den Broeck, W; Opsomer, G

    2015-07-01

    The objective of the present research was to determine the insulin response of the glucose and fatty acid metabolism in dry dairy cows with a variable body condition score (BCS). Ten pregnant Holstein Friesian dairy cows (upcoming parity 2 to 5) were selected based on BCS at the beginning of the study (2mo before expected parturition date). During the study, animals were monitored weekly for BCS and backfat thickness and in the last 2wk, blood samples were taken for determination of serum nonesterified fatty acid (NEFA) concentration. Animals underwent a hyperinsulinemic euglycemic clamp test in the third week before the expected parturition date. The hyperinsulinemic euglycemic clamp test consisted of 4 consecutive insulin infusions with increasing insulin doses: 0.1, 0.5, 2, and 5mIU/kg per minute. For each insulin infusion period, a steady state was defined as a period of 30min where no or minor changes of the glucose infusion were necessary to keep the blood glucose concentration constant and near basal levels. During the steady state, the glucose infusion rate [steady state glucose infusion rate (SSGIR) in µmol/kg per minute] and NEFA concentration [steady state NEFA concentration (SSNEFA) in mmol/L] were determined and reflect the insulin response of the glucose and fatty acid metabolism. Dose response curves were created based on the insulin concentrations during the steady state and the SSGIR or SSNEFA. The shape of the dose response curves is determined by the concentration of insulin needed to elicit the half maximal effect (EC50) and the maximal SSGIR or the minimal SSNEFA for the glucose or fatty acid metabolism, respectively. The maximal SSGIR was negatively associated with variables reflecting adiposity of the cows (BCS, backfat thickness, NEFA concentration during the dry period, and absolute weight of the different adipose depots determined after euthanasia and dissection of the different depots), whereas the EC50 of the glucose metabolism was

  13. Road transport and diet affect metabolic response to exercise in horses.

    Science.gov (United States)

    Connysson, M; Muhonen, S; Jansson, A

    2017-11-01

    This study investigated the effects of transport and diet on metabolic response during a subsequent race-like test in Standardbred horses in training fed a forage-only diet and a 50:50 forage:oats diet. Six trained and raced Standardbred trotter mares were used. Two diets, 1 forage-only diet (FONLY) and 1 diet with 50% of DM intake from forage and 50% from oats (FOATS), were fed for two 29-d periods in a crossover design. At Day 21, the horses were subjected to transport for 100 km before and after they performed an exercise test (transport test [TT]). At Day 26, the horses performed a control test (CT), in which they were kept in their stall before and after the exercise test. Blood samples were collected throughout the study, and heart rate and water intake were recorded. Heart rate and plasma cortisol, glucose, and NEFA concentrations were greater for the TT than for the CT ( = 0.008, = 0.020, = 0.010, and = 0.0002, respectively) but were not affected by diet. Plasma acetate concentration was lower during the TT than during the CT ( = 0.034) and greater for the FONLY than for the FOATS ( = 0.003). There were no overall effects of the TT compared with the CT on total plasma protein concentration (TPP), but TPP was lower with the FONLY than with the FOATS ( = 0.016). There was no overall effect of the TT compared with the CT on water intake, but water intake was greater with the FONLY than the FOATS ( = 0.011). There were no overall effects of transport or diet on BW, plasma lactate, or plasma urea concentration. It was concluded that both transport and diet affect metabolic response during exercise in horses. Aerobic energy supply was most likely elevated by transportation and by the FONLY. The FONLY also decreased exercise-induced effects on extracellular fluid regulation. These results highlight the importance of experimental design in nutrition studies. If the aim is to examine how a diet affects exercise response in competition horses, transport should

  14. Modulation of the growth and metabolic response of cyanobacteria by the multifaceted activity of naringenin.

    Directory of Open Access Journals (Sweden)

    Beata Żyszka

    Full Text Available The interactions between the plant-derived bioflavonoid, naringenin, and prokaryotic microalgae representatives (cyanobacteria, were investigated with respect to its influence on the growth and metabolic response of these microorganisms. To achieve reliable results, the growth of cyanobacteria was determined based on measurements of chlorophyll content, morphological changes were assessed through microscopic observations, and the chemical response of cells was determined using liquid and gas chromatography (HPLC; GC-FID. The results show that micromolar levels of naringenin stimulated the growth of cyanobacteria. Increased growth was observed for halophilic strains at naringenin concentrations below 40 mg L-1, and in freshwater strains at concentrations below 20 mg L-1. The most remarkable stimulation was observed for the freshwater species Nostoc muscorum, which had a growth rate that was up to 60% higher than in the control. When naringenin was examined at concentrations above 40 mg L-1, the growth of the tested microorganisms was inhibited. Simultaneously, an intensive excretion of exopolysaccharides was observed. Microscopic observations strongly suggest that these effects resulted from a structural disturbance of cyanobacterial cell walls that was exerted by naringenin. This phenomenon, in combination with the absorption of naringenin into cell wall structures, influenced cell permeability and thus the growth of bacteria. Fortunately, almost all the naringenin added to the culture was incorporated into to cell substructures and could be recovered through extraction, raising the possibility that this modulator could be recycled.

  15. Consistency of metabolic responses and appetite sensations under postabsorptive and postprandial conditions.

    Science.gov (United States)

    Gonzalez, Javier T; Veasey, Rachel C; Rumbold, Penny L S; Stevenson, Emma J

    2012-10-01

    The present study aimed to investigate the reliability of metabolic and subjective appetite responses under fasted conditions and following consumption of a cereal-based breakfast. Twelve healthy, physically active males completed two postabsorption (PA) and two postprandial (PP) trials in a randomised order. In PP trials a cereal based breakfast providing 1859 kJ of energy was consumed. Expired gas samples were used to estimate energy expenditure and fat oxidation and 100mm visual analogue scales were used to determine appetite sensations at baseline and every 30 min for 120 min. Reliability was assessed using limits of agreement, coefficient of variation (CV), intraclass coefficient of correlation and 95% confidence limits of typical error. The limits of agreement and typical error were 292.0 and 105.5 kJ for total energy expenditure, 9.3 and 3.4 g for total fat oxidation and 22.9 and 8.3mm for time-averaged AUC for hunger sensations, respectively over the 120 min period in the PP trial. The reliability of energy expenditure and appetite in the 2h response to a cereal-based breakfast would suggest that an intervention requires a 211 kJ and 16.6mm difference in total postprandial energy expenditure and time-averaged hunger AUC to be meaningful, fat oxidation would require a 6.7 g difference which may not be sensitive to most meal manipulations. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

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    Anastasia V. Ponasenko

    2017-01-01

    Full Text Available Infective endocarditis (IE is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE.

  17. Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

    Science.gov (United States)

    Rutkovskaya, Natalia V.; Kondyukova, Natalia V.; Odarenko, Yuri N.; Kazachek, Yana V.; Tsepokina, Anna V.; Barbarash, Leonid S.

    2017-01-01

    Infective endocarditis (IE) is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE. PMID:28659664

  18. Metabolic response to Klebsiella pneumoniae infection in an experimental rat model.

    Directory of Open Access Journals (Sweden)

    Fangcong Dong

    Full Text Available Bacteremia, the presence of viable bacteria in the blood stream, is often associated with several clinical conditions. Bacteremia can lead to multiple organ failure if managed incorrectly, which makes providing suitable nutritional support vital for reducing bacteremia-associated mortality. In order to provide such information, we investigated the metabolic consequences of a Klebsiella pneumoniae (K. pneumoniae infection in vivo by employing a combination of (1H nuclear magnetic resonance spectroscopy and multivariate data analysis. K. pneumoniae was intravenously infused in rats; urine and plasma samples were collected at different time intervals. We found that K. pneumoniae-induced bacteremia stimulated glycolysis and the tricarboxylic acid cycle and also promoted oxidation of fatty acids and creatine phosphate to facilitate the energy-demanding host response. In addition, K. pneumoniae bacteremia also induced anti-endotoxin, anti-inflammatory and anti-oxidization responses in the host. Furthermore, bacteremia could cause a disturbance in the gut microbiotal functions as suggested by alterations in a range of amines and bacteria-host co-metabolites. Our results suggest that supplementation with glucose and a high-fat and choline-rich diet could ameliorate the burdens associated with bacteremia. Our research provides underlying pathological processes of bacteremia and a better understanding of the clinical and biochemical manifestations of bacteremia.

  19. Plasticity in habitat use determines metabolic response of fish to global warming in stratified lakes.

    Science.gov (United States)

    Busch, Susan; Kirillin, Georgiy; Mehner, Thomas

    2012-09-01

    We used a coupled lake physics and bioenergetics-based foraging model to evaluate how the plasticity in habitat use modifies the seasonal metabolic response of two sympatric cold-water fishes (vendace and Fontane cisco, Coregonus spp.) under a global warming scenario for the year 2100. In different simulations, the vertically migrating species performed either a plastic strategy (behavioral thermoregulation) by shifting their population depth at night to maintain the temperatures occupied at current in-situ observations, or a fixed strategy (no thermoregulation) by keeping their occupied depths at night but facing modified temperatures. The lake physics model predicted higher temperatures above 20 m and lower temperatures below 20 m in response to warming. Using temperature-zooplankton relationships, the density of zooplankton prey was predicted to increase at the surface, but to decrease in hypolimnetic waters. Simulating the fixed strategy, growth was enhanced only for the deeper-living cisco due to the shift in thermal regime at about 20 m. In contrast, simulating the plastic strategy, individual growth of cisco and young vendace was predicted to increase compared to growth currently observed in the lake. Only growth rates of older vendace are reduced under future global warming scenarios irrespective of the behavioral strategy. However, performing behavioral thermoregulation would drive both species into the same depth layers, and hence will erode vertical microhabitat segregation and intensify inter-specific competition between the coexisting coregonids.

  20. Metabolomics reveals differences in postprandial responses to breads and fasting metabolic characteristics associated with postprandial insulin demand in postmenopausal women.

    Science.gov (United States)

    Moazzami, Ali A; Shrestha, Aahana; Morrison, David A; Poutanen, Kaisa; Mykkänen, Hannu

    2014-06-01

    Changes in serum metabolic profile after the intake of different food products (e.g., bread) can provide insight into their interaction with human metabolism. Postprandial metabolic responses were compared after the intake of refined wheat (RWB), whole-meal rye (WRB), and refined rye (RRB) breads. In addition, associations between the metabolic profile in fasting serum and the postprandial concentration of insulin in response to different breads were investigated. Nineteen postmenopausal women with normal fasting glucose and normal glucose tolerance participated in a randomized, controlled, crossover meal study. The test breads, RWB (control), RRB, and WRB, providing 50 g of available carbohydrate, were each served as a single meal. The postprandial metabolic profile was measured using nuclear magnetic resonance and targeted LC-mass spectrometry and was compared between different breads using ANOVA and multivariate models. Eight amino acids had a significant treatment effect (P insulin. Women with higher fasting concentrations of leucine and isoleucine and lower fasting concentrations of sphingomyelins and phosphatidylcholines had higher insulin responses despite similar glucose concentration after all kinds of bread (cross-validated ANOVA, P = 0.048). High blood concentration of branched-chain amino acids, i.e., leucine and isoleucine, has been associated with the increased risk of diabetes, which suggests that additional consideration should be given to bread proteins in understanding the beneficial health effects of different kinds of breads. The present study suggests that the fasting metabolic profile can be used to characterize the postprandial insulin demand in individuals with normal glucose metabolism that can be used for establishing strategies for the stratification of individuals in personalized nutrition. © 2014 American Society for Nutrition.

  1. The metabolic and temporal basis of muscle hypertrophy in response to resistance exercise.

    Science.gov (United States)

    Brook, Matthew S; Wilkinson, Daniel J; Smith, Kenneth; Atherton, Philip J

    2016-09-01

    Constituting ∼40% of body mass, skeletal muscle has essential locomotory and metabolic functions. As such, an insight into the control of muscle mass is of great importance for maintaining health and quality-of-life into older age, under conditions of cachectic disease and with rehabilitation. In healthy weight-bearing individuals, muscle mass is maintained by the equilibrium between muscle protein synthesis (MPS) and muscle protein breakdown; when this balance tips in favour of MPS hypertrophy occurs. Despite considerable research into pharmacological/nutraceutical interventions, resistance exercise training (RE-T) remains the most potent stimulator of MPS and hypertrophy (in the majority of individuals). However, the mechanism(s) and time course of hypertrophic responses to RE-T remain poorly understood. We would suggest that available data are very much in favour of the notion that the majority of hypertrophy occurs in the early phases of RE-T (though still controversial to some) and that, for the most part, continued gains are hard to come by. Whilst the mechanisms of muscle hypertrophy represent the culmination of mechanical, auto/paracrine and endocrine events, the measurement of MPS remains a cornerstone for understanding the control of hypertrophy - mainly because it is the underlying driving force behind skeletal muscle hypertrophy. Development of sophisticated isotopic techniques (i.e. deuterium oxide) that lend to longer term insight into the control of hypertrophy by sustained RE-T will be paramount in providing insights into the metabolic and temporal regulation of hypertrophy. Such technologies will have broad application in muscle mass intervention for both athletes and for mitigating disease/age-related cachexia and sarcopenia, alike.

  2. Metabolic stress responses in Drosophila are modulated by brain neurosecretory cells that produce multiple neuropeptides.

    Directory of Open Access Journals (Sweden)

    Lily Kahsai

    Full Text Available In Drosophila, neurosecretory cells that release peptide hormones play a prominent role in the regulation of development, growth, metabolism, and reproduction. Several types of peptidergic neurosecretory cells have been identified in the brain of Drosophila with release sites in the corpora cardiaca and anterior aorta. We show here that in adult flies the products of three neuropeptide precursors are colocalized in five pairs of large protocerebral neurosecretory cells in two clusters (designated ipc-1 and ipc-2a: Drosophila tachykinin (DTK, short neuropeptide F (sNPF and ion transport peptide (ITP. These peptides were detected by immunocytochemistry in combination with GFP expression driven by the enhancer trap Gal4 lines c929 and Kurs-6, both of which are expressed in ipc-1 and 2a cells. This mix of colocalized peptides with seemingly unrelated functions is intriguing and prompted us to initiate analysis of the function of the ten neurosecretory cells. We investigated the role of peptide signaling from large ipc-1 and 2a cells in stress responses by monitoring the effect of starvation and desiccation in flies with levels of DTK or sNPF diminished by RNA interference. Using the Gal4-UAS system we targeted the peptide knockdown specifically to ipc-1 and 2a cells with the c929 and Kurs-6 drivers. Flies with reduced DTK or sNPF levels in these cells displayed decreased survival time at desiccation and starvation, as well as increased water loss at desiccation. Our data suggest that homeostasis during metabolic stress requires intact peptide signaling by ipc-1 and 2a neurosecretory cells.

  3. Transplant experiments uncover Baltic Sea basin-specific responses in bacterioplankton community composition and metabolic activities.

    Science.gov (United States)

    Lindh, Markus V; Figueroa, Daniela; Sjöstedt, Johanna; Baltar, Federico; Lundin, Daniel; Andersson, Agneta; Legrand, Catherine; Pinhassi, Jarone

    2015-01-01

    Anthropogenically induced changes in precipitation are projected to generate increased river runoff to semi-enclosed seas, increasing loads of terrestrial dissolved organic matter and decreasing salinity. To determine how bacterial community structure and functioning adjust to such changes, we designed microcosm transplant experiments with Baltic Proper (salinity 7.2) and Bothnian Sea (salinity 3.6) water. Baltic Proper bacteria generally reached higher abundances than Bothnian Sea bacteria in both Baltic Proper and Bothnian Sea water, indicating higher adaptability. Moreover, Baltic Proper bacteria growing in Bothnian Sea water consistently showed highest bacterial production and beta-glucosidase activity. These metabolic responses were accompanied by basin-specific changes in bacterial community structure. For example, Baltic Proper Pseudomonas and Limnobacter populations increased markedly in relative abundance in Bothnian Sea water, indicating a replacement effect. In contrast, Roseobacter and Rheinheimera populations were stable or increased in abundance when challenged by either of the waters, indicating an adjustment effect. Transplants to Bothnian Sea water triggered the initial emergence of particular Burkholderiaceae populations, and transplants to Baltic Proper water triggered Alteromonadaceae populations. Notably, in the subsequent re-transplant experiment, a priming effect resulted in further increases to dominance of these populations. Correlated changes in community composition and metabolic activity were observed only in the transplant experiment and only at relatively high phylogenetic resolution. This suggested an importance of successional progression for interpreting relationships between bacterial community composition and functioning. We infer that priming effects on bacterial community structure by natural episodic events or climate change induced forcing could translate into long-term changes in bacterial ecosystem process rates.

  4. Transplant experiments uncover Baltic Sea basin-specific responses in bacterioplankton community composition and metabolic activities

    Directory of Open Access Journals (Sweden)

    Markus V Lindh

    2015-04-01

    Full Text Available Anthropogenically induced changes in precipitation are projected to generate increased river runoff to semi-enclosed seas, intensifying loads of terrestrial dissolved organic matter and decreasing salinity. To determine how bacterial community structure and functioning adjust to such changes, we designed microcosm transplant experiments with Baltic Proper (salinity 7.2 and Bothnian Sea (salinity 3.6 water. Baltic Proper bacteria generally reached higher abundance than Bothnian Sea bacteria in both Baltic Proper and Bothnian Sea water, indicating a higher adaptability. Moreover, Baltic Proper bacteria growing in Bothnian Sea water consistently showed highest bacterial production and beta-glucosidase activity. These metabolic responses were accompanied by basin-specific changes in bacterial community structure. For example, Baltic Proper Pseudomonas and Limnobacter populations increased markedly in relative abundance in Bothnian Sea water, indicating replacement. In contrast, Roseobacter and Rheinheimera populations were stable or increased in abundance when challenged by either of the waters, indicating adjustment. Transplants to Bothnian Sea water triggered the initial emergence of particular Burkholderiaceae populations, and transplants to Baltic Proper water triggered Alteromonadaceae populations. Notably, in the subsequent re-transplant experiment, the original triggering, or priming effect, resulted in further increases to dominance of these populations. Correlated changes in community composition and metabolic activity were observed only in the transplant experiment, and only at relatively high phylogenetic resolution. This suggested an importance of successional progression for interpreting relationships between bacterial community composition and functioning. We infer that priming effects on bacterial community structure by natural episodic events or climate change induced forcing could translate into long-term changes in bacterial

  5. Metabolic response to different glycemic indexes of pre-exercise meal

    Directory of Open Access Journals (Sweden)

    Valéria Cristina de Faria

    2015-08-01

    Full Text Available INTRODUCTION: To ensure performance and health, the type of food and the time of pre-exercise ingestion should be considered by practitioners of morning physical activity. Objective: This study assessed the metabolic response after pre-exercise meals with different glycemic indexes (GI and in the fasting state adopting different types of hydration.METHODS: Twelve men performed four experimental tests; two with pre-exercise meals of high GI (HGI and low GI (LGI, and two were performed in the fasting state with hydration: water (H2O and carbohydrate drink (CHO. Each test consisted of a pre-exercise rest period of 30 minutes followed by 60 minutes of cycle ergometer with continuous load equivalent to 60% of the extrapolated maximal oxygen consumption (VO2MaxExt. During the exercise, participants were hydrated every 15 minutes with 3mL per kg body weight. During each experimental test, venous blood samples were obtained for fasting and at 15-minute intervals during rest, and every 20 minutes during exercise. The gas analysis was carried out in periods of 5 minutes every 20 minutes of exercise.RESULTS: There was no difference in substrate oxidation. After 20 minutes of exercise, pre-exercise food intake procedures showed similar behavior, having only reduced blood glucose levels compared to fasting procedures (p<0.01. There was maintenance of blood glucose at stable and higher levels during exercise in relation to the other tests in the fast procedure with CHO.CONCLUSION: The data suggest that despite the similar metabolic behavior between LGI and HGI meals, the adoption of a LGI meal before the morning exercise seems to be a more suitable feeding practice due to higher tendency of rebound hypoglycemia after HGI meal and when morning exercise is performed on fasting, hydration with CHO seems to minimize the hypoglycemic risk arising from that state.

  6. Similar metabolic responses in pigs and humans to breads with different contents and compositions of dietary fibers: a metabolomics study

    DEFF Research Database (Denmark)

    Nielsen, Kirstine Lykke; Hartvigsen, Merete; Hedemann, Mette Skou

    2014-01-01

    Background: In nutritional studies, pigs are often used as models for humans because of nutritional and physiologic similarities. However, evidence supporting similar metabolic responses to nutritional interventions is lacking. Objective: The objective was to establish whether pigs and humans...... respond similarly to a nutritional intervention. Using metabolomics, we compared the acute metabolic response to 4 test breads between conventional pigs (growing) and adult human subjects (with the metabolic syndrome). Design: Six catheterized pigs and 15 human subjects were tested in a randomized...... different basal metabolome concentrations in the plasma of pigs and humans. Humans had higher contents of phosphatidylcholines, oleic acid, and carnitine in plasma, possibly reflecting a higher intake of meats and fats. In pigs, betaine, choline, creatinine, tryptophan, and phenylalanine were higher...

  7. Antioxidant gene expression and metabolic responses of earthworms (Eisenia fetida) after exposure to various concentrations of hexabromocyclododecane.

    Science.gov (United States)

    Shi, Yajuan; Xu, Xiangbo; Chen, Juan; Liang, Ruoyu; Zheng, Xiaoqi; Shi, Yajing; Wang, Yurong

    2018-01-01

    Hexabromocyclododecane (HBCD), a ubiquitous suspected contaminant, is one of the world's most prominent brominated flame retardants (BFRs). In the present study, earthworms (Eisenia fetida) were exposed to HBCD. The expression of selected antioxidant enzyme genes was measured, and the metabolic responses were assessed using nuclear magnetic resonance (NMR) to identify the molecular mechanism of the antioxidant stress reaction and the metabolic reactions of earthworms to HBCD. A significant up-regulation (p  0.05). Principal component analysis (PCA) of the metabolic responses showed that all groups could be clearly differentiated, and the highest concentration dose group was the most distant from the control group. Except for fumarate, the measured metabolites, which included adenosine triphosphate (ATP), valine, lysine, glycine, betaine and lactate, revealed significant (p earthworm exposure studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Metabolomics by proton nuclear magnetic resonance spectroscopy of the response to chloroethylnitrosourea reveals drug efficacy and tumor adaptive metabolic pathways.

    Science.gov (United States)

    Morvan, Daniel; Demidem, Aicha

    2007-03-01

    Metabolomics of tumors may allow discovery of tumor biomarkers and metabolic therapeutic targets. Metabolomics by two-dimensional proton high-resolution magic angle spinning nuclear magnetic resonance spectroscopy was applied to investigate metabolite disorders following treatment by chloroethylnitrosourea of murine B16 melanoma (n = 33) and 3LL pulmonary carcinoma (n = 31) in vivo. Treated tumors of both types resumed growth after a delay. Nitrosoureas provoke DNA damage but the metabolic consequences of genotoxic stress are little known yet. Although some differences were observed in the metabolite profile of untreated tumor types, the prominent metabolic features of the response to nitrosourea were common to both. During the growth inhibition phase, there was an accumulation of glucose (more than x10; P < 0.05), glutamine (x3 to 4; P < 0.01), and aspartate (x2 to 5; P < 0.01). This response testified to nucleoside de novo synthesis down-regulation and drug efficacy. However, this phase also involved the increase in alanine (P < 0.001 in B16 melanoma), the decrease in succinate (P < 0.001), and the accumulation of serine-derived metabolites (glycine, phosphoethanolamine, and formate; P < 0.01). This response witnessed the activation of pathways implicated in energy production and resumption of nucleotide de novo synthesis, thus metabolic pathways of DNA repair and adaptation to treatment. During the growth recovery phase, it remained polyunsaturated fatty acid accumulation (x1.5 to 2; P < 0.05) and reduced utilization of glucose compared with glutamine (P < 0.05), a metabolic fingerprint of adaptation. Thus, this study provides the proof of principle that metabolomics of tumor response to an anticancer agent may help discover metabolic pathways of drug efficacy and adaptation to treatment.

  9. Skeletal Muscle Remodeling in Response to Eccentric vs. Concentric Loading: Morphological, Molecular, and Metabolic Adaptations

    Directory of Open Access Journals (Sweden)

    Martino V. Franchi

    2017-07-01

    Full Text Available Skeletal muscle contracts either by shortening or lengthening (concentrically or eccentrically, respectively; however, the two contractions substantially differ from one another in terms of mechanisms of force generation, maximum force production and energy cost. It is generally known that eccentric actions generate greater force than isometric and concentric contractions and at a lower metabolic cost. Hence, by virtue of the greater mechanical loading involved in active lengthening, eccentric resistance training (ECC RT is assumed to produce greater hypertrophy than concentric resistance training (CON RT. Nonetheless, prevalence of either ECC RT or CON RT in inducing gains in muscle mass is still an open issue, with some studies reporting greater hypertrophy with eccentric, some with concentric and some with similar hypertrophy within both training modes. Recent observations suggest that such hypertrophic responses to lengthening vs. shortening contractions are achieved by different adaptations in muscle architecture. Whilst the changes in muscle protein synthesis in response to acute and chronic concentric and eccentric exercise bouts seem very similar, the molecular mechanisms regulating the myogenic adaptations to the two distinct loading stimuli are still incompletely understood.Thus, the present review aims to, (a critically discuss the literature on the contribution of eccentric vs. concentric loading to muscular hypertrophy and structural remodeling, and, (b clarify the molecular mechanisms that may regulate such adaptations.We conclude that, when matched for either maximum load or work, similar increase in muscle size is found between ECC and CON RT. However, such hypertrophic changes appear to be achieved through distinct structural adaptations, which may be regulated by different myogenic and molecular responses observed between lengthening and shortening contractions.

  10. Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways.

    Directory of Open Access Journals (Sweden)

    Manoj K Bhasin

    Full Text Available The relaxation response (RR is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS as top upregulated critical molecules (focus hubs and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress.

  11. Thermal and metabolic responses of military divers during a 6-hour static dive in cold water.

    Science.gov (United States)

    Riera, Florence; Horr, Reed; Xu, Xiaojiang; Melin, Bruno; Regnard, Jacques; Bourdon, Lionel

    2014-05-01

    Human thermal responses during prolonged whole-body immersion in cold water are of interest for the military, especially French SEALS. This study aims at describing the thermo-physiological responses. There were 10 male military divers who were randomly assigned to a full immersion in neutral (34 degrees C), moderately cold (18 degrees C), and cold (10 degrees C) water wearing their operational protective devices (5.5 mm wetsuit with 3.0 mm thick underwear) for 6 h in a static position. Rectal temperature (T(re)) and 14 skin temperatures (T(sk)), blood analysis (stress biomarkers, metabolic substrates), and oxygen consumption (Vo2) were collected. At 34 degrees C, there were no significant modifications of the thermo-physiological responses over time. The most interesting result was that rates of rectal temperature decrease (0.15 +/- 0.02 degrees C x min(-1)) were the same between the two cold stress experimental conditions (at 18 degrees C and 10 degrees C). At the final experiment, rectal temperature was not significantly different between the two cold stress experimental conditions. Mean T(sk) decreased significantly during the first 3 h of immersion and then stabilized at a lower level at 10 degrees C (25.6 +/- 0.8 degrees C) than at 18 degrees C (29.3 +/- 0.9 degrees C). Other results demonstrate that the well-trained subjects developed effective physiological reactions. However, these reactions are consistently too low to counterbalance the heat losses induced by cold temperature conditions and long-duration immersion. This study shows that providing divers with thermal protection is efficient for a long-duration immersion from a medical point of view, but not from an operational one when skin extremities were taken into account.

  12. Telling metabolic stories to explore metabolomics data -- A case study on the Yeast response to cadmium exposure

    NARCIS (Netherlands)

    P.V. Milreu (Paulo); C.C. Klein (Cecilia); L. Cottret; V. Acuña (Vicente); E. Birmele; M. Borassi; C. Junot; A. Marchetti Spaccamela (Alberto); A. Morino; L. Stougie (Leen); F. Jourdan; P. Crescenzi; V. Lacroix; M.-F. Sagot (Marie-France)

    2014-01-01

    htmlabstractMotivation: The increasing availability of metabolomics data enables to better understand the metabolic processes involved in the immediate response of an organism to environmental changes and stress. The data usually come in the form of a list of metabolites whose concentrations

  13. Variations in insulin responsiveness in rat fat cells are due to metabolic differences rather than insulin binding

    DEFF Research Database (Denmark)

    Hansen, Finn Mølgård; Nilsson, Poul; Sonne, Ole

    1983-01-01

    -insulin to fat cells. Insulin binding was not correlated to the plasma insulin level which however was reflected in the lipoprotein lipase activity in the adipose tissue. In conclusion, these results indicate that variations in insulin responsiveness in fat cells are due to alterations in cellular metabolism...

  14. Metabolic response to 36 hours of fasting in young men born small vs appropriate for gestational age

    DEFF Research Database (Denmark)

    Jørgensen, Sine W; Brøns, Charlotte; Bluck, Les

    2015-01-01

    AIMS/HYPOTHESIS: Being born small for gestational age (SGA) is associated with an increased risk of type 2 diabetes in an affluent society, but could confer an improved chance of survival during sparse living conditions. We studied whether insulin action and other metabolic responses to prolonged...

  15. The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans

    NARCIS (Netherlands)

    ter Horst, Kasper W.; Gilijamse, Pim W.; Demirkiran, Ahmet; van Wagensveld, Bart A.; Ackermans, Mariette T.; Verheij, Joanne; Romijn, Johannes A.; Nieuwdorp, Max; Maratos-Flier, Eleftheria; Herman, Mark A.; Serlie, Mireille J.

    2017-01-01

    Objective: Fructose consumption has been implicated in the development of obesity and insulin resistance. Emerging evidence shows that fibroblast growth factor 21 (FGF21) has beneficial effects on glucose, lipid, and energy metabolism and may also mediate an adaptive response to fructose ingestion.

  16. Predictive value of PET response combined with baseline metabolic tumor volume in peripheral T-cell lymphoma patients

    DEFF Research Database (Denmark)

    Cottereau, Anne-Segolene; El-Galaly, Tarec C; Becker, Stéphanie

    2018-01-01

    Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphomas with poor outcomes with current therapy. We investigated if response assessed with Positron Emission Tomography/computed tomography (PET/CT) combined with baseline total metabolic tumor volume (TMTV) co...

  17. Metabolic response of porcine colon explants to in vitro infection by Brachyspira hyodysenteriae : a leap into disease pathophysiology

    NARCIS (Netherlands)

    Welle, Thijs; Hoekstra, Anna T.; Daemen, Ineke A.J.J.M.; Berkers, Celia R.; de Oliveira Costa, Matheus

    2017-01-01

    Introduction: Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available. Objective: The aim of this study was to characterize the metabolic response of porcine colon

  18. Metabolic and transcriptional responses of gilthead sea bream (Sparus aurata L.) to environmental stress: New insights in fish mitochondrial phenotyping

    NARCIS (Netherlands)

    Bermejo-Nogales, A.; Nederlof, M.A.J.; Benedito-Palos, L.; Ballester-Lozano, G.F.; Folkedal, O.; Olsen, R.E.; Sitjà-Bobadilla, A.; Pérez-Sánchez, J.

    2014-01-01

    The aim of the current study was to phenotype fish metabolism and the transcriptionally-mediated response of hepatic mitochondria of gilthead sea bream to intermittent and repetitive environmental stressors: (i) changes in water temperature (T-ST), (ii) changes in water level and chasing (C-ST) and

  19. Extreme Hypoxic Conditions Induce Selective Molecular Responses and Metabolic Reset in Detached Apple Fruit

    Science.gov (United States)

    Cukrov, Dubravka; Zermiani, Monica; Brizzolara, Stefano; Cestaro, Alessandro; Licausi, Francesco; Luchinat, Claudio; Santucci, Claudio; Tenori, Leonardo; Van Veen, Hans; Zuccolo, Andrea; Ruperti, Benedetto; Tonutti, Pietro

    2016-01-01

    The ripening physiology of detached fruit is altered by low oxygen conditions with profound effects on quality parameters. To study hypoxia-related processes and regulatory mechanisms, apple (Malus domestica, cv Granny Smith) fruit, harvested at commercial ripening, were kept at 1°C under normoxic (control) and hypoxic (0.4 and 0.8 kPa oxygen) conditions for up to 60 days. NMR analyses of cortex tissue identified eight metabolites showing significantly different accumulations between samples, with ethanol and alanine displaying the most pronounced difference between hypoxic and normoxic treatments. A rapid up-regulation of alcohol dehydrogenase and pyruvate-related metabolism (lactate dehydrogenase, pyruvate decarboxylase, alanine aminotransferase) gene expression was detected under both hypoxic conditions with a more pronounced effect induced by the lowest (0.4 kPa) oxygen concentration. Both hypoxic conditions negatively affected ACC synthase and ACC oxidase transcript accumulation. Analysis of RNA-seq data of samples collected after 24 days of hypoxic treatment identified more than 1000 genes differentially expressed when comparing 0.4 vs. 0.8 kPa oxygen concentration samples. Genes involved in cell-wall, minor and major CHO, amino acid and secondary metabolisms, fermentation and glycolysis as well as genes involved in transport, defense responses, and oxidation-reduction appeared to be selectively affected by treatments. The lowest oxygen concentration induced a higher expression of transcription factors belonging to AUX/IAA, WRKY, HB, Zinc-finger families, while MADS box family genes were more expressed when apples were kept under 0.8 kPa oxygen. Out of the eight group VII ERF members present in apple genome, two genes showed a rapid up-regulation under hypoxia, and western blot analysis showed that apple MdRAP2.12 proteins were differentially accumulated in normoxic and hypoxic samples, with the highest level reached under 0.4 kPa oxygen. These data suggest

  20. Protein kinase N2 regulates AMP kinase signaling and insulin responsiveness of glucose metabolism in skeletal muscle.

    Science.gov (United States)

    Ruby, Maxwell A; Riedl, Isabelle; Massart, Julie; Åhlin, Marcus; Zierath, Juleen R

    2017-10-01

    Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. Because skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. Although Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anterior muscle in vivo. PKN2 knockdown in vitro decreased insulin-stimulated glucose uptake, incorporation into glycogen, and oxidation. PKN2 siRNA increased 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling while stimulating fatty acid oxidation and incorporation into triglycerides and decreasing protein synthesis. At the transcriptional level, PKN2 knockdown increased expression of PGC-1α and SREBP-1c and their target genes. In mature skeletal muscle, in vivo PKN2 knockdown decreased glucose uptake and increased AMPK phosphorylation. Thus, PKN2 alters key signaling pathways and transcriptional networks to regulate glucose and lipid metabolism. Identification of PKN2 as a novel regulator of insulin and AMPK signaling may provide an avenue for manipulation of skeletal muscle metabolism. Copyright © 2017 the American Physiological Society.

  1. Metabolic responses to prolonged work during treadmill and water immersion running.

    Science.gov (United States)

    Frangolias, D D; Rhodes, E C; Taunton, J E; Belcastro, A N; Coutts, K D

    2000-12-01

    The primary aim of this study was to compare the physiological responses to prolonged treadmill (TM) and water immersion to the neck (WI) running at threshold intensity. Ten endurance runners performed TM and WI running VO2max tests. Subjects completed submaximal performance tests at ventilatory threshold (Tvent) intensities under TM and WI conditions and responses at 15 and 42 minutes examined. VO2 was lower in WI (p<0.05) at maximal effort and Tvent. The Tvent VO2 intensities interpolated from the TM and WI VO2max tests were performed in both TM (i.e., TM@TM(tvent),TM@WI(tvent), corresponding to 77.6 and 71.3% respectively of TM VO2max) and WI conditions (i.e., WI@TM(tvent), WI@WI(tvent), corresponding to 85.5% and 78.2% respectively of WI VO2max). Each of the dependent variables was analyzed using a 3-way repeated measures ANOVA (2 conditions X 2 exercise intensities X 7 time points during exercise). VO2max values were significantly lower in the WI (52.4(5.1) ml.kg(-1) min(-1)) versus TM (59.7(6.5) ml.kg(-1) min(-1)) condition. VO2 during submaximal tests were similar during the TM and WI conditions. HR and [BLa] responses to exercise at and above WI(tvent) were similar during short-term exercise, but values tended to be lower during prolonged exercise in the WI condition. There were no statistical differences in VE responses in the 2 conditions, however as with HR and [BLa] an upward trend was noted with TM exercise over the 42 minute duration of the tests. RPE at WI(tvent) was similar for TM and WI exercise sessions, however, RPE at TM(tvent) was higher during WI compared to TM running. Cardiovascular drift was observed during prolonged TM but not WI running. Results suggest differences in metabolic responses to prolonged submaximal exercise in WI, however it can be used effectively for cross training.

  2. Metabonomics-based analysis of Brachyspira pilosicoli's response to tiamulin reveals metabolic activity despite significant growth inhibition.

    Science.gov (United States)

    Le Roy, Caroline Ivanne; Passey, Jade Louise; Woodward, Martin John; La Ragione, Roberto Marcello; Claus, Sandrine Paule

    2017-06-01

    Pathogenic anaerobes Brachyspira spp. are responsible for an increasing number of Intestinal Spirochaetosis (IS) cases in livestock against which few approved treatments are available. Tiamulin is used to treat swine dysentery caused by Brachyspira spp. and recently has been used to handle avian intestinal spirochaetosis (AIS). The therapeutic dose used in chickens requires further evaluation since cases of bacterial resistance to tiamulin have been reported. In this study, we evaluated the impact of tiamulin at varying concentrations on the metabolism of B. pilosicoli using a 1 H-NMR-based metabonomics approach allowing the capture of the overall bacterial metabolic response to antibiotic treatment. Based on growth curve studies, tiamulin impacted bacterial growth even at very low concentration (0.008 μg/mL) although its metabolic activity was barely affected 72 h post exposure to antibiotic treatment. Only the highest dose of tiamulin tested (0.250 μg/mL) caused a major metabolic shift. Results showed that below this concentration, bacteria could maintain a normal metabolic trajectory despite significant growth inhibition by the antibiotic, which may contribute to disease reemergence post antibiotic treatment. Indeed, we confirmed that B. pilosicoli remained viable even after exposition to the highest antibiotic dose. This paper stresses the need to ensure new evaluation of bacterial viability post bacteriostatic exposure such as tiamulin to guarantee treatment efficacy and decrease antibiotic resistance development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Aerobic metabolism and cardioventilatory responses in paraplegic athletes during an incremental wheelchair exercise.

    Science.gov (United States)

    Vinet, A; Le Gallais, D; Bernard, P L; Poulain, M; Varray, A; Mercier, J; Micallef, J P

    1997-01-01

    The aims of the present study were: (1) to assess aerobic metabolism in paraplegic (P) athletes (spinal lesion level, T4-L3) by means of peak oxygen uptake (VO2peak) and ventilatory threshold (VT), and (2) to determine the nature of exercise limitation in these athletes by means of cardioventilatory responses at peak exercise. Eight P athletes underwent conventional spirographic measurements and then performed an incremental wheelchair exercise on an adapted treadmill. Ventilatory data were collected every minute using an automated metabolic system: ventilation (l x min[-1]), oxygen uptake (VO2, l x min[-1], ml x min[-1] x kg[-1]), carbon dioxide production (VCO2, ml x min[-1]), respiratory exchange ratio, breathing frequency and tidal volume. Heart rate (HR, beats x min[-1]) was collected with the aid of a standard electrocardiogram. VO2peak was determined using conventional criteria. VT was determined by the breakpoint in the VCO2 - VO2 relationship, and is expressed as the absolute VT (VO2, ml x min[-1] x kg[-1]) and relative VT (percentage of VO2peak). Spirometric values and cardioventilatory responses at rest and at peak exercise allowed the measurement of ventilatory reserve (VR), heart rate reserve (HRr), heart rate response (HRR), and O2 pulse (O2 P). Results showed a VO2peak value of 40.6 (2.5) ml x min(-1) x kg(-1), an absolute VT detected at 23.1 (1.5) ml x min(-1) x kg(-1) VO2 and a relative VT at 56.4 (2.2)% VO2peak. HRr [15.8 (3.2) beats min(-1)], HRR [48.6 (4.3) beat x l(-1)], and O2 P [0.23 (0.02) ml x kg(-1) x beat(-1)] were normal, whereas VR at peak exercise [42.7 (2.4)%] was increased. As wheelchair exercise excluded the use of an able-bodied (AB) control group, we compared our VO2peak and VT results with those for other P subjects and AB controls reported in the literature, and we compared our cardioventilatory responses with those for respiratory and cardiac patients. The low VO2peak values obtained compared with subject values obtained during

  4. Epigenetic control and the circadian clock: linking metabolism to neuronal responses.

    Science.gov (United States)

    Orozco-Solis, R; Sassone-Corsi, P

    2014-04-04

    Experimental and epidemiological evidence reveal the profound influence that industrialized modern society has imposed on human social habits and physiology during the past 50 years. This drastic change in life-style is thought to be one of the main causes of modern diseases including obesity, type 2 diabetes, mental illness such as depression, sleep disorders, and certain types of cancer. These disorders have been associated to disruption of the circadian clock, an intrinsic time-keeper molecular system present in virtually all cells and tissues. The circadian clock is a key element in homeostatic regulation by controlling a large array of genes implicated in cellular metabolism. Importantly, intimate links between epigenetic regulation and the circadian clock exist and are likely to prominently contribute to the plasticity of the response to the environment. In this review, we summarize some experimental and epidemiological evidence showing how environmental factors such as stress, drugs of abuse and changes in circadian habits, interact through different brain areas to modulate the endogenous clock. Furthermore we point out the pivotal role of the deacetylase silent mating-type information regulation 2 homolog 1 (SIRT1) as a molecular effector of the environment in shaping the circadian epigenetic landscape. Published by Elsevier Ltd.

  5. Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism

    Science.gov (United States)

    Yang, Wei; Bai, Yibing; Xiong, Ying; Zhang, Jin; Chen, Shuokai; Zheng, Xiaojun; Meng, Xiangbo; Li, Lunyi; Wang, Jing; Xu, Chenguang; Yan, Chengsong; Wang, Lijuan; Chang, Catharine C. Y.; Chang, Ta-Yuan; Zhang, Ti; Zhou, Penghui; Song, Bao-Liang; Liu, Wanli; Sun, Shao-cong; Liu, Xiaolong; Li, Bo-liang; Xu, Chenqi

    2016-01-01

    CD8+ T cells have a central role in antitumour immunity, but their activity is suppressed in the tumour microenvironment1–4. Reactivating the cytotoxicity of CD8+ T cells is of great clinical interest in cancer immunotherapy. Here we report a new mechanism by which the antitumour response of mouse CD8+ T cells can be potentiated by modulating cholesterol metabolism. Inhibiting cholesterol esterification in T cells by genetic ablation or pharmacological inhibition of ACAT1, a key cholesterol esterification enzyme5, led to potentiated effector function and enhanced proliferation of CD8+ but not CD4+ T cells. This is due to the increase in the plasma membrane cholesterol level of CD8+ T cells, which causes enhanced T-cell receptor clustering and signalling as well as more efficient formation of the immunological synapse. ACAT1-deficient CD8+ T cells were better than wild-type CD8+ T cells at controlling melanoma growth and metastasis in mice. We used the ACAT inhibitor avasimibe, which was previously tested in clinical trials for treating atherosclerosis and showed a good human safety profile6,7, to treat melanoma in mice and observed a good antitumour effect. A combined therapy of avasimibe plus an anti-PD-1 antibody showed better efficacy than monotherapies in controlling tumour progression. ACAT1, an established target for atherosclerosis, is therefore also a potential target for cancer immunotherapy. PMID:26982734

  6. Cross-Talk between Carbon Metabolism and the DNA Damage Response in S. cerevisiae

    Directory of Open Access Journals (Sweden)

    Kobi J. Simpson-Lavy

    2015-09-01

    Full Text Available Yeast cells with DNA damage avoid respiration, presumably because products of oxidative metabolism can be harmful to DNA. We show that DNA damage inhibits the activity of the Snf1 (AMP-activated protein kinase (AMPK, which activates expression of genes required for respiration. Glucose and DNA damage upregulate SUMOylation of Snf1, catalyzed by the SUMO E3 ligase Mms21, which inhibits SNF1 activity. The DNA damage checkpoint kinases Mec1/ATR and Tel1/ATM, as well as the nutrient-sensing protein kinase A (PKA, regulate Mms21 activity toward Snf1. Mec1 and Tel1 are required for two SNF1-regulated processes—glucose sensing and ADH2 gene expression—even without exogenous genotoxic stress. Our results imply that inhibition of Snf1 by SUMOylation is a mechanism by which cells lower their respiration in response to DNA damage. This raises the possibility that activation of DNA damage checkpoint mechanisms could contribute to aerobic fermentation (Warburg effect, a hallmark of cancer cells.

  7. THE EFFECT OF ADRENAL MEDULLECTOMY ON METABOLIC RESPONSES TO CHRONIC INTERMITTENT HYPOXIA

    Science.gov (United States)

    Shin, Mi-Kyung; Han, Woobum; Bevans-Fonti, Shannon; Jun, Jonathan C.; Punjabi, Naresh M.; Polotsky, Vsevolod Y.

    2014-01-01

    Obstructive sleep apnea causes intermittent hypoxia (IH) and is associated with insulin resistance and type 2 diabetes. IH increases plasma catecholamine levels, which may increase insulin resistance and suppress insulin secretion. The objective of this study was to determine if adrenal medullectomy (MED) prevents metabolic dysfunction in IH. MED or sham surgery was performed in 60 male C57BL/6J mice, which were then exposed to IH or control conditions (intermittent air) for 6 weeks. IH increased plasma epinephrine and norepinephrine levels, increased fasting blood glucose and lowered basal and glucose-stimulated insulin secretion. MED decreased baseline epinephrine and prevented the IH induced increase in epinephrine, whereas the norepinephrine response remained intact. MED improved glucose tolerance in mice exposed to IH, attenuated the impairment in basal and glucose-stimulated insulin secretion, but did not prevent IH-induced fasting hyperglycemia or insulin resistance. We conclude that the epinephrine release from the adrenal medulla during IH suppresses insulin secretion causing hyperglycemia. PMID:25179887

  8. The Keap1-Nrf2 system in cancers: Stress response and anabolic metabolism

    Directory of Open Access Journals (Sweden)

    Yoichiro eMitsuishi

    2012-12-01

    Full Text Available The Keap1-Nrf2 pathway plays a central role in the protection of cells against oxidative and xenobiotic stresses. Nrf2 is a potent transcription activator that recognizes a unique DNA sequence known as the antioxidant response element (ARE. Under normal conditions, Nrf2 binds to Keap1 in the cytoplasm, resulting in proteasomal degradation. Following exposure to electrophiles or reactive oxygen species, Nrf2 becomes stabilized, translocates into the nucleus and activates the transcription of various cytoprotective genes. Increasing attention has been paid to the role of Nrf2 in cancer cells because the constitutive stabilization of Nrf2 has been observed in many human cancers with poor prognosis. Recent studies have shown that the antioxidant and detoxification activities of Nrf2 confer chemo- and radio-resistance to cancer cells. In this review, we provide an overview of the Keap1-Nrf2 system and discuss its role under physiological and pathological conditions, including cancers. We also introduce the results of our recent study describing Nrf2 function in the metabolism of cancer cells. Nrf2 likely confers a growth advantage to cancer cells through enhancing cytoprotection and anabolism. Finally, we discuss the possible impact of Nrf2 inhibitors on cancer therapy.

  9. Circulatory and muscle metabolic responses to draught work compared to increasing trotting velocities.

    Science.gov (United States)

    Gottlieb, M; Essén-Gustavsson, B; Lindholm, A; Persson, S G

    1988-11-01

    Circulatory and muscle metabolic responses were studied in 10 horses which all performed incremental draught work at a low trotting speed on a treadmill (D-test) and also exercise with gradually increasing velocities (S-test). Exercise was continued until the horses could no longer maintain the weights above the floor or maintain speed trotting without changing gait to a gallop. Muscle biopsies were taken from the gluteus and the semitendinosus muscles before, and immediately after, exercise. The heart rate (HR) increased linearly with both increasing draught resistance and velocity and reached mean values of 212 and 203 beats/min, respectively. Blood lactate levels increased exponentially to mean values of 12.9 and 7.9 mmol/litre in the two tests. Both HR and blood lactate levels were significantly higher at the cessation of work in the D-test compared to the S-test. The relationship between HR and blood lactate response in the S-test was similar to that in the D-test. The red cell volume was determined after a standardised exercise tolerance test and was significantly correlated both to the weightloading and to the velocity, producing a HR of 200 beats/min. The changes seen in muscle glycogen and glucose-6-phosphate were similar in the two tests, whereas significantly higher lactate levels and lower creatine phosphate and adenosine triphosphate levels were seen in the D-test compared to the S-test. It was concluded that high oxidative capacity is of importance both for fast trotting and for draught work.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

    DEFF Research Database (Denmark)

    Catoire, Milène; Alex, Sheril; Paraskevopulos, Nicolas

    2014-01-01

    Physical activity increases energy metabolism in exercising muscle. Whether acute exercise elicits metabolic changes in nonexercising muscles remains unclear. We show that one of the few genes that is more highly induced in nonexercising muscle than in exercising human muscle during acute exercis...

  11. Deciphering the Differential Effective and Toxic Responses of Bupleuri Radix following the Induction of Chronic Unpredictable Mild Stress and in Healthy Rats Based on Serum Metabolic Profiles

    Directory of Open Access Journals (Sweden)

    Xiaoxia Gao

    2018-01-01

    Full Text Available The petroleum ether fraction of Bupleuri Radix which is contained in the traditional Chinese medicine prescription of Xiaoyaosan (XYS may have a therapeutic effect in depressed subjects based on the results of our previous study. It has been reported that Bupleuri Radix can cause liver toxicity following overdosing or long-term use. Therefore, this study aimed to decipher the differential effective and toxic responses of Bupleuri Radix in chronic unpredictable mild stress (CUMS (with depression and healthy rats based on serum metabolic profiles. Serum metabolic profiles were obtained using the UHPLC- Q Exactive Orbitrap-MS technique. Our results demonstrated that the petroleum ether fraction of Bupleuri Radix (PBR produces an antidepressant effect through regulating glycometabolism, amino acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. It also induces more severe toxic reactions in the liver or kidney in healthy rats than in CUMS rats, which exhibited a comparatively mild drug-induced toxic reaction. The altered lysine degradation, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid metabolism, and bile acid metabolism could be at least partly responsible for the PBR toxic responses in healthy rats. The differential effective and toxic response of PBR in CUMS rats and healthy rats provide a new standard for the more rational and safer application of clinical drugs in the future.

  12. Robust metabolic responses to varied carbon sources in natural and laboratory strains of Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Wayne A Van Voorhies

    Full Text Available Understanding factors that regulate the metabolism and growth of an organism is of fundamental biologic interest. This study compared the influence of two different carbon substrates, dextrose and galactose, on the metabolic and growth rates of the yeast Saccharomyces cerevisiae. Yeast metabolic and growth rates varied widely depending on the metabolic substrate supplied. The metabolic and growth rates of a yeast strain maintained under long-term laboratory conditions was compared to strain isolated from natural condition when grown on different substrates. Previous studies had determined that there are numerous genetic differences between these two strains. However, the overall metabolic and growth rates of a wild isolate of yeast was very similar to that of a strain that had been maintained under laboratory conditions for many decades. This indicates that, at in least this case, metabolism and growth appear to be well buffered against genetic differences. Metabolic rate and cell number did not co-vary in a simple linear manner. When grown in either dextrose or galactose, both strains showed a growth pattern in which the number of cells continued to increase well after the metabolic rate began a sharp decline. Previous studied have reported that O₂ consumption in S. cerevisiae grown in reduced dextrose levels were elevated compared to higher levels. Low dextrose levels have been proposed to induce caloric restriction and increase life span in yeast. However, there was no evidence that reduced levels of dextrose increased metabolic rates, measured by either O₂ consumption or CO₂ production, in the strains used in this study.

  13. Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

    Energy Technology Data Exchange (ETDEWEB)

    Shannahan, Jonathan H. [Curriculum in Toxicology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Alzate, Oscar [Systems Proteomics Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Winnik, Witold M.; Andrews, Debora [Proteomics Core, Research Core Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Schladweiler, Mette C. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Ghio, Andrew J. [Clinical Research Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Chapel Hill, NC 27599 (United States); Gavett, Stephen H. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Kodavanti, Urmila P., E-mail: Kodavanti.Urmila@epa.gov [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2012-04-15

    Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins involved

  14. Common motifs in the response of cereal primary metabolism to fungal pathogens are not based on similar transcriptional reprogramming

    Directory of Open Access Journals (Sweden)

    Lars Matthias Voll

    2011-08-01

    Full Text Available During compatible interactions with their host plants, biotrophic plant pathogens subvert host metabolism to ensure the sustained provision of nutrient assimilates by the colonized host cells. To investigate, whether common motifs can be revealed in the response of primary carbon and nitrogen metabolism towards colonization with biotrophic fungi in cereal leaves, we have conducted a combined metabolome and transcriptome study of three quite divergent pathosystems, the barley powdery mildew fungus (Blumeria graminis f.sp. hordei, the corn smut fungus Ustilago maydis and the maize anthracnose fungus Colletotrichum graminicola, the latter being a hemibiotroph that only exhibits an initial biotrophic phase during its establishment.Based on the analysis of 42 water-soluble metabolites, we were able to separate early biotrophic from late biotrophic interactions by hierarchical cluster analysis and principal component analysis, irrespective of the plant host. Interestingly, the corresponding transcriptome dataset could not discriminate between these stages of biotrophy, irrespective, of whether transcript data for genes of central metabolism or the entire transcriptome dataset was used. Strong differences in the transcriptional regulation of photosynthesis, glycolysis, the TCA cycle, lipid biosynthesis, and cell wall metabolism were observed between the pathosystems. Increased contents of Gln, Asn, and glucose as well as diminished contents of PEP and 3-PGA were common to early post-penetration stages of all interactions. On the transcriptional level, genes of the TCA cycle, nucleotide energy metabolism and amino acid biosynthesis exhibited consistent trends among the compared biotrophic interactions, identifying the requirement for metabolic energy and the rearrangement of amino acid pools as common transcriptional motifs during early biotrophy. Both metabolome and transcript data were employed to generate models of leaf primary metabolism during

  15. [Supposed role of "metabolic memory" in formation of response reaction to stress-factors in young and adult organisms].

    Science.gov (United States)

    Bozhkov, A I; Dlubovskaia, V L; Dmitriev, Iu V; Meshaĭkina, N I; Maleev, V A; Klimova, E M

    2009-01-01

    The influence of the combined long-lasted influences of sulfur sulfate and diet restriction in young (3 month age) and adult (21 month age) Vistar rats on activity of glucose-6-phospatase, alaninaminotranspherase (ALT), aspartataminotranspherase (AST), and on phosphorilating activity of liver mitochondria was studied to investigate the role of metabolic memory on the peculiarities of response reaction. The young animals not differed from adult ones in the possibility of inducing activity of glucose-6-phospatase, ALT, and on phosphorilating activity after the influence of sulfur sulfate and diet restriction. The age-related differences in glucose-6-phospatase and transpherases and phosphorilating activity existing in control disappeared after the long-lasted action of sulfur sulfate and diet restriction. The answer reaction in enzyme activity to stress factors applied many times depends upon the metabolic memory formed in the process of adaptation, and the age of animals have no influence on it. In some relation the ontogenesis may be considered as a result of adaptation genesis. The metabolic memory can change the answer of the system to the stress influence. There are three types of modification of the answer to stress factors: the answer remains unchanged (metabolic memory), "paradox answer" formation, and super activation of the metabolic system.

  16. Oxidative stress protection and glutathione metabolism in response to hydrogen peroxide and menadione in riboflavinogenic fungus Ashbya gossypii.

    Science.gov (United States)

    Kavitha, S; Chandra, T S

    2014-11-01

    Ashbya gossypii is a plant pathogen and a natural overproducer of riboflavin and is used for industrial riboflavin production. A few literature reports depict a link between riboflavin overproduction and stress in this fungus. However, the stress protection mechanisms and glutathione metabolism are not much explored in A. gossypii. In the present study, an increase in the activity of catalase and superoxide dismutase was observed in response to hydrogen peroxide and menadione. The lipid peroxide and membrane lipid peroxide levels were increased by H2O2 and menadione, indicating oxidative damage. The glutathione metabolism was altered with a significant increase in oxidized glutathione (GSSG), glutathione peroxidase (GPX), glutathione S transferase (GST), and glutathione reductase (GR) and a decrease in reduced glutathione (GSH) levels in the presence of H2O2 and menadione. Expression of the genes involved in stress mechanism was analyzed in response to the stressors by semiquantitative RT-PCR. The messenger RNA (mRNA) levels of CTT1, SOD1, GSH1, YAP1, and RIB3 were increased by H2O2 and menadione, indicating the effect of stress at the transcriptional level. A preliminary bioinformatics study for the presence of stress response elements (STRE)/Yap response elements (YRE) depicted that the glutathione metabolic genes, stress genes, and the RIB genes hosted either STRE/YRE, which may enable induction of these genes during stress.

  17. Ozone modifies the metabolic and endocrine response to glucose: Reproduction of effects with the stress hormone corticosterone.

    Science.gov (United States)

    Thomson, Errol M; Pilon, Shinjini; Guénette, Josée; Williams, Andrew; Holloway, Alison C

    2018-03-01

    Air pollution is associated with increased incidence of metabolic disease (e.g. metabolic syndrome, obesity, diabetes); however, underlying mechanisms are poorly understood. Air pollutants increase the release of stress hormones (human cortisol, rodent corticosterone), which could contribute to metabolic dysregulation. We assessed acute effects of ozone, and stress axis involvement, on glucose tolerance and on the metabolic (triglyceride), endocrine/energy regulation (insulin, glucagon, GLP-1, leptin, ghrelin, corticosterone), and inflammatory/endothelial (TNF, IL-6, VEGF, PAI-1) response to exogenous glucose. Male Fischer-344 rats were exposed to clean air or 0.8 ppm ozone for 4 h in whole body chambers. Hypothalamic-pituitary-adrenal (HPA) axis involvement in ozone effects was tested through subcutaneous administration of the glucocorticoid synthesis inhibitor metyrapone (50 mg/kg body weight), corticosterone (10 mg/kg body weight), or vehicle (40% propylene glycol) prior to exposure. A glucose tolerance test (2 g/kg body weight glucose) was conducted immediately after exposure, with blood samples collected at 0, 30, 60, 90, and 120 min. Ozone exposure impaired glucose tolerance, an effect accompanied by increased plasma triglycerides but no impairment of insulin release. Ozone diminished glucagon, GLP-1, and ghrelin responses to glucose, but did not significantly impact inflammatory/endothelial analytes. Metyrapone reduced corticosterone but increased glucose and triglycerides, complicating evaluation of the impact of glucocorticoid inhibition. However, administration of corticosterone reproduced the profile of ozone effects, supporting a role for the HPA axis. The results show that ozone-dependent changes in glucose tolerance are accompanied by altered metabolic and endocrine responses to glucose challenge that are reproduced by exogenous stress hormone. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  18. Dynamical feedback between circadian clock and sucrose availability explains adaptive response of starch metabolism to various photoperiods

    Directory of Open Access Journals (Sweden)

    Francois Gabriel Feugier

    2013-01-01

    Full Text Available Plants deal with resource management during all their life. During the day they feed on photosynthetic carbon, sucrose, while storing a part into starch for night use. Careful control of carbon partitioning, starch degradation and sucrose export rates is crucial to avoid carbon starvation, insuring optimal growth whatever the photoperiod. Efficient regulation of these key metabolic rates can give an evolutionary advantage to plants. Here we propose a model of adaptive starch metabolism in response to various photoperiods. We assume the three key metabolic rates to be circadian regulated in leaves and that their phases of oscillations are shifted in response to sucrose starvation. We performed gradient descents for various photoperiod conditions to find the corresponding optimal sets of phase shifts that minimize starvation. Results at convergence were all consistent with experimental data: i diurnal starch profile showed linear increase during the day and linear decrease at night; ii shorter photoperiod tended to increase starch synthesis speed while decreasing its degradation speed during the longer night; iii sudden early dusk showed slower starch degradation during the longer night. Profiles that best explained observations corresponded to circadian regulation of all rates. This theoretical study would establish a framework for future research on feedback between starch metabolism and circadian clock as well as plant productivity.

  19. Genes responsible for vaginal extracellular matrix metabolism are modulated by women's reproductive cycle and menopause

    Directory of Open Access Journals (Sweden)

    Oksana Shynlova

    2013-04-01

    Full Text Available Objectives To analyze the expression of genes involved in extracellular matrix (ECM biogenesis and remodeling in vaginal tissue of women with clinically normal pelvic floor support (defined as controls according to the phase of menstrual cycle and postmenopausal women with and without pelvic organ prolapse (POP. Materials and Methods This study examined the expression of matrix metalloproteinases (MMPs, their tissue inhibitors (TIMPs, and the Lysyl oxidase (LOX family genes in the anterior vaginal wall of Caucasian women by real-time RT-PCR. Initially, mRNA expression was assessed in premenopausal controls in the secretory (group 1, n = 10 vs. proliferative (group 2, n = 8 phase of menstrual cycle. In addition, we compared premenopausal controls in the proliferative phase (group 2 vs. postmenopausal controls (group 3, n = 5. Finally, we analyzed postmenopausal controls (group 3 vs. postmenopausal women with advanced POP (group 4, n = 13. Results According to the phase of menstrual cycle, MMP1 was significantly reduced (p = 0.003, whereas the expression of TIMP1 and LOXL4 was significantly up-regulated during proliferative phase (both p < 0.01 when compared to the secretory phase in premenopausal control women. Regarding menopausal status/ageing, all MMPs were down-regulated, while TIMP3, TIMP4 and LOXL2 were significantly up-regulated in postmenopausal control women when compared to premenopausal controls (p = 0.005, p = 0.01 and p < 0.001, correspondingly. TIMP4 and LOXL2 mRNA levels were significantly decreased in postmenopausal POP patients compared to asymptomatic postmenopausal controls (p < 0.01 for both. Conclusions Our results indicate that ovarian cycle and age-related changes influence the expression of genes encoding proteins responsible for ECM metabolism in human vagina. Moreover, POP is associated with alteration in vaginal ECM components after menopause.

  20. PEG-induced osmotic stress in Mentha x piperita L.: Structural features and metabolic responses.

    Science.gov (United States)

    Búfalo, Jennifer; Rodrigues, Tatiane Maria; de Almeida, Luiz Fernando Rolim; Tozin, Luiz Ricardo Dos Santos; Marques, Marcia Ortiz Mayo; Boaro, Carmen Silvia Fernandes

    2016-08-01

    The present study investigated whether osmotic stress induced by the exposure of peppermint (Mentha x piperita L.) to moderate and severe stress for short periods of time changes the plant's physiological parameters, leaf anatomy and ultrastructure and essential oil. Plants were exposed to two levels of polyethyleneglycol (50 g L(-1) and 100 g L(-1) of PEG) in a hydroponic experiment. The plants exposed to 50 g L(-1) maintained metabolic functions similar to those of the control group (0 g L(-1)) without changes in gas exchange or structural characteristics. The increase in antioxidant enzyme activity reduced the presence of free radicals and protected membranes, including chloroplasts and mitochondria. In contrast, the osmotic stress caused by 100 g L(-1) of PEG inhibited leaf gas exchange, reduced the essential oil content and changed the oil composition, including a decrease in menthone and an increase in menthofuran. These plants also showed an increase in peroxidase activity, but this increase was not sufficient to decrease the lipid peroxidation level responsible for damaging the membranes of organelles. Morphological changes were correlated with the evaluated physiological features: plants exposed to 100 g L(-1) of PEG showed areas with collapsed cells, increases in mesophyll thickness and the area of the intercellular space, cuticle shrinkage, morphological changes in plastids, and lysis of mitochondria. In summary, our results revealed that PEG-induced osmotic stress in M. x piperita depends on the intensity level of the osmotic stress applied; severe osmotic stress changed the structural characteristics, caused damage at the cellular level, and reduced the essential oil content and quality. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus.

    Science.gov (United States)

    Nguyen, Long The; Saad, Sonia; Tan, Yi; Pollock, Carol; Chen, Hui

    2017-07-01

    Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity. © 2017 Society for Endocrinology.

  2. Circulatory, respiratory and metabolic responses in Thoroughbred horses during the first 400 meters of exercise.

    Science.gov (United States)

    Littlejohn, A; Snow, D H

    1988-01-01

    These studies investigated circulatory, respiratory and metabolic responses in four Thoroughbred geldings during the first 400 metres of galloping (mean speed 14.4 +/- 0.38 m.s-1), cantering (mean speed 10.0 +/- 0.61 m.s-1) and walking (mean speed 1.58 +/- 0.05 m.s-1) from a standing start. A radio-controlled device which collected blood samples anaerobically during each 100 m section of the exercise track allowed analyses of changes in and functional relationships of the variables measured. During the 400 m gallop, the mean heart rate (HR) increased from 125 to 201 beats.min-1 and the haematocrit (Hct) from 0.513 to 0.589 l/l-1. The haemoglobin [Hb], lactate [LA] and potassium [K+] concentrations increased significantly, while the pH and the partial pressure of oxygen (PaO2) decreased significantly. The arterial partial pressure of carbon dioxide (PaCO2) and the plasma bicarbonate concentration did not change significantly. There were significant correlations between HR and Hct, HR and [Hb], HR and PaO2, HR and pH, HR and PvCO2, HR and [LA], HR and [K+], pH and [K+], Hct and PaO2, [Hb] and PaO2, PaCO2 and PaO2, [LA] and PaO2, pH and PaO2, [K+] and PaO2, stride frequency and PaO2. With the exception of the PvCO2 which increased significantly, changes in venous blood during the gallop were in the same direction as those of arterial blood. Thirty seconds before the start of the gallop, both HR and [Hb] were significantly higher than at rest, providing an approximate three-fold increase in oxygen delivery compared to that of the resting state.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Dimensionality controls cytoskeleton assembly and metabolism of fibroblast cells in response to rigidity and shape.

    Directory of Open Access Journals (Sweden)

    Mirjam Ochsner

    2010-03-01

    Full Text Available Various physical parameters, including substrate rigidity, size of adhesive islands and micro-and nano-topographies, have been shown to differentially regulate cell fate in two-dimensional (2-D cell cultures. Cells anchored in a three-dimensional (3-D microenvironment show significantly altered phenotypes, from altered cell adhesions, to cell migration and differentiation. Yet, no systematic analysis has been performed that studied how the integrated cellular responses to the physical characteristics of the environment are regulated by dimensionality (2-D versus 3-D.Arrays of 5 or 10 microm deep microwells were fabricated in polydimethylsiloxane (PDMS. The actin cytoskeleton was compared for single primary fibroblasts adhering either to microfabricated adhesive islands (2-D or trapped in microwells (3-D of controlled size, shape, and wall rigidity. On rigid substrates (Young's Modulus = 1 MPa, cytoskeleton assembly within single fibroblast cells occurred in 3-D microwells of circular, rectangular, square, and triangular shapes with 2-D projected surface areas (microwell bottom surface area and total surface areas of adhesion (microwell bottom plus wall surface area that inhibited stress fiber assembly in 2-D. In contrast, cells did not assemble a detectable actin cytoskeleton in soft 3-D microwells (20 kPa, regardless of their shapes, but did so on flat, 2-D substrates. The dependency on environmental dimensionality was also reflected by cell viability and metabolism as probed by mitochondrial activities. Both were upregulated in 3-D cultured cells versus cells on 2-D patterns when surface area of adhesion and rigidity were held constant.These data indicate that cell shape and rigidity are not orthogonal parameters directing cell fate. The sensory toolbox of cells integrates mechanical (rigidity and topographical (shape and dimensionality information differently when cell adhesions are confined to 2-D or occur in a 3-D space.

  4. Metabolic Responses to Sago and Soy Supplementations during Endurance Cycling Performance in the Heat

    Directory of Open Access Journals (Sweden)

    Daniel Tarmast

    2017-10-01

    Full Text Available This study examined the effects of Sago (Sa, Soy (So, combined iso–caloric Sago+Soy (SS supplementations during cycling on metabolic responses as compared to placebo (P in the heat (31℃, 70% relative humidity. Twelve well–trained male cyclists (Age: 19.0±5.6 yr, Height: 170.8±7.6 cm, Wight: 60.1±11.2 kg, and VO2max: 56.5±6.5 mL.kg-1.min-1 participated in four experimental trials. The design of the trials was a randomized single–blind, placebo–controlled crossover trail comprising 90 min of steady–state cycling on an ergometer at 60% of VO2max followed by a 20–km time trial performance (TT. The participants of the study were supplemented 5 times at 0, 20, 40, 60, and 80 minutes during the steady–state cycling. Sa, So, and SS supplements provided 7.5% Sago, 7.5% Soy, and 6.0% Sago + 1.5% Soy respectively. Plasma glucose concentrations (PG reached a peak at 60 min after ingestion of Sa and SS as compared to baseline. At the end of the TT, PG reduced significantly to the baseline level. Plasma insulin concentrations (PI increased in all trials, but reduced gradually to the baseline level. The concentration of plasma free fatty acids (FFA increased gradually during the steady–state cycling and TT, and FFA was significantly higher in the P and So than the Sa and SS trials. At the end of the steady–state cycling, the plasma lactate concentration (LACT reached its lowest concentrations and at the end of the TT was enhanced significantly in all trials. These results suggest that sago and soy supplements increase the PG and PI during endurance exercise in the heat. These data add to the growing body of knowledge concerning endurance athletes’ glycemic and insulinemic responses to carbohydrate consumptions during exercise in the heat.

  5. Air pollution and neuroendocrine stress-mediated systemic metabolic and inflammatory response

    Science.gov (United States)

    New experimental evidence involving the role of neuroendocrine activation challenges an accepted mechanistic paradigm of how irritant air pollutants induce systemic metabolic impairment and lung injury/inflammation. We focus on recent air pollution studies highlighting how the re...

  6. Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure

    KAUST Repository

    Baud, Maxime O.; Parafita, Julia; Nguyen, Audrey; Magistretti, Pierre J.; Petit, Jean-Marie

    2016-01-01

    © 2016 European Sleep Research Society. Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs

  7. The effect of metabolic alkalosis on the ventilatory response in healthy subjects

    NARCIS (Netherlands)

    Mos-Oppersma, Eline; Doorduin, Jonne; van der Hoeven, J.G.; Veltink, Petrus H.; van Hees, H.W.H.; Heunks, L.M.A.

    Background Patients with acute respiratory failure may develop respiratory acidosis. Metabolic compensation by bicarbonate production or retention results in posthypercapnic alkalosis with an increased arterial bicarbonate concentration. The hypothesis of this study was that elevated plasma

  8. Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses.

    Science.gov (United States)

    Thwe, Phyu M; Pelgrom, Leonard; Cooper, Rachel; Beauchamp, Saritha; Reisz, Julie A; D'Alessandro, Angelo; Everts, Bart; Amiel, Eyal

    2017-09-05

    Dendritic cell (DC) activation by Toll-like receptor (TLR) agonists causes rapid glycolytic reprogramming that is required to meet the metabolic demands of their immune activation. Recent efforts in the field have identified an important role for extracellular glucose sourcing to support DC activation. However, the contributions of intracellular glucose stores to these processes have not been well characterized. We demonstrate that DCs possess intracellular glycogen stores and that cell-intrinsic glycogen metabolism supports the early effector functions of TLR-activated DCs. Inhibition of glycogenolysis significantly attenuates TLR-mediated DC maturation and impairs their ability to initiate lymphocyte activation. We further report that DCs exhibit functional compartmentalization of glucose- and glycogen-derived carbons, where these substrates preferentially contribute to distinct metabolic pathways. This work provides novel insights into nutrient homeostasis in DCs, demonstrating that differential utilization of glycogen and glucose metabolism regulates their optimal immune function. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Correlating metabolic and anatomic responses of primary lung cancers to radiotherapy by combined F-18 FDG PET-CT imaging

    Directory of Open Access Journals (Sweden)

    Grills Inga

    2007-05-01

    Full Text Available Abstract Background To correlate the metabolic changes with size changes for tumor response by concomitant PET-CT evaluation of lung cancers after radiotherapy. Methods 36 patients were studied pre- and post-radiotherapy with18FDG PET-CT scans at a median interval of 71 days. All of the patients were followed clinically and radiographically after a mean period of 342 days for assessment of local control or failure rates. Change in size (sum of maximum orthogonal diameters was correlated with that of maximum standard uptake value (SUV of the primary lung cancer before and after conventional radiotherapy. Results There was a significant reduction in both SUV and size of the primary cancer after radiotherapy (p Conclusion Correlating and incorporating metabolic change by PET into size change by concomitant CT is more sensitive in assessing therapeutic response than CT alone.

  10. Differential metabolic responses of Beauveria bassiana cultured in pupae extracts, root exudates and its interactions with insect and plant.

    Science.gov (United States)

    Luo, Feifei; Wang, Qian; Yin, Chunlin; Ge, Yinglu; Hu, Fenglin; Huang, Bo; Zhou, Hong; Bao, Guanhu; Wang, Bin; Lu, Ruili; Li, Zengzhi

    2015-09-01

    and distilled water. This indicates that fungal fatty acid metabolism is enhanced when contacting insect, but when in the absence of insect hosts NRP synthesis is increased. Ornithine, arginine and GABA are decreased in mycelia cultured in pupae extracts and root exudates but remain unchanged in distilled water, which suggests that they may be associated with fungal cross-talk with insects and plants. Trehalose and mannitol are decreased while adenine is increased in three conditions, signifying carbon shortage in cells. Together, these results unveil that B. bassiana has differential metabolic responses in pupae extracts and root exudates, and metabolic similarity in root exudates and distilled water is possibly due to the lack of insect components. Copyright © 2015. Published by Elsevier Inc.

  11. Insulin Responsiveness in Metabolic Syndrome after Eight Weeks of Cycle Training

    Science.gov (United States)

    Stuart, Charles A.; South, Mark A.; Lee, Michelle L.; McCurry, Melanie P.; Howell, Mary E. A.; Ramsey, Michael W.; Stone, Michael H.

    2013-01-01

    Introduction Insulin resistance in obesity is decreased after successful diet and exercise. Aerobic exercise training alone was evaluated as an intervention in subjects with the metabolic syndrome. Methods Eighteen non-diabetic, sedentary subjects, eleven with the metabolic syndrome, participated in eight weeks of increasing intensity stationary cycle training. Results Cycle training without weight loss did not change insulin resistance in metabolic syndrome subjects or sedentary control subjects. Maximal oxygen consumption (VO2max), activated muscle AMP-dependent kinase, and muscle mitochondrial marker ATP synthase all increased. Strength, lean body mass, and fat mass did not change. Activated mammalian target of rapamycin was not different after training. Training induced a shift in muscle fiber composition in both groups but in opposite directions. The proportion of 2x fibers decreased with a concomitant increase in 2a mixed fibers in the control subjects, but in metabolic syndrome, 2x fiber proportion increased and type 1 fibers decreased. Muscle fiber diameters increased in all three fiber types in metabolic syndrome subjects. Muscle insulin receptor expression increased in both groups and GLUT4 expression increased in the metabolic syndrome subjects. Excess phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser337 in metabolic syndrome muscle tended to increase further after training in spite of a decrease in total IRS-1. Conclusion In the absence of weight loss, cycle training of metabolic syndrome subjects resulted in enhanced mitochondrial biogenesis, and increased expression of insulin receptors and GLUT4 in muscle, but did not decrease the insulin resistance. The failure for the insulin signal to proceed past IRS-1 tyrosine phosphorylation may be related to excess serine phosphorylation at IRS-1 Ser337 and this is not ameliorated by eight weeks of endurance exercise training. PMID:23669880

  12. Metabolic response of the cerebral cortex following gentle sleep deprivation and modafinil administration.

    OpenAIRE

    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...

  13. Hair cortisol and cortisol awakening response are associated with criteria of the metabolic syndrome in opposite directions.

    Science.gov (United States)

    Kuehl, Linn K; Hinkelmann, Kim; Muhtz, Christoph; Dettenborn, Lucia; Wingenfeld, Katja; Spitzer, Carsten; Kirschbaum, Clemens; Wiedemann, Klaus; Otte, Christian

    2015-01-01

    Findings on the association between hypothalamic-pituitary-adrenal (HPA) axis activity and metabolic risk are equivocal. Different methods of measuring HPA activity might indicate adverse vs. beneficial effects of HPA activity on metabolic risk thus contributing to heterogenous findings. In this study, we aimed to determine whether (1) the salivary cortisol awakening response (CAR) as a marker of awakening-induced activation of the HPA axis and (2) hair cortisol as a marker of long-term cortisol secretion are associated with criteria of the metabolic syndrome. Therefore, we recruited 41 healthy individuals (26 women, mean age: 41.2 years) and 44 patients with major depression (28 women, 41.4 years) and assessed CAR and hair cortisol values as well as all criteria of the metabolic syndrome (abdominal obesity, blood pressure, plasma glucose, triglycerides and high-density cholesterol levels) according to the International Diabetes Federation. CAR and hair cortisol values were divided into tertiles. Across groups, participants with hair cortisol or hair cortisone in the highest tertile showed significantly more criteria of the metabolic syndrome compared to participants in the medium or low tertile (F2,64=3.37, p=.04). These results were corroborated by significant positive correlations between mean hair cortisol values with waist circumference (r=.29, p=.03), triglycerides (r=.34, p=.01) and systolic blood pressure (r=.29, p=.04) and between mean hair cortisone and triglycerides (r=.46, pcortisol and hair cortisone levels but lower CAR values are associated with an unfavorable metabolic and cardiovascular risk profile. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Circadian clock genes Per1 and Per2 regulate the response of metabolism-associated transcripts to sleep disruption.

    Directory of Open Access Journals (Sweden)

    Jana Husse

    Full Text Available Human and animal studies demonstrate that short sleep or poor sleep quality, e.g. in night shift workers, promote the development of obesity and diabetes. Effects of sleep disruption on glucose homeostasis and liver physiology are well documented. However, changes in adipokine levels after sleep disruption suggest that adipocytes might be another important peripheral target of sleep. Circadian clocks regulate metabolic homeostasis and clock disruption can result in obesity and the metabolic syndrome. The finding that sleep and clock disruption have very similar metabolic effects prompted us to ask whether the circadian clock machinery may mediate the metabolic consequences of sleep disruption. To test this we analyzed energy homeostasis and adipocyte transcriptome regulation in a mouse model of shift work, in which we prevented mice from sleeping during the first six hours of their normal inactive phase for five consecutive days (timed sleep restriction--TSR. We compared the effects of TSR between wild-type and Per1/2 double mutant mice with the prediction that the absence of a circadian clock in Per1/2 mutants would result in a blunted metabolic response to TSR. In wild-types, TSR induces significant transcriptional reprogramming of white adipose tissue, suggestive of increased lipogenesis, together with increased secretion of the adipokine leptin and increased food intake, hallmarks of obesity and associated leptin resistance. Some of these changes persist for at least one week after the end of TSR, indicating that even short episodes of sleep disruption can induce prolonged physiological impairments. In contrast, Per1/2 deficient mice show blunted effects of TSR on food intake, leptin levels and adipose transcription. We conclude that the absence of a functional clock in Per1/2 double mutants protects these mice from TSR-induced metabolic reprogramming, suggesting a role of the circadian timing system in regulating the physiological effects

  15. Seasonal variations in the pattern of RNA metabolism of tuber tissue in response to excision and culture

    International Nuclear Information System (INIS)

    Macleod, A.J.; Mills, E.D.; Yeoman, M.M.

    1979-01-01

    Between December 1975 and June 1976 explants excised from Jerusalem artichoke tubers were cultured in the presence and in the absence of 2,4-D, the cells in the tissue dividing only in the presence of 2,4-D, in which the length of the first cell cycle increased nonlinearly from 18 hours to 40 hours as the tubers aged in storage at 4 0 C. Simultaneously the amount of RNA in the tissue declined linearly from 8 to 5 μg RNA per explant. Detailed examination of the RNA metabolism in dividing and in non-dividing cells during February and June 1976 revealed superimposed but independent responses to wounding during excision and to stimulation into growth by 2,4-D. The responses to wounding involved only a very low level of metabolic activity, were complete within a few hours of excision and changed very little with the storage of the tubers. Tissue treated with 2,4-D showed a much higher level of metabolic activity including the periodic accumulation of RNA coupled to its discontinuous synthesis. The features of these growth-related responses changed considerably during the investigation. (author)

  16. Functional imaging to monitor vascular and metabolic response in canine head and neck tumors during fractionated radiotherapy.

    Science.gov (United States)

    Rødal, Jan; Rusten, Espen; Søvik, Åste; Skogmo, Hege Kippenes; Malinen, Eirik

    2013-10-01

    Radiotherapy causes alterations in tumor biology, and non-invasive early assessment of such alterations may become useful for identifying treatment resistant disease. The purpose of the current work is to assess changes in vascular and metabolic features derived from functional imaging of canine head and neck tumors during fractionated radiotherapy. Material and methods. Three dogs with spontaneous head and neck tumors received intensity-modulated radiotherapy (IMRT). Contrast-enhanced cone beam computed tomography (CE-CBCT) at the treatment unit was performed at five treatment fractions. Dynamic (18)FDG-PET (D-PET) was performed prior to the start of radiotherapy, at mid-treatment and at 3-12 weeks after the completion of treatment. Tumor contrast enhancement in the CE-CBCT images was used as a surrogate for tumor vasculature. Vascular and metabolic tumor parameters were further obtained from the D-PET images. Changes in these tumor parameters were assessed, with emphasis on intra-tumoral distributions. Results. For all three patients, metabolic imaging parameters obtained from D-PET decreased from the pre- to the inter-therapy session. Correspondingly, for two of three patients, vascular imaging parameters obtained from both CE-CBCT and D-PET increased. Only one of the tumors showed a clear metabolic response after therapy. No systematic changes in the intra-tumor heterogeneity in the imaging parameters were found. Conclusion. Changes in vascular and metabolic parameters could be detected by the current functional imaging methods. Vascular tumor features from CE-CBCT and D-PET corresponded well. CE-CBCT is a potential method for easy response assessment when the patient is at the treatment unit.

  17. Acute Cardiorespiratory and Metabolic Responses During Exoskeleton-Assisted Walking Overground Among Persons with Chronic Spinal Cord Injury.

    Science.gov (United States)

    Evans, Nicholas; Hartigan, Clare; Kandilakis, Casey; Pharo, Elizabeth; Clesson, Ismari

    2015-01-01

    Lower extremity robotic exoskeleton technology is being developed with the promise of affording people with spinal cord injury (SCI) the opportunity to stand and walk. The mobility benefits of exoskeleton-assisted walking can be realized immediately, however the cardiorespiratory and metabolic benefits of this technology have not been thoroughly investigated. The purpose of this pilot study was to evaluate the acute cardiorespiratory and metabolic responses associated with exoskeleton-assisted walking overground and to determine the degree to which these responses change at differing walking speeds. Five subjects (4 male, 1 female) with chronic SCI (AIS A) volunteered for the study. Expired gases were collected during maximal graded exercise testing and two, 6-minute bouts of exoskeleton-assisted walking overground. Outcome measures included peak oxygen consumption (V̇O2peak), average oxygen consumption (V̇O2avg), peak heart rate (HRpeak), walking economy, metabolic equivalent of tasks for SCI (METssci), walk speed, and walk distance. Significant differences were observed between walk-1 and walk-2 for walk speed, total walk distance, V̇O2avg, and METssci. Exoskeleton-assisted walking resulted in %V̇O2peak range of 51.5% to 63.2%. The metabolic cost of exoskeleton-assisted walking ranged from 3.5 to 4.3 METssci. Persons with motor-complete SCI may be limited in their capacity to perform physical exercise to the extent needed to improve health and fitness. Based on preliminary data, cardiorespiratory and metabolic demands of exoskeleton-assisted walking are consistent with activities performed at a moderate intensity.

  18. Acute Cardiorespiratory and Metabolic Responses During Exoskeleton-Assisted Walking Overground Among Persons with Chronic Spinal Cord Injury

    Science.gov (United States)

    Hartigan, Clare; Kandilakis, Casey; Pharo, Elizabeth; Clesson, Ismari

    2015-01-01

    Background: Lower extremity robotic exoskeleton technology is being developed with the promise of affording people with spinal cord injury (SCI) the opportunity to stand and walk. The mobility benefits of exoskeleton-assisted walking can be realized immediately, however the cardiorespiratory and metabolic benefits of this technology have not been thoroughly investigated. Objective: The purpose of this pilot study was to evaluate the acute cardiorespiratory and metabolic responses associated with exoskeleton-assisted walking overground and to determine the degree to which these responses change at differing walking speeds. Methods: Five subjects (4 male, 1 female) with chronic SCI (AIS A) volunteered for the study. Expired gases were collected during maximal graded exercise testing and two, 6-minute bouts of exoskeleton-assisted walking overground. Outcome measures included peak oxygen consumption (V̇O2peak), average oxygen consumption (V̇O2avg), peak heart rate (HRpeak), walking economy, metabolic equivalent of tasks for SCI (METssci), walk speed, and walk distance. Results: Significant differences were observed between walk-1 and walk-2 for walk speed, total walk distance, V̇O2avg, and METssci. Exoskeleton-assisted walking resulted in %V̇O2peak range of 51.5% to 63.2%. The metabolic cost of exoskeleton-assisted walking ranged from 3.5 to 4.3 METssci. Conclusion: Persons with motor-complete SCI may be limited in their capacity to perform physical exercise to the extent needed to improve health and fitness. Based on preliminary data, cardiorespiratory and metabolic demands of exoskeleton-assisted walking are consistent with activities performed at a moderate intensity. PMID:26364281

  19. Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Keam, Bhumsuk; Moon, Woo Kyung; Kim, Tae-You; Park, In Ae; Noh, Dong-Young; Chung, June-Key; Bang, Yung-Jue; Im, Seock-Ah; Koh, Youngil; Han, Sae-Won; Oh, Do-Youn; Cho, Nariya; Kim, Jee Hyun; Han, Wonshik; Kang, Keon Wook

    2011-01-01

    This study was aimed 1) to investigate the predictive value of FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) for histopathologic response and 2) to explore the results of FDG PET/CT by molecular phenotypes of breast cancer patients who received neoadjuvant chemotherapy. Seventy-eight stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for evaluating early metabolic response. The mean pre- and post-chemotherapy standard uptake value (SUV) were 7.5 and 3.9, respectively. The early metabolic response provided by FDG PET/CT after one cycle of neoadjuvant chemotherapy was correlated with the histopathologic response after completion of neoadjuvant chemotherapy (P = 0.002). Sensitivity and negative predictive value were 85.7% and 95.1%, respectively. The estrogen receptor negative phenotype had a higher pre-chemotherapy SUV (8.6 vs. 6.4, P = 0.047) and percent change in SUV (48% vs. 30%, P = 0.038). In triple negative breast cancer (TNBC), the pre-chemotherapy SUV was higher than in non-TNBC (9.8 vs. 6.4, P = 0.008). The early metabolic response using FDG PET/CT could have a predictive value for the assessment of histopathologic non-response of stage II/III breast cancer treated with neoadjuvant chemotherapy. Our findings suggest that the initial SUV and the decline in SUV differed based on the molecular phenotype. ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/NCT01396655

  20. Acclimation temperature affects the metabolic response of amphibian skeletal muscle to insulin.

    Science.gov (United States)

    Petersen, Ann M; Gleeson, Todd T

    2011-09-01

    Frog skeletal muscle mainly utilizes the substrates glucose and lactate for energy metabolism. The goal of this study was to determine the effect of insulin on the uptake and metabolic fate of lactate and glucose at rest in skeletal muscle of the American bullfrog, Lithobates catesbeiana, under varying temperature regimens. We hypothesize that lactate and glucose metabolic pathways will respond differently to the presence of insulin in cold versus warm acclimated frog tissues, suggesting an interaction between temperature and metabolism under varying environmental conditions. We employed radiolabeled tracer techniques to measure in vitro uptake, oxidation, and incorporation of glucose and lactate into glycogen by isolated muscles from bullfrogs acclimated to 5 °C (cold) or 25 °C (warm). Isolated bundles from Sartorius muscles were incubated at 5 °C, 15 °C, or 25 °C, and in the presence and absence of 0.05 IU/mL bovine insulin. Insulin treatment in the warm acclimated and incubated frogs resulted in an increase in glucose incorporation into glycogen, and an increase in intracellular [glucose] of 0.5 μmol/g (Pmuscle. When compared to the warm treatment group, cold acclimation and incubation resulted in increased rates of glucose oxidation and glycogen synthesis, and a reduction in free intracellular glucose levels (Pmuscles from either acclimation group were incubated at an intermediate temperature of 15 °C, insulin's effect on substrate metabolism was attenuated or even reversed. Therefore, a significant interaction between insulin and acclimation condition in controlling skeletal muscle metabolism appears to exist. Our findings further suggest that one of insulin's actions in frog muscle is to increase glucose incorporation into glycogen, and to reduce reliance on lactate as the primary metabolic fuel. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Increased Contractile Response to Noradrenaline Induced By Factors Associated with the Metabolic Syndrome in Cultured Small Mesenteric Arteries

    DEFF Research Database (Denmark)

    Blædel, Martin; Sams, Anette; Boonen, Harrie C M

    2016-01-01

    UNLABELLED: This study investigated the effect of the metabolic syndrome associated risk factors hyperglycemia (glucose [Glc]), hyperinsulinemia (insulin [Ins]) and low-grade inflammation (tumor necrosis factor α [TNFα]) on the vasomotor responses of resistance arteries. Isolated small mesenteric...... arteries from 3-month-old Sprague-Dawley rats, were suspended for 21-23 h in tissue cultures containing either elevated Glc (30 mmol/l), Ins (100 nmol/l), TNFα (100 ng/ml) or combinations thereof. After incubation, the vascular response to noradrenaline (NA), phenylephrine, isoprenaline and NA...... in vascular tone....

  2. Oxidative Metabolism Genes Are Not Responsive to Oxidative Stress in Rodent Beta Cell Lines

    Directory of Open Access Journals (Sweden)

    Faer Morrison

    2012-01-01

    Full Text Available Altered expression of oxidative metabolism genes has been described in the skeletal muscle of individuals with type 2 diabetes. Pancreatic beta cells contain low levels of antioxidant enzymes and are particularly susceptible to oxidative stress. In this study, we explored the effect of hyperglycemia-induced oxidative stress on a panel of oxidative metabolism genes in a rodent beta cell line. We exposed INS-1 rodent beta cells to low (5.6 mmol/L, ambient (11 mmol/L, and high (28 mmol/L glucose conditions for 48 hours. Increases in oxidative stress were measured using the fluorescent probe dihydrorhodamine 123. We then measured the expression levels of a panel of 90 oxidative metabolism genes by real-time PCR. Elevated reactive oxygen species (ROS production was evident in INS-1 cells after 48 hours (P<0.05. TLDA analysis revealed a significant (P<0.05 upregulation of 16 of the 90 genes under hyperglycemic conditions, although these expression differences did not reflect differences in ROS. We conclude that although altered glycemia may influence the expression of some oxidative metabolism genes, this effect is probably not mediated by increased ROS production. The alterations to the expression of oxidative metabolism genes previously observed in human diabetic skeletal muscle do not appear to be mirrored in rodent pancreatic beta cells.

  3. Seaweed supplements normalise metabolic, cardiovascular and liver responses in high-carbohydrate, high-fat fed rats.

    Science.gov (United States)

    Kumar, Senthil Arun; Magnusson, Marie; Ward, Leigh C; Paul, Nicholas A; Brown, Lindsay

    2015-02-02

    Increased seaweed consumption may be linked to the lower incidence of metabolic syndrome in eastern Asia. This study investigated the responses to two tropical green seaweeds, Ulva ohnoi (UO) and Derbesia tenuissima (DT), in a rat model of human metabolic syndrome. Male Wistar rats (330-340 g) were fed either a corn starch-rich diet or a high-carbohydrate, high-fat diet with 25% fructose in drinking water, for 16 weeks. High-carbohydrate, high-fat diet-fed rats showed the signs of metabolic syndrome leading to abdominal obesity, cardiovascular remodelling and non-alcoholic fatty liver disease. Food was supplemented with 5% dried UO or DT for the final 8 weeks only. UO lowered total final body fat mass by 24%, systolic blood pressure by 29 mmHg, and improved glucose utilisation and insulin sensitivity. In contrast, DT did not change total body fat mass but decreased plasma triglycerides by 38% and total cholesterol by 17%. UO contained 18.1% soluble fibre as part of 40.9% total fibre, and increased magnesium, while DT contained 23.4% total fibre, essentially as insoluble fibre. UO was more effective in reducing metabolic syndrome than DT, possibly due to the increased intake of soluble fibre and magnesium.

  4. Seaweed Supplements Normalise Metabolic, Cardiovascular and Liver Responses in High-Carbohydrate, High-Fat Fed Rats

    Directory of Open Access Journals (Sweden)

    Senthil Arun Kumar

    2015-02-01

    Full Text Available Increased seaweed consumption may be linked to the lower incidence of metabolic syndrome in eastern Asia. This study investigated the responses to two tropical green seaweeds, Ulva ohnoi (UO and Derbesia tenuissima (DT, in a rat model of human metabolic syndrome. Male Wistar rats (330–340 g were fed either a corn starch-rich diet or a high-carbohydrate, high-fat diet with 25% fructose in drinking water, for 16 weeks. High-carbohydrate, high-fat diet-fed rats showed the signs of metabolic syndrome leading to abdominal obesity, cardiovascular remodelling and non-alcoholic fatty liver disease. Food was supplemented with 5% dried UO or DT for the final 8 weeks only. UO lowered total final body fat mass by 24%, systolic blood pressure by 29 mmHg, and improved glucose utilisation and insulin sensitivity. In contrast, DT did not change total body fat mass but decreased plasma triglycerides by 38% and total cholesterol by 17%. UO contained 18.1% soluble fibre as part of 40.9% total fibre, and increased magnesium, while DT contained 23.4% total fibre, essentially as insoluble fibre. UO was more effective in reducing metabolic syndrome than DT, possibly due to the increased intake of soluble fibre and magnesium.

  5. Seaweed Supplements Normalise Metabolic, Cardiovascular and Liver Responses in High-Carbohydrate, High-Fat Fed Rats

    Science.gov (United States)

    Kumar, Senthil Arun; Magnusson, Marie; Ward, Leigh C.; Paul, Nicholas A.; Brown, Lindsay

    2015-01-01

    Increased seaweed consumption may be linked to the lower incidence of metabolic syndrome in eastern Asia. This study investigated the responses to two tropical green seaweeds, Ulva ohnoi (UO) and Derbesia tenuissima (DT), in a rat model of human metabolic syndrome. Male Wistar rats (330–340 g) were fed either a corn starch-rich diet or a high-carbohydrate, high-fat diet with 25% fructose in drinking water, for 16 weeks. High-carbohydrate, high-fat diet-fed rats showed the signs of metabolic syndrome leading to abdominal obesity, cardiovascular remodelling and non-alcoholic fatty liver disease. Food was supplemented with 5% dried UO or DT for the final 8 weeks only. UO lowered total final body fat mass by 24%, systolic blood pressure by 29 mmHg, and improved glucose utilisation and insulin sensitivity. In contrast, DT did not change total body fat mass but decreased plasma triglycerides by 38% and total cholesterol by 17%. UO contained 18.1% soluble fibre as part of 40.9% total fibre, and increased magnesium, while DT contained 23.4% total fibre, essentially as insoluble fibre. UO was more effective in reducing metabolic syndrome than DT, possibly due to the increased intake of soluble fibre and magnesium. PMID:25648511

  6. Cardiovascular, respiratory and metabolic responses to temperature and hypoxia of the winter frog Rana catesbeiana

    Directory of Open Access Journals (Sweden)

    Rocha P.L.

    1997-01-01

    Full Text Available The objective of the present study was to determine the effects of hypoxia and temperature on the cardiovascular and respiratory systems and plasma glucose levels of the winter bullfrog Rana catesbeiana. Body temperature was maintained at 10, 15, 25 and 35oC for measurements of breathing frequency, heart rate, arterial blood pressure, metabolic rate, plasma glucose levels, blood gases and acid-base status. Reducing body temperature from 35 to 10oC decreased (P<0.001 heart rate (bpm from 64.0 ± 3.1 (N = 5 to 12.5 ± 2.5 (N = 6 and blood pressure (mmHg (P<0.05 from 41.9 ± 2.1 (N = 5 to 33.1 ± 2.1 (N = 6, whereas no significant changes were observed under hypoxia. Hypoxia-induced changes in breathing frequency and acid-base status were proportional to body temperature, being pronounced at 25oC, less so at 15oC, and absent at 10oC. Hypoxia at 35oC was lethal. Under normoxia, plasma glucose concentration (mg/dl decreased (P<0.01 from 53.0 ± 3.4 (N = 6 to 35.9 ± 1.7 (N = 6 at body temperatures of 35 and 10oC, respectively. Hypoxia had no significant effect on plasma glucose concentration at 10 and 15oC, but at 25oC there was a significant increase under conditions of 3% inspired O2. The arterial PO2 and pH values were similar to those reported in previous studies on non-estivating Rana catesbeiana, but PaCO2 (37.5 ± 1.9 mmHg, N = 5 was 3-fold higher, indicating increased plasma bicarbonate levels. The estivating bullfrog may be exposed not only to low temperatures but also to hypoxia. These animals show temperature-dependent responses that may be beneficial since during low body temperatures the sensitivity of most physiological systems to hypoxia is reduced

  7. Ionomic and metabolic responses to neutral salt or alkaline salt stresses in maize (Zea mays L.) seedlings.

    Science.gov (United States)

    Guo, Rui; Shi, LianXuan; Yan, Changrong; Zhong, Xiuli; Gu, FengXue; Liu, Qi; Xia, Xu; Li, Haoru

    2017-02-10

    Soil salinity and alkalinity present a serious threat to global agriculture. However, most of the studies have focused on neutral salt stress, and the information on the metabolic responses of plants to alkaline salt stress is limited. This investigation aimed at determining the influence of neutral salt and alkaline salt stresses on the content of metal elements and metabolites in maize plant tissues, by using mixtures of various proportions of NaCl, NaHCO 3 , Na 2 SO 4 , and Na 2 CO 3 . We found that alkaline salt stress suppressed more pronouncedly the photosynthesis and growth of maize plants than salinity stress. Under alkaline salt stress conditions, metal ions formed massive precipitates, which ultimately reduced plant nutrient availability. On the other hand, high neutral salt stress induced metabolic changes in the direction of gluconeogenesis leading to the enhanced formation of sugars as a reaction contributing to the mitigation of osmotic stress. Thus, the active synthesis of sugars in shoots was essential to the development of salt tolerance. However, the alkaline salt stress conditions characterized by elevated pH values suppressed substantially the levels of photosynthesis, N metabolism, glycolysis, and the production of sugars and amino acids. These results indicate the presence of different defensive mechanisms responsible for the plant responses to neutral salt and alkaline salt stresses. In addition, the increased concentration of organic acids and enhanced metabolic energy might be potential major factors that can contribute to the maintenance intracellular ion balance in maize plants and counteract the negative effects of high pH under alkaline salt stress.

  8. Response of lactate metabolism in brain glucosensing areas of rainbow trout (Oncorhynchus mykiss) to changes in glucose levels.

    Science.gov (United States)

    Otero-Rodiño, Cristina; Librán-Pérez, Marta; Velasco, Cristina; Álvarez-Otero, Rosa; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

    2015-12-01

    There is no evidence in fish brain demonstrating the existence of changes in lactate metabolism in response to alterations in glucose levels. We induced in rainbow trout through intraperitoneal (IP) treatments, hypoglycaemic or hyperglycaemic changes to assess the response of parameters involved in lactate metabolism in glucosensing areas like hypothalamus and hindbrain. To distinguish those effects from those induced by peripheral changes in the levels of metabolites or hormones, we also carried out intracerebroventricular (ICV) treatments with 2-deoxy-D-glucose (2-DG, a non-metabolizable glucose analogue thus inducing local glucopenia) or glucose. Finally, we also incubated hypothalamus and hindbrain in vitro in the presence of increased glucose concentrations. The changes in glucose availability were in general correlated to changes in the amount of lactate in both areas. However, when we assessed in these areas the response of parameters related to lactate metabolism, the results obtained were contradictory. The increase in glucose levels did not produce in general the expected changes in those pathways with only a minor increase in their capacity of lactate production. The decrease in glucose levels was, however, more clearly related to a decreased capacity of the pathways involved in the production and use of lactate, and this was especially evident after ICV treatment with 2-DG in both areas. In conclusion, the present results while addressing the existence of changes in lactate metabolism after inducing changes in glucose levels in brain glucosensing areas only partially support the possible existence of an astrocyte-neuron lactate shuttle in hypothalamus and hindbrain of rainbow trout relating glucose availability to lactate production and use.

  9. Heat dissipation does not suppress an immune response in laboratory mice divergently selected for basal metabolic rate (BMR).

    Science.gov (United States)

    Książek, Aneta; Konarzewski, Marek

    2016-05-15

    The capacity for heat dissipation is considered to be one of the most important constraints on rates of energy expenditure in mammals. To date, the significance of this constraint has been tested exclusively under peak metabolic demands, such as during lactation. Here, we used a different set of metabolic stressors, which do not induce maximum energy expenditures and yet are likely to expose the potential constraining effect of heat dissipation. We compared the physiological responses of mice divergently selected for high (H-BMR) and low basal metabolic rate (L-BMR) to simultaneous exposure to the keyhole limpet haemocyanin (KLH) antigen and high ambient temperature (Ta). At 34°C (and at 23°C, used as a control), KLH challenge resulted in a transient increase in core body temperature (Tb) in mice of both line types (by approximately 0.4°C). Warm exposure did not produce line-type-dependent differences in Tb (which was consistently higher by ca. 0.6°C in H-BMR mice across both Ta values), nor did it result in the suppression of antibody synthesis. These findings were also supported by the lack of between-line-type differences in the mass of the thymus, spleen or lymph nodes. Warm exposure induced the downsizing of heat-generating internal organs (small intestine, liver and kidneys) and an increase in intrascapular brown adipose tissue mass. However, these changes were similar in scope in both line types. Mounting a humoral immune response in selected mice was therefore not affected by ambient temperature. Thus, a combined metabolic challenge of high Ta and an immune response did not appreciably compromise the capacity to dissipate heat, even in the H-BMR mice. © 2016. Published by The Company of Biologists Ltd.

  10. Transcriptome Analysis Identifies Key Metabolic Changes in the Hooded Seal (Cystophora cristata Brain in Response to Hypoxia and Reoxygenation.

    Directory of Open Access Journals (Sweden)

    Mariana Leivas Müller Hoff

    Full Text Available The brain of diving mammals tolerates low oxygen conditions better than the brain of most terrestrial mammals. Previously, it has been demonstrated that the neurons in brain slices of the hooded seal (Cystophora cristata withstand hypoxia longer than those of mouse, and also tolerate reduced glucose supply and high lactate concentrations. This tolerance appears to be accompanied by a shift in the oxidative energy metabolism to the astrocytes in the seal while in terrestrial mammals the aerobic energy production mainly takes place in neurons. Here, we used RNA-Seq to compare the effect of hypoxia and reoxygenation in vitro on brain slices from the visual cortex of hooded seals. We saw no general reduction of gene expression, suggesting that the response to hypoxia and reoxygenation is an actively regulated process. The treatments caused the preferential upregulation of genes related to inflammation, as found before e.g. in stroke studies using mammalian models. Gene ontology and KEGG pathway analyses showed a downregulation of genes involved in ion transport and other neuronal processes, indicative for a neuronal shutdown in response to a shortage of O2 supply. These differences may be interpreted in terms of an energy saving strategy in the seal's brain. We specifically analyzed the regulation of genes involved in energy metabolism. Hypoxia and reoxygenation caused a similar response, with upregulation of genes involved in glucose metabolism and downregulation of the components of the pyruvate dehydrogenase complex. We also observed upregulation of the monocarboxylate transporter Mct4, suggesting increased lactate efflux. Together, these data indicate that the seal brain responds to the hypoxic challenge by a relative increase in the anaerobic energy metabolism.

  11. Hepatic injury induces contrasting response in liver and kidney to chemicals that are metabolically activated: Role of male sex hormone

    International Nuclear Information System (INIS)

    Kim, Young C.; Yim, Hye K.; Jung, Young S.; Park, Jae H.; Kim, Sung Y.

    2007-01-01

    Injury to liver, resulting in loss of its normal physiological/biochemical functions, may adversely affect a secondary organ. We examined the response of the liver and kidney to chemical substances that require metabolic activation for their toxicities in mice with a preceding liver injury. Carbon tetrachloride treatment 24 h prior to a challenging dose of carbon tetrachloride or acetaminophen decreased the resulting hepatotoxicity both in male and female mice as determined by histopathological examination and increases in serum enzyme activities. In contrast, the renal toxicity of the challenging toxicants was elevated markedly in male, but not in female mice. Partial hepatectomy also induced similar changes in the hepatotoxicity and nephrotoxicity of a challenging toxicant, suggesting that the contrasting response of male liver and kidney was associated with the reduction of the hepatic metabolizing capacity. Carbon tetrachloride pretreatment or partial hepatectomy decreased the hepatic xenobiotic-metabolizing enzyme activities in both sexes but elevated the renal p-nitrophenol hydroxylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase activities significantly only in male mice. Increases in Cyp2e1 and Cyp2b expression were also evident in male kidney. Castration of males or testosterone administration to females diminished the sex-related differences in the renal response to an acute liver injury. The results indicate that reduction of the hepatic metabolizing capacity induced by liver injury may render secondary target organs susceptible to chemical substances activated in these organs. This effect may be sex-specific. It is also suggested that an integrated approach should be taken for proper assessment of chemical hazards

  12. Metabolomics reveals metabolic targets and biphasic responses in breast cancer cells treated by curcumin alone and in association with docetaxel.

    Directory of Open Access Journals (Sweden)

    Mathilde Bayet-Robert

    Full Text Available BACKGROUND: Curcumin (CUR has deserved extensive research due to its anti-inflammatory properties, of interest in human diseases including cancer. However, pleiotropic even paradoxical responses of tumor cells have been reported, and the mechanisms of action of CUR remain uncompletely elucidated. METHODOLOGY/PRINCIPAL FINDINGS: (1H-NMR spectroscopy-based metabolomics was applied to get novel insight into responses of MCF7 and MDA-MB-231 breast cancer cells to CUR alone, and MCF7 cells to CUR in cotreatment with docetaxel (DTX. In both cell types, a major target of CUR was glutathione metabolism. Total glutathione (GSx increased at low dose CUR (≤ 10 mg.l(-1-28 µM- (up to +121% in MCF7 cells, P<0.01, and +138% in MDA-MB-231 cells, P<0.01, but decreased at high dose (≥ 25 mg.l(-1 -70 µM- (-49%, in MCF7 cells, P<0.02, and -56% in MDA-MB-231 cells, P<0.025. At high dose, in both cell types, GSx-related metabolites decreased, including homocystein, creatine and taurine (-60 to -80%, all, P<0.05. Together with glutathione-S-transferase actvity, data established that GSx biosynthesis was upregulated at low dose, and GSx consumption activated at high dose. Another major target, in both cell types, was lipid metabolism involving, at high doses, accumulation of polyunsaturated and total free fatty acids (between ×4.5 and ×11, P<0.025, and decrease of glycerophospho-ethanolamine and -choline (about -60%, P<0.025. Multivariate statistical analyses showed a metabolic transition, even a biphasic behavior of some metabolites including GSx, between low and high doses. In addition, CUR at 10 mg.l(-1 in cotreatment with DTX induced modifications in glutathione metabolism, lipid metabolism, and glucose utilization. Some of these changes were biphasic depending on the duration of exposure to CUR. CONCLUSIONS/SIGNIFICANCE: Metabolomics reveals major metabolic targets of CUR in breast cancer cells, and biphasic responses that challenge the widely accepted

  13. Differential metabolic responses in three life stages of mussels Mytilus galloprovincialis exposed to cadmium.

    Science.gov (United States)

    Wu, Huifeng; Xu, Lanlan; Yu, Deliang; Ji, Chenglong

    2017-01-01

    Cadmium (Cd) is one of the most important metal contaminants in the Bohai Sea. In this work, NMR-based metabolomics was used to investigate the toxicological effects of Cd at an environmentally relevant concentration (50 µg L -1 ) in three different life stages (D-shape larval, juvenile and adult) of mussels Mytilus galloprovincialis. Results indicated that the D-shape larval mussel was the most sensitive life stage to Cd. The significantly different metabolic profiles meant that Cd induced differential toxicological effects in three life stages of mussels. Basically, Cd caused osmotic stress in all the three life stages via different metabolic pathways. Cd exposure reduced the anaerobiosis in D-shape larval mussels and disturbed lipid metabolism in juvenile mussels, respectively. Compared with the D-shape larval and juvenile mussels, the adult mussels reduced energy consumption to deal with Cd stress.

  14. Biphasic response of action potential duration to metabolic inhibition in rabbit and human ventricular myocytes: role of transient outward current and ATP-regulated potassium current

    NARCIS (Netherlands)

    Verkerk, A. O.; Veldkamp, M. W.; van Ginneken, A. C.; Bouman, L. N.

    1996-01-01

    Inhibition of cell metabolism is associated with significant changes in action potential duration. The aim of this study was to investigate the time course of the changes in action potential duration during metabolic inhibition and to determine what changes in membrane currents are responsible. The

  15. Physiological response to extreme fasting in subantarctic fur seal (Arctocephalus tropicalis) pups: metabolic rates, energy reserve utilization, and water fluxes.

    Science.gov (United States)

    Verrier, Delphine; Groscolas, René; Guinet, Christophe; Arnould, John P Y

    2009-11-01

    Surviving prolonged fasting requires various metabolic adaptations, such as energy and protein sparing, notably when animals are simultaneously engaged in energy-demanding processes such as growth. Due to the intermittent pattern of maternal attendance, subantarctic fur seal pups have to repeatedly endure exceptionally long fasting episodes throughout the 10-mo rearing period while preparing for nutritional independence. Their metabolic responses to natural prolonged fasting (33.4 +/- 3.3 days) were investigated at 7 mo of age. Within 4-6 fasting days, pups shifted into a stage of metabolic economy characterized by a minimal rate of body mass loss (0.7%/day) and decreased resting metabolic rate (5.9 +/- 0.1 ml O(2)xkg(-1)xday(-1)) that was only 10% above the level predicted for adult terrestrial mammals. Field metabolic rate (289 +/- 10 kJxkg(-1)xday(-1)) and water influx (7.9 +/- 0.9 mlxkg(-1)xday(-1)) were also among the lowest reported for any young otariid, suggesting minimized energy allocation to behavioral activity and thermoregulation. Furthermore, lean tissue degradation was dramatically reduced. High initial adiposity (>48%) and predominant reliance on lipid catabolism likely contributed to the exceptional degree of protein sparing attained. Blood chemistry supported these findings and suggested utilization of alternative fuels, such as beta-hydroxybutyrate and de novo synthesized glucose from fat-released glycerol. Regardless of sex and body condition, pups tended to adopt a convergent strategy of extreme energy and lean body mass conservation that appears highly adaptive for it allows some tissue growth during the repeated episodes of prolonged fasting they experience throughout their development.

  16. Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

    International Nuclear Information System (INIS)

    McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A.; Alaee, Mehran; Simpson, Andre J.; Simpson, Myrna J.

    2011-01-01

    Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: → NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. → Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. → NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - 1 H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

  17. Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

    Energy Technology Data Exchange (ETDEWEB)

    McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Alaee, Mehran [Environment Canada, 867 Lakeshore Rd., P.O. Box 5050, Burlington, ON L7R 4A6 (Canada); Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada)

    2011-12-15

    Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: > NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. > Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. > NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - {sup 1}H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

  18. METABOLIC AND HORMONAL RESPONSES TO ADRENOCEPTOR ANTAGONISTS IN 48-HOUR-STARVED EXERCISING RATS

    NARCIS (Netherlands)

    BENTHEM, L; VANDERLEEST, J; STEFFENS, AB; ZIJLSTRA, WG

    1995-01-01

    The influence of 48 hours of starvation on sympathoadrenal regulation of nutrient utilization was investigated in rats. To assess the role of alpha- and beta-adrenoceptors, rats were studied during alpha- and beta-blockade. Energy metabolism was measured using indirect calorimetry before, during,

  19. Type I Interferon Responses Drive Intrahepatic T cells to Promote Metabolic Syndrome

    DEFF Research Database (Denmark)

    Ghazarian, Magar; Revelo, Xavier S; Nøhr, Mark K

    2017-01-01

    Obesity-related insulin resistance is driven by low-grade chronic inflammation of metabolic tissues. In the liver, non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance and systemic glucose dysregulation. However, the immunological factors supporting these proces...

  20. LXR signaling couples sterol metabolism to proliferation in the acquired immune response

    NARCIS (Netherlands)

    Bensinger, Steven J.; Bradley, Michelle N.; Joseph, Sean B.; Zelcer, Noam; Janssen, Edith M.; Hausner, Mary Ann; Shih, Roger; Parks, John S.; Edwards, Peter A.; Jamieson, Beth D.; Tontonoz, Peter

    2008-01-01

    Cholesterol is essential for membrane synthesis; however, the mechanisms that link cellular lipid metabolism to proliferation are incompletely understood. We demonstrate here that cellular cholesterol levels in dividing T cells are maintained in part through reciprocal regulation of the LXR and

  1. Metabolic state defines the response of rabbit ovarian cells to leptin

    DEFF Research Database (Denmark)

    Harrath, Abdel Halim; Østrup, Olga; Rafay, Jan

    2017-01-01

    Leptin is a hormone that mediates the effect of the metabolic state on several biological functions, including reproduction. Leptin affects reproductive functions via alterations in the release of hormonal regulators. However, the extent to which caloric restriction (CR) can affect the complex...

  2. Blood flow and glucose metabolism in stage IV breast cancer: Heterogeneity of response during chemotherapy

    NARCIS (Netherlands)

    N.C. Krak (Nanda); J. van der Hoeven (John); O.S. Hoekstra (Otto); J.W.R. Twisk (Jos); E.E. van der Wall (Ernst); A.A. Lammertsma (Adriaan)

    2008-01-01

    textabstractObjective: The purpose of the study was to compare early changes in blood flow (BF) and glucose metabolism (MRglu) in metastatic breast cancer lesions of patients treated with chemotherapy. Methods: Eleven women with stage IV cancer and lesions in breast, lymph nodes, liver, and bone

  3. Exercise training and work task induced metabolic and stress-related mRNA and protein responses in myalgic muscles

    DEFF Research Database (Denmark)

    Sjøgaard, Gisela; Zebis, Mette Kreutzfeldt; Kiilerich, Kristian

    2013-01-01

    healthy controls. Those with myalgia performed similar to 7 hrs repetitive stressful work and were subsequently randomized to 10 weeks of specific strength training, general fitness training, or reference intervention. Muscles biopsies were taken from the trapezius muscle at baseline, after work and after...... 10 weeks intervention. The main findings are that the capacity of carbohydrate oxidation was reduced in myalgic compared with healthy muscle. Repetitive stressful work increased mRNA content for heat shock proteins and decreased levels of key regulators for growth and oxidative metabolism......The aim was to assess mRNA and/or protein levels of heat shock proteins, cytokines, growth regulating, and metabolic proteins in myalgic muscle at rest and in response to work tasks and prolonged exercise training. A randomized controlled trial included 28 females with trapezius myalgia and 16...

  4. Metabolic response of Pseudomonas putida during redox biocatalysis in the presence of a second octanol phase.

    Science.gov (United States)

    Blank, Lars M; Ionidis, Georgios; Ebert, Birgitta E; Bühler, Bruno; Schmid, Andreas

    2008-10-01

    A key limitation of whole-cell redox biocatalysis for the production of valuable, specifically functionalized products is substrate/product toxicity, which can potentially be overcome by using solvent-tolerant micro-organisms. To investigate the inter-relationship of solvent tolerance and energy-dependent biocatalysis, we established a model system for biocatalysis in the presence of toxic low logP(ow) solvents: recombinant solvent-tolerant Pseudomonas putida DOT-T1E catalyzing the stereospecific epoxidation of styrene in an aqueous/octanol two-liquid phase reaction medium. Using (13)C tracer based metabolic flux analysis, we investigated the central carbon and energy metabolism and quantified the NAD(P)H regeneration rate in the presence of toxic solvents and during redox biocatalysis, which both drastically increased the energy demands of solvent-tolerant P. putida. According to the driven by demand concept, the NAD(P)H regeneration rate was increased up to eightfold by two mechanisms: (a) an increase in glucose uptake rate without secretion of metabolic side products, and (b) reduced biomass formation. However, in the presence of octanol, only approximately 1% of the maximally observed NAD(P)H regeneration rate could be exploited for styrene epoxidation, of which the rate was more than threefold lower compared with operation with a non-toxic solvent. This points to a high energy and redox cofactor demand for cell maintenance, which limits redox biocatalysis in the presence of octanol. An estimated upper bound for the NAD(P)H regeneration rate available for biocatalysis suggests that cofactor availability does not limit redox biocatalysis under optimized conditions, for example, in the absence of toxic solvent, and illustrates the high metabolic capacity of solvent-tolerant P. putida. This study shows that solvent-tolerant P. putida have the remarkable ability to compensate for high energy demands by boosting their energy metabolism to levels up to an order of

  5. Comparative metabolic responses and adaptive strategies of wheat (Triticum aestivum) to salt and alkali stress.

    Science.gov (United States)

    Guo, Rui; Yang, Zongze; Li, Feng; Yan, Changrong; Zhong, Xiuli; Liu, Qi; Xia, Xu; Li, Haoru; Zhao, Long

    2015-07-07

    It is well known that salinization (high-pH) has been considered as a major environmental threat to agricultural systems. The aim of this study was to investigate the differences between salt stress and alkali stress in metabolic profiles and nutrient accumulation of wheat; these parameters were also evaluated to determine the physiological adaptive mechanisms by which wheat tolerates alkali stress. The harmful effect of alkali stress on the growth and photosynthesis of wheat were stronger than those of salt stress. High-pH of alkali stress induced the most of phosphate and metal ions to precipitate; as a result, the availability of nutrients significantly declined. Under alkali stress, Ca sharply increased in roots, however, it decreased under salt stress. In addition, we detected the 75 metabolites that were different among the treatments according to GC-MS analysis, including organic acids, amino acids, sugars/polyols and others. The metabolic data showed salt stress and alkali stress caused different metabolic shifts; alkali stress has a stronger injurious effect on the distribution and accumulation of metabolites than salt stress. These outcomes correspond to specific detrimental effects of a highly pH environment. Ca had a significant positive correlation with alkali tolerates, and increasing Ca concentration can immediately trigger SOS Na exclusion system and reduce the Na injury. Salt stress caused metabolic shifts toward gluconeogenesis with increased sugars to avoid osmotic stress; energy in roots and active synthesis in leaves were needed by wheat to develop salt tolerance. Alkali stress (at high pH) significantly inhibited photosynthetic rate; thus, sugar production was reduced, N metabolism was limited, amino acid production was reduced, and glycolysis was inhibited.

  6. Comparison of PET metabolic indices for the early assessment of tumour response in metastatic colorectal cancer patients treated by polychemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Maisonobe, Jacques-Antoine; Necib, Hatem; Buvat, Irene [IMNC UMR 8165 CNRS - Paris 7 and Paris 11 Universities, Orsay Cedex (France); Garcia, Camilo A.; Vanderlinden, Bruno; Flamen, Patrick [Universite Libre de Bruxelles, Department of Nuclear Medicine, Institut Jules Bordet, Brussels (Belgium); Hendlisz, Alain [Universite Libre de Bruxelles, Department of Gastroenterology, Institut Jules Bordet, Brussels (Belgium)

    2013-02-15

    To compare the performance of eight metabolic indices for the early assessment of tumour response in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. Forty patients with advanced mCRC underwent two FDG PET/CT scans, at baseline and on day 14 after chemotherapy initiation. For each lesion, eight metabolic indices were calculated: four standardized uptake values (SUV) without correction for the partial volume effect (PVE), two SUV with correction for PVE, a metabolic volume (MV) and a total lesion glycolysis (TLG). The relative change in each index between the two scans was calculated for each lesion. Lesions were also classified as responding and nonresponding lesions using the Response Evaluation Criteria In Solid Tumours (RECIST) 1.0 measured by contrast-enhanced CT at baseline and 6-8 weeks after starting therapy. Bland-Altman analyses were performed to compare the various indices. Based on the RECIST classification, ROC analyses were used to determine how accurately the indices predicted lesion response to therapy later seen with RECIST. RECIST showed 27 responding and 74 nonresponding lesions. Bland-Altman analyses showed that the four SUV indices uncorrected for PVE could not be used interchangeably, nor could the two SUV corrected for PVE. The areas under the ROC curves (AUC) were not significantly different between the SUV indices not corrected for PVE. The mean SUV change in a lesion better predicted lesion response without than with PVE correction. The AUC was significantly higher for SUV uncorrected for PVE than for the MV, but change in MV provided some information regarding the lesion response to therapy (AUC >0.5). In these mCRC patients, all SUV uncorrected for PVE accurately predicted the tumour response on day 14 after starting therapy as assessed 4 to 6 weeks later (i.e. 6 to 8 weeks after therapy initiation) using the RECIST criteria. Neither correcting SUV for PVE nor measuring TLG improved the assessment of tumour

  7. Genetic ancestry in relation to the metabolic response to a U.S. versus traditional Mexican diet: a randomized crossover feeding trial among women of Mexican descent

    OpenAIRE

    Santiago-Torres, Margarita; De Dieu Tapsoba, Jean; Kratz, Mario; Lampe, Johanna W.; Breymeyer, Kara L.; Levy, Lisa; Song, Xiaoling; Villase?or, Adriana; Wang, Ching-Yun; Fejerman, Laura; Neuhouser, Marian L.; Carlson, Christopher S.

    2016-01-01

    Background Certain populations with a large proportion of Indigenous American (IA) genetic ancestry may be evolutionarily adapted to traditional diets high in legumes and complex carbohydrates, and may have a detrimental metabolic response to U.S. diets high in refined carbohydrates and added sugars. We tested whether IA ancestry modified the metabolic response to a U.S. versus traditional Mexican diet in a controlled dietary intervention. Methods First and second generation Mexican immigrant...

  8. Role of Shp2 in forebrain neurons in regulating metabolic and cardiovascular functions and responses to leptin.

    Science.gov (United States)

    do Carmo, J M; da Silva, A A; Sessums, P O; Ebaady, S H; Pace, B R; Rushing, J S; Davis, M T; Hall, J E

    2014-06-01

    We examined whether deficiency of Src homology 2 containing phosphatase (Shp2) signaling in forebrain neurons alters metabolic and cardiovascular regulation under various conditions and if it attenuates the anorexic and cardiovascular effects of leptin. We also tested whether forebrain Shp2 deficiency alters blood pressure (BP) and heart rate (HR) responses to acute stress. Forebrain Shp2(-/-) mice were generated by crossing Shp2(flox/flox) mice with CamKIIα-cre mice. At 22-24 weeks of age, the mice were instrumented for telemetry for measurement of BP, HR and body temperature (BT). Oxygen consumption (VO2), energy expenditure and motor activity were monitored by indirect calorimetry. Shp2/CamKIIα-cre mice were heavier (46±3 vs 32±1 g), hyperglycemic, hyperleptinemic, hyperinsulinemic and hyperphagic compared to Shp2(flox/flox) control mice. Shp2/CamKIIα-cre mice exhibited reduced food intake responses to fasting/refeeding and impaired regulation of BT when exposed to 15 and 30 °C ambient temperatures. Despite being obese and having many features of metabolic syndrome, Shp2/CamKIIα-cre mice had similar daily average BP and HR compared to Shp2(flox/flox) mice (112±2 vs 113±1 mm Hg and 595±34 vs 650±40 b.p.m.), but exhibited increased BP and HR responses to cold exposure and acute air-jet stress test. Leptin's ability to reduce food intake and to raise BP were markedly attenuated in Shp2/CamKIIα-cre mice. These results suggest that forebrain Shp2 signaling regulates food intake, appetite responses to caloric deprivation and thermogenic control of body temperature during variations in ambient temperature. Deficiency of Shp2 signaling in the forebrain is associated with augmented cardiovascular responses to cold and acute stress but attenuated BP responses to leptin.

  9. Similar metabolic responses to calorie restriction in lean and obese Zucker rats.

    Science.gov (United States)

    Chiba, Takuya; Komatsu, Toshimitsu; Nakayama, Masahiko; Adachi, Toshiyuki; Tamashiro, Yukari; Hayashi, Hiroko; Yamaza, Haruyoshi; Higami, Yoshikazu; Shimokawa, Isao

    2009-10-15

    Calorie restriction (CR), which is thought to be largely dependent on the neuroendocrine system modulated by insulin/insulin-like growth factor-I (IGF-I) and leptin signaling, decreases morbidity and increases lifespan in many organisms. To elucidate whether insulin and leptin sensitivities are indispensable in the metabolic adaptation to CR, we investigated the effects of CR on obese Zucker (fa/fa) rats and lean control (+/+) rats. CR did not fully improve insulin resistance in (fa/fa) rats. Nonetheless, CR induced neuropeptide Y (NPY) expression in the hypothalamic arcuate nucleus and metabolism related gene expression changes in the liver in (fa/fa) rats and (+/+) rats. Up-regulation of NPY augmented plasma corticosterone levels and suppressed pituitary growth hormone (GH) expression, thereby modulating adipocytokine production to induce tissue-specific insulin sensitivity. Thus, central NPY activation via peripheral signaling might play a crucial role in the effects of CR, even in insulin resistant and leptin receptor deficient conditions.

  10. Postprandial nutrient-sensing and metabolic responses after partial dietary fishmeal replacement by soyabean meal in turbot (Scophthalmus maximus L.).

    Science.gov (United States)

    Xu, Dandan; He, Gen; Mai, Kangsen; Zhou, Huihui; Xu, Wei; Song, Fei

    2016-02-14

    In this study, we chose a carnivorous fish, turbot (Scophthalmus maximus L.), to examine its nutrient-sensing and metabolic responses after ingestion of diets with fishmeal (FM), or 45% of FM replaced by soyabean meal (34·6% dry diet) balanced with or without essential amino acids (EAA) to match the amino acid profile of FM diet for 30 d. After a 1-month feeding trial, fish growth, feed efficiency and nutrient retention were markedly reduced by soyabean meal-incorporated (SMI) diets. Compared with the FM diet, SMI led to a reduction of postprandial influx of free amino acids, hypoactivated target of rapamycin signalling and a hyperactivated amino acid response pathway after refeeding, a status associated with reduced protein synthesis, impaired postprandial glycolysis and lipogenesis. These differential effects were not ameliorated by matching an EAA profile of soyabean meal to that of the FM diet through dietary amino acid supplementation. Therefore, this study demonstrated that the FM diet and SMI diets led to distinct nutrient-sensing responses, which in turn modulated metabolism and determined the utilisation efficiency of diets. Our results provide a new molecular explanation for the role of nutrient sensing in the inferior performance of aquafeeds in which FM is replaced by soyabean meal.

  11. Interrelations between glucose-induced insulin response, metabolic indicators, and time of first ovulation in high-yielding dairy cows.

    Science.gov (United States)

    Bossaert, P; Leroy, J L M R; De Vliegher, S; Opsomer, G

    2008-09-01

    High-yielding dairy cows are more susceptible to metabolic and reproductive disorders than low-yielding cows. Insulin plays a pivotal role in the development of both problems. In the present study, we aimed to assess the glucose-induced insulin responses of dairy cows at different time points relative to calving and to relate this to the metabolic status and the time of first ovulation. Twenty-three healthy, multiparous Holstein-Friesian cows with a high genetic merit for milk yield were studied from 14 d prepartum to 42 d postpartum. Intravenous glucose tolerance tests were performed on -14, 14, and 42 d relative to calving to evaluate the plasma insulin and glucose responses to a glucose load, as estimated by the peak concentration, the area under the curve (AUC), and the clearance rates of insulin and glucose. Blood samples were obtained at 3-d intervals and analyzed for glucose, insulin, and nonesterified fatty acids (NEFA). The time of first ovulation was defined by transrectal ultrasonography and plasma progesterone analysis. Glucose-induced insulin AUC and peak concentration decreased and glucose clearance increased during lactation compared with the dry period. Plasma NEFA concentrations were negatively related to insulin AUC and peak concentrations. Fourteen cows ovulated within 42 d postpartum, and the remaining 9 cows suffered from delayed resumption of ovarian function. Survival analysis demonstrated that cows with lower NEFA concentrations during the dry period tended to have earlier resumption of ovarian activity. In conclusion, our data suggest a decreased plasma insulin response to glucose postpartum in high-yielding dairy cows, possibly contributing to metabolic stress during the early postpartum period. It is hypothesized that NEFA impair glucose-induced insulin secretion in dairy cows. Additionally, our results suggest the importance of lipolysis during the transition period as a risk factor for delayed ovulation.

  12. Metabolic Response on Post-therapy FDG-PET Predicts Patterns of Failure After Radiotherapy for Cervical Cancer

    International Nuclear Information System (INIS)

    Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh; Grigsby, Perry W.

    2012-01-01

    Purpose: To determine the patterns of failure in patients with cervical cancer treated with definitive radiotherapy and evaluated for metabolic response with early posttherapy 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods and Materials: The records of 238 patients with cervical cancer were reviewed. All patients were treated with a combination of external radiotherapy and intracavitary brachytherapy. Two hundred and nineteen patients (92%) received concurrent chemotherapy. All patients underwent pretreatment FDG-PET, and posttherapy FDG-PET was performed within 8–16 weeks of the completion of radiotherapy. Posttherapy FDG-PET results were categorized as complete metabolic response (CMR), partial metabolic response (PMR), and progressive disease (PD). Failure patterns were categorized as none, isolated local failure (central pelvis ± pelvic lymph nodes), distant failure, or combined local plus distant failure. Results: Of the 91 patients (38%) who had a recurrence, 22 had isolated local failures, and 69 had distant failures (49 distant failures and 20 combined local plus distant failures). Of the 173 patients with a CMR, 40 (23%) experienced treatment failure. All 25 patients with PD experienced treatment failure, which was distant in 24 patients (96%). Among the 40 patients with PMR, no failure has been observed for 14 patients (35%). Of the 26 failures within the PMR group, 15 (58%) were limited to the pelvis. Differences in the patterns of failure between the three groups (CMR, PMR, PD) were statistically significant (chi-square test; p < 0.0001). Conclusions: The majority of failures after definitive radiotherapy for cervical cancer include distant failures, even in the setting of concurrent chemotherapy. PMR within the cervix or lymph nodes is more commonly associated with isolated local recurrence.

  13. Systemic responses to inhaled ozone in mice: cachexia and down-regulation of liver xenobiotic metabolizing genes

    Energy Technology Data Exchange (ETDEWEB)

    Last, Jerold A [Pulmonary and Critical Care Medicine, School of Medicine, Toxic Substances Program, 1131 Surge I, University of California, Davis, CA 95616-8723 (United States); Gohil, Kishorchandra [Pulmonary and Critical Care Medicine, School of Medicine, Toxic Substances Program, 1131 Surge I, University of California, Davis, CA 95616-8723 (United States); Mathrani, Vivek C [Pulmonary and Critical Care Medicine, School of Medicine, Toxic Substances Program, 1131 Surge I, University of California, Davis, CA 95616-8723 (United States); Kenyon, Nicholas J [Pulmonary and Critical Care Medicine, School of Medicine, Toxic Substances Program, 1131 Surge I, University of California, Davis, CA 95616-8723 (United States)

    2005-10-15

    Rats or mice acutely exposed to high concentrations of ozone show an immediate and significant weight loss, even when allowed free access to food and water. The mechanisms underlying this systemic response to ozone have not been previously elucidated. We have applied the technique of global gene expression analysis to the livers of C57BL mice acutely exposed to ozone. Mice lost up to 14% of their original body weight, with a 42% decrease in total food consumption. We previously had found significant up-regulation of genes encoding proliferative enzymes, proteins related to acute phase reactions and cytoskeletal functions, and other biomarkers of a cachexia-like inflammatory state in lungs of mice exposed to ozone. These results are consistent with a general up-regulation of different gene families responsive to NF-{kappa}B in the lungs of the exposed mice. In the present study, we observed significant down-regulation of different families of mRNAs in the livers of the exposed mice, including genes related to lipid and fatty acid metabolism, and to carbohydrate metabolism in this tissue, consistent with a systemic cachexic response. Several interferon-dependent genes were down-regulated in the liver, suggesting a possible role for interferon as a signaling molecule between lung and liver. In addition, transcription of several mRNAs encoding enzymes of xenobiotic metabolism in the livers of mice exposed to ozone was decreased, suggesting cytokine-mediated suppression of cytochrome P450 expression. This finding may explain a previously controversial report from other investigators more than 20 years ago of prolongation of pentobarbital sleeping time in mice exposed to ozone.

  14. Systemic responses to inhaled ozone in mice: cachexia and down-regulation of liver xenobiotic metabolizing genes

    International Nuclear Information System (INIS)

    Last, Jerold A.; Gohil, Kishorchandra; Mathrani, Vivek C.; Kenyon, Nicholas J.

    2005-01-01

    Rats or mice acutely exposed to high concentrations of ozone show an immediate and significant weight loss, even when allowed free access to food and water. The mechanisms underlying this systemic response to ozone have not been previously elucidated. We have applied the technique of global gene expression analysis to the livers of C57BL mice acutely exposed to ozone. Mice lost up to 14% of their original body weight, with a 42% decrease in total food consumption. We previously had found significant up-regulation of genes encoding proliferative enzymes, proteins related to acute phase reactions and cytoskeletal functions, and other biomarkers of a cachexia-like inflammatory state in lungs of mice exposed to ozone. These results are consistent with a general up-regulation of different gene families responsive to NF-κB in the lungs of the exposed mice. In the present study, we observed significant down-regulation of different families of mRNAs in the livers of the exposed mice, including genes related to lipid and fatty acid metabolism, and to carbohydrate metabolism in this tissue, consistent with a systemic cachexic response. Several interferon-dependent genes were down-regulated in the liver, suggesting a possible role for interferon as a signaling molecule between lung and liver. In addition, transcription of several mRNAs encoding enzymes of xenobiotic metabolism in the livers of mice exposed to ozone was decreased, suggesting cytokine-mediated suppression of cytochrome P450 expression. This finding may explain a previously controversial report from other investigators more than 20 years ago of prolongation of pentobarbital sleeping time in mice exposed to ozone

  15. Intermittent sustained swimming in 'matrinxã' Brycon amazonicus (Bryconidae: Bryconinae: hematological and metabolic responses

    Directory of Open Access Journals (Sweden)

    Fernando Fabrizzi

    Full Text Available In fish, studies on a wide variety of physiological effects of exercise have been reported since a long time. It has been attributed special attention to some types of exercise, however, its application as a healthful practice in the rearing and welfare of farming fish is rising in last few years. In this particular, long-term intermittent sustained swimming (ISS has been not yet explored. In this work, the freshwater fish Brycon amazonicus was submitted to (ISS for 30 days at velocity of 1.0 body-length sec-1 for 12h interspaced by 12h under still water. Hematology and metabolism were evaluated. Exercised fish decreased 30% the erythrocyte number and hemoglobin was unvaried. The stores of liver glycogen and muscular triacylglycerol (TAG were increased and the metabolic profile was typically aerobic. The slight decrease of liver (TAG plus the full metabolic and hematic trait allow investing in this kind of exercise a beneficial practice in the rearing of fish species

  16. Alterations in fatty acid metabolism in response to obesity surgery combined with dietary counseling.

    Science.gov (United States)

    Walle, P; Takkunen, M; Männistö, V; Vaittinen, M; Käkelä, P; Ågren, J; Schwab, U; Lindström, J; Tuomilehto, J; Uusitupa, M; Pihlajamäki, J

    2017-09-04

    The effects of obesity surgery on serum and adipose tissue fatty acid (FA) profile and FA metabolism may modify the risk of obesity-related diseases. We measured serum (n=122) and adipose tissue (n=24) FA composition and adipose tissue mRNA expression of genes regulating FA metabolism (n=100) in participants of the Kuopio Obesity Surgery Study (KOBS, age 47.2±8.7 years, BMI 44.6±6.0, 40 men, 82 women) before and one year after obesity surgery. As part of the surgery protocol, all the subjects were instructed to add sources of unsaturated fatty acids, such as rapeseed oil and fatty fish, into their diet. The results were compared with changes in serum FA composition in 122 subjects from the Finnish Diabetes Prevention study (DPS) (age 54.3±7.1 years, BMI 32.2±4.6, 28 men, 94 women). The proportion of saturated FAs decreased and the proportion of n-3 and n-6 FAs increased in serum triglycerides after obesity surgery (all Pobesity surgery in all lipid fractions (all Pobesity surgery and lifestyle intervention, except for the change in the absolute amounts of n-3 FAs between the two studies (P=0.044). Beneficial changes in serum and adipose tissue FAs after obesity surgery could be associated with changes in endogenous metabolism and diet.

  17. Salinity modulates thermotolerance, energy metabolism and stress response in amphipods Gammarus lacustris

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    Kseniya P. Vereshchagina

    2016-11-01

    Full Text Available Temperature and salinity are important abiotic factors for aquatic invertebrates. We investigated the influence of different salinity regimes on thermotolerance, energy metabolism and cellular stress defense mechanisms in amphipods Gammarus lacustris Sars from two populations. We exposed amphipods to different thermal scenarios and determined their survival as well as activity of major antioxidant enzymes (peroxidase, catalase, glutathione S-transferase and parameters of energy metabolism (content of glucose, glycogen, ATP, ADP, AMP and lactate. Amphipods from a freshwater population were more sensitive to the thermal challenge, showing higher mortality during acute and gradual temperature change compared to their counterparts from a saline lake. A more thermotolerant population from a saline lake had high activity of antioxidant enzymes. The energy limitations of the freshwater population (indicated by low baseline glucose levels, downward shift of the critical temperature of aerobic metabolism and inability to maintain steady-state ATP levels during warming was observed, possibly reflecting a trade-off between the energy demands for osmoregulation under the hypo-osmotic condition of a freshwater environment and protection against temperature stress.

  18. Metabolic, thermoregulatory, and perceptual responses during exercise after lower vs. whole body precooling.

    Science.gov (United States)

    White, Andrea T; Davis, Scott L; Wilson, Thad E

    2003-03-01

    The purpose of this investigation was to compare the thermoregulatory, metabolic, and perceptual effects of lower body (LBI) and whole body (WBI) immersion precooling techniques during submaximal exercise. Eleven healthy men completed two 30-min cycling bouts at 60% of maximal O(2) uptake preceded by immersion to the suprailiac crest (LBI) or clavicle (WBI) in 20 degrees C water. WBI produced significantly lower rectal temperature (T(re)) during minutes 24-30 of immersion and lower T(re), mean skin temperature, and mean body temperature for the first 24, 14, and 16 min of exercise, respectively. Body heat storage rates differed significantly for LBI and WBI during immersion and exercise, although no net differences were observed between conditions. For WBI, metabolic heat production and heart rate were significantly higher during immersion but not during exercise. Thermal sensation was significantly lower (felt colder) and thermal discomfort was significantly higher (less comfortable) for WBI during immersion and exercise. In conclusion, WBI and LBI attenuated T(re) increases during submaximal exercise and produced similar net heat storage over the protocol. LBI minimized metabolic increases and negative perceptual effects associated with WBI.

  19. Respiratory, cardiovascular and metabolic responses during different modes of overground bionic ambulation in persons with motor-incomplete spinal cord injury: A case series

    Directory of Open Access Journals (Sweden)

    Jochen Kressler

    2017-09-01

    Full Text Available Objective: To investigate the effects of overground bionic ambulation with variable assistance on cardiorespiratory and metabolic responses in persons with motor-incomplete spinal cord injury. Design: Case series. Subjects: Four participants with chronic, motor-incomplete spinal cord injury. Methods: Subjects completed a maximal graded exercise test on an arm-ergometer and 3 6-min bouts of overground bionic ambulation using different modes of assistance, i.e. Maximal, Adaptive, Fixed. Cardiorespiratory (oxygen consumption and metabolic (caloric expenditure and substrate utilization measures were taken using a mobile metabolic cart at each overground bionic ambulation assistance. Results: Cardiorespiratory responses ranged from low (24% VO2peak for the least impaired and fittest individual to supramaximal (124% VO2peak for the participant with the largest impairments and the lowest level of fitness. Different overground bionic ambulation assistive modes elicited small (3–8% VO2peak differences in cardiorespiratory responses for 3 participants. One participant had a large (28% VO2peak difference in cardiorespiratory responses to different modes of overground bionic ambulation. Metabolic responses mostly tracked closely with cardiorespiratory responses. Total energy expenditure ranged from 1.39 to 7.17 kcal/min. Fat oxidation ranged from 0.00 to 0.17 g/min across participants and different overground bionic ambulation modes. Conclusion: Overground bionic ambulation with variable assistance can substantially increase cardiorespiratory and metabolic responses; however, these responses vary widely across participants and overground bionic ambulation modes.

  20. The effects of handling and anesthetic agents on the stress response and carbohydrate metabolism in northern elephant seals.

    Directory of Open Access Journals (Sweden)

    Cory D Champagne

    Full Text Available Free-ranging animals often cope with fluctuating environmental conditions such as weather, food availability, predation risk, the requirements of breeding, and the influence of anthropogenic factors. Consequently, researchers are increasingly measuring stress markers, especially glucocorticoids, to understand stress, disturbance, and population health. Studying free-ranging animals, however, comes with numerous difficulties posed by environmental conditions and the particular characteristics of study species. Performing measurements under either physical restraint or chemical sedation may affect the physiological variable under investigation and lead to values that may not reflect the standard functional state of the animal. This study measured the stress response resulting from different handling conditions in northern elephant seals and any ensuing influences on carbohydrate metabolism. Endogenous glucose production (EGP was measured using [6-(3H]glucose and plasma cortisol concentration was measured from blood samples drawn during three-hour measurement intervals. These measurements were conducted in weanlings and yearlings with and without the use of chemical sedatives--under chemical sedation, physical restraint, or unrestrained. We compared these findings with measurements in adult seals sedated in the field. The method of handling had a significant influence on the stress response and carbohydrate metabolism. Physically restrained weanlings and yearlings transported to the lab had increased concentrations of circulating cortisol (F(11, 46 = 25.2, p<0.01 and epinephrine (F(3, 12 = 5.8, p = 0.01. Physical restraint led to increased EGP (t = 3.1, p = 0.04 and elevated plasma glucose levels (t = 8.2, p<0.01. Animals chemically sedated in the field typically did not exhibit a cortisol stress response. The combination of anesthetic agents (Telazol, ketamine, and diazepam used in this study appeared to alleviate a

  1. Physiological responses in a variable environment: relationships between metabolism, hsp and thermotolerance in an intertidal-subtidal species.

    Directory of Open Access Journals (Sweden)

    Yun-wei Dong

    Full Text Available Physiological responses to temperature reflect the evolutionary adaptations of organisms to their thermal environment and the capability of animals to tolerate thermal stress. Contrary to conventional metabolism theory, increasing environmental temperatures have been shown to reduce metabolic rate in rocky-eulittoral-fringe species inhabiting highly variable environments, possibly as a strategy for energy conservation. To study the physiological adaptations of an intertidal-subtidal species to the extreme and unpredictable heat stress of the intertidal zone, oxygen consumption rate and heat shock protein expression were quantified in the sea cucumber Apostichopus japonicus. Using simulate natural temperatures, the relationship between temperature, physiological performance (oxygen consumption and heat shock proteins and thermotolerance were assessed. Depression of oxygen consumption rate and upregulation of heat shock protein genes (hsps occurred in sequence when ambient temperature was increased from 24 to 30°C. Large-scale mortality of the sea cucumber occurred when temperatures rose beyond 30°C, suggesting that the upregulation of heat shock proteins and mortality are closely related to the depression of aerobic metabolism, a phenomenon that is in line with the concept of oxygen- and capacity-limited thermal tolerance (OCLTT. The physiologically-related thermotolerance of this sea cucumber should be an adaptation to its local environment.

  2. The cardiovascular and metabolic responses to Wii Fit video game playing in middle-aged and older adults.

    Science.gov (United States)

    Guderian, B; Borreson, L A; Sletten, L E; Cable, K; Stecker, T P; Probst, M A; Dalleck, L C

    2010-12-01

    The purpose of this study was (a) to assess the cardiovascular and metabolic responses to Wii Fit video games and (b) to determine if Wii Fit video games meet the American College of Sports Medicine guidelines for improving and maintaining cardiorespiratory fitness. Twenty men and women (mean±SD age, height, and weight: = 58.1±8.8 years, 172.1±10.5 cm, 87.1±22.8 kg, respectively) completed a 20-min Wii Fit testing session consisting of six separate aerobic and balance games. Cardiovascular and metabolic data were collected via a portable calorimetric measurement system. Mean relative exercise intensity was 43.4±16.7% of heart rate reserve. Absolute exercise intensity in metabolic equivalents (METS) was 3.5±0.96. Total net energy expenditure for the Wii Fit video game playing session was 116.2±40.9 kcal/session. Results indicate that playing Wii Fit video games is a feasible alternative to more traditional aerobic exercise modalities for middle-aged and older adults that fulfills the American College of Sports Medicine guidelines for improving and maintaining cardiorespiratory fitness.

  3. Changes in energetic metabolism of Biomphalaria glabrata (Mollusca, Planorbidae in response to exogenous calcium

    Directory of Open Access Journals (Sweden)

    L. D. Silva

    Full Text Available Abstract Calcium is considered an essential element for the metabolism of aquatic snail Biomphalaria glabrata (Say, 1818, intermediate host of Schistosoma mansoni Sambon, 1907 in Brazil, and represents a limiting factor to its distribution and adaptation to the environment. This study investigated the effect of different concentrations of exogenous CaCO3 on the energetic metabolism of B. glabrata for better understanding the physiological interference of chemical elements dissolved in the environment with the physiology of this species. Sixty-day-old snails were distributed into six groups, five exposed to different concentrations of CaCO3 (20, 40, 60, 80 and 100 mg/L and a control group. The exposure to CaCO3 was assessed over time, with analysis of 15 snails of each group in the following intervals: 1, 14, 21 or 30 days for hemolymph extraction. Concentrations of calcium and glucose in the hemolymph were determined by commercial kits, and organic acids were extracted using an ion exchange column and analyzed by high-performance liquid chromatography. Concentration of calcium in the hemolymph showed no significant difference (p>0.05 from the control group and between the concentrations tested. Concentration of glucose decreased (p<0.05 in the treatments of exposure to 20 and 40 mg/L and increased when exposed to 80 and 100 mg/L CaCO3 compared to control and to other concentrations tested over 30 days. The organic acids pyruvate, oxaloacetate, citrate, succinate, fumarate, beta-hydroxybutyrate and lactate presented increased concentrations, while propionate and acetoacetate, decreased concentrations, when exposed to CaCO3 compared to control. Considering the influence of different periods of exposure to CaCO3, on the 14th day, there were stronger alterations in the metabolism of B. glabrata. In conclusion, exposure to CaCO3 reduced the concentration of glucose, which is metabolized into pyruvate, the final product of glycolysis, and also

  4. Loss of Response to Melatonin Treatment Is Associated with Slow Melatonin Metabolism

    Science.gov (United States)

    Braam, W.; van Geijlswijk, I.; Keijzer, Henry; Smits, Marcel G.; Didden, Robert; Curfs, Leopold M. G.

    2010-01-01

    Background: In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to melatonin is yet unknown. We hypothesise that this…

  5. Loss of response to melatonin treatment is associated with slow melatonin metabolism

    NARCIS (Netherlands)

    Braam, W.J.; Geijlswijk, I.M. van; Keijzer, H.; Smits, M.G.; Didden, H.C.M.; Curfs, L.M.G.

    2010-01-01

    Background In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to

  6. Responses of dairy cows with divergent residual feed intake as calves to metabolic challenges during midlactation and the nonlactating period.

    Science.gov (United States)

    DiGiacomo, K; Norris, E; Dunshea, F R; Hayes, B J; Marett, L C; Wales, W J; Leury, B J

    2018-03-28

    Residual feed intake (RFI) is defined as the difference between the actual and expected feed intake required to support animal maintenance and growth. Thus, a cow with a low RFI can obtain nutrients for maintenance and growth from a reduced amount of feed compared with a cow with a high RFI. Variation in RFI is underpinned by a combination of factors, including genetics, metabolism, thermoregulation and body composition; hypothalamic-pituitary-adrenal (HPA) axis responsiveness is also a possible contributor. Responses to 3 metabolic challenges were measured in lactating and nonlactating dairy cattle. Sixteen Holstein Friesian cows with phenotypic RFI measurements that were obtained during the growth period (188-220 d old) were grouped as either low-calfhood RFI (n = 8) or high-calfhood RFI (n = 8). An ACTH (2 µg/kg of body weight), insulin (0.12 U/kg), and epinephrine (a low dose of 0.1 µg/kg and a high dose of 1.6 µg/kg of epinephrine) challenge were each conducted during both midlactation (122 ± 23.4 d in milk) and the nonlactating period (dry period; approximately 38 d after cessation of milking). Cows were housed in metabolism stalls for the challenges and were fed a diet of alfalfa cubes ad libitum for at least 10 d before the experiment (lactating cows also were offered a total of 6 kg of dry matter/d of crushed wheat grain plus minerals fed as 3 kg of dry matter at each milking) and were fasted for 12 h before the challenges. The efficiency of conversion of feed into milk (the ratio of feed consumed to milk produced over the 7 d before the experiment) during midlactation was better (lower) in low-calfhood RFI cows, although dry matter intake did not differ between RFI groups. Low-calfhood RFI cows exhibited a lower plasma cortisol response to the ACTH challenge than high-calfhood RFI cows, particularly in midlactation (-15%). The low-calfhood RFI cows had a greater plasma insulin-like growth factor-1 response to the insulin challenge and plasma fatty

  7. The degree of saturation of fatty acids in dietary fats does not affect the metabolic response to ingested carbohydrate.

    Science.gov (United States)

    Radulescu, Angela; Hassan, Youssef; Gannon, Mary C; Nuttall, Frank Q

    2009-06-01

    We are interested in the metabolic response to ingested macronutrients, and the interaction between macronutrients in meals. Previously, we and others reported that the postprandial rise in serum glucose following ingestion of 50 g carbohydrate, consumed as potato, was markedly attenuated when butter was ingested with the carbohydrate, whereas the serum insulin response was little affected by the combination. To determine whether a similar response would be observed with three other dietary fats considerably different in fatty acid composition. Nine healthy subjects received lard, twelve received olive oil and eleven received safflower oil as a test meal. The subjects ingested meals of 25 g fat (lard, olive oil or safflower oil), 50 g CHO (potato), 25 g fat with 50 g CHO or water only. Glucose, C peptide, insulin, triacylglycerols and nonesterified fatty acids were determined. Ingestion of lard, olive oil or safflower oil with potato did not affect the quantitative glucose and insulin responses to potato alone. However, the responses were delayed, diminished and prolonged. All three fats when ingested alone modestly increased the insulin concentration when compared to ingestion of water alone. When either lard, olive oil or safflower oil was ingested with the potato, there was an accelerated rise in triacylglycerols. This was most dramatic with safflower oil. Our data indicate that the glucose and insulin response to butter is unique when compared with the three other fat sources varying in their fatty acid composition.

  8. Breeding status affects the hormonal and metabolic response to acute stress in a long-lived seabird, the king penguin.

    Science.gov (United States)

    Viblanc, Vincent A; Gineste, Benoit; Robin, Jean-Patrice; Groscolas, René

    2016-09-15

    Stress responses are suggested to physiologically underlie parental decisions promoting the redirection of behaviour away from offspring care when survival is jeopardized (e.g., when facing a predator). Besides this classical view, the "brood-value hypothesis" suggests that parents' stress responses may be adaptively attenuated to increase fitness, ensuring continued breeding when the relative value of the brood is high. Here, we test the brood-value hypothesis in breeding king penguins (Aptenodytes patagonicus), long-lived seabirds for which the energy commitment to reproduction is high. We subjected birds at different breeding stages (courtship, incubation and chick brooding) to an acute 30-min capture stress and measured their hormonal (corticosterone, CORT) and metabolic (non-esterified fatty acid, NEFA) responses to stress. We found that CORT responses were markedly attenuated in chick-brooding birds when compared to earlier stages of breeding (courtship and incubation). In addition, NEFA responses appeared to be rapidly attenuated in incubating and brooding birds, but a progressive increase in NEFA plasma levels in courting birds suggested energy mobilization to deal with the threat. Our results support the idea that stress responses may constitute an important life-history mechanism mediating parental reproductive decisions in relation to their expected fitness outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Multicompartmental nontargeted LC-MS metabolomics: explorative study on the metabolic responses of rye fiber versus refined wheat fiber intake in plasma and urine of hypercholesterolemic pigs

    DEFF Research Database (Denmark)

    Nørskov, Natalja; Hedemann, Mette Skou; Lærke, Helle Nygaard

    2013-01-01

    A multicompartmental nontargeted LC–MS metabolomics approach was used to study the metabolic responses on plasma and urine of hypercholesterolemic pigs after consumption of diets with contrasting dietary fiber composition (whole grain rye with added rye bran versus refined wheat). To study...... the metabolic responses, we performed a supervised multivariate data analyses used for pattern recognition, which revealed marked effects of the diets on both plasma and urine metabolic profiles. Diverse pools of metabolites were responsible for the discrimination between the diets. Elevated levels of phenolic...... compounds and dicarboxylic acids were detected in urine of pigs after rye consumption compared to refined wheat. Furthermore, consumption of rye was characterized by lower levels of linoleic acid derived oxylipins and cholesterol in the plasma metabolic profiles. These results indicate that higher...

  10. Effect of grape seed extract on postprandial oxidative status and metabolic responses in men and women with the metabolic syndrome - randomized, cross-over, placebo-controlled study

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    Indika Edirisinghe

    2012-12-01

    Full Text Available Objective: This investigation was undertaken to determine whether a grape seed extract (GSE that is rich in mono-, oligo- and poly- meric polyphenols would modify postprandial oxidative stress and inflammation in individuals with the metabolic syndrome (MetS.Background: MetS is known to be associated with impaired glucose tolerance and poor glycemic control. Consumption of a meal high in readily available carbohydrates and fat causes postprandial increases in glycemia and lipidemia and markers of oxidative stress, inflammation and insulin resistance. Materials/methods: After an overnight fast, twelve subjects with MetS (5 men and 7 women consumed a breakfast meal high in fat and carbohydrate in a cross-over design. A GSE (300 mg or placebo capsule was administrated 1 hr before the meal (-1 hr. Changes in plasma insulin, glucose, oxidative stress and inflammatory markers were measured hourly for 6 hr. Results: Plasma hydrophilic oxygen radical absorbance capacity (ORAC measured as the positive incremental area under the curve (-1 to 5 hr was significantly increased when the meal was preceded by GSE compared with placebo (P0.05. No changes in inflammatory markers were evident. Conclusion: These data suggest that GSE enhances postprandial plasma antioxidant status and reduces the glycemic response to a meal, high in fat and carbohydrate in subjects with the MetS.

  11. Type of diet modulates the metabolic response to sleep deprivation in rats

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    Martins Paulo JF

    2011-12-01

    Full Text Available Abstract Background Evidence suggests that sleep loss is associated with an increased risk of obesity and diabetes; however, animal models have failed to produce weight gain under sleep deprivation (SD. Previous studies have suggested that this discrepancy could be due to more extreme SD conditions in experimental animals, their higher resting metabolic rate than that of humans, and the decreased opportunity for animals to ingest high-calorie foods. Thus, our objective was to determine whether diets with different textures/compositions could modify feeding behavior and affect the metabolic repercussions in SD in rats. Methods Three groups of male rats were used: one was designated as control, one was sleep deprived for 96 h by the platform technique (SD-96h and one was SD-96h followed by a 24-h recovery (rebound. In the first experiment, the animals were fed chow pellets (CPs; in the second, they received high-fat diet and in the third, they were fed a liquid diet (LD. Results We observed that SD induces energy deficits that were related to changes in feeding behavior and affected by the type of diet consumed. Regardless of the diet consumed, SD consistently increased animals' glucagon levels and decreased their leptin and triacylglycerol levels and liver glycogen stores. However, such changes were mostly avoided in the rats on the liquid diet. SD induces a wide range of metabolic and hormonal changes that are strongly linked to the severity of weight loss. Conclusions The LD, but not the CP or high-fat diets, favored energy intake, consequently lessening the energy deficit induced by SD.

  12. Zolpidem metabolism in vitro: responsible cytochromes, chemical inhibitors, and in vivo correlations

    Science.gov (United States)

    von Moltke, Lisa L; Greenblatt, David J; Granda, Brian W; Duan, Su Xiang; Grassi, Jeffrey M; Venkatakrishnan, Karthik; Harmatz, Jerold S; Shader, Richard I

    1999-01-01

    Aims To determine the human cytochromes mediating biotransformation of the imidazopyridine hypnotic, zolpidem, and the clinical correlates of the findings. Methods Kinetic properties of zolpidem biotransformation to its three hydroxylated metabolites were studied in vitro using human liver microsomes and heterologously expressed individual human cytochromes. Results The metabolic product termed M-3 accounted for more than 80% of net intrinsic clearance by liver microsomes in vitro. Microsomes containing human cytochromes CYP1A2, 2C9, 2C19, 2D6, and 3 A4 expressed by cDNA-transfected human lymphoblastoid cells mediated zolpidem metabolism in vitro. The kinetic profile for zolpidem metabolite formation by each individual cytochrome was combined with estimated relative abundances based on immunological quantification, yielding projected contributions to net intrinsic clearance of: 61% for 3 A4, 22% for 2C9, 14% for 1A2, and less than 3% for 2D6 and 2C19. These values were consistent with inhibitory effects of ketoconazole and sulfaphenazole on zolpidem biotransformation by liver microsomes. Ketoconazole had a 50% inhibitory concentration (IC50) of 0.61 μm vs formation of the M-3 metabolite of zolpidem in vitro; in a clinical study, ketoconazole coadministration reduced zolpidem oral clearance by ≈40%, somewhat less than anticipated based on the IC50 value and total plasma ketoconazole levels, but much more than predicted based on unbound plasma ketoconazole levels. Conclusions The incomplete dependence of zolpidem clearance on CYP3A activity has clinical implications for susceptibility to metabolic inhibition. PMID:10383565

  13. The effect of aerobic exercise and starvation on growth performance and postprandial metabolic response in juvenile southern catfish (Silurus meridionalis).

    Science.gov (United States)

    Li, Xiu-Ming; Liu, Li; Yuan, Jian-Ming; Xiao, Yuan-Yuan; Fu, Shi-Jian; Zhang, Yao-Guang

    2016-03-01

    To investigate the effects of aerobic exercise and starvation on growth performance, postprandial metabolic response and their interaction in a sedentary fish species, either satiation-fed or starved juvenile southern catfish (Silurus meridionalis) were exercised at 25 °C under three water velocities, i.e., nearly still water (control), 1 body length (bl) s(-1) and 2 bl s(-1), for eight weeks. Then, the feed intake (FI), food conversion efficiency (FCE), specific growth rate (SGR), morphological parameters, resting ṀO2 (ṀO2rest) and postprandial ṀO2 responses of the experimental fish were measured. Exercise at a low velocity (1 bl s(-1)) showed no effect on any growth performance parameter, whereas exercise at a high velocity (2 bl s(-1)) exhibited higher FI but similar SGR due to the extra energy expenditure from swimming and consequent decreased FCE. Starvation led to a significant body mass loss, whereas the effect intensified in both exercise groups. Exercise resulted in improved cardio-respiratory capacity, as indicated by increased gill and heart indexes, whereas it exhibited no effect on resting and postprandial metabolism in S. meridionalis. The starved fish displayed significantly larger heart, gill and digestive tract indexes compared with the feeding fish, suggesting selective maintenance of cardio-respiratory and digestive function in this fish species during starvation. However, starved fish still exhibited impaired digestive performance, as evidenced by the prolonged duration and low postprandial metabolic increase, and this effect was further exacerbated in both the 1 and 2 bl s(-1) exercise groups. These data suggest the following: (1) aerobic exercise produced no improvement in growth performance but may have led to the impairment of growth under insufficient food conditions; (2) the mass of different organs and tissues responded differently to aerobic exercise and starvation due to the different physiological roles they play; and (3

  14. Ambulatory blood pressure response to a bout of HIIT in metabolic syndrome patients

    OpenAIRE

    Ramirez-Jimenez, Miguel; Morales Palomo, Felix Alberto; García-Pallarés, J.; Mora-Rodríguez, Ricardo; Ortega, Juan Fernando

    2017-01-01

    The effectiveness of exercise to lower blood pressure may depend on the type and intensity of exercise. We study the short-term (i.e., 14-hour) effects of a bout of high-intensity aerobic interval training (HIIT) on blood pressure in metabolic syndrome (MSyn) patients. Methods: Nineteen MSyn patients (55.2±7.3 years, 6 women) entered the study. Eight of them were normotensive and eleven hypertensive according to MSyn threshold (≥130 mmHg for SBP and/or ≥85 mmHg for DBP). In the...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    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......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...

  16. Is Metabolic Syndrome On the Radar? Improving Real-Time Detection of Metabolic Syndrome and Physician Response by Computerized Scan of the Electronic Medical Record

    Science.gov (United States)

    Lui, Kingwai; Randhawa, Gagandeep; Totten, Vicken; Smith, Adam E.; Raese, Joachim

    2016-01-01

    Objective: Metabolic syndrome is a common underdiagnosed condition among psychiatric patients exacerbated by second-generation antipsychotics, with the exception of aripiprazole and ziprasidone. This study evaluated the prescribing and treating behavior with regard to antipsychotics and metabolic syndrome of psychiatrists before and after implementation of a mandatory admission order set and electronic notification of results. Method: Baseline data from 9,100 consecutive psychiatric admissions to a mental health hospital (July 2013–July 2014) were compared to postintervention data (July 2014–January 2015), which included 1,499 consecutive patient records. The intervention initiated standardized admission testing with electronic notification to psychiatrists when patients met metabolic syndrome criteria (according to Axis III of the DSM-IV). Charts were examined for inclusion of this diagnosis at discharge and for treatment changes. Results: At baseline, only 2.4% of patients (n = 214) were evaluated for metabolic syndrome. Of these, 34.5% (0.8% of the total sample) met metabolic syndrome criteria. Only 15 patients (0.16%) were comprehensively treated. No chart listed metabolic syndrome under Axis III of the DSM-IV. After the intervention, the diagnosis of patients meeting the criteria for metabolic syndrome increased from 0% to 29.3%. Less than 3% of patients were switched to drugs with a more benign metabolic profile. All patients who continued on second-generation antipsychotics had metabolic retesting. Thirty-eight experienced a significant and rapid increase in triglyceride levels after only 3 to 17 days. Conclusions: Mandatory intake testing increases the number of patients evaluated for metabolic syndrome. Electronic alerts increase the inclusion of metabolic syndrome among discharge diagnoses but rarely affect prescribing practices. PMID:27247842

  17. A Dose-Response Strategy Reveals Differences between Normal-Weight and Obese Men in Their Metabolic and Inflammatory Responses to a High-Fat Meal123

    Science.gov (United States)

    Schwander, Flurina; Kopf-Bolanz, Katrin A.; Buri, Caroline; Portmann, Reto; Egger, Lotti; Chollet, Magali; McTernan, Philip G.; Piya, Milan K.; Gijs, Martin A. M.; Vionnet, Nathalie; Pralong, François; Laederach, Kurt; Vergères, Guy

    2014-01-01

    A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20–25 kg/m2) and 18 obese (BMI: >30 kg/m2) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068. PMID:24812072

  18. A dose-response strategy reveals differences between normal-weight and obese men in their metabolic and inflammatory responses to a high-fat meal.

    Science.gov (United States)

    Schwander, Flurina; Kopf-Bolanz, Katrin A; Buri, Caroline; Portmann, Reto; Egger, Lotti; Chollet, Magali; McTernan, Philip G; Piya, Milan K; Gijs, Martin A M; Vionnet, Nathalie; Pralong, François; Laederach, Kurt; Vergères, Guy

    2014-10-01

    A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20-25 kg/m(2)) and 18 obese (BMI: >30 kg/m(2)) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068. © 2014 American Society for Nutrition.

  19. Effect of time of day on performance, hormonal and metabolic response during a 1000-M cycling time trial.

    Directory of Open Access Journals (Sweden)

    Alan Lins Fernandes

    Full Text Available The aim of this study was to determine the effect of time of day on performance, pacing, and hormonal and metabolic responses during a 1000-m cycling time-trial. Nine male, recreational cyclists visited the laboratory four times. During the 1st visit the participants performed an incremental test and during the 2nd visit they performed a 1000-m cycling familiarization trial. On the 3rd and 4th visits, the participants performed a 1000-m TT at either 8 am or 6 pm, in randomized, repeated-measures, crossover design. The time to complete the time trial was lower in the evening than in the morning (88.2±8.7 versus 94.7±10.9 s, respectively, p0.05, but the norepinephrine response to the exercise was increased in the morning (+46%, p0.05. Our findings suggest that performance was improved in the evening, and it was accompanied by an improved hormonal and metabolic milieu.

  20. Abnormal GABAA-mediated metabolic response in the MDX mouse - an explanation for the mental deficit in Duchenne muscular dystrophy?

    International Nuclear Information System (INIS)

    Rae, C.; Bubb, W.A.; Maitland, A.; Head, S.I.

    2001-01-01

    Full text: Duchenne muscular dystrophy is an X-linked disorder associated with lack of the 728 kDa protein dystrophin. In addition to the well-known muscle wasting, sufferers also experience a 15 point downshift in IQ. Recently reduced clustering of GABA A receptors in cerebellar Purkinje and hippocampal CA1 neurons has been shown in the murine homologue of DMD, the mdx mouse. In this work, the functional efficacy of GABA A receptors in mdx mice (C57B1/10Sc-Sn-mdx) and control was tested by examining the metabolism of [1- 13 C]D-glucose under both normoxic and hypoxic conditions and also by examining the metabolic response to the GABA A agonist muscimol (5-aminomethyl-3-hydroxyisoxazole). Although total measured [ 13 C] was identical in mdx cf. control mice, the fractional enrichment of all metabolites was increased in mdx mice, suggesting decreased inhibitory input in these animals. Further, although flux into metabolites from [1- 13 C]D-glucose decreased as expected in control mice in the presence of muscimol, the GABA a agonist had weaker effect in mdx mice, consistent with weaker GABA A activation. Finally, the response of mdx mouse brain tissue slices to mild hypoxia (partially mediated by GABA A ) was altered cf. control mice, with increased production of lactate and decreased flux into Krebs cycle intermediates. These data are consistent with a functional lesion of a subset of GABA A receptors in DMD

  1. Integration of transcriptomic and metabolic data reveals hub transcription factors involved in drought stress response in sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Moschen, Sebastián; Di Rienzo, Julio A; Higgins, Janet; Tohge, Takayuki; Watanabe, Mutsumi; González, Sergio; Rivarola, Máximo; García-García, Francisco; Dopazo, Joaquin; Hopp, H Esteban; Hoefgen, Rainer; Fernie, Alisdair R; Paniego, Norma; Fernández, Paula; Heinz, Ruth A

    2017-07-01

    By integration of transcriptional and metabolic profiles we identified pathways and hubs transcription factors regulated during drought conditions in sunflower, useful for applications in molecular and/or biotechnological breeding. Drought is one of the most important environmental stresses that effects crop productivity in many agricultural regions. Sunflower is tolerant to drought conditions but the mechanisms involved in this tolerance remain unclear at the molecular level. The aim of this study was to characterize and integrate transcriptional and metabolic pathways related to drought stress in sunflower plants, by using a system biology approach. Our results showed a delay in plant senescence with an increase in the expression level of photosynthesis related genes as well as higher levels of sugars, osmoprotectant amino acids and ionic nutrients under drought conditions. In addition, we identified transcription factors that were upregulated during drought conditions and that may act as hubs in the transcriptional network. Many of these transcription factors belong to families implicated in the drought response in model species. The integration of transcriptomic and metabolomic data in this study, together with physiological measurements, has improved our understanding of the biological responses during droughts and contributes to elucidate the molecular mechanisms involved under this environmental condition. These findings will provide useful biotechnological tools to improve stress tolerance while maintaining crop yield under restricted water availability.

  2. The Impact of Drug Metabolism Gene Polymorphisms on Therapeutic Response and Survival in Diffuse Large B-Cell Lymphoma Patients.

    Science.gov (United States)

    Pál, Ildikó; Illés, Árpád; Gergely, Lajos; Pál, Tibor; Radnay, Zita; Szekanecz, Zoltán; Zilahi, Erika; Váróczy, László

    2018-04-01

    Diffuse large B-cell lymphoma (DLBCL) accounts for 30% of all non-Hodgkin lymphomas (NHL) and 80% of agressive lymphomas. Besides the traditional International Prognostic Index (IPI), some other factors may also influence the prognosis of DLBCL patients. To study how the genetic polymorphisms in the metabolic pathway influence the event-free and overall survivals and therapeutic responses in DLBCL. The study was comprised of 51 patients (32 men, 19 women). The average age was 53.1 years. DLBCL was diagnosed between 2011 and 2016 and the average follow-up time was 3.78 years. These patients received 1-8 cycles (an average of 6.2 cycles) of rituximab, cyclophosphamide, doxorubicin, vincristin, prednisolon (R-CHOP) immunochemotherapy. Real-time polymerase chain reaction was used to determine the genetic polymorphisms of CYP2E1, GSTP1, NAT1, and NAT2 genes. Our results showed that the polymorphisms of CYP2E1, GSTP1, and NAT1 genes did not influence the prognosis of DLBCL patients significantly. In terms of the NAT2 gene, GG homozygous patients showed slightly better therapeutic response and survival results compared to those bearing an A allele; however, the differences were not statistically significant. Our results could not confirm that genetic polymorphism in metabolic pathways has any predictive role in DLBCL.

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

    Science.gov (United States)

    Igarashi, Kazuhiko; Watanabe-Matsui, Miki

    2014-04-01

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

  4. Mammalian Tissue Response to Low Dose Ionizing Radiation: The Role of Oxidative Metabolism and Intercellular Communication

    Energy Technology Data Exchange (ETDEWEB)

    Azzam, Edouard I

    2013-01-16

    The objective of the project was to elucidate the mechanisms underlying the biological effects of low dose/low dose rate ionizing radiation in organs/tissues of irradiated mice that differ in their susceptibility to ionizing radiation, and in human cells grown under conditions that mimic the natural in vivo environment. The focus was on the effects of sparsely ionizing cesium-137 gamma rays and the role of oxidative metabolism and intercellular communication in these effects. Four Specific Aims were proposed. The integrated outcome of the experiments performed to investigate these aims has been significant towards developing a scientific basis to more accurately estimate human health risks from exposures to low doses ionizing radiation. By understanding the biochemical and molecular changes induced by low dose radiation, several novel markers associated with mitochondrial functions were identified, which has opened new avenues to investigate metabolic processes that may be affected by such exposure. In particular, a sensitive biomarker that is differentially modulated by low and high dose gamma rays was discovered.

  5. Cofilin/Twinstar phosphorylation levels increase in response to impaired coenzyme a metabolism.

    Directory of Open Access Journals (Sweden)

    Katarzyna Siudeja

    Full Text Available Coenzyme A (CoA is a pantothenic acid-derived metabolite essential for many fundamental cellular processes including energy, lipid and amino acid metabolism. Pantothenate kinase (PANK, which catalyses the first step in the conversion of pantothenic acid to CoA, has been associated with a rare neurodegenerative disorder PKAN. However, the consequences of impaired PANK activity are poorly understood. Here we use Drosophila and human neuronal cell cultures to show how PANK deficiency leads to abnormalities in F-actin organization. Cells with reduced PANK activity are characterized by abnormally high levels of phosphorylated cofilin, a conserved actin filament severing protein. The increased levels of phospho-cofilin coincide with morphological changes of PANK-deficient Drosophila S2 cells and human neuronal SHSY-5Y cells. The latter exhibit also markedly reduced ability to form neurites in culture--a process that is strongly dependent on actin remodeling. Our results reveal a novel and conserved link between a metabolic biosynthesis pathway, and regulation of cellular actin dynamics.

  6. Are People Responsive to a More Sustainable, Decentralized, and User-Driven Management of Urban Metabolism?

    Directory of Open Access Journals (Sweden)

    Lorenzo Chelleri

    2016-03-01

    Full Text Available Smart, green, and resilient city paradigms have been mainly promoted through top-down and technocratic approaches. However, based on the notion to return to “the right to the city”, emerging community-driven initiatives are providing self-managed infrastructures contributing to urban sustainability transitions. This paper explores the relevance of the behavioral aspects of people-centered approaches in dealing with two different facets of urban metabolism: physical infrastructure (involvement with the management of decentralized infrastructures and consumption patterns (involvement in proactive reduction of resources used. In the first case we assessed community perceptions about the roles, benefits, and willingness to proactively engage in the management of decentralized green infrastructures in Bogotá City, Colombia. For the second facet, we measured the effectiveness of change agents in re-shaping energy consumption decisions within urban social networks in South Africa and Saudi Arabia. This paper’s results show that pre-determined and standardized strategies do not guarantee positive, nor homogeneous, results in terms of meeting sustainability targets, or promoting community involvement. Hence, a better integration of people-centered and top-down approaches is needed through context-dependent policies, for enhancing both users’ appreciation of and commitment to urban metabolism participative management.

  7. Metabolic response to lipid infusion in fasting winter-acclimatized king penguin chicks (Aptenodytes patagonicus).

    Science.gov (United States)

    Teulier, Loïc; Tornos, Jérémy; Rouanet, Jean-Louis; Rey, Benjamin; Roussel, Damien

    2013-05-01

    During the cold austral winter, king penguin chicks are infrequently fed by their parents and thus experience severe nutritional deprivation under harsh environmental conditions. These energetic constraints lead to a range of energy sparing mechanisms balanced by the maintenance of efficient thermogenic processes. The present work investigated whether the high thermogenic capacities exhibited by winter-acclimatized king penguin chicks could be related to an increase in lipid substrate supply and oxidation in skeletal muscle, the main site of thermogenesis in birds. To test this hypothesis, we examined i) the effect of an experimental rise in plasma triglyceride on the whole metabolic rate in winter-acclimatized (WA) and de-acclimatized king penguin chicks kept at thermoneutrality (TN), and ii) investigated the fuel preference of muscle mitochondria. In vivo, a perfusion of a lipid emulsion induced a small 10% increase of metabolic rate in WA chicks but not in TN group. In vitro, the oxidation rate of muscle mitochondria respiring on lipid-derived substrate was +40% higher in WA chicks than in TN, while no differences were found between groups when mitochondria oxidized carbohydrate-derived substrate or succinate. Despite an enhanced fuel selection towards lipid oxidation in skeletal muscle, a rise of circulating lipids per se was not sufficient to fully unravel the thermogenic capacity of winter-acclimatized king penguin chicks. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress.

    Science.gov (United States)

    Kant, Shashi; Standen, Claire L; Morel, Caroline; Jung, Dae Young; Kim, Jason K; Swat, Wojciech; Flavell, Richard A; Davis, Roger J

    2017-09-19

    Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH 2 -terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress

    Directory of Open Access Journals (Sweden)

    Shashi Kant

    2017-09-01

    Full Text Available Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA activation of a non-receptor tyrosine kinase (SRC-dependent cJun NH2-terminal kinase (JNK signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway.

  10. Effect of 3,5,3'-triiodothyronine-induced hyperthyroidism on iodothyronine metabolism in the rat: evidence for tissue differences in metabolic responses.

    Science.gov (United States)

    Chopra, I J; Huang, T S; Hurd, R E; Solomon, D H

    1984-04-01

    tissues became maximal between 48 and 72 h after the initiation of T3 treatment. Our data suggest that most tissues, including some that have been considered unresponsive to thyroid hormones, e.g. brain and spleen, demonstrate substantial metabolic changes after T3 administration. The tissue responses are variable in degree; in some instances, they are specific for the substrate and type of tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

  11. Effects of dissolved carbon dioxide on energy metabolism and stress responses in European seabass (Dicentrarchus labrax)

    NARCIS (Netherlands)

    Santos, G.A.; Schrama, J.W.; Capelle, J.; Rombout, J.H.W.M.; Verreth, J.A.J.

    2013-01-01

    Elevated carbon dioxide concentrations reduce feed intake and growth in several fish species and induce stress responses. In this study, the effects of moderately elevated CO2 levels on performance, energy partitioning, swimming activity and stress response in European seabass were assessed.

  12. The accurate definition of metabolic volumes on 18F-FDG-PET before treatment allows the response to chemoradiotherapy to be predicted in the case of oesophagus cancers

    International Nuclear Information System (INIS)

    Hatt, M.; Cheze-Le Rest, C.; Visvikis, D.; Pradier, O.

    2011-01-01

    This study aims at assessing the possibility of prediction of the response of locally advanced oesophagus cancers, even before the beginning of treatment, by using metabolic volume measurements performed on 18 F-FDG PET images made before the treatment. Medical files of 50 patients have been analyzed. According to the observed responses, and to metabolic volume and Total Lesion Glycosis (TLG) values, it appears that the images allow the extraction of parameters, such as the TLG, which are criteria for the prediction of the therapeutic response. Short communication

  13. Emiliania Huxleyi (Prymnesiophyceae): Nitrogen-metabolism genes and their expression in response to external nitrogen souces

    DEFF Research Database (Denmark)

    Bruhn, Annette; LaRoche, Julie; Richardson, Katherine

    2010-01-01

    The availability and composition of dissolved nitrogen in ocean waters are factors that influence species composition in natural phytoplankton communities. The same factors affect the ratio of organic to inorganic carbon incorporation in calcifying species, such as the coccolithophore Emiliania...... huxleyi (Lohman) W. W. Hay et H. Mohler. E. huxleyi has been shown to thrive on various nitrogen sources, including dissolved organic nitrogen. Nevertheless, assimilation of dissolved nitrogen under nitrogen-replete and -limited conditions is not well understood in this ecologically important species....... In this study, the complete amino acid sequences for three functional genes involved in nitrogen metabolism in E. huxleyi were identified: a putative formamidase, a glutamine synthetase (GSII family), and assimilatory nitrate reductase. Expression patterns of the three enzymes in cells grown on inorganic...

  14. Myostatin promotes distinct responses on protein metabolism of skeletal and cardiac muscle fibers of rodents.

    Science.gov (United States)

    Manfredi, L H; Paula-Gomes, S; Zanon, N M; Kettelhut, I C

    2017-10-19

    Myostatin is a novel negative regulator of skeletal muscle mass. Myostatin expression is also found in heart in a much less extent, but it can be upregulated in pathological conditions, such as heart failure. Myostatin may be involved in inhibiting protein synthesis and/or increasing protein degradation in skeletal and cardiac muscles. Herein, we used cell cultures and isolated muscles from rats to determine protein degradation and synthesis. Muscles incubated with myostatin exhibited an increase in proteolysis with an increase of Atrogin-1, MuRF1 and LC3 genes. Extensor digitorum longus muscles and C2C12 myotubes exhibited a reduction in protein turnover. Cardiomyocytes showed an increase in proteolysis by activating autophagy and the ubiquitin proteasome system, and a decrease in protein synthesis by decreasing P70S6K. The effect of myostatin on protein metabolism is related to fiber type composition, which may be associated to the extent of atrophy mediated effect of myostatin on muscle.

  15. AquaMUNE, a brown seaweed extract, improves metabolism, immune response, energy and chelates heavy metals.

    Science.gov (United States)

    1998-01-01

    The National Cancer Institute (NCI) has shown interest in the curative powers of ocean plants, many of which appear to possess powerful anti-inflammatory, antiviral, antimicrobial, antifungal, anticancer, and immuno-suppressive properties. AQUAMune, a brown seaweed extract developed by Aqua-10 Laboratories, has gained marketing rights for use as a nutritional supplement. Research shows that it acts as a receptor blocker for many pathogens, including Salmonella, and is effective against Haemophilus pneumonia. AQUAMune is also reported to inhibit outbreaks of genital herpes. Other marine plants are also showing positive curative powers. Evidence reveals that a red marine algae from the Philippines has selective antitumor properties; and that carageenans, a family of sulfated polysaccharides, appear to have anti-viral capabilities. Seaweeds act as natural chelators of heavy metals that improve metabolism in cells, increase ATP production, body temperature, energy levels, and immune function.

  16. Metabolic responses of Lactobacillus plantarum strains during fermentation and storage of vegetable and fruit juices.

    Science.gov (United States)

    Filannino, P; Cardinali, G; Rizzello, C G; Buchin, S; De Angelis, M; Gobbetti, M; Di Cagno, R

    2014-04-01

    Strains of Lactobacillus plantarum were grown and stored in cherry (ChJ), pineapple (PJ), carrot (CJ), and tomato (TJ) juices to mimic the chemical composition of the respective matrices. Wheat flour hydrolysate (WFH), whey milk (W), and MRS broth were also used as representatives of other ecosystems. The growth rates and cell densities of L. plantarum strains during fermentation (24 h at 30°C) and storage (21 days at 4°C) differed only in part, being mainly influenced by the matrix. ChJ and PJ were the most stressful juices for growth and survival. Overall, the growth in juices was negatively correlated with the initial concentration of malic acid and carbohydrates. The consumption of malic acid was noticeable for all juices, but mainly during fermentation and storage of ChJ. Decreases of branched-chain amino acids (BCAA)-with the concomitant increase of their respective branched alcohols-and His and increases of Glu and gamma-aminobutyric acid (GABA) were the main traits of the catabolism of free amino acids (FAA), which were mainly evident under less acidic conditions (CJ and TJ). The increase of Tyr was found only during storage of ChJ. Some aldehydes (e.g., 3-methyl-butanal) were reduced to the corresponding alcohols (e.g., 3-methyl-1-butanol). After both fermentation and storage, acetic acid increased in all fermented juices, which implied the activation of the acetate kinase route. Diacetyl was the ketone found at the highest level, and butyric acid increased in almost all fermented juices. Data were processed through multidimensional statistical analyses. Except for CJ, the juices (mainly ChJ) seemed to induce specific metabolic traits, which differed in part among the strains. This study provided more in-depth knowledge on the metabolic mechanisms of growth and maintenance of L. plantarum in vegetable and fruit habitats, which also provided helpful information to select the most suitable starters for fermentation of targeted matrices.

  17. Daily Stressors, Past Depression, and Metabolic Responses to High-Fat Meals: A Novel Path to Obesity

    Science.gov (United States)

    Kiecolt-Glaser, Janice K.; Habash, Diane L.; Fagundes, Christopher P.; Andridge, Rebecca; Peng, Juan; Malarkey, William B.; Belury, Martha A.

    2014-01-01

    Background Depression and stress promote obesity. This study addressed the impact of daily stressors and a history of major depressive disorder (MDD) on obesity-related metabolic responses to high-fat meals. Methods This double-blind, randomized crossover study included serial assessments of resting energy expenditure (REE), fat and carbohydrate oxidation, triglycerides, cortisol, insulin and glucose before and after two high-fat meals. During two separate 9.5 hour admissions, 58 healthy women (38 breast cancer survivors and 20 demographically-similar controls), mean age 53.1 years, received either a high saturated fat meal or a high oleic sunflower oil meal. Prior day stressors were assessed by the Daily Inventory of Stressful Events and MDD history by the Structured Clinical Interview for DSM-IV. Results Greater numbers of stressors were associated with lower post-meal REE (P=.008), lower fat oxidation (P=.04), and higher insulin (P=.01), with nonsignificant effects for cortisol (P=.25) and glucose (P=.33). Women with prior MDD had higher cortisol (P=.008), and higher fat oxidation (P=.004), without significant effects for REE (P=.26), insulin (P=.25), and glucose (P=.38). Women with a depression history who also had more prior day stressors had a higher peak triglyceride response than other participants (P=.01). The only difference between meals was higher postprandial glucose following sunflower oil compared to saturated fat (P=.03). Conclusions The cumulative 6-hour difference between one prior day stressor and no stressors translates into 104 kcal, a difference that could add almost 11 pounds/year. These findings illustrate how stress and depression alter metabolic responses to high-fat meals in ways that promote obesity. PMID:25034950

  18. A comparison of 2 circuit exercise training techniques for eliciting matched metabolic responses in persons with paraplegia.

    Science.gov (United States)

    Nash, Mark S; Jacobs, Patrick L; Woods, Jeffrey M; Clark, James E; Pray, Tanya A; Pumarejo, Alex E

    2002-02-01

    To test whether acute metabolic (VO(2)), chronotropic (heart rate), and perceptual (rating of perceived exertion; RPE) responses to exercise by persons with paraplegia differ when the exercise is on a multistation isoinertial exercise system (MultiGym) or on a customized system of Thera-Band resistance bands (ElasticGym). Within-subjects comparison of 2 treatments. Academic medical center. Sixteen men and 1 woman with complete paraplegia (T4-L1), as defined by the American Spinal Injury Association. A circuit resistance training (CRT) program for persons with paraplegia was adapted to both a MultiGym and a customized ElasticGym. Exercises used for training and testing used 6 resistance maneuvers at 50% of the 1-repetition maximum (1-RM), with interposed rapid arm spinning. Subjects were habituated to both conditions for 2 weeks before testing on randomized nonconsecutive days. VO(2) (L/min) was measured by portable spirometry, heart rate (beats/min) by a chest strap monitor, and RPE by the Borg Scale of Perceived Exertion (6-20). No significant effects of test condition on average VO(2) or heart rate were observed, with differences between conditions reflecting only .08L/min and 6.4 beats/min, respectively. Average RPE was significantly higher in testing under the ElasticGym condition (P < .05). CRT on a customized ElasticGym system elicited acute metabolic and chronotropic responses that did not differ from responses to exercise on a MultiGym, though RPE was greater with the ElasticGym. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

  19. Stomatal responses to CO2 during a diel Crassulacean acid metabolism cycle in Kalanchoe daigremontiana and Kalanchoe pinnata.

    Science.gov (United States)

    von Caemmerer, Susanne; Griffiths, Howard

    2009-05-01

    To investigate the diurnal variation of stomatal sensitivity to CO2, stomatal response to a 30 min pulse of low CO2 was measured four times during a 24 h time-course in two Crassulacean acid metabolism (CAM) species Kalanchoe daigremontiana and Kalanchoe pinnata, which vary in the degree of succulence, and hence, expression and commitment to CAM. In both species, stomata opened in response to a reduction in pCO2 in the dark and in the latter half of the light period, and thus in CAM species, chloroplast photosynthesis is not required for the stomatal response to low pCO2. Stomata did not respond to a decreased pCO2 in K. daigremontiana in the light when stomata were closed, even when the supply of internal CO2 was experimentally reduced. We conclude that stomatal closure during phase III is not solely mediated by high internal pCO2, and suggest that in CAM species the diurnal variability in the responsiveness of stomata to pCO2 could be explained by hypothesizing the existence of a single CO2 sensor which interacts with other signalling pathways. When not perturbed by low pCO2, CO2 assimilation rate and stomatal conductance were correlated both in the light and in the dark in both species.

  20. Aryl hydrocarbon receptor signaling modulates antiviral immune responses: ligand metabolism rather than chemical source is the stronger predictor of outcome.

    Science.gov (United States)

    Boule, Lisbeth A; Burke, Catherine G; Jin, Guang-Bi; Lawrence, B Paige

    2018-01-29

    The aryl hydrocarbon receptor (AHR) offers a compelling target to modulate the immune system. AHR agonists alter adaptive immune responses, but the consequences differ across studies. We report here the comparison of four agents representing different sources of AHR ligands in mice infected with influenza A virus (IAV): TCDD, prototype exogenous AHR agonist; PCB126, pollutant with documented human exposure; ITE, novel pharmaceutical; and FICZ, degradation product of tryptophan. All four compounds diminished virus-specific IgM levels and increased the proportion of regulatory T cells. TCDD, PCB126 and ITE, but not FICZ, reduced virus-specific IgG levels and CD8 + T cell responses. Similarly, ITE, PCB126, and TCDD reduced Th1 and Tfh cells, whereas FICZ increased their frequency. In Cyp1a1-deficient mice, all compounds, including FICZ, reduced the response to IAV. Conditional Ahr knockout mice revealed that all four compounds require AHR within hematopoietic cells. Thus, differences in the immune response to IAV likely reflect variances in quality, magnitude, and duration of AHR signaling. This indicates that binding affinity and metabolism may be stronger predictors of immune effects than a compound's source of origin, and that harnessing AHR will require finding a balance between dampening immune-mediated pathologies and maintaining sufficient host defenses against infection.

  1. Phase I to II cross-induction of xenobiotic metabolizing enzymes: A feedforward control mechanism for potential hormetic responses

    International Nuclear Information System (INIS)

    Zhang Qiang; Pi Jingbo; Woods, Courtney G.; Andersen, Melvin E.

    2009-01-01

    Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a

  2. Phase I to II cross-induction of xenobiotic metabolizing enzymes: a feedforward control mechanism for potential hormetic responses.

    Science.gov (United States)

    Zhang, Qiang; Pi, Jingbo; Woods, Courtney G; Andersen, Melvin E

    2009-06-15

    Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a

  3. Energy metabolism and memory processing: role of glucose transport and glycogen in responses to adrenoceptor activation in the chicken.

    Science.gov (United States)

    Hutchinson, Dana S; Summers, Roger J; Gibbs, Marie E

    2008-06-15

    From experiments using a discriminated bead task in young chicks, we have defined when and where adrenoceptors (ARs) are involved in memory modulation. All three ARs subtypes (alpha(1)-, alpha(2)- and beta-ARs) are found in the chick brain and in regions associated with memory. Glucose and glycogen are important in the role of memory consolidation in the chick since increasing glucose levels improves memory consolidation while inhibiting glucose transporters (GLUTs) or glycogen breakdown inhibits memory consolidation. The selective beta(3)-AR agonist CL316243 enhances memory consolidation by a glucose-dependent mechanism and the administration of the non-metabolized glucose analogue 2-deoxyglucose reduces the ability of CL316243 to enhance memory. Agents that reduce glucose uptake by GLUTs and its incorporation into the glycolytic pathway also reduce the effectiveness of CL316243, but do not alter the dose-response relationship to the beta(2)-AR agonist zinterol. However, beta(2)-ARs do have a role in memory related to glycogen breakdown and inhibition of glycogenolysis reduces the ability of zinterol to enhance memory. Both beta(2)- and beta(3)-ARs are found on astrocytes from chick forebrain, and the actions of beta(3)-ARs on glucose uptake, and beta(2)-ARs on the breakdown of glycogen is consistent with an effect on astrocytic metabolism at the time of memory consolidation 30 min after training. We have shown that both beta(2)- and beta(3)-ARs can increase glucose uptake in chick astrocytes but do so by different mechanisms. This review will focus on the role of ARs on memory consolidation and specifically the role of energy metabolism on AR modulation of memory.

  4. Metabolic responses of Beauveria bassiana to hydrogen peroxide-induced oxidative stress using an LC-MS-based metabolomics approach.

    Science.gov (United States)

    Zhang, Chen; Wang, Wei; Lu, Ruili; Jin, Song; Chen, Yihui; Fan, Meizhen; Huang, Bo; Li, Zengzhi; Hu, Fenglin

    2016-06-01

    The entomopathogenic fungus, Beauveria bassiana, is commonly used as a biological agent for pest control. Environmental and biological factors expose the fungus to oxidative stress; as a result, B. bassiana has adopted a number of anti-oxidant mechanisms. In this study, we investigated metabolites of B. bassiana that are formed in response to oxidative stress from hydrogen peroxide (H2O2) by using a liquid chromatography mass spectrometry (LC-MS) approach. Partial least-squares discriminant analysis (PLS-DA) revealed differences between the control and the H2O2-treated groups. Hierarchical cluster analysis (HCA) showed 18 up-regulated metabolites and 25 down-regulated metabolites in the H2O2-treated fungus. Pathway analysis indicated that B. bassiana may be able to alleviate oxidative stress by enhancing lipid catabolism and glycometabolism, thus decreasing membrane polarity and preventing polar H2O2 or ROS from permeating into fungal cells and protecting cells against oxidative injury. Meanwhile, most of the unsaturated fatty acids that are derived from glycerophospholipids hydrolysis can convert into oxylipins through autoxidation, which can prevent the reactive oxygen of H2O2 from attacking important macromolecules of the fungus. Results showed also that H2O2 treatment can enhance mycotoxins production which implies that oxidative stress may be able to increase the virulence of the fungus. In comparison to the control group, citric acid and UDP-N-acetylglucosamine were down-regulated, which suggested that metabolic flux was occurring to the TCA cycle and enhancing carbohydrate metabolism. The findings from this study will contribute to the understanding of how the molecular mechanisms of fungus respond to environmental and biological stress factors as well as how the manipulation of such metabolisms may lead to selection of more effective fungal strains for pest control. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Developmental and Metabolic Plasticity of White-Skinned Grape Berries in Response to Botrytis cinerea during Noble Rot1[OPEN

    Science.gov (United States)

    Collins, Thomas S.; Vicente, Ariel R.; Doyle, Carolyn L.; Ye, Zirou; Allen, Greg; Heymann, Hildegarde

    2015-01-01

    Noble rot results from exceptional infections of ripe grape (Vitis vinifera) berries by Botrytis cinerea. Unlike bunch rot, noble rot promotes favorable changes in grape berries and the accumulation of secondary metabolites that enhance wine grape composition. Noble rot-infected berries of cv Sémillon, a white-skinned variety, were collected over 3 years from a commercial vineyard at the same time that fruit were harvested for botrytized wine production. Using an integrated transcriptomics and metabolomics approach, we demonstrate that noble rot alters the metabolism of cv Sémillon berries by inducing biotic and abiotic stress responses as well as ripening processes. During noble rot, B. cinerea induced the expression of key regulators of ripening-associated pathways, some of which are distinctive to the normal ripening of red-skinned cultivars. Enhancement of phenylpropanoid metabolism, characterized by a restricted flux in white-skinned berries, was a common outcome of noble rot and red-skinned berry ripening. Transcript and metabolite analyses together with enzymatic assays determined that the biosynthesis of anthocyanins is a consistent hallmark of noble rot in cv Sémillon berries. The biosynthesis of terpenes and fatty acid aroma precursors also increased during noble rot. We finally characterized the impact of noble rot in botrytized wines. Altogether, the results of this work demonstrated that noble rot causes a major reprogramming of berry development and metabolism. This desirable interaction between a fruit and a fungus stimulates pathways otherwise inactive in white-skinned berries, leading to a greater accumulation of compounds involved in the unique flavor and aroma of botrytized wines. PMID:26450706

  6. Caloric restriction alters the metabolic response to a mixed-meal: results from a randomized, controlled trial.

    Directory of Open Access Journals (Sweden)

    Kim M Huffman

    Full Text Available To determine if caloric restriction (CR would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to determine how any such changes relate to insulin sensitivity (S(I.Forty-six volunteers were randomized to a weight maintenance diet (Control, 25% CR, or 12.5% CR plus 12.5% energy deficit from structured aerobic exercise (CR+EX, or a liquid calorie diet (890 kcal/d until 15% reduction in body weightfor six months. Fasting and postprandial plasma samples were obtained at baseline, three, and six months. A targeted mass spectrometry-based platform was used to measure concentrations of individual free fatty acids (FFA, amino acids (AA, and acylcarnitines (AC. S(I was measured with an intravenous glucose tolerance test.Over three and six months, there were significantly larger differences in fasting-to-postprandial (FPP concentrations of medium and long chain AC (byproducts of FA oxidation in the CR relative to Control and a tendency for the same in CR+EX (CR-3 month P = 0.02; CR-6 month P = 0.002; CR+EX-3 month P = 0.09; CR+EX-6 month P = 0.08. After three months of CR, there was a trend towards a larger difference in FPP FFA concentrations (P = 0.07; CR-3 month P = 0.08. Time-varying differences in FPP concentrations of AC and AA were independently related to time-varying S(I (P<0.05 for both.Based on changes in intermediates of FA oxidation following a food challenge, CR imparted improvements in metabolic flexibility that correlated with improvements in S(I.ClinicalTrials.gov NCT00099151.

  7. Effect of adrenal medullectomy on metabolic responses to chronic intermittent hypoxia in the frequently sampled intravenous glucose tolerance test.

    Science.gov (United States)

    Shin, Mi-Kyung; Han, Woobum; Joo, Hoon; Bevans-Fonti, Shannon; Shiota, Masakazu; Stefanovski, Darko; Polotsky, Vsevolod Y

    2017-04-01

    Obstructive sleep apnea is associated with type 2 diabetes. We have previously developed a mouse model of intermittent hypoxia (IH) mimicking oxyhemoglobin desaturations in patients with sleep apnea and have shown that IH increases fasting glucose, hepatic glucose output, and plasma catecholamines. We hypothesize that adrenal medulla modulates glucose responses to IH and that such responses can be prevented by adrenal medullectomy. We performed adrenal medullectomy or sham surgery in lean C57BL/6J mice, which were exposed to IH or intermittent air (control) for 4 wk followed by the frequently sampled intravenous glucose tolerance test (FSIVGTT) in unanesthetized unrestrained animals. IH was administered during the 12-h light phase (9 AM to 9 PM) by decreasing inspired oxygen from 21 to 6.5% 60 cycles/h. Insulin sensitivity (S I ), insulin independent glucose disposal [glucose effectiveness (S G )], and the insulin response to glucose (AIR G ) were determined using the minimal model method. In contrast to our previous data obtained in restrained mice, IH did not affect fasting blood glucose and plasma insulin levels in sham-operated mice. IH significantly decreased S G but did not affect S I and AIR G Adrenal medullectomy decreased fasting blood glucose and plasma insulin levels and increased glycogen synthesis in the liver in hypoxic mice but did not have a significant effect on the FSIVGTT metrics. We conclude that, in the absence of restraints, IH has no effect on glucose metabolism in lean mice with exception of decreased S G , whereas adrenal medullectomy decreases fasting glucose and insulin levels in the IH environment. NEW & NOTEWORTHY To our knowledge, this is the first study examining the role of adrenal catecholamines in glucose metabolism during intermittent hypoxia (IH) in unanesthetized unrestrained C57BL/6J mice. We report that IH did not affect fasting glucose and insulin levels nor insulin sensitivity and insulin secretion during, whereas glucose

  8. Correlation of methylenetetrahydrofolate reductase polymorphism with Hcy metabolism and inflammatory response in patients with recurrent cerebral infarction

    Directory of Open Access Journals (Sweden)

    Gai-Zhuang Liu

    2017-07-01

    Full Text Available Objective: To study the correlation of methylenetetrahydrofolate reductase (MTHFR polymorphism with Hcy metabolism and inflammatory response in patients with recurrent cerebral infarction. Methods: 40 patients with recurrent cerebral infarction who were treated in Yulin Third Hospital between December 2013 and December 2016 were selected as recurrent group, 58 patients with primary cerebral infarction were selected as primary group, and 60 healthy volunteers were selected as control group. Peripheral blood MTHFR gene C677T polymorphism and serum levels of Hcy metabolism indexes and inflammatory response indicators were determined. Results: CC genotype constituent ratio of recurrent group was significantly lower than that of primary group and control group while CT genotype and TT genotype constituent ratio were significantly higher than those of primary group and control group; serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in recurrent group and primary group were significantly higher than those in control group while VitB12 and FA levels were significantly lower than those in control group; serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in recurrent group were significantly higher than those in primary group while VitB12 and FA levels were significantly lower than those in primary group. Serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in patients with CC genotype were significantly lower than those in patients with CT genotype and TT genotype while VitB12 and FA levels were significantly higher than those in patients with CT genotype and TT genotype; serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in patients with CT genotype were significantly lower than those in patients with TT genotype while VitB12 and FA levels were significantly higher than those in patients with TT genotype. Conclusion: MTHFR gene C677T polymorphism is closely related to the recurrence of cerebral infarction, and allele C

  9. Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Jacqueline R. Thompson

    2018-04-01

    Full Text Available Nutritional status influences brain health and gestational exposure to metabolic disorders (e.g. obesity and diabetes increases the risk of neuropsychiatric disorders. The aim of the present study was to further investigate the role of maternal Western-style diet (WSD, metabolic state, and inflammatory factors in the programming of Japanese macaque offspring behavior. Utilizing structural equation modeling, we investigated the relationships between maternal diet, prepregnancy adiposity, third trimester insulin response, and plasma cytokine levels on 11-month-old offspring behavior. Maternal WSD was associated with greater reactive and ritualized anxiety in offspring. Maternal adiposity and third trimester macrophage-derived chemokine (MDC exerted opposing effects on offspring high-energy outbursts. Elevated levels of this behavior were associated with low maternal MDC and increased prepregnancy adiposity. This is the first study to show that maternal MDC levels influence offspring behavior. We found no evidence suggesting maternal peripheral inflammatory response mediated the effect of maternal diet and metabolic state on aberrant offspring behavior. Additionally, the extent of maternal metabolic impairment differentially influenced chemokine response. Elevated prepregnancy adiposity suppressed third trimester chemokines, while obesity-induced insulin resistance augmented peripheral chemokine levels. WSD also directly increased maternal interleukin-12. This is the first non-human primate study to delineate the effects of maternal diet and metabolic state on gestational inflammatory environment and subsequent offspring behavior. Our findings give insight to the complex mechanisms by which diet, metabolic state, and inflammation during pregnancy exert unique influences on offspring behavioral regulation.

  10. Human adipose cells in vitro are either refractory or responsive to insulin, reflecting host metabolic state.

    Directory of Open Access Journals (Sweden)

    Vladimir A Lizunov

    Full Text Available While intercellular communication processes are frequently characterized by switch-like transitions, the endocrine system, including the adipose tissue response to insulin, has been characterized by graded responses. Yet here individual cells from adipose tissue biopsies are best described by a switch-like transition between the basal and insulin-stimulated states for the trafficking of the glucose transporter GLUT4. Two statistically-defined populations best describe the observed cellular heterogeneity, representing the fractions of refractive and responsive adipose cells. Furthermore, subjects exhibiting high systemic insulin sensitivity indices (SI have high fractions of responsive adipose cells in vitro, while subjects exhibiting decreasing SI have increasing fractions of refractory cells in vitro. Thus, a two-component model best describes the relationship between cellular refractory fraction and subject SI. Since isolated cells exhibit these different response characteristics in the presence of constant culture conditions and milieu, we suggest that a physiological switching mechanism at the adipose cellular level ultimately drives systemic SI.

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

    Directory of Open Access Journals (Sweden)

    Fleischmann Robert D

    2010-01-01

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

  12. Scaling dynamic response and destructive metabolism in an immunosurveillant anti-tumor system modulated by different external periodic interventions.

    Directory of Open Access Journals (Sweden)

    Yuanzhi Shao

    Full Text Available On the basis of two universal power-law scaling laws, i.e. the scaling dynamic hysteresis in physics and the allometric scaling metabolism in biosystem, we studied the dynamic response and the evolution of an immunosurveillant anti-tumor system subjected to a periodic external intervention, which is equivalent to the scheme of a radiotherapy or chemotherapy, within the framework of the growth dynamics of tumor. Under the modulation of either an abrupt or a gradual change external intervention, the population density of tumors exhibits a dynamic hysteresis to the intervention. The area of dynamic hysteresis loop characterizes a sort of dissipative-therapeutic relationship of the dynamic responding of treated tumors with the dose consumption of accumulated external intervention per cycle of therapy. Scaling the area of dynamic hysteresis loops against the intensity of an external intervention, we deduced a characteristic quantity which was defined as the theoretical therapeutic effectiveness of treated tumor and related with the destructive metabolism of tumor under treatment. The calculated dose-effectiveness profiles, namely the dose cumulant per cycle of intervention versus the therapeutic effectiveness, could be well scaled into a universal quadratic formula regardless of either an abrupt or a gradual change intervention involved. We present a new concept, i.e., the therapy-effect matrix and the dose cumulant matrix, to expound the new finding observed in the growth and regression dynamics of a modulated anti-tumor system.

  13. Metabolic Symbiosis and Immunomodulation: How Tumor Cell-Derived Lactate May Disturb Innate and Adaptive Immune Responses

    Directory of Open Access Journals (Sweden)

    Alexandre Morrot

    2018-03-01

    Full Text Available The tumor microenvironment (TME is composed by cellular and non-cellular components. Examples include the following: (i bone marrow-derived inflammatory cells, (ii fibroblasts, (iii blood vessels, (iv immune cells, and (v extracellular matrix components. In most cases, this combination of components may result in an inhospitable environment, in which a significant retrenchment in nutrients and oxygen considerably disturbs cell metabolism. Cancer cells are characterized by an enhanced uptake and utilization of glucose, a phenomenon described by Otto Warburg over 90 years ago. One of the main products of this reprogrammed cell metabolism is lactate. “Lactagenic” or lactate-producing cancer cells are characterized by their immunomodulatory properties, since lactate, the end product of the aerobic glycolysis, besides acting as an inducer of cellular signaling phenomena to influence cellular fate, might also play a role as an immunosuppressive metabolite. Over the last 10 years, it has been well accepted that in the TME, the lactate secreted by transformed cells is able to compromise the function and/or assembly of an effective immune response against tumors. Herein, we will discuss recent advances regarding the deleterious effect of high concentrations of lactate on the tumor-infiltrating immune cells, which might characterize an innovative way of understanding the tumor-immune privilege.

  14. Subcutaneous inguinal white adipose tissue is responsive to, but dispensable for, the metabolic health benefits of exercise.

    Science.gov (United States)

    Peppler, Willem T; Townsend, Logan K; Knuth, Carly M; Foster, Michelle T; Wright, David C

    2018-01-01

    Exercise training has robust effects on subcutaneous inguinal white adipose tissue (iWAT), characterized by a shift to a brown adipose tissue (BAT)-like phenotype. Consistent with this, transplantation of exercise-trained iWAT into sedentary rodents activates thermogenesis and improves glucose homeostasis, suggesting that iWAT metabolism may contribute to the beneficial effects of exercise. However, it is yet to be determined if adaptations in iWAT are necessary for the beneficial systemic effects of exercise. To test this, male C57BL/6 mice were provided access to voluntary wheel running (VWR) or remained as a cage control (SED) for 11 nights after iWAT removal via lipectomy (LIPX) or SHAM surgery. We found that SHAM and LIPX mice with access to VWR ran similar distances and had comparable reductions in body mass, increased food intake, and increased respiratory exchange ratio (RER). Further, VWR improved indexes of glucose homeostasis and insulin tolerance in both SHAM and LIPX mice. The lack of effect of LIPX in the response to VWR was not explained by compensatory increases in markers of mitochondrial biogenesis and thermogenesis in skeletal muscle, epididymal white adipose tissue, or interscapular brown adipose tissue. Together, these data demonstrate that mice with and without iWAT have comparable adaptations to VWR, suggesting that iWAT may be dispensable for the metabolic health benefits of exercise.

  15. Insulin resistance, insulin response, and obesity as indicators of metabolic risk

    DEFF Research Database (Denmark)

    Ferrannini, Ele; Balkau, Beverley; Coppack, Simon W

    2007-01-01

    CONTEXT: Insulin resistance (IR) and obesity, especially abdominal obesity, are regarded as central pathophysiological features of a cluster of cardiovascular risk factors (CVRFs), but their relative roles remain undefined. Moreover, the differential impact of IR viz. insulin response has not been...... evaluated. OBJECTIVE: The objective of this study was to dissect out the impact of obesity, abdominal obesity, and IR/insulin response on CVRF. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at 21 research centers in Europe. SUBJECTS: The study included a cohort of 1308......-cholesterol, and lower high-density lipoprotein-cholesterol, and insulin response to higher heart rate, blood pressure and fasting glucose, and the same dyslipidemic profile as IR (P

  16. Metabolic stress and inflammatory response in high-yielding, periparturient dairy cows.

    Science.gov (United States)

    Trevisi, E; Amadori, M; Cogrossi, S; Razzuoli, E; Bertoni, G

    2012-10-01

    Increased disease rates are commonly reported among high-yielding dairy cows in the transition period, extending from 3 weeks before to 3 weeks after calving, and characterized by the occurrence of an inflammatory response in terms of both positive and negative acute phase proteins (APP+ and APP-). To determine the above inflammatory response, the authors had developed the Liver Functionality Index (LFI), which defines the above condition on the basis of some APP- responses (albumin, cholesterol sensu stricto+bilirubin) during the first month of lactation. In this respect, low LFI values are associated to a high inflammatory response and vice versa. The relationship between LFI and inflammatory cytokine response was investigated from day -28 to day +28 with respect to calving in 12 periparturient dairy cows showing the six highest and six lowest LFI values within a cohort of 54 high-yielding dairy cows. The hypothesis being tested was that LFI and APP- on the whole could be used as readout of successful vs. non-successful adaptation to the transition period, with a strong association to disease occurrence. In fact, low LFI cows experienced many more disease cases (13 vs. 3 in high LFI Group) and related drug treatments till day +28. Interleukin-6 (IL-6) serum concentrations were always higher in low LFI cows (Pcows at risk in the transition period toward an improved farm management. Also, our study indicates that disease cases in periparturient, high-yielding dairy cows are correlated with signs of accentuated IL-6 response and other markers of inflammatory phenomena. These likely start in the late lactation period or around dry-off, as suggested by our prepartal data, and proceed at much greater levels after calving. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Structural and metabolic responses of microbial community to sewage-borne chlorpyrifos in constructed wetlands.

    Science.gov (United States)

    Zhang, Dan; Wang, Chuan; Zhang, Liping; Xu, Dong; Liu, Biyun; Zhou, Qiaohong; Wu, Zhenbin

    2016-06-01

    Long-term use of chlorpyrifos poses a potential threat to the environment that cannot be ignored, yet little is known about the succession of substrate microbial communities in constructed wetlands (CWs) under chlorpyrifos stress. Six pilot-scale CW systems receiving artificial wastewater containing 1mg/L chlorpyrifos were established to investigate the effects of chlorpyrifos and wetland vegetation on the microbial metabolism pattern of carbon sources and community structure, using BIOLOG and denaturing gradient gel electrophoresis (DGGE) approaches. Based on our samples, BIOLOG showed that Shannon diversity (H') and richness (S) values distinctly increased after 30days when chlorpyrifos was added. At the same time, differences between the vegetated and the non-vegetated systems disappeared. DGGE profiles indicated that H' and S had no significant differences among four different treatments. The effect of chlorpyrifos on the microbial community was mainly reflected at the physiological level. Principal component analysis (PCA) of both BIOLOG and DGGE showed that added chlorpyrifos made a difference on test results. Meanwhile, there was no difference between the vegetation and no-vegetation treatments after addition of chlorpyrifos at the physiological level. Moreover, the vegetation had no significant effect on the microbial community at the genetic level. Comparisons were made between bacteria in this experiment and other known chlorpyrifos-degrading bacteria. The potential chlorpyrifos-degrading ability of bacteria in situ may be considerable. Copyright © 2016. Published by Elsevier B.V.

  18. A new method to manipulate broiler chicken growth and metabolism: Response to mixed LED light system

    Science.gov (United States)

    Yang, Yefeng; Yu, Yonghua; Pan, Jinming; Ying, Yibin; Zhou, Hong

    2016-05-01

    Present study introduced a new method to manipulate broiler chicken growth and metabolism by mixing the growth-advantage LED. We found that the green/blue LED mixed light system (G-B and G × B) have the similar stimulatory effect on chick body weight with single green light and single blue light (G and B), compared with normal artificial light (P = 0.028). Moreover, the percentage of carcass was significantly greater in the mixed light (G × B) when compared with the single light (P = 0.003). Synchronized with body weight, the mixed light (G-B and G × B) had a significant improved influence on the feed conversion of birds compared with normal light (P = 0.002). A significant improvement in feed conversion were found in mixed light (G × B) compared with single LED light (P = 0.037). G group resulted in a greater high-density lipoprotein cholesterol level than B group (P = 0.002), whereas B group resulted in a greater low-density lipoprotein cholesterol level than G group (P = 0.017). The mixed light significantly increased the birds’ glucose level in comparison with the single light (P = 0.003). This study might establish an effective strategy for maximizing growth of chickens by mixed LED technology.

  19. Astrocyte Senescence and Metabolic Changes in Response to HIV Antiretroviral Therapy Drugs

    Directory of Open Access Journals (Sweden)

    Justin Cohen

    2017-08-01

    Full Text Available With the advent of highly active antiretroviral therapy (HAART survival rates among patients infected by HIV have increased. However, even though survival has increased HIV-associated neurocognitive disorders (HAND still persist, suggesting that HAART-drugs may play a role in the neurocognitive impairment observed in HIV-infected patients. Given previous data demonstrating that astrocyte senescence plays a role in neurocognitive disorders such as Alzheimer’s disease (AD, we examined the role of HAART on markers of senescence in primary cultures of human astrocytes (HAs. Our results indicate HAART treatment induces cell cycle arrest, senescence-associated beta-galactosidase, and the cell cycle inhibitor p21. Highly active antiretroviral therapy treatment is also associated with the induction of reactive oxygen species and upregulation of mitochondrial oxygen consumption. These changes in mitochondria correlate with increased glycolysis in HAART drug treated astrocytes. Taken together these results indicate that HAART drugs induce the senescence program in HAs, which is associated with oxidative and metabolic changes that could play a role in the development of HAND.

  20. Metabolic and spatio-taxonomic response of uncultivated seafloor bacteria following the Deepwater Horizon oil spill

    Energy Technology Data Exchange (ETDEWEB)

    Handley, K. M.; Piceno, Y. M.; Hu, P.; Tom, L. M.; Mason, O. U.; Andersen, G. L.; Jansson, J. K.; Gilbert, J. A.

    2017-08-04

    The release of 700 million liters of oil into the Gulf of Mexico over a few months in 2010 produced dramatic changes in the microbial ecology of the water and sediment. Here, we reconstructed the genomes of 57 widespread uncultivated bacteria from post-spill deep-sea sediments, and recovered their gene expression pattern across the seafloor. These genomes comprised a common collection of bacteria that were enriched in heavily affected sediments around the wellhead. Although rare in distal sediments, some members were still detectable at sites up to 60 km away. Many of these genomes exhibited phylogenetic clustering indicative of common trait selection by the environment, and within half we identified 264 genes associated with hydrocarbon degradation. Alkane degradation ability was near ubiquitous among candidate hydrocarbon degraders, whereas just three harbored elaborate gene inventories for the degradation of alkanes and aromatic and polycyclic aromatic hydrocarbons (PAHs). Differential gene expression profiles revealed a spill-promoted microbial sulfur cycle alongside gene upregulation associated with PAH degradation. Gene expression associated with alkane degradation was widespread, although active alkane degrader identities changed along the pollution gradient. Analyses suggest that a broad metabolic capacity to respond to oil inputs exists across a large array of usually rare indigenous deep-sea bacteria.

  1. Paraoxonase responses to exercise and niacin therapy in men with metabolic syndrome.

    Science.gov (United States)

    Taylor, James Kyle; Plaisance, Eric P; Mahurin, A Jack; Mestek, Michael L; Moncada-Jimenez, Jose; Grandjean, Peter W

    2015-01-01

    Our purpose was to characterize changes in paraoxonase 1 (PON1) activity and concentration after single aerobic exercise sessions conducted before and after 6 weeks of niacin therapy in men with metabolic syndrome (MetS). Twelve men with MetS expended 500 kcal by walking at 65% of VO2max before and after a 6-week regimen of niacin. Niacin doses were titrated by 500 mg/week from 500 to 1500 mg/day and maintained at 1500 mg/day for the last 4 weeks. Fasting blood samples were collected before and 24 hours after each exercise session and analyzed for PON1 activity, PON1 concentration, myeloperoxidase (MPO), apolipoprotein A1, oxidized low-density lipoprotein (oLDL), lipoprotein particle sizes and concentrations. PON1 activity, PON1 concentration, MPO, and oLDL were unaltered following the independent effects of exercise and niacin (P > 0.05 for all). High-density lipoprotein particle size decreased by 3% (P = 0.040) and concentrations of small very low-density lipoprotein increased (P = 0.016) following exercise. PON1 activity increased 6.1% (P = 0.037) and PON1 concentrations increased 11.3% (P = 0.015) with the combination of exercise and niacin. Exercise and niacin works synergistically to increase PON1 activity and concentration with little or no changes in lipoproteins or markers of lipid oxidation.

  2. Myostatin promotes distinct responses on protein metabolism of skeletal and cardiac muscle fibers of rodents

    Directory of Open Access Journals (Sweden)

    L.H. Manfredi

    2017-10-01

    Full Text Available Myostatin is a novel negative regulator of skeletal muscle mass. Myostatin expression is also found in heart in a much less extent, but it can be upregulated in pathological conditions, such as heart failure. Myostatin may be involved in inhibiting protein synthesis and/or increasing protein degradation in skeletal and cardiac muscles. Herein, we used cell cultures and isolated muscles from rats to determine protein degradation and synthesis. Muscles incubated with myostatin exhibited an increase in proteolysis with an increase of Atrogin-1, MuRF1 and LC3 genes. Extensor digitorum longus muscles and C2C12 myotubes exhibited a reduction in protein turnover. Cardiomyocytes showed an increase in proteolysis by activating autophagy and the ubiquitin proteasome system, and a decrease in protein synthesis by decreasing P70S6K. The effect of myostatin on protein metabolism is related to fiber type composition, which may be associated to the extent of atrophy mediated effect of myostatin on muscle.

  3. Chronic heat improves mechanical and metabolic response of trained rat heart on ischemia and reperfusion.

    Science.gov (United States)

    Levy, E; Hasin, Y; Navon, G; Horowitz, M

    1997-05-01

    Cardiac mechanics and metabolic performance were studied in isolated perfused hearts of rats subjected to a combined chronic stress of heat acclimation and swimming training (EXAC) or swimming training alone (EX). Diastolic (DP) and systolic pressures (SP), coronary flow (CF), and oxygen consumption were measured during normoperfusion (80 mmHg), and the appearance of ischemic contracture (IC), DP, and SP were measured during progressive graded ischemia, total ischemia (TI), and reperfusion insults. ATP, phosphocreatine, and intracellular pH were measured during TI and reperfusion with 31P nuclear magnetic resonance spectroscopy. During normoperfusion, SP and cardiac efficiency (derived from rate-pressure product-oxygen consumption relationships) were the highest in the 2-mo EXAC hearts (P pool and there was a delayed decline in intracellular pH. On reperfusion, these hearts also displayed improved ATP and phosphocreatine recovery, the 2-mo EXAC heart demonstrating significantly faster high-energy phosphate salvage, improved diastolic function, and pulse pressure recovery. The data attest to the beneficial effects of heat acclimation on cardiac mechanics of trained rats during normoperfusion and cardiac protection on ischemia and reperfusion. Possibly, energy sparing, lesser acidosis, and shorter duration of IC on ischemia and improved energy salvage on reperfusion contribute synergistically to this potent beneficial effect.

  4. Cellular metabolic responses of the marine diatom Pseudo-nitzschia multiseries associated with cell wall formation.

    Science.gov (United States)

    Xu, Bin; Luo, Chun-Shan; Liang, Jun-Rong; Chen, Dan-Dan; Zhuo, Wen-Hao; Gao, Ya-Hui; Chen, Chang-Ping; Song, Si-Si

    2014-08-01

    In this study a comparative proteomics approach involving a mass spectrometric analysis of synchronized cells was employed to investigate the cellular-level metabolic mechanisms associated with siliceous cell wall formation in the pennate diatom Pseudo-nitzschia multiseries. Cultures of P. multiseries were synchronized using the silicate limitation method. Approximately 75% of cells were arrested at the G2+M phase of the cell cycle after 48 h of silicate starvation. The majority of cells progressed to new valve synthesis within 5h of silicon replenishment. We compared the proteome of P. multiseries at 0, 4, 5, and 6h of synchronization progress upon silicon replenishment using two-dimensional gel electrophoresis. Forty-eight differentially expressed protein spots were identified in abundance (greater than two-fold change; Pwall formation. The proteomic profile analysis suggests that P. multiseries most likely employs multiple synergistic biochemical mechanisms for cell wall formation. These results improve our understanding of the molecular mechanisms underlying silicon cell wall formation and enhance our understanding of the important role played by diatoms in silicon biogeochemical cycling. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Blood and muscle metabolic responses to draught work of varying intensity and duration in horses.

    Science.gov (United States)

    Gottlieb, M; Essén-Gustavsson, B; Skoglund-Wallberg, H

    1989-07-01

    Three standardbred trotters performed treadmill exercise at a velocity of 2 m s-1 with a draught load of both 34 kiloponds (kp) (test 1) and 80 kp (test 2), and also at 7 m s-1 with 34 kp (test 3). The heart rate increased to average values of 111 (+/- 5), 157 (+/- 10) and 197 (+/- 7) beats min-1 in tests 1, 2, and 3, respectively. Plasma free fatty acids increased only during tests 1 and 2. Blood lactate and muscle glucose-6-phosphate and lactate concentrations were low after tests 1 and 2, but high after test 3, where also muscle glycogen utilisation was greatest. Muscle creatine phosphate and adenosine triphosphate concentrations decreased after test 3 only. The study indicates that oxidative metabolism is most important for energy supply in muscles when exercise is performed with draught loads of both 34 and 80 kp at a low velocity. Glycogenolysis with lactate accumulation and phosphagen breakdown becomes much more important when, with a draught load of 34 kp, the velocity of exercise increases.

  6. Cell Connections by Tunneling Nanotubes: Effects of Mitochondrial Trafficking on Target Cell Metabolism, Homeostasis, and Response to Therapy

    Science.gov (United States)

    2017-01-01

    Intercellular communications play a major role in tissue homeostasis and responses to external cues. Novel structures for this communication have recently been described. These tunneling nanotubes (TNTs) consist of thin-extended membrane protrusions that connect cells together. TNTs allow the cell-to-cell transfer of various cellular components, including proteins, RNAs, viruses, and organelles, such as mitochondria. Mesenchymal stem cells (MSCs) are both naturally present and recruited to many different tissues where their interaction with resident cells via secreted factors has been largely documented. Their immunosuppressive and repairing capacities constitute the basis for many current clinical trials. MSCs recruited to the tumor microenvironment also play an important role in tumor progression and resistance to therapy. MSCs are now the focus of intense scrutiny due to their capacity to form TNTs and transfer mitochondria to target cells, either in normal physiological or in pathological conditions, leading to changes in cell energy metabolism and functions, as described in this review. PMID:28659978

  7. Cell Connections by Tunneling Nanotubes: Effects of Mitochondrial Trafficking on Target Cell Metabolism, Homeostasis, and Response to Therapy

    Directory of Open Access Journals (Sweden)

    Marie-Luce Vignais

    2017-01-01

    Full Text Available Intercellular communications play a major role in tissue homeostasis and responses to external cues. Novel structures for this communication have recently been described. These tunneling nanotubes (TNTs consist of thin-extended membrane protrusions that connect cells together. TNTs allow the cell-to-cell transfer of various cellular components, including proteins, RNAs, viruses, and organelles, such as mitochondria. Mesenchymal stem cells (MSCs are both naturally present and recruited to many different tissues where their interaction with resident cells via secreted factors has been largely documented. Their immunosuppressive and repairing capacities constitute the basis for many current clinical trials. MSCs recruited to the tumor microenvironment also play an important role in tumor progression and resistance to therapy. MSCs are now the focus of intense scrutiny due to their capacity to form TNTs and transfer mitochondria to target cells, either in normal physiological or in pathological conditions, leading to changes in cell energy metabolism and functions, as described in this review.

  8. [Complete hormonal and metabolic response after iodine-131 metaiodobenzylguanidine treatment in a patient diagnosed of malignant pheochromocytoma].

    Science.gov (United States)

    García Alonso, M P; Balsa Bretón, M A; Paniagua Correa, C; Castillejos Rodríguez, L; Rodríguez Pelayo, E; Mendoza Paulini, A; Ortega Valle, A; Penín González, J

    2013-01-01

    Radiolabeled metaiodobenzylguanidine is an analogue of norepinephrine used to localize tumors that express the neurohormone transporters, specifically those derived from the neural crest having a neuroendocrine origin. It is also used to treat non-surgical metastases derived from them. A review of the literature revealed symptomatic improvements associated to a decrease in hormone levels in a significant percentage of patients after (131)I-MIBG treatment. However, complete tumor remission has been described only in very few cases and hardly ever when bone metastases exist. We present a case of a patient diagnosed of malignant pheochromocytoma who achieved complete hormonal and metabolic response after (131)I-MIBG treatment (600 mCi) in spite of the presence of bone metastases. Copyright © 2012 Elsevier España, S.L. and SEMNIM. All rights reserved.

  9. Muscle fatigue and metabolic responses following three different antagonist pre-load resistance exercises

    NARCIS (Netherlands)

    Carregaro, Rodrigo; Cunha, Rafael; Oliveira, Carlos Gomes; Brown, Lee E.; Bottaro, Martim

    2013-01-01

    Purpose: Preload of antagonist muscles can be achieved by reciprocal actions (RAs) or by opposing muscle actions. However, evidence concerning neuromuscular and fatigue responses are scarce. Objective: To compare the effects of different knee flexor (KF) preload methods on knee extension (KE) vastus

  10. Metabolic and Cardiovascular Responses during Aquatic Exercise in Water at Different Temperatures in Older Adults

    Science.gov (United States)

    Bergamin, Marco; Ermolao, Andrea; Matten, Sonia; Sieverdes, John C.; Zaccaria, Marco

    2015-01-01

    Purpose: The aim of this study was to investigate the physiological responses during upper-body aquatic exercises in older adults with different pool temperatures. Method: Eleven older men (aged 65 years and older) underwent 2 identical aquatic exercise sessions that consisted of 3 upper-body exercises using progressive intensities (30, 35, and 40…

  11. Metabolic and thyroidal response in air-breathing perch (Anabus testudineus) to water-borne kerosene

    NARCIS (Netherlands)

    Peter, V.S.; Joshua, E.K.; Wendelaar Bonga, S.E.; Peter, M.C.S.

    2007-01-01

    To address the physiological compensatory adaptations in air-breathing fish to a toxicant, we studied the metabolite pattern, serum and liver enzymes and thyroidal response in a tropical air-breathing perch, Anabas testudineus (kept at 30 _C in a 12-h L:D cycle) after exposing the fish for 48 h to

  12. Premature delivery reduces intestinal cytoskeleton, metabolism, and stress response proteins in newborn formula-fed pigs

    DEFF Research Database (Denmark)

    Jiang, Pingping; Wan, Jennifer Man-Fan; Cilieborg, Malene Skovsted

    2013-01-01

    OBJECTIVE:: Preterm infants often show intolerance to the first enteral feeds, and the structural and functional basis of this intolerance remains unclear. We hypothesized that preterm and term neonates show similar gut trophic responses to feeding, but different expression of intestinal function...

  13. Thermoregulatory, Cardiovascular, and Metabolic Responses to Mild Caloric Restriction in the Brown Norway Rat

    Science.gov (United States)

    Caloric restriction (CR) has been demonstrated to prolong the life span of a variety of species. CR-induced reduction in core temperature (Tc) is considered a key mechanism responsible for prolonging life span in rodents; however, little is known on the regulation of CR-induced h...

  14. Participation of the phosphoinositide metabolism in the hypersensitive response of Citrus limon against Alternaria alternata

    Directory of Open Access Journals (Sweden)

    XIMENA ORTEGA

    2001-01-01

    Full Text Available Lemon seedlings inoculated with Alternaria alternata develop a hypersensitive response (HR that includes the induction of Phenylalanine ammonia-lyase (PAL, E. C. 4.3.1.5 and the synthesis of scoparone. The signal transduction pathway involved in the development of this response is unknown. We used several inhibitors of the Phosphoinositide (PI animal system to study a possible role of Inositol-1,4,5-triphosphate (IP3 in the transduction of the fungal conidia signal in Citrus limon. The HR was only partially inhibited by EGTA, suggesting that not only external but internal calcium as well are necessary for a complete development of the HR. In this plant system, Alternaria alternata induced an early accumulation of the second messenger IP3. When lemon seedlings were watered long term with LiCl, an inhibitor of the phosphoinositide cycle, the IP3 production was reduced, and the LiCl-watered plants could neither induce PAL nor synthesize scoparone in response to fungal conidia. Furthermore, neomycin, a Phospholipase C (PLC, E. C. 3.1.4.3 inhibitor, also inhibited PAL induction and scoparone synthesis in response to A. alternata. These results suggest that IP3 could be involved in the signal transduction pathway for the development of the HR of Citrus limon against A. alternata

  15. Comparison of Cardiorespiratory and Metabolic Responses in Kettlebell High-Intensity Interval Training Versus Sprint Interval Cycling.

    Science.gov (United States)

    Williams, Brian M; Kraemer, Robert R

    2015-12-01

    The purpose of this study was to determine the effectiveness of a novel exercise protocol we developed for kettlebell high-intensity interval training (KB-HIIT) by comparing the cardiorespiratory and metabolic responses to a standard sprint interval cycling (SIC) exercise protocol. Eight men volunteered for the study and completed 2 preliminary sessions, followed by two 12-minute sessions of KB-HIIT and SIC in a counterbalanced fashion. In the KB-HITT session, 3 circuits of 4 exercises were performed using a Tabata regimen. In the SIC session, three 30-second sprints were performed, with 4 minutes of recovery in between the first 2 sprints and 2.5 minutes of recovery after the last sprint. A within-subjects' design over multiple time points was used to compare oxygen consumption (V[Combining Dot Above]O2), respiratory exchange ratio (RER), tidal volume (TV), breathing frequency (f), minute ventilation (VE), caloric expenditure rate (kcal·min), and heart rate (HR) between the exercise protocols. Additionally, total caloric expenditure was compared. A significant group effect, time effect, and group × time interaction were found for V[Combining Dot Above]O2, RER, and TV, with V[Combining Dot Above]O2 being higher and TV and RER being lower in the KB-HIIT compared with the SIC. Only a significant time effect and group × time interaction were found for f, VE, kcal·min, and HR. Additionally, total caloric expenditure was found to be significantly higher during the KB-HIIT. The results of this study suggest that KB-HIIT may be more attractive and sustainable than SIC and can be effective in stimulating cardiorespiratory and metabolic responses that could improve health and aerobic performance.

  16. Candida albicans induces Metabolic Reprogramming in human NK cells and responds to Perforin with a Zinc Depletion Response

    Directory of Open Access Journals (Sweden)

    Daniela eHellwig

    2016-05-01

    Full Text Available As part of the innate immune system, natural killer (NK cells are directly involved in the response to fungal infections. Perforin has been identified as the major effector molecule acting against many fungal pathogens. While several studies have shown that perforin mediated fungicidal effects can contribute to fungal clearance, neither the activation of NK cells by fungal pathogens nor the effects of perforin on fungal cells are well understood. In a dual approach, we have studied the global gene expression pattern of primary and cytokine activated NK cells after co-incubation with C. albicans and the transcriptomic adaptation of C. albicans to perforin exposure. NK cells responded to the fungal pathogen with an up-regulation of genes involved in immune signaling and release of cytokines. Furthermore, we observed a pronounced increase of genes involved in glycolysis and glycolysis inhibitor 2-deoxy-D-glucose impaired C. albicans induced NK cell activation. This strongly indicates that metabolic adaptation is a major part of the NK cell response to C. albicans infections. In the fungal pathogen, perforin induced a strong up-regulation of several fungal genes involved in the zinc depletion response, such as PRA1 and ZRT1. These data suggest that fungal zinc homeostasis is linked to the reaction to perforin secreted by NK cells. However, deletion mutants in PRA1 and ZRT1 did not show altered susceptibility to perforin.

  17. Macrophage Interaction with Paracoccidioides brasiliensis Yeast Cells Modulates Fungal Metabolism and Generates a Response to Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Juliana Alves Parente-Rocha

    Full Text Available Macrophages are key players during Paracoccidioides brasiliensis infection. However, the relative contribution of the fungal response to counteracting macrophage activity remains poorly understood. In this work, we evaluated the P. brasiliensis proteomic response to macrophage internalization. A total of 308 differentially expressed proteins were detected in P. brasiliensis during infection. The positively regulated proteins included those involved in alternative carbon metabolism, such as enzymes involved in gluconeogenesis, beta-oxidation of fatty acids and amino acids catabolism. The down-regulated proteins during P. brasiliensis internalization in macrophages included those related to glycolysis and protein synthesis. Proteins involved in the oxidative stress response in P. brasiliensis yeast cells were also up-regulated during macrophage infection, including superoxide dismutases (SOD, thioredoxins (THX and cytochrome c peroxidase (CCP. Antisense knockdown mutants evaluated the importance of CCP during macrophage infection. The results suggested that CCP is involved in a complex system of protection against oxidative stress and that gene silencing of this component of the antioxidant system diminished the survival of P. brasiliensis in macrophages and in a murine model of infection.

  18. Metabolic Cost of the Activation of Immune Response in the Fish-Eating Myotis (Myotis vivesi: The Effects of Inflammation and the Acute Phase Response.

    Directory of Open Access Journals (Sweden)

    Aída Otálora-Ardila

    Full Text Available Inflammation and activation of the acute phase response (APR are energetically demanding processes that protect against pathogens. Phytohaemagglutinin (PHA and lipopolysaccharide (LPS are antigens commonly used to stimulate inflammation and the APR, respectively. We tested the hypothesis that the APR after an LPS challenge was energetically more costly than the inflammatory response after a PHA challenge in the fish-eating Myotis bat (Myotis vivesi. We measured resting metabolic rate (RMR after bats were administered PHA and LPS. We also measured skin temperature (Tskin after the LPS challenge and skin swelling after the PHA challenge. Injection of PHA elicited swelling that lasted for several days but changes in RMR and body mass were not significant. LPS injection produced a significant increase in Tskin and in RMR, and significant body mass loss. RMR after LPS injection increased by 140-185% and the total cost of the response was 6.50 kJ. Inflammation was an energetically low-cost process but the APR entailed a significant energetic investment. Examination of APR in other bats suggests that the way in which bats deal with infections might not be uniform.

  19. SIRT1 genetic variants associate with the metabolic response of Caucasians to a controlled lifestyle intervention – the TULIP Study

    Directory of Open Access Journals (Sweden)

    Stefan Norbert

    2008-11-01

    Full Text Available Abstract Background Sirtuin1 (SIRT1 regulates gene expression in distinct metabolic pathways and mediates beneficial effects of caloric restriction in animal models. In humans, SIRT1 genetic variants associate with fasting energy expenditure. To investigate the relevance of SIRT1 for human metabolism and caloric restriction, we analyzed SIRT1 genetic variants in respect to the outcome of a controlled lifestyle intervention in Caucasians at risk for type 2 diabetes. Methods A total of 1013 non-diabetic Caucasians from the Tuebingen Family Study (TUEF were genotyped for four tagging SIRT1 SNPs (rs730821, rs12413112, rs7069102, rs2273773 for cross-sectional association analyses with prediabetic traits. SNPs that associated with basal energy expenditure in the TUEF cohort were additionally analyzed in 196 individuals who underwent a controlled lifestyle intervention (Tuebingen Lifestyle Intervention Program; TULIP. Multivariate regressions analyses with adjustment for relevant covariates were performed to detect associations of SIRT1 variants with the changes in anthropometrics, weight, body fat or metabolic characteristics (blood glucose, insulin sensitivity, insulin secretion and liver fat, measured by magnetic resonance techniques after the 9-month follow-up test in the TULIP study. Results Minor allele (X/A carriers of rs12413112 (G/A had a significantly lower basal energy expenditure (p = 0.04 and an increased respiratory quotient (p = 0.02. This group (rs12413112: X/A was resistant against lifestyle-induced improvement of fasting plasma glucose (GG: -2.01%, X/A: 0.53%; p = 0.04, had less increase in insulin sensitivity (GG: 17.3%, X/A: 9.6%; p = 0.05 and an attenuated decline in liver fat (GG: -38.4%, X/A: -7.5%; p = 0.01. Conclusion SIRT1 plays a role for the individual lifestyle intervention response, possibly owing to decreased basal energy expenditure and a lower lipid-oxidation rate in rs12413112 X/A allele carriers. SIRT1 genetic

  20. Metabolic responses of the isopod Porcellionides pruinosus to nickel exposure assessed by (1)H NMR metabolomics.

    Science.gov (United States)

    Ferreira, Nuno G C; Saborano, Raquel; Morgado, Rui; Cardoso, Diogo N; Rocha, Cláudia M; Soares, Amadeu M V M; Loureiro, Susana; Duarte, Iola F

    2016-03-30

    This work aimed at characterizing the metabolome of the isopod Porcellionides pruinosus and at assessing its variations over 14 days under laboratory culture conditions and upon exposure to the contaminant metal Nickel (Ni). The spectral profiles obtained by (1)H NMR spectroscopy were thoroughly assigned and subjected to multivariate analysis in order to highlight consistent changes. Over 50 metabolites could be identified, providing considerable new knowledge on the metabolome of these model organisms. Several metabolites changed non-linearly with Ni dose and exposure time, showing distinct variation patterns for initial (4 days) and later time points (7 and 14 days). In particular, at day 4, several amino acids were increased and sugars were decreased (compared to controls), whereas these variations were inverted for longer exposure, possibly reflecting earlier and more intensive moulting. Other variations, namely in betaines and choline-containing compounds, were suggested to relate with osmoregulation and detoxification mechanisms. Ni also had a marked effect on several nucleotides (increased upon exposure) and a moderate impact on lipids (decreased upon exposure). Overall, this study has provided new information on the Ni-induced metabolic adaptations of the P. pruinosus isopod, paving the way for improved mechanistic understanding of how these model organisms handle soil contamination. This study provided, for the first time to our knowledge, a detailed picture of the NMR-detectable metabolome of terrestrial isopods and of its fluctuations in time and upon exposure to the contaminant metal Nickel. Several time- and dose-dependent changes were highlighted, providing mechanistic insight into how these important model organisms handle Ni contamination.

  1. Metabolic responses to Wii Fit™ video games at different game levels.

    Science.gov (United States)

    Worley, Jennifer R; Rogers, Sharon N; Kraemer, Robert R

    2011-03-01

    The Wii Fit™ is a form of interactive gaming designed to elicit health and fitness benefits to replace sedentary gaming. This study was designed to determine the effectiveness of Wii Fit™ fitness games. The purpose of the study was to determine the %VO2max and energy expenditure from different Wii Fit™ games at different levels including the step and hula games. Eight healthy young women completed a preliminary trial to determine VO2max and later played the Wii Fit™ during 2 separate counterbalanced trials. During each session, subjects played levels of Wii Fit™ games for 10 minutes each level. One session involved beginning and intermediate hula, and the other session involved beginning and intermediate steps. The VO2 was measured continuously via metabolic cart, and rating of perceived exertion (RPE) was assessed at the end of each game level. The lowest %VO2max, kcal·min, and RPE occurred during the beginning step game and the highest values occurred during the intermediate hula game. Respiratory exchange ratio was significantly higher in the intermediate hula than beginning hula game but was not significantly different between step game levels. The intermediate hula and step games produced the greatest energy expenditure with an equivalent effect of a walking speed of >5.63 km·h (>3.5 miles·h). This is the first study to determine the percentage of VO2max and caloric expenditure elicited by different Wii Fit™ video games at different game levels in adults. Findings suggest that the Wii Fit™ can be used as an effective activity for promoting physical health in this population.

  2. Ambulatory blood pressure response to a bout of HIIT in metabolic syndrome patients.

    Science.gov (United States)

    Ramirez-Jimenez, M; Morales-Palomo, F; Pallares, J G; Mora-Rodriguez, Ricardo; Ortega, J F

    2017-07-01

    The effectiveness of exercise to lower blood pressure may depend on the type and intensity of exercise. We study the short-term (i.e., 14-h) effects of a bout of high-intensity aerobic interval training (HIIT) on blood pressure in metabolic syndrome (MetS) patients. Nineteen MetS patients (55.2 ± 7.3 years, 6 women) entered the study. Eight of them were normotensive and eleven hypertensive according to MetS threshold (≥130 mmHg for SBP and/or ≥85 mmHg for DBP). In the morning of 3 separated days, they underwent a cycling exercise bout of HIIT (>90% of maximal heart rate, ~85% VO 2max ), or a bout of isocaloric moderate-intensity continuous training (MICT; ~70% of maximal heart rate, ~60% VO 2max ), or a control no-exercise trial (REST). After exercise, ambulatory blood pressure (ABP; 14 h) was monitored, while subjects continued their habitual daily activities wearing a wrist-band activity monitor. No ABP differences were found for normotensive subjects. In hypertensive subjects, systolic ABP was reduced by 6.1 ± 2.2 mmHg after HIIT compared to MICT and REST (130.8 ± 3.9 vs. 137.4 ± 5.1 and 136.4 ± 3.8 mmHg, respectively; p HIIT exercise bout is superior to an equivalent bout of continuous exercise when used as a non-pharmacological aid in the treatment of hypertension in MetS.

  3. Insulin responsiveness of protein metabolism in vivo following bedrest in humans

    International Nuclear Information System (INIS)

    Shangraw, R.E.; Stuart, C.A.; Prince, M.J.; Peters, E.J.; Wolfe, R.R.

    1988-01-01

    To test the influence of bedrest on insulin regulation of leucine metabolism, six normal young men were subjected to a five-step hyperinsulinemic euglycemic clamp before and after 7 days of strict bedrest. A primed-constant infusion of [1- 13 C]leucine was used. Before bedrest, the basal rate of appearance (R a ) of intracellular leucine and leucine oxidation were 2.79±0.17 and 0.613±0.070 μmol·kg -1 ·min -1 , respectively. Insulin caused a dose-dependent reduction of the intracellular leucine R a and leucine oxidation to a minimum of 1.64±0.08 and 0.322±0.039 μmol·kg -1 ·min -1 , respectively, in nonbedrested subjects. Insulin also caused a dose-dependent reduction of plasma leucine concentration. After bedrest, subjects exhibited decreased glucose tolerance and increased endogenous insulin secretion, but basal and insulin-suppressed intracellular leucine R a and leucine oxidation rates were not different from control. Magnetic resonance imaging of the back and lower extremities revealed a 1-4% decrease in muscle volume and a 2-5% increase in fat volume secondary to bedrest. Bedrest also resulted in a negative nitrogen balance as compared with the control period. Thus because negative nitrogen balance and skeletal muscle atrophy occurred in six rested subjects in the absence of changes in the two indices of protein breakdown used in this study, it seems likely that muscle protein synthesis was inhibited

  4. The modifying effect of anesthetic technique on the metabolic and endocrine responses to anesthesia and surgery

    DEFF Research Database (Denmark)

    Kehlet, H

    1988-01-01

    and the widespread use of the term "stress free anesthesia" in surgery is therefore not valid. However, continuous administration of local anesthetic agents in the epidural space is the most effective technique in so far as reduction of the stress response is concerned. The clinical implication of a variable...... reduction in the stress response to surgery by different anesthetic techniques remains largely unsettled, since only few controlled studies have been published on the clinical effects of pain relief and general anesthesia. However, a vast amount of data exist from controlled studies comparing regional...... anesthesia with local anesthetics and general anesthesia. The cumulative experience from these studies have demonstrated an advantageous effect on postoperative morbidity parameters such as blood loss, postoperative thromboembolic complications, pulmonary infective complications, gastrointestinal motility...

  5. Metabolic and fibrinolytic response to changed insulin sensitivity in users of oral contraceptives

    DEFF Research Database (Denmark)

    Petersen, Kresten R.; Christiansen, Erik; Madsbad, Sten

    1999-01-01

    systems, are relevant in the evaluation of the risk of developing vascular disorders or diabetes in OC users. We studied insulin sensitivity index (S(I)), glucose effectiveness (S(g)), and insulin response in young, healthy women by frequently sampled intravenous glucose tolerance tests before and after...... randomization to 6 months of treatment with ethinyl estradiol in triphasic combination with norgestimate (n = 17) or gestodene (n = 20). Measurements of fasting triglycerides and antigen concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were also...... included. Both compounds increased fasting plasma insulin and reduced S(i) but did not affect S(g). The relationships between S(i) and insulin response were unchanged. No consistent correlation between insulin sensitivity and triglycerides, t-PA, or PAI-1 were demonstrated before or during treatment. We...

  6. Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis.

    Science.gov (United States)

    Silva, Pedro Henrique Imenez; Girardi, Adriana Castello Costa; Neri, Elida Adalgisa; Rebouças, Nancy Amaral

    2012-04-01

    The Na(+/)H(+) exchanger isoform 3 (NHE3) is essential for HCO(3)(-) reabsorption in renal proximal tubules. The expression and function of NHE3 must adapt to acid-base conditions. The goal of this study was to elucidate the mechanisms responsible for higher proton secretion in proximal tubules during acidosis and to evaluate whether there are differences between metabolic and respiratory acidosis with regard to NHE3 modulation and, if so, to identify the relevant parameters that may trigger these distinct adaptive responses. We achieved metabolic acidosis by lowering HCO(3)(-) concentration in the cell culture medium and respiratory acidosis by increasing CO(2) tension in the incubator chamber. We found that cell-surface NHE3 expression was increased in response to both forms of acidosis. Mild (pH 7.21 ± 0.02) and severe (6.95 ± 0.07) metabolic acidosis increased mRNA levels, at least in part due to up-regulation of transcription, whilst mild (7.11 ± 0.03) and severe (6.86 ± 0.01) respiratory acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter region suggested that the regulatory elements sensitive to metabolic acidosis are located between -466 and -153 bp, where two consensus binding sites for SP1, a transcription factor up-regulated in metabolic acidosis, were localised. We conclude that metabolic acidosis induces Nhe3 promoter activation, which results in higher mRNA and total protein level. At the plasma membrane surface, NHE3 expression was increased in metabolic and respiratory acidosis alike, suggesting that low pH is responsible for NHE3 displacement to the cell surface.

  7. Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate

    Energy Technology Data Exchange (ETDEWEB)

    Michaelides, M.; Wang, G.; Michaelides, M.; Pascau, J.; Gispert, J.-D.; Delis, F.; Grandy, D.K.; Wang, G.-J.; Desco, M.; Rubinstein, M.; Volkow, N.D.; Thanos, P.K.

    2010-07-16

    Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D{sub 4}) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D{sub 4}. Images were analyzed using a novel automated image registration procedure. Baseline D{sub 4}{sup -/-} mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice; when given MP, D{sub 4}{sup -/-} mice increased metabolism in the PFC and decreased it in the CBV, whereas in D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D{sub 4} polymorphisms.

  8. Repeatability of metabolic responses to a nutrient deficiency in early and mid lactation and implications for robustness of dairy cows.

    Science.gov (United States)

    Gross, J J; Bruckmaier, R M

    2015-12-01

    Nutrient partitioning toward the mammary gland during insufficient energy and nutrient supply is a strategy to ensure survival of the offspring in mammalian species. This homeorhetic priority of the mammary gland is also present in the modern dairy cow, in particular in early lactation. However, despite similar metabolic loads, the adaptive response to a given metabolic load varies considerably among animals. The aim of this study was to investigate if individual cows respond in a consistent manner to a negative energy balance (NEB) in early and mid lactation. Twenty-five dairy cows experienced the usual NEB after parturition and were subjected to a second 3-wk NEB induced by feed restriction in mid lactation. Animals were retrospectively ranked according to their highest plasma nonesterified fatty acid (NEFA) concentration in wk 1 to 4 postpartum. The animals with the 33% highest and 33% lowest values were selected and classified either as the high response (HR) or low response (LR) group. Before parturition, no differences in the studied parameters, dry matter intake, energy balance, concentrations of glucose, NEFA, β-hydroxybutyrate, cholesterol, triglycerides, growth hormone, and insulin-like growth factor-1, were detected between LR and HR. After parturition, milk yield and energy-corrected milk yield was higher for HR compared with LR in wk 2 to 14 and wk 1 to 6, respectively. During feed restriction in wk 15 to 17 postpartum, no differences in energy-corrected milk between LR and HR were found. Energy balance was more negative in HR during the NEB in early lactation, but not different from LR during feed restriction in mid lactation. Although plasma concentrations of glucose, growth hormone, triglycerides, and cholesterol showed group differences in early lactation, but not during feed restriction, the plasma concentrations of NEFA, β-hydroxybutyrate, and insulin-like growth factor-1 in HR changed repeatedly to a greater extent during the NEB at the 2

  9. Metabolic, endocrine and appetite-related responses to acute and daily milk snack consumption in healthy, adolescent males.

    Science.gov (United States)

    Green, Benjamin P; Stevenson, Emma J; Rumbold, Penny L S

    2017-01-01

    Comprising of two experiments, this study assessed the metabolic, endocrine and appetite-related responses to acute and chronic milk consumption in adolescent males (15-18 y). Eleven adolescents [mean ± SD age: 16.5 ± 0.9 y; BMI: 23.3 ± 3.3 kg/m 2 ] participated in the acute experiment and completed two laboratory visits (milk vs. fruit-juice) in a randomized crossover design, separated by 7-d. Seventeen adolescents [age: 16.1 ± 0.9 y; BMI: 21.8 ± 3.7 kg/m 2 ] completed the chronic experiment. For the chronic experiment, a parallel design with two groups was used. Participants were randomly allocated and consumed milk (n = 9) or fruit-juice (n = 8) for 28-d, completing laboratory visits on the first (baseline, day-0) and last day (follow-up, day-28) of the intervention phase. On laboratory visits (for both experiments), measures of appetite, metabolism and endocrine responses were assessed at regular intervals. In addition, eating behavior was quantified by ad libitum assessment under laboratory conditions and in the free-living environment by weighed food record. Acute milk intake stimulated glucagon (P = 0.027 [16.8 pg mL; 95% CI: 2.4, 31.3]) and reduced ad libitum energy intake relative to fruit-juice (P = 0.048 [-651.3 kJ; 95% CI: -1294.1, -8.6]), but was comparable in the free-living environment. Chronic milk intake reduced free-living energy intake at the follow-up visit compared to baseline (P = 0.013 [-1910.9 kJ; 95% CI: -554.6, -3267.2]), whereas the opposite was apparent for fruit-juice. Relative to baseline, chronic milk intake increased the insulin response to both breakfast (P = 0.031) and mid-morning milk consumption (P = 0.050) whilst attenuating blood glucose (P = 0.025). Together, these findings suggest milk consumption impacts favorably on eating behavior in adolescent males, potentially through integrated endocrine responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Effects of rumen-protected choline supplementation on metabolic and performance responses of transition dairy cows.

    Science.gov (United States)

    Leiva, T; Cooke, R F; Brandão, A P; Marques, R S; Vasconcelos, J L M

    2015-04-01

    The objective of this experiment was to compare metabolic and milk production parameters in dairy cows supplemented and nonsupplemented with rumen-protected choline (RPC) during the transition period. Twenty-three nonlactating, multiparous, pregnant Holstein cows were ranked by BW and BCS 21 d before expected date of calving and immediately were assigned to receive (n = 12) or not receive (control; n = 11) RPC until 45 d in milk (DIM). Cows supplemented with RPC received (as-fed basis) 50 and 100 g/d of RPC (18.8% choline) before and after calving, respectively. Before calving, cows were maintained in 2 drylot pens according to treatment with ad libitum access to corn silage, and individually they received (as-fed basis) 3 kg/cow daily of a concentrate. Upon calving, cows were moved to 2 adjacent drylot pens according to treatment, milked twice daily, offered (as-fed basis) 35 kg/cow daily of corn silage, and individually received a concentrate formulated to meet their nutritional requirements after milking. The RPC was individually offered to cows as a topdressing into the morning concentrate feeding. Before calving, cow BW and BCS were recorded weekly, and blood samples were collected every 5 d beginning on d -21 relative to expected calving date. Upon calving and until 45 DIM, BW and BCS were recorded weekly, individual milk production was recorded daily, and milk samples were collected once a week and analyzed for fat, protein, and total solids. Blood samples were collected every other day from 0 to 20 DIM and every 5 d from 20 to 45 DIM. Based on actual calving dates, cows receiving RPC or control began receiving treatments 16.8 ± 1.7 and 17.3 ± 2.0 d before calving, respectively. No treatment effects were detected (P ≥ 0.18) on postpartum concentrate intake, BW and BCS, or serum concentrations of cortisol, β-hydroxybutyrate, NEFA, glucose, and IGF-I. Cows supplemented with RPC had greater (P ≤ 0.01) mean serum haptoglobin and insulin concentrations

  11. Effect of energy balance profiles on metabolic and reproductive response in Holstein and Swedish Red cows.

    Science.gov (United States)

    Ntallaris, T; Humblot, P; Båge, R; Sjunnesson, Y; Dupont, J; Berglund, B

    2017-03-01

    This study examined the effect of two feeding levels during the antepartum and postpartum period on reproductive performance and blood metabolites (glucose, non-esterified fatty acids (NEFA), insulin) in primiparous Holstein and Swedish Red (SRB) cows, in order to identify possible differences in the way these breeds respond to negative energy balance after calving. A total of 44 cows (22 Holstein, 22 SRB) kept in a loose housing system were included in the study. The control group (HE, n = 23) was fed a diet for high-producing cows (target 35 kg/d energycorrected milk, ECM). A lower feeding intensity (LE, n = 21) was achieved by giving -50% concentrate to target 25 kg/d ECM. Diets were implemented 30 days before expected calving and the cows were monitored for 120 days postpartum. Milk yield and composition, dry matter intake (DMI), live body weight and body condition score (BCS) were assessed to calculate the weekly energy balance (residual feed intake). Blood sampling started before diet implementation and was repeated every 2 weeks until Day 60 postpartum and then once monthly until Day 120. Plasma was kept at -20 °C until analysis for glucose, insulin and NEFA concentrations. Mixed linear models were used to analyse data (SAS 9.3; PROC MIXED). Holstein cows had lower mean energy balance than SRB cows (-4.7 ± 1.4 and -0.9 ± 1.4 MJ, respectively; p = 0.05). SRB cows had higher (pcows (2.7 ± 0.1) and also higher plasma glucose concentrations from Day -30 to Day 120 relative to parturition (4.1 ± 0.1 and 4.2 ± 0.1 log ; mg/100 ml, respectively; p cows than in Holsteins at Day -14 before calving, indicating higher mobilisation of lipid from adipose tissue already before calving. In contrast, Holstein cows had higher NEFA at Day 14 postpartum than SRB cows (p cows prioritise milk production to a larger extent than SRB cows, resulting in a less balanced metabolic profile. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Carbon monoxide is not responsible for the cigarette smokeinduced changes in the pulmonary metabolism of arachidonic acid and prostaglandin E2

    International Nuclear Information System (INIS)

    Maennistoe, J.; Puustinen, T.; Uotila, P.

    1985-01-01

    Cigarette smoke is known to interfere with the pulmonary metabolism of arachidomic acid and prostaglandin E 2 (PGE 2 ). We investigated the possible role of carbon monoxide in these cigarette smoke-infuced alterations. 4 C-Arachidonic acid (50 nmol) was indused into the pulmonary circulation of isolated perfused hamster lungs and the radioactive metabolites in the perfusion effluent, as well as the distribution of incorporated radioactive arachidonic acid within the lung lipids, were analysed. Carbon monoxide, added into the ventilatory air, had no effect on the oxidative metabolism of arachidonic acid or on the distribution of radioactive arachidonic acid within the lung. In addition, carbon monoxide had no effect on the metabolism of PGE 2 following infusion of 100 nmol of 14 C-PGE 2 into the rat pulmonary circulation. The present study suggests that carbon monoxide is not responsible for the cigarette smoke-induced changes in the pulmonary metabolism of arachidonic acid and PGE 2 . (author)

  13. Running Mechanics and Metabolic Responses with Water Bottles and Bottle Belt Holders.

    Science.gov (United States)

    Vincent, Heather K; Zdziarski, Laura A; Fallgatter, Kyle; Negron, Giorgio; Chen, Cong; Leavitt, Trevor; Horodyski, MaryBeth; Wasser, Joseph G; Vincent, Kevin R

    2018-01-18

    This study determined whether differential kinematics, kinetics, rates of energy use and cardiopulmonary responses occurred during running with water bottles and bottle belt holders compared to running only. Trained runners (N=42; 27.2±6.4 yr) ran on an instrumented treadmill for four conditions in a randomized order: 1) control run (CON); 2) hand-held full water bottle (FULL, 16.9 fluid oz; 454 g); 3) hand-held half-full water bottle (HALF, 8.4 fluid oz.; 227 g); and 4) waist-worn bottle belt holder (BELT; hydration belt; 676 g). Gas exchange was measured using a portable gas analyzer. Kinetic and kinematic responses were determined via standard 3D videographic techniques. Interactions of limb side (right, left) by study condition (CON, FULL, HALF, BELT) were tested for rates of oxygen use and energy expenditure, and kinematic and kinetic parameters. No significant limb side × condition interactions existed for rates of oxygen use or energy expenditure. A significant interaction occurred with sagittal elbow flexion (pwater by hand or on the waist does not significantly change kinematics of running motion, rates of oxygen use and energy expenditure or cardiopulmonary measures over short durations. Runners are likely making adjustments to joint moments and powers that preserve balance and protect the lower extremity joints while maintaining the rates of oxygen use and energy expenditure.

  14. Differential RNA-seq, Multi-Network Analysis and Metabolic Regulation Analysis of Kluyveromyces marxianus Reveals a Compartmentalised Response to Xylose.

    Directory of Open Access Journals (Sweden)

    Du Toit W P Schabort

    Full Text Available We investigated the transcriptomic response of a new strain of the yeast Kluyveromyces marxianus, in glucose and xylose media using RNA-seq. The data were explored in a number of innovative ways using a variety of networks types, pathway maps, enrichment statistics, reporter metabolites and a flux simulation model, revealing different aspects of the genome-scale response in an integrative systems biology manner. The importance of the subcellular localisation in the transcriptomic response is emphasised here, revealing new insights. As was previously reported by others using a rich medium, we show that peroxisomal fatty acid catabolism was dramatically up-regulated in a defined xylose mineral medium without fatty acids, along with mechanisms to activate fatty acids and transfer products of β-oxidation to the mitochondria. Notably, we observed a strong up-regulation of the 2-methylcitrate pathway, supporting capacity for odd-chain fatty acid catabolism. Next we asked which pathways would respond to the additional requirement for NADPH for xylose utilisation, and rationalised the unexpected results using simulations with Flux Balance Analysis. On a fundamental level, we investigated the contribution of the hierarchical and metabolic regulation levels to the regulation of metabolic fluxes. Metabolic regulation analysis suggested that genetic level regulation plays a major role in regulating metabolic fluxes in adaptation to xylose, even for the high capacity reactions, which is unexpected. In addition, isozyme switching may play an important role in re-routing of metabolic fluxes in subcellular compartments in K. marxianus.

  15. The impact of metabolic syndrome on the responsiveness to α1-blocker in men with BPH/LUTS.

    Science.gov (United States)

    Lee, Y-C; Liu, C-C; Juan, Y-S; Wu, W-J; Li, W-M; Yeh, H-C; Wang, C-J; Huang, C-N; Huang, C-H; Huang, S-P

    2013-04-01

    Increasing evidence has proposed the components of metabolic syndrome (MtS) as risk factors for the development of benign prostate hyperplasia (BPH); therefore, it is thought that MtS may play a role in lower urinary tract symptoms related to BPH (BPH/LUTS) aetiology. Considering the closed relationships between MtS and BPH/LUTS, it is possible that patients with MtS might have different drug responsiveness in men with BPH/LUTS. We prospectively investigated the impact of MtS on responsiveness to α1-blocker in men with BPH/LUTS. We enrolled a total of 109 patients with a mean (SD) age of 59.8 (9.0) years, having a prostate volume of 20 cm(3) or greater with moderate to severe LUTS. All patients received doxazosin GITS (gastrointestinal therapeutic system) 4 mg once daily for a 12-week period of treatment. The efficacy measurement was assessed by the changes from baseline in the total IPSS, maximum urinary flow rate and postvoid residual urine volume. The drug responders were defined as those who had a total IPSS decrease of more than 4 points from baseline after 12 weeks of treatment. Using multiple logistic regression analysis, our results showed that MtS was an independent factor for drug non-responder (OR = 4.26, p = 0.002). The rate of drug responder and total IPSS improvements in patients with MtS significantly decreased as the number of MtS components increased (p = 0.012 and p = 0.026). Among the MtS components, abnormal fasting blood glucose (FBG) was the most significantly independent factor for drug non-responder (OR = 3.17, p = 0.020). This study suggested that the presence of MtS had a significantly negative impact on the responsiveness to α1-blocker in men with BPH/LUTS. Our results are important for BPH/LUTS patients who did not initially respond to α1-blocker or who strive to reduce these metabolic risk factors. © 2013 Blackwell Publishing Ltd.

  16. REPRODUCTIVE AND METABOLIC RESPONSES IN EWES TO DIETARY PROTEIN SUPPLEMENT DURING MATING PERIOD IN DRY SEASON OF NORTHEAST BRAZIL

    Directory of Open Access Journals (Sweden)

    Magda Rodrigues

    2015-01-01

    Full Text Available This study evaluated the effect of food supplements with different levels of protein on reproductive and metabolic response of ewes during the mating period. Forty-one ewes were supplemented during 43 days with amount protein to meet 1.0 (diet I; n = 14, 1.7 (diet II; n = 13 and 2.1 (diet III; n = 14 times the maintenance requirements. Dry matter (DM intake was higher (P < 0.01 in diet III when compared to diets I and II. Orts were lesser in diets II and III (P < 0.05 when compared to diet I. Intake of organic matter (OM, crude protein (CP and ether extract (EE was higher in diet III (P < 0.05, but NDF and ADF intake was superior in diet I (P < 0.05. In diet III, a higher frequency of female mated was observed (P < 0.05. The prolificity and twinning rate was higher in ewes of diet II (P < 0.05. Greater birth weight of lambs (P < 0.05 was verified in diet III. The progesterone levels were affected by diets II and III (P < 0.05. In conclusion, the supplementation of ewes with intermediate level of protein improves their reproductive response.

  17. Sterol metabolism regulates neuroserpin polymer degradation in the absence of the unfolded protein response in the dementia FENIB.

    Science.gov (United States)

    Roussel, Benoit D; Newton, Timothy M; Malzer, Elke; Simecek, Nikol; Haq, Imran; Thomas, Sally E; Burr, Marian L; Lehner, Paul J; Crowther, Damian C; Marciniak, Stefan J; Lomas, David A

    2013-11-15

    Mutants of neuroserpin are retained as polymers within the endoplasmic reticulum (ER) of neurones to cause the autosomal dominant dementia familial encephalopathy with neuroserpin inclusion bodies or FENIB. The cellular consequences are unusual in that the ordered polymers activate the ER overload response (EOR) in the absence of the canonical unfolded protein response. We use both cell lines and Drosophila models to show that the G392E mutant of neuroserpin that forms polymers is degraded by UBE2j1 E2 ligase and Hrd1 E3 ligase while truncated neuroserpin, a protein that lacks 132 amino acids, is degraded by UBE2g2 (E2) and gp78 (E3) ligases. The degradation of G392E neuroserpin results from SREBP-dependent activation of the cholesterol biosynthetic pathway in cells that express polymers of neuroserpin (G392E). Inhibition of HMGCoA reductase, the limiting enzyme of the cholesterol biosynthetic pathway, reduced the ubiquitination of G392E neuroserpin in our cell lines and increased the retention of neuroserpin polymers in both HeLa cells and primary neurones. Our data reveal a reciprocal relationship between cholesterol biosynthesis and the clearance of mutant neuroserpin. This represents the first description of a link between sterol metabolism and modulation of the proteotoxicity mediated by the EOR.

  18. Deficiency of PdxR in Streptococcus mutans affects vitamin B6 metabolism, acid tolerance response and biofilm formation.

    Science.gov (United States)

    Liao, S; Bitoun, J P; Nguyen, A H; Bozner, D; Yao, X; Wen, Z T

    2015-08-01

    Streptococcus mutans, a key etiological agent of the human dental caries, lives primarily on the tooth surface in tenacious biofilms. The SMU864 locus, designated pdxR, is predicted to encode a member of the novel MocR/GabR family proteins, which are featured with a winged helix DNA-binding N-terminal domain and a C-terminal domain highly homologous to the pyridoxal phosphate-dependent aspartate aminotransferases. A pdxR-deficient mutant, TW296, was constructed using allelic exchange. PdxR deficiency in S. mutans had little effect on cell morphology and growth when grown in brain heart infusion. However, when compared with its parent strain, UA159, the PdxR-deficient mutant displayed major defects in acid tolerance response and formed significantly fewer biofilms (P mutans is known to require vitamin B6 to grow in defined medium, B6 vitamers, especially pyridoxal, were strongly inhibitory at millimolar concentrations, against S. mutans growth and biofilm formation. Our results suggest that PdxR in S. mutans plays an important role in regulation of vitamin B6 metabolism, acid tolerance response and biofilm formation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. A comparative study of the metabolic response in rainbow trout and Nile tilapia to changes in dietary macronutrient composition.

    Science.gov (United States)

    Figueiredo-Silva, A Cláudia; Saravanan, Subramanian; Schrama, Johan W; Panserat, Stéphane; Kaushik, Sadasivam; Geurden, Inge

    2013-03-14

    Metabolic mechanisms underlying the divergent response of rainbow trout (Oncorhynchus mykiss) and Nile tilapia (Oreochromis niloticus) to changes in dietary macronutrient composition were assessed. Fish were fed one of four isoenergetic diets having a digestible protein-to-digestible energy (DP:DE) ratio above or below the optimal DP:DE ratio for both species. At each DP:DE ratio, fat was substituted by an isoenergetic amount of digestible starch as the non-protein energy source (NPE). Dietary DP:DE ratio did not affect growth and only slightly lowered protein gains in tilapia. In rainbow trout fed diets with low DP:DE ratios, particularly with starch as the major NPE source, growth and protein utilisation were highly reduced, underlining the importance of NPE source in this species. We also observed species-specific responses of enzymes involved in amino acid catabolism, lipogenesis and gluconeogenesis to dietary factors. Amino acid transdeamination enzyme activities were reduced by a low dietary DP:DE ratio in both species and in tilapia also by the substitution of fat by starch as the NPE source. Such decreased amino acid catabolism at high starch intakes, however, did not lead to improved protein retention. Our data further suggest that a combination of increased lipogenic and decreased gluconeogenic enzyme activities accounts for the better use of carbohydrates and to the improved glycaemia control in tilapia compared with rainbow tront fed starch-enriched diets with low DP:DE ratio.

  20. Hormonal, metabolic, and cardiorespiratory responses of young and adult athletes to a single session of high-intensity cycle exercise.

    Science.gov (United States)

    Engel, Florian; Härtel, Sascha; Wagner, Matthias Oliver; Strahler, Jana; Bös, Klaus; Sperlich, Billy

    2014-11-01

    This study aimed to determine the effects of a single high-intensity interval training (HIIT) session on salivary cortisol (SC) levels, physiological responses, and performance in trained boys and men. Twenty-three boys (11.5 ± 0.8 years) and 25 men (29.7 ± 4.6 years) performed HIIT (4 consecutive Wingate Anaerobic Tests). SC in boys and men increased after HIIT from 5.55 ± 3.3 nmol/l to 15.13 ± 9.7 nmol/l (+173%) and from 7.07 ± 4.7 nmol/l to 19.19 ± 12.7 nmol/l (+171%), respectively (p HIIT, mean heart rates in boys were higher (p HIIT in young athletes is associated with a higher activation of the hormonal stress axis than other types of exercise regimes as described in the literature. This study is the first to show a pronounced SC increase to HIIT in trained boys accompanied by elevated levels of blood lactate concentrations and heart rate suggesting a high cardio-respiratory, metabolic, and hormonal response to HIIT in 11-year-old boys.

  1. Effects of dietary chitosan on growth, lipid metabolism, immune response and antioxidant-related gene expression in Misgurnus anguillicaudatus.

    Science.gov (United States)

    Yan, J; Guo, C; Dawood, M A O; Gao, J

    2017-05-30

    This study was performed to evaluate the effects of dietary chitosan supplementation on growth performance, lipid metabolism, gut microbial, antioxidant status and immune responses of juvenile loach (Misgurnus anguillicaudatus). Five experimental diets were formulated to contain graded levels of chitosan (0 (control), 0.5, 1, 2 and 5% CHI) for 50 days. Results of the present study showed that body weight gain was significantly higher in fish fed chitosan supplemented diets in dose dependent manner than control group. Increasing dietary chitosan levels reduced gut lipid content. Meanwhile the mRNA expression levels of intestine lipoprotein lipase and fatty acid binding protein 2 were significantly reduced with incremental dietary chitosan level. The percentages of total monounsaturated fatty acid decreased, while polyunsaturated fatty acid increased with dietary chitosan. The fish fed 0.5% CHI had higher mucus lysozyme activity (LZM) than those fed 0% CHI, but the LZM activity was significantly decreased with advancing chitosan supplement. The expression levels of superoxide dismutase, catalase and glutathione peroxidase revealed a similar trend, where the highest expressions were found in fish fed 5% CHI diet. In the term of intestine microbiota between 0 and 1% CHI groups, the proportion of bacteria in the phylum Bacteroidetes increased, whereas the proportion of bacteria in the phylum Firmicutes decreased as the fish supplemented chitosan. In conclusion, supplementation of chitosan improved growth performance, antioxidant status and immunological responses in loach.

  2. Metabolic response induced by endophytic fungi and bacteria in H. marrubioides Epling in vitro micro plants

    Energy Technology Data Exchange (ETDEWEB)

    Vitorino, Luciana Cristina; Silva, Fabiano Guimaraes, E-mail: fabianocefetrv@yahoo.com.br [Instituto Federal de Educacao, Ciencia e Tecnologia Goiano, Rio Verde, GO (Brazil); Lima, William Cardoso; Soares, Marcos Antonio [Universidade Federal de Mato Grosso (UFMT), Cuiaba, MT (Brazil). Dept. de Botanica e Ecologia; Pedroso, Rita Cassia Nascimento; Silva, Maroli Rodrigues; Dias, Herbert Junior; Crotti, Antonio Eduardo Miller; Silva, Marcio Luis Andrade e; Cunha, Wilson Roberto; Pauletti, Patricia Mendonca; Januario, Ana Helena [Universidade de Franca, SP (Brazil). Nucleo de Pesquisa em Ciencias Exatas e Tecnologicas

    2013-10-01

    Hyptis marrubioides Epling is a native plant from Brazilian Cerrado. In this paper, the response of in vitro micro plants of this species to inoculation with bacterial and fungal endophytic isolates is evaluated. HPLC-DAD analysis showed the presence of 3,4-O-(Z)-dicaffeoylquinic acid and quercetin-7-O-glucoside as the main components. GC/MS analysis demonstrated that the sesquiterpenes Greek-Small-Letter-Tau -cadinol and caryophyllene oxide were only produced in micro plants inoculated with endophytic bacteria, while methyl hexadecanoate, methyl heptadecanoate and methyl (Z,Z,Z) 9,12,15-octadecatrienoate and the triterpene methyl 3{beta}-hydroxy-urs-12-en-28-oate were over expressed only when the micro plant was treated with endophytic fungi. (author)

  3. Metabolic response induced by endophytic fungi and bacteria in H. marrubioides Epling in vitro micro plants

    International Nuclear Information System (INIS)

    Vitorino, Luciana Cristina; Silva, Fabiano Guimaraes; Lima, William Cardoso; Soares, Marcos Antonio; Pedroso, Rita Cassia Nascimento; Silva, Maroli Rodrigues; Dias, Herbert Junior; Crotti, Antonio Eduardo Miller; Silva, Marcio Luis Andrade e; Cunha, Wilson Roberto; Pauletti, Patricia Mendonca; Januario, Ana Helena

    2013-01-01

    Hyptis marrubioides Epling is a native plant from Brazilian Cerrado. In this paper, the response of in vitro micro plants of this species to inoculation with bacterial and fungal endophytic isolates is evaluated. HPLC-DAD analysis showed the presence of 3,4-O-(Z)-dicaffeoylquinic acid and quercetin-7-O-glucoside as the main components. GC/MS analysis demonstrated that the sesquiterpenes τ-cadinol and caryophyllene oxide were only produced in micro plants inoculated with endophytic bacteria, while methyl hexadecanoate, methyl heptadecanoate and methyl (Z,Z,Z) 9,12,15-octadecatrienoate and the triterpene methyl 3β-hydroxy-urs-12-en-28-oate were over expressed only when the micro plant was treated with endophytic fungi. (author)

  4. Whole-genome sequencing of a malignant granular cell tumor with metabolic response to pazopanib

    Science.gov (United States)

    Wei, Lei; Liu, Song; Conroy, Jeffrey; Wang, Jianmin; Papanicolau-Sengos, Antonios; Glenn, Sean T.; Murakami, Mitsuko; Liu, Lu; Hu, Qiang; Conroy, Jacob; Miles, Kiersten Marie; Nowak, David E.; Liu, Biao; Qin, Maochun; Bshara, Wiam; Omilian, Angela R.; Head, Karen; Bianchi, Michael; Burgher, Blake; Darlak, Christopher; Kane, John; Merzianu, Mihai; Cheney, Richard; Fabiano, Andrew; Salerno, Kilian; Talati, Chetasi; Khushalani, Nikhil I.; Trump, Donald L.; Johnson, Candace S.; Morrison, Carl D.

    2015-01-01

    Granular cell tumors are an uncommon soft tissue neoplasm. Malignant granular cell tumors comprise T transitions, particularly when immediately preceded by a 5′ G. A loss-of-function mutation was detected in a newly recognized tumor suppressor candidate, BRD7. No mutations were found in known targets of pazopanib. However, we identified a receptor tyrosine kinase pathway mutation in GFRA2 that warrants further evaluation. To the best of our knowledge, this is only the second reported case of a malignant granular cell tumor exhibiting a response to pazopanib, and the first whole-genome sequencing of this uncommon tumor type. The findings provide insight into the genetic basis of malignant granular cell tumors and identify potential targets for further investigation. PMID:27148567

  5. Initial water deficit effects on Lupinus albus photosynthetic performance, carbon metabolism, and hormonal balance: metabolic reorganization prior to early stress responses

    Czech Academy of Sciences Publication Activity Database

    Pinheiro, C.; António, C.; Dobrev, Petre; Vaňková, Radomíra; Wilson, J. C.

    2011-01-01

    Roč. 62, č. 14 (2011), s. 4965-4974 ISSN 0022-0957 Institutional research plan: CEZ:AV0Z50380511 Keywords : Carbon metabolism * hormone balance * LC-MS Subject RIV: EF - Botanics Impact factor: 5.364, year: 2011

  6. Responses of catecholestrogen metabolism to acute graded exercise in normal menstruating women before and after training.

    Science.gov (United States)

    De Crée, C; Ball, P; Seidlitz, B; Van Kranenburg, G; Geurten, P; Keizer, H A

    1997-10-01

    It has been hypothesized that exercise-related hypo-estrogenemia occurs as a consequence of increased competition of catecholestrogens (CE) for catechol-O-methyltransferase (COMT). This may result in higher norepinephrine (NE) concentrations, which could interfere with normal gonadotropin pulsatility. The present study investigates the effects of training on CE responses to acute exercise stress. Nine untrained eumenorrheic women (mean percentage of body fat +/-SD: 24.8 +/- 3.1%) volunteered for an intensive 5-day training program. Resting, submaximal, and maximal (tmax) exercise plasma CE, estrogen, and catecholamine responses were determined pre- and post training in both the follicular (FPh) and luteal phase (LPh). Acute exercise stress increased total primary estrogens (E) but had little effect on total 2-hydroxyestrogens (2-OHE) and 2-hydroxyestrogen-monomethylethers (2-MeOE) (= O-methylated CE after competition for catechol-O-methyltransferase). This pattern was not significantly changed by training. However, posttraining LPh mean (+/-SE) plasma E, 2-OHE, and 2-MeOE concentrations were significantly lower (P Training produced opposite effects on 2-OHE:E ratios (an estimation of CE formation) during acute exercise in the FPh (reduction) and LPh (increase). The 2-MeOE:2-OHE ratio (an estimation of CE activity) showed significantly higher values at tmax in both menstrual phases after training (FPh: +11%; LPh: +23%; P training, NE values were significantly higher (P training lowers absolute concentrations of plasma estrogens and CE; the acute exercise challenge altered plasma estrogens but had little effect on CE; estimation of the formation and activity of CE suggests that formation and O-methylation of CE proportionately increases. These findings may be of importance for NE-mediated effects on gonadotropin release.

  7. Effect of starvation on human muscle protein metabolism and its response to insulin

    International Nuclear Information System (INIS)

    Fryburg, D.A.; Barrett, E.J.; Louard, R.J.; Gelfand, R.A.

    1990-01-01

    To assess the effect of fasting on muscle protein turnover in the basal state and in response to insulin, we measured forearm amino acid kinetics, using [3H]phenylalanine (Phe) and [14C]leucine (Leu) infused systemically, in eight healthy subjects after 12 (postabsorptive) and 60 h of fasting. After a 150-min basal period, forearm local insulin concentration was selectively raised by approximately 25 muU/ml for 150 min by intra-arterial insulin infusion (0.02 mU.kg-1. min-1). The 60-h fast increased urine nitrogen loss and whole body Leu flux and oxidation (by 50-75%, all P less than 0.02). Post-absorptively, forearm muscle exhibited a net release of Phe and Leu, which increased two- to threefold after the 60-h fast (P less than 0.05); this effect was mediated exclusively by accelerated local rates of amino acid appearance (Ra), with no reduction in rates of disposal (Rd). Local hyperinsulinemia in the postabsorptive condition caused a twofold increase in forearm glucose uptake (P less than 0.01) and completely suppressed the net forearm output of Phe and Leu (P less than 0.02). After the 60-h fast, forearm glucose disposal was depressed basally and showed no response to insulin; in contrast, insulin totally abolished the accelerated net forearm release of Phe and Leu. The action of insulin to reverse the augmented net release of Phe and Leu was mediated exclusively by approximately 40% suppression of Ra (P less than 0.02) rather than a stimulation of Rd. We conclude that in short-term fasted humans (1) muscle amino acid output accelerates due to increased proteolysis rather than reduced protein synthesis, and (2) despite its catabolic state and a marked impairment in insulin-mediated glucose disposal, muscle remains sensitive to insulin's antiproteolytic action

  8. Effect of starvation on human muscle protein metabolism and its response to insulin

    Energy Technology Data Exchange (ETDEWEB)

    Fryburg, D.A.; Barrett, E.J.; Louard, R.J.; Gelfand, R.A. (Yale Univ. School of Medicine, New Haven, CT (USA))

    1990-10-01

    To assess the effect of fasting on muscle protein turnover in the basal state and in response to insulin, we measured forearm amino acid kinetics, using (3H)phenylalanine (Phe) and (14C)leucine (Leu) infused systemically, in eight healthy subjects after 12 (postabsorptive) and 60 h of fasting. After a 150-min basal period, forearm local insulin concentration was selectively raised by approximately 25 muU/ml for 150 min by intra-arterial insulin infusion (0.02 mU.kg-1. min-1). The 60-h fast increased urine nitrogen loss and whole body Leu flux and oxidation (by 50-75%, all P less than 0.02). Post-absorptively, forearm muscle exhibited a net release of Phe and Leu, which increased two- to threefold after the 60-h fast (P less than 0.05); this effect was mediated exclusively by accelerated local rates of amino acid appearance (Ra), with no reduction in rates of disposal (Rd). Local hyperinsulinemia in the postabsorptive condition caused a twofold increase in forearm glucose uptake (P less than 0.01) and completely suppressed the net forearm output of Phe and Leu (P less than 0.02). After the 60-h fast, forearm glucose disposal was depressed basally and showed no response to insulin; in contrast, insulin totally abolished the accelerated net forearm release of Phe and Leu. The action of insulin to reverse the augmented net release of Phe and Leu was mediated exclusively by approximately 40% suppression of Ra (P less than 0.02) rather than a stimulation of Rd. We conclude that in short-term fasted humans (1) muscle amino acid output accelerates due to increased proteolysis rather than reduced protein synthesis, and (2) despite its catabolic state and a marked impairment in insulin-mediated glucose disposal, muscle remains sensitive to insulin's antiproteolytic action.

  9. Effect of Sugar versus Mixed Breakfast on Metabolic and Neurofunctional Responses in Healthy Individuals

    Directory of Open Access Journals (Sweden)

    Roberto Codella

    2017-01-01

    Full Text Available We investigated the effects of glucose and diverse breakfasts on glucose increment and ghrelin suppression and cognitive processing of sensory information assessed by frontal P300 evoked potentials. In a randomized crossover design, 12 healthy individuals (6M/6F; BMI 22.2 ± 0.4 kg/m2; 27 ± 1.3 years, mean ± SEM underwent 50 g OGTT (A and 3 breakfasts (B1: milk and cereals; B2: milk, apple, and chocolate cream-filled sponge cake; B3: milk, apple, bread, and hazelnut chocolate cream to assess plasma glucose-, insulin-, and ghrelin excursions. An electroencephalography was performed before and 100 min after consumption of each load to measure the latency of frontal P300 evoked potentials as index of cognitive performance. Breakfasts B1 and B2 exhibited significantly lower glycemic and insulinemic responses as compared to A. Breakfast B3 exhibited significantly lower glycemic, but not insulinemic response, as compared to A. Final plasma ghrelin inhibition was more pronounced, albeit not significantly, in all breakfasts with respect to A. P300 latency tended to decrease following each of the three breakfasts, but B3 was the only breakfast capable to elicit a statistically significant reduction in P300 latency with respect to A (p<0.01, suggesting ameliorated cognitive performance. Such amelioration was correlated with the 2-hour final inhibition of plasma ghrelin concentration (r=0.61, p=0.01.

  10. Plasma amino acids and metabolic profiling of dairy cows in response to a bolus duodenal infusion of leucine.

    Science.gov (United States)

    Sadri, Hassan; von Soosten, Dirk; Meyer, Ulrich; Kluess, Jeannette; Dänicke, Sven; Saremi, Behnam; Sauerwein, Helga

    2017-01-01

    kynurenine pathway were identified as the most relevant for separating the treatment groups. These results suggest that Leu regulates the plasma concentrations of branched-chain AA, and other AA, apparently by stimulating their influx into the cells from the circulation. A single-dose duodenal infusion of Leu did not elicit an apparent insulin response, but affected multiple intermediary metabolic pathways including AA and energy metabolism by mechanisms yet to be elucidated.

  11. Coping with Salt Water Habitats: Metabolic and Oxidative Responses to Salt Intake in the Rufous-Collared Sparrow

    Directory of Open Access Journals (Sweden)

    Pablo Sabat

    2017-09-01

    Full Text Available Many physiological adjustments occur in response to salt intake in several marine taxa, which manifest at different scales from changes in the concentration of individual molecules to physical traits of whole organisms. Little is known about the influence of salinity on the distribution, physiological performance, and ecology of passerines; specifically, the impact of drinking water salinity on the oxidative status of birds has been largely ignored. In this study, we evaluated whether experimental variations in the salt intake of a widely-distributed passerine (Zontotrichia capensis could generate differences in basal (BMR and maximum metabolic rates (Msum, as well as affect metabolic enzyme activity and oxidative status. We measured rates of energy expenditure of birds after 30-d acclimation to drink salt (SW or tap (fresh water (TW and assessed changes in the activity of mitochondrial enzymes (cytochrome c oxidase and citrate synthase in skeletal muscle, heart, and kidney. Finally, we evaluated the oxidative status of bird tissues by means of total antioxidant capacity (TAC and superoxide dismutase activities and lipid oxidative damage (Malondialdehyde, MDA. The results revealed a significant increase in BMR but not Msum, which resulted in a reduction in factorial aerobic scope in SW- vs. TW-acclimated birds. These changes were paralleled with increased kidney and intestine masses and catabolic activities in tissues, especially in pectoralis muscle. We also found that TAC and MDA concentrations were ~120 and ~400% higher, respectively in the liver of animals acclimated to the SW- vs. TW-treatment. Our study is the first to document changes in the oxidative status in birds that persistently drink saltwater, and shows that they undergo several physiological adjustments that range that range in scale from biochemical capacities (e.g., TAC and MDA to whole organism traits (e.g., metabolic rates. We propose that the physiological changes observed

  12. A comparative study of the bone metabolic response to dried plum supplementation and PTH treatment in adult, osteopenic ovariectomized rat.

    Science.gov (United States)

    Smith, Brenda J; Bu, So Young; Wang, Yan; Rendina, Elizabeth; Lim, Yin F; Marlow, Denver; Clarke, Stephen L; Cullen, Diane M; Lucas, Edralin A

    2014-01-01

    Dried plum has been reported to have potent effects on bone in osteopenic animal models, but the mechanisms through which bone metabolism is altered in vivo remain unclear. To address this issue, a study comparing the metabolic response of dried plum to the anabolic agent, parathyroid hormone (PTH), was undertaken. Six month-old female Sprague Dawley rats (n=84) were sham-operated (SHAM) or ovariectomized (OVX) and maintained on a control diet for 6wks until osteopenia was confirmed. Treatments were initiated consisting of a control diet (AIN-93M) supplemented with dried plum (0, 5, 15 or 25%; w/w) or a positive control group receiving PTH. At the end of 6wks of treatment, whole body and femoral bone mineral density (BMD) were restored by the two higher doses of dried plum to the level of the SHAM group. Trabecular bone volume and cortical thickness were also improved with these two doses of dried plum. Dried plum suppressed the OVX-induced increase in bone turnover as indicated by systemic biomarkers of bone metabolism, N-terminal procollagen type 1 (P1NP) and deoxypyridinoline (DPD). Dynamic bone histomorphometric analysis of the tibial metaphysis revealed that dried plum restored the OVX-induced increase in cancellous bone formation rate (BFR) and mineralizing surface (MS/BS) to the SHAM group, but some doses of dried plum increased endocortical mineral apposition rate (MAR). As expected, PTH significantly increased endocortical MAR and BFR, periosteal BFR, and trabecular MAR and BFR beyond that of the OVX and maintained the accelerated rate of bone resorption associated with OVX. Dried plum up-regulated bone morphogenetic protein 4 (Bmp4) and insulin-like growth factor 1 (Igf1) while down-regulating nuclear factor T cell activator 1 (Nfatc1). These findings demonstrate that in the adult osteopenic OVX animal, the effects of dried plum differ from that of PTH in that dried plum primarily suppressed bone turnover with the exception of the indices of bone

  13. Effect of extended morning fasting upon ad libitum lunch intake and associated metabolic and hormonal responses in obese adults.

    Science.gov (United States)

    Chowdhury, E A; Richardson, J D; Tsintzas, K; Thompson, D; Betts, J A

    2016-02-01

    Breakfast omission is positively associated with obesity and increased risk of disease. However, little is known about the acute effects of extended morning fasting upon subsequent energy intake and associated metabolic/regulatory factors in obese adults. In a randomised cross-over design, 24 obese men (n=8) and women (n=16) extended their overnight fast by omitting breakfast consumption or ingesting a typical carbohydrate-rich breakfast of 2183±393 kJ (521±94 kcal), before an ad libitum pasta lunch 3 h later. Blood samples were obtained throughout the day until 3 h post lunch and analysed for hormones implicated in appetite regulation, along with metabolic outcomes and subjective appetite measures. Lunch intake was unaffected by extended morning fasting (difference=218 kJ, 95% confidence interval -54 kJ, 490 kJ; P=0.1) resulting in lower total intake in the fasting trial (difference=-1964 kJ, 95% confidence interval -1645 kJ, -2281 kJ; Pfasting (P⩽0.06). Plasma-acylated ghrelin concentrations were also lower following the ad libitum lunch in the fasting trial (Pfasting trial (P=0.05), with plasma glucose also greater 1 h after lunch (Pfasting did not result in greater appetite ratings after lunch, with some tendency for lower appetite 3 h post lunch (P=0.09). We demonstrate for the first time that, in obese adults, extended morning fasting does not cause compensatory intake during an ad libitum lunch nor does it increase appetite during the afternoon. Morning fasting reduced satiety hormone responses to a subsequent lunch meal but counterintuitively also reduced concentrations of the appetite-stimulating hormone-acylated ghrelin during the afternoon relative to lunch consumed after breakfast.

  14. Uncooked rice of relatively low gelatinization degree resulted in lower metabolic glucose and insulin responses compared with cooked rice in female college students.

    Science.gov (United States)

    Jung, Eun Young; Suh, Hyung Joo; Hong, Wan Soo; Kim, Dong Geon; Hong, Yang Hee; Hong, In Sun; Chang, Un Jae

    2009-07-01

    Cooking processes that gelatinize granules or disrupt structure might increase the glucose and insulin responses because a disruption of the structure of starch by gelatinization increases its availability for digestion and absorption in the small intestine. We hypothesized that the uncooked form of rice, which has a relatively low degree of gelatinization even though in powder form, would result in lower metabolic glucose and insulin responses compared with cooked rice (CR). To assess the effects of the gelatinization of rice on metabolic response of glucose and insulin, we investigated the glucose and insulin responses to 3 rice meals of different gelatinization degree in female college students (n = 12): CR (76.9% gelatinized), uncooked rice powder (UP; 3.5% gelatinized), and uncooked freeze-dried rice powder (UFP; 5.4% gelatinized). Uncooked rice powders (UP and UFP) induced lower glucose and insulin responses compared with CR. The relatively low gelatinization degree of UPs resulted in low metabolic responses in terms of the glycemic index (CR: 72.4% vs UP: 49.7%, UFP: 59.8%) and insulin index (CR: 94.8% vs UP: 74.4%, UFP: 68.0%). In summary, UPs that were less gelatinized than CR induced low postprandial glucose and insulin responses.

  15. Growth platform-dependent and -independent phenotypic and metabolic responses of Arabidopsis and its halophytic relative, Eutrema salsugineum, to salt stress.

    Science.gov (United States)

    Kazachkova, Yana; Batushansky, Albert; Cisneros, Aroldo; Tel-Zur, Noemi; Fait, Aaron; Barak, Simon

    2013-07-01

    Comparative studies of the stress-tolerant Arabidopsis (Arabidopsis thaliana) halophytic relative, Eutrema salsugineum, have proven a fruitful approach to understanding natural stress tolerance. Here, we performed comparative phenotyping of Arabidopsis and E. salsugineum vegetative development under control and salt-stress conditions, and then compared the metabolic responses of the two species on different growth platforms in a defined leaf developmental stage. Our results reveal both growth platform-dependent and -independent phenotypes and metabolic responses. Leaf emergence was affected in a similar way in both species grown in vitro but the effects observed in Arabidopsis occurred at higher salt concentrations in E. salsugineum. No differences in leaf emergence were observed on soil. A new effect of a salt-mediated reduction in E. salsugineum leaf area was unmasked. On soil, leaf area reduction in E. salsugineum was mainly due to a fall in cell number, whereas both cell number and cell size contributed to the decrease in Arabidopsis leaf area. Common growth platform-independent leaf metabolic signatures such as high raffinose and malate, and low fumarate contents that could reflect core stress tolerance mechanisms, as well as growth platform-dependent metabolic responses were identified. In particular, the in vitro growth platform led to repression of accumulation of many metabolites including sugars, sugar phosphates, and amino acids in E. salsugineum compared with the soil system where these same metabolites accumulated to higher levels in E. salsugineum than in Arabidopsis. The observation that E. salsugineum maintains salt tolerance despite growth platform-specific phenotypes and metabolic responses suggests a considerable degree of phenotypic and metabolic adaptive plasticity in this extremophile.

  16. The effects of body temperature and mass on the postprandial metabolic responses of the African egg-eating snakes Dasypeltis scabra and Dasypeltis inornata.

    Science.gov (United States)

    Greene, Sara; McConnachie, Suzanne; Secor, Stephen; Perrin, Mike

    2013-06-01

    African egg-eating snakes (Dasypeltis) feed only on freshly laid bird eggs which they perforate within their esophagus before swallowing the liquid contents and regurgitating the empty shell. Compared to a snake's typical intact meal, the liquid diet of Dasypeltis would expectedly generate a more moderate postprandial metabolic response and specific dynamic action (SDA). Free-ranging Dasypeltis feed over a range of ambient temperatures and thereby experience predicted temperature-dependent shifts in the duration and magnitude of their postprandial metabolic response. Such shifts would undoubtedly be shared among different species and age classes of Dasypeltis. To examine these expectations, we measured pre- and postprandial metabolic rates of adult Dasypeltis inornata and adult and neonate Dasypeltis scabra in response to liquid egg meals weighing 20% of snake body mass at 20, 25, 27, 30, and 32 °C. With an increase in body temperature, postprandial metabolic profiles of neonate and adult snakes became narrower and shorter in duration. Specific dynamic action varied among temperature treatments, increasing from 20 to 32 °C. Standard metabolic rate, postprandial peak metabolic rate, and SDA scaled with mass exponents that typically did not differ from 1.0. As expected, Dasypeltis digesting a liquid egg diet experienced a more modest postprandial response and SDA, expending on average only 10.6% of the meal's energy on the breakdown, absorption, and assimilation of the egg meal, whereas other colubrids consuming intact rodent or fish meals expend on average 16.3% of the meal's energy on digestion and assimilation. Actively foraging and feeding throughout the avian egg laying season enable Dasypeltis to survive when eggs are not available. The adaptive suite of traits that enable Dasypeltis to consume eggs of large relative size and ingest only the liquid contents may also be joined by physiological adaptations specific to their liquid diet and extended bouts of

  17. Skin microvascular and metabolic response to pressure relief maneuvers in people with spinal cord injury

    Science.gov (United States)

    Ramella-Roman, Jessica C.; Le, Du V. N.; Ghassemi, Pejhman; Nguyen, Thu A.; Lichy, Alison; Groah, Suzanne

    2013-02-01

    Clinician's recommendations on wheelchair pressure reliefs in the context of the high prevalence of pressure ulcers that occur in people with spinal cord injury is not supported by strong experimental evidence. Some data indicates that altered tissue perfusion and oxygenation occurring under pressure loads, such as during sitting, induce various pathophysiologic changes that may lead to pressure ulcers. Pressure causes a cascade of responses, including initial tissue hypoxia, which leads to ischemia, vascular leakage, tissue acidification, compensatory angiogenesis, thrombosis, and hyperemia, all of which may lead to tissue damage. We have developed an advanced skin sensor that allows measurement of oxygenation in addition to perfusion, and can be safely used during sitting. The sensor consists of a set of fiber optics probes, spectroscopic and Laser Doppler techniques that are used to obtain parameters of interest. The overriding goal of this project is to develop the evidence base for clinical recommendations on pressure reliefs. In this paper we will illustrate the experimental apparatus as well as some preliminary results of a small clinical trial conducted at the National Rehabilitation Hospital.

  18. Understanding the Response of Photosynthetic Metabolism in Tropical Forests to Seasonal Climate Variations. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Dye, Dennis [U.S. Geological Survey, Menlo Park, CA (United States); Ivanov, Valeriy [Univ. of Michigan, Ann Arbor, MI (United States); Saleska, Scott [Univ. of Arizona, Tucson, AZ (United States); Huete, Alfredo [Univ. of Arizona, Tucson, AZ (United States); Univ. of Technology, Sydney NSW (Australia)

    2017-03-31

    This U.S-Brazil collaboration for GOAmazon has investigated a deceptively simple question: what controls the response of photosynthesis in Amazon tropical forests to seasonal variations in climate? In the past this question has been difficult to answer with modern earth system process models. We hypothesized that observed dry season increases in photosynthetic capacity are controlled by the phenology of leaf flush and litter fall, from which the seasonal pattern of LAI emerges. Our results confirm this hypothesis (Wu et al., 2016). Synthesis of data collected throughout the 3-year project period continues through December 31, 2017 under no-cost extensions granted to the project teams at University of Michigan and University of Arizona (Award 2). The USGS component (Award 1) ceased on the final date of the project performance period, December 31, 2016. This report summarizes the overall activities and achievements of the project, and constitutes the final project report for the USGS component. The University of Michigan will submit a separate final report that includes additional results and deliverables achieved during the period of their and the University of Arizona’s no-cost extension, which will end on December 31, 2017.

  19. Neuronal response of the hippocampal formation to injury: blood flow, glucose metabolism, and protein synthesis

    International Nuclear Information System (INIS)

    Kameyama, M.; Wasterlain, C.G.; Ackermann, R.F.; Finch, D.; Lear, J.; Kuhl, D.E.

    1983-01-01

    The reaction of the hippocampal formation to entorhinal lesions was studied from the viewpoints of cerebral blood flow ([ 123 I]isopropyl-iodoamphetamine[IMP])-glucose utilization ([ 14 C]2-deoxyglucose), and protein synthesis ([ 14 C]leucine), using single- and double-label autoradiography. Researchers' studies showed decreased glucose utilization in the inner part, and increased glucose utilization in the outer part of the molecular layer of the dentate gyrus, starting 3 days after the lesion; increased uptake of [ 123 I]IMP around the lesion from 1 to 3 days postlesion; and starting 3 days after the lesion, marked decrease in [ 14 C]leucine incorporation into proteins and cell loss in the dorsal CA1 and dorsal subiculum in about one-half of the rats. These changes were present only in animals with lesions which invaded the ventral hippocampal formation in which axons of CA1 cells travel. By contrast, transsection of the 3rd and 4th cranial nerves resulted, 3 to 9 days after injury, in a striking increase in protein synthesis in the oculomotor and trochlear nuclei. These results raise the possibility that in some neurons the failure of central regeneration may result from the cell's inability to increase its rate of protein synthesis in response to axonal injury

  20. The fifth leaf and spike organs of barley (Hordeum vulgare L.) display different physiological and metabolic responses to drought stress.

    Science.gov (United States)

    Hein, Jordan A; Sherrard, Mark E; Manfredi, Kirk P; Abebe, Tilahun

    2016-11-09

    Photosynthetic organs of the cereal spike (ear) provide assimilate for grain filling, but their response to drought is poorly understood. In this study, we characterized the drought response of individual organs of the barley spike (awn, lemma, and palea) and compared them with a vegetative organ (fifth leaf). Understanding differences in physiological and metabolic responses between the leaf and spike organs during drought can help us develop high yielding cultivars for environments where terminal drought is prevalent. We exposed barley plants to drought by withholding water for 4 days at the grain filling stage and compared changes in: (1) relative water content (RWC), (2) osmotic potential (Ψ s ), (3) osmotic adjustment (OA), (4) gas exchange, and (5) metabolite content between organs. Drought reduced RWC and Ψ s in all four organs, but the decrease in RWC was greater and there was a smaller change in Ψ s in the fifth leaf than the spike organs. We detected evidence of OA in the awn, lemma, and palea, but not in the fifth leaf. Rates of gas exchange declined more rapidly in the fifth leaf than awn during drought. We identified 18 metabolites but, only ten metabolites accumulated significantly during drought in one or more organs. Among these, proline accumulated in all organs during drought while accumulation of the other metabolites varied between organs. This may suggest that each organ in the same plant uses a different set of osmolytes for drought resistance. Our results suggest that photosynthetic organs of the barley spike maintain higher water content, greater osmotic adjustment, and higher rates of gas exchange than the leaf during drought.

  1. Differential metabolic responses of perennial grass Cynodon transvaalensis×Cynodon dactylon (C₄) and Poa Pratensis (C₃) to heat stress.

    Science.gov (United States)

    Du, Hongmei; Wang, Zhaolong; Yu, Wenjuan; Liu, Yimin; Huang, Bingru

    2011-03-01

    Differential metabolic responses to heat stress may be associated with variations in heat tolerance between cool-season (C₃) and warm-season (C₄) perennial grass species. The main objective of this study was to identify metabolites associated with differential heat tolerance between C₄ bermudagrass and C₃ Kentucky bluegrass by performing metabolite profile analysis using gas chromatography-mass spectrometry. Plants of Kentucky bluegrass (Poa Pratensis'Midnight') and hybrid bermudagrass (Cynodon transvaalensis x Cynodon dactylon'Tifdwarf') were grown under optimum temperature conditions (20/15 °C for Kentucky bluegrass and 30/25 °C for bermudagrass) or heat stress (35/30 °C for Kentucky bluegrass and 45/40 °C for bermudagrass). Physiological responses to heat stress were evaluated by visual rating of grass quality, measuring photochemical efficiency (variable fluorescence to maximal fluorescence) and electrolyte leakage. All of these parameters indicated that bermudagrass exhibited better heat tolerance than Kentucky bluegrass. The metabolite analysis of leaf polar extracts revealed 36 heat-responsive metabolites identified in both grass species, mainly consisting of organic acids, amino acids, sugars and sugar alcohols. Most metabolites showed higher accumulation in bermudagrass compared with Kentucky bluegrass, especially following long-term (18 days) heat stress. The differentially accumulated metabolites included seven sugars (sucrose, fructose, galactose, floridoside, melibiose, maltose and xylose), a sugar alcohol (inositol), six organic acids (malic acid, citric acid, threonic acid, galacturonic acid, isocitric acid and methyl malonic acid) and nine amino acids (Asn, Ala, Val, Thr, γ-aminobutyric acid, IIe, Gly, Lys and Met). The differential accumulation of those metabolites could be associated with the differential heat tolerance between C₃ Kentucky bluegrass and C₄ bermudagrass. Copyright © Physiologia Plantarum 2010.

  2. The metabolic, stress axis, and hematology response of zilpaterol hydrochloride supplemented beef heifers when exposed to a dual corticotropin-releasing hormone and vasopressin challenge

    Science.gov (United States)

    The objective of this study was to determine the metabolic, stress, and hematology cell response of beef heifers supplemented with zilpaterol hydrochloride (ZH) when exposed to an endocrine stress challenge. Heifers (n = 20; 556 ± 7 kg BW) were randomized into two treatment groups: 1) Control (CON):...

  3. Long-term trends of changes in pine and oak foliar nitrogen metabolism in response to chronic nitrogen amendments at Harvard Forest, MA

    Science.gov (United States)

    Rakesh Minocha; Swathi A. Turlapati; Stephanie Long; William H. McDowell; Subhash C. Minocha

    2015-01-01

    We evaluated the long-term (1995-2008) trends in foliar and sapwood metabolism, soil solution chemistry and tree mortality rates in response to chronic nitrogen (N) additions to pine and hardwood stands at the Harvard Forest Long Term Ecological Research (LTER) site. Common stress-related metabolites like polyamines (PAs), free amino acids (AAs) and inorganic elements...

  4. Plane of nutrition during the preweaned period and Mannheimia haemolytica dose influence metabolic responses in post-weaned Holstein calves challenged with bovine herpesvirus-1 and Mannheimia haemolytica

    Science.gov (United States)

    To determine whether previous plane of milk replacer nutrition (PON) and M. haemolytica (MH) dose influences metabolic responses to a combined viral-bacterial respiratory challenge, Holstein calves (1 day of age; n=30) were assigned to treatments in a 2 x 3 factorial with preweaned PON and dose of M...

  5. Multi-omics Analyses of Starvation Responses Reveal a Central Role for Lipoprotein Metabolism in Acute Starvation Survival in C. elegans

    DEFF Research Database (Denmark)

    Harvald, Eva Bang; Sprenger, Richard R; Dall, Kathrine Brændgaard

    2017-01-01

    Starvation causes comprehensive metabolic changes, which are still not fully understood. Here, we used quantitative proteomics and RNA sequencing to examine the temporal starvation responses in wild-type Caenorhabditis elegans and animals lacking the transcription factor HLH-30. Our findings show...

  6. Cardiorespiratory and Metabolic Responses to Loaded Half Squat Exercise Executed at an Intensity Corresponding to the Lactate Threshold

    Directory of Open Access Journals (Sweden)

    José Luis Maté-Muñoz, Raúl Domínguez, Manuel Barba, Antonio J. Monroy, Bárbara Rodríguez, Pedro Ruiz-Solano, Manuel V. Garnacho-Castaño

    2015-09-01

    Full Text Available This study was designed to identify the blood lactate threshold (LT2 for the half squat (HS and to examine cardiorespiratory and metabolic variables during a HS test performed at a work intensity corresponding to the LT2. Twenty-four healthy men completed 3 test sessions. In the first, their one-repetition maximum (1RM was determined for the HS. In the second session, a resistance HS incremental-load test was performed to determine LT2. Finally, in the third session, subjects performed a constant-load HS exercise at the load corresponding to the LT2 (21 sets of 15 repetitions with 1 min of rest between sets. In this last test, blood samples were collected for lactate determination before the test and 30 s after the end of set (S 3, S6, S9, S12, S15, S18 and S21. During the test, heart rate (HR was telemetrically monitored and oxygen consumption (VO2, carbon dioxide production (VCO2, minute ventilation (VE, respiratory exchange ratio (RER, ventilatory equivalent for O2 (VE·VO2-1 and ventilatory equivalent for CO2 (VE·VCO2-1 were monitored using a breath-by-breath respiratory gas analyzer. The mean LT2 for the participants was 24.8 ± 4.8% 1RM. Blood lactate concentrations showed no significant differences between sets 3 and 21 of exercise (p = 1.000. HR failed to vary between S6 and S21 (p > 1.000. The respiratory variables VO2, VCO2, and VE·VCO2-1 stabilized from S3 to the end of the constant-load HS test (p = 0.471, p = 0.136, p = 1.000, while VE and VE·VO2-1 stabilized from S6 to S21. RER did not vary significantly across exercise sets (p = 0.103. The LT2 was readily identified in the incremental HS test. Cardiorespiratory and metabolic variables remained stable during this resistance exercise conducted at an exercise intensity corresponding to the LT2. These responses need to be confirmed for other resistance exercises and adaptations in these responses after a training program also need to be addressed.

  7. Prenatal metformin exposure in a maternal high fat diet mouse model alters the transcriptome and modifies the metabolic responses of the offspring.

    Science.gov (United States)

    Salomäki, Henriikka; Heinäniemi, Merja; Vähätalo, Laura H; Ailanen, Liisa; Eerola, Kim; Ruohonen, Suvi T; Pesonen, Ullamari; Koulu, Markku

    2014-01-01

    Despite the wide use of metformin in metabolically challenged pregnancies, the long-term effects on the metabolism of the offspring are not known. We studied the long-term effects of prenatal metformin exposure during metabolically challenged pregnancy in mice. Female mice were on a high fat diet (HFD) prior to and during the gestation. Metformin was administered during gestation from E0.5 to E17.5. Male and female offspring were weaned to a regular diet (RD) and subjected to HFD at adulthood (10-11 weeks). Body weight and several metabolic parameters (e.g. body composition and glucose tolerance) were measured during the study. Microarray and subsequent pathway analyses on the liver and subcutaneous adipose tissue of the male offspring were performed at postnatal day 4 in a separate experiment. Prenatal metformin exposure changed the offspring's response to HFD. Metformin exposed offspring gained less body weight and adipose tissue during the HFD phase. Additionally, prenatal metformin exposure prevented HFD-induced impairment in glucose tolerance. Microarray and annotation analyses revealed metformin-induced changes in several metabolic pathways from which electron transport chain (ETC) was prominently affected both in the neonatal liver and adipose tissue. This study shows the beneficial effects of prenatal metformin exposure on the offspring's glucose tolerance and fat mass accumulation during HFD. The transcriptome data obtained at neonatal age indicates major effects on the genes involved in mitochondrial ATP production and adipocyte differentiation suggesting the mechanistic routes to improved metabolic phenotype at adulthood.

  8. Association between textural and morphological tumor indices on baseline PET-CT and early metabolic response on interim PET-CT in bulky malignant lymphomas.

    Science.gov (United States)

    Ben Bouallègue, Fayçal; Tabaa, Yassine Al; Kafrouni, Marilyne; Cartron, Guillaume; Vauchot, Fabien; Mariano-Goulart, Denis

    2017-09-01

    We investigated whether metabolic, textural, and morphological tumoral indices evaluated on baseline PET-CT were predictive of early metabolic response on interim PET-CT in a cohort of patients with bulky Hodgkin and non-Hodgkin malignant lymphomas. This retrospective study included 57 patients referred for initial PET-CT examination. In-house dedicated software was used to delineate tumor contours using a fixed 30% threshold of SUV max and then to compute tumoral metabolic parameters (SUV max, mean, peak, standard deviation, skewness and kurtosis, metabolic tumoral volume (MTV), total lesion glycolysis, and area under the curve of the cumulative histogram), textural parameters (Moran's and Geary's indices, energy, entropy, contrast, correlation derived from the gray-level co-occurrence matrix, area under the curve of the power spectral density, auto-correlation distance, and granularity), and shape parameters (surface, asphericity, convexity, surfacic extension, and 2D and 3D fractal dimensions). Early metabolic response was assessed on interim PET-CT using the Deauville 5-point scale and patients were ranked according to the Lugano classification as complete or not complete metabolic responders. The impact of the segmentation method (alternate threshold at 41%) and image resolution (Gaussian postsmoothing of 3, 5, and 7 mm) was investigated. The association of the proposed parameters with early response was assessed in univariate and multivariate analyses. Their added predictive value was explored using supervised classification by support vector machines (SVM). We evaluated in leave-one-out cross-validation three SVMs admitting as input features (a) MTV, (b) MTV + histological type, and (c) MTV + histology + relevant texture/shape indices. Features associated with complete metabolic response were low MTV (P = 0.01), low TLG (P = 0.003), high power spectral density AUC (P = 0.007), high surfacic extension (P = 0.006), low 2D fractal dimension (P

  9. Metabolic response assessment with 18F-FDG-PET/CT is superior to modified RECIST for the evaluation of response to platinum-based doublet chemotherapy in malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Kanemura, Shingo [Department of Respiratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Kuribayashi, Kozo, E-mail: kuririn@hyo-med.ac.jp [Department of Respiratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Funaguchi, Norihiko [Department of Respiratory Medicine, Murakami Memorial Hospital, Asahi University, 3-23 Hashimoto-cho, Gifu 500-8523 (Japan); Shibata, Eisuke; Mikami, Koji [Department of Respiratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Doi, Hiroshi [Department of Radiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Kitajima, Kazuhiro [Division of Nuclear Medicine and PET center, Department of Radiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Hasegawa, Seiki [Department of Thoracic Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Nakano, Takashi [Department of Respiratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

    2017-01-15

    Highlights: • 18F-FDG-PET/CT and mRESIST were used for tumour responsiveness evaluation in MPM. • 29% of mRESIST stable disease (SD) patients were metabolic non-responders. • Disease control rate was 93.9% and metabolic response rate was 71.9%. • Progressive metabolic disease patients had lower time to progression. • MRESIST stable disease (SD) patients should be further screened by 18F-FDG-PET/CT. - Abstract: Purpose: Efficient monitoring of tumor responsiveness to chemotherapy is essential to mitigate high mortality risks and cytotoxic effects of chemotherapeutics. However, there is no consensus on the most suitable diagnostic technique/parameters for assessing response to chemotherapy in malignant pleural mesothelioma (MPM). We compared the tumor responsiveness of MPM patients as assessed using modified RECIST (mRECIST) criteria and integrated 18F-FDG-PET/CT. Methods: Histologically confirmed MPM patients (N = 82) who were treated with three cycles of cisplatin and pemetrexed, or carboplatin and pemetrexed, were included. mRECIST and integrated 18F-FDG-PET/CT were used to evaluate MPM tumor response to chemotherapy. Metabolic non-responders were defined as those with a 25% or greater increase in SUVmax compared with the previous value. Time to progression (TTP) and overall survival (OS) were compared between metabolic-responders and non-responders. Results: After three cycles of chemotherapy, 62(75.6%) of the patients were classified as having SD, 15 (18%) with partial remission (PR), and 5 (6%) with progressive disease (PD), based on mRECIST criteria. The cumulative median OS was 728.0 days (95% confidence interval [CI]: 545.9–910.1) and cumulative median TTP was 365.0 days (95% CI: 296.9–433.1). For the 82 patients, the disease control rate was 93.9%, whereas the metabolic response rate was only 71.9% (p < 0.001). All PD and PR patients were found to be metabolic responders on 18F-FDG-PET/CT; however, among the 62mRECIST SD patients, 18 (29

  10. Performance, nutritional behavior, and metabolic responses of calves supplemented with forage depend on starch fermentability.

    Science.gov (United States)

    Mojahedi, S; Khorvash, M; Ghorbani, G R; Ghasemi, E; Mirzaei, M; Hashemzadeh-Cigari, F

    2018-05-16

    , respectively). The concentration of blood β-hydroxybutyrate was also greater in calves supplemented with forage than in unsupplemented calves. Results of the present study indicated that performance response and skeletal growth were the same between 2 corn processing methods. Forage provision improved ADG of calves fed the SF-based diet, but not the CR-based diet throughout the study. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  11. Response to ‘comment on recent modeling studies of astrocyte–neuron metabolic interactions': much ado about nothing

    OpenAIRE

    Mangia, Silvia; DiNuzzo, Mauro; Giove, Federico; Carruthers, Anthony; Simpson, Ian A; Vannucci, Susan J

    2011-01-01

    For many years, a tenet of cerebral metabolism held that glucose was the obligate energy substrate of the mammalian brain and that neuronal oxidative metabolism represented the majority of this glucose utilization. In 1994, Pellerin and Magistretti formulated the astrocyte–neuron lactate shuttle (ANLS) hypothesis, in which astrocytes, not neurons, metabolized glucose, with subsequent transport of the glycolytically derived lactate to fuel the energy needs of the neuron during neurotransmissio...

  12. Review of evidence that epidemics of type 1 diabetes and type 2 diabetes/metabolic syndrome are polar opposite responses to iatrogenic inflammation.

    Science.gov (United States)

    Classen, John B

    2012-11-01

    There is an epidemic in children of metabolic syndrome, obesity, type 2 diabetes and other individual diseases that form the components of metabolic syndrome. Poor diet and low exercise can not explain many facets of the epidemic including the onset in children 6 month of age, the protective effect of obesity on the incidence of type 1 diabetes and the epidemic of type 2 diabetes/metabolic syndrome in grass fed horses. Poor diet and exercise also do not explain the epidemic of type 1 diabetes in children that resembles the epidemic of type 2 diabetes/metabolic syndrome. Several papers have been published to indicate that the epidemics of type 1 and type 2 diabetes/metabolic syndrome in children are linked and are polar opposite responses to iatrogenic inflammation. Several lines of research support this. Data from different races indicates that there is an inverse relationship between developing type 1 diabetes and type 2 diabetes. Races with high risk of developing type 2 diabetes have a decreased risk of developing type 1 diabetes. Data from Italy confirmed an inverse association between obesity and type 1 diabetes. Further studies indicate the inverse relationship between type 1 diabetes and type 2 diabetes/obesity is due to cortisol production. Data indicates those with low cortisol responses have a predilection for type 1 diabetes and other autoimmune disorders following inflammation, while those with high cortisol/ immune suppressive responses develop type 2 diabetes/metabolic syndrome/obesity which resembles a Cushingoid state but are spared in the autoimmune disorders. Japanese children produce much more cortisol following immunization than Caucasian children. The later explains why discontinuation of BCG vaccination was associated with a decrease in type 1 diabetes in European children and a decrease in type 2 diabetes in Japanese children. Both the epidemics of type 1 diabetes and metabolic syndrome correlate with an increase in immunization. Finally

  13. Pathophysiological aspects of the acute phase response and the anaemia of chronic disease : with a focus on iron metabolism: With a focus on iron metabolism

    NARCIS (Netherlands)

    R.A. Feelders (Richard)

    1999-01-01

    textabstractThe acute phase response refers to a coordinated series of reactions in response to a variety of stimuli and involves all major body systems. This generalized host response is characterized by fever, changes in local vascular permeability, modulation of hepatic protein synthesis

  14. The mitochondrial phosphate transporters modulate plant responses to salt stress via affecting ATP and gibberellin metabolism in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Wei Zhu

    Full Text Available The mitochondrial phosphate transporter (MPT plays crucial roles in ATP production in plant cells. Three MPT genes have been identified in Arabidopsis thaliana. Here we report that the mRNA accumulations of AtMPTs were up-regulated by high salinity stress in A. thaliana seedlings. And the transgenic lines overexpressing AtMPTs displayed increased sensitivity to salt stress compared with the wild-type plants during seed germination and seedling establishment stages. ATP content and energy charge was higher in overexpressing plants than those in wild-type A. thaliana under salt stress. Accordingly, the salt-sensitive phenotype of overexpressing plants was recovered after the exogenous application of atractyloside due to the change of ATP content. Interestingly, Genevestigator survey and qRT-PCR analysis indicated a large number of genes, including those related to gibberellin synthesis could be regulated by the energy availability change under stress conditions in A. thaliana. Moreover, the exogenous application of uniconazole to overexpressing lines showed that gibberellin homeostasis was disturbed in the overexpressors. Our studies reveal a possible link between the ATP content mediated by AtMPTs and gibberellin metabolism in responses to high salinity stress in A. thaliana.

  15. A Comparison between Alpine Skiing, Cross-Country Skiing and Indoor Cycling on Cardiorespiratory and Metabolic Response

    Directory of Open Access Journals (Sweden)

    Thomas Stöggl, Christoph Schwarzl, Edith E. Müller, Masaru Nagasaki, Julia Stöggl, Peter Scheiber, Martin Schönfelder, Josef Niebauer

    2016-03-01

    Full Text Available Since physical inactivity especially prevails during winter months, we set out to identify outdoor alternatives to indoor cycling (IC by comparing the metabolic and cardiorespiratory responses during alpine skiing (AS, cross-country skiing (XCS and IC and analyse the effects of sex, age and fitness level in this comparison. Twenty one healthy subjects performed alpine skiing (AS, cross-country skiing (XCS, and IC. Oxygen uptake (VO2, total energy expenditure (EE, heart rate (HR, lactate, blood glucose and rate of perceived exertion (RPE were determined during three 4-min stages of low, moderate and high intensity. During XCS and IC VO2max and EE were higher than during AS. At least 2½ hours of AS are necessary to reach the same EE as during one hour of XCS or IC. HR, VO2, lactate, and RPEarms were highest during XCS, whereas RPEwhole-body was similar and RPElegs lower than during AS and IC, respectively. Weight adjusted VO2 and EE were higher in men than in women while fitness level had no effect. Male, fit and young participants were able to increase their EE and VO2 values more pronounced. Both AS and XCS can be individually tailored to serve as alternatives to IC and may thus help to overcome the winter activity deficit. XCS was found to be the most effective activity for generating a high EE and VO2 while AS was the most demanding activity for the legs.

  16. Aerobic exercise modulation of mental stress-induced responses in cultured endothelial progenitor cells from healthy and metabolic syndrome subjects.

    Science.gov (United States)

    Rocha, Natalia G; Sales, Allan R K; Miranda, Renan L; Silva, Mayra S; Silva, Jemima F R; Silva, Bruno M; Santos, Aline A; Nóbrega, Antonio C L

    2015-02-15

    Numerous studies have demonstrated that exercise acutely prevents the reduction in flow-mediated dilation induced by mental stress in subjects with metabolic syndrome (MetS). However, it is unknown whether a similar effect occurs in endothelial progenitors cells (EPCs). This study investigated whether exercise protects from the deleterious effect of mental stress on cultured EPCs in healthy subjects and those with MetS. Ten healthy subjects (aged 31±2) and ten subjects with MetS (aged 36±2) were enrolled. Subjects underwent a mental stress test, followed immediately by either 40 min of leg cycling or rest across two randomized sessions: mental stress+non-exercise control (MS) and mental stress+exercise (MS+EXE). The Stroop Color-Word Test was used to elicit mental stress. Blood samples were drawn at baseline and following sessions to isolate mononuclear cells. These cells were cultured in fibronectin-coated plates for seven days, and EPCs were identified by immunofluorescence (acLDL(+)/ UEA-I Lectin(+)). All subjects presented similar increases in mean blood pressure and heart rate during the mental stress test (P0.05). The EPC response to MS and MS+EXE was increased in healthy subjects, whereas it was decreased in subjects with MetS (Pexercise session increased EPCs in healthy subjects but did not prevent the EPC reduction induced by mental stress among subjects with MetS. © 2015.

  17. Photoperiodic responses of depression-like behavior, the brain serotonergic system, and peripheral metabolism in laboratory mice.

    Science.gov (United States)

    Otsuka, Tsuyoshi; Kawai, Misato; Togo, Yuki; Goda, Ryosei; Kawase, Takahiro; Matsuo, Haruka; Iwamoto, Ayaka; Nagasawa, Mao; Furuse, Mitsuhiro; Yasuo, Shinobu

    2014-02-01

    Seasonal affective disorder (SAD) is characterized by depression during specific seasons, generally winter. The pathophysiological mechanisms underlying SAD remain elusive due to a limited number of animal models with high availability and validity. Here we show that laboratory C57BL/6J mice display photoperiodic changes in depression-like behavior and brain serotonin content. C57BL/6J mice maintained under short-day conditions, as compared to those under long-day conditions, demonstrated prolonged immobility times in the forced swimming test with lower brain levels of serotonin and its precursor l-tryptophan. Fur