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Sample records for affects energy metabolism

  1. Drugs affecting glycosaminoglycan metabolism.

    PubMed

    Ghiselli, Giancarlo; Maccarana, Marco

    2016-07-01

    Glycosaminoglycans (GAGs) are charged polysaccharides ubiquitously present at the cell surface and in the extracellular matrix. GAGs are crucial for cellular homeostasis, and their metabolism is altered during pathological processes. However, little consideration has been given to the regulation of the GAG milieu through pharmacological interventions. In this review, we provide a classification of small molecules affecting GAG metabolism based on their mechanism of action. Furthermore, we present evidence to show that clinically approved drugs affect GAG metabolism and that this could contribute to their therapeutic benefit. PMID:27217160

  2. DEPTOR in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance

    PubMed Central

    Caron, Alexandre; Labbé, Sébastien M.; Mouchiroud, Mathilde; Huard, Renaud; Richard, Denis

    2016-01-01

    We have recently demonstrated that specific overexpression of DEP-domain containing mTOR-interacting protein (DEPTOR) in the mediobasal hypothalamus (MBH) protects mice against high-fat diet-induced obesity, revealing DEPTOR as a significant contributor to energy balance regulation. On the basis of evidence that DEPTOR is expressed in the proopiomelanocortin (POMC) neurons of the MBH, the present study aimed to investigate whether these neurons mediate the metabolic effects of DEPTOR. Here, we report that specific DEPTOR overexpression in POMC neurons does not recapitulate any of the phenotypes observed when the protein was overexpressed in the MBH. Unlike the previous model, mice overexpressing DEPTOR only in POMC neurons 1) did not show differences in feeding behavior, 2) did not exhibit changes in locomotion activity and oxygen consumption, 3) did not show an improvement in systemic glucose metabolism, and 4) were not resistant to high-fat diet-induced obesity. These results support the idea that other neuronal populations are responsible for these phenotypes. Nonetheless, we observed a mild elevation in fasting blood glucose, insulin resistance, and alterations in liver glucose and lipid homeostasis in mice overexpressing DEPTOR in POMC neurons. Taken together, these results show that DEPTOR overexpression in POMC neurons does not affect energy balance regulation but could modulate metabolism through a brain-liver connection. PMID:27097662

  3. DEPTOR in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance.

    PubMed

    Caron, Alexandre; Labbé, Sébastien M; Mouchiroud, Mathilde; Huard, Renaud; Richard, Denis; Laplante, Mathieu

    2016-06-01

    We have recently demonstrated that specific overexpression of DEP-domain containing mTOR-interacting protein (DEPTOR) in the mediobasal hypothalamus (MBH) protects mice against high-fat diet-induced obesity, revealing DEPTOR as a significant contributor to energy balance regulation. On the basis of evidence that DEPTOR is expressed in the proopiomelanocortin (POMC) neurons of the MBH, the present study aimed to investigate whether these neurons mediate the metabolic effects of DEPTOR. Here, we report that specific DEPTOR overexpression in POMC neurons does not recapitulate any of the phenotypes observed when the protein was overexpressed in the MBH. Unlike the previous model, mice overexpressing DEPTOR only in POMC neurons 1) did not show differences in feeding behavior, 2) did not exhibit changes in locomotion activity and oxygen consumption, 3) did not show an improvement in systemic glucose metabolism, and 4) were not resistant to high-fat diet-induced obesity. These results support the idea that other neuronal populations are responsible for these phenotypes. Nonetheless, we observed a mild elevation in fasting blood glucose, insulin resistance, and alterations in liver glucose and lipid homeostasis in mice overexpressing DEPTOR in POMC neurons. Taken together, these results show that DEPTOR overexpression in POMC neurons does not affect energy balance regulation but could modulate metabolism through a brain-liver connection. PMID:27097662

  4. Do the noncaffeine ingredients of energy drinks affect metabolic responses to heavy exercise?

    PubMed

    Pettitt, Robert W; Niemeyer, JoLynne D; Sexton, Patrick J; Lipetzky, Amanda; Murray, Steven R

    2013-07-01

    Energy drinks (EDs) such as Red Bull (RB) are marketed to enhance metabolism. Secondary ingredients of EDs (e.g., taurine) have been purported to improve time trial performance; however, little research exists on how such secondary ingredients affect aerobic metabolism during heavy exercise. The purpose of this study was to investigate the effect of the secondary ingredients of RB on aerobic metabolism during and subsequent to heavy exercise. In double-blind, counterbalanced, and crossover fashion, 8 recreationally trained individuals completed a graded exercise test to determine the gas exchange threshold (GET). Subjects returned on 2 separate occasions and ingested either a 245 ml serving of RB or a control (CTRL) drink with the equivalent caffeine before engaging in two 10-minute constant-load cycling bouts, at an intensity equivalent to GET, with 3 minutes of rest between bouts. Accumulated liters of O2 (10 minutes) were higher for the first bout (17.1 ± 3.5 L) vs. the second bout (16.7 ± 3.5 L) but did not differ between drinks. Similarly, excess postexercise oxygen consumption was higher after the initial bout (RB mean, 2.6 ± 0.85 L; CTRL mean, 2.9 ± 0.90 L) vs. the second bout (RB mean, 1.5 ± 0.85 L; CTRL mean, 1.9 ± 0.87 L) but did not differ between drinks. No differences occurred between drinks for measures of heart rate or rating of perceived exertion. These results indicate that the secondary ingredients contained in a single serving of RB do not augment aerobic metabolism during or subsequent to heavy exercise. PMID:23037611

  5. Metabolic stressors and signals differentially affect energy allocation between reproduction and immune function.

    PubMed

    Carlton, Elizabeth D; Cooper, Candace L; Demas, Gregory E

    2014-11-01

    Most free-living animals have finite energy stores that they must allocate to different physiological and behavioral processes. In times of energetic stress, trade-offs in energy allocation among these processes may occur. The manifestation of trade-offs may depend on the source (e.g., glucose, lipids) and severity of energy limitation. In this study, we investigated energetic trade-offs between the reproductive and immune systems by experimentally limiting energy availability to female Siberian hamsters (Phodopus sungorus) with 2-deoxy-d-glucose, a compound that disrupts cellular utilization of glucose. We observed how glucoprivation at two levels of severity affected allocation to reproduction and immunity. Additionally, we treated a subset of these hamsters with leptin, an adipose hormone that provides a direct signal of available fat stores, in order to determine how increasing this signal of fat stores influences glucoprivation-induced trade-offs. We observed trade-offs between the reproductive and immune systems and that these trade-offs depended on the severity of energy limitation and exogenous leptin signaling. The majority of the animals experiencing mild glucoprivation entered anestrus, whereas leptin treatment restored estrous cycling in these animals. Surprisingly, virtually all animals experiencing more severe glucoprivation maintained normal estrous cycling throughout the experiment; however, exogenous leptin resulted in lower antibody production in this group. These data suggest that variation in these trade-offs may be mediated by shifts between glucose and fatty acid utilization. Collectively, the results of the present study highlight the context-dependent nature of these trade-offs, as trade-offs induced by the same metabolic stressor can manifest differently depending on its intensity. PMID:25125082

  6. Endothelial nitric oxide synthase (NOS) deficiency affects energy metabolism pattern in murine oxidative skeletal muscle.

    PubMed Central

    Momken, Iman; Fortin, Dominique; Serrurier, Bernard; Bigard, Xavier; Ventura-Clapier, Renée; Veksler, Vladimir

    2002-01-01

    Oxidative capacity of muscles correlates with capillary density and with microcirculation, which in turn depend on various regulatory factors, including NO generated by endothelial nitric oxide synthase (eNOS). To determine the role of eNOS in patterns of regulation of energy metabolism in various muscles, we studied mitochondrial respiration in situ in saponin-permeabilized fibres as well as the energy metabolism enzyme profile in the cardiac, soleus (oxidative) and gastrocnemius (glycolytic) muscles isolated from mice lacking eNOS (eNOS(-/-)). In soleus muscle, the absence of eNOS induced a marked decrease in both basal mitochondrial respiration without ADP (-32%; P <0.05) and maximal respiration in the presence of ADP (-29%; P <0.05). Furthermore, the eNOS(-/-) soleus muscle showed a decrease in total creatine kinase (-29%; P <0.05), citrate synthase (-31%; P <0.01), adenylate kinase (-27%; P <0.05), glyceraldehyde-3-phosphate dehydrogenase (-43%; P <0.01) and pyruvate kinase (-26%; P <0.05) activities. The percentage of myosin heavy chains I (slow isoform) was significantly increased from 24.3+/-1.5% in control to 30.1+/-1.1% in eNOS(-/-) soleus muscle ( P <0.05) at the expense of a slight non-significant decrease in the three other (fast) isoforms. Besides, eNOS(-/-) soleus showed a 28% loss of weight. Interestingly, we did not find differences in any parameters in cardiac and gastrocnemius muscles compared with respective controls. These results show that eNOS knockout has an important effect on muscle oxidative capacity as well on the activities of energy metabolism enzymes in oxidative (soleus) muscle. The absence of such effects in cardiac and glycolytic (gastrocnemius) muscle suggests a specific role for eNOS-produced NO in oxidative skeletal muscle. PMID:12123418

  7. Prepartum dietary energy intake affects metabolism and health during the periparturient period in primiparous and multiparous Holstein cows.

    PubMed

    Janovick, N A; Boisclair, Y R; Drackley, J K

    2011-03-01

    An experiment was conducted to determine the effect of prepartum plane of energy intake on metabolic profiles related to lipid metabolism and health in blood and liver. Primiparous (n=24) and multiparous (n=23) Holsteins were randomly assigned by expected date of parturition to 1 of 3 prepartum energy intakes. A high energy diet [1.62 Mcal of net energy for lactation (NE(L))/kg; 15% crude protein] was fed for either ad libitum intake or restricted intake to supply 150% (OVR) or 80% (RES) of energy requirements for dry cows in late gestation. To limit energy intake to 100% of National Research Council requirements at ad libitum intake, chopped wheat straw was included as 31.8% of dry matter for a control diet (CON; 1.21 Mcal of NE(L)/kg of dry matter; 14.2% crude protein). Regardless of parity group, OVR cows had greater concentrations of glucose, insulin, and leptin in blood prepartum compared with either CON or RES cows; however, dietary effects did not carry over to the postpartum period. Prepartum nonesterified fatty acids (NEFA) were lower in OVR cows compared with either CON or RES cows. Postpartum, however, OVR cows had evidence of greater mobilization of triacylglycerol (TAG) from adipose tissue as NEFA were higher than in CON or RES cows, especially within the first 10 d postpartum. Prepartum β-hydroxybutyrate (BHBA) was not affected by diet before parturition; however, within the first 10 d postpartum, OVR cows had greater BHBA than CON or RES cows. Prepartum diet did not affect liver composition prepartum; however, OVR cows had greater total lipid and TAG concentrations and lower glycogen postpartum than CON or RES cows. Frequency of ketosis and displaced abomasum was greater for OVR cows compared with CON or RES cows postpartum. Controlling or restricting prepartum energy intake yielded metabolic results that were strikingly similar both prepartum and postpartum, independent of parity group. The use of a bulky diet controlled prepartum energy intake in

  8. Deiodinase Knockdown during Early Zebrafish Development Affects Growth, Development, Energy Metabolism, Motility and Phototransduction

    PubMed Central

    Bagci, Enise; Heijlen, Marjolein; Vergauwen, Lucia; Hagenaars, An; Houbrechts, Anne M.; Esguerra, Camila V.; Blust, Ronny; Darras, Veerle M.; Knapen, Dries

    2015-01-01

    Thyroid hormone (TH) balance is essential for vertebrate development. Deiodinase type 1 (D1) and type 2 (D2) increase and deiodinase type 3 (D3) decreases local intracellular levels of T3, the most important active TH. The role of deiodinase-mediated TH effects in early vertebrate development is only partially understood. Therefore, we investigated the role of deiodinases during early development of zebrafish until 96 hours post fertilization at the level of the transcriptome (microarray), biochemistry, morphology and physiology using morpholino (MO) knockdown. Knockdown of D1+D2 (D1D2MO) and knockdown of D3 (D3MO) both resulted in transcriptional regulation of energy metabolism and (muscle) development in abdomen and tail, together with reduced growth, impaired swim bladder inflation, reduced protein content and reduced motility. The reduced growth and impaired swim bladder inflation in D1D2MO could be due to lower levels of T3 which is known to drive growth and development. The pronounced upregulation of a large number of transcripts coding for key proteins in ATP-producing pathways in D1D2MO could reflect a compensatory response to a decreased metabolic rate, also typically linked to hypothyroidism. Compared to D1D2MO, the effects were more pronounced or more frequent in D3MO, in which hyperthyroidism is expected. More specifically, increased heart rate, delayed hatching and increased carbohydrate content were observed only in D3MO. An increase of the metabolic rate, a decrease of the metabolic efficiency and a stimulation of gluconeogenesis using amino acids as substrates may have been involved in the observed reduced protein content, growth and motility in D3MO larvae. Furthermore, expression of transcripts involved in purine metabolism coupled to vision was decreased in both knockdown conditions, suggesting that both may impair vision. This study provides new insights, not only into the role of deiodinases, but also into the importance of a correct TH balance

  9. Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity.

    PubMed

    Caldeira da Silva, Camille C; Cerqueira, Fernanda M; Barbosa, Lívea F; Medeiros, Marisa H G; Kowaltowski, Alicia J

    2008-08-01

    Caloric restriction is the most effective non-genetic intervention to enhance lifespan known to date. A major research interest has been the development of therapeutic strategies capable of promoting the beneficial results of this dietary regimen. In this sense, we propose that compounds that decrease the efficiency of energy conversion, such as mitochondrial uncouplers, can be caloric restriction mimetics. Treatment of mice with low doses of the protonophore 2,4-dinitrophenol promotes enhanced tissue respiratory rates, improved serological glucose, triglyceride and insulin levels, decrease of reactive oxygen species levels and tissue DNA and protein oxidation, as well as reduced body weight. Importantly, 2,4-dinitrophenol-treated animals also presented enhanced longevity. Our results demonstrate that mild mitochondrial uncoupling is a highly effective in vivo antioxidant strategy, and describe the first therapeutic intervention capable of effectively reproducing the physiological, metabolic and lifespan effects of caloric restriction in healthy mammals. PMID:18505478

  10. Breakfast and exercise contingently affect postprandial metabolism and energy balance in physically active males.

    PubMed

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

    2013-08-01

    The present study examined the impact of breakfast and exercise on postprandial metabolism, appetite and macronutrient balance. A sample of twelve (blood variables n 11) physically active males completed four trials in a randomised, crossover design comprising a continued overnight fast followed by: (1) rest without breakfast (FR); (2) exercise without breakfast (FE); (3) breakfast consumption (1859 kJ) followed by rest (BR); (4) breakfast consumption followed by exercise (BE). Exercise was continuous, moderate-intensity running (expending approximately 2·9 MJ of energy). The equivalent time was spent sitting during resting trials. A test drink (1500 kJ) was ingested on all trials followed 90 min later by an ad libitum lunch. The difference between the BR and FR trials in blood glucose time-averaged AUC following test drink consumption approached significance (BR: 4·33 (SEM 0·14) v. FR: 4·75 (SEM 0·16) mmol/l; P=0·08); but it was not different between FR and FE (FE: 4·77 (SEM 0·14) mmol/l; P=0·65); and was greater in BE (BE: 4·97 (SEM 0·13) mmol/l) v. BR (P=0·012). Appetite following the test drink was reduced in BR v. FR (P=0·006) and in BE v. FE (P=0·029). Following lunch, the most positive energy balance was observed in BR and least positive in FE. Regardless of breakfast, acute exercise produced a less positive energy balance following ad libitum lunch consumption. Energy and fat balance is further reduced with breakfast omission. Breakfast improved the overall appetite responses to foods consumed later in the day, but abrogated the appetite-suppressive effect of exercise. PMID:23340006

  11. Evaluation of energy metabolism and calcium homeostasis in cells affected by Shwachman-Diamond syndrome

    PubMed Central

    Ravera, Silvia; Dufour, Carlo; Cesaro, Simone; Bottega, Roberta; Faleschini, Michela; Cuccarolo, Paola; Corsolini, Fabio; Usai, Cesare; Columbaro, Marta; Cipolli, Marco; Savoia, Anna; Degan, Paolo; Cappelli, Enrico

    2016-01-01

    Isomorphic mutation of the SBDS gene causes Shwachman-Diamond syndrome (SDS). SDS is a rare genetic bone marrow failure and cancer predisposition syndrome. SDS cells have ribosome biogenesis and their protein synthesis altered, which are two high-energy consuming cellular processes. The reported changes in reactive oxygen species production, endoplasmic reticulum stress response and reduced mitochondrial functionality suggest an energy production defect in SDS cells. In our work, we have demonstrated that SDS cells display a Complex IV activity impairment, which causes an oxidative phosphorylation metabolism defect, with a consequent decrease in ATP production. These data were confirmed by an increased glycolytic rate, which compensated for the energetic stress. Moreover, the signalling pathways involved in glycolysis activation also appeared more activated; i.e. we reported AMP-activated protein kinase hyper-phosphorylation. Notably, we also observed an increase in a mammalian target of rapamycin phosphorylation and high intracellular calcium concentration levels ([Ca2+]i), which probably represent new biochemical equilibrium modulation in SDS cells. Finally, the SDS cell response to leucine (Leu) was investigated, suggesting its possible use as a therapeutic adjuvant to be tested in clinical trials. PMID:27146429

  12. Evaluation of energy metabolism and calcium homeostasis in cells affected by Shwachman-Diamond syndrome.

    PubMed

    Ravera, Silvia; Dufour, Carlo; Cesaro, Simone; Bottega, Roberta; Faleschini, Michela; Cuccarolo, Paola; Corsolini, Fabio; Usai, Cesare; Columbaro, Marta; Cipolli, Marco; Savoia, Anna; Degan, Paolo; Cappelli, Enrico

    2016-01-01

    Isomorphic mutation of the SBDS gene causes Shwachman-Diamond syndrome (SDS). SDS is a rare genetic bone marrow failure and cancer predisposition syndrome. SDS cells have ribosome biogenesis and their protein synthesis altered, which are two high-energy consuming cellular processes. The reported changes in reactive oxygen species production, endoplasmic reticulum stress response and reduced mitochondrial functionality suggest an energy production defect in SDS cells. In our work, we have demonstrated that SDS cells display a Complex IV activity impairment, which causes an oxidative phosphorylation metabolism defect, with a consequent decrease in ATP production. These data were confirmed by an increased glycolytic rate, which compensated for the energetic stress. Moreover, the signalling pathways involved in glycolysis activation also appeared more activated; i.e. we reported AMP-activated protein kinase hyper-phosphorylation. Notably, we also observed an increase in a mammalian target of rapamycin phosphorylation and high intracellular calcium concentration levels ([Ca(2+)]i), which probably represent new biochemical equilibrium modulation in SDS cells. Finally, the SDS cell response to leucine (Leu) was investigated, suggesting its possible use as a therapeutic adjuvant to be tested in clinical trials. PMID:27146429

  13. Dietary arginine affects energy metabolism through polyamine turnover in juvenile Atlantic salmon (Salmo salar).

    PubMed

    Andersen, Synne M; Holen, Elisabeth; Aksnes, Anders; Rønnestad, Ivar; Zerrahn, Jens-Erik; Espe, Marit

    2013-12-14

    In the present study, quadruplicate groups of juvenile Atlantic salmon (Salmo salar) were fed plant protein-based diets with increasing arginine inclusions (range 28·8-37·4 g/kg DM) to investigate whether arginine supplementation affects growth and lipid accumulation through an elevated polyamine turnover. Dietary lysine was held at a constant concentration, just below the requirement. All other amino acids were balanced and equal in the diets. Arginine supplementation increased protein and fat accretion, without affecting the hepatosomatic or visceralsomatic indices. Dietary arginine correlated with putrescine in the liver (R 0·78, P= 0·01) and with ornithine in the muscle, liver and plasma (P= 0·0002, 0·003 and 0·0002, respectively). The mRNA of ornithine decarboxylase, the enzyme producing putrescine, was up-regulated in the white adipose tissue of fish fed the high-arginine inclusion compared with those fed the low-arginine diet. Concomitantly, spermidine/spermine-(N1)-acetyltransferase, the rate-limiting enzyme for polyamine turnover that consumes acetyl-CoA, showed an increased activity in the liver of fish fed the arginine-supplemented diets. In addition, lower acetyl-CoA concentrations were observed in the liver of fish fed the high-arginine diet, while ATP, which is used in the process of synthesising spermidine and spermine, did not show a similar trend. Gene expression of the rate-limiting enzyme for β-oxidation of long-chain fatty acids, carnitine palmitoyl transferase-1, was up-regulated in the liver of fish fed the high-arginine diet. Taken together, the data support that increased dietary arginine activates polyamine turnover and β-oxidation in the liver of juvenile Atlantic salmon and may act to improve the metabolic status of the fish. PMID:23656796

  14. Prepartal dietary energy level affects peripartal bovine blood neutrophil metabolic, antioxidant, and inflammatory gene expression.

    PubMed

    Zhou, Z; Bu, D P; Vailati Riboni, M; Khan, M J; Graugnard, D E; Luo, J; Cardoso, F C; Loor, J J

    2015-08-01

    During the dry period, cows can easily overconsume higher-grain diets, a scenario that could impair immune function during the peripartal period. Objectives were to investigate the effects of energy overfeeding on expression profile of genes associated with inflammation, lipid metabolism, and neutrophil function, in 12 multiparous Holstein cows (n=6/dietary group) fed control [CON, 1.34 Mcal/kg of dry matter (DM)] or higher-energy (HE, 1.62 Mcal/kg of DM) diets during the last 45 d of pregnancy. Blood was collected to evaluate 43 genes in polymorphonuclear neutrophil leukocytes (PMNL) isolated at -14, 7, and 14 d relative to parturition. We detected greater expression of inflammatory-related cytokines (IL1B, STAT3, NFKB1) and eicosanoid synthesis (ALOX5AP and PLA2G4A) in HE cows than in CON cows. Around parturition, all cows had a close balance in mRNA expression of the pro-inflammatory IL1B and the anti-inflammatory IL10, with greater expression of both in cows fed HE than CON. The expression of CCL2, LEPR, TLR4, IL6, and LTC4S was undetectable. Cows in the HE group had greater expression of genes involved in PMNL adhesion, motility, migration, and phagocytosis, which was similar to expression of genes related to the pro-inflammatory cytokine. This response suggests that HE cows experienced a chronic state of inflammation. The greater expression of G6PD in HE cows could have been associated with the greater plasma insulin, which would have diverted glucose to other tissues. Cows fed the HE diet also had greater expression of transcription factors involved in metabolism of long-chain fatty acids (PPARD, RXRA), suggesting that immune cells might be predisposed to use endogenous ligands such as nonesterified fatty acids available in the circulation when glucose is in high demand for milk synthesis. The lower overall expression of SLC2A1 postpartum than prepartum supports this suggestion. Targeting interleukin-1β signaling might be of value in terms of controlling

  15. Energy metabolism affects susceptibility of A. gambiae mosquitoes to Plasmodium infection

    PubMed Central

    Oliveira, Jose Henrique M.; Gonçalves, Renata L.S.; Oliveira, Giselle A.; Oliveira, Pedro L.; Oliveira, Marcus F.; Barillas-Mury, Carolina

    2011-01-01

    Previous studies showed that A. gambiae L35 females, which are refractory (R) to Plasmodium infection, express higher levels of genes involved in redox-metabolism and mitochondrial respiration than susceptible (S) G3 females. Our studies revealed that R females have reduced longevity, faster utilization of lipid reserves, impaired mitochondrial State-3 respiration, increased rate of mitochondrial electron leak and higher expression levels of several glycolytic enzyme genes. Furthermore, when State-3 respiration was reduced in S females by silencing expression of the adenine nucleotide translocator (ANT), hydrogen peroxide generation was higher and the mRNA levels of lactate dehydrogenase increased in the midgut, while the prevalence and intensity of P. berghei infection were significantly reduced. We conclude that there are broad metabolic differences between R and S An. gambiae mosquitoes that influence their susceptibility to Plasmodium infection. PMID:21320598

  16. Energy metabolism affects susceptibility of Anopheles gambiae mosquitoes to Plasmodium infection.

    PubMed

    Oliveira, Jose Henrique M; Gonçalves, Renata L S; Oliveira, Giselle A; Oliveira, Pedro L; Oliveira, Marcus F; Barillas-Mury, Carolina

    2011-06-01

    Previous studies showed that Anopheles gambiae L3-5 females, which are refractory (R) to Plasmodium infection, express higher levels of genes involved in redox-metabolism and mitochondrial respiration than susceptible (S) G3 females. Our studies revealed that R females have reduced longevity, faster utilization of lipid reserves, impaired mitochondrial state-3 respiration, increased rate of mitochondrial electron leak and higher expression levels of several glycolytic enzyme genes. Furthermore, when state-3 respiration was reduced in S females by silencing expression of the adenine nucleotide translocator (ANT), hydrogen peroxide generation was higher and the mRNA levels of lactate dehydrogenase increased in the midgut, while the prevalence and intensity of Plasmodium berghei infection were significantly reduced. We conclude that there are broad metabolic differences between R and S An. gambiae mosquitoes that influence their susceptibility to Plasmodium infection. PMID:21320598

  17. A Small Protein Associated with Fungal Energy Metabolism Affects the Virulence of Cryptococcus neoformans in Mammals.

    PubMed

    McClelland, Erin E; Ramagopal, Udupi A; Rivera, Johanna; Cox, James; Nakouzi, Antonio; Prabu, Moses M; Almo, Steven C; Casadevall, Arturo

    2016-09-01

    The pathogenic yeast Cryptococcus neoformans causes cryptococcosis, a life-threatening fungal disease. C. neoformans has multiple virulence mechanisms that are non-host specific, induce damage and interfere with immune clearance. Microarray analysis of C. neoformans strains serially passaged in mice associated a small gene (CNAG_02591) with virulence. This gene, hereafter identified as HVA1 (hypervirulence-associated protein 1), encodes a protein that has homologs of unknown function in plant and animal fungi, consistent with a conserved mechanism. Expression of HVA1 was negatively correlated with virulence and was reduced in vitro and in vivo in both mouse- and Galleria-passaged strains of C. neoformans. Phenotypic analysis in hva1Δ and hva1Δ+HVA1 strains revealed no significant differences in established virulence factors. Mice infected intravenously with the hva1Δ strain had higher fungal burden in the spleen and brain, but lower fungal burden in the lungs, and died faster than mice infected with H99W or the hva1Δ+HVA1 strain. Metabolomics analysis demonstrated a general increase in all amino acids measured in the disrupted strain and a block in the TCA cycle at isocitrate dehydrogenase, possibly due to alterations in the nicotinamide cofactor pool. Macrophage fungal burden experiments recapitulated the mouse hypervirulent phenotype of the hva1Δ strain only in the presence of exogenous NADPH. The crystal structure of the Hva1 protein was solved, and a comparison of structurally similar proteins correlated with the metabolomics data and potential interactions with NADPH. We report a new gene that modulates virulence through a mechanism associated with changes in fungal metabolism. PMID:27583447

  18. Gustatory Perception and Fat Body Energy Metabolism Are Jointly Affected by Vitellogenin and Juvenile Hormone in Honey Bees

    PubMed Central

    Wang, Ying; Brent, Colin S.; Fennern, Erin; Amdam, Gro V.

    2012-01-01

    Honey bees (Apis mellifera) provide a system for studying social and food-related behavior. A caste of workers performs age-related tasks: young bees (nurses) usually feed the brood and other adult bees inside the nest, while older bees (foragers) forage outside for pollen, a protein/lipid source, or nectar, a carbohydrate source. The workers' transition from nursing to foraging and their foraging preferences correlate with differences in gustatory perception, metabolic gene expression, and endocrine physiology including the endocrine factors vitellogenin (Vg) and juvenile hormone (JH). However, the understanding of connections among social behavior, energy metabolism, and endocrine factors is incomplete. We used RNA interference (RNAi) to perturb the gene network of Vg and JH to learn more about these connections through effects on gustation, gene transcripts, and physiology. The RNAi perturbation was achieved by single and double knockdown of the genes ultraspiracle (usp) and vg, which encode a putative JH receptor and Vg, respectively. The double knockdown enhanced gustatory perception and elevated hemolymph glucose, trehalose, and JH. We also observed transcriptional responses in insulin like peptide 1 (ilp1), the adipokinetic hormone receptor (AKHR), and cGMP-dependent protein kinase (PKG, or “foraging gene” Amfor). Our study demonstrates that the Vg–JH regulatory module controls changes in carbohydrate metabolism, but not lipid metabolism, when worker bees shift from nursing to foraging. The module is also placed upstream of ilp1, AKHR, and PKG for the first time. As insulin, adipokinetic hormone (AKH), and PKG pathways influence metabolism and gustation in many animals, we propose that honey bees have conserved pathways in carbohydrate metabolism and conserved connections between energy metabolism and gustatory perception. Thus, perhaps the bee can make general contributions to the understanding of food-related behavior and metabolic disorders. PMID

  19. 3-Bromopyruvate induces rapid human prostate cancer cell death by affecting cell energy metabolism, GSH pool and the glyoxalase system.

    PubMed

    Valenti, Daniela; Vacca, Rosa A; de Bari, Lidia

    2015-12-01

    3-bromopyruvate (3-BP) is an anti-tumour drug effective on hepatocellular carcinoma and other tumour cell types, which affects both glycolytic and mitochondrial targets, depleting cellular ATP pool. Here we tested 3-BP on human prostate cancer cells showing, differently from other tumour types, efficient ATP production and functional mitochondrial metabolism. We found that 3-BP rapidly induced cultured androgen-insensitive (PC-3) and androgen-responsive (LNCaP) prostate cancer cell death at low concentrations (IC(50) values of 50 and 70 μM, respectively) with a multimodal mechanism of action. In particular, 3-BP-treated PC-3 cells showed a selective, strong reduction of glyceraldeide 3-phosphate dehydrogenase activity, due to the direct interaction of the drug with the enzyme. Moreover, 3-BP strongly impaired both glutamate/malate- and succinate-dependent mitochondrial respiration, membrane potential generation and ATP synthesis, concomitant with the inhibition of respiratory chain complex I, II and ATP synthase activities. The drastic reduction of cellular ATP levels and depletion of GSH pool, associated with significant increase in cell oxidative stress, were found after 3-BP treatment of PC-3 cells. Interestingly, the activity of both glyoxalase I and II, devoted to the elimination of the cytotoxic methylglyoxal, was strongly inhibited by 3-BP. Both N-acetylcysteine and aminoguanidine, GSH precursor and methylglyoxal scavenger, respectively, prevented 3-BP-induced PC-3 cell death, showing that impaired cell antioxidant and detoxifying capacities are crucial events leading to cell death. The provided information on the multi-target cytotoxic action of 3-BP, finally leading to PC-3 cell necrosis, might be useful for future development of 3-BP as a therapeutic option for prostate cancer treatment. PMID:26530987

  20. 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

  1. Leptin: a possible metabolic signal affecting reproduction.

    PubMed

    Spicer, L J

    2001-11-01

    Since its discovery in 1994, leptin, a protein hormone synthesized and secreted by adipose tissue, has been shown to regulate feed intake in several species including sheep and pigs. Although a nimiety of information exists regarding the physiological role of leptin in rodents and humans, the regulation and action of leptin in domestic animals is less certain. Emerging evidence in several species indicates that leptin may also affect the hypothalamo-pituitary-gonadal axis. Leptin receptor mRNA is present in the anterior pituitary and hypothalamus of several species, including sheep. In rats, effects of leptin on GnRH, LH and FSH secretion have been inconsistent, with leptin exhibiting both stimulatory and inhibitory action in vivo and in vitro. Evidence to support direct action of leptin at the level of the gonad indicates that the leptin receptor and its mRNA are present in ovarian tissue of several species, including cattle. These leptin receptors are functional, since leptin inhibits insulin-induced steroidogenesis of both granulosa and thecal cells of cattle in vitro. Leptin receptor mRNA is also found in the testes of rodents. As with the ovary, these receptors are functional, at least in rats, since leptin inhibits hCG-induced testosterone secretion by Leydig cells in vitro. During pregnancy, placental production of leptin may be a major contributor to the increase in maternal leptin in primates but not rodents. However, in both primates and rodents, leptin receptors exist in placental tissues and may regulate metabolism of the fetal-placental unit. As specific leptin immunoassays are developed for domestic animals, in vivo associations may then be made among leptin, body energy stores, dietary energy intake and reproductive function. This may lead to a more definitive role of leptin in domestic animal reproduction. PMID:11872320

  2. Affective Disorders, Bone Metabolism, and Osteoporosis

    PubMed Central

    2013-01-01

    The nature of the relationship between affective disorders, bone mineral density (BMD), and bone metabolism is unresolved, although there is growing evidence that many medications used to treat affective disorders are associated with low BMD or alterations in neuroendocrine systems that influence bone turnover. The objective of this review is to describe the current evidence regarding the association of unipolar and bipolar depression with BMD and indicators of bone metabolism, and to explore potential mediating and confounding influences of those relationships. The majority of studies of unipolar depression and BMD indicate that depressive symptoms are associated with low BMD. In contrast, evidence regarding the relationship between bipolar depression and BMD is inconsistent. There is limited but suggestive evidence to support an association between affective disorders and some markers of bone turnover. Many medications used to treat affective disorders have effects on physiologic systems that influence bone metabolism, and these conditions are also associated with a range of health behaviors that can influence osteoporosis risk. Future research should focus on disentangling the pathways linking psychotropic medications and their clinical indications with BMD and fracture risk. PMID:23874147

  3. Interplay between oxidant species and energy metabolism.

    PubMed

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

    2016-08-01

    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

  4. 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

  5. Dietary energy sources affect the partition of body lipids and the hierarchy of energy metabolic pathways in growing pigs differing in feed efficiency.

    PubMed

    Gondret, F; Louveau, I; Mourot, J; Duclos, M J; Lagarrigue, S; Gilbert, H; van Milgen, J

    2014-11-01

    The use and partition of feed energy are key elements in productive efficiency of pigs. This study aimed to determine whether dietary energy sources affect the partition of body lipids and tissue biochemical pathways of energy use between pigs differing in feed efficiency. Forty-eight barrows (pure Large White) from two divergent lines selected for residual feed intake (RFI), a measure of feed efficiency, were compared. From 74 d to 132 ± 0.5 d of age, pigs (n = 12 by line and by diet) were offered diets with equal protein and ME contents. A low fat, low fiber diet (LF) based on cereals and a high fat, high fiber diet (HF) where vegetal oils and wheat straw were used to partially substitute cereals, were compared. Irrespective of diet, gain to feed was 10% better (P < 0.001), and carcass yield was greater (+2.3%; P < 0.001) in the low RFI compared with the high RFI line; the most-efficient line was also leaner (+3.2% for loin proportion in the carcass, P < 0.001). In both lines, ADFI and ADG were lower when pigs were fed the HF diet (-12.3% and -15%, respectively, relatively to LF diet; P < 0.001). Feeding the HF diet reduced the perirenal fat weight and backfat proportion in the carcass to the same extent in both lines (-27% on average; P < 0.05). Lipid contents in backfat and LM also declined (-5% and -19%, respectively; P < 0.05) in pigs offered the HF diet. The proportion of saturated fatty acids (FA) was lower, but the percentage of PUFA, especially the EFA C18:2 and C18:3, was greater (P < 0.001) in backfat of HF-fed pigs. In both lines, these changes were associated with a marked decrease (P < 0.001) in the activities of two lipogenic enzymes, the fatty acid synthase (FASN) and the malic enzyme, in backfat. For the high RFI line, the hepatic lipid content was greater (P < 0.05) in pigs fed the HF diet than in pigs fed the LF diet, despite a reduced FASN activity (-32%; P < 0.001). In both lines, the HF diet also led to lower glycogen content (-70%) and

  6. 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.

  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. Mammalian Sirtuins and Energy Metabolism

    PubMed Central

    Li, Xiaoling; Kazgan, Nevzat

    2011-01-01

    Sirtuins are highly conserved NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases that can extend the lifespan of several lower model organisms including yeast, worms and flies. The seven mammalian sirtuins, SIRT1 to SIRT7, have emerged as key metabolic sensors that directly link environmental signals to mammalian metabolic homeostasis and stress response. Recent studies have shed light on the critical roles of sirtuins in mammalian energy metabolism in response to nutrient signals. This review focuses on the involvement of two nuclear sirtuins, SIRT1 and SIRT6, and three mitochondrial sirtuins, SIRT3, SIRT4, and SIRT5, in regulation of diverse metabolic processes. PMID:21614150

  9. Influence of myristic acid supplementation on energy, fatty acid and calcium metabolism of sheep as affected by dietary calcium and forage : concentrate ratio.

    PubMed

    Machmüller, A; Kreuzer, M

    2005-08-01

    In a 6 x 6 Latin square arrangement, sheep of 41 kg body weight were fed myristic acid [C14:0; 50 g/kg dry matter (DM)] supplemented to two basal diets of forage : concentrate ratios of 1 : 1.5 and 1 : 0.5 and adjusted to dietary calcium (Ca) contents of either 4.2 or 9.0 g/kg DM (the latter only together with C14:0 supplementation). Various variables of energy, fatty acid and Ca metabolism were determined in combined digestibility and respiratory chamber measurements. With C14:0 addition the energy loss via the faeces increased (p < 0.05, post hoc test) without affecting energy digestibility of the complete diet. The apparent digestibility of supplemented C14:0 was higher (p < 0.01) with approximately 0.8 in the forage-based diet than in the concentrate-based diet (approximately 0.6). The elevated levels of plasma C14:0 were mainly accompanied by reduced C18:0 and C18:1 levels. The estimated apparent content of metabolizable energy (ME) of added C14:0 was either 24.5 MJ/kg (concentrate-based diet) or 32.1 MJ/kg (forage-based diet). Extra Ca equalized these differences between basal diets and ME contents amounted to 33.0 MJ/kg on average. As expected from corresponding slight shifts in energy metabolizability, the total efficiency of ME utilization increased (p < 0.1) with C14:0. The lower level of dietary Ca was still within the range recommended, but adding C14:0 to the concentrate-based diet reduced Ca retention in the body of the sheep from 0.9 to -0.1 g/day because of an impaired (p < 0.05, post hoc test) net Ca absorption, whereas no effect was found with the forage-based diet. With C14:0 addition, plasma total phosphorus (P) and serum calcitrol levels increased (p < 0.05, post hoc test) while Ca concentrations did not clearly reflect the reduced net Ca absorption. Increasing the dietary Ca content prevented adverse effects on Ca retention in the concentrate-based diet and improved Ca retention in the forage-based diet. In conclusion, the C14

  10. Energy metabolism in nuclear reprogramming.

    PubMed

    Folmes, Clifford D L; Nelson, Timothy J; Terzic, Andre

    2011-12-01

    Nuclear reprogramming with stemness factors enables resetting of somatic differentiated tissue back to the pluripotent ground state. Recent evidence implicates mitochondrial restructuring and bioenergetic plasticity as key components underlying execution of orchestrated dedifferentiation and derivation of induced pluripotent stem cells. Aerobic to anaerobic transition of somatic oxidative energy metabolism into a glycolytic metabotype promotes proficient reprogramming, establishing a novel regulator of acquired stemness. Metabolomic profiling has further identified specific metabolic remodeling traits defining lineage redifferentiation of pluripotent cells. Therefore, mitochondrial biogenesis and energy metabolism comprise a vital axis for biomarker discovery, intimately reflecting the molecular dynamics fundamental for the resetting and redirection of cell fate. PMID:22103608

  11. Energy metabolism in nuclear reprogramming

    PubMed Central

    Folmes, Clifford DL; Nelson, Timothy J; Terzic, Andre

    2012-01-01

    Nuclear reprogramming with stemness factors enables resetting of somatic differentiated tissue back to the pluripotent ground state. Recent evidence implicates mitochondrial restructuring and bioenergetic plasticity as key components underlying execution of orchestrated dedifferentiation and derivation of induced pluripotent stem cells. Aerobic to anaerobic transition of somatic oxidative energy metabolism into a glycolytic metabotype promotes proficient reprogramming, establishing a novel regulator of acquired stemness. Metabolomic profiling has further identified specific metabolic remodeling traits defining lineage redifferentiation of pluripotent cells. Therefore, mitochondrial biogenesis and energy metabolism comprise a vital axis for biomarker discovery, intimately reflecting the molecular dynamics fundamental for the resetting and redirection of cell fate. PMID:22103608

  12. Factors affecting metabolic syndrome by lifestyle

    PubMed Central

    Ki, Nam-Kyun; Lee, Hae-Kag; Cho, Jae-Hwan; Kim, Seon-Chil; Kim, Nak-Sang

    2016-01-01

    [Purpose] The aim of this study was to explore lifestyle factors in relation to metabolic syndrome so as to be able to utilize the results as baseline data for the furtherance of health-care and medical treatment. [Subjects and Methods] This study was conducted with patients who visited a health care center located in Seoul and had abdominal ultrasonography between 2 March 2013 and 28 February, 2014. Heights, weights, and blood pressures were measured by automatic devices. Three radiologists examined the patients using abdominal ultrasonography for gallstone diagnosis. The statuses of patients with regard to smoking, alcohol, coffee, and physical activities were explored for the lifestyle investigation. For investigating baseline demographics, we first used descriptive statistics. We then used the χ2 test to analyze lifestyles and gallstone prevalence with regard to the presence of metabolic syndrome. Lastly, logistic regression analysis was conducted to discover the risk factors of metabolic syndrome. [Results] For men, body mass index, maximum gallstone size, and waist circumference were revealed as risk factors for metabolic syndrome, in descending order of the degree of risk. For females, gallstone presence was the most significant risk factor, followed by waist circumference. [Conclusion] Metabolic disease mainly presents itself along with obesity, and we should become more focused on preventing and treating this disease. A large-scale prospective study is needed in the future, as the cause of nonalcoholic steatohepatitis remained unclear in this study. PMID:26957725

  13. Protein phosphatase 2A regulatory subunits affecting plant innate immunity, energy metabolism, and flowering time – joint functions among B'η subfamily members

    PubMed Central

    Kataya, Amr RA; Heidari, Behzad; Lillo, Cathrine

    2015-01-01

    Protein phosphatase 2A (PP2A) is a heterotrimeric complex comprising a catalytic, scaffolding, and regulatory subunit. The regulatory subunits are essential for substrate specificity and localization of the complex and are classified into B/B55, B', and B” non-related families in higher plants. In Arabidopsis thaliana, the close paralogs B'η, B'θ, B'γ, and B'ζ were further classified into a subfamily of B' called B'η. Here we present results that consolidate the evidence for a role of the B'η subfamily in regulation of innate immunity, energy metabolism and flowering time. Proliferation of the virulent Pseudomonas syringae in B'θ knockout mutant decreased in comparison with wild type plants. Additionally, B'θ knockout plants were delayed in flowering, and this phenotype was supported by high expression of FLC (FLOWERING LOCUS C). B'ζ knockout seedlings showed growth retardation on sucrose-free medium, indicating a role for B'ζ in energy metabolism. This work provides insight into functions of the B'η subfamily members, highlighting their regulation of shared physiological traits while localizing to distinct cellular compartments. PMID:26039486

  14. 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

  15. Interactions between dietary boron and thiamine affect lipid metabolism

    SciTech Connect

    Herbel, J.L.; Hunt, C.D. )

    1991-03-15

    An experiment was designed to test the hypothesis that dietary boron impacts upon the function of various coenzymes involved in energy metabolism. In a 2 {times} 7 factorially-arranged experiment, weanling, vitamin D{sub 3}-deprived rats were fed a ground corn-casein-corn oil based diet supplemented with 0 or 2 mg boron/kg and 50% of the requirement for thiamine (TM), riboflavin (RF), pantothenic acid (PA) or pyridoxine (PX); 0% for folic acid (FA) or nicotinic acid (NA). All vitamins were supplemented in adequate amounts in the control diet. At 8 weeks of age, the TM dietary treatment was the one most affected by supplemental dietary boron (SDB). In rats that were fed 50% TM, SDB increased plasma concentrations of triglyceride (TG) and activity of alanine transaminase (ALT), and the liver to body weight (L/B) ratio. However, in the SDB animals, adequate amounts of TM decreased the means of those variables to near that observed in non-SDB rats fed 50% TM. The findings suggest that an interaction between dietary boron and TM affects lipid metabolism.

  16. [Pathogenetic correction of metabolic disturbances in chronic liver affections].

    PubMed

    Romantsov, M G; Petrov, A Iu; Aleksandrova, L N; Sukhanov, D S; Kovalenko, A L

    2012-01-01

    The available drugs for the treatment of chronic liver affections (the adequate model is chronic hepatitis C) include agents of metabolic therapy, whose efficacy is not always enough, that required the search for original mitochondrial substrates on the basis of succinate. Such agents were composed as a pharmaceutical group named "Substrates of Energetic Metabolism" or "Substrate Antihypoxants". The review presents the description of the pharmacological effects of remaxole and cytoflavin, evident from lower levels of active metabolites of oxygen that increases the clinical efficacy of the therapy. Their role in the metabolic reactions in chronic liver affections is exclusive and rather actual. PMID:23700935

  17. Gut microbiome phenotypes driven by host genetics affect arsenic metabolism.

    PubMed

    Lu, Kun; Mahbub, Ridwan; Cable, Peter Hans; Ru, Hongyu; Parry, Nicola M A; Bodnar, Wanda M; Wishnok, John S; Styblo, Miroslav; Swenberg, James A; Fox, James G; Tannenbaum, Steven R

    2014-02-17

    Large individual differences in susceptibility to arsenic-induced diseases are well-documented and frequently associated with different patterns of arsenic metabolism. In this context, the role of the gut microbiome in directly metabolizing arsenic and triggering systemic responses in diverse organs raises the possibility that gut microbiome phenotypes affect the spectrum of metabolized arsenic species. However, it remains unclear how host genetics and the gut microbiome interact to affect the biotransformation of arsenic. Using an integrated approach combining 16S rRNA gene sequencing and HPLC-ICP-MS arsenic speciation, we demonstrate that IL-10 gene knockout leads to a significant taxonomic change of the gut microbiome, which in turn substantially affects arsenic metabolism. PMID:24490651

  18. Changes in lipid metabolism and β-adrenergic response of adipose tissues of periparturient dairy cows affected by an energy-dense diet and nicotinic acid supplementation.

    PubMed

    Kenéz, Á; Tienken, R; Locher, L; Meyer, U; Rizk, A; Rehage, J; Dänicke, S; Huber, K

    2015-08-01

    Dairy cattle will mobilize large amounts of body fat during early lactation as an effect of decreased lipogenesis and increased lipolysis. Regulation of lipid metabolism involves fatty acid synthesis from acetate and β-adrenergic-stimulated phosphorylation of hormone-sensitive lipase (HSL) and perilipin in adipocytes. Although basic mechanisms of mobilizing fat storage in transition cows are understood, we lack a sufficiently detailed understanding to declare the exact regulatory network of these in a broad range of dairy cattle. The objective of the present study was to quantify 1) protein abundance of fatty acid synthase (FAS), 2) extent of phosphorylation of HSL and perilipin in vivo, and 3) β-adrenergic stimulated lipolytic response of adipose tissues in vitro at different stages of the periparturient period. We fed 20 German Holstein cows an energy-dense or an energetically adequate diet prepartum and 0 or 24 g/d nicotinic acid (NA) supplementation. Biopsy samples of subcutaneous and retroperitoneal adipose tissue were obtained at d 42 prepartum (d -42) and at d 1, 21, and 100 postpartum (d +1, d +21, d +100, respectively). To assess β-adrenergic response, tissue samples were incubated with 1 μ isoproterenol for 90 min at 37°C. The NEFA and glycerol release, as well as HSL and perilipin phosphorylation, was measured as indicators of in vitro stimulated lipolysis. In addition, protein expression of FAS and extent of HSL and perilipin phosphorylation were measured in fresh, nonincubated samples. There was no effect of dietary energy density or NA on the observed variables. The extent of HSL and perilipin phosphorylation under isoproterenol stimulation was strongly correlated with the release of NEFA and glycerol, consistent with the functional link between β-adrenergic-stimulated protein phosphorylation and lipolysis. In the nonincubated samples, FAS protein expression was decreased at d +1 and d +21, whereas HSL and perilipin phosphorylation increased

  19. 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

  20. Environmental factors affecting pregnancy: endocrine disrupters, nutrients and metabolic pathways.

    PubMed

    Bazer, Fuller W; Wu, Guoyao; Johnson, Gregory A; Wang, Xiaoqiu

    2014-12-01

    Uterine adenogenesis, a unique post-natal event in mammals, is vulnerable to endocrine disruption by estrogens and progestins resulting in infertility or reduced prolificacy. The absence of uterine glands results in insufficient transport of nutrients into the uterine lumen to support conceptus development. Arginine, a component of histotroph, is substrate for production of nitric oxide, polyamines and agmatine and, with secreted phosphoprotein 1, it affects cytoskeletal organization of trophectoderm. Arginine is critical for development of the conceptus, pregnancy recognition signaling, implantation and placentation. Conceptuses of ungulates and cetaceans convert glucose to fructose which is metabolized via multiple pathways to support growth and development. However, high fructose corn syrup in soft drinks and foods may increase risks for metabolic disorders and increase insulin resistance in adults. Understanding endocrine disrupters and dietary substances, and novel pathways for nutrient metabolism during pregnancy can improve survival and growth, and prevent chronic metabolic diseases in offspring. PMID:25224489

  1. Marrow fat metabolism is linked to the systemic energy metabolism

    PubMed Central

    Lecka-Czernik, Beata

    2011-01-01

    Recent advances in understanding the role of bone in the systemic regulation of energy metabolism indicate that bone marrow cells, adipocytes and osteoblasts, are involved in this process. Marrow adipocytes store significant quantities of fat and produce adipokines, leptin and adiponectin, which are known for their role in the regulation of energy metabolism, whereas osteoblasts produce osteocalcin, a bone-specific hormone that has a potential to regulate insulin production in the pancreas and adiponectin production in fat tissue. Both osteoblasts and marrow adipocytes express insulin receptor and respond to insulin-sensitizing anti-diabetic TZDs in a manner, which tightly links bone with the energy metabolism system. Metabolic profile of marrow fat resembles that of both, white and brown fat, which is reflected by its plasticity in acquiring different functions including maintenance of bone micro-environment. Marrow fat responds to physiologic and pathologic changes in energy metabolism status by changing volume and metabolic activity. This review summarizes available information on the metabolic function of marrow fat and provides hypothesis that this fat depot may acquire multiple roles depending on the local and perhaps systemic demands. These functions may include a role in bone energy maintenance and endocrine activities to serve osteogenesis during bone remodeling and bone healing. PMID:21757043

  2. 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

  3. Metabolic crosstalk between choline/1-carbon metabolism and energy homeostasis.

    PubMed

    Zeisel, Steven H

    2013-03-01

    There are multiple identified mechanisms involved in energy metabolism, insulin resistance and adiposity, but there are here-to-fore unsuspected metabolic factors that also influence these processes. Studies in animal models suggest important links between choline/1-carbon metabolism and energy homeostasis. Rodents fed choline deficient diets become hypermetabolic. Mice with deletions in one of several different genes of choline metabolism have phenotypes that include increased metabolic rate, decreased body fat/lean mass ratio, increased insulin sensitivity, decreased ATP production by mitochondria, or decreased weight gain on a high fat diet. In addition, farmers have recognized that the addition of a metabolite of choline (betaine) to cattle and swine feed reduces body fat/lean mass ratio. Choline dietary intake in humans varies over a > three-fold range, and genetic variation exists that modifies individual requirements for this nutrient. Although there are some epidemiologic studies in humans suggesting a link between choline/1-carbon metabolism and energy metabolism, there have been no controlled studies in humans that were specifically designed to examine this relationship. PMID:23072856

  4. Metabolic crosstalk between choline/1-carbon metabolism and energy homeostasis

    PubMed Central

    Zeisel, Steven H.

    2013-01-01

    There are multiple identified mechanisms involved in energy metabolism, insulin resistance and adiposity, but there are here-to-fore unsuspected metabolic factors that also influence these processes. Studies in animal models suggest important links between choline/1-carbon metabolism and energy homeostasis. Rodents fed choline deficient diets become hypermetabolic. Mice with deletions in one of several different genes of choline metabolism have phenotypes that include increased metabolic rate, decreased body fat/lean mass ratio, increased insulin sensitivity, decreased ATP production by mitochondria, or decreased weight gain on a high fat diet. In addition, farmers have recognized that the addition of a metabolite of choline (betaine) to cattle and swine feed reduces body fat/lean mass ratio. Choline dietary intake in humans varies over a >three-fold range, and genetic variation exists that modifies individual requirements for this nutrient. Although there are some epidemiologic studies in humans suggesting a link between choline/1-carbon metabolism and energy metabolism, there have been no controlled studies in humans that were specifically designed to examine this relationship. PMID:23072856

  5. Glucagon regulation of energy metabolism.

    PubMed

    Heppner, Kristy M; Habegger, Kirk M; Day, Jonathan; Pfluger, Paul T; Perez-Tilve, Diego; Ward, Brian; Gelfanov, Vasily; Woods, Steve C; DiMarchi, Richard; Tschöp, Matthias

    2010-07-14

    Glucagon has long been known as a counter-regulatory hormone to insulin of fundamental importance to glucose homeostasis. Its prominent ability to stimulate glycogenolysis and gluconeogenesis, has historically cast this peptide as one hormone where the metabolic consequences of increasing blood glucose levels, especially in obesity, are viewed largely as being deleterious. This perspective may be changing in light of emerging data and reconsideration of historic studies, which suggest that glucagon has beneficial effects on body fat mass, food intake, and energy expenditure. In this review, we discuss the mechanisms of glucagon-mediated body weight regulation as well as possible novel therapeutic approaches in the treatment of obesity and glucose intolerance that may arise from these findings. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009. PMID:20381509

  6. 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

  7. How does metabolism affect cell death in cancer?

    PubMed

    Villa, Elodie; Ricci, Jean-Ehrland

    2016-07-01

    In cancer research, identifying a specificity of tumor cells compared with 'normal' proliferating cells for targeted therapy is often considered the Holy Grail for researchers and clinicians. Although diverse in origin, most cancer cells share characteristics including the ability to escape cell death mechanisms and the utilization of different methods of energy production. In the current paradigm, aerobic glycolysis is considered the central metabolic characteristic of cancer cells (Warburg effect). However, recent data indicate that cancer cells also show significant changes in other metabolic pathways. Indeed, it was recently suggested that Kreb's cycle, pentose phosphate pathway intermediates, and essential and nonessential amino acids have key roles. Renewed interest in the fact that cancer cells have to reprogram their metabolism in order to proliferate or resist treatment must take into consideration the ability of tumor cells to adapt their metabolism to the local microenvironment (low oxygen, low nutrients). This variety of metabolic sources might be either a strength, resulting in infinite possibilities for adaptation and increased ability to resist chemotherapy-induced death, or a weakness that could be targeted to kill cancer cells. Here, we discuss recent insights showing how energetic metabolism may regulate cell death and how this might be relevant for cancer treatment. PMID:26498911

  8. Characterizing the Network of Drugs and Their Affected Metabolic Subpathways

    PubMed Central

    Li, Jing; Han, Junwei; Wang, Shuyuan; Yao, Qianlan; Wang, Yingying; Zhang, Yunpeng; Zhang, Chunlong; Xu, Yanjun; Jiang, Wei; Li, Xia

    2012-01-01

    A fundamental issue in biology and medicine is illustration of the overall drug impact which is always the consequence of changes in local regions of metabolic pathways (subpathways). To gain insights into the global relationship between drugs and their affected metabolic subpathways, we constructed a drug–metabolic subpathway network (DRSN). This network included 3925 significant drug–metabolic subpathway associations representing drug dual effects. Through analyses based on network biology, we found that if drugs were linked to the same subpathways in the DRSN, they tended to share the same indications and side effects. Furthermore, if drugs shared more subpathways, they tended to share more side effects. We then calculated the association score by integrating drug-affected subpathways and disease-related subpathways to quantify the extent of the associations between each drug class and disease class. The results showed some close drug–disease associations such as sex hormone drugs and cancer suggesting drug dual effects. Surprisingly, most drugs displayed close associations with their side effects rather than their indications. To further investigate the mechanism of drug dual effects, we classified all the subpathways in the DRSN into therapeutic and non-therapeutic subpathways representing drug therapeutic effects and side effects. Compared to drug side effects, the therapeutic effects tended to work through tissue-specific genes and these genes tend to be expressed in the adrenal gland, liver and kidney; while drug side effects always occurred in the liver, bone marrow and trachea. Taken together, the DRSN could provide great insights into understanding the global relationship between drugs and metabolic subpathways. PMID:23112813

  9. Ionizing Radiation Impairs T Cell Activation by Affecting Metabolic Reprogramming

    PubMed Central

    Li, Heng-Hong; Wang, Yi-wen; Chen, Renxiang; Zhou, Bin; Ashwell, Jonathan D.; Fornace, Albert J.

    2015-01-01

    Ionizing radiation has a variety of acute and long-lasting adverse effects on the immune system. Whereas measureable effects of radiation on immune cell cytotoxicity and population change have been well studied in human and animal models, little is known about the functional alterations of the surviving immune cells after ionizing radiation. The objective of this study was to delineate the effects of radiation on T cell function by studying the alterations of T cell receptor activation and metabolic changes in activated T cells isolated from previously irradiated animals. Using a global metabolomics profiling approach, for the first time we demonstrate that ionizing radiation impairs metabolic reprogramming of T cell activation, which leads to substantial decreases in the efficiency of key metabolic processes required for activation, such as glucose uptake, glycolysis, and energy metabolism. In-depth understanding of how radiation impacts T cell function highlighting modulation of metabolism during activation is not only a novel approach to investigate the pivotal processes in the shift of T cell homeostasis after radiation, it also may lead to new targets for therapeutic manipulation in the combination of radiotherapy and immune therapy. Given that appreciable effects were observed with as low as 10 cGy, our results also have implications for low dose environmental exposures. PMID:26078715

  10. Discontinuous gas-exchange cycle characteristics are differentially affected by hydration state and energy metabolism in gregarious and solitary desert locusts.

    PubMed

    Talal, Stav; Ayali, Amir; Gefen, Eran

    2015-12-01

    The termination of discontinuous gas exchange cycles (DGCs) in severely dehydrated insects casts doubt on the generality of the hygric hypothesis, which posits that DGCs evolved as a water conservation mechanism. We followed DGC characteristics in the two density-dependent phases of the desert locust Schistocerca gregaria throughout exposure to an experimental treatment of combined dehydration and starvation stress, and subsequent rehydration. We hypothesized that, under stressful conditions, the more stress-resistant gregarious locusts would maintain DGCs longer than solitary locusts. However, we found no phase-specific variations in body water content, water loss rates (total and respiratory) or timing of stress-induced abolishment of DGCs. Likewise, locusts of both phases re-employed DGCs after ingesting comparable volumes of water when rehydrated. Despite comparable water management performances, the effect of exposure to stressful experimental conditions on DGC characteristics varied significantly between gregarious and solitary locusts. Interburst duration, which is affected by the ability to buffer CO2, was significantly reduced in dehydrated solitary locusts compared with gregarious locusts. Moreover, despite similar rehydration levels, only gregarious locusts recovered their initial CO2 accumulation capacity, indicating that cycle characteristics are affected by factors other than haemolymph volume. Haemolymph protein measurements and calculated respiratory exchange ratios suggest that catabolism of haemolymph proteins may contribute to a reduced haemolymph buffering capacity, and thus a compromised ability for CO2 accumulation, in solitary locusts. Nevertheless, DGC was lost at similar hydration states in the two phases, suggesting that DGCs are terminated as a result of inadequate oxygen supply to the tissues. PMID:26486365

  11. 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

  12. Fermentation and Hydrogen Metabolism Affect Uranium Reduction by Clostridia

    DOE PAGESBeta

    Gao, Weimin; Francis, Arokiasamy J.

    2013-01-01

    Previously, it has been shown that not only is uranium reduction under fermentation condition common among clostridia species, but also the strains differed in the extent of their capability and the pH of the culture significantly affected uranium(VI) reduction. In this study, using HPLC and GC techniques, metabolic properties of those clostridial strains active in uranium reduction under fermentation conditions have been characterized and their effects on capability variance of uranium reduction discussed. Then, the relationship between hydrogen metabolism and uranium reduction has been further explored and the important role played by hydrogenase in uranium(VI) and iron(III) reduction bymore » clostridia demonstrated. When hydrogen was provided as the headspace gas, uranium(VI) reduction occurred in the presence of whole cells of clostridia. This is in contrast to that of nitrogen as the headspace gas. Without clostridia cells, hydrogen alone could not result in uranium(VI) reduction. In alignment with this observation, it was also found that either copper(II) addition or iron depletion in the medium could compromise uranium reduction by clostridia. In the end, a comprehensive model was proposed to explain uranium reduction by clostridia and its relationship to the overall metabolism especially hydrogen (H 2 ) production.« less

  13. Fermentation and hydrogen metabolism affect uranium reduction by clostridia.

    PubMed

    Gao, Weimin; Francis, Arokiasamy J

    2013-01-01

    Previously, it has been shown that not only is uranium reduction under fermentation condition common among clostridia species, but also the strains differed in the extent of their capability and the pH of the culture significantly affected uranium(VI) reduction. In this study, using HPLC and GC techniques, metabolic properties of those clostridial strains active in uranium reduction under fermentation conditions have been characterized and their effects on capability variance of uranium reduction discussed. Then, the relationship between hydrogen metabolism and uranium reduction has been further explored and the important role played by hydrogenase in uranium(VI) and iron(III) reduction by clostridia demonstrated. When hydrogen was provided as the headspace gas, uranium(VI) reduction occurred in the presence of whole cells of clostridia. This is in contrast to that of nitrogen as the headspace gas. Without clostridia cells, hydrogen alone could not result in uranium(VI) reduction. In alignment with this observation, it was also found that either copper(II) addition or iron depletion in the medium could compromise uranium reduction by clostridia. In the end, a comprehensive model was proposed to explain uranium reduction by clostridia and its relationship to the overall metabolism especially hydrogen (H2) production. PMID:25937978

  14. Fermentation and Hydrogen Metabolism Affect Uranium Reduction by Clostridia

    PubMed Central

    Gao, Weimin; Francis, Arokiasamy J.

    2013-01-01

    Previously, it has been shown that not only is uranium reduction under fermentation condition common among clostridia species, but also the strains differed in the extent of their capability and the pH of the culture significantly affected uranium(VI) reduction. In this study, using HPLC and GC techniques, metabolic properties of those clostridial strains active in uranium reduction under fermentation conditions have been characterized and their effects on capability variance of uranium reduction discussed. Then, the relationship between hydrogen metabolism and uranium reduction has been further explored and the important role played by hydrogenase in uranium(VI) and iron(III) reduction by clostridia demonstrated. When hydrogen was provided as the headspace gas, uranium(VI) reduction occurred in the presence of whole cells of clostridia. This is in contrast to that of nitrogen as the headspace gas. Without clostridia cells, hydrogen alone could not result in uranium(VI) reduction. In alignment with this observation, it was also found that either copper(II) addition or iron depletion in the medium could compromise uranium reduction by clostridia. In the end, a comprehensive model was proposed to explain uranium reduction by clostridia and its relationship to the overall metabolism especially hydrogen (H2) production. PMID:25937978

  15. Black leaf streak disease affects starch metabolism in banana fruit.

    PubMed

    Saraiva, Lorenzo de Amorim; Castelan, Florence Polegato; Shitakubo, Renata; Hassimotto, Neuza Mariko Aymoto; Purgatto, Eduardo; Chillet, Marc; Cordenunsi, Beatriz Rosana

    2013-06-12

    Black leaf streak disease (BLSD), also known as black sigatoka, represents the main foliar disease in Brazilian banana plantations. In addition to photosynthetic leaf area losses and yield losses, this disease causes an alteration in the pre- and postharvest behavior of the fruit. The aim of this work was to investigate the starch metabolism of fruits during fruit ripening from plants infected with BLSD by evaluating carbohydrate content (i.e., starch, soluble sugars, oligosaccharides, amylose), phenolic compound content, phytohormones, enzymatic activities (i.e., starch phosphorylases, α- and β-amylase), and starch granules. The results indicated that the starch metabolism in banana fruit ripening is affected by BLSD infection. Fruit from infested plots contained unusual amounts of soluble sugars in the green stage and smaller starch granules and showed a different pattern of superficial degradation. Enzymatic activities linked to starch degradation were also altered by the disease. Moreover, the levels of indole-acetic acid and phenolic compounds indicated an advanced fruit physiological age for fruits from infested plots. PMID:23692371

  16. Stretching Your Energetic Budget: How Tendon Compliance Affects the Metabolic Cost of Running

    PubMed Central

    Uchida, Thomas K.; Hicks, Jennifer L.; Dembia, Christopher L.; Delp, Scott L.

    2016-01-01

    Muscles attach to bones via tendons that stretch and recoil, affecting muscle force generation and metabolic energy consumption. In this study, we investigated the effect of tendon compliance on the metabolic cost of running using a full-body musculoskeletal model with a detailed model of muscle energetics. We performed muscle-driven simulations of running at 2–5 m/s with tendon force–strain curves that produced between 1 and 10% strain when the muscles were developing maximum isometric force. We computed the average metabolic power consumed by each muscle when running at each speed and with each tendon compliance. Average whole-body metabolic power consumption increased as running speed increased, regardless of tendon compliance, and was lowest at each speed when tendon strain reached 2–3% as muscles were developing maximum isometric force. When running at 2 m/s, the soleus muscle consumed less metabolic power at high tendon compliance because the strain of the tendon allowed the muscle fibers to operate nearly isometrically during stance. In contrast, the medial and lateral gastrocnemii consumed less metabolic power at low tendon compliance because less compliant tendons allowed the muscle fibers to operate closer to their optimal lengths during stance. The software and simulations used in this study are freely available at simtk.org and enable examination of muscle energetics with unprecedented detail. PMID:26930416

  17. 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. PMID:26551690

  18. 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

  19. Intermediate Energy Metabolism of Leptospira

    PubMed Central

    Baseman, J. B.; Cox, C. D.

    1969-01-01

    Metabolic studies were performed on three representative serotypes of Leptospira: a water isolate designated B16 and two pathogenic serotypes, pomona and schueffneri. Examination of whole cells of B16 for their ability to oxidize various substrates revealed that oleate significantly stimulated oxygen uptake. The respiratory quotient of 0.7 implied that oleate was degraded to carbon dioxide and water. Other substrates, such as carbohydrates, alcohols, intermediates of the citric acid cycle, and short-chain acids, including selected amino acids, did not stimulate endogenous respiration of whole cells. No oxygen uptake could be measured when cell-free extracts were tested with the substrates used with whole cells. Enzymatic analyses of cell-free extracts of the three strains demonstrated enzymes of the citric acid cycle, enzymes of the glycolytic and pentose pathways, and the general acyl coenzyme A dehydrogenase required for β-oxidation of fatty acids. Strain B16 and the two pathogenic serotypes appeared to possess similar metabolic capabilities. Enzymatic data might also explain the apparent inability of B16 to oxidize other substrates; kinases necessary for activation of common nonphosphorylated compounds were not detected in leptospiral extracts. These findings emphasized the dependence of leptospiral growth upon long-chain fatty acids. PMID:5776541

  20. Absence of cumulus cells during in vitro maturation affects lipid metabolism in bovine oocytes.

    PubMed

    Auclair, Sylvain; Uzbekov, Rustem; Elis, Sébastien; Sanchez, Laura; Kireev, Igor; Lardic, Lionel; Dalbies-Tran, Rozenn; Uzbekova, Svetlana

    2013-03-15

    Cumulus cells (CC) surround the oocyte and are coupled metabolically through regulation of nutrient intake. CC removal before in vitro maturation (IVM) decreases bovine oocyte developmental competence without affecting nuclear meiotic maturation. The objective was to investigate the influence of CC on oocyte cytoplasmic maturation in relation to energy metabolism. IVM with either cumulus-enclosed (CEO) or -denuded (DO) oocytes was performed in serum-free metabolically optimized medium. Transmission electron microscopy revealed different distribution of membrane-bound vesicles and lipid droplets between metaphase II DO and CEO. By Nile Red staining, a significant reduction in total lipid level was evidenced in DO. Global transcriptomic analysis revealed differential expression of genes regulating energy metabolism, transcription, and translation between CEO and DO. By Western blot, fatty acid synthase (FAS) and hormone-sensitive phospholipase (HSL) proteins were detected in oocytes and in CC, indicating a local lipogenesis and lypolysis. FAS protein was significantly less abundant in DO that in CEO and more highly expressed in CC than in the oocytes. On the contrary, HSL protein was more abundant in oocytes than in CC. In addition, active Ser⁵⁶³-phosphorylated HSL was detected in the oocytes only after IVM, and its level was similar in CEO and DO. In conclusion, absence of CC during IVM affected lipid metabolism in the oocyte and led to suboptimal cytoplasmic maturation. Thus, CC may influence the oocyte by orienting the consumption of nutritive storage via regulation of local fatty acid synthesis and lipolysis to provide energy for maturation. PMID:23321473

  1. Multiple dietary supplements do not affect metabolic and cardiovascular health.

    PubMed

    Soare, Andreea; Weiss, Edward P; Holloszy, John O; Fontana, Luigi

    2013-09-01

    Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m2) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals. PMID:24036417

  2. Multiple dietary supplements do not affect metabolic and cardiovascular health

    PubMed Central

    Holloszy, John O.; Fontana, Luigi

    2014-01-01

    Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m2) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals. PMID:24659610

  3. Mitochondrial Energy Metabolism and Thyroid Cancers.

    PubMed

    Lee, Junguee; Chang, Joon Young; Kang, Yea Eun; Yi, Shinae; Lee, Min Hee; Joung, Kyong Hye; Kim, Kun Soon; Shong, Minho

    2015-06-01

    Primary thyroid cancers including papillary, follicular, poorly differentiated, and anaplastic carcinomas show substantial differences in biological and clinical behaviors. Even in the same pathological type, there is wide variability in the clinical course of disease progression. The molecular carcinogenesis of thyroid cancer has advanced tremendously in the last decade. However, specific inhibition of oncogenic pathways did not provide a significant survival benefit in advanced progressive thyroid cancer that is resistant to radioactive iodine therapy. Accumulating evidence clearly shows that cellular energy metabolism, which is controlled by oncogenes and other tumor-related factors, is a critical factor determining the clinical phenotypes of cancer. However, the role and nature of energy metabolism in thyroid cancer remain unclear. In this article, we discuss the role of cellular energy metabolism, particularly mitochondrial energy metabolism, in thyroid cancer. Determining the molecular nature of metabolic remodeling in thyroid cancer may provide new biomarkers and therapeutic targets that may be useful in the management of refractory thyroid cancers. PMID:26194071

  4. Energy Metabolism of Human Neutrophils during Phagocytosis

    PubMed Central

    Borregaard, Niels; Herlin, Troels

    1982-01-01

    Detailed quantitative studies were performed on the generation and utilization of energy by resting and phagocytosing human neutrophils. The ATP content was 1.9 fmol/cell, was constant during rest, and was not influenced by the presence or absence of glucose in the medium. The intracellular content of phosphocreatine was less than 0.2 fmol/cell. In the presence of glucose, ATP was generated almost exclusively from lactate produced from glucose taken up from the surrounding medium. The amount of lactate produced could account for 85% of the glucose taken up by the cells, and the intracellular glycosyl store, glycogen, was not drawn upon. The rate of ATP generation as calculated from the rate of lactate production was 1.3 fmol/cell/min. During phagocytosis, there was no measurable increase in glucose consumption or lactate production, and the ATP content fell rapidly to 0.8 fmol/cell. This disappearance of ATP was apparently irreversible since no corresponding increase in ADP or AMP was observed. It therefore appears that this phagocytosis-induced fall in ATP concentration represents all the extra energy utilized in human neutrophils in the presence of glucose. In the absence of glucose, the rate of ATP generation in the resting cell was considerably smaller, 0.75 fmol/cell per min, as calculated from the rate of glycolysis, which is sustained exclusively by glycogenolysis. Under this condition, however, phagocytosis induces significant enhancement of glycogenolysis and the rate of lactate production is increased by 60%, raising the rate of ATP generation to 1.2 fmol/cell per min. Nonetheless, the ATP content drops significantly from 1.9 to 1.0 fmol/cell. Neutrophils from patients with chronic granulomatous disease have the same rate of glycolysis and the same ATP content as normal cells, thus confirming that the defective respiration of these cells does not affect their energy metabolism. PMID:7107894

  5. Bone Remodeling and Energy Metabolism: New Perspectives

    PubMed Central

    de Paula, Francisco J. A.; Rosen, Clifford J.

    2013-01-01

    Bone mineral, adipose tissue and energy metabolism are interconnected by a complex and multilevel series of networks. Calcium and phosphorus are utilized for insulin secretion and synthesis of high energy compounds. Adipose tissue store lipids and cholecalciferol, which, in turn, can influence calcium balance and energy expenditure. Hormones long-thought to solely modulate energy and mineral homeostasis may influence adipocytic function. Osteoblasts are a target of insulin action in bone. Moreover, endocrine mediators, such as osteocalcin, are synthesized in the skeleton but regulate carbohydrate disposal and insulin secretion. Finally, osteoblasts and adipocytes originate from the same mesenchymal progenitor. The mutual crosstalk between osteoblasts and adipocytes within the bone marrow microenvironment plays a crucial role in bone remodeling. In the present review we provide an overview of the reciprocal control between bone and energy metabolism and its clinical implications. PMID:26273493

  6. 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

  7. Energy metabolism in neuroblastoma and Wilms tumor

    PubMed Central

    Aminzadeh, Sepideh; Vidali, Silvia; Sperl, Wolfgang; 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

  8. Epigallocatechin gallate affects glucose metabolism and increases fitness and lifespan in Drosophila melanogaster

    PubMed Central

    Wagner, Anika E.; Piegholdt, Stefanie; Rabe, Doerte; Baenas, Nieves; Schloesser, Anke; Eggersdorfer, Manfred; Stocker, Achim; Rimbach, Gerald

    2015-01-01

    In this study, we tested whether a standardized epigallocatechin-3-gallate (EGCG) rich green tea extract (comprising > 90% EGCG) affects fitness and lifespan as well as parameters of glucose metabolism and energy homeostasis in the fruit fly, Drosophila melanogaster. Following the application of the green tea extract a significant increase in the mean lifespan (+ 3.3 days) and the 50% survival (+ 4.3 days) as well as improved fitness was detected. These effects went along an increased expression of Spargel, the homolog of mammalian PGC1α, which has been reported to affect lifespan in flies. Intriguingly, in flies, treatment with the green tea extract decreased glucose concentrations, which were accompanied by an inhibition of α-amylase and α-glucosidase activity. Computational docking analysis proved the potential of EGCG to dock into the substrate binding pocket of α-amylase and to a greater extent into α-glucosidase. Furthermore, we demonstrate that EGCG downregulates insulin-like peptide 5 and phosphoenolpyruvate carboxykinase, major regulators of glucose metabolism, as well as the Drosophila homolog of leptin, unpaired 2. We propose that a decrease in glucose metabolism in connection with an upregulated expression of Spargel contribute to the better fitness and the extended lifespan in EGCG-treated flies. PMID:26375250

  9. Leptin expression affects metabolic rate in zebrafish embryos (D. rerio)

    PubMed Central

    Dalman, Mark R.; Liu, Qin; King, Mason D.; Bagatto, Brian; Londraville, Richard L.

    2013-01-01

    We used antisense morpholino oligonucleotide technology to knockdown leptin-(A) gene expression in developing zebrafish embryos and measured its effects on metabolic rate and cardiovascular function. Using two indicators of metabolic rate, oxygen consumption was significantly lower in leptin morphants early in development [<48 hours post-fertilization (hpf)], while acid production was significantly lower in morphants later in development (>48 hpf). Oxygen utilization rates in <48 hpf embryos and acid production in 72 hpf embryos could be rescued to that of wildtype embryos by recombinant leptin coinjected with antisense morpholino. Leptin is established to influence metabolic rate in mammals, and these data suggest leptin signaling also influences metabolic rate in fishes. PMID:23847542

  10. Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism.

    PubMed

    Abruzzese, Giselle Adriana; Heber, Maria Florencia; Ferreira, Silvana Rocio; Velez, Leandro Martin; Reynoso, Roxana; Pignataro, Omar Pedro; Motta, Alicia Beatriz

    2016-07-01

    Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS patients have high risk of developing fatty liver and steatosis. This study aimed to evaluate the role of prenatal hyperandrogenism in liver lipid metabolism and fatty liver development. Pregnant rats were hyperandrogenized with testosterone. At pubertal age, the prenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov) and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluated hepatic transferases, liver lipid content, the balance between lipogenesis and fatty acid oxidation pathway, oxidant/antioxidant balance and proinflammatory status. We also evaluated the general metabolic status through growth rate curve, basal glucose and insulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Although neither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidation pathways were altered. The PH groups also showed impaired oxidant/antioxidant balance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 and cyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenism generates both PHov and PHanov phenotypes with signs of liver alterations, imbalance in lipid metabolism and increased risk of developing metabolic syndrome. The anovulatory phenotype showed more alterations in liver lipogenesis and a more impaired balance of insulin and glucose metabolism, being more susceptible to the development of steatosis. PMID:27179108

  11. Nectar resource limitation affects butterfly flight performance and metabolism differently in intensive and extensive agricultural landscapes.

    PubMed

    Lebeau, Julie; Wesselingh, Renate A; Van Dyck, Hans

    2016-05-11

    Flight is an essential biological ability of many insects, but is energetically costly. Environments under rapid human-induced change are characterized by habitat fragmentation and may impose constraints on the energy income budget of organisms. This may, in turn, affect locomotor performance and willingness to fly. We tested flight performance and metabolic rates in meadow brown butterflies (Maniola jurtina) of two contrasted agricultural landscapes: intensively managed, nectar-poor (IL) versus extensively managed, nectar-rich landscapes (EL). Young female adults were submitted to four nectar treatments (i.e. nectar quality and quantity) in outdoor flight cages. IL individuals had better flight capacities in a flight mill and had lower resting metabolic rates (RMR) than EL individuals, except under the severest treatment. Under this treatment, RMR increased in IL individuals, but decreased in EL individuals; flight performance was maintained by IL individuals, but dropped by a factor 2.5 in EL individuals. IL individuals had more canalized (i.e. less plastic) responses relative to the nectar treatments than EL individuals. Our results show significant intraspecific variation in the locomotor and metabolic response of a butterfly to different energy income regimes relative to the landscape of origin. Ecophysiological studies help to improve our mechanistic understanding of the eco-evolutionary impact of anthropogenic environments on rare and widespread species. PMID:27147100

  12. 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. PMID:27148161

  13. 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

  14. Energy Metabolism and Human Dosimetry of Tritium

    SciTech Connect

    Galeriu, D.; Takeda, H.; Melintescu, A.; Trivedi, A

    2005-07-15

    In the frame of current revision of human dosimetry of {sup 14}C and tritium, undertaken by the International Commission of Radiological Protection, we propose a novel approach based on energy metabolism and a simple biokinetic model for the dynamics of dietary intake (organic {sup 14}C, tritiated water and Organically Bound Tritium-OBT). The model predicts increased doses for HTO and OBT comparing to ICRP recommendations, supporting recent findings.

  15. Natural toxins that affect plant amino acid metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A diverse range of natural compounds interfere with the synthesis and other aspects of amino acid metabolism. Some are amino acid analogues, but most are not. This review covers a number of specific natural phytotoxic compounds by molecular target site. Inhibition of glutamine synthetase is of part...

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

    PubMed

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

    2016-12-01

    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. PMID:27053249

  17. Circulating follistatin in relation to energy metabolism.

    PubMed

    Hansen, Jakob Schiøler; Plomgaard, Peter

    2016-09-15

    Recently, substantial evidence has emerged that the liver contributes significantly to the circulating levels of follistatin and that circulating follistatin is tightly regulated by the glucagon-to-insulin ratio. Both observations are based on investigations of healthy subjects. These novel findings challenge the present view of circulating follistatin in human physiology, being that circulating follistatin is a result of spill-over from para/autocrine actions in various tissues and cells. Follistatin as a liver-derived protein under the regulation of glucagon-to-insulin ratio suggests a relation to energy metabolism. In this narrative review, we attempt to reconcile the existing findings on circulating follistatin with the novel concept that circulating follistatin is a liver-derived molecule regulated by the glucagon-to-insulin ratio. The picture emerging is that conditions associated with elevated levels of circulating follistatin have a metabolic denominator with decreased insulin sensitivity and/or hyperglucagoneimia. PMID:27264073

  18. Deanol affects choline metabolism in peripheral tissues of mice.

    PubMed

    Haubrich, D R; Gerber, N H; Pflueger, A B

    1981-08-01

    Administration of 2-dimethylaminoethanol (deanol) to mice induced an increase in both the concentration and the rate of turnover of free choline in blood. Treatment with deanol also caused an increase in the concentration of choline in kidneys, and markedly inhibited the rates of oxidation and phosphorylation of intravenously administered [3H-methyl]choline. In the liver, deanol inhibited the rate of phosphorylation of [3H-methyl]choline, but did not inhibit its rate of oxidation or cause an increase in the level of free choline. These findings suggest that deanol increases the choline concentration in blood by inhibition of its metabolism in tissues. Deanol may ultimately produce its central cholinergic effects by inhibition of choline metabolism in peripheral tissues, causing free choline choline to accumulate in blood, enter the brain, and stimulate cholinergic receptors. PMID:7264671

  19. Scoparone affects lipid metabolism in primary hepatocytes using lipidomics.

    PubMed

    Zhang, Aihua; Qiu, Shi; Sun, Hui; Zhang, Tianlei; Guan, Yu; Han, Ying; Yan, Guangli; Wang, Xijun

    2016-01-01

    Lipidomics, which focuses on the global study of molecular lipids in biological systems, could provide valuable insights about disease mechanisms. In this study, we present a nontargeted lipidomics strategy to determine cellular lipid alterations after scoparone exposure in primary hepatocytes. Lipid metabolic profiles were analyzed by high-performance liquid chromatography coupled with time-of-flight mass spectrometry, and a novel imaging TransOmics tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. Chemometric and statistical analyses of the obtained lipid fingerprints revealed the global lipidomic alterations and tested the therapeutic effects of scoparone. Identification of ten proposed lipids contributed to the better understanding of the effects of scoparone on lipid metabolism in hepatocytes. The most striking finding was that scoparone caused comprehensive lipid changes, as represented by significant changes of the identificated lipids. The levels of identified PG(19:1(9Z)/14:0), PE(17:1(9Z)/0:0), PE(19:1(9Z)/0:0) were found to be upregulated in ethanol-induced group, whereas the levels in scoparone group were downregulated. Lipid metabolism in primary hepatocytes was changed significantly by scoparone treatment. We believe that this novel approach could substantially broaden the applications of high mass resolution mass spectrometry for cellular lipidomics. PMID:27306123

  20. Scoparone affects lipid metabolism in primary hepatocytes using lipidomics

    PubMed Central

    Zhang, Aihua; Qiu, Shi; Sun, Hui; Zhang, Tianlei; Guan, Yu; Han, Ying; Yan, Guangli; Wang, Xijun

    2016-01-01

    Lipidomics, which focuses on the global study of molecular lipids in biological systems, could provide valuable insights about disease mechanisms. In this study, we present a nontargeted lipidomics strategy to determine cellular lipid alterations after scoparone exposure in primary hepatocytes. Lipid metabolic profiles were analyzed by high-performance liquid chromatography coupled with time-of-flight mass spectrometry, and a novel imaging TransOmics tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. Chemometric and statistical analyses of the obtained lipid fingerprints revealed the global lipidomic alterations and tested the therapeutic effects of scoparone. Identification of ten proposed lipids contributed to the better understanding of the effects of scoparone on lipid metabolism in hepatocytes. The most striking finding was that scoparone caused comprehensive lipid changes, as represented by significant changes of the identificated lipids. The levels of identified PG(19:1(9Z)/14:0), PE(17:1(9Z)/0:0), PE(19:1(9Z)/0:0) were found to be upregulated in ethanol-induced group, whereas the levels in scoparone group were downregulated. Lipid metabolism in primary hepatocytes was changed significantly by scoparone treatment. We believe that this novel approach could substantially broaden the applications of high mass resolution mass spectrometry for cellular lipidomics. PMID:27306123

  1. Environmental factors affecting indole metabolism under anaerobic conditions

    SciTech Connect

    Madsen, E.L.; Francis, A.J.; Bollag, J.M.

    1988-01-01

    The influence of physiological and environmental factors on the accumulation of oxindole during anaerobic indole metabolism was investigated by high-performance liquid chromatography. Under methanogenic conditions, indole was temporarily converted to oxindole in stoichiometric amounts in media inoculated with three freshwater sediments and an organic soil. In media inoculated with methanogenic sewage sludge, the modest amounts of oxindole detected at 35/sup 0/C reached higher concentrations and persisted longer when the incubation temperature was decreased from 35 to 15/sup 0/C. Also, decreasing the concentration of sewage sludge used as an inoculum from 50 to 1% caused an increase in the accumulation of oxindole from 10 to 75% of the indole added. Under denitrifying conditions, regardless of the concentration or source of the inoculum, oxindole appeared in trace amounts but did not accumulate during indole metabolism. In addition, denitrifying consortia which previously metabolized indole degraded oxindole with no lag period. Our data suggest that oxindole accumulation under methanogenic, but not under denitrifying conditions is caused by differences between relative rates of oxindole production and destruction.

  2. 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

  3. Glycolysis in energy metabolism during seizures.

    PubMed

    Yang, Heng; Wu, Jiongxing; Guo, Ren; Peng, Yufen; Zheng, Wen; Liu, Ding; Song, Zhi

    2013-05-15

    Studies have shown that glycolysis increases during seizures, and that the glycolytic metabolite lactic acid can be used as an energy source. However, how lactic acid provides energy for seizures and how it can participate in the termination of seizures remains unclear. We reviewed possible mechanisms of glycolysis involved in seizure onset. Results showed that lactic acid was involved in seizure onset and provided energy at early stages. As seizures progress, lactic acid reduces the pH of tissue and induces metabolic acidosis, which terminates the seizure. The specific mechanism of lactic acid-induced acidosis involves several aspects, which include lactic acid-induced inhibition of the glycolytic enzyme 6-diphosphate kinase-1, inhibition of the N-methyl-D-aspartate receptor, activation of the acid-sensitive 1A ion channel, strengthening of the receptive mechanism of the inhibitory neurotransmitter γ-minobutyric acid, and changes in the intra- and extracellular environment. PMID:25206426

  4. Endocrine regulation of energy metabolism by the skeleton

    PubMed Central

    Lee, Na Kyung; Sowa, Hideaki; Hinoi, Eiichi; Ferron, Mathieu; Ahn, Jong Deok; Confavreux, Cyrille; Dacquin, Romain; Mee, Patrick J.; McKee, Marc D.; Jung, Dae Young; Zhang, Zhiyou; Kim, Jason K.; Mauvais-Jarvis, Franck; Ducy, Patricia; Karsenty, Gerard

    2007-01-01

    SUMMARY The regulation of bone remodeling by an adipocyte-derived hormone implies that bone may exert a feedback control of energy homeostasis. To test this hypothesis we looked for genes expressed in osteoblasts, encoding signaling molecules and affecting energy metabolism. We show here that mice lacking the protein tyrosine phosphatase OST-PTP are hypoglycemic and protected from obesity and glucose intolerance because of an increase in β-cell proliferation, insulin secretion and insulin sensitivity. In contrast, mice lacking the osteoblast-secreted molecule osteocalcin display decreased β-cell proliferation, glucose intolerance and insulin resistance. Removing one Osteocalcin allele from OST-PTP-deficient mice corrects their metabolic phenotype. Ex vivo, osteocalcin can stimulate CyclinD1 and Insulin expression in β-cells and Adiponectin, an insulin-sensitizing adipokine, in adipocytes; in vivo osteocalcin can improve glucose tolerance. By revealing that the skeleton exerts an endocrine regulation of sugar homeostasis this study expands the biological importance of this organ and our understanding of energy metabolism. PMID:17693256

  5. Alteration of energy metabolism gene expression in cumulus cells affects oocyte maturation via MOS-mitogen-activated protein kinase pathway in dairy cows with an unfavorable "Fertil-" haplotype of one female fertility quantitative trait locus.

    PubMed

    Brisard, Daphné; Desmarchais, Alice; Touzé, Jean-Luc; Lardic, Lionel; Freret, Sandrine; Elis, Sebastien; Nuttinck, Fabienne; Camous, Sylvaine; Dupont, Joelle; Uzbekova, Svetlana

    2014-03-01

    Prim'Holstein heifers selected for the "Fertil-" homozygous haplotype of QTL-Female-Fert ility-BTA3 showed a greater rate of early pregnancy failure and slower embryo development after IVM suggesting lower oocyte quality than those selected for "Fertile+". We aimed to ascertain intrafollicular factors related to lower oocyte quality in "Fertil-" cows. Analysis of individual oocytes showed meiotic progression delay in "Fertil-" compared with "Fertil+" dairy cows after in vivo maturation and IVM (P < 0.05). Expression of several genes localized to QTL-F-Fert-BTA3 or related to meiosis and mitogen-activated protein kinase pathway was analyzed in individual metaphase-II oocytes using reverse transcription- real-time polymerase chain reaction. Energy metabolism, apoptosis, extracellular matrix, and QTL-F-Fert-BTA3 genes were analyzed in surrounding cumulus cells (CC). In vivo, a significant decrease in prostaglandin synthase PTGES1 and PTGS2 expression coupled with lower PTGS2 protein abundance in CC and reduced expression of MOS in enclosed metaphase-II oocytes from "Fertil-" cows was observed. IVM strongly deregulated gene expression in CC and in oocytes compared with in vivo; nevertheless, differential expression of several genes including PEX19, NAMPT and MOS was observed between the two haplotypes. During IVM, PTGS2 activity inhibitor NS398 (50 μM) led to lower expression of fatty acid synthase (FASN) in CC and of MOS in treated metaphase-II oocytes. Using immunofluorescence, MOS protein was localized to a midbody-like contractile ring separating the polar body from the ooplasm, suggesting a role in the terminal stage of oocyte maturation. Our results suggest that factors involved in prostaglandin synthesis and lipid metabolism in CC could impair oocyte maturation, and might be involved in the reduced fertility of "Fertil-" cows. PMID:24377862

  6. Bone: from a reservoir of minerals to a regulator of energy metabolism.

    PubMed

    Confavreux, Cyrille B

    2011-04-01

    Besides locomotion, organ protection, and calcium-phosphorus homeostasis, the three classical functions of the skeleton, bone remodeling affects energy metabolism through uncarboxylated osteocalcin, a recently discovered hormone secreted by osteoblasts. This review traces how energy metabolism affects osteoblasts through the central control of bone mass involving leptin, serotoninergic neurons, the hypothalamus, and the sympathetic nervous system. Next, the role of osteocalcin (insulin secretion, insulin sensitivity, and pancreas β-cell proliferation) in the regulation of energy metabolism is described. Then, the connections between insulin signaling on osteoblasts and the release of uncarboxylated osteocalcin during osteoclast bone resorption through osteoprotegerin are reported. Finally, the understanding of this new bone endocrinology will provide some insights into bone, kidney, and energy metabolism in patients with chronic kidney disease. PMID:21346725

  7. Bone: from a reservoir of minerals to a regulator of energy metabolism.

    PubMed

    Confavreux, Cyrille B

    2011-04-01

    Besides locomotion, organ protection, and calcium-phosphorus homeostasis, the three classical functions of the skeleton, bone remodeling affects energy metabolism through uncarboxylated osteocalcin, a recently discovered hormone secreted by osteoblasts. This review traces how energy metabolism affects osteoblasts through the central control of bone mass involving leptin, serotoninergic neurons, the hypothalamus, and the sympathetic nervous system. Next, the role of osteocalcin (insulin secretion, insulin sensitivity, and pancreas β-cell proliferation) in the regulation of energy metabolism is described. Then, the connections between insulin signaling on osteoblasts and the release of uncarboxylated osteocalcin during osteoclast bone resorption through osteoprotegerin are reported. Finally, the understanding of this new bone endocrinology will provide some insights into bone, kidney, and energy metabolism in patients with chronic kidney disease. PMID:26746856

  8. Albumin Supplement Affects the Metabolism and Metabolism-Related Drug-Drug Interaction of Fenoprofen Enantiomers.

    PubMed

    Wang, Nan; Wang, Feng; Meng, Yu; Yang, Guo-Hui; Chen, Ju-Wu; Wang, Jia-Xiang

    2015-07-01

    The influence of albumin towards the metabolism behavior of fenoprofen enantiomers and relevant drug-drug interaction was investigated in the present study. The metabolic behavior of fenoprofen enantiomers was compared in a phase II metabolic incubation system with and without bovine serum albumin (BSA). BSA supplement increased the binding affinity parameter (Km) of (R)-fenoprofen towards human liver microsomes (HLMs) from 148.3 to 214.4 μM. In contrast, BSA supplement decreased the Km of (S)-fenoprofen towards HLMs from 218.2 to 123.5 μM. For maximum reaction velocity (Vmax), the addition of BSA increased the Vmax of (R)-fenoprofen from 1.3 to 1.6 nmol/min/mg protein. In the contrast, BSA supplement decreased the Vmax value from 3.3 to 1.5 nmol/min/mg protein. Andrographolide-fenoprofen interaction was used as an example to investigate the influence of BSA supplement towards fenoprofen-relevant drug-drug interaction. The addition of 0.2% BSA in the incubation system significantly decreased the inhibition potential of andrographolide towards (R)-fenoprofen metabolism (P < 0.001). Different from (R)-fenoprofen, the addition of BSA significantly increased the inhibition potential of andrographolide towards the metabolism of (S)-fenoprofen. BSA supplement also changed the inhibition kinetic type and parameter of andrographolide towards the metabolism of (S)-fenoprofen. In conclusion, albumin supplement changes the metabolic behavior of fenoprofen enantiomers and the fenoprofen-andrographolide interaction. PMID:26037509

  9. Metabolic differences in temperamental Brahman cattle can affect productivity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many factors may adversely affect the growth and productivity of livestock. These include stressors associated with management practices, such as weaning, handling relative to transportation, and vaccination, that can modulate growth through the production of stress-related hormones (i.e., cortisol,...

  10. Environmentally Relevant Dose of Bisphenol A Does Not Affect Lipid Metabolism and Has No Synergetic or Antagonistic Effects on Genistein’s Beneficial Roles on Lipid Metabolism

    PubMed Central

    Fan, Ying; Li, Hongyu; Zhao, Nana; Yang, Huiqin; Ye, Xiaolei; He, Dongliang; Yang, Hui; Jin, Xin; Tian, Chong; Ying, Chenjiang

    2016-01-01

    Both bisphenol A (BPA, an endocrine disrupting chemicals) and genistein (a phytoestrogen mainly derived from leguminosae) are able to bind to estrogen receptors, but they are considered to have different effects on metabolic syndrome, surprisingly. We here investigate the effects of an environmentally relevant dose of BPA alone and the combined effects with genistein on lipid metabolism in rats. Eight groups of adult male Wistar rats, fed with either standard chow diet or high-fat diet, were treated with BPA (50μg/kg/day), genistein (10mg/kg/day), and BPA plus genistein for 35 weeks, respectively. Metabolic parameters in serum and liver were determined; the hematoxylin/eosin and oil Red O staining were used to observe liver histologically; gene expressions related to hepatic lipid metabolism were analyzed by Real-time PCR; protein expressions of PPARγ, PPARα and LC3 in liver were analyzed by western blotting. No difference of body weight gain, total energy intake, liver weight/body weight or body fat percentage in both STD- and HFD-fed sub-groups was observed after treatment with BPA, genistein, or BPA plus genistein (P>0.05). Genistein alleviated lipid metabolism disorder and decreased the mRNA and protein expression of PPARγ (P<0.05), and increased the protein expression of LC3II (P<0.05) in liver of HFD-fed rats. However, BPA treatment had no effect on lipid metabolism in rats alone (P>0.05) or combined with genistein. Our findings suggest that long-term environmentally relevant dose of BPA did not affect lipid metabolism, and had no synergetic or antagonistic roles on genistein’s beneficial function on hepatic lipid metabolism. PMID:27171397

  11. 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. PMID:26709757

  12. Spastin Binds to Lipid Droplets and Affects Lipid Metabolism

    PubMed Central

    Papadopoulos, Chrisovalantis; Orso, Genny; Mancuso, Giuseppe; Herholz, Marija; Gumeni, Sentiljana; Tadepalle, Nimesha; Jüngst, Christian; Tzschichholz, Anne; Schauss, Astrid; Höning, Stefan; Trifunovic, Aleksandra; Daga, Andrea; Rugarli, Elena I.

    2015-01-01

    Mutations in SPAST, encoding spastin, are the most common cause of autosomal dominant hereditary spastic paraplegia (HSP). HSP is characterized by weakness and spasticity of the lower limbs, owing to progressive retrograde degeneration of the long corticospinal axons. Spastin is a conserved microtubule (MT)-severing protein, involved in processes requiring rearrangement of the cytoskeleton in concert to membrane remodeling, such as neurite branching, axonal growth, midbody abscission, and endosome tubulation. Two isoforms of spastin are synthesized from alternative initiation codons (M1 and M87). We now show that spastin-M1 can sort from the endoplasmic reticulum (ER) to pre- and mature lipid droplets (LDs). A hydrophobic motif comprised of amino acids 57 through 86 of spastin was sufficient to direct a reporter protein to LDs, while mutation of arginine 65 to glycine abolished LD targeting. Increased levels of spastin-M1 expression reduced the number but increased the size of LDs. Expression of a mutant unable to bind and sever MTs caused clustering of LDs. Consistent with these findings, ubiquitous overexpression of Dspastin in Drosophila led to bigger and less numerous LDs in the fat bodies and increased triacylglycerol levels. In contrast, Dspastin overexpression increased LD number when expressed specifically in skeletal muscles or nerves. Downregulation of Dspastin and expression of a dominant-negative variant decreased LD number in Drosophila nerves, skeletal muscle and fat bodies, and reduced triacylglycerol levels in the larvae. Moreover, we found reduced amount of fat stores in intestinal cells of worms in which the spas-1 homologue was either depleted by RNA interference or deleted. Taken together, our data uncovers an evolutionarily conserved role of spastin as a positive regulator of LD metabolism and open up the possibility that dysfunction of LDs in axons may contribute to the pathogenesis of HSP. PMID:25875445

  13. 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: ...

  14. Inhibition of mitochondrial complex II affects dopamine metabolism and decreases its uptake into striatal synaptosomes.

    PubMed

    Cakała, Magdalena; Drabik, Jacek; Kaźmierczak, Anna; Kopczuk, Dorota; Adamczyk, Agata

    2006-01-01

    The mitochondrial toxin, 3-nitropropionic acid (3-NP), is a specific inhibitor of succinate dehydrogenase, complex II in the mitochondrial respiratory chain. The aim of our study was to determine the relationship between inhibition of mitochondrial complex II and dopamine (DA) metabolism and its transport into rat striatal synaptosomes after exposure to 3-NP. The study was carried out using spectrophotometric, radiochemical and HPLC methods. Our data showed that inhibition of succinate dehydrogenase by intraperitoneal (i.p.) injection of 3-NP (cumulated dose 100 mg/kg in 4 days) significantly affected DA metabolism, leading to the accumulation of its metabolites, 3,4-dihydroxylphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the rat striatum. These experimental conditions had no effect on free radical dependent lipid peroxidation in the brain. In vitro experiments revealed that DA and DOPAC significantly decrease lipid peroxidation in the brain homogenate. Moreover, 3-NP significantly inhibited [3H]DA uptake into striatal synaptosomes by specific dopamine transporter (DAT). The scavengers of superoxide radical (O2-) Tempol and Trolox had no effect on DAT function, but the nitric oxide synthase (NOS) inhibitor N w-nitro-L-arginine (100 microM) prevented 3-NP-evoked DAT down-regulation. In summary, our results indicate that inhibition of mitochondrial complex II by 3-NP enhances DA degradation and decreases its uptake into synaptosomes. It is suggested that NO and energy failure are responsible for alteration of the dopaminergic system in the striatum. PMID:17183449

  15. Metaboloepigenetics: Interrelationships between energy metabolism and epigenetic control of gene expression

    PubMed Central

    Donohoe, Dallas R.; Bultman, Scott J.

    2012-01-01

    Diet and energy metabolism affect gene expression, which influences human health and disease. Here, we discuss the role of epigenetics as a mechanistic link between energy metabolism and control of gene expression. A number of key energy metabolites including SAM, acetyl-CoA, NAD+, and ATP serve as essential co-factors for many, perhaps most, epigenetic enzymes that regulate DNA methylation, posttranslational histone modifications, and nucleosome position. The relative abundance of these energy metabolites allows a cell to sense its energetic state. And as co-factors, energy metabolites act as rheostats to modulate the activity of epigenetic enzymes and upregulate/downregulate transcription as appropriate to maintain homeostasis. PMID:22261928

  16. Energy metabolism in the acquisition and maintenance of stemness.

    PubMed

    Folmes, Clifford D L; Terzic, Andre

    2016-04-01

    Energy metabolism is traditionally considered a reactive homeostatic system addressing stage-specific cellular energy needs. There is however growing appreciation of metabolic pathways in the active control of vital cell functions. Case in point, the stem cell lifecycle--from maintenance and acquisition of stemness to lineage commitment and specification--is increasingly recognized as a metabolism-dependent process. Indeed, metabolic reprogramming is an early contributor to the orchestrated departure from or reacquisition of stemness. Recent advances in metabolomics have helped decipher the identity and dynamics of metabolic fluxes implicated in fueling cell fate choices by regulating the epigenetic and transcriptional identity of a cell. Metabolic cues, internal and/or external to the stem cell niche, facilitate progenitor pool restitution, long-term tissue renewal or ensure adoption of cytoprotective behavior. Convergence of energy metabolism with stem cell fate regulation opens a new avenue in understanding primordial developmental biology principles with future applications in regenerative medicine practice. PMID:26868758

  17. Calcineurin Links Mitochondrial Elongation with Energy Metabolism.

    PubMed

    Pfluger, Paul T; Kabra, Dhiraj G; Aichler, Michaela; Schriever, Sonja C; Pfuhlmann, Katrin; García, Verónica Casquero; Lehti, Maarit; Weber, Jon; Kutschke, Maria; Rozman, Jan; Elrod, John W; Hevener, Andrea L; Feuchtinger, Annette; Hrabě de Angelis, Martin; Walch, Axel; Rollmann, Stephanie M; Aronow, Bruce J; Müller, Timo D; Perez-Tilve, Diego; Jastroch, Martin; De Luca, Maria; Molkentin, Jeffery D; Tschöp, Matthias H

    2015-11-01

    Canonical protein phosphatase 3/calcineurin signaling is central to numerous physiological processes. Here we provide evidence that calcineurin plays a pivotal role in controlling systemic energy and body weight homeostasis. Knockdown of calcineurin in Drosophila melanogaster led to a decrease in body weight and energy stores, and increased energy expenditure. In mice, global deficiency of catalytic subunit Ppp3cb, and tissue-specific ablation of regulatory subunit Ppp3r1 from skeletal muscle, but not adipose tissue or liver, led to protection from high-fat-diet-induced obesity and comorbid sequelæ. Ser637 hyperphosphorylation of dynamin-related protein 1 (Drp1) in skeletal muscle of calcineurin-deficient mice was associated with mitochondrial elongation into power-cable-shaped filaments and increased mitochondrial respiration, but also with attenuated exercise performance. Our data suggest that calcineurin acts as highly conserved pivot for the adaptive metabolic responses to environmental changes such as high-fat, high-sugar diets or exercise. PMID:26411342

  18. Metabolic rate, latitude and thermal stability of roosts, but not phylogeny, affect rewarming rates of bats.

    PubMed

    Menzies, Allyson K; Webber, Quinn M R; Baloun, Dylan E; McGuire, Liam P; Muise, Kristina A; Coté, Damien; Tinkler, Samantha; Willis, Craig K R

    2016-10-01

    Torpor is an adaptation that allows many endotherms to save energy by abandoning the energetic cost of maintaining elevated body temperatures. Although torpor reduces energy consumption, the metabolic heat production required to arouse from torpor is energetically expensive and can impact the overall cost of torpor. The rate at which rewarming occurs can impact the cost of arousal, therefore, factors influencing rewarming rates of heterothermic endotherms could have influenced the evolution of rewarming rates and overall energetic costs of arousal from torpor. Bats are a useful taxon for studies of ecological and behavioral correlates of rewarming rate because of the widespread expression of heterothermy and ecological diversity across the >1200 known species. We used a comparative analysis of 45 bat species to test the hypothesis that ecological, behavioral, and physiological factors affect rewarming rates. We used basal metabolic rate (BMR) as an index of thermogenic capacity, and local climate (i.e., latitude of geographic range), roost stability and maximum colony size as ecological and behavioral predictors of rewarming rate. After controlling for phylogeny, high BMR was associated with rapid rewarming while species that live at higher absolute latitudes and in less thermally stable roosts also rewarmed most rapidly. These patterns suggests that some bat species rely on passive rewarming and social thermoregulation to reduce costs of rewarming, while others might rely on thermogenic capacity to maintain rapid rewarming rates in order to reduce energetic costs of arousal. Our results highlight species-specific traits associated with maintaining positive energy balance in a wide range of climates, while also providing insight into possible mechanisms underlying the evolution of heterothermy in endotherms. PMID:27317837

  19. Lactobacillus acidophilus NCFM affects vitamin E acetate metabolism and intestinal bile acid signature in monocolonized mice

    PubMed Central

    Roager, Henrik M; Sulek, Karolina; Skov, Kasper; Frandsen, Henrik L; Smedsgaard, Jørn; Wilcks, Andrea; Skov, Thomas H; Villas-Boas, Silas G; Licht, Tine R

    2014-01-01

    Monocolonization of germ-free (GF) mice enables the study of specific bacterial species in vivo. Lactobacillus acidophilus NCFMTM (NCFM) is a probiotic strain; however, many of the mechanisms behind its health-promoting effect remain unknown. Here, we studied the effects of NCFM on the metabolome of jejunum, cecum, and colon of NCFM monocolonized (MC) and GF mice using liquid chromatography coupled to mass-spectrometry (LC-MS). The study adds to existing evidence that NCFM in vivo affects the bile acid signature of mice, in particular by deconjugation. Furthermore, we confirmed that carbohydrate metabolism is affected by NCFM in the mouse intestine as especially the digestion of oligosaccharides (penta- and tetrasaccharides) was increased in MC mice. Additionally, levels of α-tocopherol acetate (vitamin E acetate) were higher in the intestine of GF mice than in MC mice, suggesting that NCFM affects the vitamin E acetate metabolism. NCFM did not digest vitamin E acetate in vitro, suggesting that direct bacterial metabolism was not the cause of the altered metabolome in vivo. Taken together, our results suggest that NCFM affects intestinal carbohydrate metabolism, bile acid metabolism and vitamin E metabolism, although it remains to be investigated whether this effect is unique to NCFM. PMID:24717228

  20. Lactobacillus acidophilus NCFM affects vitamin E acetate metabolism and intestinal bile acid signature in monocolonized mice.

    PubMed

    Roager, Henrik M; Sulek, Karolina; Skov, Kasper; Frandsen, Henrik L; Smedsgaard, Jørn; Wilcks, Andrea; Skov, Thomas H; Villas-Boas, Silas G; Licht, Tine R

    2014-01-01

    Monocolonization of germ-free (GF) mice enables the study of specific bacterial species in vivo. Lactobacillus acidophilus NCFM(TM) (NCFM) is a probiotic strain; however, many of the mechanisms behind its health-promoting effect remain unknown. Here, we studied the effects of NCFM on the metabolome of jejunum, cecum, and colon of NCFM monocolonized (MC) and GF mice using liquid chromatography coupled to mass-spectrometry (LC-MS). The study adds to existing evidence that NCFM in vivo affects the bile acid signature of mice, in particular by deconjugation. Furthermore, we confirmed that carbohydrate metabolism is affected by NCFM in the mouse intestine as especially the digestion of oligosaccharides (penta- and tetrasaccharides) was increased in MC mice. Additionally, levels of α-tocopherol acetate (vitamin E acetate) were higher in the intestine of GF mice than in MC mice, suggesting that NCFM affects the vitamin E acetate metabolism. NCFM did not digest vitamin E acetate in vitro, suggesting that direct bacterial metabolism was not the cause of the altered metabolome in vivo. Taken together, our results suggest that NCFM affects intestinal carbohydrate metabolism, bile acid metabolism and vitamin E metabolism, although it remains to be investigated whether this effect is unique to NCFM. PMID:24717228

  1. 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

  2. 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.

  3. 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.

  4. Sydnone SYD-1 affects the metabolic functions of isolated rat hepatocytes.

    PubMed

    Brandt, Anna Paula; Pires, Amanda do Rocio Andrade; Rocha, Maria Eliane Merlin; Noleto, Guilhermina Rodrigues; Acco, Alexandra; de Souza, Carlos Eduardo Alves; Echevarria, Aurea; Canuto, André Vinícius dos Santos; Cadena, Sílvia Maria Suter Correia

    2014-07-25

    Previously, we demonstrated that sydnone SYD-1 (3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate) impairs the mitochondrial functions linked to energy provision and suggested that this effect could be associated with its antitumor activity. Herein, we evaluated the effects of SYD-1 (25 and 50 μM) on rat hepatocytes to determine its cytotoxicity on non-tumor cells. SYD-1 (25 and 50 μM) did not affect the viability of hepatocytes in suspension after 1-40 min of incubation. However, the viability of the cultured hepatocytes was decreased by ∼66% as a consequence of treatment with SYD-1 (50 μM) for 18 h. Under the same conditions, SYD-1 promoted an increase in the release of LDH by ∼19%. The morphological changes in the cultured cells treated with SYD-1 (50 μM) were suggestive of cell distress, which was demonstrated by the presence of rounded hepatocytes, cell fragments and monolayer impairment. Furthermore, fluorescence microscopy showed an increase in the annexin label after treatment with SYD-1 (50 μM), suggesting that apoptosis had been induced in these cells. SYD-1 did not affect the states of respiration in the suspended hepatocytes, but the pyruvate levels were decreased by ∼36%, whereas the lactate levels were increased by ∼22% (for the 50 μM treatment). The basal and uncoupled states of respiration of the cultured hepatocytes were inhibited by ∼79% and ∼51%, respectively, by SYD-1 (50 μM). In these cells, SYD-1 (50 μM) increased the pyruvate and lactate levels by ∼84% and ∼16%, respectively. These results show that SYD-1 affects important metabolic functions related to energy provision in hepatocytes and that this effect was more pronounced on cells in culture than those in suspension. PMID:24836382

  5. Hyperketonemia during lipopolysaccharide-induced mastitis affects systemic and local intramammary metabolism in dairy cows.

    PubMed

    Zarrin, M; Wellnitz, O; van Dorland, H A; Gross, J J; Bruckmaier, R M

    2014-01-01

    Hyperketonemia interferes with the metabolic regulation in dairy cows. It is assumed that metabolic and endocrine changes during hyperketonemia also affect metabolic adaptations during inflammatory processes. We therefore studied systemic and local intramammary effects of elevated plasma β-hydroxybutyrate (BHBA) before and during the response to an intramammary lipopolysaccharide (LPS) challenge. Thirteen dairy cows received intravenously either a Na-DL-β-OH-butyrate infusion (n = 5) to achieve a constant plasma BHBA concentration (1.7 ± 0.1 mmol/L), with adjustments of the infusion rates made based on immediate measurements of plasma BHBA every 15 min, or an infusion with a 0.9% NaCl solution (control; n = 8) for 56 h. Infusions started at 0900 h on d 1 and continued until 1700 h 2 d later. Two udder quarters were challenged with 200 μg of Escherichia coli LPS and 2 udder quarters were treated with 0.9% saline solution as control quarters at 48 h after the start of infusion. Blood samples were taken at 1 wk and 2h before the start of infusions as reference samples and hourly during the infusion. Mammary gland biopsies were taken 1 wk before, and 48 and 56 h (8h after LPS challenge) after the start of infusions. The mRNA abundance of key factors related to BHBA and fatty acid metabolism, and glucose transporters was determined in mammary tissue biopsies. Blood samples were analyzed for plasma glucose, BHBA, nonesterified fatty acid, urea, insulin, glucagon, and cortisol concentrations. Differences were not different for effects of BHBA infusion on the mRNA abundance of any of the measured target genes in the mammary gland before LPS challenge. Intramammary LPS challenge increased plasma glucose, cortisol, glucagon, and insulin concentrations in both groups but increases in plasma glucose and glucagon concentration were less pronounced in the Na-DL-β-OH-butyrate infusion group than in controls. In response to LPS challenge, plasma BHBA concentration decreased

  6. Water deficit alters differentially metabolic pathways affecting important flavor and quality traits in grape berries of Cabernet Sauvignon and Chardonnay

    PubMed Central

    Deluc, Laurent G; Quilici, David R; Decendit, Alain; Grimplet, Jérôme; Wheatley, Matthew D; Schlauch, Karen A; Mérillon, Jean-Michel; Cushman, John C; Cramer, Grant R

    2009-01-01

    Background Water deficit has significant effects on grape berry composition resulting in improved wine quality by the enhancement of color, flavors, or aromas. While some pathways or enzymes affected by water deficit have been identified, little is known about the global effects of water deficit on grape berry metabolism. Results The effects of long-term, seasonal water deficit on berries of Cabernet Sauvignon, a red-wine grape, and Chardonnay, a white-wine grape were analyzed by integrated transcript and metabolite profiling. Over the course of berry development, the steady-state transcript abundance of approximately 6,000 Unigenes differed significantly between the cultivars and the irrigation treatments. Water deficit most affected the phenylpropanoid, ABA, isoprenoid, carotenoid, amino acid and fatty acid metabolic pathways. Targeted metabolites were profiled to confirm putative changes in specific metabolic pathways. Water deficit activated the expression of numerous transcripts associated with glutamate and proline biosynthesis and some committed steps of the phenylpropanoid pathway that increased anthocyanin concentrations in Cabernet Sauvignon. In Chardonnay, water deficit activated parts of the phenylpropanoid, energy, carotenoid and isoprenoid metabolic pathways that contribute to increased concentrations of antheraxanthin, flavonols and aroma volatiles. Water deficit affected the ABA metabolic pathway in both cultivars. Berry ABA concentrations were highly correlated with 9-cis-epoxycarotenoid dioxygenase (NCED1) transcript abundance, whereas the mRNA expression of other NCED genes and ABA catabolic and glycosylation processes were largely unaffected. Water deficit nearly doubled ABA concentrations within berries of Cabernet Sauvignon, whereas it decreased ABA in Chardonnay at véraison and shortly thereafter. Conclusion The metabolic responses of grapes to water deficit varied with the cultivar and fruit pigmentation. Chardonnay berries, which lack any

  7. Nitric oxide and platelet energy metabolism.

    PubMed

    Tomasiak, Marian; Stelmach, Halina; Rusak, Tomasz; Wysocka, Jolanta

    2004-01-01

    This study was undertaken to determine whether nitric oxide (NO) can affect platelet responses through the inhibition of energy production. It was found that NO donors: S-nitroso-N-acetylpenicyllamine, SNAP, (5-50 microM) and sodium nitroprusside, SNP, (5-100 microM) inhibited collagen- and ADP-induced aggregation of porcine platelets. The corresponding IC50 values for SNAP and SNP varied from 5 to 30 microM and from 9 to 75 microM, respectively. Collagen- and thrombin-induced platelet secretion was inhibited by SNAP (IC50 = 50 microM) and by SNP (IC50 = 100 microM). SNAP (20-100 microM), SNP (10-200 microM) and collagen (20 microg/ml) stimulated glycolysis in intact platelets. The degree of glycolysis stimulation exerted by NO donors was similar to that produced by respiratory chain inhibitors (cyanide and antimycin A) or uncouplers (2,4-dinitrophenol). Neither the NO donors nor the respiratory chain blockers affected glycolysis in platelet homogenate. SNAP (20-100 microM) and SNP (50-200 microM) inhibited oxygen consumption by platelets. The effect of SNP and SNAP on glycolysis and respiration was not reduced by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one, a selective inhibitor of NO-stimulated guanylate cyclase. SNAP (5-100 microM) and SNP (10-300 microM) inhibited the activity of platelet cytochrome oxidase and had no effect on NADH:ubiquinone oxidoreductase and succinate dehydrogenase. Blocking of the mitochondrial energy production by antimycin A slightly affected collagen-evoked aggregation and strongly inhibited platelet secretion. The results indicate that: 1) in porcine platelets NO is able to diminish mitochondrial energy production through the inhibition of cytochrome oxidase, 2) the inhibitory effect of NO on platelet secretion (but not aggregation) can be attributed to the reduction of mitochondrial energy production. PMID:15448739

  8. Reprogramming of energy metabolism as a driver of aging

    PubMed Central

    Feng, Zhaoyang; Berger, Nathan A.; Trubitsyn, Alexander

    2016-01-01

    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

  9. 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

  10. Metabolic syndrome - the consequence of lifelong treatment of bipolar affective disorder.

    PubMed

    Dadić-Hero, Elizabeta; Ruzić, Klementina; Grahovac, Tanja; Petranović, Duska; Graovac, Mirjana; Palijan, Tija Zarković

    2010-06-01

    Mood disturbances are characteristic and dominant feature of Mood disorders. Bipolar Affective Disorder (BAD) is a mood disorder which occurs equally in both sexes. BAD may occur in co morbidity with other mental diseases and disorders such as: Anorexia Nervosa, Bulimia Nervosa, Attention Deficit, Panic Disorder and Social Phobia. However, medical disorders (one or more) can also coexist with BAD. Metabolic syndrome is a combination of metabolic disorders that increase the risk of developing cardiovascular disease. A 61-year old female patient has been receiving continuous and systematic psychiatric treatment for Bipolar Affective Disorder for the last 39 years. The first episode was a depressive one and it occurred after a child delivery. Seventeen years ago the patient developed diabetes (diabetes type II), and twelve years ago arterial hypertension was diagnosed. High cholesterol and triglyceride levels as well as weight gain were objective findings. During the last nine years she has been treated for lower leg ulcer. Since metabolic syndrome includes abdominal obesity, hypertension, diabetes mellitus, increased cholesterol and serum triglyceride levels, the aforesaid patient can be diagnosed with Metabolic Syndrome. When treating Bipolar Affective Disorder, the antipsychotic drug choice should be careful and aware of its side-effects in order to avoid the development or aggravation of metabolic syndrome. PMID:20562789

  11. Metabolic issues in patients affected by schizophrenia: clinical characteristics and medical management

    PubMed Central

    Ventriglio, Antonio; Gentile, Alessandro; Stella, Eleonora; Bellomo, Antonello

    2015-01-01

    Patients affected by psychotic disorders are more likely to develop high rates of co-morbidities, such as obesity, type 2 diabetes, dyslipidemias, hypertension, metabolic syndrome, myocardial infarction, stroke etc., in the long-term. These morbidities have a significant impact on the life-expectancy of these patients. Patients with chronic psychoses show a 2–3-fold increased risk of death mostly from cardiovascular and metabolic diseases. Although there may be an independent link, between schizophrenia and metabolic conditions the cardio-metabolic risk is mostly related to an unhealthy lifestyle and the usage of antipsychotic agents (especially Second Generation Antipsychotics or atypical) even when these remain effective treatments in the management of major psychoses. Recently, many international organizations have developed screening and monitoring guidelines for the control of modifiable risk factors in order to reduce the rate of co-morbidity and mortality among patients affected by schizophrenia. This paper is a review of current knowledge about the metabolic issues of patients affected by schizophrenia and describes clinical characteristics and medical management strategies for such conditions. PMID:26388714

  12. 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

  13. Interrelationships between mitochondrial fusion, energy metabolism and oxidative stress during development in Caenorhabditis elegans

    SciTech Connect

    Yasuda, Kayo; Hartman, Philip S.; Ishii, Takamasa; Suda, Hitoshi; Akatsuka, Akira; Shoyama, Tetsuji; Miyazawa, Masaki; Ishii, Naoaki

    2011-01-21

    Research highlights: {yields} Growth and development of a fzo-1 mutant defective in the fusion process of mitochondria was delayed relative to the wild type of Caenorhabditis elegans. {yields} Oxygen sensitivity during larval development, superoxide production and carbonyl protein accumulation of the fzo-1 mutant were similar to wild type. {yields} fzo-1 animals had significantly lower metabolism than did N2 and mev-1 overproducing superoxide from mitochondrial electron transport complex II. {yields} Mitochondrial fusion can profoundly affect energy metabolism and development. -- Abstract: Mitochondria are known to be dynamic structures with the energetically and enzymatically mediated processes of fusion and fission responsible for maintaining a constant flux. Mitochondria also play a role of reactive oxygen species production as a byproduct of energy metabolism. In the current study, interrelationships between mitochondrial fusion, energy metabolism and oxidative stress on development were explored using a fzo-1 mutant defective in the fusion process and a mev-1 mutant overproducing superoxide from mitochondrial electron transport complex II of Caenorhabditis elegans. While growth and development of both single mutants was slightly delayed relative to the wild type, the fzo-1;mev-1 double mutant experienced considerable delay. Oxygen sensitivity during larval development, superoxide production and carbonyl protein accumulation of the fzo-1 mutant were similar to wild type. fzo-1 animals had significantly lower metabolism than did N2 and mev-1. These data indicate that mitochondrial fusion can profoundly affect energy metabolism and development.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. Xylitol affects the intestinal microbiota and metabolism of daidzein in adult male mice.

    PubMed

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-01-01

    This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health. PMID:24336061

  19. Xylitol Affects the Intestinal Microbiota and Metabolism of Daidzein in Adult Male Mice

    PubMed Central

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-01-01

    This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health. PMID:24336061

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy

    PubMed Central

    McCarthy, Antonio Desmond; Cortizo, Ana María; Sedlinsky, Claudia

    2016-01-01

    Patients with long-term type 1 and type 2 diabetes mellitus (DM) can develop skeletal complications or “diabetic osteopathy”. These include osteopenia, osteoporosis and an increased incidence of low-stress fractures. In this context, it is important to evaluate whether current anti-diabetic treatments can secondarily affect bone metabolism. Adenosine monophosphate-activated protein kinase (AMPK) modulates multiple metabolic pathways and acts as a sensor of the cellular energy status; recent evidence suggests a critical role for AMPK in bone homeostasis. In addition, AMPK activation is believed to mediate most clinical effects of the insulin-sensitizer metformin. Over the past decade, several research groups have investigated the effects of metformin on bone, providing a considerable body of pre-clinical (in vitro, ex vivo and in vivo) as well as clinical evidence for an anabolic action of metformin on bone. However, two caveats should be kept in mind when considering metformin treatment for a patient with type 2 DM at risk for diabetic osteopathy. In the first place, metformin should probably not be considered an anti-osteoporotic drug; it is an insulin sensitizer with proven macrovascular benefits that can secondarily improve bone metabolism in the context of DM. Secondly, we are still awaiting the results of randomized placebo-controlled studies in humans that evaluate the effects of metformin on bone metabolism as a primary endpoint. PMID:27022443

  6. Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy.

    PubMed

    McCarthy, Antonio Desmond; Cortizo, Ana María; Sedlinsky, Claudia

    2016-03-25

    Patients with long-term type 1 and type 2 diabetes mellitus (DM) can develop skeletal complications or "diabetic osteopathy". These include osteopenia, osteoporosis and an increased incidence of low-stress fractures. In this context, it is important to evaluate whether current anti-diabetic treatments can secondarily affect bone metabolism. Adenosine monophosphate-activated protein kinase (AMPK) modulates multiple metabolic pathways and acts as a sensor of the cellular energy status; recent evidence suggests a critical role for AMPK in bone homeostasis. In addition, AMPK activation is believed to mediate most clinical effects of the insulin-sensitizer metformin. Over the past decade, several research groups have investigated the effects of metformin on bone, providing a considerable body of pre-clinical (in vitro, ex vivo and in vivo) as well as clinical evidence for an anabolic action of metformin on bone. However, two caveats should be kept in mind when considering metformin treatment for a patient with type 2 DM at risk for diabetic osteopathy. In the first place, metformin should probably not be considered an anti-osteoporotic drug; it is an insulin sensitizer with proven macrovascular benefits that can secondarily improve bone metabolism in the context of DM. Secondly, we are still awaiting the results of randomized placebo-controlled studies in humans that evaluate the effects of metformin on bone metabolism as a primary endpoint. PMID:27022443

  7. Transcription Interference and ORF Nature Strongly Affect Promoter Strength in a Reconstituted Metabolic Pathway

    PubMed Central

    Carquet, Marie; Pompon, Denis; Truan, Gilles

    2015-01-01

    Fine tuning of individual enzyme expression level is necessary to alleviate metabolic imbalances in synthetic heterologous pathways. A known approach consists of choosing a suitable combination of promoters, based on their characterized strengths in model conditions. We questioned whether each step of a multiple-gene synthetic pathway could be independently tunable at the transcription level. Three open reading frames, coding for enzymes involved in a synthetic pathway, were combinatorially associated to different promoters on an episomal plasmid in Saccharomyces cerevisiae. We quantified the mRNA levels of the three genes in each strain of our generated combinatorial metabolic library. Our results evidenced that the ORF nature, position, and orientation induce strong discrepancies between the previously reported promoters’ strengths and the observed ones. We conclude that, in the context of metabolic reconstruction, the strength of usual promoters can be dramatically affected by many factors. Among them, transcriptional interference and ORF nature seem to be predominant. PMID:25767795

  8. Energy metabolism and energy-sensing pathways in mammalian embryonic and adult stem cell fate

    PubMed Central

    Rafalski, Victoria A.; Mancini, Elena; Brunet, Anne

    2012-01-01

    Summary Metabolism is influenced by age, food intake, and conditions such as diabetes and obesity. How do physiological or pathological metabolic changes influence stem cells, which are crucial for tissue homeostasis? This Commentary reviews recent evidence that stem cells have different metabolic demands than differentiated cells, and that the molecular mechanisms that control stem cell self-renewal and differentiation are functionally connected to the metabolic state of the cell and the surrounding stem cell niche. Furthermore, we present how energy-sensing signaling molecules and metabolism regulators are implicated in the regulation of stem cell self-renewal and differentiation. Finally, we discuss the emerging literature on the metabolism of induced pluripotent stem cells and how manipulating metabolic pathways might aid cellular reprogramming. Determining how energy metabolism regulates stem cell fate should shed light on the decline in tissue regeneration that occurs during aging and facilitate the development of therapies for degenerative or metabolic diseases. PMID:23420198

  9. Cardiac Metabolic Pathways Affected in the Mouse Model of Barth Syndrome

    PubMed Central

    Huang, Yan; Powers, Corey; Madala, Satish K.; Greis, Kenneth D.; Haffey, Wendy D.; Towbin, Jeffrey A.; Purevjav, Enkhsaikhan; Javadov, Sabzali; Strauss, Arnold W.; Khuchua, Zaza

    2015-01-01

    Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Taz-deficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacyl-CoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS. PMID:26030409

  10. Cardiac metabolic pathways affected in the mouse model of barth syndrome.

    PubMed

    Huang, Yan; Powers, Corey; Madala, Satish K; Greis, Kenneth D; Haffey, Wendy D; Towbin, Jeffrey A; Purevjav, Enkhsaikhan; Javadov, Sabzali; Strauss, Arnold W; Khuchua, Zaza

    2015-01-01

    Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Taz-deficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacyl-CoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS. PMID:26030409

  11. Leucine metabolism regulates TRI6 expression and affects deoxynivalenol production and virulence in Fusarium graminearum.

    PubMed

    Subramaniam, Rajagopal; Narayanan, Swara; Walkowiak, Sean; Wang, Li; Joshi, Manisha; Rocheleau, Hélène; Ouellet, Thérèse; Harris, Linda J

    2015-11-01

    TRI6 is a positive regulator of the trichothecene gene cluster and the production of trichothecene mycotoxins [deoxynivalenol (DON)] and acetylated forms such as 15-Acetyl-DON) in the cereal pathogen Fusarium graminearum. As a global transcriptional regulator, TRI6 expression is modulated by nitrogen-limiting conditions, sources of nitrogen and carbon, pH and light. However, the mechanism by which these diverse environmental factors affect TRI6 expression remains underexplored. In our effort to understand how nutrients affect TRI6 regulation, comparative digital expression profiling was performed with a wild-type F. graminearum and a Δtri6 mutant strain, grown in nutrient-rich conditions. Analysis showed that TRI6 negatively regulates genes of the branched-chain amino acid (BCAA) metabolic pathway. Feeding studies with deletion mutants of MCC, encoding methylcrotonyl-CoA-carboxylase, one of the key enzymes of leucine metabolism, showed that addition of leucine specifically down-regulated TRI6 expression and reduced 15-ADON accumulation. Constitutive expression of TRI6 in the Δmcc mutant strain restored 15-ADON production. A combination of cellophane breach assays and pathogenicity experiments on wheat demonstrated that disrupting the leucine metabolic pathway significantly reduced disease. These findings suggest a complex interaction between one of the primary metabolic pathways with a global regulator of mycotoxin biosynthesis and virulence in F. graminearum. PMID:26248604

  12. Bromochloromethane, a Methane Analogue, Affects the Microbiota and Metabolic Profiles of the Rat Gastrointestinal Tract

    PubMed Central

    Yang, Yu-Xiang; Mu, Chun-Long; Luo, Zhen

    2015-01-01

    Bromochloromethane (BCM), an inhibitor of methanogenesis, has been used in animal production. However, little is known about its impact on the intestinal microbiota and metabolic patterns. The present study aimed to investigate the effect of BCM on the colonic bacterial community and metabolism by establishing a Wistar rat model. Twenty male Wistar rats were randomly divided into two groups (control and treated with BCM) and raised for 6 weeks. Bacterial fermentation products in the cecum were determined, and colonic methanogens and sulfate-reducing bacteria (SRB) were quantified. The colonic microbiota was analyzed by pyrosequencing of the 16S rRNA genes, and metabolites were profiled by gas chromatography and mass spectrometry. The results showed that BCM did not affect body weight and feed intake, but it did significantly change the intestinal metabolic profiles. Cecal protein fermentation was enhanced by BCM, as methylamine, putrescine, phenylethylamine, tyramine, and skatole were significantly increased. Colonic fatty acid and carbohydrate concentrations were significantly decreased, indicating the perturbation of lipid and carbohydrate metabolism by BCM. BCM treatment decreased the abundance of methanogen populations, while SRB were increased in the colon. BCM did not affect the total colonic bacterial counts but significantly altered the bacterial community composition by decreasing the abundance of actinobacteria, acidobacteria, and proteobacteria. The results demonstrated that BCM treatment significantly altered the microbiotic and metabolite profiles in the intestines, which may provide further information on the use of BCM in animal production. PMID:26567308

  13. [Consequences of intravesical obstruction on detrusor muscle energy metabolism].

    PubMed

    Dahmani, Laurent; Bruyère, Franck; Ouaki, Frédéric; Pires, Christophe; Irani, Jacques; Doré, Bertrand

    2002-09-01

    Alteration of the emptying function of the bladder observed during the natural history of benign prostatic hyperplasia may be related to a biochemical disorder, more specifically a disorder of energy metabolism. Under conditions of obstruction, the bladder is no longer able to contract effectively as it is unable to produce a sufficient quantity of energy. This energy dysfunction is induced by anaerobic diversion of glucose metabolism. The key element of this disturbance is the mitochondrion. Morphological studies have demonstrated degeneration of this organelle controlling energy metabolism. This intracellular alteration is also reflected by functional changes. Disturbances of the various mitochondrial energy producing cycles appear to be responsible for detrusor dysfunction. Further investigations are necessary, especially clinical studies to corroborate these experimental findings. A better knowledge of the pathophysiology of vesical functional consequences of BPH would allow the use of new therapeutic categories of drugs. PMID:12463112

  14. [THE ANALYSIS OF INDICATORS OF MINERAL METABOLISM IN PATIENTS WITH DEGENERATIVE DYSTROPHIC AFFECTIONS OF JOINTS].

    PubMed

    Gasanova, A G; Matveeva, E L; Spirkina, E S

    2015-12-01

    The analysis of indicators of mineral metabolism in patients with degenerative dystrophic affections of joints demonstrated that under development of osteoarthrosis process the alteration of indicators of concentration of electrolytes in blood serum, urine and synovial fluid occurs. The stage II of process is characterized by maximal alterations of indicators. The indicator of relationship between concentration of phosphate-ion and index of phosphatases of blood serum turned out the significant coefficient of correlation. PMID:27032248

  15. Why does offspring size affect performance? Integrating metabolic scaling with life-history theory.

    PubMed

    Pettersen, Amanda K; White, Craig R; Marshall, Dustin J

    2015-11-22

    Within species, larger offspring typically outperform smaller offspring. While the relationship between offspring size and performance is ubiquitous, the cause of this relationship remains elusive. By linking metabolic and life-history theory, we provide a general explanation for why larger offspring perform better than smaller offspring. Using high-throughput respirometry arrays, we link metabolic rate to offspring size in two species of marine bryozoan. We found that metabolism scales allometrically with offspring size in both species: while larger offspring use absolutely more energy than smaller offspring, larger offspring use proportionally less of their maternally derived energy throughout the dependent, non-feeding phase. The increased metabolic efficiency of larger offspring while dependent on maternal investment may explain offspring size effects-larger offspring reach nutritional independence (feed for themselves) with a higher proportion of energy relative to structure than smaller offspring. These findings offer a potentially universal explanation for why larger offspring tend to perform better than smaller offspring but studies on other taxa are needed. PMID:26559952

  16. Oleanolic acid and ursolic acid affect peptidoglycan metabolism in Listeria monocytogenes.

    PubMed

    Kurek, Anna; Grudniak, Anna M; Szwed, Magdalena; Klicka, Anna; Samluk, Lukasz; Wolska, Krystyna I; Janiszowska, Wirginia; Popowska, Magdalena

    2010-01-01

    The plant pentacyclic triterpenoids, oleanolic and ursolic acids, inhibit the growth and survival of many bacteria, particularly Gram-positive species, including pathogenic ones. The effect of these compounds on the facultative human pathogen Listeria monocytogenes was examined. Both acids affected cell morphology and enhanced autolysis of the bacterial cells. Autolysis of isolated cell walls was inhibited by oleanolic acid, but the inhibitory activity of ursolic acid was less pronounced. Both compounds inhibited peptidoglycan turnover and quantitatively affected the profile of muropeptides obtained after digestion of peptidoglycan with mutanolysin. These results suggest that peptidoglycan metabolism is a cellular target of oleanolic and ursolic acids. PMID:19894138

  17. Altered Metabolic Homeostasis in Amyotrophic Lateral Sclerosis: Mechanisms of Energy Imbalance and Contribution to Disease Progression.

    PubMed

    Ioannides, Zara A; Ngo, Shyuan T; Henderson, Robert D; McCombe, Pamela A; Steyn, Frederik J

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurones, which leads to paralysis and death in an average of 3 years following diagnosis. The cause of ALS is unknown, but there is substantial evidence that metabolic factors, including nutritional state and body weight, affect disease progression and survival. This review provides an overview of the characteristics of metabolic dysregulation in ALS focusing on mechanisms that lead to disrupted energy supply (at a whole-body and cellular level) and altered energy expenditure. We discuss how a decrease in energy supply occurs in parallel with an increase in energy demand and leads to a state of chronic energy deficit which has a negative impact on disease outcome in ALS. We conclude by presenting potential and tested strategies to compensate for, or correct this energy imbalance, and speculate on promising areas for further research. PMID:27400276

  18. 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

  19. Dissecting Leishmania infantum Energy Metabolism - A Systems Perspective

    PubMed Central

    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

  20. 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

  1. Thermal conditions experienced during differentiation affect metabolic and contractile phenotypes of mouse myotubes.

    PubMed

    Little, Alex G; Seebacher, Frank

    2016-09-01

    Central pathways regulate metabolic responses to cold in endotherms to maintain relatively stable internal core body temperatures. However, peripheral muscles routinely experience temperatures lower than core body temperature, so that it would be advantageous for peripheral tissues to respond to temperature changes independently from core body temperature regulation. Early developmental conditions can influence offspring phenotypes, and here we tested whether developing muscle can compensate locally for the effects of cold exposure independently from central regulation. Muscle myotubes originate from undifferentiated myoblasts that are laid down during embryogenesis. We show that in a murine myoblast cell line (C2C12), cold exposure (32°C) increased myoblast metabolic flux compared with 37°C control conditions. Importantly, myotubes that differentiated at 32°C compensated for the thermodynamic effects of low temperature by increasing metabolic rates, ATP production, and glycolytic flux. Myotube responses were also modulated by the temperatures experienced by "parent" myoblasts. Myotubes that differentiated under cold exposure increased activity of the AMP-stimulated protein kinase (AMPK), which may mediate metabolic changes in response cold exposure. Moreover, cold exposure shifted myosin heavy chains from slow to fast, presumably to overcome slower contractile speeds resulting from low temperatures. Adjusting thermal sensitivities locally in peripheral tissues complements central thermoregulation and permits animals to maintain function in cold environments. Muscle also plays a major metabolic role in adults, so that developmental responses to cold are likely to influence energy expenditure later in life. PMID:27385733

  2. Systematic variation of prosthetic foot spring affects center-of-mass mechanics and metabolic cost during walking

    PubMed Central

    Zelik, Karl E.; Collins, Steven H.; Adamczyk, Peter G.; Segal, Ava D.; Klute, Glenn K.; Morgenroth, David C.; Hahn, Michael E.; Orendurff, Michael S.; Czerniecki, Joseph M.; Kuo, Arthur D.

    2014-01-01

    Lower-limb amputees expend more energy to walk than non-amputees and have an elevated risk of secondary disabilities. Insufficient push-off by the prosthetic foot may be a contributing factor. We aimed to systematically study the effect of prosthetic foot mechanics on gait, to gain insight into fundamental prosthetic design principles. We varied a single parameter in isolation, the energy-storing spring in a prototype prosthetic foot, the Controlled Energy Storage and Return (CESR) foot, and observed the effect on gait. Subjects walked on the CESR foot with three different springs. We performed parallel studies on amputees and on non-amputees wearing prosthetic simulators. In both groups, spring characteristics similarly affected ankle and body center-of-mass (COM) mechanics and metabolic cost. Softer springs led to greater energy storage, energy return and prosthetic limb COM push-off work. But metabolic energy expenditure was lowest with a spring of intermediate stiffness, suggesting biomechanical disadvantages to the softest spring despite its greater push-off. Disadvantages of the softest spring may include excessive heel displacements and COM collision losses. We also observed some differences in joint kinetics between amputees and non-amputees walking on the prototype foot. During prosthetic push-off, amputees exhibited reduced energy transfer from the prosthesis to the COM along with increased hip work, perhaps due to greater energy dissipation at the knee. Nevertheless, the results indicate that spring compliance can contribute to push-off, but with biomechanical trade-offs that limit the degree to which greater push-off might improve walking economy. PMID:21708509

  3. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism

    PubMed Central

    Park, Hyeong-Kyu; Ahima, Rexford S.

    2014-01-01

    Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases. PMID:25199978

  4. Perinatal Exposure to Perfluorooctane Sulfonate Affects Glucose Metabolism in Adult Offspring

    PubMed Central

    Wan, Hin T.; Zhao, Yin G.; Leung, Pik Y.; Wong, Chris K. C.

    2014-01-01

    Perfluoroalkyl acids (PFAAs) are globally present in the environment and are widely distributed in human populations and wildlife. The chemicals are ubiquitous in human body fluids and have a long serum elimination half-life. The notorious member of PFAAs, perfluorooctane sulfonate (PFOS) is prioritized as a global concerning chemical at the Stockholm Convention in 2009, due to its harmful effects in mammals and aquatic organisms. PFOS is known to affect lipid metabolism in adults and was found to be able to cross human placenta. However the effects of in utero exposure to the susceptibility of metabolic disorders in offspring have not yet been elucidated. In this study, pregnant CD-1 mice (F0) were fed with 0, 0.3 or 3 mg PFOS/kg body weight/day in corn oil by oral gavage daily throughout gestational and lactation periods. We investigated the immediate effects of perinatal exposure to PFOS on glucose metabolism in both maternal and offspring after weaning (PND 21). To determine if the perinatal exposure predisposes the risk for metabolic disorder to the offspring, weaned animals without further PFOS exposure, were fed with either standard or high-fat diet until PND 63. Fasting glucose and insulin levels were measured while HOMA-IR index and glucose AUCs were reported. Our data illustrated the first time the effects of the environmental equivalent dose of PFOS exposure on the disturbance of glucose metabolism in F1 pups and F1 adults at PND 21 and 63, respectively. Although the biological effects of PFOS on the elevated levels of fasting serum glucose and insulin levels were observed in both pups and adults of F1, the phenotypes of insulin resistance and glucose intolerance were only evident in the F1 adults. The effects were exacerbated under HFD, highlighting the synergistic action at postnatal growth on the development of metabolic disorders. PMID:24498028

  5. 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

  6. 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

  7. Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species

    PubMed Central

    Lee, Mi Jin; Lee, Seung Jun; Yun, Su Jin; Jang, Ji-Young; Kang, Hangoo; Kim, Kyongmin; Choi, In-Hong; Park, Sun

    2016-01-01

    The silver nanoparticle (AgNP) is a candidate for anticancer therapy because of its effects on cell survival and signaling. Although numerous reports are available regarding their effect on cell death, the effect of AgNPs on metabolism is not well understood. In this study, we investigated the effect of AgNPs on glucose metabolism in hepatoma cell lines. Lactate release from both HepG2 and Huh7 cells was reduced with 5 nm AgNPs as early as 1 hour after treatment, when cell death did not occur. Treatment with 5 nm AgNPs decreased glucose consumption in HepG2 cells but not in Huh7 cells. Treatment with 5 nm AgNPs reduced nuclear factor erythroid 2-like 2 expression in both cell types without affecting its activation at the early time points after AgNPs’ treatment. Increased reactive oxygen species (ROS) production was detected 1 hour after 5 nm AgNPs’ treatment, and lactate release was restored in the presence of an ROS scavenger. Our results suggest that 5 nm AgNPs affect glucose metabolism by producing ROS. PMID:26730190

  8. How energy policies affect public health.

    PubMed Central

    Romm, J J; Ervin, C A

    1996-01-01

    The connection between energy policy and increased levels of respiratory and cardiopulmonary disease has become clearer in the past few years. People living in cities with high levels of pollution have a higher risk of mortality than those living in less polluted cities. The pollutants most directly linked to increased morbidity and mortality include ozone, particulates, carbon monoxide, sulfur dioxide, volatile organic compounds, and oxides of nitrogen. Energy-related emissions generate the vast majority of these polluting chemicals. Technologies to prevent pollution in the transportation, manufacturing, building, and utility sectors can significantly reduce these emissions while reducing the energy bills of consumers and businesses. In short, clean energy technologies represent a very cost-effective investment in public health. Some 72% of the Federal government's investment in the research, development, and demonstration of pollution prevention technologies is made by the Department of Energy, with the largest share provided by the Office of Energy Efficiency and Renewable Energy. This article will examine the connections between air pollution and health problems and will discuss what the Department of Energy is doing to prevent air pollution now and in the future. Images p390-a p391-a p392-a p393-a p394-a p395-a p396-a p397-a PMID:8837627

  9. Evidence that high pCO2 affects protein metabolism in tropical reef corals.

    PubMed

    Edmunds, Peter J; Wall, Christopher B

    2014-08-01

    Early life stages of the coral Seriatopora caliendrum were used to test the hypothesis that the depression of dark respiration in coral recruits by high pCO2 is caused by perturbed protein metabolism. First, the contribution of protein anabolism to respiratory costs under high pCO2 was evaluated by measuring the aerobic respiration of S. caliendrum recruits with and without the protein synthesis inhibitor emetine following 1 to 4 days at 45 Pa versus 77 Pa pCO2. Second, protein catabolism under high pCO2 was evaluated by measuring the flux of ammonium (NH4 (+)) from juvenile colonies of S. caliendrum incubated in darkness at 47 Pa and 90 Pa pCO2. Two days after settlement, respiration of recruits was affected by an interaction between emetine and pCO2, with emetine reducing respiration 63% at 45 Pa pCO2 and 27% at 77 Pa pCO2. The interaction disappeared 5 days after settlement, when respiration was reduced 27% by emetine under both pCO2 conditions. These findings suggest that protein anabolism accounted for a large proportion of metabolic costs in coral recruits and was affected by high pCO2, with consequences detected in aerobic respiration. Juvenile S. caliendrum showed net uptake of NH4 (+) at 45 Pa pCO2 but net release of NH4 (+) at 90 Pa pCO2, indicating that protein catabolism, NH4 (+) recycling, or both were affected by high pCO2. Together, these results are consistent with the hypothesis that high pCO2 affects protein metabolism in corals. PMID:25216504

  10. Evolution of energy metabolism and its compartmentation in Kinetoplastida

    PubMed Central

    Hannaert, Véronique; Bringaud, Frédéric; Opperdoes, Fred R; Michels, Paul AM

    2003-01-01

    Kinetoplastida are protozoan organisms that probably diverged early in evolution from other eukaryotes. They are characterized by a number of unique features with respect to their energy and carbohydrate metabolism. These organisms possess peculiar peroxisomes, called glycosomes, which play a central role in this metabolism; the organelles harbour enzymes of several catabolic and anabolic routes, including major parts of the glycolytic and pentosephosphate pathways. The kinetoplastid mitochondrion is also unusual with regard to both its structural and functional properties. In this review, we describe the unique compartmentation of metabolism in Kinetoplastida and the metabolic properties resulting from this compartmentation. We discuss the evidence for our recently proposed hypothesis that a common ancestor of Kinetoplastida and Euglenida acquired a photosynthetic alga as an endosymbiont, contrary to the earlier notion that this event occurred at a later stage of evolution, in the Euglenida lineage alone. The endosymbiont was subsequently lost from the kinetoplastid lineage but, during that process, some of its pathways of energy and carbohydrate metabolism were sequestered in the kinetoplastid peroxisomes, which consequently became glycosomes. The evolution of the kinetoplastid glycosomes and the possible selective advantages of these organelles for Kinetoplastida are discussed. We propose that the possession of glycosomes provided metabolic flexibility that has been important for the organisms to adapt easily to changing environmental conditions. It is likely that metabolic flexibility has been an important selective advantage for many kinetoplastid species during their evolution into the highly successful parasites today found in many divergent taxonomic groups. Also addressed is the evolution of the kinetoplastid mitochondrion, from a supposedly pluripotent organelle, attributed to a single endosymbiotic event that resulted in all mitochondria and

  11. How clustering dark energy affects matter perturbations

    NASA Astrophysics Data System (ADS)

    Mehrabi, A.; Basilakos, S.; Pace, F.

    2015-09-01

    The rate of structure formation in the Universe is different in homogeneous and clustered dark energy models. The degree of dark energy clustering depends on the magnitude of its effective sound speed c2_eff and for c2_eff=0 dark energy clusters in a similar fashion to dark matter while for c2_eff=1 it stays (approximately) homogeneous. In this paper we consider two distinct equations of state for the dark energy component, wd = const and w_d=w_0+w_1(z/1+z) with c2_eff as a free parameter and we try to constrain the dark energy effective sound speed using current available data including Type Ia supernovae, baryon acoustic oscillation, cosmic microwave background shift parameter (Planck and WMAP), Hubble parameter, big bang nucleosynthesis and the growth rate of structures fσ8(z). At first we derive the most general form of the equations governing dark matter and dark energy clustering under the assumption that c2_eff=const. Finally, performing an overall likelihood analysis we find that the likelihood function peaks at c2_eff=0; however, the dark energy sound speed is degenerate with respect to the cosmological parameters, namely Ωm and wd.

  12. [Energy metabolism and myocardial function in myocardiodystrophy].

    PubMed

    Temirova, K V; Kurlygina, L A; Zavodskaia, I S; Novikova, N A

    1976-09-01

    A total of 92 patients with chronic tonsilitis and cardiovascular changes were subjected to clinical observations, ECG analysis, potassium and nitroglycerine tests, and studies of the lactic acid level and creatinekinase activity as indces of myocardial metabolism. The examinations were conducted prior to and following tonsillectomy. In a majority of patients a correlation was revealed between the degree of ECG changes and the serum lactic acid level, as well as between the ECG improvement and a reduction of the lactic acid level following tonsillectomy. Three stages of tonsillogenic myocardiodystrophy were distinguished. The obtained data indicate the rationale of the used tests for the evaluation of the myocardial meabolism alterations and of the efficacy of treatment of chronic tonsillitis patients. PMID:1011536

  13. Food chain transport of nanoparticles affects behaviour and fat metabolism in fish.

    PubMed

    Cedervall, Tommy; Hansson, Lars-Anders; Lard, Mercy; Frohm, Birgitta; Linse, Sara

    2012-01-01

    Nano-sized (10(-9)-10(-7) m) particles offer many technical and biomedical advances over the bulk material. The use of nanoparticles in cosmetics, detergents, food and other commercial products is rapidly increasing despite little knowledge of their effect on organism metabolism. We show here that commercially manufactured polystyrene nanoparticles, transported through an aquatic food chain from algae, through zooplankton to fish, affect lipid metabolism and behaviour of the top consumer. At least three independent metabolic parameters differed between control and test fish: the weight loss, the triglycerides∶cholesterol ratio in blood serum, and the distribution of cholesterol between muscle and liver. Moreover, we demonstrate that nanoparticles bind to apolipoprotein A-I in fish serum in-vitro, thereby restraining them from properly utilising their fat reserves if absorbed through ingestion. In addition to the metabolic effects, we show that consumption of nanoparticle-containing zooplankton affects the feeding behaviour of the fish. The time it took the fish to consume 95% of the food presented to them was more than doubled for nanoparticle-exposed compared to control fish. Since many nano-sized products will, through the sewage system, end up in freshwater and marine habitats, our study provides a potential bioassay for testing new nano-sized material before manufacturing. In conclusion, our study shows that from knowledge of the molecular composition of the protein corona around nanoparticles it is possible to make a testable molecular hypothesis and bioassay of the potential biological risks of a defined nanoparticle at the organism and ecosystem level. PMID:22384193

  14. Effects of monocrotaline on energy metabolism in the rat liver.

    PubMed

    Mingatto, Fábio Erminio; Maioli, Marcos Antonio; Bracht, Adelar; Ishii-Iwamoto, Emy Luiza

    2008-11-10

    Monocrotaline (MCT) is a pyrrolizidine alkaloid present in the plants of the Crotalaria species that causes cytotoxicity and genotoxicity in animals and humans, and it is hepatically metabolized to the alkylating agent dehydromonocrotaline by cytochrome P-450. The exact cellular and molecular mechanisms of MCT-induced tissue injury remain unclear. We previously demonstrated that dehydromonocrotaline, but not monocrotaline, inhibits the activity of NADH-dehydrogenase at micromolar concentrations in isolated liver mitochondria, an effect associated with significantly reduced ATP synthesis. Impairment of energy metabolism is expected to lead to several alterations in cell metabolism. In this work, the action of different concentrations of monocrotaline (250, 500, and 750microM) on energy metabolism-linked parameters was investigated in isolated perfused rat livers. In the fed state, monocrotaline increased glycogenolysis and glycolysis, whereas in the livers of fasted rats, it decreased gluconeogenesis and urea synthesis from l-alanine. These metabolic alterations were only found in livers of phenobarbital-treated rats, indicating that active metabolites including dehydromonocrotaline were responsible for the observed activity. Our findings indicate that hepatic metabolic changes may be implicated, partly at least, in the hepatotoxicity of monocrotaline in animals and humans. PMID:18835426

  15. Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases.

    PubMed

    Ruchat, Stephanie-May; Houde, Andrée-Anne; Voisin, Grégory; St-Pierre, Julie; Perron, Patrice; Baillargeon, Jean-Patrice; Gaudet, Daniel; Hivert, Marie-France; Brisson, Diane; Bouchard, Luigi

    2013-09-01

    Offspring exposed to gestational diabetes mellitus (GDM) have an increased risk for chronic diseases, and one promising mechanism for fetal metabolic programming is epigenetics. Therefore, we postulated that GDM exposure impacts the offspring's methylome and used an epigenomic approach to explore this hypothesis. Placenta and cord blood samples were obtained from 44 newborns, including 30 exposed to GDM. Women were recruited at first trimester of pregnancy and followed until delivery. GDM was assessed after a 75-g oral glucose tolerance test at 24-28 weeks of pregnancy. DNA methylation was measured at>485,000 CpG sites (Infinium HumanMethylation450 BeadChips). Ingenuity Pathway Analysis was conducted to identify metabolic pathways epigenetically affected by GDM. Our results showed that 3,271 and 3,758 genes in placenta and cord blood, respectively, were potentially differentially methylated between samples exposed or not to GDM (p-values down to 1 × 10(-06); none reached the genome-wide significance levels), with more than 25% (n = 1,029) being common to both tissues. Mean DNA methylation differences between groups were 5.7 ± 3.2% and 3.4 ± 1.9% for placenta and cord blood, respectively. These genes were likely involved in the metabolic diseases pathway (up to 115 genes (11%), p-values for pathways = 1.9 × 10(-13)metabolic diseases pathway, with consequences on fetal growth and development, and provide supportive evidence that DNA methylation is involved in fetal metabolic programming. PMID:23975224

  16. 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.

  17. 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. PMID:27041449

  18. Therapeutic Implications of Targeting Energy Metabolism in Breast Cancer

    PubMed Central

    Sakharkar, Meena K.; Shashni, Babita; Sharma, Karun; Dhillon, Sarinder K.; Ranjekar, Prabhakar R.; Sakharkar, Kishore R.

    2013-01-01

    PPARs are ligand activated transcription factors. PPARγ agonists have been reported as a new and potentially efficacious treatment of inflammation, diabetes, obesity, cancer, AD, and schizophrenia. Since cancer cells show dysregulation of glycolysis they are potentially manageable through changes in metabolic environment. Interestingly, several of the genes involved in maintaining the metabolic environment and the central energy generation pathway are regulated or predicted to be regulated by PPARγ. The use of synthetic PPARγ ligands as drugs and their recent withdrawal/restricted usage highlight the lack of understanding of the molecular basis of these drugs, their off-target effects, and their network. These data further underscores the complexity of nuclear receptor signalling mechanisms. This paper will discuss the function and role of PPARγ in energy metabolism and cancer biology in general and its emergence as a promising therapeutic target in breast cancer. PMID:23431283

  19. Factors affecting the energy cost of level running at submaximal speed.

    PubMed

    Lacour, Jean-René; Bourdin, Muriel

    2015-04-01

    Metabolic measurement is still the criterion for investigation of the efficiency of mechanical work and for analysis of endurance performance in running. Metabolic demand may be expressed either as the energy spent per unit distance (energy cost of running, C r) or as energy demand at a given running speed (running economy). Systematic studies showed a range of costs of about 20 % between runners. Factors affecting C r include body dimensions: body mass and leg architecture, mostly calcaneal tuberosity length, responsible for 60-80 % of the variability. Children show a higher C r than adults. Higher resting metabolism and lower leg length/stature ratio are the main putative factors responsible for the difference. Elastic energy storage and reuse also contribute to the variability of C r. The increase in C r with increasing running speed due to increase in mechanical work is blunted till 6-7 m s(-1) by the increase in vertical stiffness and the decrease in ground contact time. Fatigue induced by prolonged or intense running is associated with up to 10 % increased C r; the contribution of metabolic and biomechanical factors remains unclear. Women show a C r similar to men of similar body mass, despite differences in gait pattern. The superiority of black African runners is presumably related to their leg architecture and better elastic energy storage and reuse. PMID:25681108

  20. Cannibalism Affects Core Metabolic Processes in Helicoverpa armigera Larvae-A 2D NMR Metabolomics Study.

    PubMed

    Vergara, Fredd; Shino, Amiu; Kikuchi, Jun

    2016-01-01

    Cannibalism is known in many insect species, yet its impact on insect metabolism has not been investigated in detail. This study assessed the effects of cannibalism on the metabolism of fourth-instar larvae of the non-predatory insect Helicoverpa armigera (Lepidotera: Noctuidea). Two groups of larvae were analyzed: one group fed with fourth-instar larvae of H. armigera (cannibal), the other group fed with an artificial plant diet. Water-soluble small organic compounds present in the larvae were analyzed using two-dimensional nuclear magnetic resonance (NMR) and principal component analysis (PCA). Cannibalism negatively affected larval growth. PCA of NMR spectra showed that the metabolic profiles of cannibal and herbivore larvae were statistically different with monomeric sugars, fatty acid- and amino acid-related metabolites as the most variable compounds. Quantitation of ¹H-(13)C HSQC (Heteronuclear Single Quantum Coherence) signals revealed that the concentrations of glucose, glucono-1,5-lactone, glycerol phosphate, glutamine, glycine, leucine, isoleucine, lysine, ornithine, proline, threonine and valine were higher in the herbivore larvae. PMID:27598144

  1. Short photoperiod increases energy intake, metabolic thermogenesis and organ mass in silky starlings Sturnus sericeus

    PubMed Central

    WANG, Jia-Qi; WANG, Jia-Jia; WU, Xu-Jian; ZHENG, Wei-Hong; LIU, Jin-Song

    2016-01-01

    Environmental cues play important roles in the regulation of an animal’s physiology and behavior. One such cue, photoperiod, plays an important role in the seasonal acclimatization of birds. It has been demonstrated that an animal’s body mass, basal metabolic rate (BMR), and energy intake, are all affected by photoperiod. The present study was designed to examine photoperiod induced changes in the body mass, metabolism and metabolic organs of the silky starling, Sturnus sericeus. Captive silky starlings increased their body mass and BMR during four weeks of acclimation to a short photoperiod. Birds acclimated to a short photoperiod also increased the mass of certain organs (liver, gizzard and small intestine), and both gross energy intake (GEI) and digestible energy intake (DEI), relative to those acclimated to a long photoperiod. Furthermore, BMR was positively correlated with body mass, liver mass, GEI and DEI. These results suggest that silky starlings increase metabolic thermogenesis when exposed to a short photoperiod by increasing their body and metabolic organ mass, and their GEI and DEI. These findings support the hypothesis that bird species from temperate climates typically display high phenotypic flexibility in thermogenic capacity. PMID:27029864

  2. Short photoperiod increases energy intake, metabolic thermogenesis and organ mass in silky starlings Sturnus sericeus.

    PubMed

    Wang, Jia-Qi; Wang, Jia-Jia; Wu, Xu-Jian; Zheng, Wei-Hong; Liu, Jin-Song

    2016-03-18

    Environmental cues play important roles in the regulation of an animal's physiology and behavior. One such cue, photoperiod, plays an important role in the seasonal acclimatization of birds. It has been demonstrated that an animal's body mass, basal metabolic rate (BMR), and energy intake, are all affected by photoperiod. The present study was designed to examine photoperiod induced changes in the body mass, metabolism and metabolic organs of the silky starling, Sturnus sericeus. Captive silky starlings increased their body mass and BMR during four weeks of acclimation to a short photoperiod. Birds acclimated to a short photoperiod also increased the mass of certain organs (liver, gizzard and small intestine), and both gross energy intake (GEI) and digestible energy intake (DEI), relative to those acclimated to a long photoperiod. Furthermore, BMR was positively correlated with body mass, liver mass, GEI and DEI. These results suggest that silky starlings increase metabolic thermogenesis when exposed to a short photoperiod by increasing their body and metabolic organ mass, and their GEI and DEI. These findings support the hypothesis that bird species from temperate climates typically display high phenotypic flexibility in thermogenic capacity. PMID:27029864

  3. Factors affecting human heterocyclic amine intake and the metabolism of PhIP.

    PubMed

    Knize, Mark G; Kulp, Kristen S; Salmon, Cynthia P; Keating, Garrett A; Felton, James S

    2002-09-30

    We are working to understand possible human health effects from exposure to heterocyclic amines that are formed in meat during cooking. Laboratory-cooked beef, pork, and chicken are capable of producing tens of nanograms of MeIQx, IFP, and PhIP per gram of meat and smaller amounts of other heteroyclic amines. Well-done restaurant-cooked beef, pork, and chicken may contain PhIP and IFP at concentrations as high as tens of nanograms per gram and MeIQx at levels up to 3 ng/g. Although well-done chicken breast prepared in the laboratory may contain large amounts of PhIP, a survey of flame-grilled meat samples cooked in private homes showed PhIP levels in beef steak and chicken breast are not significantly different (P=0.36). The extremely high PhIP levels reported in some studies of grilled chicken are not seen in home-cooked samples.Many studies suggest individuals may have varying susceptibility to carcinogens and that diet may influence metabolism, thus affecting cancer susceptibility. To understand the human metabolism of PhIP, we examined urinary metabolites of PhIP in volunteers following a single well-done meat exposure. Using solid-phase extraction and LC/MS/MS, we quantified four major PhIP metabolites in human urine. In addition to investigating individual variation, we examined the interaction of PhIP with a potentially chemopreventive food. In a preliminary study of the effect of broccoli on PhIP metabolism, we fed chicken to six volunteers before and after eating steamed broccoli daily for 3 days. Preliminary results suggest that broccoli, which contains isothiocyanates shown to induce Phases I and II metabolism in vitro, may affect both the rate of metabolite excretion and the metabolic products of a dietary carcinogen. This newly developed methodology will allow us to assess prevention strategies that reduce the possible risks associated with PhIP exposure. PMID:12351155

  4. 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

  5. Oxygen Affects Gut Bacterial Colonization and Metabolic Activities in a Gnotobiotic Cockroach Model

    PubMed Central

    Tegtmeier, Dorothee; Thompson, Claire L.; Schauer, Christine

    2015-01-01

    The gut microbiota of termites and cockroaches represents complex metabolic networks of many diverse microbial populations. The distinct microenvironmental conditions within the gut and possible interactions among the microorganisms make it essential to investigate how far the metabolic properties of pure cultures reflect their activities in their natural environment. We established the cockroach Shelfordella lateralis as a gnotobiotic model and inoculated germfree nymphs with two bacterial strains isolated from the guts of conventional cockroaches. Fluorescence microscopy revealed that both strains specifically colonized the germfree hindgut. In diassociated cockroaches, the facultatively anaerobic strain EbSL (a new species of Enterobacteriaceae) always outnumbered the obligately anaerobic strain FuSL (a close relative of Fusobacterium varium), irrespective of the sequence of inoculation, which showed that precolonization by facultatively anaerobic bacteria does not necessarily favor colonization by obligate anaerobes. Comparison of the fermentation products of the cultures formed in vitro with those accumulated in situ indicated that the gut environment strongly affected the metabolic activities of both strains. The pure cultures formed the typical products of mixed-acid or butyrate fermentation, whereas the guts of gnotobiotic cockroaches accumulated mostly lactate and acetate. Similar shifts toward more-oxidized products were observed when the pure cultures were exposed to oxygen, which corroborated the strong effects of oxygen on the metabolic fluxes previously observed in termite guts. Oxygen microsensor profiles of the guts of germfree, gnotobiotic, and conventional cockroaches indicated that both gut tissue and microbiota contribute to oxygen consumption and suggest that the oxygen status influences the colonization success. PMID:26637604

  6. Oxygen Affects Gut Bacterial Colonization and Metabolic Activities in a Gnotobiotic Cockroach Model.

    PubMed

    Tegtmeier, Dorothee; Thompson, Claire L; Schauer, Christine; Brune, Andreas

    2016-02-01

    The gut microbiota of termites and cockroaches represents complex metabolic networks of many diverse microbial populations. The distinct microenvironmental conditions within the gut and possible interactions among the microorganisms make it essential to investigate how far the metabolic properties of pure cultures reflect their activities in their natural environment. We established the cockroach Shelfordella lateralis as a gnotobiotic model and inoculated germfree nymphs with two bacterial strains isolated from the guts of conventional cockroaches. Fluorescence microscopy revealed that both strains specifically colonized the germfree hindgut. In diassociated cockroaches, the facultatively anaerobic strain EbSL (a new species of Enterobacteriaceae) always outnumbered the obligately anaerobic strain FuSL (a close relative of Fusobacterium varium), irrespective of the sequence of inoculation, which showed that precolonization by facultatively anaerobic bacteria does not necessarily favor colonization by obligate anaerobes. Comparison of the fermentation products of the cultures formed in vitro with those accumulated in situ indicated that the gut environment strongly affected the metabolic activities of both strains. The pure cultures formed the typical products of mixed-acid or butyrate fermentation, whereas the guts of gnotobiotic cockroaches accumulated mostly lactate and acetate. Similar shifts toward more-oxidized products were observed when the pure cultures were exposed to oxygen, which corroborated the strong effects of oxygen on the metabolic fluxes previously observed in termite guts. Oxygen microsensor profiles of the guts of germfree, gnotobiotic, and conventional cockroaches indicated that both gut tissue and microbiota contribute to oxygen consumption and suggest that the oxygen status influences the colonization success. PMID:26637604

  7. Inorganic Polyphosphate and Energy Metabolism in Mammalian Cells*

    PubMed Central

    Pavlov, Evgeny; Aschar-Sobbi, Roozbeh; Campanella, Michelangelo; Turner, Raymond J.; Gómez-García, María R.; Abramov, Andrey Y.

    2010-01-01

    Inorganic polyphosphate (poly P) is a polymer made from as few as 10 to several hundred phosphate molecules linked by phosphoanhydride bonds similar to ATP. Poly P is ubiquitous in all mammalian organisms, where it plays multiple physiological roles. The metabolism of poly P in mammalian organisms is not well understood. We have examined the mechanism of poly P production and the role of this polymer in cell energy metabolism. Poly P levels in mitochondria and intact cells were estimated using a fluorescent molecular probe, 4′,6-diamidino-2-phenylindole. Poly P levels were dependent on the metabolic state of the mitochondria. Poly P levels were increased by substrates of respiration and in turn reduced by mitochondrial inhibitor (rotenone) or an uncoupler (carbonyl cyanide p-trifluoromethoxyphenylhydrazone). Oligomycin, an inhibitor of mitochondrial ATP-synthase, blocked the production of poly P. Enzymatic depletion of poly P from cells significantly altered the rate of ATP metabolism. We propose the existence of a feedback mechanism where poly P production and cell energy metabolism regulate each other. PMID:20124409

  8. Nonsense mutations in the human. beta. -globin gene affect mRNA metabolism

    SciTech Connect

    Baserga, S.J.; Benz, E.J. Jr. )

    1988-04-01

    A number of premature translation termination mutations (nonsense mutations) have been described in the human {alpha}- and {beta}-globin genes. Studies on mRNA isolated from patients with {beta}{sup 0}-thalassemia have shown that for both the {beta}-17 and the {beta}-39 mutations less than normal levels of {beta}-globin mRNA accumulate in peripheral blood cells. (The codon at which the mutation occurs designates the name of the mutation; there are 146 codons in human {beta}-globin mRNA). In vitro studies using the cloned {beta}-39 gene have reproduced this effect in a heterologous transfection system and have suggested that the defect resides in intranuclear metabolism. The authors have asked if this phenomenon of decreased mRNA accumulation is a general property of nonsense mutations and if the effect depends on the location or the type of mutation. Toward this end, they have studied the effect of five nonsense mutations and two missense mutations on the expression of human {beta}-globin mRNA in a heterologous transfection system. In all cases studied, the presence of a translation termination codon correlates with a decrease in the steady-state level of mRNA. The data suggest that the metabolism of a mammalian mRNA is affected by the presence of a mutation that affects translation.

  9. Litter Environment Affects Behavior and Brain Metabolic Activity of Adult Knockout Mice

    PubMed Central

    Crews, David; Rushworth, David; Gonzalez-Lima, Francisco; Ogawa, Sonoko

    2009-01-01

    In mammals, the formative environment for social and anxiety-related behaviors is the family unit; in the case of rodents, this is the litter and the mother-young bond. A deciding factor in this environment is the sex ratio of the litter and, in the case of mice lacking functional copies of gene(s), the ratio of the various genotypes in the litter. Both Sex and Genotype ratios of the litter affect the nature and quality of the individual's behavior later in adulthood, as well as metabolic activity in brain nuclei that underlie these behaviors. Mice were raised in litters reconstituted shortly after to birth to control for sex ratio and genotype ratio (wild type pups versus pups lacking a functional estrogen receptor α). In both males and females, the Sex and Genotype of siblings in the litter affected aggressive behaviors as well as patterns of metabolic activity in limbic nuclei in the social behavior network later in adulthood. Further, this pattern in males varied depending upon the Genotype of their brothers and sisters. Principal Components Analysis revealed two components comprised of several amygdalar and hypothalamic nuclei; the VMH showed strong correlations in both clusters, suggesting its pivotal nature in the organization of two neural networks. PMID:19707539

  10. Reversible acetylation of PGC-1: Connecting energy sensors and effectors to guarantee metabolic flexibility

    PubMed Central

    Jeninga, Ellen Helena; Schoonjans, Kristina; Auwerx, Johan

    2013-01-01

    Organisms adapt their metabolism to meet ever changing environmental conditions. This metabolic adaptation involves at a cellular level the fine-tuning of mitochondrial function, which is mainly under the control of the transcriptional coactivator PGC-1α. Changes in PGC-1α activity coordinate a transcriptional response, that boosts mitochondrial activity in times of energy needs and attenuates it when energy demands are low. Reversible acetylation has emerged as a key way to alter PGC-1α activity. Although it is well-established that PGC-1α is deacetylated and activated by Sirt1 and acetylated and inhibited by GCN5, less is known about how these enzymes themselves are regulated. Recently, it became clear that the energy sensor, AMP-activated kinase (AMPK) translates the effects of energy stress into altered Sirt1 activity by regulating the intracellular level of its co-substrate NAD+. Conversely, the enzyme ATP citrate lyase (ACL), relates energy balance to GCN5, through the control of the nuclear production of acetyl-CoA, the substrate for GCN5’s acetyltransferase activity. We review here how these metabolic signalling pathways, affecting GCN5 and Sirt1 activity, allow the reversible acetylation/deacetylation of PGC-1α and the adaptation of mitochondrial energy homeostasis to energy levels. PMID:20531298

  11. Targeting energy metabolism in brain cancer: review and hypothesis

    PubMed Central

    Seyfried, Thomas N; Mukherjee, Purna

    2005-01-01

    Malignant brain tumors are a significant health problem in children and adults and are often unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration, malignant brain cancer is potentially manageable through changes in metabolic environment. A radically different approach to brain cancer management is proposed that combines metabolic control analysis with the evolutionarily conserved capacity of normal cells to survive extreme shifts in physiological environment. In contrast to malignant brain tumors that are largely dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (β-hydroxybutyrate) for energy in vivo when glucose levels are reduced. The bioenergetic transition from glucose to ketone bodies metabolically targets brain tumors through integrated anti-inflammatory, anti-angiogenic, and pro-apoptotic mechanisms. The approach focuses more on the genomic flexibility of normal cells than on the genomic defects of tumor cells and is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with dietary energy restriction and the ketogenic diet. PMID:16242042

  12. Vocal performance affects metabolic rate in dolphins: implications for animals communicating in noisy environments.

    PubMed

    Holt, Marla M; Noren, Dawn P; Dunkin, Robin C; Williams, Terrie M

    2015-06-01

    Many animals produce louder, longer or more repetitious vocalizations to compensate for increases in environmental noise. Biological costs of increased vocal effort in response to noise, including energetic costs, remain empirically undefined in many taxa, particularly in marine mammals that rely on sound for fundamental biological functions in increasingly noisy habitats. For this investigation, we tested the hypothesis that an increase in vocal effort would result in an energetic cost to the signaler by experimentally measuring oxygen consumption during rest and a 2 min vocal period in dolphins that were trained to vary vocal loudness across trials. Vocal effort was quantified as the total acoustic energy of sounds produced. Metabolic rates during the vocal period were, on average, 1.2 and 1.5 times resting metabolic rate (RMR) in dolphin A and B, respectively. As vocal effort increased, we found that there was a significant increase in metabolic rate over RMR during the 2 min following sound production in both dolphins, and in total oxygen consumption (metabolic cost of sound production plus recovery costs) in the dolphin that showed a wider range of vocal effort across trials. Increases in vocal effort, as a consequence of increases in vocal amplitude, repetition rate and/or duration, are consistent with behavioral responses to noise in free-ranging animals. Here, we empirically demonstrate for the first time in a marine mammal, that these vocal modifications can have an energetic impact at the individual level and, importantly, these data provide a mechanistic foundation for evaluating biological consequences of vocal modification in noise-polluted habitats. PMID:25852069

  13. PPARs Integrate the Mammalian Clock and Energy Metabolism

    PubMed Central

    Chen, Lihong; Yang, Guangrui

    2014-01-01

    Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that function as transcription factors regulating the expression of numerous target genes. PPARs play an essential role in various physiological and pathological processes, especially in energy metabolism. It has long been known that metabolism and circadian clocks are tightly intertwined. However, the mechanism of how they influence each other is not fully understood. Recently, all three PPAR isoforms were found to be rhythmically expressed in given mouse tissues. Among them, PPARα and PPARγ are direct regulators of core clock components, Bmal1 and Rev-erbα, and, conversely, PPARα is also a direct Bmal1 target gene. More importantly, recent studies using knockout mice revealed that all PPARs exert given functions in a circadian manner. These findings demonstrated a novel role of PPARs as regulators in correlating circadian rhythm and metabolism. In this review, we summarize advances in our understanding of PPARs in circadian regulation. PMID:24693278

  14. 13C NMR spectroscopy applications to brain energy metabolism

    PubMed Central

    Rodrigues, Tiago B.; Valette, Julien; Bouzier-Sore, Anne-Karine

    2013-01-01

    13C nuclear magnetic resonance (NMR) spectroscopy is the method of choice for studying brain metabolism. Indeed, the most convincing data obtained to decipher metabolic exchanges between neurons and astrocytes have been obtained using this technique, thus illustrating its power. It may be difficult for non-specialists, however, to grasp thefull implication of data presented in articles written by spectroscopists. The aim of the review is, therefore, to provide a fundamental understanding of this topic to facilitate the non-specialists in their reading of this literature. In the first part of this review, we present the metabolic fate of 13C-labeled substrates in the brain in a detailed way, including an overview of some general neurochemical principles. We also address and compare the various spectroscopic strategies that can be used to study brain metabolism. Then, we provide an overview of the 13C NMR experiments performed to analyze both intracellular and intercellular metabolic fluxes. More particularly, the role of lactate as a potential energy substrate for neurons is discussed in the light of 13C NMR data. Finally, new perspectives and applications offered by 13C hyperpolarization are described. PMID:24367329

  15. Potato tuber expression of Arabidopsis WRINKLED1 increase triacylglycerol and membrane lipids while affecting central carbohydrate metabolism.

    PubMed

    Hofvander, Per; Ischebeck, Till; Turesson, Helle; Kushwaha, Sandeep K; Feussner, Ivo; Carlsson, Anders S; Andersson, Mariette

    2016-09-01

    Tuber and root crops virtually exclusively accumulate storage products in the form of carbohydrates. An exception is yellow nutsedge (Cyperus esculentus) in which tubers have the capacity to store starch and triacylglycerols (TAG) in roughly equal amounts. This suggests that a tuber crop can efficiently handle accumulation of energy dense oil. From a nutritional as well as economic aspect, it would be of interest to utilize the high yield capacity of tuber or root crops for oil accumulation similar to yellow nutsedge. The transcription factor WRINKLED1 from Arabidopsis thaliana, which in seed embryos induce fatty acid synthesis, has been shown to be a major factor for oil accumulation. WRINKLED1 was expressed in potato (Solanum tuberosum) tubers to explore whether this factor could impact tuber metabolism. This study shows that a WRINKLED1 transcription factor could induce triacylglycerol accumulation in tubers of transformed potato plants grown in field (up to 12 nmol TAG/mg dry weight, 1% of dry weight) together with a large increase in polar membrane lipids. The changes in metabolism further affected starch accumulation and composition concomitant with massive increases in sugar content. PMID:26914183

  16. Energy metabolism, enzymatic flux capacities, and metabolic flux rates in flying honeybees.

    PubMed Central

    Suarez, R K; Lighton, J R; Joos, B; Roberts, S P; Harrison, J F

    1996-01-01

    Honeybees rely primarily on the oxidation of hexose sugars to provide the energy required for flight. Measurement of VCO2 (equal to VO2, because VCO2/VO2 = 1.0 during carbohydrate oxidation) during flight allowed estimation of steady-state flux rates through pathways of flight muscle energy metabolism. Comparison of Vmax values for flight muscle hexokinase, phosphofructokinase, citrate synthase, and cytochrome c oxidase with rates of carbon and O2 flux during flight reveal that these enzymes operate closer to Vmax in the flight muscles of flying honeybees than in other muscles previously studied. Possible mechanistic and evolutionary implications of these findings are discussed. PMID:8901631

  17. Mitochondrial Mg2+ homeostasis decides cellular energy metabolism and vulnerability to stress

    PubMed Central

    Yamanaka, Ryu; Tabata, Sho; Shindo, Yutaka; Hotta, Kohji; Suzuki, Koji; Soga, Tomoyoshi; Oka, Kotaro

    2016-01-01

    Cellular energy production processes are composed of many Mg2+ dependent enzymatic reactions. In fact, dysregulation of Mg2+ homeostasis is involved in various cellular malfunctions and diseases. Recently, mitochondria, energy-producing organelles, have been known as major intracellular Mg2+ stores. Several biological stimuli alter mitochondrial Mg2+ concentration by intracellular redistribution. However, in living cells, whether mitochondrial Mg2+ alteration affect cellular energy metabolism remains unclear. Mg2+ transporter of mitochondrial inner membrane MRS2 is an essential component of mitochondrial Mg2+ uptake system. Here, we comprehensively analyzed intracellular Mg2+ levels and energy metabolism in Mrs2 knockdown (KD) cells using fluorescence imaging and metabolome analysis. Dysregulation of mitochondrial Mg2+ homeostasis disrupted ATP production via shift of mitochondrial energy metabolism and morphology. Moreover, Mrs2 KD sensitized cellular tolerance against cellular stress. These results indicate regulation of mitochondrial Mg2+ via MRS2 critically decides cellular energy status and cell vulnerability via regulation of mitochondrial Mg2+ level in response to physiological stimuli. PMID:27458051

  18. Mitochondrial Mg(2+) homeostasis decides cellular energy metabolism and vulnerability to stress.

    PubMed

    Yamanaka, Ryu; Tabata, Sho; Shindo, Yutaka; Hotta, Kohji; Suzuki, Koji; Soga, Tomoyoshi; Oka, Kotaro

    2016-01-01

    Cellular energy production processes are composed of many Mg(2+) dependent enzymatic reactions. In fact, dysregulation of Mg(2+) homeostasis is involved in various cellular malfunctions and diseases. Recently, mitochondria, energy-producing organelles, have been known as major intracellular Mg(2+) stores. Several biological stimuli alter mitochondrial Mg(2+) concentration by intracellular redistribution. However, in living cells, whether mitochondrial Mg(2+) alteration affect cellular energy metabolism remains unclear. Mg(2+) transporter of mitochondrial inner membrane MRS2 is an essential component of mitochondrial Mg(2+) uptake system. Here, we comprehensively analyzed intracellular Mg(2+) levels and energy metabolism in Mrs2 knockdown (KD) cells using fluorescence imaging and metabolome analysis. Dysregulation of mitochondrial Mg(2+) homeostasis disrupted ATP production via shift of mitochondrial energy metabolism and morphology. Moreover, Mrs2 KD sensitized cellular tolerance against cellular stress. These results indicate regulation of mitochondrial Mg(2+) via MRS2 critically decides cellular energy status and cell vulnerability via regulation of mitochondrial Mg(2+) level in response to physiological stimuli. PMID:27458051

  19. Increasing Phosphatidylinositol (4,5)-Bisphosphate Biosynthesis Affects Basal Signaling and Chloroplast Metabolism in Arabidopsis thaliana

    PubMed Central

    Im, Yang Ju; Smith, Caroline M.; Phillippy, Brian Q.; Strand, Deserah; Kramer, David M.; Grunden, Amy M.; Boss, Wendy F.

    2014-01-01

    One challenge in studying the second messenger inositol(1,4,5)-trisphosphate (InsP3) is that it is present in very low amounts and increases only transiently in response to stimuli. To identify events downstream of InsP3, we generated transgenic plants constitutively expressing the high specific activity, human phosphatidylinositol 4-phosphate 5-kinase Iα (HsPIPKIα). PIP5K is the enzyme that synthesizes phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2); this reaction is flux limiting in InsP3 biosynthesis in plants. Plasma membranes from transgenic Arabidopsis expressing HsPIPKIα had 2–3 fold higher PIP5K specific activity, and basal InsP3 levels in seedlings and leaves were >2-fold higher than wild type. Although there was no significant difference in photosynthetic electron transport, HsPIPKIα plants had significantly higher starch (2–4 fold) and 20% higher anthocyanin compared to controls. Starch content was higher both during the day and at the end of dark period. In addition, transcripts of genes involved in starch metabolism such as SEX1 (glucan water dikinase) and SEX4 (phosphoglucan phosphatase), DBE (debranching enzyme), MEX1 (maltose transporter), APL3 (ADP-glucose pyrophosphorylase) and glucose-6-phosphate transporter (Glc6PT) were up-regulated in the HsPIPKIα plants. Our results reveal that increasing the phosphoinositide (PI) pathway affects chloroplast carbon metabolism and suggest that InsP3 is one component of an inter-organelle signaling network regulating chloroplast metabolism. PMID:27135490

  20. Potato snakin-1 gene silencing affects cell division, primary metabolism, and cell wall composition.

    PubMed

    Nahirñak, Vanesa; Almasia, Natalia Inés; Fernandez, Paula Virginia; Hopp, Horacio Esteban; Estevez, José Manuel; Carrari, Fernando; Vazquez-Rovere, Cecilia

    2012-01-01

    Snakin-1 (SN1) is an antimicrobial cysteine-rich peptide isolated from potato (Solanum tuberosum) that was classified as a member of the Snakin/Gibberellic Acid Stimulated in Arabidopsis protein family. In this work, a transgenic approach was used to study the role of SN1 in planta. Even when overexpressing SN1, potato lines did not show remarkable morphological differences from the wild type; SN1 silencing resulted in reduced height, which was accompanied by an overall reduction in leaf size and severe alterations of leaf shape. Analysis of the adaxial epidermis of mature leaves revealed that silenced lines had 70% to 90% increases in mean cell size with respect to wild-type leaves. Consequently, the number of epidermal cells was significantly reduced in these lines. Confocal microscopy analysis after agroinfiltration of Nicotiana benthamiana leaves showed that SN1-green fluorescent protein fusion protein was localized in plasma membrane, and bimolecular fluorescence complementation assays revealed that SN1 self-interacted in vivo. We further focused our study on leaf metabolism by applying a combination of gas chromatography coupled to mass spectrometry, Fourier transform infrared spectroscopy, and spectrophotometric techniques. These targeted analyses allowed a detailed examination of the changes occurring in 46 intermediate compounds from primary metabolic pathways and in seven cell wall constituents. We demonstrated that SN1 silencing affects cell division, leaf primary metabolism, and cell wall composition in potato plants, suggesting that SN1 has additional roles in growth and development beyond its previously assigned role in plant defense. PMID:22080603

  1. Metabolic syndrome affects breast cancer risk in postmenopausal women: National Cancer Institute of Naples experience.

    PubMed

    Capasso, Immacolata; Esposito, Emanuela; Pentimalli, Francesca; Crispo, Anna; Montella, Maurizio; Grimaldi, Maria; De Marco, MariaRosaria; Cavalcanti, Ernestina; D'Aiuto, Massimiliano; Fucito, Alfredo; Frasci, Giuseppe; Maurea, Nicola; Esposito, Giuseppe; Pedicini, Tonino; Vecchione, Aldo; D'Aiuto, Giuseppe; Giordano, Antonio

    2010-12-15

    Postmenopausal women show the highest incidence of breast cancer in the female population and are often affected by metabolic syndrome. Metabolic syndrome (MS)--characterized by central adiposity, insulin resistance, low serum high-density lipoprotein cholesterol (HDL-C), high serum triglyceride and high blood pressure--seems to be strictly correlated to breast carcinogenesis. We enrolled 777 healthy women and women with breast cancer in our nested case-control study to evaluate the association between MS and breast cancer, analyzing anthropometric parameters (weight, height, BMI, waist and hip circumference), blood pressure, serum HDL-C, triglyceride, fasting plasma glucose, insulin, testosterone and uric acid levels and administering a questionnaire about physical activity, food intake, tobacco use, alcohol abuse, personal and familial history of disease. We found an higher prevalence of metabolic syndrome (30%) in postmenopausal breast cancer patients compared to healthy women (19%). None of the individual MS features was strong enough to be considered responsible for breast carcinogenesis alone. However, of the 63 postmenopausal breast cancer cases associated to MS, 30% presented three or more MS features, suggesting that the activation of multiple molecular pathways underlying MS might contribute to tumorigenesis. Our data support the hypothesis that MS may be an indicator of breast cancer risk in postmenopausal women. The unsettlement of the hormonal arrangement in postmenopausal, along with an increase in visceral adiposity, probably favour the hormone-dependent cell proliferation, which drives tumorigenesis. Adjustments in lifestyle with physical activity intensification and healthy diet could represent modifiable factors for the primary prevention of sporadic breast cancer. PMID:20935521

  2. Factors affecting carisoprodol metabolism in pain patients using urinary excretion data.

    PubMed

    Tse, Stephanie A; Atayee, Rabia S; Ma, Joseph D; Best, Brookie M

    2014-04-01

    Carisoprodol is a skeletal muscle relaxant prescribed to treat pain. Carisoprodol is metabolized to meprobamate, an active metabolite with anxiolytic effects, by the genetically polymorphic CYP2C19 enzyme. Concomitant use of CYP2C19 substrates or inhibitors may alter carisoprodol metabolism, with therapeutic and/or toxic implications for effectively treating patients with pain. This was a retrospective analysis of urinary excretion data collected from patients with pain from March 2008 to May 2011. Carisoprodol and meprobamate urine concentrations were measured by liquid chromatography-tandem mass spectrometry, and the metabolic ratio (MR) of meprobamate to carisoprodol concentrations was determined in 14,965 subjects. The MR geometric mean and 95% confidence interval (95% CI) of the young group (105, 95% CI = 99.1-113) were ∼47.4% higher than the middle-aged group (71.9, 95% CI = 70-73.8) and nearly two times higher than the elderly group (54.4, 95% CI = 51.3-57.6). Females had a 20.7% higher MR compared with males. No significant change in the MR was observed with overall CYP2C19 inhibitor or substrate use. However, evaluation of individual inhibitors showed co-administration with esomeprazole or fluoxetine was associated with a 31.8 and 24.6% reduction in MR, respectively, compared with controls (P < 0.05). Omeprazole did not significantly affect the MR. Patient-specific factors such as age, sex and co-medications may be important considerations for effective carisoprodol therapy. PMID:24488112

  3. 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

  4. 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

  5. Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature

    PubMed Central

    Norambuena, Fernando; Morais, Sofia; Emery, James A.; Turchini, Giovanni M.

    2015-01-01

    Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3), with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar) kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad–time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher water temperature

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

    PubMed

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

    2015-08-01

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

  7. Plasticity and epistasis strongly affect bacterial fitness after losing multiple metabolic genes.

    PubMed

    D'Souza, Glen; Waschina, Silvio; Kaleta, Christoph; Kost, Christian

    2015-05-01

    Many bacterial lineages lack seemingly essential metabolic genes. Previous work suggested selective benefits could drive the loss of biosynthetic functions from bacterial genomes when the corresponding metabolites are sufficiently available in the environment. However, the factors that govern this "genome streamlining" remain poorly understood. Here we determine the effect of plasticity and epistasis on the fitness of Escherichia coli genotypes from whose genome biosynthetic genes for one, two, or three different amino acids have been deleted. Competitive fitness experiments between auxotrophic mutants and prototrophic wild-type cells in one of two carbon environments revealed that plasticity and epistasis strongly affected the mutants' fitness individually and interactively. Positive and negative epistatic interactions were prevalent, yet on average cancelled each other out. Moreover, epistasis correlated negatively with the expected effects of combined auxotrophy-causing mutations, thus producing a pattern of diminishing returns. Moreover, computationally analyzing 1,432 eubacterial metabolic networks revealed that most pairs of auxotrophies co-occurred significantly more often than expected by chance, suggesting epistatic interactions and/or environmental factors favored these combinations. Our results demonstrate that both the genetic background and environmental conditions determine the adaptive value of a loss-of-biochemical-function mutation and that fitness gains decelerate, as more biochemical functions are lost. PMID:25765095

  8. Rice Debranching Enzyme Isoamylase3 Facilitates Starch Metabolism and Affects Plastid Morphogenesis

    PubMed Central

    Yun, Min-Soo; Umemoto, Takayuki; Kawagoe, Yasushi

    2011-01-01

    Debranching enzymes, which hydrolyze α-1 and 6-glucosidic linkages in α-polyglucans, play a dual role in the synthesis and degradation of starch in plants. A transposon-inserted rice mutant of isoamylase3 (isa3) contained an increased amount of starch in the leaf blade at the end of the night, indicating that ISA3 plays a role in the degradation of transitory starch during the night. An epitope-tagged ISA3 expressed in Escherichia coli exhibited hydrolytic activity on β-limit dextrin and amylopectin. We investigated whether ISA3 plays a role in amyloplast development and starch metabolism in the developing endosperm. ISA3–green fluorescent protein (GFP) fusion protein expressed under the control of the rice ISA3 promoter was targeted to the amyloplast stroma in the endosperm. Overexpression of ISA3 in the sugary1 mutant, which is deficient in ISA1 activity, did not convert water-soluble phytoglycogen to starch granules, indicating that ISA1 and ISA3 are not functionally redundant. Both overexpression and loss of function of ISA3 in the endosperm generated pleomorphic amyloplasts and starch granules. Furthermore, chloroplasts in the leaf blade of isa3 seedlings were large and pleomorphic. These results suggest that ISA3 facilitates starch metabolism and affects morphological characteristics of plastids in rice. PMID:21551159

  9. Campomanesia adamantium extract induces DNA damage, apoptosis, and affects cyclophosphamide metabolism.

    PubMed

    Martello, M D; David, N; Matuo, R; Carvalho, P C; Navarro, S D; Monreal, A C D; Cunha-Laura, A L; Cardoso, C A L; Kassuya, C A L; Oliveira, R J

    2016-01-01

    Campomanesia adamantium (Cambess.) O. Berg. is originally from Brazil. Its leaves and fruits have medicinal properties such as anti-inflammatory, antidiarrheal and antiseptic properties. However, the mutagenic potential of this species has been reported in few studies. This study describes the mutagenic/antimutagenic, splenic phagocytic, and apoptotic activities of C. adamantium hydroethanolic extract with or without cyclophosphamide in Swiss mice. The animals orally received the hydroethanolic extract at doses of 30, 100, or 300 mg/kg with or without 100 mg/kg cyclophosphamide. Mutagenesis was evaluated by performing the micronucleus assay after treatment for 24, 48, and 72 h, while splenic phagocytic and apoptotic effects were investigated after 72 h. Short-term exposure of 30 and 100 mg/kg extract induced mild clastogenic/aneugenic effects and increased splenic phagocytosis and apoptosis in the liver, spleen, and kidneys. When the extract was administered in combination with cyclophosphamide, micronucleus frequency and apoptosis reduced. Extract components might affect cyclophosphamide metabolism, which possibly leads to increased clearance of this chemotherapeutic agent. C. adamantium showed mutagenic activity and it may decrease the effectiveness of drugs with metabolic pathways similar to those associated with cyclophosphamide. Thus, caution should be exercised while consuming these extracts, especially when received in combination with other drugs. PMID:27173259

  10. Failure of caffeine to affect metabolism during 60 min submaximal exercise.

    PubMed

    Titlow, L W; Ishee, J H; Riggs, C E

    1991-01-01

    Caffeine consumption prior to athletic performance has become commonplace. The usual dosage is approximately 200 mg, a level of caffeine ingestion equivalent to two cups of brewed coffee. This study was designed to examine the effects of a common level of caffeine ingestion, specifically 200 mg, on metabolism during submaximal exercise performance in five males. The subjects performed two 60-min monitored treadmill workouts at 60% maximal heart rate during a 2-week period. The subjects were randomly assigned, double-blind to receive a caffeine or placebo capsule 60 min prior to exercise. Testing was performed in the afternoon following a midnight fast. Venous blood was withdrawn pre-exercise, every 15 min during the workout, and 10 min after recovery. Blood was analysed for free fatty acid, triglycerides, glucose, lactic acid, haemoglobin and haematocrit. The respiratory exchange ratio (R), perceived exertion (RPE) and oxygen uptake were measured every 4 min during exercise. An examination of the data with repeated-measures ANOVA revealed no significant differences between the two groups. Within the limitations of the study, it was concluded that 200 mg caffeine failed to affect metabolism during 60 min submaximal exercise. PMID:1856908

  11. Factors Affecting the Absorption, Metabolism, and Excretion of Cocoa Flavanols in Humans.

    PubMed

    Cifuentes-Gomez, Tania; Rodriguez-Mateos, Ana; Gonzalez-Salvador, Isidro; Alañon, María Elena; Spencer, Jeremy P E

    2015-09-01

    Cocoa is rich in a subclass of flavonoids known as flavanols, the cardiovascular health benefits of which have been extensively reported. The appearance of flavanol metabolites in the systemic circulation after flavanol-rich food consumption is likely to mediate the physiological effects on the vascular system, and these levels are influenced by numerous factors, including food matrix, processing, intake, age, gender, or genetic polymorphisms, among others. This review will focus on our current understanding of factors affecting the absorption, metabolism, and excretion of cocoa flavanols in humans. Second, it will identify gaps in these contributing factors that need to be addressed to conclusively translate our collective knowledge into the context of public health, dietary guidelines, and evidence-based dietary recommendations. PMID:25711140

  12. Escherichia coli carbon source metabolism affects longevity of its predator Caenorhabditis elegans.

    PubMed

    Brokate-Llanos, Ana María; Garzón, Andrés; Muñoz, Manuel J

    2014-01-01

    Nutrition is probably the most determinant factor affecting aging. Microorganisms of the intestinal flora lay in the interface between available nutrients and nutrients that are finally absorbed by multicellular organisms. They participate in the processing and transformation of these nutrients in a symbiotic or commensalistic relationship. In addition, they can also be pathogens. Alive Escherichia coli OP50 are usually used to culture the bacteriovorus nematode Caenorhabditis elegans. Here, we report a beneficial effect of low concentration of saccharides on the longevity of C. elegans. This effect is only observed when the bacterium can metabolize the sugar, suggesting that physiological changes in the bacterium feeding on the saccharides are the cause of this beneficial effect. PMID:25263107

  13. Metabolic depression during warm torpor in the Golden spiny mouse (Acomys russatus) does not affect mitochondrial respiration and hydrogen peroxide release.

    PubMed

    Grimpo, Kirsten; Kutschke, Maria; Kastl, Anja; Meyer, Carola W; Heldmaier, Gerhard; Exner, Cornelia; Jastroch, Martin

    2014-01-01

    Small mammals actively decrease metabolism during daily torpor and hibernation to save energy. Recently, depression of mitochondrial substrate oxidation in isolated liver mitochondria was observed and associated to hypothermic/hypometabolic states in Djungarian hamsters, mice and hibernators. We aimed to clarify whether hypothermia or hypometabolism causes mitochondrial depression during torpor by studying the Golden spiny mouse (Acomys russatus), a desert rodent which performs daily torpor at high ambient temperatures of 32°C. Notably, metabolic rate but not body temperature is significantly decreased under these conditions. In isolated liver, heart, skeletal muscle or kidney mitochondria we found no depression of respiration. Moderate cold exposure lowered torpor body temperature but had minor effects on minimal metabolic rate in torpor. Neither decreased body temperature nor metabolic rate impacted mitochondrial respiration. Measurements of mitochondrial proton leak kinetics and determination of P/O ratio revealed no differences in mitochondrial efficiency. Hydrogen peroxide release from mitochondria was not affected. We conclude that interspecies differences of mitochondrial depression during torpor do not support a general relationship between mitochondrial respiration, body temperature and metabolic rate. In Golden spiny mice, reduction of metabolic rate at mild temperatures is not triggered by depression of substrate oxidation as found in liver mitochondria from other cold-exposed rodents. PMID:24021912

  14. A bioassay to measure energy metabolism in mouse colonic crypts, organoids, and sorted stem cells.

    PubMed

    Fan, Yang-Yi; Davidson, Laurie A; Callaway, Evelyn S; Wright, Gus A; Safe, Stephen; Chapkin, Robert S

    2015-07-01

    Evidence suggests that targeting cancer cell energy metabolism might be an effective therapeutic approach for selective ablation of malignancies. Using a Seahorse Extracellular Flux Analyzer, we have demonstrated that select environmental agents can alter colonic mitochondrial function by increasing respiration-induced proton leak, thereby inducing apoptosis, a marker of colon cancer risk. To further probe bioenergetics in primary intestinal cells, we developed methodology that can be modified and adapted to measure the bioenergetic profiles of colonic crypts, the basic functional unit of the colon, and colonic organoids, an ex vivo 3D culture of colonic crypts. Furthermore, in combination with the MoFlo Astrios High-Speed Cell Sorter, we were able to measure the bioenergetic profiles of colonic adult stem and daughter cells from Lgr5-EGFP-IRES-creER(T2) transgenic mice. We examined the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a full arylhydrocarbon receptor agonist, known to affect gastrointestinal function and cancer risk, on the bioenergetic profiles of intestinal epithelial cells. Mouse colonic crypts, organoids, or sorted single cells were seeded onto Matrigel-precoated Seahorse XF24 microplates for extracellular flux analysis. Temporal analyses revealed distinct energy metabolic profiles in crypts and organoids challenged with TCDD. Furthermore, sorted Lgr5(+) stem cells exhibited a Warburg-like metabolic profile. This is noteworthy because perturbations in stem cell dynamics are generally believed to represent the earliest step toward colon tumorigenesis. We propose that our innovative methodology may facilitate future in vivo/ex vivo metabolic studies using environmental agents affecting colonocyte energy metabolism. PMID:25977509

  15. A bioassay to measure energy metabolism in mouse colonic crypts, organoids, and sorted stem cells

    PubMed Central

    Fan, Yang-Yi; Davidson, Laurie A.; Callaway, Evelyn S.; Wright, Gus A.; Safe, Stephen

    2015-01-01

    Evidence suggests that targeting cancer cell energy metabolism might be an effective therapeutic approach for selective ablation of malignancies. Using a Seahorse Extracellular Flux Analyzer, we have demonstrated that select environmental agents can alter colonic mitochondrial function by increasing respiration-induced proton leak, thereby inducing apoptosis, a marker of colon cancer risk. To further probe bioenergetics in primary intestinal cells, we developed methodology that can be modified and adapted to measure the bioenergetic profiles of colonic crypts, the basic functional unit of the colon, and colonic organoids, an ex vivo 3D culture of colonic crypts. Furthermore, in combination with the MoFlo Astrios High-Speed Cell Sorter, we were able to measure the bioenergetic profiles of colonic adult stem and daughter cells from Lgr5-EGFP-IRES-creERT2 transgenic mice. We examined the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a full arylhydrocarbon receptor agonist, known to affect gastrointestinal function and cancer risk, on the bioenergetic profiles of intestinal epithelial cells. Mouse colonic crypts, organoids, or sorted single cells were seeded onto Matrigel-precoated Seahorse XF24 microplates for extracellular flux analysis. Temporal analyses revealed distinct energy metabolic profiles in crypts and organoids challenged with TCDD. Furthermore, sorted Lgr5+ stem cells exhibited a Warburg-like metabolic profile. This is noteworthy because perturbations in stem cell dynamics are generally believed to represent the earliest step toward colon tumorigenesis. We propose that our innovative methodology may facilitate future in vivo/ex vivo metabolic studies using environmental agents affecting colonocyte energy metabolism. PMID:25977509

  16. Energy metabolism and glutamate-glutamine cycle in the brain: a stoichiometric modeling perspective

    PubMed Central

    2013-01-01

    Background The energetics of cerebral activity critically relies on the functional and metabolic interactions between neurons and astrocytes. Important open questions include the relation between neuronal versus astrocytic energy demand, glucose uptake and intercellular lactate transfer, as well as their dependence on the level of activity. Results We have developed a large-scale, constraint-based network model of the metabolic partnership between astrocytes and glutamatergic neurons that allows for a quantitative appraisal of the extent to which stoichiometry alone drives the energetics of the system. We find that the velocity of the glutamate-glutamine cycle (Vcyc) explains part of the uncoupling between glucose and oxygen utilization at increasing Vcyc levels. Thus, we are able to characterize different activation states in terms of the tissue oxygen-glucose index (OGI). Calculations show that glucose is taken up and metabolized according to cellular energy requirements, and that partitioning of the sugar between different cell types is not significantly affected by Vcyc. Furthermore, both the direction and magnitude of the lactate shuttle between neurons and astrocytes turn out to depend on the relative cell glucose uptake while being roughly independent of Vcyc. Conclusions These findings suggest that, in absence of ad hoc activity-related constraints on neuronal and astrocytic metabolism, the glutamate-glutamine cycle does not control the relative energy demand of neurons and astrocytes, and hence their glucose uptake and lactate exchange. PMID:24112710

  17. 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

  18. 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.

  19. Spermatozoa: models for studying regulatory aspects of energy metabolism.

    PubMed

    Kamp, G; Büsselmann, G; Lauterwein, J

    1996-05-15

    Spermatozoa are highly specialized cells, and they offer advantages for studying several basic aspects of metabolic control such as the role of adenosine triphosphate-(ATP)-homeostasis for cell function, the mechanisms of fatigue and metabolic depression, the metabolic channelling through the cytoplasm and the organization and regulation of glycolytic enzymes. Spermatozoa of four species with different reproductive modes are introduced and the first results are presented: Spermatozoa of the marine worm Arenicola marina are well adapted to external fertilization in sea water with fluctuating oxygen tension: they are motile for several hours in oxygen-free sea water, even when the ATP level is dramatically reduced. Anaerobic ATP production occurs by alanine, acetate and propionate fermentation probably by the same pathways known from somatic cells of this species. Under aerobic conditions the phosphagen system might function like a shuttle for energy-rich phosphate from mitochondria to the dynein-ATPases. Storage of turkey and carp spermatozoa for several hours without exogenous substrates and oxygen results in the degradation of phosphocreatine and ATP to inorganic phosphate and adenosine monophosphate (AMP), respectively. Despite low energy charges, stored spermatozoa of both species are capable of progressive movements. In carp spermatozoa fatigue of motility is not accompanied by the dramatic acidosis one discusses as an important effect in muscle fatigue. Energy metabolism of boar spermatozoa is typically based on glycolysis consuming extracellular carbohydrates and producing lactate and protons. The sperm seem to tolerate low intracellular pH (< 6.5). The lack of a phosphagen system (no energy shuttle from mitochondria to the distal dynein-ATPases) is probably compensated by a high glycolytic ATP-production in the mitochondria-free piece of the flagellum. PMID:8641386

  20. 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

  1. 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

  2. Metabolic regulation and energy homeostasis through the primary cilium

    PubMed Central

    Oh, Edwin C.; Vasanth, Shivakumar; Katsanis, Nicholas

    2015-01-01

    Obesity and diabetes represent a significant healthcare concern. In contrast to genome-wide association studies that, some exceptions notwithstanding, have offered modest clues about pathomechanism, the dissection of rare disorders in which obesity represents a core feature have highlighted key molecules and structures critical to energy regulation. Here we focus on the primary cilium, an organelle whose roles in energy homeostasis have been underscored by the high incidence of obesity and type II diabetes in patients and mouse mutants with compromised ciliary function. We discuss recent evidence linking ciliary dysfunction to metabolic defects and we explore the contribution of neuronal and non-neuronal cilia to these phenotypes. PMID:25543293

  3. 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

  4. Drought stress affects chloroplast lipid metabolism in rape (Brassica napus) leaves.

    PubMed

    Benhassaine-Kesri, Ghouziel; Aid, Fatiha; Demandre, Chantal; Kader, Jean-Claude; Mazliak, Paul

    2002-06-01

    Rape (Brassica napus L. var. Bienvenue) is a 16:3 plant which contains predominantly prokaryotic species of monogalactosyldiacylglycerol i.e. sn-1 C18, sn-2 C16 (C18/C16 MGDG). Rape plants were exposed to a restricted water supply for 12 days. Under drought conditions, considerable changes in lipid metabolism were observed. Drought stress provoked a decline in leaf polar lipids, which is mainly due to a decrease in MGDG content. Determination of molecular species in phosphatidylcholine (PC) and MGDG indicated that the prokaryotic molecular species of MGDG (C18/C16) decreased after drought stress while the eukaryotic molecular species (C18/C18) remained stable. Drought stress had different effects on two key enzymes of PC and MGDG synthesis. The in vitro activity of MGDG synthase (EC. 2.4.1.46) was reduced in drought stressed plants whereas cholinephosphotransferase (EC. 2.7.8.2) activity was not affected. Altogether these results suggest that the prokaryotic pathway leading to MGDG synthesis was strongly affected by drought stress while the eukaryotic pathway was not. It was also observed that the molecular species of leaf PC became more saturated in drought stressed plants. This could be due to a specific decrease in oleate desaturase activity. PMID:12060239

  5. Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism

    PubMed Central

    Tong, Maomeng; McHardy, Ian; Ruegger, Paul; Goudarzi, Maryam; Kashyap, Purna C; Haritunians, Talin; Li, Xiaoxiao; Graeber, Thomas G; Schwager, Emma; Huttenhower, Curtis; Fornace, Albert J; Sonnenburg, Justin L; McGovern, Dermot PB; Borneman, James; Braun, Jonathan

    2014-01-01

    Fucosyltransferase 2 (FUT2) is an enzyme that is responsible for the synthesis of the H antigen in body fluids and on the intestinal mucosa. The H antigen is an oligosaccharide moiety that acts as both an attachment site and carbon source for intestinal bacteria. Non-secretors, who are homozygous for the loss-of-function alleles of FUT2 gene (sese), have increased susceptibility to Crohn's disease (CD). To characterize the effect of FUT2 polymorphism on the mucosal ecosystem, we profiled the microbiome, meta-proteome and meta-metabolome of 75 endoscopic lavage samples from the cecum and sigmoid of 39 healthy subjects (12 SeSe, 18 Sese and 9 sese). Imputed metagenomic analysis revealed perturbations of energy metabolism in the microbiome of non-secretor and heterozygote individuals, notably the enrichment of carbohydrate and lipid metabolism, cofactor and vitamin metabolism and glycan biosynthesis and metabolism-related pathways, and the depletion of amino-acid biosynthesis and metabolism. Similar changes were observed in mice bearing the FUT2−/− genotype. Metabolomic analysis of human specimens revealed concordant as well as novel changes in the levels of several metabolites. Human metaproteomic analysis indicated that these functional changes were accompanied by sub-clinical levels of inflammation in the local intestinal mucosa. Therefore, the colonic microbiota of non-secretors is altered at both the compositional and functional levels, affecting the host mucosal state and potentially explaining the association of FUT2 genotype and CD susceptibility. PMID:24781901

  6. 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. PMID:1543386

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

    PubMed Central

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

    1992-01-01

    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. PMID:1543386

  8. A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis

    PubMed Central

    Chun, Sunwoo; Bamba, Takeshi; Suyama, Tatsuya; Ishijima, Tomoko; Fukusaki, Eiichiro; Abe, Keiko; Nakai, Yuji

    2016-01-01

    A high phosphorus (HP) diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus) or a HP diet (containing 1.2% phosphorus). Gene Ontology analysis of differentially expressed genes (DEGs) revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid β-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor for fatty acid β-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARα was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARα target gene, was higher (p = 0.054) in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty acids

  9. Effects of rutin and buckwheat seeds on energy metabolism and methane production in dairy cows.

    PubMed

    Stoldt, Ann-Kathrin; Derno, Michael; Das, Gürbüz; Weitzel, Joachim M; Wolffram, Siegfried; Metges, Cornelia C

    2016-03-01

    Flavonoids are secondary plant metabolites with several health promoting effects. As dairy cows often suffer from metabolic imbalance and health problems, interest is growing in health improvements by plant substances such as flavonoids. Our group has recently shown that the flavonoids quercetin and rutin (a glucorhamnoside of quercetin) are bioavailable in cows when given via a duodenal fistula or orally, respectively, affect glucose metabolism, and have beneficial effects on liver health. Furthermore, flavonoids may reduce rumen methane production in vitro through their antibacterial properties. To test the hypothesis that rutin has effects on energy metabolism, methane production, and production performance in dairy cows, we fed rutin trihydrate at a dose of 100mg/kg of body weight to a group of 7 lactating dairy cows for 2 wk in a crossover design. In a second experiment, 2 cows were fed the same ration but were supplemented with buckwheat seeds (Fagopyrum tartaricum), providing rutin at a dose comparable to the first experiment. Two other cows receiving barley supplements were used as controls in a change-over mode. Blood samples were taken weekly and respiration measurements were performed at the end of each treatment. Supplementation of pure rutin, but not of rutin contained in buckwheat seeds, increased the plasma quercetin content. Methane production and milk yield and composition were not affected by rutin treatment in either form. Plasma glucose, β-hydroxybutyrate, and albumin were increased by pure rutin treatment, indicating a possible metabolic effect of rutin on energy metabolism of dairy cows. In addition, we did not show that in vivo ruminal methane production was reduced by rutin. In conclusion, we could not confirm earlier reports on in vitro methane reduction by rutin supplementation in dairy cows in established lactation. PMID:26805964

  10. Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain

    PubMed Central

    Omata, Yo; Salvador, Gabriela A.; Oteiza, Patricia I.

    2013-01-01

    A deficit in zinc (Zn) availability can increase cell oxidant production, affect the antioxidant defense system, and trigger oxidant-sensitive signals in neuronal cells. This work tested the hypothesis that a decreased Zn availability can affect glutathione (GSH) metabolism in the developing rat brain and in neuronal cells in culture, as well as the capacity of human neuroblastoma IMR-32 cells to upregulate GSH when challenged with dopamine (DA). GSH levels were low in the brain of gestation day 19 (GD19) fetuses from dams fed marginal Zn diets throughout gestation and in Zn-deficient IMR-32 cells. γ-Glutamylcysteine synthetase (GCL), the first enzyme in the GSH synthetic pathway, was altered by Zn deficiency (ZD). The protein and mRNA levels of the GCL modifier (GCLM) and catalytic (GCLC) subunits were lower in the Zn-deficient GD19 fetal brain and in IMR-32 cells compared with controls. The nuclear translocation of transcription factor nuclear factor (erythroid-derived 2)-like 2, which controls GCL transcription, was impaired by ZD. Posttranslationally, the caspase-3-dependent GCLC cleavage was high in Zn-deficient IMR-32 cells. Cells challenged with DA showed an increase in GCLM and GCLC protein and mRNA levels and a consequent increase in GSH concentration. Although Zn-deficient cells partially upregulated GCL subunits after exposure to DA, GSH content remained low. In summary, results show that a low Zn availability affects the GSH synthetic pathway in neuronal cells and fetal brain both at transcriptional and posttranslational levels. This can in part underlie the GSH depletion associated with ZD and the high sensitivity of Zn-deficient neurons to pro-oxidative stressors. PMID:23377617

  11. Interaction among Skeletal Muscle Metabolic Energy Systems during Intense Exercise

    PubMed Central

    Baker, Julien S.; McCormick, Marie Clare; Robergs, Robert A.

    2010-01-01

    High-intensity exercise can result in up to a 1,000-fold increase in the rate of ATP demand compared to that at rest (Newsholme et al., 1983). To sustain muscle contraction, ATP needs to be regenerated at a rate complementary to ATP demand. Three energy systems function to replenish ATP in muscle: (1) Phosphagen, (2) Glycolytic, and (3) Mitochondrial Respiration. The three systems differ in the substrates used, products, maximal rate of ATP regeneration, capacity of ATP regeneration, and their associated contributions to fatigue. In this exercise context, fatigue is best defined as a decreasing force production during muscle contraction despite constant or increasing effort. The replenishment of ATP during intense exercise is the result of a coordinated metabolic response in which all energy systems contribute to different degrees based on an interaction between the intensity and duration of the exercise, and consequently the proportional contribution of the different skeletal muscle motor units. Such relative contributions also determine to a large extent the involvement of specific metabolic and central nervous system events that contribute to fatigue. The purpose of this paper is to provide a contemporary explanation of the muscle metabolic response to different exercise intensities and durations, with emphasis given to recent improvements in understanding and research methodology. PMID:21188163

  12. Multiple dietary supplements do not affect metabolic and cardio-vascular health.

    PubMed

    Soare, Andreea; Weiss, Edward P; Holloszy, John O; Fontana, Luigi

    2014-02-01

    Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m(2)) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals. PMID:24659610

  13. Benzothiadiazole (BTH) activates sterol pathway and affects vitamin D3 metabolism in Solanum malacoxylon cell cultures.

    PubMed

    Burlini, Nedda; Iriti, Marcello; Daghetti, Anna; Faoro, Franco; Ruggiero, Antonietta; Bernasconi, Silvana

    2011-11-01

    Benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH), a particularly efficient inducer of systemic acquired resistance (SAR), was developed as an immunizing agent to sensitize various crop species against pathogen infections. Recent works highlighted its activating effect on different metabolic pathways, concerning both primary and secondary metabolites. In this study, we investigated the effect of BTH treatment on sterol levels and vitamin D(3) metabolism in Solanum malacoxylon cultures. Calli of S. malacoxylon were incubated in Gamborg B5 liquid medium alone or added with 50 μM BTH for different times (one, two or three cycles of light). Histocytochemical investigations performed on our experimental system using 3,3'-diaminobenzidine (DAB) for hydrogen peroxide (H(2)O(2)) detection and phloroglucinol for lignin staining showed that BTH causes H(2)O(2) accumulation and lignin deposition in treated calli. Gas chromatographic analysis of principal cell membrane sterols (β-sitosterol, campesterol, stigmasterol) showed that BTH transiently increases their cellular levels. Callus cultures were found to contain also cholesterol, 7-dehydrocholesterol, the putative precursor of vitamin D(3), and the hydroxylated metabolites 25-hydroxyvitamin D(3) [25(OH)D(3)] and 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2)D(3)]. BTH treatment enhanced 7-dehydrocholesterol while reduced cholesterol. HPLC analysis of sample extracts showed that BTH does not affect the cell content of vitamin D(3), though results of ELISA tests highlighted that this elicitor moderately enhances the levels of 25(OH)D(3) and 1α,25(OH)(2)D(3) metabolites. In conclusion, BTH treatment not only causes cell wall strengthening, a typical plant defence response, as just described in other experimental models, but in the same time increases the cellular level of the main sterols and 7-dehydrocholesterol. PMID:21779826

  14. [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

  15. Compensatory elevation of voluntary activity in mouse mutants with impaired mitochondrial energy metabolism

    PubMed Central

    Lapointe, Jérôme; G. Hughes, Bryan; Bigras, Eve; Hekimi, Siegfried

    2014-01-01

    Abstract Mitochondria play a crucial role in determining whole‐body metabolism and exercise capacity. Genetic mouse models of mild mitochondrial dysfunction provide an opportunity to understand how mitochondrial function affects these parameters. MCLK1 (a.k.a. Coq7) is an enzyme implicated in the biosynthesis of ubiquinone (UQ; Coenzyme Q). Low levels of MCLK1 in Mclk1+/− heterozygous mutants lead to abnormal sub‐mitochondrial distribution of UQ, impaired mitochondrial function, elevated mitochondrial oxidative stress, and increased lifespan. Here, we report that young Mclk1+/− males, but not females, show a significant decrease in whole‐body metabolic rate as measured by indirect calorimetry. Such a sex‐specific effect of mitochondrial dysfunction on energy metabolism has also been reported for heterozygous mice carrying a mutation for the gene encoding the “Rieske” protein of mitochondrial complex III (RISP+/P224S). We find that both Mclk1+/− and RISP+/P224S males are capable of restoring their defective metabolic rates by making significantly more voluntary use of a running wheel compared to wild type. However, this increase in voluntary activity does not reflect their exercise capacity, which we found to be impaired as revealed by a shorter treadmill distance run before exhaustion. In contrast to what is observed in Mclk1+/− and RISP+/P224S mutants, Sod2+/− mice with elevated oxidative stress and major mitochondrial dysfunction did not increase voluntary activity. Our study reveals a sex‐specific effect on how impaired mitochondrial function impacts whole‐body energy metabolism and locomotory behavior, and contributes to the understanding of the metabolic and behavioral consequences of mitochondrial disorders. PMID:25413331

  16. Effects of intranasal insulin on hepatic fat accumulation and energy metabolism in humans.

    PubMed

    Gancheva, Sofiya; Koliaki, Chrysi; Bierwagen, Alessandra; Nowotny, Peter; Heni, Martin; Fritsche, Andreas; Häring, Hans-Ulrich; Szendroedi, Julia; Roden, Michael

    2015-06-01

    Studies in rodents suggest that insulin controls hepatic glucose metabolism through brain-liver crosstalk, but human studies using intranasal insulin to mimic central insulin delivery have provided conflicting results. In this randomized controlled crossover trial, we investigated the effects of intranasal insulin on hepatic insulin sensitivity (HIS) and energy metabolism in 10 patients with type 2 diabetes and 10 lean healthy participants (CON). Endogenous glucose production was monitored with [6,6-(2)H2]glucose, hepatocellular lipids (HCLs), ATP, and inorganic phosphate concentrations with (1)H/(31)P magnetic resonance spectroscopy. Intranasal insulin transiently increased serum insulin levels followed by a gradual lowering of blood glucose in CON only. Fasting HIS index was not affected by intranasal insulin in CON and patients. HCLs decreased by 35% in CON only, whereas absolute hepatic ATP concentration increased by 18% after 3 h. A subgroup of CON received intravenous insulin to mimic the changes in serum insulin and blood glucose levels observed after intranasal insulin. This resulted in a 34% increase in HCLs without altering hepatic ATP concentrations. In conclusion, intranasal insulin does not affect HIS but rapidly improves hepatic energy metabolism in healthy humans, which is independent of peripheral insulinemia. These effects are blunted in patients with type 2 diabetes. PMID:25576060

  17. 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

  18. 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

  19. Glucose Availability and AMP-Activated Protein Kinase Link Energy Metabolism and Innate Immunity in the Bovine Endometrium

    PubMed Central

    Turner, Matthew L.; Cronin, James G.; Noleto, Pablo G.; Sheldon, I. Martin

    2016-01-01

    Defences against the bacteria that usually infect the endometrium of postpartum cattle are impaired when there is metabolic energy stress, leading to endometritis and infertility. The endometrial response to bacteria depends on innate immunity, with recognition of pathogen-associated molecular patterns stimulating inflammation, characterised by secretion of interleukin (IL)-1β, IL-6 and IL-8. How metabolic stress impacts tissue responses to pathogens is unclear, but integration of energy metabolism and innate immunity means that stressing one system might affect the other. Here we tested the hypothesis that homeostatic pathways integrate energy metabolism and innate immunity in bovine endometrial tissue. Glucose deprivation reduced the secretion of IL-1β, IL-6 and IL-8 from ex vivo organ cultures of bovine endometrium challenged with the pathogen-associated molecular patterns lipopolysaccharide and bacterial lipopeptide. Endometrial inflammatory responses to lipopolysaccharide were also reduced by small molecules that activate or inhibit the intracellular sensor of energy, AMP-activated protein kinase (AMPK). However, inhibition of mammalian target of rapamycin, which is a more global metabolic sensor than AMPK, had little effect on inflammation. Similarly, endometrial inflammatory responses to lipopolysaccharide were not affected by insulin-like growth factor-1, which is an endocrine regulator of metabolism. Interestingly, the inflammatory responses to lipopolysaccharide increased endometrial glucose consumption and induced the Warburg effect, which could exacerbate deficits in glucose availability in the tissue. In conclusion, metabolic energy stress perturbed inflammatory responses to pathogen-associated molecular patterns in bovine endometrial tissue, and the most fundamental regulators of cellular energy, glucose availability and AMPK, had the greatest impact on innate immunity. PMID:26974839

  20. Glucose Availability and AMP-Activated Protein Kinase Link Energy Metabolism and Innate Immunity in the Bovine Endometrium.

    PubMed

    Turner, Matthew L; Cronin, James G; Noleto, Pablo G; Sheldon, I Martin

    2016-01-01

    Defences against the bacteria that usually infect the endometrium of postpartum cattle are impaired when there is metabolic energy stress, leading to endometritis and infertility. The endometrial response to bacteria depends on innate immunity, with recognition of pathogen-associated molecular patterns stimulating inflammation, characterised by secretion of interleukin (IL)-1β, IL-6 and IL-8. How metabolic stress impacts tissue responses to pathogens is unclear, but integration of energy metabolism and innate immunity means that stressing one system might affect the other. Here we tested the hypothesis that homeostatic pathways integrate energy metabolism and innate immunity in bovine endometrial tissue. Glucose deprivation reduced the secretion of IL-1β, IL-6 and IL-8 from ex vivo organ cultures of bovine endometrium challenged with the pathogen-associated molecular patterns lipopolysaccharide and bacterial lipopeptide. Endometrial inflammatory responses to lipopolysaccharide were also reduced by small molecules that activate or inhibit the intracellular sensor of energy, AMP-activated protein kinase (AMPK). However, inhibition of mammalian target of rapamycin, which is a more global metabolic sensor than AMPK, had little effect on inflammation. Similarly, endometrial inflammatory responses to lipopolysaccharide were not affected by insulin-like growth factor-1, which is an endocrine regulator of metabolism. Interestingly, the inflammatory responses to lipopolysaccharide increased endometrial glucose consumption and induced the Warburg effect, which could exacerbate deficits in glucose availability in the tissue. In conclusion, metabolic energy stress perturbed inflammatory responses to pathogen-associated molecular patterns in bovine endometrial tissue, and the most fundamental regulators of cellular energy, glucose availability and AMPK, had the greatest impact on innate immunity. PMID:26974839

  1. Legal and regulatory issues affecting aquifer thermal energy storage

    SciTech Connect

    Hendrickson, P.L.

    1981-10-01

    This document updates and expands the report with a similar title issued in October 1980. This document examines a number of legal and regulatory issues that potentially can affect implementation of the aquifer thermal energy storage (ATES) concept. This concept involves the storage of thermal energy in an underground aquifer until a later date when it can be effectively utilized. Either heat energy or chill can be stored. Potential end uses of the energy include district space heating and cooling, industrial process applications, and use in agriculture or aquaculture. Issues are examined in four categories: regulatory requirements, property rights, potential liability, and issues related to heat or chill delivery.

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

    PubMed

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

    2016-04-01

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

  3. Sitamaquine-resistance in Leishmania donovani affects drug accumulation and lipid metabolism.

    PubMed

    Imbert, L; Cojean, S; Libong, D; Chaminade, P; Loiseau, P M

    2014-09-01

    This study focuses on the mechanism of sitamaquine-resistance in Leishmania donovani. Sitamaquine accumulated 10 and 1.4 fold more in cytosol than in membranes of wild-type (WT) and of sitamaquine-resistant (Sita-R160) L. donovani promastigotes, respectively. The sitamaquine accumulation was a concentration-dependent process in WT whereas a saturation occurred in Sita-R160 suggesting a reduced uptake or an increase of the sitamaquine efflux. Membrane negative phospholipids being the main target for sitamaquine uptake, a lipidomic analysis showed that sitamaquine-resistance did not rely on a decrease of membrane negative phospholipid rate in Sita-R160, discarding the hypothesis of reduced uptake. However, sterol and phospholipid metabolisms were strongly affected in Sita-R160 suggesting that sitamaquine-resistance could be related to an alteration of phosphatidylethanolamine-N-methyl-transferase and choline kinase activities and to a decrease in cholesterol uptake and of ergosterol biosynthesis. Preliminary data of proteomics analysis exhibited different protein profiles between WT and Sita-160R remaining to be characterized. PMID:25201056

  4. Alkyl-methylimidazolium ionic liquids affect the growth and fermentative metabolism of Clostridium sp

    SciTech Connect

    Nancharaiah, Y.V.; Francis, A.

    2011-06-01

    In this study, the effect of ionic liquids, 1-ethyl-3-methylimidazolium acetate [EMIM][Ac], 1-ethyl-3-methylimidazolium diethylphosphate [EMIM][DEP], and 1-methyl-3-methylimidazolium dimethylphosphate [MMIM][DMP] on the growth and glucose fermentation of Clostridium sp. was investigated. Among the three ionic liquids tested, [MMIM][DMP] was found to be least toxic. Growth of Clostridium sp. was not inhibited up to 2.5, 4 and 4 g L{sup -1} of [EMIM][Ac], [EMIM][DEP] and [MMIM][DMP], respectively. [EMIM][Ac] at <2.5 g L{sup -1}, showed hormetic effect and stimulated the growth and fermentation by modulating medium pH. Total organic acid production increased in the presence of 2.5 and 2 g L{sup -1} of [EMIM][Ac] and [MMIM][DMP]. Ionic liquids had no significant influence on alcohol production at <2.5 g L{sup -1}. Total gas production was affected by ILs at {ge}2.5 g L{sup -1} and varied with type of methylimidazolium IL. Overall, the results show that the growth and fermentative metabolism of Clostridium sp. is not impacted by ILs at concentrations below 2.5 g L{sup -1}.

  5. Mono-(2-ethylhexyl) phthalate targets glycogen debranching enzyme and affects glycogen metabolism in rat testis.

    PubMed

    Kuramori, Chikanori; Hase, Yasuyoshi; Hoshikawa, Koichi; Watanabe, Keiko; Nishi, Takeyuki; Hishiki, Takako; Soga, Tomoyoshi; Nashimoto, Akihiro; Kabe, Yasuaki; Yamaguchi, Yuki; Watanabe, Hajime; Kataoka, Kohsuke; Suematsu, Makoto; Handa, Hiroshi

    2009-05-01

    Phthalate esters are commonly used plasticizers; however, some are suspected to cause reproductive toxicity. Administration of high doses of di-(2-ethylhexyl) phthalate (DEHP) induces germ cell death in male rodents. Mono-(2-ethylhexyl) phthalate (MEHP), a hydrolyzed metabolite of DEHP, appears to be responsible for this testicular toxicity; however, the underlying mechanism of this chemical's action remains unknown. Here, using a one-step affinity purification procedure, we identified glycogen debranching enzyme (GDE) as a phthalate-binding protein. GDE has oligo-1,4-1,4-glucanotransferase and amylo-1,6-glucosidase activities, which are responsible for the complete degradation of glycogen to glucose. Our findings demonstrate that MEHP inhibits the activity of oligo-1,4-1,4-glucanotransferase, but not of amylo-1,6-glucosidase. Among various phthalate esters tested, MEHP specifically binds to and inhibits GDE. We also show that DEHP administration affects glycogen metabolism in rat testis. Thus, inhibition of GDE by MEHP may play a role in germ cell apoptosis in the testis. PMID:19240039

  6. Developmental changes in carbon and nitrogen metabolism affect tea quality in different leaf position.

    PubMed

    Li, Zhi-Xin; Yang, Wei-Jun; Ahammed, Golam Jalal; Shen, Chen; Yan, Peng; Li, Xin; Han, Wen-Yan

    2016-09-01

    Leaf position represents a specific developmental stage that influences both photosynthesis and respiration. However, the precise relationships between photosynthesis and respiration in different leaf position that affect tea quality are largely unknown. Here, we show that the effective quantum yield of photosystem II [ΦPSⅡ] as well as total chlorophyll concentration (TChl) of tea leaves increased gradually with leaf maturity. Moreover, respiration rate (RR) together with total nitrogen concentration (TN) decreased persistently, but total carbon remained unchanged during leaf maturation. Analyses of major N-based organic compounds revealed that decrease in TN was attributed to a significant decrease in the concentration of caffeine and amino acids (AA) in mature leaves. Furthermore, soluble sugar (SS) decreased, but starch concentration increased with leaf maturity, indicating that source-sink relationship was altered during tea leaf development. Detailed correlation analysis showed that ΦPSⅡ was negatively correlated with RR, SS, starch, tea polyphenol (TP), total catechins and TN, but positively correlated with TChl; while RR was positively correlated with TN, SS, TP and caffeine, but negatively correlated with TChl and starch concentrations. Our results suggest that biosynthesis of chlorophyll, catechins and polyphenols is closely associated with photosynthesis and respiration in different leaf position that greatly influences the relationship between primary and secondary metabolism in tea plants. PMID:27380366

  7. 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. PMID:25825763

  8. 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

  9. [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

  10. 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

  11. 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

  12. Single nucleotide polymorphisms linked to mitochondrial uncoupling protein genes UCP2 and UCP3 affect mitochondrial metabolism and healthy aging in female nonagenarians.

    PubMed

    Kim, Sangkyu; Myers, Leann; Ravussin, Eric; Cherry, Katie E; Jazwinski, S Michal

    2016-08-01

    Energy expenditure decreases with age, but in the oldest-old, energy demand for maintenance of body functions increases with declining health. Uncoupling proteins have profound impact on mitochondrial metabolic processes; therefore, we focused attention on mitochondrial uncoupling protein genes. Alongside resting metabolic rate (RMR), two SNPs in the promoter region of UCP2 were associated with healthy aging. These SNPs mark potential binding sites for several transcription factors; thus, they may affect expression of the gene. A third SNP in the 3'-UTR of UCP3 interacted with RMR. This UCP3 SNP is known to impact UCP3 expression in tissue culture cells, and it has been associated with body weight and mitochondrial energy metabolism. The significant main effects of the UCP2 SNPs and the interaction effect of the UCP3 SNP were also observed after controlling for fat-free mass (FFM) and physical-activity related energy consumption. The association of UCP2/3 with healthy aging was not found in males. Thus, our study provides evidence that the genetic risk factors for healthy aging differ in males and females, as expected from the differences in the phenotypes associated with healthy aging between the two sexes. It also has implications for how mitochondrial function changes during aging. PMID:26965008

  13. In silico search of energy metabolism inhibitors for alternative leishmaniasis treatments.

    PubMed

    Silva, Lourival A; Vinaud, Marina C; Castro, Ana Maria; Cravo, Pedro Vítor L; Bezerra, José Clecildo B

    2015-01-01

    Leishmaniasis is a complex disease that affects mammals and is caused by approximately 20 distinct protozoa from the genus Leishmania. Leishmaniasis is an endemic disease that exerts a large socioeconomic impact on poor and developing countries. The current treatment for leishmaniasis is complex, expensive, and poorly efficacious. Thus, there is an urgent need to develop more selective, less expensive new drugs. The energy metabolism pathways of Leishmania include several interesting targets for specific inhibitors. In the present study, we sought to establish which energy metabolism enzymes in Leishmania could be targets for inhibitors that have already been approved for the treatment of other diseases. We were able to identify 94 genes and 93 Leishmania energy metabolism targets. Using each gene's designation as a search criterion in the TriTrypDB database, we located the predicted peptide sequences, which in turn were used to interrogate the DrugBank, Therapeutic Target Database (TTD), and PubChem databases. We identified 44 putative targets of which 11 are predicted to be amenable to inhibition by drugs which have already been approved for use in humans for 11 of these targets. We propose that these drugs should be experimentally tested and potentially used in the treatment of leishmaniasis. PMID:25918726

  14. In Silico Search of Energy Metabolism Inhibitors for Alternative Leishmaniasis Treatments

    PubMed Central

    Silva, Lourival A.; Vinaud, Marina C.; Cravo, Pedro Vítor L.; Bezerra, José Clecildo B.

    2015-01-01

    Leishmaniasis is a complex disease that affects mammals and is caused by approximately 20 distinct protozoa from the genus Leishmania. Leishmaniasis is an endemic disease that exerts a large socioeconomic impact on poor and developing countries. The current treatment for leishmaniasis is complex, expensive, and poorly efficacious. Thus, there is an urgent need to develop more selective, less expensive new drugs. The energy metabolism pathways of Leishmania include several interesting targets for specific inhibitors. In the present study, we sought to establish which energy metabolism enzymes in Leishmania could be targets for inhibitors that have already been approved for the treatment of other diseases. We were able to identify 94 genes and 93 Leishmania energy metabolism targets. Using each gene's designation as a search criterion in the TriTrypDB database, we located the predicted peptide sequences, which in turn were used to interrogate the DrugBank, Therapeutic Target Database (TTD), and PubChem databases. We identified 44 putative targets of which 11 are predicted to be amenable to inhibition by drugs which have already been approved for use in humans for 11 of these targets. We propose that these drugs should be experimentally tested and potentially used in the treatment of leishmaniasis. PMID:25918726

  15. Regional cerebral energy metabolism during intravenous anesthesia with etomidate, ketamine or thiopental

    SciTech Connect

    Davis, D.W.

    1987-01-01

    Regional brain glucose utilization (rCMRglc) was measured in rats during steady-state levels of intravenous anesthesia to determine if alterations in brain function due to anesthesia could provide information on the mechanisms of anesthesia. Intravenous anesthetics from three different chemical classes were studied: etomidate, ketamine and thiopental. All rCMRglc experiments were conducted in freely moving rats in isolation chambers, with the use of (6-/sup 14/C) glucose and guantitative autoradiography. Etomidate caused a rostral-to-caudal gradient of depression of rCMRglc. The four doses of etomidate did not differ in their effects on energy metabolism. Sub-anesthetic (5 mg kg/sup -1/) and anesthetic (30 mg kg /sup -1/) doses of ketamine produced markedly different patterns of behavior. Brain energy metabolism during the sub-anesthetic dose was stimulated in most regions, while the anesthetic dose selectively stimulated the hippocampus, leaving most brain regions unaffected. Thiopental produced a dose-dependent reduction of rCMRglc in all gray matter regions. No brain region was selectively affected. Comparison of the drug-specific alterations of cerebral energy metabolism suggests these anesthetics do not act through a common mechanism. The hypothesis that each acts by binding to specific cell membrane receptors is consistent with these observations.

  16. GENOME-WIDE LINKAGE ANALYSIS TO IDENTIFY CHROMOSOMAL REGIONS AFFECTING PHENOTYPIC TRAITS IN THE CHICKEN. IV. METABOLIC TRAITS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study is a comprehensive genome analysis to detect QTL affecting metabolic traits in chickens. Two unique F2 crosses generated from a commercial broiler male line and two genetically distinct lines (Leghorn and Fayoumi) were used in the present study. The plasma glucagons, insulin, lactate, g...

  17. Dietary folate and choline status differentially affect lipid metabolism and behavior-mediated neurotransmitters in young rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The relationship between choline and folate metabolisms is an important issue due to the essential role of these nutrients in brain plasticity and cognitive functions. Present study was designed to investigate whether modification of the dietary folate-choline status in young rats would affect brain...

  18. 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

  19. Bone and energy metabolism parameters in professional cyclists during the Giro d'Italia 3-weeks stage race.

    PubMed

    Lombardi, Giovanni; Lanteri, Patrizia; Graziani, Rosa; Colombini, Alessandra; Banfi, Giuseppe; Corsetti, Roberto

    2012-01-01

    Cycling is a not weight-bearing activity and is known to induce bone resorption. Stage races are really strenuous endurance performances affecting the energy homeostasis. The recently highlighted link, in the co-regulation of bone and energy metabolism, demonstrates a central role for the equilibrium between carboxylated and undercarboxylated forms of osteocalcin. Aim of this study was to understand the acute physiological responses to a cycling stage race in terms of bone turnover and energy metabolism and the possible co-regulative mechanisms underlying their relationship. We studied nine professional cyclists engaged in 2011 Giro d'Italia stage race. Pre-analytical and analytical phases tightly followed academic and anti-doping authority's recommendations. Bone and energy metabolism markers (bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b, total and undercarboxylated osteocalcin, leptin and adiponectin) and related hormones (cortisol and testosterone) were measured, by Sandwich Enzyme Immunoassays, at days -1 (pre-race), 12 and 22 during the race. The power output and the energy expenditure (mean and accumulated) were derived and correlated with the biochemical indexes. During the race, bone metabolism showed that an unbalance in behalf of resorption, which is enhanced, occurred along with a relative increase in the concentration of the undercarboxylated form of osteocalcin that was indirectly related to the enhanced energy expenditure, through adipokines modifications, with leptin decrease (high energy consumption) and adiponectin increase (optimization of energy expenditure). The exertion due to heavy effort induced a decrease of cortisol, while testosterone levels resulted unchanged. In conclusion, during a 3-weeks stage race, bone metabolism is pushed towards resorption. A possible relationship between the bone and the energy metabolisms is suggested by the relative correlations among absolute and relative concentrations trends of

  20. Bone and Energy Metabolism Parameters in Professional Cyclists during the Giro d’Italia 3-Weeks Stage Race

    PubMed Central

    Lombardi, Giovanni; Lanteri, Patrizia; Graziani, Rosa; Colombini, Alessandra; Banfi, Giuseppe; Corsetti, Roberto

    2012-01-01

    Cycling is a not weight-bearing activity and is known to induce bone resorption. Stage races are really strenuous endurance performances affecting the energy homeostasis. The recently highlighted link, in the co-regulation of bone and energy metabolism, demonstrates a central role for the equilibrium between carboxylated and undercarboxylated forms of osteocalcin. Aim of this study was to understand the acute physiological responses to a cycling stage race in terms of bone turnover and energy metabolism and the possible co-regulative mechanisms underlying their relationship. We studied nine professional cyclists engaged in 2011 Giro d’Italia stage race. Pre-analytical and analytical phases tightly followed academic and anti-doping authority’s recommendations. Bone and energy metabolism markers (bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b, total and undercarboxylated osteocalcin, leptin and adiponectin) and related hormones (cortisol and testosterone) were measured, by Sandwich Enzyme Immunoassays, at days -1 (pre-race), 12 and 22 during the race. The power output and the energy expenditure (mean and accumulated) were derived and correlated with the biochemical indexes. During the race, bone metabolism showed that an unbalance in behalf of resorption, which is enhanced, occurred along with a relative increase in the concentration of the undercarboxylated form of osteocalcin that was indirectly related to the enhanced energy expenditure, through adipokines modifications, with leptin decrease (high energy consumption) and adiponectin increase (optimization of energy expenditure). The exertion due to heavy effort induced a decrease of cortisol, while testosterone levels resulted unchanged. In conclusion, during a 3-weeks stage race, bone metabolism is pushed towards resorption. A possible relationship between the bone and the energy metabolisms is suggested by the relative correlations among absolute and relative concentrations trends of

  1. Metabolomic analysis of amino acid and energy metabolism in rats supplemented with chlorogenic acid

    PubMed Central

    Ruan, Zheng; Yang, Yuhui; Zhou, Yan; Wen, Yanmei; Ding, Sheng; Liu, Gang; Wu, Xin; Deng, Zeyuan; Assaad, Houssein; Wu, Guoyao

    2016-01-01

    This study was conducted to investigate effects of chlorogenic acid (CGA) supplementation on serum and hepatic metabolomes in rats. Rats received daily intragastric administration of either CGA (60 mg/kg body weight) or distilled water (control) for 4 weeks. Growth performance, serum biochemical profiles, and hepatic morphology were measured. Additionally, serum and liver tissue extracts were analyzed for metabolomes by high-resolution 1H nuclear magnetic resonance-based metabolomics and multivariate statistics. CGA did not affect rat growth performance, serum biochemical profiles, or hepatic morphology. However, supplementation with CGA decreased serum concentrations of lactate, pyruvate, succinate, citrate, β-hydroxybutyrate and acetoacetate, while increasing serum concentrations of glycine and hepatic concentrations of glutathione. These results suggest that CGA supplementation results in perturbation of energy and amino acid metabolism in rats. We suggest that glycine and glutathione in serum may be useful biomarkers for biological properties of CGA on nitrogen metabolism in vivo. PMID:24927697

  2. Culture surfaces coated with various implant materials affect chondrocyte growth and metabolism.

    PubMed

    Hambleton, J; Schwartz, Z; Khare, A; Windeler, S W; Luna, M; Brooks, B P; Dean, D D; Boyan, B D

    1994-07-01

    to culture surface was comparable, differing primarily in magnitude. Cell maturation-dependent effects were evident when enzyme activity in trypsinized and scraped cells was compared. These results indicate that different surface materials affect chondrocyte metabolism and phenotypic expression in vitro and suggest that implant materials may modulate the phenotypic expression of cells in vivo. PMID:7520486

  3. Body condition score at calving affects systemic and hepatic transcriptome indicators of inflammation and nutrient metabolism in grazing dairy cows.

    PubMed

    Akbar, H; Grala, T M; Vailati Riboni, M; Cardoso, F C; Verkerk, G; McGowan, J; Macdonald, K; Webster, J; Schutz, K; Meier, S; Matthews, L; Roche, J R; Loor, J J

    2015-02-01

    Calving body condition score (BCS) is an important determinant of early-lactation dry matter intake, milk yield, and disease incidence. The current study investigated the metabolic and molecular changes induced by the change in BCS. A group of cows of mixed age and breed were managed from the second half of the previous lactation to achieve mean group BCS (10-point scale) that were high (HBCS, 5.5; n=20), medium (MBCS, 4.5; n=18), or low (LBCS, 3.5; n=19). Blood was sampled at wk -4, -3, -2, 1, 3, 5, and 6 relative to parturition to measure biomarkers of energy balance, inflammation, and liver function. Liver was biopsied on wk 1, 3, and 5 relative to parturition, and 10 cows per BCS group were used for transcript profiling via quantitative PCR. Cows in HBCS and MBCS produced more milk and had greater concentrations of nonesterified fatty acids and β-hydroxybutyrate postpartum than LBCS. Peak concentrations of nonesterified fatty acids and β-hydroxybutyrate and greater hepatic triacylglycerol concentrations were recorded in HBCS at wk 3. Consistent with blood biomarkers, HBCS and MBCS had greater expression of genes associated with fatty acid oxidation (CPT1A, ACOX1), ketogenesis (HMGCS2), and hepatokines (FGF21, ANGPTL4), whereas HBCS had the lowest expression of APOB (lipoprotein transport). Greater expression during early lactation of BBOX1 in MBCS and LBCS suggested greater de novo carnitine synthesis. The greater BCS was associated with lower expression of growth hormone/insulin-like growth factor-1 signaling axis genes (GHR1A, IGF1, and IGFALS) and greater expression of gluconeogenic genes. These likely contributed to the higher milk production and greater gluconeogenesis. Despite greater serum haptoglobin around calving, cows in HBCS and MBCS had greater blood albumin. Cows in MBCS, however, had a higher albumin:globulin ratio, probably indicating a less pronounced inflammatory status and better liver function. The marked decrease in expression of NFKB1

  4. Metabolic effects of dark chocolate consumption on energy, gut microbiota, and stress-related metabolism in free-living subjects.

    PubMed

    Martin, Francois-Pierre J; Rezzi, Serge; Peré-Trepat, Emma; Kamlage, Beate; Collino, Sebastiano; Leibold, Edgar; Kastler, Jürgen; Rein, Dietrich; Fay, Laurent B; Kochhar, Sunil

    2009-12-01

    Dietary preferences influence basal human metabolism and gut microbiome activity that in turn may have long-term health consequences. The present study reports the metabolic responses of free living subjects to a daily consumption of 40 g of dark chocolate for up to 14 days. A clinical trial was performed on a population of 30 human subjects, who were classified in low and high anxiety traits using validated psychological questionnaires. Biological fluids (urine and blood plasma) were collected during 3 test days at the beginning, midtime and at the end of a 2 week study. NMR and MS-based metabonomics were employed to study global changes in metabolism due to the chocolate consumption. Human subjects with higher anxiety trait showed a distinct metabolic profile indicative of a different energy homeostasis (lactate, citrate, succinate, trans-aconitate, urea, proline), hormonal metabolism (adrenaline, DOPA, 3-methoxy-tyrosine) and gut microbial activity (methylamines, p-cresol sulfate, hippurate). Dark chocolate reduced the urinary excretion of the stress hormone cortisol and catecholamines and partially normalized stress-related differences in energy metabolism (glycine, citrate, trans-aconitate, proline, beta-alanine) and gut microbial activities (hippurate and p-cresol sulfate). The study provides strong evidence that a daily consumption of 40 g of dark chocolate during a period of 2 weeks is sufficient to modify the metabolism of free living and healthy human subjects, as per variation of both host and gut microbial metabolism. PMID:19810704

  5. Developmental accumulation of inorganic polyphosphate affects germination and energetic metabolism in Dictyostelium discoideum.

    PubMed

    Livermore, Thomas Miles; Chubb, Jonathan Robert; Saiardi, Adolfo

    2016-01-26

    Inorganic polyphosphate (polyP) is composed of linear chains of phosphate groups linked by high-energy phosphoanhydride bonds. However, this simple, ubiquitous molecule remains poorly understood. The use of nonstandardized analytical methods has contributed to this lack of clarity. By using improved polyacrylamide gel electrophoresis we were able to visualize polyP extracted from Dictyostelium discoideum. We established that polyP is undetectable in cells lacking the polyphosphate kinase (DdPpk1). Generation of this ppk1 null strain revealed that polyP is important for the general fitness of the amoebae with the mutant strain displaying a substantial growth defect. We discovered an unprecedented accumulation of polyP during the developmental program, with polyP increasing more than 100-fold. The failure of ppk1 spores to accumulate polyP results in a germination defect. These phenotypes are underpinned by the ability of polyP to regulate basic energetic metabolism, demonstrated by a 2.5-fold decrease in the level of ATP in vegetative ppk1. Finally, the lack of polyP during the development of ppk1 mutant cells is partially offset by an increase of both ATP and inositol pyrophosphates, evidence for a model in which there is a functional interplay between inositol pyrophosphates, ATP, and polyP. PMID:26755590

  6. Electrical stimulation affects metabolic enzyme phosphorylation, protease activation, and meat tenderization in beef.

    PubMed

    Li, C B; Li, J; Zhou, G H; Lametsch, R; Ertbjerg, P; Brüggemann, D A; Huang, H G; Karlsson, A H; Hviid, M; Lundström, K

    2012-05-01

    The objective of this study was to investigate the response of sarcoplasmic proteins in bovine LM to low-voltage electrical stimulation (ES; 80 V, 35 s) after dressing and its contribution to meat tenderization at an early postmortem time. Proteome analysis showed that ES resulted in decreased (P < 0.05) phosphorylation of creatine kinase M chain, fructose bisphosphate aldolase C-A, β-enolase, and pyruvate kinase at 3 h postmortem. Zymography indicated an earlier (P < 0.05) activation of μ-calpain in ES muscles. Free lysosomal cathepsin B and L activity increased faster (P < 0.05) in ES muscles up to 24 h. Immunohistochemistry and transmission electron microscopy further indicated that lysosomal enzymes were released at an early postmortem time. Electrical stimulation also induced ultrastructural disruption of sarcomeres. In addition, ES accelerated (P < 0.05) the depletion of ATP, creatine phosphate, and glycogen, as well as a pH decline and the more preferred pH/temperature decline mode. Finally, ES accelerated meat tenderization, resulting in lesser (P < 0.05) shear force values than the control over the testing time. A possible relationship was suggested between a change in the phosphorylation of energy metabolic enzymes and the postmortem tenderization of beef. Our results suggested the possible importance of the activation of μ-calpain, phosphorylation of sarcoplasmic proteins, and release of lysosomal enzymes for ES-induced tenderization of beef muscle. PMID:22147478

  7. Developmental accumulation of inorganic polyphosphate affects germination and energetic metabolism in Dictyostelium discoideum

    PubMed Central

    Livermore, Thomas Miles; Chubb, Jonathan Robert; Saiardi, Adolfo

    2016-01-01

    Inorganic polyphosphate (polyP) is composed of linear chains of phosphate groups linked by high-energy phosphoanhydride bonds. However, this simple, ubiquitous molecule remains poorly understood. The use of nonstandardized analytical methods has contributed to this lack of clarity. By using improved polyacrylamide gel electrophoresis we were able to visualize polyP extracted from Dictyostelium discoideum. We established that polyP is undetectable in cells lacking the polyphosphate kinase (DdPpk1). Generation of this ppk1 null strain revealed that polyP is important for the general fitness of the amoebae with the mutant strain displaying a substantial growth defect. We discovered an unprecedented accumulation of polyP during the developmental program, with polyP increasing more than 100-fold. The failure of ppk1 spores to accumulate polyP results in a germination defect. These phenotypes are underpinned by the ability of polyP to regulate basic energetic metabolism, demonstrated by a 2.5-fold decrease in the level of ATP in vegetative ppk1. Finally, the lack of polyP during the development of ppk1 mutant cells is partially offset by an increase of both ATP and inositol pyrophosphates, evidence for a model in which there is a functional interplay between inositol pyrophosphates, ATP, and polyP. PMID:26755590

  8. Endocrine Regulation of Bone and Energy Metabolism in Hibernating Mammals

    PubMed Central

    Doherty, Alison H.; Florant, Gregory L.; Donahue, Seth W.

    2014-01-01

    Precise coordination among organs is required to maintain homeostasis throughout hibernation. This is particularly true in balancing bone remodeling processes (bone formation and resorption) in hibernators experiencing nutritional deprivation and extreme physical inactivity, two factors normally leading to pronounced bone loss in non-hibernating mammals. In recent years, important relationships between bone, fat, reproductive, and brain tissues have come to light. These systems share interconnected regulatory mechanisms of energy metabolism that potentially protect the skeleton during hibernation. This review focuses on the endocrine and neuroendocrine regulation of bone/fat/energy metabolism in hibernators. Hibernators appear to have unique mechanisms that protect musculoskeletal tissues while catabolizing their abundant stores of fat. Furthermore, the bone remodeling processes that normally cause disuse-induced bone loss in non-hibernators are compared to bone remodeling processes in hibernators, and possible adaptations of the bone signaling pathways that protect the skeleton during hibernation are discussed. Understanding the biological mechanisms that allow hibernators to survive the prolonged disuse and fasting associated with extreme environmental challenges will provide critical information regarding the limit of convergence in mammalian systems and of skeletal plasticity, and may contribute valuable insight into the etiology and treatment of human diseases. PMID:24556365

  9. Metabolic energy requirements during manned orbital Skylab missions.

    PubMed

    Rambaut, P C; Leach, C S; Whedon, G D

    1977-01-01

    An investigation was undertaken to determine the metabolic cost of life in space. Energy intake was determined throughout the 28-, 59- and 84-day flights for each of the nine Skylab astronauts. Metabolic excretions were quantitatively collected and analyzed for a variety of biochemical constituents. Body mass was determined each day and body volume was ascertained by stereophotogrammetric means immediately pre- and post-flight. A ground-based control period of at least 3 weeks preceded each flight, and one of at least 18 days followed each flight. Examination of the data reveals that all crew members lost mass in flight, and that this loss did not result in a net increase in density. Elevated urinary and blood nitrogen, a net negative calcium and nitrogen balance and a decrease in the radiographic density of certain bones support the conclusion that lean body mass decreased. That the loss was primarily proteinaceous in nature is evidenced by the comparatively small net change in total body water and by a decrease in total body potassium each measured by isotopic dilution techniques. These changes in body composition, despite a constant caloric intake in flight and on the ground, suggest that the body's demand for exogenous nutrient energy is not measurably changed by exposure to null gravity flight up to 84 days in duration. PMID:11958214

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

    DOE PAGESBeta

    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

  11. Estrogen receptor β activation impairs mitochondrial oxidative metabolism and affects malignant mesothelioma cell growth in vitro and in vivo

    PubMed Central

    Manente, A G; Valenti, D; Pinton, G; Jithesh, P V; Daga, A; Rossi, L; Gray, S G; O'Byrne, K J; Fennell, D A; Vacca, R A; Nilsson, S; Mutti, L; Moro, L

    2013-01-01

    Estrogen receptor (ER)-β has been shown to possess a tumor suppressive effect, and is a potential target for cancer therapy. Using gene-expression meta-analysis of human malignant pleural mesothelioma, we identified an ESR2 (ERβ coding gene) signature. High ESR2 expression was strongly associated with low succinate dehydrogenase B (SDHB) (which encodes a mitochondrial respiratory chain complex II subunit) expression. We demonstrate that SDHB loss induced ESR2 expression, and that activated ERβ, by over-expression or by selective agonist stimulation, negatively affected oxidative phosphorylation compromising mitochondrial complex II and IV activity. This resulted in reduced mitochondrial ATP production, increased glycolysis dependence and impaired cell proliferation. The observed in vitro effects were phenocopied in vivo using a selective ERβ agonist in a mesothelioma mouse model. On the whole, our data highlight an unforeseen interaction between ERβ-mediated tumor suppression and energy metabolism that may be exploited to improve on the therapy for clinical management of malignant mesothelioma. PMID:24061575

  12. Effects of Dietary Protein Source and Quantity during Weight Loss on Appetite, Energy Expenditure, and Cardio-Metabolic Responses

    PubMed Central

    Li, Jia; Armstrong, Cheryl L. H.; Campbell, Wayne W.

    2016-01-01

    Higher protein meals increase satiety and the thermic effect of feeding (TEF) in acute settings, but it is unclear whether these effects remain after a person becomes acclimated to energy restriction or a given protein intake. This study assessed the effects of predominant protein source (omnivorous, beef/pork vs. lacto-ovo vegetarian, soy/legume) and quantity (10%, 20%, or 30% of energy from protein) on appetite, energy expenditure, and cardio-metabolic indices during energy restriction (ER) in overweight and obese adults. Subjects were randomly assigned to one protein source and then consumed diets with different quantities of protein (4 weeks each) in a randomized crossover manner. Perceived appetite ratings (free-living and in-lab), TEF, and fasting cardio-metabolic indices were assessed at the end of each 4-week period. Protein source and quantity did not affect TEF, hunger, or desire to eat, other than a modestly higher daily composite fullness rating with 30% vs. 10% protein diet (p = 0.03). While the 20% and 30% protein diets reduced cholesterol, triacylglycerol, and APO-B vs. 10% protein (p < 0.05), protein source did not affect cardio-metabolic indices. In conclusion, diets varying in protein quantity with either beef/pork or soy/legume as the predominant source have minimal effects on appetite control, energy expenditure and cardio-metabolic risk factors during ER-induced weight loss. PMID:26821042

  13. Effects of Dietary Protein Source and Quantity during Weight Loss on Appetite, Energy Expenditure, and Cardio-Metabolic Responses.

    PubMed

    Li, Jia; Armstrong, Cheryl L H; Campbell, Wayne W

    2016-02-01

    Higher protein meals increase satiety and the thermic effect of feeding (TEF) in acute settings, but it is unclear whether these effects remain after a person becomes acclimated to energy restriction or a given protein intake. This study assessed the effects of predominant protein source (omnivorous, beef/pork vs. lacto-ovo vegetarian, soy/legume) and quantity (10%, 20%, or 30% of energy from protein) on appetite, energy expenditure, and cardio-metabolic indices during energy restriction (ER) in overweight and obese adults. Subjects were randomly assigned to one protein source and then consumed diets with different quantities of protein (4 weeks each) in a randomized crossover manner. Perceived appetite ratings (free-living and in-lab), TEF, and fasting cardio-metabolic indices were assessed at the end of each 4-week period. Protein source and quantity did not affect TEF, hunger, or desire to eat, other than a modestly higher daily composite fullness rating with 30% vs. 10% protein diet (p = 0.03). While the 20% and 30% protein diets reduced cholesterol, triacylglycerol, and APO-B vs. 10% protein (p < 0.05), protein source did not affect cardio-metabolic indices. In conclusion, diets varying in protein quantity with either beef/pork or soy/legume as the predominant source have minimal effects on appetite control, energy expenditure and cardio-metabolic risk factors during ER-induced weight loss. PMID:26821042

  14. Energy metabolism and hindbrain AMPK: regulation by estradiol.

    PubMed

    Briski, Karen P; Ibrahim, Baher A; Tamrakar, Pratistha

    2014-03-01

    Nerve cell energy status is screened within multiple classically defined hypothalamic and hindbrain components of the energy balance control network, including the hindbrain dorsal vagal complex (DVC). Signals of caudal DVC origin have a physiological role in glucostasis, e.g., maintenance of optimal supply of the critical substrate fuel, glucose, through control of motor functions such as fuel consumption and gluco-counterregulatory hormone secretion. A2 noradrenergic neurons are a likely source of these signals as combinatory laser microdissection/high-sensitivity Western blotting reveals expression of multiple biomarkers for metabolic sensing, including adenosine 5'-monophosphate-activated protein kinase (AMPK). Hypoglycemia elicits estradiol-dependent sex differences in A2 AMPK activation as phospho-AMPK (pAMPK) expression is augmented in male and ovariectomized (OVX) female, but not estrogen-replaced, OVX rats. This dichotomy may reflect, in part, estradiol-mediated up-regulation of glycolytic and tricarboxylic acid cycle enzyme expression during hypoglycemia. Our new model for short-term feeding abstinence has physiological relevance to planned (dieting) or unplanned (meal delay) interruption of consumption in modern life, which is negatively correlated with appetite control and obesity, and is useful for investigating how estrogen may mitigate the effects of disrupted fuel acquisition on energy balance via actions within the DVC. Estradiol reduces DVC AMPK activity after local delivery of the AMP mimic, 5-aminoimidazole-4-carboxamide-riboside, or cessation of feeding for 12 h but elevates pAMPK expression when these treatments are combined. These data suggest that estrogen maintains cellular energy stability over periods of suspended fuel acquisition and yet optimizes, by DVC AMPK-dependent mechanisms, counter-regulatory responses to metabolic challenges that occur during short-span feeding abstinence. PMID:25372736

  15. Ethyl pyruvate protects against sepsis by regulating energy metabolism

    PubMed Central

    Kang, Hongjun; Mao, Zhi; Zhao, Yan; Yin, Ting; Song, Qing; Pan, Liang; Hu, Xin; Hu, Jie; Zhou, Feihu

    2016-01-01

    Background Ethyl pyruvate (EP) is a derivative of pyruvic acid that has been demonstrated to be a potential scavenger of reactive oxygen species as well as an anti-inflammatory agent. In this study, we investigated the protective effects of EP and its role in regulating the energy metabolism in the livers of cecal-ligation-and-puncture-induced septic mice. Methods The animals were treated intraperitoneally with 0.2 mL of Ringer’s lactate solution or an equivalent volume of Ringer’s lactate solution containing EP immediately after cecal ligation and puncture. Each mouse in the Sham group was only subjected to a laparotomy. At 30-, 60-, 180-, and 360-minute time points, we measured the histopathological alterations of the intestines, and the plasma levels of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α, and the total antioxidative capacity, malondialdehyde content, and lactate and lactate/pyruvate levels in livers. Furthermore, we detected the levels of adenosine triphosphate, total adenylate, and energy charge in the livers. Results Our results demonstrated that the administration of EP significantly improved the survival rate and reduced intestinal histological alterations. EP inhibited the plasma levels of IL-1β, IL-6, and tumor necrosis factor-α and increased the IL-10 level. EP significantly inhibited the elevation of the malondialdehyde, lactate, and lactate/pyruvate levels and enhanced the total antioxidative capacity levels in the liver tissues. The downregulation of the adenosine triphosphate, total adenylate, and energy charge levels in the liver tissues was reversed in the septic mice treated with EP. Conclusion The results suggest that EP administration effectively modulates the energy metabolism, which may be an important component in treatment of sepsis. PMID:26966369

  16. Host-related metabolic cues affect colonization strategies of a root endophyte

    PubMed Central

    Lahrmann, Urs; Ding, Yi; Banhara, Aline; Rath, Magnus; Hajirezaei, Mohammad R.; Döhlemann, Stefanie; von Wirén, Nicolaus; Parniske, Martin; Zuccaro, Alga

    2013-01-01

    The mechanisms underpinning broad compatibility in root symbiosis are largely unexplored. The generalist root endophyte Piriformospora indica establishes long-lasting interactions with morphologically and biochemically different hosts, stimulating their growth, alleviating salt stress, and inducing local and systemic resistance to pathogens. Cytological studies and global investigations of fungal transcriptional responses to colonization of barley and Arabidopsis at different symbiotic stages identified host-dependent colonization strategies and host-specifically induced effector candidates. Here, we show that in Arabidopsis, P. indica establishes and maintains biotrophic nutrition within living epidermal cells, whereas in barley the symbiont undergoes a nutritional switch to saprotrophy that is associated with the production of secondary thinner hyphae in dead cortex cells. Consistent with a diversified trophic behavior and with the occurrence of nitrogen deficiency at the onset of saprotrophy in barley, fungal genes encoding hydrolytic enzymes and nutrient transporters were highly induced in this host but not in Arabidopsis. Silencing of the high-affinity ammonium transporter PiAMT1 gene, whose transcripts are accumulating during nitrogen starvation and in barley, resulted in enhanced colonization of this host, whereas it had no effect on the colonization of Arabidopsis. Increased levels of free amino acids and reduced enzymatic activity for the cell-death marker VPE (vacuolar-processing enzyme) in colonized barley roots coincided with an extended biotrophic lifestyle of P. indica upon silencing of PiAMT1. This suggests that PiAmt1 functions as a nitrogen sensor mediating the signal that triggers the in planta activation of the saprotrophic program. Thus, host-related metabolic cues affect the expression of P. indica’s alternative lifestyles. PMID:23918389

  17. HypoxamiRs: regulators of cardiac hypoxia and energy metabolism.

    PubMed

    Azzouzi, Hamid El; Leptidis, Stefanos; Doevendans, Pieter A; De Windt, Leon J

    2015-09-01

    Hypoxia and its intricate regulation are at the epicenter of cardiovascular research. Mediated by hypoxia-inducible factors as well as by several microRNAs, recently termed 'hypoxamiRs', hypoxia affects several cardiac pathophysiological processes. Hypoxia is the driving force behind the regulation of the characteristic metabolic switch from predominant fatty acid oxidation in the healthy heart to glucose utilization in the failing myocardium, but also instigates reactivation of the fetal gene program, induces the cardiac hypertrophy response, alters extracellular matrix composition, influences mitochondrial biogenesis, and impacts upon myocardial contractility. HypoxamiR regulation adds a new level of complexity to this multitude of hypoxia-mediated effects, rendering the understanding of the hypoxic response a fundamental piece in solving the cardiovascular disease puzzle. PMID:26197955

  18. Endogenous and dietary lipids influencing feed intake and energy metabolism of periparturient dairy cows.

    PubMed

    Kuhla, B; Metges, C C; Hammon, H M

    2016-07-01

    The high metabolic priority of the mammary gland for milk production, accompanied by limited feed intake around parturition results in a high propensity to mobilize body fat reserves. Under these conditions, fuel selection of many peripheral organs is switched, for example, from carbohydrate to fat utilization to spare glucose for milk production and to ensure partitioning of tissue- and dietary-derived nutrients toward the mammary gland. For example, muscle tissue uses nonesterified fatty acids (NEFA) but releases lactate and amino acids in a coordinated order, thereby providing precursors for milk synthesis or hepatic gluconeogenesis. Tissue metabolism and in concert, nutrient partitioning are controlled by the endocrine system involving a reduction in insulin secretion and systemic insulin sensitivity and orchestrated changes in plasma hormones such as insulin, adiponectin, insulin growth factor-I, growth hormone, glucagon, leptin, glucocorticoids, and catecholamines. However, the endocrine system is highly sensitive and responsive to an overload of fatty acids no matter if excessive NEFA supply originates from exogenous or endogenous sources. Feeding a diet containing rumen-protected fat from late lactation to calving and beyond exerts similar negative effects on energy intake, glucose and insulin concentrations as does a high extent of body fat mobilization around parturition in regard to the risk for ketosis and fatty liver development. High plasma NEFA concentrations are thought not to act directly at the brain level, but they increase the energy charge of the liver which is, signaled to the brain to diminish feed intake. Cows differing in fat mobilization during the transition phase differ in their hepatic energy charge, whole body fat oxidation, glucose metabolism, plasma ghrelin, and leptin concentrations and in feed intake several week before parturition. Hence, a high lipid load, no matter if stored, mobilized or fed, affects the endocrine system

  19. 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

  20. Political ideology affects energy-efficiency attitudes and choices

    PubMed Central

    Gromet, Dena M.; Kunreuther, Howard; Larrick, Richard P.

    2013-01-01

    This research demonstrates how promoting the environment can negatively affect adoption of energy efficiency in the United States because of the political polarization surrounding environmental issues. Study 1 demonstrated that more politically conservative individuals were less in favor of investment in energy-efficient technology than were those who were more politically liberal. This finding was driven primarily by the lessened psychological value that more conservative individuals placed on reducing carbon emissions. Study 2 showed that this difference has consequences: In a real-choice context, more conservative individuals were less likely to purchase a more expensive energy-efficient light bulb when it was labeled with an environmental message than when it was unlabeled. These results highlight the importance of taking into account psychological value-based considerations in the individual adoption of energy-efficient technology in the United States and beyond. PMID:23630266

  1. Transient exposure to low levels of insecticide affects metabolic networks of honeybee larvae.

    PubMed

    Derecka, Kamila; Blythe, Martin J; Malla, Sunir; Genereux, Diane P; Guffanti, Alessandro; Pavan, Paolo; Moles, Anna; Snart, Charles; Ryder, Thomas; Ortori, Catharine A; Barrett, David A; Schuster, Eugene; Stöger, Reinhard

    2013-01-01

    The survival of a species depends on its capacity to adjust to changing environmental conditions, and new stressors. Such new, anthropogenic stressors include the neonicotinoid class of crop-protecting agents, which have been implicated in the population declines of pollinating insects, including honeybees (Apis mellifera). The low-dose effects of these compounds on larval development and physiological responses have remained largely unknown. Over a period of 15 days, we provided syrup tainted with low levels (2 µg/L(-1)) of the neonicotinoid insecticide imidacloprid to beehives located in the field. We measured transcript levels by RNA sequencing and established lipid profiles using liquid chromatography coupled with mass spectrometry from worker-bee larvae of imidacloprid-exposed (IE) and unexposed, control (C) hives. Within a catalogue of 300 differentially expressed transcripts in larvae from IE hives, we detect significant enrichment of genes functioning in lipid-carbohydrate-mitochondrial metabolic networks. Myc-involved transcriptional response to exposure of this neonicotinoid is indicated by overrepresentation of E-box elements in the promoter regions of genes with altered expression. RNA levels for a cluster of genes encoding detoxifying P450 enzymes are elevated, with coordinated downregulation of genes in glycolytic and sugar-metabolising pathways. Expression of the environmentally responsive Hsp90 gene is also reduced, suggesting diminished buffering and stability of the developmental program. The multifaceted, physiological response described here may be of importance to our general understanding of pollinator health. Muscles, for instance, work at high glycolytic rates and flight performance could be impacted should low levels of this evolutionarily novel stressor likewise induce downregulation of energy metabolising genes in adult pollinators. PMID:23844170

  2. Transient Exposure to Low Levels of Insecticide Affects Metabolic Networks of Honeybee Larvae

    PubMed Central

    Derecka, Kamila; Blythe, Martin J.; Malla, Sunir; Genereux, Diane P.; Guffanti, Alessandro; Pavan, Paolo; Moles, Anna; Snart, Charles; Ryder, Thomas; Ortori, Catharine A.; Barrett, David A.; Schuster, Eugene; Stöger, Reinhard

    2013-01-01

    The survival of a species depends on its capacity to adjust to changing environmental conditions, and new stressors. Such new, anthropogenic stressors include the neonicotinoid class of crop-protecting agents, which have been implicated in the population declines of pollinating insects, including honeybees (Apis mellifera). The low-dose effects of these compounds on larval development and physiological responses have remained largely unknown. Over a period of 15 days, we provided syrup tainted with low levels (2 µg/L−1) of the neonicotinoid insecticide imidacloprid to beehives located in the field. We measured transcript levels by RNA sequencing and established lipid profiles using liquid chromatography coupled with mass spectrometry from worker-bee larvae of imidacloprid-exposed (IE) and unexposed, control (C) hives. Within a catalogue of 300 differentially expressed transcripts in larvae from IE hives, we detect significant enrichment of genes functioning in lipid-carbohydrate-mitochondrial metabolic networks. Myc-involved transcriptional response to exposure of this neonicotinoid is indicated by overrepresentation of E-box elements in the promoter regions of genes with altered expression. RNA levels for a cluster of genes encoding detoxifying P450 enzymes are elevated, with coordinated downregulation of genes in glycolytic and sugar-metabolising pathways. Expression of the environmentally responsive Hsp90 gene is also reduced, suggesting diminished buffering and stability of the developmental program. The multifaceted, physiological response described here may be of importance to our general understanding of pollinator health. Muscles, for instance, work at high glycolytic rates and flight performance could be impacted should low levels of this evolutionarily novel stressor likewise induce downregulation of energy metabolising genes in adult pollinators. PMID:23844170

  3. Sleep Apnea and Fatty Liver Are Coupled Via Energy Metabolism.

    PubMed

    Arısoy, Ahmet; Sertoğullarından, Bunyamin; Ekin, Selami; Özgökçe, Mesut; Bulut, Mehmet Deniz; Huyut, Mehmet Tahir; Ölmez, Şehmus; Turan, Mahfuz

    2016-01-01

    BACKGROUND Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder characterized by intermittent hypoxia. Non-alcoholic fatty liver disease is the most common cause of chronic liver disease worldwide. We aimed to evaluate the relationship between OSA and fatty liver. MATERIAL AND METHODS We enrolled 176 subjects to this study who underwent polysomnography (PSG) for suspected OSA. The control group included 42 simple snoring subjects. PSG, biochemical tests, and ultrasonographic examination were performed all subjects. RESULTS The simple snoring and mild, moderate, and severe OSA groups included 18/42 (42.86%), 33/52 (63.5%), 27/34 (79.4%), and 28/48 (79.2%) subjects with hepatosteatosis, respectively. There were significant differences in hepatosteatosis and hepatosteatosis grade between the simple snoring and the moderate and severe OSA groups. Logistic regression analysis showed that BMI and average desaturation were independently and significantly related to hepatic steatosis. CONCLUSIONS Our study shows that BMI and the average desaturation contribute to non-alcoholic fatty liver in subjects with OSA. In this regard, sleep apnea may trigger metabolic mitochondrial energy associated processes thereby altering lipid metabolism and obesity as well. PMID:26993969

  4. Sleep Apnea and Fatty Liver Are Coupled Via Energy Metabolism

    PubMed Central

    Arısoy, Ahmet; Sertoğullarından, Bunyamin; Ekin, Selami; Özgökçe, Mesut; Bulut, Mehmet Deniz; Huyut, Mehmet Tahir; Ölmez, Şehmus; Turan, Mahfuz

    2016-01-01

    Background Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder characterized by intermittent hypoxia. Non-alcoholic fatty liver disease is the most common cause of chronic liver disease worldwide. We aimed to evaluate the relationship between OSA and fatty liver. Material/Methods We enrolled 176 subjects to this study who underwent polysomnography (PSG) for suspected OSA. The control group included 42 simple snoring subjects. PSG, biochemical tests, and ultrasonographic examination were performed all subjects. Results The simple snoring and mild, moderate, and severe OSA groups included 18/42 (42.86%), 33/52 (63.5%), 27/34 (79.4%), and 28/48 (79.2%) subjects with hepatosteatosis, respectively. There were significant differences in hepatosteatosis and hepatosteatosis grade between the simple snoring and the moderate and severe OSA groups. Logistic regression analysis showed that BMI and average desaturation were independently and significantly related to hepatic steatosis. Conclusions Our study shows that BMI and the average desaturation contribute to non-alcoholic fatty liver in subjects with OSA. In this regard, sleep apnea may trigger metabolic mitochondrial energy associated processes thereby altering lipid metabolism and obesity as well. PMID:26993969

  5. 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

  6. Metabolic dynamics analysis by massive data integration: application to tsunami-affected field soils in Japan.

    PubMed

    Ogura, Tatsuki; Date, Yasuhiro; Tsuboi, Yuuri; Kikuchi, Jun

    2015-08-21

    A new metabolic dynamics analysis approach has been developed in which massive data sets from time-series of (1)H and (13)C NMR spectra are integrated in combination with microbial variability to characterize the biomass degradation process using field soil microbial communities. On the basis of correlation analyses that revealed relationships between various metabolites and bacteria, we efficiently monitored the metabolic dynamics of saccharides, amino acids, and organic acids, by assessing time-course changes in the microbial and metabolic profiles during biomass degradation. Specific bacteria were found to support specific steps of metabolic pathways in the degradation process of biomass to short chain fatty acids. We evaluated samples from agricultural and abandoned fields contaminated by the tsunami that followed the Great East earthquake in Japan. Metabolic dynamics and activities in the biomass degradation process differed considerably between soil from agricultural and abandoned fields. In particular, production levels of short chain fatty acids, such as acetate and propionate, which were considered to be produced by soil bacteria such as Sedimentibacter sp. and Coprococcus sp., were higher in the soil from agricultural fields than from abandoned fields. Our approach could characterize soil activity based on the metabolic dynamics of microbial communities in the biomass degradation process and should therefore be useful in future investigations of the environmental effects of natural disasters on soils. PMID:25997449

  7. Bisphenol A affects early bovine embryo development and metabolism that is negated by an oestrogen receptor inhibitor.

    PubMed

    Choi, Bom-Ie; Harvey, Alexandra J; Green, Mark P

    2016-01-01

    Increasing evidence supports an association between exposure to endocrine disruptors, such as the xenoestrogen bisphenol A (BPA), a commonly used plasticiser, and the developmental programming of offspring health. To date however animal studies to investigate a direct causal have mainly focussed on supra-environmental BPA concentrations, without investigating the effect on the early embryo. In this study we investigated the effect of acute BPA exposure (days 3.5 to 7.5 post-fertilisation) at environmentally relevant concentrations (1 and 10 ng/mL) on in vitro bovine embryo development, quality and metabolism. We then examined whether culturing embryos in the presence of the oestrogen receptor inhibitor fulvestrant could negate effects of BPA and 17β-oestradiol (E2). Exposure to BPA or E2 (10 ng/mL) decreased blastocyst rate and the percentage of transferrable quality embryos, without affecting cell number, lineage allocation or metabolic gene expression compared to untreated embryos. Notably, blastocysts exposed to BPA and E2 (10 ng/mL) displayed an increase in glucose consumption. The presence of fulvestrant however negated the adverse developmental and metabolic effects, suggesting BPA elicits its effects via oestrogen-mediated pathways. This study demonstrates that even acute exposure to an environmentally relevant BPA concentration can affect early embryo development and metabolism. These may have long-term health consequences on an individual. PMID:27384909

  8. Severe dietary lysine restriction affects growth and body composition and hepatic gene expression for nitrogen metabolism in growing rats.

    PubMed

    Kim, J; Lee, K S; Kwon, D-H; Bong, J J; Jeong, J Y; Nam, Y S; Lee, M S; Liu, X; Baik, M

    2014-02-01

    Dietary lysine restriction may differentially affect body growth and lipid and nitrogen metabolism, depending on the degree of lysine restriction. This study was conducted to examine the effect of dietary lysine restriction on growth and lipid and nitrogen metabolism with two different degree of lysine restriction. Isocaloric amino acid-defined diets containing 1.4% lysine (adequate), 0.70% lysine (50% moderate lysine restriction) and 0.35% lysine (75% severe lysine restriction) were fed from the age of 52 to 77 days for 25 days in male Sprague-Dawley rats. The 75% severe lysine restriction increased (p < 0.05) food intake, but retarded (p < 0.05) growth, increased (p < 0.05) liver and muscle lipid contents and abdominal fat accumulation, increased (p < 0.05) blood urea nitrogen levels and mRNA levels of the serine-synthesizing 3-phosphoglycerate dehydrogenase gene, but decreased (p < 0.05) urea cycle arginase gene mRNA levels. In contrast, the 50% lysine restriction did not significantly (p > 0.05) affect body growth and lipid and nitrogen metabolism. Our results demonstrate that severe 75% lysine restriction has detrimental effects on body growth and deregulate lipid and nitrogen metabolism. PMID:23441935

  9. Bisphenol A affects early bovine embryo development and metabolism that is negated by an oestrogen receptor inhibitor

    PubMed Central

    Choi, Bom-Ie; Harvey, Alexandra J.; Green, Mark P.

    2016-01-01

    Increasing evidence supports an association between exposure to endocrine disruptors, such as the xenoestrogen bisphenol A (BPA), a commonly used plasticiser, and the developmental programming of offspring health. To date however animal studies to investigate a direct causal have mainly focussed on supra-environmental BPA concentrations, without investigating the effect on the early embryo. In this study we investigated the effect of acute BPA exposure (days 3.5 to 7.5 post-fertilisation) at environmentally relevant concentrations (1 and 10 ng/mL) on in vitro bovine embryo development, quality and metabolism. We then examined whether culturing embryos in the presence of the oestrogen receptor inhibitor fulvestrant could negate effects of BPA and 17β-oestradiol (E2). Exposure to BPA or E2 (10 ng/mL) decreased blastocyst rate and the percentage of transferrable quality embryos, without affecting cell number, lineage allocation or metabolic gene expression compared to untreated embryos. Notably, blastocysts exposed to BPA and E2 (10 ng/mL) displayed an increase in glucose consumption. The presence of fulvestrant however negated the adverse developmental and metabolic effects, suggesting BPA elicits its effects via oestrogen-mediated pathways. This study demonstrates that even acute exposure to an environmentally relevant BPA concentration can affect early embryo development and metabolism. These may have long-term health consequences on an individual. PMID:27384909

  10. 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

  11. The Deep Correlation between Energy Metabolism and Reproduction: A View on the Effects of Nutrition for Women Fertility.

    PubMed

    Fontana, Roberta; Della Torre, Sara

    2016-02-01

    In female mammals, mechanisms have been developed, throughout evolution, to integrate environmental, nutritional and hormonal cues in order to guarantee reproduction in favorable energetic conditions and to inhibit it in case of food scarcity. This metabolic strategy could be an advantage in nutritionally poor environments, but nowadays is affecting women's health. The unlimited availability of nutrients, in association with reduced energy expenditure, leads to alterations in many metabolic pathways and to impairments in the finely tuned inter-relation between energy metabolism and reproduction, thereby affecting female fertility. Many energetic states could influence female reproductive health being under- and over-weight, obesity and strenuous physical activity are all conditions that alter the profiles of specific hormones, such as insulin and adipokines, thus impairing women fertility. Furthermore, specific classes of nutrients might affect female fertility by acting on particular signaling pathways. Dietary fatty acids, carbohydrates, proteins and food-associated components (such as endocrine disruptors) have per se physiological activities and their unbalanced intake, both in quantitative and qualitative terms, might impair metabolic homeostasis and fertility in premenopausal women. Even though we are far from identifying a "fertility diet", lifestyle and dietary interventions might represent a promising and invaluable strategy to manage infertility in premenopausal women. PMID:26875986

  12. The Deep Correlation between Energy Metabolism and Reproduction: A View on the Effects of Nutrition for Women Fertility

    PubMed Central

    Fontana, Roberta; Della Torre, Sara

    2016-01-01

    In female mammals, mechanisms have been developed, throughout evolution, to integrate environmental, nutritional and hormonal cues in order to guarantee reproduction in favorable energetic conditions and to inhibit it in case of food scarcity. This metabolic strategy could be an advantage in nutritionally poor environments, but nowadays is affecting women’s health. The unlimited availability of nutrients, in association with reduced energy expenditure, leads to alterations in many metabolic pathways and to impairments in the finely tuned inter-relation between energy metabolism and reproduction, thereby affecting female fertility. Many energetic states could influence female reproductive health being under- and over-weight, obesity and strenuous physical activity are all conditions that alter the profiles of specific hormones, such as insulin and adipokines, thus impairing women fertility. Furthermore, specific classes of nutrients might affect female fertility by acting on particular signaling pathways. Dietary fatty acids, carbohydrates, proteins and food-associated components (such as endocrine disruptors) have per se physiological activities and their unbalanced intake, both in quantitative and qualitative terms, might impair metabolic homeostasis and fertility in premenopausal women. Even though we are far from identifying a “fertility diet”, lifestyle and dietary interventions might represent a promising and invaluable strategy to manage infertility in premenopausal women. PMID:26875986

  13. Constraints on Energy Intake in Fish: The Link between Diet Composition, Energy Metabolism, and Energy Intake in Rainbow Trout

    PubMed Central

    Saravanan, Subramanian; Schrama, Johan W.; Figueiredo-Silva, A. Claudia; Kaushik, Sadasivam J.; Verreth, Johan A. J.; Geurden, Inge

    2012-01-01

    The hypothesis was tested that fish fed to satiation with iso-energetic diets differing in macronutrient composition will have different digestible energy intakes (DEI) but similar total heat production. Four iso-energetic diets (2×2 factorial design) were formulated having a contrast in i) the ratio of protein to energy (P/E): high (HP/E) vs. low (LP/E) and ii) the type of non-protein energy (NPE) source: fat vs. carbohydrate which were iso-energetically exchanged. Triplicate groups (35 fish/tank) of rainbow trout were hand-fed each diet twice daily to satiation for 6 weeks under non-limiting water oxygen conditions. Feed intake (FI), DEI (kJ kg−0.8 d−1) and growth (g kg−0.8 d−1) of trout were affected by the interaction between P/E ratio and NPE source of the diet (P<0.05). Regardless of dietary P/E ratio, the inclusion of carbohydrate compared to fat as main NPE source reduced DEI and growth of trout by ∼20%. The diet-induced differences in FI and DEI show that trout did not compensate for the dietary differences in digestible energy or digestible protein contents. Further, changes in body fat store and plasma glucose did not seem to exert a homeostatic feedback control on DEI. Independent of the diet composition, heat production of trout did not differ (P>0.05). Our data suggest that the control of DEI in trout might be a function of heat production, which in turn might reflect a physiological limit related with oxidative metabolism. PMID:22496852

  14. Helicobacter pylori infection can affect energy modulating hormones and body weight in germ free mice

    PubMed Central

    Khosravi, Yalda; Seow, Shih Wee; Amoyo, Arlaine Anne; Chiow, Kher Hsin; Tan, Tuan Lin; Wong, Whye Yen; Poh, Qian Hui; Sentosa, Ignatius Mario Doli; Bunte, Ralph M.; Pettersson, Sven; Loke, Mun Fai; Vadivelu, Jamuna

    2015-01-01

    Helicobacter pylori, is an invariably commensal resident of the gut microbiome associated with gastric ulcer in adults. In addition, these patients also suffered from a low grade inflammation that activates the immune system and thus increased shunting of energy to host defense mechanisms. To assess whether a H. pylori infection could affect growth in early life, we determined the expression levels of selected metabolic gut hormones in germ free (GF) and specific pathogen-free (SPF) mice with and without the presence of H. pylori. Despite H. pylori-infected (SPFH) mice display alteration in host metabolism (elevated levels of leptin, insulin and peptide YY) compared to non-infected SPF mice, their growth curves remained the same. SPFH mice also displayed increased level of eotaxin-1. Interestingly, GF mice infected with H. pylori (GFH) also displayed increased levels of ghrelin and PYY. However, in contrast to SPFH mice, GFH showed reduced weight gain and malnutrition. These preliminary findings show that exposure to H. pylori alters host metabolism early in life; but the commensal microbiota in SPF mice can attenuate the growth retarding effect from H. pylori observed in GF mice. Further investigations of possible additional side effects of H. pylori are highly warranted. PMID:25736205

  15. Helicobacter pylori infection can affect energy modulating hormones and body weight in germ free mice.

    PubMed

    Khosravi, Yalda; Seow, Shih Wee; Amoyo, Arlaine Anne; Chiow, Kher Hsin; Tan, Tuan Lin; Wong, Whye Yen; Poh, Qian Hui; Sentosa, Ignatius Mario Doli; Bunte, Ralph M; Pettersson, Sven; Loke, Mun Fai; Vadivelu, Jamuna

    2015-01-01

    Helicobacter pylori, is an invariably commensal resident of the gut microbiome associated with gastric ulcer in adults. In addition, these patients also suffered from a low grade inflammation that activates the immune system and thus increased shunting of energy to host defense mechanisms. To assess whether a H. pylori infection could affect growth in early life, we determined the expression levels of selected metabolic gut hormones in germ free (GF) and specific pathogen-free (SPF) mice with and without the presence of H. pylori. Despite H. pylori-infected (SPFH) mice display alteration in host metabolism (elevated levels of leptin, insulin and peptide YY) compared to non-infected SPF mice, their growth curves remained the same. SPFH mice also displayed increased level of eotaxin-1. Interestingly, GF mice infected with H. pylori (GFH) also displayed increased levels of ghrelin and PYY. However, in contrast to SPFH mice, GFH showed reduced weight gain and malnutrition. These preliminary findings show that exposure to H. pylori alters host metabolism early in life; but the commensal microbiota in SPF mice can attenuate the growth retarding effect from H. pylori observed in GF mice. Further investigations of possible additional side effects of H. pylori are highly warranted. PMID:25736205

  16. 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

  17. Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism.

    PubMed

    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

  18. Rice folate enhancement through metabolic engineering has an impact on rice seed metabolism, but does not affect the expression of the endogenous folate biosynthesis genes.

    PubMed

    Blancquaert, Dieter; Van Daele, Jeroen; Storozhenko, Sergei; Stove, Christophe; Lambert, Willy; Van Der Straeten, Dominique

    2013-11-01

    Folates are key-players in one-carbon metabolism in all organisms. However, only micro-organisms and plants are able to synthesize folates de novo and humans rely entirely on their diet as a sole folate source. As a consequence, folate deficiency is a global problem. Although different strategies are currently implemented to fight folate deficiency, up until now, all of them have their own drawbacks. As an alternative and complementary means to those classical strategies, folate biofortification of rice by metabolic engineering was successfully achieved a couple of years ago. To gain more insight into folate biosynthesis regulation and the effect of folate enhancement on general rice seed metabolism, a transcriptomic study was conducted in developing transgenic rice seeds, overexpressing 2 genes of the folate biosynthetic pathway. Upon folate enhancement, the expression of 235 genes was significantly altered. Here, we show that rice folate biofortification has an important effect on folate dependent, seed developmental and plant stress response/defense processes, but does not affect the expression of the endogenous folate biosynthesis genes. PMID:23771598

  19. Drug-Induced Diabetes Mellitus: Evidence for Statins and Other Drugs Affecting Glucose Metabolism.

    PubMed

    Anyanwagu, U; Idris, I; Donnelly, R

    2016-04-01

    Abnormalities of glucose metabolism and glucose tolerance, either because of a reduction in tissue sensitivity to insulin (e.g., in liver, skeletal muscle, and adipose tissues) and/or a reduction in pancreatic insulin secretion, are associated with a number of unwanted health outcomes. Even small increases in circulating glucose levels (often described as dysglycemia or prediabetes) may confer an increased risk of cardiovascular (CV) disease and progression to overt type 2 diabetes. A number of drug therapies, many of them used long term in chronic disease management, have adverse effects on glucose metabolism, diabetes risk, and glycemic control among patients with preexisting diabetes. In this study, we review the evidence, underlying mechanisms, and the clinical significance of drug-related adverse effects on glucose metabolism. PMID:26440603

  20. Validation of Candidate Causal Genes for Abdominal Obesity Which Affect Shared Metabolic Pathways and Networks

    PubMed Central

    Yang, Xia; Deignan, Joshua L.; Qi, Hongxiu; Zhu, Jun; Qian, Su; Zhong, Judy; Torosyan, Gevork; Majid, Sana; Falkard, Brie; Kleinhanz, Robert R.; Karlsson, Jenny; Castellani, Lawrence W.; Mumick, Sheena; Wang, Kai; Xie, Tao; Coon, Michael; Zhang, Chunsheng; Estrada-Smith, Daria; Farber, Charles R.; Wang, Susanna S.; Van Nas, Atila; Ghazalpour, Anatole; Zhang, Bin; MacNeil, Douglas J.; Lamb, John R.; Dipple, Katrina M.; Reitman, Marc L.; Mehrabian, Margarete; Lum, Pek Y.; Schadt, Eric E.; Lusis, Aldons J.

    2010-01-01

    A major task in dissecting the genetics of complex traits is to identify causal genes for disease phenotypes. We previously developed a method to infer causal relationships among genes through the integration of DNA variation, gene transcription, and phenotypic information. Here we validated our method through the characterization of transgenic and knockout mouse models of candidate genes that were predicted to be causal for abdominal obesity. Perturbation of eight out of the nine genes, with Gas7, Me1 and Gpx3 being novel, resulted in significant changes in obesity related traits. Liver expression signatures revealed alterations in common metabolic pathways and networks contributing to abdominal obesity and overlapped with a macrophage-enriched metabolic network module that is highly associated with metabolic traits in mice and humans. Integration of gene expression in the design and analysis of traditional F2 intercross studies allows high confidence prediction of causal genes and identification of involved pathways and networks. PMID:19270708

  1. 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

  2. MAPK14/p38α-dependent modulation of glucose metabolism affects ROS levels and autophagy during starvation

    PubMed Central

    Desideri, Enrico; Vegliante, Rolando; Cardaci, Simone; Nepravishta, Ridvan; Paci, Maurizio; Ciriolo, Maria Rosa

    2014-01-01

    Increased glycolytic flux is a common feature of many cancer cells, which have adapted their metabolism to maximize glucose incorporation and catabolism to generate ATP and substrates for biosynthetic reactions. Indeed, glycolysis allows a rapid production of ATP and provides metabolic intermediates required for cancer cells growth. Moreover, it makes cancer cells less sensitive to fluctuations of oxygen tension, a condition usually occurring in a newly established tumor environment. Here, we provide evidence for a dual role of MAPK14 in driving a rearrangement of glucose metabolism that contributes to limiting reactive oxygen species (ROS) production and autophagy activation in condition of nutrient deprivation. We demonstrate that MAPK14 is phosphoactivated during nutrient deprivation and affects glucose metabolism at 2 different levels: on the one hand, it increases SLC2A3 mRNA and protein levels, resulting in a higher incorporation of glucose within the cell. This event involves the MAPK14-mediated enhancement of HIF1A protein stability. On the other hand, MAPK14 mediates a metabolic shift from glycolysis to the pentose phosphate pathway (PPP) through the modulation of PFKFB3 (6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase 3) degradation by the proteasome. This event requires the presence of 2 distinct degradation sequences, KEN box and DSG motif Ser273, which are recognized by 2 different E3 ligase complexes. The mutation of either motif increases PFKFB3 resistance to starvation-induced degradation. The MAPK14-driven metabolic reprogramming sustains the production of NADPH, an important cofactor for many reduction reactions and for the maintenance of the proper intracellular redox environment, resulting in reduced levels of ROS. The final effect is a reduced activation of autophagy and an increased resistance to nutrient deprivation. PMID:25046111

  3. Metabolic energy from arsenite oxidation in Alcaligenes faecalis

    NASA Astrophysics Data System (ADS)

    Anderson, G. L.; Love, M.; Zeider, B. K.

    2003-05-01

    The aerobic soil bacterium, Alcaligenes faecalis, survives in cultures containing greater than 10 g/L of aqueous arsenic. Toleration of arsenite occurs by the enzymatic oxidation of arsenite (As^III), to the less toxic arsenate (As^V). In defined media, the bacterium grows faster in the presence of arsenite than in its absence. This suggests that the bacterium uses the redox potential of arsenite oxidation as metabolic energy. The oxidation occurs via periplasmic arsenite oxidase, azurin, and cytochrome c [11] which presumably pass electron equivalents through an electron transport chain involving cytochrome c oxidase aud oxygen as the terminal electron acceptor. The associated proton translocation would allow synthesis of ATP and provide a useful means of harnessing the redox potential of arsenite oxidation. Arsenite and arsenate assays of the media during bacterial growth indicate that arsenite is depleted during the exponential growth phase and occurs concomitantly with the expression of arsenite oxidase. These results suggest that arsenite is detoxified to arsenate during bacterial growth and are inconsistent with previous reported interpretations of growth data. Alcaligenes faecalis is dependent on organic carbon sources and is therefore not chemolithoautotrophic. The relationship between succinate and arsenite utilisation provides evidence for the use of arsenite as a supplemental energy source. Because Alcaligenes faecalis not only tolerates, but thrives, in very high concentrations of arsenic has important implications in bioremediation of environments contaminated by aqueous arsenic.

  4. 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.

  5. 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

  6. 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

  7. Energy Metabolism and Leptin: Effects on Neuroendocrine Regulation of Reproduction in the Gilt and Sow

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is well established that reproductive function is metabolically gated. However, the mechanisms whereby energy stores and metabolic cues influence appetite, energy homeostasis and fertility are yet to be completely understood. Adipose tissue is no longer considered as only a depot to store exces...

  8. 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...

  9. High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring

    PubMed Central

    de Castro Barbosa, Thais; Ingerslev, Lars R.; Alm, Petter S.; Versteyhe, Soetkin; Massart, Julie; Rasmussen, Morten; Donkin, Ida; Sjögren, Rasmus; Mudry, Jonathan M.; Vetterli, Laurène; Gupta, Shashank; Krook, Anna; Zierath, Juleen R.; Barrès, Romain

    2015-01-01

    Objectives Chronic and high consumption of fat constitutes an environmental stress that leads to metabolic diseases. We hypothesized that high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa and metabolism of the offspring. Methods F0-male rats fed either HFD or chow diet for 12 weeks were mated with chow-fed dams to generate F1 and F2 offspring. Motile spermatozoa were isolated from F0 and F1 breeders to determine DNA methylation and small non-coding RNA (sncRNA) expression pattern by deep sequencing. Results Newborn offspring of HFD-fed fathers had reduced body weight and pancreatic beta-cell mass. Adult female, but not male, offspring of HFD-fed fathers were glucose intolerant and resistant to HFD-induced weight gain. This phenotype was perpetuated in the F2 progeny, indicating transgenerational epigenetic inheritance. The epigenome of spermatozoa from HFD-fed F0 and their F1 male offspring showed common DNA methylation and small non-coding RNA expression signatures. Altered expression of sperm miRNA let-7c was passed down to metabolic tissues of the offspring, inducing a transcriptomic shift of the let-7c predicted targets. Conclusion Our results provide insight into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations. PMID:26977389

  10. ATG7 regulates energy metabolism, differentiation and survival of Philadelphia-chromosome-positive cells.

    PubMed

    Karvela, Maria; Baquero, Pablo; Kuntz, Elodie M; Mukhopadhyay, Arunima; Mitchell, Rebecca; Allan, Elaine K; Chan, Edmond; Kranc, Kamil R; Calabretta, Bruno; Salomoni, Paolo; Gottlieb, Eyal; Holyoake, Tessa L; Helgason, G Vignir

    2016-06-01

    A major drawback of tyrosine kinase inhibitor (TKI) treatment in chronic myeloid leukemia (CML) is that primitive CML cells are able to survive TKI-mediated BCR-ABL inhibition, leading to disease persistence in patients. Investigation of strategies aiming to inhibit alternative survival pathways in CML is therefore critical. We have previously shown that a nonspecific pharmacological inhibition of autophagy potentiates TKI-induced death in Philadelphia chromosome-positive cells. Here we provide further understanding of how specific and pharmacological autophagy inhibition affects nonmitochondrial and mitochondrial energy metabolism and reactive oxygen species (ROS)-mediated differentiation of CML cells and highlight ATG7 (a critical component of the LC3 conjugation system) as a potential specific therapeutic target. By combining extra- and intracellular steady state metabolite measurements by liquid chromatography-mass spectrometry with metabolic flux assays using labeled glucose and functional assays, we demonstrate that knockdown of ATG7 results in decreased glycolysis and increased flux of labeled carbons through the mitochondrial tricarboxylic acid cycle. This leads to increased oxidative phosphorylation and mitochondrial ROS accumulation. Furthermore, following ROS accumulation, CML cells, including primary CML CD34(+) progenitor cells, differentiate toward the erythroid lineage. Finally, ATG7 knockdown sensitizes CML progenitor cells to TKI-induced death, without affecting survival of normal cells, suggesting that specific inhibitors of ATG7 in combination with TKI would provide a novel therapeutic approach for CML patients exhibiting persistent disease. PMID:27168493

  11. ATG7 regulates energy metabolism, differentiation and survival of Philadelphia-chromosome-positive cells

    PubMed Central

    Karvela, Maria; Baquero, Pablo; Kuntz, Elodie M.; Mukhopadhyay, Arunima; Mitchell, Rebecca; Allan, Elaine K.; Chan, Edmond; Kranc, Kamil R.; Calabretta, Bruno; Salomoni, Paolo; Gottlieb, Eyal; Holyoake, Tessa L.; Helgason, G. Vignir

    2016-01-01

    ABSTRACT A major drawback of tyrosine kinase inhibitor (TKI) treatment in chronic myeloid leukemia (CML) is that primitive CML cells are able to survive TKI-mediated BCR-ABL inhibition, leading to disease persistence in patients. Investigation of strategies aiming to inhibit alternative survival pathways in CML is therefore critical. We have previously shown that a nonspecific pharmacological inhibition of autophagy potentiates TKI-induced death in Philadelphia chromosome-positive cells. Here we provide further understanding of how specific and pharmacological autophagy inhibition affects nonmitochondrial and mitochondrial energy metabolism and reactive oxygen species (ROS)-mediated differentiation of CML cells and highlight ATG7 (a critical component of the LC3 conjugation system) as a potential specific therapeutic target. By combining extra- and intracellular steady state metabolite measurements by liquid chromatography-mass spectrometry with metabolic flux assays using labeled glucose and functional assays, we demonstrate that knockdown of ATG7 results in decreased glycolysis and increased flux of labeled carbons through the mitochondrial tricarboxylic acid cycle. This leads to increased oxidative phosphorylation and mitochondrial ROS accumulation. Furthermore, following ROS accumulation, CML cells, including primary CML CD34+ progenitor cells, differentiate toward the erythroid lineage. Finally, ATG7 knockdown sensitizes CML progenitor cells to TKI-induced death, without affecting survival of normal cells, suggesting that specific inhibitors of ATG7 in combination with TKI would provide a novel therapeutic approach for CML patients exhibiting persistent disease. PMID:27168493

  12. 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. PMID:22523469

  13. 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

  14. Silencing of the tomato sugar partitioning affecting protein (SPA) modifies sink strength through a shift in leaf sugar metabolism.

    PubMed

    Bermúdez, Luisa; de Godoy, Fabiana; Baldet, Pierre; Demarco, Diego; Osorio, Sonia; Quadrana, Leandro; Almeida, Juliana; Asis, Ramón; Gibon, Yves; Fernie, Alisdair R; Rossi, Magdalena; Carrari, Fernando

    2014-03-01

    Limitations in our understanding about the mechanisms that underlie source-sink assimilate partitioning are increasingly becoming a major hurdle for crop yield enhancement via metabolic engineering. By means of a comprehensive approach, this work reports the functional characterization of a DnaJ chaperone related-protein (named as SPA; sugar partition-affecting) that is involved in assimilate partitioning in tomato plants. SPA protein was found to be targeted to the chloroplast thylakoid membranes. SPA-RNAi tomato plants produced more and heavier fruits compared with controls, thus resulting in a considerable increment in harvest index. The transgenic plants also displayed increased pigment levels and reduced sucrose, glucose and fructose contents in leaves. Detailed metabolic and enzymatic activities analyses showed that sugar phosphate intermediates were increased while the activity of phosphoglucomutase, sugar kinases and invertases was reduced in the photosynthetic organs of the silenced plants. These changes would be anticipated to promote carbon export from foliar tissues. The combined results suggested that the tomato SPA protein plays an important role in plastid metabolism and mediates the source-sink relationships by affecting the rate of carbon translocation to fruits. PMID:24372694

  15. Erythropoietin, a Novel Versatile Player Regulating Energy Metabolism beyond the Erythroid System

    PubMed Central

    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

  16. 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

  17. Rh2E2, a novel metabolic suppressor, specifically inhibits energy-based metabolism of tumor cells.

    PubMed

    Wong, Vincent Kam Wai; Dong, Hang; Liang, Xu; 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

    2016-03-01

    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

  18. Factors affecting bioabsorption, metabolism, and storage of organic compounds by aquatic biota

    SciTech Connect

    Bean, R.M.; Dauble, D.D.; Thomas, B.L.; Hanf, R.W.; Chess, E.K.

    1985-12-01

    Biological concentration and transfer of organic chemicals through aquatic food webs can be influenced by a variety of environmental, biological, and biochemical factors. Bioaccumulation can be significantly altered by the presence of suspended matter or complex organic mixtures in the water column. In addition, the bioaccumulation factor of a compound is dependent on the species of an organism, its life stage, and the available food supply. Metabolic changes in structure of absorbed organics can alter both the rate and the mechanism of absorption and elimination of organics. In the case of quinoline absorption by trout, both the rate of absorption and the metabolic disposition depended upon whether exposure was through ingestion or through direct water column exposure. All of these factors can be used to explain why the physical properties of organic compounds (most notably octanol/water partition coefficients) are unreliable predictors of bioaccumulation potential. 24 refs., 1 tab.

  19. Nitrogen-Sparing Mechanisms in Chlamydomonas Affect the Transcriptome, the Proteome, and Photosynthetic Metabolism[W

    PubMed Central

    Schmollinger, Stefan; Mühlhaus, Timo; Boyle, Nanette R.; Blaby, Ian K.; Casero, David; Mettler, Tabea; Moseley, Jeffrey L.; Kropat, Janette; Sommer, Frederik; Strenkert, Daniela; Hemme, Dorothea; Pellegrini, Matteo; Grossman, Arthur R.; Stitt, Mark; Schroda, Michael; Merchant, Sabeeha S.

    2014-01-01

    Nitrogen (N) is a key nutrient that limits global primary productivity; hence, N-use efficiency is of compelling interest in agriculture and aquaculture. We used Chlamydomonas reinhardtii as a reference organism for a multicomponent analysis of the N starvation response. In the presence of acetate, respiratory metabolism is prioritized over photosynthesis; consequently, the N-sparing response targets proteins, pigments, and RNAs involved in photosynthesis and chloroplast function over those involved in respiration. Transcripts and proteins of the Calvin-Benson cycle are reduced in N-deficient cells, resulting in the accumulation of cycle metabolic intermediates. Both cytosolic and chloroplast ribosomes are reduced, but via different mechanisms, reflected by rapid changes in abundance of RNAs encoding chloroplast ribosomal proteins but not cytosolic ones. RNAs encoding transporters and enzymes for metabolizing alternative N sources increase in abundance, as is appropriate for the soil environmental niche of C. reinhardtii. Comparison of the N-replete versus N-deplete proteome indicated that abundant proteins with a high N content are reduced in N-starved cells, while the proteins that are increased have lower than average N contents. This sparing mechanism contributes to a lower cellular N/C ratio and suggests an approach for engineering increased N-use efficiency. PMID:24748044

  20. Light intensity affects the uptake and metabolism of glycine by pakchoi (Brassica chinensis L.)

    PubMed Central

    Ma, Qingxu; Cao, Xiaochuang; Wu, Lianghuan; Mi, Wenhai; Feng, Ying

    2016-01-01

    The uptake of glycine by pakchoi (Brassica chinensis L.), when supplied as single N-source or in a mixture of glycine and inorganic N, was studied at different light intensities under sterile conditions. At the optimal intensity (414 μmol m−2 s−1) for plant growth, glycine, nitrate, and ammonium contributed 29.4%, 39.5%, and 31.1% shoot N, respectively, and light intensity altered the preferential absorption of N sources. The lower 15N-nitrate in root but higher in shoot and the higher 15N-glycine in root but lower in shoot suggested that most 15N-nitrate uptake by root transported to shoot rapidly, with the shoot being important for nitrate assimilation, and the N contribution of glycine was limited by post-uptake metabolism. The amount of glycine that was taken up by the plant was likely limited by root uptake at low light intensities and by the metabolism of ammonium produced by glycine at high light intensities. These results indicate that pakchoi has the ability to uptake a large quantity of glycine, but that uptake is strongly regulated by light intensity, with metabolism in the root inhibiting its N contribution. PMID:26882864

  1. Light intensity affects the uptake and metabolism of glycine by pakchoi (Brassica chinensis L.)

    NASA Astrophysics Data System (ADS)

    Ma, Qingxu; Cao, Xiaochuang; Wu, Lianghuan; Mi, Wenhai; Feng, Ying

    2016-02-01

    The uptake of glycine by pakchoi (Brassica chinensis L.), when supplied as single N-source or in a mixture of glycine and inorganic N, was studied at different light intensities under sterile conditions. At the optimal intensity (414 μmol m-2 s-1) for plant growth, glycine, nitrate, and ammonium contributed 29.4%, 39.5%, and 31.1% shoot N, respectively, and light intensity altered the preferential absorption of N sources. The lower 15N-nitrate in root but higher in shoot and the higher 15N-glycine in root but lower in shoot suggested that most 15N-nitrate uptake by root transported to shoot rapidly, with the shoot being important for nitrate assimilation, and the N contribution of glycine was limited by post-uptake metabolism. The amount of glycine that was taken up by the plant was likely limited by root uptake at low light intensities and by the metabolism of ammonium produced by glycine at high light intensities. These results indicate that pakchoi has the ability to uptake a large quantity of glycine, but that uptake is strongly regulated by light intensity, with metabolism in the root inhibiting its N contribution.

  2. Light intensity affects the uptake and metabolism of glycine by pakchoi (Brassica chinensis L.).

    PubMed

    Ma, Qingxu; Cao, Xiaochuang; Wu, Lianghuan; Mi, Wenhai; Feng, Ying

    2016-01-01

    The uptake of glycine by pakchoi (Brassica chinensis L.), when supplied as single N-source or in a mixture of glycine and inorganic N, was studied at different light intensities under sterile conditions. At the optimal intensity (414 μmol m(-2) s(-1)) for plant growth, glycine, nitrate, and ammonium contributed 29.4%, 39.5%, and 31.1% shoot N, respectively, and light intensity altered the preferential absorption of N sources. The lower (15)N-nitrate in root but higher in shoot and the higher (15)N-glycine in root but lower in shoot suggested that most (15)N-nitrate uptake by root transported to shoot rapidly, with the shoot being important for nitrate assimilation, and the N contribution of glycine was limited by post-uptake metabolism. The amount of glycine that was taken up by the plant was likely limited by root uptake at low light intensities and by the metabolism of ammonium produced by glycine at high light intensities. These results indicate that pakchoi has the ability to uptake a large quantity of glycine, but that uptake is strongly regulated by light intensity, with metabolism in the root inhibiting its N contribution. PMID:26882864

  3. Maple Bark Biochar Affects Rhizoctonia solani Metabolism and Increases Damping-Off Severity.

    PubMed

    Copley, Tanya R; Aliferis, Konstantinos A; Jabaji, Suha

    2015-10-01

    Many studies have investigated the effect of biochar on plant yield, nutrient uptake, and soil microbial populations; however, little work has been done on its effect on soilborne plant diseases. To determine the effect of maple bark biochar on Rhizoctonia damping-off, 11 plant species were grown in a soilless potting substrate amended with different concentrations of biochar and inoculated or not with Rhizoctonia solani anastomosis group 4. Additionally, the effect of biochar amendment on R. solani growth and metabolism in vitro was evaluated. Increasing concentrations of maple bark biochar increased Rhizoctonia damping-off of all 11 plant species. Using multivariate analyses, we observed positive correlations between biochar amendments, disease severity and incidence, abundance of culturable bacterial communities, and physicochemical parameters. Additionally, biochar amendment significantly increased R. solani growth and hyphal extension in vitro, and altered its primary metabolism, notably the mannitol and tricarboxylic acid cycles and the glycolysis pathway. One or several organic compounds present in the biochar, as identified by gas chromatography-mass spectrometry analysis, may be metabolized by R. solani. Taken together, these results indicate that future studies on biochar should focus on the effect of its use as an amendment on soilborne plant pathogens before applying it to soils. PMID:25938176

  4. In Ovo injection of betaine affects hepatic cholesterol metabolism through epigenetic gene regulation in newly hatched chicks.

    PubMed

    Hu, Yun; Sun, Qinwei; Li, Xiaoliang; Wang, Min; Cai, Demin; Li, Xi; Zhao, Ruqian

    2015-01-01

    Betaine is reported to regulate hepatic cholesterol metabolism in mammals. Chicken eggs contain considerable amount of betaine, yet it remains unknown whether and how betaine in the egg affects hepatic cholesterol metabolism in chicks. In this study, eggs were injected with betaine at 2.5 mg/egg and the hepatic cholesterol metabolism was investigated in newly hatched chicks. Betaine did not affect body weight or liver weight, but significantly increased the serum concentration (P < 0.05) and the hepatic content (P < 0.01) of cholesterol. Accordingly, the cholesterol biosynthetic enzyme HMGCR was up-regulated (P < 0.05 for both mRNA and protein), while CYP7A1 which converts cholesterol to bile acids was down-regulated (P < 0.05 for mRNA and P = 0.07 for protein). Moreover, hepatic protein content of the sterol-regulatory element binding protein 1 which regulates cholesterol and lipid biosynthesis, and the mRNA abundance of ATP binding cassette sub-family A member 1 (ABCA1) which mediates cholesterol counter transport were significantly (P < 0.05) increased in betaine-treated chicks. Meanwhile, hepatic protein contents of DNA methyltransferases 1 and adenosylhomocysteinase-like 1 were increased (P < 0.05), which was associated with global genomic DNA hypermethylation (P < 0.05) and diminished gene repression mark histone H3 lysine 27 trimethylation (P < 0.05). Furthermore, CpG methylation level on gene promoters was found to be increased (P < 0.05) for CYP7A1 yet decreased (P < 0.05) for ABCA1. These results indicate that in ovo betaine injection regulates hepatic cholesterol metabolism in chicks through epigenetic mechanisms including DNA and histone methylations. PMID:25860502

  5. In Ovo Injection of Betaine Affects Hepatic Cholesterol Metabolism through Epigenetic Gene Regulation in Newly Hatched Chicks

    PubMed Central

    Hu, Yun; Sun, Qinwei; Li, Xiaoliang; Wang, Min; Cai, Demin; Li, Xi; Zhao, Ruqian

    2015-01-01

    Betaine is reported to regulate hepatic cholesterol metabolism in mammals. Chicken eggs contain considerable amount of betaine, yet it remains unknown whether and how betaine in the egg affects hepatic cholesterol metabolism in chicks. In this study, eggs were injected with betaine at 2.5 mg/egg and the hepatic cholesterol metabolism was investigated in newly hatched chicks. Betaine did not affect body weight or liver weight, but significantly increased the serum concentration (P < 0.05) and the hepatic content (P < 0.01) of cholesterol. Accordingly, the cholesterol biosynthetic enzyme HMGCR was up-regulated (P < 0.05 for both mRNA and protein), while CYP7A1 which converts cholesterol to bile acids was down-regulated (P < 0.05 for mRNA and P = 0.07 for protein). Moreover, hepatic protein content of the sterol-regulatory element binding protein 1 which regulates cholesterol and lipid biosynthesis, and the mRNA abundance of ATP binding cassette sub-family A member 1 (ABCA1) which mediates cholesterol counter transport were significantly (P < 0.05) increased in betaine-treated chicks. Meanwhile, hepatic protein contents of DNA methyltransferases 1 and adenosylhomocysteinase-like 1 were increased (P < 0.05), which was associated with global genomic DNA hypermethylation (P < 0.05) and diminished gene repression mark histone H3 lysine 27 trimethylation (P < 0.05). Furthermore, CpG methylation level on gene promoters was found to be increased (P < 0.05) for CYP7A1 yet decreased (P < 0.05) for ABCA1. These results indicate that in ovo betaine injection regulates hepatic cholesterol metabolism in chicks through epigenetic mechanisms including DNA and histone methylations. PMID:25860502

  6. 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. PMID:1447134

  7. Carbon and energy metabolism of atp mutants of Escherichia coli.

    PubMed Central

    Jensen, P R; Michelsen, O

    1992-01-01

    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. PMID:1447134

  8. Systems genetics analysis of body weight and energy metabolism traits in Drosophila melanogaster

    PubMed Central

    2010-01-01

    Background Obesity and phenotypic traits associated with this condition exhibit significant heritability in natural populations of most organisms. While a number of genes and genetic pathways have been implicated to play a role in obesity associated traits, the genetic architecture that underlies the natural variation in these traits is largely unknown. Here, we used 40 wild-derived inbred lines of Drosophila melanogaster to quantify genetic variation in body weight, the content of three major metabolites (glycogen, triacylglycerol, and glycerol) associated with obesity, and metabolic rate in young flies. We chose these lines because they were previously screened for variation in whole-genome transcript abundance and in several adult life-history traits, including longevity, resistance to starvation stress, chill-coma recovery, mating behavior, and competitive fitness. This enabled us not only to identify candidate genes and transcriptional networks that might explain variation for energy metabolism traits, but also to investigate the genetic interrelationships among energy metabolism, behavioral, and life-history traits that have evolved in natural populations. Results We found significant genetically based variation in all traits. Using a genome-wide association screen for single feature polymorphisms and quantitative trait transcripts, we identified 337, 211, 237, 553, and 152 novel candidate genes associated with body weight, glycogen content, triacylglycerol storage, glycerol levels, and metabolic rate, respectively. Weighted gene co-expression analyses grouped transcripts associated with each trait in significant modules of co-expressed genes and we interpreted these modules in terms of their gene enrichment based on Gene Ontology analysis. Comparison of gene co-expression modules for traits in this study with previously determined modules for life-history traits identified significant modular pleiotropy between glycogen content, body weight, competitive

  9. Mechanisms affecting kinetic energies of laser-ablated materials

    SciTech Connect

    Chen, K.R. |; Leboeuf, J.N.; Wood, R.F.; Geohegan, D.B.; Donato, J.M.; Liu, C.L.; Puretzky, A.A.

    1995-12-31

    Laser materials processing techniques are expected to have a dramatic impact on materials science and engineering in the near future and beyond. One of the main laser materials processing techniques is Pulsed Laser Deposition (PLD) for thin film growth. While experimentalists search for optimal approaches for thin film growth with pulsed laser deposition (PLD), a systematic effort in theory and modeling of various processes during PLD is needed. The quality of film deposited depends critically on the range and profile of the kinetic energy and density of the ablated plume. While it is to the advantage of pulsed laser deposition to have high kinetic energy, plumes that are too energetic causes film damage. A dynamic source effect was found to accelerate the plume expansion velocity much higher than that from a conventional free expansion model. A self-similar theory and a hydrodynamic model are developed to study this effect, which may help to explain experimentally observed high front expansion velocity. Background gas can also affect the kinetic energies. High background gas may cause the ablated materials to go backward. Experimentally observed plume splitting is also discussed.

  10. Increasing serotonin concentrations alter calcium and energy metabolism in dairy cows.

    PubMed

    Laporta, Jimena; Moore, Spencer A E; Weaver, Samantha R; Cronick, Callyssa M; Olsen, Megan; Prichard, Austin P; Schnell, Brian P; Crenshaw, Thomas D; Peñagaricano, Francisco; Bruckmaier, Rupert M; Hernandez, Laura L

    2015-07-01

    A 4×4 Latin square design in which varied doses (0, 0.5, 1.0, and 1.5 mg/kg) of 5-hydroxy-l-tryptophan (5-HTP, a serotonin precursor) were intravenously infused into late-lactation, non-pregnant Holstein dairy cows was used to determine the effects of serotonin on calcium and energy metabolism. Infusion periods lasted 4 days, with a 5-day washout between periods. Cows were infused at a constant rate for 1 h each day. Blood was collected pre- and 5, 10, 30, 60, 90, and 120 min post-infusion, urine was collected pre- and post-infusion, and milk was collected daily. All of the 5-HTP doses increased systemic serotonin as compared to the 0 mg/kg dose, and the 1.0 and 1.5 mg/kg doses increased circulating glucose and non-esterified fatty acids (NEFA) and decreased beta-hydroxybutyrate (βHBA) concentrations. Treatment of cows with either 1.0 or 1.5 mg/kg 5-HTP doses decreased urine calcium elimination, and the 1.5 mg/kg dose increased milk calcium concentrations. No differences were detected in the heart rates, respiration rates, or body temperatures of the cows; however, manure scores and defecation frequency were affected. Indeed, cows that received 5-HTP defecated more, and the consistency of their manure was softer. Treatment of late-lactation dairy cows with 5-HTP improved energy metabolism, decreased loss of calcium into urine, and increased calcium secretion into milk. Further research should target the effects of increasing serotonin during the transition period to determine any benefits for post-parturient calcium and glucose metabolism. PMID:26099356

  11. Metabolic imprinting: critical impact of the perinatal environment on the regulation of energy homeostasis

    PubMed Central

    Levin, Barry E

    2006-01-01

    Epidemiological studies in humans suggest that maternal undernutrition, obesity and diabetes during gestation and lactation can all produce obesity in offspring. Animal models have allowed us to investigate the independent consequences of altering the pre- versus post-natal environments on a variety of metabolic, physiological and neuroendocrine functions as they effect the development in the offspring of obesity, diabetes, hypertension and hyperlipidemia (the ‘metabolic syndrome’). During gestation, maternal malnutrition, obesity, type 1 and type 2 diabetes and psychological, immunological and pharmacological stressors can all promote offspring obesity. Normal post-natal nutrition can reduce the adverse impact of some of these pre-natal factors but maternal high-fat diets, diabetes and increased neonatal access to food all enhance the development of obesity and the metabolic syndrome in offspring. The outcome of these perturbations of the perinatal environmental is also highly dependent upon the genetic background of the individual. Those with an obesity-prone genotype are more likely to be affected by factors such as maternal obesity and high-fat diets than are obesity-resistant individuals. Many perinatal manipulations appear to promote offspring obesity by permanently altering the development of central neural pathways, which regulate food intake, energy expenditure and storage. Given their strong neurotrophic properties, either excess or an absence of insulin and leptin during the perinatal period are likely to be effectors of these developmental changes. Because obesity is associated with an increased morbidity and mortality and because of its resistance to treatment, prevention is likely to be the best strategy for stemming the tide of the obesity epidemic. Such prevention should begin in the perinatal period with the identification and avoidance of factors which produce permanent, adverse alterations in neural pathways which control energy homeostasis

  12. Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children

    PubMed Central

    Dufault, Renee; Schnoll, Roseanne; Lukiw, Walter J; LeBlanc, Blaise; Cornett, Charles; Patrick, Lyn; Wallinga, David; Gilbert, Steven G; Crider, Raquel

    2009-01-01

    Among dietary factors, learning and behavior are influenced not only by nutrients, but also by exposure to toxic food contaminants such as mercury that can disrupt metabolic processes and alter neuronal plasticity. Neurons lacking in plasticity are a factor in neurodevelopmental disorders such as autism and mental retardation. Essential nutrients help maintain normal neuronal plasticity. Nutritional deficiencies, including deficiencies in the long chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, the amino acid methionine, and the trace minerals zinc and selenium, have been shown to influence neuronal function and produce defects in neuronal plasticity, as well as impact behavior in children with attention deficit hyperactivity disorder. Nutritional deficiencies and mercury exposure have been shown to alter neuronal function and increase oxidative stress among children with autism. These dietary factors may be directly related to the development of behavior disorders and learning disabilities. Mercury, either individually or in concert with other factors, may be harmful if ingested in above average amounts or by sensitive individuals. High fructose corn syrup has been shown to contain trace amounts of mercury as a result of some manufacturing processes, and its consumption can also lead to zinc loss. Consumption of certain artificial food color additives has also been shown to lead to zinc deficiency. Dietary zinc is essential for maintaining the metabolic processes required for mercury elimination. Since high fructose corn syrup and artificial food color additives are common ingredients in many foodstuffs, their consumption should be considered in those individuals with nutritional deficits such as zinc deficiency or who are allergic or sensitive to the effects of mercury or unable to effectively metabolize and eliminate it from the body. PMID:19860886

  13. Heat exposure of Cannabis sativa extracts affects the pharmacokinetic and metabolic profile in healthy male subjects.

    PubMed

    Eichler, Martin; Spinedi, Luca; Unfer-Grauwiler, Sandra; Bodmer, Michael; Surber, Christian; Luedi, Markus; Drewe, Juergen

    2012-05-01

    The most important psychoactive constituent of CANNABIS SATIVA L. is Δ (9)-tetrahydrocannabinol (THC). Cannabidiol (CBD), another important constituent, is able to modulate the distinct unwanted psychotropic effect of THC. In natural plant extracts of C. SATIVA, large amounts of THC and CBD appear in the form of THCA-A (THC-acid-A) and CBDA (cannabidiolic acid), which can be transformed to THC and CBD by heating. Previous reports of medicinal use of cannabis or cannabis preparations with higher CBD/THC ratios and use in its natural, unheated form have demonstrated that pharmacological effects were often accompanied with a lower rate of adverse effects. Therefore, in the present study, the pharmacokinetics and metabolic profiles of two different C. SATIVA extracts (heated and unheated) with a CBD/THC ratio > 1 were compared to synthetic THC (dronabinol) in a double-blind, randomized, single center, three-period cross-over study involving 9 healthy male volunteers. The pharmacokinetics of the cannabinoids was highly variable. The metabolic pattern was significantly different after administration of the different forms: the heated extract showed a lower median THC plasma AUC (24 h) than the unheated extract of 2.84 vs. 6.59 pmol h/mL, respectively. The later was slightly higher than that of dronabinol (4.58 pmol h/mL). On the other hand, the median sum of the metabolites (THC, 11-OH-THC, THC-COOH, CBN) plasma AUC (24 h) was higher for the heated than for the unheated extract. The median CBD plasma AUC (24 h) was almost 2-fold higher for the unheated than for the heated extract. These results indicate that use of unheated extracts may lead to a beneficial change in metabolic pattern and possibly better tolerability. PMID:22411724

  14. Preprandial ghrelin is not affected by macronutrient intake, energy intake or energy expenditure

    PubMed Central

    Paul, David R; Kramer, Matthew; Rhodes, Donna G; Rumpler, William V

    2005-01-01

    Background Ghrelin, a peptide secreted by endocrine cells in the gastrointestinal tract, is a hormone purported to have a significant effect on food intake and energy balance in humans. The influence of factors related to energy balance on ghrelin, such as daily energy expenditure, energy intake, and macronutrient intake, have not been reported. Secondly, the effect of ghrelin on food intake has not been quantified under free-living conditions over a prolonged period of time. To investigate these effects, 12 men were provided with an ad libitum cafeteria-style diet for 16 weeks. The macronutrient composition of the diets were covertly modified with drinks containing 2.1 MJ of predominantly carbohydrate (Hi-CHO), protein (Hi-PRO), or fat (Hi-FAT). Total energy expenditure was measured for seven days on two separate occasions (doubly labeled water and physical activity logs). Results Preprandial ghrelin concentrations were not affected by macronutrient intake, energy expenditure or energy intake (all P > 0.05). In turn, daily energy intake was significantly influenced by energy expenditure, but not ghrelin. Conclusion Preprandial ghrelin does not appear to be influenced by macronutrient composition, energy intake, or energy expenditure. Similarly, ghrelin does not appear to affect acute or chronic energy intake under free-living conditions. PMID:15745452

  15. 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

    2015-01-01

    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

  16. 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

  17. Legal and regulatory issues affecting compressed air energy storage

    SciTech Connect

    Hendrickson, P.L.

    1981-07-01

    Several regulatory and legal issues that can potentially affect implementation of a compressed air energy storage (CAES) system are discussed. This technology involves the compression of air using base load electric power for storage in an underground storage medium. The air is subsequently released and allowed to pass through a turbine to generate electricity during periods of peak demand. The storage media considered most feasible are a mined hard rock cavern, a solution-mined cavern in a salt deposit, and a porous geologic formation (normally an aquifer) of suitable structure. The issues are discussed in four categories: regulatory issues common to most CAES facilities regardless of storage medium, regulatory issues applicable to particular CAES reservoir media, issues related to possible liability from CAES operations, and issues related to acquisition of appropriate property rights for CAES implementation. The focus is on selected federal regulation. Lesser attention is given to state and local regulation. (WHK)

  18. Progress in drug development for Alzheimer's disease: An overview in relation to mitochondrial energy metabolism.

    PubMed

    Hroudová, Jana; Singh, Namrata; Fišar, Zdeněk; Ghosh, Kallol K

    2016-10-01

    Current possibilities of Alzheimer's disease (AD) treatment are very limited and are based on administration of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or N-methyl-d-aspartate receptor antagonist, memantine. Newly synthesized drugs affect multiple AD pathophysiological pathways and can act as inhibitors of cholinesterases (AChE, BuChE), inhibitors of monoamine oxidases (MAO-A, MAO-B), modulators of mitochondrial permeability transition pores, modulators of amyloid-beta binding alcohol dehydrogenase and antioxidants. Effects of clinically used as well as newly developed AD drugs were studied in relation to energy metabolism and mitochondrial functions, including oxidative phosphorylation, activities of enzymes of citric acid cycle or electron transfer system, mitochondrial membrane potential, calcium homeostasis, production of reactive oxygen species and MAO activity. PMID:27094132

  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. Can you boost your metabolism?

    MedlinePlus

    Resting metabolism rate (RMR); Total daily energy expenditure (TDEE); Non-exercise activity thermogenesis (NEAT); Weight loss - metabolism; Overweight - metabolism; Obesity - metabolism; Diet - metabolism

  1. Global proteomic analysis of protein acetylation affecting metabolic regulation in Daphnia pulex.

    PubMed

    Kwon, Oh Kwang; Sim, Juhee; Kim, Sun Ju; Oh, Hye Ryeung; Nam, Doo Hyun; Lee, Sangkyu

    2016-02-01

    Daphnia (Daphnia pulex) is a small planktonic crustacean and a key constituent of aquatic ecosystems. It is generally used as a model organism to study environmental toxic problems. In the past decade, genomic and proteomic datasets of Daphnia have been developed. The proteomic dataset allows for the investigation of toxicological effects in the context of "Daphnia proteomics," resulting in greater insights for toxicological research. To exploit Daphnia for ecotoxicological research, information on the post-translational modification (PTM) of proteins is necessary, as this is a critical regulator of biological processes. Acetylation of lysine (Kac) is a reversible and highly regulated PTM that is associated with diverse biological functions. However, a comprehensive description of Kac in Daphnia is not yet available. To understand the cellular distribution of lysine acetylation in Daphnia, we identified 98 acetylation sites in 65 proteins by immunoprecipitation using an anti-acetyllysine antibody and a liquid chromatography system supported by mass spectroscopy. We identified 28 acetylated sites related to metabolic proteins and six acetylated enzymes associated with the TCA cycle in Daphnia. From GO and KEGG enrichment analyses, we showed that Kac in D. pulex is highly enriched in proteins associated with metabolic processes. Our data provide the first global analysis of Kac in D. pulex and is an important resource for the functional analysis of Kac in this organism. PMID:26700148

  2. Lysine Malonylome May Affect the Central Metabolism and Erythromycin Biosynthesis Pathway in Saccharopolyspora erythraea.

    PubMed

    Xu, Jun-Yu; Xu, Zhen; Zhou, Ying; Ye, Bang-Ce

    2016-05-01

    Lysine acylation is a dynamic, reversible post-translational modification that can regulate cellular and organismal metabolism in bacteria. Acetylome has been studied well in bacteria. However, to our knowledge, there are no proteomic data on the lysine malonylation in prokaryotes, especially in actinomycetes, which are the major producers of therapeutic antibiotics. In our study, the first malonylome of the erythromycin-producing Saccharopolyspora erythraea was described by using a high-resolution mass spectrometry-based proteomics approach and high-affinity antimalonyllysine antibodies. We identified 192 malonylated sites on 132 substrates. Malonylated proteins are enriched in many biological processes such as protein synthesis, glycolysis and gluconeogenesis, the TCA cycle, and the feeder metabolic pathways of erythromycin synthesis according to GO analysis and KEGG pathway analysis. A total of 238 S/T/Y/H-phosphorylated sites on 158 proteins were also identified in our study, which aimed to explore the potential cross-talk between acylation and phosphorylation. After that, site-specific mutations showed that malonylation is a negative regulatory modification on the enzymatic activity of the acetyl-CoA synthetase (Acs) and glutamine synthetase (Gs). Furthermore, we compared the malonylation levels of the two-growth state to explore the potential effect of malonylation on the erythromycin biosynthesis. These findings expand our current knowledge of the actinomycetes malonylome and supplement the acylproteome databases of the whole bacteria. PMID:27090497

  3. Natural allelic variations of xenobiotic-metabolizing enzymes affect sexual dimorphism in Oryzias latipes

    PubMed Central

    Katsumura, Takafumi; Oda, Shoji; Nakagome, Shigeki; Hanihara, Tsunehiko; Kataoka, Hiroshi; Mitani, Hiroshi; Kawamura, Shoji; Oota, Hiroki

    2014-01-01

    Sexual dimorphisms, which are phenotypic differences between males and females, are driven by sexual selection. Interestingly, sexually selected traits show geographical variations within species despite strong directional selective pressures. This paradox has eluded many evolutionary biologists for some time, and several models have been proposed (e.g. ‘indicator model’ and ‘trade-off model’). However, disentangling which of these theories explains empirical patterns remains difficult, because genetic polymorphisms that cause variation in sexual differences are still unknown. In this study, we show that polymorphisms in cytochrome P450 (CYP) 1B1, which encodes a xenobiotic-metabolizing enzyme, are associated with geographical differences in sexual dimorphism in the anal fin morphology of medaka fish (Oryzias latipes). Biochemical assays and genetic cross experiments show that high- and low-activity CYP1B1 alleles enhanced and declined sex differences in anal fin shapes, respectively. Behavioural and phylogenetic analyses suggest maintenance of the high-activity allele by sexual selection, whereas the low-activity allele possibly has experienced positive selection due to by-product effects of CYP1B1 in inferred ancestral populations. The present data can elucidate evolutionary mechanisms behind genetic variations in sexual dimorphism and indicate trade-off interactions between two distinct mechanisms acting on the two alleles with pleiotropic effects of xenobiotic-metabolizing enzymes. PMID:25377463

  4. [How do transport and metabolism affect the biological effects of polycyclic aromatic hydrocarbons?].

    PubMed

    Bekki, Kanae; Toriba, Akira; Tang, Ning; Kameda, Takayuki; Takigami, Hidetaka; Suzuki, Go; Hayakawa, Kazuichi

    2012-01-01

    Polycyclic aromatic hydrocarbons (PAHs), some of which are carcinogenic/mutagenic, are generated by combustion of fossil fuels and also released through tanker or oilfield accident to cause a large scale environmental pollution. PAHs concentration in China is especially high in East Asia because of many kinds of generation sources such as coal heating systems, vehicles and factories without exhaust gas/particulate treatment systems. So, the atmospheric pollution caused by PAHs in China has been seriously concerned from the view point of health effects. Like yellow sand and sulfur oxide, PAHs exhausted in China are also transported to Japan. Additionally, strongly mutagenic nitrated PAHs (NPAHs), estrogenic/antiestrogenic PAH hydroxides (PAHOHs) and reactive oxygen species-producing PAH quinones (PAHQs) are formed from PAHs by the chemical reaction during the transport. Furthermore these PAHOHs and PAHQs are produced by the metabolism in animal body. In the biological activities caused by the above PAH derivatives, the structure-activity relationship was observed. In this review, our recent results on the generation of PAH derivatives by atmospheric transport and metabolism are reported. Also, the existing condition of PAHs as atmospheric pollutants is considered. PMID:22382837

  5. Paraoxonase-1 is not affected in polycystic ovary syndrome without metabolic syndrome and insulin resistance, but oxidative stress is altered.

    PubMed

    Torun, Ayse Nur; Vural, Mehmet; Cece, Hasan; Camuzcuoglu, Hakan; Toy, Harun; Aksoy, Nurten

    2011-12-01

    Paraoxonase-1 (PON1) activity is decreased in polycystic ovary syndrome (PCOS) having metabolic syndrome (MetS) or insulin resistance (IR). We aimed to assess PON1 activity and oxidative stress in PCOS without MetS or IR. Metabolic and hormonal parameters, high-sensitive C-reactive protein (hs-CRP), oxidative stress parameters (total antioxidant status (TAS), total oxidative stress (TOS), oxidative stress index (OSI), lipid hydroperoxide (LOOH), total free sulfhydryl (--SH) groups), PON and arylesterase were analyzed in 30 normal weighed patients with PCOS without MetS or IR and 20 normal controls. Hs-CRP, PON, arylesterase, and TAS levels of PCOS and control groups were similar. LOOH, TOS, and OSI of PCOS group were higher than in the controls (p < 0.05; p < 0.001, and p < 0.001, respectively). - SH group levels showed a positive correlation with free testosterone (fT). TOS positively correlated with free androgen index (FAI), body mass index (BMI), waist-to-hip ratio (WHR), LOOH, and OSI. This study showed that oxidative stress is increased in PCOS even in the absence of MetS or IR. PON1 activity appears not to be affected in PCOS without MetS and IR. Several metabolic and antropometric risk factors may aggravate this altered oxidative state in PCOS. PMID:21557696

  6. Synchrotron X-ray diffraction and scanning electron microscopy to understand enamel affected by metabolic disorder mucopolysaccharidosis.

    PubMed

    Khan, Malik Arshman; Addison, Owen; James, Alison; Hendriksz, Christian J; Al-Jawad, Maisoon

    2016-04-01

    Mucopolysaccharidosis (MPS) is an inherited metabolic disorder that can affect the tooth structure leading to defects. Synchrotron X-ray diffraction being a state of the art technique has been used to determine the enamel crystallite orientation in deciduous enamel affected by Mucopolysaccharidosis Type I and Mucopolysaccharidosis Type IVA and comparing these with that of healthy deciduous enamel. Using this technique it was observed that there is a loss of texture in deciduous enamel affected by Mucopolysaccharidosis Type I and Mucopolysaccharidosis Type IVA when compared to the healthy deciduous enamel. Generally it was observed that the incisal surface of the deciduous teeth possessed a higher texture or preferred orientation of enamel crystallites and on progression towards the cervical region there was a decrease in the texture or preferred orientation of enamel crystallites. Scanning electron microscopy showed that the presence of a poorly calcified layer between the enamel and dentine at the enamel-dentine junction (EDJ) in MPS affected samples was likely to be responsible for rendering the tooth structure weak and prone to fracture as is often the case in MPS affected deciduous enamel. PMID:26896739

  7. Estrogen-related receptor gamma modulates energy metabolism target genes in human trophoblast.

    PubMed

    Poidatz, D; Dos Santos, E; Brulé, A; De Mazancourt, P; Dieudonné, M N

    2012-09-01

    Placenta growth and functions depend on correct trophoblast migration, proliferation, and differentiation. The placenta has a critical role in gas and nutrient transport. To accomplish these numerous functions, the placenta depends on a highly efficient energy metabolism control. Recent studies showed that the orphan nuclear receptor Estrogen-Related Receptor gamma (ERRγ) is highly expressed in human placentas. As ERRγ has been described as a major energy metabolism regulator, we investigated ERRγ expression and putative roles on energy homeostasis in human trophoblast from first trimester placentas. First, we showed that ERRγ expression level increased during pregnancy and that ERRγ was more abundant in villous than in extravillous trophoblasts. We also observed that ERRγ expression increased during trophoblast differentiation. Second, we demonstrated that mitochondrial biogenesis and expression of some energy metabolism target genes decreased when ERRγ expression was impaired. Altogether, these results suggest that ERRγ could be implicated in the energy metabolism regulation of human trophoblasts. PMID:22763271

  8. 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

  9. Effect of carbon/nitrogen ratio on carbohydrate metabolism and light energy dissipation mechanisms in Arabidopsis thaliana.

    PubMed

    Huarancca Reyes, Thais; Scartazza, Andrea; Lu, Yu; Yamaguchi, Junji; Guglielminetti, Lorenzo

    2016-08-01

    Carbon (C) and nitrogen (N) nutrient sources are essential elements for metabolism, and their availability must be tightly coordinated for the optimal growth and development in plants. Plants are able to sense and respond to different C/N conditions via specific partitioning of C and N sources and the regulation of a complex cellular metabolic activity. We studied how the interaction between C and N signaling could affect carbohydrate metabolism, soluble sugar levels, photochemical efficiency of photosystem II (PSII) and the ability to drive the excess energy in Arabidopsis seedlings under moderated and disrupted C/N-nutrient conditions. Invertase and sucrose synthase activities were markedly affected by C/N-nutrient status depending on the phosphorylation status, suggesting that these enzymes may necessarily be modulated by their direct phosphorylation or phosphorylation of proteins that form complex with them in response to C/N stress. In addition, the enzymatic activity of these enzymes was also correlated with the amount of sugars, which not only act as substrate but also as signaling compounds. Analysis of chlorophyll fluorescence in plants under disrupted C/N condition suggested a reduction of electron transport rate at PSII level associated with a higher capacity for non-radiative energy dissipation in comparison with plants under moderated C/N condition. In conclusion, the tight coordination between C and N not only affects the carbohydrates metabolism and their concentration within plant tissues, but also the partitioning of the excitation energy at PSII level between radiative (electron transport) and non-radiative (heat) dissipation pathways. PMID:27108206

  10. Effects of Intracerebroventricular Administration of Neuropeptide Y on Metabolic Gene Expression and Energy Metabolism in Male Rats.

    PubMed

    Su, Yan; Foppen, Ewout; Fliers, Eric; Kalsbeek, Andries

    2016-08-01

    Neuropeptide Y (NPY) is an important neurotransmitter in the control of energy metabolism. Several studies have shown that obesity is associated with increased levels of NPY in the hypothalamus. We hypothesized that the central release of NPY has coordinated and integrated effects on energy metabolism in different tissues, resulting in increased energy storage and decreased energy expenditure (EE). We first investigated the acute effects of an intracerebroventricular (ICV) infusion of NPY on gene expression in liver, brown adipose tissue, soleus muscle, and sc and epididymal white adipose tissue (WAT). We found increased expression of genes involved in gluconeogenesis and triglyceride secretion in the liver already 2-hour after the start of the NPY administration. In brown adipose tissue, the expression of thermogenic genes was decreased. In sc WAT, the expression of genes involved in lipogenesis was increased, whereas in soleus muscle, the expression of lipolytic genes was decreased after ICV NPY. These findings indicate that the ICV infusion of NPY acutely and simultaneously increases lipogenesis and decreases lipolysis in different tissues. Subsequently, we investigated the acute effects of ICV NPY on locomotor activity, respiratory exchange ratio, EE, and body temperature. The ICV infusion of NPY increased locomotor activity, body temperature, and EE as well as respiratory exchange ratio. Together, these results show that an acutely increased central availability of NPY results in a shift of metabolism towards lipid storage and an increased use of carbohydrates, while at the same time increasing activity, EE, and body temperature. PMID:27267712

  11. 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.

  12. Starch Granule Re-Structuring by Starch Branching Enzyme and Glucan Water Dikinase Modulation Affects Caryopsis Physiology and Metabolism.

    PubMed

    Shaik, Shahnoor S; Obata, Toshihiro; Hebelstrup, Kim H; Schwahn, Kevin; Fernie, Alisdair R; Mateiu, Ramona V; Blennow, Andreas

    2016-01-01

    Starch is of fundamental importance for plant development and reproduction and its optimized molecular assembly is potentially necessary for correct starch metabolism. Re-structuring of starch granules in-planta can therefore potentially affect plant metabolism. Modulation of granule micro-structure was achieved by decreasing starch branching and increasing starch-bound phosphate content in the barley caryopsis starch by RNAi suppression of all three Starch Branching Enzyme (SBE) isoforms or overexpression of potato Glucan Water Dikinase (GWD). The resulting lines displayed Amylose-Only (AO) and Hyper-Phosphorylated (HP) starch chemotypes, respectively. We studied the influence of these alterations on primary metabolism, grain composition, starch structural features and starch granule morphology over caryopsis development at 10, 20 and 30 days after pollination (DAP) and at grain maturity. While HP showed relatively little effect, AO showed significant reduction in starch accumulation with re-direction to protein and β-glucan (BG) accumulation. Metabolite profiling indicated significantly higher sugar accumulation in AO, with re-partitioning of carbon to accumulate amino acids, and interestingly it also had high levels of some important stress-related metabolites and potentially protective metabolites, possibly to elude deleterious effects. Investigations on starch molecular structure revealed significant increase in starch phosphate and amylose content in HP and AO respectively with obvious differences in starch granule morphology at maturity. The results demonstrate that decreasing the storage starch branching resulted in metabolic adjustments and re-directions, tuning to evade deleterious effects on caryopsis physiology and plant performance while only little effect was evident by increasing starch-bound phosphate as a result of overexpressing GWD. PMID:26891365

  13. Low-Dose Aspartame Consumption Differentially Affects Gut Microbiota-Host Metabolic Interactions in the Diet-Induced Obese Rat

    PubMed Central

    Palmnäs, Marie S. A.; Cowan, Theresa E.; Bomhof, Marc R.; Su, Juliet; Reimer, Raylene A.; Vogel, Hans J.; Hittel, Dustin S.; Shearer, Jane

    2014-01-01

    Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose aspartame (A, 5–7 mg/kg/d in drinking water) treatments for 8 week (n = 10–12 animals/treatment). Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation. PMID:25313461

  14. Starch Granule Re-Structuring by Starch Branching Enzyme and Glucan Water Dikinase Modulation Affects Caryopsis Physiology and Metabolism

    PubMed Central

    Shaik, Shahnoor S.; Obata, Toshihiro; Hebelstrup, Kim H.; Schwahn, Kevin; Fernie, Alisdair R.; Mateiu, Ramona V.; Blennow, Andreas

    2016-01-01

    Starch is of fundamental importance for plant development and reproduction and its optimized molecular assembly is potentially necessary for correct starch metabolism. Re-structuring of starch granules in-planta can therefore potentially affect plant metabolism. Modulation of granule micro-structure was achieved by decreasing starch branching and increasing starch-bound phosphate content in the barley caryopsis starch by RNAi suppression of all three Starch Branching Enzyme (SBE) isoforms or overexpression of potato Glucan Water Dikinase (GWD). The resulting lines displayed Amylose-Only (AO) and Hyper-Phosphorylated (HP) starch chemotypes, respectively. We studied the influence of these alterations on primary metabolism, grain composition, starch structural features and starch granule morphology over caryopsis development at 10, 20 and 30 days after pollination (DAP) and at grain maturity. While HP showed relatively little effect, AO showed significant reduction in starch accumulation with re-direction to protein and β-glucan (BG) accumulation. Metabolite profiling indicated significantly higher sugar accumulation in AO, with re-partitioning of carbon to accumulate amino acids, and interestingly it also had high levels of some important stress-related metabolites and potentially protective metabolites, possibly to elude deleterious effects. Investigations on starch molecular structure revealed significant increase in starch phosphate and amylose content in HP and AO respectively with obvious differences in starch granule morphology at maturity. The results demonstrate that decreasing the storage starch branching resulted in metabolic adjustments and re-directions, tuning to evade deleterious effects on caryopsis physiology and plant performance while only little effect was evident by increasing starch-bound phosphate as a result of overexpressing GWD. PMID:26891365

  15. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat.

    PubMed

    Palmnäs, Marie S A; Cowan, Theresa E; Bomhof, Marc R; Su, Juliet; Reimer, Raylene A; Vogel, Hans J; Hittel, Dustin S; Shearer, Jane

    2014-01-01

    Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose aspartame (A, 5-7 mg/kg/d in drinking water) treatments for 8 week (n = 10-12 animals/treatment). Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation. PMID:25313461

  16. 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…

  17. Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse

    PubMed Central

    Pellegrino, Rosa Maria; Boda, Enrica; Montarolo, Francesca; Boero, Martina; Mezzanotte, Mariarosa; Saglio, Giuseppe; Buffo, Annalisa; Roetto, Antonella

    2016-01-01

    The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response. Moreover, Tfr2-KO mice presented a selective overactivation of neurons in the limbic circuit and the emergence of an anxious-like behaviour. Furthermore, microglial cells showed a particular sensitivity to iron perturbation. We conclude that Tfr2 is a key regulator of brain iron homeostasis and propose a role for Tfr2 alpha in the regulation of anxiety circuits. PMID:27477597

  18. Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse.

    PubMed

    Pellegrino, Rosa Maria; Boda, Enrica; Montarolo, Francesca; Boero, Martina; Mezzanotte, Mariarosa; Saglio, Giuseppe; Buffo, Annalisa; Roetto, Antonella

    2016-01-01

    The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response. Moreover, Tfr2-KO mice presented a selective overactivation of neurons in the limbic circuit and the emergence of an anxious-like behaviour. Furthermore, microglial cells showed a particular sensitivity to iron perturbation. We conclude that Tfr2 is a key regulator of brain iron homeostasis and propose a role for Tfr2 alpha in the regulation of anxiety circuits. PMID:27477597

  19. Smoking and polymorphisms in xenobiotic metabolism and DNA repair genes are additive risk factors affecting bladder cancer in Northern Tunisia.

    PubMed

    Rouissi, Kamel; Ouerhani, Slah; Hamrita, Bechr; Bougatef, Karim; Marrakchi, Raja; Cherif, Mohamed; Ben Slama, Mohamed Riadh; Bouzouita, Mohamed; Chebil, Mohamed; Ben Ammar Elgaaied, Amel

    2011-12-01

    Cancer epidemiology has undergone marked development since the nineteen-fifties. One of the most spectacular and specific contributions was the demonstration of the massive effect of smoking and genetic polymorphisms on the occurrence of bladder cancer. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). DNA repair is essential to an individual's ability to respond to damage caused by tobacco carcinogens. Alterations in DNA repair genes may affect cancer risk by influencing individual susceptibility to this environmental exposure. Polymorphisms in NAT2, GST and DNA repair genes alter the ability of these enzymes to metabolize carcinogens or to repair alterations caused by this process. We have conducted a case-control study to assess the role of smoking, slow NAT2 variants, GSTM1 and GSTT1 null, and XPC, XPD, XPG nucleotide excision-repair (NER) genotypes in bladder cancer development in North Tunisia. Taken alone, each gene unless NAT2 did not appear to be a factor affecting bladder cancer susceptibility. For the NAT2 slow acetylator genotypes, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk to develop bladder cancer (OR = 7.14; 95% CI: 1.30-51.41). However, in tobacco consumers, we have shown that Null GSTM1, Wild GSTT1, Slow NAT2, XPC (CC) and XPG (CC) are genetic risk factors for the disease. When combined together in susceptible individuals compared to protected individuals these risk factors give an elevated OR (OR = 61). So, we have shown a strong cumulative effect of tobacco and different combinations of studied genetic risk factors which lead to a great susceptibility to bladder cancer. PMID:21647780

  20. [Carbon source metabolic diversity of soil microbial community under different climate types in the area affected by Wenchuan earthquake].

    PubMed

    Zhang, Guang-Shuai; Lin, Yong-Ming; Ma, Rui-Feng; Deng, Hao-Jun; Du, Kun; Wu, Cheng-Zhen; Hong, Wei

    2015-02-01

    The MS8.0 Wenchuan earthquake in 2008 led to huge damage to land covers in northwest Sichuan, one of the critical fragile eco-regions in China which can be divided into Semi-arid dry hot climate zone (SDHC) and Subtropical humid monsoon climate zone (SHMC). Using the method of Bilog-ECO-microplate technique, this paper aimed to determine the functional diversity of soil microbial community in the earthquake-affected areas which can be divided into undamaged area (U), recover area (R) and damaged area without recovery (D) under different climate types, in order to provide scientific basis for ecological recovery. The results indicated that the average-well-color-development (AWCD) in undamaged area and recovery area showed SDHC > SHMC, which was contrary to the AWCD in the damaged area without recovery. The AWCD of damaged area without recovery was the lowest in both climate zones. The number of carbon source utilization types of soil microbial in SHMC zone was significantly higher than that in SDHC zone. The carbon source utilization types in both climate zones presented a trend of recover area > undamaged area > damaged area without recovery. The carbon source metabolic diversity characteristic of soil microbial community was significantly different in different climate zones. The diversity index and evenness index both showed a ranking of undamaged area > recover area > damaged area without recovery. In addition, the recovery area had the highest richness index. The soil microbial carbon sources metabolism characteristic was affected by soil nutrient, aboveground vegetation biomass and vegetation coverage to some extent. In conclusion, earthquake and its secondary disasters influenced the carbon source metabolic diversity characteristic of soil microbial community mainly through the change of aboveground vegetation and soil environmental factors. PMID:26031097

  1. Can N-acetyl-L-cysteine affect zinc metabolism when used as a paracetamol antidote?

    PubMed

    Brumas, V; Hacht, B; Filella, M; Berthon, G

    1992-07-01

    N-Acetyl-L-cysteine (NAC) has long been used in the treatment of chronic lung diseases. Inhalation and oral administration of the drug are both effective in reducing mucus viscosity. In addition, NAC oral therapy allows to restore normal mucoprotein secretion in the long term. Although displaying heavy metal-complexing potential, NAC exerts no detectable influence on the metabolism of essential trace metals when used in the above context (i.e. at doses near 600 mg day-1). However, this may no longer be the case when NAC is used as an oxygen radical scavenger, like in the treatment of paracetamol poisoning. In the latter case, intravenous doses as high as 20 g day-1 are administered, which may induce excessive zinc urinary excretion. In order to allow a better appreciation of the risk of zinc depletion during NAC therapy, the present work addresses the role of this drug towards zinc metabolism at the molecular level. First, formation constants for zinc-NAC complexes have been determined under physiological conditions. Then, computer simulations for blood plasma and gastrointestinal fluid have been run to assess the influence of NAC and its metabolites (e.g. cysteine and glutathione) on zinc excretion and absorption. Blood plasma simulations reveal that NAC can effectively mobilise an important fraction of zinc into urinary excretable complexes as from concentrations of 10(-3) mol dm-3 (which corresponds to a dose of about 800 mg). This effect can still be enhanced by the action of NAC metabolites, among which cysteine is the most powerful zinc sequestering agent. In contrast, simulations relative to gastrointestinal conditions suggest that NAC should tend to increase zinc absorption, regardless of its dose. PMID:1529808

  2. Cocoa and Whey Protein Differentially Affect Markers of Lipid and Glucose Metabolism and Satiety.

    PubMed

    Campbell, Caroline L; Foegeding, E Allen; Harris, G Keith

    2016-03-01

    Food formulation with bioactive ingredients is a potential strategy to promote satiety and weight management. Whey proteins are high in leucine and are shown to decrease hunger ratings and increase satiety hormone levels; cocoa polyphenolics moderate glucose levels and slow digestion. This study examined the effects of cocoa and whey proteins on lipid and glucose metabolism and satiety in vitro and in a clinical trial. In vitro, 3T3-L1 preadipocytes were treated with 0.5-100 μg/mL cocoa polyphenolic extract (CPE) and/or 1-15 mM leucine (Leu) and assayed for lipid accumulation and leptin production. In vivo, a 6-week clinical trial consisted of nine panelists (age: 22.6 ± 1.7; BMI: 22.3 ± 2.1) consuming chocolate-protein beverages once per week, including placebo, whey protein isolate (WPI), low polyphenolic cocoa (LP), high polyphenolic cocoa (HP), LP-WPI, and HP-WPI. Measurements included blood glucose and adiponectin levels, and hunger ratings at baseline and 0.5-4.0 h following beverage consumption. At levels of 50 and 100 μg/mL, CPE significantly inhibited preadipocyte lipid accumulation by 35% and 50%, respectively, and by 22% and 36% when combined with 15 mM Leu. Leu treatment increased adipocyte leptin production by 26-37%. In the clinical trial, all beverages significantly moderated blood glucose levels 30 min postconsumption. WPI beverages elicited lowest peak glucose levels and HP levels were significantly lower than LP. The WPI and HP beverage treatments significantly increased adiponectin levels, but elicited no significant changes in hunger ratings. These trends suggest that combinations of WPI and cocoa polyphenols may improve markers of metabolic syndrome and satiety. PMID:26987021

  3. Overexpression of Arabidopsis Ceramide Synthases Differentially Affects Growth, Sphingolipid Metabolism, Programmed Cell Death, and Mycotoxin Resistance.

    PubMed

    Luttgeharm, Kyle D; Chen, Ming; Mehra, Amit; Cahoon, Rebecca E; Markham, Jonathan E; Cahoon, Edgar B

    2015-10-01

    Ceramide synthases catalyze an N-acyltransferase reaction using fatty acyl-coenzyme A (CoA) and long-chain base (LCB) substrates to form the sphingolipid ceramide backbone and are targets for inhibition by the mycotoxin fumonisin B1 (FB1). Arabidopsis (Arabidopsis thaliana) contains three genes encoding ceramide synthases with distinct substrate specificities: LONGEVITY ASSURANCE GENE ONE HOMOLOG1 (LOH1; At3g25540)- and LOH3 (At1g19260)-encoded ceramide synthases use very-long-chain fatty acyl-CoA and trihydroxy LCB substrates, and LOH2 (At3g19260)-encoded ceramide synthase uses palmitoyl-CoA and dihydroxy LCB substrates. In this study, complementary DNAs for each gene were overexpressed to determine the role of individual isoforms in physiology and sphingolipid metabolism. Differences were observed in growth resulting from LOH1 and LOH3 overexpression compared with LOH2 overexpression. LOH1- and LOH3-overexpressing plants had enhanced biomass relative to wild-type plants, due in part to increased cell division, suggesting that enhanced synthesis of very-long-chain fatty acid/trihydroxy LCB ceramides promotes cell division and growth. Conversely, LOH2 overexpression resulted in dwarfing. LOH2 overexpression also resulted in the accumulation of sphingolipids with C16 fatty acid/dihydroxy LCB ceramides, constitutive induction of programmed cell death, and accumulation of salicylic acid, closely mimicking phenotypes observed previously in LCB C-4 hydroxylase mutants defective in trihydroxy LCB synthesis. In addition, LOH2- and LOH3-overexpressing plants acquired increased resistance to FB1, whereas LOH1-overexpressing plants showed no increase in FB1 resistance, compared with wild-type plants, indicating that LOH1 ceramide synthase is most strongly inhibited by FB1. Overall, the findings described here demonstrate that overexpression of Arabidopsis ceramide synthases results in strongly divergent physiological and metabolic phenotypes, some of which have significance

  4. Fluoxetine Treatment Rescues Energy Metabolism Pathway Alterations in a Posttraumatic Stress Disorder Mouse Model.

    PubMed

    Kao, Chi-Ya; He, Zhisong; Henes, Kathrin; Asara, John M; Webhofer, Christian; Filiou, Michaela D; Khaitovich, Philipp; Wotjak, Carsten T; Turck, Christoph W

    2016-05-01

    Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder. Several studies have attempted to characterize molecular alterations associated with PTSD, but most findings were limited to the investigation of specific cellular markers in the periphery or defined brain regions. In the current study, we aimed to unravel affected molecular pathways/mechanisms in the fear circuitry associated with PTSD. We interrogated a foot shock-induced PTSD mouse model by integrating proteomics and metabolomics profiling data. Alterations at the proteome level were analyzed using in vivo (15)N metabolic labeling combined with mass spectrometry in the prelimbic cortex (PrL), anterior cingulate cortex (ACC), basolateral amygdala, central nucleus of the amygdala and CA1 of the hippocampus between shocked and nonshocked (control) mice, with and without fluoxetine treatment. In silico pathway analyses revealed an upregulation of the citric acid cycle pathway in PrL, and downregulation in ACC and nucleus accumbens (NAc). Chronic fluoxetine treatment prevented decreased citric acid cycle activity in NAc and ACC and ameliorated conditioned fear response in shocked mice. Our results shed light on the role of energy metabolism in PTSD pathogenesis and suggest potential therapy through mitochondrial targeting. PMID:27606320

  5. Basking hamsters reduce resting metabolism, body temperature and energy costs during rewarming from torpor.

    PubMed

    Geiser, Fritz; Gasch, Kristina; Bieber, Claudia; Stalder, Gabrielle L; Gerritsmann, Hanno; Ruf, Thomas

    2016-07-15

    Basking can substantially reduce thermoregulatory energy expenditure of mammals. We tested the hypothesis that the largely white winter fur of hamsters (Phodopus sungorus), originating from Asian steppes, may be related to camouflage to permit sun basking on or near snow. Winter-acclimated hamsters in our study were largely white and had a high proclivity to bask when resting and torpid. Resting hamsters reduced metabolic rate (MR) significantly (>30%) when basking at ambient temperatures (Ta) of ∼15 and 0°C. Interestingly, body temperature (Tb) also was significantly reduced from 34.7±0.6°C (Ta 15°C, not basking) to 30.4±2.0°C (Ta 0°C, basking), which resulted in an extremely low (<50% of predicted) apparent thermal conductance. Induced torpor (food withheld) during respirometry at Ta 15°C occurred on 83.3±36.0% of days and the minimum torpor MR was 36% of basal MR at an average Tb of 22.0±2.6°C; movement to the basking lamp occurred at Tb<20.0°C. Energy expenditure for rewarming was significantly reduced (by >50%) during radiant heat-assisted rewarming; however, radiant heat per se without an endogenous contribution by animals did not strongly affect metabolism and Tb during torpor. Our data show that basking substantially modifies thermal energetics in hamsters, with a drop of resting Tb and MR not previously observed and a reduction of rewarming costs. The energy savings afforded by basking in hamsters suggest that this behaviour is of energetic significance not only for mammals living in deserts, where basking is common, but also for P. sungorus and probably other cold-climate mammals. PMID:27207637

  6. 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

  7. Transcriptional Factors Mediating Retinoic Acid Signals in the Control of Energy Metabolism.

    PubMed

    Zhang, Rui; Wang, Yueqiao; Li, Rui; Chen, Guoxun

    2015-01-01

    Retinoic acid (RA), an active metabolite of vitamin A (VA), is important for many physiological processes including energy metabolism. This is mainly achieved through RA-regulated gene expression in metabolically active cells. RA regulates gene expression mainly through the activation of two subfamilies in the nuclear receptor superfamily, retinoic acid receptors (RARs) and retinoid X receptors (RXRs). RAR/RXR heterodimers or RXR/RXR homodimers bind to RA response element in the promoters of RA target genes and regulate their expressions upon ligand binding. The development of metabolic diseases such as obesity and type 2 diabetes is often associated with profound changes in the expressions of genes involved in glucose and lipid metabolism in metabolically active cells. RA regulates some of these gene expressions. Recently, in vivo and in vitro studies have demonstrated that status and metabolism of VA regulate macronutrient metabolism. Some studies have shown that, in addition to RARs and RXRs, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter-transcription factor II, and peroxisome proliferator activated receptor β/δ may function as transcriptional factors mediating RA response. Herein, we summarize current progresses regarding the VA metabolism and the role of nuclear receptors in mediating RA signals, with an emphasis on their implication in energy metabolism. PMID:26110391

  8. Transcriptional Factors Mediating Retinoic Acid Signals in the Control of Energy Metabolism

    PubMed Central

    Zhang, Rui; Wang, Yueqiao; Li, Rui; Chen, Guoxun

    2015-01-01

    Retinoic acid (RA), an active metabolite of vitamin A (VA), is important for many physiological processes including energy metabolism. This is mainly achieved through RA-regulated gene expression in metabolically active cells. RA regulates gene expression mainly through the activation of two subfamilies in the nuclear receptor superfamily, retinoic acid receptors (RARs) and retinoid X receptors (RXRs). RAR/RXR heterodimers or RXR/RXR homodimers bind to RA response element in the promoters of RA target genes and regulate their expressions upon ligand binding. The development of metabolic diseases such as obesity and type 2 diabetes is often associated with profound changes in the expressions of genes involved in glucose and lipid metabolism in metabolically active cells. RA regulates some of these gene expressions. Recently, in vivo and in vitro studies have demonstrated that status and metabolism of VA regulate macronutrient metabolism. Some studies have shown that, in addition to RARs and RXRs, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter-transcription factor II, and peroxisome proliferator activated receptor β/δ may function as transcriptional factors mediating RA response. Herein, we summarize current progresses regarding the VA metabolism and the role of nuclear receptors in mediating RA signals, with an emphasis on their implication in energy metabolism. PMID:26110391

  9. 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 ...

  10. 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 ...

  11. Metabolism

    MedlinePlus

    ... convert or use energy, such as: Breathing Circulating blood Controlling body temperature Contracting muscles Digesting food and nutrients Eliminating waste through urine and feces Functioning of the brain and nerves

  12. Swimming improves high-fat induced insulin resistance by regulating lipid and energy metabolism and the insulin pathway in rats.

    PubMed

    Song, An; Wang, Chao; Ren, Luping; Zhao, Jiajun

    2014-06-01

    muscle, energy metabolism in skeletal muscle and insulin signaling transduction were all markedly upregulated. In conclusion, swimming can effectively improve insulin sensitivity and even prevent insulin resistance by affecting the expression of proteins related to lipid metabolism, energy metabolism and insulin signaling transduction in rats fed a high-fat diet. PMID:24715199

  13. 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

  14. 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

  15. Dasatinib improves insulin sensitivity and affects lipid metabolism in a patient with chronic myeloid leukaemia.

    PubMed

    Iizuka, Katsumi; Niwa, Hiroyuki; Kato, Takehiro; Takeda, Jun

    2016-01-01

    A 65-year-old woman had been visiting our department for the treatment of type-2 diabetes mellitus since December 2012. Her glycated haemoglobin levels were well controlled (≈5.8% (40 mmol/mol)) by metformin (500 mg). In July 2014, her white cell count increased suddenly to 33 530 cells/μL and she was diagnosed with Ph+ chronic myeloid leukaemia. She was started on dasatinib (100 mg), which immediately normalised plasma levels of WCC. Dasatinib improved the glycaemic index to <6.0% and also improved plasma levels of triglycerides (TGs) and high-density lipoprotein-cholesterol (HDL-c). Levels of low-density lipoprotein-cholesterol were increased but remained within the normal range. The TG:HDL-c ratio and Quantitative Insulin Sensitivity Check Index rapidly improved. Followed by an improvement in insulin sensitivity, plasma levels of adiponectin and leptin were increased. This case study suggests that dasatinib might have positive as well as negative effects on the metabolism of glucose and lipids. PMID:26873919

  16. Methyl jasmonate affects phenolic metabolism and gene expression in blueberry (Vaccinium corymbosum).

    PubMed

    Cocetta, Giacomo; Rossoni, Mara; Gardana, Claudio; Mignani, Ilaria; Ferrante, Antonio; Spinardi, Anna

    2015-02-01

    Blueberry (Vaccinium corymbosum) is a fruit very much appreciated by consumers for its antioxidant potential and health-promoting traits. Its beneficial potential properties are mainly due to a high content of anthocyanins and their amount can change after elicitation with methyl jasmonate. The aim of this work is to evaluate the changes in expression of several genes, accumulation of phenolic compounds and alterations in antioxidant potential in two different blueberry cultivars ('Duke' and 'Blueray') in response to methyl jasmonate (0.1 mM). Results showed that 9 h after treatment, the expression of phenylalanine ammonium lyase, chalcone synthase and anthocyanidin synthase genes was stimulated more in the 'Blueray' variety. Among the phenols measured an increase was recorded also for epicatechin and anthocyanin concentrations. 'Duke' is a richer sourche of anthocyanins compared to 'Blueray', treatment with methyl jasmonate promoted in 'Blueray' an increase in pigments as well as in the antioxidant potential, especially in fully ripe berries, but treated 'Duke' berries had greater levels, which were not induced by methyl jasmonate treatment. In conclusion, methyl jasmonate was, in some cases, an effective elicitor of phenolic metabolism and gene expression in blueberry, though with different intensity between cultivars. PMID:24943920

  17. Early life stress affects cerebral glucose metabolism in adult rhesus monkeys (Macaca mulatta).

    PubMed

    Parr, Lisa A; Boudreau, Matthew; Hecht, Erin; Winslow, James T; Nemeroff, Charles B; Sánchez, Mar M

    2012-01-01

    Early life stress (ELS) is a risk factor for anxiety, mood disorders and alterations in stress responses. Less is known about the long-term neurobiological impact of ELS. We used [(18)F]-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) to assess neural responses to a moderate stress test in adult monkeys that experienced ELS as infants. Both groups of monkeys showed hypothalamic-pituitary-adrenal (HPA) axis stress-induced activations and cardiac arousal in response to the stressor. A whole brain analysis detected significantly greater regional cerebral glucose metabolism (rCGM) in superior temporal sulcus, putamen, thalamus, and inferotemporal cortex of ELS animals compared to controls. Region of interest (ROI) analyses performed in areas identified as vulnerable to ELS showed greater activity in the orbitofrontal cortex of ELS compared to control monkeys, but greater hippocampal activity in the control compared to ELS monkeys. Together, these results suggest hyperactivity in emotional and sensory processing regions of adult monkeys with ELS, and greater activity in stress-regulatory areas in the controls. Despite these neural responses, no group differences were detected in neuroendocrine, autonomic or behavioral responses, except for a trend towards increased stillness in the ELS monkeys. Together, these data suggest hypervigilance in the ELS monkeys in the absence of immediate danger. PMID:22682736

  18. A common telomeric gene silencing assay is affected by nucleotide metabolism

    PubMed Central

    Rossmann, Marlies P.; Luo, Weijun; Tsaponina, Olga; Chabes, Andrei; Stillman, Bruce

    2011-01-01

    Telomere-associated position effect variegation (TPEV) in budding yeast has been used as a model for understanding epigenetic inheritance and gene silencing. A widely used assay to identify mutants with improper TPEV employs the URA3 gene at the telomere of chromosome VII-L that can be counter-selected with 5-fluoroorotic acid (5-FOA). 5-FOA resistance has been inferred to represent lack of transcription of URA3 and therefore to represent heterochromatin-induced gene silencing. For two genes implicated in telomere silencing, POL30 and DOT1, we show that the URA3 telomere reporter assay does not reflect their role in heterochromatin formation. Rather, an imbalance in ribonucleotide reductase (RNR), which is induced by 5-FOA, and the specific promoter of URA3 fused to ADH4 at telomere VII-L are jointly responsible for the variegated phenotype. We conclude that metabolic changes caused by the drug employed and certain mutants being studied are incompatible with the use of certain prototrophic markers for TPEV. PMID:21474074

  19. [Metabolic Syndrome and Bipolar Affective Disorder: A Review of the Literature].

    PubMed

    Jaramillo, Carlos López; Mejía, Adelaida Castaño; Velásquez, Alicia Henao; Restrepo Palacio, Tomás Felipe; Zuluaga, Julieta Osorio

    2013-09-01

    Bipolar disorder (BD) is a chronic psychiatric disorder that is found within the first ten causes of disability and premature mortality. The metabolic syndrome (MS) is a group of risk factors (RF) that predispose to cardiovascular disease (CV), diabetes and early mortality. Both diseases generate high costs to the health system. Major studies have shown that MS has a higher prevalence in patients with mental disorders compared to the general population. The incidence of MS in BD is multifactorial, and due to iatrogenic, genetic, economic, psychological, and behavioral causes related to the health system. The most common RF found is these patients was an increased abdominal circumference, and it was found that the risk of suffering this disease was greater in women and Hispanic patients. As regards the increase in RF to develop a CV in patients with BD, there have been several explanations based on the risky behavior of patients with mental illness, included tobacco abuse, physical inactivity and high calorie diets. An additional explanation described in literature is the view of BD as a multisystemic inflammatory illness, supported by the explanation that inflammation is a crucial element in atherosclerosis, endothelial dysfunction, platelet rupture, and thrombosis. The pathophysiology of MS and BD include factors such as adrenal, thyroid and sympathetic nervous system dysfunction, as well as poor lifestyle and medication common in these patients. This article attempts to give the reader an overall view of the information published in literature to date, as regards the association between BD and MS. PMID:26572949

  20. Deciphering the roles of the constitutive androstane receptor in energy metabolism

    PubMed Central

    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. 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

  2. Combination of inositol and alpha lipoic acid in metabolic syndrome-affected women: a randomized placebo-controlled trial

    PubMed Central

    2013-01-01

    Background Inositol has been reported to improve insulin sensitivity since it works as a second messenger achieving insulin-like effects on metabolic enzymes. The aim of this study was to evaluate the inositol and alpha lipoic acid combination effectiveness on metabolic syndrome features in postmenopausal women at risk of breast cancer. Methods A six-month prospective, randomized placebo-controlled trial was carried out on a total of 155 postmenopausal women affected by metabolic syndrome at risk of breast cancer, the INOSIDEX trial. All women were asked to follow a low-calorie diet and were assigned randomly to daily consumption of a combination of inositol and alpha lipoic acid (77 pts) or placebo (78 pts) for six months. Primary outcomes we wanted to achieve were both reduction of more than 20% of the HOMA-IR index and of triglycerides serum levels. Secondary outcomes expected were both the improvement of high-density lipoprotein cholesterol levels and the reduction of anthropometric features such as body mass index and waist-hip ratio. Results A significant HOMA-IR reduction of more than 20% was evidenced in 66.7% (P <0.0001) of patients, associated with a serum insulin level decrease in 89.3% (P <0.0000). A decrease in triglycerides was evidenced in 43.2% of patients consuming the supplement (P <0.0001). An increase in HDL cholesterol (48.6%) was found in the group consuming inositol with respect to the placebo group. A reduction in waist circumference and waist-hip ratio was found in the treated group with respect to the placebo group. Conclusions Inositol combined with alpha lipoic acid can be used as a dietary supplement in insulin-resistant patients in order to increase their insulin sensitiveness. Daily consumption of inositol combined with alpha lipoic acid has a significant bearing on metabolic syndrome. As metabolic syndrome is considered a modifiable risk factor of breast tumorigenesis, further studies are required to assess whether inositol combined

  3. Isolation of a Genomic Region Affecting Most Components of Metabolic Syndrome in a Chromosome-16 Congenic Rat Model

    PubMed Central

    Šedová, Lucie; Pravenec, Michal; Křenová, Drahomíra; Kazdová, Ludmila; Zídek, Václav; Krupková, Michaela; Liška, František; Křen, Vladimír; Šeda, Ondřej

    2016-01-01

    Metabolic syndrome is a highly prevalent human disease with substantial genomic and environmental components. Previous studies indicate the presence of significant genetic determinants of several features of metabolic syndrome on rat chromosome 16 (RNO16) and the syntenic regions of human genome. We derived the SHR.BN16 congenic strain by introgression of a limited RNO16 region from the Brown Norway congenic strain (BN-Lx) into the genomic background of the spontaneously hypertensive rat (SHR) strain. We compared the morphometric, metabolic, and hemodynamic profiles of adult male SHR and SHR.BN16 rats. We also compared in silico the DNA sequences for the differential segment in the BN-Lx and SHR parental strains. SHR.BN16 congenic rats had significantly lower weight, decreased concentrations of total triglycerides and cholesterol, and improved glucose tolerance compared with SHR rats. The concentrations of insulin, free fatty acids, and adiponectin were comparable between the two strains. SHR.BN16 rats had significantly lower systolic (18–28 mmHg difference) and diastolic (10–15 mmHg difference) blood pressure throughout the experiment (repeated-measures ANOVA, P < 0.001). The differential segment spans approximately 22 Mb of the telomeric part of the short arm of RNO16. The in silico analyses revealed over 1200 DNA variants between the BN-Lx and SHR genomes in the SHR.BN16 differential segment, 44 of which lead to missense mutations, and only eight of which (in Asb14, Il17rd, Itih1, Syt15, Ercc6, RGD1564958, Tmem161a, and Gatad2a genes) are predicted to be damaging to the protein product. Furthermore, a number of genes within the RNO16 differential segment associated with metabolic syndrome components in human studies showed polymorphisms between SHR and BN-Lx (including Lpl, Nrg3, Pbx4, Cilp2, and Stab1). Our novel congenic rat model demonstrates that a limited genomic region on RNO16 in the SHR significantly affects many of the features of metabolic syndrome

  4. Understanding metabolic alterations in space flight using quantitative models: fluid and energy balance

    NASA Technical Reports Server (NTRS)

    Leonard, J. I.

    1986-01-01

    This report summarizes many of the results obtained during the Skylab program, on metabolic changes during weightlessness. The examination of the data was conducted following an integrated multi-disciplinary and multi-experimental approach. Emphasis is given on several major aspects of metabolic adaptation to space flight: fluid-electrolyte regulation, mechanisms of hormone disturbances, energy balance and etiology of weight loss. The aim is to obtain a composite picture of the fluid, electrolyte and energy response to weightlessness.

  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. Molybdate:sulfate ratio affects redox metabolism and viability of the dinoflagellate Lingulodinium polyedrum.

    PubMed

    Barros, M P; Hollnagel, H C; Glavina, A B; Soares, C O; Ganini, D; Dagenais-Bellefeuille, S; Morse, D; Colepicolo, P

    2013-10-15

    Molybdenum is a transition metal used primarily (90% or more) as an additive to steel and corrosion-resistant alloys in metallurgical industries and its release into the environment is a growing problem. As a catalytic center of some redox enzymes, molybdenum is an essential element for inorganic nitrogen assimilation/fixation, phytohormone synthesis, and free radical metabolism in photosynthesizing species. In oceanic and estuarine waters, microalgae absorb molybdenum as the water-soluble molybdate anion (MoO4(2-)), although MoO4(2-) uptake is thought to compete with uptake of the much more abundant sulfate anion (SO4(2-), approximately 25 mM in seawater). Thus, those aspects of microalgal biology impacted by molybdenum would be better explained by considering both MoO4(2-) and SO4(2-) concentrations in the aquatic milieu. This work examines toxicological, physiological and redox imbalances in the dinoflagellate Lingulodinium polyedrum that have been induced by changes in the molybdate:sulfate ratios. We prepared cultures of Lingulodinium polyedrum grown in artificial seawater containing eight different MoO4(2-) concentrations (from 0 to 200 μM) and three different SO4(2-) concentrations (3.5 mM, 9.6 mM and 25 mM). We measured sulfur content in cells, the activities of the three major antioxidant enzymes (superoxide dismutase, catalase, and ascorbate peroxidase), indexes of oxidative modifications in proteins (carbonyl content) and lipids (thiobarbituric acid-reactive substances, TBARS), the activities of the molybdenum-dependent enzymes xanthine oxidase and nitrate reductase, expression of key protein components of dinoflagellate photosynthesis (peridinin-chlorophyll a protein and ribulose-1,5-biphosphate carboxylase/oxidase) and growth curves. We find evidence for Mo toxicity at relatively high [MoO4(2-)]:[SO4(2-)] ratios. We also find evidence for extensive redox adaptations at Mo levels well below lethal levels. PMID:24036534

  7. Ecdysteroids affect in vivo protein metabolism of the flight muscle of the tobacco hornworm (Manduca sexta)

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.; Wu, M.; Cook, P.; Hodsden, S.

    1990-01-01

    Ecdysteroid growth promotion of the dorsolongitudinal flight muscle of Manduca sexta was studied by measuring in vivo protein metabolism using both "flooding-dose" and "non-carrier" techniques. These procedures differ in that the former method includes injection of non-labelled phenylalanine (30 micromoles/insect) together with the [3H]amino acid. Injected radioactivity plateaued in the haemolymph within 7 min. With the flooding-dose method, haemolymph and intramuscular specific radioactivities were similar between 15 min and 2 h. Incorporation of [3H]phenylalanine into muscle protein was linear with either method between 30 and 120 min. Fractional rates (%/12 h) of synthesis with the flooding-dose technique were best measured after 1 h because of the initial delay in radioactivity equilibration. Estimation of body phenylalanine turnover with the non-carrier method showed 24-53%/h which was negligible with the flooding-dose method. Since the two methods yielded similar rates of protein synthesis, the large injection of non-labelled amino acid did not alter the rate of synthesis. Because the flooding-dose technique requires only a single time point measurement, it is the preferred method. The decline and eventual cessation of flight-muscle growth was mostly a consequence of declining protein synthesis though degradation increased between 76-86 h before eclosion and was relatively rapid. This decline in muscle growth could be prevented by treating pupae with 20-hydroxyecdysone (10 micrograms/insect). Protein accretion was promoted by a decline of up to 80% in protein breakdown, which was offset in part by a concurrent though much smaller decrease in protein synthesis. Therefore, ecdysteroids may increase flight-muscle growth by inhibiting proteolysis.

  8. Sex-Dependent Metabolic, Neuroendocrine, and Cognitive Responses to Dietary Energy Restriction and Excess

    PubMed Central

    Martin, Bronwen; Pearson, Michele; Kebejian, Lisa; Golden, Erin; Keselman, Alex; Bender, Meredith; Carlson, Olga; Egan, Josephine; Ladenheim, Bruce; Cadet, Jean-Lud; Becker, Kevin G.; Wood, William; Duffy, Kara; Vinayakumar, Prabhu; Maudsley, Stuart; Mattson, Mark P.

    2008-01-01

    Females and males typically play different roles in survival of the species and would be expected to respond differently to food scarcity or excess. To elucidate the physiological basis of sex differences in responses to energy intake, we maintained groups of male and female rats for 6 months on diets with usual, reduced [20% and 40% caloric restriction (CR), and intermittent fasting (IF)], or elevated (high-fat/high-glucose) energy levels and measured multiple physiological variables related to reproduction, energy metabolism, and behavior. In response to 40% CR, females became emaciated, ceased cycling, underwent endocrine masculinization, exhibited a heightened stress response, increased their spontaneous activity, improved their learning and memory, and maintained elevated levels of circulating brain-derived neurotrophic factor. In contrast, males on 40% CR maintained a higher body weight than the 40% CR females and did not change their activity levels as significantly as the 40% CR females. Additionally, there was no significant change in the cognitive ability of the males on the 40% CR diet. Males and females exhibited similar responses of circulating lipids (cholesterols/triglycerides) and energy-regulating hormones (insulin, leptin, adiponectin, ghrelin) to energy restriction, with the changes being quantitatively greater in males. The high-fat/high-glucose diet had no significant effects on most variables measured but adversely affected the reproductive cycle in females. Heightened cognition and motor activity, combined with reproductive shutdown, in females may maximize the probability of their survival during periods of energy scarcity and may be an evolutionary basis for the vulnerability of women to anorexia nervosa. PMID:17569758

  9. Corticosterone metabolism by chicken follicle cells does not affect ovarian reproductive hormone synthesis in vitro

    PubMed Central

    Rettenbacher, Sophie; Henriksen, Rie; Groothuids, Ton G.; Lepschy, Michael

    2013-01-01

    Glucocorticoids affect reproductive hormone production in many species. In chickens, elevated plasma corticosterone down-regulates testosterone and progesterone concentrations in plasma, but also in egg yolk. This suppression could be mediated via the hypothalamic-pituitary system but also via local inhibition of gonadal activity by glucocorticoids. As the latter has not been tested in birds yet, we tested if corticosterone directly inhibits ovarian steroid synthesis under in vitro conditions. We hypothesized that degradation of corticosterone by follicular cells impairs their ability to synthesize reproductive hormones due to either inhibition of enzymes or competition for common co-factors. Therefore, we first established whether follicles degrade corticosterone. Follicular tissue was harvested from freshly euthanized laying hens and incubated with radiolabelled corticosterone. Radioactive metabolites were visualized and quantified by autoradiography. Follicles converted corticosterone in a time-dependent manner into metabolites with a higher polarity than corticosterone. The predominant metabolite co-eluted with 20β-dihydrocorticosterone. Other chicken tissues mostly formed the same metabolite when incubated with corticosterone. In a second experiment, follicles were incubated with either progesterone or dehydroepiandrosterone. Corticosterone was added in increasing dosages up to 1000 ng per ml medium. Corticosterone did not inhibit the conversion of progesterone and dehydroepiandrosterone into a number of different metabolites, including 17α-hydroxyprogesterone, androstenedione and testosterone. In conclusion, avian tissues degrade corticosterone mostly to 20β-dihydrocorticosterone and even high corticosterone dosages do not affect follicular hormone production under in vitro conditions. PMID:23333751

  10. Markers of Bone Metabolism Are Affected by Renal Function and Growth Hormone Therapy in Children with Chronic Kidney Disease

    PubMed Central

    Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun Karabay; Canpolat, Nur; Duzova, Ali; Sözeri, Betül; Bacchetta, Justine; Balat, Ayse; Büscher, Anja; Candan, Cengiz; Cakar, Nilgun; Donmez, Osman; Dusek, Jiri; Heckel, Martina; Klaus, Günter; Mir, Sevgi; Özcelik, Gül; Sever, Lale; Shroff, Rukshana; Vidal, Enrico; Wühl, Elke; Gondan, Matthias; Melk, Anette; Querfeld, Uwe; Haffner, Dieter; Schaefer, Franz

    2015-01-01

    Objectives The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Methods Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6–18 years with an estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Conclusion Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity. PMID:25659076

  11. Do altered energy metabolism or spontaneous locomotion 'mediate' decelerated senescence?

    PubMed

    Arum, Oge; Dawson, John Alexander; Smith, Daniel Larry; Kopchick, John J; Allison, David B; Bartke, Andrzej

    2015-06-01

    That one or multiple measures of metabolic rate may be robustly associated with, or possibly even causative of, the progression of aging-resultant phenotypes such as lifespan is a long-standing, well-known mechanistic hypothesis. To broach this hypothesis, we assessed metabolic function and spontaneous locomotion in two genetic and one dietary mouse models for retarded aging, and subjected the data to mediation analyses to determine whether any metabolic or locomotor trait could be identified as a mediator of the effect of any of the interventions on senescence. We do not test the hypothesis of causality (which would require some experiments), but instead test whether the correlation structure of certain variables is consistent with one possible pathway model in which a proposed mediating variable has a causal role. Results for metabolic measures, including oxygen consumption and respiratory quotient, failed to support this hypothesis; similar negative results were obtained for three behavioral motion metrics. Therefore, our mediation analyses did not find support that any of these correlates of decelerated senescence was a substantial mediator of the effect of either of these genetic alterations (with or without caloric restriction) on longevity. Further studies are needed to relate the examined phenotypic characteristics to mechanisms of aging and control of longevity. PMID:25720347

  12. Substrate availability regulates energy metabolism via transcriptional mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigated the mechanisms by which enhanced substrate availability regulates cardiac metabolism and function. Chronic elevation of intracellular glucose levels were achieved by overexpressing GLUT1 in mouse hearts (TG), while chronic elevation of fatty acids (FA) availability wer...

  13. GlmS and NagB Regulate Amino Sugar Metabolism in Opposing Directions and Affect Streptococcus mutans Virulence

    PubMed Central

    Kawada-Matsuo, Miki; Mazda, Yusuke; Oogai, Yuichi; Kajiya, Mikihito; Kawai, Toshihisa; Yamada, Sakuo; Miyawaki, Shouichi; Oho, Takahiko; Komatsuzawa, Hitoshi

    2012-01-01

    Streptococcus mutans is a cariogenic pathogen that produces an extracellular polysaccharide (glucan) from dietary sugars, which allows it to establish a reproductive niche and secrete acids that degrade tooth enamel. While two enzymes (GlmS and NagB) are known to be key factors affecting the entrance of amino sugars into glycolysis and cell wall synthesis in several other bacteria, their roles in S. mutans remain unclear. Therefore, we investigated the roles of GlmS and NagB in S. mutans sugar metabolism and determined whether they have an effect on virulence. NagB expression increased in the presence of GlcNAc while GlmS expression decreased, suggesting that the regulation of these enzymes, which functionally oppose one another, is dependent on the concentration of environmental GlcNAc. A glmS-inactivated mutant could not grow in the absence of GlcNAc, while nagB-inactivated mutant growth was decreased in the presence of GlcNAc. Also, nagB inactivation was found to decrease the expression of virulence factors, including cell-surface protein antigen and glucosyltransferase, and to decrease biofilm formation and saliva-induced S. mutans aggregation, while glmS inactivation had the opposite effects on virulence factor expression and bacterial aggregation. Our results suggest that GlmS and NagB function in sugar metabolism in opposing directions, increasing and decreasing S. mutans virulence, respectively. PMID:22438919

  14. 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. PMID:25293552

  15. 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. PMID:27379971

  16. Continual feeding of two types of microalgal biomass affected protein digestion and metabolism in laying hens.

    PubMed

    Ekmay, R D; Chou, K; Magnuson, A; Lei, X G

    2015-01-01

    A 14-wk study was conducted to determine the nutritional efficacy and ssmetabolic impact of 2 types of microalgal biomass as alternative protein sources in laying hen diets. Shaver hens (total = 150 and 26 wk old) were fed 1 of 5 diets: a control or a defatted green microalgal biomass (DG; Desmodesmus spp.) at 25% and a full-fatted diatom biomass (FD; Staurosira spp.) at 11.7% inclusion with or without protease. This experiment consisted of 5 replicates per treatment and each replicate contained 6 hens individually reared in cages (1 hen for biochemical data/replicate). Despite decreased ADFI (P = 0.03), hens fed DG or FD had final BW, overall hen-day egg production, and egg quality similar to the controls. Feeding DG or FD did not alter plasma concentrations of insulin, glutamine, and uric acid or alkaline phosphatase activity at wk 8 or 14 but decreased plasma 3-methyhistine concentrations (P = 0.03) and tartrate-resistant acid phosphatase (TRAP) activities (P < 0.001) at wk 14 and improved (P = 0.002) ileal total AA digestibility. Although DG or FD exhibited moderate effects on intestinal brush border protease activities and mRNA levels of duodenal transporters Pept1, Lat1, and Cat1, both substantially enhanced (P < 0.05) phosphorylation of hepatic protein synthesis key regulator S6 ribosomal protein (S6) and the ratio of phospho-S6 to S6 in the liver of hens. However, DG and FD manifested with different impacts on weights of egg and egg albumen, proteolytic activity of jejunal digesta, plasma TRAP activity, ileal total AA digestibility, and several intestinal genes and hepatic proteins. Supplemental protease in the DG and FD diets produced mixed effects on a number of measures. In conclusion, our findings revealed the feasibility of including greater levels of microalgal biomass as a source of feed protein for laying hens and a novel potential of the biomass in improving dietary protein digestion and body protein metabolism than previously perceived. PMID

  17. 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. PMID:23180608

  18. Irisin ameliorates depressive-like behaviors in rats by regulating energy metabolism.

    PubMed

    Wang, Sisi; Pan, Jiyang

    2016-05-20

    Depression is a common psychiatric disorder that affects millions of people around the world, however, little is known about the pathophysiology of depression and the therapeutic strategy for anti-depression. In this study, we investigated the role of irisin, a regulator of energy metabolism, in the modulation of depressive-like behaviors in chronic unpredictable stress (CUS) exposed rats. ELISA showed that irisin was aberrantly regulated by CUS in the prefrontal cortex tissues and cerebrospinal fluid (CSF) of rats. CUS-induced behavioral deficits in rats were reversed by injection treatment with recombinant irisin in a dose dependent manner. Treatment with irisin at concentrations of 100 ng/ml or higher significantly increased the sucrose preference and reduced the immobility time in CUS rats. Additionally, irisin treatment also increased the activities of mitochondrial complexes I, II and IV as well as creatine kinase, which were inhibited by CUS in the prefrontal cortex of rats. We then confirmed that irisin significantly increased the levels of glucose transport and phosphorylation, as reflected by the increased type I and type II hexokinase (Hx-1 and Hx-2) and GLUT-4 as well as the ATP level in vivo and vitro. Further studies indicated that AMPK pathway was involved in the regulation of irisin on depressive-like behaviors in CUS rats. In conclusion, we demonstrated that irisin has a crucial role in inducing antidepressant-like effects in CUS rats by regulating energy metabolism in the prefrontal cortex of brain, which may provide a new insight into the biological mechanism of depression. PMID:27079240

  19. Negative energy balance affects imprint stability in oocytes recovered from postpartum dairy cows.

    PubMed

    O'Doherty, Alan M; O'Gorman, Aoife; al Naib, Abdullah; Brennan, Lorraine; Daly, Edward; Duffy, Pat; Fair, Trudee

    2014-09-01

    Ovarian follicle development in post-partum, high-producing dairy cows, occurs in a compromised endogenous metabolic environment (referred to as negative energy balance, NEB). Key events that occur during oocyte/follicle growth, such as the vital process of genomic imprinting, may be detrimentally affected by this altered ovarian environment. Imprinting is crucial for placental function and regulation of fetal growth, therefore failure to establish and maintain imprints during oocyte growth may contribute to early embryonic loss. Using ovum pick-up (OPU), oocytes and follicular fluid samples were recovered from cows between days 20 and 115 post-calving, encompassing the NEB period. In a complimentary study, cumulus oocyte complexes were in vitro matured under high non-esterified fatty acid (NEFA) concentrations and in the presence of the methyl-donor S-adenosylmethionine (SAM). Pyrosequencing revealed the loss of methylation at several imprinted loci in the OPU derived oocytes. The loss of DNA methylation was observed at the PLAGL1 locus in oocytes, following in vitro maturation (IVM) in the presence of elevated NEFAs and SAM. Finally, metabolomic analysis of postpartum follicular fluid samples revealed significant differences in several branched chain amino acids, with fatty acid profiles bearing similarities to those characteristic of lactating dairy cows. These results provide the first evidence that (1) the postpartum ovarian environment may affect maternal imprint acquisition and (2) elevated NEFAs during IVM can lead to the loss of imprinted gene methylation in bovine oocytes. PMID:25084396

  20. Roostocks/Scion/Nitrogen Interactions Affect Secondary Metabolism in the Grape Berry.

    PubMed

    Habran, Aude; Commisso, Mauro; Helwi, Pierre; Hilbert, Ghislaine; Negri, Stefano; Ollat, Nathalie; Gomès, Eric; van Leeuwen, Cornelis; Guzzo, Flavia; Delrot, Serge

    2016-01-01

    The present work investigates the interactions between soil content, rootstock, and scion by focusing on the effects of roostocks and nitrogen supply on grape berry content. Scions of Cabernet Sauvignon (CS) and Pinot Noir (PN) varieties were grafted either on Riparia Gloire de Montpellier (RGM) or 110 Richter (110R) rootstock. The 4 rooststock/scion combinations were fertilized with 3 different levels of nitrogen after fruit set. Both in 2013 and 2014, N supply increased N uptake by the plants, and N content both in vegetative and reproductory organs. Rootstock, variety and year affected berry weight at harvest, while nitrogen did not affect significantly this parameter. Grafting on RGM consistently increased berry weight compared to 110R. PN consistently produced bigger berries than CS. CS berries were heavier in 2014 than in 2013, but the year effect was less marked for PN berries. The berries were collected between veraison and maturity, separated in skin and pulp, and their content was analyzed by conventional analytical procedures and untargeted metabolomics. For anthocyanins, the relative quantitation was fairly comparable with both LC-MS determination and HPLC-DAD, which is a fully quantitative technique. The data show complex responses of the metabolite content (sugars, organic acids, amino acids, anthocyanins, flavonols, flavan-3-ols/procyanidins, stilbenes, hydroxycinnamic, and hydroxybenzoic acids) that depend on the rootstock, the scion, the vintage, the nitrogen level, the berry compartment. This opens a wide range of possibilities to adjust the content of these compounds through the choice of the roostock, variety and nitrogen fertilization. PMID:27555847

  1. Roostocks/Scion/Nitrogen Interactions Affect Secondary Metabolism in the Grape Berry

    PubMed Central

    Habran, Aude; Commisso, Mauro; Helwi, Pierre; Hilbert, Ghislaine; Negri, Stefano; Ollat, Nathalie; Gomès, Eric; van Leeuwen, Cornelis; Guzzo, Flavia; Delrot, Serge

    2016-01-01

    The present work investigates the interactions between soil content, rootstock, and scion by focusing on the effects of roostocks and nitrogen supply on grape berry content. Scions of Cabernet Sauvignon (CS) and Pinot Noir (PN) varieties were grafted either on Riparia Gloire de Montpellier (RGM) or 110 Richter (110R) rootstock. The 4 rooststock/scion combinations were fertilized with 3 different levels of nitrogen after fruit set. Both in 2013 and 2014, N supply increased N uptake by the plants, and N content both in vegetative and reproductory organs. Rootstock, variety and year affected berry weight at harvest, while nitrogen did not affect significantly this parameter. Grafting on RGM consistently increased berry weight compared to 110R. PN consistently produced bigger berries than CS. CS berries were heavier in 2014 than in 2013, but the year effect was less marked for PN berries. The berries were collected between veraison and maturity, separated in skin and pulp, and their content was analyzed by conventional analytical procedures and untargeted metabolomics. For anthocyanins, the relative quantitation was fairly comparable with both LC-MS determination and HPLC-DAD, which is a fully quantitative technique. The data show complex responses of the metabolite content (sugars, organic acids, amino acids, anthocyanins, flavonols, flavan-3-ols/procyanidins, stilbenes, hydroxycinnamic, and hydroxybenzoic acids) that depend on the rootstock, the scion, the vintage, the nitrogen level, the berry compartment. This opens a wide range of possibilities to adjust the content of these compounds through the choice of the roostock, variety and nitrogen fertilization. PMID:27555847

  2. 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

  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. Mechanisms Linking Energy Substrate Metabolism to the Function of the Heart

    PubMed Central

    Carley, Andrew N.; Taegtmeyer, Heinrich; Lewandowski, E. Douglas

    2015-01-01

    Metabolic signaling mechanisms are increasingly recognized to mediate the cellular response to alterations in workload demand, as a consequence of physiological and pathophysiological challenges. Thus, an understanding of the metabolic mechanisms coordinating activity in the cytosol with the energy-providing pathways in the mitochondrial matrix becomes critical for deepening our insights into the pathogenic changes that occur in the stressed cardiomyocyte. Processes that exchange both metabolic intermediates and cations between the cytosol and mitochondria enable transduction of dynamic changes in contractile state to the mitochondrial compartment of the cell. Disruption of such metabolic transduction pathways has severe consequences for the energetic support of contractile function in the heart and is implicated in the pathogenesis of heart failure. Deficiencies in metabolic reserve and impaired metabolic transduction in the cardiomyocyte can result from inherent deficiencies in metabolic phenotype or maladaptive changes in metabolic enzyme expression and regulation in the response to pathogenic stress. This review examines both current and emerging concepts of the functional linkage between the cytosol and the mitochondrial matrix with a specific focus on metabolic reserve and energetic efficiency. These principles of exchange and transport mechanisms across the mitochondrial membrane are reviewed for the failing heart from the perspectives of chronic pressure overload and diabetes mellitus. PMID:24526677

  5. Genotype and allele frequencies of drug-metabolizing enzymes and drug transporter genes affecting immunosuppressants in the Spanish white population.

    PubMed

    Bosó, Virginia; Herrero, María J; Buso, Enrique; Galán, Juan; Almenar, Luis; Sánchez-Lázaro, Ignacio; Sánchez-Plumed, Jaime; Bea, Sergio; Prieto, Martín; García, María; Pastor, Amparo; Sole, Amparo; Poveda, José Luis; Aliño, Salvador F

    2014-04-01

    Interpatient variability in drug response can be widely explained by genetically determined differences in metabolizing enzymes, drug transporters, and drug targets, leading to different pharmacokinetic and/or pharmacodynamic behaviors of drugs. Genetic variations affect or do not affect drug responses depending on their influence on protein activity and the relevance of such proteins in the pathway of the drug. Also, the frequency of such genetic variations differs among populations, so the clinical relevance of a specific variation is not the same in all of them. In this study, a panel of 33 single nucleotide polymorphisms in 14 different genes (ABCB1, ABCC2, ABCG2, CYP2B6, CYP2C19, CYP2C9, CYP3A4, CYP3A5, MTHFR, NOD2/CARD15, SLCO1A2, SLCO1B1, TPMT, and UGT1A9), encoding for the most relevant metabolizing enzymes and drug transporters relating to immunosuppressant agents, was analyzed to determine the genotype profile and allele frequencies in comparison with HapMap data. A total of 570 Spanish white recipients and donors of solid organ transplants were included. In 24 single nucleotide polymorphisms, statistically significant differences in allele frequency were observed. The largest differences (>100%) occurred in ABCB1 rs2229109, ABCG2 rs2231137, CYP3A5 rs776746, NOD2/CARD15 rs2066844, TPMT rs1800462, and UGT1A9 rs72551330. In conclusion, differences were recorded between the Spanish and other white populations in terms of allele frequency and genotypic distribution. Such differences may have implications in relation to dose requirements and drug-induced toxicity. These data are important for further research to help explain interindividual pharmacokinetic and pharmacodynamic variability in response to drug therapy. PMID:24232128

  6. High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model

    PubMed Central

    Larmonier, C. B.; McFadden, R.-M. T.; Hill, F. M.; Schreiner, R.; Ramalingam, R.; Besselsen, D. G.; Ghishan, F. K.

    2013-01-01

    Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D3 has been considered a viable adjunctive therapy in IBD. However, vitamin D3 plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D3 supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10−/− CD4+ T cell transfer model of chronic colitis. High-dose vitamin D3 supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D3 metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D3 supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D3 diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D3 group. Our data suggest that vitamin D3, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D3 supplementation in patients with active IBD. PMID:23639807

  7. Long-term affected energy production of waste to energy technologies identified by use of energy system analysis.

    PubMed

    Münster, M; Meibom, P

    2010-12-01

    Affected energy production is often decisive for the outcome of consequential life-cycle assessments when comparing the potential environmental impact of products or services. Affected energy production is however difficult to determine. In this article the future long-term affected energy production is identified by use of energy system analysis. The focus is on different uses of waste for energy production. The Waste-to-Energy technologies analysed include co-combustion of coal and waste, anaerobic digestion and thermal gasification. The analysis is based on optimization of both investments and production of electricity, district heating and bio-fuel in a future possible energy system in 2025 in the countries of the Northern European electricity market (Denmark, Norway, Sweden, Finland and Germany). Scenarios with different CO(2) quota costs are analysed. It is demonstrated that the waste incineration continues to treat the largest amount of waste. Investments in new waste incineration capacity may, however, be superseded by investments in new Waste-to-Energy technologies, particularly those utilising sorted fractions such as organic waste and refuse derived fuel. The changed use of waste proves to always affect a combination of technologies. What is affected varies among the different Waste-to-Energy technologies and is furthermore dependent on the CO(2) quota costs and on the geographical scope. The necessity for investments in flexibility measures varies with the different technologies such as storage of heat and waste as well as expansion of district heating networks. Finally, inflexible technologies such as nuclear power plants are shown to be affected. PMID:20471819

  8. Long-term affected energy production of waste to energy technologies identified by use of energy system analysis

    SciTech Connect

    Muenster, M.; Meibom, P.

    2010-12-15

    Affected energy production is often decisive for the outcome of consequential life-cycle assessments when comparing the potential environmental impact of products or services. Affected energy production is however difficult to determine. In this article the future long-term affected energy production is identified by use of energy system analysis. The focus is on different uses of waste for energy production. The Waste-to-Energy technologies analysed include co-combustion of coal and waste, anaerobic digestion and thermal gasification. The analysis is based on optimization of both investments and production of electricity, district heating and bio-fuel in a future possible energy system in 2025 in the countries of the Northern European electricity market (Denmark, Norway, Sweden, Finland and Germany). Scenarios with different CO{sub 2} quota costs are analysed. It is demonstrated that the waste incineration continues to treat the largest amount of waste. Investments in new waste incineration capacity may, however, be superseded by investments in new Waste-to-Energy technologies, particularly those utilising sorted fractions such as organic waste and refuse derived fuel. The changed use of waste proves to always affect a combination of technologies. What is affected varies among the different Waste-to-Energy technologies and is furthermore dependent on the CO{sub 2} quota costs and on the geographical scope. The necessity for investments in flexibility measures varies with the different technologies such as storage of heat and waste as well as expansion of district heating networks. Finally, inflexible technologies such as nuclear power plants are shown to be affected.

  9. Effect of the sesquiterpene lactone incomptine A in the energy metabolism of Entamoeba histolytica.

    PubMed

    Velázquez-Domínguez, José; Marchat, Laurence A; López-Camarillo, Cesar; Mendoza-Hernández, Guillermo; Sánchez-Espíndola, Esther; Calzada, Fernando; Ortega-Hernández, Alfredo; Sánchez-Monroy, Virginia; Ramírez-Moreno, Esther

    2013-11-01

    Entamoeba histolytica is the causative agent of human amoebiasis, which mainly affects developing countries. Although several drugs are effective against E. histolytica trophozoites, the control of amoebiasis requires the development of new and better alternative therapies. Medicinal plants have been the source of new molecules with remarkable antiprotozoal activity. Incomptine A isolated from Decachaeta incompta leaves, is a sesquiterpene lactone of the heliangolide type which has the major in vitro activity against E. histolytica trophozoites. However the molecular mechanisms involved in its antiprotozoal activity are still unknown. Using a proteomic approach based on two-dimensional gel electrophoresis and mass spectrometry (ESI-MS/MS) analysis, we evidenced that 21 E. histolytica proteins were differentially expressed in response to incomptine A treatment. Notably, three glycolytic enzymes, namely enolase, pyruvate:ferredoxin oxidoreductase and fructose-1,6-biphosphate aldolase, were down-regulated. Moreover, ultrastructural analysis of trophozoites through electronic microscopy showed an increased number of glycogen granules. Taken together, our data suggested that incomptine A could affect E. histolytica growth through alteration of its energy metabolism. PMID:23994114

  10. Oxalic acid alleviates chilling injury in peach fruit by regulating energy metabolism and fatty acid contents.

    PubMed

    Jin, Peng; Zhu, Hong; Wang, Lei; Shan, Timin; Zheng, Yonghua

    2014-10-15

    The effects of postharvest oxalic acid (OA) treatment on chilling injury, energy metabolism and membrane fatty acid content in 'Baifeng' peach fruit stored at 0°C were investigated. Internal browning was significantly reduced by OA treatment in peaches. OA treatment markedly inhibited the increase of ion leakage and the accumulation of malondialdehyde. Meanwhile, OA significantly increased the contents of adenosine triphosphate and energy charge in peach fruit. Enzyme activities of energy metabolism including H(+)-adenosine triphosphatase, Ca(2+)-adenosine triphosphatase, succinic dehydrogenase and cytochrome C oxidase were markedly enhanced by OA treatment. The ratio of unsaturated/saturated fatty acid in OA-treated fruit was significantly higher than that in control fruit. These results suggest that the alleviation in chilling injury by OA may be due to enhanced enzyme activities related to energy metabolism and higher levels of energy status and unsaturated/saturated fatty acid ratio. PMID:24837925

  11. Calcium-Vitamin D Co-supplementation Affects Metabolic Profiles, but not Pregnancy Outcomes, in Healthy Pregnant Women

    PubMed Central

    Asemi, Zatollah; Samimi, Mansooreh; Siavashani, Mehrnush Amiri; Mazloomi, Maryam; Tabassi, Zohreh; Karamali, Maryam; Jamilian, Mehri; Esmaillzadeh, Ahmad

    2016-01-01

    Background: Pregnancy is associated with unfavorable metabolic profile, which might in turn result in adverse pregnancy outcomes. The current study was designed to evaluate the effects of calcium plus Vitamin D administration on metabolic status and pregnancy outcomes in healthy pregnant women. Methods: This randomized double-blind placebo-controlled clinical trial was performed among 42 pregnant women aged 18–40 years who were at week 25 of gestation. Subjects were randomly allocated to consume either 500 mg calcium-200 IU cholecalciferol supplements (n = 21) or placebo (n = 21) for 9 weeks. Blood samples were obtained at the onset of the study and after 9-week trial to determine related markers. Post-delivery, the newborn's weight, length, and head circumference were measured during the first 24 h after birth. Results: Consumption of calcium-Vitamin D co-supplements resulted in a significant reduction of serum high-sensitivity C-reactive protein levels compared with placebo (−1856.8 ± 2657.7 vs. 707.1 ± 3139.4 μg/mL, P = 0.006). We also found a significant elevation of plasma total antioxidant capacity (89.3 ± 118.0 vs. −9.4 ± 164.9 mmol/L, P = 0.03), serum 25-hydroxyvitamin D (2.5 ± 3.5 vs. −1.7 ± 1.7 ng/mL, P < 0.0001), and calcium levels (0.6 ± 0.6 vs. −0.1 ± 0.4 mg/dL, P < 0.0001). The supplementation led to a significant decrease in diastolic blood pressure (−1.9 ± 8.3 vs. 3.1 ± 5.2 mmHg, P = 0.02) compared with placebo. No significant effect of calcium-Vitamin D co-supplements was seen on other metabolic profiles. We saw no significant change of the co-supplementation on pregnancy outcomes as well. Conclusions: Although calcium-Vitamin D co-supplementation for 9 weeks in pregnant women resulted in improved metabolic profiles, it did not affect pregnancy outcomes. PMID:27076887

  12. Early infancy microbial and metabolic alterations affect risk of childhood asthma.

    PubMed

    Arrieta, Marie-Claire; Stiemsma, Leah T; Dimitriu, Pedro A; Thorson, Lisa; Russell, Shannon; Yurist-Doutsch, Sophie; Kuzeljevic, Boris; Gold, Matthew J; Britton, Heidi M; Lefebvre, Diana L; Subbarao, Padmaja; Mandhane, Piush; Becker, Allan; McNagny, Kelly M; Sears, Malcolm R; Kollmann, Tobias; Mohn, William W; Turvey, Stuart E; Finlay, B Brett

    2015-09-30

    Asthma is the most prevalent pediatric chronic disease and affects more than 300 million people worldwide. Recent evidence in mice has identified a "critical window" early in life where gut microbial changes (dysbiosis) are most influential in experimental asthma. However, current research has yet to establish whether these changes precede or are involved in human asthma. We compared the gut microbiota of 319 subjects enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study, and show that infants at risk of asthma exhibited transient gut microbial dysbiosis during the first 100 days of life. The relative abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia was significantly decreased in children at risk of asthma. This reduction in bacterial taxa was accompanied by reduced levels of fecal acetate and dysregulation of enterohepatic metabolites. Inoculation of germ-free mice with these four bacterial taxa ameliorated airway inflammation in their adult progeny, demonstrating a causal role of these bacterial taxa in averting asthma development. These results enhance the potential for future microbe-based diagnostics and therapies, potentially in the form of probiotics, to prevent the development of asthma and other related allergic diseases in children. PMID:26424567

  13. 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

  14. [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

  15. 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

  16. Energy metabolism in neuronal/glial induction and in iPSC models of brain disorders.

    PubMed

    Mlody, Barbara; Lorenz, Carmen; Inak, Gizem; Prigione, Alessandro

    2016-04-01

    The metabolic switch associated with the reprogramming of somatic cells to pluripotency has received increasing attention in recent years. However, the impact of mitochondrial and metabolic modulation on stem cell differentiation into neuronal/glial cells and related brain disease modeling still remains to be fully addressed. Here, we seek to focus on this aspect by first addressing brain energy metabolism and its inter-cellular metabolic compartmentalization. We then review the findings related to the mitochondrial and metabolic reconfiguration occurring upon neuronal/glial specification from pluripotent stem cells (PSCs). Finally, we provide an update of the PSC-based models of mitochondria-related brain disorders and discuss the challenges and opportunities that may exist on the road to develop a new era of brain disease modeling and therapy. PMID:26877213

  17. Natural merodiploidy involving duplicated rpoB alleles affects secondary metabolism in a producer actinomycete.

    PubMed

    Vigliotta, Giovanni; Tredici, Salvatore Maurizio; Damiano, Fabrizio; Montinaro, Maria Rosa; Pulimeno, Rita; di Summa, Roberta; Massardo, Domenica Rita; Gnoni, Gabriele V; Alifano, Pietro

    2005-01-01

    Actinomadura sp. ATCC 39727 produces the glycopeptide antibiotic A40926, structurally similar to teicoplanin. Production of A40926 is governed by the stringent response at the transcriptional level. In fact, addition of an amino acid pool prevented the transcription of dbv cluster genes involved in the A40926 biosynthesis and the antibiotic production in chemically defined media, and a thiostrepton-resistant relaxed mutant was severely impaired in its ability to produce the antibiotic. The derivative strain rif19, highly resistant to rifampicin (minimal inhibitory concentration, MIC > 200 microg ml(-1)), was isolated from the wild type strain that exhibited low resistance to rifampicin (MIC < 25 microg ml(-1)). In this strain A40926 production started earlier than in the wild type, and reached higher final levels. Moreover, the antibiotic production was not subjected to the stringent control. Molecular analysis led to the identification of two distinct rpoB alleles, rpoBS and rpoBR, in both the wild type and the rif19. rpoBR harboured the H426N missense which is responsible for rifampicin-resistance in bacteria, in addition to other nucleotide substitutions affecting the primary structure of the RNA polymerase beta-chain. Transcript analysis revealed that rpoBR was expressed at a very low level in the wild type strain during the pseudo-exponential growth phase, and that the amount of rpoBR mRNA increased during the transition to the stationary phase. In contrast, expression of rpoBR was constitutive in the rif19. The results of mRNA half-life analysis did not support the hypothesis that post-transcriptional events are responsible for the different rpoB expression patterns in the two strains, suggesting a role of transcriptional mechanisms. PMID:15659159

  18. The non-psychoactive plant cannabinoid, cannabidiol affects cholesterol metabolism-related genes in microglial cells.

    PubMed

    Rimmerman, Neta; Juknat, Ana; Kozela, Ewa; Levy, Rivka; Bradshaw, Heather B; Vogel, Zvi

    2011-08-01

    Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that is clinically used in a 1:1 mixture with the psychoactive cannabinoid Δ(9)-tetrahydrocannabinol (THC) for the treatment of neuropathic pain and spasticity in multiple sclerosis. Our group previously reported that CBD exerts anti-inflammatory effects on microglial cells. In addition, we found that CBD treatment increases the accumulation of the endocannabinoid N-arachidonoyl ethanolamine (AEA), thus enhancing endocannabinoid signaling. Here we proceeded to investigate the effects of CBD on the modulation of lipid-related genes in microglial cells. Cell viability was tested using FACS analysis, AEA levels were measured using LC/MS/MS, gene array analysis was validated with real-time qPCR, and cytokine release was measured using ELISA. We report that CBD significantly upregulated the mRNAs of the enzymes sterol-O-acyl transferase (Soat2), which synthesizes cholesteryl esters, and of sterol 27-hydroxylase (Cyp27a1). In addition, CBD increased the mRNA of the lipid droplet-associated protein, perilipin2 (Plin2). Moreover, we found that pretreatment of the cells with the cholesterol chelating agent, methyl-β-cyclodextrin (MBCD), reversed the CBD-induced increase in Soat2 mRNA but not in Plin2 mRNA. Incubation with AEA increased the level of Plin2, but not of Soat2 mRNA. Furthermore, MBCD treatment did not affect the reduction by CBD of the LPS-induced release of the proinflammatory cytokine IL-1β. CBD treatment modulates cholesterol homeostasis in microglial cells, and pretreatment with MBCD reverses this effect without interfering with CBD's anti-inflammatory effects. The effects of the CBD-induced increase in AEA accumulation on lipid-gene expression are discussed. PMID:21533611

  19. Interleukin-6 and leptin as markers of energy metabolic changes in advanced ovarian cancer patients.

    PubMed

    Macciò, Antonio; Madeddu, Clelia; Massa, Daniela; Astara, Giorgio; Farci, Daniele; Melis, Gian Benedetto; Mantovani, Giovanni

    2009-09-01

    The progression of the neoplastic disease is characterized by specific alterations of energy metabolism and by symptoms like fatigue, anorexia, nausea, anaemia, immunodepression and poor performance status (PS). The main cause of these symptoms and metabolic abnormalities is the chronic action of proinflammatory cytokines released both by tumour and immune cells. The present study aimed to assess the relationship between markers of inflammation (C-Reactive Protein, Fibrinogen, proinflammatory cytokines) and energy metabolic status (BMI, leptin, oxidative stress) according to clinical parameters in 104 ovarian cancer patients at different stage and, moreover, to evaluate prospectively the changes of these parameters in accordance to tumour response in a subgroup of 70 advanced stage ovarian cancer patients. Advanced stage and poor PS were associated to high-grade inflammation and impaired energy metabolism. Among inflammatory mediators, interleukin (IL)-6 had a central role as predictive factor of leptin, reactive oxygen species and glutathione peroxidase. In turn, leptin considered the key marker of the nutritional status and energy metabolism, was independently determined from stage and IL-6, not only from BMI. Moreover, the evaluation of the changes of these parameters during the course of the neoplastic disease in the subgroup of advanced ovarian cancer patients clearly unveils the central role of IL-6 and leptin as early markers of the metabolic alterations and symptoms associated to disease progression in advanced stage ovarian cancer. Their assessment should be included in monitoring disease outcome, especially when cancer is no longer curable and quality of life becomes the primary endpoint. PMID:18624749

  20. Energy metabolism in intestinal epithelial cells during maturation along the crypt-villus axis

    PubMed Central

    Yang, Huansheng; Wang, Xiaocheng; Xiong, Xia; Yin, Yulong

    2016-01-01

    Intestinal epithelial cells continuously migrate and mature along crypt-villus axis (CVA), while the changes in energy metabolism during maturation are unclear in neonates. The present study was conducted to test the hypothesis that the energy metabolism in intestinal epithelial cells would be changed during maturation along CVA in neonates. Eight 21-day-old suckling piglets were used. Intestinal epithelial cells were isolated sequentially along CVA, and proteomics was used to analyze the changes in proteins expression in epithelial cells along CVA. The identified differentially expressed proteins were mainly involved in cellular process, metabolic process, biological regulation, pigmentation, multicellular organizational process and so on. The energy metabolism in intestinal epithelial cells of piglets was increased from the bottom of crypt to the top of villi. Moreover, the expression of proteins related to the metabolism of glucose, most of amino acids, and fatty acids was increased in intestinal epithelial cells during maturation along CVA, while the expression of proteins related to glutamine metabolism was decreased from crypt to villus tip. The expression of proteins involved in citrate cycle was also increased intestinal epithelial cells during maturation along CVA. Moreover, dietary supplementation with different energy sources had different effects on intestinal structure of weaned piglets. PMID:27558220

  1. Energy metabolism in intestinal epithelial cells during maturation along the crypt-villus axis.

    PubMed

    Yang, Huansheng; Wang, Xiaocheng; Xiong, Xia; Yin, Yulong

    2016-01-01

    Intestinal epithelial cells continuously migrate and mature along crypt-villus axis (CVA), while the changes in energy metabolism during maturation are unclear in neonates. The present study was conducted to test the hypothesis that the energy metabolism in intestinal epithelial cells would be changed during maturation along CVA in neonates. Eight 21-day-old suckling piglets were used. Intestinal epithelial cells were isolated sequentially along CVA, and proteomics was used to analyze the changes in proteins expression in epithelial cells along CVA. The identified differentially expressed proteins were mainly involved in cellular process, metabolic process, biological regulation, pigmentation, multicellular organizational process and so on. The energy metabolism in intestinal epithelial cells of piglets was increased from the bottom of crypt to the top of villi. Moreover, the expression of proteins related to the metabolism of glucose, most of amino acids, and fatty acids was increased in intestinal epithelial cells during maturation along CVA, while the expression of proteins related to glutamine metabolism was decreased from crypt to villus tip. The expression of proteins involved in citrate cycle was also increased intestinal epithelial cells during maturation along CVA. Moreover, dietary supplementation with different energy sources had different effects on intestinal structure of weaned piglets. PMID:27558220

  2. Early detection of metabolic and energy disorders by thermal time series stochastic complexity analysis

    PubMed Central

    Lutaif, N.A.; Palazzo, R.; Gontijo, J.A.R.

    2014-01-01

    Maintenance of thermal homeostasis in rats fed a high-fat diet (HFD) is associated with changes in their thermal balance. The thermodynamic relationship between heat dissipation and energy storage is altered by the ingestion of high-energy diet content. Observation of thermal registers of core temperature behavior, in humans and rodents, permits identification of some characteristics of time series, such as autoreference and stationarity that fit adequately to a stochastic analysis. To identify this change, we used, for the first time, a stochastic autoregressive model, the concepts of which match those associated with physiological systems involved and applied in male HFD rats compared with their appropriate standard food intake age-matched male controls (n=7 per group). By analyzing a recorded temperature time series, we were able to identify when thermal homeostasis would be affected by a new diet. The autoregressive time series model (AR model) was used to predict the occurrence of thermal homeostasis, and this model proved to be very effective in distinguishing such a physiological disorder. Thus, we infer from the results of our study that maximum entropy distribution as a means for stochastic characterization of temperature time series registers may be established as an important and early tool to aid in the diagnosis and prevention of metabolic diseases due to their ability to detect small variations in thermal profile. PMID:24519093

  3. Early detection of metabolic and energy disorders by thermal time series stochastic complexity analysis.

    PubMed

    Lutaif, N A; Palazzo, R; Gontijo, J A R

    2014-01-01

    Maintenance of thermal homeostasis in rats fed a high-fat diet (HFD) is associated with changes in their thermal balance. The thermodynamic relationship between heat dissipation and energy storage is altered by the ingestion of high-energy diet content. Observation of thermal registers of core temperature behavior, in humans and rodents, permits identification of some characteristics of time series, such as autoreference and stationarity that fit adequately to a stochastic analysis. To identify this change, we used, for the first time, a stochastic autoregressive model, the concepts of which match those associated with physiological systems involved and applied in male HFD rats compared with their appropriate standard food intake age-matched male controls (n=7 per group). By analyzing a recorded temperature time series, we were able to identify when thermal homeostasis would be affected by a new diet. The autoregressive time series model (AR model) was used to predict the occurrence of thermal homeostasis, and this model proved to be very effective in distinguishing such a physiological disorder. Thus, we infer from the results of our study that maximum entropy distribution as a means for stochastic characterization of temperature time series registers may be established as an important and early tool to aid in the diagnosis and prevention of metabolic diseases due to their ability to detect small variations in thermal profile. PMID:24519093

  4. Metabolic Free Energy and Biological Codes: A 'Data Rate Theorem' Aging Model.

    PubMed

    Wallace, Rodrick

    2015-06-01

    A famous argument by Maturana and Varela (Autopoiesis and cognition. Reidel, Dordrecht, 1980) holds that the living state is cognitive at every scale and level of organization. Since it is possible to associate many cognitive processes with 'dual' information sources, pathologies can sometimes be addressed using statistical models based on the Shannon Coding, the Shannon-McMillan Source Coding, the Rate Distortion, and the Data Rate Theorems, which impose necessary conditions on information transmission and system control. Deterministic-but-for-error biological codes do not directly invoke cognition, but may be essential subcomponents within larger cognitive processes. A formal argument, however, places such codes within a similar framework, with metabolic free energy serving as a 'control signal' stabilizing biochemical code-and-translator dynamics in the presence of noise. Demand beyond available energy supply triggers punctuated destabilization of the coding channel, affecting essential biological functions. Aging, normal or prematurely driven by psychosocial or environmental stressors, must interfere with the routine operation of such mechanisms, initiating the chronic diseases associated with senescence. Amyloid fibril formation, intrinsically disordered protein logic gates, and cell surface glycan/lectin 'kelp bed' logic gates are reviewed from this perspective. The results generalize beyond coding machineries having easily recognizable symmetry modes, and strip a layer of mathematical complication from the study of phase transitions in nonequilibrium biological systems. PMID:25185747

  5. 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

  6. Altered Phenylpropanoid Metabolism in the Maize Lc-Expressed Sweet Potato (Ipomoea batatas) Affects Storage Root Development.

    PubMed

    Wang, Hongxia; Yang, Jun; Zhang, Min; Fan, Weijuan; Firon, Nurit; Pattanaik, Sitakanta; Yuan, Ling; Zhang, Peng

    2016-01-01

    There is no direct evidence of the effect of lignin metabolism on early storage root development in sweet potato. In this study, we found that heterologous expression of the maize leaf color (Lc) gene in sweet potato increased anthocyanin pigment accumulation in the whole plant and resulted in reduced size with an increased length/width ratio, low yield and less starch content in the early storage roots. RT-PCR analysis revealed dramatic up-regulation of the genes involved in the lignin biosynthesis pathway in developing storage roots, leading to greater lignin content in the Lc transgenic lines, compared to the wild type. This was also evidenced by the enhanced lignification of vascular cells in the early storage roots. Furthermore, increased expression of the β-amylase gene in leaves and storage roots also accelerated starch degradation and increased the sugar use efficiency, providing more energy and carbohydrate sources for lignin biosynthesis in the Lc transgenic sweet potato. Lesser starch accumulation was observed in the developing storage roots at the initiation stage in the Lc plants. Our study provides experimental evidence of the basic carbohydrate metabolism underlying the development of storage roots, which is the transformation of lignin biosynthesis to starch biosynthesis. PMID:26727353

  7. Altered Phenylpropanoid Metabolism in the Maize Lc-Expressed Sweet Potato (Ipomoea batatas) Affects Storage Root Development

    PubMed Central

    Wang, Hongxia; Yang, Jun; Zhang, Min; Fan, Weijuan; Firon, Nurit; Pattanaik, Sitakanta; Yuan, Ling; Zhang, Peng

    2016-01-01

    There is no direct evidence of the effect of lignin metabolism on early storage root development in sweet potato. In this study, we found that heterologous expression of the maize leaf color (Lc) gene in sweet potato increased anthocyanin pigment accumulation in the whole plant and resulted in reduced size with an increased length/width ratio, low yield and less starch content in the early storage roots. RT-PCR analysis revealed dramatic up-regulation of the genes involved in the lignin biosynthesis pathway in developing storage roots, leading to greater lignin content in the Lc transgenic lines, compared to the wild type. This was also evidenced by the enhanced lignification of vascular cells in the early storage roots. Furthermore, increased expression of the β-amylase gene in leaves and storage roots also accelerated starch degradation and increased the sugar use efficiency, providing more energy and carbohydrate sources for lignin biosynthesis in the Lc transgenic sweet potato. Lesser starch accumulation was observed in the developing storage roots at the initiation stage in the Lc plants. Our study provides experimental evidence of the basic carbohydrate metabolism underlying the development of storage roots, which is the transformation of lignin biosynthesis to starch biosynthesis. PMID:26727353

  8. Failure of weight training to affect urinary indices of protein metabolism in men.

    PubMed

    Hickson, J F; Wolinsky, I; Rodriguez, G P; Pivarnik, J M; Kent, M C; Shier, N W

    1986-10-01

    It is commonly believed by some athletes that strength building exercise "tears down" skeletal muscle tissue, thereby enhancing the dietary need for protein, but this has not been demonstrated. Ten college-age males served as subjects in a 15-d, controlled feeding study. The men were 23.1 +/- 2.2 yr old (mean +/- SD), 177 +/- 5 cm in height, and 71.7 +/- 9.1 kg in body weight (study days = 1 to 15). The lacto-ovo-vegetarian diet provided 0.9 g/kg protein and 15.1 +/- 0.4 MJ (3,604 +/- 104 kcal) . d-1 energy (study days = 6 to 15). On days 8 and 12, subjects participated in a standardized strength building, weight training exercise regimen. Post-exercise days 9 to 11 and 13 to 15 were designated for recovery. Daily (24-h) urine collections were analyzed for ammonia, creatinine, 3-methylhistidine, total nitrogen, and urea. There was no acute (24-h) effect of weight training exercise on any excretion levels. In particular, urinary 3-methylhistidine excretion data indicate that skeletal muscle protein catabolism was not changed by isolated bouts of weight training exercise. PMID:3773673

  9. Role of NADH/NAD+ transport activity and glycogen store on skeletal muscle energy metabolism during exercise: in silico studies

    PubMed Central

    Li, Yanjun; Dash, Ranjan K.; Kim, Jaeyeon; Saidel, Gerald M.; Cabrera, Marco E.

    2009-01-01

    Skeletal muscle can maintain ATP concentration constant during the transition from rest to exercise, whereas metabolic reaction rates may increase substantially. Among the key regulatory factors of skeletal muscle energy metabolism during exercise, the dynamics of cytosolic and mitochondrial NADH and NAD+ have not been characterized. To quantify these regulatory factors, we have developed a physiologically based computational model of skeletal muscle energy metabolism. This model integrates transport and reaction fluxes in distinct capillary, cytosolic, and mitochondrial domains and investigates the roles of mitochondrial NADH/NAD+ transport (shuttling) activity and muscle glycogen concentration (stores) during moderate intensity exercise (60% maximal O2 consumption). The underlying hypothesis is that the cytosolic redox state (NADH/NAD+) is much more sensitive to a metabolic disturbance in contracting skeletal muscle than the mitochondrial redox state. This hypothesis was tested by simulating the dynamic metabolic responses of skeletal muscle to exercise while altering the transport rate of reducing equivalents (NADH and NAD+) between cytosol and mitochondria and muscle glycogen stores. Simulations with optimal parameter estimates showed good agreement with the available experimental data from muscle biopsies in human subjects. Compared with these simulations, a 20% increase (or ∼20% decrease) in mitochondrial NADH/NAD+ shuttling activity led to an ∼70% decrease (or ∼3-fold increase) in cytosolic redox state and an ∼35% decrease (or ∼25% increase) in muscle lactate level. Doubling (or halving) muscle glycogen concentration resulted in an ∼50% increase (or ∼35% decrease) in cytosolic redox state and an ∼30% increase (or ∼25% decrease) in muscle lactate concentration. In both cases, changes in mitochondrial redox state were minimal. In conclusion, the model simulations of exercise response are consistent with the hypothesis that mitochondrial NADH

  10. 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

  11. 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

  12. Dietary energy density is associated with obesity and the metabolic syndrome in U.S. adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rising obesity rates have been linked to the consumption of energy-dense diets. We examined whether dietary energy density was associated with obesity and related disorders, including insulin resistance and the metabolic syndrome. We conducted a cross-sectional study using nationally representative ...

  13. An Integrative Approach to Energy Carbon and Redox Metabolism In Cyanobacterium Synechocystis

    SciTech Connect

    Dr. Ross Overbeek

    2003-06-30

    The main objectives for the first year were to produce a detailed metabolic reconstruction of synechocystis sp.pcc6803 especially in interrelated arrears of photosynthesis respiration and central carbon metabolism to support a more complete understanding and modeling of this organism. Additionally, IG, Inc. provided detailed bioinformatic analysis of selected functional systems related to carbon and energy generation and utilization, and of the corresponding pathways functional roles and individual genes to support wet lab experiments by collaborators.

  14. Identification of key components in the energy metabolism of the hyperthermophilic sulfate-reducing archaeon Archaeoglobus fulgidus by transcriptome analyses

    PubMed Central

    Hocking, William P.; Stokke, Runar; Roalkvam, Irene; Steen, Ida H.

    2014-01-01

    Energy conservation via the pathway of dissimilatory sulfate reduction is present in a diverse group of prokaryotes, but is most comprehensively studied in Deltaproteobacteria. In this study, whole-genome microarray analyses were used to provide a model of the energy metabolism of the sulfate-reducing archaeon Archaeoglobus fulgidus, based on comparative analysis of litoautotrophic growth with H2/CO2 and thiosulfate, and heterotrophic growth on lactate with sulfate or thiosulfate. Only 72 genes were expressed differentially between the cultures utilizing sulfate or thiosulfate, whereas 269 genes were affected by a shift in energy source. We identified co-located gene cluster encoding putative lactate dehydrogenases (LDHs; lldD, dld, lldEFG), also present in sulfate-reducing bacteria. These enzymes may take part in energy conservation in A. fulgidus by specifically linking lactate oxidation with APS reduction via the Qmo complex. High transcriptional levels of Fqo confirm an important role of F420H2, as well as a menaquinone-mediated electron transport chain, during heterotrophic growth. A putative periplasmic thiosulfate reductase was identified by specific up-regulation. Also, putative genes for transport of sulfate and sulfite are discussed. We present a model for hydrogen metabolism, based on the probable bifurcation reaction of the Mvh:Hdl hydrogenase, which may inhibit the utilization of Fdred for energy conservation. Energy conservation is probably facilitated via menaquinone to multiple membrane-bound heterodisulfide reductase (Hdr) complexes and the DsrC protein—linking periplasmic hydrogenase (Vht) to the cytoplasmic reduction of sulfite. The ambiguous roles of genes corresponding to fatty acid metabolism induced during growth with H2 are discussed. Putative co-assimilation of organic acids is favored over a homologous secondary carbon fixation pathway, although both mechanisms may contribute to conserve the amount of Fdred needed during autotrophic

  15. Adenylate Kinase and AMP Signaling Networks: Metabolic Monitoring, Signal Communication and Body Energy Sensing

    PubMed Central

    Dzeja, Petras; Terzic, Andre

    2009-01-01

    Adenylate kinase and downstream AMP signaling is an integrated metabolic monitoring system which reads the cellular energy state in order to tune and report signals to metabolic sensors. A network of adenylate kinase isoforms (AK1-AK7) are distributed throughout intracellular compartments, interstitial space and body fluids to regulate energetic and metabolic signaling circuits, securing efficient cell energy economy, signal communication and stress response. The dynamics of adenylate kinase-catalyzed phosphotransfer regulates multiple intracellular and extracellular energy-dependent and nucleotide signaling processes, including excitation-contraction coupling, hormone secretion, cell and ciliary motility, nuclear transport, energetics of cell cycle, DNA synthesis and repair, and developmental programming. Metabolomic analyses indicate that cellular, interstitial and blood AMP levels are potential metabolic signals associated with vital functions including body energy sensing, sleep, hibernation and food intake. Either low or excess AMP signaling has been linked to human disease such as diabetes, obesity and hypertrophic cardiomyopathy. Recent studies indicate that derangements in adenylate kinase-mediated energetic signaling due to mutations in AK1, AK2 or AK7 isoforms are associated with hemolytic anemia, reticular dysgenesis and ciliary dyskinesia. Moreover, hormonal, food and antidiabetic drug actions are frequently coupled to alterations of cellular AMP levels and associated signaling. Thus, by monitoring energy state and generating and distributing AMP metabolic signals adenylate kinase represents a unique hub within the cellular homeostatic network. PMID:19468337

  16. Energy metabolism and metabolic sensors in stem cells: the metabostem crossroads of aging and cancer.

    PubMed

    Menendez, Javier A; Joven, Jorge

    2014-01-01

    We are as old as our adult stem cells are; therefore, stem cell exhaustion is considered a hallmark of aging. Our tumors are as aggressive as the number of cancer stem cells (CSCs) they bear because CSCs can survive treatments with hormones, radiation, chemotherapy, and molecularly targeted drugs, thus increasing the difficulty of curing cancer. Not surprisingly, interest in stem cell research has never been greater among members of the public, politicians, and scientists. But how can we slow the rate at which our adult stem cells decline over our lifetime, reducing the regenerative potential of tissues, while efficiently eliminating the aberrant, life-threatening activity of "selfish", immortal, and migrating CSCs? Frustrated by the gene-centric limitations of conventional approaches to aging diseases, our group and other groups have begun to appreciate that bioenergetic metabolism, i.e., the production of fuel & building blocks for growth and division, and autophagy/mitophagy, i.e., the quality-control, self-cannibalistic system responsible for "cleaning house" and "recycling the trash", can govern the genetic and epigenetic networks that facilitate stem cell behaviors. Indeed, it is reasonable to suggest the existence of a "metabostem" infrastructure that operates as a shared hallmark of aging and cancer, thus making it physiologically plausible to maintain or even increase the functionality of adult stem cells while reducing the incidence of cancer and extending the lifespan. This "metabostemness" property could lead to the discovery of new drugs that reprogram cell metabotypes to increase the structural and functional integrity of adult stem cells and positively influence their lineage determination, while preventing the development and aberrant function of stem cells in cancer tissues. While it is obvious that the antifungal antibiotic rapamycin, the polyphenol resveratrol, and the biguanide metformin already belong to this new family of metabostemness

  17. Low temperature and defoliation affect fructan-metabolizing enzymes in different regions of the rhizophores of Vernonia herbacea.

    PubMed

    Portes, Maria Teresa; Figueiredo-Ribeiro, Rita de Cássia L; de Carvalho, Maria Angela M

    2008-10-01

    In addition to the storage function, fructans in Asteraceae from floras with seasonal growth have been associated with drought and freezing tolerance. Vernonia herbacea, native of the Brazilian Cerrado, bears underground reserve organs, rhizophores, accumulating inulin-type fructans. The rhizophore is a cauline branched system with positive geotropic growth, with the apex (distal region) presenting younger tissues; sprouting of new shoots occurs by development of buds located on the opposite end (proximal region). Plants induced to sprouting by excision of the aerial organs present increased 1-fructan exohydrolase (1-FEH) activity in the proximal region, while plants at the vegetative stage present high 1-sucrose:sucrose fructosyltransferase (1-SST) in the distal region. The aim of the present study was to analyze how low temperature (5 degrees C) could affect fructan-metabolizing enzymes and fructan composition in the different regions of the rhizophores of intact and excised plants. 1-SST and 1-fructan:fructan fructosyltransferase (1-FFT) were higher in the distal region decreasing towards the proximal region in intact plants at the vegetative phase, and were drastically diminished when cold and/or excision were imposed. In contrast, 1-FEH increased in the proximal region of treated plants, mainly in excised plants subjected to cold. The ratio fructo-oligo to fructo-polysaccharides was significantly higher in plants exposed to low temperature (1.17 in intact plants and 1.64 in excised plants) than in plants exposed to natural temperature conditions (0.84 in intact vegetative plants and 0.58 in excised plants), suggesting that oligosaccharides are involved in the tolerance of plants to low temperature via 1-FEH, in addition to 1-FFT. Principal component analysis indicated different response mechanisms in fructan metabolism under defoliation and low temperature, which could be interpreted as part of the strategies to undergo unfavorable environmental conditions

  18. In Vitro Fertilization Affects Growth and Glucose Metabolism in a Sex-Specific Manner in an Outbred Mouse Model1

    PubMed Central

    Donjacour, Annemarie; Liu, Xiaowei; Lin, Wingka; Simbulan, Rhodel; Rinaudo, Paolo F.

    2014-01-01

    ABSTRACT The preimplantation period is a time of reprogramming that may be vulnerable to disruption. This question has wide clinical relevance since the number of children conceived by in vitro fertilization (IVF) is rising. To examine this question, outbred mice (CF1 × B6D2F1) conceived by IVF and cultured using Whitten medium and 20% O2 (IVFWM group, less optimal) or K simplex optimized medium with amino acids and 5% O2 (IVFKAA group, more optimal and similar to conditions used in human IVF) were studied postnatally. We found that flushed blastocysts transferred to recipient mice provided the best control group (FB group), as this accounted for the effects of superovulation, embryo transfer, and litter size. We observed that many physiological parameters were normal. Reassuringly, IVFKAA offspring did not differ significantly from FB offspring. However, male IVFWM mice (but not females) were larger during the first 19 wk of life and exhibited glucose intolerance. Male IVFWM mice also showed enlarged left heart despite normal blood pressure. Expression of candidate imprinted genes (H19, Igf2, and Slc38a4) in multiple adult tissues did not show differences among the groups; only Slc38a4 was down-regulated following IVF (in both culture conditions) in female adipose tissue. These studies demonstrate that adult metabolism is affected by the type of conditions encountered during the preimplantation stage. Further, the postnatal growth trajectory and glucose homeostasis following ex vivo manipulation may be sexual dimorphic. Future work on the long-term effects of IVF offspring should focus on glucose metabolism and the cardiovascular system. PMID:24621920

  19. Rhodanese functions as sulfur supplier for key enzymes in sulfur energy metabolism.

    PubMed

    Aussignargues, Clément; Giuliani, Marie-Cécile; Infossi, Pascale; Lojou, Elisabeth; Guiral, Marianne; Giudici-Orticoni, Marie-Thérèse; Ilbert, Marianne

    2012-06-01

    How microorganisms obtain energy is a challenging topic, and there have been numerous studies on the mechanisms involved. Here, we focus on the energy substrate traffic in the hyperthermophilic bacterium Aquifex aeolicus. This bacterium can use insoluble sulfur as an energy substrate and has an intricate sulfur energy metabolism involving several sulfur-reducing and -oxidizing supercomplexes and enzymes. We demonstrate that the cytoplasmic rhodanese SbdP participates in this sulfur energy metabolism. Rhodaneses are a widespread family of proteins known to transfer sulfur atoms. We show that SbdP has also some unusual characteristics compared with other rhodaneses; it can load a long sulfur chain, and it can interact with more than one partner. Its partners (sulfur reductase and sulfur oxygenase reductase) are key enzymes of the sulfur energy metabolism of A. aeolicus and share the capacity to use long sulfur chains as substrate. We demonstrate a positive effect of SbdP, once loaded with sulfur chains, on sulfur reductase activity, most likely by optimizing substrate uptake. Taken together, these results lead us to propose a physiological role for SbdP as a carrier and sulfur chain donor to these key enzymes, therefore enabling channeling of sulfur substrate in the cell as well as greater efficiency of the sulfur energy metabolism of A. aeolicus. PMID:22496367

  20. Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*

    PubMed Central

    Carrer, Michele; Liu, Ning; Grueter, Chad E.; Williams, Andrew H.; Frisard, Madlyn I.; Hulver, Matthew W.; Bassel-Duby, Rhonda; Olson, Eric N.

    2012-01-01

    Obesity and metabolic syndrome are associated with mitochondrial dysfunction and deranged regulation of metabolic genes. Peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) is a transcriptional coactivator that regulates metabolism and mitochondrial biogenesis through stimulation of nuclear hormone receptors and other transcription factors. We report that the PGC-1β gene encodes two microRNAs (miRNAs), miR-378 and miR-378*, which counterbalance the metabolic actions of PGC-1β. Mice genetically lacking miR-378 and miR-378* are resistant to high-fat diet-induced obesity and exhibit enhanced mitochondrial fatty acid metabolism and elevated oxidative capacity of insulin-target tissues. Among the many targets of these miRNAs, carnitine O-acetyltransferase, a mitochondrial enzyme involved in fatty acid metabolism, and MED13, a component of the Mediator complex that controls nuclear hormone receptor activity, are repressed by miR-378 and miR-378*, respectively, and are elevated in the livers of miR-378/378* KO mice. Consistent with these targets as contributors to the metabolic actions of miR-378 and miR-378*, previous studies have implicated carnitine O-acetyltransferase and MED13 in metabolic syndrome and obesity. Our findings identify miR-378 and miR-378* as integral components of a regulatory circuit that functions under conditions of metabolic stress to control systemic energy homeostasis and the overall oxidative capacity of insulin target tissues. Thus, these miRNAs provide potential targets for pharmacologic intervention in obesity and metabolic syndrome. PMID:22949648

  1. Altered feeding differentially regulates circadian rhythms and energy metabolism in liver and muscle of rats.

    PubMed

    Reznick, Jane; Preston, Elaine; Wilks, Donna L; Beale, Susan M; Turner, Nigel; Cooney, Gregory J

    2013-01-01

    Energy metabolism follows a diurnal pattern responding to the light/dark cycle and food availability. This study investigated the impact of restricting feeding to the daylight hours and feeding a high fat diet on circadian clock (bmal1, dbp, tef and e4bp4) and metabolic (pepck, fas, ucp3, pdk4) gene expression and markers of energy metabolism in muscle and liver of rats. The results show that in chow-fed rats switched to daylight feeding, the peak diurnal expression of genes in liver was shifted by 6-12h while expression of these genes in muscle remained in a similar phase to rats feeding ad libitum. High fat feeding during the daylight hours had limited effect on clock gene expression in liver or muscle but shifted the peak expression of metabolic genes (pepck, fas) in liver by 6-12h. The differential effects of daylight feeding on gene and protein expression in muscle and liver were accompanied by an 8% reduction in whole body energy expenditure, a 20-30% increased glycogen content during the light phase in muscle of day-fed rats and increased adipose tissue deposition per gram food consumed. These data demonstrate that a mismatch of feeding and light/dark cycle disrupts tissue metabolism in muscle with significant consequences for whole body energy homeostasis. PMID:22952003

  2. Disrupting proton dynamics and energy metabolism for cancer therapy.

    PubMed

    Parks, Scott K; Chiche, Johanna; Pouysségur, Jacques

    2013-09-01

    Intense interest in the 'Warburg effect' has been revived by the discovery that hypoxia-inducible factor 1 (HIF1) reprogrammes pyruvate oxidation to lactic acid conversion; lactic acid is the end product of fermentative glycolysis. The most aggressive and invasive cancers, which are often hypoxic, rely on exacerbated glycolysis to meet the increased demand for ATP and biosynthetic precursors and also rely on robust pH-regulating systems to combat the excessive generation of lactic and carbonic acids. In this Review, we present the key pH-regulating systems and synthesize recent advances in strategies that combine the disruption of pH control with bioenergetic mechanisms. We discuss the possibility of exploiting, in rapidly growing tumours, acute cell death by 'metabolic catastrophe'. PMID:23969692

  3. Effect of simulated weightlessness on energy metabolism in the rat

    NASA Technical Reports Server (NTRS)

    Jordan, J. P.; Sykes, H. A.; Crownover, J. C.; Schatte, C. L.; Simmons, J. B., II; Jordan, D. P.

    1982-01-01

    Results of measurements of food uptake and body weight changes occurring in rats suspended from a harness so that the antigravity muscles were not used for locomotion are presented. The rats were tested in pairs, with both in a harness but only one suspended off its hind legs; this section lasted 7 days. A second phase of the experiment involved feeding the nonsuspended rat the same amount of food the experimental rat had consumed the previous day. All rats experienced decreased in body weight and food intake in the first stage, while in the second stage the suspended rat lost more weight. The total oxygen uptake, CO2 output, and rate of C-14O2 production were depressed in the suspended rats, then returned to normal levels once the rats were back on the ground. It is concluded that the gross metabolic processes are unaffected by simulated weightlessness.

  4. Role of Energy Metabolism in the Brown Fat Gene Program

    PubMed Central

    Nam, Minwoo; Cooper, Marcus P.

    2015-01-01

    In murine and human brown adipose tissue (BAT), mitochondria are powerful generators of heat that safely metabolize fat, a feature that has great promise in the fight against obesity and diabetes. Recent studies suggest that the actions of mitochondria extend beyond their conventional role as generators of heat. There is mounting evidence that impaired mitochondrial respiratory capacity is accompanied by attenuated expression of Ucp1 and other BAT-selective genes, implying that mitochondria exert transcriptional control over the brown fat gene program. In this review, we discuss the current understanding of brown fat mitochondria, their potential role in transcriptional control of the brown fat gene program, and potential strategies to treat obesity in humans by leveraging thermogenesis in brown adipocytes. PMID:26175716

  5. Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats.

    PubMed

    Ferreira, Gabriela Kozuchovski; Cardoso, Eria; Vuolo, Francieli Silva; Michels, Monique; Zanoni, Elton Torres; Carvalho-Silva, Milena; Gomes, Lara Mezari; Dal-Pizzol, Felipe; Rezin, Gislaine Tezza; Streck, Emilio L; Paula, Marcos Marques da Silva

    2015-12-01

    This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism. PMID:26583437

  6. 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

  7. Metabolic disruption in context: Clinical avenues for synergistic perturbations in energy homeostasis by endocrine disrupting chemicals

    PubMed Central

    Sargis, Robert M

    2015-01-01

    The global epidemic of metabolic disease is a clear and present danger to both individual and societal health. Understanding the myriad factors contributing to obesity and diabetes is essential for curbing their decades-long expansion. Emerging data implicate environmental endocrine disrupting chemicals (EDCs) in the pathogenesis of metabolic diseases such as obesity and diabetes. The phenylsulfamide fungicide and anti-fouling agent tolylfluanid (TF) was recently added to the list of EDCs promoting metabolic dysfunction. Dietary exposure to this novel metabolic disruptor promoted weight gain, increased adiposity, and glucose intolerance as well as systemic and cellular insulin resistance. Interestingly, the increase in body weight and adipose mass was not a consequence of increased food consumption; rather, it may have resulted from disruptions in diurnal patterns of energy intake, raising the possibility that EDCs may promote metabolic dysfunction through alterations in circadian rhythms. While these studies provide further evidence that EDCs may promote the development of obesity and diabetes, many questions remain regarding the clinical factors that modulate patient-specific consequences of EDC exposure, including the impact of genetics, diet, lifestyle, underlying disease, pharmacological treatments, and clinical states of fat redistribution. Currently, little is known regarding the impact of these factors on an individual’s susceptibility to environmentally-mediated metabolic disruption. Advances in these areas will be critical for translating EDC science into the clinic to enable physicians to stratify an individual’s risk of developing EDC-induced metabolic disease and to provide direction for treating exposed patients. PMID:27011951

  8. Intraspecies variation in BMR does not affect estimates of early hominin total daily energy expenditure.

    PubMed

    Froehle, Andrew W; Schoeninger, Margaret J

    2006-12-01

    We conducted a meta-analysis of 45 studies reporting basal metabolic rate (BMR) data for Homo sapiens and Pan troglodytes to determine the effects of sex, age, and latitude (a proxy for climate, in humans only). BMR was normalized for body size using fat-free mass in humans and body mass in chimpanzees. We found no effect of sex in either species and no age effect in chimpanzees. In humans, juveniles differed significantly from adults (ANCOVA: P < 0.001), and senescent adults differed significantly from adults younger than 50 years (P < 0.001). Europeans differed significantly from tropical populations (P < 0.001). On the basis of these observations, we derived new equations describing the relationship between BMR and body size, and used them to predict total daily energy expenditure (TEE) in four early hominin species. Our predictions concur with previous TEE estimates (i.e. Leonard and Robertson: Am J Phys Anthropol 102 (1997) 265-281), and support the conclusion that TEE increased greatly with H. erectus. Our results show that intraspecific variation in BMR does not affect TEE estimates for interspecific comparisons. Comparisons of more closely related groups such as humans and Neandertals, however, may benefit from consideration of this variation. PMID:16941603

  9. The workshop on energy development issues affecting Appalachia. Final report

    SciTech Connect

    Blaney, B.L.; Jelen, V.F.; Waldman, M.; Evans, J.; Bovee, R.

    1981-08-01

    This report describes the results of a workshop involving representatives of private industries, government agencies and public interest groups that was held in January of 1979 to raise and discuss issues related to Appalachian energy development.

  10. THE WORKSHOP ON ENERGY DEVELOPMENT ISSUES AFFECTING APPALACHIA

    EPA Science Inventory

    This report describes the results of a workshop involving representatives of private industries, government agencies and public interest groups that was held in January of 1979 to raise and discuss issues related to Appalachian energy development.

  11. Metabolism of acetyl-L-carnitine for energy and neurotransmitter synthesis in the immature rat brain

    PubMed Central

    Scafidi, Susanna; Fiskum, Gary; Lindauer, Steven L.; Bamford, Penelope; Shi, Da; Hopkins, Irene; McKenna, Mary C.

    2016-01-01

    Acetyl-L-carnitine (ALCAR) is an endogenous metabolic intermediate that facilitates the influx and efflux of acetyl groups across the mitochondrial inner membrane. Exogenously administered ALCAR has been used as a nutritional supplement and also as an experimental drug with reported neuroprotective properties and effects on brain metabolism. The aim of this study was to determine oxidative metabolism of ALCAR in the immature rat forebrain. Metabolism was studied in 21 day old rat brain at 15, 60 and 120 minutes after an intraperitoneal injection of [2-13C]acetyl-L-carnitine. The amount, pattern, and fractional enrichment of 13C-labeled metabolites were determined by ex vivo 13C-NMR spectroscopy. Metabolism of the acetyl moiety from [2-13C]ALCAR via the tricarboxylic acid (TCA) cycle led to incorporation of label into the C4, C3 and C2 positions of glutamate (GLU), glutamine (GLN) and GABA. Labeling patterns indicated that [2-13C]ALCAR was metabolized by both neurons and glia; however, the percent enrichment was higher in GLN and GABA than in GLU, demonstrating high metabolism in astrocytes and GABAergic neurons. Incorporation of label into the C3 position of alanine, both C3 and C2 of lactate, and the C1 and C5 positions of glutamate and glutamine demonstrated that [2-13C]ALCAR was actively metabolized via the pyruvate recycling pathway. The enrichment of metabolites with 13C from metabolism of ALCAR was highest in alanine C3 (10%) and lactate C3 (9%), with considerable enrichment in GABA C4 (8%), GLN C3 (~4%) and GLN C5 (5%). Overall, our 13C-NMR studies reveal that the acetyl moiety of ALCAR is metabolized for energy in both astrocytes and neurons and the label incorporated into the neurotransmitters glutamate and GABA. Cycling ratios showed prolonged cycling of carbon from the acetyl moiety of ALCAR in the TCA cycle. Labeling of compounds formed from metabolism of [2-13C]ALCAR via the pyruvate recycling pathway was higher than values reported for other

  12. Effects of mitoxantrone and doxorubicin on energy metabolism of the rat heart.

    PubMed

    Bachmann, E; Weber, E; Zbinden, G

    1987-04-01

    In animal models anthracyclines and anthracenediones show similar antineoplastic activity but somewhat different cardiotoxicity. The effects of doxorubicin and the free base of mitoxantrone (NSC-279836) on the energy metabolism of the rat heart were compared. Both compounds not only reduced oxygen consumption in heart mitochondria ex vivo, but also uncoupled oxidative phosphorylation, inhibited creatine phosphate kinase, and damaged the semipermeability of the inner mitochondrial membrane (measured as creatine influx). The effects on the myocyte membrane activities, calcium transport, and Na/K, Mg, and Ca ATPases were slightly different for the two compounds. Cardiotoxicity of the two compounds may have its origin in their interference with heart cell energy metabolism. PMID:3829012

  13. Influence of NO-containing gas flow on various parameters of energy metabolism in erythrocytes.

    PubMed

    Martusevich, A K; Solov'yova, A G; Peretyagin, S P; Karelin, V I; Selemir, V D

    2014-11-01

    We studied the influence of NO-containing gas phase on some parameters of energy metabolism in human erythrocytes. Whole blood samples were aerated with gas flows from the Plazon instrument (NO concentrations 800 and 80 ppm) and from the experimental generator (75 ppm). Activity of lactate dehydrogenase in direct and reverse reactions, lactate level, and a number of derived coefficients were estimated. Treatment of blood with 800 ppm NO inhibited erythrocyte energy metabolism, and its 10-fold dilution attenuated the effect. The use of ROS-free gas flow containing 75 ppm of NO promoted optimization of the process under investigation. PMID:25403392

  14. Kinetics of metabolism of glucose, propionate and CO2 in steers as affected by injecting phlorizin and feeding propionate

    SciTech Connect

    Veenhuizen, J.J.; Russell, R.W.; Young, J.W.

    1988-11-01

    Effects of injecting phlorizin subcutaneously and/or feeding propionate on metabolism of glucose, propionate and CO2 were determined for four steers used in a 4 x 4 Latin square design. Isotope dilution techniques were used to determine a four-pool kinetic solution for the flux of carbon among plasma glucose, rumen propionate, blood CO2 and rumen CO2. Injecting 1 g of phlorizin twice daily for 19 d resulted in 7.1 mol glucose C/d being excreted in urine. The basal glucose production of 13.4 mol C/d was increased to 17.9 mol C/d with phlorizin. There was no change in glucose oxidation or propionate production. The percentage of plasma glucose derived from propionate was unaffected by phlorizin, but 54 +/- 0.4% of total propionate was converted to plasma glucose during phlorizin treatment versus 40 +/- 0.6% during the basal treatment. When propionate was fed (18.3 mol C/d) glucose production increased to 21.2 mol C/d from the basal value of 13.4 mol C/d, and propionate oxidation to CO2 increased to 14.9 mol C/d from the basal value of 4.1 mol C/d. Glucose derived from propionate was 43 +/- 5% for the basal treatment and 67 +/- 3% during propionate feeding. The percentage of propionate converted to plasma glucose and blood and rumen CO2 was not affected by feeding propionate. An increased need for glucose, because of glucose excretion during phlorizin treatment, caused an increased utilization of propionate for gluconeogenesis, but an increased availability of propionate caused an increase in glucose production without affecting the relative distribution of carbon from propionate.

  15. Early life origins of metabolic disease: Developmental programming of hypothalamic pathways controlling energy homeostasis.

    PubMed

    Dearden, Laura; Ozanne, Susan E

    2015-10-01

    A wealth of animal and human studies demonstrate that perinatal exposure to adverse metabolic conditions - be it maternal obesity, diabetes or under-nutrition - results in predisposition of offspring to develop obesity later in life. This mechanism is a contributing factor to the exponential rise in obesity rates. Increased weight gain in offspring exposed to maternal obesity is usually associated with hyperphagia, implicating altered central regulation of energy homeostasis as an underlying cause. Perinatal development of the hypothalamus (a brain region key to metabolic regulation) is plastic and sensitive to metabolic signals during this critical time window. Recent research in non-human primate and rodent models has demonstrated that exposure to adverse maternal environments impairs the development of hypothalamic structure and consequently function, potentially underpinning metabolic phenotypes in later life. This review summarizes our current knowledge of how adverse perinatal environments program hypothalamic development and explores the mechanisms that could mediate these effects. PMID:26296796

  16. The Gustatory Signaling Pathway and Bitter Taste Receptors Affect the Development of Obesity and Adipocyte Metabolism in Mice

    PubMed Central

    Avau, Bert; Bauters, Dries; Steensels, Sandra; Vancleef, Laurien; Laermans, Jorien; Lesuisse, Jens; Buyse, Johan; Lijnen, H. Roger; Tack, Jan; Depoortere, Inge

    2015-01-01

    Intestinal chemosensory signaling pathways involving the gustatory G-protein, gustducin, and bitter taste receptors (TAS2R) have been implicated in gut hormone release. Alterations in gut hormone profiles may contribute to the success of bariatric surgery. This study investigated the involvement of the gustatory signaling pathway in the development of diet-induced obesity and the therapeutic potential of targeting TAS2Rs to induce body weight loss. α-gustducin-deficient (α-gust-/-) mice became less obese than wild type (WT) mice when fed a high-fat diet (HFD). White adipose tissue (WAT) mass was lower in α-gust-/- mice due to increased heat production as a result of increases in brown adipose tissue (BAT) thermogenic activity, involving increased protein expression of uncoupling protein 1. Intra-gastric treatment of obese WT and α-gust-/- mice with the bitter agonists denatonium benzoate (DB) or quinine (Q) during 4 weeks resulted in an α-gustducin-dependent decrease in body weight gain associated with a decrease in food intake (DB), but not involving major changes in gut peptide release. Both WAT and 3T3-F442A pre-adipocytes express TAS2Rs. Treatment of pre-adipocytes with DB or Q decreased differentiation into mature adipocytes. In conclusion, interfering with the gustatory signaling pathway protects against the development of HFD-induced obesity presumably through promoting BAT activity. Intra-gastric bitter treatment inhibits weight gain, possibly by directly affecting adipocyte metabolism. PMID:26692363

  17. Osteoblast-specific expression of Fra-2/AP-1 controls adiponectin and osteocalcin expression and affects metabolism.

    PubMed

    Bozec, Aline; Bakiri, Latifa; Jimenez, Maria; Rosen, Evan D; Catalá-Lehnen, Philip; Schinke, Thorsten; Schett, Georg; Amling, Michael; Wagner, Erwin F

    2013-12-01

    Recent studies have established that the skeleton functions as an endocrine organ affecting metabolism through the osteoblast-derived hormone osteocalcin (Ocn). However, it is not fully understood how many transcription factors expressed in osteoblasts regulate the endocrine function. Here, we show that mice with osteoblast-specific deletion of Fra-2 (Fosl2) have low bone mass but increased body weight. In contrast, transgenic expression of Fra-2 in osteoblasts leads to increased bone mass and decreased body weight accompanied by reduced serum glucose and insulin levels, improved glucose tolerance and insulin sensitivity. In addition, mice lacking Fra-2 have reduced levels of circulating Ocn, but high adiponectin (Adipoq), whereas Fra-2 transgenic mice exhibit high Ocn and low Adipoq levels. Moreover, we found that Adipoq was expressed in osteoblasts and that this expression was transcriptionally repressed by Fra-2. These results demonstrate that Fra-2 expression in osteoblasts represents a novel paradigm for a transcription factor controlling the endocrine function of the skeleton. PMID:24046454

  18. Placental Hypoxia Developed During Preeclampsia Induces Telocytes Apoptosis in Chorionic Villi Affecting The Maternal-Fetus Metabolic Exchange.

    PubMed

    Bosco, Cleofina Becerra; Díaz, Eugenia Guerra; Gutierrez, Rodrigo Rojas; González, Jaime Montero; Parra-Cordero, Mauro; Rodrigo, Ramón Salinas; Barja, Pilar Yañez

    2016-01-01

    Telocytes (TC) are a new type of stromal cells initially found and studied in digestive and extra- digestive organs. These cells have a small cell body with 2 to 5 thin and extremely long cytoplasmic prolongations named telopodes. In recent years, TC have also been described in placental chorionic villi, located in a strategical position between the smooth muscle cells from fetal vessels and the myofibroblasts in the stromal villi. Unlike other organs, the placenta is not innervated and considering the strategic location of TC is has been postulated that TC function would be related to signal transduction mechanisms involved in the regulation of the fetal vessels blood flow, as well as in the shortening/lengthening of the chorionic villi, providing the necessary rhythmicity to the process of maternal/fetal metabolic exchange. Preeclampsia (PE) is a systemic syndrome that affects 4%-6% of pregnancies worldwide. It is characterized by a placental state of ischemia-hypoxia which triggers an oxidative stress stage with the concomitant production of reactive oxygen species (ROS) leading to an increase in the degree of placental apoptosis. Placental vascular tone is regulated by the vasodilator nitric oxide (NO) and, in PE cases, NO is diverted towards the formation of peroxynitrite, a powerful oxidative agent whose activity leads to an increase of placental apoptosis degree that compromises TC and myofibroblasts, a key feature we would like to emphasize in this work. PMID:25643124

  19. A premature termination codon within an alternative exon affecting only the metabolism of transcripts that retain this exon.

    PubMed

    Maillet, P; Dalla Venezia, N; Lorenzo, F; Morinière, M; Bozon, M; Noël, B; Delaunay, J; Baklouti, F

    1999-01-01

    Protein 4.1 pre-mRNA splicing is regulated in tissue- and development-specific manners. Exon 16, which encodes the N-terminal region of the spectrin/actin-binding domain, is one of the alternatively spliced sequence motifs. It is present in late differentiated erythroid cells but absent from early erythroblasts and from lymphoid cells. We describe a single nucleotide deletion of the erythroid protein 4.1 gene associated with hereditary elliptocytosis. The deletion located in exon 16 leads to a frameshift and a premature termination codon within the same exon. In an effort to examine the premature stop codon effect in relationship with exon 16 alternative splicing, we analyzed erythroid and lymphoid protein 4.1 mRNAs using the mutation and a linked downstream polymorphism as markers. We found that the premature stop codon does not affect the tissue-specific alternative splicing among the two cell types analyzed and that the resulting alteration of mRNA metabolism correlates with the retention of exon 16 in reticulocytes. Conversely, skipping of exon 16 in lymphoid cells converts the mutant mRNA to a normal lymphoid-specific mRNA isoform, hence bypassing the nonsense codon. Consistent with data obtained on constitutive nonsense exons, our observations argue in favor of a stop codon recognition mechanism that occurs after the regulated splicing status of the nonsense exon has been achieved. PMID:10425037

  20. Effects of dietary energy and calcium levels on performance, egg shell quality and bone metabolism in hens.

    PubMed

    Jiang, Sha; Cui, Luying; Shi, Cheng; Ke, Xiao; Luo, Jingwen; Hou, Jiafa

    2013-10-01

    This study investigated the effects of dietary energy and calcium levels on laying performance, eggshell quality and bone metabolism of layers. One hundred and sixty-two 19-week-old Hy-Line brown laying hens in 54 battery cages were allocated to one of nine dietary treatments with control, middle and high levels of energy (11.50, 12.68 and 13.37 MJ/kg, respectively) and low, control and high levels of calcium (2.62%, 3.7% and 4.4%, respectively) for 60 days, using a 3 × 3 factorial arrangement. Compared with the control energy diet, high- and middle-energy diets increased fat deposition and egg weight, decreased feed intake and bone quality and had no effects on eggshell quality. The high-energy diet reduced the serum phosphate concentration and elevated osteocalcin mRNA expression in the keel bone without increasing osteocalcin protein. Dietary calcium intake did not affect fat deposition, feed intake or egg weight. Low dietary calcium resulted in weaker eggshells and poorer bone quality than that from hens fed the control diet. High dietary calcium increased serum calcium concentration, osteoprotegerin mRNA and osteocalcin protein and inhibited serum alkaline phosphatase activity and decreased its mRNA compared with low or control dietary calcium. The high-energy and high-calcium diet significantly reduced egg production. Compared with the control energy diet, high- and middle-energy diets increased fat deposition but had negative effects on bone metabolic homeostasis. Dietary calcium did not influence fat deposition but a high-calcium diet benefited bone homeostasis, while a low-calcium diet was associated with poorer eggshell quality and bone homeostasis. PMID:24054908

  1. Interleukin 1B genetic polymorphisms interact with polyunsaturated fatty acids to affect risk of the metabolic syndrome in the GOLDN Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic inflammation has been identified as an important component of the metabolic syndrome (MetS). Therefore, environmental and genetic factors contributing to the variation of inflammatory responses could affect individuals’ susceptibility to the MetS. We investigated the association between comm...

  2. 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

  3. Altered Energy Metabolism Pathways in the Posterior Cingulate in Young Adult Apolipoprotein E ɛ4 Carriers.

    PubMed

    Perkins, Michelle; Wolf, Andrew B; Chavira, Bernardo; Shonebarger, Daniel; Meckel, J P; Leung, Lana; Ballina, Lauren; Ly, Sarah; Saini, Aman; Jones, T Bucky; Vallejo, Johana; Jentarra, Garilyn; Valla, Jon

    2016-04-23

    The APOE gene, encoding apolipoprotein E, is the primary genetic risk factor for late-onset Alzheimer's disease (AD). Apolipoprotein E ɛ4 allele (APOE4) carriers have alterations in brain structure and function (as measured by brain imaging) even as young adults. Examination of this population is valuable in further identifying details of these functional changes and their association with vulnerability to AD decades later. Previous work demonstrates functional declines in mitochondrial activity in the posterior cingulate cortex, a key region in the default mode network, which appears to be strongly associated with functional changes relevant to AD risk. Here, we demonstrate alterations in the pathways underlying glucose, ketone, and mitochondrial energy metabolism. Young adult APOE4 carriers displayed upregulation of specific glucose (GLUT1 & GLUT3) and monocarboxylate (MCT2) transporters, the glucose metabolism enzyme hexokinase, the SCOT & AACS enzymes involved in ketone metabolism, and complexes I, II, and IV of the mitochondrial electron transport chain. The monocarboxylate transporter (MCT4) was found to be downregulated in APOE4 carriers. These data suggest that widespread dysregulation of energy metabolism in this at-risk population, even decades before possible disease onset. Therefore, these findings support the idea that alterations in brain energy metabolism may contribute significantly to the risk that APOE4 confers for AD. PMID:27128370

  4. Altered Energy Metabolism Pathways in the Posterior Cingulate in Young Adult Apolipoprotein E ɛ4 Carriers

    PubMed Central

    Perkins, Michelle; Wolf, Andrew B.; Chavira, Bernardo; Shonebarger, Daniel; Meckel, J.P.; Leung, Lana; Ballina, Lauren; Ly, Sarah; Saini, Aman; Jones, T. Bucky; Vallejo, Johana; Jentarra, Garilyn; Valla, Jon

    2016-01-01

    The APOE gene, encoding apolipoprotein E, is the primary genetic risk factor for late-onset Alzheimer’s disease (AD). Apolipoprotein E ɛ4 allele (APOE4) carriers have alterations in brain structure and function (as measured by brain imaging) even as young adults. Examination of this population is valuable in further identifying details of these functional changes and their association with vulnerability to AD decades later. Previous work demonstrates functional declines in mitochondrial activity in the posterior cingulate cortex, a key region in the default mode network, which appears to be strongly associated with functional changes relevant to AD risk. Here, we demonstrate alterations in the pathways underlying glucose, ketone, and mitochondrial energy metabolism. Young adult APOE4 carriers displayed upregulation of specific glucose (GLUT1 & GLUT3) and monocarboxylate (MCT2) transporters, the glucose metabolism enzyme hexokinase, the SCOT & AACS enzymes involved in ketone metabolism, and complexes I, II, and IV of the mitochondrial electron transport chain. The monocarboxylate transporter (MCT4) was found to be downregulated in APOE4 carriers. These data suggest that widespread dysregulation of energy metabolism in this at-risk population, even decades before possible disease onset. Therefore, these findings support the idea that alterations in brain energy metabolism may contribute significantly to the risk that APOE4 confers for AD. PMID:27128370

  5. Factors affecting the energy consumption of two refrigerator-freezers

    SciTech Connect

    Kao, J.Y.; Kelley, G.E.

    1996-12-31

    Two refrigerator-freezers, one with a top-mounted freezer and one with side-by-side doors, were tested in the laboratory to determine the sensitivity of their energy consumption to various operational factors. Room temperature, room humidity, door openings, and the setting of the anti-sweat heater switch were the factors examined. The results indicated that the room temperature and door openings had a significantly greater effect on energy consumption than the other two factors. More detailed tests were then performed under different room temperature and door-opening combinations. The relationship of door openings and the equivalent test room temperature was established. Finally, the effect on energy of different temperature settings was studied. Test results are presented and discussed.

  6. Energy metabolism in developing chicken lymphocytes is altered during the embryonic to posthatch transition.

    PubMed

    Rudrappa, Shashidhara G; Humphrey, Brooke D

    2007-02-01

    Adequate energy status in lymphocytes is vital for their development. The ability of developing chicken lymphocytes to acquire and metabolize energy substrates was determined during embryonic days (e) and neonatal days (d) of life when primary-energy substrate metabolism is altered at the whole-animal level. In 3 experiments, bursacytes and thymocytes were isolated on e17, e20, d1, d3, d7, or d14 to analyze markers associated with glucose, glutamine, and lipid metabolism. Bursacyte glucose transporter-3 (Glut-3) mRNA abundance increased from d1 to d14 and hexokinase-1 (HK-1) mRNA abundance was maximum on e20 (P<0.05). Thymocyte Glut-1, Glut-3, and HK-1 mRNA abundance increased from e17 to d14 (P<0.05). HK enzyme activity increased from e20 to d3 in bursacytes and d3 to d7 in thymocytes (P<0.05). Glucose uptake by bursacytes and thymocytes was greater on d14 compared to d1 and d7 (P<0.05). Bursacyte and thymocyte sodium coupled neutral amino acid transporter-2 and glutaminase (GA) mRNA abundance increased from e20 to d7 (P<0.05). GA enzyme activity increased from e20 to d7 in bursacytes (P<0.05) and did not change in thymocytes. Carnitine palmitoyl transferase enzyme activity did not change over time in either cell type. These studies suggest that developing B and T lymphocytes adapt their metabolism during the first 2 wk after hatch. Developing lymphocytes increase glucose metabolism with no change in fatty acid metabolism and bursacytes, but not thymocytes, increase glutamine metabolism. Understanding the factors that regulate lymphocyte development in neonatal chicks may help promote their adaptive immune responses to pathogens in early life. PMID:17237322

  7. Global energy issues affecting aeronautics: a reasoned conjecture

    NASA Astrophysics Data System (ADS)

    Allen, John E.

    1999-07-01

    This paper is a reasoned conjecture of the future up to 2050 AD including estimates of energy supply and consumption, transport system developments and corresponding pollution effects. Results of the logistic substitution methods (Volterra-Lotka) are used in forecasting trends in innovation, transport and energy. Later work on normative forecasts is also included. The future of aeronautics cannot be isolated from events in other transport modes which together create the major problem of crude oil replacement during the next century. Natural gas will be the dominant energy source for the next 80 years and a major question is how best to use it for aviation. The work on which this paper is based was started in 1992 to answer the following questions: Is the future oil shortfall sufficient to restrict aviation traffic and growth in the next 50 years? If so, what is its substitute? Can a substitute be obtained cheaply enough to free aviation from future kerosine shortages? Is it paramount to change to liquid hydrogen fuel to avoid future fuel shortage in aeronautics, incidentally conferring possible environmental advantages? There was no adequate evidence available to answer these questions, hence a method was devised to bring together several sets of partial data that contributed to the solution. The essence is to use the mean annual growth rate of traffic or energy over a future period as a pseudo-independent variable. This allows the inclusion of alternative high and low estimates of all the important quantities involved.

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

    PubMed Central

    Jansen, S. W.; Akintola, A. A.; Roelfsema, F.; van der Spoel, E.; Cobbaert, C. M.; Ballieux, B. E.; Egri, P.; Kvarta-Papp, Z.; Gereben, B.; Fekete, C.; Slagboom, P. E.; van der Grond, J.; Demeneix, B. A.; Pijl, H.; Westendorp, R. G. J.; van Heemst, D.

    2015-01-01

    Few studies have included subjects with the propensity to reach old age in good health, with the aim to disentangle mechanisms contributing to staying healthier for longer. The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating levels of thyroid stimulating hormone (TSH) and thyroid hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis may favour longevity without altering energy metabolism. PMID:26089239

  9. Degradation of IF1 controls energy metabolism during osteogenic differentiation of stem cells

    PubMed Central

    Sánchez-Aragó, María; García-Bermúdez, Javier; Martínez-Reyes, Inmaculada; Santacatterina, Fulvio; Cuezva, José M

    2013-01-01

    Differentiation of human mesenchymal stem cells (hMSCs) requires the rewiring of energy metabolism. Herein, we demonstrate that the ATPase inhibitory factor 1 (IF1) is expressed in hMSCs and in prostate and colon stem cells but is not expressed in the differentiated cells. IF1 inhibits oxidative phosphorylation and regulates the activity of aerobic glycolysis in hMSCs. Silencing of IF1 in hMSCs mimics the metabolic changes observed in osteocytes and accelerates cellular differentiation. Activation of IF1 degradation acts as the switch that regulates energy metabolism during differentiation. We conclude that IF1 is a stemness marker important for maintaining the quiescence state. PMID:23722655

  10. Socioeconomic Factors Affecting Household Energy Consumption in Qom, Iran

    NASA Astrophysics Data System (ADS)

    Mehrzad, Ebrahimi; Masoud, Alizadeh; Mansour, Ebrahimi

    Petrol is heavily subsidized in Iran which has led both to very high consumption levels and a big smuggling problem as petrol is transported out of Iran's border areas for re-sale in neighboring countries, where petrol prices are much higher. Also, a shortage of refineries combined with wasteful consumption means that Iran regularly imports petrol despite being one of the world's biggest oil producers. To look at the different variables contributing to wasteful consumption of fuel in Iran and the effect of governmental gradual increase of fuel prices, this study questioned 600 family warden views in Qom, Iran. The results showed that more than two third of samples have heard or read at least one news about energy saving and quoted TV as main source of their information while 55% mentioned all fossils resources would be finish in near future and urged optimum energy consumption as the best way to tackle energy crisis (82%), with 85% asked for more media propagation to change wrong cultural behaviors in Qom. Nearly half of the people said that governmental plan to increase domestic price of high octane and regular gasoline annually had little or no effect on fuel consumption and majority of them mentioned cultural changes as the best tools and nearly the same rate were worried about air pollution as the immediate result of uncontrolled fuel consumption in Qom. The results also showed that with increase in each year education of family warden, decreases fuel expenses 11.2% in hot seasons and 1240000 Iranian Rials (IR-R) in cold seasons while increase in family members' size adds 288660 (IR-R) per member to base family size (2) and for each member of family which works outside the house, family energy expenses increase 234470 IR-R. And finally the results showed fuel (or energy) expenses in cold months in Qom is higher than other months and family warden education showed more effect to reduce those expenses during mild months but less during hot months. Therefore it is

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

    PubMed

    Bhasin, Manoj K; Dusek, Jeffery A; Chang, Bei-Hung; Joseph, Marie G; Denninger, John W; Fricchione, Gregory L; Benson, Herbert; Libermann, Towia A

    2013-01-01

    The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress. PMID:23650531

  12. Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice.

    PubMed

    Kliewer, Kara L; Ke, Jia-Yu; Tian, Min; Cole, Rachel M; Andridge, Rebecca R; Belury, Martha A

    2015-01-01

    Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia - before severe fat loss - in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34-42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A - activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition. PMID:25457061

  13. Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    HIV infection is associated with abnormal lipid metabolism, body fat redistribution, and altered energy expenditure. The pathogenesis of these complex abnormalities is unclear. Viral protein R (Vpr), an HIV-1 accessory protein, can regulate gene transcription mediated by the glucocorticoid receptor ...

  14. The cancer cell 'energy grid': TGF-β1 signaling coordinates metabolism for migration.

    PubMed

    Jiang, Lei; Deberardinis, Ralph; Boothman, David A

    2015-01-01

    Cancer cells have an increased reliance on lipogenesis, which is required for uncontrolled cell division. We recently reported transcriptional and functional 'reprogramming' of the cellular energy grid, allowing cancer cells to divert metabolism from biosynthesis to bioenergetic pathways and thus supplying enhanced mobility during epithelial-mesenchymal transition (EMT) induced by transforming growth factor β (TGF-β1) (Fig. 1). PMID:27308459

  15. EFFECTS OF CONTINUOUS-WAVE, PULSED, AND SINUSOIDAL-AMPLITUDE-MODULATED MICROWAVES ON BRAIN ENERGY METABOLISM

    EPA Science Inventory

    A comparison of the effects of continuous wave, sinusoidal-amplitude modulated, and pulsed square-wave-modulated 591-MHz microwave exposures on brain energy metabolism was made in male Sprague Dawley rats (175-225g). Brain NADH fluorescence, adensine triphosphate (ATP) concentrat...

  16. CHANGES IN THE PHYSIOLOGICAL PERFORMANCE AND ENERGY METABOLISM OF AN ESTUARINE MYSID

    EPA Science Inventory

    Measures of physiological performance and energy metabolism were made on an estuarine mysid (Mysidopsis bahia) exposed throughout a life cycle to the defoliant DEF. EF concentrations > 0.246 ug/l reduced survival through release of the first brood. oung production was completely ...

  17. Hepatic ERK activity plays a role in energy metabolism.

    PubMed

    Jiao, Ping; Feng, Bin; Li, Yujie; He, Qin; Xu, Haiyan

    2013-08-15

    Mitogen activated protein kinases (MAPKs), such as c-Jun N-terminal kinase (JNK) and P38, have been reported to play important roles in energy homeostasis. In this study, we show that the activity of extracellular signal-regulated kinase (ERK) is increased in the livers of diet induced and genetically obese mice. Activation of ERK in the livers of lean mice by over-expressing the constitutively active MAPK kinase 1 (MEK CA) results in decreased energy expenditure, lowered expression of genes involved in fatty acid oxidation, increases fasting hyperglycemia and causes systemic insulin resistance. Interestingly, hepatic glycogen content is markedly increased and expression of G6Pase gene is decreased in mice over-expressing MEK CA compared to control mice expressing green fluorescent protein (GFP), therefore hepatic glucose output is not likely the major contributor of hyperglycemia. One potential mechanism of decreased expression of G6Pase gene by MEK CA is likely due to ERK mediated phosphorylation and cytosolic retention of FOXO1. Adipocytes isolated from MEK CA mice display increased lipolysis. Circulating levels of free fatty acids (FFAs) in these mice are also increased, which possibly contribute to systemic insulin resistance and subsequent hyperglycemia. Consistent with these results, knocking down ERK expression in the liver of diet induced obese (DIO) mice improves systemic insulin and glucose tolerance. These results indicate that increased hepatic ERK activity in DIO mice may contribute to increased liver glycogen content and decreased energy expenditure in obesity. PMID:23732116

  18. Metabolic Restructuring during Energy-Limited States: Insights from Artemia franciscana Embryos and Other Animals

    PubMed Central

    Hand, Steven C.; Menze, Michael A.; Borcar, Apu; Patil, Yuvraj; Covi, Joseph A.; Reynolds, Julie A.; Toner, Mehmet

    2011-01-01

    Many life history stages of animals that experience environmental insults enter developmental arrested states that are characterized by reduced cellular proliferation, with or without a concurrent reduction in overall metabolism. In the case of the most profound metabolic arrest reported in invertebrates, i.e., anaerobic quiescence in Artemia franciscana embryos, acidification of the intracellular milieu is a major factor governing catabolic and anabolic downregulation. Release of ion gradients from intracellular compartments is the source for approximately 50% of the proton equivalents needed for the 1.5 unit acidification that is observed. Recovery from the metabolic arrest requires re-sequestration of the protons with a vacuolar-type ATPase (V-ATPase). The remarkable facet of this mechanism is the ability of embryonic cells to survive the dissipation of intracellular ion gradients. Across many diapause-like states, the metabolic reduction and subsequent matching of energy demand is accomplished by shifting energy metabolism from oxidative phosphorylation to aerobic glycolysis. Molecular pathways that are activated to induce these resilient hypometabolic states include stimulation of the AMP-activated protein kinase (AMPK) and insulin signaling via suite of daf (dauer formation) genes for diapause-like states in nematodes and insects. Contributing factors for other metabolically-depressed states involve hypoxia-inducible factor-1 and downregulation of the pyruvate dehydrogenase complex. Metabolic similarities between natural states of stasis and some cancer phenotypes are noteworthy. Reduction of flux through oxidative phosphorylation helps prevent cell death in certain cancer types, similar to the way it increases viability of dauer stages in Caenorhabditis elegans. Mechanisms that underlie natural stasis are being used to precondition mammalian cells prior to cell biostabilization and storage. PMID:21335009

  19. Eyeless Mexican cavefish save energy by eliminating the circadian rhythm in metabolism.

    PubMed

    Moran, Damian; Softley, Rowan; Warrant, Eric J

    2014-01-01

    The eyed surface form and eyeless cave form of the Mexican tetra Astyanax mexicanus experience stark differences in the daily periodicities of light, food and predation, factors which are likely to have a profound influence on metabolism. We measured the metabolic rate of Pachón cave and surface fish at a fixed swimming speed under light/dark and constant dark photoperiods. In constant darkness surface forms exhibited a circadian rhythm in metabolism with an increase in oxygen demand during the subjective daytime, whereas cave forms did not. The lack of circadian rhythm in metabolism leads to a 27% energy savings for Pachón cave fish compared to surface fish when comparing both forms in their natural photoperiods. When surface forms were tested under constant dark conditions they expended 38% more energy than cave forms under equivalent conditions. Elimination of the circadian rhythm in metabolism may be a general feature of animals that live in perpetually dark food-limited environments such as caves or the deep sea. PMID:25251018

  20. Eyeless Mexican Cavefish Save Energy by Eliminating the Circadian Rhythm in Metabolism

    PubMed Central

    Moran, Damian; Softley, Rowan; Warrant, Eric J.

    2014-01-01

    The eyed surface form and eyeless cave form of the Mexican tetra Astyanax mexicanus experience stark differences in the daily periodicities of light, food and predation, factors which are likely to have a profound influence on metabolism. We measured the metabolic rate of Pachón cave and surface fish at a fixed swimming speed under light/dark and constant dark photoperiods. In constant darkness surface forms exhibited a circadian rhythm in metabolism with an increase in oxygen demand during the subjective daytime, whereas cave forms did not. The lack of circadian rhythm in metabolism leads to a 27% energy savings for Pachón cave fish compared to surface fish when comparing both forms in their natural photoperiods. When surface forms were tested under constant dark conditions they expended 38% more energy than cave forms under equivalent conditions. Elimination of the circadian rhythm in metabolism may be a general feature of animals that live in perpetually dark food-limited environments such as caves or the deep sea. PMID:25251018

  1. Energy metabolism during larval development of green and white abalone, Haliotis fulgens and H. sorenseni.

    PubMed

    Moran, Amy L; Manahan, Donal T

    2003-06-01

    An understanding of the biochemical and physiological energetics of lecithotrophic development is useful for interpreting patterns of larval development, dispersal potential, and life-history evolution. This study investigated the metabolic rates and use of biochemical reserves in two species of abalone, Haliotis fulgens (the green abalone) and H. sorenseni (the white abalone). Larvae of H. fulgens utilized triacylglycerol as a primary source of endogenous energy reserves for development ( approximately 50% depletion from egg to metamorphic competence). Amounts of phospholipid remained constant, and protein dropped by about 30%. After embryogenesis, larvae of H. fulgens had oxygen consumption rates of 81.7 +/- 5.9 (SE) pmol larva(-1) h(-1) at 15 degrees C through subsequent development. The loss of biochemical reserves fully met the needs of metabolism, as measured by oxygen consumption. Larvae of H. sorenseni were examined during later larval development and were metabolically and biochemically similar to H. fulgens larvae at a comparable stage. Metabolic rates of both species were very similar t