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Sample records for adaptive energy metabolism

  1. Adaptive evolution of mitochondrial energy metabolism genes associated with increased energy demand in flying insects.

    PubMed

    Yang, Yunxia; Xu, Shixia; Xu, Junxiao; Guo, Yan; Yang, Guang

    2014-01-01

    Insects are unique among invertebrates for their ability to fly, which raises intriguing questions about how energy metabolism in insects evolved and changed along with flight. Although physiological studies indicated that energy consumption differs between flying and non-flying insects, the evolution of molecular energy metabolism mechanisms in insects remains largely unexplored. Considering that about 95% of adenosine triphosphate (ATP) is supplied by mitochondria via oxidative phosphorylation, we examined 13 mitochondrial protein-encoding genes to test whether adaptive evolution of energy metabolism-related genes occurred in insects. The analyses demonstrated that mitochondrial DNA protein-encoding genes are subject to positive selection from the last common ancestor of Pterygota, which evolved primitive flight ability. Positive selection was also found in insects with flight ability, whereas no significant sign of selection was found in flightless insects where the wings had degenerated. In addition, significant positive selection was also identified in the last common ancestor of Neoptera, which changed its flight mode from direct to indirect. Interestingly, detection of more positively selected genes in indirect flight rather than direct flight insects suggested a stronger selective pressure in insects having higher energy consumption. In conclusion, mitochondrial protein-encoding genes involved in energy metabolism were targets of adaptive evolution in response to increased energy demands that arose during the evolution of flight ability in insects.

  2. NF-κB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration.

    PubMed

    Mauro, Claudio; Leow, Shi Chi; Anso, Elena; Rocha, Sonia; Thotakura, Anil K; Tornatore, Laura; Moretti, Marta; De Smaele, Enrico; Beg, Amer A; Tergaonkar, Vinay; Chandel, Navdeep S; Franzoso, Guido

    2011-10-01

    Cell proliferation is a metabolically demanding process. It requires active reprogramming of cellular bioenergetic pathways towards glucose metabolism to support anabolic growth. NF-κB/Rel transcription factors coordinate many of the signals that drive proliferation during immunity, inflammation and oncogenesis, but whether NF-κB regulates the metabolic reprogramming required for cell division during these processes is unknown. Here, we report that NF-κB organizes energy metabolism networks by controlling the balance between the utilization of glycolysis and mitochondrial respiration. NF-κB inhibition causes cellular reprogramming to aerobic glycolysis under basal conditions and induces necrosis on glucose starvation. The metabolic reorganization that results from NF-κB inhibition overcomes the requirement for tumour suppressor mutation in oncogenic transformation and impairs metabolic adaptation in cancer in vivo. This NF-κB-dependent metabolic pathway involves stimulation of oxidative phosphorylation through upregulation of mitochondrial synthesis of cytochrome c oxidase 2 (SCO2; ref. ). Our findings identify NF-κB as a physiological regulator of mitochondrial respiration and establish a role for NF-κB in metabolic adaptation in normal cells and cancer. PMID:21968997

  3. Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans.

    PubMed

    Pontzer, Herman; Durazo-Arvizu, Ramon; Dugas, Lara R; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Cooper, Richard S; Schoeller, Dale A; Luke, Amy

    2016-02-01

    Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology.

  4. Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans.

    PubMed

    Pontzer, Herman; Durazo-Arvizu, Ramon; Dugas, Lara R; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Cooper, Richard S; Schoeller, Dale A; Luke, Amy

    2016-02-01

    Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology. PMID:26832439

  5. Metabolic Adaptation to Muscle Ischemia

    NASA Technical Reports Server (NTRS)

    Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

    2000-01-01

    Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

  6. Metabolic adaptation to decreases in energy intake due to changes in the energy cost of low energy expenditure regimen.

    PubMed

    Garby, L

    1990-01-01

    (1) The energy content in food is used in the human body for three main purposes. The first is to maintain the dissipative structures. Most of the structures of the body are of this kind, i.e. they represent stationary non-equilibrium states, or (generalized) stationary potentials, and are inherently unstable. The second is to maintain a body temperature independent of and usually higher than that of the surroundings. The third is to provide energy for performance of external work. The functional structure of the system providing these results consists of a large number of coupled processes (chemical reactions and translocations), in series and in parallel, whose general nature is well understood but whose quantitative extents are mainly unknown. The coupled processes are driven by the spontaneous reaction of the main substrates with oxygen. Energy flows through the system and is converted to heat (and external work) with simultaneous creation of stationary generalized potentials. For each potential there is an associated flow of energy and the relation between the two is an expression of the efficiency with which the potential is maintained. The processes giving rise to the potentials are likely to be controlled with respect to the efficiency with which the potentials are maintained. The control is partly provided through feedback from the potentials themselves: the potentials are regulated. In this way, the system can respond in a non-linear fashion to perturbations in the energy intake (or energy expenditure): the potentials are maintained at constant, or nearly constant, values. The concept of metabolic adaptation implies that control of the efficiency by feedback from the potentials is an important element in the overall regulation of the potentials, including that of the body temperature. (2) The concept of metabolic adaptation can be framed in such a way that it becomes operational. Quantities such as maintained potentials and efficiency can be revealed in

  7. The globally widespread genus Sulfurimonas: versatile energy metabolisms and adaptations to redox clines.

    PubMed

    Han, Yuchen; Perner, Mirjam

    2015-01-01

    Sulfurimonas species are commonly isolated from sulfidic habitats and numerous 16S rRNA sequences related to Sulfurimonas species have been identified in chemically distinct environments, such as hydrothermal deep-sea vents, marine sediments, the ocean's water column, and terrestrial habitats. In some of these habitats, Sulfurimonas have been demonstrated to play an important role in chemoautotrophic processes. Sulfurimonas species can grow with a variety of electron donors and acceptors, which may contribute to their widespread distribution. Multiple copies of one type of enzyme (e.g., sulfide:quinone reductases and hydrogenases) may play a pivotal role in Sulfurimonas' flexibility to colonize disparate environments. Many of these genes appear to have been acquired through horizontal gene transfer which has promoted adaptations to the distinct habitats. Here we summarize Sulfurimonas' versatile energy metabolisms and link their physiological properties to their global distribution.

  8. The globally widespread genus Sulfurimonas: versatile energy metabolisms and adaptations to redox clines

    PubMed Central

    Han, Yuchen; Perner, Mirjam

    2015-01-01

    Sulfurimonas species are commonly isolated from sulfidic habitats and numerous 16S rRNA sequences related to Sulfurimonas species have been identified in chemically distinct environments, such as hydrothermal deep-sea vents, marine sediments, the ocean’s water column, and terrestrial habitats. In some of these habitats, Sulfurimonas have been demonstrated to play an important role in chemoautotrophic processes. Sulfurimonas species can grow with a variety of electron donors and acceptors, which may contribute to their widespread distribution. Multiple copies of one type of enzyme (e.g., sulfide:quinone reductases and hydrogenases) may play a pivotal role in Sulfurimonas’ flexibility to colonize disparate environments. Many of these genes appear to have been acquired through horizontal gene transfer which has promoted adaptations to the distinct habitats. Here we summarize Sulfurimonas’ versatile energy metabolisms and link their physiological properties to their global distribution. PMID:26441918

  9. The globally widespread genus Sulfurimonas: versatile energy metabolisms and adaptations to redox clines.

    PubMed

    Han, Yuchen; Perner, Mirjam

    2015-01-01

    Sulfurimonas species are commonly isolated from sulfidic habitats and numerous 16S rRNA sequences related to Sulfurimonas species have been identified in chemically distinct environments, such as hydrothermal deep-sea vents, marine sediments, the ocean's water column, and terrestrial habitats. In some of these habitats, Sulfurimonas have been demonstrated to play an important role in chemoautotrophic processes. Sulfurimonas species can grow with a variety of electron donors and acceptors, which may contribute to their widespread distribution. Multiple copies of one type of enzyme (e.g., sulfide:quinone reductases and hydrogenases) may play a pivotal role in Sulfurimonas' flexibility to colonize disparate environments. Many of these genes appear to have been acquired through horizontal gene transfer which has promoted adaptations to the distinct habitats. Here we summarize Sulfurimonas' versatile energy metabolisms and link their physiological properties to their global distribution. PMID:26441918

  10. Regulation of skeletal muscle energy/nutrient-sensing pathways during metabolic adaptation to fasting in healthy humans.

    PubMed

    Wijngaarden, Marjolein A; Bakker, Leontine E H; van der Zon, Gerard C; 't Hoen, Peter A C; van Dijk, Ko Willems; Jazet, Ingrid M; Pijl, Hanno; Guigas, Bruno

    2014-11-15

    During fasting, rapid metabolic adaptations are required to maintain energy homeostasis. This occurs by a coordinated regulation of energy/nutrient-sensing pathways leading to transcriptional activation and repression of specific sets of genes. The aim of the study was to investigate how short-term fasting affects whole body energy homeostasis and skeletal muscle energy/nutrient-sensing pathways and transcriptome in humans. For this purpose, 12 young healthy men were studied during a 24-h fast. Whole body glucose/lipid oxidation rates were determined by indirect calorimetry, and blood and skeletal muscle biopsies were collected and analyzed at baseline and after 10 and 24 h of fasting. As expected, fasting induced a time-dependent decrease in plasma insulin and leptin levels, whereas levels of ketone bodies and free fatty acids increased. This was associated with a metabolic shift from glucose toward lipid oxidation. At the molecular level, activation of the protein kinase B (PKB/Akt) and mammalian target of rapamycin pathways was time-dependently reduced in skeletal muscle during fasting, whereas the AMP-activated protein kinase activity remained unaffected. Furthermore, we report some changes in the phosphorylation and/or content of forkhead protein 1, sirtuin 1, and class IIa histone deacetylase 4, suggesting that these pathways might be involved in the transcriptional adaptation to fasting. Finally, transcriptome profiling identified genes that were significantly regulated by fasting in skeletal muscle at both early and late time points. Collectively, our study provides a comprehensive map of the main energy/nutrient-sensing pathways and transcriptomic changes during short-term adaptation to fasting in human skeletal muscle.

  11. Adaptation of energy metabolism to undernutrition in ewes. Contribution of portal-drained viscera, liver and hindquarters.

    PubMed

    Ortigues, I; Durand, D

    1995-02-01

    Adaptation of energy metabolism to undernutrition and to the duration of undernutrition was studied in adult, non-pregnant, non-lactating ewes at the whole-animal, portal-drained viscera, liver and hindquarters levels. Arterio-venous and indirect calorimetry techniques were used. Animals were successively fed at 1 times (3 weeks) and at 0.5 times (7 weeks) their metabolizable energy requirements for maintenance (MEm). Portal, hepatic and hindquarters blood flows in quietly standing ewes decreased by 22, 19 and 11% respectively within the first week of undernutrition and remained at that level thereafter. Standardizing hindquarters blood flow to that in a given posture (quietly standing) reduced blood flow by 9.8%. In the portal-drained viscera and liver, O2 extraction rates decreased, leading to 34 and 38% drops in O2 consumption with underfeeding respectively. In the hindquarters, O2 extraction rate increased, partly counterbalancing the drop in blood flow. Thus O2 consumption of hindquarters tended to decrease but the effect was not significant. All changes appeared to be completed from day 5 of underfeeding. Consequently, the portal-drained viscera, liver and carcass were responsible for 39, 32 and 5% respectively of the drop in whole-animal O2 consumption with underfeeding. At the end of the 0.5 x MEm period, in vivo metabolic rates averaged 1.65, 4.89 and 0.38 mmol O2 consumed/d per g fresh weight of adipose-tissue-free portal-drained viscera, liver and boneless hindquarters respectively. Undernutrition imposed a much greater nutritional challenge to splanchnic tissues than to hindquarters. The former reduced their energy expenditure whereas hindquarters metabolism adapted by counteracting the slight drop in nutrient supply.

  12. Role of Hypothalamic VGF in Energy Balance and Metabolic Adaption to Environmental Enrichment in Mice.

    PubMed

    Foglesong, Grant D; Huang, Wei; Liu, Xianglan; Slater, Andrew M; Siu, Jason; Yildiz, Vedat; Salton, Stephen R J; Cao, Lei

    2016-03-01

    Environmental enrichment (EE), a housing condition providing complex physical, social, and cognitive stimulation, leads to improved metabolic health and resistance to diet-induced obesity and cancer. One underlying mechanism is the activation of the hypothalamic-sympathoneural-adipocyte axis with hypothalamic brain-derived neurotrophic factor (BDNF) as the key mediator. VGF, a peptide precursor particularly abundant in the hypothalamus, was up-regulated by EE. Overexpressing BDNF or acute injection of BDNF protein to the hypothalamus up-regulated VGF, whereas suppressing BDNF signaling down-regulated VGF expression. Moreover, hypothalamic VGF expression was regulated by leptin, melanocortin receptor agonist, and food deprivation mostly paralleled to BDNF expression. Recombinant adeno-associated virus-mediated gene transfer of Cre recombinase to floxed VGF mice specifically decreased VGF expression in the hypothalamus. In contrast to the lean and hypermetabolic phenotype of homozygous germline VGF knockout mice, specific knockdown of hypothalamic VGF in male adult mice led to increased adiposity, decreased core body temperature, reduced energy expenditure, and impaired glucose tolerance, as well as disturbance of molecular features of brown and white adipose tissues without effects on food intake. However, VGF knockdown failed to block the EE-induced BDNF up-regulation or decrease of adiposity indicating a minor role of VGF in the hypothalamic-sympathoneural-adipocyte axis. Taken together, our results suggest hypothalamic VGF responds to environmental demands and plays an important role in energy balance and glycemic control likely acting in the melanocortin pathway downstream of BDNF.

  13. Role of Hypothalamic VGF in Energy Balance and Metabolic Adaption to Environmental Enrichment in Mice.

    PubMed

    Foglesong, Grant D; Huang, Wei; Liu, Xianglan; Slater, Andrew M; Siu, Jason; Yildiz, Vedat; Salton, Stephen R J; Cao, Lei

    2016-03-01

    Environmental enrichment (EE), a housing condition providing complex physical, social, and cognitive stimulation, leads to improved metabolic health and resistance to diet-induced obesity and cancer. One underlying mechanism is the activation of the hypothalamic-sympathoneural-adipocyte axis with hypothalamic brain-derived neurotrophic factor (BDNF) as the key mediator. VGF, a peptide precursor particularly abundant in the hypothalamus, was up-regulated by EE. Overexpressing BDNF or acute injection of BDNF protein to the hypothalamus up-regulated VGF, whereas suppressing BDNF signaling down-regulated VGF expression. Moreover, hypothalamic VGF expression was regulated by leptin, melanocortin receptor agonist, and food deprivation mostly paralleled to BDNF expression. Recombinant adeno-associated virus-mediated gene transfer of Cre recombinase to floxed VGF mice specifically decreased VGF expression in the hypothalamus. In contrast to the lean and hypermetabolic phenotype of homozygous germline VGF knockout mice, specific knockdown of hypothalamic VGF in male adult mice led to increased adiposity, decreased core body temperature, reduced energy expenditure, and impaired glucose tolerance, as well as disturbance of molecular features of brown and white adipose tissues without effects on food intake. However, VGF knockdown failed to block the EE-induced BDNF up-regulation or decrease of adiposity indicating a minor role of VGF in the hypothalamic-sympathoneural-adipocyte axis. Taken together, our results suggest hypothalamic VGF responds to environmental demands and plays an important role in energy balance and glycemic control likely acting in the melanocortin pathway downstream of BDNF. PMID:26730934

  14. Oxygen availability and metabolic adaptations.

    PubMed

    Nakazawa, Michael S; Keith, Brian; Simon, M Celeste

    2016-09-23

    Oxygen availability, along with the abundance of nutrients (such as glucose, glutamine, lipids and albumin), fluctuates significantly during tumour evolution and the recruitment of blood vessels, leukocytes and reactive fibroblasts to complex tumour microenvironments. As such, hypoxia and concomitant nutrient scarcity affect large gene expression programmes, signalling pathways, diverse metabolic reactions and various stress responses. This Review summarizes our current understanding of how these adaptations are integrated in hypoxic tumour cells and their role in disease progression. PMID:27658636

  15. Energy and metabolism.

    PubMed

    Suarez, Raul K

    2012-10-01

    Although firmly grounded in metabolic biochemistry, the study of energy metabolism has gone well beyond this discipline and become integrative and comparative as well as ecological and evolutionary in scope. At the cellular level, ATP is hydrolyzed by energy-expending processes and resynthesized by pathways in bioenergetics. A significant development in the study of bioenergetics is the realization that fluxes through pathways as well as metabolic rates in cells, tissues, organs, and whole organisms are "system properties." Therefore, studies of energy metabolism have become, increasingly, experiments in systems biology. A significant challenge continues to be the integration of phenomena over multiple levels of organization. Body mass and temperature are said to account for most of the variation in metabolic rates found in nature. A mechanistic foundation for the understanding of these patterns is outlined. It is emphasized that evolution, leading to adaptation to diverse lifestyles and environments, has resulted in a tremendous amount of deviation from popularly accepted scaling "rules." This is especially so in the deep sea which constitutes most of the biosphere. PMID:23720257

  16. Cerebral metabolic adaptation and ketone metabolism after brain injury

    PubMed Central

    Prins, Mayumi L

    2010-01-01

    The developing central nervous system has the capacity to metabolize ketone bodies. It was once accepted that on weaning, the ‘post-weaned/adult’ brain was limited solely to glucose metabolism. However, increasing evidence from conditions of inadequate glucose availability or increased energy demands has shown that the adult brain is not static in its fuel options. The objective of this review is to summarize the body of literature specifically regarding cerebral ketone metabolism at different ages, under conditions of starvation and after various pathologic conditions. The evidence presented supports the following findings: (1) there is an inverse relationship between age and the brain’s capacity for ketone metabolism that continues well after weaning; (2) neuroprotective potentials of ketone administration have been shown for neurodegenerative conditions, epilepsy, hypoxia/ischemia, and traumatic brain injury; and (3) there is an age-related therapeutic potential for ketone as an alternative substrate. The concept of cerebral metabolic adaptation under various physiologic and pathologic conditions is not new, but it has taken the contribution of numerous studies over many years to break the previously accepted dogma of cerebral metabolism. Our emerging understanding of cerebral metabolism is far more complex than could have been imagined. It is clear that in addition to glucose, other substrates must be considered along with fuel interactions, metabolic challenges, and cerebral maturation. PMID:17684514

  17. Metabolic and developmental adaptations of growing potato tubers in response to specific manipulations of the adenylate energy status.

    PubMed

    Riewe, David; Grosman, Lukasz; Zauber, Henrik; Wucke, Cornelia; Fernie, Alisdair R; Geigenberger, Peter

    2008-04-01

    Heterotrophic carbon metabolism has been demonstrated to be limited by oxygen availability in a variety of plant tissues, which in turn inevitably affects the adenylate status. To study the effect of altering adenylate energy metabolism, without changing the oxygen supply, we expressed a plastidially targeted ATP/ADP hydrolyzing phosphatase (apyrase) in tubers of growing potato (Solanum tuberosum) plants under the control of either inducible or constitutive promoters. Inducible apyrase expression in potato tubers, for a period of 24 h, resulted in a decrease in the ATP-content and the ATP-ADP ratio in the tubers. As revealed by metabolic profiling, this was accompanied by a decrease in the intermediates of sucrose to starch conversion and several plastidially synthesized amino acids, indicating a general depression of tuber metabolism. Constitutive tuber-specific apyrase expression did not lead to a reduction of ATP, but rather a decrease in ADP and an increase in AMP levels. Starch accumulation was strongly inhibited and shifted to the production of amylopectin instead of amylose in these tubers. Furthermore, the levels of almost all amino acids were decreased, although soluble sugars and hexose-Ps were highly abundant. Respiration was elevated in the constitutively expressing lines indicating a compensation for the dramatic increase in ATP hydrolysis. The increase in respiration did not affect the internal oxygen tensions in the tubers. However, the tubers developed a ginger-like phenotype having an elevated surface-volume ratio and a reduced mass per tuber. Decreased posttranslational redox activation of ADP-glucose pyrophosphorylase and a shift in the ratio of soluble starch synthase activity to granule-bound starch synthase activity were found to be partially responsible for the alterations in starch structure and abundance. The activity of alcohol dehydrogenase was decreased and pyruvate decarboxylase was induced, but this was neither reflected by an increase

  18. Long Term Effects of Energy-Restricted Diets Differing in Glycemic Load on Metabolic Adaptation and Body Composition*

    PubMed Central

    Das, Sai Krupa; Gilhooly, Cheryl H.; Golden, Julie K.; Pittas, Anastassios G.; Fuss, Paul J.; Dallal, Gerard E.; McCrory, Megan A.; Saltzman, Edward; Roberts, Susan B.

    2010-01-01

    A randomized controlled trial of high glycemic load (HG) and low glycemic load (LG) diets with food provided for 6 months and self-administered for 6 additional months at 30% caloric restriction (CR) was performed in 29 overweight adults (mean±SD, age 35±5y; BMI 27.5±1.5 kg/m2). Total energy expenditure (TEE), resting metabolic rate (RMR), fat and fat free mass (FFM), were measured at 3, 6 and 12 months. Changes in TEE, but not changes in RMR, were greater than accounted for by the loss of FFM and fat mass (P=0.001-0.013) suggesting an adaptive response to long-term CR. There was no significant effect of diet group on change in RMR or TEE. However, in subjects who lost >5% body weight (n=26), the LG diet group had a higher percentage of weight loss as fat than the HG group (p<0.05), a finding that may have implications for dietary recommendations during weight reduction. PMID:20711415

  19. The correlation of sodium and potassium metabolism with the level of energy consumption in man during adaptation to heat

    NASA Technical Reports Server (NTRS)

    Afanasyev, B. G.; Zhestovskiy, V. A.

    1978-01-01

    The sodium and potassium metabolism was studied in a thermal chamber at 35 deg and 80 percent relative humidity in 8 men for a period of 6 days. The control group (3 subjects) were outside of the chamber at a comfortable ambient temperature. The intracellular sodium and potassium metabolism were assessed based on their content in the erythrocytes. The finding was that during adaptation to heat, a considerable amount of sodium was excreted by the body in the sweat and urine (about 1/3 of the sodium content of the human body) as compared with its intake and the amount of potassium retained in the body. Changes in the concentration of sodium and potassium may serve as indexes of the state of adaptation processes during constant exposure to heat.

  20. Mitochondria-Mediated Energy Adaption in Cancer: The H+-ATP Synthase-Geared Switch of Metabolism in Human Tumors

    PubMed Central

    Sánchez-Aragó, María; Formentini, Laura

    2013-01-01

    Abstract Significance: Since the signing of the National Cancer Act in 1971, cancer still remains a major cause of death despite significant progresses made in understanding the biology and treatment of the disease. After many years of ostracism, the peculiar energy metabolism of tumors has been recognized as an additional phenotypic trait of the cancer cell. Recent Advances: While the enhanced aerobic glycolysis of carcinomas has already been translated to bedside for precise tumor imaging and staging of cancer patients, accepting that an impaired bioenergetic function of mitochondria is pivotal to understand energy metabolism of tumors and in its progression is debated. However, mitochondrial bioenergetics and cell death are tightly connected. Critical Issues: Recent clinical findings indicate that H+-ATP synthase, a core component of mitochondrial oxidative phosphorylation, is repressed at both the protein and activity levels in human carcinomas. This review summarizes the relevance that mitochondrial function has to understand energy metabolism of tumors and explores the connection between the bioenergetic function of the organelle and the activity of mitochondria as tumor suppressors. Future Directions: The reversible nature of energy metabolism in tumors highlights the relevance that the microenvironment has for tumor progression. Moreover, the stimulation of mitochondrial activity or the inhibition of glycolysis suppresses tumor growth. Future research should elucidate the mechanisms promoting the silencing of oxidative phosphorylation in carcinomas. The aim is the development of new therapeutic strategies tackling energy metabolism to eradicate tumors or at least, to maintain tumor dormancy and transform cancer into a chronic disease. Antioxid. Redox Signal. 19, 285–298. PMID:22901241

  1. ERRα mediates metabolic adaptations driving lapatinib resistance in breast cancer

    PubMed Central

    Deblois, Geneviève; Smith, Harvey W.; Tam, Ingrid S.; Gravel, Simon-Pierre; Caron, Maxime; Savage, Paul; Labbé, David P.; Bégin, Louis R.; Tremblay, Michel L.; Park, Morag; Bourque, Guillaume; St-Pierre, Julie; Muller, William J.; Giguère, Vincent

    2016-01-01

    Despite the initial benefits of treating HER2-amplified breast cancer patients with the tyrosine kinase inhibitor lapatinib, resistance inevitably develops. Here we report that lapatinib induces the degradation of the nuclear receptor ERRα, a master regulator of cellular metabolism, and that the expression of ERRα is restored in lapatinib-resistant breast cancer cells through reactivation of mTOR signalling. Re-expression of ERRα in resistant cells triggers metabolic adaptations favouring mitochondrial energy metabolism through increased glutamine metabolism, as well as ROS detoxification required for cell survival under therapeutic stress conditions. An ERRα inverse agonist counteracts these metabolic adaptations and overcomes lapatinib resistance in a HER2-induced mammary tumour mouse model. This work reveals a molecular mechanism by which ERRα-induced metabolic reprogramming promotes survival of lapatinib-resistant cancer cells and demonstrates the potential of ERRα inhibition as an effective adjuvant therapy in poor outcome HER2-positive breast cancer. PMID:27402251

  2. ERRα mediates metabolic adaptations driving lapatinib resistance in breast cancer.

    PubMed

    Deblois, Geneviève; Smith, Harvey W; Tam, Ingrid S; Gravel, Simon-Pierre; Caron, Maxime; Savage, Paul; Labbé, David P; Bégin, Louis R; Tremblay, Michel L; Park, Morag; Bourque, Guillaume; St-Pierre, Julie; Muller, William J; Giguère, Vincent

    2016-01-01

    Despite the initial benefits of treating HER2-amplified breast cancer patients with the tyrosine kinase inhibitor lapatinib, resistance inevitably develops. Here we report that lapatinib induces the degradation of the nuclear receptor ERRα, a master regulator of cellular metabolism, and that the expression of ERRα is restored in lapatinib-resistant breast cancer cells through reactivation of mTOR signalling. Re-expression of ERRα in resistant cells triggers metabolic adaptations favouring mitochondrial energy metabolism through increased glutamine metabolism, as well as ROS detoxification required for cell survival under therapeutic stress conditions. An ERRα inverse agonist counteracts these metabolic adaptations and overcomes lapatinib resistance in a HER2-induced mammary tumour mouse model. This work reveals a molecular mechanism by which ERRα-induced metabolic reprogramming promotes survival of lapatinib-resistant cancer cells and demonstrates the potential of ERRα inhibition as an effective adjuvant therapy in poor outcome HER2-positive breast cancer. PMID:27402251

  3. Bevacizumab treatment induces metabolic adaptation toward anaerobic metabolism in glioblastomas.

    PubMed

    Fack, Fred; Espedal, Heidi; Keunen, Olivier; Golebiewska, Anna; Obad, Nina; Harter, Patrick N; Mittelbronn, Michel; Bähr, Oliver; Weyerbrock, Astrid; Stuhr, Linda; Miletic, Hrvoje; Sakariassen, Per Ø; Stieber, Daniel; Rygh, Cecilie B; Lund-Johansen, Morten; Zheng, Liang; Gottlieb, Eyal; Niclou, Simone P; Bjerkvig, Rolf

    2015-01-01

    Anti-angiogenic therapy in glioblastoma (GBM) has unfortunately not led to the anticipated improvement in patient prognosis. We here describe how human GBM adapts to bevacizumab treatment at the metabolic level. By performing (13)C6-glucose metabolic flux analysis, we show for the first time that the tumors undergo metabolic re-programming toward anaerobic metabolism, thereby uncoupling glycolysis from oxidative phosphorylation. Following treatment, an increased influx of (13)C6-glucose was observed into the tumors, concomitant to increased lactate levels and a reduction of metabolites associated with the tricarboxylic acid cycle. This was confirmed by increased expression of glycolytic enzymes including pyruvate dehydrogenase kinase in the treated tumors. Interestingly, L-glutamine levels were also reduced. These results were further confirmed by the assessment of in vivo metabolic data obtained by magnetic resonance spectroscopy and positron emission tomography. Moreover, bevacizumab led to a depletion in glutathione levels indicating that the treatment caused oxidative stress in the tumors. Confirming the metabolic flux results, immunohistochemical analysis showed an up-regulation of lactate dehydrogenase in the bevacizumab-treated tumor core as well as in single tumor cells infiltrating the brain, which may explain the increased invasion observed after bevacizumab treatment. These observations were further validated in a panel of eight human GBM patients in which paired biopsy samples were obtained before and after bevacizumab treatment. Importantly, we show that the GBM adaptation to bevacizumab therapy is not mediated by clonal selection mechanisms, but represents an adaptive response to therapy.

  4. Endocannabinoids and energy metabolism.

    PubMed

    Pagotto, U; Pasquali, R

    2006-01-01

    Although adjustments to nutritional lifestyle and increased physical activity remain the milestones of weight loss therapy, it is evident from the exponential increase of the number of obese subjects in Western countries that these two approaches alone are no longer able to limit this progression. This alarming phenomenon occurs in spite of a great effort exerted in the last 10 yr to shed light on the pathogenetic mechanisms inducing obesity, although many inconclusive hopes have been generated in the field of pharmacotherapeutics to tackle obesity. Among the several targets exploited in recent years, the endocannabinoid system nowadays constitutes the most promising and the most intriguing proposed so far. On one hand, our aim is to provide an overview on the role of the endocannabinoid system in the physiology of energy metabolism, on the other hand a further aim is to summarize how the system also controls food intake and energy balance by acting at both cerebral and peripheral level. PMID:16751710

  5. Permeability of the infective juveniles of Steinernema carpocapsae to glycerol during osmotic dehydration and its effect on biochemical adaptation and energy metabolism.

    PubMed

    Qiu, L; Lacey, M J; Bedding, R A

    2000-03-01

    Permeability of the sheath and cuticle of the infective juveniles (IJs) of Steinernema carpocapsae to glycerol and its effect on biochemical adaptation of the IJs to osmotic dehydration were examined by incubating both sheathed and exsheathed IJs in glycerol-d5 solution then monitoring the changes in levels of deuterium labelled and non-labelled glycerol and trehalose. Energy metabolism of the IJs during osmotic dehydration and subsequent rehydration and the effect of the permeated glycerol on this process were investigated by examining and comparing the changes in mean dry weight and key biochemical composition of the IJs dehydrated in glycerol and sodium chloride solutions. The results show: (1) similarly to evaporative dehydration, osmotic dehydration induces IJs to synthesise the protectants glycerol and trehalose; (2) glycerol permeates the sheath and the cuticle into the body of IJs during dehydration in glycerol solution. Part of the permeated glycerol plays a role as protectant like that synthesised by IJs from their energy reserve materials while part is incorporated into trehalose; (3) the sheath reduces the rate of permeation of glycerol and therefore affects the equilibrium glycerol and trehalose levels of the IJs and also the time needed to reach the equilibrium levels; (4) the reduction in mean dry weight and lipids of the IJs during dehydration in glycerol solution is substantially less than those dehydrated in sodium chloride solution. Both the total protectant level and the ratio of glycerol to trehalose of the IJs dehydrated in glycerol solution are higher than those dehydrated in sodium chloride solution; (5) glycogen reserves of the IJs play a role as a buffer reservoir of the protectants during both dehydration and rehydration but the principal sources of the protectants during dehydration are more likely to be lipids and proteins rather than glycogen.

  6. Effects of starvation, refeeding, and insulin on energy-linked metabolic processes in catfish (Rhamdia hilarii) adapted to a carbohydrate-rich diet

    SciTech Connect

    Machado, C.R.; Garofalo, M.A.; Roselino, J.E.; Kettelhut, I.C.; Migliorini, R.H.

    1988-09-01

    The effects of starvation and of a short period of refeeding on energy-linked metabolic processes, as well as the effects of insulin administration, were investigated in an omnivorous fish (catfish, Rhamdia hilarii) previously adapted to a carbohydrate-rich diet. Following food deprivation blood sugar levels declined progressively to about 50% of fed values after 30 days. During the same period plasma free fatty acid (FFA) concentration increased twofold. Starvation resulted in reduced concentrations of lipid and glycogen in the liver and of glycogen, lipid, and protein in white muscle. However, taking into account the initial and final concentrations of tissue constituents, the liver weight, and the large fractions of body weight represented by muscle, it could be estimated that most of the energy utilized during starvation derived from the catabolism of muscle lipid and protein. Refeeding starved fishes for 48 hr induced several-fold increases in the rates of in vivo and in vitro incorporation of (14C)glucose into liver and muscle lipid and of (14C)glycine into liver and muscle protein. Incorporation of (14C)glucose into liver glycogen was also increased. However; refeeding did not affect the incorporation of labeled glucose into muscle glycogen, neither in vivo nor in vitro. Administration of pharmacological doses of insulin to normally fed catfishes resulted in marked increases in the in vivo incorporation of 14C from glucose into lipid and protein in both liver and muscle. In contrast, labeled glucose incorporation into muscle glycogen was not affected by insulin and label incorporation into liver glycogen was actually lower than that in noninjected controls.

  7. Changes in body composition and resting energy expenditure after rapid weight loss: is there an energy-metabolism adaptation in obese patients?

    PubMed

    Valtueña, S; Blanch, S; Barenys, M; Solà, R; Salas-Salvadó, J

    1995-02-01

    The aim of this study was to assess changes in resting energy expenditure (REE) related to changes in fat free mass (FFM) in nine morbid obese (BMI 43 +/- 5.1 kg/m2) hospitalised females on VLCD. REE was measured by 30 min indirect calorimetry before and after 28 days of hospitalisation. Changes in FFM were assessed by bioelectrical impedance analysis (BIA), hydrostatic weighing (HW) and nitrogen balance (N). REE decreased 11.5% from 7.8 +/- 1.0 to 6.9 +/- 0.8 MJ/d. Total weight loss was 8.4 +/- 1.9 kg or 7.4% with an estimated FFM loss of 3.4 +/- 1.8 (BIA), 2.9 +/- 1.9 (HW) and 1.8 +/- 1.0 (N). As the fall in REE was larger than the loss of FFM, it is concluded that morbid obese patients develop an energy saving adaptation during rapid weight loss. PMID:7735338

  8. Targeting mitochondrial energy metabolism with TSPO ligands.

    PubMed

    Gut, Philipp

    2015-08-01

    The translocator protein (18 kDa) (TSPO) resides on the outer mitochondrial membrane where it is believed to participate in cholesterol transport and steroid hormone synthesis. Although it is almost ubiquitously expressed, what TSPO does in non-steroidogenic tissues is largely unexplored. Recent studies report changes in glucose homoeostasis and cellular energy production when TSPO function is modulated by selective ligands or by genetic loss-of-function. This review summarizes findings that connect TSPO function with the regulation of mitochondrial energy metabolism. The juxtaposition of TSPO at the cytosolic/mitochondrial interface and the existence of endogenous ligands that are regulated by metabolism suggest that TSPO functions to adapt mitochondrial to cellular metabolism. From a pharmacological perspective the specific up-regulation of TSPO in neuro-inflammatory and injury-induced conditions make TSPO an interesting, druggable target of mitochondrial metabolism.

  9. Endocrine and metabolic adaptations to pregnancy; impact of obesity.

    PubMed

    Mouzon, Sylvie Hauguel-de; Lassance, Luciana

    2015-10-01

    Adaptations of maternal endocrine and metabolic homeostasis are central to successful pregnancy. They insure that an adequate and continuous supply of metabolic fuels is available for the growing fetus. Healthy pregnancy is classically described as a mild diabetogenic state with significant adjustments in both insulin production and sensitivity. The placenta contributes to the endocrine adaptations to pregnancy through the synthesis of various hormones which may impact insulin action. Obesity has the highest prevalence among metabolic disease in pregnancy. This article summarizes the literature addressing the endocrine and metabolic adaptations implemented during normal pregnancy. Mechanisms of regulation are further examined in the context of maternal obesity.

  10. Adaptive evolution of complex innovations through stepwise metabolic niche expansion.

    PubMed

    Szappanos, Balázs; Fritzemeier, Jonathan; Csörgő, Bálint; Lázár, Viktória; Lu, Xiaowen; Fekete, Gergely; Bálint, Balázs; Herczeg, Róbert; Nagy, István; Notebaart, Richard A; Lercher, Martin J; Pál, Csaba; Papp, Balázs

    2016-01-01

    A central challenge in evolutionary biology concerns the mechanisms by which complex metabolic innovations requiring multiple mutations arise. Here, we propose that metabolic innovations accessible through the addition of a single reaction serve as stepping stones towards the later establishment of complex metabolic features in another environment. We demonstrate the feasibility of this hypothesis through three complementary analyses. First, using genome-scale metabolic modelling, we show that complex metabolic innovations in Escherichia coli can arise via changing nutrient conditions. Second, using phylogenetic approaches, we demonstrate that the acquisition patterns of complex metabolic pathways during the evolutionary history of bacterial genomes support the hypothesis. Third, we show how adaptation of laboratory populations of E. coli to one carbon source facilitates the later adaptation to another carbon source. Our work demonstrates how complex innovations can evolve through series of adaptive steps without the need to invoke non-adaptive processes. PMID:27197754

  11. Metabolic energy required for flight

    NASA Technical Reports Server (NTRS)

    Lane, H. W.; Gretebeck, R. J.

    1994-01-01

    This paper reviews data available from U.S. and U.S.S.R. studies on energy metabolism in the microgravity of space flight. Energy utilization and energy availability in space seem to be similar to those on Earth. However, negative nitrogen balances in space in the presence of adequate energy and protein intakes and in-flight exercise, suggest that lean body mass decreases in space. Metabolic studies during simulated (bed rest) and actual microgravity have shown changes in blood glucose, fatty acids, and insulin levels, suggesting that energy metabolism may be altered during flight. Future research should focus on the interactions of lean body mass, diet, and exercise in spaced and their roles in energy metabolism during space flight.

  12. Metabolic energy required for flight

    NASA Astrophysics Data System (ADS)

    Lane, H. W.; Gretebeck, R. J.

    1994-11-01

    This paper reviews data available from U.S. and U.S.S.R. studies on energy metabolism in the microgravity of space flight. Energy utilization and energy availability in space seem to be similar to those on Earth. However, negative nitrogen balances in space in the presence of adequate energy and protein intakes and in-flight exercise, suggest that lean body mass decreases in space. Metabolic studies during simulated (bed rest) and actual microgravity have shown changes in blood glucose, fatty acids, and insulin levels, suggesting that energy metabolism may be altered during flight. Future research should focus on the interactions of lean body mass, diet, and exercise in space and their roles in energy metabolism during space flight.

  13. Respiration, respiratory metabolism and energy consumption under weightless conditions

    NASA Technical Reports Server (NTRS)

    Kasyan, I. I.; Makarov, G. F.

    1975-01-01

    Changes in the physiological indices of respiration, respiratory metabolism and energy consumption in spacecrews under weightlessness conditions manifest themselves in increased metabolic rates, higher pulmonary ventilation volume, oxygen consumption and carbon dioxide elimination, energy consumption levels in proportion to reduction in neuroemotional and psychic stress, adaptation to weightlessness and work-rest cycles, and finally in a relative stabilization of metabolic processes due to hemodynamic shifts.

  14. Warming reduces metabolic rate in marine snails: adaptation to fluctuating high temperatures challenges the metabolic theory of ecology

    PubMed Central

    Marshall, David J.; McQuaid, Christopher D.

    2011-01-01

    The universal temperature-dependence model (UTD) of the metabolic theory of ecology (MTE) proposes that temperature controls mass-scaled, whole-animal resting metabolic rate according to the first principles of physics (Boltzmann kinetics). Controversy surrounds the model's implication of a mechanistic basis for metabolism that excludes the effects of adaptive regulation, and it is unclear how this would apply to organisms that live in fringe environments and typically show considerable metabolic adaptation. We explored thermal scaling of metabolism in a rocky-shore eulittoral-fringe snail (Echinolittorina malaccana) that experiences constrained energy gain and fluctuating high temperatures (between 25°C and approximately 50°C) during prolonged emersion (weeks). In contrast to the prediction of the UTD model, metabolic rate was often negatively related to temperature over a benign range (30–40°C), the relationship depending on (i) the temperature range, (ii) the degree of metabolic depression (related to the quiescent period), and (iii) whether snails were isolated within their shells. Apparent activation energies (E) varied between 0.05 and −0.43 eV, deviating excessively from the UTD's predicted range of between 0.6 and 0.7 eV. The lowering of metabolism when heated should improve energy conservation in a high-temperature environment and challenges both the theory's generality and its mechanistic basis. PMID:20685714

  15. Perturbed Energy Metabolism and Neuronal Circuit Dysfunction in Cognitive Impairment

    PubMed Central

    Kapogiannis, Dimitrios; Mattson, Mark P.

    2010-01-01

    Summary Epidemiological, neuropathological and functional neuroimaging evidence implicates global and regional derangements in brain metabolism and energetics in the pathogenesis of cognitive impairment. Nerve cell microcircuits are modified adaptively by excitatory and inhibitory synaptic activity and neurotrophic factors. Aging and Alzheimer’s disease (AD) cause perturbations in cellular energy metabolism, level of excitation/inhibition and neurotrophic factor release that overwhelm compensatory mechanisms and result in neuronal microcircuit and brain network dysfunction. A prolonged positive energy balance impairs the ability of neurons to respond adaptively to oxidative and metabolic stress. Experimental studies in animals demonstrate how derangements related to chronic positive energy balance, such as diabetes, set the stage for accelerated cognitive aging and AD. Therapeutic interventions to allay cognitive dysfunction that target energy metabolism and adaptive stress responses (such as neurotrophin signaling) have shown efficacy in animal models and preliminary studies in humans. PMID:21147038

  16. Evolution of adaptation mechanisms: Adaptation energy, stress, and oscillating death.

    PubMed

    Gorban, Alexander N; Tyukina, Tatiana A; Smirnova, Elena V; Pokidysheva, Lyudmila I

    2016-09-21

    In 1938, Selye proposed the notion of adaptation energy and published 'Experimental evidence supporting the conception of adaptation energy.' Adaptation of an animal to different factors appears as the spending of one resource. Adaptation energy is a hypothetical extensive quantity spent for adaptation. This term causes much debate when one takes it literally, as a physical quantity, i.e. a sort of energy. The controversial points of view impede the systematic use of the notion of adaptation energy despite experimental evidence. Nevertheless, the response to many harmful factors often has general non-specific form and we suggest that the mechanisms of physiological adaptation admit a very general and nonspecific description. We aim to demonstrate that Selye׳s adaptation energy is the cornerstone of the top-down approach to modelling of non-specific adaptation processes. We analyze Selye׳s axioms of adaptation energy together with Goldstone׳s modifications and propose a series of models for interpretation of these axioms. Adaptation energy is considered as an internal coordinate on the 'dominant path' in the model of adaptation. The phenomena of 'oscillating death' and 'oscillating remission' are predicted on the base of the dynamical models of adaptation. Natural selection plays a key role in the evolution of mechanisms of physiological adaptation. We use the fitness optimization approach to study of the distribution of resources for neutralization of harmful factors, during adaptation to a multifactor environment, and analyze the optimal strategies for different systems of factors.

  17. Energy Metabolism in the Liver

    PubMed Central

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

  18. Causes of metabolic syndrome and obesity-related co-morbidities Part 1: A composite unifying theory review of human-specific co-adaptations to brain energy consumption

    PubMed Central

    2014-01-01

    One line summary Metabolic syndrome and obesity-related co-morbidities are largely explained by co-adaptations to the energy use of the large human brain in the cortico-limbic-striatal and NRF2 systems. The medical, research and general community is unable to effect significantly decreased rates of central obesity and related type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer. All conditions seem to be linked by the concept of the metabolic syndrome (MetS), but the underlying causes are not known. MetS markers may have been mistaken for causes, thus many treatments are destined to be suboptimal. The current paper aims to critique current paradigms, give explanations for their persistence, and to return to first principles in an attempt to determine and clarify likely causes of MetS and obesity related comorbidities. A wide literature has been mined, study concepts analysed and the basics of human evolution and new biochemistry reviewed. A plausible, multifaceted composite unifying theory is formulated. The basis of the theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A ‘dual system’ is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals, becoming highly energy efficient in humans. The still-evolving, complex human cortico-limbic-striatal system generates strong behavioural drives for energy dense food procurement, including motivating agricultural technologies and social system development. Addiction to such foods, leading to neglect of nutritious but less appetizing ‘common or garden’ food, appears to have occurred

  19. Natural diversity and adaptation in plant secondary metabolism.

    PubMed

    Kroymann, Juergen

    2011-06-01

    Technological advances in metabolomics, transcriptomics and genomics have facilitated the detection of genes that contribute to diversification in plant secondary metabolism. Statistical tools from molecular population genetics may help in evaluating whether the corresponding genes or genomic regions carry a signature of selection and answering the question of whether novel compounds are 'adaptive'. Gene duplication fuels diversification in plant secondary metabolism and the evolutionary mechanism for adaptation may follow a path of neofunctionalization subsequent to gene duplication, or gene duplication may occur subsequent to--and resolve--an adaptive conflict present in a single ancestral gene sequence.

  20. Hypoxia and metabolic adaptation of cancer cells

    PubMed Central

    Eales, K L; Hollinshead, K E R; Tennant, D A

    2016-01-01

    Low oxygen tension (hypoxia) is a pervasive physiological and pathophysiological stimulus that metazoan organisms have contended with since they evolved from their single-celled ancestors. The effect of hypoxia on a tissue can be either positive or negative, depending on the severity, duration and context. Over the long-term, hypoxia is not usually consistent with normal function and so multicellular organisms have had to evolve both systemic and cellular responses to hypoxia. Our reliance on oxygen for efficient adenosine triphosphate (ATP) generation has meant that the cellular metabolic network is particularly sensitive to alterations in oxygen tension. Metabolic changes in response to hypoxia are elicited through both direct mechanisms, such as the reduction in ATP generation by oxidative phosphorylation or inhibition of fatty-acid desaturation, and indirect mechanisms including changes in isozyme expression through hypoxia-responsive transcription factor activity. Significant regions of cancers often grow in hypoxic conditions owing to the lack of a functional vasculature. As hypoxic tumour areas contain some of the most malignant cells, it is important that we understand the role metabolism has in keeping these cells alive. This review will outline our current understanding of many of the hypoxia-induced changes in cancer cell metabolism, how they are affected by other genetic defects often present in cancers, and how these metabolic alterations support the malignant hypoxic phenotype. PMID:26807645

  1. Cold adaptation mechanisms in the ghost moth Hepialus xiaojinensis: Metabolic regulation and thermal compensation.

    PubMed

    Zhu, Wei; Zhang, Huan; Li, Xuan; Meng, Qian; Shu, Ruihao; Wang, Menglong; Zhou, Guiling; Wang, Hongtuo; Miao, Lin; Zhang, Jihong; Qin, Qilian

    2016-02-01

    Ghost moths (Lepidoptera: Hepialidae) are cold-adapted stenothermal species inhabiting alpine meadows on the Tibetan Plateau. They have an optimal developmental temperature of 12-16 °C but can maintain feeding and growth at 0 °C. Their survival strategies have received little attention, but these insects are a promising model for environmental adaptation. Here, biochemical adaptations and energy metabolism in response to cold were investigated in larvae of the ghost moth Hepialus xiaojinensis. Metabolic rate and respiratory quotient decreased dramatically with decreasing temperature (15-4 °C), suggesting that the energy metabolism of ghost moths, especially glycometabolism, was sensitive to cold. However, the metabolic rate at 4 °C increased with the duration of cold exposure, indicating thermal compensation to sustain energy budgets under cold conditions. Underlying regulation strategies were studied by analyzing metabolic differences between cold-acclimated (4 °C for 48 h) and control larvae (15 °C). In cold-acclimated larvae, the energy generating pathways of carbohydrates, instead of the overall consumption of carbohydrates, was compensated in the fat body by improving the transcription of related enzymes. The mobilization of lipids was also promoted, with higher diacylglycerol, monoacylglycerol and free fatty acid content in hemolymph. These results indicated that cold acclimation induced a reorganization on metabolic structure to prioritise energy metabolism. Within the aerobic process, flux throughout the tricarboxylic acid (TCA) cycle was encouraged in the fat body, and the activity of α-ketoglutarate dehydrogenase was the likely compensation target. Increased mitochondrial cristae density was observed in the midgut of cold-acclimated larvae. The thermal compensation strategies in this ghost moth span the entire process of energy metabolism, including degration of metabolic substrate, TCA cycle and oxidative phosphorylation, and from an energy budget

  2. Carbon metabolism and the sign of control coefficients in metabolic adaptations underlying K-ras transformation.

    PubMed

    de Atauri, Pedro; Benito, Adrian; Vizán, Pedro; Zanuy, Miriam; Mangues, Ramón; Marín, Silvia; Cascante, Marta

    2011-06-01

    Metabolic adaptations are associated with changes in enzyme activities. These adaptations are characterized by patterns of positive and negative changes in metabolic fluxes and concentrations of intermediate metabolites. Knowledge of the mechanism and parameters governing enzyme kinetics is rarely available. However, the signs-increases or decreases-of many of these changes can be predicted using the signs of metabolic control coefficients. These signs require the only knowledge of the structure of the metabolic network and a limited qualitative knowledge of the regulatory dependences, which is widely available for carbon metabolism. Here, as a case study, we identified control coefficients with fixed signs in order to predict the pattern of changes in key enzyme activities which can explain the observed changes in fluxes and concentrations underlying the metabolic adaptations in oncogenic K-ras transformation in NIH-3T3 cells. The fixed signs of control coefficients indicate that metabolic changes following the oncogenic transformation-increased glycolysis and oxidative branch of the pentose-phosphate pathway, and decreased concentration in sugar-phosphates-could be associated with increases in activity for glucose-6-phosphate dehydrogenase, pyruvate kinase and lactate dehydrogenase, and decrease for transketolase. These predictions were validated experimentally by measuring specific activities. We conclude that predictions based on fixed signs of control coefficients are a very robust tool for the identification of changes in enzyme activities that can explain observed metabolic adaptations in carbon metabolism.

  3. Metabolic profiling reveals ethylene mediated metabolic changes and a coordinated adaptive mechanism of 'Jonagold' apple to low oxygen stress.

    PubMed

    Bekele, Elias A; Beshir, Wasiye F; Hertog, Maarten L A T M; Nicolai, Bart M; Geeraerd, Annemie H

    2015-11-01

    Apples are predominantly stored in controlled atmosphere (CA) storage to delay ripening and prolong their storage life. Profiling the dynamics of metabolic changes during ripening and CA storage is vital for understanding the governing molecular mechanism. In this study, the dynamics of the primary metabolism of 'Jonagold' apples during ripening in regular air (RA) storage and initiation of CA storage was profiled. 1-Methylcyclopropene (1-MCP) was exploited to block ethylene receptors and to get insight into ethylene mediated metabolic changes during ripening of the fruit and in response to hypoxic stress. Metabolic changes were quantified in glycolysis, the tricarboxylic acid (TCA) cycle, the Yang cycle and synthesis of the main amino acids branching from these metabolic pathways. Partial least square discriminant analysis of the metabolic profiles of 1-MCP treated and control apples revealed a metabolic divergence in ethylene, organic acid, sugar and amino acid metabolism. During RA storage at 18°C, most amino acids were higher in 1-MCP treated apples, whereas 1-aminocyclopropane-1-carboxylic acid (ACC) was higher in the control apples. The initial response of the fruit to CA initiation was accompanied by an increase of alanine, succinate and glutamate, but a decline in aspartate. Furthermore, alanine and succinate accumulated to higher levels in control apples than 1-MCP treated apples. The observed metabolic changes in these interlinked metabolites may indicate a coordinated adaptive strategy to maximize energy production. PMID:26031836

  4. Metabolic profiling reveals ethylene mediated metabolic changes and a coordinated adaptive mechanism of 'Jonagold' apple to low oxygen stress.

    PubMed

    Bekele, Elias A; Beshir, Wasiye F; Hertog, Maarten L A T M; Nicolai, Bart M; Geeraerd, Annemie H

    2015-11-01

    Apples are predominantly stored in controlled atmosphere (CA) storage to delay ripening and prolong their storage life. Profiling the dynamics of metabolic changes during ripening and CA storage is vital for understanding the governing molecular mechanism. In this study, the dynamics of the primary metabolism of 'Jonagold' apples during ripening in regular air (RA) storage and initiation of CA storage was profiled. 1-Methylcyclopropene (1-MCP) was exploited to block ethylene receptors and to get insight into ethylene mediated metabolic changes during ripening of the fruit and in response to hypoxic stress. Metabolic changes were quantified in glycolysis, the tricarboxylic acid (TCA) cycle, the Yang cycle and synthesis of the main amino acids branching from these metabolic pathways. Partial least square discriminant analysis of the metabolic profiles of 1-MCP treated and control apples revealed a metabolic divergence in ethylene, organic acid, sugar and amino acid metabolism. During RA storage at 18°C, most amino acids were higher in 1-MCP treated apples, whereas 1-aminocyclopropane-1-carboxylic acid (ACC) was higher in the control apples. The initial response of the fruit to CA initiation was accompanied by an increase of alanine, succinate and glutamate, but a decline in aspartate. Furthermore, alanine and succinate accumulated to higher levels in control apples than 1-MCP treated apples. The observed metabolic changes in these interlinked metabolites may indicate a coordinated adaptive strategy to maximize energy production.

  5. Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption.

    PubMed

    McGill, Anne-Thea

    2014-01-01

    Metabolic syndrome (MetS) predicts type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer, and their rates have escalated over the last few decades. Obesity related co-morbidities also overlap the concept of the metabolic syndrome (MetS). However, understanding of the syndrome's underlying causes may have been misapprehended. The current paper follows on from a theory review by McGill, A-T in Archives of Public Health, 72: 30. This accompanying paper utilises research on human evolution and new biochemistry to theorise on why MetS and obesity arise and how they affect the population. The basis of this composite unifying theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A 'dual system' is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals. In humans who consume a nutritious diet, the NRF2 system has become highly energy efficient. Other relevant human-specific co-adaptations are explored. In order to 'test' this composite unifying theory it is important to show that the hypothesis and sub-theories pertain throughout the whole of human evolution and history up till the current era. Corollaries of the composite unifying theory of MetS are examined with respect to past under-nutrition and malnutrition since agriculture began 10,000 years ago. The effects of man-made pollutants on degenerative change are examined. Projections are then made from current to future patterns on the state of 'insufficient micronutrient and/or unbalanced high energy malnutrition with central obesity and metabolic dysregulation' or 'malnubesity'. Forecasts

  6. Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption.

    PubMed

    McGill, Anne-Thea

    2014-01-01

    Metabolic syndrome (MetS) predicts type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer, and their rates have escalated over the last few decades. Obesity related co-morbidities also overlap the concept of the metabolic syndrome (MetS). However, understanding of the syndrome's underlying causes may have been misapprehended. The current paper follows on from a theory review by McGill, A-T in Archives of Public Health, 72: 30. This accompanying paper utilises research on human evolution and new biochemistry to theorise on why MetS and obesity arise and how they affect the population. The basis of this composite unifying theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A 'dual system' is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals. In humans who consume a nutritious diet, the NRF2 system has become highly energy efficient. Other relevant human-specific co-adaptations are explored. In order to 'test' this composite unifying theory it is important to show that the hypothesis and sub-theories pertain throughout the whole of human evolution and history up till the current era. Corollaries of the composite unifying theory of MetS are examined with respect to past under-nutrition and malnutrition since agriculture began 10,000 years ago. The effects of man-made pollutants on degenerative change are examined. Projections are then made from current to future patterns on the state of 'insufficient micronutrient and/or unbalanced high energy malnutrition with central obesity and metabolic dysregulation' or 'malnubesity'. Forecasts

  7. Energetic Metabolism and Biochemical Adaptation: A Bird Flight Muscle Model

    ERIC Educational Resources Information Center

    Rioux, Pierre; Blier, Pierre U.

    2006-01-01

    The main objective of this class experiment is to measure the activity of two metabolic enzymes in crude extract from bird pectoral muscle and to relate the differences to their mode of locomotion and ecology. The laboratory is adapted to stimulate the interest of wildlife management students to biochemistry. The enzymatic activities of cytochrome…

  8. Causes of metabolic syndrome and obesity-related co-morbidities Part 1: A composite unifying theory review of human-specific co-adaptations to brain energy consumption.

    PubMed

    McGill, Anne-Thea

    2014-01-01

    The medical, research and general community is unable to effect significantly decreased rates of central obesity and related type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer. All conditions seem to be linked by the concept of the metabolic syndrome (MetS), but the underlying causes are not known. MetS markers may have been mistaken for causes, thus many treatments are destined to be suboptimal. The current paper aims to critique current paradigms, give explanations for their persistence, and to return to first principles in an attempt to determine and clarify likely causes of MetS and obesity related comorbidities. A wide literature has been mined, study concepts analysed and the basics of human evolution and new biochemistry reviewed. A plausible, multifaceted composite unifying theory is formulated. The basis of the theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A 'dual system' is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals, becoming highly energy efficient in humans. The still-evolving, complex human cortico-limbic-striatal system generates strong behavioural drives for energy dense food procurement, including motivating agricultural technologies and social system development. Addiction to such foods, leading to neglect of nutritious but less appetizing 'common or garden' food, appears to have occurred. Insufficient consumption of food micronutrients prevents optimal human NRF2 function. Inefficient oxidation of excess energy forces central and non-adipose cells to store excess toxic lipid. Oxidative stress and

  9. Causes of metabolic syndrome and obesity-related co-morbidities Part 1: A composite unifying theory review of human-specific co-adaptations to brain energy consumption.

    PubMed

    McGill, Anne-Thea

    2014-01-01

    The medical, research and general community is unable to effect significantly decreased rates of central obesity and related type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer. All conditions seem to be linked by the concept of the metabolic syndrome (MetS), but the underlying causes are not known. MetS markers may have been mistaken for causes, thus many treatments are destined to be suboptimal. The current paper aims to critique current paradigms, give explanations for their persistence, and to return to first principles in an attempt to determine and clarify likely causes of MetS and obesity related comorbidities. A wide literature has been mined, study concepts analysed and the basics of human evolution and new biochemistry reviewed. A plausible, multifaceted composite unifying theory is formulated. The basis of the theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A 'dual system' is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals, becoming highly energy efficient in humans. The still-evolving, complex human cortico-limbic-striatal system generates strong behavioural drives for energy dense food procurement, including motivating agricultural technologies and social system development. Addiction to such foods, leading to neglect of nutritious but less appetizing 'common or garden' food, appears to have occurred. Insufficient consumption of food micronutrients prevents optimal human NRF2 function. Inefficient oxidation of excess energy forces central and non-adipose cells to store excess toxic lipid. Oxidative stress and

  10. Computational Approaches for Understanding Energy Metabolism

    PubMed Central

    Shestov, Alexander A; Barker, Brandon; Gu, Zhenglong; Locasale, Jason W

    2013-01-01

    There has been a surge of interest in understanding the regulation of metabolic networks involved in disease in recent years. Quantitative models are increasingly being used to i nterrogate the metabolic pathways that are contained within this complex disease biology. At the core of this effort is the mathematical modeling of central carbon metabolism involving glycolysis and the citric acid cycle (referred to as energy metabolism). Here we discuss several approaches used to quantitatively model metabolic pathways relating to energy metabolism and discuss their formalisms, successes, and limitations. PMID:23897661

  11. Cold adaptation shapes the robustness of metabolic networks in Drosophila melanogaster.

    PubMed

    Williams, Caroline M; Watanabe, Miki; Guarracino, Mario R; Ferraro, Maria B; Edison, Arthur S; Morgan, Theodore J; Boroujerdi, Arezue F B; Hahn, Daniel A

    2014-12-01

    When ectotherms are exposed to low temperatures, they enter a cold-induced coma (chill coma) that prevents resource acquisition, mating, oviposition, and escape from predation. There is substantial variation in time taken to recover from chill coma both within and among species, and this variation is correlated with habitat temperatures such that insects from cold environments recover more quickly. This suggests an adaptive response, but the mechanisms underlying variation in recovery times are unknown, making it difficult to decisively test adaptive hypotheses. We use replicated lines of Drosophila melanogaster selected in the laboratory for fast (hardy) or slow (susceptible) chill-coma recovery times to investigate modifications to metabolic profiles associated with cold adaptation. We measured metabolite concentrations of flies before, during, and after cold exposure using nuclear magnetic resonance (NMR) spectroscopy to test the hypotheses that hardy flies maintain metabolic homeostasis better during cold exposure and recovery, and that their metabolic networks are more robust to cold-induced perturbations. The metabolites of cold-hardy flies were less cold responsive and their metabolic networks during cold exposure were more robust, supporting our hypotheses. Metabolites involved in membrane lipid synthesis, tryptophan metabolism, oxidative stress, energy balance, and proline metabolism were altered by selection on cold tolerance. We discuss the potential significance of these alterations.

  12. Cold adaptation shapes the robustness of metabolic networks in Drosophila melanogaster

    PubMed Central

    Williams, CM; Watanabe, M; Guarracino, MR; Ferraro, MB; Edison, AS; Morgan, TJ; Boroujerdi, AFB; Hahn, DA

    2015-01-01

    When ectotherms are exposed to low temperatures, they enter a cold-induced coma (chill coma) that prevents resource acquisition, mating, oviposition, and escape from predation. There is substantial variation in time taken to recover from chill coma both within and among species, and this variation is correlated with habitat temperatures such that insects from cold environments recover more quickly. This suggests an adaptive response, but the mechanisms underlying variation in recovery times are unknown, making it difficult to decisively test adaptive hypotheses. We use replicated lines of Drosophila melanogaster selected in the laboratory for fast (hardy) or slow (susceptible) chill-coma recovery times to investigate modifications to metabolic profiles associated with cold adaptation. We measured metabolite concentrations of flies before, during, and after cold exposure using NMR spectroscopy to test the hypotheses that hardy flies maintain metabolic homeostasis better during cold exposure and recovery, and that their metabolic networks are more robust to cold-induced perturbations. The metabolites of cold-hardy flies were less cold responsive and their metabolic networks during cold exposure were more robust, supporting our hypotheses. Metabolites involved in membrane lipid synthesis, tryptophan metabolism, oxidative stress, energy balance, and proline metabolism were altered by selection on cold tolerance. We discuss the potential significance of these alterations. PMID:25308124

  13. Long–Term Effects of High-and Low-Glycemic Load Energy-Restricted Diets on Metabolic Adaptation and the Composition of Weight Loss

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of high glycemic load (HG) and low glycemic load (LG) diets on resting metabolic rate (RMR) and body composition changes in response to caloric restriction (CR) remains controversial. Objective To examine the effects of two CR diets differing primarily in glycemic load on RMR and the % o...

  14. Energy flows, metabolism and translation.

    PubMed

    Pascal, Robert; Boiteau, Laurent

    2011-10-27

    Thermodynamics provides an essential approach to understanding how living organisms survive in an organized state despite the second law. Exchanges with the environment constantly produce large amounts of entropy compensating for their own organized state. In addition to this constraint on self-organization, the free energy delivered to the system, in terms of potential, is essential to understand how a complex chemistry based on carbon has emerged. Accordingly, the amount of free energy brought about through discrete events must reach the strength needed to induce chemical changes in which covalent bonds are reorganized. The consequence of this constraint was scrutinized in relation to both the development of a carbon metabolism and that of translation. Amino acyl adenylates involved as aminoacylation intermediates of the latter process reach one of the higher free energy levels found in biochemistry, which may be informative on the range in which energy was exchanged in essential early biochemical processes. The consistency of this range with the amount of energy needed to weaken covalent bonds involving carbon may not be accidental but the consequence of the above mentioned thermodynamic constraints. This could be useful in building scenarios for the emergence and early development of translation.

  15. Energy flows, metabolism and translation

    PubMed Central

    Pascal, Robert; Boiteau, Laurent

    2011-01-01

    Thermodynamics provides an essential approach to understanding how living organisms survive in an organized state despite the second law. Exchanges with the environment constantly produce large amounts of entropy compensating for their own organized state. In addition to this constraint on self-organization, the free energy delivered to the system, in terms of potential, is essential to understand how a complex chemistry based on carbon has emerged. Accordingly, the amount of free energy brought about through discrete events must reach the strength needed to induce chemical changes in which covalent bonds are reorganized. The consequence of this constraint was scrutinized in relation to both the development of a carbon metabolism and that of translation. Amino acyl adenylates involved as aminoacylation intermediates of the latter process reach one of the higher free energy levels found in biochemistry, which may be informative on the range in which energy was exchanged in essential early biochemical processes. The consistency of this range with the amount of energy needed to weaken covalent bonds involving carbon may not be accidental but the consequence of the abovementioned thermodynamic constraints. This could be useful in building scenarios for the emergence and early development of translation. PMID:21930587

  16. Evolutionary constraint and adaptation in the metabolic network of Drosophila.

    PubMed

    Greenberg, Anthony J; Stockwell, Sarah R; Clark, Andrew G

    2008-12-01

    Organisms must carefully control their metabolism in order to survive. On the other hand, enzymes must adapt in response to evolutionary pressures on the pathways in which they are imbedded. Taking advantage of the newly available whole-genome sequences of 12 Drosophila species, we examined how protein function and metabolic network architecture influence rates of enzyme evolution. We found that despite high overall constraint, there were significant differences in rates of amino acid substitution among functional classes of enzymes. This heterogeneity arises because proteins involved in the metabolism of foreign compounds evolve relatively rapidly, whereas enzymes that act in "core" metabolism exhibit much slower rates of amino acid replacement, suggesting strong selective constraint. Network architecture also influences enzymes' rates of amino acid replacement. In particular, enzymes that share metabolites with many other enzymes are relatively constrained, although apparently not because they are more likely to be essential. Our analyses suggest that this pattern is driven by strong constraint of enzymes acting at branch points in metabolic pathways. We conclude that metabolic network architecture and enzyme function separately affect enzyme evolution rates.

  17. Patient-adaptive lesion metabolism analysis by dynamic PET images.

    PubMed

    Gao, Fei; Liu, Huafeng; Shi, Pengcheng

    2012-01-01

    Dynamic PET imaging provides important spatial-temporal information for metabolism analysis of organs and tissues, and generates a great reference for clinical diagnosis and pharmacokinetic analysis. Due to poor statistical properties of the measurement data in low count dynamic PET acquisition and disturbances from surrounding tissues, identifying small lesions inside the human body is still a challenging issue. The uncertainties in estimating the arterial input function will also limit the accuracy and reliability of the metabolism analysis of lesions. Furthermore, the sizes of the patients and the motions during PET acquisition will yield mismatch against general purpose reconstruction system matrix, this will also affect the quantitative accuracy of metabolism analyses of lesions. In this paper, we present a dynamic PET metabolism analysis framework by defining a patient adaptive system matrix to improve the lesion metabolism analysis. Both patient size information and potential small lesions are incorporated by simulations of phantoms of different sizes and individual point source responses. The new framework improves the quantitative accuracy of lesion metabolism analysis, and makes the lesion identification more precisely. The requirement of accurate input functions is also reduced. Experiments are conducted on Monte Carlo simulated data set for quantitative analysis and validation, and on real patient scans for assessment of clinical potential. PMID:23286175

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

    PubMed

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

    2015-05-01

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

  19. MFN1 deacetylation activates adaptive mitochondrial fusion and protects metabolically challenged mitochondria.

    PubMed

    Lee, Joo-Yong; Kapur, Meghan; Li, Ming; Choi, Moon-Chang; Choi, Sujin; Kim, Hak-June; Kim, Inhye; Lee, Eunji; Taylor, J Paul; Yao, Tso-Pang

    2014-11-15

    Fasting and glucose shortage activate a metabolic switch that shifts more energy production to mitochondria. This metabolic adaptation ensures energy supply, but also elevates the risk of mitochondrial oxidative damage. Here, we present evidence that metabolically challenged mitochondria undergo active fusion to suppress oxidative stress. In response to glucose starvation, mitofusin 1 (MFN1) becomes associated with the protein deacetylase HDAC6. This interaction leads to MFN1 deacetylation and activation, promoting mitochondrial fusion. Deficiency in HDAC6 or MFN1 prevents mitochondrial fusion induced by glucose deprivation. Unexpectedly, failure to undergo fusion does not acutely affect mitochondrial adaptive energy production; instead, it causes excessive production of mitochondrial reactive oxygen species and oxidative damage, a defect suppressed by an acetylation-resistant MFN1 mutant. In mice subjected to fasting, skeletal muscle mitochondria undergo dramatic fusion. Remarkably, fasting-induced mitochondrial fusion is abrogated in HDAC6-knockout mice, resulting in extensive mitochondrial degeneration. These findings show that adaptive mitochondrial fusion protects metabolically challenged mitochondria.

  20. Adaptive reciprocity of lipid and glucose metabolism in human short-term starvation.

    PubMed

    Soeters, Maarten R; Soeters, Peter B; Schooneman, Marieke G; Houten, Sander M; Romijn, Johannes A

    2012-12-15

    The human organism has tools to cope with metabolic challenges like starvation that are crucial for survival. Lipolysis, lipid oxidation, ketone body synthesis, tailored endogenous glucose production and uptake, and decreased glucose oxidation serve to protect against excessive erosion of protein mass, which is the predominant supplier of carbon chains for synthesis of newly formed glucose. The starvation response shows that the adaptation to energy deficit is very effective and coordinated with different adaptations in different organs. From an evolutionary perspective, this lipid-induced effect on glucose oxidation and uptake is very strong and may therefore help to understand why insulin resistance in obesity and type 2 diabetes mellitus is difficult to treat. The importance of reciprocity in lipid and glucose metabolism during human starvation should be taken into account when studying lipid and glucose metabolism in general and in pathophysiological conditions in particular.

  1. Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption

    PubMed Central

    2014-01-01

    Forward A composite unifying theory on causes of obesity related-MetS has been formulated and published in an accompanying article (1). In the current article, the historical and recent past, present and future corollaries of this theory are discussed. By presenting this composite theory and corollaries, it is hoped that human evolution and physiology will be viewed and studied from a new vantage point. The politics of management of ecological farming and nutrition will change, a profound reconfiguration of scientific theory generation and advancement in a ‘high-tech’ world can be made, and pathways for solutions recognised. Metabolic syndrome (MetS) predicts type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer, and their rates have escalated over the last few decades. Obesity related co-morbidities also overlap the concept of the metabolic syndrome (MetS). However, understanding of the syndrome’s underlying causes may have been misapprehended. The current paper follows on from a theory review by McGill, A-T in Archives of Public Health, 72: 30. This accompanying paper utilises research on human evolution and new biochemistry to theorise on why MetS and obesity arise and how they affect the population. The basis of this composite unifying theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A ‘dual system’ is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals. In humans who consume a nutritious diet, the NRF2 system has become highly energy efficient. Other relevant human-specific co-adaptations are explored. In order to

  2. Metabolism as a tool for understanding human brain evolution: lipid energy metabolism as an example.

    PubMed

    Wang, Shu Pei; Yang, Hao; Wu, Jiang Wei; Gauthier, Nicolas; Fukao, Toshiyuki; Mitchell, Grant A

    2014-12-01

    Genes and the environment both influence the metabolic processes that determine fitness. To illustrate the importance of metabolism for human brain evolution and health, we use the example of lipid energy metabolism, i.e. the use of fat (lipid) to produce energy and the advantages that this metabolic pathway provides for the brain during environmental energy shortage. We briefly describe some features of metabolism in ancestral organisms, which provided a molecular toolkit for later development. In modern humans, lipid energy metabolism is a regulated multi-organ pathway that links triglycerides in fat tissue to the mitochondria of many tissues including the brain. Three important control points are each suppressed by insulin. (1) Lipid reserves in adipose tissue are released by lipolysis during fasting and stress, producing fatty acids (FAs) which circulate in the blood and are taken up by cells. (2) FA oxidation. Mitochondrial entry is controlled by carnitine palmitoyl transferase 1 (CPT1). Inside the mitochondria, FAs undergo beta oxidation and energy production in the Krebs cycle and respiratory chain. (3) In liver mitochondria, the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) pathway produces ketone bodies for the brain and other organs. Unlike most tissues, the brain does not capture and metabolize circulating FAs for energy production. However, the brain can use ketone bodies for energy. We discuss two examples of genetic metabolic traits that may be advantageous under most conditions but deleterious in others. (1) A CPT1A variant prevalent in Inuit people may allow increased FA oxidation under nonfasting conditions but also predispose to hypoglycemic episodes. (2) The thrifty genotype theory, which holds that energy expenditure is efficient so as to maximize energy stores, predicts that these adaptations may enhance survival in periods of famine but predispose to obesity in modern dietary environments.

  3. Metabolic adaptations to over--and underfeeding--still a matter of debate?

    PubMed

    Westerterp, K R

    2013-05-01

    Weight changes in response to a change in energy intake are smaller than calculated from the excess or deficit of energy intake. Digestion efficiency is not affected by intake level when consuming the same diet. Over- or underfeeding induces an increase or decrease in energy expenditure. Intake-induced expenditure changes are largely explained by proportional changes in diet-induced energy expenditure, in activity-induced energy expenditure and in maintenance expenditure as a function of changes in body weight and body composition. Additionally, underfeeding causes a metabolic adaptation as reflected in a reduction of maintenance expenditure below predicted values and defined as adaptive thermogenesis. Thus, alternating overfeeding and underfeeding with an iso-energetic amount results in a positive energy balance. The latter might be one of the explanations for the increasing incidence of obesity in our current society with an ample food supply.

  4. Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect.

    PubMed

    Shlomi, Tomer; Benyamini, Tomer; Gottlieb, Eyal; Sharan, Roded; Ruppin, Eytan

    2011-03-01

    The Warburg effect--a classical hallmark of cancer metabolism--is a counter-intuitive phenomenon in which rapidly proliferating cancer cells resort to inefficient ATP production via glycolysis leading to lactate secretion, instead of relying primarily on more efficient energy production through mitochondrial oxidative phosphorylation, as most normal cells do. The causes for the Warburg effect have remained a subject of considerable controversy since its discovery over 80 years ago, with several competing hypotheses. Here, utilizing a genome-scale human metabolic network model accounting for stoichiometric and enzyme solvent capacity considerations, we show that the Warburg effect is a direct consequence of the metabolic adaptation of cancer cells to increase biomass production rate. The analysis is shown to accurately capture a three phase metabolic behavior that is observed experimentally during oncogenic progression, as well as a prominent characteristic of cancer cells involving their preference for glutamine uptake over other amino acids. PMID:21423717

  5. Adaptations to pressure in the RBC metabolism of diving mammals.

    PubMed

    Castellini, M A; Castellini, J M; Rivera, P M

    2001-07-01

    Marine mammals are known to dive up to 2000 m and, therefore, tolerate as much as 200 atm. of hydrostatic pressure. To examine possible metabolic adaptations to these elevated pressures, fresh blood samples from marine and terrestrial mammals were incubated for 2 h at 37 degrees C under 136 atm (2000 psi) of hydrostatic pressure. The consumption of plasma glucose and the production of lactate over the 2-h period were used to assess glycolytic flux in the red cells. The results indicate that glycolytic flux as measured by lactate production under pressure can be significantly depressed in most terrestrial mammals and either not altered or accelerated in marine mammals. The data also suggest that there is a significant shift in the ratio of lactate produced to glucose consumed under pressure. Interestingly, human and dolphin blood do not react to pressure. These combined data imply a metabolic adaptation to pressure in marine mammal RBC that may not be necessary in human or dolphin cells due to their unique patterns of glucose metabolism.

  6. Dissecting Leishmania infantum Energy Metabolism - A Systems Perspective.

    PubMed

    Subramanian, Abhishek; Jhawar, Jitesh; Sarkar, Ram Rup

    2015-01-01

    Leishmania infantum, causative agent of visceral leishmaniasis in humans, illustrates a complex lifecycle pertaining to two extreme environments, namely, the gut of the sandfly vector and human macrophages. Leishmania is capable of dynamically adapting and tactically switching between these critically hostile situations. The possible metabolic routes ventured by the parasite to achieve this exceptional adaptation to its varying environments are still poorly understood. In this study, we present an extensively reconstructed energy metabolism network of Leishmania infantum as an attempt to identify certain strategic metabolic routes preferred by the parasite to optimize its survival in such dynamic environments. The reconstructed network consists of 142 genes encoding for enzymes performing 237 reactions distributed across five distinct model compartments. We annotated the subcellular locations of different enzymes and their reactions on the basis of strong literature evidence and sequence-based detection of cellular localization signal within a protein sequence. To explore the diverse features of parasite metabolism the metabolic network was implemented and analyzed as a constraint-based model. Using a systems-based approach, we also put forth an extensive set of lethal reaction knockouts; some of which were validated using published data on Leishmania species. Performing a robustness analysis, the model was rigorously validated and tested for the secretion of overflow metabolites specific to Leishmania under varying extracellular oxygen uptake rate. Further, the fate of important non-essential amino acids in L. infantum metabolism was investigated. Stage-specific scenarios of L. infantum energy metabolism were incorporated in the model and key metabolic differences were outlined. Analysis of the model revealed the essentiality of glucose uptake, succinate fermentation, glutamate biosynthesis and an active TCA cycle as driving forces for parasite energy metabolism

  7. Metabolic Disorders in the Transition Period Indicate that the Dairy Cows' Ability to Adapt is Overstressed.

    PubMed

    Sundrum, Albert

    2015-01-01

    Metabolic disorders are a key problem in the transition period of dairy cows and often appear before the onset of further health problems. They mainly derive from difficulties the animals have in adapting to changes and disturbances occurring both outside and inside the organisms and due to varying gaps between nutrient supply and demand. Adaptation is a functional and target-oriented process involving the whole organism and thus cannot be narrowed down to single factors. Most problems which challenge the organisms can be solved in a number of different ways. To understand the mechanisms of adaptation, the interconnectedness of variables and the nutrient flow within a metabolic network need to be considered. Metabolic disorders indicate an overstressed ability to balance input, partitioning and output variables. Dairy cows will more easily succeed in adapting and in avoiding dysfunctional processes in the transition period when the gap between nutrient and energy demands and their supply is restricted. Dairy farms vary widely in relation to the living conditions of the animals. The complexity of nutritional and metabolic processes Animals 2015, 5 979 and their large variations on various scales contradict any attempts to predict the outcome of animals' adaptation in a farm specific situation. Any attempts to reduce the prevalence of metabolic disorders and associated production diseases should rely on continuous and comprehensive monitoring with appropriate indicators on the farm level. Furthermore, low levels of disorders and diseases should be seen as a further significant goal which carries weight in addition to productivity goals. In the long run, low disease levels can only be expected when farmers realize that they can gain a competitive advantage over competitors with higher levels of disease. PMID:26479480

  8. Interplay between oxidant species and energy metabolism

    PubMed Central

    Quijano, Celia; Trujillo, Madia; Castro, Laura; Trostchansky, Andrés

    2015-01-01

    It has long been recognized that energy metabolism is linked to the production of reactive oxygen species (ROS) and critical enzymes allied to metabolic pathways can be affected by redox reactions. This interplay between energy metabolism and ROS becomes most apparent during the aging process and in the onset and progression of many age-related diseases (i.e. diabetes, metabolic syndrome, atherosclerosis, neurodegenerative diseases). As such, the capacity to identify metabolic pathways involved in ROS formation, as well as specific targets and oxidative modifications is crucial to our understanding of the molecular basis of age-related diseases and for the design of novel therapeutic strategies. Herein we review oxidant formation associated with the cell's energetic metabolism, key antioxidants involved in ROS detoxification, and the principal targets of oxidant species in metabolic routes and discuss their relevance in cell signaling and age-related diseases. PMID:26741399

  9. Metabolic Disorders in the Transition Period Indicate that the Dairy Cows’ Ability to Adapt is Overstressed

    PubMed Central

    Sundrum, Albert

    2015-01-01

    Simple Summary Metabolic disorders are a key problem in the transition period of dairy cows and often appear before the onset of further health problems. Problems derive from difficulties animals have to adapt to large variations and disturbances occurring both outside and inside the organism. A lack of success in solving these issues may be due to predominant approaches in farm management and agricultural science, dealing with such disorders as merely negative side effects. Instead, a successful adaptation of animals to their living conditions should be seen as an important end in itself. Both farm management and agricultural sciences should support animals in their ability to cope with nutritional and metabolic challenges by employing a functional and result-driven approach. Abstract Metabolic disorders are a key problem in the transition period of dairy cows and often appear before the onset of further health problems. They mainly derive from difficulties the animals have in adapting to changes and disturbances occurring both outside and inside the organisms and due to varying gaps between nutrient supply and demand. Adaptation is a functional and target-oriented process involving the whole organism and thus cannot be narrowed down to single factors. Most problems which challenge the organisms can be solved in a number of different ways. To understand the mechanisms of adaptation, the interconnectedness of variables and the nutrient flow within a metabolic network need to be considered. Metabolic disorders indicate an overstressed ability to balance input, partitioning and output variables. Dairy cows will more easily succeed in adapting and in avoiding dysfunctional processes in the transition period when the gap between nutrient and energy demands and their supply is restricted. Dairy farms vary widely in relation to the living conditions of the animals. The complexity of nutritional and metabolic processes and their large variations on various scales

  10. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders.

    PubMed

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  11. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders

    PubMed Central

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response. PMID:27148161

  12. Multivariate adaptive regression splines models for the prediction of energy expenditure in children and adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Advanced mathematical models have the potential to capture the complex metabolic and physiological processes that result in heat production, or energy expenditure (EE). Multivariate adaptive regression splines (MARS), is a nonparametric method that estimates complex nonlinear relationships by a seri...

  13. Apicomplexan Energy Metabolism: Carbon Source Promiscuity and the Quiescence Hyperbole.

    PubMed

    Jacot, Damien; Waller, Ross F; Soldati-Favre, Dominique; MacPherson, Dougal A; MacRae, James I

    2016-01-01

    The nature of energy metabolism in apicomplexan parasites has been closely investigated in the recent years. Studies in Plasmodium spp. and Toxoplasma gondii in particular have revealed that these parasites are able to employ enzymes in non-traditional ways, while utilizing multiple anaplerotic routes into a canonical tricarboxylic acid (TCA) cycle to satisfy their energy requirements. Importantly, some life stages of these parasites previously considered to be metabolically quiescent are, in fact, active and able to adapt their carbon source utilization to survive. We compare energy metabolism across the life cycle of malaria parasites and consider how this varies in other apicomplexans and related organisms, while discussing how this can be exploited for therapeutic intervention in these diseases.

  14. Dynamic Role of the GTP Energy Metabolism in Cancers.

    PubMed

    Sasaki, Atsuo T

    2016-01-01

    Rapid growing cells like tumor cells need a vast amount of energy to match their high metabolic demand. Guanine triphosphate (GTP) is one of major cellular metabolites and served as a building block for RNA and DNA as well as an energy source to drive cellular activities such as intracellular trafficking, the cell migration and translation. However, how cancer cells regulate GTP energy levels to adapt for their high demand remain largely unknown yet. In addition, how cells detect GTP levels remains unknown. In this seminar, I will introduce our recent findings that uncover dramatic change of GTP metabolism in cancer cells and a GTP sensing kinase that regulate metabolism for tumorigenesis.(Presented at the 1918th Meeting, March 3, 2016). PMID:27040886

  15. Exercise Effects on White Adipose Tissue: Beiging and Metabolic Adaptations.

    PubMed

    Stanford, Kristin I; Middelbeek, Roeland J W; Goodyear, Laurie J

    2015-07-01

    Regular physical activity and exercise training have long been known to cause adaptations to white adipose tissue (WAT), including decreases in cell size and lipid content and increases in mitochondrial proteins. In this article, we discuss recent studies that have investigated the effects of exercise training on mitochondrial function, the "beiging" of WAT, regulation of adipokines, metabolic effects of trained adipose tissue on systemic metabolism, and depot-specific responses to exercise training. The major WAT depots in the body are found in the visceral cavity (vWAT) and subcutaneously (scWAT). In rodent models, exercise training increases mitochondrial biogenesis and activity in both these adipose tissue depots. Exercise training also increases expression of the brown adipocyte marker uncoupling protein 1 (UCP1) in both adipose tissue depots, although these effects are much more pronounced in scWAT. Consistent with the increase in UCP1, exercise training increases the presence of brown-like adipocytes in scWAT, also known as browning or beiging. Training results in changes in the gene expression of thousands of scWAT genes and an altered adipokine profile in both scWAT and vWAT. Transplantation of trained scWAT in sedentary recipient mice results in striking improvements in skeletal muscle glucose uptake and whole-body metabolic homeostasis. Human and rodent exercise studies have indicated that exercise training can alter circulating adipokine concentration as well as adipokine expression in adipose tissue. Thus, the profound changes to WAT in response to exercise training may be part of the mechanism by which exercise improves whole-body metabolic health.

  16. A Non-Traditional Model of the Metabolic Syndrome: The Adaptive Significance of Insulin Resistance in Fasting-Adapted Seals

    PubMed Central

    Houser, Dorian S.; Champagne, Cory D.; Crocker, Daniel E.

    2013-01-01

    Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris), which fasts from food and water for periods of up to 4 months. During this time, ∼90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7–3.2 mM). All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures and therapies

  17. A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals.

    PubMed

    Houser, Dorian S; Champagne, Cory D; Crocker, Daniel E

    2013-01-01

    Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris), which fasts from food and water for periods of up to 4 months. During this time, ∼90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7-3.2 mM). All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures and therapies

  18. Misregulation of an adaptive metabolic response contributes to the age-related disruption of lipid homeostasis in Drosophila.

    PubMed

    Karpac, Jason; Biteau, Benoit; Jasper, Heinrich

    2013-09-26

    Loss of metabolic homeostasis is a hallmark of aging and is commonly characterized by the deregulation of adaptive signaling interactions that coordinate energy metabolism with dietary changes. The mechanisms driving age-related changes in these adaptive responses remain unclear. Here, we characterize the deregulation of an adaptive metabolic response and the development of metabolic dysfunction in the aging intestine of Drosophila. We find that activation of the insulin-responsive transcription factor Foxo in intestinal enterocytes is required to inhibit the expression of evolutionarily conserved lipases as part of a metabolic response to dietary changes. This adaptive mechanism becomes chronically activated in the aging intestine, mediated by changes in Jun-N-terminal kinase (JNK) signaling. Age-related chronic JNK/Foxo activation in enterocytes is deleterious, leading to sustained repression of intestinal lipase expression and the disruption of lipid homeostasis. Changes in the regulation of Foxo-mediated adaptive responses thus contribute to the age-associated breakdown of metabolic homeostasis.

  19. Impaired mitochondrial fat oxidation induces adaptive remodeling of muscle metabolism

    PubMed Central

    Wicks, Shawna E.; Vandanmagsar, Bolormaa; Haynie, Kimberly R.; Fuller, Scott E.; Warfel, Jaycob D.; Stephens, Jacqueline M.; Wang, Miao; Han, Xianlin; Zhang, Jingying; Noland, Robert C.; Mynatt, Randall L.

    2015-01-01

    The correlations between intramyocellular lipid (IMCL), decreased fatty acid oxidation (FAO), and insulin resistance have led to the hypothesis that impaired FAO causes accumulation of lipotoxic intermediates that inhibit muscle insulin signaling. Using a skeletal muscle-specific carnitine palmitoyltransferase-1 KO model, we show that prolonged and severe mitochondrial FAO inhibition results in increased carbohydrate utilization, along with reduced physical activity; increased circulating nonesterified fatty acids; and increased IMCLs, diacylglycerols, and ceramides. Perhaps more importantly, inhibition of mitochondrial FAO also initiates a local, adaptive response in muscle that invokes mitochondrial biogenesis, compensatory peroxisomal fat oxidation, and amino acid catabolism. Loss of its major fuel source (lipid) induces an energy deprivation response in muscle coordinated by signaling through AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) to maintain energy supply for locomotion and survival. At the whole-body level, these adaptations result in resistance to obesity. PMID:26056297

  20. Mitochondria in Cancer Energy Metabolism

    PubMed Central

    2015-01-01

    Cancer is a disease characterized by uncontrolled growth. Metabolic demands to sustain rapid proliferation must be compelling since aerobic glycolysis is the first as well as the most commonly shared characteristic of cancer. During the last decade, the significance of metabolic reprogramming of cancer has been at the center of attention. Nonetheless, despite all the knowledge gained on cancer biology, the field is not able to reach agreement on the issue of mitochondria: Are damaged mitochondria the cause for aerobic glycolysis in cancer? Warburg proposed the damaged mitochondria theory over 80 years ago; the field has been testing the theory equally long. In this review, we will discuss alterations in metabolic fluxes of cancer cells, and provide an opinion on the damaged mitochondria theory. PMID:26877834

  1. Adaptations to Climate in Candidate Genes for Common Metabolic Disorders

    PubMed Central

    Hancock, Angela M; Witonsky, David B; Gordon, Adam S; Eshel, Gidon; Pritchard, Jonathan K; Coop, Graham; Di Rienzo, Anna

    2008-01-01

    Evolutionary pressures due to variation in climate play an important role in shaping phenotypic variation among and within species and have been shown to influence variation in phenotypes such as body shape and size among humans. Genes involved in energy metabolism are likely to be central to heat and cold tolerance. To test the hypothesis that climate shaped variation in metabolism genes in humans, we used a bioinformatics approach based on network theory to select 82 candidate genes for common metabolic disorders. We genotyped 873 tag SNPs in these genes in 54 worldwide populations (including the 52 in the Human Genome Diversity Project panel) and found correlations with climate variables using rank correlation analysis and a newly developed method termed Bayesian geographic analysis. In addition, we genotyped 210 carefully matched control SNPs to provide an empirical null distribution for spatial patterns of allele frequency due to population history alone. For nearly all climate variables, we found an excess of genic SNPs in the tail of the distributions of the test statistics compared to the control SNPs, implying that metabolic genes as a group show signals of spatially varying selection. Among our strongest signals were several SNPs (e.g., LEPR R109K, FABP2 A54T) that had previously been associated with phenotypes directly related to cold tolerance. Since variation in climate may be correlated with other aspects of environmental variation, it is possible that some of the signals that we detected reflect selective pressures other than climate. Nevertheless, our results are consistent with the idea that climate has been an important selective pressure acting on candidate genes for common metabolic disorders. PMID:18282109

  2. Metabolic adaptation of skeletal muscles to gravitational unloading

    NASA Astrophysics Data System (ADS)

    Ohira, Y.; Yasui, W.; Kariya, F.; Wakatsuki, T.; Nakamura, K.; Asakura, T.; Edgerton, V. R.

    Responses of high-energy phosphates and metabolic properties to hindlimb suspension were studied in adult rats. The relative content of phosphocreatine (PCr) in the calf muscles was significantly higher in rats suspended for 10 days than in age-matched cage controls. The Pi/PCr ratio, where Pi is inorganic phosphate, in suspended muscles was less than controls. The absolute weights of soleus and medial gastrocnemius (MG) were approximately 40% less than controls. Although the % fiber distribution in MG was unchanged, the % slow fibers decreased and the % fibers which were classified as both slow and fast was increased in soleus. The activities (per unit weight or protein) of succinate dehydrogenase and lactate dehydrogenase in soleus were unchanged but those of cytochrome oxidase, β-hydroxyacyl CoA dehydrogenase, and citrate synthase were decreased following unloading. None of these enzyme activities in MG changed. However, the total levels of all enzymes in whole muscles decreased by suspension. It is suggested that shift of slow muscle toward fast type by unloading is associated with a decrease in mitochondrial biogenesis. Further, gravitational unloading affected the levels of muscle proteins differently even in the same mitochondrial enzymes. Unloading-related atrophy is prominent in red muscle or slow-twitch fiber 1, 2. Such atrophy is accompanied by a shift of contractile properties toward fast-twitch type 2-9. Further, inhibition of mitochondrial metabolism in these muscles is also reported by some studies 10-14 suggesting a lowered mitochondrial biogenesis, although results from some studies do not necessarily agree 1, 7, 15. However, the precise mechanism responsible for such alterations of muscle properties in response to gravitational unloading is unclear. On the contrary, mitochondrial biogenesis, suggested by mitochondrial enzyme activities and/or mass, is stimulated in muscles with depleted high-energy phosphates by cold exposure 16 and/or by feeding

  3. Glucocorticoids, bone and energy metabolism.

    PubMed

    Cooper, Mark S; Seibel, Markus J; Zhou, Hong

    2016-01-01

    Prolonged exposure to excessive levels of endogenous or exogenous glucocorticoids is associated with serious clinical features including altered body composition and the development of insulin resistance, impaired glucose tolerance and diabetes. It had been assumed that these adverse effects were mediated by direct effects of glucocorticoids on tissues such as adipose or liver. Recent studies have however indicated that these effects are, at least in part, mediated through the actions of glucocorticoids on bone and specifically the osteoblast. In mice, targeted abrogation of glucocorticoid signalling in osteoblasts significantly attenuated the changes in body composition and systemic fuel metabolism seen during glucocorticoid treatment. Heterotopic expression of osteocalcin in the liver of normal mice was also able to protect against the metabolic changes induced by glucocorticoids indicating that osteocalcin was the likely factor connecting bone osteoblasts to systemic fuel metabolism. Studies are now needed in humans to determine the extent to which glucocorticoid induced changes in body composition and systemic fuel metabolism are mediated through bone. This article is part of a Special Issue entitled Bone and diabetes. PMID:26051468

  4. Adaptation of Myocardial Substrate Metabolism to a Ketogenic Nutrient Environment*

    PubMed Central

    Wentz, Anna E.; d'Avignon, D. André; Weber, Mary L.; Cotter, David G.; Doherty, Jason M.; Kerns, Robnet; Nagarajan, Rakesh; Reddy, Naveen; Sambandam, Nandakumar; Crawford, Peter A.

    2010-01-01

    Heart muscle is metabolically versatile, converting energy stored in fatty acids, glucose, lactate, amino acids, and ketone bodies. Here, we use mouse models in ketotic nutritional states (24 h of fasting and a very low carbohydrate ketogenic diet) to demonstrate that heart muscle engages a metabolic response that limits ketone body utilization. Pathway reconstruction from microarray data sets, gene expression analysis, protein immunoblotting, and immunohistochemical analysis of myocardial tissue from nutritionally modified mouse models reveal that ketotic states promote transcriptional suppression of the key ketolytic enzyme, succinyl-CoA:3-oxoacid CoA transferase (SCOT; encoded by Oxct1), as well as peroxisome proliferator-activated receptor α-dependent induction of the key ketogenic enzyme HMGCS2. Consistent with reduction of SCOT, NMR profiling demonstrates that maintenance on a ketogenic diet causes a 25% reduction of myocardial 13C enrichment of glutamate when 13C-labeled ketone bodies are delivered in vivo or ex vivo, indicating reduced procession of ketones through oxidative metabolism. Accordingly, unmetabolized substrate concentrations are higher within the hearts of ketogenic diet-fed mice challenged with ketones compared with those of chow-fed controls. Furthermore, reduced ketone body oxidation correlates with failure of ketone bodies to inhibit fatty acid oxidation. These results indicate that ketotic nutrient environments engage mechanisms that curtail ketolytic capacity, controlling the utilization of ketone bodies in ketotic states. PMID:20529848

  5. Adaptation of myocardial substrate metabolism to a ketogenic nutrient environment.

    PubMed

    Wentz, Anna E; d'Avignon, D André; Weber, Mary L; Cotter, David G; Doherty, Jason M; Kerns, Robnet; Nagarajan, Rakesh; Reddy, Naveen; Sambandam, Nandakumar; Crawford, Peter A

    2010-08-01

    Heart muscle is metabolically versatile, converting energy stored in fatty acids, glucose, lactate, amino acids, and ketone bodies. Here, we use mouse models in ketotic nutritional states (24 h of fasting and a very low carbohydrate ketogenic diet) to demonstrate that heart muscle engages a metabolic response that limits ketone body utilization. Pathway reconstruction from microarray data sets, gene expression analysis, protein immunoblotting, and immunohistochemical analysis of myocardial tissue from nutritionally modified mouse models reveal that ketotic states promote transcriptional suppression of the key ketolytic enzyme, succinyl-CoA:3-oxoacid CoA transferase (SCOT; encoded by Oxct1), as well as peroxisome proliferator-activated receptor alpha-dependent induction of the key ketogenic enzyme HMGCS2. Consistent with reduction of SCOT, NMR profiling demonstrates that maintenance on a ketogenic diet causes a 25% reduction of myocardial (13)C enrichment of glutamate when (13)C-labeled ketone bodies are delivered in vivo or ex vivo, indicating reduced procession of ketones through oxidative metabolism. Accordingly, unmetabolized substrate concentrations are higher within the hearts of ketogenic diet-fed mice challenged with ketones compared with those of chow-fed controls. Furthermore, reduced ketone body oxidation correlates with failure of ketone bodies to inhibit fatty acid oxidation. These results indicate that ketotic nutrient environments engage mechanisms that curtail ketolytic capacity, controlling the utilization of ketone bodies in ketotic states. PMID:20529848

  6. Current Understanding of the Formation and Adaptation of Metabolic Systems Based on Network Theory

    PubMed Central

    Takemoto, Kazuhiro

    2012-01-01

    Formation and adaptation of metabolic networks has been a long-standing question in biology. With recent developments in biotechnology and bioinformatics, the understanding of metabolism is progressively becoming clearer from a network perspective. This review introduces the comprehensive metabolic world that has been revealed by a wide range of data analyses and theoretical studies; in particular, it illustrates the role of evolutionary events, such as gene duplication and horizontal gene transfer, and environmental factors, such as nutrient availability and growth conditions, in evolution of the metabolic network. Furthermore, the mathematical models for the formation and adaptation of metabolic networks have also been described, according to the current understanding from a perspective of metabolic networks. These recent findings are helpful in not only understanding the formation of metabolic networks and their adaptation, but also metabolic engineering. PMID:24957641

  7. Energy Balance and Metabolism after Cancer Treatment

    PubMed Central

    Tonorezos, Emily S.; Jones, Lee W.

    2013-01-01

    Unfavorable physiological, biological, and behavioral alterations during and following treatment for cancer may lead to chronic energy imbalance predisposing to a myriad of deleterious health conditions including obesity, dyslipidemia, and the metabolic syndrome. In addition to the cardiovascular and musculoskeletal effects of these conditions, energy imbalance and metabolic changes after cancer treatment can also affect cancer-related morbidity and mortality. To this end, lifestyle interventions such as diet and physical activity are especially relevant to mitigate the deleterious impact of chronic energy imbalance in cancer survivors. PMID:24331194

  8. Cardiomyocyte Health: Adapting to Metabolic Changes Through Autophagy

    PubMed Central

    Kubli, Dieter A.; Gustafsson, Åsa B.

    2014-01-01

    Autophagy is important in the heart for maintaining homeostasis when changes in nutrient levels occur. Autophagy is involved in the turnover of cellular components, and is rapidly upregulated during stress. Studies have found that autophagy is reduced in metabolic disorders including obesity and diabetes. This leads to accumulation of protein aggregates and dysfunctional organelles, which contributes to the pathogenesis of cardiovascular disease. Autophagy is primarily regulated by two components: the mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK). While mTOR integrates information about growth factors and nutrients and is a negative regulator of autophagy, AMPK is an energy sensor and activates autophagy when energy levels are low. These pathways therefore present targets for the development of autophagy-modulating therapies. PMID:24370004

  9. Lipid mobilisation and oxidative stress as metabolic adaptation processes in dairy heifers during transition period.

    PubMed

    Turk, R; Podpečan, O; Mrkun, J; Kosec, M; Flegar-Meštrić, Z; Perkov, S; Starič, J; Robić, M; Belić, M; Zrimšek, P

    2013-10-01

    The objective of this study was to evaluate metabolic disorders and oxidative stress in dairy heifers during the transition period. Possible relationships between lipid mobilisation indicators and oxidative stress markers were investigated as well. Nineteen dairy heifers were included in the study. Blood samples were collected at the time of estrus synchronisation in heifers, at insemination, three weeks after insemination, one week before calving, at calving and 1, 2, 4 and 8 weeks postpartum. Common metabolic parameters, beta-hydroxybutyrate (BHB), free fatty acids (FFA), paraoxonase-1 (PON1) activity and total antioxidative status (TAS) were analysed. Around insemination, no significant difference was observed in the majority of tested parameters (P>0.05). However, the transition period markedly affected the concentration of triglycerides, total cholesterol, HDL-C, BHB, FFA, TAS and PON1activity. Positive correlations between PON1 activity and total cholesterol, HDL-C and triglycerides were noted but inverse correlations with FFA, BHB and bilirubin were found indicating that PON1 activity changed with lipid metabolism and was influenced by negative energy balance. These findings suggest that lipid mobilisation and oxidative stress are part of a complex metabolic adaptation to low energy balance which reaches equilibrium later in advanced lactation.

  10. Teaching Energy Metabolism Using Scientific Articles: Implementation of a Virtual Learning Environment for Medical Students

    ERIC Educational Resources Information Center

    de Espindola, Marina Bazzo; El-Bacha, Tatiana; Giannella, Tais Rabetti; Struchiner, Miriam; da Silva, Wagner S.; Da Poian, Andrea T.

    2010-01-01

    This work describes the use of a virtual learning environment (VLE) applied to the biochemistry class for undergraduate, first-year medical students at the Federal University of Rio de Janeiro. The course focused on the integration of energy metabolism, exploring metabolic adaptations in different physiological or pathological states such as…

  11. Energy metabolism of the visual system

    PubMed Central

    Wong-Riley, Margaret T.T.

    2012-01-01

    The visual system is one of the most energetically demanding systems in the brain. The currency of energy is ATP, which is generated most efficiently from oxidative metabolism in the mitochondria. ATP supports multiple neuronal functions. Foremost is repolarization of the membrane potential after depolarization. Neuronal activity, ATP generation, blood flow, oxygen consumption, glucose utilization, and mitochondrial oxidative metabolism are all interrelated. In the retina, phototransduction, neurotransmitter utilization, and protein/organelle transport are energy-dependent, yet repolarization-after-depolarization consumes the bulk of the energy. Repolarization in photoreceptor inner segments maintains the dark current. Repolarization by all neurons along the visual pathway following depolarizing excitatory glutamatergic neurotransmission preserves cellular integrity and permits reactivation. The higher metabolic activity in the magno- versus the parvo-cellular pathway, the ON- versus the OFF-pathway in some (and the reverse in other) species, and in specialized functional representations in the visual cortex all reflect a greater emphasis on the processing of specific visual attributes. Neuronal activity and energy metabolism are tightly coupled processes at the cellular and even at the molecular levels. Deficiencies in energy metabolism, such as in diabetes, mitochondrial DNA mutation, mitochondrial protein malfunction, and oxidative stress can lead to retinopathy, visual deficits, neuronal degeneration, and eventual blindness. PMID:23226947

  12. Adaptation of maize source leaf metabolism to stress related disturbances in carbon, nitrogen and phosphorus balance

    PubMed Central

    2013-01-01

    Background Abiotic stress causes disturbances in the cellular homeostasis. Re-adjustment of balance in carbon, nitrogen and phosphorus metabolism therefore plays a central role in stress adaptation. However, it is currently unknown which parts of the primary cell metabolism follow common patterns under different stress conditions and which represent specific responses. Results To address these questions, changes in transcriptome, metabolome and ionome were analyzed in maize source leaves from plants suffering low temperature, low nitrogen (N) and low phosphorus (P) stress. The selection of maize as study object provided data directly from an important crop species and the so far underexplored C4 metabolism. Growth retardation was comparable under all tested stress conditions. The only primary metabolic pathway responding similar to all stresses was nitrate assimilation, which was down-regulated. The largest group of commonly regulated transcripts followed the expression pattern: down under low temperature and low N, but up under low P. Several members of this transcript cluster could be connected to P metabolism and correlated negatively to different phosphate concentration in the leaf tissue. Accumulation of starch under low temperature and low N stress, but decrease in starch levels under low P conditions indicated that only low P treated leaves suffered carbon starvation. Conclusions Maize employs very different strategies to manage N and P metabolism under stress. While nitrate assimilation was regulated depending on demand by growth processes, phosphate concentrations changed depending on availability, thus building up reserves under excess conditions. Carbon and energy metabolism of the C4 maize leaves were particularly sensitive to P starvation. PMID:23822863

  13. Metabolic insight into mechanisms of high-altitude adaptation in Tibetans.

    PubMed

    Ge, Ri-Li; Simonson, Tatum S; Cooksey, Robert C; Tanna, Uran; Qin, Ga; Huff, Chad D; Witherspoon, David J; Xing, Jinchuan; Zhengzhong, Bai; Prchal, Josef T; Jorde, Lynn B; McClain, Donald A

    2012-06-01

    Recent studies have identified genes involved in high-altitude adaptation in Tibetans. Genetic variants/haplotypes within regions containing three of these genes (EPAS1, EGLN1, and PPARA) are associated with relatively decreased hemoglobin levels observed in Tibetans at high altitude, providing corroborative evidence for genetic adaptation to this extreme environment. The mechanisms that afford adaptation to high-altitude hypoxia, however, remain unclear. Considering the strong metabolic demands imposed by hypoxia, we hypothesized that a shift in fuel preference to glucose oxidation and glycolysis at the expense of fatty acid oxidation would improve adaptation to decreased oxygen availability. Correlations between serum free fatty acid and lactate concentrations in Tibetan groups living at high altitude and putatively selected haplotypes provide insight into this hypothesis. An EPAS1 haplotype that exhibits a signal of positive selection is significantly associated with increased lactate concentration, the product of anaerobic glycolysis. Furthermore, the putatively advantageous PPARA haplotype is correlated with serum free fatty acid concentrations, suggesting a possible decrease in the activity of fatty acid oxidation. Although further studies are required to assess the molecular mechanisms underlying these patterns, these associations suggest that genetic adaptation to high altitude involves alteration in energy utilization pathways.

  14. Energy metabolism of Inuit sled dogs.

    PubMed

    Gerth, Nadine; Redman, Paula; Speakman, John; Jackson, Sue; Starck, J Matthias

    2010-04-01

    We explored how seasonal changes in temperature, exercise and food supply affected energy metabolism and heart rate of Inuit dogs in Greenland. Using open flow respirometry, doubly labeled water, and heart rate recording, we measured metabolic rates of the same dogs at two different locations: at one location the dogs were fed with high energy food throughout the year while at the other location they were fed with low energy food during summer. Our key questions were: is resting metabolic rate (RMR) increased during the winter season when dogs are working? Does feeding regime affect RMR during summer? What is the proportion of metabolic rate (MR) devoted to specific dynamic action (SDA), and what is the metabolic scope of working Inuit sled dogs? The Inuit dogs had an extremely wide thermoneutral zone extending down to -25 degrees C. Temperature changes between summer and winter did not affect RMR, thus summer fasting periods were defined as baseline RMR. Relative to this baseline, summer MR was upregulated in the group of dogs receiving low energy food, whereas heart rate was downregulated. However, during food digestion, both MR and HR were twice their respective baseline values. A continuously elevated MR was observed during winter. Because temperature effects were excluded and because there were also no effects of training, we attribute winter elevated MR to SDA because of the continuous food supply. Working MR during winter was 7.9 times the MR of resting dogs in winter, or 12.2 times baseline MR.

  15. Leptin regulates energy metabolism in MCF-7 breast cancer cells.

    PubMed

    Blanquer-Rosselló, Maria del Mar; Oliver, Jordi; Sastre-Serra, Jorge; Valle, Adamo; Roca, Pilar

    2016-03-01

    Obesity is known to be a poorer prognosis factor for breast cancer in postmenopausal women. Among the diverse endocrine factors associated to obesity, leptin has received special attention since it promotes breast cancer cell growth and invasiveness, processes which force cells to adapt their metabolism to satisfy the increased demands of energy and biosynthetic intermediates. Taking this into account, our aim was to explore the effects of leptin in the metabolism of MCF-7 breast cancer cells. Polarographic analysis revealed that leptin increased oxygen consumption rate and cellular ATP levels were more dependent on mitochondrial oxidative metabolism in leptin-treated cells compared to the more glycolytic control cells. Experiments with selective inhibitors of glycolysis (2-DG), fatty acid oxidation (etomoxir) or aminoacid deprivation showed that ATP levels were more reliant on fatty acid oxidation. In agreement, levels of key proteins involved in lipid catabolism (FAT/CD36, CPT1, PPARα) and phosphorylation of the energy sensor AMPK were increased by leptin. Regarding glucose, cellular uptake was not affected by leptin, but lactate release was deeply repressed. Analysis of pyruvate dehydrogenase (PDH), lactate dehydrogenase (LDH) and pyruvate carboxylase (PC) together with the pentose-phosphate pathway enzyme glucose-6 phosphate dehydrogenase (G6PDH) revealed that leptin favors the use of glucose for biosynthesis. These results point towards a role of leptin in metabolic reprogramming, consisting of an enhanced use of glucose for biosynthesis and lipids for energy production. This metabolic adaptations induced by leptin may provide benefits for MCF-7 growth and give support to the reverse Warburg effect described in breast cancer. PMID:26772821

  16. Leptin regulates energy metabolism in MCF-7 breast cancer cells.

    PubMed

    Blanquer-Rosselló, Maria del Mar; Oliver, Jordi; Sastre-Serra, Jorge; Valle, Adamo; Roca, Pilar

    2016-03-01

    Obesity is known to be a poorer prognosis factor for breast cancer in postmenopausal women. Among the diverse endocrine factors associated to obesity, leptin has received special attention since it promotes breast cancer cell growth and invasiveness, processes which force cells to adapt their metabolism to satisfy the increased demands of energy and biosynthetic intermediates. Taking this into account, our aim was to explore the effects of leptin in the metabolism of MCF-7 breast cancer cells. Polarographic analysis revealed that leptin increased oxygen consumption rate and cellular ATP levels were more dependent on mitochondrial oxidative metabolism in leptin-treated cells compared to the more glycolytic control cells. Experiments with selective inhibitors of glycolysis (2-DG), fatty acid oxidation (etomoxir) or aminoacid deprivation showed that ATP levels were more reliant on fatty acid oxidation. In agreement, levels of key proteins involved in lipid catabolism (FAT/CD36, CPT1, PPARα) and phosphorylation of the energy sensor AMPK were increased by leptin. Regarding glucose, cellular uptake was not affected by leptin, but lactate release was deeply repressed. Analysis of pyruvate dehydrogenase (PDH), lactate dehydrogenase (LDH) and pyruvate carboxylase (PC) together with the pentose-phosphate pathway enzyme glucose-6 phosphate dehydrogenase (G6PDH) revealed that leptin favors the use of glucose for biosynthesis. These results point towards a role of leptin in metabolic reprogramming, consisting of an enhanced use of glucose for biosynthesis and lipids for energy production. This metabolic adaptations induced by leptin may provide benefits for MCF-7 growth and give support to the reverse Warburg effect described in breast cancer.

  17. Dynamic scenario of metabolic pathway adaptation in tumors and therapeutic approach

    PubMed Central

    Peppicelli, Silvia; Bianchini, Francesca; Calorini, Lido

    2015-01-01

    Cancer cells need to regulate their metabolic program to fuel several activities, including unlimited proliferation, resistance to cell death, invasion and metastasis. The aim of this work is to revise this complex scenario. Starting from proliferating cancer cells located in well-oxygenated regions, they may express the so-called “Warburg effect” or aerobic glycolysis, meaning that although a plenty of oxygen is available, cancer cells choose glycolysis, the sole pathway that allows a biomass formation and DNA duplication, needed for cell division. Although oxygen does not represent the primary font of energy, diffusion rate reduces oxygen tension and the emerging hypoxia promotes “anaerobic glycolysis” through the hypoxia inducible factor-1α-dependent up-regulation. The acquired hypoxic phenotype is endowed with high resistance to cell death and high migration capacities, although these cells are less proliferating. Cells using aerobic or anaerobic glycolysis survive only in case they extrude acidic metabolites acidifying the extracellular space. Acidosis drives cancer cells from glycolysis to OxPhos, and OxPhos transforms the available alternative substrates into energy used to fuel migration and distant organ colonization. Thus, metabolic adaptations sustain different energy-requiring ability of cancer cells, but render them responsive to perturbations by anti-metabolic agents, such as inhibitors of glycolysis and/or OxPhos. PMID:25897425

  18. Dynamic scenario of metabolic pathway adaptation in tumors and therapeutic approach.

    PubMed

    Peppicelli, Silvia; Bianchini, Francesca; Calorini, Lido

    2015-01-01

    Cancer cells need to regulate their metabolic program to fuel several activities, including unlimited proliferation, resistance to cell death, invasion and metastasis. The aim of this work is to revise this complex scenario. Starting from proliferating cancer cells located in well-oxygenated regions, they may express the so-called "Warburg effect" or aerobic glycolysis, meaning that although a plenty of oxygen is available, cancer cells choose glycolysis, the sole pathway that allows a biomass formation and DNA duplication, needed for cell division. Although oxygen does not represent the primary font of energy, diffusion rate reduces oxygen tension and the emerging hypoxia promotes "anaerobic glycolysis" through the hypoxia inducible factor-1α-dependent up-regulation. The acquired hypoxic phenotype is endowed with high resistance to cell death and high migration capacities, although these cells are less proliferating. Cells using aerobic or anaerobic glycolysis survive only in case they extrude acidic metabolites acidifying the extracellular space. Acidosis drives cancer cells from glycolysis to OxPhos, and OxPhos transforms the available alternative substrates into energy used to fuel migration and distant organ colonization. Thus, metabolic adaptations sustain different energy-requiring ability of cancer cells, but render them responsive to perturbations by anti-metabolic agents, such as inhibitors of glycolysis and/or OxPhos. PMID:25897425

  19. NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus

    PubMed Central

    Cantó, Carles; Menzies, Keir; Auwerx, Johan

    2015-01-01

    NAD+ has emerged as a vital cofactor that can rewire metabolism, activate sirtuins and maintain mitochondrial fitness through mechanisms such as the mitochondrial unfolded protein response. This improved understanding of NAD+ metabolism revived interest in NAD+ boosting strategies to manage a wide spectrum of diseases, ranging from diabetes to cancer. In this review, we summarize how NAD+ metabolism links energy status with adaptive cellular and organismal responses and how this knowledge can be therapeutically exploited. PMID:26118927

  20. NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus.

    PubMed

    Cantó, Carles; Menzies, Keir J; Auwerx, Johan

    2015-07-01

    NAD(+) has emerged as a vital cofactor that can rewire metabolism, activate sirtuins, and maintain mitochondrial fitness through mechanisms such as the mitochondrial unfolded protein response. This improved understanding of NAD(+) metabolism revived interest in NAD(+)-boosting strategies to manage a wide spectrum of diseases, ranging from diabetes to cancer. In this review, we summarize how NAD(+) metabolism links energy status with adaptive cellular and organismal responses and how this knowledge can be therapeutically exploited.

  1. Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism.

    PubMed

    Saab, Aiman S; Tzvetavona, Iva D; Trevisiol, Andrea; Baltan, Selva; Dibaj, Payam; Kusch, Kathrin; Möbius, Wiebke; Goetze, Bianka; Jahn, Hannah M; Huang, Wenhui; Steffens, Heinz; Schomburg, Eike D; Pérez-Samartín, Alberto; Pérez-Cerdá, Fernando; Bakhtiari, Davood; Matute, Carlos; Löwel, Siegrid; Griesinger, Christian; Hirrlinger, Johannes; Kirchhoff, Frank; Nave, Klaus-Armin

    2016-07-01

    Oligodendrocytes make myelin and support axons metabolically with lactate. However, it is unknown how glucose utilization and glycolysis are adapted to the different axonal energy demands. Spiking axons release glutamate and oligodendrocytes express NMDA receptors of unknown function. Here we show that the stimulation of oligodendroglial NMDA receptors mobilizes glucose transporter GLUT1, leading to its incorporation into the myelin compartment in vivo. When myelinated optic nerves from conditional NMDA receptor mutants are challenged with transient oxygen-glucose deprivation, they show a reduced functional recovery when returned to oxygen-glucose but are indistinguishable from wild-type when provided with oxygen-lactate. Moreover, the functional integrity of isolated optic nerves, which are electrically silent, is extended by preincubation with NMDA, mimicking axonal activity, and shortened by NMDA receptor blockers. This reveals a novel aspect of neuronal energy metabolism in which activity-dependent glutamate release enhances oligodendroglial glucose uptake and glycolytic support of fast spiking axons. PMID:27292539

  2. Sodium signaling and astrocyte energy metabolism.

    PubMed

    Chatton, Jean-Yves; Magistretti, Pierre J; Barros, L Felipe

    2016-10-01

    The Na(+) gradient across the plasma membrane is constantly exploited by astrocytes as a secondary energy source to regulate the intracellular and extracellular milieu, and discard waste products. One of the most prominent roles of astrocytes in the brain is the Na(+) -dependent clearance of glutamate released by neurons during synaptic transmission. The intracellular Na(+) load collectively generated by these processes converges at the Na,K-ATPase pump, responsible for Na(+) extrusion from the cell, which is achieved at the expense of cellular ATP. These processes represent pivotal mechanisms enabling astrocytes to increase the local availability of metabolic substrates in response to neuronal activity. This review presents basic principles linking the intracellular handling of Na(+) following activity-related transmembrane fluxes in astrocytes and the energy metabolic pathways involved. We propose a role of Na(+) as an energy currency and as a mediator of metabolic signals in the context of neuron-glia interactions. We further discuss the possible impact of the astrocytic syncytium for the distribution and coordination of the metabolic response, and the compartmentation of these processes in cellular microdomains and subcellular organelles. Finally, we illustrate future avenues of investigation into signaling mechanisms aimed at bridging the gap between Na(+) and the metabolic machinery. GLIA 2016;64:1667-1676. PMID:27027636

  3. Thyroid hormone signaling in energy homeostasis and energy metabolism

    PubMed Central

    McAninch, Elizabeth A.; Bianco, Antonio C.

    2014-01-01

    The thyroid hormone plays a significant role in diverse processes related to growth, development, differentiation, and metabolism. Thyroid hormone signaling modulates energy expenditure through both central and peripheral pathways. At the cellular level, the thyroid hormone exerts its effects after concerted mechanisms facilitate binding to the thyroid hormone receptor. In the hypothalamus, signals from a range of metabolic pathways, including appetite, temperature, afferent stimuli via the autonomic nervous system, availability of energy substrates, hormones, and other biologically active molecules, converge to maintain plasma thyroid hormone at the appropriate level to preserve energy homeostasis. At the tissue level, thyroid hormone actions on metabolism are controlled by transmembrane transporters, deiodinases, and thyroid hormone receptors. In the modern environment, humans are susceptible to an energy surplus, which has resulted in an obesity epidemic and thus understanding the contribution of the thyroid hormone to cellular and organism metabolism is increasingly relevant. PMID:24697152

  4. Adaptation to extreme stress: post-traumatic stress disorder, neuropeptide Y and metabolic syndrome.

    PubMed

    Rasmusson, Ann M; Schnurr, Paula P; Zukowska, Zofia; Scioli, Erica; Forman, Daniel E

    2010-10-01

    The prevalence rates of obesity and metabolic syndrome are on the rise in the United States. Epidemiological surveys suggest that the rates of these medical conditions are especially high among persons with psychiatric disorders, including post-traumatic stress disorder (PTSD). A variety of factors are thought to contribute to the risk for metabolic syndrome, including excessive caloric intake, decreased activity and energy expenditure, use of certain medications, stress and genetic influences. Recent research demonstrates that stress, acting through the neuropeptide Y (NPY) and glucocorticoid systems, potentiates the development of obesity and other aspects of metabolic syndrome in mice fed a high caloric, fat and sugar diet. Alterations in the NPY and glucocorticoid systems also impact behavioral adaptation to stress, as indicated by studies in animals and persons exposed to severe, life-threatening or traumatic stress. The following review examines the biology of the NPY and neuroactive steroid systems as physiological links between metabolic syndrome and PTSD, a paradigmatic neuropsychiatric stress disorder. Hopefully, understanding the function of these systems from both a translational and systems biology point of view in relation to stress will enable development of more effective methods for preventing and treating the negative physical and mental health consequences of stress.

  5. Body size, energy metabolism and lifespan.

    PubMed

    Speakman, John R

    2005-05-01

    Bigger animals live longer. The scaling exponent for the relationship between lifespan and body mass is between 0.15 and 0.3. Bigger animals also expend more energy, and the scaling exponent for the relationship of resting metabolic rate (RMR) to body mass lies somewhere between 0.66 and 0.8. Mass-specific RMR therefore scales with a corresponding exponent between -0.2 and -0.33. Because the exponents for mass-specific RMR are close to the exponents for lifespan, but have opposite signs, their product (the mass-specific expenditure of energy per lifespan) is independent of body mass (exponent between -0.08 and 0.08). This means that across species a gram of tissue on average expends about the same amount of energy before it dies regardless of whether that tissue is located in a shrew, a cow, an elephant or a whale. This fact led to the notion that ageing and lifespan are processes regulated by energy metabolism rates and that elevating metabolism will be associated with premature mortality--the rate of living theory. The free-radical theory of ageing provides a potential mechanism that links metabolism to ageing phenomena, since oxygen free radicals are formed as a by-product of oxidative phosphorylation. Despite this potential synergy in these theoretical approaches, the free-radical theory has grown in stature while the rate of living theory has fallen into disrepute. This is primarily because comparisons made across classes (for example, between birds and mammals) do not conform to the expectations, and even within classes there is substantial interspecific variability in the mass-specific expenditure of energy per lifespan. Using interspecific data to test the rate of living hypothesis is, however, confused by several major problems. For example, appeals that the resultant lifetime expenditure of energy per gram of tissue is 'too variable' depend on the biological significance rather than the statistical significance of the variation observed. Moreover, maximum

  6. Pareto optimality in organelle energy metabolism analysis.

    PubMed

    Angione, Claudio; Carapezza, Giovanni; Costanza, Jole; Lió, Pietro; Nicosia, Giuseppe

    2013-01-01

    In low and high eukaryotes, energy is collected or transformed in compartments, the organelles. The rich variety of size, characteristics, and density of the organelles makes it difficult to build a general picture. In this paper, we make use of the Pareto-front analysis to investigate the optimization of energy metabolism in mitochondria and chloroplasts. Using the Pareto optimality principle, we compare models of organelle metabolism on the basis of single- and multiobjective optimization, approximation techniques (the Bayesian Automatic Relevance Determination), robustness, and pathway sensitivity analysis. Finally, we report the first analysis of the metabolic model for the hydrogenosome of Trichomonas vaginalis, which is found in several protozoan parasites. Our analysis has shown the importance of the Pareto optimality for such comparison and for insights into the evolution of the metabolism from cytoplasmic to organelle bound, involving a model order reduction. We report that Pareto fronts represent an asymptotic analysis useful to describe the metabolism of an organism aimed at maximizing concurrently two or more metabolite concentrations.

  7. Adaptive, full-spectrum solar energy system

    DOEpatents

    Muhs, Jeffrey D.; Earl, Dennis D.

    2003-08-05

    An adaptive full spectrum solar energy system having at least one hybrid solar concentrator, at least one hybrid luminaire, at least one hybrid photobioreactor, and a light distribution system operably connected to each hybrid solar concentrator, each hybrid luminaire, and each hybrid photobioreactor. A lighting control system operates each component.

  8. Energy metabolism in neuroblastoma and Wilms tumor.

    PubMed

    Aminzadeh, Sepideh; Vidali, Silvia; Sperl, Wolfgang; Kofler, Barbara; Feichtinger, René G

    2015-01-01

    To support high proliferation, the majority of cancer cells undergo fundamental metabolic changes such as increasing their glucose uptake and shifting to glycolysis for ATP production at the expense of far more efficient mitochondrial energy production by oxidative phosphorylation (OXPHOS), which at first glance is a paradox. This phenomenon is known as the Warburg effect. However, enhanced glycolysis is necessary to provide building blocks for anabolic growth. Apart from the generation of ATP, intermediates of glycolysis serve as precursors for a variety of biosynthetic pathways essential for cell proliferation. In the last 10-15 years the field of tumor metabolism has experienced an enormous boom in interest. It is now well established that tumor suppressor genes and oncogenes often play a central role in the regulation of cellular metabolism. Therefore, they significantly contribute to the manifestation of the Warburg effect. While much attention has focused on adult solid tumors, so far there has been comparatively little effort directed at elucidation of the mechanism responsible for the Warburg effect in childhood cancers. In this review we focus on metabolic pathways in neuroblastoma (NB) and Wilms tumor (WT), the two most frequent solid tumors in children. Both tumor types show alterations of the OXPHOS system and glycolytic features. Chromosomal alterations and activation of oncogenes like MYC or inactivation of tumor suppressor genes like TP53 can in part explain the changes of energy metabolism in these cancers. The strict dependence of cancer cells on glucose metabolism is a fairly common feature among otherwise biologically diverse types of cancer. Therefore, inhibition of glycolysis or starvation of cancer cells through glucose deprivation via a high-fat low-carbohydrate diet may be a promising avenue for future adjuvant therapeutic strategies. PMID:26835356

  9. The genus Pseudovibrio contains metabolically versatile bacteria adapted for symbiosis

    PubMed Central

    Bondarev, Vladimir; Richter, Michael; Romano, Stefano; Piel, Jörn; Schwedt, Anne; Schulz-Vogt, Heide N

    2013-01-01

    The majority of strains belonging to the genus Pseudovibrio have been isolated from marine invertebrates such as tunicates, corals and particularly sponges, but the physiology of these bacteria is poorly understood. In this study, we analyse for the first time the genomes of two Pseudovibrio strains – FO-BEG1 and JE062. The strain FO-BEG1 is a required symbiont of a cultivated Beggiatoa strain, a sulfide-oxidizing, autotrophic bacterium, which was initially isolated from a coral. Strain JE062 was isolated from a sponge. The presented data show that both strains are generalistic bacteria capable of importing and oxidizing a wide range of organic and inorganic compounds to meet their carbon, nitrogen, phosphorous and energy requirements under both, oxic and anoxic conditions. Several physiological traits encoded in the analysed genomes were verified in laboratory experiments with both isolates. Besides the versatile metabolic abilities of both Pseudovibrio strains, our study reveals a number of open reading frames and gene clusters in the genomes that seem to be involved in symbiont–host interactions. Both Pseudovibrio strains have the genomic potential to attach to host cells, interact with the eukaryotic cell machinery, produce secondary metabolites and supply the host with cofactors. PMID:23601235

  10. Gene regulatory and metabolic adaptation processes of Dinoroseobacter shibae DFL12T during oxygen depletion.

    PubMed

    Laass, Sebastian; Kleist, Sarah; Bill, Nelli; Drüppel, Katharina; Kossmehl, Sebastian; Wöhlbrand, Lars; Rabus, Ralf; Klein, Johannes; Rohde, Manfred; Bartsch, Annekathrin; Wittmann, Christoph; Schmidt-Hohagen, Kerstin; Tielen, Petra; Jahn, Dieter; Schomburg, Dietmar

    2014-05-01

    Metabolic flexibility is the key to the ecological success of the marine Roseobacter clade bacteria. We investigated the metabolic adaptation and the underlying changes in gene expression of Dinoroseobacter shibae DFL12(T) to anoxic life by a combination of metabolome, proteome, and transcriptome analyses. Time-resolved studies during continuous oxygen depletion were performed in a chemostat using nitrate as the terminal electron acceptor. Formation of the denitrification machinery was found enhanced on the transcriptional and proteome level, indicating that D. shibae DFL12(T) established nitrate respiration to compensate for the depletion of the electron acceptor oxygen. In parallel, arginine fermentation was induced. During the transition state, growth and ATP concentration were found to be reduced, as reflected by a decrease of A578 values and viable cell counts. In parallel, the central metabolism, including gluconeogenesis, protein biosynthesis, and purine/pyrimidine synthesis was found transiently reduced in agreement with the decreased demand for cellular building blocks. Surprisingly, an accumulation of poly-3-hydroxybutanoate was observed during prolonged incubation under anoxic conditions. One possible explanation is the storage of accumulated metabolites and the regeneration of NADP(+) from NADPH during poly-3-hydroxybutanoate synthesis (NADPH sink). Although D. shibae DFL12(T) was cultivated in the dark, biosynthesis of bacteriochlorophyll was increased, possibly to prepare for additional energy generation via aerobic anoxygenic photophosphorylation. Overall, oxygen depletion led to a metabolic crisis with partly blocked pathways and the accumulation of metabolites. In response, major energy-consuming processes were reduced until the alternative respiratory denitrification machinery was operative. PMID:24648520

  11. Urinary Metabolite Profiles in Premature Infants Show Early Postnatal Metabolic Adaptation and Maturation

    PubMed Central

    Moltu, Sissel J.; Sachse, Daniel; Blakstad, Elin W.; Strømmen, Kenneth; Nakstad, Britt; Almaas, Astrid N.; Westerberg, Ane C.; Rønnestad, Arild; Brække, Kristin; Veierød, Marit B.; Iversen, Per O.; Rise, Frode; Berg, Jens P.; Drevon, Christian A.

    2014-01-01

    Objectives: Early nutrition influences metabolic programming and long-term health. We explored the urinary metabolite profiles of 48 premature infants (birth weight < 1500 g) randomized to an enhanced or a standard diet during neonatal hospitalization. Methods: Metabolomics using nuclear magnetic resonance spectroscopy (NMR) was conducted on urine samples obtained during the first week of life and thereafter fortnightly. Results: The intervention group received significantly higher amounts of energy, protein, lipids, vitamin A, arachidonic acid and docosahexaenoic acid as compared to the control group. Enhanced nutrition did not appear to affect the urine profiles to an extent exceeding individual variation. However, in all infants the glucogenic amino acids glycine, threonine, hydroxyproline and tyrosine increased substantially during the early postnatal period, along with metabolites of the tricarboxylic acid cycle (succinate, oxoglutarate, fumarate and citrate). The metabolite changes correlated with postmenstrual age. Moreover, we observed elevated threonine and glycine levels in first-week urine samples of the small for gestational age (SGA; birth weight < 10th percentile for gestational age) as compared to the appropriate for gestational age infants. Conclusion: This first nutri-metabolomics study in premature infants demonstrates that the physiological adaptation during the fetal-postnatal transition as well as maturation influences metabolism during the breastfeeding period. Elevated glycine and threonine levels were found in the first week urine samples of the SGA infants and emerged as potential biomarkers of an altered metabolic phenotype. PMID:24824288

  12. Cold adaptation increases rates of nutrient flow and metabolic plasticity during cold exposure in Drosophila melanogaster.

    PubMed

    Williams, Caroline M; McCue, Marshall D; Sunny, Nishanth E; Szejner-Sigal, Andre; Morgan, Theodore J; Allison, David B; Hahn, Daniel A

    2016-09-14

    Metabolic flexibility is an important component of adaptation to stressful environments, including thermal stress and latitudinal adaptation. A long history of population genetic studies suggest that selection on core metabolic enzymes may shape life histories by altering metabolic flux. However, the direct relationship between selection on thermal stress hardiness and metabolic flux has not previously been tested. We investigated flexibility of nutrient catabolism during cold stress in Drosophila melanogaster artificially selected for fast or slow recovery from chill coma (i.e. cold-hardy or -susceptible), specifically testing the hypothesis that stress adaptation increases metabolic turnover. Using (13)C-labelled glucose, we first showed that cold-hardy flies more rapidly incorporate ingested carbon into amino acids and newly synthesized glucose, permitting rapid synthesis of proline, a compound shown elsewhere to improve survival of cold stress. Second, using glucose and leucine tracers we showed that cold-hardy flies had higher oxidation rates than cold-susceptible flies before cold exposure, similar oxidation rates during cold exposure, and returned to higher oxidation rates during recovery. Additionally, cold-hardy flies transferred compounds among body pools more rapidly during cold exposure and recovery. Increased metabolic turnover may allow cold-adapted flies to better prepare for, resist and repair/tolerate cold damage. This work illustrates for the first time differences in nutrient fluxes associated with cold adaptation, suggesting that metabolic costs associated with cold hardiness could invoke resource-based trade-offs that shape life histories. PMID:27605506

  13. Cold adaptation increases rates of nutrient flow and metabolic plasticity during cold exposure in Drosophila melanogaster.

    PubMed

    Williams, Caroline M; McCue, Marshall D; Sunny, Nishanth E; Szejner-Sigal, Andre; Morgan, Theodore J; Allison, David B; Hahn, Daniel A

    2016-09-14

    Metabolic flexibility is an important component of adaptation to stressful environments, including thermal stress and latitudinal adaptation. A long history of population genetic studies suggest that selection on core metabolic enzymes may shape life histories by altering metabolic flux. However, the direct relationship between selection on thermal stress hardiness and metabolic flux has not previously been tested. We investigated flexibility of nutrient catabolism during cold stress in Drosophila melanogaster artificially selected for fast or slow recovery from chill coma (i.e. cold-hardy or -susceptible), specifically testing the hypothesis that stress adaptation increases metabolic turnover. Using (13)C-labelled glucose, we first showed that cold-hardy flies more rapidly incorporate ingested carbon into amino acids and newly synthesized glucose, permitting rapid synthesis of proline, a compound shown elsewhere to improve survival of cold stress. Second, using glucose and leucine tracers we showed that cold-hardy flies had higher oxidation rates than cold-susceptible flies before cold exposure, similar oxidation rates during cold exposure, and returned to higher oxidation rates during recovery. Additionally, cold-hardy flies transferred compounds among body pools more rapidly during cold exposure and recovery. Increased metabolic turnover may allow cold-adapted flies to better prepare for, resist and repair/tolerate cold damage. This work illustrates for the first time differences in nutrient fluxes associated with cold adaptation, suggesting that metabolic costs associated with cold hardiness could invoke resource-based trade-offs that shape life histories.

  14. Anaerobic energy metabolism in unicellular photosynthetic eukaryotes.

    PubMed

    Atteia, Ariane; van Lis, Robert; Tielens, Aloysius G M; Martin, William F

    2013-02-01

    Anaerobic metabolic pathways allow unicellular organisms to tolerate or colonize anoxic environments. Over the past ten years, genome sequencing projects have brought a new light on the extent of anaerobic metabolism in eukaryotes. A surprising development has been that free-living unicellular algae capable of photoautotrophic lifestyle are, in terms of their enzymatic repertoire, among the best equipped eukaryotes known when it comes to anaerobic energy metabolism. Some of these algae are marine organisms, common in the oceans, others are more typically soil inhabitants. All these species are important from the ecological (O(2)/CO(2) budget), biotechnological, and evolutionary perspectives. In the unicellular algae surveyed here, mixed-acid type fermentations are widespread while anaerobic respiration, which is more typical of eukaryotic heterotrophs, appears to be rare. The presence of a core anaerobic metabolism among the algae provides insights into its evolutionary origin, which traces to the eukaryote common ancestor. The predicted fermentative enzymes often exhibit an amino acid extension at the N-terminus, suggesting that these proteins might be compartmentalized in the cell, likely in the chloroplast or the mitochondrion. The green algae Chlamydomonas reinhardtii and Chlorella NC64 have the most extended set of fermentative enzymes reported so far. Among the eukaryotes with secondary plastids, the diatom Thalassiosira pseudonana has the most pronounced anaerobic capabilities as yet. From the standpoints of genomic, transcriptomic, and biochemical studies, anaerobic energy metabolism in C. reinhardtii remains the best characterized among photosynthetic protists. This article is part of a Special Issue entitled: The evolutionary aspects of bioenergetic systems.

  15. Role of cardiomyocyte circadian clock in myocardial metabolic adaptation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marked circadian rhythmicities in cardiovascular physiology and pathophysiology exist. The cardiomyocyte circadian clock has recently been linked to circadian rhythms in myocardial gene expression, metabolism, and contractile function. For instance, the cardiomyocyte circadian clock is essential f...

  16. Energy metabolic dysfunction as a carcinogenic factor in cancer cells.

    PubMed

    Sun, Yongyan; Shi, Zhenhua; Lian, Huiyong; Cai, Peng

    2016-03-01

    Cancer, as a leading cause of death, has attracted enormous public attention. Reprogramming of cellular energy metabolism is deemed to be one of the principal hallmarks of cancer. In this article, we reviewed the mutual relationships among environmental pollution factors, energy metabolic dysfunction, and various cancers. We found that most environmental pollution factors could induce cancers mainly by disturbing the energy metabolism. By triggering microenvironment alteration, energy metabolic dysfunction can be treated as a factor in carcinogenesis. Thus, we put forward that energy metabolism might be as a key point for studying carcinogenesis and tumor development to propose new methods for cancer prevention and therapy.

  17. Mutations in global regulators lead to metabolic selection during adaptation to complex environments

    DOE PAGES

    Saxer, Gerda; Krepps, Michael D.; Merkley, Eric D.; Ansong, Charles; Deatherage Kaiser, Brooke L.; Valovska, Marie -Thérèse; Ristic, Nikola; Yeh, Ping T.; Prakash, Vittal P.; Leiser, Owen P.; et al

    2014-12-11

    Adaptation to ecologically complex environments can provide insights into the evolutionary dynamics and functional constraints encountered by organisms during natural selection. Unlike adaptation to a single limiting resource, adaptation to a new environment with abundant and varied resources can be difficult to achieve by small incremental changes since many mutations are required to achieve even modest gains in fitness. Since changing complex environments are quite common in nature, we investigated how such an epistatic bottleneck can be avoided to allow rapid adaptation. We show that adaptive mutations arise repeatedly in independently evolved populations in the context of greatly increased geneticmore » and phenotypic diversity. We go on to show that weak selection requiring substantial metabolic reprogramming can be readily achieved by mutations in the global response regulator arcA and the stress response regulator rpoS. We identified 46 unique single-nucleotide variants of arcA and 18 mutations in rpoS, nine of which resulted in stop codons or large deletions, suggesting that a subtle modulation of ArcA function and knockouts of rpoS are largely responsible for the metabolic shifts leading to adaptation. These mutations allow a higher order “metabolic selection” that eliminates epistatic bottlenecks, which could occur when many changes would be required. Proteomic and carbohydrate analysis of adapting E. coli populations revealed an up-regulation of enzymes associated with the TCA cycle and amino acid metabolism and an increase in the secretion of putrescine. The overall effect of adaptation across populations is to redirect and efficiently utilize uptake and catabolism of abundant amino acids. Concomitantly, there is a pronounced spread of more ecologically limited strains that results from specialization through metabolic erosion. Remarkably, the global regulators arcA and rpoS can provide a “one-step” mechanism of adaptation to a novel

  18. Protein phosphorylation and prevention of cytochrome oxidase inhibition by ATP: coupled mechanisms of energy metabolism regulation.

    PubMed

    Acin-Perez, Rebeca; Gatti, Domenico L; Bai, Yidong; Manfredi, Giovanni

    2011-06-01

    Rapid regulation of oxidative phosphorylation is crucial for mitochondrial adaptation to swift changes in fuels availability and energy demands. An intramitochondrial signaling pathway regulates cytochrome oxidase (COX), the terminal enzyme of the respiratory chain, through reversible phosphorylation. We find that PKA-mediated phosphorylation of a COX subunit dictates mammalian mitochondrial energy fluxes and identify the specific residue (S58) of COX subunit IV-1 (COXIV-1) that is involved in this mechanism of metabolic regulation. Using protein mutagenesis, molecular dynamics simulations, and induced fit docking, we show that mitochondrial energy metabolism regulation by phosphorylation of COXIV-1 is coupled with prevention of COX allosteric inhibition by ATP. This regulatory mechanism is essential for efficient oxidative metabolism and cell survival. We propose that S58 COXIV-1 phosphorylation has evolved as a metabolic switch that allows mammalian mitochondria to rapidly toggle between energy utilization and energy storage.

  19. Mutations in Global Regulators Lead to Metabolic Selection during Adaptation to Complex Environments

    PubMed Central

    Saxer, Gerda; Krepps, Michael D.; Merkley, Eric D.; Ansong, Charles; Deatherage Kaiser, Brooke L.; Valovska, Marie-Thérèse; Ristic, Nikola; Yeh, Ping T.; Prakash, Vittal P.; Leiser, Owen P.; Nakhleh, Luay; Gibbons, Henry S.; Kreuzer, Helen W.; Shamoo, Yousif

    2014-01-01

    Adaptation to ecologically complex environments can provide insights into the evolutionary dynamics and functional constraints encountered by organisms during natural selection. Adaptation to a new environment with abundant and varied resources can be difficult to achieve by small incremental changes if many mutations are required to achieve even modest gains in fitness. Since changing complex environments are quite common in nature, we investigated how such an epistatic bottleneck can be avoided to allow rapid adaptation. We show that adaptive mutations arise repeatedly in independently evolved populations in the context of greatly increased genetic and phenotypic diversity. We go on to show that weak selection requiring substantial metabolic reprogramming can be readily achieved by mutations in the global response regulator arcA and the stress response regulator rpoS. We identified 46 unique single-nucleotide variants of arcA and 18 mutations in rpoS, nine of which resulted in stop codons or large deletions, suggesting that subtle modulations of ArcA function and knockouts of rpoS are largely responsible for the metabolic shifts leading to adaptation. These mutations allow a higher order metabolic selection that eliminates epistatic bottlenecks, which could occur when many changes would be required. Proteomic and carbohydrate analysis of adapting E. coli populations revealed an up-regulation of enzymes associated with the TCA cycle and amino acid metabolism, and an increase in the secretion of putrescine. The overall effect of adaptation across populations is to redirect and efficiently utilize uptake and catabolism of abundant amino acids. Concomitantly, there is a pronounced spread of more ecologically limited strains that results from specialization through metabolic erosion. Remarkably, the global regulators arcA and rpoS can provide a “one-step” mechanism of adaptation to a novel environment, which highlights the importance of global resource management

  20. Melatonin, energy metabolism, and obesity: a review.

    PubMed

    Cipolla-Neto, J; Amaral, F G; Afeche, S C; Tan, D X; Reiter, R J

    2014-05-01

    Melatonin is an old and ubiquitous molecule in nature showing multiple mechanisms of action and functions in practically every living organism. In mammals, pineal melatonin functions as a hormone and a chronobiotic, playing a major role in the regulation of the circadian temporal internal order. The anti-obesogen and the weight-reducing effects of melatonin depend on several mechanisms and actions. Experimental evidence demonstrates that melatonin is necessary for the proper synthesis, secretion, and action of insulin. Melatonin acts by regulating GLUT4 expression and/or triggering, via its G-protein-coupled membrane receptors, the phosphorylation of the insulin receptor and its intracellular substrates mobilizing the insulin-signaling pathway. Melatonin is a powerful chronobiotic being responsible, in part, by the daily distribution of metabolic processes so that the activity/feeding phase of the day is associated with high insulin sensitivity, and the rest/fasting is synchronized to the insulin-resistant metabolic phase of the day. Furthermore, melatonin is responsible for the establishment of an adequate energy balance mainly by regulating energy flow to and from the stores and directly regulating the energy expenditure through the activation of brown adipose tissue and participating in the browning process of white adipose tissue. The reduction in melatonin production, as during aging, shift-work or illuminated environments during the night, induces insulin resistance, glucose intolerance, sleep disturbance, and metabolic circadian disorganization characterizing a state of chronodisruption leading to obesity. The available evidence supports the suggestion that melatonin replacement therapy might contribute to restore a more healthy state of the organism.

  1. Mitochondrial uncoupling proteins and energy metabolism

    PubMed Central

    Busiello, Rosa A.; Savarese, Sabrina; Lombardi, Assunta

    2015-01-01

    Understanding the metabolic factors that contribute to energy metabolism (EM) is critical for the development of new treatments for obesity and related diseases. Mitochondrial oxidative phosphorylation is not perfectly coupled to ATP synthesis, and the process of proton-leak plays a crucial role. Proton-leak accounts for a significant part of the resting metabolic rate (RMR) and therefore enhancement of this process represents a potential target for obesity treatment. Since their discovery, uncoupling proteins have stimulated great interest due to their involvement in mitochondrial-inducible proton-leak. Despite the widely accepted uncoupling/thermogenic effect of uncoupling protein one (UCP1), which was the first in this family to be discovered, the reactions catalyzed by its homolog UCP3 and the physiological role remain under debate. This review provides an overview of the role played by UCP1 and UCP3 in mitochondrial uncoupling/functionality as well as EM and suggests that they are a potential therapeutic target for treating obesity and its related diseases such as type II diabetes mellitus. PMID:25713540

  2. Understanding diversity of hepatic metabolism and related adaptations in the early lactating dairy cow.

    PubMed

    van Dorland, H A; Bruckmaier, R M

    2013-08-01

    The onset of lactation in dairy cows represents a major metabolic challenge that involves large adaptations in glucose, fatty acid, and mineral metabolism to support lactation and to avoid metabolic dysfunction. The complex system of adaptation can differ considerably between cows, and may have a genetic base. In the present review, the variation in adaptive reactions in dairy cows is discussed. In these studies, the liver being a key metabolic regulator for understanding the variation in adaptive performance of the dairy cow was the main focus of research. Liver function was evaluated through gene expression measurements; to explain the associated phenotypic variability and to identify descriptors for metabolic robustness in dairy cows. Hence, the identified genes involved act as a connecting link between the genotype encoded on the DNA and the phenotypic expression of the target factors at a protein level. The integration of phenotypic data, including gene expression profiles, and genomic data will facilitate a better characterization of the complex interplay between these levels, and will improve the genetic understanding necessary to unravel a certain trait or multi-trait such as metabolic robustness in dairy cows.

  3. Energy metabolism and the high-altitude environment.

    PubMed

    Murray, Andrew J

    2016-01-01

    At high altitude the barometric pressure falls, challenging oxygen delivery to the tissues. Thus, whilst hypoxia is not the only physiological stress encountered at high altitude, low arterial P(O2) is a sustained feature, even after allowing adequate time for acclimatization. Cardiac and skeletal muscle energy metabolism is altered in subjects at, or returning from, high altitude. In the heart, energetic reserve falls, as indicated by lower phosphocreatine-to-ATP ratios. The underlying mechanism is unknown, but in the hypoxic rat heart fatty acid oxidation and respiratory capacity are decreased, whilst pyruvate oxidation is also lower after sustained hypoxic exposure. In skeletal muscle, there is not a consensus. With prolonged exposure to extreme high altitude (>5500 m) a loss of muscle mitochondrial density is seen, but this was not observed in a simulated ascent of Everest in hypobaric chambers. At more moderate high altitude, decreased respiratory capacity may occur without changes in mitochondrial volume density, and fat oxidation may be downregulated, although this is not seen in all studies. The underlying mechanisms, including the possible role of hypoxia-signalling pathways, remain to be resolved, particularly in light of confounding factors in the high-altitude environment. In high-altitude-adapted Tibetan natives, however, there is evidence of natural selection centred around the hypoxia-inducible factor pathway, and metabolic features in this population (e.g. low cardiac phosphocreatine-to-ATP ratios, increased cardiac glucose uptake and lower muscle mitochondrial densities) share similarities with those in acclimatized lowlanders, supporting a possible role for the hypoxia-inducible factor pathway in the metabolic response of cardiac and skeletal muscle energy metabolism to high altitude. PMID:26315373

  4. Energy metabolism and the high-altitude environment.

    PubMed

    Murray, Andrew J

    2016-01-01

    At high altitude the barometric pressure falls, challenging oxygen delivery to the tissues. Thus, whilst hypoxia is not the only physiological stress encountered at high altitude, low arterial P(O2) is a sustained feature, even after allowing adequate time for acclimatization. Cardiac and skeletal muscle energy metabolism is altered in subjects at, or returning from, high altitude. In the heart, energetic reserve falls, as indicated by lower phosphocreatine-to-ATP ratios. The underlying mechanism is unknown, but in the hypoxic rat heart fatty acid oxidation and respiratory capacity are decreased, whilst pyruvate oxidation is also lower after sustained hypoxic exposure. In skeletal muscle, there is not a consensus. With prolonged exposure to extreme high altitude (>5500 m) a loss of muscle mitochondrial density is seen, but this was not observed in a simulated ascent of Everest in hypobaric chambers. At more moderate high altitude, decreased respiratory capacity may occur without changes in mitochondrial volume density, and fat oxidation may be downregulated, although this is not seen in all studies. The underlying mechanisms, including the possible role of hypoxia-signalling pathways, remain to be resolved, particularly in light of confounding factors in the high-altitude environment. In high-altitude-adapted Tibetan natives, however, there is evidence of natural selection centred around the hypoxia-inducible factor pathway, and metabolic features in this population (e.g. low cardiac phosphocreatine-to-ATP ratios, increased cardiac glucose uptake and lower muscle mitochondrial densities) share similarities with those in acclimatized lowlanders, supporting a possible role for the hypoxia-inducible factor pathway in the metabolic response of cardiac and skeletal muscle energy metabolism to high altitude.

  5. Adaptation to Low Temperature Exposure Increases Metabolic Rates Independently of Growth Rates.

    PubMed

    Williams, Caroline M; Szejner-Sigal, Andre; Morgan, Theodore J; Edison, Arthur S; Allison, David B; Hahn, Daniel A

    2016-07-01

    Metabolic cold adaptation is a pattern where ectotherms from cold, high-latitude, or -altitude habitats have higher metabolic rates than ectotherms from warmer habitats. When found, metabolic cold adaptation is often attributed to countergradient selection, wherein short, cool growing seasons select for a compensatory increase in growth rates and development times of ectotherms. Yet, ectotherms in high-latitude and -altitude environments face many challenges in addition to thermal and time constraints on lifecycles. In addition to short, cool growing seasons, high-latitude and - altitude environments are characterized by regular exposure to extreme low temperatures, which cause ectotherms to enter a transient state of immobility termed chill coma. The ability to resume activity quickly after chill coma increases with latitude and altitude in patterns consistent with local adaptation to cold conditions. We show that artificial selection for fast and slow chill coma recovery among lines of the fly Drosophila melanogaster also affects rates of respiratory metabolism. Cold-hardy fly lines, with fast recovery from chill coma, had higher respiratory metabolic rates than control lines, with cold-susceptible slow-recovering lines having the lowest metabolic rates. Fast chill coma recovery was also associated with higher respiratory metabolism in a set of lines derived from a natural population. Although their metabolic rates were higher than control lines, fast-recovering cold-hardy lines did not have faster growth rates or development times than control lines. This suggests that raised metabolic rates in high-latitude and -altitude species may be driven by adaptation to extreme low temperatures, illustrating the importance of moving "Beyond the Mean". PMID:27103615

  6. Is there metabolic cold adaptation in terrestrial ectotherms? Exploring latitudinal compensation in the invasive snail Cornu aspersum.

    PubMed

    Gaitán-Espitia, Juan Diego; Nespolo, Roberto

    2014-07-01

    Lower temperatures, extreme seasonality and shorter growing seasons at higher latitudes are expected to cause a decline in metabolic rates and annual growth rates of ectotherms. If a reduction in the rates of these biological processes involves a reduction in fitness, then organisms may evolve compensatory responses for the constraints imposed by high-latitude habitats. To test the existence of a latitudinal compensation in ectotherms, we used a common-garden experiment to investigate the extent to which the level of energy turnover (measured as standard metabolic rate, SMR) and the energy budget (energy allocation to growth) are affected by climatic constraints in three populations of the land snail Cornu aspersum, distributed across a latitudinal gradient of 1300 km in Chile. Our results did not support the existence of a latitudinal compensation in metabolic rates (metabolic cold adaptation). However, there was a countergradient variation (CnGV) for growth rate in which the highest latitudinal population exhibited greater growth rates than their counterparts from lower latitudes. Surprisingly, this CnGV pattern was accompanied by a lower apparent dry-matter digestibility, which could highlight a differential assimilation of ingested nutrients into somatic tissue, revealing enhanced growth efficiency in snails from the highest latitudinal habitat. Our evidence highlights that adjustments in energy allocation to the digestive machinery and to protein storage could act as a latitudinal compensation for enhanced growth efficiency in snails from the highest latitudinal population.

  7. Metabolic Adaptation of the Small Intestine to Short- and Medium-Term High-Fat Diet Exposure.

    PubMed

    Clara, Rosmarie; Schumacher, Manuel; Ramachandran, Deepti; Fedele, Shahana; Krieger, Jean-Philippe; Langhans, Wolfgang; Mansouri, Abdelhak

    2017-01-01

    The small intestine is the main organ involved in the digestion and absorption of nutrients. It is in an ideal position to sense the availability of energy in the lumen in addition to its absorptive function. Consumption of a high-fat diet (HFD) influences the metabolic characteristics of the small intestine. Therefore, to better understand the metabolic features of the small intestine and their changes in response to dietary fat, we characterized the metabolism of duodenal, jejunal, and hepatic cell lines and assessed the metabolic changes in the enterocytes and the liver after short-term (3 days) or medium-term (14 days) HFD feeding in mice. Experiments with immortalized enterocytes indicated a higher glycolytic capacity in the duodenal cell line compared to the other two cell lines, whereas the jejunal cell line exhibited a high oxidative metabolism. Short-term HFD feeding induced changes in the expression of glucose and lipid metabolism-related genes in the duodenum and the jejunum of mice, but not in the liver. When focusing on fatty acid oxidation both, short- and medium-term HFD feeding induced an upregulation of 3-hydroxy-3-methylglutaryl-coenzyme A, the key enzyme of ketogenesis, at the protein level in the intestinal epithelial cells, but not in the liver. These results suggest that HFD feeding induces an early adaptation of the small intestine rather than the liver in response to a substantial fat load. This highlights the importance of the small intestine in the adaptation of the body to the metabolic changes induced by HFD exposure. J. Cell. Physiol. 232: 167-175, 2017. © 2016 Wiley Periodicals, Inc. PMID:27061934

  8. Metabolic Adaptation of the Small Intestine to Short- and Medium-Term High-Fat Diet Exposure.

    PubMed

    Clara, Rosmarie; Schumacher, Manuel; Ramachandran, Deepti; Fedele, Shahana; Krieger, Jean-Philippe; Langhans, Wolfgang; Mansouri, Abdelhak

    2017-01-01

    The small intestine is the main organ involved in the digestion and absorption of nutrients. It is in an ideal position to sense the availability of energy in the lumen in addition to its absorptive function. Consumption of a high-fat diet (HFD) influences the metabolic characteristics of the small intestine. Therefore, to better understand the metabolic features of the small intestine and their changes in response to dietary fat, we characterized the metabolism of duodenal, jejunal, and hepatic cell lines and assessed the metabolic changes in the enterocytes and the liver after short-term (3 days) or medium-term (14 days) HFD feeding in mice. Experiments with immortalized enterocytes indicated a higher glycolytic capacity in the duodenal cell line compared to the other two cell lines, whereas the jejunal cell line exhibited a high oxidative metabolism. Short-term HFD feeding induced changes in the expression of glucose and lipid metabolism-related genes in the duodenum and the jejunum of mice, but not in the liver. When focusing on fatty acid oxidation both, short- and medium-term HFD feeding induced an upregulation of 3-hydroxy-3-methylglutaryl-coenzyme A, the key enzyme of ketogenesis, at the protein level in the intestinal epithelial cells, but not in the liver. These results suggest that HFD feeding induces an early adaptation of the small intestine rather than the liver in response to a substantial fat load. This highlights the importance of the small intestine in the adaptation of the body to the metabolic changes induced by HFD exposure. J. Cell. Physiol. 232: 167-175, 2017. © 2016 Wiley Periodicals, Inc.

  9. Cold climate specialization: adaptive covariation between metabolic rate and thermoregulation in pregnant vipers.

    PubMed

    Lourdais, Olivier; Guillon, Michaël; Denardo, Dale; Blouin-Demers, Gabriel

    2013-07-01

    We compared thermoregulatory strategies during pregnancy in two congeneric viperid snakes (Vipera berus and Vipera aspis) with parapatric geographic ranges. V. berus is a boreal specialist with the largest known distribution among terrestrial snakes while V. aspis is a south-European species. Despite contrasted climatic affinities, the two species displayed identical thermal preferences (Tset) in a laboratory thermal gradient. Under identical natural conditions, however, V. berus was capable of maintaining Tset for longer periods, especially when the weather was constraining. Consistent with the metabolic cold adaptation hypothesis, V. berus displayed higher standard metabolic rate at all temperatures considered. We used the thermal dependence of metabolic rate to calculate daily metabolic profiles from body temperature under natural conditions. The boreal specialist experienced higher daily metabolic rate and minimized gestation duration chiefly because of differences in the metabolic reaction norms, but also superior thermoregulatory efficiency. Under cold climates, thermal constraints should make precise thermoregulation costly. However, a shift in the metabolic reaction norm may compensate for thermal constraints and modify the cost-benefit balance of thermoregulation. Covariation between metabolic rate and thermoregulation efficiency is likely an important adaptation to cold climates.

  10. Dynamic adaption of metabolic pathways during germination and growth of lily pollen tubes after inhibition of the electron transport chain.

    PubMed

    Obermeyer, Gerhard; Fragner, Lena; Lang, Veronika; Weckwerth, Wolfram

    2013-08-01

    Investigation of the metabolome and the transcriptome of pollen of lily (Lilium longiflorum) gave a comprehensive overview of metabolic pathways active during pollen germination and tube growth. More than 100 different metabolites were determined simultaneously by gas chromatography coupled to mass spectrometry, and expressed genes of selected metabolic pathways were identified by next-generation sequencing of lily pollen transcripts. The time-dependent changes in metabolite abundances, as well as the changes after inhibition of the mitochondrial electron transport chain, revealed a fast and dynamic adaption of the metabolic pathways in the range of minutes. The metabolic state prior to pollen germination differed clearly from the metabolic state during pollen tube growth, as indicated by principal component analysis of all detected metabolites and by detailed observation of individual metabolites. For instance, the amount of sucrose increased during the first 60 minutes of pollen culture but decreased during tube growth, while glucose and fructose showed the opposite behavior. Glycolysis, tricarbonic acid cycle, glyoxylate cycle, starch, and fatty acid degradation were activated, providing energy during pollen germination and tube growth. Inhibition of the mitochondrial electron transport chain by antimycin A resulted in an immediate production of ethanol and a fast rearrangement of metabolic pathways, which correlated with changes in the amounts of the majority of identified metabolites, e.g. a rapid increase in γ-aminobutyric acid indicated the activation of a γ-aminobutyric acid shunt in the tricarbonic acid cycle, while ethanol fermentation compensated the reduced ATP production after inhibition of the oxidative phosphorylation.

  11. Dietary composition and physiologic adaptations to energy restriction

    PubMed Central

    Agus, Michael SD; Swain, Janis F; Larson, Courtney L; Eckert, Elizabeth A; Ludwig, David S

    2010-01-01

    Background The concept of a body weight set point, determined predominantly by genetic mechanisms, has been proposed to explain the poor long-term results of conventional energy-restricted diets in the treatment of obesity. Objective The objective of this study was to examine whether dietary composition affects hormonal and metabolic adaptations to energy restriction. Design A randomized, crossover design was used to compare the effects of a high-glycemic-index (high-GI) and a low-glycemic-index (low-GI) energy-restricted diet. The macronutrient composition of the high-GI diet was (as percent of energy) 67% carbohydrate, 15% protein, and 18% fat and that of the low-GI diet was 43% carbohydrate, 27% protein, and 30% fat; the diets had similar total energy, energy density, and fiber contents. The subjects, 10 moderately overweight young men, were studied for 9 d on 2 separate occasions. On days −1 to 0, they consumed self-selected foods ad libitum. On days 1–6, they received an energy-restricted high- or low-GI diet. On days 7–8, the high-or low-GI diets were consumed ad libitum. Results Serum leptin decreased to a lesser extent from day 0 to day 6 with the high-GI diet than with the low-GI diet. Resting energy expenditure declined by 10.5% during the high-GI diet but by only 4.6% during the low-GI diet (7.38 ± 0.39 and 7.78 ± 0.36 MJ/d, respectively, on days 5–6; P = 0.04). Nitrogen balance tended to be more negative, and energy intake from snacks on days 7–8 was greater, with the high-GI than the low-GI diet. Conclusion Diets with identical energy contents can have different effects on leptin concentrations, energy expenditure, voluntary food intake, and nitrogen balance, suggesting that the physiologic adaptations to energy restriction can be modified by dietary composition. PMID:10731495

  12. Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease.

    PubMed

    Hyötyläinen, Tuulia; Jerby, Livnat; Petäjä, Elina M; Mattila, Ismo; Jäntti, Sirkku; Auvinen, Petri; Gastaldelli, Amalia; Yki-Järvinen, Hannele; Ruppin, Eytan; Orešič, Matej

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a major risk factor leading to chronic liver disease and type 2 diabetes. Here we chart liver metabolic activity and functionality in NAFLD by integrating global transcriptomic data, from human liver biopsies, and metabolic flux data, measured across the human splanchnic vascular bed, within a genome-scale model of human metabolism. We show that an increased amount of liver fat induces mitochondrial metabolism, lipolysis, glyceroneogenesis and a switch from lactate to glycerol as substrate for gluconeogenesis, indicating an intricate balance of exacerbated opposite metabolic processes in glycemic regulation. These changes were associated with reduced metabolic adaptability on a network level in the sense that liver fat accumulation puts increasing demands on the liver to adaptively regulate metabolic responses to maintain basic liver functions. We propose that failure to meet excessive metabolic challenges coupled with reduced metabolic adaptability may lead to a vicious pathogenic cycle leading to the co-morbidities of NAFLD. PMID:26839171

  13. Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease

    PubMed Central

    Hyötyläinen, Tuulia; Jerby, Livnat; Petäjä, Elina M.; Mattila, Ismo; Jäntti, Sirkku; Auvinen, Petri; Gastaldelli, Amalia; Yki-Järvinen, Hannele; Ruppin, Eytan; Orešič, Matej

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a major risk factor leading to chronic liver disease and type 2 diabetes. Here we chart liver metabolic activity and functionality in NAFLD by integrating global transcriptomic data, from human liver biopsies, and metabolic flux data, measured across the human splanchnic vascular bed, within a genome-scale model of human metabolism. We show that an increased amount of liver fat induces mitochondrial metabolism, lipolysis, glyceroneogenesis and a switch from lactate to glycerol as substrate for gluconeogenesis, indicating an intricate balance of exacerbated opposite metabolic processes in glycemic regulation. These changes were associated with reduced metabolic adaptability on a network level in the sense that liver fat accumulation puts increasing demands on the liver to adaptively regulate metabolic responses to maintain basic liver functions. We propose that failure to meet excessive metabolic challenges coupled with reduced metabolic adaptability may lead to a vicious pathogenic cycle leading to the co-morbidities of NAFLD. PMID:26839171

  14. Phylogeography, Salinity Adaptations and Metabolic Potential of the Candidate Division KB1 Bacteria Based on a Partial Single Cell Genome.

    PubMed

    Nigro, Lisa M; Hyde, Andrew S; MacGregor, Barbara J; Teske, Andreas

    2016-01-01

    Deep-sea hypersaline anoxic basins and other hypersaline environments contain abundant and diverse microbial life that has adapted to these extreme conditions. The bacterial Candidate Division KB1 represents one of several uncultured groups that have been consistently observed in hypersaline microbial diversity studies. Here we report the phylogeography of KB1, its phylogenetic relationships to Candidate Division OP1 Bacteria, and its potential metabolic and osmotic stress adaptations based on a partial single cell amplified genome of KB1 from Orca Basin, the largest hypersaline seafloor brine basin in the Gulf of Mexico. Our results are consistent with the hypothesis - previously developed based on (14)C incorporation experiments with mixed-species enrichments from Mediterranean seafloor brines - that KB1 has adapted its proteins to elevated intracellular salinity, but at the same time KB1 apparently imports glycine betaine; this compatible solute is potentially not limited to osmoregulation but could also serve as a carbon and energy source. PMID:27597842

  15. Phylogeography, Salinity Adaptations and Metabolic Potential of the Candidate Division KB1 Bacteria Based on a Partial Single Cell Genome

    PubMed Central

    Nigro, Lisa M.; Hyde, Andrew S.; MacGregor, Barbara J.; Teske, Andreas

    2016-01-01

    Deep-sea hypersaline anoxic basins and other hypersaline environments contain abundant and diverse microbial life that has adapted to these extreme conditions. The bacterial Candidate Division KB1 represents one of several uncultured groups that have been consistently observed in hypersaline microbial diversity studies. Here we report the phylogeography of KB1, its phylogenetic relationships to Candidate Division OP1 Bacteria, and its potential metabolic and osmotic stress adaptations based on a partial single cell amplified genome of KB1 from Orca Basin, the largest hypersaline seafloor brine basin in the Gulf of Mexico. Our results are consistent with the hypothesis – previously developed based on 14C incorporation experiments with mixed-species enrichments from Mediterranean seafloor brines – that KB1 has adapted its proteins to elevated intracellular salinity, but at the same time KB1 apparently imports glycine betaine; this compatible solute is potentially not limited to osmoregulation but could also serve as a carbon and energy source.

  16. Perturbative Interpretation of Adaptive Thouless-Anderson-Palmer Free Energy

    NASA Astrophysics Data System (ADS)

    Yasuda, Muneki; Takahashi, Chako; Tanaka, Kazuyuki

    2016-07-01

    In conventional well-known derivation methods for the adaptive Thouless-Anderson-Palmer (TAP) free energy, special assumptions that are difficult to mathematically justify except in some mean-field models, must be made. Here, we present a new adaptive TAP free energy derivation method. Using this derivation technique, without any special assumptions, the adaptive TAP free energy can be simply obtained as a high-temperature expansion of the Gibbs free energy.

  17. Adaptation to different types of stress converge on mitochondrial metabolism.

    PubMed

    Lahtvee, Petri-Jaan; Kumar, Rahul; Hallström, Björn M; Nielsen, Jens

    2016-08-01

    Yeast cell factories encounter physical and chemical stresses when used for industrial production of fuels and chemicals. These stresses reduce productivity and increase bioprocess costs. Understanding the mechanisms of the stress response is essential for improving cellular robustness in platform strains. We investigated the three most commonly encountered industrial stresses for yeast (ethanol, salt, and temperature) to identify the mechanisms of general and stress-specific responses under chemostat conditions in which specific growth rate-dependent changes are eliminated. By applying systems-level analysis, we found that most stress responses converge on mitochondrial processes. Our analysis revealed that stress-specific factors differ between applied stresses; however, they are underpinned by an increased ATP demand. We found that when ATP demand increases to high levels, respiration cannot provide sufficient ATP, leading to onset of respirofermentative metabolism. Although stress-specific factors increase ATP demand for cellular growth under stressful conditions, increased ATP demand for cellular maintenance underpins a general stress response and is responsible for the onset of overflow metabolism.

  18. Adaptation to different types of stress converge on mitochondrial metabolism

    PubMed Central

    Lahtvee, Petri-Jaan; Kumar, Rahul; Hallström, Björn M.; Nielsen, Jens

    2016-01-01

    Yeast cell factories encounter physical and chemical stresses when used for industrial production of fuels and chemicals. These stresses reduce productivity and increase bioprocess costs. Understanding the mechanisms of the stress response is essential for improving cellular robustness in platform strains. We investigated the three most commonly encountered industrial stresses for yeast (ethanol, salt, and temperature) to identify the mechanisms of general and stress-specific responses under chemostat conditions in which specific growth rate–dependent changes are eliminated. By applying systems-level analysis, we found that most stress responses converge on mitochondrial processes. Our analysis revealed that stress-specific factors differ between applied stresses; however, they are underpinned by an increased ATP demand. We found that when ATP demand increases to high levels, respiration cannot provide sufficient ATP, leading to onset of respirofermentative metabolism. Although stress-specific factors increase ATP demand for cellular growth under stressful conditions, increased ATP demand for cellular maintenance underpins a general stress response and is responsible for the onset of overflow metabolism. PMID:27307591

  19. Molecular evolution of aerobic energy metabolism in primates.

    PubMed

    Grossman, L I; Schmidt, T R; Wildman, D E; Goodman, M

    2001-01-01

    As part of our goal to reconstruct human evolution at the DNA level, we have been examining changes in the biochemical machinery for aerobic energy metabolism. We find that protein subunits of two of the electron transfer complexes, complex III and complex IV, and cytochrome c, the protein carrier that connects them, have all undergone a period of rapid protein evolution in the anthropoid lineage that ultimately led to humans. Indeed, subunit IV of cytochrome c oxidase (COX; complex IV) provides one of the best examples of positively selected changes of any protein studied. The rate of subunit IV evolution accelerated in our catarrhine ancestors in the period between 40 to 18 million years ago and then decelerated in the descendant hominid lineages, a pattern of rate changes indicative of positive selection of adaptive changes followed by purifying selection acting against further changes. Besides clear evidence that adaptive evolution occurred for cytochrome c and subunits of complexes III (e.g., cytochrome c(1)) and IV (e.g., COX2 and COX4), modest rate accelerations in the lineage that led to humans are seen for other subunits of both complexes. In addition the contractile muscle-specific isoform of COX subunit VIII became a pseudogene in an anthropoid ancestor of humans but appears to be a functional gene in the nonanthropoid primates. These changes in the aerobic energy complexes coincide with the expansion of the energy-dependent neocortex during the emergence of the higher primates. Discovering the biochemical adaptations suggested by molecular evolutionary analysis will be an exciting challenge.

  20. Monoterpenol Oxidative Metabolism: Role in Plant Adaptation and Potential Applications.

    PubMed

    Ilc, Tina; Parage, Claire; Boachon, Benoît; Navrot, Nicolas; Werck-Reichhart, Danièle

    2016-01-01

    Plants use monoterpenols as precursors for the production of functionally and structurally diverse molecules, which are key players in interactions with other organisms such as pollinators, flower visitors, herbivores, fungal, or microbial pathogens. For humans, many of these monoterpenol derivatives are economically important because of their pharmaceutical, nutraceutical, flavor, or fragrance applications. The biosynthesis of these derivatives is to a large extent catalyzed by enzymes from the cytochrome P450 superfamily. Here we review the knowledge on monoterpenol oxidative metabolism in plants with special focus on recent elucidations of oxidation steps leading to diverse linalool and geraniol derivatives. We evaluate the common features between oxidation pathways of these two monoterpenols, such as involvement of the CYP76 family, and highlight the differences. Finally, we discuss the missing steps and other open questions in the biosynthesis of oxygenated monoterpenol derivatives.

  1. Monoterpenol Oxidative Metabolism: Role in Plant Adaptation and Potential Applications

    PubMed Central

    Ilc, Tina; Parage, Claire; Boachon, Benoît; Navrot, Nicolas; Werck-Reichhart, Danièle

    2016-01-01

    Plants use monoterpenols as precursors for the production of functionally and structurally diverse molecules, which are key players in interactions with other organisms such as pollinators, flower visitors, herbivores, fungal, or microbial pathogens. For humans, many of these monoterpenol derivatives are economically important because of their pharmaceutical, nutraceutical, flavor, or fragrance applications. The biosynthesis of these derivatives is to a large extent catalyzed by enzymes from the cytochrome P450 superfamily. Here we review the knowledge on monoterpenol oxidative metabolism in plants with special focus on recent elucidations of oxidation steps leading to diverse linalool and geraniol derivatives. We evaluate the common features between oxidation pathways of these two monoterpenols, such as involvement of the CYP76 family, and highlight the differences. Finally, we discuss the missing steps and other open questions in the biosynthesis of oxygenated monoterpenol derivatives. PMID:27200002

  2. Metabolic adaptations to change of nutrition at birth.

    PubMed

    Girard, J

    1990-01-01

    Birth represents a dramatic change of nutrition from a fetal diet rich in carbohydrates and poor in fat to a neonatal diet rich in fat and poor in carbohydrates. Gluconeogenesis and ketogenesis are absent or very low in the fetal liver when the mother is correctly fed, and these metabolic pathways emerge after birth to reach adult values after 24 h. Gluconeogenesis increases rapidly in the liver of the newborn in parallel with the appearance of phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme of this metabolic pathway. The rise in plasma glucagon, the fall in plasma insulin and the resulting increase in liver cAMP which occur immediately after birth are the factors which induce the activation of liver PEPCK gene transcription. The appearance of ketogenesis is also controlled by the changes of plasma insulin and glucagon that increase the capacity for liver fatty acid oxidation by decreasing lipogenesis and malonyl-CoA concentration, by reducing the sensitivity of carnitine palmitoyl-CoA I to the inhibitory influence of malonyl-CoA, and by activating hydroxymethylglutaryl-CoA synthase by desuccinylation. Once liver PEPCK has reached adult value, i.e. 12 h after birth, other factors are involved in the regulation of hepatic gluconeogenesis. Indeed, the supply of gluconeogenic substrates and of free fatty acid is of crucial importance to support a high rate of gluconeogenesis and to maintain normoglycemia in the newborn. In the liver, fatty acid oxidation provides essential co-factors (acetyl-CoA, NADH and ATP) to support gluconeogenesis, and in peripheral tissue fatty acid oxidation inhibits glucose oxidation and stimulates the production of gluconeogenic precursors (lactate, pyruvate and alanine). Similar mechanisms are operative in human newborn. A defective hepatic fatty acid oxidation is likely to explain the frequent hypoglycemia observed in small-for-date neonates. Administration of oral triglycerides is an efficient mean to prevent

  3. Locomotor Adaptation Improves Balance Control, Multitasking Ability and Reduces the Metabolic Cost of Postural Instability

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Brady, R. A.; Batson, C. D.; Miller, C. A.; Ploutz-Snyder, R. J.; Guined, J. R.; Buxton, R. E.; Cohen, H. S.

    2011-01-01

    During exploration-class missions, sensorimotor disturbances may lead to disruption in the ability to ambulate and perform functional tasks during the initial introduction to a novel gravitational environment following a landing on a planetary surface. The overall goal of our current project is to develop a sensorimotor adaptability training program to facilitate rapid adaptation to these environments. We have developed a unique training system comprised of a treadmill placed on a motion-base facing a virtual visual scene. It provides an unstable walking surface combined with incongruent visual flow designed to enhance sensorimotor adaptability. Greater metabolic cost incurred during balance instability means more physical work is required during adaptation to new environments possibly affecting crewmembers? ability to perform mission critical tasks during early surface operations on planetary expeditions. The goal of this study was to characterize adaptation to a discordant sensory challenge across a number of performance modalities including locomotor stability, multi-tasking ability and metabolic cost. METHODS: Subjects (n=15) walked (4.0 km/h) on a treadmill for an 8 -minute baseline walking period followed by 20-minutes of walking (4.0 km/h) with support surface motion (0.3 Hz, sinusoidal lateral motion, peak amplitude 25.4 cm) provided by the treadmill/motion-base system. Stride frequency and auditory reaction time were collected as measures of locomotor stability and multi-tasking ability, respectively. Metabolic data (VO2) were collected via a portable metabolic gas analysis system. RESULTS: At the onset of lateral support surface motion, subj ects walking on our treadmill showed an increase in stride frequency and auditory reaction time indicating initial balance and multi-tasking disturbances. During the 20-minute adaptation period, balance control and multi-tasking performance improved. Similarly, throughout the 20-minute adaptation period, VO2 gradually

  4. Endocrine and metabolic adaptation following caesarean section or vaginal delivery.

    PubMed Central

    Bird, J. A.; Spencer, J. A.; Mould, T.; Symonds, M. E.

    1996-01-01

    The endocrine profile (umbilical venous plasma) of three groups of infants was compared. Samples were taken after eight vaginal deliveries, 11 emergency caesarean sections during labour, and 13 elective caesarean sections before labour. Mean umbilical plasma concentrations of thyroxine and triiodothyronine were significantly higher and cortisol concentration were lower after elective caesarean section compared with the two labour groups. Mean umbilical plasma thyroid stimulating hormone (TSH) concentration was significantly lower after vaginal delivery compared with elective caesarean section. These results suggest that labour reduces plasma thyroid hormone concentrations at birth in association with a rise in cortisol. These adaptations may be the stimulus for the subsequent surge in triiodothyronine previously reported to occur over the first few hours after birth in vaginally delivered infants. PMID:8777662

  5. Mutations in global regulators lead to metabolic selection during adaptation to complex environments

    SciTech Connect

    Saxer, Gerda; Krepps, Michael D.; Merkley, Eric D.; Ansong, Charles; Deatherage Kaiser, Brooke L.; Valovska, Marie -Thérèse; Ristic, Nikola; Yeh, Ping T.; Prakash, Vittal P.; Leiser, Owen P.; Nakhleh, Luay; Gibbons, Henry S.; Kreuzer, Helen W.; Shamoo, Yousif; Matic, Ivan

    2014-12-11

    Adaptation to ecologically complex environments can provide insights into the evolutionary dynamics and functional constraints encountered by organisms during natural selection. Unlike adaptation to a single limiting resource, adaptation to a new environment with abundant and varied resources can be difficult to achieve by small incremental changes since many mutations are required to achieve even modest gains in fitness. Since changing complex environments are quite common in nature, we investigated how such an epistatic bottleneck can be avoided to allow rapid adaptation. We show that adaptive mutations arise repeatedly in independently evolved populations in the context of greatly increased genetic and phenotypic diversity. We go on to show that weak selection requiring substantial metabolic reprogramming can be readily achieved by mutations in the global response regulator arcA and the stress response regulator rpoS. We identified 46 unique single-nucleotide variants of arcA and 18 mutations in rpoS, nine of which resulted in stop codons or large deletions, suggesting that a subtle modulation of ArcA function and knockouts of rpoS are largely responsible for the metabolic shifts leading to adaptation. These mutations allow a higher order “metabolic selection” that eliminates epistatic bottlenecks, which could occur when many changes would be required. Proteomic and carbohydrate analysis of adapting E. coli populations revealed an up-regulation of enzymes associated with the TCA cycle and amino acid metabolism and an increase in the secretion of putrescine. The overall effect of adaptation across populations is to redirect and efficiently utilize uptake and catabolism of abundant amino acids. Concomitantly, there is a pronounced spread of more ecologically limited strains that results from specialization through metabolic erosion. Remarkably, the global regulators arcA and rpoS can provide a

  6. Selection for increased mass-independent maximal metabolic rate suppresses innate but not adaptive immune function

    PubMed Central

    Downs, Cynthia J.; Brown, Jessi L.; Wone, Bernard; Donovan, Edward R.; Hunter, Kenneth; Hayes, Jack P.

    2013-01-01

    Both appropriate metabolic rates and sufficient immune function are essential for survival. Consequently, eco-immunologists have hypothesized that animals may experience trade-offs between metabolic rates and immune function. Previous work has focused on how basal metabolic rate (BMR) may trade-off with immune function, but maximal metabolic rate (MMR), the upper limit to aerobic activity, might also trade-off with immune function. We used mice artificially selected for high mass-independent MMR to test for trade-offs with immune function. We assessed (i) innate immune function by quantifying cytokine production in response to injection with lipopolysaccharide and (ii) adaptive immune function by measuring antibody production in response to injection with keyhole limpet haemocyanin. Selection for high mass-independent MMR suppressed innate immune function, but not adaptive immune function. However, analyses at the individual level also indicate a negative correlation between MMR and adaptive immune function. By contrast BMR did not affect immune function. Evolutionarily, natural selection may favour increasing MMR to enhance aerobic performance and endurance, but the benefits of high MMR may be offset by impaired immune function. This result could be important in understanding the selective factors acting on the evolution of metabolic rates. PMID:23303541

  7. Leptin Gene Epigenetic Adaptation to Impaired Glucose Metabolism During Pregnancy

    PubMed Central

    Bouchard, Luigi; Thibault, Stéphanie; Guay, Simon-Pierre; Santure, Marta; Monpetit, Alexandre; St-Pierre, Julie; Perron, Patrice; Brisson, Diane

    2010-01-01

    OBJECTIVE To verify whether the leptin gene epigenetic (DNA methylation) profile is altered in the offspring of mothers with gestational impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS Placental tissues and maternal and cord blood samples were obtained from 48 women at term including 23 subjects with gestational IGT. Leptin DNA methylation, gene expression levels, and circulating concentration were measured using the Sequenom EpiTYPER system, quantitative real-time RT-PCR, and enzyme-linked immunosorbent assay, respectively. IGT was assessed after a 75-g oral glucose tolerance test (OGTT) at 24–28 weeks of gestation. RESULTS We have shown that placental leptin gene DNA methylation levels were correlated with glucose levels (2-h post-OGTT) in women with IGT (fetal side: ρ = −0.44, P ≤ 0.05; maternal side: ρ = 0.53, P ≤ 0.01) and with decreased leptin gene expression (n = 48; ρ ≥ −0.30, P ≤ 0.05) in the whole cohort. Placental leptin mRNA levels accounted for 16% of the variance in maternal circulating leptin concentration (P < 0.05). CONCLUSIONS IGT during pregnancy was associated with leptin gene DNA methylation adaptations with potential functional impacts. These epigenetic changes provide novel mechanisms that could contribute to explaining the detrimental health effects associated with fetal programming, such as long-term increased risk of developing obesity and type 2 diabetes. PMID:20724651

  8. Metabolic energy requirements for space flight

    NASA Technical Reports Server (NTRS)

    Lane, Helen W.

    1992-01-01

    The international space community, including the USSR, Japan, Germany, the European Space Agency, and the US, is preparing for extended stays in space. Much of the research planned for space will be tended by humans, thus, maintaining adequate nutritional status during long stays in space has lately become an issue of much interest. Historically, it appears that minimum nutritional requirements are being met during stays in space. Thus far, crewmembers have been able to consume food adequate for maintaining nominal performance in microgravity. The physiological data obtained from ground-based and flight research that may enable us to understand the biochemical alterations that effect energy utilization and performance. Focus is on energy utilization during the Apollo lunar missions, Skylab's extended space lab missions, and Space Shuttle flights. Available data includes those recorded during intra- and extravehicular activities as well as during microgravity simulation (bed rest). Data on metabolism during flight and during bed rest are discussed, with a follow-up on human gastrointestinal function.

  9. [Energy metabolism of Ehrlich ascites cancer cells].

    PubMed

    del Pozo, A M; Valladares, Y; Alvarez Rodríguez, Y

    1983-01-01

    Cell respiration (CR) and glycolysis (GL) are the main sources cell energy, since along their metabolic pathways ATP is produced. Expressed as microM/100 mg/h, normal cells produce 63 by CR, 0.2 by aerobic GL, and 9.37 by anaerobic GL, while cancer cells produce 35 by CR, 18 by aerobic GL, and 29 by anaerobic GL. The ascites fluid from EAC increases the anaerobic GL to 38, while it does not change the aerobic GL to 7 and diminishes the CR to 26. Insulin produces a lowering of CR to 26, aerobic GL to 26 and anaerobic GL to 22. Glucose inhibits CR and stimulates GL. Ribose does not modify CR and inhibits GL. Mannose inhibits both CR and GL. Ribonuclease increases GL in the presence of glucose but not of ribose. Glucose-phosphate and ribose-phosphate have no action because they do not enter into the cell. Expressed as QLN2/100 mg, the main localization of GL is the cytosol (480), but it is significant in the nucleus (170), and diminishes in microsomes (100) and mitochondria (52). Mitochondria inhibit the cytosol glycolytic activity when they are either in the usual proportion they have in the cell or in a higher proportion. It is curious the observation that a diminution of the relative concentration of mitochondria with regard to cytosol (1/100 to 1/1000) produces a marked increase of GL. The addition of nuclear fraction stabilizes the cytosol-mitochondria complex and modifies the metabolic pathway of the CO2 that is produced during the GL.

  10. The Gut Microbiota Modulates Energy Metabolism in the Hibernating Brown Bear Ursus arctos.

    PubMed

    Sommer, Felix; Ståhlman, Marcus; Ilkayeva, Olga; Arnemo, Jon M; Kindberg, Jonas; Josefsson, Johan; Newgard, Christopher B; Fröbert, Ole; Bäckhed, Fredrik

    2016-02-23

    Hibernation is an adaptation that helps many animals to conserve energy during food shortage in winter. Brown bears double their fat depots during summer and use these stored lipids during hibernation. Although bears seasonally become obese, they remain metabolically healthy. We analyzed the microbiota of free-ranging brown bears during their active phase and hibernation. Compared to the active phase, hibernation microbiota had reduced diversity, reduced levels of Firmicutes and Actinobacteria, and increased levels of Bacteroidetes. Several metabolites involved in lipid metabolism, including triglycerides, cholesterol, and bile acids, were also affected by hibernation. Transplantation of the bear microbiota from summer and winter to germ-free mice transferred some of the seasonal metabolic features and demonstrated that the summer microbiota promoted adiposity without impairing glucose tolerance, suggesting that seasonal variation in the microbiota may contribute to host energy metabolism in the hibernating brown bear. PMID:26854221

  11. Adaptive Changes in Basal Metabolic Rate in Humans in Different Eco-Geographical Areas.

    PubMed

    Maximov, Arkady L; Belkin, Victor Sh; Kalichman, Leonid; Kobyliansky, Eugene D

    2015-12-01

    Our aim was to establish whether the human basal metabolic rate (BMR) shifts towards the reduction of vital functions as an adaptation response to extreme environmental conditions. Data was collected in arid and Extreme North zones. The arid zone samples included Bedouins living in the Sinai Peninsula in Egypt, Turkmen students, the Pedagogical University of Chardzhou, Turkmenistan born Russians and Russian soldiers. Soldiers were divided into 3 groups according to the length of their tour of duty in the area: 1st group: up to six months, 2nd group: up to 2 years and the 3rd group: 3-5 years. The Extreme North samples comprised Chukchi natives, 1st generation Russian immigrants born in the area and 3 groups of soldiers comparable to the soldiers from Turkmenistan. BMR values of the new recruits had the highest values of total and relative BMR (1769 ± 16 and 28.3 ± 0.6, correspondingly). The total and relative BMR tended to decrease within a longer adaptation period. The BMR values of officers who served >3 years in Turkmenistan were very similar to the Turkmenistan born Russians (1730 ± 14 vs. 1726 ± 18 and 26.5 ± 0.6 vs. 27.3 ± 0.7, correspondingly). Similarly, in Chukotka, the highest relative BMR was found in the new recruits, serving up to 6 months (28.1 ± 0.7) and was significantly (p < 0.05) lower in the Russians serving in Chukotka over 1.5 years (27.1 ± 0.3). The BMR was virtually similar in Russian officers serving > 3 years, compared to the middle-aged Chukchi or Chukotka-born Russians (25.8 ± 0.5 vs. 25.6 ± 0.5 and 25.5 ± 0.6, correspondingly). The BMR parameters demonstrated a stronger association with body weight than with age. In extreme environmental conditions, migrant populations showed a decrease in BMR, thus reducing its vital functions. The BMR reduction effect with the adequate adaptive transformation is likely to be the key strategy for developing programs to facilitate human and animal adaptation to extreme factors. This process is

  12. Metabolism

    MedlinePlus

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

  13. p300 is not required for metabolic adaptation to endurance exercise training.

    PubMed

    LaBarge, Samuel A; Migdal, Christopher W; Buckner, Elisa H; Okuno, Hiroshi; Gertsman, Ilya; Stocks, Ben; Barshop, Bruce A; Nalbandian, Sarah R; Philp, Andrew; McCurdy, Carrie E; Schenk, Simon

    2016-04-01

    The acetyltransferase, E1a-binding protein (p300), is proposed to regulate various aspects of skeletal muscle development, metabolism, and mitochondrial function,viaits interaction with numerous transcriptional regulators and other proteins. Remarkably, however, the contribution of p300 to skeletal muscle function and metabolism,in vivo, is poorly understood. To address this, we used Cre-LoxP methodology to generate mice with skeletal muscle-specific knockout of E1a-binding protein (mKO). mKO mice were indistinguishable from their wild-type/floxed littermates, with no differences in lean mass, skeletal muscle structure, fiber type, respirometry flux, or metabolites of fatty acid and amino acid metabolism.Ex vivomuscle function in extensor digitorum longus and soleus muscles, including peak stress and time to fatigue, as well asin vivorunning capacity were also comparable. Moreover, expected adaptations to a 20 d voluntary wheel running regime were not compromised in mKO mice. Taken together, these findings demonstrate that p300 is not required for the normal development or functioning of adult skeletal muscle, nor is it required for endurance exercise-mediated mitochondrial adaptations.-LaBarge, S. A., Migdal, C. W., Buckner, E. H., Okuno, H., Gertsman, I., Stocks, B., Barshop, B. A., Nalbandian, S. R., Philp, A., McCurdy, C. E., Schenk, S. p300 is not required for metabolic adaptation to endurance exercise training.

  14. Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation.

    PubMed

    Kreft, Marko; Bak, Lasse K; Waagepetersen, Helle S; Schousboe, Arne

    2012-04-27

    Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation.

  15. The role of astrocytes in the hypothalamic response and adaptation to metabolic signals.

    PubMed

    Chowen, Julie A; Argente-Arizón, Pilar; Freire-Regatillo, Alejandra; Frago, Laura M; Horvath, Tamas L; Argente, Jesús

    2016-09-01

    The hypothalamus is crucial in the regulation of homeostatic functions in mammals, with the disruption of hypothalamic circuits contributing to chronic conditions such as obesity, diabetes mellitus, hypertension, and infertility. Metabolic signals and hormonal inputs drive functional and morphological changes in the hypothalamus in attempt to maintain metabolic homeostasis. However, the dramatic increase in the incidence of obesity and its secondary complications, such as type 2 diabetes, have evidenced the need to better understand how this system functions and how it can go awry. Growing evidence points to a critical role of astrocytes in orchestrating the hypothalamic response to metabolic cues by participating in processes of synaptic transmission, synaptic plasticity and nutrient sensing. These glial cells express receptors for important metabolic signals, such as the anorexigenic hormone leptin, and determine the type and quantity of nutrients reaching their neighboring neurons. Understanding the mechanisms by which astrocytes participate in hypothalamic adaptations to changes in dietary and metabolic signals is fundamental for understanding the neuroendocrine control of metabolism and key in the search for adequate treatments of metabolic diseases.

  16. Coregulation of host-adapted metabolism and virulence by pathogenic yersiniae.

    PubMed

    Heroven, Ann Kathrin; Dersch, Petra

    2014-01-01

    Deciphering the principles how pathogenic bacteria adapt their metabolism to a specific host microenvironment is critical for understanding bacterial pathogenesis. The enteric pathogenic Yersinia species Yersinia pseudotuberculosis and Yersinia enterocolitica and the causative agent of plague, Yersinia pestis, are able to survive in a large variety of environmental reservoirs (e.g., soil, plants, insects) as well as warm-blooded animals (e.g., rodents, pigs, humans) with a particular preference for lymphatic tissues. In order to manage rapidly changing environmental conditions and interbacterial competition, Yersinia senses the nutritional composition during the course of an infection by special molecular devices, integrates this information and adapts its metabolism accordingly. In addition, nutrient availability has an impact on expression of virulence genes in response to C-sources, demonstrating a tight link between the pathogenicity of yersiniae and utilization of nutrients. Recent studies revealed that global regulatory factors such as the cAMP receptor protein (Crp) and the carbon storage regulator (Csr) system are part of a large network of transcriptional and posttranscriptional control strategies adjusting metabolic changes and virulence in response to temperature, ion and nutrient availability. Gained knowledge about the specific metabolic requirements and the correlation between metabolic and virulence gene expression that enable efficient host colonization led to the identification of new potential antimicrobial targets. PMID:25368845

  17. Coregulation of host-adapted metabolism and virulence by pathogenic yersiniae

    PubMed Central

    Heroven, Ann Kathrin; Dersch, Petra

    2014-01-01

    Deciphering the principles how pathogenic bacteria adapt their metabolism to a specific host microenvironment is critical for understanding bacterial pathogenesis. The enteric pathogenic Yersinia species Yersinia pseudotuberculosis and Yersinia enterocolitica and the causative agent of plague, Yersinia pestis, are able to survive in a large variety of environmental reservoirs (e.g., soil, plants, insects) as well as warm-blooded animals (e.g., rodents, pigs, humans) with a particular preference for lymphatic tissues. In order to manage rapidly changing environmental conditions and interbacterial competition, Yersinia senses the nutritional composition during the course of an infection by special molecular devices, integrates this information and adapts its metabolism accordingly. In addition, nutrient availability has an impact on expression of virulence genes in response to C-sources, demonstrating a tight link between the pathogenicity of yersiniae and utilization of nutrients. Recent studies revealed that global regulatory factors such as the cAMP receptor protein (Crp) and the carbon storage regulator (Csr) system are part of a large network of transcriptional and posttranscriptional control strategies adjusting metabolic changes and virulence in response to temperature, ion and nutrient availability. Gained knowledge about the specific metabolic requirements and the correlation between metabolic and virulence gene expression that enable efficient host colonization led to the identification of new potential antimicrobial targets. PMID:25368845

  18. Integration of Posttranscriptional Gene Networks into Metabolic Adaptation and Biofilm Maturation in Candida albicans

    PubMed Central

    Harrison, Paul F.; Lo, Tricia L.; Quenault, Tara; Dagley, Michael J.; Bellousoff, Matthew; Powell, David R.; Beilharz, Traude H.; Traven, Ana

    2015-01-01

    The yeast Candida albicans is a human commensal and opportunistic pathogen. Although both commensalism and pathogenesis depend on metabolic adaptation, the regulatory pathways that mediate metabolic processes in C. albicans are incompletely defined. For example, metabolic change is a major feature that distinguishes community growth of C. albicans in biofilms compared to suspension cultures, but how metabolic adaptation is functionally interfaced with the structural and gene regulatory changes that drive biofilm maturation remains to be fully understood. We show here that the RNA binding protein Puf3 regulates a posttranscriptional mRNA network in C. albicans that impacts on mitochondrial biogenesis, and provide the first functional data suggesting evolutionary rewiring of posttranscriptional gene regulation between the model yeast Saccharomyces cerevisiae and C. albicans. A proportion of the Puf3 mRNA network is differentially expressed in biofilms, and by using a mutant in the mRNA deadenylase CCR4 (the enzyme recruited to mRNAs by Puf3 to control transcript stability) we show that posttranscriptional regulation is important for mitochondrial regulation in biofilms. Inactivation of CCR4 or dis-regulation of mitochondrial activity led to altered biofilm structure and over-production of extracellular matrix material. The extracellular matrix is critical for antifungal resistance and immune evasion, and yet of all biofilm maturation pathways extracellular matrix biogenesis is the least understood. We propose a model in which the hypoxic biofilm environment is sensed by regulators such as Ccr4 to orchestrate metabolic adaptation, as well as the regulation of extracellular matrix production by impacting on the expression of matrix-related cell wall genes. Therefore metabolic changes in biofilms might be intimately linked to a key biofilm maturation mechanism that ultimately results in untreatable fungal disease. PMID:26474309

  19. Reprogramming of energy metabolism as a driver of aging.

    PubMed

    Feng, Zhaoyang; Hanson, Richard W; Berger, Nathan A; Trubitsyn, Alexander

    2016-03-29

    Aging is characterized by progressive loss of cellular function and integrity. It has been thought to be driven by stochastic molecular damage. However, genetic and environmental maneuvers enhancing mitochondrial function or inhibiting glycolysis extend lifespan and promote healthy aging in many species. In post-fertile Caenorhabditis elegans, a progressive decline in phosphoenolpyruvate carboxykinase with age, and a reciprocal increase in pyruvate kinase shunt energy metabolism from oxidative metabolism to anaerobic glycolysis. This reduces the efficiency and total of energy generation. As a result, energy-dependent physical activity and other cellular functions decrease due to unmatched energy demand and supply. In return, decrease in physical activity accelerates this metabolic shift, forming a vicious cycle. This metabolic event is a determinant of aging, and is retarded by caloric restriction to counteract aging. In this review, we summarize these and other evidence supporting the idea that metabolic reprogramming is a driver of aging. We also suggest strategies to test this hypothesis. PMID:26919253

  20. Metabolic Plasticity of Metastatic Breast Cancer Cells: Adaptation to Changes in the Microenvironment1

    PubMed Central

    Simões, Rui V.; Serganova, Inna S.; Kruchevsky, Natalia; Leftin, Avigdor; Shestov, Alexander A.; Thaler, Howard T.; Sukenick, George; Locasale, Jason W.; Blasberg, Ronald G.; Koutcher, Jason A.; Ackerstaff, Ellen

    2015-01-01

    Cancer cells adapt their metabolism during tumorigenesis. We studied two isogenic breast cancer cells lines (highly metastatic 4T1; nonmetastatic 67NR) to identify differences in their glucose and glutamine metabolism in response to metabolic and environmental stress. Dynamic magnetic resonance spectroscopy of 13C-isotopomers showed that 4T1 cells have higher glycolytic and tricarboxylic acid (TCA) cycle flux than 67NR cells and readily switch between glycolysis and oxidative phosphorylation (OXPHOS) in response to different extracellular environments. OXPHOS activity increased with metastatic potential in isogenic cell lines derived from the same primary breast cancer: 4T1 > 4T07 and 168FARN (local micrometastasis only) > 67NR. We observed a restricted TCA cycle flux at the succinate dehydrogenase step in 67NR cells (but not in 4T1 cells), leading to succinate accumulation and hindering OXPHOS. In the four isogenic cell lines, environmental stresses modulated succinate dehydrogenase subunit A expression according to metastatic potential. Moreover, glucose-derived lactate production was more glutamine dependent in cell lines with higher metastatic potential. These studies show clear differences in TCA cycle metabolism between 4T1 and 67NR breast cancer cells. They indicate that metastases-forming 4T1 cells are more adept at adjusting their metabolism in response to environmental stress than isogenic, nonmetastatic 67NR cells. We suggest that the metabolic plasticity and adaptability are more important to the metastatic breast cancer phenotype than rapid cell proliferation alone, which could 1) provide a new biomarker for early detection of this phenotype, possibly at the time of diagnosis, and 2) lead to new treatment strategies of metastatic breast cancer by targeting mitochondrial metabolism. PMID:26408259

  1. Adaptation of Bacillus subtilis carbon core metabolism to simultaneous nutrient limitation and osmotic challenge: a multi-omics perspective.

    PubMed

    Kohlstedt, Michael; Sappa, Praveen K; Meyer, Hanna; Maaß, Sandra; Zaprasis, Adrienne; Hoffmann, Tamara; Becker, Judith; Steil, Leif; Hecker, Michael; van Dijl, Jan Maarten; Lalk, Michael; Mäder, Ulrike; Stülke, Jörg; Bremer, Erhard; Völker, Uwe; Wittmann, Christoph

    2014-06-01

    The Gram-positive bacterium Bacillus subtilis encounters nutrient limitations and osmotic stress in its natural soil ecosystem. To ensure survival and sustain growth, highly integrated adaptive responses are required. Here, we investigated the system-wide response of B. subtilis to different, simultaneously imposed stresses. To address the anticipated complexity of the cellular response networks, we combined chemostat experiments under conditions of carbon limitation, salt stress and osmoprotection with multi-omics analyses of the transcriptome, proteome, metabolome and fluxome. Surprisingly, the flux through central carbon and energy metabolism is very robust under all conditions studied. The key to achieve this robustness is the adjustment of the biocatalytic machinery to compensate for solvent-induced impairment of enzymatic activities during osmotic stress. Specifically, increased production of several enzymes of central carbon metabolism compensates for their reduced activity in the presence of high salt. A major response of the cell during osmotic stress is the production of the compatible solute proline. This is achieved through the concerted adjustment of multiple reactions around the 2-oxoglutarate node, which drives metabolism towards the proline precursor glutamate. The fine-tuning of the transcriptional and metabolic networks involves functional modules that overarch the individual pathways.

  2. The plasma membrane as a capacitor for energy and metabolism.

    PubMed

    Ray, Supriyo; Kassan, Adam; Busija, Anna R; Rangamani, Padmini; Patel, Hemal H

    2016-02-01

    When considering which components of the cell are the most critical to function and physiology, we naturally focus on the nucleus, the mitochondria that regulate energy and apoptotic signaling, or other organelles such as the endoplasmic reticulum, Golgi, ribosomes, etc. Few people will suggest that the membrane is the most critical element of a cell in terms of function and physiology. Those that consider the membrane critical will point to its obvious barrier function regulated by the lipid bilayer and numerous ion channels that regulate homeostatic gradients. What becomes evident upon closer inspection is that not all membranes are created equal and that there are lipid-rich microdomains that serve as platforms of signaling and a means of communication with the intracellular environment. In this review, we explore the evolution of membranes, focus on lipid-rich microdomains, and advance the novel concept that membranes serve as "capacitors for energy and metabolism." Within this framework, the membrane then is the primary and critical regulator of stress and disease adaptation of the cell.

  3. The plasma membrane as a capacitor for energy and metabolism.

    PubMed

    Ray, Supriyo; Kassan, Adam; Busija, Anna R; Rangamani, Padmini; Patel, Hemal H

    2016-02-01

    When considering which components of the cell are the most critical to function and physiology, we naturally focus on the nucleus, the mitochondria that regulate energy and apoptotic signaling, or other organelles such as the endoplasmic reticulum, Golgi, ribosomes, etc. Few people will suggest that the membrane is the most critical element of a cell in terms of function and physiology. Those that consider the membrane critical will point to its obvious barrier function regulated by the lipid bilayer and numerous ion channels that regulate homeostatic gradients. What becomes evident upon closer inspection is that not all membranes are created equal and that there are lipid-rich microdomains that serve as platforms of signaling and a means of communication with the intracellular environment. In this review, we explore the evolution of membranes, focus on lipid-rich microdomains, and advance the novel concept that membranes serve as "capacitors for energy and metabolism." Within this framework, the membrane then is the primary and critical regulator of stress and disease adaptation of the cell. PMID:26771520

  4. Impact of Metformin on Exercise-Induced Metabolic Adaptations to Lower Type 2 Diabetes Risk.

    PubMed

    Malin, Steven K; Braun, Barry

    2016-01-01

    Combining metformin with exercise has been proposed to improve glucose homeostasis. However, we primarily discuss evidence suggesting that metformin and other pharmacological agents/dietary supplements (e.g., statins, resveratol, or antioxidants) may in fact oppose exercise-induced benefits on insulin sensitivity and cardiometabolic health. We explore the novel hypothesis that attenuation of oxidative stress from exercise by these exogenous compounds blunts metabolic adaptation. PMID:26583801

  5. Analysis of metabolic energy utilization in the Skylab astronauts

    NASA Technical Reports Server (NTRS)

    Leonard, J. I.

    1977-01-01

    Skylab biomedical data regarding man's metabolic processes for extended periods of weightlessness is presented. The data was used in an integrated metabolic balance analysis which included analysis of Skylab water balance, electrolyte balance, evaporative water loss, and body composition. A theoretical analysis of energy utilization in man is presented. The results of the analysis are presented in tabular and graphic format.

  6. Adaptive Benefits of Storage Strategy and Dual AMPK/TOR Signaling in Metabolic Stress Response

    PubMed Central

    Pfeuty, Benjamin; Thommen, Quentin

    2016-01-01

    Cellular metabolism must ensure that supply of nutrient meets the biosynthetic and bioenergetic needs. Cells have therefore developed sophisticated signaling and regulatory pathways in order to cope with dynamic fluctuations of both resource and demand and to regulate accordingly diverse anabolic and catabolic processes. Intriguingly, these pathways are organized around a relatively small number of regulatory hubs, such as the highly conserved AMPK and TOR kinase families in eukaryotic cells. Here, the global metabolic adaptations upon dynamic environment are investigated using a prototypical model of regulated metabolism. In this model, the optimal enzyme profiles as well as the underlying regulatory architecture are identified by combining perturbation and evolutionary methods. The results reveal the existence of distinct classes of adaptive strategies, which differ in the management of storage reserve depending on the intensity of the stress and in the regulation of ATP-producing reaction depending on the nature of the stress. The regulatory architecture that optimally implements these adaptive features is characterized by a crosstalk between two specialized signaling pathways, which bears close similarities with the sensing and regulatory properties of AMPK and TOR pathways. PMID:27505075

  7. Adaptive Benefits of Storage Strategy and Dual AMPK/TOR Signaling in Metabolic Stress Response.

    PubMed

    Pfeuty, Benjamin; Thommen, Quentin

    2016-01-01

    Cellular metabolism must ensure that supply of nutrient meets the biosynthetic and bioenergetic needs. Cells have therefore developed sophisticated signaling and regulatory pathways in order to cope with dynamic fluctuations of both resource and demand and to regulate accordingly diverse anabolic and catabolic processes. Intriguingly, these pathways are organized around a relatively small number of regulatory hubs, such as the highly conserved AMPK and TOR kinase families in eukaryotic cells. Here, the global metabolic adaptations upon dynamic environment are investigated using a prototypical model of regulated metabolism. In this model, the optimal enzyme profiles as well as the underlying regulatory architecture are identified by combining perturbation and evolutionary methods. The results reveal the existence of distinct classes of adaptive strategies, which differ in the management of storage reserve depending on the intensity of the stress and in the regulation of ATP-producing reaction depending on the nature of the stress. The regulatory architecture that optimally implements these adaptive features is characterized by a crosstalk between two specialized signaling pathways, which bears close similarities with the sensing and regulatory properties of AMPK and TOR pathways. PMID:27505075

  8. Aging and longevity of yeast colony populations: metabolic adaptation and differentiation.

    PubMed

    Váchová, Libuše; Palková, Zdena

    2011-10-01

    Yeast multicellular colonies possess several traits that are absent from individual yeasts. These include the ability to synchronize colony population development and adapt its metabolism to different environmental changes, such as nutrient depletion. This, together with cell diversification to cell variants with distinct metabolic and other properties, contributes to the main goal of the colony population: to achieve longevity. In this respect, a benefit to individual cells is subordinated to the benefit to the whole population, exhibiting a kind of altruistic behaviour. For example, some colony cells located at particular positions undergo regulated cell dying and provide components to other cells located in more propitious areas. The enhancement of techniques that enable the in vivo investigation of three-dimensional spatiotemporal colony development may lead to new discoveries on metabolic differentiation and regulation in the near future.

  9. Energy metabolism of the developing brain

    SciTech Connect

    Abrams, R.M.; Hutchison, A.A.

    1985-04-01

    Cerebral metabolism in utero and in the neonatal period remains incompletely understood. A major investigative technique uses /sup 14/C deoxyglucose. Species differences, behavioral states and gestational age all have an impact. Hormonal and sensory stimuli have potential influences. The use of this new investigative technique in the human will allow detailed study of the effects of a variety of pathophysiologic events and possibly of drug therapy on cerebral glucose metabolism.

  10. Genomic islands link secondary metabolism to functional adaptation in marine Actinobacteria.

    PubMed

    Penn, Kevin; Jenkins, Caroline; Nett, Markus; Udwary, Daniel W; Gontang, Erin A; McGlinchey, Ryan P; Foster, Brian; Lapidus, Alla; Podell, Sheila; Allen, Eric E; Moore, Bradley S; Jensen, Paul R

    2009-10-01

    Genomic islands have been shown to harbor functional traits that differentiate ecologically distinct populations of environmental bacteria. A comparative analysis of the complete genome sequences of the marine Actinobacteria Salinispora tropica and Salinispora arenicola reveals that 75% of the species-specific genes are located in 21 genomic islands. These islands are enriched in genes associated with secondary metabolite biosynthesis providing evidence that secondary metabolism is linked to functional adaptation. Secondary metabolism accounts for 8.8% and 10.9% of the genes in the S. tropica and S. arenicola genomes, respectively, and represents the major functional category of annotated genes that differentiates the two species. Genomic islands harbor all 25 of the species-specific biosynthetic pathways, the majority of which occur in S. arenicola and may contribute to the cosmopolitan distribution of this species. Genome evolution is dominated by gene duplication and acquisition, which in the case of secondary metabolism provide immediate opportunities for the production of new bioactive products. Evidence that secondary metabolic pathways are exchanged horizontally, coupled with earlier evidence for fixation among globally distributed populations, supports a functional role and suggests that the acquisition of natural product biosynthetic gene clusters represents a previously unrecognized force driving bacterial diversification. Species-specific differences observed in clustered regularly interspaced short palindromic repeat sequences suggest that S. arenicola may possess a higher level of phage immunity, whereas a highly duplicated family of polymorphic membrane proteins provides evidence for a new mechanism of marine adaptation in Gram-positive bacteria.

  11. Hypoxia causes autophagic stress and derangement of metabolic adaptation in a cell model of amyotrophic lateral sclerosis.

    PubMed

    Cimini, Sara; Rizzardini, Milena; Biella, Gloria; Cantoni, Lavinia

    2014-05-01

    stress and inappropriate handling of energy metabolism. Defective adaptation to hypoxia may contribute to neurodegeneration.

  12. Modelling chronotaxicity of cellular energy metabolism to facilitate the identification of altered metabolic states.

    PubMed

    Lancaster, Gemma; Suprunenko, Yevhen F; Jenkins, Kirsten; Stefanovska, Aneta

    2016-01-01

    Altered cellular energy metabolism is a hallmark of many diseases, one notable example being cancer. Here, we focus on the identification of the transition from healthy to abnormal metabolic states. To do this, we study the dynamics of energy production in a cell. Due to the thermodynamic openness of a living cell, the inability to instantaneously match fluctuating supply and demand in energy metabolism results in nonautonomous time-varying oscillatory dynamics. However, such oscillatory dynamics is often neglected and treated as stochastic. Based on experimental evidence of metabolic oscillations, we show that changes in metabolic state can be described robustly by alterations in the chronotaxicity of the corresponding metabolic oscillations, i.e. the ability of an oscillator to resist external perturbations. We also present a method for the identification of chronotaxicity, applicable to general oscillatory signals and, importantly, apply this to real experimental data. Evidence of chronotaxicity was found in glycolytic oscillations in real yeast cells, verifying that chronotaxicity could be used to study transitions between metabolic states. PMID:27483987

  13. Modelling chronotaxicity of cellular energy metabolism to facilitate the identification of altered metabolic states.

    PubMed

    Lancaster, Gemma; Suprunenko, Yevhen F; Jenkins, Kirsten; Stefanovska, Aneta

    2016-08-03

    Altered cellular energy metabolism is a hallmark of many diseases, one notable example being cancer. Here, we focus on the identification of the transition from healthy to abnormal metabolic states. To do this, we study the dynamics of energy production in a cell. Due to the thermodynamic openness of a living cell, the inability to instantaneously match fluctuating supply and demand in energy metabolism results in nonautonomous time-varying oscillatory dynamics. However, such oscillatory dynamics is often neglected and treated as stochastic. Based on experimental evidence of metabolic oscillations, we show that changes in metabolic state can be described robustly by alterations in the chronotaxicity of the corresponding metabolic oscillations, i.e. the ability of an oscillator to resist external perturbations. We also present a method for the identification of chronotaxicity, applicable to general oscillatory signals and, importantly, apply this to real experimental data. Evidence of chronotaxicity was found in glycolytic oscillations in real yeast cells, verifying that chronotaxicity could be used to study transitions between metabolic states.

  14. Modelling chronotaxicity of cellular energy metabolism to facilitate the identification of altered metabolic states

    PubMed Central

    Lancaster, Gemma; Suprunenko, Yevhen F.; Jenkins, Kirsten; Stefanovska, Aneta

    2016-01-01

    Altered cellular energy metabolism is a hallmark of many diseases, one notable example being cancer. Here, we focus on the identification of the transition from healthy to abnormal metabolic states. To do this, we study the dynamics of energy production in a cell. Due to the thermodynamic openness of a living cell, the inability to instantaneously match fluctuating supply and demand in energy metabolism results in nonautonomous time-varying oscillatory dynamics. However, such oscillatory dynamics is often neglected and treated as stochastic. Based on experimental evidence of metabolic oscillations, we show that changes in metabolic state can be described robustly by alterations in the chronotaxicity of the corresponding metabolic oscillations, i.e. the ability of an oscillator to resist external perturbations. We also present a method for the identification of chronotaxicity, applicable to general oscillatory signals and, importantly, apply this to real experimental data. Evidence of chronotaxicity was found in glycolytic oscillations in real yeast cells, verifying that chronotaxicity could be used to study transitions between metabolic states. PMID:27483987

  15. Sex differences in substrate metabolism and energy homeostasis.

    PubMed

    Cortright, R N; Koves, T R

    2000-08-01

    Females differ remarkably from males in the mechanisms that regulate substrate utilization and energy homeostasis. Females appear to be less affected in terms of growth and loss of body tissues when subjected to chronic periods of negative energy balance. The physiological trade-off appears to be a stronger propensity toward retention of fat mass during times of energy surfeit. The mechanism(s) that account for sex differences in energy metabolism are not known but most likely involve the sex steroids. Recent discoveries in the areas of endocrinology and metabolism may provide new insights into differences in the control of food intake and energy conservation between the sexes. Finally, the study of the mechanism(s) involved in the regulation of skeletal muscle lipid metabolism represents a new frontier in skeletal muscle bioenergetics, and new discoveries may provide further explanations for the observed sex differences in substrate utilization and response(s) to alterations in energy homeostasis. PMID:10953067

  16. Pronounced Metabolic Changes in Adaptation to Biofilm Growth by Streptococcus pneumoniae

    PubMed Central

    Allan, Raymond N.; Skipp, Paul; Jefferies, Johanna; Clarke, Stuart C.; Faust, Saul N.

    2014-01-01

    Streptococcus pneumoniae accounts for a significant global burden of morbidity and mortality and biofilm development is increasingly recognised as important for colonization and infection. Analysis of protein expression patterns during biofilm development may therefore provide valuable insights to the understanding of pneumococcal persistence strategies and to improve vaccines. iTRAQ (isobaric tagging for relative and absolute quantification), a high-throughput gel-free proteomic approach which allows high resolution quantitative comparisons of protein profiles between multiple phenotypes, was used to interrogate planktonic and biofilm growth in a clinical serotype 14 strain. Comparative analyses of protein expression between log-phase planktonic and 1-day and 7-day biofilm cultures representing nascent and late phase biofilm growth were carried out. Overall, 244 proteins were identified, of which >80% were differentially expressed during biofilm development. Quantitatively and qualitatively, metabolic regulation appeared to play a central role in the adaptation from the planktonic to biofilm phenotype. Pneumococci adapted to biofilm growth by decreasing enzymes involved in the glycolytic pathway, as well as proteins involved in translation, transcription, and virulence. In contrast, proteins with a role in pyruvate, carbohydrate, and arginine metabolism were significantly increased during biofilm development. Downregulation of glycolytic and translational proteins suggests that pneumococcus adopts a covert phenotype whilst adapting to an adherent lifestyle, while utilization of alternative metabolic pathways highlights the resourcefulness of pneumococcus to facilitate survival in diverse environmental conditions. These metabolic proteins, conserved across both the planktonic and biofilm phenotypes, may also represent target candidates for future vaccine development and treatment strategies. Data are available via ProteomeXchange with identifier PXD001182. PMID

  17. Selection of physiological and metabolic adaptations to food deprivation in the Pyrenean newt Calotriton asper during cave colonisation.

    PubMed

    Issartel, Julien; Voituron, Yann; Guillaume, Olivier; Clobert, Jean; Hervant, Frédéric

    2010-01-01

    Food restriction is one of the major and most common constraints that subterranean animals face in their biotope. Cave-dwelling organisms thus have to cope with fasting periods that can extend from a month to a year. However, adaptive fasting resistance previously found in subterranean fauna has only been highlighted by direct comparisons with phylogenetically distant epigean organisms, which could severely impact conclusions. Here we report physiological and metabolic responses to 42 days of fasting followed by 10 days of refeeding in two populations (one subterranean and one epigean) of Calotriton asper. In the fed state (control), the hypogean population exhibited a hypometabolism together with higher glycogen (+25% in liver and muscles) and triglyceride stores (+50% in muscles). During the fasting period, cave individuals exhibited a 20% decrease in VO(2) whereas epigean individuals experienced no significant change. In addition, the energetic reserves always remained higher in the hypogean population. According to phylogenic and biogeographic data, cave colonization by this species dates back to less than 10,000 years, suggesting a rapid selection of adaptive traits related to fasting. This study strongly suggests that cave colonization induces a decrease in metabolism together with a higher capacity to accumulate energy reserves and therefore to withstand unpredictable fasting periods.

  18. Micromanaging metabolism-a role for miRNAs in teleost energy metabolism.

    PubMed

    Mennigen, Jan A

    2016-09-01

    MicroRNAs (miRNAs) are small, non-protein coding RNA sequences, which are found in most eukaryotes. Since their initial discovery, miRNAs have emerged as important regulators of many biological processes. One of the most important processes profoundly regulated by miRNAs is energy metabolism. Traditionally, metabolic functions of miRNAs have been studied in genome-sequenced mammalian organisms, especially the mouse model. However, partially driven by commercial interest in aquaculture, increasingly feasible large-scale molecular techniques have resulted in the characterization of miRNA repertoires, and importantly, several genome sequences of several (commercially important) teleost species, which also hold important roles as research models in the comparative physiology of energy metabolism. This review aims to introduce the recent advances in miRNA research in teleost fish and to describe the current knowledge of miRNA function in teleost energy metabolism. The most pressing research needs and questions to determine metabolic roles of miRNAs in teleost models are presented, as well as applicable technical approaches and current bottlenecks. Rainbow trout, which possess the advantages of newly available molecular tools and a long history as comparative research model in teleost energy metabolism, are discussed as a promising research model to address these questions. PMID:26384523

  19. Micromanaging metabolism-a role for miRNAs in teleost energy metabolism.

    PubMed

    Mennigen, Jan A

    2016-09-01

    MicroRNAs (miRNAs) are small, non-protein coding RNA sequences, which are found in most eukaryotes. Since their initial discovery, miRNAs have emerged as important regulators of many biological processes. One of the most important processes profoundly regulated by miRNAs is energy metabolism. Traditionally, metabolic functions of miRNAs have been studied in genome-sequenced mammalian organisms, especially the mouse model. However, partially driven by commercial interest in aquaculture, increasingly feasible large-scale molecular techniques have resulted in the characterization of miRNA repertoires, and importantly, several genome sequences of several (commercially important) teleost species, which also hold important roles as research models in the comparative physiology of energy metabolism. This review aims to introduce the recent advances in miRNA research in teleost fish and to describe the current knowledge of miRNA function in teleost energy metabolism. The most pressing research needs and questions to determine metabolic roles of miRNAs in teleost models are presented, as well as applicable technical approaches and current bottlenecks. Rainbow trout, which possess the advantages of newly available molecular tools and a long history as comparative research model in teleost energy metabolism, are discussed as a promising research model to address these questions.

  20. Inborn Errors of Energy Metabolism Associated with Myopathies

    PubMed Central

    Das, Anibh M.; Steuerwald, Ulrike; Illsinger, Sabine

    2010-01-01

    Inherited neuromuscular disorders affect approximately one in 3,500 children. Structural muscular defects are most common; however functional impairment of skeletal and cardiac muscle in both children and adults may be caused by inborn errors of energy metabolism as well. Patients suffering from metabolic myopathies due to compromised energy metabolism may present with exercise intolerance, muscle pain, reversible or progressive muscle weakness, and myoglobinuria. In this review, the physiology of energy metabolism in muscle is described, followed by the presentation of distinct disorders affecting skeletal and cardiac muscle: glycogen storage diseases types III, V, VII, fatty acid oxidation defects, and respiratory chain defects (i.e., mitochondriopathies). The diagnostic work-up and therapeutic options in these disorders are discussed. PMID:20589068

  1. Adaptive Thermogenesis in Resistance to Obesity Therapies: Issues in Quantifying Thrifty Energy Expenditure Phenotypes in Humans.

    PubMed

    Dulloo, Abdul G; Schutz, Yves

    2015-06-01

    Dieting and exercise are likely to remain the core approaches in the management of obesity in the foreseeable future despite their well-documented failures for achieving long-term weight loss. Explanations for such poor prognosis are centered on patient's self-regulatory failure and lack of compliance to the prescribed diet or exercise regimen. While a role for physiological adaptations leading to diminished rates of heat production has also been advocated, there are considerable uncertainties about the quantitative importance of such regulated heat production (i.e., adaptive thermogenesis) to the less-than-expected weight loss and ease for weight regain. This paper first reviews the most compelling evidence of what is often considered as weight loss-induced adaptive thermogenesis in various compartments of daily energy expenditure. It then discusses the major limitations and issues in quantifying such thrifty energy expenditure phenotypes and underscores the plausibility of diminished core temperature as a thrifty metabolic trait in resistance to weight loss. Although an accurate quantification of adaptive thermogenesis will have to await the applications of deep body composition phenotyping and better discrimination of physical activity energy expenditures, the magnitude of diminished energy expenditure in response to weight loss in certain individuals is large enough to support the concept that adaptive thermogenesis contribute importantly to their resistance to obesity therapies.

  2. Adaptive Thermogenesis in Resistance to Obesity Therapies: Issues in Quantifying Thrifty Energy Expenditure Phenotypes in Humans.

    PubMed

    Dulloo, Abdul G; Schutz, Yves

    2015-06-01

    Dieting and exercise are likely to remain the core approaches in the management of obesity in the foreseeable future despite their well-documented failures for achieving long-term weight loss. Explanations for such poor prognosis are centered on patient's self-regulatory failure and lack of compliance to the prescribed diet or exercise regimen. While a role for physiological adaptations leading to diminished rates of heat production has also been advocated, there are considerable uncertainties about the quantitative importance of such regulated heat production (i.e., adaptive thermogenesis) to the less-than-expected weight loss and ease for weight regain. This paper first reviews the most compelling evidence of what is often considered as weight loss-induced adaptive thermogenesis in various compartments of daily energy expenditure. It then discusses the major limitations and issues in quantifying such thrifty energy expenditure phenotypes and underscores the plausibility of diminished core temperature as a thrifty metabolic trait in resistance to weight loss. Although an accurate quantification of adaptive thermogenesis will have to await the applications of deep body composition phenotyping and better discrimination of physical activity energy expenditures, the magnitude of diminished energy expenditure in response to weight loss in certain individuals is large enough to support the concept that adaptive thermogenesis contribute importantly to their resistance to obesity therapies. PMID:26627218

  3. Mitochondrial adaptations to utilize hydrogen sulfide for energy and signaling.

    PubMed

    Olson, Kenneth R

    2012-10-01

    Sulfur is a versatile molecule with oxidation states ranging from -2 to +6. From the beginning, sulfur has been inexorably entwined with the evolution of organisms. Reduced sulfur, prevalent in the prebiotic Earth and supplied from interstellar sources, was an integral component of early life as it could provide energy through oxidization, even in a weakly oxidizing environment, and it spontaneously reacted with iron to form iron-sulfur clusters that became the earliest biological catalysts and structural components of cells. The ability to cycle sulfur between reduced and oxidized states may have been key in the great endosymbiotic event that incorporated a sulfide-oxidizing α-protobacteria into a host sulfide-reducing Archea, resulting in the eukaryotic cell. As eukaryotes slowly adapted from a sulfidic and anoxic (euxinic) world to one that was highly oxidizing, numerous mechanisms developed to deal with increasing oxidants; namely, oxygen, and decreasing sulfide. Because there is rarely any reduced sulfur in the present-day environment, sulfur was historically ignored by biologists, except for an occasional report of sulfide toxicity. Twenty-five years ago, it became evident that the organisms in sulfide-rich environments could synthesize ATP from sulfide, 10 years later came the realization that animals might use sulfide as a signaling molecule, and only within the last 4 years did it become apparent that even mammals could derive energy from sulfide generated in the gastrointestinal tract. It has also become evident that, even in the present-day oxic environment, cells can exploit the redox chemistry of sulfide, most notably as a physiological transducer of oxygen availability. This review will examine how the legacy of sulfide metabolism has shaped natural selection and how some of these ancient biochemical pathways are still employed by modern-day eukaryotes. PMID:22430869

  4. Rethinking energy in parkinsonian motor symptoms: a potential role for neural metabolic deficits.

    PubMed

    Amano, Shinichi; Kegelmeyer, Deborah; Hong, S Lee

    2014-01-01

    Parkinson's disease (PD) is characterized as a chronic and progressive neurodegenerative disorder that results in a variety of debilitating symptoms, including bradykinesia, resting tremor, rigidity, and postural instability. Research spanning several decades has emphasized basal ganglia dysfunction, predominantly resulting from dopaminergic (DA) cell loss, as the primarily cause of the aforementioned parkinsonian features. But, why those particular features manifest themselves remains an enigma. The goal of this paper is to develop a theoretical framework that parkinsonian motor features are behavioral consequence of a long-term adaptation to their inability (inflexibility or lack of capacity) to meet energetic demands, due to neural metabolic deficits arising from mitochondrial dysfunction associated with PD. Here, we discuss neurophysiological changes that are generally associated with PD, such as selective degeneration of DA neurons in the substantia nigra pars compacta (SNc), in conjunction with metabolic and mitochondrial dysfunction. We then characterize the cardinal motor symptoms of PD, bradykinesia, resting tremor, rigidity and gait disturbance, reviewing literature to demonstrate how these motor patterns are actually energy efficient from a metabolic perspective. We will also develop three testable hypotheses: (1) neural metabolic deficits precede the increased rate of neurodegeneration and onset of behavioral symptoms in PD; (2) motor behavior of persons with PD are more sensitive to changes in metabolic/bioenergetic state; and (3) improvement of metabolic function could lead to better motor performance in persons with PD. These hypotheses are designed to introduce a novel viewpoint that can elucidate the connections between metabolic, neural and motor function in PD. PMID:25610377

  5. Energy mitigation, adaptation and biodiversity: Synergies and antagonisms

    NASA Astrophysics Data System (ADS)

    Berry, P. M.; Paterson, J. S.

    2009-11-01

    In this paper we review the current impacts of different energy producers (and energy conservation) on biodiversity and investigate the potential for achieving positive biodiversity effects along with mitigation and adaptation objectives. Very few energy producers achieve all three aims - although it may be possible with careful choice of location and management. In some instances, energy conservation can provide mitigation, adaptation and biodiversity benefits. There is still a gap in knowledge regarding the effects of newer energy technologies on biodiversity. There is an additional concern that many supposedly 'green' renewable energy projects may actually harm biodiversity to such a degree that their overall human benefits are negated. The increasing understanding that ecosystem services are vital for human well-being though means that attempting positive mitigation, adaptation and biodiversity conservation in the energy sector should be an imperative goal for international policy. Whilst research into synergies between mitigation and adaptation is established, there has been very little that has examined the impacts on biodiversity as well. Further work is required to identify and provide evidence of the best ways of optimising mitigation, adaptation and biodiversity in the energy sector.

  6. Flavonoids: a metabolic network mediating plants adaptation to their real estate

    PubMed Central

    Mouradov, Aidyn; Spangenberg, German

    2014-01-01

    From an evolutionary perspective, the emergence of the sophisticated chemical scaffolds of flavonoid molecules represents a key step in the colonization of Earth’s terrestrial environment by vascular plants nearly 500 million years ago. The subsequent evolution of flavonoids through recruitment and modification of ancestors involved in primary metabolism has allowed vascular plants to cope with pathogen invasion and damaging UV light. The functional properties of flavonoids as a unique combination of different classes of compounds vary significantly depending on the demands of their local real estate. Apart from geographical location, the composition of flavonoids is largely dependent on the plant species, their developmental stage, tissue type, subcellular localization, and key ecological influences of both biotic and abiotic origin. Molecular and metabolic cross-talk between flavonoid and other pathways as a result of the re-direction of intermediate molecules have been well investigated. This metabolic plasticity is a key factor in plant adaptive strength and is of paramount importance for early land plants adaptation to their local ecosystems. In human and animal health the biological and pharmacological activities of flavonoids have been investigated in great depth and have shown a wide range of anti-inflammatory, anti-oxidant, anti-microbial, and anti-cancer properties. In this paper we review the application of advanced gene technologies for targeted reprogramming of the flavonoid pathway in plants to understand its molecular functions and explore opportunities for major improvements in forage plants enhancing animal health and production. PMID:25426130

  7. Metabolic and hypoxic adaptation to anti-angiogenic therapy: a target for induced essentiality

    PubMed Central

    McIntyre, Alan; Harris, Adrian L

    2015-01-01

    Anti-angiogenic therapy has increased the progression-free survival of many cancer patients but has had little effect on overall survival, even in colon cancer (average 6–8 weeks) due to resistance. The current licensed targeted therapies all inhibit VEGF signalling (Table1). Many mechanisms of resistance to anti-VEGF therapy have been identified that enable cancers to bypass the angiogenic blockade. In addition, over the last decade, there has been increasing evidence for the role that the hypoxic and metabolic responses play in tumour adaptation to anti-angiogenic therapy. The hypoxic tumour response, through the transcription factor hypoxia-inducible factors (HIFs), induces major gene expression, metabolic and phenotypic changes, including increased invasion and metastasis. Pre-clinical studies combining anti-angiogenics with inhibitors of tumour hypoxic and metabolic adaptation have shown great promise, and combination clinical trials have been instigated. Understanding individual patient response and the response timing, given the opposing effects of vascular normalisation versus reduced perfusion seen with anti-angiogenics, provides a further hurdle in the paradigm of personalised therapeutic intervention. Additional approaches for targeting the hypoxic tumour microenvironment are being investigated in pre-clinical and clinical studies that have potential for producing synthetic lethality in combination with anti-angiogenic therapy as a future therapeutic strategy. PMID:25700172

  8. Global Profiling of Metabolic Adaptation to Hypoxic Stress in Human Glioblastoma Cells

    PubMed Central

    Kucharzewska, Paulina; Christianson, Helena C.; Belting, Mattias

    2015-01-01

    Oncogenetic events and unique phenomena of the tumor microenvironment together induce adaptive metabolic responses that may offer new diagnostic tools and therapeutic targets of cancer. Hypoxia, or low oxygen tension, represents a well-established and universal feature of the tumor microenvironment and has been linked to increased tumor aggressiveness as well as resistance to conventional oncological treatments. Previous studies have provided important insights into hypoxia induced changes of the transcriptome and proteome; however, how this translates into changes at the metabolite level remains to be defined. Here, we have investigated dynamic, time-dependent effects of hypoxia on the cancer cell metabolome across all families of macromolecules, i.e., carbohydrate, protein, lipid and nucleic acid, in human glioblastoma cells. Using GC/MS and LC/MS/MS, 345 and 126 metabolites were identified and quantified in cells and corresponding media, respectively, at short (6 h), intermediate (24 h), and prolonged (48 h) incubation at normoxic or hypoxic (1% O2) conditions. In conjunction, we performed gene array studies with hypoxic and normoxic cells following short and prolonged incubation. We found that levels of several key metabolites varied with the duration of hypoxic stress. In some cases, metabolic changes corresponded with hypoxic regulation of key pathways at the transcriptional level. Our results provide new insights into the metabolic response of glioblastoma cells to hypoxia, which should stimulate further work aimed at targeting cancer cell adaptive mechanisms to microenvironmental stress. PMID:25633823

  9. An adaptive interpolation scheme for molecular potential energy surfaces

    NASA Astrophysics Data System (ADS)

    Kowalewski, Markus; Larsson, Elisabeth; Heryudono, Alfa

    2016-08-01

    The calculation of potential energy surfaces for quantum dynamics can be a time consuming task—especially when a high level of theory for the electronic structure calculation is required. We propose an adaptive interpolation algorithm based on polyharmonic splines combined with a partition of unity approach. The adaptive node refinement allows to greatly reduce the number of sample points by employing a local error estimate. The algorithm and its scaling behavior are evaluated for a model function in 2, 3, and 4 dimensions. The developed algorithm allows for a more rapid and reliable interpolation of a potential energy surface within a given accuracy compared to the non-adaptive version.

  10. An adaptive interpolation scheme for molecular potential energy surfaces.

    PubMed

    Kowalewski, Markus; Larsson, Elisabeth; Heryudono, Alfa

    2016-08-28

    The calculation of potential energy surfaces for quantum dynamics can be a time consuming task-especially when a high level of theory for the electronic structure calculation is required. We propose an adaptive interpolation algorithm based on polyharmonic splines combined with a partition of unity approach. The adaptive node refinement allows to greatly reduce the number of sample points by employing a local error estimate. The algorithm and its scaling behavior are evaluated for a model function in 2, 3, and 4 dimensions. The developed algorithm allows for a more rapid and reliable interpolation of a potential energy surface within a given accuracy compared to the non-adaptive version. PMID:27586901

  11. An adaptive interpolation scheme for molecular potential energy surfaces.

    PubMed

    Kowalewski, Markus; Larsson, Elisabeth; Heryudono, Alfa

    2016-08-28

    The calculation of potential energy surfaces for quantum dynamics can be a time consuming task-especially when a high level of theory for the electronic structure calculation is required. We propose an adaptive interpolation algorithm based on polyharmonic splines combined with a partition of unity approach. The adaptive node refinement allows to greatly reduce the number of sample points by employing a local error estimate. The algorithm and its scaling behavior are evaluated for a model function in 2, 3, and 4 dimensions. The developed algorithm allows for a more rapid and reliable interpolation of a potential energy surface within a given accuracy compared to the non-adaptive version.

  12. Multifunctional essentiality of succinate metabolism in adaptation to hypoxia in Mycobacterium tuberculosis

    PubMed Central

    Eoh, Hyungjin; Rhee, Kyu Y.

    2013-01-01

    Mycobacterium tuberculosis is a chronic, facultative intracellular pathogen that spends the majority of its decades-long life cycle in a non- or slowly replicating state. However, the bacterium remains poised to resume replicating so that it can transmit itself to a new host. Knowledge of the metabolic adaptations used to facilitate entry into and exit from nonreplicative states remains incomplete. Here, we apply 13C-based metabolomic profiling to characterize the activity of M. tuberculosis tricarboxylic acid cycle during adaptation to and recovery from hypoxia, a physiologically relevant condition associated with nonreplication. We show that, as M. tuberculosis adapts to hypoxia, it slows and remodels its tricarboxylic acid cycle to increase production of succinate, which is used to flexibly sustain membrane potential, ATP synthesis, and anaplerosis, in response to varying degrees of O2 limitation and the presence or absence of the alternate electron acceptor nitrate. This remodeling is mediated by the bifunctional enzyme isocitrate lyase acting in a noncanonical role distinct from fatty acid catabolism. Isocitrate lyase-dependent production of succinate affords M. tuberculosis with a unique and bioenergetically efficient metabolic means of entry into and exit from hypoxia-induced quiescence. PMID:23576728

  13. Stepwise metabolic adaption from pure metabolization to balanced anaerobic growth on xylose explored for recombinant Saccharomyces cerevisiae

    PubMed Central

    2014-01-01

    Background To effectively convert lignocellulosic feedstocks to bio-ethanol anaerobic growth on xylose constitutes an essential trait that Saccharomyces cerevisiae strains normally do not adopt through the selective integration of a xylose assimilation route as the rate of ATP-formation is below energy requirements for cell maintenance (mATP). To enable cell growth extensive evolutionary and/or elaborate rational engineering is required. However the number of available strains meeting demands for process integration are limited. In this work evolutionary engineering in just two stages coupled to strain selection under strict anaerobic conditions was carried out with BP10001 as progenitor. BP10001 is an efficient (Yethanol = 0.35 g/g) but slow (qethanol = 0.05 ± 0.01 g/gBM/h) xylose-metabolizing recombinant strain of Saccharomyces cerevisiae that expresses an optimized yeast-type xylose assimilation pathway. Results BP10001 was adapted in 5 generations to anaerobic growth on xylose by prolonged incubation for 91 days in sealed flasks. Resultant strain IBB10A02 displayed a specific growth rate μ of 0.025 ± 0.002 h-1 but produced large amounts of glycerol and xylitol. In addition growth was strongly impaired at pH below 6.0 and in the presence of weak acids. Using sequential batch selection and IBB10A02 as basis, IBB10B05 was evolved (56 generations). IBB10B05 was capable of fast (μ = 0.056 ± 0.003 h-1; qethanol = 0.28 ± 0.04 g/gBM/h), efficient (Yethanol = 0.35 ± 0.02 g/g), robust and balanced fermentation of xylose. Importantly, IBB10A02 and IBB10B05 displayed a stable phenotype. Unlike BP10001 both strains displayed an unprecedented biphasic formation of glycerol and xylitol along the fermentation time. Transition from a glycerol- to a xylitol-dominated growth phase, probably controlled by CO2/HCO3-, was accompanied by a 2.3-fold increase of mATP while YATP (= 87 ± 7 mmolATP/gBM) remained unaffected. As

  14. Quantification of correlational selection on thermal physiology, thermoregulatory behavior, and energy metabolism in lizards

    PubMed Central

    Artacho, Paulina; Saravia, Julia; Ferrandière, Beatriz Decencière; Perret, Samuel; Le Galliard, Jean-François

    2015-01-01

    Phenotypic selection is widely accepted as the primary cause of adaptive evolution in natural populations, but selection on complex functional properties linking physiology, behavior, and morphology has been rarely quantified. In ectotherms, correlational selection on thermal physiology, thermoregulatory behavior, and energy metabolism is of special interest because of their potential coadaptation. We quantified phenotypic selection on thermal sensitivity of locomotor performance (sprint speed), thermal preferences, and resting metabolic rate in captive populations of an ectothermic vertebrate, the common lizard, Zootoca vivipara. No correlational selection between thermal sensitivity of performance, thermoregulatory behavior, and energy metabolism was found. A combination of high body mass and resting metabolic rate was positively correlated with survival and negatively correlated with fecundity. Thus, different mechanisms underlie selection on metabolism in lizards with small body mass than in lizards with high body mass. In addition, lizards that selected the near average preferred body temperature grew faster that their congeners. This is one of the few studies that quantifies significant correlational selection on a proxy of energy expenditure and stabilizing selection on thermoregulatory behavior. PMID:26380689

  15. Phylogeography, Salinity Adaptations and Metabolic Potential of the Candidate Division KB1 Bacteria Based on a Partial Single Cell Genome

    PubMed Central

    Nigro, Lisa M.; Hyde, Andrew S.; MacGregor, Barbara J.; Teske, Andreas

    2016-01-01

    Deep-sea hypersaline anoxic basins and other hypersaline environments contain abundant and diverse microbial life that has adapted to these extreme conditions. The bacterial Candidate Division KB1 represents one of several uncultured groups that have been consistently observed in hypersaline microbial diversity studies. Here we report the phylogeography of KB1, its phylogenetic relationships to Candidate Division OP1 Bacteria, and its potential metabolic and osmotic stress adaptations based on a partial single cell amplified genome of KB1 from Orca Basin, the largest hypersaline seafloor brine basin in the Gulf of Mexico. Our results are consistent with the hypothesis – previously developed based on 14C incorporation experiments with mixed-species enrichments from Mediterranean seafloor brines – that KB1 has adapted its proteins to elevated intracellular salinity, but at the same time KB1 apparently imports glycine betaine; this compatible solute is potentially not limited to osmoregulation but could also serve as a carbon and energy source. PMID:27597842

  16. Ontogenetic phase shifts in metabolism: links to development and anti-predator adaptation.

    PubMed

    Yagi, Mitsuharu; Kanda, Takeshi; Takeda, Tatsusuke; Ishimatsu, Atsushi; Oikawa, Shin

    2010-09-22

    The allometric relationships between resting metabolism (VO(2)) and body mass (M), VO(2) = a(i)M(b), are considered a fundamental law of nature. A distinction though needs to be made between the ontogeny (within a species) and phylogeny (among species) of metabolism. However, the nature and significance of the intraspecific allometry (ontogeny of metabolism) have not been established in fishes. In this study, we present experimental evidence that a puffer fish ranging 0.0008-3 g in wet body mass has four distinct allometric phases in which three stepwise increases in scaling constants (a(i), i = 1-4), i.e. ontogenetic phase shifts in metabolism, occur with growth during its early life stages at around 0.002, 0.01 and 0.1 g, keeping each scaling exponent constant in each phase (b = 0.795). Three stepwise increases in a(i) accompanied behavioural and morphological changes and three peaks of severe cannibalism, in which the majority of predation occurred on smaller fish that had a lower value of a(i). Though fishes are generally highly fecund, producing a large number of small eggs, their survivability is very low. These results suggest that individuals with the ability to rapidly grow and step up 'a(i)' develop more anti-predator adaptation as a result of the decreased predatory risk. PMID:20444717

  17. Metabolic compensation during high energy output in fasting, lactating grey seals (Halichoerus grypus): metabolic ceilings revisited.

    PubMed Central

    Mellish, J A; Iverson, S J; Bowen, W D

    2000-01-01

    Lactation is the most energetically expensive period for female mammals and is associated with some of the highest sustained metabolic rates (SusMR) in vertebrates (reported as total energy throughput). Females typically deal with this energy demand by increasing food intake and the structure of the alimentary tract may act as the central constraint to ceilings on SusMR at about seven times resting or standard metabolic rate (SMR). However, demands of lactation may also be met by using a form of metabolic compensation such as reducing locomotor activities or entering torpor. In some phocid seals, cetaceans and bears, females fast throughout lactation and thus cannot offset the high energetic costs of lactation through increased food intake. We demonstrate that fasting grey seal females sustain, for several weeks, one of the highest total daily energy expenditures (DEE; 7.4 x SMR) reported in mammals, while progressively reducing maintenance metabolic expenditures during lactation through means not explained by reduction in lean body mass or behavioural changes. Simultaneously, the energy-exported in milk is progressively increased, associated with increased lipoprotein lipase activity in the mammary gland, resulting in greater offspring growth. Our results suggest that females use compensatory mechanisms to help meet the extraordinary energetic costs of lactation. Additionally, although the concepts of SusMR and ceilings on total DEE may be somewhat different in fasting lactating species, our data on phocid seals demonstrate that metabolic ceilings on milk energy output, in general, are not constrained by the same kind of peripheral limitations as are other energy-consuming tissues. In phocid seals, the high ceilings on DEE during lactation, coupled with metabolic compensation, are undoubtedly important factors enabling shortened lactation. PMID:10902691

  18. Co-evolution of Hormone Metabolism and Signaling Networks Expands Plant Adaptive Plasticity.

    PubMed

    Weng, Jing-Ke; Ye, Mingli; Li, Bin; Noel, Joseph P

    2016-08-11

    Classically, hormones elicit specific cellular responses by activating dedicated receptors. Nevertheless, the biosynthesis and turnover of many of these hormone molecules also produce chemically related metabolites. These molecules may also possess hormonal activities; therefore, one or more may contribute to the adaptive plasticity of signaling outcomes in host organisms. Here, we show that a catabolite of the plant hormone abscisic acid (ABA), namely phaseic acid (PA), likely emerged in seed plants as a signaling molecule that fine-tunes plant physiology, environmental adaptation, and development. This trait was facilitated by both the emergence-selection of a PA reductase that modulates PA concentrations and by the functional diversification of the ABA receptor family to perceive and respond to PA. Our results suggest that PA serves as a hormone in seed plants through activation of a subset of ABA receptors. This study demonstrates that the co-evolution of hormone metabolism and signaling networks can expand organismal resilience.

  19. Co-evolution of Hormone Metabolism and Signaling Networks Expands Plant Adaptive Plasticity.

    PubMed

    Weng, Jing-Ke; Ye, Mingli; Li, Bin; Noel, Joseph P

    2016-08-11

    Classically, hormones elicit specific cellular responses by activating dedicated receptors. Nevertheless, the biosynthesis and turnover of many of these hormone molecules also produce chemically related metabolites. These molecules may also possess hormonal activities; therefore, one or more may contribute to the adaptive plasticity of signaling outcomes in host organisms. Here, we show that a catabolite of the plant hormone abscisic acid (ABA), namely phaseic acid (PA), likely emerged in seed plants as a signaling molecule that fine-tunes plant physiology, environmental adaptation, and development. This trait was facilitated by both the emergence-selection of a PA reductase that modulates PA concentrations and by the functional diversification of the ABA receptor family to perceive and respond to PA. Our results suggest that PA serves as a hormone in seed plants through activation of a subset of ABA receptors. This study demonstrates that the co-evolution of hormone metabolism and signaling networks can expand organismal resilience. PMID:27518563

  20. Effect of Capsinoids on Energy Metabolism in Humans

    PubMed Central

    Galgani, Jose E.; Ryan, Donna H.; Ravussin, Eric

    2015-01-01

    Capsinoids are non-pungent compounds with molecular structures similar to capsaicin, which has accepted thermogenic properties. To assess the acute effect of a plant-derived preparation of capsinoids on energy metabolism, we determined resting metabolic rate and non-protein respiratory quotient after ingestion of different doses of the capsinoids. Thirteen healthy subjects received four doses of the capsinoids (1, 3, 6 and 12 mg) and placebo using a crossover, randomized, double-blind trial. After a 10-h overnight fast as inpatients, resting metabolic rate was measured by indirect calorimetry for 45 min before and 120 min after ingesting capsinoids or placebo. Blood pressure and axillary temperature were measured before (-55 and -5 min) and after (60 and 120 min) dosing. Prior to dosing, mean resting metabolic rate was 6247 ± 92 kJ/d and non-protein respiratory quotient 0.86 ± 0.01. At 120 minutes after dosing, metabolic rate and non-protein respiratory quotient remained similar across the 4 capsinoids and placebo doses. Capsinoids also had no influence on blood pressure or axillary temperature. Capsinoids provided in four doses did not affect metabolic rate and fuel partitioning in humans when measured two hours after exposure. Longer exposure and higher capsinoids doses may be required to cause meaningful acute effects on energy metabolism. PMID:19671203

  1. Biochemistry and Evolution of Anaerobic Energy Metabolism in Eukaryotes

    PubMed Central

    Müller, Miklós; Mentel, Marek; van Hellemond, Jaap J.; Henze, Katrin; Woehle, Christian; Gould, Sven B.; Yu, Re-Young; van der Giezen, Mark

    2012-01-01

    Summary: Major insights into the phylogenetic distribution, biochemistry, and evolutionary significance of organelles involved in ATP synthesis (energy metabolism) in eukaryotes that thrive in anaerobic environments for all or part of their life cycles have accrued in recent years. All known eukaryotic groups possess an organelle of mitochondrial origin, mapping the origin of mitochondria to the eukaryotic common ancestor, and genome sequence data are rapidly accumulating for eukaryotes that possess anaerobic mitochondria, hydrogenosomes, or mitosomes. Here we review the available biochemical data on the enzymes and pathways that eukaryotes use in anaerobic energy metabolism and summarize the metabolic end products that they generate in their anaerobic habitats, focusing on the biochemical roles that their mitochondria play in anaerobic ATP synthesis. We present metabolic maps of compartmentalized energy metabolism for 16 well-studied species. There are currently no enzymes of core anaerobic energy metabolism that are specific to any of the six eukaryotic supergroup lineages; genes present in one supergroup are also found in at least one other supergroup. The gene distribution across lineages thus reflects the presence of anaerobic energy metabolism in the eukaryote common ancestor and differential loss during the specialization of some lineages to oxic niches, just as oxphos capabilities have been differentially lost in specialization to anoxic niches and the parasitic life-style. Some facultative anaerobes have retained both aerobic and anaerobic pathways. Diversified eukaryotic lineages have retained the same enzymes of anaerobic ATP synthesis, in line with geochemical data indicating low environmental oxygen levels while eukaryotes arose and diversified. PMID:22688819

  2. Neuron Specific Metabolic Adaptations Following Multi-Day Exposures to Oxygen Glucose Deprivation

    PubMed Central

    Zeiger, Stephanie L. H.; McKenzie, Jennifer R.; Stankowski, Jeannette N.; Martin, Jacob A.; Cliffel, David E.; McLaughlin, BethAnn

    2010-01-01

    Prior exposure to sub toxic insults can induce a powerful endogenous neuroprotective program known as ischemic preconditioning. Current models typically rely on a single stress episode to induce neuroprotection whereas the clinical reality is that patients may experience multiple transient ischemic attacks (TIAs) prior to suffering a stroke. We sought to develop a neuron enriched preconditioning model using multiple oxygen glucose deprivation (OGD) episodes to assess the endogenous protective mechanisms neurons implement at the metabolic and cellular level for stress adaptations. We found that neurons exposed to a five minute period of glucose deprivation recovered oxygen utilization and lactate production using novel microphysiometry techniques. Using the non-toxic and energetically favorable five minute exposure, we developed a preconditioning paradigm where neurons are exposed to this brief OGD for three consecutive days. These cells experienced 45% greater survival following an otherwise lethal event and exhibited a longer lasting window of protection in comparison to our previous in vitro preconditioning model using a single stress. As in other models, preconditioned cells exhibited mild caspase activation, an increase in oxidized proteins and a requirement for reactive oxygen species for neuroprotection. Heat shock protein 70 was upregulated during preconditioning, yet the majority of this protein was released extracellularly. We believe coupling this neuron enriched multiday model with microphysiometry will allow us to assess neuronal specific real-time metabolic adaptations necessary for preconditioning. PMID:20656023

  3. Inferring metabolic networks using the Bayesian adaptive graphical lasso with informative priors

    PubMed Central

    PETERSON, CHRISTINE; VANNUCCI, MARINA; KARAKAS, CEMAL; CHOI, WILLIAM; MA, LIHUA; MALETIĆ-SAVATIĆ, MIRJANA

    2014-01-01

    Metabolic processes are essential for cellular function and survival. We are interested in inferring a metabolic network in activated microglia, a major neuroimmune cell in the brain responsible for the neuroinflammation associated with neurological diseases, based on a set of quantified metabolites. To achieve this, we apply the Bayesian adaptive graphical lasso with informative priors that incorporate known relationships between covariates. To encourage sparsity, the Bayesian graphical lasso places double exponential priors on the off-diagonal entries of the precision matrix. The Bayesian adaptive graphical lasso allows each double exponential prior to have a unique shrinkage parameter. These shrinkage parameters share a common gamma hyperprior. We extend this model to create an informative prior structure by formulating tailored hyperpriors on the shrinkage parameters. By choosing parameter values for each hyperprior that shift probability mass toward zero for nodes that are close together in a reference network, we encourage edges between covariates with known relationships. This approach can improve the reliability of network inference when the sample size is small relative to the number of parameters to be estimated. When applied to the data on activated microglia, the inferred network includes both known relationships and associations of potential interest for further investigation. PMID:24533172

  4. IKKβ promotes metabolic adaptation to glutamine deprivation via phosphorylation and inhibition of PFKFB3.

    PubMed

    Reid, Michael A; Lowman, Xazmin H; Pan, Min; Tran, Thai Q; Warmoes, Marc O; Ishak Gabra, Mari B; Yang, Ying; Locasale, Jason W; Kong, Mei

    2016-08-15

    Glutamine is an essential nutrient for cancer cell survival and proliferation. Enhanced utilization of glutamine often depletes its local supply, yet how cancer cells adapt to low glutamine conditions is largely unknown. Here, we report that IκB kinase β (IKKβ) is activated upon glutamine deprivation and is required for cell survival independently of NF-κB transcription. We demonstrate that IKKβ directly interacts with and phosphorylates 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase isoform 3 (PFKFB3), a major driver of aerobic glycolysis, at Ser269 upon glutamine deprivation to inhibit its activity, thereby down-regulating aerobic glycolysis when glutamine levels are low. Thus, due to lack of inhibition of PFKFB3, IKKβ-deficient cells exhibit elevated aerobic glycolysis and lactate production, leading to less glucose carbons contributing to tricarboxylic acid (TCA) cycle intermediates and the pentose phosphate pathway, which results in increased glutamine dependence for both TCA cycle intermediates and reactive oxygen species suppression. Therefore, coinhibition of IKKβ and glutamine metabolism results in dramatic synergistic killing of cancer cells both in vitro and in vivo. In all, our results uncover a previously unidentified role of IKKβ in regulating glycolysis, sensing low-glutamine-induced metabolic stress, and promoting cellular adaptation to nutrient availability. PMID:27585591

  5. Metabolic modelling reveals the specialization of secondary replicons for niche adaptation in Sinorhizobium meliloti.

    PubMed

    diCenzo, George C; Checcucci, Alice; Bazzicalupo, Marco; Mengoni, Alessio; Viti, Carlo; Dziewit, Lukasz; Finan, Turlough M; Galardini, Marco; Fondi, Marco

    2016-01-01

    The genome of about 10% of bacterial species is divided among two or more large chromosome-sized replicons. The contribution of each replicon to the microbial life cycle (for example, environmental adaptations and/or niche switching) remains unclear. Here we report a genome-scale metabolic model of the legume symbiont Sinorhizobium meliloti that is integrated with carbon utilization data for 1,500 genes with 192 carbon substrates. Growth of S. meliloti is modelled in three ecological niches (bulk soil, rhizosphere and nodule) with a focus on the role of each of its three replicons. We observe clear metabolic differences during growth in the tested ecological niches and an overall reprogramming following niche switching. In silico examination of the inferred fitness of gene deletion mutants suggests that secondary replicons evolved to fulfil a specialized function, particularly host-associated niche adaptation. Thus, genes on secondary replicons might potentially be manipulated to promote or suppress host interactions for biotechnological purposes. PMID:27447951

  6. Metabolic modelling reveals the specialization of secondary replicons for niche adaptation in Sinorhizobium meliloti

    PubMed Central

    diCenzo, George C.; Checcucci, Alice; Bazzicalupo, Marco; Mengoni, Alessio; Viti, Carlo; Dziewit, Lukasz; Finan, Turlough M.; Galardini, Marco; Fondi, Marco

    2016-01-01

    The genome of about 10% of bacterial species is divided among two or more large chromosome-sized replicons. The contribution of each replicon to the microbial life cycle (for example, environmental adaptations and/or niche switching) remains unclear. Here we report a genome-scale metabolic model of the legume symbiont Sinorhizobium meliloti that is integrated with carbon utilization data for 1,500 genes with 192 carbon substrates. Growth of S. meliloti is modelled in three ecological niches (bulk soil, rhizosphere and nodule) with a focus on the role of each of its three replicons. We observe clear metabolic differences during growth in the tested ecological niches and an overall reprogramming following niche switching. In silico examination of the inferred fitness of gene deletion mutants suggests that secondary replicons evolved to fulfil a specialized function, particularly host-associated niche adaptation. Thus, genes on secondary replicons might potentially be manipulated to promote or suppress host interactions for biotechnological purposes. PMID:27447951

  7. Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans.

    PubMed

    Burgomaster, Kirsten A; Howarth, Krista R; Phillips, Stuart M; Rakobowchuk, Mark; Macdonald, Maureen J; McGee, Sean L; Gibala, Martin J

    2008-01-01

    Low-volume 'sprint' interval training (SIT) stimulates rapid improvements in muscle oxidative capacity that are comparable to levels reached following traditional endurance training (ET) but no study has examined metabolic adaptations during exercise after these different training strategies. We hypothesized that SIT and ET would induce similar adaptations in markers of skeletal muscle carbohydrate (CHO) and lipid metabolism and metabolic control during exercise despite large differences in training volume and time commitment. Active but untrained subjects (23 +/- 1 years) performed a constant-load cycling challenge (1 h at 65% of peak oxygen uptake (.VO(2peak)) before and after 6 weeks of either SIT or ET (n = 5 men and 5 women per group). SIT consisted of four to six repeats of a 30 s 'all out' Wingate Test (mean power output approximately 500 W) with 4.5 min recovery between repeats, 3 days per week. ET consisted of 40-60 min of continuous cycling at a workload that elicited approximately 65% (mean power output approximately 150 W) per day, 5 days per week. Weekly time commitment (approximately 1.5 versus approximately 4.5 h) and total training volume (approximately 225 versus approximately 2250 kJ week(-1)) were substantially lower in SIT versus ET. Despite these differences, both protocols induced similar increases (P < 0.05) in mitochondrial markers for skeletal muscle CHO (pyruvate dehydrogenase E1alpha protein content) and lipid oxidation (3-hydroxyacyl CoA dehydrogenase maximal activity) and protein content of peroxisome proliferator-activated receptor-gamma coactivator-1alpha. Glycogen and phosphocreatine utilization during exercise were reduced after training, and calculated rates of whole-body CHO and lipid oxidation were decreased and increased, respectively, with no differences between groups (all main effects, P < 0.05). Given the markedly lower training volume in the SIT group, these data suggest that high-intensity interval training is a time

  8. Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans

    PubMed Central

    Burgomaster, Kirsten A; Howarth, Krista R; Phillips, Stuart M; Rakobowchuk, Mark; MacDonald, Maureen J; McGee, Sean L; Gibala, Martin J

    2008-01-01

    Low-volume ‘sprint’ interval training (SIT) stimulates rapid improvements in muscle oxidative capacity that are comparable to levels reached following traditional endurance training (ET) but no study has examined metabolic adaptations during exercise after these different training strategies. We hypothesized that SIT and ET would induce similar adaptations in markers of skeletal muscle carbohydrate (CHO) and lipid metabolism and metabolic control during exercise despite large differences in training volume and time commitment. Active but untrained subjects (23 ± 1 years) performed a constant-load cycling challenge (1 h at 65% of peak oxygen uptake before and after 6 weeks of either SIT or ET (n = 5 men and 5 women per group). SIT consisted of four to six repeats of a 30 s ‘all out’ Wingate Test (mean power output ∼500 W) with 4.5 min recovery between repeats, 3 days per week. ET consisted of 40–60 min of continuous cycling at a workload that elicited ∼65% (mean power output ∼150 W) per day, 5 days per week. Weekly time commitment (∼1.5 versus∼4.5 h) and total training volume (∼225 versus∼2250 kJ week−1) were substantially lower in SIT versus ET. Despite these differences, both protocols induced similar increases (P < 0.05) in mitochondrial markers for skeletal muscle CHO (pyruvate dehydrogenase E1α protein content) and lipid oxidation (3-hydroxyacyl CoA dehydrogenase maximal activity) and protein content of peroxisome proliferator-activated receptor-γ coactivator-1α. Glycogen and phosphocreatine utilization during exercise were reduced after training, and calculated rates of whole-body CHO and lipid oxidation were decreased and increased, respectively, with no differences between groups (all main effects, P < 0.05). Given the markedly lower training volume in the SIT group, these data suggest that high-intensity interval training is a time-efficient strategy to increase skeletal muscle oxidative capacity and induce specific metabolic

  9. Energy metabolism of Macaca mulatta during spaceflight

    NASA Technical Reports Server (NTRS)

    Hoban-Higgins, T. M.; Stein, T. P.; Dotsenko, M. A.; Korolkov, V. I.; Fuller, C. A.

    2000-01-01

    The mean daily energy expenditure rates of two rhesus monkeys (Macaca mulatta) were determined during spaceflight on the joint U.S./Russian Bion 11 mission by the doubly labeled water (DLW, 2H218O) method. Control values were obtained from two studies performed under flight-like conditions (n = 4). The mean inflight energy expenditure for the two Bion 11 monkeys was 81.3 kcal/kg/day, which was higher than that seen previously. The average energy expenditure (77.6 +/- 4.4 kcal/kg/day) for the four ground control monkeys was slightly lower than had been measured previously.

  10. Fatty acids from diet and microbiota regulate energy metabolism

    PubMed Central

    Alcock, Joe; Lin, Henry C.

    2015-01-01

    A high-fat diet and elevated levels of free fatty acids are known risk factors for metabolic syndrome, insulin resistance, and visceral obesity. Although these disease associations are well established, it is unclear how different dietary fats change the risk of insulin resistance and metabolic syndrome. Here, we review emerging evidence that insulin resistance and fat storage are linked to changes in the gut microbiota. The gut microbiota and intestinal barrier function, in turn, are highly influenced by the composition of fat in the diet. We review findings that certain fats (for example, long-chain saturated fatty acids) are associated with dysbiosis, impairment of intestinal barrier function, and metabolic endotoxemia. In contrast, other fatty acids, including short-chain and certain unsaturated fatty acids, protect against dysbiosis and impairment of barrier function caused by other dietary fats. These fats may promote insulin sensitivity by inhibiting metabolic endotoxemia and dysbiosis-driven inflammation. During dysbiosis, the modulation of metabolism by diet and microbiota may represent an adaptive process that compensates for the increased fuel demands of an activated immune system. PMID:27006755

  11. Growth, metabolic status and ovarian function in buffalo (Bubalus bubalis) heifers fed a low energy or high energy diet.

    PubMed

    Campanile, G; Baruselli, P S; Vecchio, D; Prandi, A; Neglia, G; Carvalho, N A T; Sales, J N S; Gasparrini, B; D'Occhio, M J

    2010-10-01

    The aim was to establish the capacity of buffalo heifers to adapt their metabolic requirements to a low energy diet. Murrah buffalo (Bubalus bubalis) heifers undergoing regular estrous cycles were randomly assigned by age, live weight (LW) and body condition score (BCS) to a high energy group (HE, 5.8 milk forage units (MFU)/day, n=6) or low energy group (LE, 3.6 MFU/day, n=6). Circulating concentrations of metabolic substrates, metabolic hormones and reproductive hormones were determined weekly for 19 weeks. Ovarian follicular characteristics and oocyte parameters were also ascertained weekly. Heifers fed the LE diet had a better dry matter conversion than heifers fed the HE diet and the calculated daily energy provision was negative for heifers fed the LE diet (-0.248 MFU) and positive for heifers fed the HE diet (5.4 MFU). Heifers fed the HE diet had an increase in 50 kg LW over the duration of the study whereas LW remained constant for heifers fed the LE diet. The BCS of heifers fed the HE diet (4.2) was greater (P<0.05) than the BCS for heifers fed the LE diet (3.4). Heifers fed the HE diet had greater (P<0.05) circulating concentrations of metabolic substrates (glucose, total cholesterol and HDL cholesterol) and metabolic hormones (insulin, glucagon, leptin and T3) compared with heifers fed the LE diet. There were no significant differences in circulating reproductive hormones between the two groups of heifers. Ovarian follicular characteristics were similar for the two groups of heifers while heifers fed the LE diet tended to have oocytes of reduced quality compared with heifers fed the HE diet. The most notable finding was that heifers fed the LE diet had a negative calculated daily energy provision but were able to maintain LW and reproductive activity. It was concluded that buffalo heifers may potentially have the capacity to undergo metabolic adjustment and reduce their energy requirements when dietary energy is limiting. This adaptive capacity would

  12. Chemotactic signal transduction and phosphate metabolism as adaptive strategies during citrus canker induction by Xanthomonas citri.

    PubMed

    Moreira, Leandro Marcio; Facincani, Agda Paula; Ferreira, Cristiano Barbalho; Ferreira, Rafael Marine; Ferro, Maria Inês Tiraboshi; Gozzo, Fabio Cesar; de Oliveira, Julio Cezar Franco; Ferro, Jesus Aparecido; Soares, Márcia Regina

    2015-03-01

    The genome of Xanthomonas citri subsp. Citri strain 306 pathotype A (Xac) was completely sequenced more than 10 years; to date, few studies involving functional genomics Xac and its host compatible have been developed, specially related to adaptive events that allow the survival of Xac within the plant. Proteomic analysis of Xac showed that the processes of chemotactic signal transduction and phosphate metabolism are key adaptive strategies during the interaction of a pathogenic bacterium with its plant host. The results also indicate the importance of a group of proteins that may not be directly related to the classical virulence factors, but that are likely fundamental to the success of the initial stages of the infection, such as methyl-accepting chemotaxis protein (Mcp) and phosphate specific transport (Pst). Furthermore, the analysis of the mutant of the gene pstB which codifies to an ABC phosphate transporter subunit revealed a complete absence of citrus canker symptoms when inoculated in compatible hosts. We also conducted an in silico analysis which established the possible network of genes regulated by two-component systems PhoPQ and PhoBR (related to phosphate metabolism), and possible transcriptional factor binding site (TFBS) motifs of regulatory proteins PhoB and PhoP, detaching high degree of conservation of PhoB TFBS in 84 genes of Xac genome. This is the first time that chemotaxis signal transduction and phosphate metabolism were therefore indicated to be fundamental to the process of colonization of plant tissue during the induction of disease associated with Xanthomonas genus bacteria.

  13. Adipose energy stores, physical work, and the metabolic syndrome: lessons from hummingbirds.

    PubMed

    Hargrove, James L

    2005-12-13

    Hummingbirds and other nectar-feeding, migratory birds possess unusual adaptive traits that offer important lessons concerning obesity, diabetes and the metabolic syndrome. Hummingbirds consume a high sugar diet and have fasting glucose levels that would be severely hyperglycemic in humans, yet these nectar-fed birds recover most glucose that is filtered into the urine. Hummingbirds accumulate over 40% body fat shortly before migrations in the spring and autumn. Despite hyperglycemia and seasonally elevated body fat, the birds are not known to become diabetic in the sense of developing polyuria (glucosuria), polydipsia and polyphagia. The tiny (3-4 g) Ruby-throated hummingbird has among the highest mass-specific metabolic rates known, and loses most of its stored fat in 20 h by flying up to 600 miles across the Gulf of Mexico. During the breeding season, it becomes lean and maintains an extremely accurate energy balance. In addition, hummingbirds can quickly enter torpor and reduce resting metabolic rates by 10-fold. Thus, hummingbirds are wonderful examples of the adaptive nature of fat tissue, and may offer lessons concerning prevention of metabolic syndrome in humans.

  14. Control of metabolic adaptation to fasting by dILP6-induced insulin signaling in Drosophila oenocytes.

    PubMed

    Chatterjee, Debamita; Katewa, Subhash D; Qi, Yanyan; Jackson, Susan A; Kapahi, Pankaj; Jasper, Heinrich

    2014-12-16

    Metabolic adaptation to changing dietary conditions is critical to maintain homeostasis of the internal milieu. In metazoans, this adaptation is achieved by a combination of tissue-autonomous metabolic adjustments and endocrine signals that coordinate the mobilization, turnover, and storage of nutrients across tissues. To understand metabolic adaptation comprehensively, detailed insight into these tissue interactions is necessary. Here we characterize the tissue-specific response to fasting in adult flies and identify an endocrine interaction between the fat body and liver-like oenocytes that regulates the mobilization of lipid stores. Using tissue-specific expression profiling, we confirm that oenocytes in adult flies play a central role in the metabolic adaptation to fasting. Furthermore, we find that fat body-derived Drosophila insulin-like peptide 6 (dILP6) induces lipid uptake in oenocytes, promoting lipid turnover during fasting and increasing starvation tolerance of the animal. Selective activation of insulin/IGF signaling in oenocytes by a fat body-derived peptide represents a previously unidentified regulatory principle in the control of metabolic adaptation and starvation tolerance. PMID:25472843

  15. Control of metabolic adaptation to fasting by dILP6-induced insulin signaling in Drosophila oenocytes.

    PubMed

    Chatterjee, Debamita; Katewa, Subhash D; Qi, Yanyan; Jackson, Susan A; Kapahi, Pankaj; Jasper, Heinrich

    2014-12-16

    Metabolic adaptation to changing dietary conditions is critical to maintain homeostasis of the internal milieu. In metazoans, this adaptation is achieved by a combination of tissue-autonomous metabolic adjustments and endocrine signals that coordinate the mobilization, turnover, and storage of nutrients across tissues. To understand metabolic adaptation comprehensively, detailed insight into these tissue interactions is necessary. Here we characterize the tissue-specific response to fasting in adult flies and identify an endocrine interaction between the fat body and liver-like oenocytes that regulates the mobilization of lipid stores. Using tissue-specific expression profiling, we confirm that oenocytes in adult flies play a central role in the metabolic adaptation to fasting. Furthermore, we find that fat body-derived Drosophila insulin-like peptide 6 (dILP6) induces lipid uptake in oenocytes, promoting lipid turnover during fasting and increasing starvation tolerance of the animal. Selective activation of insulin/IGF signaling in oenocytes by a fat body-derived peptide represents a previously unidentified regulatory principle in the control of metabolic adaptation and starvation tolerance.

  16. Metabolic adaptation of Mycobacterium avium subsp. paratuberculosis to the gut environment.

    PubMed

    Weigoldt, Mathias; Meens, Jochen; Bange, Franz-Christoph; Pich, Andreas; Gerlach, Gerald F; Goethe, Ralph

    2013-02-01

    Knowledge on the proteome level about the adaptation of pathogenic mycobacteria to the environment in their natural hosts is limited. Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease, a chronic and incurable granulomatous enteritis of ruminants, and has been suggested to be a putative aetiological agent of Crohn's disease in humans. Using a comprehensive LC-MS-MS and 2D difference gel electrophoresis (DIGE) approach, we compared the protein profiles of clinical strains of MAP prepared from the gastrointestinal tract of diseased cows with the protein profiles of the same strains after they were grown in vitro. LC-MS-MS analyses revealed that the principal enzymes for the central carbon metabolic pathways, including glycolysis, gluconeogenesis, the tricaboxylic acid cycle and the pentose phosphate pathway, were present under both conditions. Moreover, a broad spectrum of enzymes for β-oxidation of lipids, nine of which have been shown to be necessary for mycobacterial growth on cholesterol, were detected in vivo and in vitro. Using 2D-DIGE we found increased levels of several key enzymes that indicated adaptation of MAP to the host. Among these, FadE5, FadE25 and AdhB indicated that cholesterol is used as a carbon source in the bovine intestinal mucosa; the respiratory enzymes AtpA, NuoG and SdhA suggested increased respiration during infection. Furthermore higher levels of the pentose phosphate pathway enzymes Gnd2, Zwf and Tal as well as of KatG, SodA and GroEL indicated a vigorous stress response of MAP in vivo. In conclusion, our results provide novel insights into the metabolic adaptation of a pathogenic mycobacterium in its natural host. PMID:23223439

  17. Metabolic adaptation of Mycobacterium avium subsp. paratuberculosis to the gut environment.

    PubMed

    Weigoldt, Mathias; Meens, Jochen; Bange, Franz-Christoph; Pich, Andreas; Gerlach, Gerald F; Goethe, Ralph

    2013-02-01

    Knowledge on the proteome level about the adaptation of pathogenic mycobacteria to the environment in their natural hosts is limited. Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease, a chronic and incurable granulomatous enteritis of ruminants, and has been suggested to be a putative aetiological agent of Crohn's disease in humans. Using a comprehensive LC-MS-MS and 2D difference gel electrophoresis (DIGE) approach, we compared the protein profiles of clinical strains of MAP prepared from the gastrointestinal tract of diseased cows with the protein profiles of the same strains after they were grown in vitro. LC-MS-MS analyses revealed that the principal enzymes for the central carbon metabolic pathways, including glycolysis, gluconeogenesis, the tricaboxylic acid cycle and the pentose phosphate pathway, were present under both conditions. Moreover, a broad spectrum of enzymes for β-oxidation of lipids, nine of which have been shown to be necessary for mycobacterial growth on cholesterol, were detected in vivo and in vitro. Using 2D-DIGE we found increased levels of several key enzymes that indicated adaptation of MAP to the host. Among these, FadE5, FadE25 and AdhB indicated that cholesterol is used as a carbon source in the bovine intestinal mucosa; the respiratory enzymes AtpA, NuoG and SdhA suggested increased respiration during infection. Furthermore higher levels of the pentose phosphate pathway enzymes Gnd2, Zwf and Tal as well as of KatG, SodA and GroEL indicated a vigorous stress response of MAP in vivo. In conclusion, our results provide novel insights into the metabolic adaptation of a pathogenic mycobacterium in its natural host.

  18. Energy Sector Adaptation in Response to Water Scarcity

    NASA Astrophysics Data System (ADS)

    Johnson, N. A.; Fricko, O.; Parkinson, S.; Riahi, K.

    2015-12-01

    Global energy systems models have largely ignored the impacts of water scarcity on the energy sector and the related implications for climate change mitigation. However, significant water is required in the production of energy, including for thermoelectric power plant cooling, hydropower generation, irrigation for bioenergy, and the extraction and refining of liquid fuels. With a changing climate and expectations of increasing competition for water from the agricultural and municipal sectors, it is unclear whether sufficient water will be available where needed to support water-intensive energy technologies in the future. Thus, it is important that water use and water constraints are incorporated into energy systems models to better understand energy sector adaptation to water scarcity. The global energy systems model, MESSAGE, has recently been updated to quantify the water consumption and withdrawal requirements of the energy sector and now includes several cooling technologies for addressing water scarcity. This study introduces water constraints into the model to examine whether and how the energy sector can adapt to water scarcity over the next century. In addition, the implications for climate mitigation are evaluated under a scenario in which warming is limited to 2˚C over the pre-industrial level. Given the difficulty of introducing meaningful water constraints into global models, we use a simplistic approach and evaluate a series of scenarios in which the water available to the energy sector is systematically reduced. This approach allows for the evaluation of energy sector adaptations under various levels of water scarcity and can provide insight into how water scarcity, whether from climate change or competing demands, may impact the energy sector in different world regions. This study will provide insight into the following questions: How does the energy sector adapt to water scarcity in different regions? What are the costs associated with adaptation

  19. An Energy Aware Adaptive Sampling Algorithm for Energy Harvesting WSN with Energy Hungry Sensors.

    PubMed

    Srbinovski, Bruno; Magno, Michele; Edwards-Murphy, Fiona; Pakrashi, Vikram; Popovici, Emanuel

    2016-03-28

    Wireless sensor nodes have a limited power budget, though they are often expected to be functional in the field once deployed for extended periods of time. Therefore, minimization of energy consumption and energy harvesting technology in Wireless Sensor Networks (WSN) are key tools for maximizing network lifetime, and achieving self-sustainability. This paper proposes an energy aware Adaptive Sampling Algorithm (ASA) for WSN with power hungry sensors and harvesting capabilities, an energy management technique that can be implemented on any WSN platform with enough processing power to execute the proposed algorithm. An existing state-of-the-art ASA developed for wireless sensor networks with power hungry sensors is optimized and enhanced to adapt the sampling frequency according to the available energy of the node. The proposed algorithm is evaluated using two in-field testbeds that are supplied by two different energy harvesting sources (solar and wind). Simulation and comparison between the state-of-the-art ASA and the proposed energy aware ASA (EASA) in terms of energy durability are carried out using in-field measured harvested energy (using both wind and solar sources) and power hungry sensors (ultrasonic wind sensor and gas sensors). The simulation results demonstrate that using ASA in combination with an energy aware function on the nodes can drastically increase the lifetime of a WSN node and enable self-sustainability. In fact, the proposed EASA in conjunction with energy harvesting capability can lead towards perpetual WSN operation and significantly outperform the state-of-the-art ASA.

  20. Fetal endocrine and metabolic adaptations to hypoxia: the role of the hypothalamic-pituitary-adrenal axis.

    PubMed

    Newby, Elizabeth A; Myers, Dean A; Ducsay, Charles A

    2015-09-01

    In utero, hypoxia is a significant yet common stress that perturbs homeostasis and can occur due to preeclampsia, preterm labor, maternal smoking, heart or lung disease, obesity, and high altitude. The fetus has the extraordinary capacity to respond to stress during development. This is mediated in part by the hypothalamic-pituitary-adrenal (HPA) axis and more recently explored changes in perirenal adipose tissue (PAT) in response to hypoxia. Obvious ethical considerations limit studies of the human fetus, and fetal studies in the rodent model are limited due to size considerations and major differences in developmental landmarks. The sheep is a common model that has been used extensively to study the effects of both acute and chronic hypoxia on fetal development. In response to high-altitude-induced, moderate long-term hypoxia (LTH), both the HPA axis and PAT adapt to preserve normal fetal growth and development while allowing for responses to acute stress. Although these adaptations appear beneficial during fetal development, they may become deleterious postnatally and into adulthood. The goal of this review is to examine the role of the HPA axis in the convergence of endocrine and metabolic adaptive responses to hypoxia in the fetus.

  1. Fetal endocrine and metabolic adaptations to hypoxia: the role of the hypothalamic-pituitary-adrenal axis

    PubMed Central

    Newby, Elizabeth A.; Myers, Dean A.

    2015-01-01

    In utero, hypoxia is a significant yet common stress that perturbs homeostasis and can occur due to preeclampsia, preterm labor, maternal smoking, heart or lung disease, obesity, and high altitude. The fetus has the extraordinary capacity to respond to stress during development. This is mediated in part by the hypothalamic-pituitary-adrenal (HPA) axis and more recently explored changes in perirenal adipose tissue (PAT) in response to hypoxia. Obvious ethical considerations limit studies of the human fetus, and fetal studies in the rodent model are limited due to size considerations and major differences in developmental landmarks. The sheep is a common model that has been used extensively to study the effects of both acute and chronic hypoxia on fetal development. In response to high-altitude-induced, moderate long-term hypoxia (LTH), both the HPA axis and PAT adapt to preserve normal fetal growth and development while allowing for responses to acute stress. Although these adaptations appear beneficial during fetal development, they may become deleterious postnatally and into adulthood. The goal of this review is to examine the role of the HPA axis in the convergence of endocrine and metabolic adaptive responses to hypoxia in the fetus. PMID:26173460

  2. Mitochondria-associated endoplasmic reticulum membranes allow adaptation of mitochondrial metabolism to glucose availability in the liver.

    PubMed

    Theurey, Pierre; Tubbs, Emily; Vial, Guillaume; Jacquemetton, Julien; Bendridi, Nadia; Chauvin, Marie-Agnès; Alam, Muhammad Rizwan; Le Romancer, Muriel; Vidal, Hubert; Rieusset, Jennifer

    2016-04-01

    Mitochondria-associated endoplasmic reticulum membranes (MAM) play a key role in mitochondrial dynamics and function and in hepatic insulin action. Whereas mitochondria are important regulators of energy metabolism, the nutritional regulation of MAM in the liver and its role in the adaptation of mitochondria physiology to nutrient availability are unknown. In this study, we found that the fasted to postprandial transition reduced the number of endoplasmic reticulum-mitochondria contact points in mouse liver. Screening of potential hormonal/metabolic signals revealed glucose as the main nutritional regulator of hepatic MAM integrity both in vitro and in vivo Glucose reduced organelle interactions through the pentose phosphate-protein phosphatase 2A (PP-PP2A) pathway, induced mitochondria fission, and impaired respiration. Blocking MAM reduction counteracted glucose-induced mitochondrial alterations. Furthermore, disruption of MAM integrity mimicked effects of glucose on mitochondria dynamics and function. This glucose-sensing system is deficient in the liver of insulin-resistant ob/ob and cyclophilin D-KO mice, both characterized by chronic disruption of MAM integrity, mitochondrial fission, and altered mitochondrial respiration. These data indicate that MAM contribute to the hepatic glucose-sensing system, allowing regulation of mitochondria dynamics and function during nutritional transition. Chronic disruption of MAM may participate in hepatic mitochondrial dysfunction associated with insulin resistance.

  3. Water-energy links in cities: the urban metabolism of London

    NASA Astrophysics Data System (ADS)

    Mijic, A.; Ruiz Cazorla, J.; Keirstead, J.

    2014-12-01

    Rapid urbanisation results in increased water consumption in cities, requiring improved tools for understanding adaptive measures for water resources management under climate change. The energy sector is facing the same challenges and requires equally comprehensive solutions. More frequent water shortages due to climate and land use changes and potential limits on CO2 emissions from fossil fuels that science demands indicate clearly that the next step in the sustainable city development will be to look for the most efficient use of these highly interdependent resources. One of the concepts that could be used for quantifying fundamental flows in an urban environment such as water and energy is the urban metabolism framework. This paper will examine the concept of urban metabolism by quantifying amounts and trends of water and energy consumed in London by four main sectors: residential, industrial, commercial and public. Key data requirements at the sector level will be identified and initial mapping of critical factors for urban sustainability will be provided. Finally, the work will examine the potential of urban metabolism framework to provide data and information for implementing water, energy and greenhouse emissions trade-off 'fit-for-purpose' strategy for water supply security. The paper is a part of the Panta Rhei Research Initiative of the International Association of Hydrological Sciences (IAHS) under the working group of Energy and Food Impacts on Water.

  4. ADAPTIVE FULL-SPECTRUM SOLOR ENERGY SYSTEMS

    SciTech Connect

    Byard D. Wood

    2004-04-01

    This RD&D project is a three year team effort to develop a hybrid solar lighting (HSL) system that transports solar light from a paraboloidal dish concentrator to a luminaire via a large core polymer fiber optic. The luminaire can be a device to distribute sunlight into a space for the production of algae or it can be a device that is a combination of solar lighting and electric lighting. A benchmark prototype system has been developed to evaluate the HSL system. Sunlight is collected using a one-meter paraboloidal concentrator dish with two-axis tracking. A secondary mirror consisting of eight planar-segmented mirrors directs the visible part of the spectrum to eight fibers (receiver) and subsequently to eight luminaires. This results in about 8,200 lumens incident at each fiber tip. Each fiber can illuminate about 16.7 m{sup 2} (180 ft{sup 2}) of office space. The IR spectrum is directed to a thermophotovoltaic (TPV) array to produce electricity. During this reporting period, the project team made advancements in the design of the second generation (Alpha) system. For the Alpha system, the eight individual 12 mm fibers have been replaced with a centralized bundle of 3 mm fibers. The TRNSYS Full-Spectrum Solar Energy System model has been updated and new components have been added. The TPV array and nonimaging device have been tested and progress has been made in the fiber transmission models. A test plan was developed for both the high-lumen tests and the study to determine the non-energy benefits of daylighting. The photobioreactor team also made major advancements in the testing of model scale and bench top lab-scale systems.

  5. Fatty Acids in Energy Metabolism of the Central Nervous System

    PubMed Central

    Orynbayeva, Zulfiya; Vavilin, Valentin; Lyakhovich, Vyacheslav

    2014-01-01

    In this review, we analyze the current hypotheses regarding energy metabolism in the neurons and astroglia. Recently, it was shown that up to 20% of the total brain's energy is provided by mitochondrial oxidation of fatty acids. However, the existing hypotheses consider glucose, or its derivative lactate, as the only main energy substrate for the brain. Astroglia metabolically supports the neurons by providing lactate as a substrate for neuronal mitochondria. In addition, a significant amount of neuromediators, glutamate and GABA, is transported into neurons and also serves as substrates for mitochondria. Thus, neuronal mitochondria may simultaneously oxidize several substrates. Astrocytes have to replenish the pool of neuromediators by synthesis de novo, which requires large amounts of energy. In this review, we made an attempt to reconcile β-oxidation of fatty acids by astrocytic mitochondria with the existing hypothesis on regulation of aerobic glycolysis. We suggest that, under condition of neuronal excitation, both metabolic pathways may exist simultaneously. We provide experimental evidence that isolated neuronal mitochondria may oxidize palmitoyl carnitine in the presence of other mitochondrial substrates. We also suggest that variations in the brain mitochondrial metabolic phenotype may be associated with different mtDNA haplogroups. PMID:24883315

  6. Metabolomic profiling of the heart during acute ischemic preconditioning reveals a role for SIRT1 in rapid cardioprotective metabolic adaptation.

    PubMed

    Nadtochiy, Sergiy M; Urciuoli, William; Zhang, Jimmy; Schafer, Xenia; Munger, Joshua; Brookes, Paul S

    2015-11-01

    Ischemic preconditioning (IPC) protects tissues such as the heart from prolonged ischemia-reperfusion (IR) injury. We previously showed that the lysine deacetylase SIRT1 is required for acute IPC, and has numerous metabolic targets. While it is known that metabolism is altered during IPC, the underlying metabolic regulatory mechanisms are unknown, including the relative importance of SIRT1. Thus, we sought to test the hypothesis that some of the metabolic adaptations that occur in IPC may require SIRT1 as a regulatory mediator. Using both ex-vivo-perfused and in-vivo mouse hearts, LC-MS/MS based metabolomics and (13)C-labeled substrate tracing, we found that acute IPC altered several metabolic pathways including: (i) stimulation of glycolysis, (ii) increased synthesis of glycogen and several amino acids, (iii) increased reduced glutathione levels, (iv) elevation in the oncometabolite 2-hydroxyglutarate, and (v) inhibition of fatty-acid dependent respiration. The majority (83%) of metabolic alterations induced by IPC were ablated when SIRT1 was acutely inhibited with splitomicin, and a principal component analysis revealed that metabolic changes in response to IPC were fundamentally different in nature when SIRT1 was inhibited. Furthermore, the protective benefit of IPC was abrogated by eliminating glucose from perfusion media while sustaining normal cardiac function by burning fat, thus indicating that glucose dependency is required for acute IPC. Together, these data suggest that SIRT1 signaling is required for rapid cardioprotective metabolic adaptation in acute IPC.

  7. Cardiac Resynchronization Therapy Induces Adaptive Metabolic Transitions in the Metabolomic Profile of Heart Failure

    PubMed Central

    Nemutlu, Emirhan; Zhang, Song; Xu, Yi-Zhou; Terzic, Andre; Zhong, Li; Dzeja, Petras D.; Cha, Yong-Mei

    2015-01-01

    Background Heart failure (HF) is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT). The aim of this study was to determine the metabolomic signature in HF and its prognostic value for the response to CRT. Methods This prospective study consisted of 24 patients undergoing CRT for advanced HF and 10 control patients who underwent catheter ablation for supraventricular arrhythmia but not CRT. Blood samples were collected before and 3 months after CRT. Metabolomic profiling of plasma samples was performed using gas chromatography–mass spectrometry and nuclear magnetic resonance. Results The plasma metabolomic profile was altered in the HF patients, with a distinct panel of metabolites, including Krebs cycle and lipid, amino acid, and nucleotide metabolism. CRT improved the metabolic profile. The succinate/glutamate ratio, an index of Krebs cycle activity, improved from 0.58±0.13 to 2.84±0.60 (P<.05). The glucose/palmitate ratio, an indicator of the balance between glycolytic and fatty acid metabolism, increased from 0.96±0.05 to 1.54±0.09 (P<.01). Compared with the nonresponders to CRT, the responders had a distinct baseline plasma metabolomic profile, including higher isoleucine, phenylalanine, leucine, glucose, and valine levels and lower glutamate levels at baseline (P<.05). Conclusion CRT improves plasma metabolomic profile of HF patients indicating harmonization of myocardial energy substrate metabolism. CRT responders may have a favorable metabolic profile as a potential biomarker for predicting CRT outcome. PMID:25911126

  8. Clinical Neurochemistry of Subarachnoid Hemorrhage: Toward Predicting Individual Outcomes via Biomarkers of Brain Energy Metabolism.

    PubMed

    Tholance, Yannick; Barcelos, Gleicy; Dailler, Frederic; Perret-Liaudet, Armand; Renaud, Bernard

    2015-12-16

    The functional outcome of patients with subarachnoid hemorrhage is difficult to predict at the individual level. The monitoring of brain energy metabolism has proven to be useful in improving the pathophysiological understanding of subarachnoid hemorrhage. Nonetheless, brain energy monitoring has not yet clearly been included in official guidelines for the management of subarachnoid hemorrhage patients, likely because previous studies compared only biological data between two groups of patients (unfavorable vs favorable outcomes) and did not determine decision thresholds that could be useful in clinical practice. Therefore, this Viewpoint discusses recent findings suggesting that monitoring biomarkers of brain energy metabolism at the level of individuals can be used to predict the outcomes of subarachnoid hemorrhage patients. Indeed, by taking into account specific neurochemical patterns obtained by local or global monitoring of brain energy metabolism, it may become possible to predict routinely, and with sufficient sensitivity and specificity, the individual outcomes of subarachnoid hemorrhage patients. Moreover, combining both local and global monitoring improves the overall performance of individual outcome prediction. Such a combined neurochemical monitoring approach may become, after prospective clinical validation, an important component in the management of subarachnoid hemorrhage patients to adapt individualized therapeutic interventions. PMID:26595414

  9. Staphylococcus aureus Metabolic Adaptations during the Transition from a Daptomycin Susceptibility Phenotype to a Daptomycin Nonsusceptibility Phenotype

    PubMed Central

    Gaupp, Rosmarie; Lei, Shulei; Reed, Joseph M.; Peisker, Henrik; Boyle-Vavra, Susan; Bayer, Arnold S.; Bischoff, Markus; Herrmann, Mathias; Daum, Robert S.

    2015-01-01

    Staphylococcus aureus is a major cause of nosocomial and community-acquired infections. The success of S. aureus as a pathogen is due in part to its many virulence determinants and resistance to antimicrobials. In particular, methicillin-resistant S. aureus has emerged as a major cause of infections and led to increased use of the antibiotics vancomycin and daptomycin, which has increased the isolation of vancomycin-intermediate S. aureus and daptomycin-nonsusceptible S. aureus strains. The most common mechanism by which S. aureus acquires intermediate resistance to antibiotics is by adapting its physiology and metabolism to permit growth in the presence of these antibiotics, a process known as adaptive resistance. To better understand the physiological and metabolic changes associated with adaptive resistance, six daptomycin-susceptible and -nonsusceptible isogenic strain pairs were examined for changes in growth, competitive fitness, and metabolic alterations. Interestingly, daptomycin nonsusceptibility coincides with a slightly delayed transition to the postexponential growth phase and alterations in metabolism. Specifically, daptomycin-nonsusceptible strains have decreased tricarboxylic acid cycle activity, which correlates with increased synthesis of pyrimidines and purines and increased carbon flow to pathways associated with wall teichoic acid and peptidoglycan biosynthesis. Importantly, these data provided an opportunity to alter the daptomycin nonsusceptibility phenotype by manipulating bacterial metabolism, a first step in developing compounds that target metabolic pathways that can be used in combination with daptomycin to reduce treatment failures. PMID:25963986

  10. Adaptive Control Model Reveals Systematic Feedback and Key Molecules in Metabolic Pathway Regulation

    PubMed Central

    Moffitt, Richard A.; Merrill, Alfred H.; Wang, May D.

    2011-01-01

    Abstract Robust behavior in metabolic pathways resembles stabilized performance in systems under autonomous control. This suggests we can apply control theory to study existing regulation in these cellular networks. Here, we use model-reference adaptive control (MRAC) to investigate the dynamics of de novo sphingolipid synthesis regulation in a combined theoretical and experimental case study. The effects of serine palmitoyltransferase over-expression on this pathway are studied in vitro using human embryonic kidney cells. We report two key results from comparing numerical simulations with observed data. First, MRAC simulations of pathway dynamics are comparable to simulations from a standard model using mass action kinetics. The root-sum-square (RSS) between data and simulations in both cases differ by less than 5%. Second, MRAC simulations suggest systematic pathway regulation in terms of adaptive feedback from individual molecules. In response to increased metabolite levels available for de novo sphingolipid synthesis, feedback from molecules along the main artery of the pathway is regulated more frequently and with greater amplitude than from other molecules along the branches. These biological insights are consistent with current knowledge while being new that they may guide future research in sphingolipid biology. In summary, we report a novel approach to study regulation in cellular networks by applying control theory in the context of robust metabolic pathways. We do this to uncover potential insight into the dynamics of regulation and the reverse engineering of cellular networks for systems biology. This new modeling approach and the implementation routines designed for this case study may be extended to other systems. Supplementary Material is available at www.liebertonline.com/cmb. PMID:21314456

  11. Analysis of Anoxybacillus Genomes from the Aspects of Lifestyle Adaptations, Prophage Diversity, and Carbohydrate Metabolism

    PubMed Central

    Goh, Kian Mau; Gan, Han Ming; Chan, Kok-Gan; Chan, Giek Far; Shahar, Saleha; Chong, Chun Shiong; Kahar, Ummirul Mukminin; Chai, Kian Piaw

    2014-01-01

    Species of Anoxybacillus are widespread in geothermal springs, manure, and milk-processing plants. The genus is composed of 22 species and two subspecies, but the relationship between its lifestyle and genome is little understood. In this study, two high-quality draft genomes were generated from Anoxybacillus spp. SK3-4 and DT3-1, isolated from Malaysian hot springs. De novo assembly and annotation were performed, followed by comparative genome analysis with the complete genome of Anoxybacillus flavithermus WK1 and two additional draft genomes, of A. flavithermus TNO-09.006 and A. kamchatkensis G10. The genomes of Anoxybacillus spp. are among the smaller of the family Bacillaceae. Despite having smaller genomes, their essential genes related to lifestyle adaptations at elevated temperature, extreme pH, and protection against ultraviolet are complete. Due to the presence of various competence proteins, Anoxybacillus spp. SK3-4 and DT3-1 are able to take up foreign DNA fragments, and some of these transferred genes are important for the survival of the cells. The analysis of intact putative prophage genomes shows that they are highly diversified. Based on the genome analysis using SEED, many of the annotated sequences are involved in carbohydrate metabolism. The presence of glycosyl hydrolases among the Anoxybacillus spp. was compared, and the potential applications of these unexplored enzymes are suggested here. This is the first study that compares Anoxybacillus genomes from the aspect of lifestyle adaptations, the capacity for horizontal gene transfer, and carbohydrate metabolism. PMID:24603481

  12. Transcriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP(+).

    PubMed

    Krug, A K; Gutbier, S; Zhao, L; Pöltl, D; Kullmann, C; Ivanova, V; Förster, S; Jagtap, S; Meiser, J; Leparc, G; Schildknecht, S; Adam, M; Hiller, K; Farhan, H; Brunner, T; Hartung, T; Sachinidis, A; Leist, M

    2014-05-08

    Assessment of the network of toxicity pathways by Omics technologies and bioinformatic data processing paves the road toward a new toxicology for the twenty-first century. Especially, the upstream network of responses, taking place in toxicant-treated cells before a point of no return is reached, is still little explored. We studied the effects of the model neurotoxicant 1-methyl-4-phenylpyridinium (MPP(+)) by a combined metabolomics (mass spectrometry) and transcriptomics (microarrays and deep sequencing) approach to provide unbiased data on earliest cellular adaptations to stress. Neural precursor cells (LUHMES) were differentiated to homogeneous cultures of fully postmitotic human dopaminergic neurons, and then exposed to the mitochondrial respiratory chain inhibitor MPP(+) (5 μM). At 18-24 h after treatment, intracellular ATP and mitochondrial integrity were still close to control levels, but pronounced transcriptome and metabolome changes were seen. Data on altered glucose flux, depletion of phosphocreatine and oxidative stress (e.g., methionine sulfoxide formation) confirmed the validity of the approach. New findings were related to nuclear paraspeckle depletion, as well as an early activation of branches of the transsulfuration pathway to increase glutathione. Bioinformatic analysis of our data identified the transcription factor ATF-4 as an upstream regulator of early responses. Findings on this signaling pathway and on adaptive increases of glutathione production were confirmed biochemically. Metabolic and transcriptional profiling contributed complementary information on multiple primary and secondary changes that contribute to the cellular response to MPP(+). Thus, combined 'Omics' analysis is a new unbiased approach to unravel earliest metabolic changes, whose balance decides on the final cell fate.

  13. Glucose metabolic adaptations in the intrauterine growth-restricted adult female rat offspring.

    PubMed

    Garg, Meena; Thamotharan, Manikkavasagar; Rogers, Lisa; Bassilian, Sara; Lee, W N Paul; Devaskar, Sherin U

    2006-06-01

    We studied glucose metabolic adaptations in the intrauterine growth-restricted (IUGR) rat offspring to decipher glucose homeostasis in metabolic programming. Glucose futile cycling (GFC), which is altered when there is imbalance between glucose production and utilization, was studied during a glucose tolerance test (GTT) in 2-day-old (n = 8), 2-mo-old (n = 22), and 15-mo-old (n = 22) female rat offspring. The IUGR rats exposed to either prenatal (CM/SP, n = 5 per age), postnatal (SM/CP, n = 6), or pre- and postnatal (SM/SP, n = 6) nutrient restriction were compared with age-matched controls (CM/CP, n = 5). At 2 days, IUGR pups (SP) were smaller and glucose intolerant and had increased hepatic glucose production and increased glucose disposal (P < 0.01) compared with controls (CP). At 2 mo, the GTT, glucose clearance, and GFC did not change. However, a decline in hepatic glucose-6-phosphatase (P < 0.05) and fructose-1,6-biphosphatase (P < 0.05) enzyme activities in the IUGR offspring was detected. At 15 mo, prenatal nutrient restriction (CM/SP) resulted in greater weight gain (P < 0.01) and hyperinsulinemia (P < 0.001) compared with postnatal nutrient restriction (SM/CP). A decline in GFC in the face of a normal GTT occurred in both the prenatal (CM/SP, P < 0.01) and postnatal calorie (SM/CP, P < 0.03) and growth-restricted offspring. The IUGR offspring with pre- and postnatal nutrient restriction (SM/SP) were smaller, hypoinsulinemic (P < 0.03), and hypoleptinemic (P < 0.03), with no change in GTT, hepatic glucose production, GFC, or glucose clearance. We conclude that there is pre- and postnatal programming that affects the postnatal compensatory adaptation of GFC and disposal initiated by changes in circulating insulin concentrations, thereby determining hepatic insulin sensitivity in a phenotype-specific manner. PMID:16449299

  14. Severe Obesity Shifts Metabolic Thresholds but Does Not Attenuate Aerobic Training Adaptations in Zucker Rats

    PubMed Central

    Rosa, Thiago S.; Simões, Herbert G.; Rogero, Marcelo M.; Moraes, Milton R.; Denadai, Benedito S.; Arida, Ricardo M.; Andrade, Marília S.; Silva, Bruno M.

    2016-01-01

    Severe obesity affects metabolism with potential to influence the lactate and glycemic response to different exercise intensities in untrained and trained rats. Here we evaluated metabolic thresholds and maximal aerobic capacity in rats with severe obesity and lean counterparts at pre- and post-training. Zucker rats (obese: n = 10, lean: n = 10) were submitted to constant treadmill bouts, to determine the maximal lactate steady state, and an incremental treadmill test, to determine the lactate threshold, glycemic threshold and maximal velocity at pre and post 8 weeks of treadmill training. Velocities of the lactate threshold and glycemic threshold agreed with the maximal lactate steady state velocity on most comparisons. The maximal lactate steady state velocity occurred at higher percentage of the maximal velocity in Zucker rats at pre-training than the percentage commonly reported and used for training prescription for other rat strains (i.e., 60%) (obese = 78 ± 9% and lean = 68 ± 5%, P < 0.05 vs. 60%). The maximal lactate steady state velocity and maximal velocity were lower in the obese group at pre-training (P < 0.05 vs. lean), increased in both groups at post-training (P < 0.05 vs. pre), but were still lower in the obese group at post-training (P < 0.05 vs. lean). Training-induced increase in maximal lactate steady state, lactate threshold and glycemic threshold velocities was similar between groups (P > 0.05), whereas increase in maximal velocity was greater in the obese group (P < 0.05 vs. lean). In conclusion, lactate threshold, glycemic threshold and maximal lactate steady state occurred at similar exercise intensity in Zucker rats at pre- and post-training. Severe obesity shifted metabolic thresholds to higher exercise intensity at pre-training, but did not attenuate submaximal and maximal aerobic training adaptations. PMID:27148063

  15. Experimental Resistance to Drug Combinations in Leishmania donovani: Metabolic and Phenotypic Adaptations

    PubMed Central

    Berg, Maya; García-Hernández, Raquel; Cuypers, Bart; Vanaerschot, Manu; Manzano, José I.; Poveda, José A.; Ferragut, José A.; Castanys, Santiago

    2015-01-01

    Together with vector control, chemotherapy is an essential tool for the control of visceral leishmaniasis (VL), but its efficacy is jeopardized by growing resistance and treatment failure against first-line drugs. To delay the emergence of resistance, the use of drug combinations of existing antileishmanial agents has been tested systematically in clinical trials for the treatment of visceral leishmaniasis (VL). In vitro, Leishmania donovani promastigotes are able to develop experimental resistance to several combinations of different antileishmanial drugs after 10 weeks of drug pressure. Using an untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach, we identified metabolic changes in lines that were experimentally resistant to drug combinations and their respective single-resistant lines. This highlighted both collective metabolic changes (found in all combination therapy-resistant [CTR] lines) and specific ones (found in certain CTR lines). We demonstrated that single-resistant and CTR parasite cell lines show distinct metabolic adaptations, which all converge on the same defensive mechanisms that were experimentally validated: protection against drug-induced and external oxidative stress and changes in membrane fluidity. The membrane fluidity changes were accompanied by changes in drug uptake only in the lines that were resistant against drug combinations with antimonials, and surprisingly, drug accumulation was higher in these lines. Together, these results highlight the importance and the central role of protection against oxidative stress in the different resistant lines. Ultimately, these phenotypic changes might interfere with the mode of action of all drugs that are currently used for the treatment of VL and should be taken into account in drug development. PMID:25645828

  16. Assessment of the metabolic capacity and adaptability of aromatic hydrocarbon degrading strain Pseudomonas putida CSV86 in aerobic chemostat culture.

    PubMed

    Nigam, Anshul; Phale, Prashant S; Wangikar, Pramod P

    2012-06-01

    Pseudomonas putida CSV86 utilizes aromatic compounds preferentially over sugars and co-metabolizes aromatics along with organic acids. In the present study, the metabolic capacity and adaptability of strain CSV86 were assessed in a chemostat at benzyl alcohol concentrations ranging from 1 g l(-1) to 3 g l(-1) and in the presence of glucose and succinate by systematically varying the dilution rate. Complete removal of benzyl alcohol was achieved for loadings up to 640 mg l(-1) h(-1) in presence of benzyl alcohol alone. The strain responded within 1 min towards step changes in substrate loading as indicated by an increase in the oxygen uptake rate, presumably as a result of excess metabolic capacity. These results suggest that CSV86 exhibits considerable metabolic elasticity upon increase in substrate load. Metabolic elasticity of the microorganism is an important parameter in wastewater treatment plants due to the changing substrate loads. PMID:22494573

  17. Metabolic Adaptations of White Lupin Roots and Shoots under Phosphorus Deficiency.

    PubMed

    Müller, Julia; Gödde, Victoria; Niehaus, Karsten; Zörb, Christian

    2015-01-01

    White lupin (Lupinus albus L.) is highly adapted to phosphorus-diminished soils. P-deficient white lupin plants modify their root architecture and physiology to acquire sparingly available soil phosphorus. We employed gas chromatography-mass spectrometry (GC-MS) for metabolic profiling of P-deficient white lupins, to investigate biochemical pathways involved in the P-acquiring strategy. After 14 days of P-deficiency, plants showed reduced levels of fructose, glucose, and sucrose in shoots. Phosphorylated metabolites such as glucose-6-phosphate, fructose-6-phosphate, myo-inositol-phosphate and glycerol-3-phosphate were reduced in both shoots and roots. After 22 days of P-deficiency, no effect on shoot or root sugar metabolite levels was found, but the levels of phosphorylated metabolites were further reduced. Organic acids, amino acids and several shikimate pathway products showed enhanced levels in 22-day-old P-deficient roots and shoots. These results indicate that P-deficient white lupins adapt their carbohydrate partitioning between shoot and root in order to supply their growing root system as an early response to P-deficiency. Organic acids are released into the rhizosphere to mobilize phosphorus from soil particles. A longer period of P-deficiency leads to scavenging of Pi from P-containing metabolites and reduced protein anabolism, but enhanced formation of secondary metabolites. The latter can serve as stress protection molecules or actively acquire phosphorus from the soil. PMID:26635840

  18. Hominids adapted to metabolize ethanol long before human-directed fermentation.

    PubMed

    Carrigan, Matthew A; Uryasev, Oleg; Frye, Carole B; Eckman, Blair L; Myers, Candace R; Hurley, Thomas D; Benner, Steven A

    2015-01-13

    Paleogenetics is an emerging field that resurrects ancestral proteins from now-extinct organisms to test, in the laboratory, models of protein function based on natural history and Darwinian evolution. Here, we resurrect digestive alcohol dehydrogenases (ADH4) from our primate ancestors to explore the history of primate-ethanol interactions. The evolving catalytic properties of these resurrected enzymes show that our ape ancestors gained a digestive dehydrogenase enzyme capable of metabolizing ethanol near the time that they began using the forest floor, about 10 million y ago. The ADH4 enzyme in our more ancient and arboreal ancestors did not efficiently oxidize ethanol. This change suggests that exposure to dietary sources of ethanol increased in hominids during the early stages of our adaptation to a terrestrial lifestyle. Because fruit collected from the forest floor is expected to contain higher concentrations of fermenting yeast and ethanol than similar fruits hanging on trees, this transition may also be the first time our ancestors were exposed to (and adapted to) substantial amounts of dietary ethanol.

  19. Metabolic adaptation to sugar/O2 deficiency for anaerobic germination and seedling growth in rice.

    PubMed

    Lee, Kuo-Wei; Chen, Peng Wen; Yu, Su-May

    2014-10-01

    Rice is characterized by a broad range of metabolic and morphological adaptations to flooding, such as germination and mobilization of stored nutrients under submergence until seedlings reach the water surface to carry out photosynthesis, and sustainable growth of mature plants for long durations under partial submergence. The underlying mechanisms of the molecular basis of adaptation to anaerobic germination and seedling growth in rice are being uncovered. Induction of an ensemble of hydrolases to mobilize endosperm nutrient reserves is one of the key factors for successful germination and coleoptile elongation in rice under submergence. To compensate for reduced efficiency of Tricarboxylic Acid cycle and oxidative respiration in mitochondria under O2 deficient conditions, α-amylases play a central role in the hydrolysis of starch to provide sugar substrates for glycolysis and alcohol fermentation for generating ATP. We review the progress on the molecular mechanism regulating α-amylase expression that involves the integration of signals generated by the hormone gibberellin (GA), sugar starvation and O2 deprivation that results in germination and sustainable seedling growth in rice under anaerobic conditions. Comparisons are also made between dicots and monocots for the molecular mechanism of induction of genes involved in alcohol fermentation and sugar/O2 deficiency sensing system.

  20. Metabolic Adaptations of White Lupin Roots and Shoots under Phosphorus Deficiency

    PubMed Central

    Müller, Julia; Gödde, Victoria; Niehaus, Karsten; Zörb, Christian

    2015-01-01

    White lupin (Lupinus albus L.) is highly adapted to phosphorus-diminished soils. P-deficient white lupin plants modify their root architecture and physiology to acquire sparingly available soil phosphorus. We employed gas chromatography–mass spectrometry (GC-MS) for metabolic profiling of P-deficient white lupins, to investigate biochemical pathways involved in the P-acquiring strategy. After 14 days of P-deficiency, plants showed reduced levels of fructose, glucose, and sucrose in shoots. Phosphorylated metabolites such as glucose-6-phosphate, fructose-6-phosphate, myo-inositol-phosphate and glycerol-3-phosphate were reduced in both shoots and roots. After 22 days of P-deficiency, no effect on shoot or root sugar metabolite levels was found, but the levels of phosphorylated metabolites were further reduced. Organic acids, amino acids and several shikimate pathway products showed enhanced levels in 22-day-old P-deficient roots and shoots. These results indicate that P-deficient white lupins adapt their carbohydrate partitioning between shoot and root in order to supply their growing root system as an early response to P-deficiency. Organic acids are released into the rhizosphere to mobilize phosphorus from soil particles. A longer period of P-deficiency leads to scavenging of Pi from P-containing metabolites and reduced protein anabolism, but enhanced formation of secondary metabolites. The latter can serve as stress protection molecules or actively acquire phosphorus from the soil. PMID:26635840

  1. Hominids adapted to metabolize ethanol long before human-directed fermentation

    PubMed Central

    Carrigan, Matthew A.; Uryasev, Oleg; Frye, Carole B.; Eckman, Blair L.; Myers, Candace R.; Hurley, Thomas D.; Benner, Steven A.

    2015-01-01

    Paleogenetics is an emerging field that resurrects ancestral proteins from now-extinct organisms to test, in the laboratory, models of protein function based on natural history and Darwinian evolution. Here, we resurrect digestive alcohol dehydrogenases (ADH4) from our primate ancestors to explore the history of primate–ethanol interactions. The evolving catalytic properties of these resurrected enzymes show that our ape ancestors gained a digestive dehydrogenase enzyme capable of metabolizing ethanol near the time that they began using the forest floor, about 10 million y ago. The ADH4 enzyme in our more ancient and arboreal ancestors did not efficiently oxidize ethanol. This change suggests that exposure to dietary sources of ethanol increased in hominids during the early stages of our adaptation to a terrestrial lifestyle. Because fruit collected from the forest floor is expected to contain higher concentrations of fermenting yeast and ethanol than similar fruits hanging on trees, this transition may also be the first time our ancestors were exposed to (and adapted to) substantial amounts of dietary ethanol. PMID:25453080

  2. Rethinking energy in parkinsonian motor symptoms: a potential role for neural metabolic deficits

    PubMed Central

    Amano, Shinichi; Kegelmeyer, Deborah; Hong, S. Lee

    2015-01-01

    Parkinson’s disease (PD) is characterized as a chronic and progressive neurodegenerative disorder that results in a variety of debilitating symptoms, including bradykinesia, resting tremor, rigidity, and postural instability. Research spanning several decades has emphasized basal ganglia dysfunction, predominantly resulting from dopaminergic (DA) cell loss, as the primarily cause of the aforementioned parkinsonian features. But, why those particular features manifest themselves remains an enigma. The goal of this paper is to develop a theoretical framework that parkinsonian motor features are behavioral consequence of a long-term adaptation to their inability (inflexibility or lack of capacity) to meet energetic demands, due to neural metabolic deficits arising from mitochondrial dysfunction associated with PD. Here, we discuss neurophysiological changes that are generally associated with PD, such as selective degeneration of DA neurons in the substantia nigra pars compacta (SNc), in conjunction with metabolic and mitochondrial dysfunction. We then characterize the cardinal motor symptoms of PD, bradykinesia, resting tremor, rigidity and gait disturbance, reviewing literature to demonstrate how these motor patterns are actually energy efficient from a metabolic perspective. We will also develop three testable hypotheses: (1) neural metabolic deficits precede the increased rate of neurodegeneration and onset of behavioral symptoms in PD; (2) motor behavior of persons with PD are more sensitive to changes in metabolic/bioenergetic state; and (3) improvement of metabolic function could lead to better motor performance in persons with PD. These hypotheses are designed to introduce a novel viewpoint that can elucidate the connections between metabolic, neural and motor function in PD. PMID:25610377

  3. Deciphering the adaptation strategies of Desulfovibrio piezophilus to hydrostatic pressure through metabolic and transcriptional analyses.

    PubMed

    Amrani, Amira; van Helden, Jacques; Bergon, Aurélie; Aouane, Aicha; Ben Hania, Wajdi; Tamburini, Christian; Loriod, Béatrice; Imbert, Jean; Ollivier, Bernard; Pradel, Nathalie; Dolla, Alain

    2016-08-01

    Desulfovibrio piezophilus strain C1TLV30(T) is a mesophilic piezophilic sulfate-reducer isolated from Wood Falls at 1700 m depth in the Mediterranean Sea. In this study, we analysed the effect of the hydrostatic pressure on this deep-sea living bacterium at the physiologic and transcriptomic levels. Our results showed that lactate oxidation and energy metabolism were affected by the hydrostatic pressure. Especially, acetyl-CoA oxidation pathway and energy conservation through hydrogen and formate recycling would be more important when the hydrostatic pressure is above (26 MPa) than below (0.1 MPa) the optimal one (10 MPa). This work underlines also the role of the amino acid glutamate as a piezolyte for the Desulfovibrio genus. The transcriptomic analysis revealed 146 differentially expressed genes emphasizing energy production and conversion, amino acid transport and metabolism and cell motility and signal transduction mechanisms as hydrostatic pressure responding processes. This dataset allowed us to identify a sequence motif upstream of a subset of differentially expressed genes as putative pressure-dependent regulatory element. PMID:27264199

  4. Deciphering the adaptation strategies of Desulfovibrio piezophilus to hydrostatic pressure through metabolic and transcriptional analyses.

    PubMed

    Amrani, Amira; van Helden, Jacques; Bergon, Aurélie; Aouane, Aicha; Ben Hania, Wajdi; Tamburini, Christian; Loriod, Béatrice; Imbert, Jean; Ollivier, Bernard; Pradel, Nathalie; Dolla, Alain

    2016-08-01

    Desulfovibrio piezophilus strain C1TLV30(T) is a mesophilic piezophilic sulfate-reducer isolated from Wood Falls at 1700 m depth in the Mediterranean Sea. In this study, we analysed the effect of the hydrostatic pressure on this deep-sea living bacterium at the physiologic and transcriptomic levels. Our results showed that lactate oxidation and energy metabolism were affected by the hydrostatic pressure. Especially, acetyl-CoA oxidation pathway and energy conservation through hydrogen and formate recycling would be more important when the hydrostatic pressure is above (26 MPa) than below (0.1 MPa) the optimal one (10 MPa). This work underlines also the role of the amino acid glutamate as a piezolyte for the Desulfovibrio genus. The transcriptomic analysis revealed 146 differentially expressed genes emphasizing energy production and conversion, amino acid transport and metabolism and cell motility and signal transduction mechanisms as hydrostatic pressure responding processes. This dataset allowed us to identify a sequence motif upstream of a subset of differentially expressed genes as putative pressure-dependent regulatory element.

  5. Cooperative energy harvesting-adaptive MAC protocol for WBANs.

    PubMed

    Esteves, Volker; Antonopoulos, Angelos; Kartsakli, Elli; Puig-Vidal, Manel; Miribel-Català, Pere; Verikoukis, Christos

    2015-05-28

    In this paper, we introduce a cooperative medium access control (MAC) protocol, named cooperative energy harvesting (CEH)-MAC, that adapts its operation to the energy harvesting (EH) conditions in wireless body area networks (WBANs). In particular, the proposed protocol exploits the EH information in order to set an idle time that allows the relay nodes to charge their batteries and complete the cooperation phase successfully. Extensive simulations have shown that CEH-MAC significantly improves the network performance in terms of throughput, delay and energy efficiency compared to the cooperative operation of the baseline IEEE 802.15.6 standard.

  6. Cooperative Energy Harvesting-Adaptive MAC Protocol for WBANs

    PubMed Central

    Esteves, Volker; Antonopoulos, Angelos; Kartsakli, Elli; Puig-Vidal, Manel; Miribel-Català, Pere; Verikoukis, Christos

    2015-01-01

    In this paper, we introduce a cooperative medium access control (MAC) protocol, named cooperative energy harvesting (CEH)-MAC, that adapts its operation to the energy harvesting (EH) conditions in wireless body area networks (WBANs). In particular, the proposed protocol exploits the EH information in order to set an idle time that allows the relay nodes to charge their batteries and complete the cooperation phase successfully. Extensive simulations have shown that CEH-MAC significantly improves the network performance in terms of throughput, delay and energy efficiency compared to the cooperative operation of the baseline IEEE 802.15.6 standard. PMID:26029950

  7. Cooperative energy harvesting-adaptive MAC protocol for WBANs.

    PubMed

    Esteves, Volker; Antonopoulos, Angelos; Kartsakli, Elli; Puig-Vidal, Manel; Miribel-Català, Pere; Verikoukis, Christos

    2015-01-01

    In this paper, we introduce a cooperative medium access control (MAC) protocol, named cooperative energy harvesting (CEH)-MAC, that adapts its operation to the energy harvesting (EH) conditions in wireless body area networks (WBANs). In particular, the proposed protocol exploits the EH information in order to set an idle time that allows the relay nodes to charge their batteries and complete the cooperation phase successfully. Extensive simulations have shown that CEH-MAC significantly improves the network performance in terms of throughput, delay and energy efficiency compared to the cooperative operation of the baseline IEEE 802.15.6 standard. PMID:26029950

  8. An Energy Aware Adaptive Sampling Algorithm for Energy Harvesting WSN with Energy Hungry Sensors.

    PubMed

    Srbinovski, Bruno; Magno, Michele; Edwards-Murphy, Fiona; Pakrashi, Vikram; Popovici, Emanuel

    2016-01-01

    Wireless sensor nodes have a limited power budget, though they are often expected to be functional in the field once deployed for extended periods of time. Therefore, minimization of energy consumption and energy harvesting technology in Wireless Sensor Networks (WSN) are key tools for maximizing network lifetime, and achieving self-sustainability. This paper proposes an energy aware Adaptive Sampling Algorithm (ASA) for WSN with power hungry sensors and harvesting capabilities, an energy management technique that can be implemented on any WSN platform with enough processing power to execute the proposed algorithm. An existing state-of-the-art ASA developed for wireless sensor networks with power hungry sensors is optimized and enhanced to adapt the sampling frequency according to the available energy of the node. The proposed algorithm is evaluated using two in-field testbeds that are supplied by two different energy harvesting sources (solar and wind). Simulation and comparison between the state-of-the-art ASA and the proposed energy aware ASA (EASA) in terms of energy durability are carried out using in-field measured harvested energy (using both wind and solar sources) and power hungry sensors (ultrasonic wind sensor and gas sensors). The simulation results demonstrate that using ASA in combination with an energy aware function on the nodes can drastically increase the lifetime of a WSN node and enable self-sustainability. In fact, the proposed EASA in conjunction with energy harvesting capability can lead towards perpetual WSN operation and significantly outperform the state-of-the-art ASA. PMID:27043559

  9. An Energy Aware Adaptive Sampling Algorithm for Energy Harvesting WSN with Energy Hungry Sensors

    PubMed Central

    Srbinovski, Bruno; Magno, Michele; Edwards-Murphy, Fiona; Pakrashi, Vikram; Popovici, Emanuel

    2016-01-01

    Wireless sensor nodes have a limited power budget, though they are often expected to be functional in the field once deployed for extended periods of time. Therefore, minimization of energy consumption and energy harvesting technology in Wireless Sensor Networks (WSN) are key tools for maximizing network lifetime, and achieving self-sustainability. This paper proposes an energy aware Adaptive Sampling Algorithm (ASA) for WSN with power hungry sensors and harvesting capabilities, an energy management technique that can be implemented on any WSN platform with enough processing power to execute the proposed algorithm. An existing state-of-the-art ASA developed for wireless sensor networks with power hungry sensors is optimized and enhanced to adapt the sampling frequency according to the available energy of the node. The proposed algorithm is evaluated using two in-field testbeds that are supplied by two different energy harvesting sources (solar and wind). Simulation and comparison between the state-of-the-art ASA and the proposed energy aware ASA (EASA) in terms of energy durability are carried out using in-field measured harvested energy (using both wind and solar sources) and power hungry sensors (ultrasonic wind sensor and gas sensors). The simulation results demonstrate that using ASA in combination with an energy aware function on the nodes can drastically increase the lifetime of a WSN node and enable self-sustainability. In fact, the proposed EASA in conjunction with energy harvesting capability can lead towards perpetual WSN operation and significantly outperform the state-of-the-art ASA. PMID:27043559

  10. Energy metabolism of hyperthyroid gilthead sea bream Sparus aurata L.

    PubMed

    Vargas-Chacoff, Luis; Ruiz-Jarabo, Ignacio; Arjona, Francisco J; Laiz-Carrión, Raúl; Flik, Gert; Klaren, Peter H M; Mancera, Juan M

    2016-01-01

    Thyroid hormones, in particular 3,5,3'-triiodothyronine or T3, are involved in multiple physiological processes in mammals such as protein, fat and carbohydrate metabolism. However, the metabolic actions of T3 in fish are still not fully elucidated. We therefore tested the effects of T3 on Sparus aurata energy metabolism and osmoregulatory system, a hyperthyroid-induced model that was chosen. Fish were implanted with coconut oil depots (containing 0, 2.5, 5.0 and 10.0μg T3/g body weight) and sampled at day 3 and 6 post-implantation. Plasma levels of free T3 as well as glucose, lactate and triglyceride values increased with increasing doses of T3 at days 3 and 6 post-implantation. Changes in plasma and organ metabolite levels (glucose, glycogen, triglycerides, lactate and total α amino acid) and enzyme activities related to carbohydrate, lactate, amino acid and lipid pathways were detected in organs involved in metabolism (liver) and osmoregulation (gills and kidney). Our data implicate that the liver uses amino acids as an energy source in response to the T3 treatment, increasing protein catabolism and gluconeogenic pathways. The gills, the most important extruder of ammonia, are fuelled not only by amino acids, but also by lactate. The kidney differs significantly in its substrate preference from the gills, as it obtained metabolic energy from lactate but also from lipid oxidation processes. We conclude that in S. aurata lipid catabolism and protein turnover are increased as a consequence of experimentally induced hyperthyroidism, with secondary osmoregulatory effects. PMID:26419695

  11. Exploration of Energy Metabolism in the Mouse Using Indirect Calorimetry: Measurement of Daily Energy Expenditure (DEE) and Basal Metabolic Rate (BMR).

    PubMed

    Meyer, Carola W; Reitmeir, Peter; Tschöp, Matthias H

    2015-09-01

    Current comprehensive mouse metabolic phenotyping involves studying energy balance in cohorts of mice via indirect calorimetry, which determines heat release from changes in respiratory air composition. Here, we describe the measurement of daily energy expenditure (DEE) and basal metabolic rate (BMR) in mice. These well-defined metabolic descriptors serve as meaningful first-line read-outs for metabolic phenotyping and should be reported when exploring energy expenditure in mice. For further guidance, the issue of appropriate sample sizes and the frequency of sampling of metabolic measurements is also discussed.

  12. Mechanistic modeling of aberrant energy metabolism in human disease

    PubMed Central

    Sangar, Vineet; Eddy, James A.; Simeonidis, Evangelos; Price, Nathan D.

    2012-01-01

    Dysfunction in energy metabolism—including in pathways localized to the mitochondria—has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these molecular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based (CB) models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages—and also provides a powerful means to integrate and interpret—information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we review a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regions in the cell. PMID:23112774

  13. Bone endocrine regulation of energy metabolism and male reproduction.

    PubMed

    Karsenty, Gerard

    2011-10-01

    Usually vertebrate physiology is studied within the confined limits of a given organ, if not cell type. This approach has progressively changed with the emergence of mouse genetics that has rejuvenated the concept of a whole body study of physiology. A vivid example of how mouse genetics has profoundly affected our understanding of physiology is skeleton physiology. A genetic approach to bone physiology revealed that bone via osteocalcin, an osteoblast-secreted molecule, is a true endocrine organ regulating energy metabolism and male reproduction. This ongoing body of work that takes bone out of its traditional roles is connecting it to a growing number of peripheral organs. These novel important hormonal connections between bone, energy metabolism and reproduction underscore the concept of functional dependence in physiology and the importance of genetic approaches to identify novel endocrine regulations.

  14. Alveolar type II cells maintain bioenergetic homeostasis in hypoxia through metabolic and molecular adaptation.

    PubMed

    Lottes, Robyn G; Newton, Danforth A; Spyropoulos, Demetri D; Baatz, John E

    2014-05-15

    Although many lung diseases are associated with hypoxia, alveolar type II epithelial (ATII) cell impairment, and pulmonary surfactant dysfunction, the effects of O(2) limitation on metabolic pathways necessary to maintain cellular energy in ATII cells have not been studied extensively. This report presents results of targeted assays aimed at identifying specific metabolic processes that contribute to energy homeostasis using primary ATII cells and a model ATII cell line, mouse lung epithelial 15 (MLE-15), cultured in normoxic and hypoxic conditions. MLEs cultured in normoxia demonstrated a robust O(2) consumption rate (OCR) coupled to ATP generation and limited extracellular lactate production, indicating reliance on oxidative phosphorylation for ATP production. Pharmacological uncoupling of respiration increased OCR in normoxic cultures to 175% of basal levels, indicating significant spare respiratory capacity. However, when exposed to hypoxia for 20 h, basal O(2) consumption fell to 60% of normoxic rates, and cells maintained only ∼50% of normoxic spare respiratory capacity, indicating suppression of mitochondrial function, although intracellular ATP levels remained at near normoxic levels. Moreover, while hypoxic exposure stimulated glycogen synthesis and storage in MLE-15, glycolytic rate (as measured by lactate generation) was not significantly increased in the cells, despite enhanced expression of several enzymes related to glycolysis. These results were largely recapitulated in murine primary ATII, demonstrating MLE-15 suitability for modeling ATII metabolism. The ability of ATII cells to maintain ATP levels in hypoxia without enhancing glycolysis suggests that these cells are exceptionally efficient at conserving ATP to maintain bioenergetic homeostasis under O(2) limitation. PMID:24682450

  15. Continued protein synthesis at low [ATP] and [GTP] enables cell adaptation during energy limitation.

    PubMed

    Jewett, Michael C; Miller, Mark L; Chen, Yvonne; Swartz, James R

    2009-02-01

    One of biology's critical ironies is the need to adapt to periods of energy limitation by using the energy-intensive process of protein synthesis. Although previous work has identified the individual energy-requiring steps in protein synthesis, we still lack an understanding of the dependence of protein biosynthesis rates on [ATP] and [GTP]. Here, we used an integrated Escherichia coli cell-free platform that mimics the intracellular, energy-limited environment to show that protein synthesis rates are governed by simple Michaelis-Menten dependence on [ATP] and [GTP] (K(m)(ATP), 27 +/- 4 microM; K(m)(GTP), 14 +/- 2 microM). Although the system-level GTP affinity agrees well with the individual affinities of the GTP-dependent translation factors, the system-level K(m)(ATP) is unexpectedly low. Especially under starvation conditions, when energy sources are limited, cells need to replace catalysts that become inactive and to produce new catalysts in order to effectively adapt. Our results show how this crucial survival priority for synthesizing new proteins can be enforced after rapidly growing cells encounter energy limitation. A diminished energy supply can be rationed based on the relative ATP and GTP affinities, and, since these affinities for protein synthesis are high, the cells can adapt with substantial changes in protein composition. Furthermore, our work suggests that characterization of individual enzymes may not always predict the performance of multicomponent systems with complex interdependencies. We anticipate that cell-free studies in which complex metabolic systems are activated will be valuable tools for elucidating the behavior of such systems.

  16. Energy metabolism in Desulfovibrio vulgaris Hildenborough: insights from transcriptome analysis

    SciTech Connect

    Pereira, Patricia M.; He, Qiang; Valente, Filipa M.A.; Xavier, Antonio V.; Zhou, Jizhong; Pereira, Ines A.C.; Louro, Ricardo O.

    2007-11-01

    Sulphate-reducing bacteria are important players in the global sulphur and carbon cycles, with considerable economical and ecological impact. However, the process of sulphate respiration is still incompletely understood. Several mechanisms of energy conservation have been proposed, but it is unclear how the different strategies contribute to the overall process. In order to obtain a deeper insight into the energy metabolism of sulphate-reducers whole-genome microarrays were used to compare the transcriptional response of Desulfovibrio vulgaris Hildenborough grown with hydrogen/sulphate, pyruvate/sulphate, pyruvate with limiting sulphate, and lactate/thiosulphate, relative to growth in lactate/sulphate. Growth with hydrogen/sulphate showed the largest number of differentially expressed genes and the largest changes in transcript levels. In this condition the most up-regulated energy metabolism genes were those coding for the periplasmic [NiFeSe]hydrogenase, followed by the Ech hydrogenase. The results also provide evidence for the involvement of formate cycling and the recently proposed ethanol pathway during growth in hydrogen. The pathway involving CO cycling is relevant during growth on lactate and pyruvate, but not during growth in hydrogen as the most down-regulated genes were those coding for the CO-induced hydrogenase. Growth on lactate/thiosulphate reveals a down-regulation of several energymetabolism genes similar to what was observed in the presence of nitrite. This study identifies the role of several proteins involved in the energy metabolism of D. vulgaris and highlights several novel genes related to this process, revealing a more complex bioenergetic metabolism than previously considered.

  17. Impaired cardiac energy metabolism in embryos lacking adrenergic stimulation.

    PubMed

    Baker, Candice N; Gidus, Sarah A; Price, George F; Peoples, Jessica N R; Ebert, Steven N

    2015-03-01

    As development proceeds from the embryonic to fetal stages, cardiac energy demands increase substantially, and oxidative phosphorylation of ADP to ATP in mitochondria becomes vital. Relatively little, however, is known about the signaling mechanisms regulating the transition from anaerobic to aerobic metabolism that occurs during the embryonic period. The main objective of this study was to test the hypothesis that adrenergic hormones provide critical stimulation of energy metabolism during embryonic/fetal development. We examined ATP and ADP concentrations in mouse embryos lacking adrenergic hormones due to targeted disruption of the essential dopamine β-hydroxylase (Dbh) gene. Embryonic ATP concentrations decreased dramatically, whereas ADP concentrations rose such that the ATP/ADP ratio in the adrenergic-deficient group was nearly 50-fold less than that found in littermate controls by embryonic day 11.5. We also found that cardiac extracellular acidification and oxygen consumption rates were significantly decreased, and mitochondria were significantly larger and more branched in adrenergic-deficient hearts. Notably, however, the mitochondria were intact with well-formed cristae, and there was no significant difference observed in mitochondrial membrane potential. Maternal administration of the adrenergic receptor agonists isoproterenol or l-phenylephrine significantly ameliorated the decreases in ATP observed in Dbh-/- embryos, suggesting that α- and β-adrenergic receptors were effective modulators of ATP concentrations in mouse embryos in vivo. These data demonstrate that adrenergic hormones stimulate cardiac energy metabolism during a critical period of embryonic development. PMID:25516547

  18. A unique in vivo experimental approach reveals metabolic adaptation of the probiotic Propionibacterium freudenreichii to the colon environment

    PubMed Central

    2013-01-01

    Background Propionibacterium freudenreichii is a food grade bacterium consumed both in cheeses and in probiotic preparations. Its promising probiotic potential, relying largely on the active release of beneficial metabolites within the gut as well as the expression of key surface proteins involved in immunomodulation, deserves to be explored more deeply. Adaptation to the colon environment is requisite for the active release of propionibacterial beneficial metabolites and constitutes a bottleneck for metabolic activity in vivo. Mechanisms allowing P. freudenreichii to adapt to digestive stresses have been only studied in vitro so far. Our aim was therefore to study P. freudenreichii metabolic adaptation to intra-colonic conditions in situ. Results We maintained a pure culture of the type strain P. freudenreichii CIRM BIA 1, contained in a dialysis bag, within the colon of vigilant piglets during 24 hours. A transcriptomic analysis compared gene expression to identify the metabolic pathways induced by this environment, versus control cultures maintained in spent culture medium. We observed drastic changes in the catabolism of sugars and amino-acids. Glycolysis, the Wood-Werkman cycle and the oxidative phosphorylation pathways were down-regulated but induction of specific carbohydrate catabolisms and alternative pathways were induced to produce NADH, NADPH, ATP and precursors (utilizing of propanediol, gluconate, lactate, purine and pyrimidine and amino-acids). Genes involved in stress response were down-regulated and genes specifically expressed during cell division were induced, suggesting that P. freudenreichii adapted its metabolism to the conditions encountered in the colon. Conclusions This study constitutes the first molecular demonstration of P. freudenreichii activity and physiological adaptation in vivo within the colon. Our data are likely specific to our pig microbiota composition but opens an avenue towards understanding probiotic action within the gut

  19. Evolution and significance of the Lon gene family in Arabidopsis organelle biogenesis and energy metabolism.

    PubMed

    Rigas, Stamatis; Daras, Gerasimos; Tsitsekian, Dikran; Alatzas, Anastasios; Hatzopoulos, Polydefkis

    2014-01-01

    Lon is the first identified ATP-dependent protease highly conserved across all kingdoms. Model plant species Arabidopsis thaliana has a small Lon gene family of four members. Although these genes share common structural features, they have distinct properties in terms of gene expression profile, subcellular targeting and substrate recognition motifs. This supports the notion that their functions under different environmental conditions are not necessarily redundant. This article intends to unravel the biological role of Lon proteases in energy metabolism and plant growth through an evolutionary perspective. Given that plants are sessile organisms exposed to diverse environmental conditions and plant organelles are semi-autonomous, it is tempting to suggest that Lon genes in Arabidopsis are paralogs. Adaptive evolution through repetitive gene duplication events of a single archaic gene led to Lon genes with complementing sets of subfunctions providing to the organism rapid adaptability for canonical development under different environmental conditions. Lon1 function is adequately characterized being involved in mitochondrial biogenesis, modulating carbon metabolism, oxidative phosphorylation and energy supply, all prerequisites for seed germination and seedling establishment. Lon is not a stand-alone proteolytic machine in plant organelles. Lon in association with other nuclear-encoded ATP-dependent proteases builds up an elegant nevertheless, tight interconnected circuit. This circuitry channels properly and accurately, proteostasis and protein quality control among the distinct subcellular compartments namely mitochondria, chloroplasts, and peroxisomes.

  20. Evolution and significance of the Lon gene family in Arabidopsis organelle biogenesis and energy metabolism.

    PubMed

    Rigas, Stamatis; Daras, Gerasimos; Tsitsekian, Dikran; Alatzas, Anastasios; Hatzopoulos, Polydefkis

    2014-01-01

    Lon is the first identified ATP-dependent protease highly conserved across all kingdoms. Model plant species Arabidopsis thaliana has a small Lon gene family of four members. Although these genes share common structural features, they have distinct properties in terms of gene expression profile, subcellular targeting and substrate recognition motifs. This supports the notion that their functions under different environmental conditions are not necessarily redundant. This article intends to unravel the biological role of Lon proteases in energy metabolism and plant growth through an evolutionary perspective. Given that plants are sessile organisms exposed to diverse environmental conditions and plant organelles are semi-autonomous, it is tempting to suggest that Lon genes in Arabidopsis are paralogs. Adaptive evolution through repetitive gene duplication events of a single archaic gene led to Lon genes with complementing sets of subfunctions providing to the organism rapid adaptability for canonical development under different environmental conditions. Lon1 function is adequately characterized being involved in mitochondrial biogenesis, modulating carbon metabolism, oxidative phosphorylation and energy supply, all prerequisites for seed germination and seedling establishment. Lon is not a stand-alone proteolytic machine in plant organelles. Lon in association with other nuclear-encoded ATP-dependent proteases builds up an elegant nevertheless, tight interconnected circuit. This circuitry channels properly and accurately, proteostasis and protein quality control among the distinct subcellular compartments namely mitochondria, chloroplasts, and peroxisomes. PMID:24782883

  1. Fungal Inositol Pyrophosphate IP7 Is Crucial for Metabolic Adaptation to the Host Environment and Pathogenicity

    PubMed Central

    Lev, Sophie; Li, Cecilia; Desmarini, Desmarini; Saiardi, Adolfo; Fewings, Nicole L.; Schibeci, Stephen D.; Sharma, Raghwa; Sorrell, Tania C.

    2015-01-01

    ABSTRACT Inositol pyrophosphates (PP-IPs) comprising inositol, phosphate, and pyrophosphate (PP) are essential for multiple functions in eukaryotes. Their role in fungal pathogens has never been addressed. Cryptococcus neoformans is a model pathogenic fungus causing life-threatening meningoencephalitis. We investigate the cryptococcal kinases responsible for the production of PP-IPs (IP7/IP8) and the hierarchy of PP-IP importance in pathogenicity. Using gene deletion and inositol polyphosphate profiling, we identified Kcs1 as the major IP6 kinase (producing IP7) and Asp1 as an IP7 kinase (producing IP8). We show that Kcs1-derived IP7 is the most crucial PP-IP for cryptococcal drug susceptibility and the production of virulence determinants. In particular, Kcs1 kinase activity is essential for cryptococcal infection of mouse lungs, as reduced fungal burdens were observed in the absence of Kcs1 or when Kcs1 was catalytically inactive. Transcriptome and carbon source utilization analysis suggested that compromised growth of the KCS1 deletion strain (Δkcs1 mutant) in the low-glucose environment of the host lung is due to its inability to utilize alternative carbon sources. Despite this metabolic defect, the Δkcs1 mutant established persistent, low-level asymptomatic pulmonary infection but failed to elicit a strong immune response in vivo and in vitro and was not readily phagocytosed by primary or immortalized monocytes. Reduced recognition of the Δkcs1 cells by monocytes correlated with reduced exposure of mannoproteins on the Δkcs1 mutant cell surface. We conclude that IP7 is essential for fungal metabolic adaptation to the host environment, immune recognition, and pathogenicity. PMID:26037119

  2. p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance.

    PubMed

    Yogev, Orli; Barker, Karen; Sikka, Arti; Almeida, Gilberto S; Hallsworth, Albert; Smith, Laura M; Jamin, Yann; Ruddle, Ruth; Koers, Alexander; Webber, Hannah T; Raynaud, Florence I; Popov, Sergey; Jones, Chris; Petrie, Kevin; Robinson, Simon P; Keun, Hector C; Chesler, Louis

    2016-05-15

    Neuroblastoma is the most common childhood extracranial solid tumor. In high-risk cases, many of which are characterized by amplification of MYCN, outcome remains poor. Mutations in the p53 (TP53) tumor suppressor are rare at diagnosis, but evidence suggests that p53 function is often impaired in relapsed, treatment-resistant disease. To address the role of p53 loss of function in the development and pathogenesis of high-risk neuroblastoma, we generated a MYCN-driven genetically engineered mouse model in which the tamoxifen-inducible p53ER(TAM) fusion protein was expressed from a knock-in allele (Th-MYCN/Trp53(KI)). We observed no significant differences in tumor-free survival between Th-MYCN mice heterozygous for Trp53(KI) (n = 188) and Th-MYCN mice with wild-type p53 (n = 101). Conversely, the survival of Th-MYCN/Trp53(KI/KI) mice lacking functional p53 (n = 60) was greatly reduced. We found that Th-MYCN/Trp53(KI/KI) tumors were resistant to ionizing radiation (IR), as expected. However, restoration of functional p53ER(TAM) reinstated sensitivity to IR in only 50% of Th-MYCN/Trp53(KI/KI) tumors, indicating the acquisition of additional resistance mechanisms. Gene expression and metabolic analyses indicated that the principal acquired mechanism of resistance to IR in the absence of functional p53 was metabolic adaptation in response to chronic oxidative stress. Tumors exhibited increased antioxidant metabolites and upregulation of glutathione S-transferase pathway genes, including Gstp1 and Gstz1, which are associated with poor outcome in human neuroblastoma. Accordingly, glutathione depletion by buthionine sulfoximine together with restoration of p53 activity resensitized tumors to IR. Our findings highlight the complex pathways operating in relapsed neuroblastomas and the need for combination therapies that target the diverse resistance mechanisms at play. Cancer Res; 76(10); 3025-35. ©2016 AACR.

  3. Energy intake and basal metabolic rate during maintenance chemotherapy.

    PubMed

    Bond, S A; Han, A M; Wootton, S A; Kohler, J A

    1992-02-01

    Energy intakes and basal metabolic rates were determined in 26 children receiving chemotherapy in remission from acute lymphoblastic leukaemia or solid tumours and 26 healthy controls matched for age and sex. Body weight and height on the two groups were comparable, although one patient was stunted (height for age) and three others wasted (weight for height). Energy intake in the patients at 7705 kJ/day (1842 kcal) and controls at 7773 kJ/day (1866 kcal)) and basal metabolic rate (BMR) in the patients at 4873 kJ/day (1172 kcal) and controls 4987 kJ/day (1196 kcal) for the two groups were not significantly different. Although the energy intake:BMR ratio for both groups was 1.59, the range of values for the patient group was large (0.96-2.73) and appeared to be greater than that observed in the control group (1.23-2.46). These results demonstrated that during this period of chemotherapy there was no evidence of raised energy expenditure at rest or reduced energy intake in the patient group. No indication of undernutrition in the patients as a group was evident, although some individuals might require further clinical nutritional assessment.

  4. Validated Predictions of Metabolic Energy Consumption for Submaximal Effort Movement

    PubMed Central

    Tsianos, George A.; MacFadden, Lisa N.

    2016-01-01

    Physical performance emerges from complex interactions among many physiological systems that are largely driven by the metabolic energy demanded. Quantifying metabolic demand is an essential step for revealing the many mechanisms of physical performance decrement, but accurate predictive models do not exist. The goal of this study was to investigate if a recently developed model of muscle energetics and force could be extended to reproduce the kinematics, kinetics, and metabolic demand of submaximal effort movement. Upright dynamic knee extension against various levels of ergometer load was simulated. Task energetics were estimated by combining the model of muscle contraction with validated models of lower limb musculotendon paths and segment dynamics. A genetic algorithm was used to compute the muscle excitations that reproduced the movement with the lowest energetic cost, which was determined to be an appropriate criterion for this task. Model predictions of oxygen uptake rate (VO2) were well within experimental variability for the range over which the model parameters were confidently known. The model's accurate estimates of metabolic demand make it useful for assessing the likelihood and severity of physical performance decrement for a given task as well as investigating underlying physiologic mechanisms. PMID:27248429

  5. A genome-wide expression profile and system-level integration of nuclear factor kappa B regulated genes reveals fundamental metabolic adaptations during cell growth and survival.

    PubMed

    Andela, Valentine B; Schwarz, Edward M; O'Keefe, Regis J; Puzas, Edward J; Rosenblatt, Joseph D; Rosier, Randy N

    2005-12-19

    A murine lung alveolar carcinoma cell line (WT-Line 1) and its equally tumorigenic but non-malignant derivative transduced with a dominant negative inhibitor of NF-kappaB (mI-kappaB-Line 1), were profiled on the Affymetrix 19000 gene array platform. Two differentially expressed gene clusters were identified and integrated into a functional model. The downregulation of anti-oxidant defenses, in mI-kappaB-Line 1 cells, correlates with high levels of reactive oxygen species (ROS) and ROS damage to cellular macromolecules while the upregulation of metabolic nuclear receptors correlates with an adaptive/survival response, which involves a shift in energy metabolism toward beta-oxidative respiration. Accordingly, mI-kappaB-Line 1 cells are markedly sensitized to pharmacologic inhibition of beta-oxidative respiration. These findings are indicative of compensatory changes that could undermine anti-cancer therapies targeting NF-kappaB.

  6. Active and passive biomonitoring suggest metabolic adaptation in blue mussels (Mytilus spp.) chronically exposed to a moderate contamination in Brest harbor (France).

    PubMed

    Lacroix, Camille; Richard, Gaëlle; Seguineau, Catherine; Guyomarch, Julien; Moraga, Dario; Auffret, Michel

    2015-05-01

    oxidative stress and energy-related biomarkers were observed compared to native harbor mussels. Overall, these results suggested mussels chronically exposed to contamination have set up metabolic adaptation, which may contribute to their survival in the moderately contaminated harbor of Brest. Whether these adaptive traits result from phenotypic plasticity or genetic adaptation needs to be further investigated.

  7. Molecular links between early energy metabolism alterations and Alzheimer's disease.

    PubMed

    Pedros, Ignacio; Patraca, Ivan; Martinez, Nohora; Petrov, Dmitry; Sureda, Francesc X; Auladell, Carme; Beas-Zarate, Carlos; Folch, Jaume

    2016-01-01

    Recent studies suggest that the neurobiology of Alzheimer's disease (AD) pathology could not be explained solely by an increase in beta-amyloid levels. In fact, success with potential therapeutic drugs that inhibit the generation of beta amyloid has been low. Therefore, due to therapeutic failure in recent years, the scientists are looking for alternative hypotheses to explain the causes of the disease and the cognitive loss. Accordingly, alternative hypothesis propose a link between AD and peripheral metabolic alteration. Then, we review in depth changes related to insulin signalling and energy metabolism in the context of the APPSwe/PS1dE9 (APP/PS1) mice model of AD. We show an integrated view of the changes that occur in the early stages of the amyloidogenic process in the APP/PS1 double transgenic mice model. These early changes affect several key metabolic processes related to glucose uptake and insulin signalling, cellular energy homeostasis, mitochondrial biogenesis and increased Tau phosphorylation by kinase molecules like mTOR and Cdk5.

  8. [Modifications in myocardial energy metabolism in diabetic patients

    NASA Technical Reports Server (NTRS)

    Grynberg, A.

    2001-01-01

    The capacity of cardiac myocyte to regulate ATP production to face any change in energy demand is a major determinant of cardiac function. Because FA is the main heart fuel (although the most expensive one in oxygen, and prompt to induce deleterious effects), this process is based on a balanced fatty acid (FA) metabolism. Several pathological situations are associated with an accumulation of FA or derivatives, or with an excessive b-oxidation. The diabetic cardiomyocyte is characterised by an over consumption of FA. The control of the FA/glucose balance clearly appears as a new strategy for cytoprotection, particularly in diabetes and requires a reduced FA contribution to ATP production. Cardiac myocytes can control FA mitochondrial entry, but display weak ability to control FA uptake, thus the fate of non beta-oxidized FA appear as a new impairment for the cell. Both the trigger and the regulation of cardiac contraction result from membrane activity, and the other major FA function in the myocardium is their role in membrane homeostasis, through the phospholipid synthesis and remodeling pathways. Sudden death, hypercatecholaminemia, diabetes and heart failure have been associated with an altered PUFA content in cardiac membranes. Experimental data suggest that the 2 metabolic pathways involved in membrane homeostasis may represent therapeutic targets for cytoprotection. The drugs that increase cardiac phospholipid turnover (trimetazidine, ranolazine,...) display anti-ischemic non hemodynamic effect. This effect is based on a redirection of FA utilization towards phospholipid synthesis, which decrease their availability for energy production. A nutritional approach gave also promising results. Besides its anti-arrhythmic effect, the dietary docosahexaenoic acid is able to reduce FA energy consumption and hence oxygen demand. The cardiac metabolic pathways involving FA should be considered as a whole, precariously balanced. The diabetic heart being characterised by

  9. Clear differences in metabolic and morphological adaptations of akinetes of two Nostocales living in different habitats.

    PubMed

    Perez, Rebeca; Forchhammer, Karl; Salerno, Graciela; Maldener, Iris

    2016-02-01

    Akinetes are resting spore-like cells formed by some heterocyst-forming filamentous cyanobacteria for surviving long periods of unfavourable conditions. We studied the development of akinetes in two model strains of cyanobacterial cell differentiation, the planktonic freshwater Anabaena variabilis ATCC 29413 and the terrestrial or symbiotic Nostoc punctiforme ATCC 29133, in response to low light and phosphate starvation. The best trigger of akinete differentiation of Anabaena variabilis was low light; that of N. punctiforme was phosphate starvation. Light and electron microscopy revealed that akinetes of both species differed from vegetative cells by their larger size, different cell morphology and large number of intracellular granules. Anabaena variabilis akinetes had a multilayer envelope; those of N. punctiforme had a simpler envelope. During akinete development of Anabaena variabilis, the amount of the storage compounds cyanophycin and glycogen increased transiently, whereas in N. punctiforme, cyanophycin and lipid droplets increased transiently. Photosynthesis and respiration decreased during akinete differentiation in both species, and remained at a low level in mature akinetes. The clear differences in the metabolic and morphological adaptations of akinetes of the two species could be related to their different lifestyles. The results pave the way for genetic and functional studies of akinete differentiation in these species. PMID:26679176

  10. Integrative Phosphoproteomics Links IL-23R Signaling with Metabolic Adaptation in Lymphocytes

    PubMed Central

    Lochmatter, Corinne; Fischer, Roman; Charles, Philip D.; Yu, Zhanru; Powrie, Fiona; Kessler, Benedikt M.

    2016-01-01

    Interleukin (IL)-23 mediated signal transduction represents a major molecular mechanism underlying the pathology of inflammatory bowel disease, Crohn’s disease and ulcerative colitis. In addition, emerging evidence supports the role of IL-23-driven Th17 cells in inflammation. Components of the IL-23 signaling pathway, such as IL-23R, JAK2 and STAT3, have been characterized, but elements unique to this network as compared to other interleukins have not been readily explored. In this study, we have undertaken an integrative phosphoproteomics approach to better characterise downstream signaling events. To this end, we performed and compared phosphopeptide and phosphoprotein enrichment methodologies after activation of T lymphocytes by IL-23. We demonstrate the complementary nature of the two phosphoenrichment approaches by maximizing the capture of phosphorylation events. A total of 8202 unique phosphopeptides, and 4317 unique proteins were identified, amongst which STAT3, PKM2, CDK6 and LASP-1 showed induction of specific phosphorylation not readily observed after IL-2 stimulation. Interestingly, quantitative analysis revealed predominant phosphorylation of pre-existing STAT3 nuclear subsets in addition to translocation of phosphorylated STAT3 within 30 min after IL-23 stimulation. After IL-23R activation, a small subset of PKM2 also translocates to the nucleus and may contribute to STAT3 phosphorylation, suggesting multiple cellular responses including metabolic adaptation. PMID:27080861

  11. Metabolic adaptation to prolonged anoxia in leaves of American cranberry (Vaccinium macrocarpon).

    PubMed

    Schlüter, Urte; Crawford, Robert M. M.

    2003-04-01

    The indigenous North American Cranberry (Vaccinium macrocarpon), when cultivated in specially constructed cranberry bogs, is normally flooded in winter to prevent frost injury. This protection under ice can give rise to prolonged periods of anoxia, which depending on the state of the vines and environmental conditions, can cause severe oxygen-deprivation injury. An experimental study of the tolerance of cranberry vines to controlled total anoxia reveals that mature dark-green perennating leaves with high carbohydrate levels are able to survive prolonged periods of total oxygen-deprivation while younger newly formed leaves are readily damaged. During the anoxic treatment the mature leaves exhibit a marked downregulation of metabolism. Carbohydrate consumption and energy metabolism stabilize at low levels soon after the switch from aerobic to anaerobic pathways. Pathways such as TCA cycle or photosynthesis, which are non-operating during the anoxia treatment, are severely affected but still measurable after 28 days anoxia. In the post-anoxic period the perennating leaves rapidly re-establish their capacity for aerobic respiration and photosynthesis.

  12. Metabolic adaptation to prolonged anoxia in leaves of American cranberry (Vaccinium macrocarpon).

    PubMed

    Schlüter, Urte; Crawford, Robert M. M.

    2003-04-01

    The indigenous North American Cranberry (Vaccinium macrocarpon), when cultivated in specially constructed cranberry bogs, is normally flooded in winter to prevent frost injury. This protection under ice can give rise to prolonged periods of anoxia, which depending on the state of the vines and environmental conditions, can cause severe oxygen-deprivation injury. An experimental study of the tolerance of cranberry vines to controlled total anoxia reveals that mature dark-green perennating leaves with high carbohydrate levels are able to survive prolonged periods of total oxygen-deprivation while younger newly formed leaves are readily damaged. During the anoxic treatment the mature leaves exhibit a marked downregulation of metabolism. Carbohydrate consumption and energy metabolism stabilize at low levels soon after the switch from aerobic to anaerobic pathways. Pathways such as TCA cycle or photosynthesis, which are non-operating during the anoxia treatment, are severely affected but still measurable after 28 days anoxia. In the post-anoxic period the perennating leaves rapidly re-establish their capacity for aerobic respiration and photosynthesis. PMID:12675739

  13. Polyphosphate - an ancient energy source and active metabolic regulator

    PubMed Central

    2011-01-01

    There are a several molecules on Earth that effectively store energy within their covalent bonds, and one of these energy-rich molecules is polyphosphate. In microbial cells, polyphosphate granules are synthesised for both energy and phosphate storage and are degraded to produce nucleotide triphosphate or phosphate. Energy released from these energetic carriers is used by the cell for production of all vital molecules such as amino acids, nucleobases, sugars and lipids. Polyphosphate chains directly regulate some processes in the cell and are used as phosphate donors in gene regulation. These two processes, energetic metabolism and regulation, are orchestrated by polyphosphate kinases. Polyphosphate kinases (PPKs) can currently be categorized into three groups (PPK1, PPK2 and PPK3) according their functionality; they can also be divided into three groups according their homology (EcPPK1, PaPPK2 and ScVTC). This review discusses historical information, similarities and differences, biochemical characteristics, roles in stress response regulation and possible applications in the biotechnology industry of these enzymes. At the end of the review, a hypothesis is discussed in view of synthetic biology applications that states polyphosphate and calcium-rich organelles have endosymbiotic origins from ancient protocells that metabolized polyphosphate. PMID:21816086

  14. Legal pre-event nutritional supplements to assist energy metabolism.

    PubMed

    Spriet, Lawrence L; Perry, Christopher G R; Talanian, Jason L

    2008-01-01

    Physical training and proper nutrition are paramount for success in sport. A key tissue is skeletal muscle, as the metabolic pathways that produce energy or ATP allow the muscles to complete the many activities critical to success in sport. The energy-producing pathways must rapidly respond to the need for ATP during sport and produce energy at a faster rate or for a longer duration through training and proper nutrition which should translate into improved performance in sport activities. There is also continual interest in the possibility that nutritional supplements could further improve muscle metabolism and the provision of energy during sport. Most legal sports supplements do not improve performance following oral ingestion. However, three legal supplements that have received significant attention over the years include creatine, carnitine and sodium bicarbonate. The ingestion of large amounts of creatine for 4-6 days increases skeletal muscle creatine and phosphocreatine contents. The majority of the experimental evidence suggests that creatine supplementation can improve short-term exercise performance, especially in sports that require repeated short-term sprints. It may also augment the accretion of skeletal muscle when taken in combination with a resistance-exercise training programme. Supplementary carnitine has been touted to increase the uptake and oxidation of fat in the mitochondria. However, muscle carnitine levels are not augmented following oral carnitine supplementation and the majority of well-controlled studies have reported no effect of carnitine on enhancing fat oxidation, Vo(2max) or prolonged endurance exercise performance. The ingestion of sodium bicarbonate before intense exercise decreases the blood [H+] to potentially assist the efflux of H+ from the muscle and temper the metabolic acidosis associated with intense exercise. Many studies have reported performance increases in laboratory-based cycling tests and simulated running races in

  15. Autonomous and Adaptive Voltage Control using Multiple Distributed Energy Resources

    SciTech Connect

    Li, Huijuan; Li, Fangxing; Xu, Yan; Rizy, D Tom

    2012-01-01

    Voltage regulation using distributed energy resources (DE) or distributed generators (DG) with power electronics interfaces and logic control has drawn increasing interests. This paper addresses the challenges of controlling multiple DEs to regulate voltages in distribution systems using an autonomous and adaptive control approach. Theoretical analysis shows that there exists a corresponding formulation of the dynamic control parameters with multiple DEs. Hence, the proposed control method is theoretically solid. Simulation results confirm that this method is capable of satisfying the fast response requirement for operational use without causing oscillation or inefficiency. This method is autonomous based on local information and the other DEs input without the instructions from any control center, is widely adaptive to variable power system operational situations, and has a high tolerance to data shortage of systems parameter. Hence, it is suitable for broad utility application

  16. Effects of hypothermic hypoxia on anaerobic energy metabolism in isolated anuran livers.

    PubMed

    Fedorow, C A; Churchill, T A; Kneteman, N M

    1998-12-01

    Many lower vertebrates (reptilian and amphibian species) are capable of surviving natural episodes of hypoxia and hypothermia. It is by specific metabolic adaptations that anurans are able to tolerate prolonged exposure to harsh environmental stresses. In this study, it was hypothesized that livers from an aquatic frog would possess an inherent metabolic ability to sustain high levels of ATP in an isolated organ system, providing insight into a metabolic system that is well-adapted for low temperature in vitro organ storage. Frogs of the species, R. pipiens were acclimated at 20 degrees C and at 5 degrees C. Livers were preserved using a clinical preservation solution after flushing. Livers from 20 degrees C-acclimated frogs were stored at 20 degrees C and 5 degrees C and livers from 5 degrees C-acclimated frogs were stored at 5 degrees C. The results indicated that hepatic adenylate status was maintained for 96 h during 5 degrees C storage, but not longer than 4-10 h during 20 degrees C storage. In livers from 5 degrees C-acclimated animals subjected to 5 degrees C storage, ATP was maintained at 100% throughout the 96-h period. Warm acclimation (20 degrees C) and 20 degrees C storage resulted in poorer maintenance of ATP; energy charge values dropped to 0.50 within 2 h and by 24 h, only 24% of control ATP remained. Lactate levels remained less than 25 mumol/g dry weight in all 5 degrees C-stored livers; 20 degrees C-stored livers exhibited greater accumulation of this anaerobic endproduct (lactate reached 45-50 mumol/g by 10 h). The data imply that hepatic adenylate status is largely dependent on exposure to hypothermic hypoxia and although small amounts of ATP were accounted for by anaerobic glycolysis, there must have been either a substantial reduction in cellular energy-utilization or an efficient use of low oxygen tensions.

  17. Primary cilia in energy balance signaling and metabolic disorder

    PubMed Central

    Lee, Hankyu; Song, Jieun; Jung, Joo Hyun; Ko, Hyuk Wan

    2015-01-01

    Energy homeostasis in our body system is maintained by balancing the intake and expenditure of energy. Excessive accumulation of fat by disrupting the balance system causes overweight and obesity, which are increasingly becoming global health concerns. Understanding the pathogenesis of obesity focused on studying the genes related to familial types of obesity. Recently, a rare human genetic disorder, ciliopathy, links the role for genes regulating structure and function of a cellular organelle, the primary cilium, to metabolic disorder, obesity and type II diabetes. Primary cilia are microtubule based hair-like membranous structures, lacking motility and functions such as sensing the environmental cues, and transducing extracellular signals within the cells. Interestingly, the subclass of ciliopathies, such as Bardet-Biedle and Alström syndrome, manifest obesity and type II diabetes in human and mouse model systems. Moreover, studies on genetic mouse model system indicate that more ciliary genes affect energy homeostasis through multiple regulatory steps such as central and peripheral actions of leptin and insulin. In this review, we discuss the latest findings in primary cilia and metabolic disorders, and propose the possible interaction between primary cilia and the leptin and insulin signal pathways which might enhance our understanding of the unambiguous link of a cell’s antenna to obesity and type II diabetes. [BMB Reports 2015; 48(12): 647-654] PMID:26538252

  18. [Lipids composition and speed of energy metabolism in gastropods].

    PubMed

    Arakelova, E S

    2008-01-01

    Lipid composition of digestive gland and pedal muscle of two northern freshwater pulmonate snails Lymnaea stagnalis and Lymnaea ovata and three marine prosobranch gastropods Littorina obtusata, Littorina littorea, Buccinum undatum from the White Sea was studied. The species differ in ecology, particularly in trophic nabits and motor activity. The content of triacilglycerides both in digestive gland and pedal was higher in littoral dwellers Littorina the activity of which depends on the tide level. The phospholipids content in digestive gland does not differ in quantity in all cases and does not relate to type of feeding or resource quality. In a pedal muscle of marine species the quantity of common phospholipids is higher in comparison with the freshwater ones. The amount of total phospholipids in pedal muscle correlates with mass of metabolic inert formation which constitutes a part of whole mass of snails. The presence of massive shell enhances demands in energy needed for supporting movement and activity. Because the intensity of energy metabolism is related to quantity of total phospholipids, mitochondria and activity of their oxidizing ferments, the presence of thick shell in marine snails together with motor activity costs more in terms of energy than in freshwater snails with thin shell. This hypothesis is supported by the higher specific rate of oxygen consumption in marine snails than in freshwaters. PMID:19140337

  19. [Lipids composition and speed of energy metabolism in gastropods].

    PubMed

    Arakelova, E S

    2008-01-01

    Lipid composition of digestive gland and pedal muscle of two northern freshwater pulmonate snails Lymnaea stagnalis and Lymnaea ovata and three marine prosobranch gastropods Littorina obtusata, Littorina littorea, Buccinum undatum from the White Sea was studied. The species differ in ecology, particularly in trophic nabits and motor activity. The content of triacilglycerides both in digestive gland and pedal was higher in littoral dwellers Littorina the activity of which depends on the tide level. The phospholipids content in digestive gland does not differ in quantity in all cases and does not relate to type of feeding or resource quality. In a pedal muscle of marine species the quantity of common phospholipids is higher in comparison with the freshwater ones. The amount of total phospholipids in pedal muscle correlates with mass of metabolic inert formation which constitutes a part of whole mass of snails. The presence of massive shell enhances demands in energy needed for supporting movement and activity. Because the intensity of energy metabolism is related to quantity of total phospholipids, mitochondria and activity of their oxidizing ferments, the presence of thick shell in marine snails together with motor activity costs more in terms of energy than in freshwater snails with thin shell. This hypothesis is supported by the higher specific rate of oxygen consumption in marine snails than in freshwaters.

  20. Experimental ocean acidification alters the allocation of metabolic energy

    PubMed Central

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

    2015-01-01

    Energy is required to maintain physiological homeostasis in response to environmental change. Although responses to environmental stressors frequently are assumed to involve high metabolic costs, the biochemical bases of actual energy demands are rarely quantified. We studied the impact of a near-future scenario of ocean acidification [800 µatm partial pressure of CO2 (pCO2)] during the development and growth of an important model organism in developmental and environmental biology, the sea urchin Strongylocentrotus purpuratus. Size, metabolic rate, biochemical content, and gene expression were not different in larvae growing under control and seawater acidification treatments. Measurements limited to those levels of biological analysis did not reveal the biochemical mechanisms of response to ocean acidification that occurred at the cellular level. In vivo rates of protein synthesis and ion transport increased ∼50% under acidification. Importantly, the in vivo physiological increases in ion transport were not predicted from total enzyme activity or gene expression. Under acidification, the increased rates of protein synthesis and ion transport that were sustained in growing larvae collectively accounted for the majority of available ATP (84%). In contrast, embryos and prefeeding and unfed larvae in control treatments allocated on average only 40% of ATP to these same two processes. Understanding the biochemical strategies for accommodating increases in metabolic energy demand and their biological limitations can serve as a quantitative basis for assessing sublethal effects of global change. Variation in the ability to allocate ATP differentially among essential functions may be a key basis of resilience to ocean acidification and other compounding environmental stressors. PMID:25825763

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

    PubMed

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

    2015-04-14

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

  2. Coordination Pattern Adaptability: Energy Cost of Degenerate Behaviors

    PubMed Central

    Seifert, Ludovic; Komar, John; Crettenand, Florent; Millet, Grégoire

    2014-01-01

    This study investigated behavioral adaptability, which could be defined as a blend between stability and flexibility of the limbs movement and their inter-limb coordination, when individuals received informational constraints. Seven expert breaststroke swimmers performed three 200-m in breaststroke at constant submaximal intensity. Each trial was performed randomly in a different coordination pattern: ‘freely-chosen’, ‘maximal glide’ and ‘minimal glide’. Two underwater and four aerial cameras enabled 3D movement analysis in order to assess elbow and knee angles, elbow-knee pair coordination, intra-cyclic velocity variations of the center of mass, stroke rate and stroke length and inter-limb coordination. The energy cost of locomotion was calculated from gas exchanges and blood lactate concentration. The results showed significantly higher glide, intra-cyclic velocity variations and energy cost under ‘maximal glide’ compared to ‘freely-chosen’ instructional conditions, as well as higher reorganization of limb movement and inter-limb coordination (p<0.05). In the ‘minimal glide’ condition, the swimmers did not show significantly shorter glide and lower energy cost, but they exhibited significantly lower deceleration of the center of mass, as well as modified limb movement and inter-limb coordination (p<0.05). These results highlight that a variety of structural adaptations can functionally satisfy the task-goal. PMID:25255016

  3. Modular organization of cardiac energy metabolism: energy conversion, transfer and feedback regulation

    PubMed Central

    Guzun, R.; Kaambre, T.; Bagur, R.; Grichine, A.; Usson, Y.; Varikmaa, M.; Anmann, T.; Tepp, K.; Timohhina, N.; Shevchuk, I.; Chekulayev, V.; Boucher, F.; Santos, P. Dos; Schlattner, U.; Wallimann, T.; Kuznetsov, A. V.; Dzeja, P.; Aliev, M.; Saks, V.

    2014-01-01

    To meet high cellular demands, the energy metabolism of cardiac muscles is organized by precise and coordinated functioning of intracellular energetic units (ICEUs). ICEUs represent structural and functional modules integrating multiple fluxes at sites of ATP generation in mitochondria and ATP utilization by myofibrillar, sarcoplasmic reticulum and sarcolemma ion-pump ATPases. The role of ICEUs is to enhance the efficiency of vectorial intracellular energy transfer and fine tuning of oxidative ATP synthesis maintaining stable metabolite levels to adjust to intracellular energy needs through the dynamic system of compartmentalized phosphoryl transfer networks. One of the key elements in regulation of energy flux distribution and feedback communication is the selective permeability of mitochondrial outer membrane (MOM) which represents a bottleneck in adenine nucleotide and other energy metabolite transfer and microcompartmentalization. Based on the experimental and theoretical (mathematical modelling) arguments, we describe regulation of mitochondrial ATP synthesis within ICEUs allowing heart workload to be linearly correlated with oxygen consumption ensuring conditions of metabolic stability, signal communication and synchronization. Particular attention was paid to the structure–function relationship in the development of ICEU, and the role of mitochondria interaction with cytoskeletal proteins, like tubulin, in the regulation of MOM permeability in response to energy metabolic signals providing regulation of mitochondrial respiration. Emphasis was given to the importance of creatine metabolism for the cardiac energy homoeostasis. PMID:24666671

  4. Modular organization of cardiac energy metabolism: energy conversion, transfer and feedback regulation.

    PubMed

    Guzun, R; Kaambre, T; Bagur, R; Grichine, A; Usson, Y; Varikmaa, M; Anmann, T; Tepp, K; Timohhina, N; Shevchuk, I; Chekulayev, V; Boucher, F; Dos Santos, P; Schlattner, U; Wallimann, T; Kuznetsov, A V; Dzeja, P; Aliev, M; Saks, V

    2015-01-01

    To meet high cellular demands, the energy metabolism of cardiac muscles is organized by precise and coordinated functioning of intracellular energetic units (ICEUs). ICEUs represent structural and functional modules integrating multiple fluxes at sites of ATP generation in mitochondria and ATP utilization by myofibrillar, sarcoplasmic reticulum and sarcolemma ion-pump ATPases. The role of ICEUs is to enhance the efficiency of vectorial intracellular energy transfer and fine tuning of oxidative ATP synthesis maintaining stable metabolite levels to adjust to intracellular energy needs through the dynamic system of compartmentalized phosphoryl transfer networks. One of the key elements in regulation of energy flux distribution and feedback communication is the selective permeability of mitochondrial outer membrane (MOM) which represents a bottleneck in adenine nucleotide and other energy metabolite transfer and microcompartmentalization. Based on the experimental and theoretical (mathematical modelling) arguments, we describe regulation of mitochondrial ATP synthesis within ICEUs allowing heart workload to be linearly correlated with oxygen consumption ensuring conditions of metabolic stability, signal communication and synchronization. Particular attention was paid to the structure-function relationship in the development of ICEU, and the role of mitochondria interaction with cytoskeletal proteins, like tubulin, in the regulation of MOM permeability in response to energy metabolic signals providing regulation of mitochondrial respiration. Emphasis was given to the importance of creatine metabolism for the cardiac energy homoeostasis.

  5. p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance.

    PubMed

    Yogev, Orli; Barker, Karen; Sikka, Arti; Almeida, Gilberto S; Hallsworth, Albert; Smith, Laura M; Jamin, Yann; Ruddle, Ruth; Koers, Alexander; Webber, Hannah T; Raynaud, Florence I; Popov, Sergey; Jones, Chris; Petrie, Kevin; Robinson, Simon P; Keun, Hector C; Chesler, Louis

    2016-05-15

    Neuroblastoma is the most common childhood extracranial solid tumor. In high-risk cases, many of which are characterized by amplification of MYCN, outcome remains poor. Mutations in the p53 (TP53) tumor suppressor are rare at diagnosis, but evidence suggests that p53 function is often impaired in relapsed, treatment-resistant disease. To address the role of p53 loss of function in the development and pathogenesis of high-risk neuroblastoma, we generated a MYCN-driven genetically engineered mouse model in which the tamoxifen-inducible p53ER(TAM) fusion protein was expressed from a knock-in allele (Th-MYCN/Trp53(KI)). We observed no significant differences in tumor-free survival between Th-MYCN mice heterozygous for Trp53(KI) (n = 188) and Th-MYCN mice with wild-type p53 (n = 101). Conversely, the survival of Th-MYCN/Trp53(KI/KI) mice lacking functional p53 (n = 60) was greatly reduced. We found that Th-MYCN/Trp53(KI/KI) tumors were resistant to ionizing radiation (IR), as expected. However, restoration of functional p53ER(TAM) reinstated sensitivity to IR in only 50% of Th-MYCN/Trp53(KI/KI) tumors, indicating the acquisition of additional resistance mechanisms. Gene expression and metabolic analyses indicated that the principal acquired mechanism of resistance to IR in the absence of functional p53 was metabolic adaptation in response to chronic oxidative stress. Tumors exhibited increased antioxidant metabolites and upregulation of glutathione S-transferase pathway genes, including Gstp1 and Gstz1, which are associated with poor outcome in human neuroblastoma. Accordingly, glutathione depletion by buthionine sulfoximine together with restoration of p53 activity resensitized tumors to IR. Our findings highlight the complex pathways operating in relapsed neuroblastomas and the need for combination therapies that target the diverse resistance mechanisms at play. Cancer Res; 76(10); 3025-35. ©2016 AACR. PMID:27197232

  6. Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism.

    PubMed

    Yen, Chi-Liang Eric; Nelson, David W; Yen, Mei-I

    2015-03-01

    The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation. PMID:25231105

  7. Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism

    PubMed Central

    Yen, Chi-Liang Eric; Nelson, David W.; Yen, Mei-I

    2015-01-01

    The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation. PMID:25231105

  8. Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism.

    PubMed

    Yen, Chi-Liang Eric; Nelson, David W; Yen, Mei-I

    2015-03-01

    The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation.

  9. Metabolic models to investigate energy limited anaerobic ecosystems.

    PubMed

    Rodríguez, J; Premier, G C; Guwy, A J; Dinsdale, R; Kleerebezem, R

    2009-01-01

    Anaerobic wastewater treatment is shifting from a philosophy of solely pollutants removal to a philosophy of combined resource recovery and waste treatment. Simultaneous wastewater treatment with energy recovery in the form of energy rich products, brings renewed interest to non-methanogenic anaerobic bioprocesses such as the anaerobic production of hydrogen, ethanol, solvents, VFAs, bioplastics and even electricity from microbial fuel cells. The existing kinetic-based modelling approaches, widely used in aerobic and methanogenic wastewater treatment processes, do not seem adequate in investigating such energy limited microbial ecosystems. The great diversity of similar microbial species, which share many of the fermentative reaction pathways, makes quantify microbial groups very difficult and causes identifiability problems. A modelling approach based on the consideration of metabolic reaction networks instead of on separated microbial groups is suggested as an alternative to describe anaerobic microbial ecosystems and in particular for the prediction of product formation as a function of environmental conditions imposed. The limited number of existing relevant fermentative pathways in conjunction with the fact that anaerobic reactions proceed very close to thermodynamic equilibrium reduces the complexity of such approach and the degrees of freedom in terms of product formation fluxes. In addition, energy limitation in these anaerobic microbial ecosystems makes plausible that selective forces associated with energy further define the system activity by favouring those conversions/microorganisms which provide the most energy for growth under the conditions imposed. PMID:19809129

  10. Elevated dopamine concentration in light-adapted zebrafish retinas is correlated with increased dopamine synthesis and metabolism.

    PubMed

    Connaughton, Victoria P; Wetzell, Bradley; Arneson, Lynne S; DeLucia, Vittoria; Riley, Anthony L

    2015-10-01

    Probing zebrafish (Danio rerio) retinal cryostat sections, collected either 8 h into the light or dark cycle, with an antibody against tyrosine hydroxylase (TH) identified a single population of immunopositive cells in the inner retina. However, the observed labeling patterns were not identical in both sets of tissues - label intensity was brighter in light-adapted tissue. This difference was quantified by probing western blots of retinal homogenates with the same TH antibody, which showed that TH expression increased by 42% in light-adapted tissue. High-performance liquid chromatography with electrochemical detection revealed that the concentrations of both dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) are also elevated in light-adapted zebrafish retinal tissue. Dopamine levels increased by 14% and DOPAC levels increased by 25% when measured in retinal homogenates harvested during the light cycle. These results indicate that dopamine levels in zebrafish retina are significantly increased in light-adapted tissue. The increase in dopamine content is correlated with an increase in both TH and DOPAC, suggesting that changes in dopamine concentration are due to light-adaptive changes in the synthesis, release and metabolism of dopamine. Dopamine concentration is elevated in lighted-adapted zebrafish retinas. This increase is correlated with an increase in both tyrosine hydroxylase (TH) and DOPAC (3,4-dihydroxyphenylacetic acid), suggesting that changes in dopamine concentration are due to light-adaptive changes in the synthesis, release and metabolism of dopamine. This is applicable to studies examining retinal mutants, the role of dopamine in disease or visual system development.

  11. Role of redox metabolism for adaptation of aquatic animals to drastic changes in oxygen availability.

    PubMed

    Welker, Alexis F; Moreira, Daniel C; Campos, Élida G; Hermes-Lima, Marcelo

    2013-08-01

    Large changes in oxygen availability in aquatic environments, ranging from anoxia through to hyperoxia, can lead to corresponding wide variation in the production of reactive oxygen species (ROS) by animals with aquatic respiration. Therefore, animals living in marine, estuarine and freshwater environments have developed efficient antioxidant defenses to minimize oxidative stress and to regulate the cellular actions of ROS. Changes in oxygen levels may lead to bursts of ROS generation that can be particularly harmful. This situation is commonly experienced by aquatic animals during abrupt transitions from periods of hypoxia/anoxia back to oxygenated conditions (e.g. intertidal cycles). The strategies developed differ significantly among aquatic species and are (i) improvement of their endogenous antioxidant system under hyperoxia (that leads to increased ROS formation) or other similar ROS-related stresses, (ii) increase in antioxidant levels when displaying higher metabolic rates, (iii) presence of constitutively high levels of antioxidants, that attenuates oxidative stress derived from fluctuations in oxygen availability, or (iv) increase in the activity of antioxidant enzymes (and/or the levels of their mRNAs) during hypometabolic states associated with anoxia/hypoxia. This enhancement of the antioxidant system - coined over a decade ago as "preparation for oxidative stress" - controls the possible harmful effects of increased ROS formation during hypoxia/reoxygenation. The present article proposes a novel explanation for the biochemical and molecular mechanisms involved in this phenomenon that could be triggered by hypoxia-induced ROS formation. We also discuss the connections among oxygen sensing, oxidative damage and regulation of the endogenous antioxidant defense apparatus in animals adapted to many natural or man-made challenges of the aquatic environment. PMID:23587877

  12. Differential Molecular Responses of Rapeseed Cotyledons to Light and Dark Reveal Metabolic Adaptations toward Autotrophy Establishment

    PubMed Central

    He, Dongli; Damaris, Rebecca N.; Fu, Jinlei; Tu, Jinxing; Fu, Tingdong; Xi, Chen; Yi, Bin; Yang, Pingfang

    2016-01-01

    Photosynthesis competent autotrophy is established during the postgerminative stage of plant growth. Among the multiple factors, light plays a decisive role in the switch from heterotrophic to autotrophic growth. Under dark conditions, the rapeseed hypocotyl extends quickly with an apical hook, and the cotyledon is yellow and folded, and maintains high levels of the isocitrate lyase (ICL). By contrast, in the light, the hypocotyl extends slowly, the cotyledon unfolds and turns green, the ICL content changes in parallel with cotyledon greening. To reveal metabolic adaptations during the establishment of postgerminative autotrophy in rapeseed, we conducted comparative proteomic and metabolomic analyses of the cotyledons of seedlings grown under light versus dark conditions. Under both conditions, the increase in proteases, fatty acid β-oxidation and glyoxylate-cycle related proteins was accompanied by rapid degradation of the stored proteins and lipids with an accumulation of the amino acids. While light condition partially retarded these conversions. Light significantly induced the expression of chlorophyll-binding and photorespiration related proteins, resulting in an increase in reducing-sugars. However, the levels of some chlorophyllide conversion, Calvin-cycle and photorespiration related proteins also accumulated in dark grown cotyledons, implying that the transition from heterotrophy to autotrophy is programmed in the seed rather than induced by light. Various anti-stress systems, e.g., redox related proteins, salicylic acid, proline and chaperones, were employed to decrease oxidative stress, which was mainly derived from lipid oxidation or photorespiration, under both conditions. This study provides a comprehensive understanding of the differential molecular responses of rapeseed cotyledons to light and dark conditions, which will facilitate further study on the complex mechanism underlying the transition from heterotrophy to autotrophy. PMID:27471506

  13. Differential Molecular Responses of Rapeseed Cotyledons to Light and Dark Reveal Metabolic Adaptations toward Autotrophy Establishment.

    PubMed

    He, Dongli; Damaris, Rebecca N; Fu, Jinlei; Tu, Jinxing; Fu, Tingdong; Xi, Chen; Yi, Bin; Yang, Pingfang

    2016-01-01

    Photosynthesis competent autotrophy is established during the postgerminative stage of plant growth. Among the multiple factors, light plays a decisive role in the switch from heterotrophic to autotrophic growth. Under dark conditions, the rapeseed hypocotyl extends quickly with an apical hook, and the cotyledon is yellow and folded, and maintains high levels of the isocitrate lyase (ICL). By contrast, in the light, the hypocotyl extends slowly, the cotyledon unfolds and turns green, the ICL content changes in parallel with cotyledon greening. To reveal metabolic adaptations during the establishment of postgerminative autotrophy in rapeseed, we conducted comparative proteomic and metabolomic analyses of the cotyledons of seedlings grown under light versus dark conditions. Under both conditions, the increase in proteases, fatty acid β-oxidation and glyoxylate-cycle related proteins was accompanied by rapid degradation of the stored proteins and lipids with an accumulation of the amino acids. While light condition partially retarded these conversions. Light significantly induced the expression of chlorophyll-binding and photorespiration related proteins, resulting in an increase in reducing-sugars. However, the levels of some chlorophyllide conversion, Calvin-cycle and photorespiration related proteins also accumulated in dark grown cotyledons, implying that the transition from heterotrophy to autotrophy is programmed in the seed rather than induced by light. Various anti-stress systems, e.g., redox related proteins, salicylic acid, proline and chaperones, were employed to decrease oxidative stress, which was mainly derived from lipid oxidation or photorespiration, under both conditions. This study provides a comprehensive understanding of the differential molecular responses of rapeseed cotyledons to light and dark conditions, which will facilitate further study on the complex mechanism underlying the transition from heterotrophy to autotrophy. PMID:27471506

  14. Energy Expenditure and Metabolic Changes of Free-Flying Migrating Northern Bald Ibis.

    PubMed

    Bairlein, Franz; Fritz, Johannes; Scope, Alexandra; Schwendenwein, Ilse; Stanclova, Gabriela; van Dijk, Gertjan; Meijer, Harro A J; Verhulst, Simon; Dittami, John

    2015-01-01

    Many migrating birds undertake extraordinary long flights. How birds are able to perform such endurance flights of over 100-hour durations is still poorly understood. We examined energy expenditure and physiological changes in Northern Bald Ibis Geronticus eremite during natural flights using birds trained to follow an ultra-light aircraft. Because these birds were tame, with foster parents, we were able to bleed them immediately prior to and after each flight. Flight duration was experimentally designed ranging between one and almost four hours continuous flights. Energy expenditure during flight was estimated using doubly-labelled-water while physiological properties were assessed through blood chemistry including plasma metabolites, enzymes, electrolytes, blood gases, and reactive oxygen compounds. Instantaneous energy expenditure decreased with flight duration, and the birds appeared to balance aerobic and anaerobic metabolism, using fat, carbohydrate and protein as fuel. This made flight both economic and tolerable. The observed effects resemble classical exercise adaptations that can limit duration of exercise while reducing energetic output. There were also in-flight benefits that enable power output variation from cruising to manoeuvring. These adaptations share characteristics with physiological processes that have facilitated other athletic feats in nature and might enable the extraordinary long flights of migratory birds as well.

  15. Energy Expenditure and Metabolic Changes of Free-Flying Migrating Northern Bald Ibis.

    PubMed

    Bairlein, Franz; Fritz, Johannes; Scope, Alexandra; Schwendenwein, Ilse; Stanclova, Gabriela; van Dijk, Gertjan; Meijer, Harro A J; Verhulst, Simon; Dittami, John

    2015-01-01

    Many migrating birds undertake extraordinary long flights. How birds are able to perform such endurance flights of over 100-hour durations is still poorly understood. We examined energy expenditure and physiological changes in Northern Bald Ibis Geronticus eremite during natural flights using birds trained to follow an ultra-light aircraft. Because these birds were tame, with foster parents, we were able to bleed them immediately prior to and after each flight. Flight duration was experimentally designed ranging between one and almost four hours continuous flights. Energy expenditure during flight was estimated using doubly-labelled-water while physiological properties were assessed through blood chemistry including plasma metabolites, enzymes, electrolytes, blood gases, and reactive oxygen compounds. Instantaneous energy expenditure decreased with flight duration, and the birds appeared to balance aerobic and anaerobic metabolism, using fat, carbohydrate and protein as fuel. This made flight both economic and tolerable. The observed effects resemble classical exercise adaptations that can limit duration of exercise while reducing energetic output. There were also in-flight benefits that enable power output variation from cruising to manoeuvring. These adaptations share characteristics with physiological processes that have facilitated other athletic feats in nature and might enable the extraordinary long flights of migratory birds as well. PMID:26376193

  16. Energy Expenditure and Metabolic Changes of Free-Flying Migrating Northern Bald Ibis

    PubMed Central

    Bairlein, Franz; Fritz, Johannes; Scope, Alexandra; Schwendenwein, Ilse; Stanclova, Gabriela; van Dijk, Gertjan; Meijer, Harro A. J.; Verhulst, Simon

    2015-01-01

    Many migrating birds undertake extraordinary long flights. How birds are able to perform such endurance flights of over 100-hour durations is still poorly understood. We examined energy expenditure and physiological changes in Northern Bald Ibis Geronticus eremite during natural flights using birds trained to follow an ultra-light aircraft. Because these birds were tame, with foster parents, we were able to bleed them immediately prior to and after each flight. Flight duration was experimentally designed ranging between one and almost four hours continuous flights. Energy expenditure during flight was estimated using doubly-labelled-water while physiological properties were assessed through blood chemistry including plasma metabolites, enzymes, electrolytes, blood gases, and reactive oxygen compounds. Instantaneous energy expenditure decreased with flight duration, and the birds appeared to balance aerobic and anaerobic metabolism, using fat, carbohydrate and protein as fuel. This made flight both economic and tolerable. The observed effects resemble classical exercise adaptations that can limit duration of exercise while reducing energetic output. There were also in-flight benefits that enable power output variation from cruising to manoeuvring. These adaptations share characteristics with physiological processes that have facilitated other athletic feats in nature and might enable the extraordinary long flights of migratory birds as well. PMID:26376193

  17. Perilipin 5 is dispensable for normal substrate metabolism and in the adaptation of skeletal muscle to exercise training.

    PubMed

    Mohktar, Ruzaidi A M; Montgomery, Magda K; Murphy, Robyn M; Watt, Matthew J

    2016-07-01

    Cytoplasmic lipid droplets provide a reservoir for triglyceride storage and are a central hub for fatty acid trafficking in cells. The protein perilipin 5 (PLIN5) is highly expressed in oxidative tissues such as skeletal muscle and regulates lipid metabolism by coordinating the trafficking and the reversible interactions of effector proteins at the lipid droplet. PLIN5 may also regulate mitochondrial function, although this remains unsubstantiated. Hence, the aims of this study were to examine the role of PLIN5 in the regulation of skeletal muscle substrate metabolism during acute exercise and to determine whether PLIN5 is required for the metabolic adaptations and enhancement in exercise tolerance following endurance exercise training. Using muscle-specific Plin5 knockout mice (Plin5(MKO)), we show that PLIN5 is dispensable for normal substrate metabolism during exercise, as reflected by levels of blood metabolites and rates of glycogen and triglyceride depletion that were indistinguishable from control (lox/lox) mice. Plin5(MKO) mice exhibited a functional impairment in their response to endurance exercise training, as reflected by reduced maximal running capacity (20%) and reduced time to fatigue during prolonged submaximal exercise (15%). The reduction in exercise performance was not accompanied by alterations in carbohydrate and fatty acid metabolism during submaximal exercise. Similarly, mitochondrial capacity (mtDNA, respiratory complex proteins, citrate synthase activity) and mitochondrial function (oxygen consumption rate in muscle fiber bundles) were not different between lox/lox and Plin5(MKO) mice. Thus, PLIN5 is dispensable for normal substrate metabolism during exercise and is not required to promote mitochondrial biogenesis or enhance the cellular adaptations to endurance exercise training. PMID:27189934

  18. Perilipin 5 is dispensable for normal substrate metabolism and in the adaptation of skeletal muscle to exercise training.

    PubMed

    Mohktar, Ruzaidi A M; Montgomery, Magda K; Murphy, Robyn M; Watt, Matthew J

    2016-07-01

    Cytoplasmic lipid droplets provide a reservoir for triglyceride storage and are a central hub for fatty acid trafficking in cells. The protein perilipin 5 (PLIN5) is highly expressed in oxidative tissues such as skeletal muscle and regulates lipid metabolism by coordinating the trafficking and the reversible interactions of effector proteins at the lipid droplet. PLIN5 may also regulate mitochondrial function, although this remains unsubstantiated. Hence, the aims of this study were to examine the role of PLIN5 in the regulation of skeletal muscle substrate metabolism during acute exercise and to determine whether PLIN5 is required for the metabolic adaptations and enhancement in exercise tolerance following endurance exercise training. Using muscle-specific Plin5 knockout mice (Plin5(MKO)), we show that PLIN5 is dispensable for normal substrate metabolism during exercise, as reflected by levels of blood metabolites and rates of glycogen and triglyceride depletion that were indistinguishable from control (lox/lox) mice. Plin5(MKO) mice exhibited a functional impairment in their response to endurance exercise training, as reflected by reduced maximal running capacity (20%) and reduced time to fatigue during prolonged submaximal exercise (15%). The reduction in exercise performance was not accompanied by alterations in carbohydrate and fatty acid metabolism during submaximal exercise. Similarly, mitochondrial capacity (mtDNA, respiratory complex proteins, citrate synthase activity) and mitochondrial function (oxygen consumption rate in muscle fiber bundles) were not different between lox/lox and Plin5(MKO) mice. Thus, PLIN5 is dispensable for normal substrate metabolism during exercise and is not required to promote mitochondrial biogenesis or enhance the cellular adaptations to endurance exercise training.

  19. Selenocysteine, Pyrrolysine, and the Unique Energy Metabolism of Methanogenic Archaea

    DOE PAGES

    Rother, Michael; Krzycki, Joseph A.

    2010-01-01

    Methanogenic archaea are a group of strictly anaerobic microorganisms characterized by their strict dependence on the process of methanogenesis for energy conservation. Among the archaea, they are also the only known group synthesizing proteins containing selenocysteine or pyrrolysine. All but one of the known archaeal pyrrolysine-containing and all but two of the confirmed archaeal selenocysteine-containing protein are involved in methanogenesis. Synthesis of these proteins proceeds through suppression of translational stop codons but otherwise the two systems are fundamentally different. This paper highlights these differences and summarizes the recent developments in selenocysteine- and pyrrolysine-related research on archaea and aims to putmore » this knowledge into the context of their unique energy metabolism.« less

  20. Selenocysteine, Pyrrolysine, and the Unique Energy Metabolism of Methanogenic Archaea

    PubMed Central

    Rother, Michael; Krzycki, Joseph A.

    2010-01-01

    Methanogenic archaea are a group of strictly anaerobic microorganisms characterized by their strict dependence on the process of methanogenesis for energy conservation. Among the archaea, they are also the only known group synthesizing proteins containing selenocysteine or pyrrolysine. All but one of the known archaeal pyrrolysine-containing and all but two of the confirmed archaeal selenocysteine-containing protein are involved in methanogenesis. Synthesis of these proteins proceeds through suppression of translational stop codons but otherwise the two systems are fundamentally different. This paper highlights these differences and summarizes the recent developments in selenocysteine- and pyrrolysine-related research on archaea and aims to put this knowledge into the context of their unique energy metabolism. PMID:20847933

  1. Follistatin promotes adipocyte differentiation, browning, and energy metabolism.

    PubMed

    Braga, Melissa; Reddy, Srinivasa T; Vergnes, Laurent; Pervin, Shehla; Grijalva, Victor; Stout, David; David, John; Li, Xinmin; Tomasian, Venina; Reid, Christopher B; Norris, Keith C; Devaskar, Sherin U; Reue, Karen; Singh, Rajan

    2014-03-01

    Follistatin (Fst) functions to bind and neutralize the activity of members of the transforming growth factor-β superfamily. Fst has a well-established role in skeletal muscle, but we detected significant Fst expression levels in interscapular brown and subcutaneous white adipose tissue, and further investigated its role in adipocyte biology. Fst expression was induced during adipogenic differentiation of mouse brown preadipocytes and mouse embryonic fibroblasts (MEFs) as well as in cold-induced brown adipose tissue from mice. In differentiated MEFs from Fst KO mice, the induction of brown adipocyte proteins including uncoupling protein 1, PR domain containing 16, and PPAR gamma coactivator-1α was attenuated, but could be rescued by treatment with recombinant FST. Furthermore, Fst enhanced thermogenic gene expression in differentiated mouse brown adipocytes and MEF cultures from both WT and Fst KO groups, suggesting that Fst produced by adipocytes may act in a paracrine manner. Our microarray gene expression profiling of WT and Fst KO MEFs during adipogenic differentiation identified several genes implicated in lipid and energy metabolism that were significantly downregulated in Fst KO MEFs. Furthermore, Fst treatment significantly increases cellular respiration in Fst-deficient cells. Our results implicate a novel role of Fst in the induction of brown adipocyte character and regulation of energy metabolism. PMID:24443561

  2. Non-resonant energy harvesting via an adaptive bistable potential

    NASA Astrophysics Data System (ADS)

    Haji Hosseinloo, Ashkan; Turitsyn, Konstantin

    2016-01-01

    Narrow bandwidth and easy detuning, inefficiency in broadband and non-stationary excitations, and difficulties in matching a linear harvester’s resonance frequency to low-frequency excitations at small scales, have convinced researchers to investigate nonlinear, and in particular bistable, energy harvesters in recent years. However, bistable harvesters suffer from co-existing low and high energy orbits, and sensitivity to initial conditions, and have recently been proven inefficient when subjected to many real-world random and non-stationary excitations. Here, we propose a novel non-resonant buy-low-sell-high strategy that can significantly improve the harvester’s effectiveness at low frequencies in a much more robust fashion. This strategy could be realized by a passive adaptive bistable system. Simulation results confirm the high effectiveness of the adaptive bistable system following a buy-low-sell-high logic when subjected to harmonic and random non-stationary walking excitations compared to its conventional bistable and linear counterparts.

  3. The metabolic energy cost of action potential velocity

    NASA Astrophysics Data System (ADS)

    Crotty, Patrick; Sangrey, Thomas; Levy, William

    2006-03-01

    Voltage changes in neurons and other active cells are caused by the passage of ions across the cell membrane. These ionic currents depend on the transmembrane ion concentration gradients, which in unmyelinated axons are maintained during rest and restored after electrical activity by an ATPase sodium-potassium exchanger in the membrane. The amount of ATP consumed by this exchanger can be taken as the metabolic energy cost of any electrical activity in the axon. We use this measure, along with biophysical models of voltage-gated sodium and potassium ion channels, to quantify the energy cost of action potentials propagating in squid giant axons. We find that the energy of an action potential can be naturally divided into three separate components associated with different aspects of the action potential. We calculate these energy components as functions of the ion channel densities and axon diameters and find that the component associated with the rising phase and velocity of the action potential achieves a minimum near the biological values of these parameters. This result, which is robust with respect to other parameters such as temperature, suggests that evolution has optimized the axon for the energy of the action potential wavefront.

  4. Comparative ionomics and metabolomics in extremophile and glycophytic Lotus species under salt stress challenge the metabolic pre-adaptation hypothesis.

    PubMed

    Sanchez, Diego H; Pieckenstain, Fernando L; Escaray, Francisco; Erban, Alexander; Kraemer, Ute; Udvardi, Michael K; Kopka, Joachim

    2011-04-01

    The legume genus Lotus includes glycophytic forage crops and other species adapted to extreme environments, such as saline soils. Understanding salt tolerance mechanisms will contribute to the discovery of new traits which may enhance the breeding efforts towards improved performance of legumes in marginal agricultural environments. Here, we used a combination of ionomic and gas chromatography-mass spectrometry (GC-MS)-based metabolite profilings of complete shoots (pooling leaves, petioles and stems) to compare the extremophile Lotus creticus, adapted to highly saline coastal regions, and two cultivated glycophytic grassland forage species, Lotus corniculatus and Lotus tenuis. L. creticus exhibited better survival after exposure to long-term lethal salinity and was more efficient at excluding Cl⁻ from the shoots than the glycophytes. In contrast, Na+ levels were higher in the extremophile under both control and salt stress, a trait often observed in halophytes. Ionomics demonstrated a differential rearrangement of shoot nutrient levels in the extremophile upon salt exposure. Metabolite profiling showed that responses to NaCl in L. creticus shoots were globally similar to those of the glycophytes, providing little evidence for metabolic pre-adaptation to salinity. This study is the first comparing salt acclimation responses between extremophile and non-extremophile legumes, and challenges the generalization of the metabolic salt pre-adaptation hypothesis. PMID:21251019

  5. Metabolic adaptations of Azospirillum brasilense to oxygen stress by cell-to-cell clumping and flocculation.

    PubMed

    Bible, Amber N; Khalsa-Moyers, Gurusahai K; Mukherjee, Tanmoy; Green, Calvin S; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B; Alexandre, Gladys

    2015-12-01

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacterium Azospirillum brasilense navigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motile A. brasilense cells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Cell-to-cell clumping may thus license diazotrophy to microaerophilic A. brasilense cells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists. PMID:26407887

  6. Metabolic adaptations of Azospirillum brasilense to oxygen stress by cell-to-cell clumping and flocculation.

    PubMed

    Bible, Amber N; Khalsa-Moyers, Gurusahai K; Mukherjee, Tanmoy; Green, Calvin S; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B; Alexandre, Gladys

    2015-12-01

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacterium Azospirillum brasilense navigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motile A. brasilense cells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Cell-to-cell clumping may thus license diazotrophy to microaerophilic A. brasilense cells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists.

  7. Metabolic Adaptations of Azospirillum brasilense to Oxygen Stress by Cell-to-Cell Clumping and Flocculation

    PubMed Central

    Bible, Amber N.; Khalsa-Moyers, Gurusahai K.; Mukherjee, Tanmoy; Green, Calvin S.; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B.

    2015-01-01

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacterium Azospirillum brasilense navigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motile A. brasilense cells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Cell-to-cell clumping may thus license diazotrophy to microaerophilic A. brasilense cells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists. PMID:26407887

  8. Metabolic analysis of adaptation to short-term changes in culture conditions of the marine diatom Thalassiosira pseudonana.

    PubMed

    Bromke, Mariusz A; Giavalisco, Patrick; Willmitzer, Lothar; Hesse, Holger

    2013-01-01

    This report describes the metabolic and lipidomic profiling of 97 low-molecular weight compounds from the primary metabolism and 124 lipid compounds of the diatom Thalassiosira pseudonana. The metabolic profiles were created for diatoms perturbed for 24 hours with four different treatments: (I) removal of nitrogen, (II) lower iron concentration, (III) addition of sea salt, (IV) addition of carbonate to their growth media. Our results show that as early as 24 hours after nitrogen depletion significant qualitative and quantitative change in lipid composition as well as in the primary metabolism of Thalassiosira pseudonana occurs. So we can observe the accumulation of several storage lipids, namely triacylglycerides, and TCA cycle intermediates, of which citric acid increases more than 10-fold. These changes are positively correlated with expression of TCA enzymes genes. Next to the TCA cycle intermediates and storage lipid changes, we have observed decrease in N-containing lipids and primary metabolites such as amino acids. As a measure of counteracting nitrogen starvation, we have observed elevated expression levels of nitrogen uptake and amino acid biosynthetic genes. This indicates that diatoms can fast and efficiently adapt to changing environment by altering the metabolic fluxes and metabolite abundances. Especially, the accumulation of proline and the decrease of dimethylsulfoniopropionate suggest that the proline is the main osmoprotectant for the diatom in nitrogen rich conditions. PMID:23799147

  9. Triheptanoin improves brain energy metabolism in patients with Huntington disease

    PubMed Central

    Adanyeguh, Isaac Mawusi; Rinaldi, Daisy; Henry, Pierre-Gilles; Caillet, Samantha; Valabregue, Romain; Durr, Alexandra

    2015-01-01

    Objective: Based on our previous work in Huntington disease (HD) showing improved energy metabolism in muscle by providing substrates to the Krebs cycle, we wished to obtain a proof-of-concept of the therapeutic benefit of triheptanoin using a functional biomarker of brain energy metabolism validated in HD. Methods: We performed an open-label study using 31P brain magnetic resonance spectroscopy (MRS) to measure the levels of phosphocreatine (PCr) and inorganic phosphate (Pi) before (rest), during (activation), and after (recovery) a visual stimulus. We performed 31P brain MRS in 10 patients at an early stage of HD and 13 controls. Patients with HD were then treated for 1 month with triheptanoin after which they returned for follow-up including 31P brain MRS scan. Results: At baseline, we confirmed an increase in Pi/PCr ratio during brain activation in controls—reflecting increased adenosine triphosphate synthesis—followed by a return to baseline levels during recovery (p = 0.013). In patients with HD, we validated the existence of an abnormal brain energy profile as previously reported. After 1 month, this profile remained abnormal in patients with HD who did not receive treatment. Conversely, the MRS profile was improved in patients with HD treated with triheptanoin for 1 month with the restoration of an increased Pi/PCr ratio during visual stimulation (p = 0.005). Conclusion: This study suggests that triheptanoin is able to correct the bioenergetic profile in the brain of patients with HD at an early stage of the disease. Classification of evidence: This study provides Class III evidence that, for patients with HD, treatment with triheptanoin for 1 month restores an increased MRS Pi/PCr ratio during visual stimulation. PMID:25568297

  10. Ghrelin O-acyltransferase (GOAT) and energy metabolism.

    PubMed

    Li, Ziru; Mulholland, Michael; Zhang, Weizhen

    2016-03-01

    Ghrelin O-acyltransferase (GOAT), a member of MBOATs family, is essential for octanoylation of ghrelin, which is required for active ghrelin to bind with and activate its receptor. GOAT is expressed mainly in the stomach, pancreas and hypothalamus. Levels of GOAT are altered by energy status. GOAT contains 11 transmembrane helices and one reentrant loop. Its invariant residue His-338 and conserved Asn-307 are located in the endoplasmic reticulum lumen and cytosol respectively. GOAT contributes to the regulation of food intake and energy expenditure, as well as glucose and lipids homeostasis. Deletion of GOAT blocks the acylation of ghrelin leading to subsequent impairment in energy homeostasis and survival when mice are challenged with high energy diet or severe caloric restriction. GO-CoA-Tat, a peptide GOAT inhibitor, attenuates acyl-ghrelin production and prevents weight gain induced by a medium-chain triglycerides-rich high fat diet. Further, GO-CoA-Tat increases glucose- induced insulin secretion. Overall, inhibition of GOAT is a novel strategy for treatment of obesity and related metabolic disorders. PMID:26732975

  11. Natural selection reduces energy metabolism in the garden snail, helix aspersa (cornu aspersum).

    PubMed

    Artacho, Paulina; Nespolo, Roberto F

    2009-04-01

    Phenotypic selection is widely recognized as the primary cause of adaptive evolution in natural populations, a fact that has been documented frequently over the last few decades, mainly in morphological and life-history traits. The energetic definition of fitness predicts that natural selection will maximize the residual energy available for growth and reproduction, suggesting that energy metabolism could be a target of selection. To address this problem, we chose the garden snail, Helix aspersa (Cornu aspersum). We performed a seminatural experiment for measuring phenotypic selection on standard metabolic rate (SMR), the minimum cost of maintenance in ectotherm organisms. To discount selection on correlated traits, we included two additional whole-organism performance traits (mean speed and maximum force of dislodgement). We found a combination of linear (negative directional selection, beta=-0.106 +/- 0.06; P= 0.001) and quadratic (stabilizing selection, gamma=-0.012 +/- 0.033; P= 0.061) selection on SMR. Correlational selection was not significant for any possible pair of traits. This suggests that individuals with average-to-reduced SMRs were promoted by selection. To the best of our knowledge, this is the first study showing significant directional selection on the obligatory cost of maintenance in an animal, providing support for the energetic definition of fitness.

  12. Energy metabolism and fasting in male and female insectivorous bats Molossus molossus (Chiroptera: Molossidae).

    PubMed

    Freitas, M B; Goulart, L S; Barros, M S; Morais, D B; Amaral, T S; Matta, S L P

    2010-08-01

    Metabolic adaptations induced by 24 and 48 hours of fasting were investigated in male and female insectivorous bats (Molossus molossus Pallas, 1766). For this purpose, plasma glucose, non esterified fatty acids (NEFA), glycogen, protein and lipids concentrations in liver and muscles were obtained. Data presented here demonstrate that fed bats showed plasma glucose levels similar to those reported for other mammal species. In response to fasting, glycemia was decreased only in 48 hours fasted females. Plasma NEFA levels were similar in both sexes, and did not exhibit any changes during fasting. Considering the data from energy reserve variations, fed females presented an increased content of liver glycogen as well as higher breast muscle protein and limbs lipids concentrations, compared to fed males. In response to fasting, liver and muscle glycogen levels remained unchanged. Considering protein and lipid reserves, only females showed decreased values following fasting, as seen in breast, limbs and carcass lipids and breast muscle protein reserves, but still fail to keep glucose homeostasis after 48 hours without food. Taken together, our data suggest that the energy metabolism of insectivorous bats may vary according to sexual differences, a pattern that might be associated to different reproduction investments and costs between genders.

  13. Streptococcus mutans copes with heat stress by multiple transcriptional regulons modulating virulence and energy metabolism

    PubMed Central

    Liu, Chengcheng; Niu, Yulong; Zhou, Xuedong; Zheng, Xin; Wang, Shida; Guo, Qiang; Li, Yuqing; Li, Mingyun; Li, Jiyao; Yang, Yi; Ding, Yi; Lamont, Richard J.; Xu, Xin

    2015-01-01

    Dental caries is closely associated with the virulence of Streptococcus mutans. The virulence expression of S. mutans is linked to its stress adaptation to the changes in the oral environment. In this work we used whole-genome microarrays to profile the dynamic transcriptomic responses of S. mutans during physiological heat stress. In addition, we evaluated the phenotypic changes, including, eDNA release, initial biofilm formation, extracellular polysaccharides generation, acid production/acid tolerance, and ATP turnover of S. mutans during heat stress. There were distinct patterns observed in the way that S. mutans responded to heat stress that included 66 transcription factors for the expression of functional genes being differentially expressed. Especially, response regulators of two component systems (TCSs), the repressors of heat shock proteins and regulators involved in sugar transporting and metabolism co-ordinated to enhance the cell’s survival and energy generation against heat stress in S. mutans. PMID:26251057

  14. Actions of juglone on energy metabolism in the rat liver

    SciTech Connect

    Saling, Simoni Cristina; Comar, Jurandir Fernando; Mito, Marcio Shigueaki; Peralta, Rosane Marina; Bracht, Adelar

    2011-12-15

    Juglone is a phenolic compound used in popular medicine as a phytotherapic to treat inflammatory and infectious diseases. However, it also acts as an uncoupler of oxidative phosphorylation in isolated liver mitochondria and, thus, may interfere with the hepatic energy metabolism. The purpose of this work was to evaluate the effect of juglone on several metabolic parameters in the isolated perfused rat liver. Juglone, in the concentration range of 5 to 50 {mu}M, stimulated glycogenolysis, glycolysis and oxygen uptake. Gluconeogenesis from both lactate and alanine was inhibited with half-maximal effects at the concentrations of 14.9 and 15.7 {mu}M, respectively. The overall alanine transformation was increased by juglone, as indicated by the stimulated release of ammonia, urea, L-glutamate, lactate and pyruvate. A great increase (9-fold) in the tissue content of {alpha}-ketoglutarate was found, without a similar change in the L-glutamate content. The tissue contents of ATP were decreased, but those of ADP and AMP were increased. Experiments with isolated mitochondria fully confirmed previous notions about the uncoupling action of juglone. It can be concluded that juglone is active on metabolism at relatively low concentrations. In this particular it resembles more closely the classical uncoupler 2,4-dinitrophenol. Ingestion of high doses of juglone, thus, presents the same risks as the ingestion of 2,4-dinitrophenol which comprise excessive compromising of ATP production, hyperthermia and even death. Low doses, i.e., moderate consumption of natural products containing juglone, however, could be beneficial to health if one considers recent reports about the consequences of chronic mild uncoupling. -- Highlights: Black-Right-Pointing-Pointer We investigated how juglone acts on liver metabolism. Black-Right-Pointing-Pointer The actions on hepatic gluconeogenesis, glycolysis and ureogenesis. Black-Right-Pointing-Pointer Juglone stimulates glycolysis and ureagenesis and

  15. Metabolic heat production and thermal conductance are mass-independent adaptations to thermal environment in birds and mammals

    PubMed Central

    Fristoe, Trevor S.; Burger, Joseph R.; Balk, Meghan A.; Khaliq, Imran; Hof, Christian; Brown, James H.

    2015-01-01

    The extent to which different kinds of organisms have adapted to environmental temperature regimes is central to understanding how they respond to climate change. The Scholander–Irving (S-I) model of heat transfer lays the foundation for explaining how endothermic birds and mammals maintain their high, relatively constant body temperatures in the face of wide variation in environmental temperature. The S-I model shows how body temperature is regulated by balancing the rates of heat production and heat loss. Both rates scale with body size, suggesting that larger animals should be better adapted to cold environments than smaller animals, and vice versa. However, the global distributions of ∼9,000 species of terrestrial birds and mammals show that the entire range of body sizes occurs in nearly all climatic regimes. Using physiological and environmental temperature data for 211 bird and 178 mammal species, we test for mass-independent adaptive changes in two key parameters of the S-I model: basal metabolic rate (BMR) and thermal conductance. We derive an axis of thermal adaptation that is independent of body size, extends the S-I model, and highlights interactions among physiological and morphological traits that allow endotherms to persist in a wide range of temperatures. Our macrophysiological and macroecological analyses support our predictions that shifts in BMR and thermal conductance confer important adaptations to environmental temperature in both birds and mammals. PMID:26668359

  16. Metabolic heat production and thermal conductance are mass-independent adaptations to thermal environment in birds and mammals.

    PubMed

    Fristoe, Trevor S; Burger, Joseph R; Balk, Meghan A; Khaliq, Imran; Hof, Christian; Brown, James H

    2015-12-29

    The extent to which different kinds of organisms have adapted to environmental temperature regimes is central to understanding how they respond to climate change. The Scholander-Irving (S-I) model of heat transfer lays the foundation for explaining how endothermic birds and mammals maintain their high, relatively constant body temperatures in the face of wide variation in environmental temperature. The S-I model shows how body temperature is regulated by balancing the rates of heat production and heat loss. Both rates scale with body size, suggesting that larger animals should be better adapted to cold environments than smaller animals, and vice versa. However, the global distributions of ∼9,000 species of terrestrial birds and mammals show that the entire range of body sizes occurs in nearly all climatic regimes. Using physiological and environmental temperature data for 211 bird and 178 mammal species, we test for mass-independent adaptive changes in two key parameters of the S-I model: basal metabolic rate (BMR) and thermal conductance. We derive an axis of thermal adaptation that is independent of body size, extends the S-I model, and highlights interactions among physiological and morphological traits that allow endotherms to persist in a wide range of temperatures. Our macrophysiological and macroecological analyses support our predictions that shifts in BMR and thermal conductance confer important adaptations to environmental temperature in both birds and mammals.

  17. Metabolic heat production and thermal conductance are mass-independent adaptations to thermal environment in birds and mammals.

    PubMed

    Fristoe, Trevor S; Burger, Joseph R; Balk, Meghan A; Khaliq, Imran; Hof, Christian; Brown, James H

    2015-12-29

    The extent to which different kinds of organisms have adapted to environmental temperature regimes is central to understanding how they respond to climate change. The Scholander-Irving (S-I) model of heat transfer lays the foundation for explaining how endothermic birds and mammals maintain their high, relatively constant body temperatures in the face of wide variation in environmental temperature. The S-I model shows how body temperature is regulated by balancing the rates of heat production and heat loss. Both rates scale with body size, suggesting that larger animals should be better adapted to cold environments than smaller animals, and vice versa. However, the global distributions of ∼9,000 species of terrestrial birds and mammals show that the entire range of body sizes occurs in nearly all climatic regimes. Using physiological and environmental temperature data for 211 bird and 178 mammal species, we test for mass-independent adaptive changes in two key parameters of the S-I model: basal metabolic rate (BMR) and thermal conductance. We derive an axis of thermal adaptation that is independent of body size, extends the S-I model, and highlights interactions among physiological and morphological traits that allow endotherms to persist in a wide range of temperatures. Our macrophysiological and macroecological analyses support our predictions that shifts in BMR and thermal conductance confer important adaptations to environmental temperature in both birds and mammals. PMID:26668359

  18. Adaptability of solar energy conversion systems on ships

    NASA Astrophysics Data System (ADS)

    Visa, I.; Cotorcea, A.; Neagoe, M.; Moldovan, M.

    2016-08-01

    International trade of goods largely uses maritime/transoceanic ships driven by engines using fossil fuels. This two centuries tradition is technologically mature but significantly adds to the CO2 emissions; therefore, recent trends focus on on-board implementation of systems converting the solar energy into power (photovoltaic systems) or heat (solar-thermal systems). These systems are carbon-emissions free but are still under research and plenty of effort is devoted to fast reach maturity and feasibility. Unlike the systems implemented in a specific continental location, the design of solar energy conversion systems installed on shipboard has to face the problem generated by the system base motion along with the ship travelling on routes at different latitudes: the navigation direction and sense and roll-pitch combined motion with reduced amplitude, but with relatively high frequency. These raise highly interesting challenges in the design and development of mechanical systems that support the maximal output in terms of electricity or heat. The paper addresses the modelling of the relative position of a solar energy conversion surface installed on a ship according to the current position of the sun; the model is based on the navigation trajectory/route, ship motion generated by waves and the relative sun-earth motion. The model describes the incidence angle of the sunray on the conversion surface through five characteristic angles: three used to define the ship orientation and two for the solar angles; based on, their influence on the efficiency in solar energy collection is analyzed by numerical simulations and appropriate recommendations are formulated for increasing the solar energy conversion systems adaptability on ships.

  19. Hepatic IRE1α regulates fasting-induced metabolic adaptive programs through the XBP1s-PPARα axis signalling.

    PubMed

    Shao, Mengle; Shan, Bo; Liu, Yang; Deng, Yiping; Yan, Cheng; Wu, Ying; Mao, Ting; Qiu, Yifu; Zhou, Yubo; Jiang, Shan; Jia, Weiping; Li, Jingya; Li, Jia; Rui, Liangyou; Yang, Liu; Liu, Yong

    2014-01-01

    Although the mammalian IRE1α-XBP1 branch of the cellular unfolded protein response has been implicated in glucose and lipid metabolism, the exact metabolic role of IRE1α signalling in vivo remains poorly understood. Here we show that hepatic IRE1α functions as a nutrient sensor that regulates the metabolic adaptation to fasting. We find that prolonged deprivation of food or consumption of a ketogenic diet activates the IRE1α-XBP1 pathway in mouse livers. Hepatocyte-specific abrogation of Ire1α results in impairment of fatty acid β-oxidation and ketogenesis in the liver under chronic fasting or ketogenic conditions, leading to hepatosteatosis; liver-specific restoration of XBP1s reverses the defects in IRE1α null mice. XBP1s directly binds to and activates the promoter of PPARα, the master regulator of starvation responses. Hence, our results demonstrate that hepatic IRE1α promotes the adaptive shift of fuel utilization during starvation by stimulating mitochondrial β-oxidation and ketogenesis through the XBP1s-PPARα axis.

  20. Pseudo-transition Analysis Identifies the Key Regulators of Dynamic Metabolic Adaptations from Steady-State Data.

    PubMed

    Gerosa, Luca; Haverkorn van Rijsewijk, Bart R B; Christodoulou, Dimitris; Kochanowski, Karl; Schmidt, Thomas S B; Noor, Elad; Sauer, Uwe

    2015-10-28

    Hundreds of molecular-level changes within central metabolism allow a cell to adapt to the changing environment. A primary challenge in cell physiology is to identify which of these molecular-level changes are active regulatory events. Here, we introduce pseudo-transition analysis, an approach that uses multiple steady-state observations of (13)C-resolved fluxes, metabolites, and transcripts to infer which regulatory events drive metabolic adaptations following environmental transitions. Pseudo-transition analysis recapitulates known biology and identifies an unexpectedly sparse, transition-dependent regulatory landscape: typically a handful of regulatory events drive adaptation between carbon sources, with transcription mainly regulating TCA cycle flux and reactants regulating EMP pathway flux. We verify these observations using time-resolved measurements of the diauxic shift, demonstrating that some dynamic transitions can be approximated as monotonic shifts between steady-state extremes. Overall, we show that pseudo-transition analysis can explore the vast regulatory landscape of dynamic transitions using relatively few steady-state data, thereby guiding time-consuming, hypothesis-driven molecular validations. PMID:27136056

  1. Does overfeeding enhance genotype effects on energy metabolism and lipid deposition in breast muscle of ducks?

    PubMed

    Chartrin, Pascal; Bernadet, Marie-Dominique; Guy, Gérard; Mourot, Jacques; Hocquette, Jean-François; Rideau, Nicole; Duclos, Michel Jacques; Baéza, Elisabeth

    2006-12-01

    We evaluated the effects of genotype (Muscovy, Pekin and their crossbreed hinny and mule ducks) and feeding levels (overfeeding between 12 and 14 weeks of age vs ad libitum feeding) on energy metabolism and lipid deposition in breast muscle of ducks. Samples of breast muscle (Pectoralis major) were collected at 14 weeks of age from 8 birds per group. Overfeeding induced an accumulation of lipids in breast muscle (1.5- to 1.7-fold, depending on genotype) mainly induced by triglyceride deposition. It also induced a considerable increase in the amounts (expressed as g/100 g of tissue) of saturated and mono-unsaturated fatty acids (SFA, MUFA), while the amounts of poly-unsaturated fatty acids (PUFA) remained unchanged in hinny and Muscovy ducks or slightly increased in Pekin and mule ducks. In breast muscle, overfeeding decreased the activity of the main enzymes involved in lipogenesis from glucose (glucose-6-phosphate dehydrogenase, G6PDH, malic enzyme, ME, acetyl CoA carboxylase, ACX). Lipoprotein lipase (LPL) activity in Pectoralis major muscle was also significantly decreased (-21%). The ability of muscle tissues to catabolize long-chain fatty acids, as assessed by beta-hydroxyacyl CoA dehydrogenase (HAD) activity, was increased in Pectoralis major muscle, as was cytochrome-c oxidase (COX) activity. Hybrid and Pekin ducks exhibited higher levels of ACX and LPL activity in Pectoralis major muscle than Muscovy ducks, suggesting a greater ability to synthesise lipids in situ, and to take up circulating lipids. Total lipid content in breast muscle of hybrid and Pekin ducks was higher than in that of Muscovy ducks. In hybrid and Pekin ducks, lipid composition of breast muscle was characterized by higher amounts of triglycerides, SFA and MUFA than in Muscovy ducks. Finally, oxidative metabolism was greater in Pectoralis major muscles of hybrid and Pekin ducks than in Muscovy ducks, suggesting an adaptative strategy of muscle energy metabolism according to lipid level.

  2. Recent Advances in Targeting Tumor Energy Metabolism with Tumor Acidosis as a Biomarker of Drug Efficacy

    PubMed Central

    Akhenblit, Paul J; Pagel, Mark D

    2016-01-01

    Cancer cells employ a deregulated cellular metabolism to leverage survival and growth advantages. The unique tumor energy metabolism presents itself as a promising target for chemotherapy. A pool of tumor energy metabolism targeting agents has been developed after several decades of efforts. This review will cover glucose and fatty acid metabolism, PI3K/AKT/mTOR, HIF-1 and glutamine pathways in tumor energy metabolism, and how they are being exploited for treatments and therapies by promising pre-clinical or clinical drugs being developed or investigated. Additionally, acidification of the tumor extracellular microenvironment is hypothesized to be the result of active tumor metabolism. This implies that tumor extracellular pH (pHe) can be a biomarker for assessing the efficacy of therapies that target tumor metabolism. Several translational molecular imaging methods (PET, MRI) for interrogating tumor acidification and its suppression are discussed as well. PMID:26962408

  3. Analysis of the metatranscriptome of microbial communities of an alkaline hot sulfur spring revealed different gene encoding pathway enzymes associated with energy metabolism.

    PubMed

    Tripathy, Swetaleena; Padhi, Soumesh Kumar; Mohanty, Sriprakash; Samanta, Mrinal; Maiti, Nikhil Kumar

    2016-07-01

    Alkaline sulfur hot springs notable for their specialized and complex ecosystem powered by geothermal energy are abundantly rich in different chemotrophic and phototrophic thermophilic microorganisms. Survival and adaptation of these organisms in the extreme environment is specifically related to energy metabolism. To gain a better understanding of survival mechanism of the organisms in these ecosystems, we determined the different gene encoding enzymes associated with anaerobic pathways of energy metabolism by applying the metatranscriptomics approach. The analysis of the microbial population of hot sulfur spring revealed the presence of both aerobic and anaerobic organisms indicating dual mode of lifestyle of the community members. Proteobacteria (28.1 %) was the most dominant community. A total of 988 reads were associated with energy metabolism, out of which 33.7 % of the reads were assigned to nitrogen, sulfur, and methane metabolism based on KEGG classification. The major lineages of hot spring communities were linked with the anaerobic pathways. Different gene encoding enzymes (hao, nir, nar, cysH, cysI, acs) showed the involvement of microbial members in nitrification, denitrification, dissimilatory sulfate reduction, and methane generation. This study enhances our understanding of important gene encoding enzymes involved in energy metabolism, required for the survival and adaptation of microbial communities in the hot spring.

  4. Analysis of the metatranscriptome of microbial communities of an alkaline hot sulfur spring revealed different gene encoding pathway enzymes associated with energy metabolism.

    PubMed

    Tripathy, Swetaleena; Padhi, Soumesh Kumar; Mohanty, Sriprakash; Samanta, Mrinal; Maiti, Nikhil Kumar

    2016-07-01

    Alkaline sulfur hot springs notable for their specialized and complex ecosystem powered by geothermal energy are abundantly rich in different chemotrophic and phototrophic thermophilic microorganisms. Survival and adaptation of these organisms in the extreme environment is specifically related to energy metabolism. To gain a better understanding of survival mechanism of the organisms in these ecosystems, we determined the different gene encoding enzymes associated with anaerobic pathways of energy metabolism by applying the metatranscriptomics approach. The analysis of the microbial population of hot sulfur spring revealed the presence of both aerobic and anaerobic organisms indicating dual mode of lifestyle of the community members. Proteobacteria (28.1 %) was the most dominant community. A total of 988 reads were associated with energy metabolism, out of which 33.7 % of the reads were assigned to nitrogen, sulfur, and methane metabolism based on KEGG classification. The major lineages of hot spring communities were linked with the anaerobic pathways. Different gene encoding enzymes (hao, nir, nar, cysH, cysI, acs) showed the involvement of microbial members in nitrification, denitrification, dissimilatory sulfate reduction, and methane generation. This study enhances our understanding of important gene encoding enzymes involved in energy metabolism, required for the survival and adaptation of microbial communities in the hot spring. PMID:27290724

  5. Metabolic Adaptations of Azospirillum brasilense to Oxygen Stress by Cell-to-Cell Clumping and Flocculation

    SciTech Connect

    Bible, Amber N.; Khalsa-Moyers, Gurusahai K.; Mukherjee, Tanmoy; Green, Calvin S.; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B.; Alexandre, Gladys

    2015-09-25

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacteriumAzospirillum brasilensenavigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motileA. brasilensecells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Finally, cell-to-cell clumping may thus license diazotrophy to microaerophilicA. brasilensecells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists.

  6. Metabolic Adaptations of Azospirillum brasilense to Oxygen Stress by Cell-to-Cell Clumping and Flocculation

    DOE PAGES

    Bible, Amber N.; Khalsa-Moyers, Gurusahai K.; Mukherjee, Tanmoy; Green, Calvin S.; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B.; Alexandre, Gladys

    2015-09-25

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacteriumAzospirillum brasilensenavigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motileA. brasilensecells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities,more » we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Finally, cell-to-cell clumping may thus license diazotrophy to microaerophilicA. brasilensecells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists.« less

  7. Physiological aspects of energy metabolism and gastrointestinal effects of carbohydrates.

    PubMed

    Elia, M; Cummings, J H

    2007-12-01

    The energy values of carbohydrates continue to be debated. This is because of the use of different energy systems, for example, combustible, digestible, metabolizable, and so on. Furthermore, ingested macronutrients may not be fully available to tissues, and the tissues themselves may not be able fully to oxidize substrates made available to them. Therefore, for certain carbohydrates, the discrepancies between combustible energy (cEI), digestible energy (DE), metabolizable energy (ME) and net metabolizable energy (NME) may be considerable. Three food energy systems are in use in food tables and for food labelling in different world regions based on selective interpretation of the digestive physiology and metabolism of food carbohydrates. This is clearly unsatisfactory and confusing to the consumer. While it has been suggested that an enormous amount of work would have to be undertaken to change the current ME system into an NME system, the additional changes may not be as great as anticipated. In experimental work, carbohydrate is high in the macronutrient hierarchy of satiation. However, studies of eating behaviour indicate that it does not unconditionally depend on the oxidation of one nutrient, and argue against the operation of a simple carbohydrate oxidation or storage model of feeding behaviour to the exclusion of other macronutrients. The site, rate and extent of carbohydrate digestion in, and absorption from the gut are key to understanding the many roles of carbohydrate, although the concept of digestibility has different meanings. Within the nutrition community, the characteristic patterns of digestion that occur in the small (upper) vs large (lower) bowel are known to impact in contrasting ways on metabolism, while in the discussion of the energy value of foods, digestibility is defined as the proportion of combustible energy that is absorbed over the entire length of the gastrointestinal tract. Carbohydrates that reach the large bowel are fermented to

  8. Metabolic adaptation and oxaloacetate homeostasis in P. fluorescens exposed to aluminum toxicity.

    PubMed

    Lemire, Joseph; Kumar, Puja; Mailloux, Ryan; Cossar, Kathyrn; Appanna, Vasu D

    2008-08-01

    Microbial systems are known to elaborate intricate metabolic strategies in an effort to fend the toxic impact of numerous metals. In this study, we show that the exposure of Pseudomonas fluorescens to aluminum (Al) resulted in a metabolic shift aimed at diverting oxaloacetate towards the biogenesis of an aluminophore. This metabolic alteration was characterized by uncoupling of two gluconeogenic enzymes, namely pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK). While PC displayed a sharp increase in activity and expression, PEPCK was severely diminished. Malic enzyme (ME) and NAD kinase (NADK), two enzymes involved in maintaining a reductive environment, were markedly increased in the Al-stressed cells. Hence, Al-exposed Pseudomonas fluorescens evoked a metabolic response aimed at generating oxaloacetate and promoting an intracellular reductive environment.

  9. Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism

    PubMed Central

    Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

    2016-01-01

    Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism. PMID:26964832

  10. Regulatory and metabolic networks for the adaptation of Pseudomonas aeruginosa biofilms to urinary tract-like conditions.

    PubMed

    Tielen, Petra; Rosin, Nathalie; Meyer, Ann-Kathrin; Dohnt, Katrin; Haddad, Isam; Jänsch, Lothar; Klein, Johannes; Narten, Maike; Pommerenke, Claudia; Scheer, Maurice; Schobert, Max; Schomburg, Dietmar; Thielen, Bernhard; Jahn, Dieter

    2013-01-01

    Biofilms of the Gram-negative bacterium Pseudomonas aeruginosa are one of the major causes of complicated urinary tract infections with detrimental outcome. To develop novel therapeutic strategies the molecular adaption strategies of P. aeruginosa biofilms to the conditions of the urinary tract were investigated thoroughly at the systems level using transcriptome, proteome, metabolome and enzyme activity analyses. For this purpose biofilms were grown anaerobically in artificial urine medium (AUM). Obtained data were integrated bioinformatically into gene regulatory and metabolic networks. The dominating response at the transcriptome and proteome level was the adaptation to iron limitation via the broad Fur regulon including 19 sigma factors and up to 80 regulated target genes or operons. In agreement, reduction of the iron cofactor-dependent nitrate respiratory metabolism was detected. An adaptation of the central metabolism to lactate, citrate and amino acid as carbon sources with the induction of the glyoxylate bypass was observed, while other components of AUM like urea and creatinine were not used. Amino acid utilization pathways were found induced, while fatty acid biosynthesis was reduced. The high amounts of phosphate found in AUM explain the reduction of phosphate assimilation systems. Increased quorum sensing activity with the parallel reduction of chemotaxis and flagellum assembly underscored the importance of the biofilm life style. However, reduced formation of the extracellular polysaccharide alginate, typical for P. aeruginosa biofilms in lungs, indicated a different biofilm type for urinary tract infections. Furthermore, the obtained quorum sensing response results in an increased production of virulence factors like the extracellular lipase LipA and protease LasB and AprA explaining the harmful cause of these infections.

  11. Regulatory and Metabolic Networks for the Adaptation of Pseudomonas aeruginosa Biofilms to Urinary Tract-Like Conditions

    PubMed Central

    Dohnt, Katrin; Haddad, Isam; Jänsch, Lothar; Klein, Johannes; Narten, Maike; Pommerenke, Claudia; Scheer, Maurice; Schobert, Max; Schomburg, Dietmar; Thielen, Bernhard; Jahn, Dieter

    2013-01-01

    Biofilms of the Gram-negative bacterium Pseudomonas aeruginosa are one of the major causes of complicated urinary tract infections with detrimental outcome. To develop novel therapeutic strategies the molecular adaption strategies of P. aeruginosa biofilms to the conditions of the urinary tract were investigated thoroughly at the systems level using transcriptome, proteome, metabolome and enzyme activity analyses. For this purpose biofilms were grown anaerobically in artificial urine medium (AUM). Obtained data were integrated bioinformatically into gene regulatory and metabolic networks. The dominating response at the transcriptome and proteome level was the adaptation to iron limitation via the broad Fur regulon including 19 sigma factors and up to 80 regulated target genes or operons. In agreement, reduction of the iron cofactor-dependent nitrate respiratory metabolism was detected. An adaptation of the central metabolism to lactate, citrate and amino acid as carbon sources with the induction of the glyoxylate bypass was observed, while other components of AUM like urea and creatinine were not used. Amino acid utilization pathways were found induced, while fatty acid biosynthesis was reduced. The high amounts of phosphate found in AUM explain the reduction of phosphate assimilation systems. Increased quorum sensing activity with the parallel reduction of chemotaxis and flagellum assembly underscored the importance of the biofilm life style. However, reduced formation of the extracellular polysaccharide alginate, typical for P. aeruginosa biofilms in lungs, indicated a different biofilm type for urinary tract infections. Furthermore, the obtained quorum sensing response results in an increased production of virulence factors like the extracellular lipase LipA and protease LasB and AprA explaining the harmful cause of these infections. PMID:23967252

  12. Equine lamellar energy metabolism studied using tissue microdialysis.

    PubMed

    Medina-Torres, C E; Pollitt, C C; Underwood, C; Castro-Olivera, E M; Collins, S N; Allavena, R E; Richardson, D W; van Eps, A W

    2014-09-01

    Failure of lamellar energy metabolism may contribute to the pathophysiology of equine laminitis. Tissue microdialysis has the potential to dynamically monitor lamellar energy balance over time. The objectives of this study were to develop a minimally invasive lamellar microdialysis technique and use it to measure normal lamellar energy metabolite concentrations over 24 h. Microdialysis probes were placed (through the white line) into either the lamellar dermis (LAM) (n = 6) or the sublamellar dermis (SUBLAM) (n = 6) and perfused continuously over a 24 h study period. Probes were placed in the skin dermis (SKIN) for simultaneous comparison to LAM (n = 6). Samples were collected every 2 h and analysed for glucose, lactate, pyruvate, urea and glycerol concentrations. LAM was further compared with SUBLAM by simultaneous placement and sampling in four feet from two horses over 4 h. Horses were monitored for lameness, and either clinically evaluated for 1 month after probe removal (n = 4) or subjected to histological evaluation of the probe site (n = 10). There were no deleterious clinical effects of probe placement and the histological response was mild. Sample fluid recovery and metabolite concentrations were stable for 24 h. Glucose was lower (and lactate:glucose ratio higher) in LAM compared with SUBLAM and SKIN (P < 0.05). Pyruvate was lower in SUBLAM than SKIN and urea was lower in LAM than SKIN (P < 0.05). These differences suggest lower perfusion and increased glucose consumption in LAM compared with SUBLAM and SKIN. In conclusion, lamellar tissue microdialysis was well tolerated and may be useful for determining the contribution of energy failure in laminitis pathogenesis. PMID:24947715

  13. Transcriptome Profiles of the Protoscoleces of Echinococcus granulosus Reveal that Excretory-Secretory Products Are Essential to Metabolic Adaptation

    PubMed Central

    Pan, Wei; Shen, Yujuan; Han, Xiuming; Wang, Ying; Liu, Hua; Jiang, Yanyan; Zhang, Yumei; Wang, Yanjuan; Xu, Yuxin; Cao, Jianping

    2014-01-01

    Background Cystic hydatid disease (CHD) is caused by the larval stages of the cestode and affects humans and domestic animals worldwide. Protoscoleces (PSCs) are one component of the larval stages that can interact with both definitive and intermediate hosts. Previous genomic and transcriptomic data have provided an overall snapshot of the genomics of the growth and development of this parasite. However, our understanding of how PSCs subvert the immune response of hosts and maintains metabolic adaptation remains unclear. In this study, we used Roche 454 sequencing technology and in silico secretome analysis to explore the transcriptome profiles of the PSCs from E. granulosus and elucidate the potential functions of the excretory-secretory proteins (ESPs) released by the parasite. Methodology/Principal Findings A large number of nonredundant sequences as unigenes were generated (26,514), of which 22,910 (86.4%) were mapped to the newly published E. granulosus genome and 17,705 (66.8%) were distributed within the coding sequence (CDS) regions. Of the 2,280 ESPs predicted from the transcriptome, 138 ESPs were inferred to be involved in the metabolism of carbohydrates, while 124 ESPs were inferred to be involved in the metabolism of protein. Eleven ESPs were identified as intracellular enzymes that regulate glycolysis/gluconeogenesis (GL/GN) pathways, while a further 44 antigenic proteins, 25 molecular chaperones and four proteases were highly represented. Many proteins were also found to be significantly enriched in development-related signaling pathways, such as the TGF-β receptor pathways and insulin pathways. Conclusions/Significance This study provides valuable information on the metabolic adaptation of parasites to their hosts that can be used to aid the development of novel intervention targets for hydatid treatment and control. PMID:25500817

  14. Adaptation of the symbiotic Mesorhizobium-chickpea relationship to phosphate deficiency relies on reprogramming of whole-plant metabolism.

    PubMed

    Nasr Esfahani, Maryam; Kusano, Miyako; Nguyen, Kien Huu; Watanabe, Yasuko; Ha, Chien Van; Saito, Kazuki; Sulieman, Saad; Herrera-Estrella, Luis; Tran, L S

    2016-08-01

    Low inorganic phosphate (Pi) availability is a major constraint for efficient nitrogen fixation in legumes, including chickpea. To elucidate the mechanisms involved in nodule acclimation to low Pi availability, two Mesorhizobium-chickpea associations exhibiting differential symbiotic performances, Mesorhizobium ciceri CP-31 (McCP-31)-chickpea and Mesorhizobium mediterranum SWRI9 (MmSWRI9)-chickpea, were comprehensively studied under both control and low Pi conditions. MmSWRI9-chickpea showed a lower symbiotic efficiency under low Pi availability than McCP-31-chickpea as evidenced by reduced growth parameters and down-regulation of nifD and nifK These differences can be attributed to decline in Pi level in MmSWRI9-induced nodules under low Pi stress, which coincided with up-regulation of several key Pi starvation-responsive genes, and accumulation of asparagine in nodules and the levels of identified amino acids in Pi-deficient leaves of MmSWRI9-inoculated plants exceeding the shoot nitrogen requirement during Pi starvation, indicative of nitrogen feedback inhibition. Conversely, Pi levels increased in nodules of Pi-stressed McCP-31-inoculated plants, because these plants evolved various metabolic and biochemical strategies to maintain nodular Pi homeostasis under Pi deficiency. These adaptations involve the activation of alternative pathways of carbon metabolism, enhanced production and exudation of organic acids from roots into the rhizosphere, and the ability to protect nodule metabolism against Pi deficiency-induced oxidative stress. Collectively, the adaptation of symbiotic efficiency under Pi deficiency resulted from highly coordinated processes with an extensive reprogramming of whole-plant metabolism. The findings of this study will enable us to design effective breeding and genetic engineering strategies to enhance symbiotic efficiency in legume crops. PMID:27450089

  15. Adaptation of the symbiotic Mesorhizobium–chickpea relationship to phosphate deficiency relies on reprogramming of whole-plant metabolism

    PubMed Central

    Nasr Esfahani, Maryam; Kusano, Miyako; Nguyen, Kien Huu; Watanabe, Yasuko; Ha, Chien Van; Saito, Kazuki; Sulieman, Saad; Herrera-Estrella, Luis; Tran, Lam-Son Phan

    2016-01-01

    Low inorganic phosphate (Pi) availability is a major constraint for efficient nitrogen fixation in legumes, including chickpea. To elucidate the mechanisms involved in nodule acclimation to low Pi availability, two Mesorhizobium–chickpea associations exhibiting differential symbiotic performances, Mesorhizobium ciceri CP-31 (McCP-31)–chickpea and Mesorhizobium mediterranum SWRI9 (MmSWRI9)–chickpea, were comprehensively studied under both control and low Pi conditions. MmSWRI9–chickpea showed a lower symbiotic efficiency under low Pi availability than McCP-31–chickpea as evidenced by reduced growth parameters and down-regulation of nifD and nifK. These differences can be attributed to decline in Pi level in MmSWRI9-induced nodules under low Pi stress, which coincided with up-regulation of several key Pi starvation-responsive genes, and accumulation of asparagine in nodules and the levels of identified amino acids in Pi-deficient leaves of MmSWRI9-inoculated plants exceeding the shoot nitrogen requirement during Pi starvation, indicative of nitrogen feedback inhibition. Conversely, Pi levels increased in nodules of Pi-stressed McCP-31–inoculated plants, because these plants evolved various metabolic and biochemical strategies to maintain nodular Pi homeostasis under Pi deficiency. These adaptations involve the activation of alternative pathways of carbon metabolism, enhanced production and exudation of organic acids from roots into the rhizosphere, and the ability to protect nodule metabolism against Pi deficiency-induced oxidative stress. Collectively, the adaptation of symbiotic efficiency under Pi deficiency resulted from highly coordinated processes with an extensive reprogramming of whole-plant metabolism. The findings of this study will enable us to design effective breeding and genetic engineering strategies to enhance symbiotic efficiency in legume crops. PMID:27450089

  16. Transcriptional coregulators: fine-tuning metabolism

    PubMed Central

    Mouchiroud, Laurent; Eichner, Lillian J.; Shaw, Reuben; Auwerx, Johan

    2014-01-01

    Metabolic homeostasis requires that cellular energy levels are adapted to environmental cues. This adaptation is largely regulated at the transcriptional level, through the interaction between transcription factors, coregulators, and the basal transcriptional machinery. Coregulators, which function both as metabolic sensors and transcriptional effectors, are ideally positioned to synchronize metabolic pathways to environmental stimuli. The balance between inhibitory actions of corepressors and stimulatory effects of coactivators enables the fine-tuning of metabolic processes. The tight regulation opens therapeutic opportunities to manage metabolic dysfunction, by directing the activity of cofactors towards specific transcription factors, pathways, or cells/tissues, thereby restoring whole body metabolic homeostasis. PMID:24794975

  17. Yeast vitality during cider fermentation: assessment by energy metabolism.

    PubMed

    Dinsdale, M G; Lloyd, D; McIntyre, P; Jarvis, B

    1999-03-15

    In an apple juice-based medium, an ethanol-tolerant Australian wine-yeast used for cider manufacture produced more than 10% ethanol over a 5 week period. Growth of the inoculum (10(6) organisms ml(-1)) occurred to a population of 3.1 x 10(7) ml(-1) during the first few days; at the end of the fermentation only 5 x 10(5) yeasts ml(-1) could be recovered as colony-forming units on plates. Respiratory and fermentative activities were measured by mass spectrometric measurements (O2 consumption and CO2 and ethanol production) of washed yeast suspensions taken from the cider fermentation at intervals. Both endogenous and glucose-supported energy-yielding metabolism declined, especially during the first 20 days. Levels of adenine nucleotides also showed decreases after day 1, as did adenylate energy charge, although in a prolonged (16.5 week) fermentation the lowest value calculated was 0.55. AMP was released into the medium. 31P-NMR spectra showed that by comparison with aerobically grown yeast, that from the later stages of the cider fermentation showed little polyphosphate. However, as previously concluded from studies of 'acidification power' and fluorescent oxonol dye exclusion (Dinsdale et al., 1995), repitching of yeast indicated little loss of viability despite considerable loss of vitality.

  18. Growth states of catalytic reaction networks exhibiting energy metabolism

    NASA Astrophysics Data System (ADS)

    Kondo, Yohei; Kaneko, Kunihiko

    2011-07-01

    All cells derive nutrition by absorbing some chemical and energy resources from the environment; these resources are used by the cells to reproduce the chemicals within them, which in turn leads to an increase in their volume. In this study we introduce a protocell model exhibiting catalytic reaction dynamics, energy metabolism, and cell growth. Results of extensive simulations of this model show the existence of four phases with regard to the rates of both the influx of resources and cell growth. These phases include an active phase with high influx and high growth rates, an inefficient phase with high influx but low growth rates, a quasistatic phase with low influx and low growth rates, and a death phase with negative growth rate. A mean field model well explains the transition among these phases as bifurcations. The statistical distribution of the active phase is characterized by a power law, and that of the inefficient phase is characterized by a nearly equilibrium distribution. We also discuss the relevance of the results of this study to distinct states in the existing cells.

  19. Growth states of catalytic reaction networks exhibiting energy metabolism.

    PubMed

    Kondo, Yohei; Kaneko, Kunihiko

    2011-07-01

    All cells derive nutrition by absorbing some chemical and energy resources from the environment; these resources are used by the cells to reproduce the chemicals within them, which in turn leads to an increase in their volume. In this study we introduce a protocell model exhibiting catalytic reaction dynamics, energy metabolism, and cell growth. Results of extensive simulations of this model show the existence of four phases with regard to the rates of both the influx of resources and cell growth. These phases include an active phase with high influx and high growth rates, an inefficient phase with high influx but low growth rates, a quasistatic phase with low influx and low growth rates, and a death phase with negative growth rate. A mean field model well explains the transition among these phases as bifurcations. The statistical distribution of the active phase is characterized by a power law, and that of the inefficient phase is characterized by a nearly equilibrium distribution. We also discuss the relevance of the results of this study to distinct states in the existing cells. PMID:21867233

  20. Body size, body composition, and metabolic profile explain higher energy expenditure in overweight children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lower relative rates of energy expenditure (EE), increased energetic efficiency, and altered fuel utilization purportedly associated with obesity have not been demonstrated indisputably in overweight children. We hypothesized that differences in energy metabolism between nonoverweight and overweight...

  1. Energy adaptive MAC protocol for IEEE 802.15.7 with energy harvesting

    NASA Astrophysics Data System (ADS)

    Wang, Hong-qiao; Chi, Xue-fen; Zhao, Lin-lin

    2016-09-01

    The medium access control (MAC) protocol for indoor visible light communication (VLC) with energy harvesting is explored in this paper. The unfairness of throughput exists among devices due to the significant difference of their energy harvesting rates which changes with distance, acceptance angle and the obstruction probability. We propose an energy harvesting model, a new obstruction probability model and an energy adaptive contention algorithm to overcome the unfairness problem. This device can adjust its contention window according to the energy harvesting rate. As a result, the device with lower energy harvesting rate can get shorter contention window to improve its transmission opportunity. Simulation results show that our MAC protocol can achieve a higher degree of fairness.

  2. Metabolomics analysis of Cistus monspeliensis leaf extract on energy metabolism activation in human intestinal cells.

    PubMed

    Shimoda, Yoichi; Han, Junkyu; Kawada, Kiyokazu; Smaoui, Abderrazak; Isoda, Hiroko

    2012-01-01

    Energy metabolism is a very important process to improve and maintain health from the point of view of physiology. It is well known that the intracellular ATP production is contributed to energy metabolism in cells. Cistus monspeliensis is widely used as tea, spices, and medical herb; however, it has not been focusing on the activation of energy metabolism. In this study, C. monspeliensis was investigated as the food resources by activation of energy metabolism in human intestinal epithelial cells. C. monspeliensis extract showed high antioxidant ability. In addition, the promotion of metabolites of glycolysis and TCA cycle was induced by C. monspeliensis treatment. These results suggest that C. monspeliensis extract has an ability to enhance the energy metabolism in human intestinal cells.

  3. Metabolomics Analysis of Cistus monspeliensis Leaf Extract on Energy Metabolism Activation in Human Intestinal Cells

    PubMed Central

    Shimoda, Yoichi; Han, Junkyu; Kawada, Kiyokazu; Smaoui, Abderrazak; Isoda, Hiroko

    2012-01-01

    Energy metabolism is a very important process to improve and maintain health from the point of view of physiology. It is well known that the intracellular ATP production is contributed to energy metabolism in cells. Cistus monspeliensis is widely used as tea, spices, and medical herb; however, it has not been focusing on the activation of energy metabolism. In this study, C. monspeliensis was investigated as the food resources by activation of energy metabolism in human intestinal epithelial cells. C. monspeliensis extract showed high antioxidant ability. In addition, the promotion of metabolites of glycolysis and TCA cycle was induced by C. monspeliensis treatment. These results suggest that C. monspeliensis extract has an ability to enhance the energy metabolism in human intestinal cells. PMID:22523469

  4. Adapt

    NASA Astrophysics Data System (ADS)

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  5. Mitochondrial sirtuins: emerging roles in metabolic regulations, energy homeostasis and diseases.

    PubMed

    Parihar, Priyanka; Solanki, Isha; Mansuri, Mohammad Lukman; Parihar, Mordhwaj S

    2015-01-01

    The energy production and metabolic homeostasis are well-orchestrated networks of carbohydrate, lipid and protein metabolism. These metabolic pathways are integrated by a key cytoplasmic organelle, the mitochondria, leading to production of many metabolic intermediates and harvest cellular energy in the form of ATP. Sirtuins are a highly conserved family of proteins that mediate cellular physiology and energy demands in response to metabolic inputs. Mitochondria inhabit three main types of sirtuins classified as Sirt3, Sirt4 and Sirt5. These sirtuins regulate mitochondrial metabolic functions mainly through controlling post-translational modifications of mitochondrial protein. However, the biological mechanism involved in controlling mitochondrial metabolic functions is not well understood at this stage. In this review the current knowledge on how mitochondrial sirtuins govern mitochondrial functions including energy production, metabolism, biogenesis and their involvement in different metabolic pathways are discussed. The identifications of potential pharmacological targets of sirtuins in the mitochondria and the bioactive compounds that target mitochondrial sirtuins will increase our understanding on regulation of mitochondrial metabolism in normal and disease state.

  6. Erythropoietin, a novel versatile player regulating energy metabolism beyond the erythroid system.

    PubMed

    Wang, Li; Di, Lijun; Noguchi, Constance Tom

    2014-01-01

    Erythropoietin (EPO), the required cytokine for promoting the proliferation and differentiation of erythroid cells to stimulate erythropoiesis, has been reported to act as a pleiotropic cytokine beyond hematopoietic system. The various activities of EPO are determined by the widespread distribution of its cell surface EPO receptor (EpoR) in multiple tissues including endothelial, neural, myoblasts, adipocytes and other cell types. EPO activity has been linked to angiogenesis, neuroprotection, cardioprotection, stress protection, anti-inflammation and especially the energy metabolism regulation that is recently revealed. The investigations of EPO activity in animals and the expression analysis of EpoR provide more insights on the potential of EPO in regulating energy metabolism and homeostasis. The findings of crosstalk between EPO and some important energy sensors and the regulation of EPO in the cellular respiration and mitochondrial function further provide molecular mechanisms for EPO activity in metabolic activity regulation. In this review, we will summarize the roles of EPO in energy metabolism regulation and the activity of EPO in tissues that are tightly associated with energy metabolism. We will also discuss the effects of EPO in regulating oxidative metabolism and mitochondrial function, the interactions between EPO and important energy regulation factors, and the protective role of EPO from stresses that are related to metabolism, providing a brief overview of previously less appreciated EPO biological function in energy metabolism and homeostasis. PMID:25170305

  7. Dynamic changes in energy metabolism upon embryonic stem cell differentiation support developmental toxicant identification.

    PubMed

    van Dartel, Dorien A M; Schulpen, Sjors H; Theunissen, Peter T; Bunschoten, Annelies; Piersma, Aldert H; Keijer, Jaap

    2014-10-01

    Embryonic stem cells (ESC) are widely used to study embryonic development and to identify developmental toxicants. Particularly, the embryonic stem cell test (EST) is well known as in vitro model to identify developmental toxicants. Although it is clear that energy metabolism plays a crucial role in embryonic development, the modulation of energy metabolism in in vitro models, such as the EST, is not yet described. The present study is among the first studies that analyses whole genome expression data to specifically characterize metabolic changes upon ESC early differentiation. Our transcriptomic analyses showed activation of glycolysis, truncated activation of the tricarboxylic acid (TCA) cycle, activation of lipid synthesis, as well as activation of glutaminolysis during the early phase of ESC differentiation. Taken together, this energy metabolism profile points towards energy metabolism reprogramming in the provision of metabolites for biosynthesis of cellular constituents. Next, we defined a gene set that describes this energy metabolism profile. We showed that this gene set could be successfully applied in the EST to identify developmental toxicants known to modulate cellular biosynthesis (5-fluorouracil and methoxyacetic acid), while other developmental toxicants or the negative control did not modulate the expression of this gene set. Our description of dynamic changes in energy metabolism during early ESC differentiation, as well as specific identification of developmental toxicants modulating energy metabolism, is an important step forward in the definition of the applicability domain of the EST.

  8. Expression proteomics identifies biochemical adaptations and defense responses in transgenic plants with perturbed polyamine metabolism.

    PubMed

    Franceschetti, Marina; Perry, Barry; Thompson, Benjamin; Hanfrey, Colin; Michael, Anthony J

    2004-10-22

    Soluble proteins from leaves of transgenic tobacco plants with perturbed polyamine metabolism, caused by S-adenosylmethionine decarboxylase overexpression, were analysed by comparative proteomics. A group of proteins was found to be increasingly repressed, in parallel with the degree of polyamine perturbation, in each of the three independent transgenic lines. These were identified as isoforms of chloroplast ribonucleoproteins, known to be involved in chloroplast mRNA stability, processing and translation. Another group of eight proteins strongly induced in the most metabolically perturbed line was identified as multiple, uncharacterised isoforms of the defense protein PR-1, a known marker for systemic acquired resistance.

  9. KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response.

    PubMed

    Rabhi, Nabil; Denechaud, Pierre-Damien; Gromada, Xavier; Hannou, Sarah Anissa; Zhang, Hongbo; Rashid, Talha; Salas, Elisabet; Durand, Emmanuelle; Sand, Olivier; Bonnefond, Amélie; Yengo, Loic; Chavey, Carine; Bonner, Caroline; Kerr-Conte, Julie; Abderrahmani, Amar; Auwerx, Johan; Fajas, Lluis; Froguel, Philippe; Annicotte, Jean-Sébastien

    2016-05-01

    The endoplasmic reticulum (ER) unfolded protein response (UPR(er)) pathway plays an important role in helping pancreatic β cells to adapt their cellular responses to environmental cues and metabolic stress. Although altered UPR(er) gene expression appears in rodent and human type 2 diabetic (T2D) islets, the underlying molecular mechanisms remain unknown. We show here that germline and β cell-specific disruption of the lysine acetyltransferase 2B (Kat2b) gene in mice leads to impaired insulin secretion and glucose intolerance. Genome-wide analysis of Kat2b-regulated genes and functional assays reveal a critical role for Kat2b in maintaining UPR(er) gene expression and subsequent β cell function. Importantly, Kat2b expression is decreased in mouse and human diabetic β cells and correlates with UPR(er) gene expression in normal human islets. In conclusion, Kat2b is a crucial transcriptional regulator for adaptive β cell function during metabolic stress by controlling UPR(er) and represents a promising target for T2D prevention and treatment. PMID:27117420

  10. Energy requirements, protein-energy metabolism and balance, and carbohydrates in preterm infants.

    PubMed

    Hay, William W; Brown, Laura D; Denne, Scott C

    2014-01-01

    Energy is necessary for all vital functions of the body at molecular, cellular, organ, and systemic levels. Preterm infants have minimum energy requirements for basal metabolism and growth, but also have requirements for unique physiology and metabolism that influence energy expenditure. These include body size, postnatal age, physical activity, dietary intake, environmental temperatures, energy losses in the stool and urine, and clinical conditions and diseases, as well as changes in body composition. Both energy and protein are necessary to produce normal rates of growth. Carbohydrates (primarily glucose) are principle sources of energy for the brain and heart until lipid oxidation develops over several days to weeks after birth. A higher protein/energy ratio is necessary in most preterm infants to approximate normal intrauterine growth rates. Lean tissue is predominantly produced during early gestation, which continues through to term. During later gestation, fat accretion in adipose tissue adds increasingly large caloric requirements to the lean tissue growth. Once protein intake is sufficient to promote net lean body accretion, additional energy primarily produces more body fat, which increases almost linearly at energy intakes >80-90 kcal/kg/day in normal, healthy preterm infants. Rapid gains in adiposity have the potential to produce later life obesity, an increasingly recognized risk of excessive energy intake. In addition to fundamental requirements for glucose, protein, and fat, a variety of non-glucose carbohydrates found in human milk may have important roles in promoting growth and development, as well as production of a gut microbiome that could protect against necrotizing enterocolitis.

  11. Differential metabolic and endocrine adaptations in llamas, sheep, and goats fed high- and low-protein grass-based diets.

    PubMed

    Kiani, A; Alstrup, L; Nielsen, M O

    2015-10-01

    This study aimed to elucidate whether distinct endocrine and metabolic adaptations provide llamas superior ability to adapt to low protein content grass-based diets as compared with the true ruminants. Eighteen adult, nonpregnant females (6 llamas, 6 goats, and 6 sheep) were fed either green grass hay with (HP) or grass seed straw (LP) in a cross-over design experiment over 2 periods of 21 d. Blood samples were taken on day 21 in each period at -30, 60, 150, and 240 min after feeding the morning meal and analyzed for plasma contents of glucose, triglyceride, nonesterified fatty acids, β-hydroxy butyrate (BOHB), urea, creatinine, insulin, and leptin. Results showed that llamas vs sheep and goats had higher plasma concentrations of glucose (7.1 vs 3.5 and 3.6 ± 0.18 mmol/L), creatinine (209 vs 110 and 103 ± 10 μmol/L), and urea (6.7 vs 5.6 and 4.9 ± 0.5 mmol/L) but lower leptin (0.33 vs 1.49 and 1.05 ± 0.1 ng/mL) and BOHB (0.05 vs 0.26 and 0.12 ± 0.02 mmol/L), respectively. BOHB in llamas was extremely low for a ruminating animal. Llamas showed that hyperglycemia coexisted with hyperinsulinemia (in general on the HP diet; postprandially on the LP diet). Llamas were clearly hypercreatinemic compared with the true ruminants, which became further exacerbated on the LP diet, where they also sustained plasma urea at markedly higher concentrations. However, llamas had markedly lower leptin concentrations than the true ruminants. In conclusion, llamas appear to have an intrinsic insulin resistant phenotype. Augmentation of creatinine and sustenance of elevated plasma urea concentrations in llamas when fed the LP diet must reflect distinct metabolic adaptations of intermediary protein and/or nitrogen metabolism, not observed in the true ruminants. These features can contribute to explain lower metabolic rates in llamas compared with the true ruminants, which must improve the chances of survival on low protein content diets.

  12. Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation

    PubMed Central

    Petrovska, Ivana; Nüske, Elisabeth; Munder, Matthias C; Kulasegaran, Gayathrie; Malinovska, Liliana; Kroschwald, Sonja; Richter, Doris; Fahmy, Karim; Gibson, Kimberley; Verbavatz, Jean-Marc; Alberti, Simon

    2014-01-01

    One of the key questions in biology is how the metabolism of a cell responds to changes in the environment. In budding yeast, starvation causes a drop in intracellular pH, but the functional role of this pH change is not well understood. Here, we show that the enzyme glutamine synthetase (Gln1) forms filaments at low pH and that filament formation leads to enzymatic inactivation. Filament formation by Gln1 is a highly cooperative process, strongly dependent on macromolecular crowding, and involves back-to-back stacking of cylindrical homo-decamers into filaments that associate laterally to form higher order fibrils. Other metabolic enzymes also assemble into filaments at low pH. Hence, we propose that filament formation is a general mechanism to inactivate and store key metabolic enzymes during a state of advanced cellular starvation. These findings have broad implications for understanding the interplay between nutritional stress, the metabolism and the physical organization of a cell. DOI: http://dx.doi.org/10.7554/eLife.02409.001 PMID:24771766

  13. A transcription factor links growth rate and metabolism in the hypersaline adapted archaeon Halobacterium salinarum.

    PubMed

    Todor, Horia; Dulmage, Keely; Gillum, Nicholas; Bain, James R; Muehlbauer, Michael J; Schmid, Amy K

    2014-09-01

    Co-ordinating metabolism and growth is a key challenge for all organisms. Despite fluctuating environments, cells must produce the same metabolic outputs to thrive. The mechanisms underlying this 'growth homeostasis' are known in bacteria and eukaryotes, but remain unexplored in archaea. In the model archaeon Halobacterium salinarum, the transcription factor TrmB regulates enzyme-coding genes in diverse metabolic pathways in response to glucose. However, H. salinarum is thought not to catabolize glucose. To resolve this discrepancy, we demonstrate that TrmB regulates the gluconeogenic production of sugars incorporated into the cell surface S-layer glycoprotein. Additionally, we show that TrmB-DNA binding correlates with instantaneous growth rate, likely because S-layer glycosylation is proportional to growth. This suggests that TrmB transduces a growth rate signal to co-regulated metabolic pathways including amino acid, purine, and cobalamin biosynthesis. Remarkably, the topology and function of this growth homeostatic network appear conserved across domains despite extensive alterations in protein components.

  14. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells.

    PubMed

    Chano, Tokuhiro; Avnet, Sofia; Kusuzaki, Katsuyuki; Bonuccelli, Gloria; Sonveaux, Pierre; Rotili, Dante; Mai, Antonello; Baldini, Nicola

    2016-01-01

    The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N(8)-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID:27186436

  15. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells

    PubMed Central

    Chano, Tokuhiro; Avnet, Sofia; Kusuzaki, Katsuyuki; Bonuccelli, Gloria; Sonveaux, Pierre; Rotili, Dante; Mai, Antonello; Baldini, Nicola

    2016-01-01

    The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N8-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID:27186436

  16. Food restriction during pregnancy in rabbits: effects on hormones and metabolites involved in energy homeostasis and metabolic programming.

    PubMed

    Menchetti, L; Brecchia, G; Canali, C; Cardinali, R; Polisca, A; Zerani, M; Boiti, C

    2015-02-01

    This study examined the effects of food restriction during rabbit pregnancy on hormones and metabolites involved in energy homeostasis and metabolic programming. Pregnant does were assigned to four groups: the control group was fed a standard ration while the others received a restricted amount of food (30% restriction) during early (0-9 days), mid (9-18 days), and late (19-28 days) pregnancy. The pregnancy induced a coordinated range of adaptations to fulfil energy requirements of both mother and foetus, such as hyperleptinaemia and hyperinsulinaemia, reduced insulin sensitivity, increased cortisol and non-esterified fatty acid. Food restriction altered leptin, insulin, T3, non-esterified fatty acids and glucose concentrations depending on the gestational phase in which it was applied. Collectively, present data confirm that the endocrinology of pregnancy and the adaptive responses to energy deficit make the rabbit an ideal model for studying nutritional-related disorders and foetal programming of metabolic disease.

  17. Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health.

    PubMed

    Rothman, Sarah M; Griffioen, Kathleen J; Wan, Ruiqian; Mattson, Mark P

    2012-08-01

    Overweight sedentary individuals are at increased risk for cardiovascular disease, diabetes, and some neurological disorders. Beneficial effects of dietary energy restriction (DER) and exercise on brain structural plasticity and behaviors have been demonstrated in animal models of aging and acute (stroke and trauma) and chronic (Alzheimer's and Parkinson's diseases) neurological disorders. The findings described later, and evolutionary considerations, suggest brain-derived neurotrophic factor (BDNF) plays a critical role in the integration and optimization of behavioral and metabolic responses to environments with limited energy resources and intense competition. In particular, BDNF signaling mediates adaptive responses of the central, autonomic, and peripheral nervous systems from exercise and DER. In the hypothalamus, BDNF inhibits food intake and increases energy expenditure. By promoting synaptic plasticity and neurogenesis in the hippocampus, BDNF mediates exercise- and DER-induced improvements in cognitive function and neuroprotection. DER improves cardiovascular stress adaptation by a mechanism involving enhancement of brainstem cholinergic activity. Collectively, findings reviewed in this paper provide a rationale for targeting BDNF signaling for novel therapeutic interventions in a range of metabolic and neurological disorders.

  18. Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health

    PubMed Central

    Rothman, Sarah M; Griffioen, Kathleen J; Wan, Ruiqian; Mattson, Mark P

    2012-01-01

    Overweight sedentary individuals are at increased risk for cardiovascular disease, diabetes, and some neurological disorders. Beneficial effects of dietary energy restriction (DER) and exercise on brain structural plasticity and behaviors have been demonstrated in animal models of aging and acute (stroke and trauma) and chronic (Alzheimer's and Parkinson's diseases) neurological disorders. The findings described later, and evolutionary considerations, suggest brain-derived neurotrophic factor (BDNF) plays a critical role in the integration and optimization of behavioral and metabolic responses to environments with limited energy resources and intense competition. In particular, BDNF signaling mediates adaptive responses of the central, autonomic, and peripheral nervous systems from exercise and DER. In the hypothalamus, BDNF inhibits food intake and increases energy expenditure. By promoting synaptic plasticity and neurogenesis in the hippocampus, BDNF mediates exercise- and DER-induced improvements in cognitive function and neuroprotection. DER improves cardiovascular stress adaptation by a mechanism involving enhancement of brainstem cholinergic activity. Collectively, findings reviewed in this paper provide a rationale for targeting BDNF signaling for novel therapeutic interventions in a range of metabolic and neurological disorders. PMID:22548651

  19. Rh2E2, a novel metabolic suppressor, specifically inhibits energy-based metabolism of tumor cells

    PubMed Central

    Bai, Li-Ping; Jiang, Zhi-Hong; Guo, Yue; Kong, Ah-Ng Tony; Wang, Rui; Kam, Richard Kin Ting; Law, Betty Yuen Kwan; Hsiao, Wendy Wen Luen; Chan, Ka Man; Wang, Jingrong; Chan, Rick Wai Kit; Guo, Jianru; Zhang, Wei; Yen, Feng Gen; Zhou, Hua; Leung, Elaine Lai Han; Yu, Zhiling; Liu, Liang

    2016-01-01

    Energy metabolism in cancer cells is often increased to meet their higher proliferative rate and biosynthesis demands. Suppressing cancer cell metabolism using agents like metformin has become an attractive strategy for treating cancer patients. We showed that a novel ginsenoside derivative, Rh2E2, is as effective as aspirin in preventing the development of AOM/DSS-induced colorectal cancer and suppresses tumor growth and metastasis in a LLC-1 xenograft. A sub-chronic and acute toxicity LD50 test of Rh2E2 showed no harmful reactions at the maximum oral dosage of 5000 mg/kg body weight in mice. Proteomic profiling revealed that Rh2E2 specifically inhibited ATP production in cancer cells via down-regulation of metabolic enzymes involving glycolysis, fatty acid β-oxidation and the tricarboxylic acid cycle, leading to specific cytotoxicity and S-phase cell cycle arrest in cancer cells. Those findings suggest that Rh2E2 possesses a novel and safe anti-metabolic agent for cancer patients by specific reduction of energy-based metabolism in cancer cells. PMID:26799418

  20. FGF21 as a mediator of adaptive responses to stress and metabolic benefits of anti-diabetic drugs.

    PubMed

    Kim, Kook Hwan; Lee, Myung-Shik

    2015-07-01

    Most hormones secreted from specific organs of the body in response to diverse stimuli contribute to the homeostasis of the whole organism. Fibroblast growth factor 21 (FGF21), a hormone induced by a variety of environmental or metabolic stimuli, plays a crucial role in the adaptive response to these stressful conditions. In addition to its role as a stress hormone, FGF21 appears to function as a mediator of the therapeutic effects of currently available drugs and those under development for treatment of metabolic diseases. In this review, we highlight molecular mechanisms and the functional importance of FGF21 induction in response to diverse stress conditions such as changes of nutritional status, cold exposure, and exercise. In addition, we describe recent findings regarding the role of FGF21 in the pathogenesis and treatment of diabetes associated with obesity, liver diseases, pancreatitis, muscle atrophy, atherosclerosis, cardiac hypertrophy, and diabetic nephropathy. Finally, we discuss the current understanding of the actions of FGF21 as a crucial regulator mediating beneficial metabolic effects of therapeutic agents such as metformin, glucagon/glucagon-like peptide 1 analogues, thiazolidinedione, sirtuin 1 activators, and lipoic acid. PMID:26116622

  1. Systemic adaptation of lipid metabolism in response to low- and high-fat diet in Nile tilapia (Oreochromis niloticus)

    PubMed Central

    He, An-Yuan; Ning, Li-Jun; Chen, Li-Qiao; Chen, Ya-Li; Xing, Qi; Li, Jia-Min; Qiao, Fang; Li, Dong-Liang; Zhang, Mei-Ling; Du, Zhen-Yu

    2015-01-01

    Natural selection endows animals with the abilities to store lipid when food is abundant and to synthesize lipid when it is limited. However, the relevant adaptive strategy of lipid metabolism has not been clearly elucidated in fish. This study examined the systemic metabolic strategies of Nile tilapia to maintain lipid homeostasis when fed with low- or high-fat diets. Three diets with different lipid contents (1%, 7%, and 13%) were formulated and fed to tilapias for 10 weeks. At the end of the feeding trial, the growth rate, hepatic somatic index, and the triglyceride (TG) contents of serum, liver, muscle, and adipose tissue were comparable among three groups, whereas the total body lipid contents and the mass of adipose tissue increased with the increased dietary lipid levels. Overall quantitative PCR, western blotting and transcriptomic assays indicated that the liver was the primary responding organ to low-fat (LF) diet feeding, and the elevated glycolysis and accelerated biosynthesis of fatty acids (FA) in the liver is likely to be the main strategies of tilapia toward LF intake. In contrast, excess ingested lipid was preferentially stored in adipose tissue through increasing the capability of FA uptake and TG synthesis. Increasing numbers, but not enlarging size, of adipocytes may be the main strategy of Nile tilapia responding to continuous high-fat (HF) diet feeding. This is the first study illuminating the systemic adaptation of lipid metabolism responding to LF or HF diet in fish, and our results shed new light on fish physiology. PMID:26265749

  2. Adaptation of myocardial blood flow to increased metabolic demand is not dependent on endothelial vasodilators in the rat heart.

    PubMed Central

    Tiefenbacher, C. P.; Tillmanns, H.; Niroomand, F.; Zimmermann, R.; Kübler, W.

    1997-01-01

    OBJECTIVE: To investigate the role of endothelial vasodilating factors in adaptation of myocardial blood flow to increased metabolic demands. DESIGN: Alterations in the effects of endothelium dependent (acetylcholine) and independent (sodium nitroprusside) vasodilators and the beta 1 receptor agonist dobutamine were studied after inhibition of endothelium derived relaxing factor (EDRF) with L-NG-nitro-arginine methyl ester (L-NAME), prostanoid synthesis with indomethacin, and ATP sensitive potassium channels with glibenclamide. EXPERIMENTAL ANIMALS: Female Wistar rats, in situ perfused heart. MAIN OUTCOME MEASURES: Myocardial blood flow (H2 clearance); systolic fractional thickening (pulsed Doppler); mean arterial blood pressure. RESULTS: L-NAME reduced myocardial blood flow by 58 (12)% (mean (SD), P < 0.001) and systolic thickening fraction (FT) by 36 (9)% (P < 0.05). These effects were significantly reversed by administration of L-arginine but not D-arginine. Pretreatment with L-NAME inhibited the increase in myocardial blood flow caused by acetylcholine (control: +42 (9)%; L-NAME: -29 (7)%, P < 0.001) but did not affect the increase in myocardial blood flow caused by sodium nitroprusside (control: +44 (5)%; L-NAME: +34 (10)%, NS). Pretreatment with L-NAME did not change the effect of dobutamine on myocardial blood flow (+61 (3)%) and FT (+32 (8)%) compared with baseline values (P < 0.001). Neither pretreatment with indomethacin nor with glibenclamide reduced the dobutamine induced increase in myocardial blood flow. CONCLUSIONS: Inhibition of EDRF, prostanoid synthesis, and ATP sensitive potassium channels did not reduce the vasodilator reserve during increased metabolic demands induced by beta 1 adrenergic stimulation. Therefore, adaptation of myocardial blood flow to increased metabolic demands is independent of endothelial relaxing factors in the rat heart. PMID:9068398

  3. Comparative Genomic Analysis Indicates that Niche Adaptation of Terrestrial Flavobacteria Is Strongly Linked to Plant Glycan Metabolism

    PubMed Central

    Kolton, Max; Sela, Noa; Elad, Yigal; Cytryn, Eddie

    2013-01-01

    Flavobacteria are important members of aquatic and terrestrial bacterial communities, displaying extreme variations in lifestyle, geographical distribution and genome size. They are ubiquitous in soil, but are often strongly enriched in the rhizosphere and phyllosphere of plants. In this study, we compared the genome of a root-associated Flavobacterium that we recently isolated, physiologically characterized and sequenced, to 14 additional Flavobacterium genomes, in order to pinpoint characteristics associated with its high abundance in the rhizosphere. Interestingly, flavobacterial genomes vary in size by approximately two-fold, with terrestrial isolates having predominantly larger genomes than those from aquatic environments. Comparative functional gene analysis revealed that terrestrial and aquatic Flavobacteria generally segregated into two distinct clades. Members of the aquatic clade had a higher ratio of peptide and protein utilization genes, whereas members of the terrestrial clade were characterized by a significantly higher abundance and diversity of genes involved in metabolism of carbohydrates such as xylose, arabinose and pectin. Interestingly, genes encoding glycoside hydrolase (GH) families GH78 and GH106, responsible for rhamnogalacturonan utilization (exclusively associated with terrestrial plant hemicelluloses), were only present in terrestrial clade genomes, suggesting adaptation of the terrestrial strains to plant-related carbohydrate metabolism. The Peptidase/GH ratio of aquatic clade Flavobacteria was significantly higher than that of terrestrial strains (1.7±0.7 and 9.7±4.7, respectively), supporting the concept that this relation can be used to infer Flavobacterium lifestyles. Collectively, our research suggests that terrestrial Flavobacteria are highly adapted to plant carbohydrate metabolism, which appears to be a key to their profusion in plant environments. PMID:24086761

  4. Carbon and energy metabolism of atp mutants of Escherichia coli.

    PubMed

    Jensen, P R; Michelsen, O

    1992-12-01

    The membrane-bound H(+)-ATPase plays a key role in free-energy transduction of biological systems. We report how the carbon and energy metabolism of Escherichia coli changes in response to deletion of the atp operon that encodes this enzyme. Compared with the isogenic wild-type strain, the growth rate and growth yield were decreased less than expected for a shift from oxidative phosphorylation to glycolysis alone as a source of ATP. Moreover, the respiration rate of a atp deletion strain was increased by 40% compared with the wild-type strain. This result is surprising, since the atp deletion strain is not able to utilize the resulting proton motive force for ATP synthesis. Indeed, the ratio of ATP concentration to ADP concentration was decreased from 19 in the wild type to 7 in the atp mutant, and the membrane potential of the atp deletion strain was increased by 20%, confirming that the respiration rate was not controlled by the magnitude of the opposing membrane potential. The level of type b cytochromes in the mutant cells was 80% higher than the level in the wild-type cells, suggesting that the increased respiration was caused by an increase in the expression of the respiratory genes. The atp deletion strain produced twice as much by-product (acetate) and exhibited increased flow through the tricarboxylic acid cycle and the glycolytic pathway. These three changes all lead to an increase in substrate level phosphorylation; the first two changes also lead to increased production of reducing equivalents. We interpret these data as indicating that E. coli makes use of its ability to respire even if it cannot directly couple this ability to ATP synthesis; by respiring away excess reducing equivalents E. coli enhances substrate level ATP synthesis.

  5. Energy metabolism and intracellular pH in boar spermatozoa.

    PubMed

    Kamp, G; Büsselmann, G; Jones, N; Wiesner, B; Lauterwein, J

    2003-10-01

    The effect of energy metabolism on intracellular pH was studied in boar spermatozoa using nuclear magnetic resonance (NMR) spectroscopy and confocal microscopy with the pH-sensitive dye seminaphthorhodafluor (SNARF-1). Freshly ejaculated spermatozoa had a high adenylate energy charge (AEC=0.8), which decreased to 0.6 under aerobic conditions and to 0.2 under anaerobic conditions. Correspondingly, no ATP resonances but high AMP resonance were visible in (31)P-NMR-spectra of the spermatozoa. When an artificial oxygen buffer (Fluosol) and a purpose-built air supply system were used during (31)P-NMR data acquisition, ATP resonances reappeared whereas the AMP resonance disappeared. Boar spermatozoa kept under aerobic conditions have intracellular compartments that differ markedly in pH, as demonstrated by both (31)P-NMR spectroscopy and confocal microscopy. Using confocal microscopy, the midpiece of the flagellum in which all mitochondria are located was identified as an acidic compartment (pH(i-mp) 6.7). The intracellular pH of both the head (pH(i-h)) and the long principal piece of the flagellum (pH(i-pp)) were 7.2 and, thus, only slightly below the extracellular pH (pH(e) 7.3). Storage of spermatozoa in a glucose-free medium at 15 degrees C when they are immotile slowly shifted the pH(i-mp) from 6.7 to 6.9 within 20 h, whereas pH(i-h) and pH(i-pp) remained unchanged (pH 7.1-7.2). When glucose was present in the medium, all visible compartments of the spermatozoa as well as the medium were acidified to pH 6.2 within 20 h. Under these conditions a resonance at 4.8 mg kg(-1) appeared representing glycerol 3-phosphate.

  6. Multi‐omic profiling ­of EPO‐producing Chinese hamster ovary cell panel reveals metabolic adaptation to heterologous protein production

    PubMed Central

    Ley, Daniel; Seresht, Ali Kazemi; Engmark, Mikael; Magdenoska, Olivera; Nielsen, Kristian Fog; Kildegaard, Helene Faustrup

    2015-01-01

    ABSTRACT Chinese hamster ovary (CHO) cells are the preferred production host for many therapeutic proteins. The production of heterologous proteins in CHO cells imposes a burden on the host cell metabolism and impact cellular physiology on a global scale. In this work, a multi‐omics approach was applied to study the production of erythropoietin (EPO) in a panel of CHO‐K1 cells under growth‐limited and unlimited conditions in batch and chemostat cultures. Physiological characterization of the EPO‐producing cells included global transcriptome analysis, targeted metabolome analysis, including intracellular pools of glycolytic intermediates, NAD(P)H/NAD(P)+, adenine nucleotide phosphates (ANP), and extracellular concentrations of sugars, organic acids, and amino acids. Potential impact of EPO expression on the protein secretory pathway was assessed at multiple stages using quantitative PCR (qPCR), reverse transcription PCR (qRT‐PCR), Western blots (WB), and global gene expression analysis to assess EPO gene copy numbers, EPO gene expression, intracellular EPO retention, and differentially expressed genes functionally related to secretory protein processing, respectively. We found no evidence supporting the existence of production bottlenecks in energy metabolism (i.e., glycolytic metabolites, NAD(P)H/NAD(P)+ and ANPs) in batch culture or in the secretory protein production pathway (i.e., gene dosage, transcription and post‐translational processing of EPO) in chemostat culture at specific productivities up to 5 pg/cell/day. Time‐course analysis of high‐ and low‐producing clones in chemostat culture revealed rapid adaptation of transcription levels of amino acid catabolic genes in favor of EPO production within nine generations. Interestingly, the adaptation was followed by an increase in specific EPO productivity. Biotechnol. Bioeng. 2015;112: 2373–2387. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. PMID

  7. Leukemic Stem Cells Evade Chemotherapy by Metabolic Adaptation to an Adipose Tissue Niche.

    PubMed

    Ye, Haobin; Adane, Biniam; Khan, Nabilah; Sullivan, Timothy; Minhajuddin, Mohammad; Gasparetto, Maura; Stevens, Brett; Pei, Shanshan; Balys, Marlene; Ashton, John M; Klemm, Dwight J; Woolthuis, Carolien M; Stranahan, Alec W; Park, Christopher Y; Jordan, Craig T

    2016-07-01

    Adipose tissue (AT) has previously been identified as an extra-medullary reservoir for normal hematopoietic stem cells (HSCs) and may promote tumor development. Here, we show that a subpopulation of leukemic stem cells (LSCs) can utilize gonadal adipose tissue (GAT) as a niche to support their metabolism and evade chemotherapy. In a mouse model of blast crisis chronic myeloid leukemia (CML), adipose-resident LSCs exhibit a pro-inflammatory phenotype and induce lipolysis in GAT. GAT lipolysis fuels fatty acid oxidation in LSCs, especially within a subpopulation expressing the fatty acid transporter CD36. CD36(+) LSCs have unique metabolic properties, are strikingly enriched in AT, and are protected from chemotherapy by the GAT microenvironment. CD36 also marks a fraction of human blast crisis CML and acute myeloid leukemia (AML) cells with similar biological properties. These findings suggest striking interplay between leukemic cells and AT to create a unique microenvironment that supports the metabolic demands and survival of a distinct LSC subpopulation. PMID:27374788

  8. Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism

    PubMed Central

    Aughey, Gabriel N.; Grice, Stuart J.; Shen, Qing-Ji; Xu, Yichi; Chang, Chia-Chun; Azzam, Ghows; Wang, Pei-Yu; Freeman-Mills, Luke; Pai, Li-Mei; Sung, Li-Ying; Yan, Jun; Liu, Ji-Long

    2014-01-01

    ABSTRACT The essential metabolic enzyme CTP synthase (CTPsyn) can be compartmentalised to form an evolutionarily-conserved intracellular structure termed the cytoophidium. Recently, it has been demonstrated that the enzymatic activity of CTPsyn is attenuated by incorporation into cytoophidia in bacteria and yeast cells. Here we demonstrate that CTPsyn is regulated in a similar manner in Drosophila tissues in vivo. We show that cytoophidium formation occurs during nutrient deprivation in cultured cells, as well as in quiescent and starved neuroblasts of the Drosophila larval central nervous system. We also show that cytoophidia formation is reversible during neurogenesis, indicating that filament formation regulates pyrimidine synthesis in a normal developmental context. Furthermore, our global metabolic profiling demonstrates that CTPsyn overexpression does not significantly alter CTPsyn-related enzymatic activity, suggesting that cytoophidium formation facilitates metabolic stabilisation. In addition, we show that overexpression of CTPsyn only results in moderate increase of CTP pool in human stable cell lines. Together, our study provides experimental evidence, and a mathematical model, for the hypothesis that inactive CTPsyn is incorporated into cytoophidia. PMID:25326513

  9. Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism

    PubMed Central

    Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Nowacki, Przemysław; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

    2015-01-01

    Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, some of which is transported to the neurons. Thus, glycogen from astrocytes functions as a kind of protection against hypoglycemia, ensuring preservation of neuronal function. The neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported in literature. This review goes on to emphasize that while neurons and astrocytes differ in metabolic profile, they interact to form a common metabolic cooperation. PMID:26528968

  10. Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism.

    PubMed

    Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Nowacki, Przemysław; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

    2015-10-29

    Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, some of which is transported to the neurons. Thus, glycogen from astrocytes functions as a kind of protection against hypoglycemia, ensuring preservation of neuronal function. The neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported in literature. This review goes on to emphasize that while neurons and astrocytes differ in metabolic profile, they interact to form a common metabolic cooperation.

  11. Energy Metabolism and Drug Efflux in Mycobacterium tuberculosis

    PubMed Central

    Black, Philippa A.; Warren, Robin M.; Louw, Gail E.; van Helden, Paul D.; Victor, Thomas C.

    2014-01-01

    The inherent drug susceptibility of microorganisms is determined by multiple factors, including growth state, the rate of drug diffusion into and out of the cell, and the intrinsic vulnerability of drug targets with regard to the corresponding antimicrobial agent. Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains a significant source of global morbidity and mortality, further exacerbated by its ability to readily evolve drug resistance. It is well accepted that drug resistance in M. tuberculosis is driven by the acquisition of chromosomal mutations in genes encoding drug targets/promoter regions; however, a comprehensive description of the molecular mechanisms that fuel drug resistance in the clinical setting is currently lacking. In this context, there is a growing body of evidence suggesting that active extrusion of drugs from the cell is critical for drug tolerance. M. tuberculosis encodes representatives of a diverse range of multidrug transporters, many of which are dependent on the proton motive force (PMF) or the availability of ATP. This suggests that energy metabolism and ATP production through the PMF, which is established by the electron transport chain (ETC), are critical in determining the drug susceptibility of M. tuberculosis. In this review, we detail advances in the study of the mycobacterial ETC and highlight drugs that target various components of the ETC. We provide an overview of some of the efflux pumps present in M. tuberculosis and their association, if any, with drug transport and concomitant effects on drug resistance. The implications of inhibiting drug extrusion, through the use of efflux pump inhibitors, are also discussed. PMID:24614376

  12. Enhanced Energy Metabolism Contributes to the Extended Life Span of Calorie-restricted Caenorhabditis elegans*

    PubMed Central

    Yuan, Yiyuan; Kadiyala, Chandra S.; Ching, Tsui-Ting; Hakimi, Parvin; Saha, Sudipto; Xu, Hua; Yuan, Chao; Mullangi, Vennela; Wang, Liwen; Fivenson, Elayne; Hanson, Richard W.; Ewing, Rob; Hsu, Ao-Lin; Miyagi, Masaru; Feng, Zhaoyang

    2012-01-01

    Caloric restriction (CR) markedly extends life span and improves the health of a broad number of species. Energy metabolism fundamentally contributes to the beneficial effects of CR, but the underlying mechanisms that are responsible for this effect remain enigmatic. A multidisciplinary approach that involves quantitative proteomics, immunochemistry, metabolic quantification, and life span analysis was used to determine how CR, which occurs in the Caenorhabditis elegans eat-2 mutants, modifies energy metabolism of the worm, and whether the observed modifications contribute to the CR-mediated physiological responses. A switch to fatty acid metabolism as an energy source and an enhanced rate of energy metabolism by eat-2 mutant nematodes were detected. Life span analyses validated the important role of these previously unknown alterations of energy metabolism in the CR-mediated longevity of nematodes. As observed in mice, the overexpression of the gene for the nematode analog of the cytosolic form of phosphoenolpyruvate carboxykinase caused a marked extension of the life span in C. elegans, presumably by enhancing energy metabolism via an altered rate of cataplerosis of tricarboxylic acid cycle anions. We conclude that an increase, not a decrease in fuel consumption, via an accelerated oxidation of fuels in the TCA cycle is involved in life span regulation; this mechanism may be conserved across phylogeny. PMID:22810224

  13. Caenorhabditis elegans AGXT-1 is a mitochondrial and temperature-adapted ortholog of peroxisomal human AGT1: New insights into between-species divergence in glyoxylate metabolism.

    PubMed

    Mesa-Torres, Noel; Calvo, Ana C; Oppici, Elisa; Titelbaum, Nicholas; Montioli, Riccardo; Miranda-Vizuete, Antonio; Cellini, Barbara; Salido, Eduardo; Pey, Angel L

    2016-09-01

    In humans, glyoxylate is an intermediary product of metabolism, whose concentration is finely balanced. Mutations in peroxisomal alanine:glyoxylate aminotransferase (hAGT1) cause primary hyperoxaluria type 1 (PH1), which results in glyoxylate accumulation that is converted to toxic oxalate. In contrast, glyoxylate is used by the nematode Caenorhabditis elegans through a glyoxylate cycle to by-pass the decarboxylation steps of the tricarboxylic acid cycle and thus contributing to energy production and gluconeogenesis from stored lipids. To investigate the differences in glyoxylate metabolism between humans and C. elegans and to determine whether the nematode might be a suitable model for PH1, we have characterized here the predicted nematode ortholog of hAGT1 (AGXT-1) and compared its molecular properties with those of the human enzyme. Both enzymes form active PLP-dependent dimers with high specificity towards alanine and glyoxylate, and display similar three-dimensional structures. Interestingly, AGXT-1 shows 5-fold higher activity towards the alanine/glyoxylate pair than hAGT1. Thermal and chemical stability of AGXT-1 is lower than that of hAGT1, suggesting temperature-adaptation of the nematode enzyme linked to the lower optimal growth temperature of C. elegans. Remarkably, in vivo experiments demonstrate the mitochondrial localization of AGXT-1 in contrast to the peroxisomal compartmentalization of hAGT1. Our results support the view that the different glyoxylate metabolism in the nematode is associated with the divergent molecular properties and subcellular localization of the alanine:glyoxylate aminotransferase activity.

  14. Caenorhabditis elegans AGXT-1 is a mitochondrial and temperature-adapted ortholog of peroxisomal human AGT1: New insights into between-species divergence in glyoxylate metabolism.

    PubMed

    Mesa-Torres, Noel; Calvo, Ana C; Oppici, Elisa; Titelbaum, Nicholas; Montioli, Riccardo; Miranda-Vizuete, Antonio; Cellini, Barbara; Salido, Eduardo; Pey, Angel L

    2016-09-01

    In humans, glyoxylate is an intermediary product of metabolism, whose concentration is finely balanced. Mutations in peroxisomal alanine:glyoxylate aminotransferase (hAGT1) cause primary hyperoxaluria type 1 (PH1), which results in glyoxylate accumulation that is converted to toxic oxalate. In contrast, glyoxylate is used by the nematode Caenorhabditis elegans through a glyoxylate cycle to by-pass the decarboxylation steps of the tricarboxylic acid cycle and thus contributing to energy production and gluconeogenesis from stored lipids. To investigate the differences in glyoxylate metabolism between humans and C. elegans and to determine whether the nematode might be a suitable model for PH1, we have characterized here the predicted nematode ortholog of hAGT1 (AGXT-1) and compared its molecular properties with those of the human enzyme. Both enzymes form active PLP-dependent dimers with high specificity towards alanine and glyoxylate, and display similar three-dimensional structures. Interestingly, AGXT-1 shows 5-fold higher activity towards the alanine/glyoxylate pair than hAGT1. Thermal and chemical stability of AGXT-1 is lower than that of hAGT1, suggesting temperature-adaptation of the nematode enzyme linked to the lower optimal growth temperature of C. elegans. Remarkably, in vivo experiments demonstrate the mitochondrial localization of AGXT-1 in contrast to the peroxisomal compartmentalization of hAGT1. Our results support the view that the different glyoxylate metabolism in the nematode is associated with the divergent molecular properties and subcellular localization of the alanine:glyoxylate aminotransferase activity. PMID:27179589

  15. Mitochondrial SIRT3 Mediates Adaptive Responses of Neurons to Exercise and Metabolic and Excitatory Challenges.

    PubMed

    Cheng, Aiwu; Yang, Ying; Zhou, Ye; Maharana, Chinmoyee; Lu, Daoyuan; Peng, Wei; Liu, Yong; Wan, Ruiqian; Marosi, Krisztina; Misiak, Magdalena; Bohr, Vilhelm A; Mattson, Mark P

    2016-01-12

    The impact of mitochondrial protein acetylation status on neuronal function and vulnerability to neurological disorders is unknown. Here we show that the mitochondrial protein deacetylase SIRT3 mediates adaptive responses of neurons to bioenergetic, oxidative, and excitatory stress. Cortical neurons lacking SIRT3 exhibit heightened sensitivity to glutamate-induced calcium overload and excitotoxicity and oxidative and mitochondrial stress; AAV-mediated Sirt3 gene delivery restores neuronal stress resistance. In models relevant to Huntington's disease and epilepsy, Sirt3(-/-) mice exhibit increased vulnerability of striatal and hippocampal neurons, respectively. SIRT3 deficiency results in hyperacetylation of several mitochondrial proteins, including superoxide dismutase 2 and cyclophilin D. Running wheel exercise increases the expression of Sirt3 in hippocampal neurons, which is mediated by excitatory glutamatergic neurotransmission and is essential for mitochondrial protein acetylation homeostasis and the neuroprotective effects of running. Our findings suggest that SIRT3 plays pivotal roles in adaptive responses of neurons to physiological challenges and resistance to degeneration. PMID:26698917

  16. Regulation of Adaptive Immunity in Health and Disease by Cholesterol Metabolism

    PubMed Central

    Fessler, Michael B.

    2015-01-01

    Four decades ago, it was observed that stimulation of T cells induces rapid changes in cellular cholesterol that are required before proliferation can commence. Investigators returning to this phenomenon have finally revealed its molecular underpinnings. Cholesterol trafficking and its dysregulation are now also recognized to strongly influence dendritic cell function, T cell polarization, and antibody responses. In this review, the state of the literature is reviewed on how cholesterol and its trafficking regulate the cells of the adaptive immune response and in vivo disease phenotypes of dysregulated adaptive immunity, including allergy, asthma, and autoimmune disease. Emerging evidence supporting a potential role for statins and other lipid-targeted therapies in the treatment of these diseases is presented. Just as vascular biologists have embraced immunity in the pathogenesis and treatment of atherosclerosis, so should basic and clinical immunologists in allergy, pulmonology, and other disciplines seek to encompass a basic understanding of lipid science. PMID:26149587

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

    PubMed

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

    2010-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  19. Investigation into the acute effects of total and partial energy restriction on postprandial metabolism among overweight/obese participants.

    PubMed

    Antoni, Rona; Johnston, Kelly L; Collins, Adam L; Robertson, M Denise

    2016-03-28

    The intermittent energy restriction (IER) approach to weight loss involves short periods of substantial (75-100 %) energy restriction (ER) interspersed with normal eating. This study aimed to characterise the early metabolic response to these varying degrees of ER, which occurs acutely and prior to weight loss. Ten (three female) healthy, overweight/obese participants (36 (SEM 5) years; 29·0 (sem 1·1) kg/m2) took part in this acute three-way cross-over study. Participants completed three 1-d dietary interventions in a randomised order with a 1-week washout period: isoenergetic intake, partial 75 % ER and total 100 % ER. Fasting and postprandial (6-h) metabolic responses to a liquid test meal were assessed the following morning via serial blood sampling and indirect calorimetry. Food intake was also recorded for two subsequent days of ad libitum intake. Relative to the isoenergetic control, postprandial glucose responses were increased following total ER (+142 %; P=0·015) and to a lesser extent after partial ER (+76 %; P=0·051). There was also a delay in the glucose time to peak after total ER only (P=0·024). Both total and partial ER interventions produced comparable reductions in postprandial TAG responses (-75 and -59 %, respectively; both P<0·05) and 3-d energy intake deficits of approximately 30 % (both P=0·015). Resting and meal-induced thermogenesis were not significantly affected by either ER intervention. In conclusion, our data demonstrate the ability of substantial ER to acutely alter postprandial glucose-lipid metabolism (with partial ER producing the more favourable overall response), as well as incomplete energy-intake compensation amongst overweight/obese participants. Further investigations are required to establish how metabolism adapts over time to the repeated perturbations experienced during IER, as well as the implications for long-term health. PMID:26819200

  20. Investigation into the acute effects of total and partial energy restriction on postprandial metabolism among overweight/obese participants.

    PubMed

    Antoni, Rona; Johnston, Kelly L; Collins, Adam L; Robertson, M Denise

    2016-03-28

    The intermittent energy restriction (IER) approach to weight loss involves short periods of substantial (75-100 %) energy restriction (ER) interspersed with normal eating. This study aimed to characterise the early metabolic response to these varying degrees of ER, which occurs acutely and prior to weight loss. Ten (three female) healthy, overweight/obese participants (36 (SEM 5) years; 29·0 (sem 1·1) kg/m2) took part in this acute three-way cross-over study. Participants completed three 1-d dietary interventions in a randomised order with a 1-week washout period: isoenergetic intake, partial 75 % ER and total 100 % ER. Fasting and postprandial (6-h) metabolic responses to a liquid test meal were assessed the following morning via serial blood sampling and indirect calorimetry. Food intake was also recorded for two subsequent days of ad libitum intake. Relative to the isoenergetic control, postprandial glucose responses were increased following total ER (+142 %; P=0·015) and to a lesser extent after partial ER (+76 %; P=0·051). There was also a delay in the glucose time to peak after total ER only (P=0·024). Both total and partial ER interventions produced comparable reductions in postprandial TAG responses (-75 and -59 %, respectively; both P<0·05) and 3-d energy intake deficits of approximately 30 % (both P=0·015). Resting and meal-induced thermogenesis were not significantly affected by either ER intervention. In conclusion, our data demonstrate the ability of substantial ER to acutely alter postprandial glucose-lipid metabolism (with partial ER producing the more favourable overall response), as well as incomplete energy-intake compensation amongst overweight/obese participants. Further investigations are required to establish how metabolism adapts over time to the repeated perturbations experienced during IER, as well as the implications for long-term health.

  1. Energy metabolism and hematology of white-tailed deer fawns

    USGS Publications Warehouse

    Rawson, R.E.; DelGiudice, G.D.; Dziuk, H.E.; Mech, L.D.

    1992-01-01

    Resting metabolic rates, weight gains and hematologic profiles of six newborn, captive white-tailed deer (Odocoileus virginianus) fawns (four females, two males) were determined during the first 3 mo of life. Estimated mean daily weight gain of fawns was 0.2 kg. The regression equation for metabolic rate was: Metabolic rate (kcal/kg0.75/day) = 56.1 +/- 1.3 (age in days), r = 0.65, P less than 0.001). Regression equations were also used to relate age to red blood cell count (RBC), hemoglobin concentration (Hb), packed cell volume, white blood cell count, mean corpuscular volume, mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular hemoglobin. The age relationships of Hb, MCHC, and smaller RBC's were indicative of an increasing and more efficient oxygen-carrying and exchange capacity to fulfill the increasing metabolic demands for oxygen associated with increasing body size.

  2. High incubation temperatures enhance mitochondrial energy metabolism in reptile embryos

    PubMed Central

    Sun, Bao-Jun; Li, Teng; Gao, Jing; Ma, Liang; Du, Wei-Guo

    2015-01-01

    Developmental rate increases exponentially with increasing temperature in ectothermic animals, but the biochemical basis underlying this thermal dependence is largely unexplored. We measured mitochondrial respiration and metabolic enzyme activities of turtle embryos (Pelodiscus sinensis) incubated at different temperatures to identify the metabolic basis of the rapid development occurring at high temperatures in reptile embryos. Developmental rate increased with increasing incubation temperatures in the embryos of P. sinensis. Correspondingly, in addition to the thermal dependence of mitochondrial respiration and metabolic enzyme activities, high-temperature incubation further enhanced mitochondrial respiration and COX activities in the embryos. This suggests that embryos may adjust mitochondrial respiration and metabolic enzyme activities in response to developmental temperature to achieve high developmental rates at high temperatures. Our study highlights the importance of biochemical investigations in understanding the proximate mechanisms by which temperature affects embryonic development. PMID:25749301

  3. Regulation of hepatic energy metabolism by the nuclear receptor PXR.

    PubMed

    Hakkola, Jukka; Rysä, Jaana; Hukkanen, Janne

    2016-09-01

    The pregnane X receptor (PXR) is a nuclear receptor that is traditionally thought to be specialized for sensing xenobiotic exposure. In concurrence with this feature PXR was originally identified to regulate drug-metabolizing enzymes and transporters. During the last ten years it has become clear that PXR harbors broader functions. Evidence obtained both in experimental animals and humans indicate that ligand-activated PXR regulates hepatic glucose and lipid metabolism and affects whole body metabolic homeostasis. Currently, the consequences of PXR activation on overall metabolic health are not yet fully understood and varying results on the effect of PXR activation or knockout on metabolic disorders and weight gain have been published in mouse models. Rifampicin and St. John's wort, the prototypical human PXR agonists, impair glucose tolerance in healthy volunteers. Chronic exposure to PXR agonists could potentially represent a risk factor for diabetes and metabolic syndrome. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie.

  4. Cooperation of two mRNA-binding proteins drives metabolic adaptation to iron deficiency

    PubMed Central

    Puig, Sergi; Vergara, Sandra V.; Thiele, Dennis J.

    2008-01-01

    Summary Iron (Fe) is an essential co-factor for a wide range of cellular processes. We have previously demonstrated that during Fe-deficiency yeast Cth2 is expressed and promotes degradation of a battery of mRNAs leading to reprogramming of Fe-dependent metabolism and Fe-storage. We report that the Cth2-homologous protein, Cth1, is transiently expressed during Fe-deprivation and participates in the response to Fe-deficiency through the degradation of mRNAs primarily involved in mitochondrially-localized activities including respiration and amino acid biosynthesis. In parallel, wild type but not cth1Δ cth2Δ cells accumulate mRNAs encoding proteins that function in glucose import and storage and store high levels of glycogen. In addition, Fe-deficiency leads to Snf1 phosphorylation, a member of the AMP-activated protein kinase family required for the cellular response to glucose starvation. These studies demonstrate a metabolic reprogramming as a consequence of Fe-starvation that is dependent on the coordinated activities of two mRNA-binding proteins. PMID:18522836

  5. Effect of desipramine and fluoxetine on energy metabolism of cerebral mitochondria.

    PubMed

    Villa, Roberto Federico; Ferrari, Federica; Gorini, Antonella; Brunello, Nicoletta; Tascedda, Fabio

    2016-08-25

    Brain bioenergetic abnormalities in mood disorders were detected by neuroimaging in vivo studies in humans. Because of the increasing importance of mitochondrial pathogenetic hypothesis of Depression, in this study the effects of sub-chronic treatment (21days) with desipramine (15mg/kg) and fluoxetine (10mg/kg) were evaluated on brain energy metabolism. On mitochondria in vivo located in neuronal soma (somatic) and on mitochondria of synapses (synaptic), the catalytic activities of regulatory enzymes of mitochondrial energy-yielding metabolic pathways were assayed. Antidepressants in vivo treatment modified the activities of selected enzymes of different mitochondria, leading to metabolic modifications in the energy metabolism of brain cortex: (a) the enhancement of cytochrome oxidase activity on somatic mitochondria; (b) the decrease of malate, succinate dehydrogenase and glutamate-pyruvate transaminase activities of synaptic mitochondria; (c) the selective effect of fluoxetine on enzymes related to glutamate metabolism. These results overcome the conflicting data so far obtained with antidepressants on brain energy metabolism, because the enzymatic analyses were made on mitochondria with diversified neuronal in vivo localization, i.e. on somatic and synaptic. This research is the first investigation on the pharmacodynamics of antidepressants studied at subcellular level, in the perspective of (i) assessing the role of energy metabolism of cerebral mitochondria in animal models of mood disorders, and (ii) highlighting new therapeutical strategies for antidepressants targeting brain bioenergetics. PMID:27268280

  6. The regulative effect of galanin family members on link of energy metabolism and reproduction.

    PubMed

    Fang, Penghua; He, Biao; Shi, Mingyi; Kong, Guimei; Dong, Xiaoyun; Zhu, Yan; Bo, Ping; Zhang, Zhenwen

    2015-09-01

    It is essential for the species survival that an efficient coordination between energy storage and reproduction through endocrine regulation. The neuropeptide galanin, one of the endocrine hormones, can potently coordinate energy metabolism and the activities of hypothalamic-pituitary-gonadal reproductive axis to adjust synthesis and release of metabolic and reproductive hormones in animals and humans. However, few papers have summarized the regulative effect of the galanin family members on the link of energy storage and reproduction as yet. To address this issue, this review attempts to summarize the current information available about the regulative effect of galanin, galanin-like peptide and alarin on the metabolic and reproductive events, with special emphasis on the interactions between galanin and hypothalamic gonadotropin-releasing hormone, pituitary luteinizing hormone and ovarian hormones. This research line will further deepen our understanding of the physiological roles of the galanin family in regulating the link of energy metabolism and reproduction.

  7. Metabolic adaptations to short-term every-other-day feeding in long-living Ames dwarf mice.

    PubMed

    Brown-Borg, Holly M; Rakoczy, Sharlene

    2013-09-01

    Restrictive dietary interventions exert significant beneficial physiological effects in terms of aging and age-related disease in many species. Every other day feeding (EOD) has been utilized in aging research and shown to mimic many of the positive outcomes consequent with dietary restriction. This study employed long living Ames dwarf mice subjected to EOD feeding to examine the adaptations of the oxidative phosphorylation and antioxidative defense systems to this feeding regimen. Every other day feeding lowered liver glutathione (GSH) concentrations in dwarf and wild type (WT) mice but altered GSH biosynthesis and degradation in WT mice only. The activities of liver OXPHOS enzymes and corresponding proteins declined in WT mice fed EOD while in dwarf animals, the levels were maintained or increased with this feeding regimen. Antioxidative enzymes were differentially affected depending on the tissue, whether proliferative or post-mitotic. Gene expression of components of liver methionine metabolism remained elevated in dwarf mice when compared to WT mice as previously reported however, enzymes responsible for recycling homocysteine to methionine were elevated in both genotypes in response to EOD feeding. The data suggest that the differences in anabolic hormone levels likely affect the sensitivity of long living and control mice to this dietary regimen, with dwarf mice exhibiting fewer responses in comparison to WT mice. These results provide further evidence that dwarf mice may be better protected against metabolic and environmental perturbations which may in turn, contribute to their extended longevity.

  8. Metabolic adaptations to short-term every-other-day feeding in long-living Ames dwarf mice.

    PubMed

    Brown-Borg, Holly M; Rakoczy, Sharlene

    2013-09-01

    Restrictive dietary interventions exert significant beneficial physiological effects in terms of aging and age-related disease in many species. Every other day feeding (EOD) has been utilized in aging research and shown to mimic many of the positive outcomes consequent with dietary restriction. This study employed long living Ames dwarf mice subjected to EOD feeding to examine the adaptations of the oxidative phosphorylation and antioxidative defense systems to this feeding regimen. Every other day feeding lowered liver glutathione (GSH) concentrations in dwarf and wild type (WT) mice but altered GSH biosynthesis and degradation in WT mice only. The activities of liver OXPHOS enzymes and corresponding proteins declined in WT mice fed EOD while in dwarf animals, the levels were maintained or increased with this feeding regimen. Antioxidative enzymes were differentially affected depending on the tissue, whether proliferative or post-mitotic. Gene expression of components of liver methionine metabolism remained elevated in dwarf mice when compared to WT mice as previously reported however, enzymes responsible for recycling homocysteine to methionine were elevated in both genotypes in response to EOD feeding. The data suggest that the differences in anabolic hormone levels likely affect the sensitivity of long living and control mice to this dietary regimen, with dwarf mice exhibiting fewer responses in comparison to WT mice. These results provide further evidence that dwarf mice may be better protected against metabolic and environmental perturbations which may in turn, contribute to their extended longevity. PMID:23832075

  9. The adaptive metabolic response involves specific protein glutathionylation during the filamentation process in the pathogen Candida albicans.

    PubMed

    Gergondey, R; Garcia, C; Serre, V; Camadro, J M; Auchère, F

    2016-07-01

    Candida albicans is an opportunist pathogen responsible for a large spectrum of infections, from superficial mycosis to the systemic disease candidiasis. Its ability to adopt various morphological forms, such as unicellular yeasts, filamentous pseudohyphae and hyphae, contributes to its ability to survive within the host. It has been suggested that the antioxidant glutathione is involved in the filamentation process. We investigated S-glutathionylation, the reversible binding of glutathione to proteins, and the functional consequences on C. albicans metabolic remodeling during the yeast-to-hyphae transition. Our work provided evidence for the specific glutathionylation of mitochondrial proteins involved in bioenergetics pathways in filamentous forms and a regulation of the main enzyme of the glyoxylate cycle, isocitrate lyase, by glutathionylation. Isocitrate lyase inactivation in the hyphal forms was reversed by glutaredoxin treatment, in agreement with a glutathionylation process, which was confirmed by proteomic data showing the binding of one glutathione molecule to the enzyme (data are available via ProteomeXchange with identifier PXD003685). We also assessed the effect of alternative carbon sources on glutathione levels and isocitrate lyase activity. Changes in nutrient availability led to morphological flexibility and were related to perturbations in glutathione levels and isocitrate lyase activity, confirming the key role of the maintenance of intracellular redox status in the adaptive metabolic strategy of the pathogen.

  10. The adaptive metabolic response involves specific protein glutathionylation during the filamentation process in the pathogen Candida albicans.

    PubMed

    Gergondey, R; Garcia, C; Serre, V; Camadro, J M; Auchère, F

    2016-07-01

    Candida albicans is an opportunist pathogen responsible for a large spectrum of infections, from superficial mycosis to the systemic disease candidiasis. Its ability to adopt various morphological forms, such as unicellular yeasts, filamentous pseudohyphae and hyphae, contributes to its ability to survive within the host. It has been suggested that the antioxidant glutathione is involved in the filamentation process. We investigated S-glutathionylation, the reversible binding of glutathione to proteins, and the functional consequences on C. albicans metabolic remodeling during the yeast-to-hyphae transition. Our work provided evidence for the specific glutathionylation of mitochondrial proteins involved in bioenergetics pathways in filamentous forms and a regulation of the main enzyme of the glyoxylate cycle, isocitrate lyase, by glutathionylation. Isocitrate lyase inactivation in the hyphal forms was reversed by glutaredoxin treatment, in agreement with a glutathionylation process, which was confirmed by proteomic data showing the binding of one glutathione molecule to the enzyme (data are available via ProteomeXchange with identifier PXD003685). We also assessed the effect of alternative carbon sources on glutathione levels and isocitrate lyase activity. Changes in nutrient availability led to morphological flexibility and were related to perturbations in glutathione levels and isocitrate lyase activity, confirming the key role of the maintenance of intracellular redox status in the adaptive metabolic strategy of the pathogen. PMID:27083931

  11. Adaptive modification of membrane phospholipid fatty acid composition and metabolic thermosuppression of brown adipose tissue in heat-acclimated rats

    NASA Astrophysics Data System (ADS)

    Saha, S. K.; Ohno, T.; Tsuchiya, K.; Kuroshima, A.

    Thermogenesis, especially facultative thermogenesis by brown adipose tissue (BAT), is less important in high ambient temperature and the heat-acclimated animals show a lower metabolic rate. Adaptive changes in the metabolic activity of BAT are generally found to be associated with a modification of membrane phospholipid fatty acid composition. However, the effect of heat acclimation on membrane phospholipid fatty acid composition is as yet unknown. In this study, we examined the thermogenic activity and phospholipid fatty acid composition of interscapular BAT from heat-acclimated rats (control: 25+/-1°C, 50% relative humidity and heat acclimation: 32+/-0.5°C, 50% relative humidity). Basal thermogenesis and the total thermogenic capacity after noradrenaline stimulation, as estimated by in vitro oxygen consumption of BAT (measured polarographically using about 1-mm3 tissue blocks), were smaller in the heat-acclimated group than in the control group. There was no difference in the tissue content of phospholipids between the groups when expressed per microgram of DNA. The phospholipid fatty acid composition was analyzed by a capillary gas chromatograph. The state of phospholipid unsaturation, as estimated by the number of double bonds per fatty acid molecule, was similar between the groups. The saturated fatty acid level was higher in the heat-acclimated group. Among the unsaturated fatty acids, heat acclimation decreased docosahexaenoic acid and oleic acid levels, and increased the arachidonic acid level. The tissue level of docosahexaenoic acid correlated with the basal oxygen consumption of BAT (r=0.6, P<0.01) and noradrenaline-stimulated maximum values of oxygen consumption (r=0.5, P<0.05). Our results show that heat acclimation modifies the BAT phospholipid fatty acids, especially the n-3 polyunsaturated fatty acid docosahexaenoic acid, which is possibly involved in the metabolic thermosuppression.

  12. Thyroid hormones correlate with resting metabolic rate, not daily energy expenditure, in two charadriiform seabirds.

    PubMed

    Elliott, Kyle H; Welcker, Jorg; Gaston, Anthony J; Hatch, Scott A; Palace, Vince; Hare, James F; Speakman, John R; Anderson, W Gary

    2013-06-15

    Thyroid hormones affect in vitro metabolic intensity, increase basal metabolic rate (BMR) in the lab, and are sometimes correlated with basal and/or resting metabolic rate (RMR) in a field environment. Given the difficulty of measuring metabolic rate in the field-and the likelihood that capture and long-term restraint necessary to measure metabolic rate in the field jeopardizes other measurements-we examined the possibility that circulating thyroid hormone levels were correlated with RMR in two free-ranging bird species with high levels of energy expenditure (the black-legged kittiwake, Rissa tridactyla, and thick-billed murre, Uria lomvia). Because BMR and daily energy expenditure (DEE) are purported to be linked, we also tested for a correlation between thyroid hormones and DEE. We examined the relationships between free and bound levels of the thyroid hormones thyroxine (T4) and triiodothyronine (T3) with DEE and with 4-hour long measurements of post-absorptive and thermoneutral resting metabolism (resting metabolic rate; RMR). RMR but not DEE increased with T3 in both species; both metabolic rates were independent of T4. T3 and T4 were not correlated with one another. DEE correlated with body mass in kittiwakes but not in murres, presumably owing to the larger coefficient of variation in body mass during chick rearing for the more sexually dimorphic kittiwakes. We suggest T3 provides a good proxy for resting metabolism but not DEE in these seabird species.

  13. Thyroid hormones correlate with resting metabolic rate, not daily energy expenditure, in two charadriiform seabirds

    PubMed Central

    Elliott, Kyle H.; Welcker, Jorg; Gaston, Anthony J.; Hatch, Scott A.; Palace, Vince; Hare, James F.; Speakman, John R.; Anderson, W. Gary

    2013-01-01

    Summary Thyroid hormones affect in vitro metabolic intensity, increase basal metabolic rate (BMR) in the lab, and are sometimes correlated with basal and/or resting metabolic rate (RMR) in a field environment. Given the difficulty of measuring metabolic rate in the field—and the likelihood that capture and long-term restraint necessary to measure metabolic rate in the field jeopardizes other measurements—we examined the possibility that circulating thyroid hormone levels were correlated with RMR in two free-ranging bird species with high levels of energy expenditure (the black-legged kittiwake, Rissa tridactyla, and thick-billed murre, Uria lomvia). Because BMR and daily energy expenditure (DEE) are purported to be linked, we also tested for a correlation between thyroid hormones and DEE. We examined the relationships between free and bound levels of the thyroid hormones thyroxine (T4) and triiodothyronine (T3) with DEE and with 4-hour long measurements of post-absorptive and thermoneutral resting metabolism (resting metabolic rate; RMR). RMR but not DEE increased with T3 in both species; both metabolic rates were independent of T4. T3 and T4 were not correlated with one another. DEE correlated with body mass in kittiwakes but not in murres, presumably owing to the larger coefficient of variation in body mass during chick rearing for the more sexually dimorphic kittiwakes. We suggest T3 provides a good proxy for resting metabolism but not DEE in these seabird species. PMID:23789108

  14. PKCε Promotes Cardiac Mitochondrial and Metabolic Adaptation to Chronic Hypobaric Hypoxia by GSK3β Inhibition

    PubMed Central

    McCarthy, Joy; Lochner, Amanda; Opie, Lionel H.; Sack, Michael N.; Essop, M. Faadiel

    2012-01-01

    PKCε is central to cardioprotection. Sub-proteome analysis demonstrated co-localization of activated cardiac PKCε (aPKCε) with metabolic, mitochondrial, and cardioprotective modulators like hypoxia-inducible factor 1α (HIF-1α). aPKCε relocates to the mitochondrion, inactivating glycogen synthase kinase 3β (GSK3β) to modulate glycogen metabolism, hypertrophy and HIF-1α. However, there is no established mechanistic link between PKCε, p-GSK3β and HIF1-α. Here we hypothesized that cardiac-restricted aPKCε improves mitochondrial response to hypobaric hypoxia by altered substrate fuel selection via a GSK3β/HIF-1α-dependent mechanism. aPKCε and wild-type (WT) mice were exposed to 14 days of hypobaric hypoxia (45 kPa, 11% O2) and cardiac metabolism, functional parameters, p-GSK3β/HIF-1α expression, mitochondrial function and ultrastructure analyzed versus normoxic controls. Mitochondrial ADP-dependent respiration, ATP production and membrane potential were attenuated in hypoxic WT but maintained in hypoxic aPKCε mitochondria (P< 0.005, n = 8). Electron microscopy revealed a hypoxia-associated increase in mitochondrial number with ultrastructural disarray in WT versus aPKCε hearts. Concordantly, left ventricular work was diminished in hypoxic WT but not aPKCε mice (glucose only perfusions). However, addition of palmitate abrogated this (P<0.05 vs. WT). aPKCε hearts displayed increased glucose utilization at baseline and with hypoxia. In parallel, p-GSK3β and HIF1-α peptide levels were increased in hypoxic aPKCε hearts versus WT. Our study demonstrates that modest, sustained PKCε activation blunts cardiac pathophysiologic responses usually observed in response to chronic hypoxia. Moreover, we propose that preferential glucose utilization by PKCε hearts is orchestrated by a p-GSK3β/HIF-1α-mediated mechanism, playing a crucial role to sustain contractile function in response to chronic hypobaric hypoxia. PMID:21660969

  15. Long-Term Impacts of Foetal Malnutrition Followed by Early Postnatal Obesity on Fat Distribution Pattern and Metabolic Adaptability in Adult Sheep

    PubMed Central

    Khanal, Prabhat; Johnsen, Lærke; Axel, Anne Marie Dixen; Hansen, Pernille Willert; Kongsted, Anna Hauntoft; Lyckegaard, Nette Brinch; Nielsen, Mette Olaf

    2016-01-01

    We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin-pregnant ewes were fed NORM (100% of daily energy and protein requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein requirements) diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF) or moderate (CONV) diets until 6 months of age, and a moderate (obesity correcting) diet thereafter. At 2½ years of age (adulthood), plasma metabolite profiles during fasting, glucose, insulin and propionate (in fed and fasted states) tolerance tests were examined. Organ weights were determined at autopsy. Early obesity development was associated with lack of expansion of perirenal, but not other adipose tissues from adolescence to adulthood, resulting in 10% unit increased proportion of mesenteric of intra-abdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, urea-nitrogen, creatinine, and lactate. Sex specific differences were observed, particularly with respect to fat deposition, but direction of responses to early nutrition impacts were similar. However, prenatal undernutrition induced greater metabolic alterations in adult females than males. Foetal undernutrition, but not overnutrition, predisposed for adult hypercholesterolaemia, hyperureaemia, hypercreatinaemia and hyperlactataemia, which became manifested only in combination with early obesity development. Perirenal expandability may play a special role in this context. Differential nutrition recommendations may be advisable for individuals with low versus high birth weights. PMID:27257993

  16. Long-Term Impacts of Foetal Malnutrition Followed by Early Postnatal Obesity on Fat Distribution Pattern and Metabolic Adaptability in Adult Sheep.

    PubMed

    Khanal, Prabhat; Johnsen, Lærke; Axel, Anne Marie Dixen; Hansen, Pernille Willert; Kongsted, Anna Hauntoft; Lyckegaard, Nette Brinch; Nielsen, Mette Olaf

    2016-01-01

    We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin-pregnant ewes were fed NORM (100% of daily energy and protein requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein requirements) diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF) or moderate (CONV) diets until 6 months of age, and a moderate (obesity correcting) diet thereafter. At 2½ years of age (adulthood), plasma metabolite profiles during fasting, glucose, insulin and propionate (in fed and fasted states) tolerance tests were examined. Organ weights were determined at autopsy. Early obesity development was associated with lack of expansion of perirenal, but not other adipose tissues from adolescence to adulthood, resulting in 10% unit increased proportion of mesenteric of intra-abdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, urea-nitrogen, creatinine, and lactate. Sex specific differences were observed, particularly with respect to fat deposition, but direction of responses to early nutrition impacts were similar. However, prenatal undernutrition induced greater metabolic alterations in adult females than males. Foetal undernutrition, but not overnutrition, predisposed for adult hypercholesterolaemia, hyperureaemia, hypercreatinaemia and hyperlactataemia, which became manifested only in combination with early obesity development. Perirenal expandability may play a special role in this context. Differential nutrition recommendations may be advisable for individuals with low versus high birth weights. PMID:27257993

  17. Adaptations to fasting in the American mink (Mustela vison): carbohydrate and lipid metabolism.

    PubMed

    Mustonen, Anne-Mari; Pyykönen, Teija; Paakkonen, Tommi; Ryökkynen, Ari; Asikainen, Juha; Aho, Jari; Mononen, Jaakko; Nieminen, Petteri

    2005-02-01

    The aim of this study was to investigate whether the actively wintering American mink Mustela vison is strictly dependent on continuous food availability or if it has evolved physiological adaptations to tolerate nutritional scarcity. Fifty farm-bred male minks were divided into a fed control group and four experimental groups fasted for 2, 3, 5 or 7 days. The rate of weight loss was several-fold higher (1.5-3.2% day(-1)) in the mink than recorded previously in larger carnivores utilizing passive wintering strategies. The minks remained normoglycaemic, although their liver glycogen stores and glucose-6-phosphatase activities decreased during fasting. Adipose tissue constituted approximately 36% of their body mass after 7 days of food deprivation. Intra-abdominal fat, especially retroperitoneal but also mesenteric adipose tissue, were the most important fat depots to be hydrolyzed, but the ability of the mink to utilize its body lipids during fasting may be limited. The increased liver size, hepatic triacylglycerol accumulation and increases in the activities of plasma aminotransferases indicated liver dysfunction. Food deprivation also affected the red blood cell indices, and the blood monocyte and lymphocyte counts decreased suggesting immunosuppression during fasting. The results of the present study suggest that the mink has not evolved sophisticated adaptations to wintertime fasting. PMID:15748859

  18. Changes in chloroplast ultrastructure in some high-alpine plants: adaptation to metabolic demands and climate?

    PubMed

    Lütz, C; Engel, L

    2007-01-01

    The cytology of leaf cells from five different high-alpine plants was studied and compared with structures in chloroplasts from the typical high-alpine plant Ranunculus glacialis previously described as having frequent envelope plus stroma protrusions. The plants under investigation ranged from subalpine/alpine Geum montanum through alpine Geum reptans, Poa alpina var. vivipara, and Oxyria digyna to nival Cerastium uniflorum and R. glacialis. The general leaf structure (by light microscopy) and leaf mesophyll cell ultrastructure (by transmission electron microscopy [TEM]) did not show any specialized structures unique to these mountain species. However, chloroplast protrusion formation could be found in G. reptans and, to a greater extent, in O. digyna. The other species exhibited only a low percentage of such chloroplast structural changes. Occurrence of protrusions in samples of G. montanum and O. digyna growing in a mild climate at about 50 m above sea level was drastically reduced. Serial TEM sections of O. digyna cells showed that the protrusions can appear as rather broad and long appendices of plastids, often forming pocketlike structures where mitochondria and microbodies are in close vicinity to the plastid and to each other. It is suggested that some high-alpine plants may form such protrusions to facilitate fast exchange of molecules between cytoplasm and plastid as an adaptation to the short, often unfavorable vegetation period in the Alps, while other species may have developed different types of adaptation that are not expressed in ultrastructural changes of the plastids.

  19. The Central Carbon and Energy Metabolism of Marine Diatoms

    PubMed Central

    Obata, Toshihiro; Fernie, Alisdair R.; Nunes-Nesi, Adriano

    2013-01-01

    Diatoms are heterokont algae derived from a secondary symbiotic event in which a eukaryotic host cell acquired an eukaryotic red alga as plastid. The multiple endosymbiosis and horizontal gene transfer processes provide diatoms unusual opportunities for gene mixing to establish distinctive biosynthetic pathways and metabolic control structures. Diatoms are also known to have significant impact on global ecosystems as one of the most dominant phytoplankton species in the contemporary ocean. As such their metabolism and growth regulating factors have been of particular interest for many years. The publication of the genomic sequences of two independent species of diatoms and the advent of an enhanced experimental toolbox for molecular biological investigations have afforded far greater opportunities than were previously apparent for these species and re-invigorated studies regarding the central carbon metabolism of diatoms. In this review we discuss distinctive features of the central carbon metabolism of diatoms and its response to forthcoming environmental changes and recent advances facilitating the possibility of industrial use of diatoms for oil production. Although the operation and importance of several key pathways of diatom metabolism have already been demonstrated and determined, we will also highlight other potentially important pathways wherein this has yet to be achieved. PMID:24957995

  20. Deciphering the roles of the constitutive androstane receptor in energy metabolism.

    PubMed

    Yan, Jiong; Chen, Baian; Lu, Jing; Xie, Wen

    2015-01-01

    The constitutive androstane receptor (CAR) is initially defined as a xenobiotic nuclear receptor that protects the liver from injury. Detoxification of damaging chemicals is achieved by CAR-mediated induction of drug-metabolizing enzymes and transporters. More recent research has implicated CAR in energy metabolism, suggesting a therapeutic potential for CAR in metabolic diseases, such as type 2 diabetes and obesity. A better understanding of the mechanisms by which CAR regulates energy metabolism will allow us to take advantage of its effectiveness while avoiding its side effects. This review summarizes the current progress on the regulation of CAR nuclear translocation, upstream modulators of CAR activity, and the crosstalk between CAR and other transcriptional factors, with the aim of elucidating how CAR regulates glucose and lipid metabolism. PMID:25500869

  1. Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy.

    PubMed

    Gürke, Jacqueline; Hirche, Frank; Thieme, René; Haucke, Elisa; Schindler, Maria; Stangl, Gabriele I; Fischer, Bernd; Navarrete Santos, Anne

    2015-01-01

    During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. In the cavity fluid of blastocysts from diabetic rabbits BCAA concentrations were twice as high as those from controls, indicating a close link between maternal diabetes and embryonic BCAA metabolism. The expression of BCAA oxidizing enzymes and BCAA transporter was analysed in maternal tissues and in blastocysts. The RNA amounts of three oxidizing enzymes, i.e. branched chain aminotransferase 2 (Bcat2), branched chain ketoacid dehydrogenase (Bckdha) and dehydrolipoyl dehydrogenase (Dld), were markedly increased in maternal adipose tissue and decreased in liver and skeletal muscle of diabetic rabbits than in those of controls. Blastocysts of diabetic rabbits revealed a higher Bcat2 mRNA and protein abundance in comparison to control blastocysts. The expression of BCAA transporter LAT1 and LAT2 were unaltered in endometrium of diabetic and healthy rabbits, whereas LAT2 transcripts were increased in blastocysts of diabetic rabbits. In correlation to high embryonic BCAA levels the phosphorylation amount of the nutrient sensor mammalian target of rapamycin (mTOR) was enhanced in blastocysts caused by maternal diabetes. These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling. PMID:26020623

  2. Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy

    PubMed Central

    Gürke, Jacqueline; Hirche, Frank; Thieme, René; Haucke, Elisa; Schindler, Maria; Stangl, Gabriele I.; Fischer, Bernd; Navarrete Santos, Anne

    2015-01-01

    During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. In the cavity fluid of blastocysts from diabetic rabbits BCAA concentrations were twice as high as those from controls, indicating a close link between maternal diabetes and embryonic BCAA metabolism. The expression of BCAA oxidizing enzymes and BCAA transporter was analysed in maternal tissues and in blastocysts. The RNA amounts of three oxidizing enzymes, i.e. branched chain aminotransferase 2 (Bcat2), branched chain ketoacid dehydrogenase (Bckdha) and dehydrolipoyl dehydrogenase (Dld), were markedly increased in maternal adipose tissue and decreased in liver and skeletal muscle of diabetic rabbits than in those of controls. Blastocysts of diabetic rabbits revealed a higher Bcat2 mRNA and protein abundance in comparison to control blastocysts. The expression of BCAA transporter LAT1 and LAT2 were unaltered in endometrium of diabetic and healthy rabbits, whereas LAT2 transcripts were increased in blastocysts of diabetic rabbits. In correlation to high embryonic BCAA levels the phosphorylation amount of the nutrient sensor mammalian target of rapamycin (mTOR) was enhanced in blastocysts caused by maternal diabetes. These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling. PMID:26020623

  3. The Role of Isocitrate Lyase (ICL1) in the Metabolic Adaptation of Candida albicans Biofilms

    PubMed Central

    Ishola, Oluwaseun Ayodeji; Ting, Seng Yeat; Tabana, Yasser M; Ahmed, Mowaffaq Adam; Yunus, Muhammad Amir; Mohamed, Rafeezul; Lung Than, Leslie Thian; Sandai, Doblin

    2016-01-01

    Background A major characteristic of Candida biofilm cells that differentiates them from free-floating cells is their high tolerance to antifungal drugs. This high resistance is attributed to particular biofilm properties, including the accumulation of extrapolymeric substances, morphogenetic switching, and metabolic flexibility. Objectives This study evaluated the roles of metabolic processes (in particular the glyoxylate cycle) on biofilm formation, antifungal drug resistance, morphology, and cell wall components. Methods Growth, adhesion, biofilm formation, and cell wall carbohydrate composition were quantified for isogenic Candida albicans ICL1/ICL1, ICL1/icl1, and icl1/icl1 strains. The morphology and topography of these strains were compared by light microscopy and scanning electron microscopy. FKS1 (glucan synthase), ERG11 (14-α-demethylase), and CDR2 (efflux pump) mRNA levels were quantified using qRT-PCR. Results The ICL1/icl1 and icl1/icl1 strains formed similar biofilms and exhibited analogous drug-tolerance levels to the control ICL1/ICL1 strains. Furthermore, the drug sequestration ability of β-1, 3-glucan, a major carbohydrate component of the extracellular matrix, was not impaired. However, the inactivation of ICL1 did impair morphogenesis. ICL1 deletion also had a considerable effect on the expression of the FKS1, ERG11, and CDR2 genes. FKS1 and ERG11 were upregulated in ICL1/icl1 and icl1/icl1 cells throughout the biofilm developmental stages, and CDR2 was upregulated at the early phase. However, their expression was downregulated compared to the control ICL1/ICL1 strain. Conclusions We conclude that the glyoxylate cycle is not a specific determinant of biofilm drug resistance. PMID:27800147

  4. Human Behavior & Low Energy Architecture: Linking Environmental Adaptation, Personal Comfort, & Energy Use in the Built Environment

    NASA Astrophysics Data System (ADS)

    Langevin, Jared

    Truly sustainable buildings serve to enrich the daily sensory experience of their human inhabitants while consuming the least amount of energy possible; yet, building occupants and their environmentally adaptive behaviors remain a poorly characterized variable in even the most "green" building design and operation approaches. This deficiency has been linked to gaps between predicted and actual energy use, as well as to eventual problems with occupant discomfort, productivity losses, and health issues. Going forward, better tools are needed for considering the human-building interaction as a key part of energy efficiency strategies that promote good Indoor Environmental Quality (IEQ) in buildings. This dissertation presents the development and implementation of a Human and Building Interaction Toolkit (HABIT), a framework for the integrated simulation of office occupants' thermally adaptive behaviors, IEQ, and building energy use as part of sustainable building design and operation. Development of HABIT begins with an effort to devise more reliable methods for predicting individual occupants' thermal comfort, considered the driving force behind the behaviors of focus for this project. A long-term field study of thermal comfort and behavior is then presented, and the data it generates are used to develop and validate an agent-based behavior simulation model. Key aspects of the agent-based behavior model are described, and its predictive abilities are shown to compare favorably to those of multiple other behavior modeling options. Finally, the agent-based behavior model is linked with whole building energy simulation in EnergyPlus, forming the full HABIT program. The program is used to evaluate the energy and IEQ impacts of several occupant behavior scenarios in the simulation of a case study office building for the Philadelphia climate. Results indicate that more efficient local heating/cooling options may be paired with wider set point ranges to yield up to 24

  5. Myocardial Energy Substrate Metabolism in Heart Failure : from Pathways to Therapeutic Targets.

    PubMed

    Fukushima, Arata; Milner, Kenneth; Gupta, Abhishek; Lopaschuk, Gary D

    2015-01-01

    Despite recent advances in therapy, heart failure remains a major cause of mortality and morbidity and is a growing healthcare burden worldwide. Alterations in myocardial energy substrate metabolism are a hallmark of heart failure, and are associated with an energy deficit in the failing heart. Previous studies have shown that a metabolic shift from mitochondrial oxidative metabolism to glycolysis, as well as an uncoupling between glycolysis and glucose oxidation, plays a crucial role in the development of cardiac inefficiency and functional impairment in heart failure. Therefore, optimizing energy substrate utilization, particularly by increasing mitochondrial glucose oxidation, can be a potentially promising approach to decrease the severity of heart failure by improving mechanical cardiac efficiency. One approach to stimulating myocardial glucose oxidation is to inhibit fatty acid oxidation. This review will overview the physiological regulation of both myocardial fatty acid and glucose oxidation in the heart, and will discuss what alterations in myocardial energy substrate metabolism occur in the failing heart. Furthermore, lysine acetylation has been recently identified as a novel post-translational pathway by which mitochondrial enzymes involved in all aspects of cardiac energy metabolism can be regulated. Thus, we will also discuss the effect of acetylation of metabolic enzymes on myocardial energy substrate preference in the settings of heart failure. Finally, we will focus on pharmacological interventions that target enzymes involved in fatty acid uptake, fatty acid oxidation, transcriptional regulation of fatty acid oxidation, and glucose oxidation to treat heart failure. PMID:26166604

  6. Myocardial Energy Substrate Metabolism in Heart Failure : from Pathways to Therapeutic Targets.

    PubMed

    Fukushima, Arata; Milner, Kenneth; Gupta, Abhishek; Lopaschuk, Gary D

    2015-01-01

    Despite recent advances in therapy, heart failure remains a major cause of mortality and morbidity and is a growing healthcare burden worldwide. Alterations in myocardial energy substrate metabolism are a hallmark of heart failure, and are associated with an energy deficit in the failing heart. Previous studies have shown that a metabolic shift from mitochondrial oxidative metabolism to glycolysis, as well as an uncoupling between glycolysis and glucose oxidation, plays a crucial role in the development of cardiac inefficiency and functional impairment in heart failure. Therefore, optimizing energy substrate utilization, particularly by increasing mitochondrial glucose oxidation, can be a potentially promising approach to decrease the severity of heart failure by improving mechanical cardiac efficiency. One approach to stimulating myocardial glucose oxidation is to inhibit fatty acid oxidation. This review will overview the physiological regulation of both myocardial fatty acid and glucose oxidation in the heart, and will discuss what alterations in myocardial energy substrate metabolism occur in the failing heart. Furthermore, lysine acetylation has been recently identified as a novel post-translational pathway by which mitochondrial enzymes involved in all aspects of cardiac energy metabolism can be regulated. Thus, we will also discuss the effect of acetylation of metabolic enzymes on myocardial energy substrate preference in the settings of heart failure. Finally, we will focus on pharmacological interventions that target enzymes involved in fatty acid uptake, fatty acid oxidation, transcriptional regulation of fatty acid oxidation, and glucose oxidation to treat heart failure.

  7. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism

    PubMed Central

    Ferron, Mathieu; Wei, Jianwen; Yoshizawa, Tatsuya; Fattore, Andrea Del; DePinho, Ronald A.; Teti, Anna; Ducy, Patricia; Karsenty, Gerard

    2010-01-01

    The broad expression of the insulin receptor suggests that the spectrum of insulin function has not been fully described. A cell type expressing this receptor is the osteoblast, a bone-specific cell favoring glucose metabolism through a hormone, osteocalcin, that becomes active once uncarboxylated. We show here that insulin signaling in osteoblasts is necessary for whole-body glucose homeostasis because it increases osteocalcin activity. To achieve this function insulin signaling in osteoblasts takes advantage of the regulation of osteoclastic bone resorption exerted by osteoblasts. Indeed, since bone resorption occurs at a pH acid enough to decarboxylate proteins, osteoclasts determine the carboxylation status and function of osteocalcin. Accordingly, increasing or decreasing insulin signaling in osteoblasts promotes or hampers glucose metabolism in a bone resorption-dependent manner in mice and humans. Hence, in a feed-forward loop, insulin signals in osteoblasts to activate a hormone, osteocalcin, that promotes glucose metabolism. PMID:20655470

  8. Energy metabolism in hypoxia: reinterpreting some features of muscle physiology on molecular grounds.

    PubMed

    Cerretelli, Paolo; Gelfi, Cecilia

    2011-03-01

    An holistic approach for interpreting classical data on the adaptation of the animal and, particularly, of the human body to hypoxic stress was promoted by the discovery of HIF-1, the "master regulator" of cell hypoxic signaling. Mitochondrial production of ROS stabilizes the O(2)-regulated HIF-1α subunit of the HIF-1 dimer promoting transaction functions in a large number of potential target genes, activating transcription of sequences into RNA and, eventually, protein production. The aim of the present preliminary study is to assess whether adaptive changes in oxygen sensing and metabolic signaling, particularly in the control of energy turnover known to occur in cultured cells exposed to hypoxia, are detectable also in the muscles of animals and man. For the present analysis, data obtained from the proteome of the rat gastrocnemius and of the vastus lateralis muscle of humans together with functional measurements were compared with homologous data from hypoxic cultured cells. In particular, the following variables were assessed: (1) the role of stress response proteins in the maintenance of ROS homeostasis, (2) the activity of the PDK1 gene on the shunting of pyruvate away from the TCA cycle in rodents and in humans, (3) the COX-4/COX-2 ratio in hypoxic rodents, (4) the overall efficiency of oxidative phosphorylation in humans during exercise in hypoxia, (5) some features of muscle mitochondrial autophagy in humans undergoing subchronic and chronic altitude exposure. Despite the limited number of observations and the differences in the experimental approach, some initial interesting results were obtained encouraging to pursue this innovative effort. PMID:20352258

  9. In vivo imaging of cerebral energy metabolism with two-photon fluorescence lifetime microscopy of NADH

    PubMed Central

    Yaseen, Mohammad A.; Sakadžić, Sava; Wu, Weicheng; Becker, Wolfgang; Kasischke, Karl A.; Boas, David A.

    2013-01-01

    Minimally invasive, specific measurement of cellular energy metabolism is crucial for understanding cerebral pathophysiology. Here, we present high-resolution, in vivo observations of autofluorescence lifetime as a biomarker of cerebral energy metabolism in exposed rat cortices. We describe a customized two-photon imaging system with time correlated single photon counting detection and specialized software for modeling multiple-component fits of fluorescence decay and monitoring their transient behaviors. In vivo cerebral NADH fluorescence suggests the presence of four distinct components, which respond differently to brief periods of anoxia and likely indicate different enzymatic formulations. Individual components show potential as indicators of specific molecular pathways involved in oxidative metabolism. PMID:23412419

  10. Ablation of Lgr4 enhances energy adaptation in skeletal muscle via activation of Ampk/Sirt1/Pgc1α pathway.

    PubMed

    Sun, Yingkai; Hong, Jie; Chen, Maopei; Ke, Yingying; Zhao, Shaoqian; Liu, Wen; Ma, Qinyun; Shi, Juan; Zou, Yaoyu; Ning, Tinglu; Zhang, Zhiguo; Liu, Ruixin; Wang, Jiqiu; Ning, Guang

    2015-08-21

    Leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) is a newfound obese-associated gene. Previous study reveals that heterozygous mutation of Lgr4 correlates with decreased body weight in human. In our recent study, we demonstrate that Lgr4 ablation promotes browning of white adipose tissue and improves whole-body metabolic status. However little is known about its role in other metabolic tissues. Herein, we show that Lgr4 homozygous mutant (Lgr4(m/m)) mice show increased respiratory exchange ratio (RER, closer to 1.0) than wild-type mice at 12:00 AM (food-intake time for mice) while decreased RER (closer to 0.75) at 12:00 PM (fasting for mice), indicating a glucose-prone versus fatty acid-prone metabolic pattern, respectively. Furthermore, Lgr4 ablation increases lipid oxidation-related gene expression while suppresses glucose transporter type 4 (Glut4) levels in skeletal muscle under fasting condition. These data suggest that Lgr4 ablation enhances the flexibility of skeletal muscle to switch energy provider from glucose to fatty acid in response to glucose depletion. We further reveal the activation of Ampk/Sirt1/Pgc1α pathway during this adaptive fuel shift due to Lgr4 ablation. This study suggests that Lgr4 might serve as an adaptive regulator between glucose and lipid metabolism in skeletal muscle and reveals a potentially new regulator for a well-established adaptive network.

  11. Energy metabolism and nutritional status in hospitalized patients with lung cancer

    PubMed Central

    Takemura, Yumi; Sasaki, Masaya; Goto, Kenichi; Takaoka, Azusa; Ohi, Akiko; Kurihara, Mika; Nakanishi, Naoko; Nakano, Yasutaka; Hanaoka, Jun

    2016-01-01

    This study aimed to investigate the energy metabolism of patients with lung cancer and the relationship between energy metabolism and proinflammatory cytokines. Twenty-eight patients with lung cancer and 18 healthy controls were enrolled in this study. The nutritional status upon admission was analyzed using nutritional screening tools and laboratory tests. The resting energy expenditure and respiratory quotient were measured using indirect calorimetry, and the predicted resting energy expenditure was calculated using the Harris–Benedict equation. Energy expenditure was increased in patients with advanced stage disease, and there were positive correlations between measured resting energy expenditure/body weight and interleukin-6 levels and between measured resting energy expenditure/predicted resting energy expenditure and interleukin-6 levels. There were significant relationships between body mass index and plasma leptin or acylated ghrelin levels. However, the level of appetite controlling hormones did not affect dietary intake. There was a negative correlation between plasma interleukin-6 levels and dietary intake, suggesting that interleukin-6 plays a role in reducing dietary intake. These results indicate that energy expenditure changes significantly with lung cancer stage and that plasma interleukin-6 levels affect energy metabolism and dietary intake. Thus, nutritional management that considers the changes in energy metabolism is important in patients with lung cancer.

  12. URBAN EFFICIENT ENERGY EVALUATION IN HIGH RESOLUTION URBAN AREAS BY USING ADAPTED WRF-UCM AND MICROSYS CFD MODELS

    NASA Astrophysics Data System (ADS)

    San Jose, R.; Perez, J. L.; Gonzalez, R. M.

    2009-12-01

    Urban metabolism modeling has advanced substantially during the last years due to the increased detail in mesoscale urban parameterization in meteorological mesoscale models and CFD numerical tools. Recently the implementation of the “urban canopy model” (UCM) into the WRF mesoscale meteorological model has produced a substantial advance on the understanding of the urban atmospheric heat flux exchanges in the urban canopy. The need to optimize the use of heat energy in urban environment has produced a substantial increase in the detailed investigation of the urban heat flux exchanges. In this contribution we will show the performance of using a tool called MICROSYS (MICRO scale CFD modelling SYStem) which is an adaptation of the classical urban canopy model but on a high resolution environment by using a classical CFD approach. The energy balance in the urban system can be determined in a micrometeorologicl sense by considering the energy flows in and out of a control volume. For such a control volume reaching from ground to a certain height above buildings, the energy balance equation includes the net radiation, the anthropogenic heat flux, the turbulent sensible heat flux, the turbulent latent heat flux, the net storage change within the control volume, the net advected flux and other sources and sinks. We have applied the MICROSYS model to an area of 5 km x 5 km with 200 m spatial resolution by using the WRF-UCM (adapted and the MICROSYS CFD model. The anthropogenic heat flux has been estimated by using the Flanner M.G. (2009) database and detailed GIS information (50 m resolution) of Madrid city. The Storage energy has been estimated by calculating the energy balance according to the UCM procedure and implementing it into the MICROSYS tool. Results show that MICROSYS can be used as an energy efficient tool to estimate the energy balance of different urban areas and buildings.

  13. Neural control and adaptive neural forward models for insect-like, energy-efficient, and adaptable locomotion of walking machines

    PubMed Central

    Manoonpong, Poramate; Parlitz, Ulrich; Wörgötter, Florentin

    2013-01-01

    Living creatures, like walking animals, have found fascinating solutions for the problem of locomotion control. Their movements show the impression of elegance including versatile, energy-efficient, and adaptable locomotion. During the last few decades, roboticists have tried to imitate such natural properties with artificial legged locomotion systems by using different approaches including machine learning algorithms, classical engineering control techniques, and biologically-inspired control mechanisms. However, their levels of performance are still far from the natural ones. By contrast, animal locomotion mechanisms seem to largely depend not only on central mechanisms (central pattern generators, CPGs) and sensory feedback (afferent-based control) but also on internal forward models (efference copies). They are used to a different degree in different animals. Generally, CPGs organize basic rhythmic motions which are shaped by sensory feedback while internal models are used for sensory prediction and state estimations. According to this concept, we present here adaptive neural locomotion control consisting of a CPG mechanism with neuromodulation and local leg control mechanisms based on sensory feedback and adaptive neural forward models with efference copies. This neural closed-loop controller enables a walking machine to perform a multitude of different walking patterns including insect-like leg movements and gaits as well as energy-efficient locomotion. In addition, the forward models allow the machine to autonomously adapt its locomotion to deal with a change of terrain, losing of ground contact during stance phase, stepping on or hitting an obstacle during swing phase, leg damage, and even to promote cockroach-like climbing behavior. Thus, the results presented here show that the employed embodied neural closed-loop system can be a powerful way for developing robust and adaptable machines. PMID:23408775

  14. Neural control and adaptive neural forward models for insect-like, energy-efficient, and adaptable locomotion of walking machines.

    PubMed

    Manoonpong, Poramate; Parlitz, Ulrich; Wörgötter, Florentin

    2013-01-01

    Living creatures, like walking animals, have found fascinating solutions for the problem of locomotion control. Their movements show the impression of elegance including versatile, energy-efficient, and adaptable locomotion. During the last few decades, roboticists have tried to imitate such natural properties with artificial legged locomotion systems by using different approaches including machine learning algorithms, classical engineering control techniques, and biologically-inspired control mechanisms. However, their levels of performance are still far from the natural ones. By contrast, animal locomotion mechanisms seem to largely depend not only on central mechanisms (central pattern generators, CPGs) and sensory feedback (afferent-based control) but also on internal forward models (efference copies). They are used to a different degree in different animals. Generally, CPGs organize basic rhythmic motions which are shaped by sensory feedback while internal models are used for sensory prediction and state estimations. According to this concept, we present here adaptive neural locomotion control consisting of a CPG mechanism with neuromodulation and local leg control mechanisms based on sensory feedback and adaptive neural forward models with efference copies. This neural closed-loop controller enables a walking machine to perform a multitude of different walking patterns including insect-like leg movements and gaits as well as energy-efficient locomotion. In addition, the forward models allow the machine to autonomously adapt its locomotion to deal with a change of terrain, losing of ground contact during stance phase, stepping on or hitting an obstacle during swing phase, leg damage, and even to promote cockroach-like climbing behavior. Thus, the results presented here show that the employed embodied neural closed-loop system can be a powerful way for developing robust and adaptable machines. PMID:23408775

  15. Translational Targeted Proteomics Profiling of Mitochondrial Energy Metabolic Pathways in Mouse and Human Samples.

    PubMed

    Wolters, Justina C; Ciapaite, Jolita; van Eunen, Karen; Niezen-Koning, Klary E; Matton, Alix; Porte, Robert J; Horvatovich, Peter; Bakker, Barbara M; Bischoff, Rainer; Permentier, Hjalmar P

    2016-09-01

    Absolute measurements of protein abundance are important in the understanding of biological processes and the precise computational modeling of biological pathways. We developed targeted LC-MS/MS assays in the selected reaction monitoring (SRM) mode to quantify over 50 mitochondrial proteins in a single run. The targeted proteins cover the tricarboxylic acid cycle, fatty acid β-oxidation, oxidative phosphorylation, and the detoxification of reactive oxygen species. Assays used isotopically labeled concatemers as internal standards designed to target murine mitochondrial proteins and their human orthologues. Most assays were also suitable to quantify the corresponding protein orthologues in rats. After exclusion of peptides that did not pass the selection criteria, we arrived at SRM assays for 55 mouse, 52 human, and 51 rat proteins. These assays were optimized in isolated mitochondrial fractions from mouse and rat liver and cultured human fibroblasts and in total liver extracts from mouse, rat, and human. The developed proteomics approach is suitable for the quantification of proteins in the mitochondrial energy metabolic pathways in mice, rats, and humans as a basis for translational research. Initial data show that the assays have great potential for elucidating the adaptive response of human patients to mutations in mitochondrial proteins in a clinical setting.

  16. Cautious but committed: moving toward adaptive planning and operation strategies for renewable energy's wildlife implications.

    PubMed

    Köppel, Johann; Dahmen, Marie; Helfrich, Jennifer; Schuster, Eva; Bulling, Lea

    2014-10-01

    Wildlife planning for renewable energy must cope with the uncertainties of potential wildlife impacts. Unfortunately, the environmental policies which instigate renewable energy and those which protect wildlife are not coherently aligned-creating a green versus green dilemma. Thus, climate mitigation efforts trigger renewable energy development, but then face substantial barriers from biodiversity protection instruments and practices. This article briefly reviews wind energy and wildlife interactions, highlighting the lively debated effects on bats. Today, planning and siting of renewable energy are guided by the precautionary principle in an attempt to carefully address wildlife challenges. However, this planning attitude creates limitations as it struggles to negotiate the aforementioned green versus green dilemma. More adaptive planning and management strategies and practices hold the potential to reconcile these discrepancies to some degree. This adaptive approach is discussed using facets of case studies from policy, planning, siting, and operational stages of wind energy in Germany and the United States, with one case showing adaptive planning in action for solar energy as well. This article attempts to highlight the benefits of more adaptive approaches as well as the possible shortcomings, such as reduced planning security for renewable energy developers. In conclusion, these studies show that adaptive planning and operation strategies can be designed to supplement and enhance the precautionary principle in wildlife planning for green energy. PMID:25096164

  17. Cautious but committed: moving toward adaptive planning and operation strategies for renewable energy's wildlife implications.

    PubMed

    Köppel, Johann; Dahmen, Marie; Helfrich, Jennifer; Schuster, Eva; Bulling, Lea

    2014-10-01

    Wildlife planning for renewable energy must cope with the uncertainties of potential wildlife impacts. Unfortunately, the environmental policies which instigate renewable energy and those which protect wildlife are not coherently aligned-creating a green versus green dilemma. Thus, climate mitigation efforts trigger renewable energy development, but then face substantial barriers from biodiversity protection instruments and practices. This article briefly reviews wind energy and wildlife interactions, highlighting the lively debated effects on bats. Today, planning and siting of renewable energy are guided by the precautionary principle in an attempt to carefully address wildlife challenges. However, this planning attitude creates limitations as it struggles to negotiate the aforementioned green versus green dilemma. More adaptive planning and management strategies and practices hold the potential to reconcile these discrepancies to some degree. This adaptive approach is discussed using facets of case studies from policy, planning, siting, and operational stages of wind energy in Germany and the United States, with one case showing adaptive planning in action for solar energy as well. This article attempts to highlight the benefits of more adaptive approaches as well as the possible shortcomings, such as reduced planning security for renewable energy developers. In conclusion, these studies show that adaptive planning and operation strategies can be designed to supplement and enhance the precautionary principle in wildlife planning for green energy.

  18. Methodological and metabolic considerations in the study of caffeine-containing energy drinks.

    PubMed

    Shearer, Jane

    2014-10-01

    Caffeine-containing energy drinks are popular and widely available beverages. Despite large increases in consumption, studies documenting the nutritional, metabolic, and health implications of these beverages are limited. This review provides some important methodological considerations in the examination of these drinks and highlights their potential impact on the gastrointestinal system, liver, and metabolic health. The gastrointestinal system is important as it comes into contact with the highest concentration of energy drink ingredients and initiates a chain of events to communicate with peripheral tissues. Although energy drinks have diverse compositions, including taurine, ginseng, and carnitine, the most metabolically deleterious ingredients appear to be simple sugars (such as glucose and fructose) and caffeine. In combination, these last two ingredients have the greatest metabolic impact and potential influence on overall health.

  19. Impaired cellular energy metabolism contributes to bluetongue-virus-induced autophagy.

    PubMed

    Lv, Shuang; Xu, Qingyuan; Sun, Encheng; Zhang, Jikai; Wu, Donglai

    2016-10-01

    Bluetongue virus (BTV) has been found to trigger autophagy to favor its replication, but the underlying mechanisms have not been clarified. Here, we show that cellular energy metabolism is involved in BTV-induced autophagy. Cellular ATP synthesis was impaired by BTV1 infection, causing metabolic stress, which was responsible for activation of autophagy, since the conversion of LC3 and aggregation of GFP-LC3 (autophagy markers) were suppressed when infection-caused energy depletion was reversed via MP (metabolic substrate) treatment. The reduced virus yields with MP further supported this view. Overall, our findings suggest that BTV1-induced disruption of cellular energy metabolism contributes to autophagy, and this provides new insights into BTV-host interactions.

  20. Metabolic Noise, Vestigial Metabolites or the Raw Material of Ecological Adaptation? Opportunitistic Enzymes, Catalytic Promiscuity and the Evolution of chemodiversity in Nature (2010 JGI User Meeting)

    ScienceCinema

    Noel, Joseph

    2016-07-12

    Joseph Noel from the Salk Institute on "Metabolic Noise, Vestigial Metabolites or the Raw Material of Ecological Adaptation? Enzymes, Catalytic Promiscuity and the Evolution of Chemodiversity in Nature" on March 26, 2010 at the 5th Annual DOE JGI User Meeting

  1. Metabolic Noise, Vestigial Metabolites or the Raw Material of Ecological Adaptation? Opportunitistic Enzymes, Catalytic Promiscuity and the Evolution of chemodiversity in Nature (2010 JGI User Meeting)

    SciTech Connect

    Noel, Joseph

    2010-03-26

    Joseph Noel from the Salk Institute on "Metabolic Noise, Vestigial Metabolites or the Raw Material of Ecological Adaptation? Enzymes, Catalytic Promiscuity and the Evolution of Chemodiversity in Nature" on March 26, 2010 at the 5th Annual DOE JGI User Meeting

  2. Effects of Excess Energy Intake on Glucose and Lipid Metabolism in C57BL/6 Mice.

    PubMed

    Pang, Jing; Xi, Chao; Huang, Xiuqing; Cui, Ju; Gong, Huan; Zhang, Tiemei

    2016-01-01

    Excess energy intake correlates with the development of metabolic disorders. However, different energy-dense foods have different effects on metabolism. To compare the effects of a high-fat diet, a high-fructose diet and a combination high-fat/high-fructose diet on glucose and lipid metabolism, male C57BL/6 mice were fed with one of four different diets for 3 months: standard chow; standard diet and access to fructose water; a high fat diet; and a high fat diet with fructose water. After 3 months of feeding, the high-fat and the combined high-fat/high-fructose groups showed significantly increased body weights, accompanied by hyperglycemia and insulin resistance; however, the high-fructose group was not different from the control group. All three energy-dense groups showed significantly higher visceral fat weights, total cholesterol concentrations, and low-density lipoprotein cholesterol concentrations compared with the control group. Assays of basal metabolism showed that the respiratory quotient of the high-fat, the high-fructose, and the high-fat/high-fructose groups decreased compared with the control group. The present study confirmed the deleterious effect of high energy diets on body weight and metabolism, but suggested that the energy efficiency of the high-fructose diet was much lower than that of the high-fat diet. In addition, fructose supplementation did not worsen the detrimental effects of high-fat feeding alone on metabolism in C57BL/6 mice. PMID:26745179

  3. Effects of Excess Energy Intake on Glucose and Lipid Metabolism in C57BL/6 Mice

    PubMed Central

    Huang, Xiuqing; Cui, Ju; Gong, Huan; Zhang, Tiemei

    2016-01-01

    Excess energy intake correlates with the development of metabolic disorders. However, different energy-dense foods have different effects on metabolism. To compare the effects of a high-fat diet, a high-fructose diet and a combination high-fat/high-fructose diet on glucose and lipid metabolism, male C57BL/6 mice were fed with one of four different diets for 3 months: standard chow; standard diet and access to fructose water; a high fat diet; and a high fat diet with fructose water. After 3 months of feeding, the high-fat and the combined high-fat/high-fructose groups showed significantly increased body weights, accompanied by hyperglycemia and insulin resistance; however, the high-fructose group was not different from the control group. All three energy-dense groups showed significantly higher visceral fat weights, total cholesterol concentrations, and low-density lipoprotein cholesterol concentrations compared with the control group. Assays of basal metabolism showed that the respiratory quotient of the high-fat, the high-fructose, and the high-fat/high-fructose groups decreased compared with the control group. The present study confirmed the deleterious effect of high energy diets on body weight and metabolism, but suggested that the energy efficiency of the high-fructose diet was much lower than that of the high-fat diet. In addition, fructose supplementation did not worsen the detrimental effects of high-fat feeding alone on metabolism in C57BL/6 mice. PMID:26745179

  4. Tributyltin disrupts feeding and energy metabolism in the goldfish (Carassius auratus).

    PubMed

    Zhang, Jiliang; Sun, Ping; Yang, Fan; Kong, Tao; Zhang, Ruichen

    2016-06-01

    Tributyltin (TBT) can induce obesogen response. However, little is known about the adverse effects of TBT on food intake and energy metabolism. The present study was designed to investigate the effects of TBT, at environmental concentrations of 2.44 and 24.4 ng/L (1 and 10 ng/L as Sn), on feeding and energy metabolism in goldfish (Carassius auratus). After exposure for 54 d, TBT increased the weight gain and food intake in fish. The patterns of brain neuropeptide genes expression were in line with potential orexigenic effects, with increased expression of neuropeptide Y and apelin, and decreased expression of pro-opiomelanocortin, ghrelin, cocaine and amphetamine-regulated transcript, and corticotropin-releasing factor. Interestingly, the energy metabolism indicators (oxygen consumption, ammonia exertion and swimming activity) and the serum thyroid hormones were all significantly increased at the 2.44 ng/L TBT group in fish. However, no changes of energy metabolism indicators or a decrease of thyroid hormones was found at the 24.4 ng/L TBT group, which indicated a complex disrupting effect on metabolism of TBT. In short, TBT can alter feeding and energy metabolism in fish, which might promote the obesogenic responses. PMID:26971175

  5. Physiological Interactions of Nanoparticles in Energy Metabolism, Immune Function and Their Biosafety: A Review.

    PubMed

    Gomes, Antony; Sengupta, Jayeeta; Datta, Poulami; Ghosh, Sourav; Gomes, Aparna

    2016-01-01

    Nanoparticles owing to their unique physico-chemical properties have found its application in various biological processes, including metabolic pathways taking place within the body. This review tried to focus the involvement of nanoparticles in metabolic pathways and its influence in the energy metabolism, a fundamental criteria for the survival and physiological activity of living beings. The human body utilizes energy derived from food resources through a series of biochemical reactions involving several enzymes, co-factors (metals, non-metals, vitamins etc.) through the metabolic pathways (glycolysis, tri carboxylic acid cycle, oxidative phosphorylation, electron transport chain, etc.) in cellular system. Energy metabolism is also involved in the immune networking of the body for self defence and against pathophysiology. The immune system comprises of different cells and tissues, bioactive molecules for self defence and to fight against diseases. In the recent times, it has been reported through in vivo and in vitro studies that nanoparticles have direct influence on body's immune functions, and can modulate immunity by either suppressing or enhancing it. A comprehensive overview of nanoparticles and its involvement in immune function of the body in normal and pathophysiological conditions has been discussed. Considering these perspectives on nanoparticle interaction another important area which has been highlighted is the biosafety issues which are necessary before therapeutic applications. It is expected that development of physiologically compatible nanoparticles controlling energy metabolic processes, immune functions may show new dimension in the pathophysiology linked with energy and immunity.

  6. Physiological Interactions of Nanoparticles in Energy Metabolism, Immune Function and Their Biosafety: A Review.

    PubMed

    Gomes, Antony; Sengupta, Jayeeta; Datta, Poulami; Ghosh, Sourav; Gomes, Aparna

    2016-01-01

    Nanoparticles owing to their unique physico-chemical properties have found its application in various biological processes, including metabolic pathways taking place within the body. This review tried to focus the involvement of nanoparticles in metabolic pathways and its influence in the energy metabolism, a fundamental criteria for the survival and physiological activity of living beings. The human body utilizes energy derived from food resources through a series of biochemical reactions involving several enzymes, co-factors (metals, non-metals, vitamins etc.) through the metabolic pathways (glycolysis, tri carboxylic acid cycle, oxidative phosphorylation, electron transport chain, etc.) in cellular system. Energy metabolism is also involved in the immune networking of the body for self defence and against pathophysiology. The immune system comprises of different cells and tissues, bioactive molecules for self defence and to fight against diseases. In the recent times, it has been reported through in vivo and in vitro studies that nanoparticles have direct influence on body's immune functions, and can modulate immunity by either suppressing or enhancing it. A comprehensive overview of nanoparticles and its involvement in immune function of the body in normal and pathophysiological conditions has been discussed. Considering these perspectives on nanoparticle interaction another important area which has been highlighted is the biosafety issues which are necessary before therapeutic applications. It is expected that development of physiologically compatible nanoparticles controlling energy metabolic processes, immune functions may show new dimension in the pathophysiology linked with energy and immunity. PMID:27398436

  7. Differential remodelling of peroxisome function underpins the environmental and metabolic adaptability of diplonemids and kinetoplastids.

    PubMed

    Morales, Jorge; Hashimoto, Muneaki; Williams, Tom A; Hirawake-Mogi, Hiroko; Makiuchi, Takashi; Tsubouchi, Akiko; Kaga, Naoko; Taka, Hikari; Fujimura, Tsutomu; Koike, Masato; Mita, Toshihiro; Bringaud, Frédéric; Concepción, Juan L; Hashimoto, Tetsuo; Embley, T Martin; Nara, Takeshi

    2016-05-11

    The remodelling of organelle function is increasingly appreciated as a central driver of eukaryotic biodiversity and evolution. Kinetoplastids including Trypanosoma and Leishmania have evolved specialized peroxisomes, called glycosomes. Glycosomes uniquely contain a glycolytic pathway as well as other enzymes, which underpin the physiological flexibility of these major human pathogens. The sister group of kinetoplastids are the diplonemids, which are among the most abundant eukaryotes in marine plankton. Here we demonstrate the compartmentalization of gluconeogenesis, or glycolysis in reverse, in the peroxisomes of the free-living marine diplonemid, Diplonema papillatum Our results suggest that peroxisome modification was already under way in the common ancestor of kinetoplastids and diplonemids, and raise the possibility that the central importance of gluconeogenesis to carbon metabolism in the heterotrophic free-living ancestor may have been an important selective driver. Our data indicate that peroxisome modification is not confined to the kinetoplastid lineage, but has also been a factor in the success of their free-living euglenozoan relatives.

  8. Complementary substrate-selectivity of metabolic adaptive convergence in the lignocellulolytic performance by Dichomitus squalens

    PubMed Central

    Bak, Jin Seop

    2014-01-01

    The lignocellulolytic platform of the wood-decaying organism Dichomitus squalens is important for production of biodegradable elements; however, the system has not yet been fully characterized. In this study, using statistical target optimization, we analysed substrate selectivity based on a variety of D. squalens metabolic pathways using combined omics tools. As compared with the alkali-lignin (AL) programme, the rice straw (RS) programme has the advantage of multilayered signalling to regulate cellulolytic-related genes or to connect their pathways. The spontaneous instability of the AL programme was accelerated by harsh starvation as compared with that of the RS programme. Therefore, the AL programme converged on cellular maintenance much easier and more rapidly. However, regardless of external substrate/concentration type, the compensatory pattern of the major targets (especially peroxidases and growth regulators) was similar, functioning to maintain cellular homeostasis. Interestingly, ligninolytic-mediated targets under non-kaleidoscopic conditions were induced by a substrate-input-control, and especially this mechanism had an important effect on the early stages of the biodegradation process. This optimized target analysis could be used to understand lignocellulolytic network and to improve downstream efficiency. PMID:24894915

  9. Staphylococcus epidermidis: metabolic adaptation and biofilm formation in response to different oxygen concentrations.

    PubMed

    Uribe-Alvarez, Cristina; Chiquete-Félix, Natalia; Contreras-Zentella, Martha; Guerrero-Castillo, Sergio; Peña, Antonio; Uribe-Carvajal, Salvador

    2016-02-01

    Staphylococcus epidermidis has become a major health hazard. It is necessary to study its metabolism and hopefully uncover therapeutic targets. Cultivating S. epidermidis at increasing oxygen concentration [O2] enhanced growth, while inhibiting biofilm formation. Respiratory oxidoreductases were differentially expressed, probably to prevent reactive oxygen species formation. Under aerobiosis, S. epidermidis expressed high oxidoreductase activities, including glycerol-3-phosphate dehydrogenase, pyruvate dehydrogenase, ethanol dehydrogenase and succinate dehydrogenase, as well as cytochromes bo and aa3; while little tendency to form biofilms was observed. Under microaerobiosis, pyruvate dehydrogenase and ethanol dehydrogenase decreased while glycerol-3-phosphate dehydrogenase and succinate dehydrogenase nearly disappeared; cytochrome bo was present; anaerobic nitrate reductase activity was observed; biofilm formation increased slightly. Under anaerobiosis, biofilms grew; low ethanol dehydrogenase, pyruvate dehydrogenase and cytochrome bo were still present; nitrate dehydrogenase was the main terminal electron acceptor. KCN inhibited the aerobic respiratory chain and increased biofilm formation. In contrast, methylamine inhibited both nitrate reductase and biofilm formation. The correlation between the expression and/or activity or redox enzymes and biofilm-formation activities suggests that these are possible therapeutic targets to erradicate S. epidermidis.

  10. Differential remodelling of peroxisome function underpins the environmental and metabolic adaptability of diplonemids and kinetoplastids.

    PubMed

    Morales, Jorge; Hashimoto, Muneaki; Williams, Tom A; Hirawake-Mogi, Hiroko; Makiuchi, Takashi; Tsubouchi, Akiko; Kaga, Naoko; Taka, Hikari; Fujimura, Tsutomu; Koike, Masato; Mita, Toshihiro; Bringaud, Frédéric; Concepción, Juan L; Hashimoto, Tetsuo; Embley, T Martin; Nara, Takeshi

    2016-05-11

    The remodelling of organelle function is increasingly appreciated as a central driver of eukaryotic biodiversity and evolution. Kinetoplastids including Trypanosoma and Leishmania have evolved specialized peroxisomes, called glycosomes. Glycosomes uniquely contain a glycolytic pathway as well as other enzymes, which underpin the physiological flexibility of these major human pathogens. The sister group of kinetoplastids are the diplonemids, which are among the most abundant eukaryotes in marine plankton. Here we demonstrate the compartmentalization of gluconeogenesis, or glycolysis in reverse, in the peroxisomes of the free-living marine diplonemid, Diplonema papillatum Our results suggest that peroxisome modification was already under way in the common ancestor of kinetoplastids and diplonemids, and raise the possibility that the central importance of gluconeogenesis to carbon metabolism in the heterotrophic free-living ancestor may have been an important selective driver. Our data indicate that peroxisome modification is not confined to the kinetoplastid lineage, but has also been a factor in the success of their free-living euglenozoan relatives. PMID:27170716

  11. Metabolism

    MedlinePlus

    ... digestive system called enzymes break proteins down into amino acids, fats into fatty acids, and carbohydrates into simple ... for example, glucose). In addition to sugar, both amino acids and fatty acids can be used as energy ...

  12. Metabolism

    MedlinePlus

    ... digestive system called enzymes break proteins down into amino acids, fats into fatty acids, and carbohydrates into simple ... e.g., glucose). In addition to sugar, both amino acids and fatty acids can be used as energy ...

  13. Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

    PubMed

    Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

    2013-01-01

    Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities.

  14. Quantitative steps in the evolution of metabolic organisation as specified by the Dynamic Energy Budget theory.

    PubMed

    Kooijman, S A L M; Troost, T A

    2007-02-01

    The Dynamic Energy Budget (DEB) theory quantifies the metabolic organisation of organisms on the basis of mechanistically inspired assumptions. We here sketch a scenario for how its various modules, such as maintenance, storage dynamics, development, differentiation and life stages could have evolved since the beginning of life. We argue that the combination of homeostasis and maintenance induced the development of reserves and that subsequent increases in the maintenance costs came with increases of the reserve capacity. Life evolved from a multiple reserves - single structure system (prokaryotes, many protoctists) to systems with multiple reserves and two structures (plants) or single reserve and single structure (animals). This had profound consequences for the possible effects of temperature on rates. We present an alternative explanation for what became known as the down-regulation of maintenance at high growth rates in microorganisms; the density of the limiting reserve increases with the growth rate, and reserves do not require maintenance while structure-specific maintenance costs are independent of the growth rate. This is also the mechanism behind the variation of the respiration rate with body size among species. The DEB theory specifies reserve dynamics on the basis of the requirements of weak homeostasis and partitionability. We here present a new and simple mechanism for this dynamics which accounts for the rejection of mobilised reserve by busy maintenance/growth machinery. This module, like quite a few other modules of DEB theory, uses the theory of Synthesising Units; we review recent progress in this field. The plasticity of membranes that evolved in early eukaryotes is a major step forward in metabolic evolution; we discuss quantitative aspects of the efficiency of phagocytosis relative to the excretion of digestive enzymes to illustrate its importance. Some processes of adaptation and gene expression can be understood in terms of allocation

  15. Drivers of grazing livestock efficiency: how physiology, metabolism, experience, and adaptability influence productivity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beef cow efficiency, a century’s old debate, on what the criteria, certain phenotypic traits, and definition of an “efficient” cow really should be. However, we do know that energy utilization by the cow herd is proportionally large compared to the rest of the sector. This requirement accounts up to...

  16. Adaptation and failure of pancreatic β cells in murine models with different degrees of metabolic syndrome

    PubMed Central

    Medina-Gomez, Gema; Yetukuri, Laxman; Velagapudi, Vidya; Campbell, Mark; Blount, Margaret; Jimenez-Linan, Mercedes; Ros, Manuel; Orešič, Matej; Vidal-Puig, Antonio

    2009-01-01

    SUMMARY The events that contribute to the expansion of β-cell mass and enhanced β-cell function in insulin-resistant states have not been elucidated fully. Recently, we showed that β-cell adaptation failed dramatically in adult, insulin-resistant POKO mice, which contrasts with the appropriate expansion of β cells in their ob/ob littermates. Thus, we hypothesised that characterisation of the islets in these mouse models at an early age should provide a unique opportunity to: (1) identify mechanisms involved in sensing insulin resistance at the level of the β cells, (2) identify molecular effectors that contribute to increasing β-cell mass and function, and (3) distinguish primary events from secondary events that are more likely to be present at more advanced stages of diabetes. Our results define the POKO mouse as a model of early lipotoxicity. At 4 weeks of age, it manifests with inappropriate β-cell function and defects in proliferation markers. Other well-recognised pathogenic effectors that were observed previously in 16-week-old mice, such as increased reactive oxygen species (ROS), macrophage infiltration and endoplasmic reticulum (ER) stress, are also present in both young POKO and young ob/ob mice, indicating the lack of predictive power with regards to the severity of β-cell failure. Of interest, the relatively preserved lipidomic profile in islets from young POKO mice contrasted with the large changes in lipid composition and the differences in the chain length of triacylglycerols in the serum, liver, muscle and adipose tissue in adult POKO mice. Later lipotoxic insults in adult β cells contribute to the failure of the POKO β cell. Our results indicate that the rapid development of insulin resistance and β-cell failure in POKO mice makes this model a useful tool to study early molecular events leading to insulin resistance and β-cell failure. Furthermore, comparisons with ob/ob mice might reveal important adaptive mechanisms in β cells with

  17. Mapping determinants of variation in energy metabolism, respiration and flight in Drosophila.

    PubMed Central

    Montooth, Kristi L; Marden, James H; Clark, Andrew G

    2003-01-01

    We employed quantitative trait locus (QTL) mapping to dissect the genetic architecture of a hierarchy of functionally related physiological traits, including metabolic enzyme activity, metabolite storage, metabolic rate, and free-flight performance in recombinant inbred lines of Drosophila melanogaster. We identified QTL underlying variation in glycogen synthase, hexokinase, phosphoglucomutase, and trehalase activity. In each case variation mapped away from the enzyme-encoding loci, indicating that trans-acting regions of the genome are important sources of variation within the metabolic network. Individual QTL associated with variation in metabolic rate and flight performance explained between 9 and 35% of the phenotypic variance. Bayesian QTL analysis identified epistatic effects underlying variation in flight velocity, metabolic rate, glycogen content, and several metabolic enzyme activities. A region on the third chromosome was associated with expression of the glucose-6-phosphate branchpoint enzymes and with metabolic rate and flight performance. These genomic regions are of special interest as they may coordinately regulate components of energy metabolism with effects on whole-organism physiological performance. The complex biochemical network is encoded by an equally complex network of interacting genetic elements with potentially pleiotropic effects. This has important consequences for the evolution of performance traits that depend upon these metabolic networks. PMID:14573475

  18. Metabolic engineering and adaptive evolution for efficient production of D-lactic acid in Saccharomyces cerevisiae.

    PubMed

    Baek, Seung-Ho; Kwon, Eunice Y; Kim, Yong Hwan; Hahn, Ji-Sook

    2016-03-01

    There is an increasing demand for microbial production of lactic acid (LA) as a monomer of biodegradable poly lactic acid (PLA). Both optical isomers, D-LA and L-LA, are required to produce stereocomplex PLA with improved properties. In this study, we developed Saccharomyces cerevisiae strains for efficient production of D-LA. D-LA production was achieved by expressing highly stereospecific D-lactate dehydrogenase gene (ldhA, LEUM_1756) from Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293 in S. cerevisiae lacking natural LA production activity. D-LA consumption after glucose depletion was inhibited by deleting DLD1 encoding D-lactate dehydrogenase and JEN1 encoding monocarboxylate transporter. In addition, ethanol production was reduced by deleting PDC1 and ADH1 genes encoding major pyruvate decarboxylase and alcohol dehydrogenase, respectively, and glycerol production was eliminated by deleting GPD1 and GPD2 genes encoding glycerol-3-phosphate dehydrogenase. LA tolerance of the engineered D-LA-producing strain was enhanced by adaptive evolution and overexpression of HAA1 encoding a transcriptional activator involved in weak acid stress response, resulting in effective D-LA production up to 48.9 g/L without neutralization. In a flask fed-batch fermentation under neutralizing condition, our evolved strain produced 112.0 g/L D-LA with a yield of 0.80 g/g glucose and a productivity of 2.2 g/(L · h).

  19. Mass-Specific Metabolic Rate Influences Sperm Performance through Energy Production in Mammals.

    PubMed

    Tourmente, Maximiliano; Roldan, Eduardo R S

    2015-01-01

    Mass-specific metabolic rate, the rate at which organisms consume energy per gram of body weight, is negatively associated with body size in metazoans. As a consequence, small species have higher cellular metabolic rates and are able to process resources at a faster rate than large species. Since mass-specific metabolic rate has been shown to constrain evolution of sperm traits, and most of the metabolic activity of sperm cells relates to ATP production for sperm motility, we hypothesized that mass-specific metabolic rate could influence sperm energetic metabolism at the cellular level if sperm cells maintain the metabolic rate of organisms that generate them. We compared data on sperm straight-line velocity, mass-specific metabolic rate, and sperm ATP content from 40 mammalian species and found that the mass-specific metabolic rate positively influences sperm swimming velocity by (a) an indirect effect of sperm as the result of an increased sperm length, and (b) a direct effect independent of sperm length. In addition, our analyses show that species with higher mass-specific metabolic rate have higher ATP content per sperm and higher concentration of ATP per μm of sperm length, which are positively associated with sperm velocity. In conclusion, our results suggest that species with high mass-specific metabolic rate have been able to evolve both long and fast sperm. Moreover, independently of its effect on the production of larger sperm, the mass-specific metabolic rate is able to influence sperm velocity by increasing sperm ATP content in mammals.

  20. Adapting classical Systems Engineering to Department of Energy (DOE) needs

    SciTech Connect

    1996-07-01

    Rather than discuss Systems Engineering (SE) as applied by aerospace contractors to military programs, this document provides an adapted model well suited for use by DOE and represents 18 months of applying SE principles to the challenges faced by INEL. The real-life examples are drawn from INEL`s ongoing effort to integrate activities across the entire spectrum of within its Environmental Management program. Since the traditional SE process, with its initial focus on requirements identification and analysis, must be modified to provide tangible results in the short term, the adapted SE model starts with the external driver of ``reducing costs without increasing risks`` and performs an initial integration effort to identify high-potential, cost-saving opportunities. Elements from traditional alternatives development and analysis stages are used; then the adapted model cycles back to include more traditional requirements analysis activities. These cycles continue in an iterative manner, adding rigor and detail at each successive iteration, throughout the life-cycle of a program or project. Detailed lessons learned are included.

  1. Ontogeny of hepatic energy metabolism genes in mice as revealed by RNA-sequencing.

    PubMed

    Renaud, Helen J; Cui, Yue Julia; Lu, Hong; Zhong, Xiao-bo; Klaassen, Curtis D

    2014-01-01

    The liver plays a central role in metabolic homeostasis by coordinating synthesis, storage, breakdown, and redistribution of nutrients. Hepatic energy metabolism is dynamically regulated throughout different life stages due to different demands for energy during growth and development. However, changes in gene expression patterns throughout ontogeny for factors important in hepatic energy metabolism are not well understood. We performed detailed transcript analysis of energy metabolism genes during various stages of liver development in mice. Livers from male C57BL/6J mice were collected at twelve ages, including perinatal and postnatal time points (n = 3/age). The mRNA was quantified by RNA-Sequencing, with transcript abundance estimated by Cufflinks. One thousand sixty energy metabolism genes were examined; 794 were above detection, of which 627 were significantly changed during at least one developmental age compared to adult liver. Two-way hierarchical clustering revealed three major clusters dependent on age: GD17.5-Day 5 (perinatal-enriched), Day 10-Day 20 (pre-weaning-enriched), and Day 25-Day 60 (adolescence/adulthood-enriched). Clustering analysis of cumulative mRNA expression values for individual pathways of energy metabolism revealed three patterns of enrichment: glycolysis, ketogenesis, and glycogenesis were all perinatally-enriched; glycogenolysis was the only pathway enriched during pre-weaning ages; whereas lipid droplet metabolism, cholesterol and bile acid metabolism, gluconeogenesis, and lipid metabolism were all enriched in adolescence/adulthood. This study reveals novel findings such as the divergent expression of the fatty acid β-oxidation enzymes Acyl-CoA oxidase 1 and Carnitine palmitoyltransferase 1a, indicating a switch from mitochondrial to peroxisomal β-oxidation after weaning; as well as the dynamic ontogeny of genes implicated in obesity such as Stearoyl-CoA desaturase 1 and Elongation of very long chain fatty acids-like 3. These

  2. Ontogeny of Hepatic Energy Metabolism Genes in Mice as Revealed by RNA-Sequencing

    PubMed Central

    Renaud, Helen J.; Cui, Yue Julia; Lu, Hong; Zhong, Xiao-bo; Klaassen, Curtis D.

    2014-01-01

    The liver plays a central role in metabolic homeostasis by coordinating synthesis, storage, breakdown, and redistribution of nutrients. Hepatic energy metabolism is dynamically regulated throughout different life stages due to different demands for energy during growth and development. However, changes in gene expression patterns throughout ontogeny for factors important in hepatic energy metabolism are not well understood. We performed detailed transcript analysis of energy metabolism genes during various stages of liver development in mice. Livers from male C57BL/6J mice were collected at twelve ages, including perinatal and postnatal time points (n = 3/age). The mRNA was quantified by RNA-Sequencing, with transcript abundance estimated by Cufflinks. One thousand sixty energy metabolism genes were examined; 794 were above detection, of which 627 were significantly changed during at least one developmental age compared to adult liver. Two-way hierarchical clustering revealed three major clusters dependent on age: GD17.5–Day 5 (perinatal-enriched), Day 10–Day 20 (pre-weaning-enriched), and Day 25–Day 60 (adolescence/adulthood-enriched). Clustering analysis of cumulative mRNA expression values for individual pathways of energy metabolism revealed three patterns of enrichment: glycolysis, ketogenesis, and glycogenesis were all perinatally-enriched; glycogenolysis was the only pathway enriched during pre-weaning ages; whereas lipid droplet metabolism, cholesterol and bile acid metabolism, gluconeogenesis, and lipid metabolism were all enriched in adolescence/adulthood. This study reveals novel findings such as the divergent expression of the fatty acid β-oxidation enzymes Acyl-CoA oxidase 1 and Carnitine palmitoyltransferase 1a, indicating a switch from mitochondrial to peroxisomal β-oxidation after weaning; as well as the dynamic ontogeny of genes implicated in obesity such as Stearoyl-CoA desaturase 1 and Elongation of very long chain fatty acids-like 3

  3. Global transcriptome analysis of Atlantic cod (Gadus morhua) liver after in vivo methylmercury exposure suggests effects on energy metabolism pathways.

    PubMed

    Yadetie, Fekadu; Karlsen, Odd Andre; Lanzén, Anders; Berg, Karin; Olsvik, Pål; Hogstrand, Christer; Goksøyr, Anders

    2013-01-15

    Methylmercury (MeHg) is a widely distributed contaminant polluting many aquatic environments, with health risks to humans exposed mainly through consumption of seafood. The mechanisms of toxicity of MeHg are not completely understood. In order to map the range of molecular targets and gain better insights into the mechanisms of toxicity, we prepared Atlantic cod (Gadus morhua) 135k oligonucleotide arrays and performed global analysis of transcriptional changes in the liver of fish treated with MeHg (0.5 and 2 mg/kg of body weight) for 14 days. Inferring from the observed transcriptional changes, the main pathways significantly affected by the treatment were energy metabolism, oxidative stress response, immune response and cytoskeleton remodeling. Consistent with known effects of MeHg, many transcripts for genes in oxidative stress pathways such as glutathione metabolism and Nrf2 regulation of oxidative stress response were differentially regulated. Among the differentially regulated genes, there were disproportionate numbers of genes coding for enzymes involved in metabolism of amino acids, fatty acids and glucose. In particular, many genes coding for enzymes of fatty acid beta-oxidation were up-regulated. The coordinated effects observed on many transcripts coding for enzymes of energy pathways may suggest disruption of nutrient metabolism by MeHg. Many transcripts for genes coding for enzymes in the synthetic pathways of sulphur containing amino acids were also up-regulated, suggesting adaptive responses to MeHg toxicity. By this toxicogenomics approach, we were also able to identify many potential biomarker candidate genes for monitoring environmental MeHg pollution. These results based on changes on transcript levels, however, need to be confirmed by other methods such as proteomics.

  4. Environmental Endocrine Disruption of Energy Metabolism and Cardiovascular Risk

    PubMed Central

    Kirkley, Andrew G.; Sargis, Robert M.

    2014-01-01

    Rates of metabolic and cardiovascular diseases have increased at an astounding rate in recent decades. While poor diet and physical inactivity are central drivers, these lifestyle changes alone fail to fully account for the magnitude and rapidity of the epidemic. Thus, attention has turned to identifying novel risk factors, including the contribution of environmental endocrine disrupting chemicals. Epidemiological and preclinical data support a role for various contaminants in the pathogenesis of diabetes. In addition to the vascular risk associated with dysglycemia, emerging evidence implicates multiple pollutants in the pathogenesis of atherosclerosis and cardiovascular disease. Reviewed herein are studies linking endocrine disruptors to these key diseases that drive significant individual and societal morbidity and mortality. Identifying chemicals associated with metabolic and cardiovascular disease as well as their mechanisms of action is critical for developing novel treatment strategies and public policy to mitigate the impact of these diseases on human health. PMID:24756343

  5. [Optimization of energy metabolism in patients with chronic heart failure].

    PubMed

    Korzh, A N

    2010-01-01

    Nowadays particular interest of clinicians is attracted by metabolic therapy of patients with chronic heart failure (CHF). The objective of this study was to investigate the influence of complex therapy with addition of Vasonat on the dynamics of remodeling indexes of left ventricle and functional class of CHF on classification of NYHA. It has been shown that application of metabolic modulator Vasonat in addition to conventional therapy of CHF facilitated the clinical improvement and significant decline of functional class. Vasonat use resulted in the meaningful improvement of the contractive function of myocardium and increase of tolerance to the physical exercise. Moreover, high efficiency of Vasonat has been demonstrated in the control of the syndrome of oxidizing stress, by decrease in intensity of free-radical processes and activation of the antioxidant defense system. PMID:21265120

  6. The Effects of Cholera Toxin on Cellular Energy Metabolism

    PubMed Central

    Snider, Rachel M.; McKenzie, Jennifer R.; Kraft, Lewis; Kozlov, Eugene; Wikswo, John P.; Cliffel, David E.

    2010-01-01

    Multianalyte microphysiometry, a real-time instrument for simultaneous measurement of metabolic analytes in a microfluidic environment, was used to explore the effects of cholera toxin (CTx). Upon exposure of CTx to PC-12 cells, anaerobic respiration was triggered, measured as increases in acid and lactate production and a decrease in the oxygen uptake. We believe the responses observed are due to a CTx-induced activation of adenylate cyclase, increasing cAMP production and resulting in a switch to anaerobic respiration. Inhibitors (H-89, brefeldin A) and stimulators (forskolin) of cAMP were employed to modulate the CTx-induced cAMP responses. The results of this study show the utility of multianalyte microphysiometry to quantitatively determine the dynamic metabolic effects of toxins and affected pathways. PMID:22069603

  7. Changes in C-N metabolism under elevated CO2 and temperature in Indian mustard (Brassica juncea L.): an adaptation strategy under climate change scenario.

    PubMed

    Seth, Chandra Shekhar; Misra, Virendra

    2014-11-01

    The present study was performed to investigate the possible role of carbon (C) and nitrogen (N) metabolism in adaptation of Indian mustard (Brassica juncea L.) growing under ambient (370 ± 15 ppm) and elevated CO2 (700 ± 15 ppm), and jointly in elevated CO2 and temperature (30/22 °C for day/night). The key enzymes responsible for C-N metabolism were studied in different samples of Brassica juncea L. collected from ambient (AMB), elevated (ELE) and ELExT growth conditions. Total percent amount of C and N in leaves were particularly estimated to establish a clear understanding of aforesaid metabolism in plant adaptation. Furthermore, key morphological and physiological parameters such as plant height, leaf area index, dry biomass, net photosynthetic rate, stomatal conductance, transpiration, total protein and chlorophyll contents were also studied in relation to C/N metabolism. The results indicated that the C-metabolizing enzymes, such as (ribulose-1,5-bisphosphate carboxylase/oxygenase, phosphoenolpyruvate carboxylase, malate dehydrogenase, NAD-malic enzyme, NADP-malic enzyme and citrate synthase) and the N-metabolizing enzymes, such as (aspartate amino transferase, glutamine synthetase, nitrate reductase and nitrite reductase) showed significantly (P < 0.05) higher activities along with the aforesaid physiological and biochemical parameters in order of ELE > ELExT > AMB growth conditions. This is also evident by significant (P < 0.05) increase in percent contents of C and N in leaves as per said order. These findings suggested that improved performance of C-N metabolism could be a possible approach for CO2 assimilation and adaptation in Brassica juncea L. against elevated CO2 and temperature prevailing in climate change scenarios.

  8. Evidence for Cascades of Perturbation and Adaptation in the Metabolic Genes of Higher Termite Gut Symbionts

    PubMed Central

    Zhang, Xinning; Leadbetter, Jared R.

    2012-01-01

    ABSTRACT Termites and their gut microbes engage in fascinating dietary mutualis