Sample records for affects energy metabolism

  1. Ibogaine affects brain energy metabolism.

    PubMed

    Paskulin, Roman; Jamnik, Polona; Zivin, Marko; Raspor, Peter; Strukelj, Borut

    2006-12-15

    Ibogaine is an indole alkaloid present in the root of the plant Tabernanthe iboga. It is known to attenuate abstinence syndrome in animal models of drug addiction. Since the anti-addiction effect lasts longer than the presence of ibogaine in the body, some profound metabolic changes are expected. The aim of this study was to investigate the effect of ibogaine on protein expression in rat brains. Rats were treated with ibogaine at 20 mg/kg body weight i.p. and subsequently examined at 24 and 72 h. Proteins were extracted from whole brain and separated by two-dimensional (2-D) electrophoresis. Individual proteins were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). Enzymes of glycolysis and tricarboxylic acid (TCA) cycle namely glyceraldehyde-3-phosphate dehydrogenase, aldolase A, pyruvate kinase and malate dehydrogenase were induced. The results suggest that the remedial effect of ibogaine could be mediated by the change in energy availability. Since energy dissipating detoxification and reversion of tolerance to different drugs of abuse requires underlying functional and structural changes in the cell, higher metabolic turnover would be favourable. Understanding the pharmacodynamics of anti-addiction drugs highlights the subcellular aspects of addiction diseases, in addition to neurological and psychological perspectives.

  2. Olanzapine and aripiprazole differentially affect glucose uptake and energy metabolism in human mononuclear blood cells.

    PubMed

    Stapel, Britta; Kotsiari, Alexandra; Scherr, Michaela; Hilfiker-Kleiner, Denise; Bleich, Stefan; Frieling, Helge; Kahl, Kai G

    2017-05-01

    The use of antipsychotics carries the risk of metabolic side effects, such as weight gain and new onset type-2 diabetes mellitus. The mechanisms of the observed metabolic alterations are not fully understood. We compared the effects of two atypical antipsychotics, one known to favor weight gain (olanzapine), the other not (aripiprazole), on glucose metabolism. Primary human peripheral blood mononuclear cells (PBMC) were isolated and stimulated with olanzapine or aripiprazole for 72 h. Cellular glucose uptake was analyzed in vitro by 18F-FDG uptake. Further measurements comprised mRNA expression of glucose transporter (GLUT) 1 and 3, GLUT1 protein expression, DNA methylation of GLUT1 promoter region, and proteins involved in downstream glucometabolic processes. We observed a 2-fold increase in glucose uptake after stimulation with aripiprazole. In contrast, olanzapine stimulation decreased glucose uptake by 40%, accompanied by downregulation of the cellular energy sensor AMP activated protein kinase (AMPK). GLUT1 protein expression increased, GLUT1 mRNA expression decreased, and GLUT1 promoter was hypermethylated with both antipsychotics. Pyruvat-dehydrogenase (PDH) complex activity decreased with olanzapine only. Our findings suggest that the atypical antipsychotics olanzapine and aripiprazole differentially affect energy metabolism in PBMC. The observed decrease in glucose uptake in olanzapine stimulated PBMC, accompanied by decreased PDH point to a worsening in cellular energy metabolism not compensated by AMKP upregulation. In contrast, aripiprazole stimulation lead to increased glucose uptake, while not affecting PDH complex expression. The observed differences may be involved in the different metabolic profiles observed in aripiprazole and olanzapine treated patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. High-fat diets affect energy and bone metabolism in growing rats.

    PubMed

    Macri, Elisa V; Gonzales Chaves, Macarena M; Rodriguez, Patricia N; Mandalunis, Patricia; Zeni, Susana; Lifshitz, Fima; Friedman, Silvia M

    2012-06-01

    High-fat diets are usually associated with greater weight (W) gain and body fat (BF). However, it is still unclear whether the type and amount of fat consumed influence BF. Additionally, dietary fat intake may also have consequences on skeletal health. To evaluate in healthy growing rats the effects of high-fat diets and type of dietary fat intake (saturated or vegetable oils) on energy and bone metabolism. At weaning, male Wistar rats (n = 50) were fed either a control diet (C; fat = 7% w/w) or a high-fat diet (20% w/w) containing either: soybean oil, corn oil (CO), linseed oil (LO), or beef tallow (BT) for 8 weeks. Zoometric parameters, BF, food intake and digestibility, and total and bone alkaline phosphatase (b-AP) were assessed. Total skeleton bone mineral density (BMD) and content (BMC), BMC/W, spine BMD, and bone volume (static-histomorphometry) were measured. Animals fed BT diet achieved lower W versus C. Rats fed high-fat vegetable oil diets showed similar effects on the zoometric parameters but differed in BF. BT showed the lowest lipid digestibility and BMC. In contrast, high vegetable oil diets produced no significant differences in BMC, BMC/W, BMD, spine BMD, and bone volume. Marked differences were observed for LO and BT groups in b-AP and CO and BT groups in bone volume. BT diet rich in saturated fatty acids had decreased digestibility and adversely affected energy and bone metabolisms, in growing healthy male rats. There were no changes in zoometric and bone parameters among rats fed high vegetable oil diets.

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

    PubMed Central

    Confavreux, Cyrille B

    2011-01-01

    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

  5. 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; Lanfray, Damien; 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. Copyright © 2016 the American Physiological Society.

  6. Energy metabolism and nutritional status in hospitalized patients with lung cancer.

    PubMed

    Takemura, Yumi; Sasaki, Masaya; Goto, Kenichi; Takaoka, Azusa; Ohi, Akiko; Kurihara, Mika; Nakanishi, Naoko; Nakano, Yasutaka; Hanaoka, Jun

    2016-09-01

    This study aimed to investigate the energy metabolism of patients with lung cancer and the relationship between energy metabolism and proinflammatory cytokines. Twenty-eight patients with lung cancer and 18 healthy controls were enrolled in this study. The nutritional status upon admission was analyzed using nutritional screening tools and laboratory tests. The resting energy expenditure and respiratory quotient were measured using indirect calorimetry, and the predicted resting energy expenditure was calculated using the Harris-Benedict equation. Energy expenditure was increased in patients with advanced stage disease, and there were positive correlations between measured resting energy expenditure/body weight and interleukin-6 levels and between measured resting energy expenditure/predicted resting energy expenditure and interleukin-6 levels. There were significant relationships between body mass index and plasma leptin or acylated ghrelin levels. However, the level of appetite controlling hormones did not affect dietary intake. There was a negative correlation between plasma interleukin-6 levels and dietary intake, suggesting that interleukin-6 plays a role in reducing dietary intake. These results indicate that energy expenditure changes significantly with lung cancer stage and that plasma interleukin-6 levels affect energy metabolism and dietary intake. Thus, nutritional management that considers the changes in energy metabolism is important in patients with lung cancer.

  7. Positive affect predicts cerebral glucose metabolism in late middle-aged adults

    PubMed Central

    Nicholas, Christopher R.; Hoscheidt, Siobhan M.; Clark, Lindsay R.; Racine, Annie M.; Berman, Sara E.; Koscik, Rebecca L.; Maritza Dowling, N.; Asthana, Sanjay; Christian, Bradley T.; Sager, Mark A.

    2017-01-01

    Abstract Positive affect is associated with a number of health benefits; however, few studies have examined the relationship between positive affect and cerebral glucose metabolism, a key energy source for neuronal function and a possible index of brain health. We sought to determine if positive affect was associated with cerebral glucose metabolism in late middle-aged adults (n = 133). Participants completed the positive affect subscale of the Center for Epidemiological Studies Depression Scale at two time points over a two-year period and underwent 18F-fluorodeoxyglucose-positron emission tomography scanning. After controlling for age, sex, perceived health status, depressive symptoms, anti-depressant use, family history of Alzheimer’s disease, APOE ε4 status and interval between visits, positive affect was associated with greater cerebral glucose metabolism across para-/limbic, frontal, temporal and parietal regions. Our findings provide evidence that positive affect in late midlife is associated with greater brain health in regions involved in affective processing and also known to be susceptible to early neuropathological processes. The current findings may have implications for interventions aimed at increasing positive affect to attenuate early neuropathological changes in at-risk individuals. PMID:28402542

  8. Astrocytes and energy metabolism.

    PubMed

    Prebil, Mateja; Jensen, Jørgen; Zorec, Robert; Kreft, Marko

    2011-05-01

    Astrocytes are glial cells, which play a significant role in a number of processes, including the brain energy metabolism. Their anatomical position between blood vessels and neurons make them an interface for effective glucose uptake from blood. After entering astrocytes, glucose can be involved in different metabolic pathways, e.g. in glycogen production. Glycogen in the brain is localized mainly in astrocytes and is an important energy source in hypoxic conditions and normal brain functioning. The portion of glucose metabolized into glycogen molecules in astrocytes is as high as 40%. It is thought that the release of gliotransmitters (such as glutamate, neuroactive peptides and ATP) into the extracellular space by regulated exocytosis supports a significant part of communication between astrocytes and neurons. On the other hand, neurotransmitter action on astrocytes has a significant role in brain energy metabolism. Therefore, understanding the astrocytes energy metabolism may help understanding neuron-astrocyte interactions.

  9. Effect of hemoglobin and immunization status on energy metabolism of weanling pigs.

    PubMed

    Gentry, J L; Swinkels, J W; Lindemann, M D; Schrama, J W

    1997-04-01

    We investigated the effect of (Hb) and immunization status on energy metabolism of newly weaned pigs. An additional focus of the study was to determine the development of circadian rhythms as evidenced by heat production patterns. Twenty-four 4-wk-old crossbred weanling barrows were placed into groups of three based on weight and litter origin, and the groups were allotted to one of four treatments. Treatments were arranged as a 2 x 2 factorial. The factors included 1) Hb status (low vs high) and 2) immunization status (antigen vs placebo). Hemoglobin status was obtained by injecting 3-d-old barrows with 100 (low) or 200 mg (high) of Fe. At 4 wk, initial blood Hb concentrations were 6.0 mM for the low group and 7.8 mM for the high group. Energy metabolism was measured using two weekly total energy and nitrogen balance collections. Energy intake and retention were higher (P < .05) in pigs with a high Hb level. Energy metabolism was not affected (P > .10) by immunization status, and heat production was not affected (P > .10) by either Hb or immunization status. Total heat production (HTOT) increased (P < .001) daily and reflected a daily increase (P < .001) in activity (HACT) and activity-free (HCOR) heat production. An increase (P < .001) in HTOT and HACT was detected for the light period compared with the dark period over the total experimental period but a decrease (P < .001) in HCOR was detected; however, HACT for the dark period was approximately half of that measured during the light period. In conclusion, Hb status affected energy metabolism; pigs having a high Hb status had a higher energy retention. Immunization status had minimal effects on energy metabolism and heat production. Additionally, the diurnal circadian rhythm seen in older pigs had not been established by 2 wk after weaning.

  10. Disruption of quercetin metabolism by fungicide affects energy production in honey bees (Apis mellifera).

    PubMed

    Mao, Wenfu; Schuler, Mary A; Berenbaum, May R

    2017-03-07

    Cytochrome P450 monooxygenases (P450) in the honey bee, Apis mellifera , detoxify phytochemicals in honey and pollen. The flavonol quercetin is found ubiquitously and abundantly in pollen and frequently at lower concentrations in honey. Worker jelly consumed during the first 3 d of larval development typically contains flavonols at very low levels, however. RNA-Seq analysis of gene expression in neonates reared for three days on diets with and without quercetin revealed that, in addition to up-regulating multiple detoxifying P450 genes, quercetin is a negative transcriptional regulator of mitochondrion-related nuclear genes and genes encoding subunits of complexes I, III, IV, and V in the oxidative phosphorylation pathway. Thus, a consequence of inefficient metabolism of this phytochemical may be compromised energy production. Several P450s metabolize quercetin in adult workers. Docking in silico of 121 pesticide contaminants of American hives into the active pocket of CYP9Q1, a broadly substrate-specific P450 with high quercetin-metabolizing activity, identified six triazole fungicides, all fungal P450 inhibitors, that dock in the catalytic site. In adults fed combinations of quercetin and the triazole myclobutanil, the expression of five of six mitochondrion-related nuclear genes was down-regulated. Midgut metabolism assays verified that adult bees consuming quercetin with myclobutanil metabolized less quercetin and produced less thoracic ATP, the energy source for flight muscles. Although fungicides lack acute toxicity, they may influence bee health by interfering with quercetin detoxification, thereby compromising mitochondrial regeneration and ATP production. Thus, agricultural use of triazole fungicides may put bees at risk of being unable to extract sufficient energy from their natural food.

  11. Disruption of quercetin metabolism by fungicide affects energy production in honey bees (Apis mellifera)

    PubMed Central

    Mao, Wenfu; Schuler, Mary A.; Berenbaum, May R.

    2017-01-01

    Cytochrome P450 monooxygenases (P450) in the honey bee, Apis mellifera, detoxify phytochemicals in honey and pollen. The flavonol quercetin is found ubiquitously and abundantly in pollen and frequently at lower concentrations in honey. Worker jelly consumed during the first 3 d of larval development typically contains flavonols at very low levels, however. RNA-Seq analysis of gene expression in neonates reared for three days on diets with and without quercetin revealed that, in addition to up-regulating multiple detoxifying P450 genes, quercetin is a negative transcriptional regulator of mitochondrion-related nuclear genes and genes encoding subunits of complexes I, III, IV, and V in the oxidative phosphorylation pathway. Thus, a consequence of inefficient metabolism of this phytochemical may be compromised energy production. Several P450s metabolize quercetin in adult workers. Docking in silico of 121 pesticide contaminants of American hives into the active pocket of CYP9Q1, a broadly substrate-specific P450 with high quercetin-metabolizing activity, identified six triazole fungicides, all fungal P450 inhibitors, that dock in the catalytic site. In adults fed combinations of quercetin and the triazole myclobutanil, the expression of five of six mitochondrion-related nuclear genes was down-regulated. Midgut metabolism assays verified that adult bees consuming quercetin with myclobutanil metabolized less quercetin and produced less thoracic ATP, the energy source for flight muscles. Although fungicides lack acute toxicity, they may influence bee health by interfering with quercetin detoxification, thereby compromising mitochondrial regeneration and ATP production. Thus, agricultural use of triazole fungicides may put bees at risk of being unable to extract sufficient energy from their natural food. PMID:28193870

  12. Metabolic energy required for flight

    NASA Astrophysics Data System (ADS)

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

    1994-11-01

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

  13. 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.

  14. Epilepsy and astrocyte energy metabolism.

    PubMed

    Boison, Detlev; Steinhäuser, Christian

    2018-06-01

    Epilepsy is a complex neurological syndrome characterized by neuronal hyperexcitability and sudden, synchronized electrical discharges that can manifest as seizures. It is now increasingly recognized that impaired astrocyte function and energy homeostasis play key roles in the pathogenesis of epilepsy. Excessive neuronal discharges can only happen, if adequate energy sources are made available to neurons. Conversely, energy depletion during seizures is an endogenous mechanism of seizure termination. Astrocytes control neuronal energy homeostasis through neurometabolic coupling. In this review, we will discuss how astrocyte dysfunction in epilepsy leads to distortion of key metabolic and biochemical mechanisms. Dysfunctional glutamate metabolism in astrocytes can directly contribute to neuronal hyperexcitability. Closure of astrocyte intercellular gap junction coupling as observed early during epileptogenesis limits activity-dependent trafficking of energy metabolites, but also impairs clearance of the extracellular space from accumulation of K + and glutamate. Dysfunctional astrocytes also increase the metabolism of adenosine, a metabolic product of ATP degradation that broadly inhibits energy-consuming processes as an evolutionary adaptation to conserve energy. Due to the critical role of astroglial energy homeostasis in the control of neuronal excitability, metabolic therapeutic approaches that prevent the utilization of glucose might represent a potent antiepileptic strategy. In particular, high fat low carbohydrate "ketogenic diets" as well as inhibitors of glycolysis and lactate metabolism are of growing interest for the therapy of epilepsy. © 2017 Wiley Periodicals, Inc.

  15. Top single nucleotide polymorphisms affecting carbohydrate metabolism in metabolic syndrome: from the LIPGENE study.

    PubMed

    Delgado-Lista, Javier; Perez-Martinez, Pablo; Solivera, Juan; Garcia-Rios, Antonio; Perez-Caballero, A I; Lovegrove, Julie A; Drevon, Christian A; Defoort, Catherine; Blaak, Ellen E; Dembinska-Kieć, Aldona; Risérus, Ulf; Herruzo-Gomez, Ezequiel; Camargo, Antonio; Ordovas, Jose M; Roche, Helen; Lopez-Miranda, José

    2014-02-01

    Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk. Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS. A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study. From 382 initial gene-phenotype associations between SNPs and any phenotypic variables, 61 (16% of the preselected variables) remained significant after bootstrapping. Top SNPs affecting glucose metabolism variables were as follows: fasting glucose, rs26125 (PPARGC1B); fasting insulin, rs4759277 (LRP1); C-peptide, rs4759277 (LRP1); homeostasis assessment of insulin resistance, rs4759277 (LRP1); quantitative insulin sensitivity check index, rs184003 (AGER); sensitivity index, rs7301876 (ABCC9), acute insulin response to glucose, rs290481 (TCF7L2); and disposition index, rs12691 (CEBPA). We describe here the top SNPs linked to phenotypic features in carbohydrate metabolism among approximately 1000 candidate gene variations in fasting and postprandial samples of 450 patients with MetS from the LIPGENE study.

  16. 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

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

    PubMed

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

    2010-08-11

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

  18. Energy Metabolism Impairment in Migraine.

    PubMed

    Cevoli, Sabina; Favoni, Valentina; Cortelli, Pietro

    2018-06-22

    Migraine is a common disabling neurological disorder which is characterised by recurring headache associated with a variety of sensory and autonomic symptoms. The pathophysiology of migraine remains not entirely understood, although many mechanisms involving the central and peripheral nervous system are now becoming clear. In particular, it is widely accepted that migraine is associated with energy metabolic impairment of the brain. The purpose of this review is to present an update overview of the energy metabolism involvement in the migraine pathophysiology. Several biochemical, morphological and magnetic resonance spectroscopy studies have confirmed the presence of energy production deficiency together with an increment of energy consumption in migraine patients. An increment of energy demand over a certain threshold create metabolic and biochemical preconditions for the onset of the migraine attack. The defect of oxidative energy metabolism in migraine is generalized. It remains to be determined if the mitochondrial deficit in migraine is primary or secondary. Riboflavin and Co-Enzyme Q10, both physiologically implicated in mitochondrial respiratory chain functioning, are effective in migraine prophylaxis, supporting the hypothesis that improving brain energy metabolism may reduce the susceptibility to migraine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. 4 Things That Affect Your Metabolism

    Cancer.gov

    Metabolism is how your body uses food as energy and then burns that energy to keep your body going. Even if you did nothing all day, your body would still need to use energy just to stay alive—for things like breathing and keeping your heart beating.

  20. 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

  1. Temperature, energy metabolism, and adaptive divergence in two oyster subspecies.

    PubMed

    Li, Ao; Li, Li; Song, Kai; Wang, Wei; Zhang, Guofan

    2017-08-01

    Comparisons of related species that have diverse spatial distributions provide an efficient way to investigate adaptive evolution in face of increasing global warming. The oyster subjected to high environmental selections is a model species as sessile marine invertebrate. This study aimed to detect the adaptive divergence of energy metabolism in two oyster subspecies from the genus Crassostrea - C. gigas gigas and C. gigas angulata -which are broadly distributed along the northern and southern coasts of China, respectively. We examined the effects of acute thermal stress on energy metabolism in two oyster subspecies after being common gardened for one generation in identical conditions. Thermal responses were assessed by incorporating physiological, molecular, and genomic approaches. Southern oysters exhibited higher fluctuations in metabolic rate, activities of key energetic enzymes, and levels of thermally induced gene expression than northern oysters. For genes involved in energy metabolism, the former displayed higher basal levels of gene expression and a more pronounced downregulation of thermally induced expression, while the later exhibited lower basal levels and a less pronounced downregulation of gene expression. Contrary expression pattern was observed in oxidative stress gene. Besides, energy metabolic tradeoffs were detected in both subspecies. Furthermore, the genetic divergence of a nonsynonymous SNP ( SOD-132 ) and five synonymous SNPs in other genes was identified and validated in these two subspecies, which possibly affects downstream functions and explains the aforementioned phenotypic variations. Our study demonstrates that differentiations in energy metabolism underlie the plasticity of adaptive divergence in two oyster subspecies and suggest C. gigas angulata with moderate phenotypic plasticity has higher adaptive potential to cope with exacerbated global warming.

  2. Atrogin-1 affects muscle protein synthesis and degradation when energy metabolism is impaired by the antidiabetes drug berberine.

    PubMed

    Wang, Huiling; Liu, Dajun; Cao, Peirang; Lecker, Stewart; Hu, Zhaoyong

    2010-08-01

    Defects in insulin/IGF-1 signaling stimulate muscle protein loss by suppressing protein synthesis and increasing protein degradation. Since an herbal compound, berberine, lowers blood levels of glucose and lipids, we proposed that it would improve insulin/IGF-1 signaling, blocking muscle protein losses. We evaluated whether berberine ameliorates muscle atrophy in db/db mice, a model of type 2 diabetes, by measuring protein synthesis and degradation in muscles of normal and db/db mice treated with or without berberine. We also examined mechanisms for berberine-induced changes in muscle protein metabolism. Berberine administration decreased protein synthesis and increased degradation in muscles of normal and db/db mice. The protein catabolic mechanism depended on berberine-stimulated expression of the E3 ubiquitin ligase, atrogin-1. Atrogin-1 not only increased proteolysis but also reduced protein synthesis by mechanisms that were independent of decreased phosphorylation of Akt or forkhead transcription factors. Impaired protein synthesis was dependent on a reduction in eIF3-f, an essential regulator of protein synthesis. Berberine impaired energy metabolism, activating AMP-activated protein kinase and providing an alternative mechanism for the stimulation of atrogin-1 expression. When we increased mitochondrial biogenesis by expressing peroxisome proliferator-activated receptor gamma coactivator-1alpha, berberine-induced changes in muscle protein metabolism were prevented. Berberine impairs muscle metabolism by two novel mechanisms. It impairs mitochonidrial function stimulating the expression of atrogin-1 without affecting phosphorylation of forkhead transcription factors. The increase in atrogin-1 not only stimulated protein degradation but also suppressed protein synthesis, causing muscle atrophy.

  3. The gut microbiota modulates host energy and lipid metabolism in mice[S

    PubMed Central

    Velagapudi, Vidya R.; Hezaveh, Rahil; Reigstad, Christopher S.; Gopalacharyulu, Peddinti; Yetukuri, Laxman; Islam, Sama; Felin, Jenny; Perkins, Rosie; Borén, Jan; Orešič, Matej; Bäckhed, Fredrik

    2010-01-01

    The gut microbiota has recently been identified as an environmental factor that may promote metabolic diseases. To investigate the effect of gut microbiota on host energy and lipid metabolism, we compared the serum metabolome and the lipidomes of serum, adipose tissue, and liver of conventionally raised (CONV-R) and germ-free mice. The serum metabolome of CONV-R mice was characterized by increased levels of energy metabolites, e.g., pyruvic acid, citric acid, fumaric acid, and malic acid, while levels of cholesterol and fatty acids were reduced. We also showed that the microbiota modified a number of lipid species in the serum, adipose tissue, and liver, with its greatest effect on triglyceride and phosphatidylcholine species. Triglyceride levels were lower in serum but higher in adipose tissue and liver of CONV-R mice, consistent with increased lipid clearance. Our findings show that the gut microbiota affects both host energy and lipid metabolism and highlights its role in the development of metabolic diseases. PMID:20040631

  4. Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation.

    PubMed

    Bélanger, Mireille; Allaman, Igor; Magistretti, Pierre J

    2011-12-07

    The energy requirements of the brain are very high, and tight regulatory mechanisms operate to ensure adequate spatial and temporal delivery of energy substrates in register with neuronal activity. Astrocytes-a type of glial cell-have emerged as active players in brain energy delivery, production, utilization, and storage. Our understanding of neuroenergetics is rapidly evolving from a "neurocentric" view to a more integrated picture involving an intense cooperativity between astrocytes and neurons. This review focuses on the cellular aspects of brain energy metabolism, with a particular emphasis on the metabolic interactions between neurons and astrocytes. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Energy metabolism in the liver.

    PubMed

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic function is controlled by insulin and other metabolic hormones. Glucose is converted into pyruvate through glycolysis in the cytoplasm, and pyruvate is subsequently oxidized in the mitochondria to generate ATP through the TCA cycle and oxidative phosphorylation. 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/or cholesterol esters in hepatocytes. These complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as very low-density lipoprotein particles. In the fasted state, the liver secretes glucose through both glycogenolysis and gluconeogenesis. During pronged fasting, hepatic gluconeogenesis is the primary source for endogenous glucose production. Fasting also promotes lipolysis in adipose tissue, resulting in release of nonesterified fatty acids which are converted into ketone bodies in hepatic mitochondria though β-oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver energy metabolism is tightly regulated by neuronal and hormonal signals. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis but suppresses gluconeogenesis, and 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 key steps of metabolic pathways, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases. © 2014 American Physiological Society.

  6. 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.

  7. Dietary carbohydrate deprivation increases 24-hour nitrogen excretion without affecting postabsorptive hepatic or whole body protein metabolism in healthy men.

    PubMed

    Bisschop, P H; De Sain-Van Der Velden, M G M; Stellaard, F; Kuipers, F; Meijer, A J; Sauerwein, H P; Romijn, J A

    2003-08-01

    Because insulin is an important regulator of protein metabolism, we hypothesized that physiological modulation of insulin secretion, by means of extreme variations in dietary carbohydrate content, affects postabsorptive protein metabolism. Therefore, we studied the effects of three isocaloric diets with identical protein content and low-carbohydrate/high-fat (2% and 83% of total energy, respectively), intermediate-carbohydrate/intermediate-fat (44% and 41% of total energy, respectively), and high-carbohydrate/low-fat (85% and 0% of total energy, respectively) content in six healthy men. Whole body protein metabolism was assessed by 24-h urinary nitrogen excretion, postabsorptive leucine kinetics, and fibrinogen and albumin synthesis by infusion of [1-(13)C]leucine and [1-(13)C]valine. The low-carbohydrate/high-fat diet resulted in lower absorptive and postabsorptive plasma insulin concentrations, and higher rates of nitrogen excretion compared with the other two diets: 15.3 +/- 0.9 vs. 12.1 +/- 1.1 (P = 0.03) and 10.8 +/- 0.5 g/24 h (P = 0.005), respectively. Postabsorptive rates of appearance of leucine and of leucine oxidation were not different among the three diets. In addition, dietary carbohydrate content did not affect the synthesis rates of fibrinogen and albumin. In conclusion, eucaloric carbohydrate deprivation increases 24-h nitrogen loss but does not affect postabsorptive protein metabolism at the hepatic and whole body level. By deduction, dietary carbohydrate is required for an optimal regulation of absorptive, rather than postabsorptive, protein metabolism.

  8. Interactions of the PPARγ2 polymorphism with fat intake affecting energy metabolism and nutritional outcomes in obese women.

    PubMed

    Rosado, Eliane L; Bressan, Josefina; Martínez, J Alfredo; Marques-Lopes, Iva

    2010-01-01

    To determine the influence of the Pro12Ala polymorphism of the PPARγ2 gene and the dietary lipid intake on energy metabolism and nutritional outcomes in obese women after an acute fat load or following a low-calorie diet for 10 weeks. Sixty obese women (aged 30-46 years) participated in the study and were assigned to 2 groups depending on the genotype: Pro12Pro and Pro12Ala/Ala12Ala carriers. At baseline and after 2 nutritional (short- or long-term) interventions, measurement of anthropometrical and body composition (bioelectrical impedance) variables, dietary assessments, energy metabolism (indirect calorimetry) measurements as well as biochemical and molecular (PPARγ2 genotype) analyses were performed. All women received a high-fat test meal to determine the postprandial metabolism (short term) and an energy-restricted diet for 10 weeks (long term). The frequencies of the Pro12Pro and Pro12Ala/Ala12Ala genotypes were 83.33 and 16.67%, respectively, and reached Hardy-Weinberg equilibrium. Interestingly, the postprandial energy expenditure after the fat load was higher in subjects carrying the Ala allele. At baseline, the habitual monounsaturated fatty acid (MUFA) intake inversely correlated with fat oxidation and body mass index in the obese Pro12Ala/Ala12Ala carriers, while a lower PUFA intake (%) in the long-term trial was associated with an increase in the respiratory quotient only in Ala carriers but not in the Pro12Pro genotyped group. The Pro12Ala polymorphism in the PPARγ2 gene influenced energy metabolism in the assayed short- and long-term situations since the response to both nutritional interventions differed according to the genotype. The results suggest that fat oxidation and energy expenditure may be lower in Pro12Pro carriers compared to Pro12Ala/Ala12Ala genotypes, while in obese women with Pro12Ala/Ala12Ala polymorphisms in the PPARγ2 gene fat oxidation was negatively correlated with the MUFA and PUFA (%) intake. Copyright © 2010 S. Karger AG

  9. 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

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

    PubMed

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

    2011-01-21

    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. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Gustatory perception and fat body energy metabolism are jointly affected by vitellogenin and juvenile hormone in honey bees.

    PubMed

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

    2012-06-01

    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.

  12. Mitochondrial energy metabolism in a model of undernutrition induced by dexamethasone

    PubMed Central

    Dumas, Jean-François; Simard, Gilles; Roussel, Damien; Douay, Olivier; Foussard, Françoise; Malthiery, Yves; Ritz, Patrick

    2003-01-01

    This investigation was undertaken to evaluate whether mitochondrial energy metabolism is altered in a malnutrition model associated with dexamethasone treatment (1.5mg/kg/day for 5 days). Gastrocnemius and liver mitochondria were isolated from dexamethasone (DEX)-treated, pair-fed (PF) and control (CON) rats. Body weight was significantly more reduced in DEX-treated group (−16%) than in PF group (−9%). Dexamethasone increased the liver mass (+59% vs. PF and +23% vs. CON) and decreased gastrocnemius mass. Moreover, in DEX-treated rats, liver mitochondria exhibited an increased rate of non-phosphorylative oxygen consumption with all substrates (approximately +42%). There was no difference in enzymatic complex activities in liver mitochondria between rat groups. Collectively, these results suggest an increased proton leak and/or redox slipping in liver mitochondria of DEX-treated rats. In addition, dexamethasone decreased the thermodynamic coupling and efficiency of oxidative phosphorylation. We therefore suggest that this increase in the proton leak and/or of redox slip in liver is responsible for the decrease in the thermodynamic efficiency of energy conversion. In contrast, none of the determined parameters of energy metabolism were altered by dexamethasone in gastrocnemius mitochondria. Therefore, it appears that dexamethasone specifically affects mitochondrial energy metabolism in liver. PMID:14667190

  13. Metabolic intervention to affect myocardial recovery following ischemia.

    PubMed Central

    Pasque, M K; Wechsler, A S

    1984-01-01

    Myocardial recovery during reperfusion following ischemia is critical to patient survival in a broad spectrum of clinical settings. Myocardial functional recovery following ischemia correlates well with recovery of myocardial adenosine triphosphate (ATP). Adenosine triphosphate recovery is uniformly incomplete during reperfusion following moderate ischemic injury and is therefore subject to manipulation by metabolic intervention. By definition ATP recovery is limited either by (1) energy availability and application in the phosphorylation of adenosine monophosphate (AMP) to ATP or (2) availability of AMP for this conversion. Experimental data suggest that substrate energy and the mechanisms required for its application in the creation of high energy phosphate bonds (AMP conversion to ATP) are more than adequate during reperfusion following moderate ischemic injury. Adenosine monophosphate availability, however, is inadequate following ischemia due to loss of diffusable adenine nucleotide purine metabolites. These purine precursors are necessary to fuel adenine nucleotide salvage pathways. Metabolic interventions that enhance AMP recovery rather than those that improve substrate energy availability during reperfusion are therefore recommended. The mechanisms of various metabolic interventions are discussed in this framework along with the rationale for or against their clinical application. PMID:6428332

  14. Spruce Budworm and Energy Metabolism?

    Treesearch

    Thakor R.  Patel

    1983-01-01

    The utilization of stored lipids (fat) for energy metabolism appears to be a fundamental process for many biological systems especially during the early stages of their development. The participation of the glyoxylate cycle (GOG) together with other metabolic sequences like gluconeogenesis and beta oxidation are necessary for the conversion of lipids to carbohydrates....

  15. Radiant heat affects thermoregulation and energy expenditure during rewarming from torpor.

    PubMed

    Geiser, F; Drury, R L

    2003-02-01

    The high expenditure of energy required for endogenous rewarming is one of the widely perceived disadvantages of torpor. However, recent evidence demonstrates that passive rewarming either by the increase of ambient temperature or by basking in the sun appears to be common in heterothermic birds and mammals. As it is presently unknown how radiant heat affects energy expenditure during rewarming from torpor and little is known about how it affects normothermic thermoregulation, we quantified the effects of radiant heat on body temperature and metabolic rate of the small (body mass 25 g) marsupial Sminthopsis macroura in the laboratory. Normothermic resting individuals exposed to radiant heat were able to maintain metabolic rates near basal levels (at 0.91 ml O(2) g(-1) h(-1)) and a constant body temperature down to an ambient temperature of 12 degrees C. In contrast, metabolic rates of individuals without access to radiant heat were 4.5-times higher at an ambient temperature of 12 degrees C and body temperature fell with ambient temperature. During radiant heat-assisted passive rewarming from torpor, animals did not employ shivering but appeared to maximise uptake of radiant heat. Their metabolic rate increased only 3.2-times with a 15- degrees C rise of body temperature (Q(10)=2.2), as predicted by Q(10) effects. In contrast, during active rewarming shivering was intensive and metabolic rates showed an 11.6-times increase. Although body temperature showed a similar absolute change between the beginning and the end of the rewarming process, the overall energetic cost during active rewarming was 6.3-times greater than that during passive, radiant heat-assisted rewarming. Our study demonstrates that energetic models assuming active rewarming from torpor at low ambient temperatures can substantially over-estimate energetic costs. The low energy expenditure during passive arousal provides an alternative explanation as to why daily torpor is common in sunny regions and

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

    PubMed

    Blanquer-Rosselló, Mª 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. 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. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. 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. © 2016 Wiley Periodicals, Inc.

  19. Skeletal Muscle Thermogenesis and Its Role in Whole Body Energy Metabolism

    PubMed Central

    Herrera, Jose Luis; Reis, Felipe C. G.

    2017-01-01

    Obesity and diabetes has become a major epidemic across the globe. Controlling obesity has been a challenge since this would require either increased physical activity or reduced caloric intake; both are difficult to enforce. There has been renewed interest in exploiting pathways such as uncoupling protein 1 (UCP1)-mediated uncoupling in brown adipose tissue (BAT) and white adipose tissue to increase energy expenditure to control weight gain. However, relying on UCP1-based thermogenesis alone may not be sufficient to control obesity in humans. On the other hand, skeletal muscle is the largest organ and a major contributor to basal metabolic rate and increasing energy expenditure in muscle through nonshivering thermogenic mechanisms, which can substantially affect whole body metabolism and weight gain. In this review we will describe the role of Sarcolipin-mediated uncoupling of Sarcoplasmic Reticulum Calcium ATPase (SERCA) as a potential mechanism for increased energy expenditure both during cold and diet-induced thermogenesis. PMID:29086530

  20. Lactate rescues neuronal sodium homeostasis during impaired energy metabolism.

    PubMed

    Karus, Claudia; Ziemens, Daniel; Rose, Christine R

    2015-01-01

    Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle.

  1. Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

    PubMed Central

    Karus, Claudia; Ziemens, Daniel; Rose, Christine R

    2015-01-01

    Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle. PMID:26039160

  2. [Assessment of energy metabolism and nutritional supply in children with mechanical ventilation].

    PubMed

    Ji, Jian; Qian, Suyun; Yan, Jie

    2016-01-01

    To determine the resting energy expenditure on mechanical ventilation in pediatric intensive care unit (PICU) by indirect calorimetry, and analyze the distribution of metabolic states. The nutrition supply was assessed according to the resting energy expenditure. An observational study which was held in PICU of Beijing Children's Hospital from November 2013 to April 2014. Critically ill children with mechanical ventilation were enrolled in this study. The inclusion criteria included the following: (1) pediatric critical illness score < 90, or meet the United States PICU admission criteria; (2) age > 29 days, < 18 years old; (3) time of mechanical ventilation > 24 hours; (4) volume of mechanical ventilation > 60 ml. Resting energy expenditure was determined by US Med Graphic Company CCM/D energy metabolism test system. Predictive resting energy expenditure was calculated for each subject with age-appropriate equation (Schofield-HTWT). According to the actual energy intake records and required energy intake (10% higher than the measured value) to define the nutritional status. The selected subjects were grouped according to gender, age, types of disease and nutritional status, and compared the metabolic status and nutritional supply of different groups. Sixty-eight children were enrolled in this study, 46 were boys and 22 were girls, including 25 cases of pneumonia with respiratory failure, 23 cases of central nervous system diseases complicated with respiratory failure and 20 cases of postoperative tracheal intubation. The ratio of boys and girls was 2:1. The results showed 36 patients in a low metabolic state, accounting for 53%, 23 patients in a high metabolic state, accounting for 34% and 9 patients (13%) in the metabolism of the normal state. In the male children, 12 cases (26%) were in the high metabolism and 26 cases (57%) were in the low metabolism, and 8 cases (17%) were in the normal metabolism. In the female children, 11 cases (50%) were classified into

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

    PubMed

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

    2014-12-01

    Genes and the environment both influence the metabolic processes that determine fitness. To illustrate the importance of metabolism for human brain evolution and health, we use the example of lipid energy metabolism, i.e. the use of fat (lipid) to produce energy and the advantages that this metabolic pathway provides for the brain during environmental energy shortage. We briefly describe some features of metabolism in ancestral organisms, which provided a molecular toolkit for later development. In modern humans, lipid energy metabolism is a regulated multi-organ pathway that links triglycerides in fat tissue to the mitochondria of many tissues including the brain. Three important control points are each suppressed by insulin. (1) Lipid reserves in adipose tissue are released by lipolysis during fasting and stress, producing fatty acids (FAs) which circulate in the blood and are taken up by cells. (2) FA oxidation. Mitochondrial entry is controlled by carnitine palmitoyl transferase 1 (CPT1). Inside the mitochondria, FAs undergo beta oxidation and energy production in the Krebs cycle and respiratory chain. (3) In liver mitochondria, the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) pathway produces ketone bodies for the brain and other organs. Unlike most tissues, the brain does not capture and metabolize circulating FAs for energy production. However, the brain can use ketone bodies for energy. We discuss two examples of genetic metabolic traits that may be advantageous under most conditions but deleterious in others. (1) A CPT1A variant prevalent in Inuit people may allow increased FA oxidation under nonfasting conditions but also predispose to hypoglycemic episodes. (2) The thrifty genotype theory, which holds that energy expenditure is efficient so as to maximize energy stores, predicts that these adaptations may enhance survival in periods of famine but predispose to obesity in modern dietary environments. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Differential regulation of metabolic parameters by energy deficit and hunger.

    PubMed

    Kitka, Tamás; Tuza, Sebestyén; Varga, Balázs; Horváth, Csilla; Kovács, Péter

    2015-10-01

    Hypocaloric diet decreases both energy expenditure (EE) and respiratory exchange rate (RER), affecting the efficacy of dieting inversely. Energy deficit and hunger may be modulated separately both in human and animal studies by drug treatment or food restriction. Thus it is important to separate the effects of energy deficit and hunger on EE and RER. Three parallel and analogous experiments were performed using three pharmacologically distinct anorectic drugs: rimonabant, sibutramine and tramadol. Metabolic parameters of vehicle- and drug-treated and pair-fed diet-induced obese mice from the three experiments underwent common statistical analysis to identify effects independent of the mechanisms of action. Diet-induced obesity (DIO) test of tramadol was also performed to examine its anti-obesity efficacy. RER was decreased similarly by drug treatments and paired feeding throughout the experiment irrespective of the cause of reduced food intake. Contrarily, during the passive phase, EE was decreased more by paired feeding than by both vehicle and drug treatment irrespective of the drug used. In the active phase, EE was influenced by the pharmacological mechanisms of action. Tramadol decreased body weight in the DIO test. Our results suggest that RER is mainly affected by the actual state of energy balance; conversely, EE is rather influenced by hunger. Therefore, pharmacological medications that decrease hunger may enhance the efficacy of a hypocaloric diet by maintaining metabolic rate. Furthermore, our results yield the proposal that effects of anorectic drugs on EE and RER should be determined compared to vehicle and pair-fed groups, respectively, in animal models. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Deiodinase knockdown during early zebrafish development affects growth, development, energy metabolism, motility and phototransduction.

    PubMed

    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

  6. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    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.

  8. 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.

  9. Increasing levels of rapeseed expeller meal in diets for pigs: effects on protein and energy metabolism.

    PubMed

    Pérez de Nanclares, M; Marcussen, C; Tauson, A-H; Hansen, J Ø; Kjos, N P; Mydland, L T; Bach Knudsen, K E; Øverland, M

    2018-05-28

    The heavy reliance on imported soybean meal (SBM) as a protein source makes it necessary for the European pig industry to search for alternatives and to develop pigs that perform efficiently when fed such ingredients. Digestion and metabolism are major physiological processes contributing to variation in feed efficiency. Therefore, an experiment was conducted to assess the effects of replacing SBM with increasing levels of rapeseed meal (RSM) in diets for young pigs on apparent total tract digestibility (ATTD) of energy and nutrients, nitrogen (N) balance, energy metabolism and carbohydrate, protein and fat oxidation. Four diets were fed to 32 pigs (22.7±4.1 kg initial BW) for three weeks. The diets consisted of a control cereal grain-SBM basal diet and three test diets where SBM and wheat were partially replaced with 10%, 20%, and 30% of expeller RSM. Increasing level of RSM in the diets linearly reduced ATTD of organic matter, CP, total carbohydrates, dietary fiber and energy. Utilization of digested nitrogen (DN) for N retention and total N excretion were not affected by RSM inclusion, however, RSM inclusion induced a shift in N excretion from urine to feces. Despite a linear increase in liver to metabolic BW ratio, heat production and utilization of metabolizable energy (ME) for retention were not affected by increasing RSM inclusion. In conclusion, replacing SBM with up to 30% of expeller RSM in nutritionally balanced diets for young pigs reduced the ATTD of most nutrients and energy, but did not affect N and energy retention in the body or efficiency of utilization of DN or ME for retention.

  10. INSECT FAT BODY: ENERGY, METABOLISM, AND REGULATION

    PubMed Central

    Arrese, Estela L.; Soulages, Jose L.

    2010-01-01

    The fat body plays major roles in the life of insects. It is a dynamic tissue involved in multiple metabolic functions. One of these functions is to store and release energy in response to the energy demands of the insect. Insects store energy reserves in the form of glycogen and triglycerides in the adipocytes, the main fat body cell. Insect adipocytes can store a great amount of lipid reserves as cytoplasmic lipid droplets. Lipid metabolism is essential for growth and reproduction and provides energy needed during extended nonfeeding periods. This review focuses on energy storage and release and summarizes current understanding of the mechanisms underlying these processes in insects. PMID:19725772

  11. 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

    2016-01-26

    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.

  12. 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

  13. Early Postnatal Cardiomyocyte Proliferation Requires High Oxidative Energy Metabolism.

    PubMed

    de Carvalho, Ana Elisa Teófilo Saturi; Bassaneze, Vinícius; Forni, Maria Fernanda; Keusseyan, Aline Alfonso; Kowaltowski, Alicia Juliana; Krieger, José Eduardo

    2017-11-13

    Cardiac energy metabolism must cope with early postnatal changes in tissue oxygen tensions, hemodynamics, and cell proliferation to sustain development. Here, we tested the hypothesis that proliferating neonatal cardiomyocytes are dependent on high oxidative energy metabolism. We show that energy-related gene expression does not correlate with functional oxidative measurements in the developing heart. Gene expression analysis suggests a gradual overall upregulation of oxidative-related genes and pathways, whereas functional assessment in both cardiac tissue and cultured cardiomyocytes indicated that oxidative metabolism decreases between the first and seventh days after birth. Cardiomyocyte extracellular flux analysis indicated that the decrease in oxidative metabolism between the first and seventh days after birth was mostly related to lower rates of ATP-linked mitochondrial respiration, suggesting that overall energetic demands decrease during this period. In parallel, the proliferation rate was higher for early cardiomyocytes. Furthermore, in vitro nonlethal chemical inhibition of mitochondrial respiration reduced the proliferative capacity of early cardiomyocytes, indicating a high energy demand to sustain cardiomyocyte proliferation. Altogether, we provide evidence that early postnatal cardiomyocyte proliferative capacity correlates with high oxidative energy metabolism. The energy requirement decreases as the proliferation ceases in the following days, and both oxidative-dependent metabolism and anaerobic glycolysis subside.

  14. Dietary electrolyte balance affects growth performance, amylase activity and metabolic response in the meagre (Argyrosomus regius).

    PubMed

    Magnoni, Leonardo J; Salas-Leiton, Emilio; Peixoto, Maria-João; Pereira, Luis; Silva-Brito, Francisca; Fontinha, Filipa; Gonçalves, José F M; Wilson, Jonathan M; Schrama, Johan W; Ozório, Rodrigo O A

    2017-09-01

    Dietary ion content is known to alter the acid-base balance in freshwater fish. The current study investigated the metabolic impact of acid-base disturbances produced by differences in dietary electrolyte balance (DEB) in the meagre (Argyrosomus regius), an euryhaline species. Changes in fish performance, gastric chyme characteristics, pH and ion concentrations in the bloodstream, digestive enzyme activities and metabolic rates were analyzed in meagre fed ad libitum two experimental diets (DEB 200 or DEB 700mEq/kg) differing in the Na 2 CO 3 content for 69days. Fish fed the DEB 200 diet had 60-66% better growth performance than the DEB 700 group. Meagre consuming the DEB 200 diet were 90-96% more efficient than fish fed the DEB 700 diet at allocating energy from feed into somatic growth. The pH values in blood were significantly lower in the DEB 700 group 2h after feeding when compared to DEB 200, indicating that acid-base balance in meagre was affected by electrolyte balance in diet. Osmolality, and Na + and K + concentrations in plasma did not vary with the dietary treatment. Gastric chyme in the DEB 700 group had higher pH values, dry matter, protein and energy contents, but lower lipid content than in the DEB 200 group. Twenty-four hours after feeding, amylase activity was higher in the gastrointestinal tract of DEB 700 group when compared to the DEB 200 group. DEB 700 group had lower routine metabolic (RMR) and standard metabolic (SMR) rates, indicating a decrease in maintenance energy expenditure 48h after feeding the alkaline diet. The current study demonstrates that feeding meagre with an alkaline diet not only causes acid-base imbalance, but also negatively affects digestion and possibly nutrient assimilation, resulting in decreased growth performance. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Monoglyceride lipase deficiency affects hepatic cholesterol metabolism and lipid-dependent gut transit in ApoE-/- mice.

    PubMed

    Vujic, Nemanja; Korbelius, Melanie; Leopold, Christina; Duta-Mare, Madalina; Rainer, Silvia; Schlager, Stefanie; Goeritzer, Madeleine; Kolb, Dagmar; Eichmann, Thomas O; Diwoky, Clemens; Zimmer, Andreas; Zimmermann, Robert; Lass, Achim; Radovic, Branislav; Kratky, Dagmar

    2017-05-16

    Monoglyceride lipase (MGL) hydrolyzes monoglycerides (MGs) to glycerol and fatty acids. Among various MG species MGL also degrades 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid and potent activator of cannabinoid receptors (CBR) 1 and 2. MGL-knockout (-/-) mice exhibit pronounced 2-AG accumulation, but lack central cannabimimetic effects due to CB1R desensitization. We have previously shown that MGL affects plaque stability in apolipoprotein E (ApoE)-/- mice, an established animal model for dyslipidemia and atherosclerosis. In the current study, we investigated functional consequences of MGL deficiency on lipid and energy metabolism in ApoE/MGL double knockout (DKO) mice. MGL deficiency affected hepatic cholesterol metabolism by causing increased cholesterol elimination via the biliary pathway. Moreover, DKO mice exhibit lipid-triggered delay in gastric emptying without major effects on overall triglyceride and cholesterol absorption. The observed phenotype of DKO mice is likely not a consequence of potentiated CB1R signaling but rather dependent on the activation of alternative signaling pathways. We conclude that MGL deficiency causes complex metabolic changes including cholesterol metabolism and regulation of gut transit independent of the endocannabinoid system.

  16. Cellular energy metabolism in T-lymphocytes.

    PubMed

    Gaber, Timo; Strehl, Cindy; Sawitzki, Birgit; Hoff, Paula; Buttgereit, Frank

    2015-01-01

    Energy homeostasis is a hallmark of cell survival and maintenance of cell function. Here we focus on the impact of cellular energy metabolism on T-lymphocyte differentiation, activation, and function in health and disease. We describe the role of transcriptional and posttranscriptional regulation of lymphocyte metabolism on immune functions of T cells. We also summarize the current knowledge about T-lymphocyte adaptations to inflammation and hypoxia, and the impact on T-cell behavior of pathophysiological hypoxia (as found in tumor tissue, chronically inflamed joints in rheumatoid arthritis and during bone regeneration). A better understanding of the underlying mechanisms that control immune cell metabolism and immune response may provide therapeutic opportunities to alter the immune response under conditions of either immunosuppression or inflammation, potentially targeting infections, vaccine response, tumor surveillance, autoimmunity, and inflammatory disorders.

  17. Microglia energy metabolism in metabolic disorder.

    PubMed

    Kalsbeek, Martin J T; Mulder, Laurie; Yi, Chun-Xia

    2016-12-15

    Microglia are the resident macrophages of the CNS, and are in charge of maintaining a healthy microenvironment to ensure neuronal survival. Microglia carry out a non-stop patrol of the CNS, make contact with neurons and look for abnormalities, all of which requires a vast amount of energy. This non-signaling energy demand increases after activation by pathogens, neuronal damage or other kinds of stimulation. Of the three major energy substrates - glucose, fatty acids and glutamine - glucose is crucial for microglia survival and several glucose transporters are expressed to supply sufficient glucose influx. Fatty acids are another source of energy for microglia and have also been shown to strongly influence microglial immune activity. Glutamine, although possibly suitable for use as an energy substrate by microglia, has been shown to have neurotoxic effects when overloaded. Microglial fuel metabolism might be associated with microglial reactivity under different pathophysiological conditions and a microglial fuel switch may thus be the underlying cause of hypothalamic dysregulation, which is associated with obesity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. A cellular perspective on brain energy metabolism and functional imaging.

    PubMed

    Magistretti, Pierre J; Allaman, Igor

    2015-05-20

    The energy demands of the brain are high: they account for at least 20% of the body's energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and point at a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Hypothalamic control of energy and glucose metabolism.

    PubMed

    Sisley, Stephanie; Sandoval, Darleen

    2011-09-01

    The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

  20. 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

  1. Current technical approaches to brain energy metabolism.

    PubMed

    Barros, L Felipe; Bolaños, Juan P; Bonvento, Gilles; Bouzier-Sore, Anne-Karine; Brown, Angus; Hirrlinger, Johannes; Kasparov, Sergey; Kirchhoff, Frank; Murphy, Anne N; Pellerin, Luc; Robinson, Michael B; Weber, Bruno

    2018-06-01

    Neuroscience is a technology-driven discipline and brain energy metabolism is no exception. Once satisfied with mapping metabolic pathways at organ level, we are now looking to learn what it is exactly that metabolic enzymes and transporters do and when, where do they reside, how are they regulated, and how do they relate to the specific functions of neurons, glial cells, and their subcellular domains and organelles, in different areas of the brain. Moreover, we aim to quantify the fluxes of metabolites within and between cells. Energy metabolism is not just a necessity for proper cell function and viability but plays specific roles in higher brain functions such as memory processing and behavior, whose mechanisms need to be understood at all hierarchical levels, from isolated proteins to whole subjects, in both health and disease. To this aim, the field takes advantage of diverse disciplines including anatomy, histology, physiology, biochemistry, bioenergetics, cellular biology, molecular biology, developmental biology, neurology, and mathematical modeling. This article presents a well-referenced synopsis of the technical side of brain energy metabolism research. Detail and jargon are avoided whenever possible and emphasis is given to comparative strengths, limitations, and weaknesses, information that is often not available in regular articles. © 2017 Wiley Periodicals, Inc.

  2. Difference in Energy Metabolism of Annulus Fibrosus and Nucleus Pulposus Cells of the Intervertebral Disc

    PubMed Central

    Salvatierra, Jessica Czamanski; Yuan, Tai Yi; Fernando, Hanan; Castillo, Andre; Gu, Wei Yong; Cheung, Herman S.; Huant, C.-Y. Charles

    2011-01-01

    Low back pain is associated with intervertebral disc degeneration. One of the main signs of degeneration is the inability to maintain extracellular matrix integrity. Extracellular matrix synthesis is closely related to production of adenosine triphosphate (i.e. energy) of the cells. The intervertebral disc is composed of two major anatomical regions: annulus fibrosus and nucleus pulposus, which are structurally and compositionally different, indicating that their cellular metabolisms may also be distinct. The objective of this study was to investigate energy metabolism of annulus fibrosus and nucleus pulposus cells with and without dynamic compression, and examine differences between the two cell types. Porcine annulus and nucleus tissues were harvested and enzymatically digested. Cells were isolated and embedded into agarose constructs. Dynamically loaded samples were subjected to a sinusoidal displacement at 2 Hz and 15% strain for 4 h. Energy metabolism of cells was analyzed by measuring adenosine triphosphate content and release, glucose consumption, and lactate/nitric oxide production. A comparison of those measurements between annulus and nucleus cells was conducted. Annulus and nucleus cells exhibited different metabolic pathways. Nucleus cells had higher adenosine triphosphate content with and without dynamic loading, while annulus cells had higher lactate production and glucose consumption. Compression increased adenosine triphosphate release from both cell types and increased energy production of annulus cells. Dynamic loading affected energy metabolism of intervertebral disc cells, with the effect being greater in annulus cells. PMID:21625336

  3. Impaired brain energy metabolism in the BACHD mouse model of Huntington's disease: critical role of astrocyte–neuron interactions

    PubMed Central

    Boussicault, Lydie; Hérard, Anne-Sophie; Calingasan, Noel; Petit, Fanny; Malgorn, Carole; Merienne, Nicolas; Jan, Caroline; Gaillard, Marie-Claude; Lerchundi, Rodrigo; Barros, Luis F; Escartin, Carole; Delzescaux, Thierry; Mariani, Jean; Hantraye, Philippe; Flint Beal, M; Brouillet, Emmanuel; Véga, Céline; Bonvento, Gilles

    2014-01-01

    Huntington's disease (HD) is caused by cytosine-adenine-guanine (CAG) repeat expansions in the huntingtin (Htt) gene. Although early energy metabolic alterations in HD are likely to contribute to later neurodegenerative processes, the cellular and molecular mechanisms responsible for these metabolic alterations are not well characterized. Using the BACHD mice that express the full-length mutant huntingtin (mHtt) protein with 97 glutamine repeats, we first demonstrated localized in vivo changes in brain glucose use reminiscent of what is observed in premanifest HD carriers. Using biochemical, molecular, and functional analyses on different primary cell culture models from BACHD mice, we observed that mHtt does not directly affect metabolic activity in a cell autonomous manner. However, coculture of neurons with astrocytes from wild-type or BACHD mice identified mutant astrocytes as a source of adverse non-cell autonomous effects on neuron energy metabolism possibly by increasing oxidative stress. These results suggest that astrocyte-to-neuron signaling is involved in early energy metabolic alterations in HD. PMID:24938402

  4. The Energy Maintenance Theory of Aging: Maintaining Energy Metabolism to Allow Longevity.

    PubMed

    Chaudhari, Snehal N; Kipreos, Edward T

    2018-06-14

    Fused, elongated mitochondria are more efficient in generating ATP than fragmented mitochondria. In diverse C. elegans longevity pathways, increased levels of fused mitochondria are associated with lifespan extension. Blocking mitochondrial fusion in these animals abolishes their extended longevity. The long-lived C. elegans vhl-1 mutant is an exception that does not have increased fused mitochondria, and is not dependent on fusion for longevity. Loss of mammalian VHL upregulates alternate energy generating pathways. This suggests that mitochondrial fusion facilitates longevity in C. elegans by increasing energy metabolism. In diverse animals, ATP levels broadly decreases with age. Substantial evidence supports the theory that increasing or maintaining energy metabolism promotes the survival of older animals. Increased ATP levels in older animals allow energy-intensive repair and homeostatic mechanisms such as proteostasis that act to prevent cellular aging. These observations support the emerging paradigm that maintaining energy metabolism promotes the survival of older animals. © 2018 WILEY Periodicals, Inc.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 mgmore » 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.« less

  6. 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

  7. 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.

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

    PubMed

    Massucci, Francesco A; DiNuzzo, Mauro; Giove, Federico; Maraviglia, Bruno; Castillo, Isaac Perez; Marinari, Enzo; De Martino, Andrea

    2013-10-10

    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. 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. 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.

  9. 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

  10. Monoglyceride lipase deficiency affects hepatic cholesterol metabolism and lipid-dependent gut transit in ApoE−/− mice

    PubMed Central

    Vujic, Nemanja; Korbelius, Melanie; Leopold, Christina; Duta-Mare, Madalina; Rainer, Silvia; Schlager, Stefanie; Goeritzer, Madeleine; Kolb, Dagmar; Eichmann, Thomas O.; Diwoky, Clemens; Zimmer, Andreas; Zimmermann, Robert; Lass, Achim; Radovic, Branislav; Kratky, Dagmar

    2017-01-01

    Monoglyceride lipase (MGL) hydrolyzes monoglycerides (MGs) to glycerol and fatty acids. Among various MG species MGL also degrades 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid and potent activator of cannabinoid receptors (CBR) 1 and 2. MGL-knockout (−/−) mice exhibit pronounced 2-AG accumulation, but lack central cannabimimetic effects due to CB1R desensitization. We have previously shown that MGL affects plaque stability in apolipoprotein E (ApoE)−/− mice, an established animal model for dyslipidemia and atherosclerosis. In the current study, we investigated functional consequences of MGL deficiency on lipid and energy metabolism in ApoE/MGL double knockout (DKO) mice. MGL deficiency affected hepatic cholesterol metabolism by causing increased cholesterol elimination via the biliary pathway. Moreover, DKO mice exhibit lipid-triggered delay in gastric emptying without major effects on overall triglyceride and cholesterol absorption. The observed phenotype of DKO mice is likely not a consequence of potentiated CB1R signaling but rather dependent on the activation of alternative signaling pathways. We conclude that MGL deficiency causes complex metabolic changes including cholesterol metabolism and regulation of gut transit independent of the endocannabinoid system. PMID:28380440

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

    PubMed

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

    2016-10-01

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

  12. Energy metabolism in human obesity.

    PubMed

    Jéquier, E

    1989-01-01

    Obesity results from a chronic imbalance between energy intake and expenditure. Accurate measurements of total energy expenditure of lean and obese individuals with a respiration chamber have clearly shown that obese individuals expand more energy than lean sedentary subjects. Studies on the body composition of obese individuals reveal that not only the fat mass is enlarged, but the fat-free mass is also increased as compared with that of lean subjects. Since basal metabolic rate is proportional to the fat-free mass, obese subjects have a greater basal metabolic rate than lean controls. The energy cost of weight bearing activities such as walking and standing is related to body weight, and is therefore increased in obese individuals. The thermogenic response to food ingestion, the diet-induced thermogenesis, has been found to be reduced in some groups of obese people, but not in all obese individuals. The thermic effect of glucose or to meal ingestion is blunted in obese subjects with insulin resistance. Any alteration in thermogenic responses to a caloric excess can be important to store or to oxidize part of the excessive energy intake. After weight reduction in obese subjects due to a hypocaloric diet, the total 24-hour energy expenditure decreases by 20 to 25 kcal/day for each kilogram of weight loss. Failure to adapt the every day energy intake accordingly will result in body weight gain and relapse of obesity.

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

    PubMed Central

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

    2012-01-01

    Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation. PMID:22435484

  14. Down-regulated energy metabolism genes associated with mitochondria oxidative phosphorylation and fatty acid metabolism in viral cardiomyopathy mouse heart.

    PubMed

    Xu, Jing; Nie, Hong-gang; Zhang, Xiao-dong; Tian, Ye; Yu, Bo

    2011-08-01

    The majority of experimental and clinical studies indicates that the hypertrophied and failing myocardium are characterized by changes in energy and substrate metabolism that attributed to failing heart changes at the genomic level, in fact, heart failure is caused by various diseases, their energy metabolism and substrate are in different genetic variations, then the potential significance of the molecular mechanisms for the aetiology of heart failure is necessary to be evaluated. Persistent viral infection (especially coxsackievirus group B3) of the myocardium in viral myocarditis and viral dilated cardiomyopathy has never been neglected by experts. This study aimed to explore the role and regulatory mechanism of the altered gene expression for energy metabolism involved in mitochondrial oxidative phosphorylation, fatty acid metabolism in viral dilated cardiomyopathy. cDNA Microarray technology was used to evaluate the expression of >35,852 genes in a mice model of viral dilated cardiomyopathy. In total 1385 highly different genes expression, we analyzed 33 altered genes expression for energy metabolism involved in mitochondrial oxidative phosphorylation, fatty acid metabolism and further selected real-time-PCR for quantity one of regulatory mechanisms for energy including fatty acid metabolism-the UCP2 and assayed cytochrome C oxidase activity by Spectrophotometer to explore mitochondrial oxidative phosphorylation function. We found obviously different expression of 33 energy metabolism genes associated with mitochondria oxidative phosphorylation, fatty acid metabolism in cardiomyopathy mouse heart, the regulatory gene for energy metabolism: UCP2 was down-regulated and cytochrome C oxidase activity was decreased. Genes involved in both fatty acid metabolism and mitochondrial oxidative phosphorylation were down-regulated, mitochondrial uncoupling proteins (UCP2) expression did not increase but decrease which might be a kind of adaptive protection response to

  15. 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

  16. Synergistic effects of citrulline supplementation and exercise on performance in male rats: evidence for implication of protein and energy metabolisms.

    PubMed

    Goron, Arthur; Lamarche, Frédéric; Cunin, Valérie; Dubouchaud, Hervé; Hourdé, Christophe; Noirez, Philippe; Corne, Christelle; Couturier, Karine; Sève, Michel; Fontaine, Eric; Moinard, Christophe

    2017-04-25

    Background: Exercise and citrulline (CIT) are both regulators of muscle protein metabolism. However, the combination of both has been under-studied yet may have synergistic effects on muscle metabolism and performance. Methods: Three-month-old healthy male rats were randomly assigned to be fed ad libitum for 4 weeks with either a citrulline-enriched diet (1 g·kg -1 ·day -1 ) ( CIT ) or an isonitrogenous standard diet (by addition of nonessential amino acid) ( Ctrl ) and trained (running on treadmill 5 days·week -1 ) ( ex ) or not. Maximal endurance activity and body composition were assessed, and muscle protein metabolism (protein synthesis, proteomic approach) and energy metabolism [energy expenditure, mitochondrial metabolism] were explored. Results: Body composition was affected by exercise but not by CIT supplementation. Endurance training was associated with a higher maximal endurance capacity than sedentary groups ( P <0.001), and running time was 14% higher in the CITex group than the Ctrlex group (139±4 min versus 122±6 min, P <0.05). Both endurance training and CIT supplementation alone increased muscle protein synthesis (by +27% and +33%, respectively, versus Ctrl , P <0.05) with an additive effect (+48% versus Ctrl , P <0.05). Mitochondrial metabolism was modulated by exercise but not directly by CIT supplementation. However, the proteomic approach demonstrated that CIT supplementation was able to affect energy metabolism, probably due to activation of pathways generating acetyl-CoA. Conclusion: CIT supplementation and endurance training in healthy male rats modulates both muscle protein and energy metabolisms, with synergic effects on an array of parameters, including performance and protein synthesis. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  17. Unraveling Interfaces between Energy Metabolism and Cell Cycle in Plants.

    PubMed

    Siqueira, João Antonio; Hardoim, Pablo; Ferreira, Paulo C G; Nunes-Nesi, Adriano; Hemerly, Adriana S

    2018-06-19

    Oscillation in energy levels is widely variable in dividing and differentiated cells. To synchronize cell proliferation and energy fluctuations, cell cycle-related proteins have been implicated in the regulation of mitochondrial energy-generating pathways in yeasts and animals. Plants have chloroplasts and mitochondria, coordinating the cell energy flow. Recent findings suggest an integrated regulation of these organelles and the nuclear cell cycle. Furthermore, reports indicate a set of interactions between the cell cycle and energy metabolism, coordinating the turnover of proteins in plants. Here, we discuss how cell cycle-related proteins directly interact with energy metabolism-related proteins to modulate energy homeostasis and cell cycle progression. We provide interfaces between cell cycle and energy metabolism-related proteins that could be explored to maximize plant yield. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. 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

  19. The role of Klotho in energy metabolism

    PubMed Central

    Razzaque, M. Shawkat

    2013-01-01

    A disproportionate expansion of white adipose tissue and abnormal recruitment of adipogenic precursor cells can not only lead to obesity but also impair glucose metabolism, which are both common causes of insulin resistance and diabetes mellitus. The development of novel and effective therapeutic strategies to slow the progression of obesity, diabetes mellitus and their associated complications will require improved understanding of adipogenesis and glucose metabolism. Klotho might have a role in adipocyte maturation and systemic glucose metabolism. Klotho increases adipocyte differentiation in vitro, and mice that lack Klotho activity are lean owing to reduced white adipose tissue accumulation; moreover, mice that lack the Kl gene (which encodes Klotho) are resistant to obesity induced by a high-fat diet. Knockout of Kl in leptin-deficient Lepob/ob mice reduces obesity and increases insulin sensitivity, which lowers blood glucose levels. Energy metabolism might also be influenced by Klotho. However, further studies are needed to explore the possibility that Klotho could be a novel therapeutic target to reduce obesity and related complications, and to determine whether and how Klotho might influence the regulation and function of a related protein, β-Klotho, which is also involved in energy metabolism. PMID:22641000

  20. Metabolic costs of capital energy storage in a small-bodied ectotherm.

    PubMed

    Griffen, Blaine D

    2017-04-01

    Reproduction is energetically financed using strategies that fall along a continuum from animals that rely on stored energy acquired prior to reproduction (i.e., capital breeders) to those that rely on energy acquired during reproduction (i.e., income breeders). Energy storage incurs a metabolic cost. However, previous studies suggest that this cost may be minimal for small-bodied ectotherms. Here I test this assumption. I use a laboratory feeding experiment with the European green crab Carcinus maenas to establish individuals with different amounts of energy storage. I then demonstrate that differences in energy storage account for 26% of the variation in basal metabolic costs. The magnitudes of these costs for any individual crab vary through time depending on the amount of energy it has stored, as well as on temperature-dependent metabolism. I use previously established relationships between temperature- and mass-dependent metabolic rates, combined with a feasible annual pattern of energy storage in the Gulf of Maine and annual sea surface temperature patterns in this region, to estimate potential annual metabolic costs expected for mature female green crabs. Results indicate that energy storage should incur an ~8% increase in metabolic costs for female crabs, relative to a hypothetical crab that did not store any energy. Translated into feeding, for a medium-sized mature female (45 mm carapace width), this requires the consumption of an additional ~156 mussels annually to support the metabolic cost of energy storage. These results indicate, contrary to previous assumptions, that the cost of energy storage for small-bodied ectotherms may represent a considerable portion of their basic operating energy budget. An inability to meet these additional costs of energy storage may help explain the recent decline of green crabs in the Gulf of Maine where reduced prey availability and increased consumer competition have combined to hamper green crab foraging success in

  1. 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. © 2015 FEBS.

  2. Comparison of Various Indices of Energy Metabolism in Recumbent and Healthy Dairy Cows.

    PubMed

    Guyot, Hugues; Detilleux, Johann; Lebreton, Pascal; Garnier, Catherine; Bonvoisin, Marie; Rollin, Frederic; Sandersen, Charlotte

    2017-01-01

    Downer cow syndrome (DCS) is often diagnosed in dairy cattle during the early post-partum period. The etiology of this condition is not completely understood, as it can be related to the energetic or electrolyte metabolism, as well as to infectious diseases or to trauma. The aim of this study is to compare energy metabolism and insulin sensitivity indices and various biochemical parameters between recumbent and healthy dairy cows. A prospective study has been undertaken on 361 recumbent and 80 healthy Holstein cows. Plasmatic glucose, insulin, non-esterified fatty acid (NEFA) and β-hydroxybutyrate (BHB) were assayed in all cows in order to calculate the insulin sensitivity indices but also minerals (Calcium, Phosphorous and Magnesium), thyroxin and creatine kinase. Body Condition Scores (BCS) was assessed. Significant differences in NEFA, and the glucose and insulin sensitivity indices ("Homeostasis Model Assessment" HOMA, "Revised Quantitative Insulin Sensitivity Check Index" RQUICKI, RQUICKI-BHB) were observed between healthy and recumbent cows in the early post-parturient period indicating disturbances of glucose and insulin homeostasis in the recumbent cows. In the same manner, mineral concentrations were significantly different between healthy and recumbent cows. Glucose, insulin NEFA, and HOMA, were different between early post-partum downer cows and the DCS-affected cows later in lactation. Results indicate disturbances in energy homeostasis in DCS-affected dairy cows. Further research should determine a prognostic value of the indices in cows suffering from recumbency of metabolic origin.

  3. 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. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  4. Energy metabolism of rat cerebral cortex, hypothalamus and hypophysis during ageing.

    PubMed

    Villa, R F; Ferrari, F; Gorini, A

    2012-12-27

    Ageing is one of the main risk factors for brain disorders. According to the neuroendocrine theory, ageing modifies the sensitivity of hypothalamus-pituitary-adrenal axis to homoeostatic signals coming from the cerebral cortex. The relationships between the energy metabolism of these areas have not been considered yet, in particular with respect to ageing. For these reasons, this study was undertaken to systematically investigate in female Sprague-Dawley rats aged 4, 6, 12, 18, 24, 28 months and in 4-month-old male ones, the catalytic properties of energy-linked enzymes of the Krebs' cycle, electron transport chain, glutamate and related amino acids on different mitochondrial subpopulations, i.e. non-synaptic perikaryal and intra-synaptic (two types) mitochondria. The biochemical enzymatic pattern of these mitochondria shows different expression of the above-mentioned enzymatic activities in the investigated brain areas, including frontal cerebral cortex, hippocampus, striatum, hypothalamus and hypophysis. The study shows that: (i) the energy metabolism of the frontal cerebral cortex is poorly affected by physiological ageing; (ii) the biochemical machinery of non-synaptic perikaryal mitochondria is differently expressed in the considered brain areas; (iii) at 4-6 months, hypothalamus and hypophysis possess lower oxidative metabolism with respect to the frontal cerebral cortex while (iv), during ageing, the opposite situation occurs. We hypothesised that these metabolic modifications likely try to grant HPA functionality in response to the incoming external stress stimuli increased during ageing. It is particularly notable that age-related changes in brain bioenergetics and in mitochondrial functionality may be considered as remarkable factors during physiological ageing and should play important roles in predisposing the brain to physiopathological events, tightly related to molecular mechanisms evoked for pharmacological treatments. Copyright © 2012 IBRO

  5. C75, a fatty acid synthase inhibitor, modulates AMP-activated protein kinase to alter neuronal energy metabolism.

    PubMed

    Landree, Leslie E; Hanlon, Andrea L; Strong, David W; Rumbaugh, Gavin; Miller, Ian M; Thupari, Jagan N; Connolly, Erin C; Huganir, Richard L; Richardson, Christine; Witters, Lee A; Kuhajda, Francis P; Ronnett, Gabriele V

    2004-01-30

    C75, a synthetic inhibitor of fatty acid synthase (FAS), is hypothesized to alter the metabolism of neurons in the hypothalamus that regulate feeding behavior to contribute to the decreased food intake and profound weight loss seen with C75 treatment. In the present study, we characterize the suitability of primary cultures of cortical neurons for studies designed to investigate the consequences of C75 treatment and the alteration of fatty acid metabolism in neurons. We demonstrate that in primary cortical neurons, C75 inhibits FAS activity and stimulates carnitine palmitoyltransferase-1 (CPT-1), consistent with its effects in peripheral tissues. C75 alters neuronal ATP levels and AMP-activated protein kinase (AMPK) activity. Neuronal ATP levels are affected in a biphasic manner with C75 treatment, decreasing initially, followed by a prolonged increase above control levels. Cerulenin, a FAS inhibitor, causes a similar biphasic change in ATP levels, although levels do not exceed control. C75 and cerulenin modulate AMPK phosphorylation and activity. TOFA, an inhibitor of acetyl-CoA carboxylase, increases ATP levels, but does not affect AMPK activity. Several downstream pathways are affected by C75 treatment, including glucose metabolism and acetyl-CoA carboxylase (ACC) phosphorylation. These data demonstrate that C75 modulates the levels of energy intermediates, thus, affecting the energy sensor AMPK. Similar effects in hypothalamic neurons could form the basis for the effects of C75 on feeding behavior.

  6. Metabolism, obesity and the metabolic syndrome.

    PubMed

    Persson, Pontus B; Bondke Persson, Anja

    2018-05-13

    The current obesity epidemic has not only spread from Western to developing economies, but is affecting ever younger individuals. While oftentimes blamed on a slow metabolism or a hereditary component, one might consider whether family recipes and dietary habits are hereditary to a much higher degree than slow metabolism or big bones could ever be. Education is critical, so how do we explain metabolism to a layman, e.g. a parent of an obese child? - Metabolism denotes all the processes, which turn nutrients from our food into energy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Chronic exposure of mice to environmental endocrine-disrupting chemicals disturbs their energy metabolism.

    PubMed

    Jin, Yuanxiang; Lin, Xiaojian; Miao, Wenyu; Wu, Tao; Shen, Hangjie; Chen, Shan; Li, Yanhong; Pan, Qiaoqiao; Fu, Zhengwei

    2014-03-21

    We evaluated the effects of a 20-week chronic exposure of mice to a low dose of cypermethrin (CYP), atrazine (ATZ) and 17α-ethynyestradiol (EE2) on energy metabolism. Here, male mice were exposed to 50 μg/kg BW/day CYP, 100 μg/kg BW/day ATZ or 1 μg/kg BW/day EE2 supplied in their drinking water for 20 weeks. During the exposure, mice were fed a high energy diet (HD). The bodyweights were not significantly affected by chronic exposure to EDCs, while the serum-free fatty acids (FFA) levels, hepatic lipid accumulation and triacylglycerol (TG) contents increased significantly in the ATZ- and CYP-HD groups. To determine the mechanism involved, we determined the expression levels of the genes in the glucose and fat metabolism pathways in the liver and adipose tissue. The results showed that chronic exposure to ATZ and CYP increased the mRNA levels of a number of key genes involved in both the de novo FFA synthesis pathway and the transport of FFA from blood. The increased amount of FFA was partially consumed as energy through β-oxidation in the mitochondria. Some of the FFA was used to synthesize TG in the liver by up-regulating primary genes, which resulted in increased TG levels and lipid accumulation. The results indicate that chronic exposure to EDCs has the potential to cause energy metabolic dysregulation and hepatotoxicity in mice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments

    PubMed Central

    Brownlow, Milene L.; Jung, Seung H.; Moore, Raquel J.; Bechmann, Naomi; Jankord, Ryan

    2017-01-01

    Nutritional ketosis may enhance cerebral energy metabolism and has received increased interest as a way to improve or preserve performance and resilience. Most studies to date have focused on metabolic or neurological disorders while anecdotal evidence suggests that ketosis may enhance performance in the absence of underlying dysfunction. Moreover, decreased availability of glucose in the brain following stressful events is associated with impaired cognition, suggesting the need for more efficient energy sources. We tested the hypotheses that ketosis induced by endogenous or exogenous ketones could: (a) augment cognitive outcomes in healthy subjects; and (b) prevent stress-induced detriments in cognitive parameters. Adult, male, Sprague Dawley rats were used to investigate metabolic and behavioral outcomes in 3 dietary conditions: ketogenic (KD), ketone supplemented (KS), or NIH-31 control diet in both control or chronic stress conditions. Acute administration of exogenous ketones resulted in reduction in blood glucose and sustained ketosis. Chronic experiments showed that in control conditions, only KD resulted in pronounced metabolic alterations and improved performance in the novel object recognition test. The hypothalamic-pituitary-adrenal (HPA) axis response revealed that KD-fed rats maintained peripheral ketosis despite increases in glucose whereas no diet effects were observed in ACTH or CORT levels. Both KD and KS-fed rats decreased escape latencies on the third day of water maze, whereas only KD prevented stress-induced deficits on the last testing day and improved probe test performance. Stress-induced decrease in hippocampal levels of β-hydroxybutyrate was attenuated in KD group while both KD and KS prevented stress effects on BDNF levels. Mitochondrial enzymes associated with ketogenesis were increased in both KD and KS hippocampal samples and both endothelial and neuronal glucose transporters were affected by stress but only in the control diet group

  9. Comparison of Various Indices of Energy Metabolism in Recumbent and Healthy Dairy Cows

    PubMed Central

    Guyot, Hugues; Detilleux, Johann; Lebreton, Pascal; Garnier, Catherine; Bonvoisin, Marie; Rollin, Frederic

    2017-01-01

    Background Downer cow syndrome (DCS) is often diagnosed in dairy cattle during the early post-partum period. The etiology of this condition is not completely understood, as it can be related to the energetic or electrolyte metabolism, as well as to infectious diseases or to trauma. Hypothesis/Objectives The aim of this study is to compare energy metabolism and insulin sensitivity indices and various biochemical parameters between recumbent and healthy dairy cows. Animals A prospective study has been undertaken on 361 recumbent and 80 healthy Holstein cows. Methods Plasmatic glucose, insulin, non-esterified fatty acid (NEFA) and β-hydroxybutyrate (BHB) were assayed in all cows in order to calculate the insulin sensitivity indices but also minerals (Calcium, Phosphorous and Magnesium), thyroxin and creatine kinase. Body Condition Scores (BCS) was assessed. Results Significant differences in NEFA, and the glucose and insulin sensitivity indices (“Homeostasis Model Assessment” HOMA, “Revised Quantitative Insulin Sensitivity Check Index” RQUICKI, RQUICKI-BHB) were observed between healthy and recumbent cows in the early post-parturient period indicating disturbances of glucose and insulin homeostasis in the recumbent cows. In the same manner, mineral concentrations were significantly different between healthy and recumbent cows. Glucose, insulin NEFA, and HOMA, were different between early post-partum downer cows and the DCS-affected cows later in lactation. Conclusion and clinical importance Results indicate disturbances in energy homeostasis in DCS-affected dairy cows. Further research should determine a prognostic value of the indices in cows suffering from recumbency of metabolic origin. PMID:28107442

  10. Energy metabolism in astrocytes and neurons treated with manganese: relation among cell-specific energy failure, glucose metabolism, and intercellular trafficking using multinuclear NMR-spectroscopic analysis.

    PubMed

    Zwingmann, Claudia; Leibfritz, Dieter; Hazell, Alan S

    2003-06-01

    A central question in manganese neurotoxicity concerns mitochondrial dysfunction leading to cerebral energy failure. To obtain insight into the underlying mechanism(s), the authors investigated cell-specific pathways of [1-13C]glucose metabolism by high-resolution multinuclear NMR-spectroscopy. Five-day treatment of neurons with 100-micro mol/L MnCl(2) led to 50% and 70% decreases of ATP/ADP and phosphocreatine-creatine ratios, respectively. An impaired flux of [1-13C]glucose through pyruvate dehydrogenase, which was associated with Krebs cycle inhibition and hence depletion of [4-13C]glutamate, [2-13C]GABA, and [13C]glutathione, hindered the ability of neurons to compensate for mitochondrial dysfunction by oxidative glucose metabolism and further aggravated neuronal energy failure. Stimulated glycolysis and oxidative glucose metabolism protected astrocytes against energy failure and oxidative stress, leading to twofold increased de novo synthesis of [3-13C]lactate and fourfold elevated [4-13C]glutamate and [13C]glutathione levels. Manganese, however, inhibited the synthesis and release of glutamine. Comparative NMR data obtained from cocultures showed disturbed astrocytic function and a failure of astrocytes to provide neurons with substrates for energy and neurotransmitter metabolism, leading to deterioration of neuronal antioxidant capacity (decreased glutathione levels) and energy metabolism. The results suggest that, concomitant to impaired neuronal glucose oxidation, changes in astrocytic metabolism may cause a loss of intercellular homeostatic equilibrium, contributing to neuronal dysfunction in manganese neurotoxicity.

  11. A High Protein Diet during Pregnancy Affects Hepatic Gene Expression of Energy Sensing Pathways along Ontogenesis in a Porcine Model

    PubMed Central

    Oster, Michael; Murani, Eduard; Metges, Cornelia C.; Ponsuksili, Siriluck; Wimmers, Klaus

    2011-01-01

    In rodent models and in humans the impact of gestational diets on the offspring's phenotype was shown experimentally and epidemiologically. The underlying programming of fetal development was shown to be associated with an increased risk of degenerative diseases in adulthood, including the metabolic syndrome. There are clues that diet-dependent modifications of the metabolism during fetal life can persist until adulthood. This leads to the hypothesis that the offspring's transcriptomes show short-term and long-term changes depending on the maternal diet. To this end pregnant German landrace gilts were fed either a high protein diet (HP, 30% CP) or an adequate protein diet (AP, 12% CP) throughout pregnancy. Hepatic transcriptome profiles of the offspring were analyzed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn). Depending on the gestational dietary exposure, mRNA expression levels of genes related to energy metabolism, N-metabolism, growth factor signaling pathways, lipid metabolism, nucleic acid metabolism and stress/immune response were affected either in a short-term or in a long-term manner. Gene expression profiles at fetal stage 94 dpc were almost unchanged between the diets. The gestational HP diet affected the hepatic expression profiles at prenatal and postnatal stages. The effects encompassed a modulation of the genome in terms of an altered responsiveness of energy and nutrient sensing pathways. Differential expression of genes related to energy production and nutrient utilization contribute to the maintenance of development and growth performance within physiological norms, however the modulation of these pathways may be accompanied by a predisposition for metabolic disturbances up to adult stages. PMID:21789176

  12. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Adaptive Evolution of Mitochondrial Energy Metabolism Genes Associated with Increased Energy Demand in Flying Insects

    PubMed Central

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

    2014-01-01

    Insects are unique among invertebrates for their ability to fly, which raises intriguing questions about how energy metabolism in insects evolved and changed along with flight. Although physiological studies indicated that energy consumption differs between flying and non-flying insects, the evolution of molecular energy metabolism mechanisms in insects remains largely unexplored. Considering that about 95% of adenosine triphosphate (ATP) is supplied by mitochondria via oxidative phosphorylation, we examined 13 mitochondrial protein-encoding genes to test whether adaptive evolution of energy metabolism-related genes occurred in insects. The analyses demonstrated that mitochondrial DNA protein-encoding genes are subject to positive selection from the last common ancestor of Pterygota, which evolved primitive flight ability. Positive selection was also found in insects with flight ability, whereas no significant sign of selection was found in flightless insects where the wings had degenerated. In addition, significant positive selection was also identified in the last common ancestor of Neoptera, which changed its flight mode from direct to indirect. Interestingly, detection of more positively selected genes in indirect flight rather than direct flight insects suggested a stronger selective pressure in insects having higher energy consumption. In conclusion, mitochondrial protein-encoding genes involved in energy metabolism were targets of adaptive evolution in response to increased energy demands that arose during the evolution of flight ability in insects. PMID:24918926

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

    PubMed

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

    2014-01-01

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

  15. 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. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  16. Dietary Whey and Casein Differentially Affect Energy Balance, Gut Hormones, Glucose Metabolism, and Taste Preference in Diet-Induced Obese Rats.

    PubMed

    Pezeshki, Adel; Fahim, Andrew; Chelikani, Prasanth K

    2015-10-01

    Dietary whey and casein proteins decrease food intake and body weight and improve glycemic control; however, little is known about the underlying mechanisms. We determined the effects of dietary whey, casein, and a combination of the 2 on energy balance, hormones, glucose metabolism, and taste preference in rats. In Expt. 1, Obesity Prone CD (OP-CD) rats were fed a high-fat control diet (33% fat energy) for 8 wk, and then randomly assigned to 4 isocaloric dietary treatments (n = 12/group): the control treatment (CO; 14% protein energy from egg white), the whey treatment (WH; 26% whey + 14% egg white), the casein treatment (CA; 26% casein + 14% egg white), or the whey plus casein treatment (WHCA; 13% whey + 13% casein + 14% egg white) for 28 d. Measurements included food intake, energy expenditure, body composition, metabolic hormones, glucose tolerance and key tissue markers of glucose and energy metabolism. In Expt. 2, naïve OP-CD rats were randomly assigned to 3 groups (n = 8/group). During an 8 d conditioning period, each group received on alternate days either the CO or WH, CO or CA, or CO or WHCA. Subsequently, preferences for the test diets were assessed on 2 consecutive days with food intake measurements at regular intervals. In Expt. 1, food intake was decreased by 17-37% for the first 14 d in the WH and CA rats, and by 18-34% only for the first 4 d in the WHCA compared with the CO rats. Fat mass decreased by 21-28% for the WH rats and 17-33% for the CA rats from day 14 onward, but by 30% only on day 28 in WHCA rats, relative to CO rats. Thus, food intake, body weight, and fat mass decreased more rapidly in WH and CA rats than in WHCA rats. Energy expenditure in WH rats decreased for the first 4 d compared with CA and WHCA rats, and for the first 7 d compared with the CO rats. Circulating leptin, glucose-dependent insulinotropic polypeptide, interleukin 6, and glucose concentrations were lower in WH, CA, and WHCA rats than in CO rats. Plasma glucagon

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

    PubMed

    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

    2011-08-01

    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. © 2011 IEEE

  18. 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

  19. 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. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. 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.

  1. Energy transfer in “parasitic” cancer metabolism

    PubMed Central

    Martinez-Outschoorn, Ubaldo E; Pestell, Richard G; Howell, Anthony; Tykocinski, Mark L; Nagajyothi, Fnu; Machado, Fabiana S; Tanowitz, Herbert B

    2011-01-01

    It is now widely recognized that the tumor microenvironment promotes cancer cell growth and metastasis via changes in cytokine secretion and extra-cellular matrix remodeling. However, the role of tumor stromal cells in providing energy for epithelial cancer cell growth is a newly emerging paradigm. For example, we and others have recently proposed that tumor growth and metastasis is related to an energy imbalance. Host cells produce energy-rich nutrients via catabolism (through autophagy, mitophagy and aerobic glycolysis), which are then transferred to cancer cells, to fuel anabolic tumor growth. Stromal cell derived L-lactate is taken up by cancer cells and is used for mitochondrial oxidative phosphorylation (OXPHOS), to produce ATP efficiently. However, “parasitic” energy transfer may be a more generalized mechanism in cancer biology than previously appreciated. Two recent papers in Science and Nature Medicine now show that lipolysis in host tissues also fuels tumor growth. These studies demonstrate that free fatty acids produced by host cell lipolysis are re-used via β-oxidation (β-OX) in cancer cell mitochondria. Thus, stromal catabolites (such as lactate, ketones, glutamine and free fatty acids) promote tumor growth by acting as high-energy onco-metabolites. As such, host catabolism via autophagy, mitophagy and lipolysis may explain the pathogenesis of cancer-associated cachexia and provides exciting new druggable targets for novel therapeutic interventions. Taken together, these findings also suggest that tumor cells promote their own growth and survival by behaving as a “parasitic organism.” Hence, we propose the term “parasitic cancer metabolism” to describe this type of metabolic-coupling in tumors. Targeting tumor cell mitochondria (OXPHOS and β-OX) would effectively uncouple tumor cells from their hosts, leading to their acute starvation. In this context, we discuss new evidence that high-energy onco-metabolites (produced by the stroma

  2. Modeling central metabolism and energy biosynthesis across microbial life.

    PubMed

    Edirisinghe, Janaka N; Weisenhorn, Pamela; Conrad, Neal; Xia, Fangfang; Overbeek, Ross; Stevens, Rick L; Henry, Christopher S

    2016-08-08

    Automatically generated bacterial metabolic models, and even some curated models, lack accuracy in predicting energy yields due to poor representation of key pathways in energy biosynthesis and the electron transport chain (ETC). Further compounding the problem, complex interlinking pathways in genome-scale metabolic models, and the need for extensive gapfilling to support complex biomass reactions, often results in predicting unrealistic yields or unrealistic physiological flux profiles. To overcome this challenge, we developed methods and tools ( http://coremodels.mcs.anl.gov ) to build high quality core metabolic models (CMM) representing accurate energy biosynthesis based on a well studied, phylogenetically diverse set of model organisms. We compare these models to explore the variability of core pathways across all microbial life, and by analyzing the ability of our core models to synthesize ATP and essential biomass precursors, we evaluate the extent to which the core metabolic pathways and functional ETCs are known for all microbes. 6,600 (80 %) of our models were found to have some type of aerobic ETC, whereas 5,100 (62 %) have an anaerobic ETC, and 1,279 (15 %) do not have any ETC. Using our manually curated ETC and energy biosynthesis pathways with no gapfilling at all, we predict accurate ATP yields for nearly 5586 (70 %) of the models under aerobic and anaerobic growth conditions. This study revealed gaps in our knowledge of the central pathways that result in 2,495 (30 %) CMMs being unable to produce ATP under any of the tested conditions. We then established a methodology for the systematic identification and correction of inconsistent annotations using core metabolic models coupled with phylogenetic analysis. We predict accurate energy yields based on our improved annotations in energy biosynthesis pathways and the implementation of diverse ETC reactions across the microbial tree of life. We highlighted missing annotations that were essential to

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed

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

    2017-02-01

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

  5. Hypothalamic carnitine metabolism integrates nutrient and hormonal feedback to regulate energy homeostasis.

    PubMed

    Stark, Romana; Reichenbach, Alex; Andrews, Zane B

    2015-12-15

    The maintenance of energy homeostasis requires the hypothalamic integration of nutrient feedback cues, such as glucose, fatty acids, amino acids, and metabolic hormones such as insulin, leptin and ghrelin. Although hypothalamic neurons are critical to maintain energy homeostasis research efforts have focused on feedback mechanisms in isolation, such as glucose alone, fatty acids alone or single hormones. However this seems rather too simplistic considering the range of nutrient and endocrine changes associated with different metabolic states, such as starvation (negative energy balance) or diet-induced obesity (positive energy balance). In order to understand how neurons integrate multiple nutrient or hormonal signals, we need to identify and examine potential intracellular convergence points or common molecular targets that have the ability to sense glucose, fatty acids, amino acids and hormones. In this review, we focus on the role of carnitine metabolism in neurons regulating energy homeostasis. Hypothalamic carnitine metabolism represents a novel means for neurons to facilitate and control both nutrient and hormonal feedback. In terms of nutrient regulation, carnitine metabolism regulates hypothalamic fatty acid sensing through the actions of CPT1 and has an underappreciated role in glucose sensing since carnitine metabolism also buffers mitochondrial matrix levels of acetyl-CoA, an allosteric inhibitor of pyruvate dehydrogenase and hence glucose metabolism. Studies also show that hypothalamic CPT1 activity also controls hormonal feedback. We hypothesis that hypothalamic carnitine metabolism represents a key molecular target that can concurrently integrate nutrient and hormonal information, which is critical to maintain energy homeostasis. We also suggest this is relevant to broader neuroendocrine research as it predicts that hormonal signaling in the brain varies depending on current nutrient status. Indeed, the metabolic action of ghrelin, leptin or insulin

  6. Energy metabolism regulated by HDAC inhibitor attenuates cardiac injury in hemorrhagic rat model

    PubMed Central

    Kuai, Qiyuan; Wang, Chunyan; Wang, Yanbing; Li, Weijing; Zhang, Gongqing; Qiao, Zhixin; He, Min; Wang, Xuanlin; Wang, Yu; Jiang, Xingwei; Su, Lihua; He, Yuezhong; Ren, Suping; Yu, Qun

    2016-01-01

    A disturbance of energy metabolism reduces cardiac function in acute severe hemorrhagic patients. Alternatively, adequate energy supply reduces heart failure and increases survival. However, the approach to regulating energy metabolism conductive to vital organs is limited, and the underlying molecular mechanism remains unknown. This study assesses the ability of histone deacetylase inhibitors (HDACIs) to preserve cardiac energy metabolism during lethal hemorrhagic injury. In the lethally hemorrhagic rat and hypoxic myocardial cells, energy metabolism and heart function were well maintained following HDACI treatment, as evident by continuous ATP production with normal cardiac contraction. Valproic acid (VPA) regulated the energy metabolism of hemorrhagic heart by reducing lactate synthesis and protecting the mitochondrial ultrastructure and respiration, which were attributable to the inhibition of lactate dehydrogenase A activity and the increased myeloid cell leukemia-1 (mcl-1) gene expression, ultimately facilitating ATP production and consumption. MCL-1, the key target of VPA, mediated this cardioprotective effect under acute severe hemorrhage conditions. Our results suggest that HDACIs promote cardioprotection by improving energy metabolism during hemorrhagic injury and could therefore be an effective strategy to counteract this process in the clinical setting. PMID:27910887

  7. Statins Affect Skeletal Muscle Performance: Evidence for Disturbances in Energy Metabolism.

    PubMed

    Allard, Neeltje A E; Schirris, Tom J J; Verheggen, Rebecca J; Russel, Frans G M; Rodenburg, Richard J; Smeitink, Jan A M; Thompson, Paul D; Hopman, Maria T E; Timmers, Silvie

    2018-01-01

    Statin myopathy is linked to disturbances in mitochondrial function and exercise intolerance. To determine whether differences exist in exercise performance, muscle function, and muscle mitochondrial oxidative capacity and content between symptomatic and asymptomatic statin users, and control subjects. Cross-sectional study. Department of Physiology, Radboud University Medical Center. Long-term symptomatic and asymptomatic statin users, and control subjects (n = 10 per group). Maximal incremental cycling tests, involuntary electrically stimulated isometric quadriceps-muscle contractions, and biopsy of vastus lateralis muscle. Maximal exercise capacity, substrate use during exercise, muscle function, and mitochondrial energy metabolism. Peak oxygen uptake, maximal work load, and ventilatory efficiency were comparable between groups, but both statin groups had a depressed anaerobic threshold compared with the control group (P = 0.01). Muscle relaxation time was prolonged in both statin groups compared with the control group and rate of maximal force rise was decreased (Ptime×group < 0.001 for both measures). Mitochondrial activity of complexes II and IV was lower in symptomatic statin users than control subjects and tended to be lower for complex (C) III (CII: P = 0.03; CIII: P = 0.05; CIV: P = 0.04). Mitochondrial content tended to be lower in both statin groups than in control subjects. Statin use attenuated substrate use during maximal exercise performance, induced muscle fatigue during repeated muscle contractions, and decreased muscle mitochondrial oxidative capacity. This suggests disturbances in mitochondrial oxidative capacity occur with statin use even in patients without statin-induced muscle complaints. Copyright © 2017 Endocrine Society

  8. 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. © 2016 The Author(s).

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

    PubMed Central

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

    2016-01-01

    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

  10. Fatty acids in energy metabolism of the central nervous system.

    PubMed

    Panov, Alexander; 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.

  11. 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

  12. A Conserved Role for Syndecan Family Members in the Regulation of Whole-Body Energy Metabolism

    PubMed Central

    De Luca, Maria; Klimentidis, Yann C.; Casazza, Krista; Moses Chambers, Michelle; Cho, Ruth; Harbison, Susan T.; Jumbo-Lucioni, Patricia; Zhang, Shaoyan; Leips, Jeff; Fernandez, Jose R.

    2010-01-01

    Syndecans are a family of type-I transmembrane proteins that are involved in cell-matrix adhesion, migration, neuronal development, and inflammation. Previous quantitative genetic studies pinpointed Drosophila Syndecan (dSdc) as a positional candidate gene affecting variation in fat storage between two Drosophila melanogaster strains. Here, we first used quantitative complementation tests with dSdc mutants to confirm that natural variation in this gene affects variability in Drosophila fat storage. Next, we examined the effects of a viable dSdc mutant on Drosophila whole-body energy metabolism and associated traits. We observed that young flies homozygous for the dSdc mutation had reduced fat storage and slept longer than homozygous wild-type flies. They also displayed significantly reduced metabolic rate, lower expression of spargel (the Drosophila homologue of PGC-1), and reduced mitochondrial respiration. Compared to control flies, dSdc mutants had lower expression of brain insulin-like peptides, were less fecund, more sensitive to starvation, and had reduced life span. Finally, we tested for association between single nucleotide polymorphisms (SNPs) in the human SDC4 gene and variation in body composition, metabolism, glucose homeostasis, and sleep traits in a cohort of healthy early pubertal children. We found that SNP rs4599 was significantly associated with resting energy expenditure (P = 0.001 after Bonferroni correction) and nominally associated with fasting glucose levels (P = 0.01) and sleep duration (P = 0.044). On average, children homozygous for the minor allele had lower levels of glucose, higher resting energy expenditure, and slept shorter than children homozygous for the common allele. We also observed that SNP rs1981429 was nominally associated with lean tissue mass (P = 0.035) and intra-abdominal fat (P = 0.049), and SNP rs2267871 with insulin sensitivity (P = 0.037). Collectively, our results in Drosophila and humans

  13. A conserved role for syndecan family members in the regulation of whole-body energy metabolism.

    PubMed

    De Luca, Maria; Klimentidis, Yann C; Casazza, Krista; Chambers, Michelle Moses; Cho, Ruth; Harbison, Susan T; Jumbo-Lucioni, Patricia; Zhang, Shaoyan; Leips, Jeff; Fernandez, Jose R

    2010-06-23

    Syndecans are a family of type-I transmembrane proteins that are involved in cell-matrix adhesion, migration, neuronal development, and inflammation. Previous quantitative genetic studies pinpointed Drosophila Syndecan (dSdc) as a positional candidate gene affecting variation in fat storage between two Drosophila melanogaster strains. Here, we first used quantitative complementation tests with dSdc mutants to confirm that natural variation in this gene affects variability in Drosophila fat storage. Next, we examined the effects of a viable dSdc mutant on Drosophila whole-body energy metabolism and associated traits. We observed that young flies homozygous for the dSdc mutation had reduced fat storage and slept longer than homozygous wild-type flies. They also displayed significantly reduced metabolic rate, lower expression of spargel (the Drosophila homologue of PGC-1), and reduced mitochondrial respiration. Compared to control flies, dSdc mutants had lower expression of brain insulin-like peptides, were less fecund, more sensitive to starvation, and had reduced life span. Finally, we tested for association between single nucleotide polymorphisms (SNPs) in the human SDC4 gene and variation in body composition, metabolism, glucose homeostasis, and sleep traits in a cohort of healthy early pubertal children. We found that SNP rs4599 was significantly associated with resting energy expenditure (P = 0.001 after Bonferroni correction) and nominally associated with fasting glucose levels (P = 0.01) and sleep duration (P = 0.044). On average, children homozygous for the minor allele had lower levels of glucose, higher resting energy expenditure, and slept shorter than children homozygous for the common allele. We also observed that SNP rs1981429 was nominally associated with lean tissue mass (P = 0.035) and intra-abdominal fat (P = 0.049), and SNP rs2267871 with insulin sensitivity (P = 0.037). Collectively, our results in Drosophila and humans argue that syndecan family

  14. 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

  15. Energy metabolism, body composition, and urea generation rate in hemodialysis patients.

    PubMed

    Sridharan, Sivakumar; Vilar, Enric; Berdeprado, Jocelyn; Farrington, Ken

    2013-10-01

    Hemodialysis (HD) adequacy is currently assessed using normalized urea clearance (Kt/V), although scaling based on Watson volume (V) may disadvantage women and men with low body weight. Alternative scaling factors such as resting energy expenditure and high metabolic rate organ mass have been suggested. The relationship between such factors and uremic toxin generation has not been established. We aimed to study the relationship between body size, energy metabolism, and urea generation rate. A cross-sectional cohort of 166 HD patients was studied. Anthropometric measurements were carried on all. Resting energy expenditure was measured by indirect calorimetry, fat-free mass by bio-impedance and total energy expenditure by combining resting energy expenditure with a questionnaire-derived physical activity data. High metabolic rate organ mass was calculated using a published equation and urea generation rate using formal urea kinetic modeling. Metabolic factors including resting energy expenditure, total energy expenditure and fat-free mass correlated better with urea generation rate than did Watson volume. Total energy expenditure and fat-free mass (but not Watson Volume) were independent predictors of urea generation rate, the model explaining 42% of its variation. Small women (energy expenditure correlated significantly with urea generation rate. Energy metabolism, body composition and physical activity play important roles in small solute uremic toxin generation in HD patients and hence may impact on minimum dialysis requirements. Small women generate relatively more small solute toxins than other groups and thus may have a higher relative need for dialysis. © 2013 The Authors. Hemodialysis

  16. 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

  17. Chronic Heat Stress Impairs the Quality of Breast-Muscle Meat in Broilers by Affecting Redox Status and Energy-Substance Metabolism.

    PubMed

    Lu, Zhuang; He, Xiaofang; Ma, Bingbing; Zhang, Lin; Li, Jiaolong; Jiang, Yun; Zhou, Guanghong; Gao, Feng

    2017-12-27

    We investigated the molecular mechanisms by which chronic heat stress impairs the breast-meat quality of broilers. Broilers were assigned to three groups: the normal control (NC) group, heat-stress (HS) group, and pair-fed (PF) group. After 7 days of heat exposure (32 °C), the high temperature had caused oxidative stress; elevated the activity of citrate synthase (CS), the mRNA expression of M-CPT1, and the phosphorylation level of AMPKα; and reduced the mRNA expression of avUCP. After 14 days of heat exposure, the heat stress had increased the lightness and drip loss and decreased the pH and shear force of the breast meat. Additionally, the heat exposure had increased the mRNA expressions of FAS, ACC, and PDK4; the content of lipids; and the activities of lactic dehydrogenase and pyruvate kinase, and it had decreased the mRNA expression of M-CPT1 and the activity of CS. In conclusion, chronic heat stress impairs meat quality by causing mitochondria to malfunction and affecting energy-substance aerobic metabolism, resulting in increased glycolysis and intramuscular fat deposition.

  18. Relationship between energy dense diets and white adipose tissue inflammation in metabolic syndrome.

    PubMed

    Alemany, Marià

    2013-01-01

    Metabolic syndrome (MS) is a widespread pathologic state that manifests as multiple intertwined diseases affecting the entire body. This review analyzes the contribution of adipose tissue inflammation to its development. The main factor in the appearance of MS is an excess of dietary energy (largely fats), eliciting insulin resistance and creating the problem of excess energy disposal. Under these conditions, amino acid catabolism is diminished, which indirectly alters the production of nitric oxide and affects blood flow regulation. The oxidation of nitric oxide to nitrite and nitrate affects microbiota composition and functions. Adipose tissue cannot incorporate excessive nutrients after cell enlargement and loss of function. Tissue damage is a form of aggression, and the response is proinflammatory cytokine release. Cytokines favor the massive penetration of immune system cells, such as macrophages, which unsuccessfully try to fight an elusive danger for which they are not prepared. The consequence is low-level maintenance of the inflammatory state, which affects endoplasmic reticulum function and the endothelial response to excess regulatory mechanisms affecting blood flow and substrate/oxygen supply. When inflammation becomes chronic, the pathologic consequences are disseminated throughout the body because unused substrates and signals from adipose tissue affect energy partitioning and organ function. This maintenance of an unbalanced state ultimately results in the establishment of MS and associated pathologies. New research should focus on identifying ways to disarm the inflammatory response of adipose tissue when the dangers of dietary excess have already been controlled. Copyright © 2013. Published by Elsevier Inc.

  19. MYC-induced cancer cell energy metabolism and therapeutic opportunities.

    PubMed

    Dang, Chi V; Le, Anne; Gao, Ping

    2009-11-01

    Although cancers have altered glucose metabolism, termed the Warburg effect, which describes the increased uptake and conversion of glucose to lactate by cancer cells under adequate oxygen tension, changes in the metabolism of glutamine and fatty acid have also been documented. The MYC oncogene, which contributes to the genesis of many human cancers, encodes a transcription factor c-Myc, which links altered cellular metabolism to tumorigenesis. c-Myc regulates genes involved in the biogenesis of ribosomes and mitochondria, and regulation of glucose and glutamine metabolism. With E2F1, c-Myc induces genes involved in nucleotide metabolism and DNA replication, and microRNAs that homeostatically attenuate E2F1 expression. With the hypoxia inducible transcription factor HIF-1, ectopic c-Myc cooperatively induces a transcriptional program for hypoxic adaptation. Myc regulates gene expression either directly, such as glycolytic genes including lactate dehydrogenase A (LDHA), or indirectly, such as repression of microRNAs miR-23a/b to increase glutaminase (GLS) protein expression and glutamine metabolism. Ectopic MYC expression in cancers, therefore, could concurrently drive aerobic glycolysis and/or oxidative phosphorylation to provide sufficient energy and anabolic substrates for cell growth and proliferation in the context of the tumor microenvironment. Collectively, these studies indicate that Myc-mediated altered cancer cell energy metabolism could be translated for the development of new anticancer therapies.

  20. Modeling central metabolism and energy biosynthesis across microbial life

    DOE PAGES

    Edirisinghe, Janaka N.; Weisenhorn, Pamela; Conrad, Neal; ...

    2016-08-08

    Here, automatically generated bacterial metabolic models, and even some curated models, lack accuracy in predicting energy yields due to poor representation of key pathways in energy biosynthesis and the electron transport chain (ETC). Further compounding the problem, complex interlinking pathways in genome-scale metabolic models, and the need for extensive gapfilling to support complex biomass reactions, often results in predicting unrealistic yields or unrealistic physiological flux profiles. As a result, to overcome this challenge, we developed methods and tools to build high quality core metabolic models (CMM) representing accurate energy biosynthesis based on a well studied, phylogenetically diverse set of modelmore » organisms. We compare these models to explore the variability of core pathways across all microbial life, and by analyzing the ability of our core models to synthesize ATP and essential biomass precursors, we evaluate the extent to which the core metabolic pathways and functional ETCs are known for all microbes. 6,600 (80 %) of our models were found to have some type of aerobic ETC, whereas 5,100 (62 %) have an anaerobic ETC, and 1,279 (15 %) do not have any ETC. Using our manually curated ETC and energy biosynthesis pathways with no gapfilling at all, we predict accurate ATP yields for nearly 5586 (70 %) of the models under aerobic and anaerobic growth conditions. This study revealed gaps in our knowledge of the central pathways that result in 2,495 (30 %) CMMs being unable to produce ATP under any of the tested conditions. We then established a methodology for the systematic identification and correction of inconsistent annotations using core metabolic models coupled with phylogenetic analysis. In conclusion, we predict accurate energy yields based on our improved annotations in energy biosynthesis pathways and the implementation of diverse ETC reactions across the microbial tree of life. We highlighted missing annotations that were essential

  1. Modeling central metabolism and energy biosynthesis across microbial life

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Edirisinghe, Janaka N.; Weisenhorn, Pamela; Conrad, Neal

    Here, automatically generated bacterial metabolic models, and even some curated models, lack accuracy in predicting energy yields due to poor representation of key pathways in energy biosynthesis and the electron transport chain (ETC). Further compounding the problem, complex interlinking pathways in genome-scale metabolic models, and the need for extensive gapfilling to support complex biomass reactions, often results in predicting unrealistic yields or unrealistic physiological flux profiles. As a result, to overcome this challenge, we developed methods and tools to build high quality core metabolic models (CMM) representing accurate energy biosynthesis based on a well studied, phylogenetically diverse set of modelmore » organisms. We compare these models to explore the variability of core pathways across all microbial life, and by analyzing the ability of our core models to synthesize ATP and essential biomass precursors, we evaluate the extent to which the core metabolic pathways and functional ETCs are known for all microbes. 6,600 (80 %) of our models were found to have some type of aerobic ETC, whereas 5,100 (62 %) have an anaerobic ETC, and 1,279 (15 %) do not have any ETC. Using our manually curated ETC and energy biosynthesis pathways with no gapfilling at all, we predict accurate ATP yields for nearly 5586 (70 %) of the models under aerobic and anaerobic growth conditions. This study revealed gaps in our knowledge of the central pathways that result in 2,495 (30 %) CMMs being unable to produce ATP under any of the tested conditions. We then established a methodology for the systematic identification and correction of inconsistent annotations using core metabolic models coupled with phylogenetic analysis. In conclusion, we predict accurate energy yields based on our improved annotations in energy biosynthesis pathways and the implementation of diverse ETC reactions across the microbial tree of life. We highlighted missing annotations that were essential

  2. Does methamphetamine affect bone metabolism?

    PubMed

    Tomita, Masafumi; Katsuyama, Hironobu; Watanabe, Yoko; Okuyama, Toshiko; Fushimi, Shigeko; Ishikawa, Takaki; Nata, Masayuki; Miyamoto, Osamu

    2014-05-07

    There is a close relationship between the central nervous system activity and bone metabolism. Therefore, methamphetamine (METH), which stimulates the central nervous system, is expected to affect bone turnover. The aim of this study was to investigate the role of METH in bone metabolism. Mice were divided into 3 groups, the control group receiving saline injections, and the 5 and 10mg/kg METH groups (n=6 in each group). All groups received an injection of saline or METH every other day for 8 weeks. Bone mineral density (BMD) was assessed by X-ray computed tomography. We examined biochemical markers and histomorphometric changes in the second cancellous bone of the left femoral distal end. The animals that were administered 5mg/kg METH showed an increased locomotor activity, whereas those receiving 10mg/kg displayed an abnormal and stereotyped behavior. Serum calcium and phosphorus concentrations were normal compared to the controls, whereas the serum protein concentration was lower in the METH groups. BMD was unchanged in all groups. Bone formation markers such as alkaline phosphatase and osteocalcin significantly increased in the 5mg/kg METH group, but not in the 10mg/kg METH group. In contrast, bone resorption markers such as C-terminal telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b did not change in any of the METH groups. Histomorphometric analyses were consistent with the biochemical markers data. A significant increase in osteoblasts, especially in type III osteoblasts, was observed in the 5mg/kg METH group, whereas other parameters of bone resorption and mineralization remained unchanged. These results indicate that bone remodeling in this group was unbalanced. In contrast, in the 10mg/kg METH group, some parameters of bone formation were significantly or slightly decreased, suggesting a low turnover metabolism. Taken together, our results suggest that METH had distinct dose-dependent effects on bone turnover and that METH might

  3. Ontogeny of hepatic energy metabolism genes in mice as revealed by RNA-sequencing.

    PubMed

    Renaud, Helen J; Cui, Yue Julia; Lu, Hong; Zhong, Xiao-bo; Klaassen, Curtis D

    2014-01-01

    The liver plays a central role in metabolic homeostasis by coordinating synthesis, storage, breakdown, and redistribution of nutrients. Hepatic energy metabolism is dynamically regulated throughout different life stages due to different demands for energy during growth and development. However, changes in gene expression patterns throughout ontogeny for factors important in hepatic energy metabolism are not well understood. We performed detailed transcript analysis of energy metabolism genes during various stages of liver development in mice. Livers from male C57BL/6J mice were collected at twelve ages, including perinatal and postnatal time points (n = 3/age). The mRNA was quantified by RNA-Sequencing, with transcript abundance estimated by Cufflinks. One thousand sixty energy metabolism genes were examined; 794 were above detection, of which 627 were significantly changed during at least one developmental age compared to adult liver. Two-way hierarchical clustering revealed three major clusters dependent on age: GD17.5-Day 5 (perinatal-enriched), Day 10-Day 20 (pre-weaning-enriched), and Day 25-Day 60 (adolescence/adulthood-enriched). Clustering analysis of cumulative mRNA expression values for individual pathways of energy metabolism revealed three patterns of enrichment: glycolysis, ketogenesis, and glycogenesis were all perinatally-enriched; glycogenolysis was the only pathway enriched during pre-weaning ages; whereas lipid droplet metabolism, cholesterol and bile acid metabolism, gluconeogenesis, and lipid metabolism were all enriched in adolescence/adulthood. This study reveals novel findings such as the divergent expression of the fatty acid β-oxidation enzymes Acyl-CoA oxidase 1 and Carnitine palmitoyltransferase 1a, indicating a switch from mitochondrial to peroxisomal β-oxidation after weaning; as well as the dynamic ontogeny of genes implicated in obesity such as Stearoyl-CoA desaturase 1 and Elongation of very long chain fatty acids-like 3. These

  4. Flavanol plasma bioavailability is affected by metabolic syndrome in rats.

    PubMed

    Margalef, Maria; Pons, Zara; Iglesias-Carres, Lisard; Bravo, Francisca Isabel; Muguerza, Begoña; Arola-Arnal, Anna

    2017-09-15

    Flavanols, which exert several health benefits, are metabolized after ingestion. Factors such as the host physiological condition could affect the metabolism and bioavailability of flavanols, influencing their bioactivities. This study aimed to qualitatively evaluate whether a pathological state influenced flavanol plasma bioavailability. Standard and cafeteria (CAF) diet fed rats, a robust model of metabolic syndrome (MeS), were administered 1000mg/kg of flavanol enriched grape seed polyphenol extract (GSPE). Flavanols and their metabolites were quantified by HPLC-MS/MS in plasma before and at 2, 4, 7, 24, and 48h after GSPE ingestion. Results showed that in CAF administered rats the maximum time of plasma flavanol concentration was delayed and these animals presented higher levels of plasma phase-II metabolites as well as altered microbial metabolites. In conclusion, this study demonstrated that MeS pathological state modified flavanol bioavailability, supporting the hypothesis that flavanol metabolism, and therefore flavanol functionality, depend on the organism's state of health. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. 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

  6. Thermodynamics of the living organisms. Allometric relationship between the total metabolic energy, chemical energy and body temperature in mammals

    NASA Astrophysics Data System (ADS)

    Atanasov, Atanas Todorov

    2017-11-01

    The study present relationship between the total metabolic energy (ETME(c), J) derived as a function of body chemical energy (Gchem, J) and absolute temperature (Tb, K) in mammals: ETME(c) =Gchem (Tb/Tn). In formula the temperature Tn =2.73K appears normalization temperature. The calculated total metabolic energy ETME(c) differs negligible from the total metabolic energy ETME(J), received as a product between the basal metabolic rate (Pm, J/s) and the lifespan (Tls, s) of mammals: ETME = Pm×Tls. The physical nature and biological mean of the normalization temperature (Tn, K) is unclear. It is made the hypothesis that the kTn energy (where k= 1.3806×10-23 J/K -Boltzmann constant) presents energy of excitation states (modes) in biomolecules and body structures that could be in equilibrium with chemical energy accumulated in body. This means that the accumulated chemical energy allows trough all body molecules and structures to propagate excitations states with kTn energy with wavelength in the rage of width of biological membranes. The accumulated in biomolecules chemical energy maintains spread of the excited states through biomolecules without loss of energy.

  7. Central Metabolic Responses to Ozone and Herbivory Affect Photosynthesis and Stomatal Closure1[OPEN

    PubMed Central

    Khaling, Eliezer; Lassueur, Steve

    2016-01-01

    Plants have evolved adaptive mechanisms that allow them to tolerate a continuous range of abiotic and biotic stressors. Tropospheric ozone (O3), a global anthropogenic pollutant, directly affects living organisms and ecosystems, including plant-herbivore interactions. In this study, we investigate the stress responses of Brassica nigra (wild black mustard) exposed consecutively to O3 and the specialist herbivore Pieris brassicae. Transcriptomics and metabolomics data were evaluated using multivariate, correlation, and network analyses for the O3 and herbivory responses. O3 stress symptoms resembled those of senescence and phosphate starvation, while a sequential shift from O3 to herbivory induced characteristic plant defense responses, including a decrease in central metabolism, induction of the jasmonic acid/ethylene pathways, and emission of volatiles. Omics network and pathway analyses predicted a link between glycerol and central energy metabolism that influences the osmotic stress response and stomatal closure. Further physiological measurements confirmed that while O3 stress inhibited photosynthesis and carbon assimilation, sequential herbivory counteracted the initial responses induced by O3, resulting in a phenotype similar to that observed after herbivory alone. This study clarifies the consequences of multiple stress interactions on a plant metabolic system and also illustrates how omics data can be integrated to generate new hypotheses in ecology and plant physiology. PMID:27758847

  8. 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

  9. A neuronal lactate uptake inhibitor slows recovery of extracellular ion concentration changes in the hippocampal CA3 region by affecting energy metabolism

    PubMed Central

    Angamo, Eskedar Ayele; Rösner, Joerg; Liotta, Agustin; Kovács, Richard

    2016-01-01

    Astrocyte-derived lactate supports pathologically enhanced neuronal metabolism, but its role under physiological conditions is still a matter of debate. Here, we determined the contribution of astrocytic neuronal lactate shuttle for maintenance of ion homeostasis and energy metabolism. We tested for the effects of α-cyano-4-hydroxycinnamic acid (4-CIN), which could interfere with energy metabolism by blocking monocarboxylate-transporter 2 (MCT2)-mediated neuronal lactate uptake, on evoked potentials, stimulus-induced changes in K+, Na+, Ca2+, and oxygen concentrations as well as on changes in flavin adenine dinucleotide (FAD) autofluorescence in the hippocampal area CA3. MCT2 blockade by 4-CIN reduced synaptically evoked but not antidromic population spikes. This effect was dependent on the activation of KATP channels indicating reduced neuronal ATP synthesis. By contrast, lactate receptor activation by 3,5-dihydroxybenzoic acid (3,5-DHBA) resulted in increased antidromic and orthodromic population spikes suggesting that 4-CIN effects are not mediated by lactate accumulation and subsequent activation of lactate receptors. Recovery kinetics of all ion transients were prolonged and baseline K+ concentration became elevated by blockade of lactate uptake. Lactate contributed to oxidative metabolism as both baseline respiration and stimulus-induced changes in Po2 were decreased, while FAD fluorescence increased likely due to a reduced conversion of FAD into FADH2. These data suggest that lactate shuttle contributes to regulation of ion homeostatsis and synaptic signaling even in the presence of ample glucose. PMID:27559140

  10. Anaerobic energy metabolism in unicellular photosynthetic eukaryotes.

    PubMed

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

    2013-02-01

    Anaerobic metabolic pathways allow unicellular organisms to tolerate or colonize anoxic environments. Over the past ten years, genome sequencing projects have brought a new light on the extent of anaerobic metabolism in eukaryotes. A surprising development has been that free-living unicellular algae capable of photoautotrophic lifestyle are, in terms of their enzymatic repertoire, among the best equipped eukaryotes known when it comes to anaerobic energy metabolism. Some of these algae are marine organisms, common in the oceans, others are more typically soil inhabitants. All these species are important from the ecological (O(2)/CO(2) budget), biotechnological, and evolutionary perspectives. In the unicellular algae surveyed here, mixed-acid type fermentations are widespread while anaerobic respiration, which is more typical of eukaryotic heterotrophs, appears to be rare. The presence of a core anaerobic metabolism among the algae provides insights into its evolutionary origin, which traces to the eukaryote common ancestor. The predicted fermentative enzymes often exhibit an amino acid extension at the N-terminus, suggesting that these proteins might be compartmentalized in the cell, likely in the chloroplast or the mitochondrion. The green algae Chlamydomonas reinhardtii and Chlorella NC64 have the most extended set of fermentative enzymes reported so far. Among the eukaryotes with secondary plastids, the diatom Thalassiosira pseudonana has the most pronounced anaerobic capabilities as yet. From the standpoints of genomic, transcriptomic, and biochemical studies, anaerobic energy metabolism in C. reinhardtii remains the best characterized among photosynthetic protists. This article is part of a Special Issue entitled: The evolutionary aspects of bioenergetic systems. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Lethal Dysregulation of Energy Metabolism During Embryonic Vitamin E Deficiency

    PubMed Central

    McDougall, Melissa; Choi, Jaewoo; Kim, Hye-Kyeong; Bobe, Gerd; Stevens, J. Frederik; Cadenas, Enrique; Tanguay, Robert; Traber, Maret G.

    2017-01-01

    Vitamin E (α-tocopherol, VitE) was discovered in 1922 for its role in preventing embryonic mortality. We investigated the underlying mechanisms causing lethality using targeted metabolomics analyses of zebrafish VitE-deficient embryos over five days of development, which coincided with their increased morbidity and mortality. VitE deficiency resulted in peroxidation of docosahexaenoic acid (DHA), depleting DHA-containing phospholipids, especially phosphatidylcholine, which also caused choline depletion. This increased lipid peroxidation also increased NADPH oxidation, which depleted glucose by shunting it to the pentose phosphate pathway. VitE deficiency was associated with mitochondrial dysfunction with concomitant impairment of energy homeostasis. The observed morbidity and mortality outcomes could be attenuated, but not fully reversed, by glucose injection into VitE-deficient embryos at developmental day one. Thus, embryonic VitE deficiency in vertebrates leads to a metabolic reprogramming that adversely affects methyl donor status and cellular energy homeostasis with lethal outcomes. PMID:28095320

  12. Coping, affect, and the metabolic syndrome in older men: how does coping get under the skin?

    PubMed

    Yancura, Loriena A; Aldwin, Carolyn M; Levenson, Michael R; Spiro, Avron

    2006-09-01

    The metabolic syndrome is a complex construct with interrelated factors of obesity, blood pressure, lipids, and glucose. It is a risk factor for a number of chronic diseases in late life. This study tested a model in which the relationship between stress and the metabolic syndrome was mediated by appraisal, coping, and affect. Data were collected from 518 male participants in the Normative Aging Study (X(age) = 68.17 years). The model was partially confirmed. Relationships among stress, appraisal, coping, and affect were valenced along positive and negative pathways. However, affect was not directly related to the metabolic syndrome. The metabolic syndrome was related to positive coping as operationalized by self-regulatory strategies. The results of this study suggest that the influence of coping on physical health may occur through emotional regulation.

  13. Changes in cardiac energy metabolic pathways in overweighed rats fed a high-fat diet.

    PubMed

    Modrego, Javier; de las Heras, Natalia; Zamorano-León, Jose J; Mateos-Cáceres, Petra J; Martín-Fernández, Beatriz; Valero-Muñoz, Maria; Lahera, Vicente; López-Farré, Antonio J

    2013-03-01

    Heart produces ATP through long-chain fatty acids beta oxidation. To analyze whether in ventricular myocardium, high-fat diet may modify the expression of proteins associated with energy metabolism before myocardial function was affected. Wistar Kyoto rats were divided into two groups: (a) rats fed standard diet (control; n = 6) and (b) rats fed high-fat diet (HFD; n = 6). Proteins from left ventricles were analyzed by two-dimensional electrophoresis, mass spectrometry and Western blotting. Rats fed with HFD showed higher body weight, insulin, glucose, leptin and total cholesterol plasma levels as compared with those fed with standard diet. However, myocardial functional parameters were not different between them. The protein expression of 3-ketoacyl-CoA thiolase, acyl-CoA hydrolase mitochondrial precursor and enoyl-CoA hydratase, three long-chain fatty acid β-oxidation-related enzymes, and carnitine-O-palmitoyltransferase I was significantly higher in left ventricles from HFD rats. Protein expression of triosephosphate isomerase was higher in left ventricles from HFD rats than in those from control. Two α/β-enolase isotypes and glyceraldehyde-3-phosphate isomerase were significantly increased in HFD rats as compared with control. Pyruvate and lactate contents were similar in HFD and control groups. Expression of proteins associated with Krebs cycle and mitochondrial oxidative phosphorylation was higher in HFD rats. Expression of proteins involved in left ventricle metabolic energy was enhanced before myocardial functionality was affected in rats fed with HFD. These findings may probably indicate higher cardiac energy requirement due to weight increase by HFD.

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

    PubMed

    Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

    2016-03-11

    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.

  15. 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

  16. State-dependent metabolic partitioning and energy conservation: A theoretical framework for understanding the function of sleep.

    PubMed

    Schmidt, Markus H; Swang, Theodore W; Hamilton, Ian M; Best, Janet A

    2017-01-01

    Metabolic rate reduction has been considered the mechanism by which sleep conserves energy, similar to torpor or hibernation. This mechanism of energy savings is in conflict with the known upregulation (compared to wake) of diverse functions during sleep and neglects a potential role in energy conservation for partitioning of biological operations by behavioral state. Indeed, energy savings as derived from state-dependent resource allocations have yet to be examined. A mathematical model is presented based on relative rates of energy deployment for biological processes upregulated during either wake or sleep. Using this model, energy savings from sleep-wake cycling over constant wakefulness is computed by comparing stable limit cycles for systems of differential equations. A primary objective is to compare potential energy savings derived from state-dependent metabolic partitioning versus metabolic rate reduction. Additionally, energy conservation from sleep quota and the circadian system are also quantified in relation to a continuous wake condition. As a function of metabolic partitioning, our calculations show that coupling of metabolic operations with behavioral state may provide comparatively greater energy savings than the measured decrease in metabolic rate, suggesting that actual energy savings derived from sleep may be more than 4-fold greater than previous estimates. A combination of state-dependent metabolic partitioning and modest metabolic rate reduction during sleep may enhance energy savings beyond what is achievable through metabolic partitioning alone; however, the relative contribution from metabolic partitioning diminishes as metabolic rate is decreased during the rest phase. Sleep quota and the circadian system further augment energy savings in the model. Finally, we propose that state-dependent resource allocation underpins both sleep homeostasis and the optimization of daily energy conservation across species. This new paradigm identifies an

  17. Energy metabolism of intervertebral disc under mechanical loading.

    PubMed

    Wang, Chong; Gonzales, Silvia; Levene, Howard; Gu, Weiyong; Huang, Chun-Yuh Charles

    2013-11-01

    Intervertebral disc (IVD) degeneration is closely associated with low back pain (LBP), which is a major health concern in the U.S. Cellular biosynthesis of extracellular matrix (ECM), which is important for maintaining tissue integrity and preventing tissue degeneration, is an energy demanding process. Due to impaired nutrient support in avascular IVD, adenosine triphosphate (ATP) supply could be a limiting factor for maintaining normal ECM synthesis. Therefore, the objective of this study was to investigate the energy metabolism in the annulus fibrosus (AF) and nucleus pulposus (NP) of porcine IVD under static and dynamic compressions. Under compression, pH decreased and the contents of lactate and ATP increased significantly in both AF and NP regions, suggesting that compression can promote ATP production via glycolysis and reduce pH by increasing lactate accumulation. A high level of extracellular ATP content was detected in the NP region and regulated by compressive loading. Since ATP can serve not only as an intra-cellular energy currency, but also as a regulator of a variety of cellular activities extracellularly through the purinergic signaling pathway, our findings suggest that compression-mediated ATP metabolism could be a novel mechanobiological pathway for regulating IVD metabolism. © 2013 Orthopaedic Research Society.

  18. Metabolic effects of altering the 24 h energy intake in man, using direct and indirect calorimetry.

    PubMed

    Dauncey, M J

    1980-03-01

    expenditure of over-feeding for only 1 d do not differ markedly from those estimated by some other workers after several weeks of increasing the energy intake: (b) the resting metabolic rate, measured at least 14 h after the last meal, can be affected by the previous day's energy intake; (c) the zone of ambient temperature within which metabolism is minimal is probably altered by the level of energy intake.

  19. Deletion of Adseverin in Osteoclasts Affects Cell Structure But Not Bone Metabolism.

    PubMed

    Cao, Yixuan; Wang, Yongqiang; Sprangers, Sara; Picavet, Daisy I; Glogauer, Michael; McCulloch, Christopher A; Everts, Vincent

    2017-08-01

    Adseverin is an actin-severing/capping protein that may contribute to osteoclast differentiation in vitro but its role in bone remodeling of healthy animals is not defined. We analyzed bone and osteoclast structure in adseverin conditional null mice at alveolar and long bone sites. In wild-type and adseverin null mice, as measured by dual-energy X-ray absorptiometry, there were no differences of bone mineral content or bone mineral density, indicating no change of bone metabolism. In tibiae, TRAcP + osteoclasts were formed in comparable numbers in adseverin null and wild-type mice. Ultrastructural analysis showed normal and similar abundance of ruffled borders, sealing zones, and mitochondria, and with no difference of osteoclast nuclear numbers. In contrast, analyses of long bone showed that in the absence of adseverin osteoclasts were smaller (120 ± 13 vs. 274 ± 19 µm 2 ; p < 0.05), as were nuclear size and the surface area of cytoplasm. The nuclei of adseverin null osteoclasts exhibited more heterochromatin (31 ± 3%) than wild-type cells (8 ± 1%), suggesting that adseverin affects cell differentiation. The data indicate that in healthy, developing tissues, adseverin contributes to the regulation of osteoclast structure but not to bone metabolism in vivo.

  20. Energy requirements, protein-energy metabolism and balance, and carbohydrates in preterm infants.

    PubMed

    Hay, William W; Brown, Laura D; Denne, Scott C

    2014-01-01

    Energy is necessary for all vital functions of the body at molecular, cellular, organ, and systemic levels. Preterm infants have minimum energy requirements for basal metabolism and growth, but also have requirements for unique physiology and metabolism that influence energy expenditure. These include body size, postnatal age, physical activity, dietary intake, environmental temperatures, energy losses in the stool and urine, and clinical conditions and diseases, as well as changes in body composition. Both energy and protein are necessary to produce normal rates of growth. Carbohydrates (primarily glucose) are principle sources of energy for the brain and heart until lipid oxidation develops over several days to weeks after birth. A higher protein/energy ratio is necessary in most preterm infants to approximate normal intrauterine growth rates. Lean tissue is predominantly produced during early gestation, which continues through to term. During later gestation, fat accretion in adipose tissue adds increasingly large caloric requirements to the lean tissue growth. Once protein intake is sufficient to promote net lean body accretion, additional energy primarily produces more body fat, which increases almost linearly at energy intakes >80-90 kcal/kg/day in normal, healthy preterm infants. Rapid gains in adiposity have the potential to produce later life obesity, an increasingly recognized risk of excessive energy intake. In addition to fundamental requirements for glucose, protein, and fat, a variety of non-glucose carbohydrates found in human milk may have important roles in promoting growth and development, as well as production of a gut microbiome that could protect against necrotizing enterocolitis. © 2014 S. Karger AG, Basel.

  1. Mitochondrial Energy Metabolism and Redox Signaling in Brain Aging and Neurodegeneration

    PubMed Central

    Yin, Fei; Boveris, Alberto

    2014-01-01

    Abstract Significance: The mitochondrial energy-transducing capacity is essential for the maintenance of neuronal function, and the impairment of energy metabolism and redox homeostasis is a hallmark of brain aging, which is particularly accentuated in the early stages of neurodegenerative diseases. Recent Advances: The communications between mitochondria and the rest of the cell by energy- and redox-sensitive signaling establish a master regulatory device that controls cellular energy levels and the redox environment. Impairment of this regulatory devise is critical for aging and the early stages of neurodegenerative diseases. Critical Issues: This review focuses on a coordinated metabolic network—cytosolic signaling, transcriptional regulation, and mitochondrial function—that controls the cellular energy levels and redox status as well as factors which impair this metabolic network during brain aging and neurodegeneration. Future Directions: Characterization of mitochondrial function and mitochondria-cytosol communications will provide pivotal opportunities for identifying targets and developing new strategies aimed at restoring the mitochondrial energy-redox axis that is compromised in brain aging and neurodegeneration. Antioxid. Redox Signal. 20, 353–371. PMID:22793257

  2. 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

  3. [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

  4. 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. © 2015 Society for Endocrinology.

  5. A neuronal lactate uptake inhibitor slows recovery of extracellular ion concentration changes in the hippocampal CA3 region by affecting energy metabolism.

    PubMed

    Angamo, Eskedar Ayele; Rösner, Joerg; Liotta, Agustin; Kovács, Richard; Heinemann, Uwe

    2016-11-01

    Astrocyte-derived lactate supports pathologically enhanced neuronal metabolism, but its role under physiological conditions is still a matter of debate. Here, we determined the contribution of astrocytic neuronal lactate shuttle for maintenance of ion homeostasis and energy metabolism. We tested for the effects of α-cyano-4-hydroxycinnamic acid (4-CIN), which could interfere with energy metabolism by blocking monocarboxylate-transporter 2 (MCT2)-mediated neuronal lactate uptake, on evoked potentials, stimulus-induced changes in K + , Na + , Ca 2+ , and oxygen concentrations as well as on changes in flavin adenine dinucleotide (FAD) autofluorescence in the hippocampal area CA3. MCT2 blockade by 4-CIN reduced synaptically evoked but not antidromic population spikes. This effect was dependent on the activation of K ATP channels indicating reduced neuronal ATP synthesis. By contrast, lactate receptor activation by 3,5-dihydroxybenzoic acid (3,5-DHBA) resulted in increased antidromic and orthodromic population spikes suggesting that 4-CIN effects are not mediated by lactate accumulation and subsequent activation of lactate receptors. Recovery kinetics of all ion transients were prolonged and baseline K + concentration became elevated by blockade of lactate uptake. Lactate contributed to oxidative metabolism as both baseline respiration and stimulus-induced changes in Po 2 were decreased, while FAD fluorescence increased likely due to a reduced conversion of FAD into FADH 2 These data suggest that lactate shuttle contributes to regulation of ion homeostatsis and synaptic signaling even in the presence of ample glucose. Copyright © 2016 the American Physiological Society.

  6. Source of metabolizable energy affects gene transcription in metabolic pathways in adipose and liver tissue of nonlactating, pregnant dairy cows.

    PubMed

    Crookenden, M A; Mandok, K S; Grala, T M; Phyn, C V C; Kay, J K; Greenwood, S L; Roche, J R

    2015-02-01

    The objective of this experiment was to determine if transcript abundance of genes involved in metabolic pathways in adipose and liver tissue could provide some explanation for the low efficiency with which ME in autumn pasture is used for BW gain. Nonlactating, pregnant (208 ± 19 d of gestation or approximately 75 d precalving) dairy cows (n = 90) were randomly allocated to either a control diet (i.e., offered fresh autumn pasture to maintenance requirements: 0.55 MJ ME/kg of measured metabolic BW [BW0.75] per day) or, in addition to the control diet, 1 of 2 supplement amounts (2.5 and 5.0 kg DM/d) of autumn pasture or 1 of 4 supplementary feeds (i.e., a control and 2 levels of feeding for each of 5 feeds: 11 groups of cows). Along with autumn pasture, evaluated feeds included spring pasture silage, maize silage, maize grain, and palm kernel expeller. Adipose and liver tissues were biopsied in wk 4 of the experiment and transcript abundance of genes involved in metabolic pathways associated with energy metabolism, lipolysis, and lipogenesis was determined. Additional feed, irrespective of type, increased BW gain (P < 0.01) and this effect was reflected in the expression of genes in adipose and liver tissue. However, autumn pasture had lower energy-use efficiency than the other feeds. Genes involved in both lipogenesis (ACACA, THRSP, GPAM, GPD1, and LPL) and lipolysis (PNPLA2) were upregulated (P < 0.05) in adipose tissue in response to increased ME intake/kilogram BW0.75. Hepatic expression of APOA1 decreased and that of APOB increased (P < 0.05) in cows offered maize grain and maize silage (i.e., starch-containing feeds). In comparison, pasture-fed cows demonstrated a degree of uncoupling of the somatotropic axis, with lower hepatic transcript abundance of both GHR1A and IGF-1 compared with cows offered any of the other 4 feeds. Changes to gene transcription indicate a possible molecular mechanism for the poor BW gain evident in ruminants consuming autumn

  7. Cellular energy metabolism maintains young status in old queen honey bees (Apis mellifera).

    PubMed

    Lu, Cheng-Yen; Qiu, Jiantai Timothy; Hsu, Chin-Yuan

    2018-05-02

    Trophocytes and oenocytes of queen honey bees are used in studies of cellular longevity, but their cellular energy metabolism with age is poorly understood. In this study, the molecules involved in cellular energy metabolism were evaluated in the trophocytes and oenocytes of young and old queen bees. The findings indicated that there were no significant differences between young and old queen bees in β-oxidation, glycolysis, and protein synthesis. These results indicate that the cellular energy metabolism of trophocytes and oenocytes in old queen bees is similar to young queen bees and suggests that maintaining cellular energy metabolism in a young status may be associated with the longevity of queen bees. Fat and glycogen accumulation increased with age indicating that old queen bees are older than young queen bees. © 2018 Wiley Periodicals, Inc.

  8. L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner.

    PubMed

    Cartwright, Stephanie P; Bill, Roslyn M; Hipkiss, Alan R

    2012-01-01

    The dipeptide L-carnosine (β-alanyl-L-histidine) has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose), 10-30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol), L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine, the cells showed resistance to its inhibitory effects. These findings suggest that L-carnosine affects cells in a metabolism-dependent manner and provide a rationale for its effects on different cell types.

  9. 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

  10. Select nutrients, progesterone, and interferon tau affect conceptus metabolism and development

    PubMed Central

    Bazer, Fuller W; Kim, Jingyoung; Song, Gwonhwa; Ka, Hakhyun; Tekwe, Carmen D; Wu, Guoyao

    2012-01-01

    Interferon tau (IFNT), a novel multifunctional type I interferon secreted by trophectoderm, is the pregnancy recognition signal in ruminants that also has antiviral, antiproliferative, and immunomodulatory bioactivities. IFNT, with progesterone, affects availability of the metabolic substrate in the uterine lumen by inducing expression of genes for transport of select nutrients into the uterine lumen that activate mammalian target of rapamycin (mTOR) cell signaling responsible for proliferation, migration, and protein synthesis by conceptus trophectoderm. As an immunomodulatory protein, IFNT induces an anti-inflammatory state affecting metabolic events that decrease adiposity and glutamine:fructose-6-phosphate amidotransferase 1 activity, while increasing insulin sensitivity, nitric oxide production by endothelial cells, and brown adipose tissue in rats. This short review focuses on effects of IFNT and progesterone affecting transport of select nutrients into the uterine lumen to stimulate mTOR cell signaling required for conceptus development, as well as effects of IFNT on the immune system and adiposity in rats with respect to its potential therapeutic value in reducing obesity. PMID:23050969

  11. Energy metabolism, fuel selection and body weight regulation

    PubMed Central

    Galgani, J; Ravussin, E

    2010-01-01

    Energy homeostasis is critical for the survival of species. Therefore, multiple and complex mechanisms have evolved to regulate energy intake and expenditure to maintain body weight. For weight maintenance, not only does energy intake have to match energy expenditure, but also macronutrient intake must balance macronutrient oxidation. However, this equilibrium seems to be particularly difficult to achieve in individuals with low fat oxidation, low energy expenditure, low sympathetic activity or low levels of spontaneous physical activity, as in addition to excess energy intake, all of these factors explain the tendency of some people to gain weight. Additionally, large variability in weight change is observed when energy surplus is imposed experimentally or spontaneously. Clearly, the data suggest a strong genetic influence on body weight regulation implying a normal physiology in an ‘obesogenic’ environment. In this study, we also review evidence that carbohydrate balance may represent the potential signal that regulates energy homeostasis by impacting energy intake and body weight. Because of the small storage capacity for carbohydrate and its importance for metabolism in many tissues and organs, carbohydrate balance must be maintained at a given level. This drive for balance may in turn cause increased energy intake when consuming a diet high in fat and low in carbohydrate. If sustained over time, such an increase in energy intake cannot be detected by available methods, but may cause meaningful increases in body weight. The concept of metabolic flexibility and its impact on body weight regulation is also presented. PMID:19136979

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

    PubMed

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-12-10

    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.

  13. Metabolic sensing neurons and the control of energy homeostasis.

    PubMed

    Levin, Barry E

    2006-11-30

    The brain and periphery carry on a constant conversation; the periphery informs the brain about its metabolic needs and the brain provides for these needs through its control of somatomotor, autonomic and neurohumoral pathways involved in energy intake, expenditure and storage. Metabolic sensing neurons are the integrators of a variety of metabolic, humoral and neural inputs from the periphery. Such neurons, originally called "glucosensing", also respond to fatty acids, hormones and metabolites from the periphery. They are integrated within neural pathways involved in the regulation of energy homeostasis. Unlike most neurons, they utilize glucose and other metabolites as signaling molecules to regulate their membrane potential and firing rate. For glucosensing neurons, glucokinase acts as the rate-limiting step in glucosensing while the pathways that mediate responses to metabolites like lactate, ketone bodies and fatty acids are less well characterized. Many metabolic sensing neurons also respond to insulin and leptin and other peripheral hormones and receive neural inputs from peripheral organs. Each set of afferent signals arrives with different temporal profiles and by different routes and these inputs are summated at the level of the membrane potential to produce a given neural firing pattern. In some obese individuals, the relative sensitivity of metabolic sensing neurons to various peripheral inputs is genetically reduced. This may provide one mechanism underlying their propensity to become obese when exposed to diets high in fat and caloric density. Thus, metabolic sensing neurons may provide a potential therapeutic target for the treatment of obesity.

  14. Effect of dietary energy and polymorphisms in BRAP and GHRL on obesity and metabolic traits.

    PubMed

    Imaizumi, Takahiro; Ando, Masahiko; Nakatochi, Masahiro; Yasuda, Yoshinari; Honda, Hiroyuki; Kuwatsuka, Yachiyo; Kato, Sawako; Kondo, Takaaki; Iwata, Masamitsu; Nakashima, Toru; Yasui, Hiroshi; Takamatsu, Hideki; Okajima, Hiroshi; Yoshida, Yasuko; Maruyama, Shoichi

    Obesity, a risk factor for all-cause and cardiovascular mortality, is a major health concerns among middle-aged men. The aim of this study was to investigate a possible association of dietary habits and obesity related single nucleotide polymorphisms (SNPs) with obesity and metabolic abnormalities. We conducted a retrospective cohort study using annual health examination data of 5112 male workers, obtained between 2007 and 2011. Average dietary energy was estimated using electronically collected meal purchase data from cafeteria. We examined 8 SNPs related to obesity: GHRL rs696217, PPARG rs1175544, ADIPOQ rs2241766, ADIPOQ rs1501299, PPARD rs2016520, APOA5 rs662799, BRAP rs3782886, and ITGB2 rs235326. We also examined whether SNPs that were shown to associate with obesity affect other metabolic abnormalities such as blood pressure (BP), glucose, and lipid profile. Average dietary energy significantly associated with increased abdominal circumference (AC) and body mass index (BMI). The odds ratios (ORs) of overweight and obesity also increased. The major allele of rs696217 significantly increased BMI and an increased OR with obesity, while the minor allele of rs3782886 was associated with significantly decreased AC and the decreased ORs with overweight and obesity. The minor allele of rs3782886 was also associated with significantly decreased systolic BP (SBP), triglyceride (TG), high-density lipoprotein (HDL), and fasting blood sugar (FBS), while rs696217 was not associated with other metabolic abnormalities. Average dietary energy in lunch, rs3782886, and rs696217 were associated with obesity, and rs3782886 was associated with other metabolic abnormalities. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  15. Estimation of metabolic energy expenditure from core temperature using a human thermoregulatory model

    USDA-ARS?s Scientific Manuscript database

    Measuring metabolic energy expenditure in humans may provide a means of monitoring and reducing obesity, estimating nutritional requirements, reducing obesity, maintaining energy balance during athletics, and modeling human thermoregulatory responses. However, measuring metabolic rate (M) is challen...

  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. Metabolic Power in Team Sports - Part 2: Aerobic and Anaerobic Energy Yields.

    PubMed

    Osgnach, Cristian; di Prampero, Pietro Enrico

    2018-06-14

    A previous approach to estimate the time course of instantaneous metabolic power and O 2 consumption in team sports has been updated to assess also energy expenditure against air resistance and to identify walking and running separately. Whole match energy expenditure turned out ≈14% smaller than previously obtained, the fraction against the air resistance amounting to ≈2% of the total. Estimated net O 2 consumption and overall energy expenditure are fairly close to those measured by means of a portable metabolic cart; the average difference, after a 45 min exercise period of variable intensity and mode, amounting to ≈10%. Aerobic and anaerobic energy yields, metabolic power, energy expenditure and duration of High (HI) and Low (LI) intensity bouts can also be estimated. Indeed, data on 497 soccer players during the 2014/2015 Italian "Serie A" show that the number of HI efforts decreased from the first to the last 15-min periods of the match, without substantial changes in mean metabolic power (≈22 W·kg -1 ) and duration (≈6.5 s). On the contrary, mean metabolic power of the LI decreased (5.8 to 4.8 W·kg -1 ), mainly because of a longer duration thereof, thus underscoring the need for longer recovery periods between HI. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Metabolic control analysis of integrated energy metabolism in permeabilized cardiomyocytes - experimental study.

    PubMed

    Tepp, Kersti; Timohhina, Natalja; Chekulayev, Vladimir; Shevchuk, Igor; Kaambre, Tuuli; Saks, Valdur

    2010-01-01

    The main focus of this research was to apply Metabolic Control Analysis to quantitative investigation of the regulation of respiration by components of the Mitochondrial Interactosome (MI, a supercomplex consisting of ATP Synthasome, mitochondrial creatine kinase (MtCK), voltage dependent anion channel (VDAC), and tubulin) in permeabilized cardiomyocytes. Flux control coefficients (FCC) were measured using two protocols: 1) with direct ADP activation, and 2) with MtCK activation by creatine (Cr) in the presence of ATP and pyruvate kinase-phosphoenolpyruvate system. The results show that the metabolic control is much stronger in the latter case: the sum of the measured FCC is 2.7 versus 0.74 (ADP activation). This is consistent with previous data showing recycling of ADP and ATP inside the MI due to the functional coupling between MtCK and ANT and limited permeability of VDAC for these compounds, PCr being the major energy carrier between the mitochondria and ATPases. In physiological conditions, when the MI is activated, the key sites of regulation of respiration in mitochondria are MtCK (FCC = 0.93), adenine nucleotide translocase ANT (FCC = 0.95) and CoQ cytochrome c oxidoreductase (FCC = 0.4). These results show clearly that under the physiological conditions the energy transfer from mitochondria to the cytoplasm is regulated by the MI supercomplex and is very sensitive to metabolic signals.

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

    PubMed

    Connysson, M; Muhonen, S; Jansson, A

    2017-11-01

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

  20. A pocket-sized metabolic analyzer for assessment of resting energy expenditure.

    PubMed

    Zhao, Di; Xian, Xiaojun; Terrera, Mirna; Krishnan, Ranganath; Miller, Dylan; Bridgeman, Devon; Tao, Kevin; Zhang, Lihua; Tsow, Francis; Forzani, Erica S; Tao, Nongjian

    2014-04-01

    The assessment of metabolic parameters related to energy expenditure has a proven value for weight management; however these measurements remain too difficult and costly for monitoring individuals at home. The objective of this study is to evaluate the accuracy of a new pocket-sized metabolic analyzer device for assessing energy expenditure at rest (REE) and during sedentary activities (EE). The new device performs indirect calorimetry by measuring an individual's oxygen consumption (VO2) and carbon dioxide production (VCO2) rates, which allows the determination of resting- and sedentary activity-related energy expenditure. VO2 and VCO2 values of 17 volunteer adult subjects were measured during resting and sedentary activities in order to compare the metabolic analyzer with the Douglas bag method. The Douglas bag method is considered the Gold Standard method for indirect calorimetry. Metabolic parameters of VO2, VCO2, and energy expenditure were compared using linear regression analysis, paired t-tests, and Bland-Altman plots. Linear regression analysis of measured VO2 and VCO2 values, as well as calculated energy expenditure assessed with the new analyzer and Douglas bag method, had the following linear regression parameters (linear regression slope LRS0, and R-squared coefficient, r(2)) with p = 0: LRS0 (SD) = 1.00 (0.01), r(2) = 0.9933 for VO2; LRS0 (SD) = 1.00 (0.01), r(2) = 0.9929 for VCO2; and LRS0 (SD) = 1.00 (0.01), r(2) = 0.9942 for energy expenditure. In addition, results from paired t-tests did not show statistical significant difference between the methods with a significance level of α = 0.05 for VO2, VCO2, REE, and EE. Furthermore, the Bland-Altman plot for REE showed good agreement between methods with 100% of the results within ±2SD, which was equivalent to ≤10% error. The findings demonstrate that the new pocket-sized metabolic analyzer device is accurate for determining VO2, VCO2, and energy expenditure. Copyright © 2013 Elsevier Ltd and

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

    PubMed Central

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

    2016-01-01

    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

  2. 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.

  3. Rhodanese Functions as Sulfur Supplier for Key Enzymes in Sulfur Energy Metabolism

    PubMed Central

    Aussignargues, Clément; Giuliani, Marie-Cécile; Infossi, Pascale; Lojou, Elisabeth; Guiral, Marianne; Giudici-Orticoni, Marie-Thérèse; Ilbert, Marianne

    2012-01-01

    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

  4. Metabolic Adaptation to Muscle Ischemia

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  5. Energy metabolism in mobile, wild-sampled sharks inferred by plasma lipids.

    PubMed

    Gallagher, Austin J; Skubel, Rachel A; Pethybridge, Heidi R; Hammerschlag, Neil

    2017-01-01

    Evaluating how predators metabolize energy is increasingly useful for conservation physiology, as it can provide information on their current nutritional condition. However, obtaining metabolic information from mobile marine predators is inherently challenging owing to their relative rarity, cryptic nature and often wide-ranging underwater movements. Here, we investigate aspects of energy metabolism in four free-ranging shark species ( n  = 281; blacktip, bull, nurse, and tiger) by measuring three metabolic parameters [plasma triglycerides (TAG), free fatty acids (FFA) and cholesterol (CHOL)] via non-lethal biopsy sampling. Plasma TAG, FFA and total CHOL concentrations (in millimoles per litre) varied inter-specifically and with season, year, and shark length varied within a species. The TAG were highest in the plasma of less active species (nurse and tiger sharks), whereas FFA were highest among species with relatively high energetic demands (blacktip and bull sharks), and CHOL concentrations were highest in bull sharks. Although temporal patterns in all metabolites were varied among species, there appeared to be peaks in the spring and summer, with ratios of TAG/CHOL (a proxy for condition) in all species displaying a notable peak in summer. These results provide baseline information of energy metabolism in large sharks and are an important step in understanding how the metabolic parameters can be assessed through non-lethal sampling in the future. In particular, this study emphasizes the importance of accounting for intra-specific and temporal variability in sampling designs seeking to monitor the nutritional condition and metabolic responses of shark populations.

  6. Energy metabolism in mobile, wild-sampled sharks inferred by plasma lipids

    PubMed Central

    Skubel, Rachel A.; Pethybridge, Heidi R.; Hammerschlag, Neil

    2017-01-01

    Abstract Evaluating how predators metabolize energy is increasingly useful for conservation physiology, as it can provide information on their current nutritional condition. However, obtaining metabolic information from mobile marine predators is inherently challenging owing to their relative rarity, cryptic nature and often wide-ranging underwater movements. Here, we investigate aspects of energy metabolism in four free-ranging shark species (n = 281; blacktip, bull, nurse, and tiger) by measuring three metabolic parameters [plasma triglycerides (TAG), free fatty acids (FFA) and cholesterol (CHOL)] via non-lethal biopsy sampling. Plasma TAG, FFA and total CHOL concentrations (in millimoles per litre) varied inter-specifically and with season, year, and shark length varied within a species. The TAG were highest in the plasma of less active species (nurse and tiger sharks), whereas FFA were highest among species with relatively high energetic demands (blacktip and bull sharks), and CHOL concentrations were highest in bull sharks. Although temporal patterns in all metabolites were varied among species, there appeared to be peaks in the spring and summer, with ratios of TAG/CHOL (a proxy for condition) in all species displaying a notable peak in summer. These results provide baseline information of energy metabolism in large sharks and are an important step in understanding how the metabolic parameters can be assessed through non-lethal sampling in the future. In particular, this study emphasizes the importance of accounting for intra-specific and temporal variability in sampling designs seeking to monitor the nutritional condition and metabolic responses of shark populations. PMID:28852506

  7. Extra-metabolic energy use and the rise in human hyper-density

    NASA Astrophysics Data System (ADS)

    Burger, Joseph R.; Weinberger, Vanessa P.; Marquet, Pablo A.

    2017-03-01

    Humans, like all organisms, are subject to fundamental biophysical laws. Van Valen predicted that, because of zero-sum dynamics, all populations of all species in a given environment flux the same amount of energy on average. Damuth’s ’energetic equivalence rule’ supported Van Valen´s conjecture by showing a tradeoff between few big animals per area with high individual metabolic rates compared to abundant small species with low energy requirements. We use metabolic scaling theory to compare variation in densities and individual energy use in human societies to other land mammals. We show that hunter-gatherers occurred at densities lower than the average for a mammal of our size. Most modern humans, in contrast, concentrate in large cities at densities up to four orders of magnitude greater than hunter-gatherers, yet consume up to two orders of magnitude more energy per capita. Today, cities across the globe flux greater energy than net primary productivity on a per area basis. This is possible by importing enormous amounts of energy and materials required to sustain hyper-dense, modern humans. The metabolic rift with nature created by modern cities fueled largely by fossil energy poses formidable challenges for establishing a sustainable relationship on a rapidly urbanizing, yet finite planet.

  8. Extra-metabolic energy use and the rise in human hyper-density.

    PubMed

    Burger, Joseph R; Weinberger, Vanessa P; Marquet, Pablo A

    2017-03-02

    Humans, like all organisms, are subject to fundamental biophysical laws. Van Valen predicted that, because of zero-sum dynamics, all populations of all species in a given environment flux the same amount of energy on average. Damuth's 'energetic equivalence rule' supported Van Valen´s conjecture by showing a tradeoff between few big animals per area with high individual metabolic rates compared to abundant small species with low energy requirements. We use metabolic scaling theory to compare variation in densities and individual energy use in human societies to other land mammals. We show that hunter-gatherers occurred at densities lower than the average for a mammal of our size. Most modern humans, in contrast, concentrate in large cities at densities up to four orders of magnitude greater than hunter-gatherers, yet consume up to two orders of magnitude more energy per capita. Today, cities across the globe flux greater energy than net primary productivity on a per area basis. This is possible by importing enormous amounts of energy and materials required to sustain hyper-dense, modern humans. The metabolic rift with nature created by modern cities fueled largely by fossil energy poses formidable challenges for establishing a sustainable relationship on a rapidly urbanizing, yet finite planet.

  9. [Energy power in mountains: difference in metabolism pattern results in different adaption traits in Tibetans].

    PubMed

    Bai, Zhen-Zhong; Jin, Guo-En; Wu-Ren, Tana; Ga, Qin; Ge, Ri-Li

    2012-11-01

    Energy metabolism plays an important role in life survival for species living in high altitude hypoxia condition. Air-breathing organisms require oxygen to create energy. Tibetans are the well-adapted highlanders in Qinghai-Tibetan Plateau. It was thought that different metabolic approaches could lead to different adaptation traits to high altitude hypoxia. Recently identified hypoxia inducible factors pathway regulators, endothelial PAS domain protein1 (EPAS1)/HIF-2a and PPARA, were involved in decreasing hemoglobin concentrations in Tibetans. Because EPAS1 and PPARA also modulated the energy metabolism during hypoxia, we hypothesized that positive selected EPAS1 and PPARA genes were also involved in unique energy metabolisms in Tibetans. In this brief review, we take a look into genetic determinations to energy metabolisms for hypoxia adaptations traits in Tibetans and mal-adaptive conditions such as high altitude diseases.

  10. 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

  11. Elucidating the role of copper in CHO cell energy metabolism using (13)C metabolic flux analysis.

    PubMed

    Nargund, Shilpa; Qiu, Jinshu; Goudar, Chetan T

    2015-01-01

    (13)C-metabolic flux analysis was used to understand copper deficiency-related restructuring of energy metabolism, which leads to excessive lactate production in recombinant protein-producing CHO cells. Stationary-phase labeling experiments with U-(13)C glucose were conducted on CHO cells grown under high and limiting copper in 3 L fed-batch bioreactors. The resultant labeling patterns of soluble metabolites were measured by GC-MS and used to estimate metabolic fluxes in the central carbon metabolism pathways using OpenFlux. Fluxes were evaluated 300 times from stoichiometrically feasible random guess values and their confidence intervals calculated by Monte Carlo simulations. Results from metabolic flux analysis exhibited significant carbon redistribution throughout the metabolic network in cells under Cu deficiency. Specifically, glycolytic fluxes increased (25%-79% relative to glucose uptake) whereas fluxes through the TCA and pentose phosphate pathway (PPP) were lower (15%-23% and 74%, respectively) compared with the Cu-containing condition. Furthermore, under Cu deficiency, 33% of the flux entering TCA via the pyruvate node was redirected to lactate and malate production. Based on these results, we hypothesize that Cu deficiency disrupts the electron transport chain causing ATP deficiency, redox imbalance, and oxidative stress, which in turn drive copper-deficient CHO cells to produce energy via aerobic glycolysis, which is associated with excessive lactate production, rather than the more efficient route of oxidative phosphorylation. © 2015 American Institute of Chemical Engineers.

  12. 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

  13. Glycogen metabolism in brain and neurons - astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure.

    PubMed

    Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Gąssowska, Magdalena; Kolasa-Wołosiuk, Agnieszka; Tarnowski, Maciej; Chibowska, Karina; Goschorska, Marta; Lubkowska, Anna; Chlubek, Dariusz

    2017-09-01

    Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase β (PHKB). Moreover, the expression of connexin 43 (Cx43) was evaluated to analyze whether Pb poisoning during the early phase of life may affect the neuron-astrocytes' metabolic cooperation. This work shows for the first time that exposure to Pb in early life can impair brain energy metabolism by reducing the amount of glycogen and decreasing the rate of its metabolism. This reduction in brain glycogen level was accompanied by a decrease in Gys1 expression. We noted a reduction in the immunoreactivity and the gene expression of both PYGB and PYGM isoform, as well as an increase in the expression of PHKB in Pb-treated rats. Moreover, exposure to Pb induced decrease in connexin 43 immunoexpression in all the brain structures analyzed, both in astrocytes as well as in neurons. Our data suggests that exposure to Pb in the pre- and neonatal periods results in a decrease in the level of brain glycogen and a reduction in the rate of its metabolism, thereby reducing glucose availability, which as a further consequence may lead to the impairment of brain energy metabolism and the metabolic cooperation between neurons and astrocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Short-term fructose ingestion affects the brain independently from establishment of metabolic syndrome.

    PubMed

    Jiménez-Maldonado, Alberto; Ying, Zhe; Byun, Hyae Ran; Gomez-Pinilla, Fernando

    2018-01-01

    Chronic fructose ingestion is linked to the global epidemic of metabolic syndrome (MetS), and poses a serious threat to brain function. We asked whether a short period (one week) of fructose ingestion potentially insufficient to establish peripheral metabolic disorder could impact brain function. We report that the fructose treatment had no effect on liver/body weight ratio, weight gain, glucose tolerance and insulin sensitivity, was sufficient to reduce several aspects of hippocampal plasticity. Fructose consumption reduced the levels of the neuronal nuclear protein NeuN, Myelin Basic Protein, and the axonal growth-associated protein 43, concomitant with a decline in hippocampal weight. A reduction in peroxisome proliferator-activated receptor gamma coactivator-1 alpha and Cytochrome c oxidase subunit II by fructose treatment is indicative of mitochondrial dysfunction. Furthermore, the GLUT5 fructose transporter was increased in the hippocampus after fructose ingestion suggesting that fructose may facilitate its own transport to brain. Fructose elevated levels of ketohexokinase in the liver but did not affect SIRT1 levels, suggesting that fructose is metabolized in the liver, without severely affecting liver function commensurable to an absence of metabolic syndrome condition. These results advocate that a short period of fructose can influence brain plasticity without a major peripheral metabolic dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. MiRNA-210 modulates a nickel-induced cellular energy metabolism shift by repressing the iron-sulfur cluster assembly proteins ISCU1/2 in Neuro-2a cells.

    PubMed

    He, M; Lu, Y; Xu, S; Mao, L; Zhang, L; Duan, W; Liu, C; Pi, H; Zhang, Y; Zhong, M; Yu, Z; Zhou, Z

    2014-02-27

    The cellular energy metabolism shift, characterized by the inhibition of oxidative phosphorylation (OXPHOS) and enhancement of glycolysis, is involved in nickel-induced neurotoxicity. MicroRNA-210 (miR-210) is regulated by hypoxia-inducible transcription factor-1α (HIF-1α) under hypoxic conditions and controls mitochondrial energy metabolism by repressing the iron-sulfur cluster assembly protein (ISCU1/2). ISCU1/2 facilitates the assembly of iron-sulfur clusters (ISCs), the prosthetic groups that are critical for mitochondrial oxidation-reduction reactions. This study aimed to investigate whether miR-210 modulates alterations in energy metabolism after nickel exposure through suppressing ISCU1/2 and inactivating ISCs-containing metabolic enzymes. We determined that NiCl2 exposure leads to a significant accumulation of HIF-1α, rather than HIF-1β, in Neuro-2a cells. The miR-210 overexpression and ISCU1/2 downregulation was observed in a dose- and time-dependent manner. The gain-of-function and loss-of-dysfunction assays revealed that miR-210 mediated the ISCU1/2 suppression, energy metabolism alterations, and ISC-containing metabolic enzyme inactivation after nickel exposure. In addition, the impact of miR-210 on ISC-containing metabolic enzymes was independent from cellular iron regulation. Overall, these data suggest that repression of miR-210 on ISCU1/2 may contribute to HIF-1α-triggered alterations in energy metabolism after nickel exposure. A better understanding of how nickel impacts cellular energy metabolism may facilitate the elucidation of the mechanisms by which nickel affects the human health.

  16. Vascular affection in relation to oxidative DNA damage in metabolic syndrome.

    PubMed

    Abd El Aziz, Rokayaa; Fawzy, Mary Wadie; Khalil, Noha; Abdel Atty, Sahar; Sabra, Zainab

    2018-02-01

    Obesity has become an important issue affecting both males and females. Obesity is now regarded as an independent risk factor for atherosclerosis-related diseases. Metabolic syndrome is associated with increased risk for development of cardiovascular disease. Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine concentration has been used to express oxidation status. Twenty-seven obese patients with metabolic syndrome, 25 obese patients without metabolic syndrome and 31 healthy subjects were included in our study. They were subjected to full history and clinical examination; fasting blood sugar (FBS), 2 hour post prandial blood sugar (2HPP), lipid profile, urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine and carotid duplex, A/B index and tibial diameters were all assessed. There was a statistically significant difference ( p = 0.027) in diameter of the right anterior tibial artery among the studied groups, with decreased diameter of the right anterior tibial artery in obese patients with metabolic syndrome compared to those without metabolic syndrome; the ankle brachial index revealed a lower index in obese patients with metabolic syndrome compared to those without metabolic syndrome. There was a statistically insignificant difference ( p = 0.668) in the 8-oxodG in the studied groups. In obese patients with metabolic syndrome there was a positive correlation between 8-oxodG and total cholesterol and LDL. Urinary 8-oxodG is correlated to total cholesterol and LDL in obese patients with metabolic syndrome; signifying its role in the mechanism of dyslipidemia in those patients. Our study highlights the importance of anterior tibial artery diameter measurement and ankle brachial index as an early marker of atherosclerosis, and how it may be an earlier marker than carotid intima-media thickness.

  17. Exposure of embryos to cyclically cold incubation temperatures durably affects energy metabolism and antioxidant pathways in broiler chickens.

    PubMed

    Loyau, T; Collin, A; Yenisey, C; Crochet, S; Siegel, P B; Akşit, M; Yalçin, S

    2014-08-01

    Cyclically cold incubation temperatures have been suggested as a means to improve resistance of broiler chickens to ascites; however, the underlying mechanisms are not known. Nine hundred eggs obtained from 48 wk Ross broiler breeders were randomly assigned to 2 incubation treatments: control I eggs were incubated at 37.6°C throughout, whereas for cold I eggs the incubation temperature was reduced by 1°C for 6 h daily from 10 to 18 d of incubation. Thereafter, chickens were reared at standard temperatures or under cold exposure that was associated or not with a postnatal cold acclimation at d 5 posthatch. At hatch, hepatic catalase activity and malondialdehyde content were measured. Serum thyroid hormone and triglyceride concentrations, and muscle expression of several genes involved in the regulation of energy metabolism and oxidative stress were also measured at hatch and 5 and 25 d posthatch. Cold incubation induced modifications in antioxidant pathways with higher catalase activity, but lower expression of avian uncoupling protein 3 at hatch. However, long-term enhancement in the expression of avian uncoupling protein 3 was observed, probably caused by an increase in the expression of the transcription factor peroxisome proliferator activated receptor-γ coactivator-1α. These effects were not systematically associated with an increase in serum triiodothyronine concentrations that were observed only in chickens exposed to both cold incubation and later acclimation at 5 d with cold rearing. Our results suggest that these conditions of cyclically cold incubation resulted in the long-term in changes in antioxidant pathways and energy metabolism, which could enhance the health of chickens reared under cold conditions. © Poultry Science Association Inc.

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  19. Mind your step: metabolic energy cost while walking an enforced gait pattern.

    PubMed

    Wezenberg, D; de Haan, A; van Bennekom, C A M; Houdijk, H

    2011-04-01

    The energy cost of walking could be attributed to energy related to the walking movement and energy related to balance control. In order to differentiate between both components we investigated the energy cost of walking an enforced step pattern, thereby perturbing balance while the walking movement is preserved. Nine healthy subjects walked three times at comfortable walking speed on an instrumented treadmill. The first trial consisted of unconstrained walking. In the next two trials, subject walked while following a step pattern projected on the treadmill. The steps projected were either composed of the averaged step characteristics (periodic trial), or were an exact copy including the variability of the steps taken while walking unconstrained (variable trial). Metabolic energy cost was assessed and center of pressure profiles were analyzed to determine task performance, and to gain insight into the balance control strategies applied. Results showed that the metabolic energy cost was significantly higher in both the periodic and variable trial (8% and 13%, respectively) compared to unconstrained walking. The variation in center of pressure trajectories during single limb support was higher when a gait pattern was enforced, indicating a more active ankle strategy. The increased metabolic energy cost could originate from increased preparatory muscle activation to ensure proper foot placement and a more active ankle strategy to control for lateral balance. These results entail that metabolic energy cost of walking can be influenced significantly by control strategies that do not necessary alter global gait characteristics. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Physical activity and metabolic disease among people with affective disorders: Prevention, management and implementation.

    PubMed

    Vancampfort, Davy; Stubbs, Brendon

    2017-12-15

    One in ten and one in three of people with affective disorders experience diabetes and metabolic syndrome respectively. Physical activity (PA) and sedentary behaviour (SB) are key risk factors that can ameliorate the risk of metabolic disease among this population. However, PA is often seen as luxury and/or a secondary component within the management of people with affective disorders. The current article provides a non-systematic best-evidence synthesis of the available literature, detailing a number of suggestions for the implementation of PA into clinical practice. Whilst the evidence is unequivocal for the efficacy of PA to prevent and manage metabolic disease in the general population, it is in its infancy in this patient group. Nonetheless, action must be taken now to ensure that PA and reducing SB are given a priority to prevent and manage metabolic diseases and improve wider health outcomes. PA should be treated as a vital sign and all people with affective disorders asked about their activity levels and if appropriate advised to increase this. There is a need for investment in qualified exercise specialists in clinical practice such as physiotherapists to undertake and oversee PA in practice. Behavioural strategies such as the self-determined theory should be employed to encourage adherence. Funding is required to develop the evidence base and elucidate the optimal intervention characteristics. PA interventions should form an integral part of the multidisciplinary management of people with affective disorders and our article outlines the evidence and strategies to implement this in practice. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. 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.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pereira, Patricia M.; He, Qiang; Valente, Filipa M.A.

    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 expressedmore » 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.« less

  3. Assessment of Chitosan-Affected Metabolic Response by Peroxisome Proliferator-Activated Receptor Bioluminescent Imaging-Guided Transcriptomic Analysis

    PubMed Central

    Kao, Chia-Hung; Hsiang, Chien-Yun; Ho, Tin-Yun

    2012-01-01

    Chitosan has been widely used in food industry as a weight-loss aid and a cholesterol-lowering agent. Previous studies have shown that chitosan affects metabolic responses and contributes to anti-diabetic, hypocholesteremic, and blood glucose-lowering effects; however, the in vivo targeting sites and mechanisms of chitosan remain to be clarified. In this study, we constructed transgenic mice, which carried the luciferase genes driven by peroxisome proliferator-activated receptor (PPAR), a key regulator of fatty acid and glucose metabolism. Bioluminescent imaging of PPAR transgenic mice was applied to report the organs that chitosan acted on, and gene expression profiles of chitosan-targeted organs were further analyzed to elucidate the mechanisms of chitosan. Bioluminescent imaging showed that constitutive PPAR activities were detected in brain and gastrointestinal tract. Administration of chitosan significantly activated the PPAR activities in brain and stomach. Microarray analysis of brain and stomach showed that several pathways involved in lipid and glucose metabolism were regulated by chitosan. Moreover, the expression levels of metabolism-associated genes like apolipoprotein B (apoB) and ghrelin genes were down-regulated by chitosan. In conclusion, these findings suggested the feasibility of PPAR bioluminescent imaging-guided transcriptomic analysis on the evaluation of chitosan-affected metabolic responses in vivo. Moreover, we newly identified that downregulated expression of apoB and ghrelin genes were novel mechanisms for chitosan-affected metabolic responses in vivo. PMID:22496881

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

    PubMed

    Park, Hyeong-Kyu; Ahima, Rexford S

    2015-01-01

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Body Temperature and Energy Metabolism of Brown Lemming in Relation to Running Speed,

    DTIC Science & Technology

    1979-01-01

    ADASOG 382 ARCTIC INST OF NORTH AMERICA ARLINGTON VA F/B 6/16 BOOT TEMPERATURE AND ENERGY METABOLISM OF BROWN LEMMING IN RELA--ETC(U) W4LSIID 1979 T...M CASEY N00014-75-C-0635UNCLASSIFIEDh l o I - Body temperature and energy metabolism *of brown lemming in relation to running speed) by Timothy M...Casey Dept. of E. Physiology Cook College, Rutgers University New Brunswick, New Jersey 08903 C2 Running head: Metabolism and Tb of running lemmings. ALU

  6. Atmospheric oxygen level affects growth trajectory, cardiopulmonary allometry and metabolic rate in the American alligator (Alligator mississippiensis)

    PubMed Central

    Owerkowicz, Tomasz; Elsey, Ruth M.; Hicks, James W.

    2009-01-01

    Summary Recent palaeoatmospheric models suggest large-scale fluctuations in ambient oxygen level over the past 550 million years. To better understand how global hypoxia and hyperoxia might have affected the growth and physiology of contemporary vertebrates, we incubated eggs and raised hatchlings of the American alligator. Crocodilians are one of few vertebrate taxa that survived these global changes with distinctly conservative morphology. We maintained animals at 30°C under chronic hypoxia (12% O2), normoxia (21% O2) or hyperoxia (30% O2). At hatching, hypoxic animals were significantly smaller than their normoxic and hyperoxic siblings. Over the course of 3 months, post-hatching growth was fastest under hyperoxia and slowest under hypoxia. Hypoxia, but not hyperoxia, caused distinct scaling of major visceral organs–reduction of liver mass, enlargement of the heart and accelerated growth of lungs. When absorptive and post-absorptive metabolic rates were measured in juvenile alligators, the increase in oxygen consumption rate due to digestion/absorption of food was greatest in hyperoxic alligators and smallest in hypoxic ones. Hyperoxic alligators exhibited the lowest breathing rate and highest oxygen consumption per breath. We suggest that, despite compensatory cardiopulmonary remodelling, growth of hypoxic alligators is constrained by low atmospheric oxygen supply, which may limit their food utilisation capacity. Conversely, the combination of elevated metabolism and low cost of breathing in hyperoxic alligators allows for a greater proportion of metabolised energy to be available for growth. This suggests that growth and metabolic patterns of extinct vertebrates would have been significantly affected by changes in the atmospheric oxygen level. PMID:19376944

  7. Impaired copper and iron metabolism in blood cells and muscles of patients affected by copper deficiency myeloneuropathy.

    PubMed

    Spinazzi, Marco; Sghirlanzoni, Angelo; Salviati, Leonardo; Angelini, Corrado

    2014-12-01

    Severe copper deficiency leads in humans to a treatable multisystem disease characterized by anaemia and degeneration of spinal cord and nerves, but its mechanisms have not been investigated. We tested whether copper deficit leads to alterations in fundamental copper-dependent proteins and in iron metabolism in blood and muscles of patients affected by copper deficiency myeloneuropathy, and if these metabolic abnormalities are associated with compensatory mechanisms for copper maintenance. We evaluated the expression of critical copper enzymes, of iron-related proteins, and copper chaperones and transporters in blood and muscles from five copper-deficient patients presenting with subacute sensory ataxia, muscle paralysis, liver steatosis and variable anaemia. Severe copper deficiency was caused by chronic zinc intoxication in all of the patients, with an additional history of gastrectomy in two cases. The antioxidant enzyme SOD1 and subunit 2 of cytochrome c oxidase were significantly decreased in blood cells and in muscles of copper-deficient patients compared with controls. In muscle, the iron storage protein ferritin was dramatically reduced despite normal serum ferritin, and the expression of the haem-proteins cytochrome c and myoglobin was impaired. Muscle expression of the copper transporter CTR1 and of the copper chaperone CCS, was strikingly increased, while antioxidant protein 1 was diminished. copper-dependent enzymes with critical functions in antioxidant defences, in mitochondrial energy production, and in iron metabolism are affected in blood and muscles of patients with profound copper deficiency leading to myeloneuropathy. Homeostatic mechanisms are strongly activated to increase intracellular copper retention. © 2013 British Neuropathological Society.

  8. A practice-changing culture method relying on shaking substantially increases mitochondrial energy metabolism and functionality of human liver cell lines.

    PubMed

    Adam, Aziza A A; van der Mark, Vincent A; Donkers, Joanne M; Wildenberg, Manon E; Oude Elferink, Ronald P J; Chamuleau, Robert A F M; Hoekstra, Ruurdtje

    2018-01-01

    Practice-changing culturing techniques of hepatocytes are highly required to increase their differentiation. Previously, we found that human liver cell lines HepaRG and C3A acquire higher functionality and increased mitochondrial biogenesis when cultured in the AMC-Bioartificial liver (BAL). Dynamic medium flow (DMF) is one of the major contributors to this stimulatory effect. Recently, we found that DMF-culturing by shaking of HepaRG monolayers resulted in higher mitochondrial biogenesis. Here we further investigated the effect of DMF-culturing on energy metabolism and hepatic functionality of HepaRG and C3A monolayers. HepaRG and C3A DMF-monolayers were incubated with orbital shaking at 60 rpm during the differentiation phase, while control monolayers were maintained statically. Subsequently, energy metabolism and hepatic functionality were compared between static and DMF-cultures. DMF-culturing of HepaRG cells substantially increased hepatic differentiation; transcript levels of hepatic structural genes and hepatic transcription regulators were increased up to 15-fold (Cytochrome P450 3A4) and nuclear translocation of hepatic transcription factor CEBPα was stimulated. Accordingly, hepatic functions were positively affected, including ammonia elimination, urea production, bile acid production, and CYP3A4 activity. DMF-culturing shifted energy metabolism from aerobic glycolysis towards oxidative phosphorylation, as indicated by a decline in lactate production and glucose consumption, and an increase in oxygen consumption. Similarly, DMF-culturing increased mitochondrial energy metabolism and hepatic functionality of C3A cells. In conclusion, simple shaking of monolayer cultures substantially improves mitochondrial energy metabolism and hepatic differentiation of human liver cell lines. This practice-changing culture method may prove to prolong the in-vitro maintenance of primary hepatocytes and increase hepatic differentiation of stem cells.

  9. Mathematical modelling of metabolic pathways affected by an enzyme deficiency. Energy and redox metabolism of glucose-6-phosphate-dehydrogenase-deficient erythrocytes.

    PubMed

    Schuster, R; Jacobasch, G; Holzhütter, H G

    1989-07-01

    The effects of various forms of glucose-6-phosphate dehydrogenase deficiency on erythrocyte metabolism have been studied on the basis of a complex mathematical model which comprises the main pathways of this cell: glycolysis, pentose pathway, reactions of the glutathione and adenine nucleotide metabolism. The calculated flux rates through the oxidative pentose pathway with and without methylene blue are in good accord with experimental results. The degree of deficiency as predicted by the model on the basis of calculated upper oxidative load boundaries, as well as of maximal methylene blue stimulation, correlates with the individual clinical manifestation of the metabolic disease. Therefore, the model allows one to judge the degree of metabolic disorder in the presence of glucose-6-phosphate dehydrogenase enzymopathies if the kinetic properties of the defect enzyme are known. Experimentally accessible parameters for an assessment of the oxidative load capacity of cells in vivo are proposed. It is pointed out that the threshold of tolerance as to energetic load is drastically reduced in the case of severe glucose-6-phosphate dehydrogenase deficiency.

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

    PubMed

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

    2016-01-01

    Thyroid hormones, in particular 3,5,3'-triiodothyronine or T3, are involved in multiple physiological processes in mammals such as protein, fat and carbohydrate metabolism. However, the metabolic actions of T3 in fish are still not fully elucidated. We therefore tested the effects of T3 on Sparus aurata energy metabolism and osmoregulatory system, a hyperthyroid-induced model that was chosen. Fish were implanted with coconut oil depots (containing 0, 2.5, 5.0 and 10.0μg T3/g body weight) and sampled at day 3 and 6 post-implantation. Plasma levels of free T3 as well as glucose, lactate and triglyceride values increased with increasing doses of T3 at days 3 and 6 post-implantation. Changes in plasma and organ metabolite levels (glucose, glycogen, triglycerides, lactate and total α amino acid) and enzyme activities related to carbohydrate, lactate, amino acid and lipid pathways were detected in organs involved in metabolism (liver) and osmoregulation (gills and kidney). Our data implicate that the liver uses amino acids as an energy source in response to the T3 treatment, increasing protein catabolism and gluconeogenic pathways. The gills, the most important extruder of ammonia, are fuelled not only by amino acids, but also by lactate. The kidney differs significantly in its substrate preference from the gills, as it obtained metabolic energy from lactate but also from lipid oxidation processes. We conclude that in S. aurata lipid catabolism and protein turnover are increased as a consequence of experimentally induced hyperthyroidism, with secondary osmoregulatory effects. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Fermentation and Hydrogen Metabolism Affect Uranium Reduction by Clostridia

    DOE PAGES

    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 clostridiamore » 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

  12. Gut microbiota and metabolic syndrome.

    PubMed

    Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

    2014-11-21

    Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal "superorganism" seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host's immune system could culminate in the intestinal translocation of bacterial fragments and the development of "metabolic endotoxemia", leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use.

  13. Metabolic flexibility as an adaptation to energy resources and requirements in health and disease.

    PubMed

    Smith, Reuben L; Soeters, Maarten R; Wüst, Rob C I; Houtkooper, Riekelt H

    2018-04-24

    The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage and utilization, dependent on availability and requirement is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy homeostasis in times of either caloric excess or caloric restriction, and in times of either low or high energy demand, such as during exercise. The liver, adipose tissue and muscle govern systemic metabolic flexibility and manage nutrient sensing, uptake, transport, storage and expenditure by communication via endocrine cues. At a molecular level, metabolic flexibility relies on the configuration of metabolic pathways which is regulated by key metabolic enzymes and transcription factors, many of which interact closely with the mitochondria. Disrupted metabolic flexibility, or metabolic inflexibility, however, is associated with many pathological conditions including metabolic syndrome, type 2 diabetes mellitus, and cancer. Multiple factors like dietary composition and feeding frequency, exercise training, and use of pharmacological compounds influence metabolic flexibility and will be discussed here. Lastly, we outline important advances in metabolic flexibility research and discuss medical horizons and translational aspects.

  14. Mitofusin 2 as a driver that controls energy metabolism and insulin signaling.

    PubMed

    Zorzano, Antonio; Hernández-Alvarez, María Isabel; Sebastián, David; Muñoz, Juan Pablo

    2015-04-20

    Mitochondrial dynamics is a complex process that impacts on mitochondrial biology. Recent evidence indicates that proteins participating in mitochondrial dynamics have additional cellular roles. Mitofusin 2 (Mfn2) is a potent modulator of mitochondrial metabolism with an impact on energy metabolism in muscle, liver, and hypothalamic neurons. In addition, Mfn2 is subjected to tight regulation. Hence, factors such as proinflammatory cytokines, lipid availability, or glucocorticoids block its expression, whereas exercise and increased energy expenditure promote its upregulation. Importantly, Mfn2 controls cell metabolism and insulin signaling by limiting reactive oxygen species production and by modulation of endoplasmic reticulum stress. In this connection, it is critical to understand precisely the molecular mechanisms involved in the global actions of Mfn2. Future directions should concentrate into the analysis of those mechanisms, and to fully demonstrate that Mfn2 represents a cellular hub that senses the metabolic and hormonal milieu and drives the control of metabolic homeostasis.

  15. Ubiquitin-Dependent Degradation of Mitochondrial Proteins Regulates Energy Metabolism.

    PubMed

    Lavie, Julie; De Belvalet, Harmony; Sonon, Sessinou; Ion, Ana Madalina; Dumon, Elodie; Melser, Su; Lacombe, Didier; Dupuy, Jean-William; Lalou, Claude; Bénard, Giovanni

    2018-06-05

    The ubiquitin proteasome system (UPS) regulates many cellular functions by degrading key proteins. Notably, the role of UPS in regulating mitochondrial metabolic functions is unclear. Here, we show that ubiquitination occurs in different mitochondrial compartments, including the inner mitochondrial membrane, and that turnover of several metabolic proteins is UPS dependent. We specifically detailed mitochondrial ubiquitination and subsequent UPS-dependent degradation of succinate dehydrogenase subunit A (SDHA), which occurred when SDHA was minimally involved in mitochondrial energy metabolism. We demonstrate that SDHA ubiquitination occurs inside the organelle. In addition, we show that the specific inhibition of SDHA degradation by UPS promotes SDHA-dependent oxygen consumption and increases ATP, malate, and citrate levels. These findings suggest that the mitochondrial metabolic machinery is also regulated by the UPS. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  16. 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. © 2013.

  17. Insulin receptor substrate signaling controls cardiac energy metabolism and heart failure.

    PubMed

    Guo, Cathy A; Guo, Shaodong

    2017-06-01

    The heart is an insulin-dependent and energy-consuming organ in which insulin and nutritional signaling integrates to the regulation of cardiac metabolism, growth and survival. Heart failure is highly associated with insulin resistance, and heart failure patients suffer from the cardiac energy deficiency and structural and functional dysfunction. Chronic pathological conditions, such as obesity and type 2 diabetes mellitus, involve various mechanisms in promoting heart failure by remodeling metabolic pathways, modulating cardiac energetics and impairing cardiac contractility. Recent studies demonstrated that insulin receptor substrates 1 and 2 (IRS-1,-2) are major mediators of both insulin and insulin-like growth factor-1 (IGF-1) signaling responsible for myocardial energetics, structure, function and organismal survival. Importantly, the insulin receptor substrates (IRS) play an important role in the activation of the phosphatidylinositide-3-dependent kinase (PI-3K) that controls Akt and Foxo1 signaling cascade, regulating the mitochondrial function, cardiac energy metabolism and the renin-angiotensin system. Dysregulation of this branch in signaling cascades by insulin resistance in the heart through the endocrine system promotes heart failure, providing a novel mechanism for diabetic cardiomyopathy. Therefore, targeting this branch of IRS→PI-3K→Foxo1 signaling cascade and associated pathways may provide a fundamental strategy for the therapeutic and nutritional development in control of metabolic and cardiovascular diseases. In this review, we focus on insulin signaling and resistance in the heart and the role energetics play in cardiac metabolism, structure and function. © 2017 Society for Endocrinology.

  18. Mitochondrial DNA variation in human metabolic rate and energy expenditure

    PubMed Central

    Tranah, Gregory J.; Manini, Todd M.; Lohman, Kurt K.; Nalls, Michael A.; Kritchevsky, Stephen; Newman, Anne B.; Harris, Tamara B.; Miljkovic, Iva; Biffi, Alessandro; Cummings, Steven R.; Liu, Yongmei

    2014-01-01

    The role of climate in driving selection of mtDNA as Homo sapiens migrated out of Africa into Eurasia remains controversial. We evaluated the role of mtDNA variation in resting metabolic rate (RMR) and total energy expenditure (TEE) among 294 older, community-dwelling African and European American adults from the Health, Aging and Body Composition Study. Common African haplogroups L0, L2 and L3 had significantly lower RMRs than European haplogroups H, JT and UK with haplogroup L1 RMR being intermediate to these groups. This study links mitochondrial haplogroups with ancestry-associated differences in metabolic rate and energy expenditure. PMID:21586348

  19. Connecting metabolism and reproduction: roles of central energy sensors and key molecular mediators.

    PubMed

    Roa, Juan; Tena-Sempere, Manuel

    2014-11-01

    It is well established that pubertal activation of the reproductive axis and maintenance of fertility are critically dependent on the magnitude of body energy reserves and the metabolic state of the organism. Hence, conditions of impaired energy homeostasis often result in deregulation of puberty and reproduction, whereas gonadal dysfunction can be associated with the worsening of the metabolic profile and, eventually, changes in body weight. While much progress has taken place in our knowledge about the neuroendocrine mechanisms linking metabolism and reproduction, our understanding of how such dynamic interplay happens is still incomplete. As paradigmatic example, much has been learned in the last two decades on the reproductive roles of key metabolic hormones (such as leptin, insulin and ghrelin), their brain targets and the major transmitters and neuropeptides involved. Yet, the molecular mechanisms whereby metabolic information is translated and engages into the reproductive circuits remain largely unsolved. In this work, we will summarize recent developments in the characterization of the putative central roles of key cellular energy sensors, such as mTOR, in this phenomenon, and will relate these with other molecular mechanisms likely contributing to the brain coupling of energy balance and fertility. In doing so, we aim to provide an updated view of an area that, despite still underdeveloped, may be critically important to fully understand how reproduction and metabolism are tightly connected in health and disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. 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.

  1. Glycolysis in energy metabolism during seizures☆

    PubMed Central

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

    2013-01-01

    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

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

    PubMed

    Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

    2017-08-01

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

  3. Predicting growth of the healthy infant using a genome scale metabolic model.

    PubMed

    Nilsson, Avlant; Mardinoglu, Adil; Nielsen, Jens

    2017-01-01

    An estimated 165 million children globally have stunted growth, and extensive growth data are available. Genome scale metabolic models allow the simulation of molecular flux over each metabolic enzyme, and are well adapted to analyze biological systems. We used a human genome scale metabolic model to simulate the mechanisms of growth and integrate data about breast-milk intake and composition with the infant's biomass and energy expenditure of major organs. The model predicted daily metabolic fluxes from birth to age 6 months, and accurately reproduced standard growth curves and changes in body composition. The model corroborates the finding that essential amino and fatty acids do not limit growth, but that energy is the main growth limiting factor. Disruptions to the supply and demand of energy markedly affected the predicted growth, indicating that elevated energy expenditure may be detrimental. The model was used to simulate the metabolic effect of mineral deficiencies, and showed the greatest growth reduction for deficiencies in copper, iron, and magnesium ions which affect energy production through oxidative phosphorylation. The model and simulation method were integrated to a platform and shared with the research community. The growth model constitutes another step towards the complete representation of human metabolism, and may further help improve the understanding of the mechanisms underlying stunting.

  4. Aroclor 1254, a developmental neurotoxicant, alters energy metabolism- and intracellular signaling-associated protein networks in rat cerebellum and hippocampus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kodavanti, Prasada Rao S., E-mail: kodavanti.prasada@epa.gov; Osorio, Cristina; Program on Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, North Carolina

    2011-11-15

    The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca{sup 2+}-mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studiesmore » showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0 mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit {beta} (ATP5B), creatine kinase, and malate dehydrogenase), calcium signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and intracellular signaling, which might result in developmental neurotoxicity. -- Highlights: Black-Right-Pointing-Pointer We performed brain proteomic analysis of rats exposed to the

  5. Effect of Acute Negative and Positive Energy Balance on Basal Very-Low Density Lipoprotein Triglyceride Metabolism in Women

    PubMed Central

    Bellou, Elena; Maraki, Maria; Magkos, Faidon; Botonaki, Helena; Panagiotakos, Demosthenes B.; Kavouras, Stavros A.; Sidossis, Labros S.

    2013-01-01

    Background Acute reduction in dietary energy intake reduces very low-density lipoprotein triglyceride (VLDL-TG) concentration. Although chronic dietary energy surplus and obesity are associated with hypertriglyceridemia, the effect of acute overfeeding on VLDL-TG metabolism is not known. Objective The aim of the present study was to investigate the effects of acute negative and positive energy balance on VLDL-TG metabolism in healthy women. Design Ten healthy women (age: 22.0±2.9 years, BMI: 21.2±1.3 kg/m2) underwent a stable isotopically labeled tracer infusion study to determine basal VLDL-TG kinetics after performing, in random order, three experimental trials on the previous day: i) isocaloric feeding (control) ii) hypocaloric feeding with a dietary energy restriction of 2.89±0.42 MJ and iii) hypercaloric feeding with a dietary energy surplus of 2.91±0.32 MJ. The three diets had the same macronutrient composition. Results Fasting plasma VLDL-TG concentrations decreased by ∼26% after hypocaloric feeding relative to the control trial (P = 0.037), owing to decreased hepatic VLDL-TG secretion rate (by 21%, P = 0.023) and increased VLDL-TG plasma clearance rate (by ∼12%, P = 0.016). Hypercaloric feeding increased plasma glucose concentration (P = 0.042) but had no effect on VLDL-TG concentration and kinetics compared to the control trial. Conclusion Acute dietary energy deficit (∼3MJ) leads to hypotriglyceridemia via a combination of decreased hepatic VLDL-TG secretion and increased VLDL-TG clearance. On the other hand, acute dietary energy surplus (∼3MJ) does not affect basal VLDL-TG metabolism but disrupts glucose homeostasis in healthy women. PMID:23533676

  6. 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

  7. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Alterations in energy substrate metabolism in mice with different degrees of sepsis.

    PubMed

    Irahara, Takayuki; Sato, Norio; Otake, Kosuke; Matsumura, Shigenobu; Inoue, Kazuo; Ishihara, Kengo; Fushiki, Tohru; Yokota, Hiroyuki

    2018-07-01

    Nutritional management is crucial during the acute phase of severe illnesses. However, the appropriate nutritional requirements for patients with sepsis are poorly understood. We investigated alterations in carbohydrate, fat, and protein metabolism in mice with different degrees of sepsis. C57BL/6 mice were divided into three groups: control mice group, administered with saline, and low- and high-dose lipopolysaccharide (LPS) groups, intraperitoneally administered with 1 and 5 mg of LPS/kg, respectively. Rectal temperature, food intake, body weight, and spontaneous motor activity were measured. Indirect calorimetry was performed using a respiratory gas analysis for 120 h, after which carbohydrate oxidation and fatty acid oxidation were calculated. Urinary nitrogen excretion was measured to evaluate protein metabolism. The substrate utilization ratio was recalculated. Plasma and liver carbohydrate and lipid levels were evaluated at 24, 72, and 120 h after LPS administration. Biological reactions decreased significantly in the low- and high-LPS groups. Fatty acid oxidation and protein oxidation increased significantly 24 h after LPS administration, whereas carbohydrate oxidation decreased significantly. Energy substrate metabolism changed from glucose to predominantly lipid metabolism depending on the degree of sepsis, and protein metabolism was low. Plasma lipid levels decreased, whereas liver lipid levels increased at 24 h, suggesting that lipids were transported to the liver as the energy source. Our findings revealed that energy substrate metabolism changed depending on the degree of sepsis. Therefore, in nutritional management, such metabolic alterations must be considered, and further studies on the optimum nutritional intervention during severe sepsis are necessary. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Energy stress-induced lncRNA HAND2-AS1 represses HIF1α-mediated energy metabolism and inhibits osteosarcoma progression

    PubMed Central

    Kang, Yao; Zhu, Xiaojun; Xu, Yanyang; Tang, Qinglian; Huang, Zongwen; Zhao, Zhiqiang; Lu, Jinchang; Song, Guohui; Xu, Huaiyuan; Deng, Chuangzhong; Wang, Jin

    2018-01-01

    During recent years, long noncoding RNAs (lncRNAs) have been recognized as key regulators in the development and progression of human cancers, however, their roles in osteosarcoma metabolism are still not well understood. The present study aims to investigate the expression profiles and potential modulation of specific lncRNA(s) in osteosarcoma metabolism. The high-throughput Hiseq sequencing was performed to screen for abnormally expressed lncRNAs in osteosarcoma cells cultured under glucose starvation condition, and lncRNA HAND2-AS1 was eventually identified as one that was significantly up-regulated when compared with normal cultured cells. Mechanistic investigations indicated that knockdown of HAND2-AS1 abrogated the energy stress-induced effect on cell apoptosis and proliferation, and promoted osteosarcoma progression. Moreover, knockdown of HAND2-AS1 promoted glucose uptake, lactate production, and the expression level of a serious of enzymes that involved in energy metabolism. Subsequently, RNA pull-down and RNA immuneprecipitation revealed that, upon energy stress, HAND2-AS1 regulated osteosarcoma metabolism through sequestering FBP1 from binding to HIF1α, thereby releasing HIF1α expression and promoting the protein level. Taken together, our integrated approach reveals a regulatory mechanism by lncRNA HAND2-AS1 to control energy metabolism and tumor development in osteosarcoma. Thus, HAND2-AS1 may be a potential biomarker and therapeutic target for the repression of osteosarcoma metabolism. PMID:29637006

  10. Association Between Energy Balance and Metabolic Hormone Suppression During Ultraendurance Exercise.

    PubMed

    Geesmann, Bjoern; Gibbs, Jenna C; Mester, Joachim; Koehler, Karsten

    2017-08-01

    Ultraendurance athletes often accumulate an energy deficit when engaging in ultraendurance exercise, and on completion of the exercise, they exhibit endocrine changes that are reminiscent of starvation. However, it remains unclear whether these endocrine changes are a result of the exercise per se or secondary to the energy deficit and, more important, whether these changes can be attenuated by increased dietary intake. The goal of the study was to assess the relationship between changes in key metabolic hormones after ultraendurance exercise and measures of energy balance. Metabolic hormones, as well as energy intake and expenditure, were assessed in 14 well-trained male cyclists who completed a 1230-km ultraendurance cycling event. After completion of the event, serum testosterone (-67% ± 18%), insulin-like growth factor-1 (IGF-1) (-45% ± 8%), and leptin (-79% ± 9%) were significantly suppressed (P < .001) and remained suppressed after a 12-h recovery period (P < .001). Changes in IGF-1 were positively correlated with energy balance over the course of the event (r = .65, P = .037), which ranged from an 11,859-kcal deficit to a 3593-kcal surplus. The marked suppression of testosterone, IGF-1, and leptin after ultraendurance exercise is comparable to changes occurring during acute starvation. The suppression of IGF-1, but not that of other metabolic hormones, was strongly associated with the magnitude of the energy deficit, indicating that athletes who attained a greater energy deficit exhibited a more pronounced drop in IGF-1. Future studies are needed to determine whether increased dietary intake can attenuate the endocrine response to ultraendurance exercise.

  11. Cytosolic Calcium Coordinates Mitochondrial Energy Metabolism with Presynaptic Activity

    PubMed Central

    Chouhan, Amit K.; Ivannikov, Maxim V.; Lu, Zhongmin; Sugimori, Mutsuyuki; Llinas, Rodolfo R.; Macleod, Gregory T.

    2012-01-01

    Most neurons fire in bursts, imposing episodic energy demands, but how these demands are coordinated with oxidative phosphorylation is still unknown. Here, using fluorescence imaging techniques on presynaptic termini of Drosophila motor neurons (MNs), we show that mitochondrial matrix pH (pHm), inner membrane potential (Δψm), and NAD(P)H levels ([NAD(P)H]m) increase within seconds of nerve stimulation. The elevations of pHm, Δψm, and [NAD(P)H]m indicate an increased capacity for ATP production. Elevations in pHm were blocked by manipulations which blocked mitochondrial Ca2+ uptake, including replacement of extracellular Ca2+ with Sr2+, and application of either tetraphenylphosphonium chloride or KB-R7943, indicating that it is Ca2+ that stimulates presynaptic mitochondrial energy metabolism. To place this phenomenon within the context of endogenous neuronal activity, the firing rates of a number of individually identified MNs were determined during fictive locomotion. Surprisingly, although endogenous firing rates are significantly different, there was little difference in presynaptic cytosolic Ca2+ levels ([Ca2+]c) between MNs when each fires at its endogenous rate. The average [Ca2+]c level (329±11nM) was slightly above the average Ca2+ affinity of the mitochondria (281±13nM). In summary, we show that when MNs fire at endogenous rates [Ca2+]c is driven into a range where mitochondria rapidly acquire Ca2+. As we also show that Ca2+ stimulates presynaptic mitochondrial energy metabolism, we conclude that [Ca2+]c levels play an integral role in coordinating mitochondrial energy metabolism with presynaptic activity in Drosophila MNs. PMID:22279208

  12. 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.

  13. In Vitro Effects of Sports and Energy Drinks on Streptococcus mutans Biofilm Formation and Metabolic Activity.

    PubMed

    Vinson, LaQuia A; Goodlett, Amy K; Huang, Ruijie; Eckert, George J; Gregory, Richard L

    2017-09-15

    Sports and energy drinks are being increasingly consumed and contain large amounts of sugars, which are known to increase Streptococcus mutans biofilm formation and metabolic activity. The purpose of this in vitro study was to investigate the effects of sports and energy drinks on S. mutans biofilm formation and metabolic activity. S. mutans UA159 was cultured with and without a dilution (1:3 ratio) of a variety of sports and energy drinks in bacterial media for 24 hours. The biofilm was washed, fixed, and stained. Biofilm growth was evaluated by reading absorbance of the crystal violet. Biofilm metabolic activity was measured by the biofilm-reducing XTT to a water-soluble orange compound. Gatorade Protein Recovery Shake and Starbucks Doubleshot Espresso Energy were found to significantly increase biofilm (30-fold and 22-fold, respectively) and metabolic activity (2-fold and 3-fold, respectively). However, most of the remaining drinks significantly inhibited biofilm growth and metabolic activity. Several sports and energy drinks, with sugars or sugar substitutes as their main ingredients inhibited S. mutans biofilm formation. Among the drinks evaluated, Gatorade Protein Recovery Chocolate Shake and Starbucks Doubleshot Energy appear to have cariogenic potential since they increased the biofilm formation and metabolic activity of S. mutans.

  14. Energy metabolism during endurance flight and the post-flight recovery phase.

    PubMed

    Jenni-Eiermann, Susanne

    2017-07-01

    Migrating birds are known to fly non-stop for thousands of kilometres without food or water intake and at a high metabolic rate thereby relying on energy stores which were built up preceding a flight bout. Hence, from a physiological point of view the metabolism of a migrant has to switch between an active fasting phase during flight and a fuelling phase during stopover. To meet the energetic and water requirements of endurance flight, migratory birds have to store an optimal fuel composition and they have to be able to quickly mobilize and deliver sufficient energy to the working flight muscles. After flight, birds have to recover from a strenuous exercise and sleeplessness, but, at the same time, they have to be alert to escape from predators and to prepare the next flight bout. In this overview, metabolic adaptations of free-ranging migrants to both phases will be presented and compared with results from windtunnel studies. The questions whether migratory strategy (long distance versus short distance) and diet composition influence the metabolic pathways will be discussed.

  15. Roles for Orexin/Hypocretin in the Control of Energy Balance and Metabolism.

    PubMed

    Goforth, Paulette B; Myers, Martin G

    The neuropeptide hypocretin is also commonly referred to as orexin, since its orexigenic action was recognized early. Orexin/hypocretin (OX) neurons project widely throughout the brain and the physiologic and behavioral functions of OX are much more complex than initially conceived based upon the stimulation of feeding. OX most notably controls functions relevant to attention, alertness, and motivation. OX also plays multiple crucial roles in the control of food intake, metabolism, and overall energy balance in mammals. OX signaling not only promotes food-seeking behavior upon short-term fasting to increase food intake and defend body weight, but, conversely, OX signaling also supports energy expenditure to protect against obesity. Furthermore, OX modulates the autonomic nervous system to control glucose metabolism, including during the response to hypoglycemia. Consistently, a variety of nutritional cues (including the hormones leptin and ghrelin) and metabolites (e.g., glucose, amino acids) control OX neurons. In this chapter, we review the control of OX neurons by nutritional/metabolic cues, along with our current understanding of the mechanisms by which OX and OX neurons contribute to the control of energy balance and metabolism.

  16. 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. Copyright © 2015 the American Physiological Society.

  17. Impaired cardiac energy metabolism in embryos lacking adrenergic stimulation

    PubMed Central

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

    2014-01-01

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

  18. Physiological aspects of energy metabolism and gastrointestinal effects of carbohydrates.

    PubMed

    Elia, M; Cummings, J H

    2007-12-01

    The energy values of carbohydrates continue to be debated. This is because of the use of different energy systems, for example, combustible, digestible, metabolizable, and so on. Furthermore, ingested macronutrients may not be fully available to tissues, and the tissues themselves may not be able fully to oxidize substrates made available to them. Therefore, for certain carbohydrates, the discrepancies between combustible energy (cEI), digestible energy (DE), metabolizable energy (ME) and net metabolizable energy (NME) may be considerable. Three food energy systems are in use in food tables and for food labelling in different world regions based on selective interpretation of the digestive physiology and metabolism of food carbohydrates. This is clearly unsatisfactory and confusing to the consumer. While it has been suggested that an enormous amount of work would have to be undertaken to change the current ME system into an NME system, the additional changes may not be as great as anticipated. In experimental work, carbohydrate is high in the macronutrient hierarchy of satiation. However, studies of eating behaviour indicate that it does not unconditionally depend on the oxidation of one nutrient, and argue against the operation of a simple carbohydrate oxidation or storage model of feeding behaviour to the exclusion of other macronutrients. The site, rate and extent of carbohydrate digestion in, and absorption from the gut are key to understanding the many roles of carbohydrate, although the concept of digestibility has different meanings. Within the nutrition community, the characteristic patterns of digestion that occur in the small (upper) vs large (lower) bowel are known to impact in contrasting ways on metabolism, while in the discussion of the energy value of foods, digestibility is defined as the proportion of combustible energy that is absorbed over the entire length of the gastrointestinal tract. Carbohydrates that reach the large bowel are fermented to

  19. Hypothalamic Alterations in Neurodegenerative Diseases and Their Relation to Abnormal Energy Metabolism

    PubMed Central

    Vercruysse, Pauline; Vieau, Didier; Blum, David; Petersén, Åsa; Dupuis, Luc

    2018-01-01

    Neurodegenerative diseases (NDDs) are disorders characterized by progressive deterioration of brain structure and function. Selective neuronal populations are affected leading to symptoms which are prominently motor in amyotrophic lateral sclerosis (ALS) or Huntington’s disease (HD), or cognitive in Alzheimer’s disease (AD) and fronto-temporal dementia (FTD). Besides the common existence of neuronal loss, NDDs are also associated with metabolic changes such as weight gain, weight loss, loss of fat mass, as well as with altered feeding behavior. Importantly, preclinical research as well as clinical studies have demonstrated that altered energy homeostasis influences disease progression in ALS, AD and HD, suggesting that identification of the pathways leading to perturbed energy balance might provide valuable therapeutic targets Signals from both the periphery and central inputs are integrated in the hypothalamus, a major hub for the control of energy balance. Recent research identified major hypothalamic changes in multiple NDDs. Here, we review these hypothalamic alterations and seek to identify commonalities and differences in hypothalamic involvement between the different NDDs. These hypothalamic defects could be key in the development of perturbations in energy homeostasis in NDDs and further understanding of the underlying mechanisms might open up new avenues to not only treat weight loss but also to ameliorate overall neurological symptoms. PMID:29403354

  20. Gut Microbiota and Metabolic Disorders

    PubMed Central

    Hur, Kyu Yeon

    2015-01-01

    Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders. PMID:26124989

  1. Fasting energy metabolism of the Yucatan miniature pig.

    PubMed

    Parsons, A H; Mathieson, K W; Tagliaferro, A R

    1990-03-01

    The fasting metabolic rates (FMR) of Yucatan miniature swine were determined using an open-circuit indirect respiration calorimeter. Mature nulliparous females had a mean FMR of 93 kcal/kg BW.75 and did not change significantly during the estrous cycle. This value is comparable to that observed in mature domestic swine. The calculated metabolizable energy requirement for maintenance for the Yucatan sow is 116 kcal/kg BW.75. Growing Yucatan boars had FMR of 127, 119 and 101 kcal/kg BW.75 at 15, 21 and 38 weeks of age, respectively, and were similar to values for comparably aged domestic swine. The calculated estimate for the metabolizable energy requirement for maintenance for Yucatan boars ranged from 158 kcal at 15 weeks of age to 126 kcal/kg BW.75 for 38 week old animals. Based on the similarity between the FMR of the Yucatan miniature swine in the present study and values published for standard size commercial hogs, it is concluded that the metabolic rates of these breeds of pig are similar. It is suggested that the daily energy needs of the Yucatan miniature pig may be met using values published for production livestock having similar physiological condition when adjusted for the smaller body size of the Yucatan breed.

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

    PubMed

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

    2015-09-01

    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.

  4. Gut microbiota and metabolic syndrome

    PubMed Central

    Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

    2014-01-01

    Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal “superorganism” seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host’s immune system could culminate in the intestinal translocation of bacterial fragments and the development of “metabolic endotoxemia”, leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use. PMID:25473159

  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.

  6. GeneChip Expression Profiling Reveals the Alterations of Energy Metabolism Related Genes in Osteocytes under Large Gradient High Magnetic Fields

    PubMed Central

    Wang, Yang; Chen, Zhi-Hao; Yin, Chun; Ma, Jian-Hua; Li, Di-Jie; Zhao, Fan; Sun, Yu-Long; Hu, Li-Fang; Shang, Peng; Qian, Ai-Rong

    2015-01-01

    The diamagnetic levitation as a novel ground-based model for simulating a reduced gravity environment has recently been applied in life science research. In this study a specially designed superconducting magnet with a large gradient high magnetic field (LG-HMF), which can provide three apparent gravity levels (μ-g, 1-g, and 2-g), was used to simulate a space-like gravity environment. Osteocyte, as the most important mechanosensor in bone, takes a pivotal position in mediating the mechano-induced bone remodeling. In this study, the effects of LG-HMF on gene expression profiling of osteocyte-like cell line MLO-Y4 were investigated by Affymetrix DNA microarray. LG-HMF affected osteocyte gene expression profiling. Differentially expressed genes (DEGs) and data mining were further analyzed by using bioinfomatic tools, such as DAVID, iReport. 12 energy metabolism related genes (PFKL, AK4, ALDOC, COX7A1, STC1, ADM, CA9, CA12, P4HA1, APLN, GPR35 and GPR84) were further confirmed by real-time PCR. An integrated gene interaction network of 12 DEGs was constructed. Bio-data mining showed that genes involved in glucose metabolic process and apoptosis changed notablly. Our results demostrated that LG-HMF affected the expression of energy metabolism related genes in osteocyte. The identification of sensitive genes to special environments may provide some potential targets for preventing and treating bone loss or osteoporosis. PMID:25635858

  7. GeneChip expression profiling reveals the alterations of energy metabolism related genes in osteocytes under large gradient high magnetic fields.

    PubMed

    Wang, Yang; Chen, Zhi-Hao; Yin, Chun; Ma, Jian-Hua; Li, Di-Jie; Zhao, Fan; Sun, Yu-Long; Hu, Li-Fang; Shang, Peng; Qian, Ai-Rong

    2015-01-01

    The diamagnetic levitation as a novel ground-based model for simulating a reduced gravity environment has recently been applied in life science research. In this study a specially designed superconducting magnet with a large gradient high magnetic field (LG-HMF), which can provide three apparent gravity levels (μ-g, 1-g, and 2-g), was used to simulate a space-like gravity environment. Osteocyte, as the most important mechanosensor in bone, takes a pivotal position in mediating the mechano-induced bone remodeling. In this study, the effects of LG-HMF on gene expression profiling of osteocyte-like cell line MLO-Y4 were investigated by Affymetrix DNA microarray. LG-HMF affected osteocyte gene expression profiling. Differentially expressed genes (DEGs) and data mining were further analyzed by using bioinfomatic tools, such as DAVID, iReport. 12 energy metabolism related genes (PFKL, AK4, ALDOC, COX7A1, STC1, ADM, CA9, CA12, P4HA1, APLN, GPR35 and GPR84) were further confirmed by real-time PCR. An integrated gene interaction network of 12 DEGs was constructed. Bio-data mining showed that genes involved in glucose metabolic process and apoptosis changed notablly. Our results demostrated that LG-HMF affected the expression of energy metabolism related genes in osteocyte. The identification of sensitive genes to special environments may provide some potential targets for preventing and treating bone loss or osteoporosis.

  8. Changes in energy metabolism in relation to physical activity due to fermentable carbohydrates in group-housed growing pigs.

    PubMed

    Schrama, J W; Bakker, G C

    1999-12-01

    Fermentable nonstarch polysaccharides (dietary fiber) affect energy retention in group-housed growing pigs by reducing physical activity. This study assessed the effects of fermentation and bulkiness of dietary carbohydrates on physical activity in relation to energy metabolism. Eight clusters of 14 pigs were fed one of four diets in a 2x2 factorial arrangement. Factors included 1) gastrointestinal fermentation and 2) dietary bulkiness. Contrasts in fermentation were created by exchanging gelatinized maize starch with raw potato starch on a volume basis. Bulkiness was altered by adding 15% milled wheat straw to the diets. Apart from these differences, amounts of other dietary ingredients fed to the pigs were similar. Pigs were housed in groups. Nitrogen and energy balances were measured per cluster during a 14-d period. Dietary bulkiness did not affect ME intake, heat production, or energy retention. Metabolizability decreased when maize starch was replaced with raw potato starch (P< .01), resulting in a lower energy retention on the potato starch diets (P<.01). However, the lower ME intake on the potato diets was partially compensated by a reduced energy expenditure on physical activity (P< .01), which was 17.6% lower than that of pigs fed the maize starch diets. Dietary bulkiness did not affect physical activity. The effect of fiber-rich diets (nonstarch polysaccharides) on activity in growing group-housed pigs seems to be related to fermentation in the gastrointestinal tract, and not to bulkiness (volume).

  9. 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

  10. Environmental effects on nutrient and energy metabolism in ruminants.

    PubMed

    Tamminga, S; Schrama, J W

    1998-01-01

    Domesticated animals all over the world are subjected to a wide variety of environmental conditions and challenges. Any deviation from "normal" may result in adaptive behavior of which changes in feed intake or feed intake pattern is by far the most important. Adaptive behavior may further include influences on passage rate of feed residues through the digestive tract, resulting in changes in digestibility. Adaptive behavior may also result in changes in heat production, either to maintain body temperature constant, or as a result of an elevated body temperature. Important environmental challenges are infectious diseases. Mild (sub-clinical) infections usually result in reduced performance, without affecting feed intake or digestibility. Severe infections may disrupt the barriers between the internal metabolism and the respiratory and/or digestive tract, resulting in severe losses of energy and protein. This situation is notably apparent in severe infections with parasites of the gastrointestinal tract and may be associated with severe protein losses. Feeding high protein diets may partly alleviate the negative effects. Contamination of air, water and feed may occasionally cause problems in farm animals. Such contamination may include pathogenic microbes, toxic secondary fungal metabolites and heavy metals. Negative effects associated with such contamination often show an impaired reproductive efficiency, but their influence on the utilization of energy and nutrients is not well documented.

  11. 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.

  12. 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

  13. 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.

  14. The gut hormone ghrelin partially reverses energy substrate metabolic alterations in the failing heart.

    PubMed

    Mitacchione, Gianfranco; Powers, Jeffrey C; Grifoni, Gino; Woitek, Felix; Lam, Amy; Ly, Lien; Settanni, Fabio; Makarewich, Catherine A; McCormick, Ryan; Trovato, Letizia; Houser, Steven R; Granata, Riccarda; Recchia, Fabio A

    2014-07-01

    The gut-derived hormone ghrelin, especially its acylated form, plays a major role in the regulation of systemic metabolism and exerts also relevant cardioprotective effects; hence, it has been proposed for the treatment of heart failure (HF). We tested the hypothesis that ghrelin can directly modulate cardiac energy substrate metabolism. We used chronically instrumented dogs, 8 with pacing-induced HF and 6 normal controls. Human des-acyl ghrelin [1.2 nmol/kg per hour] was infused intravenously for 15 minutes, followed by washout (rebaseline) and infusion of acyl ghrelin at the same dose. (3)H-oleate and (14)C-glucose were coinfused and arterial and coronary sinus blood sampled to measure cardiac free fatty acid and glucose oxidation and lactate uptake. As expected, cardiac substrate metabolism was profoundly altered in HF because baseline oxidation levels of free fatty acids and glucose were, respectively, >70% lower and >160% higher compared with control. Neither des-acyl ghrelin nor acyl ghrelin significantly affected function and metabolism in normal hearts. However, in HF, des-acyl and acyl ghrelin enhanced myocardial oxygen consumption by 10.2±3.5% and 9.9±3.7%, respectively (P<0.05), and cardiac mechanical efficiency was not significantly altered. This was associated, respectively, with a 41.3±6.7% and 32.5±10.9% increase in free fatty acid oxidation and a 31.3±9.2% and 41.4±8.9% decrease in glucose oxidation (all P<0.05). Acute increases in des-acyl or acyl ghrelin do not interfere with cardiac metabolism in normal dogs, whereas they enhance free fatty acid oxidation and reduce glucose oxidation in HF dogs, thus partially correcting metabolic alterations in HF. This novel mechanism might contribute to the cardioprotective effects of ghrelin in HF. © 2014 American Heart Association, Inc.

  15. Skeletal muscle-specific eukaryotic translation initiation factor 2α phosphorylation controls amino acid metabolism and fibroblast growth factor 21-mediated non-cell-autonomous energy metabolism.

    PubMed

    Miyake, Masato; Nomura, Akitoshi; Ogura, Atsushi; Takehana, Kenji; Kitahara, Yoshihiro; Takahara, Kazuna; Tsugawa, Kazue; Miyamoto, Chinobu; Miura, Naoko; Sato, Ryosuke; Kurahashi, Kiyoe; Harding, Heather P; Oyadomari, Miho; Ron, David; Oyadomari, Seiichi

    2016-02-01

    The eukaryotic translation initiation factor 2α (eIF2α) phosphorylation-dependent integrated stress response (ISR), a component of the unfolded protein response, has long been known to regulate intermediary metabolism, but the details are poorly worked out. We report that profiling of mRNAs of transgenic mice harboring a ligand-activated skeletal muscle-specific derivative of the eIF2α protein kinase R-like ER kinase revealed the expected up-regulation of genes involved in amino acid biosynthesis and transport but also uncovered the induced expression and secretion of a myokine, fibroblast growth factor 21 (FGF21), that stimulates energy consumption and prevents obesity. The link between the ISR and FGF21 expression was further reinforced by the identification of a small-molecule ISR activator that promoted Fgf21 expression in cell-based screens and by implication of the ISR-inducible activating transcription factor 4 in the process. Our findings establish that eIF2α phosphorylation regulates not only cell-autonomous proteostasis and amino acid metabolism, but also affects non-cell-autonomous metabolic regulation by induced expression of a potent myokine. © FASEB.

  16. 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

  17. 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

  18. Mitochondrial biogenesis and energy production in differentiating murine stem cells: a functional metabolic study.

    PubMed

    Han, Sungwon; Auger, Christopher; Thomas, Sean C; Beites, Crestina L; Appanna, Vasu D

    2014-02-01

    The significance of metabolic networks in guiding the fate of the stem cell differentiation is only beginning to emerge. Oxidative metabolism has been suggested to play a major role during this process. Therefore, it is critical to understand the underlying mechanisms of metabolic alterations occurring in stem cells to manipulate the ultimate outcome of these pluripotent cells. Here, using P19 murine embryonal carcinoma cells as a model system, the role of mitochondrial biogenesis and the modulation of metabolic networks during dimethyl sulfoxide (DMSO)-induced differentiation are revealed. Blue native polyacrylamide gel electrophoresis (BN-PAGE) technology aided in profiling key enzymes, such as hexokinase (HK) [EC 2.7.1.1], glucose-6-phosphate isomerase (GPI) [EC 5.3.1.9], pyruvate kinase (PK) [EC 2.7.1.40], Complex I [EC 1.6.5.3], and Complex IV [EC 1.9.3.1], that are involved in the energy budget of the differentiated cells. Mitochondrial adenosine triphosphate (ATP) production was shown to be increased in DMSO-treated cells upon exposure to the tricarboxylic acid (TCA) cycle substrates, such as succinate and malate. The increased mitochondrial activity and biogenesis were further confirmed by immunofluorescence microscopy. Collectively, the results indicate that oxidative energy metabolism and mitochondrial biogenesis were sharply upregulated in DMSO-differentiated P19 cells. This functional metabolic and proteomic study provides further evidence that modulation of mitochondrial energy metabolism is a pivotal component of the cellular differentiation process and may dictate the final destiny of stem cells.

  19. 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.

  20. Cyclic mechanical stretch promotes energy metabolism in osteoblast-like cells through an mTOR signaling-associated mechanism.

    PubMed

    Zeng, Zhaobin; Jing, Da; Zhang, Xiaodong; Duan, Yinzhong; Xue, Feng

    2015-10-01

    Energy metabolism is essential for maintaining function and substance metabolism in osteoblasts. However, the role of cyclic stretch in regulating osteoblastic energy metabolism and the underlying mechanisms remain poorly understood. In this study, we found that cyclic stretch (10% elongation at 0.1 Hz) significantly enhanced glucose consumption, lactate levels (determined using a glucose/lactate assay kit), intracellular adenosine triphosphate (ATP) levels (quantified using rLuciferase/Luciferin reagent) and the mRNA expression of energy metabolism-related enzymes [mitochondrial ATP synthase, L-lactate dehydrogenase A (LDHA) and enolase 1; measured by RT-qPCR], and increased the phosphorylation levels of Akt, mammalian target of rapamycin (mTOR) and p70s6k (measured by western blot analysis) in human osteoblast‑like MG‑63 cells. Furthermore, the inhibition of Akt or mTOR with an antagonist (wortmannin or rapamycin) suppressed the stretch-induced increase in glucose consumption, lactate levels, intracellular ATP levels and the expression of mitochondrial ATP synthase and LDHA, indicating the significance of the Akt/mTOR/p70s6k pathway in regulating osteoblastic energy metabolism in response to mechanical stretch. Thus, we concluded that cyclic stretch regulates energy metabolism in MG‑63 cells partially through the Akt/mTOR/p70s6k signaling pathway. The present findings provide novel insight into osteoblastic mechanobiology from the perspective of energy metabolism.

  1. Geochemical constraints on sources of metabolic energy for chemolithoautotrophy in ultramafic-hosted deep-sea hydrothermal systems.

    PubMed

    McCollom, Thomas M

    2007-12-01

    Numerical models are employed to investigate sources of chemical energy for autotrophic microbial metabolism that develop during mixing of oxidized seawater with strongly reduced fluids discharged from ultramafic-hosted hydrothermal systems on the seafloor. Hydrothermal fluids in these systems are highly enriched in H(2) and CH(4) as a result of alteration of ultramafic rocks (serpentinization) in the subsurface. Based on the availability of chemical energy sources, inferences are made about the likely metabolic diversity, relative abundance, and spatial distribution of microorganisms within ultramafic-hosted systems. Metabolic reactions involving H(2) and CH(4), particularly hydrogen oxidation, methanotrophy, sulfate reduction, and methanogenesis, represent the predominant sources of chemical energy during fluid mixing. Owing to chemical gradients that develop from fluid mixing, aerobic metabolisms are likely to predominate in low-temperature environments (<20-30 degrees C), while anaerobes will dominate higher-temperature environments. Overall, aerobic metabolic reactions can supply up to approximately 7 kJ of energy per kilogram of hydrothermal fluid, while anaerobic metabolic reactions can supply about 1 kJ, which is sufficient to support a maximum of approximately 120 mg (dry weight) of primary biomass production by aerobic organisms and approximately 20-30 mg biomass by anaerobes. The results indicate that ultramafic-hosted systems are capable of supplying about twice as much chemical energy as analogous deep-sea hydrothermal systems hosted in basaltic rocks.

  2. Energy metabolism in feasting and fasting.

    PubMed

    Owen, O E; Reichard, G A; Patel, M S; Boden, G

    1979-01-01

    During feasting on a balanced carbohydrate, fat, and protein meal resting metabolic rate, body temperature and respiratory quotient all increase. The dietary components are utilized to replenish and augment glycogen and fat stores in the body. Excessive carbohydrate is also converted to lipid in the liver and stored along with the excessive lipids of dietary origin as triglycerides in adipose tissue, the major fuel storage depot. Amino acids in excess of those needed for protein synthesis are preferentially catabolized over glucose and fat for energy production. This occurs because there are no significant storage sites for amino acids or proteins, and the accumulation of nitrogenous compounds is ill tolerated. During fasting, adipose tissue, muscle, liver, and kidneys work in concert to supply, to convert, and to conserve fuels for the body. During the brief postabsorptive period, blood fuel homeostasis is maintained primarily by hepatic glycogenolysis and adipose tissue lipolysis. As fasting progresses, muscle proteolysis supplies glycogenic amino acids for heightened hepatic gluconeogenesis for a short period of time. After about three days of starvation, the metabolic profile is set to conserve protein and to supply greater quantities of alternate fuels. In particular, free fatty acids and ketone bodies are utilized to maintain energy needs. The ability of the kidney to conserve ketone bodies prevents the loss of large quantities of these valuable fuels in the urine. This delicate interplay among liver, muscle, kidney, and adipose tissue maintains blood fuel homeostasis and allows humans to survive caloric deprivation for extended periods.

  3. In vivo monitoring of cellular energy metabolism using SoNar, a highly responsive sensor for NAD(+)/NADH redox state.

    PubMed

    Zhao, Yuzheng; Wang, Aoxue; Zou, Yejun; Su, Ni; Loscalzo, Joseph; Yang, Yi

    2016-08-01

    NADH and its oxidized form NAD(+) have a central role in energy metabolism, and their concentrations are often considered to be among the most important readouts of metabolic state. Here, we present a detailed protocol to image and monitor NAD(+)/NADH redox state in living cells and in vivo using a highly responsive, genetically encoded fluorescent sensor known as SoNar (sensor of NAD(H) redox). The chimeric SoNar protein was initially developed by inserting circularly permuted yellow fluorescent protein (cpYFP) into the NADH-binding domain of Rex protein from Thermus aquaticus (T-Rex). It functions by binding to either NAD(+) or NADH, thus inducing protein conformational changes that affect its fluorescent properties. We first describe steps for how to establish SoNar-expressing cells, and then discuss how to use the system to quantify the intracellular redox state. This approach is sensitive, accurate, simple and able to report subtle perturbations of various pathways of energy metabolism in real time. We also detail the application of SoNar to high-throughput chemical screening of candidate compounds targeting cell metabolism in a microplate-reader-based assay, along with in vivo fluorescence imaging of tumor xenografts expressing SoNar in mice. Typically, the approximate time frame for fluorescence imaging of SoNar is 30 min for living cells and 60 min for living mice. For high-throughput chemical screening in a 384-well-plate assay, the whole procedure generally takes no longer than 60 min to assess the effects of 380 compounds on cell metabolism.

  4. Metabolic regulation of inflammation.

    PubMed

    Gaber, Timo; Strehl, Cindy; Buttgereit, Frank

    2017-05-01

    Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

  5. Energy metabolism during activity-promoting video games practice in subjects with spinal cord injury: evidences for health promotion.

    PubMed

    Gaffurini, P; Bissolotti, L; Calza, S; Calabretto, C; Orizio, C; Gobbo, M

    2013-02-01

    Activity promoting video game (APVG) practice significantly affects energy metabolism through energy expenditure (EE) increase and has been recently included in strategies for health promotion. It is not known if the APVG practice provides similar outcomes in subjects with spinal cord injury (SCI). Aim of the study was to evaluate cardio-pulmonary and metabolic adaptations during APVG practice and to find whether EE increase above resting condition could suggest the inclusion of this exercise in a more general strategy for health promotion and body weight control in subjects with SCI. Repeated measures study. Rehabilitation Institute. Ten male subjects with SCI (lesion levels from C7 to L1) age 26 to 55 years. We recorded pulmonary ventilation (VE), oxygen consumption (VO2) for EE esteem and heart rate (HR) at rest and while playing virtual bowling, tennis and boxing games using a portable metabolimeter equipped with ECG electrodes. The standard metabolic equivalent of task (METs) was calculated offline. The metabolic and functional parameters were referred to the 10th minute of each activity. Metabolic and functional parameters increased significantly from rest to bowling, tennis and boxing. METs exceeded in average 3 during boxing. One hour of APVG can increase daily EE by about 6% (bowling), 10% (tennis) and 15% (boxing). These considerable results suggest that physical exertion during APVG practice in subjects with SCI could contribute to health promotion as well as caloric balance control, especially when boxing is considered. This can be safely achieved at home with regular activity. These findings substantiate the potential for novel exercise modalities to counteract deconditioning due to inactivity in subjects with SCI by promoting physical activity through implementation of APVG exercise programs.

  6. Short- and medium-chain fatty acids in energy metabolism: the cellular perspective

    PubMed Central

    Schönfeld, Peter; Wojtczak, Lech

    2016-01-01

    Short- and medium-chain fatty acids (SCFAs and MCFAs), independently of their cellular signaling functions, are important substrates of the energy metabolism and anabolic processes in mammals. SCFAs are mostly generated by colonic bacteria and are predominantly metabolized by enterocytes and liver, whereas MCFAs arise mostly from dietary triglycerides, among them milk and dairy products. A common feature of SCFAs and MCFAs is their carnitine-independent uptake and intramitochondrial activation to acyl-CoA thioesters. Contrary to long-chain fatty acids, the cellular metabolism of SCFAs and MCFAs depends to a lesser extent on fatty acid-binding proteins. SCFAs and MCFAs modulate tissue metabolism of carbohydrates and lipids, as manifested by a mostly inhibitory effect on glycolysis and stimulation of lipogenesis or gluconeogenesis. SCFAs and MCFAs exert no or only weak protonophoric and lytic activities in mitochondria and do not significantly impair the electron transport in the respiratory chain. SCFAs and MCFAs modulate mitochondrial energy production by two mechanisms: they provide reducing equivalents to the respiratory chain and partly decrease efficacy of oxidative ATP synthesis. PMID:27080715

  7. Energy metabolism in BPH/2J genetically hypertensive mice.

    PubMed

    Jackson, Kristy L; Nguyen-Huu, Thu-Phuc; Davern, Pamela J; Head, Geoffrey A

    2014-05-01

    Recent evidence indicates that genetic hypertension in BPH/2J mice is sympathetically mediated, but these mice also have lower body weight (BW) and elevated locomotor activity compared with BPN/3J normotensive mice, suggestive of metabolic abnormalities. The aim of the present study was to determine whether hypertension in BPH/2J mice is associated with metabolic differences. Whole-body metabolic and cardiovascular parameters were measured over 24 h by indirect calorimetry and radiotelemetry respectively, in conscious young (10-13 weeks) and older (22-23 weeks) BPH/2J, normotensive BPN/3J and C57Bl6 mice. Blood pressure (BP) was greater in BPH/2J compared with both normotensive strains at both ages (P<0.01). Metabolic rate was greater in young BPH/2J compared with BPN/3J mice (P<0.01) but similar to C57Bl6 mice indicating that high metabolic rate is not necessarily related to the hypertension per say. The slope of the BP-metabolic rate relationship was comparable between BPH/2J and normotensive mice when adjusted for activity (P>0.1) suggesting differences in this relationship are not responsible for hypertension. EchoMRI revealed that percentage body composition was comparable in BPN/3J and BPH/2J mice (P>0.1) and both strains gained weight similarly with age (P=0.3). Taken together, the present findings indicate that hypertension in BPH/2J mice does not appear to be related to altered energy metabolism.

  8. Energy Metabolism in Human Pluripotent Stem Cells and Their Differentiated Counterparts

    PubMed Central

    Moura, Michelle B.; Momcilovic, Olga; Easley, Charles A.; Ramalho-Santos, João; Van Houten, Bennett; Schatten, Gerald

    2011-01-01

    Background Human pluripotent stem cells have the ability to generate all cell types present in the adult organism, therefore harboring great potential for the in vitro study of differentiation and for the development of cell-based therapies. Nonetheless their use may prove challenging as incomplete differentiation of these cells might lead to tumoregenicity. Interestingly, many cancer types have been reported to display metabolic modifications with features that might be similar to stem cells. Understanding the metabolic properties of human pluripotent stem cells when compared to their differentiated counterparts can thus be of crucial importance. Furthermore recent data has stressed distinct features of different human pluripotent cells lines, namely when comparing embryo-derived human embryonic stem cells (hESCs) and induced pluripotent stem cells (IPSCs) reprogrammed from somatic cells. Methodology/Principal Findings We compared the energy metabolism of hESCs, IPSCs, and their somatic counterparts. Focusing on mitochondria, we tracked organelle localization and morphology. Furthermore we performed gene expression analysis of several pathways related to the glucose metabolism, including glycolysis, the pentose phosphate pathway and the tricarboxylic acid (TCA) cycle. In addition we determined oxygen consumption rates (OCR) using a metabolic extracellular flux analyzer, as well as total intracellular ATP levels by high performance liquid chromatography (HPLC). Finally we explored the expression of key proteins involved in the regulation of glucose metabolism. Conclusions/Findings Our results demonstrate that, although the metabolic signature of IPSCs is not identical to that of hESCs, nonetheless they cluster with hESCs rather than with their somatic counterparts. ATP levels, lactate production and OCR revealed that human pluripotent cells rely mostly on glycolysis to meet their energy demands. Furthermore, our work points to some of the strategies which human

  9. Energy expenditure during tennis play: a preliminary video analysis and metabolic model approach.

    PubMed

    Botton, Florent; Hautier, Christophe; Eclache, Jean-Paul

    2011-11-01

    The aim of this study was to estimate, using video analysis, what proportion of the total energy expenditure during a tennis match is accounted for by aerobic and anaerobic metabolism, respectively. The method proposed involved estimating the metabolic power (MP) of 5 activities, which are inherent to tennis: walking, running, hitting the ball, serving, and sitting down to rest. The energy expenditure concerned was calculated by sequencing the activity by video analysis. A bioenergetic model calculated the aerobic energy expenditure (EEO2mod) in terms of MP, and the anaerobic energy expenditure was calculated by subtracting this (MP - EEO2mod). Eight tennis players took part in the experiment as subjects (mean ± SD: age 25.2 ± 1.9 years, weight 79.3 ± 10.8 kg, VO2max 54.4 ± 5.1 ml·kg(-1)·min(-1)). The players started off by participating in 2 games while wearing the K4b2, with their activity profile measured by the video analysis system, and then by playing a set without equipment but with video analysis. There was no significant difference between calculated and measured oxygen consumptions over the 16 games (p = 0.763), and these data were strongly related (r = 0.93, p < 0.0001). The EEO2mod was quite weak over all the games (49.4 ± 4.8% VO2max), whereas the MP during points was up to 2 or 3 times the VO2max. Anaerobic metabolism reached 32% of the total energy expenditure across all the games 67% for points and 95% for hitting the ball. This method provided a good estimation of aerobic energy expenditure and made it possible to calculate the anaerobic energy expenditure. This could make it possible to estimate the metabolic intensity of training sessions and matches using video analysis.

  10. Role of Gts1p in regulation of energy-metabolism oscillation in continuous cultures of the yeast Saccharomyces cerevisiae.

    PubMed

    Xu, Zhaojun; Tsurugi, Kunio

    2007-03-01

    Energy-metabolism oscillation (EMO) in an aerobic chemostat culture of yeast is basically regulated by a feedback loop of redox reactions in energy metabolism and modulated by metabolism of storage carbohydrates. In this study, we investigated the role of Gts1p in the stabilization of EMO, using the GTS1-deleted transformant gts1Delta. We found that fluctuations in the redox state of the NAD co-factor and levels of redox-regulated metabolites in glycolysis, especially of ethanol, are markedly reduced in amplitude during EMO of gts1Delta, while respiration indicated by the oxygen uptake rate (OUR) and energy charge is not so affected throughout EMO in gts1Delta. Further, the transitions of the levels of OUR, NAD(+) : NADH ratio and intracellular pH between the two phases were apparently retarded compared with those in the wild-type, suggesting attenuation of EMO in gts1Delta. Furthermore, the mRNA levels of genes encoding enzymes for the synthesis of trehalose and glycogen are fairly reduced in gts1Delta, consistent with the decreased synthesis of storage carbohydrates. In addition, the level of inorganic phosphate, which is required for the reduction of NAD(+) and mainly supplied from trehalose synthesis, was decreased in the early respiro-fermentative phase in gts1Delta. Thus, we suggested that the deletion of GTS1 as a transcriptional co-activator for these genes inhibited the metabolism of storage carbohydrates, which causes attenuation of the feedback loop of dehydrogenase reactions in glycolysis with the restricted fluctuation of ethanol as a main synchronizing agent for EMO in a cell population.

  11. Resting and exercise energy metabolism in weight-reduced adults with severe obesity.

    PubMed

    Hames, Kazanna C; Coen, Paul M; King, Wendy C; Anthony, Steven J; Stefanovic-Racic, Maja; Toledo, Frederico G S; Lowery, Jolene B; Helbling, Nicole L; Dubé, John J; DeLany, James P; Jakicic, John M; Goodpaster, Bret H

    2016-06-01

    To determine effects of physical activity (PA) with diet-induced weight loss on energy metabolism in adults with severe obesity. Adults with severe obesity (n = 11) were studied across 6 months of intervention, then compared with controls with less severe obesity (n = 7) or normal weight (n = 9). Indirect calorimetry measured energy metabolism during exercise and rest. Markers of muscle oxidation were determined by immunohistochemistry. Data were presented as medians. The intervention induced 7% weight loss (P = 0.001) and increased vigorous PA by 24 min/wk (P = 0.02). During exercise, energy expenditure decreased, efficiency increased (P ≤ 0.03), and fatty acid oxidation (FAO) did not change. Succinate dehydrogenase increased (P = 0.001), but fiber type remained the same. Post-intervention subjects' resting metabolism remained similar to controls. Efficiency was lower in post-intervention subjects compared with normal-weight controls exercising at 25 W (P ≤ 0.002) and compared with all controls exercising at 60% VO2peak (P ≤ 0.019). Resting and exercise FAO of post-intervention subjects remained similar to adults with less severe obesity. Succinate dehydrogenase and fiber type were similar across all body weight statuses. While metabolic adaptations to PA during weight loss occur in adults with severe obesity, FAO does not change. Resulting FAO during rest and exercise remains similar to adults with less severe obesity. © 2016 The Obesity Society.

  12. [Specific growth rate and the rate of energy metabolism in the ontogenesis of axolotl, Ambystoma mexicanum (Amphibia: Ambystomatidae)].

    PubMed

    Vladimirova, I G; Kleĭmenov, S Iu; Alekseeva, T A; Radzinskaia, L I

    2003-01-01

    Concordant changes in the rate of energy metabolism and specific growth rate of axolotls have been revealed. Several periods of ontogeny are distinguished, which differ in the ratio of energy metabolism to body weight and, therefore, are described by different allometric equations. It is suggested that the specific growth rate of an animal determines the type of dependence of energy metabolism on body weight.

  13. Computational Flux Balance Analysis Predicts that Stimulation of Energy Metabolism in Astrocytes and their Metabolic Interactions with Neurons Depend on Uptake of K+ Rather than Glutamate.

    PubMed

    DiNuzzo, Mauro; Giove, Federico; Maraviglia, Bruno; Mangia, Silvia

    2017-01-01

    Brain activity involves essential functional and metabolic interactions between neurons and astrocytes. The importance of astrocytic functions to neuronal signaling is supported by many experiments reporting high rates of energy consumption and oxidative metabolism in these glial cells. In the brain, almost all energy is consumed by the Na + /K + ATPase, which hydrolyzes 1 ATP to move 3 Na + outside and 2 K + inside the cells. Astrocytes are commonly thought to be primarily involved in transmitter glutamate cycling, a mechanism that however only accounts for few % of brain energy utilization. In order to examine the participation of astrocytic energy metabolism in brain ion homeostasis, here we attempted to devise a simple stoichiometric relation linking glutamatergic neurotransmission to Na + and K + ionic currents. To this end, we took into account ion pumps and voltage/ligand-gated channels using the stoichiometry derived from available energy budget for neocortical signaling and incorporated this stoichiometric relation into a computational metabolic model of neuron-astrocyte interactions. We aimed at reproducing the experimental observations about rates of metabolic pathways obtained by 13 C-NMR spectroscopy in rodent brain. When simulated data matched experiments as well as biophysical calculations, the stoichiometry for voltage/ligand-gated Na + and K + fluxes generated by neuronal activity was close to a 1:1 relationship, and specifically 63/58 Na + /K + ions per glutamate released. We found that astrocytes are stimulated by the extracellular K + exiting neurons in excess of the 3/2 Na + /K + ratio underlying Na + /K + ATPase-catalyzed reaction. Analysis of correlations between neuronal and astrocytic processes indicated that astrocytic K + uptake, but not astrocytic Na + -coupled glutamate uptake, is instrumental for the establishment of neuron-astrocytic metabolic partnership. Our results emphasize the importance of K + in stimulating the activation of

  14. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism

    PubMed Central

    den Besten, Gijs; van Eunen, Karen; Groen, Albert K.; Venema, Koen; Reijngoud, Dirk-Jan; Bakker, Barbara M.

    2013-01-01

    Short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibers by the anaerobic intestinal microbiota, have been shown to exert multiple beneficial effects on mammalian energy metabolism. The mechanisms underlying these effects are the subject of intensive research and encompass the complex interplay between diet, gut microbiota, and host energy metabolism. This review summarizes the role of SCFAs in host energy metabolism, starting from the production by the gut microbiota to the uptake by the host and ending with the effects on host metabolism. There are interesting leads on the underlying molecular mechanisms, but there are also many apparently contradictory results. A coherent understanding of the multilevel network in which SCFAs exert their effects is hampered by the lack of quantitative data on actual fluxes of SCFAs and metabolic processes regulated by SCFAs. In this review we address questions that, when answered, will bring us a great step forward in elucidating the role of SCFAs in mammalian energy metabolism. PMID:23821742

  15. Energy Metabolism during Anaerobic Methane Oxidation in ANME Archaea

    PubMed Central

    McGlynn, Shawn E.

    2017-01-01

    Anaerobic methane oxidation in archaea is often presented to operate via a pathway of “reverse methanogenesis”. However, if the cumulative reactions of a methanogen are run in reverse there is no apparent way to conserve energy. Recent findings suggest that chemiosmotic coupling enzymes known from their use in methylotrophic and acetoclastic methanogens—in addition to unique terminal reductases—biochemically facilitate energy conservation during complete CH4 oxidation to CO2. The apparent enzyme modularity of these organisms highlights how microbes can arrange their energy metabolisms to accommodate diverse chemical potentials in various ecological niches, even in the extreme case of utilizing “reverse” thermodynamic potentials. PMID:28321009

  16. RAS signalling in energy metabolism and rare human diseases.

    PubMed

    Dard, L; Bellance, N; Lacombe, D; Rossignol, R

    2018-05-08

    The RAS pathway is a highly conserved cascade of protein-protein interactions and phosphorylation that is at the heart of signalling networks that govern proliferation, differentiation and cell survival. Recent findings indicate that the RAS pathway plays a role in the regulation of energy metabolism via the control of mitochondrial form and function but little is known on the participation of this effect in RAS-related rare human genetic diseases. Germline mutations that hyperactivate the RAS pathway have been discovered and linked to human developmental disorders that are known as RASopathies. Individuals with RASopathies, which are estimated to affect approximately 1/1000 human birth, share many overlapping characteristics, including cardiac malformations, short stature, neurocognitive impairment, craniofacial dysmorphy, cutaneous, musculoskeletal, and ocular abnormalities, hypotonia and a predisposition to developing cancer. Since the identification of the first RASopathy, type 1 neurofibromatosis (NF1), which is caused by the inactivation of neurofibromin 1, several other syndromes have been associated with mutations in the core components of the RAS-MAPK pathway. These syndromes include Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), which was formerly called LEOPARD syndrome, Costello syndrome (CS), cardio-facio-cutaneous syndrome (CFC), Legius syndrome (LS) and capillary malformation-arteriovenous malformation syndrome (CM-AVM). Here, we review current knowledge about the bioenergetics of the RASopathies and discuss the molecular control of energy homeostasis and mitochondrial physiology by the RAS pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Energy Metabolism Rewiring Precedes UVB-Induced Primary Skin Tumor Formation.

    PubMed

    Hosseini, Mohsen; Dousset, Léa; Mahfouf, Walid; Serrano-Sanchez, Martin; Redonnet-Vernhet, Isabelle; Mesli, Samir; Kasraian, Zeinab; Obre, Emilie; Bonneu, Marc; Claverol, Stephane; Vlaski, Marija; Ivanovic, Zoran; Rachidi, Walid; Douki, Thierry; Taieb, Alain; Bouzier-Sore, Anne-Karine; Rossignol, Rodrigue; Rezvani, Hamid Reza

    2018-06-19

    Although growing evidence indicates that bioenergetic metabolism plays an important role in the progression of tumorigenesis, little information is available on the contribution of reprogramming of energy metabolism in cancer initiation. By applying a quantitative proteomic approach and targeted metabolomics, we find that specific metabolic modifications precede primary skin tumor formation. Using a multistage model of ultraviolet B (UVB) radiation-induced skin cancer, we show that glycolysis, tricarboxylic acid (TCA) cycle, and fatty acid β-oxidation are decreased at a very early stage of photocarcinogenesis, while the distal part of the electron transport chain (ETC) is upregulated. Reductive glutamine metabolism and the activity of dihydroorotate dehydrogenase (DHODH) are both necessary for maintaining high ETC. Mice with decreased DHODH activity or impaired ETC failed to develop pre-malignant and malignant lesions. DHODH activity represents a major link between DNA repair efficiency and bioenergetic patterning during skin carcinogenesis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Macrophage-Mediated Clofazimine Sequestration is Accompanied by a Shift in Host Energy Metabolism

    PubMed Central

    Trexel, Julie; Yoon, Gi S.; Keswani, Rahul K.; McHugh, Cora; Yeomans, Larisa; Vitvitsky, Victor; Banerjee, Ruma; Sud, Sudha; Sun, Yihan; Rosania, Gus R.; Stringer, Kathleen A.

    2017-01-01

    Prolonged (8 weeks) oral administration of clofazimine results in a profound pharmacodynamic response- bioaccumulation in macrophages (including Kupffer cells) as intracellular crystal-like drug inclusions (CLDIs) with an associated increase in interleukin-1 receptor antagonist production. Notably, CLDI formation in Kupffer cells concomitantly occurs with the formation of macrophage-centric granulomas. Accordingly, we sought to understand the impact of these events on host metabolism using 1H-nuclear magnetic resonance metabolomics. Mice received a clofazimine - or vehicle-enriched (sham) diet for at least 8 weeks. At two weeks, the antimicrobial activity of clofazimine was evident by changes in urine metabolites. From 2 to 8 weeks, there was a striking change in metabolite levels indicative of a reorientation of host energy metabolism paralleling the onset of CLDI and granuloma formation. This was evidenced by a progressive reduction in urine levels of metabolites involved in one-carbon metabolism with corresponding increases in whole blood, and changes in metabolites associated with lipid, nucleotide and amino acid metabolism, and glycolysis. Although clofazimine-fed mice ate more, they gained less weight than control mice. Together, these results indicate that macrophage sequestration of clofazimine as CLDIs and granuloma formation is accompanied by a profound metabolic disruption in energy homeostasis and one-carbon metabolism. PMID:28007559

  19. The AMPK β2 subunit is required for energy homeostasis during metabolic stress.

    PubMed

    Dasgupta, Biplab; Ju, Jeong Sun; Sasaki, Yo; Liu, Xiaona; Jung, Su-Ryun; Higashida, Kazuhiko; Lindquist, Diana; Milbrandt, Jeffrey

    2012-07-01

    AMP activated protein kinase (AMPK) plays a key role in the regulatory network responsible for maintaining systemic energy homeostasis during exercise or nutrient deprivation. To understand the function of the regulatory β2 subunit of AMPK in systemic energy metabolism, we characterized β2 subunit-deficient mice. Using these mutant mice, we demonstrated that the β2 subunit plays an important role in regulating glucose, glycogen, and lipid metabolism during metabolic stress. The β2 mutant animals failed to maintain euglycemia and muscle ATP levels during fasting. In addition, β2-deficient animals showed classic symptoms of metabolic syndrome, including hyperglycemia, glucose intolerance, and insulin resistance when maintained on a high-fat diet (HFD), and were unable to maintain muscle ATP levels during exercise. Cell surface-associated glucose transporter levels were reduced in skeletal muscle from β2 mutant animals on an HFD. In addition, they displayed poor exercise performance and impaired muscle glycogen metabolism. These mutant mice had decreased activation of AMPK and deficits in PGC1α-mediated transcription in skeletal muscle. Our results highlight specific roles of AMPK complexes containing the β2 subunit and suggest the potential utility of AMPK isoform-specific pharmacological modulators for treatment of metabolic, cardiac, and neurological disorders.

  20. Trichoderma secondary metabolites that affect plant metabolism.

    PubMed

    Vinale, Francesco; Sivasithamparam, Krishnapillai; Ghisalberti, Emilio L; Ruocco, Michelina; Wood, Sheridan; Lorito, Matteo

    2012-11-01

    Recently, there have been many exciting new developments relating to the use of Trichoderma spp. as agents for biocontrol of pathogens and as plant growth promoters. Several mechanisms have been proposed to explain the positive effects of these microorganisms on the plant host. One factor that contributes to their beneficial biological activities is related to the wide variety of metabolites that they produce. These metabolites have been found not only to directly inhibit the growth and pathogenic activities of the parasites, but also to increase disease resistance by triggering the system of defence in the plant host. In addition, these metabolites are also capable of enhancing plant growth, which enables the plant to counteract the disease with compensatory vegetative growth by the augmented production of root and shoot systems. This review takes into account the Trichoderma secondary metabolites that affect plant metabolism and that may play an important role in the complex interactions of this biocontrol agent with the plant and pathogens.

  1. [Effects of aconite root on energy metabolism and expression of related genes in rats].

    PubMed

    Yu, Huayun; Ji, Xuming; Wu, Zhichun; Wang, Shijun

    2011-09-01

    To study the influence of aconite root, a Chinese medicinal herb with hot property, on energy metabolism and gene expression spectrum, and to analyze the possible mechanism of it effect. Thirty two SPF Wistar rats were randomly divided into aconite root group and control group. Decoction of aconite root and NS were intragastrically administrated with the concentration of 10 mL x kg(-1) respectively once a day for 20 days. Temperature, energy intake (EI), digestive energy (DE) and metabolic energy (ME) were measured. The activity of ATPase and succinate dehydrogenase (SDH) in liver was detected by colorimetry. The gene expression of liver was detected with Illumina's rat ref-12 gene array. The differential expression genes were selected, annotated and classified based on gene ontology (GO). Real-time quantitative reverse-transcriptase PCR (Q-RT-PCR) was used to test the accuracy of the array results. Compared with the control group, the toe temperature (TT) on the 10th and 20th day after the administration,the EI/BM( body mass), DE/BM, ME/BM and the activity of Na+ - K+ - ATPase, Ca2+ - Mg2+ - ATPase and SDH of liver in the aconite root group increased significantly (P<0.05). There were 592 differential expression genes in aconite root group compared with the control group. Based on Go analysis, the most significant genes was related to metabolic process (lgP = - 15.5897). Aconite root could improve the energy metabolism in rats, by influencing the metabolic process of sugar, lipid and amino acid, which may be the main molecular mechanism of warming yang and dispelling cold for the treatment of the cold syndrome according to Chinese medicine theory.

  2. Alterations of energy metabolism and glutathione levels of HL-60 cells induced by methacrylates present in composite resins.

    PubMed

    Nocca, G; De Palma, F; Minucci, A; De Sole, P; Martorana, G E; Callà, C; Morlacchi, C; Gozzo, M L; Gambarini, G; Chimenti, C; Giardina, B; Lupi, A

    2007-03-01

    Methacrylic compounds such as 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA) and bisphenol A glycerolate (1 glycerol/phenol) dimethacrylate (Bis-GMA) are largely present in auto- or photopolymerizable composite resins. Since the polymerization reaction is never complete, these molecules are released into the oral cavity tissues and biological fluids where they could cause local adverse effects. The aim of this work was to verify the hypothesis that the biological effects of HEMA, TEGDMA and Bis-GMA - at a non-cytotoxic concentration - depend on the interaction with mitochondria and exert consequent alterations of energy metabolism, GSH levels and the related pathways in human promyelocytic cell line (HL-60). The biological effects of methacrylic monomers were determined by analyzing the following parameters: GSH concentration, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR) activity, oxygen and glucose consumption and lactate production along with cell differentiation and proliferation. All monomers induced both cellular differentiation and decrease in oxygen consumption. Cells treated with TEGDMA and Bis-GMA showed a significant enhancement of glucose consumption and lactate production. TEGDMA and HEMA induced GSH depletion stimulating G6PDH and GR activity. All the monomers under study affect the metabolism of HL-60 cells and show differentiating activity. Since alterations in cellular metabolism occurred at compound concentrations well below cytotoxic levels, the changes in energy metabolism and glutathione redox balance could be considered as potential mechanisms for inducing clinical and sub-clinical adverse effects and thus providing useful parameters when testing biocompatibility of dental materials.

  3. Circulating vaspin and visfatin are not affected by acute or chronic energy deficiency or leptin administration in humans.

    PubMed

    Kang, Eun Seok; Magkos, Faidon; Sienkiewicz, Elizabeth; Mantzoros, Christos S

    2011-06-01

    Animal and in vitro studies indicate that leptin alleviates starvation-induced reduction in circulating vaspin and stimulates the production of visfatin. We thus examined whether vaspin and visfatin are affected by short- and long-term energy deprivation and leptin administration in human subjects in vivo. We measured circulating levels of vaspin and visfatin i) before and after 72 h of starvation (leading to severe hypoleptinemia) with or without leptin administration in replacement doses in 13 normal-weight subjects, ii) before and after 72 h of starvation with leptin administration in pharmacological doses in 13 lean and obese subjects, iii) during chronic energy deficiency in eight women with hypothalamic amenorrhea on leptin replacement for 3 months, and iv) during chronic energy deficiency in 18 women with hypothalamic amenorrhea on leptin replacement or placebo for 3 months. Acute starvation decreased serum leptin to 21% of baseline values, (P=0.002) but had no significant effect on vaspin and visfatin concentrations (P>0.05). Nor did normalization of leptin levels affect the concentrations of these two adipokines (P>0.9). Leptin replacement in women with hypothalamic amenorrhea did not significantly alter vaspin and visfatin concentrations, whether relative to baseline or placebo administration (P>0.25). Pharmacological doses of leptin did not affect circulating vaspin and visfatin concentrations (P>0.9). Circulating vaspin and visfatin are not affected by acute or chronic energy deficiency leading to hypoleptinemia and are not regulated by leptin in human subjects, indicating that these adipocyte-secreted hormonal regulators of metabolism are independently regulated in humans.

  4. Day–Night Changes of Energy-rich Compounds in Crassulacean Acid Metabolism (CAM) Species Utilizing Hexose and Starch

    PubMed Central

    CHEN, LI-SONG; NOSE, AKIHIRO

    2004-01-01

    • Background and Aims Plants with crassulacean acid metabolism (CAM) can be divided into two groups according to the major carbohydrates used for malic acid synthesis, either polysaccharide (starch) or monosaccharide (hexose). This is related to the mechanism and affects energy metabolism in the two groups. In Kalanchoë pinnata and K. daigremontiana, which utilize starch, ATP-dependent phosphofructokinase (tonoplast inorganic pyrophosphatase) activity is greater than inorganic pyrophosphate-dependent phosphofructokinase (tonoplast adenosine triphosphatase) activity, but the reverse is the case in pineapple (Ananas comosus) utilizing hexose. To test the hypothesis that the energy metabolism of the two groups differs, day-night changes in the contents of ATP, ADP, AMP, inorganic phosphate (Pi), phosphoenolpyruvate (PEP) and inorganic pyrophosphate (PPi) in K. pinnata and K. daigremontiana leaves and in pineapple chlorenchyma were analysed. • Methods The contents of energy-rich compounds were measured spectrophotometrically in extracts of tissue sampled in the light and dark, using potted plants, kept for 15 d before the experiments in a growth chamber. • Key Results In the three species, ATP content and adenylate energy charge (AEC) increased in the dark and decreased in the light, in contrast to ADP and AMP. Changes in ATP and AEC were greater in Kalanchoë leaves than in pineapple chlorenchyma. PPi content in the three species increased in the dark, but on illumination it decreased rapidly and substantially, remaining little changed through the rest of the light period. Pi content of Kalanchoë leaves did not change between dark and light, whereas Pi in pineapple chlorenchyma increased in the dark and decreased in the light, and the changes were far greater than in Kalanchoë leaves. Light-dark changes in PEP content in the three species were similar. • Conclusions These results corroborate our hypothesis that day–night changes in the contents of energy

  5. Extracellular Citrate Affects Critical Elements of Cancer Cell Metabolism and Supports Cancer Development In Vivo.

    PubMed

    Mycielska, Maria E; Dettmer, Katja; Rümmele, Petra; Schmidt, Katharina; Prehn, Cornelia; Milenkovic, Vladimir M; Jagla, Wolfgang; Madej, Gregor M; Lantow, Margareta; Schladt, Moritz; Cecil, Alexander; Koehl, Gudrun E; Eggenhofer, Elke; Wachsmuth, Christian J; Ganapathy, Vadivel; Schlitt, Hans J; Kunzelmann, Karl; Ziegler, Christine; Wetzel, Christian H; Gaumann, Andreas; Lang, Sven A; Adamski, Jerzy; Oefner, Peter J; Geissler, Edward K

    2018-05-15

    Glycolysis and fatty acid synthesis are highly active in cancer cells through cytosolic citrate metabolism, with intracellular citrate primarily derived from either glucose or glutamine via the tricarboxylic acid cycle. We show here that extracellular citrate is supplied to cancer cells through a plasma membrane-specific variant of the mitochondrial citrate transporter (pmCiC). Metabolomic analysis revealed that citrate uptake broadly affected cancer cell metabolism through citrate-dependent metabolic pathways. Treatment with gluconate specifically blocked pmCiC and decreased tumor growth in murine xenografts of human pancreatic cancer. This treatment altered metabolism within tumors, including fatty acid metabolism. High expression of pmCiC was associated with invasion and advanced tumor stage across many human cancers. These findings support the exploration of extracellular citrate transport as a novel potential target for cancer therapy. Significance: Uptake of extracellular citrate through pmCiC can be blocked with gluconate to reduce tumor growth and to alter metabolic characteristics of tumor tissue. Cancer Res; 78(10); 2513-23. ©2018 AACR . ©2018 American Association for Cancer Research.

  6. Astrocyte glycogen and brain energy metabolism.

    PubMed

    Brown, Angus M; Ransom, Bruce R

    2007-09-01

    The brain contains glycogen but at low concentration compared with liver and muscle. In the adult brain, glycogen is found predominantly in astrocytes. Astrocyte glycogen content is modulated by a number of factors including some neurotransmitters and ambient glucose concentration. Compelling evidence indicates that astrocyte glycogen breaks down during hypoglycemia to lactate that is transferred to adjacent neurons or axons where it is used aerobically as fuel. In the case of CNS white matter, this source of energy can extend axon function for 20 min or longer. Likewise, during periods of intense neural activity when energy demand exceeds glucose supply, astrocyte glycogen is degraded to lactate, a portion of which is transferred to axons for fuel. Astrocyte glycogen, therefore, offers some protection against hypoglycemic neural injury and ensures that neurons and axons can maintain their function during very intense periods of activation. These emerging principles about the roles of astrocyte glycogen contradict the long held belief that this metabolic pool has little or no functional significance.

  7. 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.

  8. Predicting metabolic adaptation, body weight change, and energy intake in humans

    PubMed Central

    2010-01-01

    Complex interactions between carbohydrate, fat, and protein metabolism underlie the body's remarkable ability to adapt to a variety of diets. But any imbalances between the intake and utilization rates of these macronutrients will result in changes in body weight and composition. Here, I present the first computational model that simulates how diet perturbations result in adaptations of fuel selection and energy expenditure that predict body weight and composition changes in both obese and nonobese men and women. No model parameters were adjusted to fit these data other than the initial conditions for each subject group (e.g., initial body weight and body fat mass). The model provides the first realistic simulations of how diet perturbations result in adaptations of whole body energy expenditure, fuel selection, and various metabolic fluxes that ultimately give rise to body weight change. The validated model was used to estimate free-living energy intake during a long-term weight loss intervention, a variable that has never previously been measured accurately. PMID:19934407

  9. Effects of diabetes on brain metabolism--is brain glycogen a significant player?

    PubMed

    Sickmann, Helle M; Waagepetersen, Helle S

    2015-02-01

    Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose to the brain may be affected and have important impacts on brain metabolism and neurotransmission. This also implies that brain glycogen may serve an essential role in the diabetic state to sustain appropriate brain function. There are two main types of diabetes; type 1 and type 2 diabetes and both types may be associated with brain impairments e.g. cognitive decline and dementia. It is however, not clear how these impairments on brain function are linked to alterations in brain energy and neurotransmitter metabolism. In this review, we will illuminate how rodent diabetes models have contributed to a better understanding of how brain energy and neurotransmitter metabolism is affected in diabetes. There will be a particular focus on the role of brain glycogen to support glycolytic and TCA cycle activity as well as glutamate-glutamine cycle in type 1 and type 2 diabetes.

  10. Regulation of Hepatic Energy Metabolism and Gluconeogenesis by BAD

    PubMed Central

    Giménez-Cassina, Alfredo; Garcia-Haro, Luisa; Choi, Cheol Soo; Osundiji, Mayowa A.; Lane, Elizabeth; Huang, Hu; Yildirim, Muhammed A.; Szlyk, Benjamin; Fisher, Jill K.; Polak, Klaudia; Patton, Elaura; Wiwczar, Jessica; Godes, Marina; Lee, Dae Ho; Robertson, Kirsten; Kim, Sheene; Kulkarni, Ameya; Distefano, Alberto; Samuel, Varman; Cline, Gary; Kim, Young-Bum; Shulman, Gerald I.; Danial, Nika N.

    2014-01-01

    SUMMARY The homeostatic balance of hepatic glucose utilization, storage and production is exquisitely controlled by hormonal signals and hepatic carbon metabolism during fed and fasted states. How the liver senses extracellular glucose to cue glucose utilization versus production is not fully understood. Here, we show that the physiologic balance of hepatic glycolysis and gluconeogenesis is regulated by BAD, a dual function protein with roles in apoptosis and metabolism. BAD deficiency reprograms hepatic substrate and energy metabolism towards diminished glycolysis, excess fatty acid oxidation and exaggerated glucose production that escapes suppression by insulin. Genetic and biochemical evidence suggest that BAD’s suppression of gluconeogenesis is actuated by phosphorylation of its BH3 domain and subsequent activation of glucokinase. The physiologic relevance of these findings is evident from the ability of a BAD phospho-mimic variant to counteract unrestrained gluconeogenesis and improve glycemia in leptin resistant and high-fat diet models of diabetes and insulin resistance. PMID:24506868

  11. Military training elicits marked increases in plasma metabolomic signatures of energy metabolism, lipolysis, fatty acid oxidation, and ketogenesis.

    PubMed

    Karl, J Philip; Margolis, Lee M; Murphy, Nancy E; Carrigan, Christopher T; Castellani, John W; Madslien, Elisabeth H; Teien, Hilde-Kristin; Martini, Svein; Montain, Scott J; Pasiakos, Stefan M

    2017-09-01

    Military training studies provide unique insight into metabolic responses to extreme physiologic stress induced by multiple stressor environments, and the impacts of nutrition in mediating these responses. Advances in metabolomics have provided new approaches for extending current understanding of factors modulating dynamic metabolic responses in these environments. In this study, whole-body metabolic responses to strenuous military training were explored in relation to energy balance and macronutrient intake by performing nontargeted global metabolite profiling on plasma collected from 25 male soldiers before and after completing a 4-day, 51-km cross-country ski march that produced high total daily energy expenditures (25.4 MJ/day [SD 2.3]) and severe energy deficits (13.6 MJ/day [SD 2.5]). Of 737 identified metabolites, 478 changed during the training. Increases in 88% of the free fatty acids and 91% of the acylcarnitines, and decreases in 88% of the mono- and diacylglycerols detected within lipid metabolism pathways were observed. Smaller increases in 75% of the tricarboxylic acid cycle intermediates, and 50% of the branched-chain amino acid metabolites detected were also observed. Changes in multiple metabolites related to lipid metabolism were correlated with body mass loss and energy balance, but not with energy and macronutrient intakes or energy expenditure. These findings are consistent with an increase in energy metabolism, lipolysis, fatty acid oxidation, ketogenesis, and branched-chain amino acid catabolism during strenuous military training. The magnitude of the energy deficit induced by undereating relative to high energy expenditure, rather than macronutrient intake, appeared to drive these changes, particularly within lipid metabolism pathways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  12. Short- and medium-chain fatty acids in energy metabolism: the cellular perspective.

    PubMed

    Schönfeld, Peter; Wojtczak, Lech

    2016-06-01

    Short- and medium-chain fatty acids (SCFAs and MCFAs), independently of their cellular signaling functions, are important substrates of the energy metabolism and anabolic processes in mammals. SCFAs are mostly generated by colonic bacteria and are predominantly metabolized by enterocytes and liver, whereas MCFAs arise mostly from dietary triglycerides, among them milk and dairy products. A common feature of SCFAs and MCFAs is their carnitine-independent uptake and intramitochondrial activation to acyl-CoA thioesters. Contrary to long-chain fatty acids, the cellular metabolism of SCFAs and MCFAs depends to a lesser extent on fatty acid-binding proteins. SCFAs and MCFAs modulate tissue metabolism of carbohydrates and lipids, as manifested by a mostly inhibitory effect on glycolysis and stimulation of lipogenesis or gluconeogenesis. SCFAs and MCFAs exert no or only weak protonophoric and lytic activities in mitochondria and do not significantly impair the electron transport in the respiratory chain. SCFAs and MCFAs modulate mitochondrial energy production by two mechanisms: they provide reducing equivalents to the respiratory chain and partly decrease efficacy of oxidative ATP synthesis. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  13. Changes in energy metabolism accompanying pitting in blueberries stored at low temperature.

    PubMed

    Zhou, Qian; Zhang, Chunlei; Cheng, Shunchang; Wei, Baodong; Liu, Xiuying; Ji, Shujuan

    2014-12-01

    Low-temperature storage and transport of blueberries is widely practiced in commercial blueberry production. In this research, the storage life of blueberries was extended at low temperature, but fruit stored for 30 d at 0°C pitted after 2d at room-temperature. Fruit cellular structure and physiological parameters accompanying pitting in blueberries were changed. The objective of this research was to characterise properties of energy metabolism accompanying pitting in blueberries during storage, including adenosine phosphates and mitochondrial enzymes involved in stress responses. Physiological and metabolic disorders, changes in cell ultrastructure, energy content and ATPase enzyme activity were observed in pitting blueberries. Energy shortages and increased activity of phenylalanine ammonia lyase (PAL) and lipoxygenase (LOX) were observed in fruit kept at shelf life. The results suggested that sufficient available energy status and a stable enzymatic system in blueberries collectively contribute to improve chilling tolerance, thereby alleviating pitting and maintaining quality of blueberry fruit in long-term cold storage. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Demyelination in Multiple Sclerosis: Reprogramming Energy Metabolism and Potential PPARγ Agonist Treatment Approaches

    PubMed Central

    Lecarpentier, Yves; Guillevin, Rémy; Vallée, Jean-Noël

    2018-01-01

    Demyelination in multiple sclerosis (MS) cells is the site of several energy metabolic abnormalities driven by dysregulation between the opposed interplay of peroxisome proliferator-activated receptor γ (PPARγ) and WNT/β-catenin pathways. We focus our review on the opposing interactions observed in demyelinating processes in MS between the canonical WNT/β-catenin pathway and PPARγ and their reprogramming energy metabolism implications. Demyelination in MS is associated with chronic inflammation, which is itself associated with the release of cytokines by CD4+ Th17 cells, and downregulation of PPARγ expression leading to the upregulation of the WNT/β-catenin pathway. Upregulation of WNT/β-catenin signaling induces activation of glycolytic enzymes that modify their energy metabolic behavior. Then, in MS cells, a large portion of cytosolic pyruvate is converted into lactate. This phenomenon is called the Warburg effect, despite the availability of oxygen. The Warburg effect is the shift of an energy transfer production from mitochondrial oxidative phosphorylation to aerobic glycolysis. Lactate production is correlated with increased WNT/β-catenin signaling and demyelinating processes by inducing dysfunction of CD4+ T cells leading to axonal and neuronal damage. In MS, downregulation of PPARγ decreases insulin sensitivity and increases neuroinflammation. PPARγ agonists inhibit Th17 differentiation in CD4+ T cells and then diminish release of cytokines. In MS, abnormalities in the regulation of circadian rhythms stimulate the WNT pathway to initiate the demyelination process. Moreover, PPARγ contributes to the regulation of some key circadian genes. Thus, PPARγ agonists interfere with reprogramming energy metabolism by directly inhibiting the WNT/β-catenin pathway and circadian rhythms and could appear as promising treatments in MS due to these interactions. PMID:29659554

  15. Within-Day Energy Deficiency and Metabolic Perturbation in Male Endurance Athletes.

    PubMed

    Torstveit, Monica Klungland; Fahrenholtz, Ida; Stenqvist, Thomas B; Sylta, Øystein; Melin, Anna

    2018-06-26

    Endurance athletes are at increased risk of relative energy deficiency associated with metabolic perturbation and impaired health. We aimed to estimate and compare within-day energy balance in male athletes with suppressed and normal resting metabolic rate (RMR) and explore whether within-day energy deficiency is associated with endocrine markers of energy deficiency. A total of 31 male cyclists, triathletes, and long-distance runners recruited from regional competitive sports clubs were included. The protocol comprised measurements of RMR by ventilated hood and energy intake and energy expenditure to predict RMR ratio (measured RMR/predicted RMR), energy availability, 24-hr energy balance and within-day energy balance in 1-hr intervals, assessment of body composition by dual-energy X-ray absorptiometry, and blood plasma analysis. Subjects were categorized as having suppressed (RMR ratio  < 0.90, n = 20) or normal (RMR ratio  > 0.90, n = 11) RMR. Despite there being no observed differences in 24-hr energy balance or energy availability between the groups, subjects with suppressed RMR spent more time in an energy deficit exceeding 400 kcal (20.9 [18.8-21.8] hr vs. 10.8 [2.5-16.4], p = .023) and had larger single-hour energy deficits compared with subjects with normal RMR (3,265 ± 1,963 kcal vs. -1,340 ± 2,439, p = .023). Larger single-hour energy deficits were associated with higher cortisol levels (r = -.499, p = .004) and a lower testosterone:cortisol ratio (r = .431, p = .015), but no associations with triiodothyronine or fasting blood glucose were observed. In conclusion, within-day energy deficiency was associated with suppressed RMR and catabolic markers in male endurance athletes.

  16. Effect of protein overfeeding on energy expenditure measured in a metabolic chamber.

    PubMed

    Bray, George A; Redman, Leanne M; de Jonge, Lilian; Covington, Jeffrey; Rood, Jennifer; Brock, Courtney; Mancuso, Susan; Martin, Corby K; Smith, Steven R

    2015-03-01

    Energy expenditure (EE) increases with overfeeding, but it is unclear how rapidly this is related to changes in body composition, increased body weight, or diet. The objective was to quantify the effects of excess energy from fat or protein on energy expenditure of men and women living in a metabolic chamber. We conducted a randomized controlled trial in 25 participants who ate ∼40% excess energy for 56 d from 5%, 15%, or 25% protein diets. Twenty-four-hour EE (24EE) and sleeping EE (SleepEE) were measured on days 1, 14, and 56 of overfeeding and on day 57 while consuming the baseline diet (usually day 57). Metabolic and molecular markers of muscle metabolism were measured in skeletal muscle biopsy specimens. In the low-protein diet group whose excess energy was fat, the 24EE and SleepEE did not increase during the first day of overfeeding. When extra energy contained protein, both 24EE and SleepEE increased in relation to protein intake (r = 0.50, P = 0.02). The 24EE over 8 wk in all 3 groups was correlated with protein intake (r = 0.60, P = 0.004) but not energy intake (r = 0.16; P = 0.70). SleepEE was unchanged by overfeeding in the low-protein diet group, and baseline surface area predicted increased 24EE in this group. Protein and fat oxidation were reciprocally related during overfeeding. Observed 24EE was higher than predicted on days 1 (P ≤ 0.05), 14 (P = 0.0001), and 56 (P = 0.0007). There was no relation between change in fat mass and change in EE. Excess energy, as fat, does not acutely increase 24EE, which rises slowly as body weight increases. Excess energy as protein acutely stimulates 24EE and SleepEE. The strongest relation with change in 24EE was the change in energy expenditure in tissue other than muscle or fat-free mass. © 2015 American Society for Nutrition.

  17. Effects of a block in cysteine catabolism on energy balance and fat metabolism in mice

    PubMed Central

    Niewiadomski, Julie; Zhou, James Q.; Roman, Heather B.; Liu, Xiaojing; Hirschberger, Lawrence L.; Locasale, Jason W.; Stipanuk, Martha H.

    2016-01-01

    To gain further insights into the effect of elevated cysteine levels on energy metabolism and the possible mechanisms by which cysteine may have these effects, we conducted studies in cysteine dioxygenase (Cdo1)–null mice. Cysteine dioxygenase (CDO) catalyzes the first step of the major pathway for cysteine catabolism. When CDO is absent, tissue and plasma cysteine levels are elevated, resulting in enhanced flux of cysteine through desulfhydration reactions. When Cdo1-null mice were fed a high-fat diet, they gained more weight than their wild-type controls, regardless of whether the diet was supplemented with taurine. Cdo1-null mice had markedly lower leptin levels, higher feed intakes, and markedly higher abundance of hepatic stearoyl-CoA desaturase 1 (SCD1) compared to wild-type control mice, and these differences were not affected by the fat or taurine content of the diet. Thus, reported associations of elevated cysteine levels with greater weight gain and with elevated hepatic Scd1 expression holds in the Cdo1-null mouse model. Hepatic accumulation of acylcarnitines suggested impaired mitochondrial β-oxidation of fatty acids in Cdo1-null mice. The strong associations of elevated cysteine levels with excess H2S production and impairments in energy metabolism suggest that H2S signaling could be involved. PMID:26995761

  18. Effects of a block in cysteine catabolism on energy balance and fat metabolism in mice.

    PubMed

    Niewiadomski, Julie; Zhou, James Q; Roman, Heather B; Liu, Xiaojing; Hirschberger, Lawrence L; Locasale, Jason W; Stipanuk, Martha H

    2016-01-01

    To gain further insights into the effects of elevated cysteine levels on energy metabolism and the possible mechanisms underlying these effects, we conducted studies in cysteine dioxygenase (Cdo1)-null mice. Cysteine dioxygenase (CDO) catalyzes the first step of the major pathway for cysteine catabolism. When CDO is absent, tissue and plasma cysteine levels are elevated, resulting in enhanced flux of cysteine through desulfhydration reactions. When Cdo1-null mice were fed a high-fat diet, they gained more weight than their wild-type controls, regardless of whether the diet was supplemented with taurine. Cdo1-null mice had markedly lower leptin levels, higher feed intakes, and markedly higher abundance of hepatic stearoyl-CoA desaturase 1 (SCD1) compared to wild-type control mice, and these differences were not affected by the fat or taurine content of the diet. Thus, reported associations of elevated cysteine levels with greater weight gain and with elevated hepatic Scd1 expression are also seen in the Cdo1-null mouse model. Hepatic accumulation of acylcarnitines suggests impaired mitochondrial β-oxidation of fatty acids in Cdo1-null mice. The strong associations of elevated cysteine levels with excess H2 S production and impairments in energy metabolism suggest that H2 S signaling could be involved. © 2016 New York Academy of Sciences.

  19. A link between hepatic glucose production and peripheral energy metabolism via hepatokines

    PubMed Central

    Abdul-Wahed, Aya; Gautier-Stein, Amandine; Casteras, Sylvie; Soty, Maud; Roussel, Damien; Romestaing, Caroline; Guillou, Hervé; Tourette, Jean-André; Pleche, Nicolas; Zitoun, Carine; Gri, Blandine; Sardella, Anne; Rajas, Fabienne; Mithieux, Gilles

    2014-01-01

    Type 2 diabetes is characterized by a deterioration of glucose tolerance, which associates insulin resistance of glucose uptake by peripheral tissues and increased endogenous glucose production. Here we report that the specific suppression of hepatic glucose production positively modulates whole-body glucose and energy metabolism. We used mice deficient in liver glucose-6 phosphatase that is mandatory for endogenous glucose production. When they were fed a high fat/high sucrose diet, they resisted the development of diabetes and obesity due to the activation of peripheral glucose metabolism and thermogenesis. This was linked to the secretion of hepatic hormones like fibroblast growth factor 21 and angiopoietin-like factor 6. Interestingly, the deletion of hepatic glucose-6 phosphatase in previously obese and insulin-resistant mice resulted in the rapid restoration of glucose and body weight controls. Therefore, hepatic glucose production is an essential lever for the control of whole-body energy metabolism during the development of obesity and diabetes. PMID:25061558

  20. A link between hepatic glucose production and peripheral energy metabolism via hepatokines.

    PubMed

    Abdul-Wahed, Aya; Gautier-Stein, Amandine; Casteras, Sylvie; Soty, Maud; Roussel, Damien; Romestaing, Caroline; Guillou, Hervé; Tourette, Jean-André; Pleche, Nicolas; Zitoun, Carine; Gri, Blandine; Sardella, Anne; Rajas, Fabienne; Mithieux, Gilles

    2014-08-01

    Type 2 diabetes is characterized by a deterioration of glucose tolerance, which associates insulin resistance of glucose uptake by peripheral tissues and increased endogenous glucose production. Here we report that the specific suppression of hepatic glucose production positively modulates whole-body glucose and energy metabolism. We used mice deficient in liver glucose-6 phosphatase that is mandatory for endogenous glucose production. When they were fed a high fat/high sucrose diet, they resisted the development of diabetes and obesity due to the activation of peripheral glucose metabolism and thermogenesis. This was linked to the secretion of hepatic hormones like fibroblast growth factor 21 and angiopoietin-like factor 6. Interestingly, the deletion of hepatic glucose-6 phosphatase in previously obese and insulin-resistant mice resulted in the rapid restoration of glucose and body weight controls. Therefore, hepatic glucose production is an essential lever for the control of whole-body energy metabolism during the development of obesity and diabetes.

  1. α/β-Hydrolase Domain 6 in the Ventromedial Hypothalamus Controls Energy Metabolism Flexibility.

    PubMed

    Fisette, Alexandre; Tobin, Stephanie; Décarie-Spain, Léa; Bouyakdan, Khalil; Peyot, Marie-Line; Madiraju, S R Murthy; Prentki, Marc; Fulton, Stephanie; Alquier, Thierry

    2016-10-25

    α/β-Hydrolase domain 6 (ABHD6) is a monoacylglycerol hydrolase that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG). Although complete or peripheral ABHD6 loss of function is protective against diet-induced obesity and insulin resistance, the role of ABHD6 in the central control of energy balance is unknown. Using a viral-mediated knockout approach, targeted endocannabinoid measures, and pharmacology, we discovered that mice lacking ABHD6 from neurons of the ventromedial hypothalamus (VMH KO ) have higher VMH 2-AG levels in conditions of endocannabinoid recruitment and fail to physiologically adapt to key metabolic challenges. VMH KO mice exhibited blunted fasting-induced feeding and reduced food intake, energy expenditure, and adaptive thermogenesis in response to cold exposure, high-fat feeding, and dieting (transition to a low-fat diet). Our findings identify ABHD6 as a regulator of the counter-regulatory responses to major metabolic shifts, including fasting, nutrient excess, cold, and dieting, thereby highlighting the importance of ABHD6 in the VMH in mediating energy metabolism flexibility. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Sense and Nonsense in Metabolic Control of Reproduction

    PubMed Central

    Schneider, Jill E.; Klingerman, Candice M.; Abdulhay, Amir

    2012-01-01

    An exciting synergistic interaction occurs among researchers working at the interface of reproductive biology and energy homeostasis. Reproductive biologists benefit from the theories, experimental designs, and methodologies used by experts on energy homeostasis while they bring context and meaning to the study of energy homeostasis. There is a growing recognition that identification of candidate genes for obesity is little more than meaningless reductionism unless those genes and their expression are placed in a developmental, environmental, and evolutionary context. Reproductive biology provides this context because metabolic energy is the most important factor that controls reproductive success and gonadal hormones affect energy intake, storage, and expenditure. Reproductive hormone secretion changes during development, and reproductive success is key to evolutionary adaptation, the process that most likely molded the mechanisms that control energy balance. It is likely that by viewing energy intake, storage, and expenditure in the context of reproductive success, we will gain insight into human obesity, eating disorders, diabetes, and other pathologies related to fuel homeostasis. This review emphasizes the metabolic hypothesis: a sensory system monitors the availability of oxidizable metabolic fuels and orchestrates behavioral motivation to optimize reproductive success in environments where energy availability fluctuates or is unpredictable. PMID:22649413

  3. Sense and nonsense in metabolic control of reproduction.

    PubMed

    Schneider, Jill E; Klingerman, Candice M; Abdulhay, Amir

    2012-01-01

    An exciting synergistic interaction occurs among researchers working at the interface of reproductive biology and energy homeostasis. Reproductive biologists benefit from the theories, experimental designs, and methodologies used by experts on energy homeostasis while they bring context and meaning to the study of energy homeostasis. There is a growing recognition that identification of candidate genes for obesity is little more than meaningless reductionism unless those genes and their expression are placed in a developmental, environmental, and evolutionary context. Reproductive biology provides this context because metabolic energy is the most important factor that controls reproductive success and gonadal hormones affect energy intake, storage, and expenditure. Reproductive hormone secretion changes during development, and reproductive success is key to evolutionary adaptation, the process that most likely molded the mechanisms that control energy balance. It is likely that by viewing energy intake, storage, and expenditure in the context of reproductive success, we will gain insight into human obesity, eating disorders, diabetes, and other pathologies related to fuel homeostasis. This review emphasizes the metabolic hypothesis: a sensory system monitors the availability of oxidizable metabolic fuels and orchestrates behavioral motivation to optimize reproductive success in environments where energy availability fluctuates or is unpredictable.

  4. The Choice of Euthanasia Method Affects Metabolic Serum Biomarkers.

    PubMed

    Pierozan, Paula; Jernerén, Fredrik; Ransome, Yusuf; Karlsson, Oskar

    2017-08-01

    The impact of euthanasia methods on endocrine and metabolic parameters in rodent tissues and biological fluids is highly relevant for the accuracy and reliability of the data collected. However, few studies concerning this issue are found in the literature. We compared the effects of three euthanasia methods currently used in animal experimentation (i.e. decapitation, CO 2 inhalation and pentobarbital injection) on the serum levels of corticosterone, insulin, glucose, triglycerides, cholesterol and a range of free fatty acids in rats. The corticosterone and insulin levels were not significantly affected by the euthanasia protocol used. However, euthanasia by an overdose of pentobarbital (120 mg/kg intraperitoneal injection) increased the serum levels of glucose, and decreased cholesterol, stearic and arachidonic acids levels compared with euthanasia by CO 2 inhalation and decapitation. CO 2 inhalation appears to increase the serum levels of triglycerides, while euthanasia by decapitation induced no individual discrepant biomarker level. We conclude that choice of the euthanasia methods is critical for the reliability of serum biomarkers and indicate the importance of selecting adequate euthanasia methods for metabolic analysis in rodents. Decapitation without anaesthesia may be the most adequate method of euthanasia when taking both animal welfare and data quality in consideration. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  5. The Choice of Euthanasia Method Affects Metabolic Serum Biomarkers

    PubMed Central

    Pierozan, Paula; Jernerén, Fredrik; Ransome, Yusuf; Karlsson, Oskar

    2018-01-01

    The impact of euthanasia methods on endocrine and metabolic parameters in rodent tissues and biological fluids is highly relevant for the accuracy and reliability of the data collected. However, few studies concerning this issue are found in the literature. We compared the effects of three euthanasia methods currently used in animal experimentation (i.e. decapitation, CO2 inhalation and pentobarbital injection) on the serum levels of corticosterone, insulin, glucose, triglycerides, cholesterol and a range of free fatty acids in rats. The corticosterone and insulin levels were not significantly affected by the euthanasia protocol used. However, euthanasia by an overdose of pentobarbital (120 mg/kg intraperitoneal injection) increased the serum levels of glucose, and decreased cholesterol, stearic and arachidonic acids levels compared with euthanasia by CO2 inhalation and decapitation. CO2 inhalation appears to increase the serum levels of triglycerides, while euthanasia by decapitation induced no individual discrepant biomarker level. We conclude that choice of the euthanasia methods is critical for the reliability of serum biomarkers and indicate the importance of selecting adequate euthanasia methods for metabolic analysis in rodents. Decapitation without anaesthesia may be the most adequate method of euthanasia when taking both animal welfare and data quality in consideration. PMID:28244216

  6. Restriction of rapid eye movement sleep during adolescence increases energy gain and metabolic efficiency in young adult rats.

    PubMed

    Ribeiro-Silva, Neila; Nejm, Mariana Bocca; da Silva, Sylvia Maria Affonso; Suchecki, Deborah; Luz, Jacqueline

    2016-02-01

    What is the central question of this study? Sleep curtailment in infancy and adolescence may lead to long-term risk for obesity, but the mechanisms involved have not yet been determined. This study examined the immediate and long-term metabolic effects produced by sleep restriction in young rats. What is the main finding and its importance? Prolonged sleep restriction reduced weight gain (body fat stores) in young animals. After prolonged recovery, sleep-restricted rats tended to save more energy and to store more fat, possibly owing to increased gross food efficiency. This could be the first step to understand this association. Sleep curtailment is associated with obesity and metabolic changes in adults and children. The aim of the present study was to evaluate the immediate and long-term metabolic alterations produced by sleep restriction in pubertal male rats. Male Wistar rats (28 days old) were allocated to a control (CTL) group or a sleep-restricted (SR) group. This was accomplished by the single platform technique for 18 h per day for 21 days. These groups were subdivided into the following four time points for assessment: sleep restriction and 1, 2 and 4 months of recovery. Body weight and food intake were monitored throughout the experiment. At the end of each time period, blood was collected for metabolic profiling, and the carcasses were processed for measurement of body composition and energy balance. During the period of sleep restriction, SR animals consumed less food in the home cages. This group also displayed lower body weight, body fat, triglycerides and glucose levels than CTL rats. At the end of the first month of recovery, despite eating as much as CTL rats, SR animals showed greater energy and body weight gain, increased gross food efficiency and decreased energy expenditure. At the end of the second and fourth months of recovery, the groups were no longer different, except for energy gain and gross food efficiency, which remained higher in SR

  7. Consequences of complex environments: Temperature and energy intake interact to influence growth and metabolic rate.

    PubMed

    Stahlschmidt, Zachary R; Jodrey, Alicia D; Luoma, Rachel L

    2015-09-01

    The field of comparative physiology has a rich history of elegantly examining the effects of individual environmental factors on performance traits linked to fitness (e.g., thermal performance curves for locomotion). However, animals live in complex environments wherein multiple environmental factors co-vary. Thus, we investigated the independent and interactive effects of temperature and energy intake on the growth and metabolic rate of juvenile corn snakes (Pantherophis guttatus) in the context of shifts in complex environments. Unlike previous studies that imposed constant or fluctuating temperature regimes, we manipulated the availability of preferred thermal microclimates (control vs. relatively warm regimes) for eight weeks and allowed snakes to behaviorally thermoregulate among microclimates. By also controlling for energy intake, we demonstrate an interactive effect of temperature and energy on growth-relevant temperature shifts had no effect on snakes' growth when energy intake was low and a positive effect on growth when energy intake was high. Thus, acclimation to relatively warm thermal options can result in increased rates of growth when food is abundant in a taxon in which body size confers fitness advantages. Temperature and energy also interactively influenced metabolic rate-snakes in the warmer temperature regime exhibited reduced metabolic rate (O2 consumption rate at 25 °C and 30 °C) if they had relatively high energy intake. Although we advocate for continued investigation into the effects of complex environments on other traits, our results indicate that warming may actually benefit important life history traits in some taxa and that metabolic shifts may underlie thermal acclimation. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Unique Flexibility in Energy Metabolism Allows Mycobacteria to Combat Starvation and Hypoxia

    PubMed Central

    Berney, Michael; Cook, Gregory M.

    2010-01-01

    Mycobacteria are a group of obligate aerobes that require oxygen for growth, but paradoxically have the ability to survive and metabolize under hypoxia. The mechanisms responsible for this metabolic plasticity are unknown. Here, we report on the adaptation of Mycobacterium smegmatis to slow growth rate and hypoxia using carbon-limited continuous culture. When M. smegmatis is switched from a 4.6 h to a 69 h doubling time at a constant oxygen saturation of 50%, the cells respond through the down regulation of respiratory chain components and the F1Fo-ATP synthase, consistent with the cells lower demand for energy at a reduced growth rate. This was paralleled by an up regulation of molecular machinery that allowed more efficient energy generation (i.e. Complex I) and the use of alternative electron donors (e.g. hydrogenases and primary dehydrogenases) to maintain the flow of reducing equivalents to the electron transport chain during conditions of severe energy limitation. A hydrogenase mutant showed a 40% reduction in growth yield highlighting the importance of this enzyme in adaptation to low energy supply. Slow growing cells at 50% oxygen saturation subjected to hypoxia (0.6% oxygen saturation) responded by switching on oxygen scavenging cytochrome bd, proton-translocating cytochrome bc1-aa3 supercomplex, another putative hydrogenase, and by substituting NAD+-dependent enzymes with ferredoxin-dependent enzymes thus highlighting a new pattern of mycobacterial adaptation to hypoxia. The expression of ferredoxins and a hydrogenase provides a potential conduit for disposing of and transferring electrons in the absence of exogenous electron acceptors. The use of ferredoxin-dependent enzymes would allow the cell to maintain a high carbon flux through its central carbon metabolism independent of the NAD+/NADH ratio. These data demonstrate the remarkable metabolic plasticity of the mycobacterial cell and provide a new framework for understanding their ability to survive

  9. Dietary energy availability affects primary and metastatic breast cancer and metformin efficacy

    PubMed Central

    Phoenix, Kathryn N.; Vumbaca, Frank; Fox, Melissa M.; Evans, Rebecca

    2010-01-01

    Dietary energy restriction has been shown to repress both mammary tumorigenesis and aggressive mammary tumor growth in animal studies. Metformin, a caloric restriction mimetic, has a long history of safe use as an insulin sensitizer in diabetics and has been shown to reduce cancer incidence and cancer-related mortality in humans. To determine the potential impact of dietary energy availability and metformin therapy on aggressive breast tumor growth and metastasis, an orthotopic syngeneic model using triple negative 66cl4 tumor cells in Balb/c mice was employed. The effect of dietary restriction, a standard maintenance diet or a diet with high levels of free sugar, were tested for their effects on tumor growth and secondary metastases to the lung. Metformin therapy with the various diets indicated that metformin can be highly effective at suppressing systemic metabolic biomarkers such as IGF-1, insulin and glucose, especially in the high energy diet treated animals. Long-term metformin treatment demonstrated moderate yet significant effects on primary tumor growth, most significantly in conjunction with the high energy diet. When compared to the control diet, the high energy diet promoted tumor growth, expression of the inflammatory adipokines leptin and resistin, induced lung priming by bone marrow-derived myeloid cells and promoted metastatic potential. Metformin had no effect on adipokine expression or the development of lung metastases with the standard or the high energy diet. These data indicate that metformin may have tumor suppressing activity where a metabolic phenotype of high fuel intake, metabolic syndrome, and diabetes exist, but may have little or no effect on events controlling the metastatic niche driven by proinflammatory events. PMID:20204498

  10. Age and the metabolic syndrome affect salivary cortisol rhythm: data from a community sample.

    PubMed

    Ceccato, Filippo; Barbot, Mattia; Zilio, Marialuisa; Ferasin, Sergio; De Lazzari, Paola; Lizzul, Laura; Boscaro, Marco; Scaroni, Carla

    2015-01-01

    Measurement of cortisol levels in saliva is a marker of free hormone. How salivary cortisol rhythm is affected by age, gender, the metabolic syndrome and estrogen-progestin therapy was evaluated in a community sample of adults. One hundred twenty volunteers recruited from the Hospital staff and family members of the Endocrinology Unit were instructed to collect 7 salivary samples: the first on awakening (F(0)) and 6 more (F(1.5), F(5), F(6), F(10), F(11.5) and F(14)) over the next 14 hours. Each volunteer also underwent a complete physical evaluation and a comprehensive medical history was taken. Salivary cortisol was measured using a radioimmunometric assay. Daily cortisol secretion was evaluated computing the Area Under the Curve (AUC(F0)(→)(F14)); the F(14)/F(0) ratio was calculated as a marker of cortisol rhythm. Median F(14) levels were higher in the subjects in the third tertile of age than in those falling in the second or in the first age tertile (respectively, 2.09 vs 1.33 vs 1.25 ng/mL, p=0.023 and p=0.006), in the hypertensive volunteers (2.44 vs 1.44 ng/mL, p=0.030) and in those with the metabolic syndrome (2.95 vs 1.4 ng/mL, p=0.002), with an elevated median F(14)/F(0) ratio (0.48 vs 0.19, p=0.006). According to the Kruskal-Wallis analysis of variance, the most important factor affecting F(14) value was age (p=0.001). AUC(F0)(→)(F14) was not influenced by gender, age, metabolic syndrome or estrogen-progestin therapy. While it did not affect the daily cortisol rate, late-night salivary cortisol levels were found to be increased in the subjects in the higher age tertile and in those with the metabolic syndrome.

  11. 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. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Metabolism

    MedlinePlus

    ... El metabolismo Metabolism Basics Our bodies get the energy they need from food through metabolism, the chemical ... that convert the fuel from food into the energy needed to do everything from moving to thinking ...

  13. Diet-induced alterations of host cholesterol metabolism are likely to affect the gut microbiota composition in hamsters.

    PubMed

    Martínez, Inés; Perdicaro, Diahann J; Brown, Andrew W; Hammons, Susan; Carden, Trevor J; Carr, Timothy P; Eskridge, Kent M; Walter, Jens

    2013-01-01

    The gastrointestinal microbiota affects the metabolism of the mammalian host and has consequences for health. However, the complexity of gut microbial communities and host metabolic pathways make functional connections difficult to unravel, especially in terms of causation. In this study, we have characterized the fecal microbiota of hamsters whose cholesterol metabolism was extensively modulated by the dietary addition of plant sterol esters (PSE). PSE intake induced dramatic shifts in the fecal microbiota, reducing several bacterial taxa within the families Coriobacteriaceae and Erysipelotrichaceae. The abundance of these taxa displayed remarkably high correlations with host cholesterol metabolites. Most importantly, the associations between several bacterial taxa with fecal and biliary cholesterol excretion showed an almost perfect fit to a sigmoidal nonlinear model of bacterial inhibition, suggesting that host cholesterol excretion can shape microbiota structure through the antibacterial action of cholesterol. In vitro experiments suggested a modest antibacterial effect of cholesterol, and especially of cholesteryl-linoleate, but not plant sterols when included in model bile micelles. The findings obtained in this study are relevant to our understanding of gut microbiota-host lipid metabolism interactions, as they provide the first evidence for a role of cholesterol excreted with the bile as a relevant host factor that modulates the gut microbiota. The findings further suggest that the connections between Coriobacteriaceae and Erysipelotrichaceae and host lipid metabolism, which have been observed in several studies, could be caused by a metabolic phenotype of the host (cholesterol excretion) affecting the gut microbiota.

  14. Demyelination in Multiple Sclerosis: Reprogramming Energy Metabolism and Potential PPARγ Agonist Treatment Approaches.

    PubMed

    Vallée, Alexandre; Lecarpentier, Yves; Guillevin, Rémy; Vallée, Jean-Noël

    2018-04-16

    Demyelination in multiple sclerosis (MS) cells is the site of several energy metabolic abnormalities driven by dysregulation between the opposed interplay of peroxisome proliferator-activated receptor γ (PPARγ) and WNT/β-catenin pathways. We focus our review on the opposing interactions observed in demyelinating processes in MS between the canonical WNT/β-catenin pathway and PPARγ and their reprogramming energy metabolism implications. Demyelination in MS is associated with chronic inflammation, which is itself associated with the release of cytokines by CD4⁺ Th17 cells, and downregulation of PPARγ expression leading to the upregulation of the WNT/β-catenin pathway. Upregulation of WNT/β-catenin signaling induces activation of glycolytic enzymes that modify their energy metabolic behavior. Then, in MS cells, a large portion of cytosolic pyruvate is converted into lactate. This phenomenon is called the Warburg effect, despite the availability of oxygen. The Warburg effect is the shift of an energy transfer production from mitochondrial oxidative phosphorylation to aerobic glycolysis. Lactate production is correlated with increased WNT/β-catenin signaling and demyelinating processes by inducing dysfunction of CD4⁺ T cells leading to axonal and neuronal damage. In MS, downregulation of PPARγ decreases insulin sensitivity and increases neuroinflammation. PPARγ agonists inhibit Th17 differentiation in CD4⁺ T cells and then diminish release of cytokines. In MS, abnormalities in the regulation of circadian rhythms stimulate the WNT pathway to initiate the demyelination process. Moreover, PPARγ contributes to the regulation of some key circadian genes. Thus, PPARγ agonists interfere with reprogramming energy metabolism by directly inhibiting the WNT/β-catenin pathway and circadian rhythms and could appear as promising treatments in MS due to these interactions.

  15. Changes in Microbial Energy Metabolism Measured by Nanocalorimetry during Growth Phase Transitions

    PubMed Central

    Robador, Alberto; LaRowe, Douglas E.; Finkel, Steven E.; Amend, Jan P.; Nealson, Kenneth H.

    2018-01-01

    Calorimetric measurements of the change in heat due to microbial metabolic activity convey information about the kinetics, as well as the thermodynamics, of all chemical reactions taking place in a cell. Calorimetric measurements of heat production made on bacterial cultures have recorded the energy yields of all co-occurring microbial metabolic reactions, but this is a complex, composite signal that is difficult to interpret. Here we show that nanocalorimetry can be used in combination with enumeration of viable cell counts, oxygen consumption rates, cellular protein content, and thermodynamic calculations to assess catabolic rates of an isolate of Shewanella oneidensis MR-1 and infer what fraction of the chemical energy is assimilated by the culture into biomass and what fraction is dissipated in the form of heat under different limiting conditions. In particular, our results demonstrate that catabolic rates are not necessarily coupled to rates of cell division, but rather, to physiological rearrangements of S. oneidensis MR-1 upon growth phase transitions. In addition, we conclude that the heat released by growing microorganisms can be measured in order to understand the physiochemical nature of the energy transformation and dissipation associated with microbial metabolic activity in conditions approaching those found in natural systems. PMID:29449836

  16. Nanomolar nitric oxide concentrations quickly and reversibly modulate astrocytic energy metabolism

    PubMed Central

    San Martín, Alejandro; Arce-Molina, Robinson; Galaz, Alex; Pérez-Guerra, Gustavo; Barros, L. Felipe

    2017-01-01

    Nitric oxide (NO) is an intercellular messenger involved in multiple bodily functions. Prolonged NO exposure irreversibly inhibits respiration by covalent modification of mitochondrial cytochrome oxidase, a phenomenon of pathological relevance. However, the speed and potency of NO's metabolic effects at physiological concentrations are incompletely characterized. To this end, we set out to investigate the metabolic effects of NO in cultured astrocytes from mice by taking advantage of the high spatiotemporal resolution afforded by genetically encoded Förster resonance energy transfer (FRET) nanosensors. NO exposure resulted in immediate and reversible intracellular glucose depletion and lactate accumulation. Consistent with cytochrome oxidase involvement, the glycolytic effect was enhanced at a low oxygen level and became irreversible at a high NO concentration or after prolonged exposure. Measurements of both glycolytic rate and mitochondrial pyruvate consumption revealed significant effects even at nanomolar NO concentrations. We conclude that NO can modulate astrocytic energy metabolism in the short term, reversibly, and at concentrations known to be released by endothelial cells under physiological conditions. These findings suggest that NO modulates the size of the astrocytic lactate reservoir involved in neuronal fueling and signaling. PMID:28341740

  17. Nanomolar nitric oxide concentrations quickly and reversibly modulate astrocytic energy metabolism.

    PubMed

    San Martín, Alejandro; Arce-Molina, Robinson; Galaz, Alex; Pérez-Guerra, Gustavo; Barros, L Felipe

    2017-06-02

    Nitric oxide (NO) is an intercellular messenger involved in multiple bodily functions. Prolonged NO exposure irreversibly inhibits respiration by covalent modification of mitochondrial cytochrome oxidase, a phenomenon of pathological relevance. However, the speed and potency of NO's metabolic effects at physiological concentrations are incompletely characterized. To this end, we set out to investigate the metabolic effects of NO in cultured astrocytes from mice by taking advantage of the high spatiotemporal resolution afforded by genetically encoded Förster resonance energy transfer (FRET) nanosensors. NO exposure resulted in immediate and reversible intracellular glucose depletion and lactate accumulation. Consistent with cytochrome oxidase involvement, the glycolytic effect was enhanced at a low oxygen level and became irreversible at a high NO concentration or after prolonged exposure. Measurements of both glycolytic rate and mitochondrial pyruvate consumption revealed significant effects even at nanomolar NO concentrations. We conclude that NO can modulate astrocytic energy metabolism in the short term, reversibly, and at concentrations known to be released by endothelial cells under physiological conditions. These findings suggest that NO modulates the size of the astrocytic lactate reservoir involved in neuronal fueling and signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Triptolide improves systolic function and myocardial energy metabolism of diabetic cardiomyopathy in streptozotocin-induced diabetic rats.

    PubMed

    Liang, Zhongshu; Leo, Sunnar; Wen, Helin; Ouyang, Mao; Jiang, Weihong; Yang, Kan

    2015-05-13

    Triptolide treatment leads to an improvement in Diabetic Cardiomyopathy (DCM) in streptozotocin-induced diabetic rat model. DCM is characterized by abnormal cardiac energy metabolism. We hypothesized that triptolide ameliorated cardiac metabolic abnormalities in DCM. We proposed (31)P nuclear magnetic resonance ((31)P NMR) spectrometry method for assessing cardiac energy metabolism in vivo and evaluating the effect of triptolide treatment in DCM rats. Six weeks triptolide treatment was conducted on streptozotocin-induced diabetic rats with dose of 100, 200 or 400 μg/kg/day respectively. Sex- and age-matched non-diabetic rats were used as control group. Cardiac chamber dimension and function were determined with echocardiography. Whole heart preparations were perfused with Krebs-Henseleit buffer and (31)P NMR spectroscopy was performed. Cardiac p38 Mitogen Activating Protein Kinase (MAPK) was measured using real time PCR and western blot analysis. In diabetic rats, cardiac mass index was significantly higher, where as cardiac EF was lower than control group. (31)P NMR spectroscopy showed that ATP and pCr concentrations in diabetic groups were also remarkably lower than control group. Compared to non-treated diabetic rats, triptolide-treated diabetic groups showed remarkable lower cardiac mass index and higher EF, ATP, pCr concentrations, and P38 MAPK expressions. Best improvement was seen in group treated with Triptolide with dose 200 μg/kg/day. (31)P NMR spectroscopy enables assessment of cardiac energy metabolism in whole heart preparations. It detects energy metabolic abnormalities in DCM hearts. Triptolide therapy improves cardiac function and increases cardiac energy metabolism at least partly through upregulation of MAPK signaling transduction.

  19. Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets.

    PubMed

    Seyfried, Thomas N; Kiebish, Michael; Mukherjee, Purna; Marsh, Jeremy

    2008-11-01

    Information is presented on the calorically restricted ketogenic diet (CRKD) as an alternative therapy for brain cancer. In contrast to normal neurons and glia, which evolved to metabolize ketone bodies as an alternative fuel to glucose under energy-restricted conditions, brain tumor cells are largely glycolytic due to mitochondrial defects and have a reduced ability to metabolize ketone bodies. The CRKD is effective in managing brain tumor growth in animal models and in patients, and appears to act through antiangiogenic, anti-inflammatory, and proapoptotic mechanisms.

  20. Chronobiology, endocrinology, and energy- and food-reward homeostasis.

    PubMed

    Gonnissen, H K J; Hulshof, T; Westerterp-Plantenga, M S

    2013-05-01

    Energy- and food-reward homeostasis is the essential component for maintaining energy balance and its disruption may lead to metabolic disorders, including obesity and diabetes. Circadian alignment, quality sleep and sleep architecture in relation to energy- and food-reward homeostasis are crucial. A reduced sleep duration, quality sleep and rapid-eye movement sleep affect substrate oxidation, leptin and ghrelin concentrations, sleeping metabolic rate, appetite, food reward, hypothalamic-pituitary-adrenal (HPA)-axis activity, and gut-peptide concentrations, enhancing a positive energy balance. Circadian misalignment affects sleep architecture and the glucose-insulin metabolism, substrate oxidation, homeostasis model assessment of insulin resistance (HOMA-IR) index, leptin concentrations and HPA-axis activity. Mood disorders such as depression occur; reduced dopaminergic neuronal signaling shows decreased food reward. A good sleep hygiene, together with circadian alignment of food intake, a regular meal frequency, and attention for protein intake or diets, contributes in curing sleep abnormalities and overweight/obesity features by preventing overeating; normalizing substrate oxidation, stress, insulin and glucose metabolism including HOMA-IR index, and leptin, GLP-1 concentrations, lipid metabolism, appetite, energy expenditure and substrate oxidation; and normalizing food reward. Synchrony between circadian and metabolic processes including meal patterns plays an important role in the regulation of energy balance and body-weight control. Additive effects of circadian alignment including meal patterns, sleep restoration, and protein diets in the treatment of overweight and obesity are suggested. © 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.

  1. GH and IGF1: roles in energy metabolism of long-living GH mutant mice.

    PubMed

    Brown-Borg, Holly M; Bartke, Andrzej

    2012-06-01

    Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50% longer and exhibit significant differences in several aspects of energy metabolism as compared with wild-type mice. Mitochondrial metabolism is upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice treated with GH, multiple aspects of these pathways are suppressed. Core body temperature is markedly lower in dwarf mice, yet whole-body metabolism, as measured by indirect calorimetry, is surprisingly higher in Ames dwarf and Ghr-/- mice compared with normal controls. Elevated adiponectin, a key antiinflammatory cytokine, is also very likely to contribute to longevity in these mice. Thus, several important components related to energy metabolism are altered in GH mutant mice, and these differences are likely critical in aging processes and life-span extension.

  2. Regulation of lipid metabolism by energy availability: a role for the central nervous system.

    PubMed

    Nogueiras, R; López, M; Diéguez, C

    2010-03-01

    The central nervous system (CNS) is crucial in the regulation of energy homeostasis. Many neuroanatomical studies have shown that the white adipose tissue (WAT) is innervated by the sympathetic nervous system, which plays a critical role in adipocyte lipid metabolism. Therefore, there are currently numerous reports indicating that signals from the CNS control the amount of fat by modulating the storage or oxidation of fatty acids. Importantly, some CNS pathways regulate adipocyte metabolism independently of food intake, suggesting that some signals possess alternative mechanisms to regulate energy homeostasis. In this review, we mainly focus on how neuronal circuits within the hypothalamus, such as leptin- ghrelin-and resistin-responsive neurons, as well as melanocortins, neuropeptide Y, and the cannabinoid system exert their actions on lipid metabolism in peripheral tissues such as WAT, liver or muscle. Dissecting the complicated interactions between peripheral signals and neuronal circuits regulating lipid metabolism might open new avenues for the development of new therapies preventing and treating obesity and its associated cardiometabolic sequelae.

  3. Metabolism pathways in chronic lymphocytic leukemia

    PubMed Central

    Rozovski, Uri; Hazan-Halevy, Inbal; Barzilay, Merav; Keating, Michael J.; Estrov, Zeev

    2016-01-01

    Alterations in CLL cell metabolism have been studied by several investigators. Unlike normal B lymphocytes or other leukemia cells, CLL cells, like adipocytes, store lipids and utilize free fatty acids (FFA) to produce chemical energy. None of the recently identified mutations in CLL directly affects metabolic pathways, suggesting that genetic alterations do not directly contribute to CLL cells’ metabolic reprogramming. Conversely, recent data suggest that activation of STAT3 or downregulation of microRNA-125 levels plays a crucial role in the utilization of FFA to meet CLL cells’ metabolic needs. STAT3, known to be constitutively activated in CLL, increases the levels of lipoprotein lipase that mediates lipoprotein uptake and shifts CLL cells’ metabolism towards utilization of FFA. Herein we review the evidence for altered lipid metabolism, increased mitochondrial activity, and formation of reactive oxygen species in CLL cells, and discuss possible therapeutic strategies to inhibit lipid metabolism pathways in patient with CLL. PMID:26643954

  4. OCIAD1 Controls Electron Transport Chain Complex I Activity to Regulate Energy Metabolism in Human Pluripotent Stem Cells.

    PubMed

    Shetty, Deeti K; Kalamkar, Kaustubh P; Inamdar, Maneesha S

    2018-06-14

    Pluripotent stem cells (PSCs) derive energy predominantly from glycolysis and not the energy-efficient oxidative phosphorylation (OXPHOS). Differentiation is initiated with energy metabolic shift from glycolysis to OXPHOS. We investigated the role of mitochondrial energy metabolism in human PSCs using molecular, biochemical, genetic, and pharmacological approaches. We show that the carcinoma protein OCIAD1 interacts with and regulates mitochondrial complex I activity. Energy metabolic assays on live pluripotent cells showed that OCIAD1-depleted cells have increased OXPHOS and may be poised for differentiation. OCIAD1 maintains human embryonic stem cells, and its depletion by CRISPR/Cas9-mediated knockout leads to rapid and increased differentiation upon induction, whereas OCIAD1 overexpression has the opposite effect. Pharmacological alteration of complex I activity was able to rescue the defects of OCIAD1 modulation. Thus, hPSCs can exist in energy metabolic substates. OCIAD1 provides a target to screen for additional modulators of mitochondrial activity to promote transient multipotent precursor expansion or enhance differentiation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  5. A Dynamic Energy Budget (DEB) model to describe Laternula elliptica (King, 1832) seasonal feeding and metabolism

    PubMed Central

    Ahn, In-Young; Guillaumot, Charlène; Danis, Bruno

    2017-01-01

    Antarctic marine organisms are adapted to an extreme environment, characterized by a very low but stable temperature and a strong seasonality in food availability arousing from variations in day length. Ocean organisms are particularly vulnerable to global climate change with some regions being impacted by temperature increase and changes in primary production. Climate change also affects the biotic components of marine ecosystems and has an impact on the distribution and seasonal physiology of Antarctic marine organisms. Knowledge on the impact of climate change in key species is highly important because their performance affects ecosystem functioning. To predict the effects of climate change on marine ecosystems, a holistic understanding of the life history and physiology of Antarctic key species is urgently needed. DEB (Dynamic Energy Budget) theory captures the metabolic processes of an organism through its entire life cycle as a function of temperature and food availability. The DEB model is a tool that can be used to model lifetime feeding, growth, reproduction, and their responses to changes in biotic and abiotic conditions. In this study, we estimate the DEB model parameters for the bivalve Laternula elliptica using literature-extracted and field data. The DEB model we present here aims at better understanding the biology of L. elliptica and its levels of adaptation to its habitat with a special focus on food seasonality. The model parameters describe a metabolism specifically adapted to low temperatures, with a low maintenance cost and a high capacity to uptake and mobilise energy, providing this organism with a level of energetic performance matching that of related species from temperate regions. It was also found that L. elliptica has a large energy reserve that allows enduring long periods of starvation. Additionally, we applied DEB parameters to time-series data on biological traits (organism condition, gonad growth) to describe the effect of a

  6. A Dynamic Energy Budget (DEB) model to describe Laternula elliptica (King, 1832) seasonal feeding and metabolism.

    PubMed

    Agüera, Antonio; Ahn, In-Young; Guillaumot, Charlène; Danis, Bruno

    2017-01-01

    Antarctic marine organisms are adapted to an extreme environment, characterized by a very low but stable temperature and a strong seasonality in food availability arousing from variations in day length. Ocean organisms are particularly vulnerable to global climate change with some regions being impacted by temperature increase and changes in primary production. Climate change also affects the biotic components of marine ecosystems and has an impact on the distribution and seasonal physiology of Antarctic marine organisms. Knowledge on the impact of climate change in key species is highly important because their performance affects ecosystem functioning. To predict the effects of climate change on marine ecosystems, a holistic understanding of the life history and physiology of Antarctic key species is urgently needed. DEB (Dynamic Energy Budget) theory captures the metabolic processes of an organism through its entire life cycle as a function of temperature and food availability. The DEB model is a tool that can be used to model lifetime feeding, growth, reproduction, and their responses to changes in biotic and abiotic conditions. In this study, we estimate the DEB model parameters for the bivalve Laternula elliptica using literature-extracted and field data. The DEB model we present here aims at better understanding the biology of L. elliptica and its levels of adaptation to its habitat with a special focus on food seasonality. The model parameters describe a metabolism specifically adapted to low temperatures, with a low maintenance cost and a high capacity to uptake and mobilise energy, providing this organism with a level of energetic performance matching that of related species from temperate regions. It was also found that L. elliptica has a large energy reserve that allows enduring long periods of starvation. Additionally, we applied DEB parameters to time-series data on biological traits (organism condition, gonad growth) to describe the effect of a

  7. NOVEL POLYPHENOLS THAT INHIBIT COLON CANCER CELL GROWTH AFFECTING CANCER CELL METABOLISM.

    PubMed

    Gomez de Cedron, Marta; Vargas, Teodoro; Madrona, Andres; Jimenez, Aranza; Perez Perez, Maria Jesus; Quintela, Jose Carlos; Reglero, Guillermo; San-Felix, Ana Rosa; Ramirez de Molina, Ana

    2018-06-05

    New series of polyphenols with a hydrophilic galloyl based "head" and a hydrophobic N-acyl "tail", linked through a serinol moiety, have been synthesized and tested against colon cancer cell growth. Our structure activity relationship studies revealed that galloyl moieties are essential for growth inhibition. Moreover, the length of the N-acyl chain is crucial for the activity. Introduction of a (Z) double bond in the acyl chain increased the anti-cancer properties. Our findings demonstrate that 16, the most potent compound within this series, has inhibitory effects on colon cancer cell growth and metabolism (glycolysis and mitochondrial respiration) at the same time that activates AMPK and induces apoptotic cell death. Based on these results we propose that 16 might reprogram colon cancer cell metabolism through AMPK activation. This might lead to alterations on cancer cell bioenergy compromising cancer cell viability. Importantly, these anti-proliferative and pro-apoptotic effects are selective for cancer cells. Accordingly, these results indicate that 16, with an unsaturated C18 chain, might be a useful prototype for the development of novel colon cancer cell growth inhibitors affecting cell metabolism. The American Society for Pharmacology and Experimental Therapeutics.

  8. The metabolic burden of sleep loss.

    PubMed

    Schmid, Sebastian M; Hallschmid, Manfred; Schultes, Bernd

    2015-01-01

    In parallel with the increasing prevalence of obesity and type 2 diabetes, sleep loss has become common in modern societies. An increasing number of epidemiological studies show an association between short sleep duration, sleep disturbances, and circadian desynchronisation of sleep with adverse metabolic traits, in particular obesity and type 2 diabetes. Furthermore, experimental studies point to distinct mechanisms by which insufficient sleep adversely affects metabolic health. Changes in the activity of neuroendocrine systems seem to be major mediators of the detrimental metabolic effects of insufficient sleep, through favouring neurobehavioural outcomes such as increased appetite, enhanced sensitivity to food stimuli, and, ultimately, a surplus in energy intake. The effect of curtailed sleep on physical activity and energy expenditure is less clear, but changes are unlikely to outweigh increases in food intake. Although long-term interventional studies proving a cause and effect association are still scarce, sleep loss seems to be an appealing target for the prevention, and probably treatment, of metabolic disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Effects of dietary history on energy metabolism and physiological parameters in C57BL/6J mice.

    PubMed

    Hoevenaars, Femke P M; Keijer, Jaap; Swarts, Hans J; Snaas-Alders, Sophie; Bekkenkamp-Grovenstein, Melissa; van Schothorst, Evert M

    2013-05-01

    Understanding body weight regulation is essential to fight obesity. Mouse studies, using different types of diets, showed conflicting results in terms of body weight persistence after changing from an ad libitum high-fat diet to an ad libitum low-fat diet. In this study, we questioned specifically whether the energy content of the diet has a lasting effect on energy balance and body weight, using multiple switches and two purified diets with a different fat-to-sugar ratio, but otherwise identical ingredients. Young-adult obesity-prone male C57BL/6J mice were fed single or double switches of semi-purified diets with either 10 energy % (en%) fat (LF) or 40en% fat (HF), with starch replaced by fat, while protein content remained equal. After none, one or two dietary changes, energy metabolism was assessed at 5, 14 and 19 weeks. We observed no systematic continuous compensation in diet and energy intake when returning to LF after HF consumption. Body weight, white adipose tissue mass and histology, serum metabolic parameters, energy expenditure and substrate usage all significantly reflected the current diet intake, independent of dietary changes. This contrasts with studies that used diets with different ingredients and showed persistent effects of dietary history on body weight, suggesting diet-dependent metabolic set points. We conclude that body weight and metabolic parameters 'settle', based on current energetic input and output. This study also highlights the importance of considering the choice of diet in physiological and metabolic intervention studies.

  10. Inbreeding, energy use and condition.

    PubMed

    Ketola, T; Kotiaho, J S

    2009-04-01

    In energetic terms, fitness may be seen to be dependent on successful allocation of energy between life-history traits. In addition, fitness will be constrained by the energy allocation ability, which has also been defined as condition. We suggest here that the allocation ability, estimated as the difference between total energy budget and maintenance metabolism, may be used as a measure of condition. We studied this possibility by measuring the resting metabolic rate and metabolism during forced exercise in Gryllodes sigillatus crickets. To verify that these metabolic traits are closely related to fitness, we experimentally manipulated the degree of inbreeding of individuals belonging to the same pedigree, hence enabling analysis of both inbreeding depression and heritability of traits. We found that inbreeding increased maintenance metabolism, whereas total energy budget was rather insensitive to inbreeding. Despite this, inbreeding led to decreased allocation ability. Overall, metabolic traits exhibited strong inbreeding depression and rather low heritabilities, a pattern that is typical of traits under strong selection. However, traditionally used condition indices were not affected by inbreeding and did not covary with metabolic traits. Moreover, in contrast to the common, but largely untested, tenet, it seems that high resting metabolic rate is indicative of low rather than high quality.

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

    PubMed

    Petersen, Ann M; Gleeson, Todd T

    2011-09-01

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

  12. Mass-Specific Metabolic Rate Influences Sperm Performance through Energy Production in Mammals

    PubMed Central

    Tourmente, Maximiliano; Roldan, Eduardo R. S.

    2015-01-01

    Mass-specific metabolic rate, the rate at which organisms consume energy per gram of body weight, is negatively associated with body size in metazoans. As a consequence, small species have higher cellular metabolic rates and are able to process resources at a faster rate than large species. Since mass-specific metabolic rate has been shown to constrain evolution of sperm traits, and most of the metabolic activity of sperm cells relates to ATP production for sperm motility, we hypothesized that mass-specific metabolic rate could influence sperm energetic metabolism at the cellular level if sperm cells maintain the metabolic rate of organisms that generate them. We compared data on sperm straight-line velocity, mass-specific metabolic rate, and sperm ATP content from 40 mammalian species and found that the mass-specific metabolic rate positively influences sperm swimming velocity by (a) an indirect effect of sperm as the result of an increased sperm length, and (b) a direct effect independent of sperm length. In addition, our analyses show that species with higher mass-specific metabolic rate have higher ATP content per sperm and higher concentration of ATP per μm of sperm length, which are positively associated with sperm velocity. In conclusion, our results suggest that species with high mass-specific metabolic rate have been able to evolve both long and fast sperm. Moreover, independently of its effect on the production of larger sperm, the mass-specific metabolic rate is able to influence sperm velocity by increasing sperm ATP content in mammals. PMID:26371474

  13. Rewiring carbohydrate catabolism differentially affects survival of pancreatic cancer cell lines with diverse metabolic profiles

    PubMed Central

    Tataranni, Tiziana; Agriesti, Francesca; Ruggieri, Vitalba; Mazzoccoli, Carmela; Simeon, Vittorio; Laurenzana, Ilaria; Scrima, Rosella; Pazienza, Valerio; Capitanio, Nazzareno; Piccoli, Claudia

    2017-01-01

    An increasing body of evidence suggests that targeting cellular metabolism represents a promising effective approach to treat pancreatic cancer, overcome chemoresistance and ameliorate patient's prognosis and survival. In this study, following whole-genome expression analysis, we selected two pancreatic cancer cell lines, PANC-1 and BXPC-3, hallmarked by distinct metabolic profiles with specific concern to carbohydrate metabolism. Functional comparative analysis showed that BXPC-3 displayed a marked deficit of the mitochondrial respiratory and oxidative phosphorylation activity and a higher production of reactive oxygen species and a reduced NAD+/NADH ratio, indicating their bioenergetic reliance on glycolysis and a different redox homeostasis as compared to PANC-1. Both cell lines were challenged to rewire their metabolism by substituting glucose with galactose as carbon source, a condition inhibiting the glycolytic flux and fostering full oxidation of the sugar carbons. The obtained data strikingly show that the mitochondrial respiration-impaired-BXPC-3 cell line was unable to sustain the metabolic adaptation required by glucose deprivation/substitution, thereby resulting in a G2\\M cell cycle shift, unbalance of the redox homeostasis, apoptosis induction. Conversely, the mitochondrial respiration-competent-PANC-1 cell line did not show clear evidence of cell sufferance. Our findings provide a strong rationale to candidate metabolism as a promising target for cancer therapy. Defining the metabolic features at time of pancreatic cancer diagnosis and likely of other tumors, appears to be crucial to predict the responsiveness to therapeutic approaches or coadjuvant interventions affecting metabolism. PMID:28476035

  14. Metabolic consequences of physical inactivity.

    PubMed

    Biolo, Gianni; Ciocchi, Beniamino; Stulle, Manuela; Piccoli, Arianna; Lorenzon, Stefania; Dal Mas, Viviana; Barazzoni, Rocco; Zanetti, Michela; Guarnieri, Gianfranco

    2005-01-01

    Physical inactivity is associated with alteration of normal physiologic processes leading to muscle atrophy, reduced exercise capacity, insulin resistance, and altered energy balance. Bed rest studies in human beings using stable isotopes of amino acids indicate that muscle unloading decreases the turnover rates of muscle and whole-body proteins, with a prevailing inhibition of protein synthesis. In the fasting state, muscle and whole-body nitrogen loss was not accelerated during bed rest. In experimental postprandial states, the amino acid-mediated stimulation of protein synthesis was impaired, whereas the ability of combined insulin and glucose infusion to decrease whole-body proteolysis was not affected by muscle inactivity. Thus, an impaired ability of protein/amino acid feeding to stimulate body protein synthesis is the major catabolic mechanism for the effect of bed rest on protein metabolism. This suggests that a protein intake level greater than normal could be required to achieve the same postprandial anabolic effect during muscle inactivity. Metabolic adaptation to muscle inactivity also involves development of resistance to the glucoregulatory action of insulin, decreased energy requirements, and increased insulin and leptin secretion. These alterations may lead to the development of the metabolic syndrome that is defined as the association of hyperinsulinemia, dyslipidemia, hypertension, hyperglycemia, and abdominal obesity. This cluster of metabolic abnormalities is a risk factor for coronary artery disease and stroke. Evidence indicates that exercise training programs may counteract all of these abnormalities both in healthy sedentary subjects and in patients affected by a variety of chronic disease states.

  15. Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism.

    PubMed

    Ikizler, T Alp; Cano, Noel J; Franch, Harold; Fouque, Denis; Himmelfarb, Jonathan; Kalantar-Zadeh, Kamyar; Kuhlmann, Martin K; Stenvinkel, Peter; TerWee, Pieter; Teta, Daniel; Wang, Angela Yee-Moon; Wanner, Christoph

    2013-12-01

    Protein energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes, especially in individuals receiving maintenance dialysis therapy. A multitude of factors can affect the nutritional and metabolic status of CKD patients requiring a combination of therapeutic maneuvers to prevent or reverse protein and energy depletion. These include optimizing dietary nutrient intake, appropriate treatment of metabolic disturbances such as metabolic acidosis, systemic inflammation, and hormonal deficiencies, and prescribing optimized dialytic regimens. In patients where oral dietary intake from regular meals cannot maintain adequate nutritional status, nutritional supplementation, administered orally, enterally, or parenterally, is shown to be effective in replenishing protein and energy stores. In clinical practice, the advantages of oral nutritional supplements include proven efficacy, safety, and compliance. Anabolic strategies such as anabolic steroids, growth hormone, and exercise, in combination with nutritional supplementation or alone, have been shown to improve protein stores and represent potential additional approaches for the treatment of PEW. Appetite stimulants, anti-inflammatory interventions, and newer anabolic agents are emerging as novel therapies. While numerous epidemiological data suggest that an improvement in biomarkers of nutritional status is associated with improved survival, there are no large randomized clinical trials that have tested the effectiveness of nutritional interventions on mortality and morbidity.

  16. Whey Protein Components - Lactalbumin and Lactoferrin - Improve Energy Balance and Metabolism.

    PubMed

    Zapata, Rizaldy C; Singh, Arashdeep; Pezeshki, Adel; Nibber, Traj; Chelikani, Prasanth K

    2017-08-30

    Whey protein promotes weight loss and improves diabetic control, however, less is known of its bioactive components that produce such benefits. We compared the effects of normal protein (control) diet with high protein diets containing whey, or its fractions lactalbumin and lactoferrin, on energy balance and metabolism. Diet-induced obese rats were randomized to isocaloric diets: Control, Whey, Lactalbumin, Lactoferrin, or pair-fed to lactoferrin. Whey and lactalbumin produced transient hypophagia, whereas lactoferrin caused prolonged hypophagia; the hypophagia was likely due to decreased preference. Lactalbumin decreased weight and fat gain. Notably, lactoferrin produced sustained weight and fat loss, and attenuated the reduction in energy expenditure associated with calorie restriction. Lactalbumin and lactoferrin decreased plasma leptin and insulin, and lactalbumin increased peptide YY. Whey, lactalbumin and lactoferrin improved glucose clearance partly through differential upregulation of glucoregulatory transcripts in the liver and skeletal muscle. Interestingly, lactalbumin and lactoferrin decreased hepatic lipidosis partly through downregulation of lipogenic and/or upregulation of β-oxidation transcripts, and differentially modulated cecal bacterial populations. Our findings demonstrate that protein quantity and quality are important for improving energy balance. Dietary lactalbumin and lactoferrin improved energy balance and metabolism, and decreased adiposity, with the effects of lactoferrin being partly independent of caloric intake.

  17. Genotype by energy expenditure interaction with metabolic syndrome traits: the Portuguese healthy family study.

    PubMed

    Santos, Daniel M V; Katzmarzyk, Peter T; Diego, Vincent P; Souza, Michele C; Chaves, Raquel N; Blangero, John; Maia, José A R

    2013-01-01

    Moderate-to-high levels of physical activity are established as preventive factors in metabolic syndrome development. However, there is variability in the phenotypic expression of metabolic syndrome under distinct physical activity conditions. In the present study we applied a Genotype X Environment interaction method to examine the presence of GxEE interaction in the phenotypic expression of metabolic syndrome. A total of 958 subjects, from 294 families of The Portuguese Healthy Family study, were included in the analysis. Total daily energy expenditure was assessed using a 3 day physical activity diary. Six metabolic syndrome related traits, including waist circumference, systolic blood pressure, glucose, HDL cholesterol, total cholesterol and triglycerides, were measured and adjusted for age and sex. GxEE examination was performed on SOLAR 4.3.1. All metabolic syndrome indicators were significantly heritable. The GxEE interaction model fitted the data better than the polygenic model (p<0.001) for waist circumference, systolic blood pressure, glucose, total cholesterol and triglycerides. For waist circumference, glucose, total cholesterol and triglycerides, the significant GxEE interaction was due to rejection of the variance homogeneity hypothesis. For waist circumference and glucose, GxEE was also significant by the rejection of the genetic correlation hypothesis. The results showed that metabolic syndrome traits expression is significantly influenced by the interaction established between total daily energy expenditure and genotypes. Physical activity may be considered an environmental variable that promotes metabolic differences between individuals that are distinctively active.

  18. 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

  19. Secondary metabolism and interspecific competition affect accumulation of spontaneous mutants in the GacS-GacA regulatory system in Pseudomonas protegens

    USDA-ARS?s Scientific Manuscript database

    Secondary metabolites are synthesized by many microorganisms and provide a fitness benefit in the presence of competitors and predators. Secondary metabolism also can be costly, as it shunts energy and intermediates from primary metabolism. In Pseudomonas spp., secondary metabolism is controlled by ...

  20. Metabolic plasticity and the energy economizing effect of ibogaine, the principal alkaloid of Tabernanthe iboga.

    PubMed

    Paškulin, Roman; Jamnik, Polona; Danevčič, Tjaša; Koželj, Gordana; Krašovec, Rok; Krstić-Milošević, Dijana; Blagojević, Duško; Strukelj, Borut

    2012-08-30

    The root bark of iboga plant-Tabernanthe iboga has been used traditionally in Central Africa as a psychoactive substance in religious rituals, while in smaller doses it is appreciated due to its stimulant properties. The iboga root bark, iboga extract or pure ibogaine are being recognized in the West as an anti-addiction remedy and their use is increasing. Our previous studies have demonstrated a transient ATP pool reduction under ibogaine accompanied by the induction of energy metabolism related enzymes. The present study aimed to find the cause of this energy deprivation and to foresee its immediate and long-term impact on metabolism. The overall project is designed to disclose the common mechanism of action at these seemingly diverse indications for iboga use, to predict eventual adverse effects and to build the grounds for its safe and beneficial utilization. The rate of carbon dioxide (CO(2)) as a marker of energy metabolism in stationary yeast model under aerobic conditions in the presence of ibogaine at concentration of 1, 4 and 20mg/l was measured for 5h by gas chromatography. The overall oxidative load was determined fluorimetrically by 2',7'-dichlorofluorescein diacetate (H(2)DCFDA) and in vitro antioxidant properties of ibogaine were defined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) test. The CO(2) production under ibogaine was temporarily increased in a dose dependent manner. The increased energy consumption as an early effect of ibogaine was proven by the fact that in spite of energy mobilization, the ATP pool has been simultaneously decreased. Although increased cellular respiration co-produces reactive oxygen species (ROS), the overall oxidative load was significantly lowered by ibogaine. Since ibogaine does not show any significant in vitro antioxidant properties, the results indicate its stimulating influence on physiological oxidative stress defence system. Ibogaine triggers remodeling of the housekeeping metabolism. Under the initial energy cost it

  1. Acidosis, but Not Alkalosis, Affects Anaerobic Metabolism and Performance in a 4-km Time Trial.

    PubMed

    Correia-Oliveira, Carlos Rafaell; Lopes-Silva, João Paulo; Bertuzzi, Romulo; McConell, Glenn K; Bishop, David John; Lima-Silva, Adriano Eduardo; Kiss, Maria Augusta Peduti Dal'molin

    2017-09-01

    This study aimed to determine the effect of preexercise metabolic acidosis and alkalosis on power output (PO) and aerobic and anaerobic energy expenditure during a 4-km cycling time trial (TT). Eleven recreationally trained cyclists (V˙O2peak 54.1 ± 9.3 mL·kg·min) performed a 4-km TT 100 min after ingesting in a double-blind matter 0.15 g·kg of body mass of ammonium chloride (NH4Cl, acidosis), 0.3 g·kg of sodium bicarbonate (NaHCO3, alkalosis), or 0.15 g·kg of CaCO3 (placebo). A preliminary study (n = 7) was conducted to establish the optimal doses to promote the desirable preexercise blood pH alterations without gastrointestinal distress. Data for PO, aerobic and anaerobic energy expenditure, and blood and respiratory parameters were averaged for each 1 km and compared between conditions using two-way repeated-measures ANOVA (condition and distance factors). Gastrointestinal discomfort was analyzed qualitatively. Compared with placebo (pH 7.37 ± 0.02, [HCO3]: 27.5 ± 2.6 mmol·L), the NaHCO3 ingestion resulted in a preexercise blood alkalosis (pH +0.06 ± 0.04, [HCO3]: +4.4 ± 2.0 mmol·L, P < 0.05), whereas NH4Cl resulted in a blood acidosis (pH -0.05 ± 0.03, [HCO3]: -4.8 ± 2.1 mmol·L, P < 0.05). Anaerobic energy expenditure rate and PO were reduced throughout the trial in NH4Cl compared with placebo and NaHCO3, resulting in a lower total anaerobic work and impaired performance (P < 0.05). Plasma lactate, V˙CO2, and end-tidal CO2 partial pressure were lower and the V˙E/V˙CO2 higher throughout the trial in NH4Cl compared with placebo and NaHCO3 (P < 0.05). There was no difference between NaHCO3 and placebo for any of these variables (P > 0.05). Minimal gastrointestinal distress was noted in all conditions. Preexercise acidosis, but not alkalosis, affects anaerobic metabolism and PO during a 4-km cycling TT.

  2. Do fatty acids affect fetal programming?

    PubMed

    Kabaran, Seray; Besler, H Tanju

    2015-08-13

    In this study discussed the primary and regulatory roles of fatty acids, and investigated the affects of fatty acids on metabolic programming. Review of the literature was carried out on three electronic databases to assess the roles of fatty acids in metabolic programming. All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review. The mother's nutritional environment during fetal period has important effects on long term health. Fatty acids play a primary role in growth and development. Alterations in fatty acid intake in the fetal period may increase the risk of obesity and metabolic disorders in later life. Maternal fatty acid intakes during pregnancy and lactation are passed to the fetus and the newborn via the placenta and breast milk, respectively. Imbalances in fatty acid intake during the fetal period change the fatty acid composition of membrane phospholipids, which can cause structural and functional problems in cells. Additionally, the metabolic and neuroendocrine environments of the fetus and the newborn play key roles in the regulation of energy balance. Imbalances in fatty acid intake during pregnancy and lactation may result in permanent changes in appetite control, neuroendocrine function and energy metabolism in the fetus, leading to metabolic programming. Further studies are needed to determine the role of fatty acid intake in metabolic programming.

  3. Effects of subacute ingestion of chlorogenic acids on sleep architecture and energy metabolism through activity of the autonomic nervous system: a randomised, placebo-controlled, double-blinded cross-over trial.

    PubMed

    Park, Insung; Ochiai, Ryuji; Ogata, Hitomi; Kayaba, Momoko; Hari, Sayaka; Hibi, Masanobu; Katsuragi, Yoshihisa; Satoh, Makoto; Tokuyama, Kumpei

    2017-04-01

    Chlorogenic acids (CGA) are the most abundant polyphenols in coffee. Continuous consumption of CGA reduces body fat and body weight. Since energy metabolism and sleep are controlled by common regulatory factors, consumption of CGA might modulate sleep. Lack of sleep has been identified as a risk factor for obesity, hypertension and type 2 diabetes. The aim of this study was to determine the effects of ingesting CGA over 5 d on energy metabolism and sleep quality in humans. A total of nine healthy subjects (four male and five female) completed a placebo-controlled, double-blinded, cross-over intervention study. Subjects consumed a test beverage containing 0 or 600 mg of CGA for 5 d. On the fifth night, subjects stayed in a whole-room metabolic chamber to measure energy metabolism; sleep was evaluated using polysomnographic recording. It was found that CGA shortened sleep latency (9 (sem 2) v. 16 (sem 4) min, P<0·05) compared with the control, whereas no effect on sleep architecture, such as slow-wave sleep, rapid eye movement or waking after sleep onset, was observed. Indirect calorimetry revealed that consumption of CGA increased fat oxidation (510 (sem 84) kJ/8 h (122 (sem 20) kcal/8 h) v. 331 (sem 79) kJ/8 h (81 (sem 19) kcal/8 h), P<0·05) but did not affect energy expenditure during sleep. Consumption of CGA enhanced parasympathetic activity assessed from heart-rate variability during sleep (999 (sem 77) v. 919 (sem 54), P<0·05). A period of 5-d CGA consumption significantly increased fat oxidation during sleep, suggesting that beverages containing CGA may be beneficial to reduce body fat and prevent obesity. Consumption of CGA shortened sleep latency and did not adversely affect sleep quality.

  4. Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer's Disease.

    PubMed

    Croteau, Etienne; Castellano, Christian-Alexandre; Richard, Marie Anne; Fortier, Mélanie; Nugent, Scott; Lepage, Martin; Duchesne, Simon; Whittingstall, Kevin; Turcotte, Éric E; Bocti, Christian; Fülöp, Tamàs; Cunnane, Stephen C

    2018-06-09

    In Alzheimer's disease (AD), it is unknown whether the brain can utilize additional ketones as fuel when they are derived from a medium chain triglyceride (MCT) supplement. To assess whether brain ketone uptake in AD increases in response to MCT as it would in young healthy adults. Mild-moderate AD patients sequentially consumed 30 g/d of two different MCT supplements, both for one month: a mixture of caprylic (55%) and capric acids (35%) (n = 11), followed by a wash-out and then tricaprylin (95%; n = 6). Brain ketone (11C-acetoacetate) and glucose (FDG) uptake were quantified by PET before and after each MCT intervention. Brain ketone consumption doubled on both types of MCT supplement. The slope of the relationship between plasma ketones and brain ketone uptake was the same as in healthy young adults. Both types of MCT increased total brain energy metabolism by increasing ketone supply without affecting brain glucose utilization. Ketones from MCT compensate for the brain glucose deficit in AD in direct proportion to the level of plasma ketones achieved.

  5. Breeding of D(-)-lactic acid high producing strain by low-energy ion implantation and preliminary analysis of related metabolism.

    PubMed

    Xu, Ting-Ting; Bai, Zhong-Zhong; Wang, Li-Juan; He, Bing-Fang

    2010-01-01

    The low-energy nitrogen ion beam implantation technique was used in the breeding of mutant D(-)-lactic-acid-producing strains. The wild strain Sporolactobacillus sp. DX12 was mutated by an N(+) ion beam with energy of 10keV and doses ranging from 0.4 x 10(15) to 6.60 x 10(15) ions/cm(2). Combined with an efficient screening method, an efficient mutant Y2-8 was selected after two times N(+) ion beam implantation. By using the mutant Y2-8, 121.6g/l of D-lactic acid was produced with the molar yields of 162.1% to the glucose. The yield of D-lactic acid by strain Y2-8 was 198.8% higher than the wild strain. Determination of anaerobic metabolism by Biolog MT2 was used to analyze the activities of the concerned enzymes in the lactic acid metabolic pathway. The results showed that the activities of the key enzymes responded on the substrates such as 6-phosphofructokinase, pyruvate kinase, and D-lactate dehydrogenase were considerably higher in the mutants than the wild strain. These might be affected by ion beam implantation.

  6. Elevated temperature and acclimation time affect metabolic performance in the heavily exploited Nile perch of Lake Victoria.

    PubMed

    Nyboer, Elizabeth A; Chapman, Lauren J

    2017-10-15

    Increasing water temperatures owing to anthropogenic climate change are predicted to negatively impact the aerobic metabolic performance of aquatic ectotherms. Specifically, it has been hypothesized that thermal increases result in reductions in aerobic scope (AS), which lead to decreases in energy available for essential fitness and performance functions. Consequences of warming are anticipated to be especially severe for warm-adapted tropical species as they are thought to have narrow thermal windows and limited plasticity for coping with elevated temperatures. In this study we test how predicted warming may affect the aerobic performance of Nile perch ( Lates niloticus ), a commercially harvested fish species in the Lake Victoria basin of East Africa. We measured critical thermal maxima (CT max ) and key metabolic variables such as AS and excess post-exercise oxygen consumption (EPOC) across a range of temperatures, and compared responses between acute (3-day) exposures and 3-week acclimations. CT max increased with acclimation temperature; however, 3-week-acclimated fish had higher overall CT max than acutely exposed individuals. Nile perch also showed the capacity to increase or maintain high AS even at temperatures well beyond their current range; however, acclimated Nile perch had lower AS compared with acutely exposed fish. These changes were accompanied by lower EPOC, suggesting that drops in AS may reflect improved energy utilization after acclimation, a finding that is supported by improvements in growth at high temperatures over the acclimation period. Overall, the results challenge predictions that tropical species have limited thermal plasticity, and that high temperatures will be detrimental because of limitations in AS. © 2017. Published by The Company of Biologists Ltd.

  7. Effects of energy-dense nutrient-poor snacks on the incidence of metabolic syndrome: a prospective approach in Tehran Lipid and Glucose Study.

    PubMed

    Mirmiran, Parvin; Bahadoran, Zahra; Delshad, Hossein; Azizi, Fereidoun

    2014-05-01

    Increased consumption of energy-dense, nutrient-poor snacks is one of the major, growing concerns in relation to the alarming trend of overweight, obesity, and metabolic disorders worldwide. The aim of this study was to investigate whether consumption of energy-dense snacks could affect the occurrence of metabolic syndrome after 3 y of follow-up in adults. This longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study between 2006 and 2008 and 2009 and 2011, on 1466 adults, ages 19 to 70 y. The usual intake of participants was measured using a validated semiquantitative food frequency questionnaire at baseline. Biochemical and anthropometric measurements were assessed at baseline and 3 y later. Multiple logistic regression models were used to estimate the occurrence of metabolic syndrome (MetS) in each quartile of energy-dense snacks. Participants in the highest quartile of energy-dense snack consumption were significantly younger (33.8 versus 43.1 y; P < 0.01). There were non-significant increased risks for MetS in the highest quartile of biscuits and cakes (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.77-1.66), and candies and chocolates (OR, 1.31; 95% CI, 0.88-1.94). The risk for MetS in participants with highest consumption of salty snacks increased more than 50% (OR, 1.56; 95% CI, 1.01-2.40). Consumption of soft drinks had a borderline effect on the risk for MetS. More than 361 kcal/d from total energy-dense snacks independently increased the occurrence of MetS in the fourth compared the first quartile category (OR, 1.53; 95% CI, 1.03-2.29). The findings of this study demonstrated that higher consumption of energy-dense snacks could be a dietary risk factor for development of MetS. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Effects of a nonnutritive sweetener on body adiposity and energy metabolism in mice with diet-induced obesity.

    PubMed

    Mitsutomi, Kimihiko; Masaki, Takayuki; Shimasaki, Takanobu; Gotoh, Koro; Chiba, Seiichi; Kakuma, Tetsuya; Shibata, Hirotaka

    2014-01-01

    Nonnutritive sweeteners (NNSs) have been studied in terms of their potential roles in type 2 diabetes, obesity, and related metabolic disorders. Several studies have suggested that NNSs have several specific effects on metabolism such as reduced postprandial hyperglycemia and insulin resistance. However, the detailed effects of NNSs on body adiposity and energy metabolism have not been fully elucidated. We investigated the effects of an NNS on energy metabolism in mice with diet-induced obesity (DIO). DIO mice were divided into NNS-administered (4% NNS in drinking water), sucrose-administered (33% sucrose in drinking water), and control (normal water) groups. After supplementation for 4 weeks, metabolic parameters, including uncoupling protein (UCP) levels and energy expenditure, were assessed. Sucrose supplementation increased hyperglycemia, body adiposity, and body weight compared to the NNS-administered and control groups (P<0.05 for each). In addition, NNS supplementation decreased hyperglycemia compared to the sucrose-administered group (P<0.05). Interestingly, NNS supplementation increased body adiposity, which was accompanied by hyperinsulinemia, compared to controls (P<0.05 for each). NNS also increased leptin levels in white adipose tissue and triglyceride levels in tissues compared to controls (P<0.05 for each). Notably, compared to controls, NNS supplementation decreased the UCP1 level in brown adipose tissue and decreased O2 consumption in the dark phase. NNSs may be good sugar substitutes for people with hyperglycemia, but appear to influence energy metabolism in DIO mice. © 2013.

  9. Diet and cognition: interplay between cell metabolism and neuronal plasticity.

    PubMed

    Gomez-Pinilla, Fernando; Tyagi, Ethika

    2013-11-01

    To discuss studies in humans and animals revealing the ability of foods to benefit the brain: new information with regards to mechanisms of action and the treatment of neurological and psychiatric disorders. Dietary factors exert their effects on the brain by affecting molecular events related to the management of energy metabolism and synaptic plasticity. Energy metabolism influences neuronal function, neuronal signaling, and synaptic plasticity, ultimately affecting mental health. Epigenetic regulation of neuronal plasticity appears as an important mechanism by which foods can prolong their effects on long-term neuronal plasticity. The prime focus of the discussion is to emphasize the role of cell metabolism as a mediator for the action of foods on the brain. Oxidative stress promotes damage to phospholipids present in the plasma membrane such as the omega-3 fatty acid docosahexenoic acid, disrupting neuronal signaling. Thus, dietary docosahexenoic acid seems crucial for supporting plasma membrane function, interneuronal signaling, and cognition. The dual action of brain-derived neurotrophic factor in neuronal metabolism and synaptic plasticity is crucial for activating signaling cascades under the action of diet and other environmental factors, using mechanisms of epigenetic regulation.

  10. Diet and cognition: interplay between cell metabolism and neuronal plasticity

    PubMed Central

    Gomez-Pinilla, Fernando; Tyagi, Ethika

    2014-01-01

    Purpose of Study To discuss studies in humans and animals revealing the ability of foods to benefit the brain: new information with regards to mechanisms of action and the treatment of neurological and psychiatric disorders. Recent Findings Dietary factors exert their effects on the brain by affecting molecular events related to the management of energy metabolism and synaptic plasticity. Energy metabolism influences neuronal function, neuronal signaling, and synaptic plasticity, ultimately affecting mental health. Epigenetic regulation of neuronal plasticity appears as an important mechanism by which foods can prolong their effects on long term neuronal plasticity. Summary The prime focus of the discussion is to emphasize the role of cell metabolism as a mediator for the action of foods on the brain. Oxidative stress promotes damage to phospholipids present in the plasma membrane such as the omega-3 fatty acid DHA, disrupting neuronal signaling. Thus, dietary DHA seems crucial for supporting plasma membrane function, interneuronal signaling, and cognition. The dual action of brain-derived neurotrophic factor (BDNF) in neuronal metabolism and synaptic plasticity is crucial for activating signaling cascades under the action of diet and other environmental factors, using mechanisms of epigenetic regulation. PMID:24071781

  11. Differential expression of alternatively spliced transcripts related to energy metabolism in colorectal cancer.

    PubMed

    Snezhkina, Anastasiya Vladimirovna; Krasnov, George Sergeevich; Zaretsky, Andrew Rostislavovich; Zhavoronkov, Alex; Nyushko, Kirill Mikhailovich; Moskalev, Alexey Alexandrovich; Karpova, Irina Yurievna; Afremova, Anastasiya Isaevna; Lipatova, Anastasiya Valerievna; Kochetkov, Dmitriy Vladimitovich; Fedorova, Maria Sergeena; Volchenko, Nadezhda Nikolaevna; Sadritdinova, Asiya Fayazovna; Melnikova, Nataliya Vladimirovna; Sidorov, Dmitry Vladimirovich; Popov, Anatoly Yurievich; Kalinin, Dmitry Valerievich; Kaprin, Andrey Dmitrievich; Alekseev, Boris Yakovlevich; Dmitriev, Alexey Alexandrovich; Kudryavtseva, Anna Viktorovna

    2016-12-28

    Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. CRC molecular pathogenesis is heterogeneous and may be followed by mutations in oncogenes and tumor suppressor genes, chromosomal and microsatellite instability, alternative splicing alterations, hypermethylation of CpG islands, oxidative stress, impairment of different signaling pathways and energy metabolism. In the present work, we have studied the alterations of alternative splicing patterns of genes related to energy metabolism in CRC. Using CrossHub software, we analyzed The Cancer Genome Atlas (TCGA) RNA-Seq datasets derived from colon tumor and matched normal tissues. The expression of 1014 alternative mRNA isoforms involved in cell energy metabolism was examined. We found 7 genes with differentially expressed alternative transcripts whereas overall expression of these genes was not significantly altered in CRC. A set of 8 differentially expressed transcripts of interest has been validated by qPCR. These eight isoforms encoded by OGDH, COL6A3, ICAM1, PHPT1, PPP2R5D, SLC29A1, and TRIB3 genes were up-regulated in colorectal tumors, and this is in concordance with the bioinformatics data. The alternative transcript NM_057167 of COL6A3 was also strongly up-regulated in breast, lung, prostate, and kidney tumors. Alternative transcript of SLC29A1 (NM_001078177) was up-regulated only in CRC samples, but not in the other tested tumor types. We identified tumor-specific expression of alternative spliced transcripts of seven genes involved in energy metabolism in CRC. Our results bring new knowledge on alternative splicing in colorectal cancer and suggest a set of mRNA isoforms that could be used for cancer diagnosis and development of treatment methods.

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

    PubMed

    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

    2015-06-19

    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.

  13. Human, donkey and cow milk differently affects energy efficiency and inflammatory state by modulating mitochondrial function and gut microbiota.

    PubMed

    Trinchese, Giovanna; Cavaliere, Gina; Canani, Roberto Berni; Matamoros, Sebastien; Bergamo, Paolo; De Filippo, Chiara; Aceto, Serena; Gaita, Marcello; Cerino, Pellegrino; Negri, Rossella; Greco, Luigi; Cani, Patrice D; Mollica, Maria Pina

    2015-11-01

    Different nutritional components are able, by modulating mitochondrial function and gut microbiota composition, to influence body composition, metabolic homeostasis and inflammatory state. In this study, we aimed to evaluate the effects produced by the supplementation of different milks on energy balance, inflammatory state, oxidative stress and antioxidant/detoxifying enzyme activities and to investigate the role of the mitochondrial efficiency and the gut microbiota in the regulation of metabolic functions in an animal model. We compared the intake of human milk, gold standard for infant nutrition, with equicaloric supplementation of donkey milk, the best substitute for newborns due to its nutritional properties, and cow milk, the primary marketed product. The results showed a hypolipidemic effect produced by donkey and human milk intake in parallel with enhanced mitochondrial activity/proton leakage. Reduced mitochondrial energy efficiency and proinflammatory signals (tumor necrosis factor α, interleukin-1 and lipopolysaccharide levels) were associated with a significant increase of antioxidants (total thiols) and detoxifying enzyme activities (glutathione-S-transferase, NADH quinone oxidoreductase) in donkey- and human milk-treated animals. The beneficial effects were attributable, at least in part, to the activation of the nuclear factor erythroid-2-related factor-2 pathway. Moreover, the metabolic benefits induced by human and donkey milk may be related to the modulation of gut microbiota. In fact, milk treatments uniquely affected the proportions of bacterial phyla and genera, and we hypothesized that the increased concentration of fecal butyrate in human and donkey milk-treated rats was related to the improved lipid and glucose metabolism and detoxifying activities. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Impact of hypothalamic reactive oxygen species in the regulation of energy metabolism and food intake.

    PubMed

    Drougard, Anne; Fournel, Audren; Valet, Philippe; Knauf, Claude

    2015-01-01

    Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites) from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS) as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC) and agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,…), neurotransmitters and nutrients (glucose, lipids,…). The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes. In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders.

  15. How coffee affects metabolic syndrome and its components.

    PubMed

    Baspinar, B; Eskici, G; Ozcelik, A O

    2017-06-21

    Metabolic syndrome, with its increasing prevalence, is becoming a major public health problem throughout the world. Many risk factors including nutrition play a role in the emergence of metabolic syndrome. Of the most-consumed beverages in the world, coffee contains more than 1000 components such as caffeine, chlorogenic acid, diterpenes and trigonelline. It has been proven in many studies that coffee consumption has a positive effect on chronic diseases. In this review, starting from the beneficial effects of coffee on health, the relationship between coffee consumption and metabolic syndrome and its components has been investigated. There are few studies investigating the relationship between coffee and metabolic syndrome, and the existing ones put forward different findings. The factors leading to the differences are thought to stem from coffee variety, the physiological effects of coffee elements, and the nutritional ingredients (such as milk and sugar) added to coffee. It is reported that consumption of coffee in adults up to three cups a day reduces the risk of Type-2 diabetes and metabolic syndrome.

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

    PubMed

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

    2016-02-08

    Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. C282Y-HFE Gene Variant Affects Cholesterol Metabolism in Human Neuroblastoma Cells

    PubMed Central

    Ali-Rahmani, Fatima; Huang, Michael A.; Schengrund, C.-L.; Connor, James R.; Lee, Sang Y.

    2014-01-01

    Although disruptions in the maintenance of iron and cholesterol metabolism have been implicated in several cancers, the association between variants in the HFE gene that is associated with cellular iron uptake and cholesterol metabolism has not been studied. The C282Y-HFE variant is a risk factor for different cancers, is known to affect sphingolipid metabolism, and to result in increased cellular iron uptake. The effect of this variant on cholesterol metabolism and its possible relevance to cancer phenotype was investigated using wild type (WT) and C282Y-HFE transfected human neuroblastoma SH-SY5Y cells. Expression of C282Y-HFE in SH-SY5Y cells resulted in a significant increase in total cholesterol as well as increased transcription of a number of genes involved in its metabolism compared to cells expressing WT-HFE. The marked increase in expression of NPC1L1 relative to that of most other genes, was accompanied by a significant increase in expression of NPC1, a protein that functions in cholesterol uptake by cells. Because inhibitors of cholesterol metabolism have been proposed to be beneficial for treating certain cancers, their effect on the viability of C282Y-HFE neuroblastoma cells was ascertained. C282Y-HFE cells were significantly more sensitive than WT-HFE cells to U18666A, an inhibitor of desmosterol Δ24-reductase the enzyme catalyzing the last step in cholesterol biosynthesis. This was not seen for simvastatin, ezetimibe, or a sphingosine kinase inhibitor. These studies indicate that cancers presenting in carriers of the C282Y-HFE allele might be responsive to treatment designed to selectively reduce cholesterol content in their tumor cells. PMID:24533143

  18. C282Y-HFE gene variant affects cholesterol metabolism in human neuroblastoma cells.

    PubMed

    Ali-Rahmani, Fatima; Huang, Michael A; Schengrund, C-L; Connor, James R; Lee, Sang Y

    2014-01-01

    Although disruptions in the maintenance of iron and cholesterol metabolism have been implicated in several cancers, the association between variants in the HFE gene that is associated with cellular iron uptake and cholesterol metabolism has not been studied. The C282Y-HFE variant is a risk factor for different cancers, is known to affect sphingolipid metabolism, and to result in increased cellular iron uptake. The effect of this variant on cholesterol metabolism and its possible relevance to cancer phenotype was investigated using wild type (WT) and C282Y-HFE transfected human neuroblastoma SH-SY5Y cells. Expression of C282Y-HFE in SH-SY5Y cells resulted in a significant increase in total cholesterol as well as increased transcription of a number of genes involved in its metabolism compared to cells expressing WT-HFE. The marked increase in expression of NPC1L1 relative to that of most other genes, was accompanied by a significant increase in expression of NPC1, a protein that functions in cholesterol uptake by cells. Because inhibitors of cholesterol metabolism have been proposed to be beneficial for treating certain cancers, their effect on the viability of C282Y-HFE neuroblastoma cells was ascertained. C282Y-HFE cells were significantly more sensitive than WT-HFE cells to U18666A, an inhibitor of desmosterol Δ24-reductase the enzyme catalyzing the last step in cholesterol biosynthesis. This was not seen for simvastatin, ezetimibe, or a sphingosine kinase inhibitor. These studies indicate that cancers presenting in carriers of the C282Y-HFE allele might be responsive to treatment designed to selectively reduce cholesterol content in their tumor cells.

  19. Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism.

    PubMed

    Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Nowacki, Przemysław; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

    2015-10-29

    Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, some of which is transported to the neurons. Thus, glycogen from astrocytes functions as a kind of protection against hypoglycemia, ensuring preservation of neuronal function. The neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported in literature. This review goes on to emphasize that while neurons and astrocytes differ in metabolic profile, they interact to form a common metabolic cooperation.

  20. 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

  1. Non-Targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo

    PubMed Central

    Abdullah, Muhammad; Kornegay, Joe N.; Honcoop, Aubree; Parry, Traci L.; Balog-Alvarez, Cynthia J.; Muehlbauer, Michael J.; Newgard, Christopher B.; Patterson, Cam

    2017-01-01

    Background: Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype includes moderate atrophy of the biceps femoris (BF) as compared to unaffected normal dogs, while the long digital extensor (LDE), which functions to flex the tibiotarsal joint and serves as a digital extensor, undergoes the most pronounced atrophy. A recent microarray analysis of GRMD identified alterations in genes associated with lipid metabolism and energy production. Methods: We, therefore, undertook a non-targeted metabolomics analysis of the milder/earlier stage disease GRMD BF muscle versus the more severe/chronic LDE using GC-MS to identify underlying metabolic defects specific for affected GRMD skeletal muscle. Results: Untargeted metabolomics analysis of moderately-affected GRMD muscle (BF) identified eight significantly altered metabolites, including significantly decreased stearamide (0.23-fold of controls, p = 2.89 × 10−3), carnosine (0.40-fold of controls, p = 1.88 × 10−2), fumaric acid (0.40-fold of controls, p = 7.40 × 10−4), lactamide (0.33-fold of controls, p = 4.84 × 10−2), myoinositol-2-phosphate (0.45-fold of controls, p = 3.66 × 10−2), and significantly increased oleic acid (1.77-fold of controls, p = 9.27 × 10−2), glutamic acid (2.48-fold of controls, p = 2.63 × 10−2), and proline (1.73-fold of controls, p = 3.01 × 10−2). Pathway enrichment analysis identified significant enrichment for arginine/proline metabolism (p = 5.88 × 10−4, FDR 4.7 × 10−2), where alterations in L-glutamic acid, proline, and carnosine were found. Additionally, multiple Krebs cycle intermediates were significantly decreased (e.g., malic acid, fumaric acid, citric/isocitric acid, and succinic acid), suggesting that altered energy metabolism may be underlying the observed GRMD BF muscle

  2. Non-Targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo.

    PubMed

    Abdullah, Muhammad; Kornegay, Joe N; Honcoop, Aubree; Parry, Traci L; Balog-Alvarez, Cynthia J; O'Neal, Sara K; Bain, James R; Muehlbauer, Michael J; Newgard, Christopher B; Patterson, Cam; Willis, Monte S

    2017-07-29

    Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype includes moderate atrophy of the biceps femoris (BF) as compared to unaffected normal dogs, while the long digital extensor (LDE), which functions to flex the tibiotarsal joint and serves as a digital extensor, undergoes the most pronounced atrophy. A recent microarray analysis of GRMD identified alterations in genes associated with lipid metabolism and energy production. We, therefore, undertook a non-targeted metabolomics analysis of the milder/earlier stage disease GRMD BF muscle versus the more severe/chronic LDE using GC-MS to identify underlying metabolic defects specific for affected GRMD skeletal muscle. Untargeted metabolomics analysis of moderately-affected GRMD muscle (BF) identified eight significantly altered metabolites, including significantly decreased stearamide (0.23-fold of controls, p = 2.89 × 10 -3 ), carnosine (0.40-fold of controls, p = 1.88 × 10 -2 ), fumaric acid (0.40-fold of controls, p = 7.40 × 10 -4 ), lactamide (0.33-fold of controls, p = 4.84 × 10 -2 ), myoinositol-2-phosphate (0.45-fold of controls, p = 3.66 × 10 -2 ), and significantly increased oleic acid (1.77-fold of controls, p = 9.27 × 10 -2 ), glutamic acid (2.48-fold of controls, p = 2.63 × 10 -2 ), and proline (1.73-fold of controls, p = 3.01 × 10 -2 ). Pathway enrichment analysis identified significant enrichment for arginine/proline metabolism (p = 5.88 × 10 -4 , FDR 4.7 × 10 -2 ), where alterations in L-glutamic acid, proline, and carnosine were found. Additionally, multiple Krebs cycle intermediates were significantly decreased (e.g., malic acid, fumaric acid, citric/isocitric acid, and succinic acid), suggesting that altered energy metabolism may be underlying the observed GRMD BF muscle dysfunction. In contrast, two

  3. AMP-Activated Protein Kinase (AMPK) Regulates Energy Metabolism through Modulating Thermogenesis in Adipose Tissue

    PubMed Central

    Wu, Lingyan; Zhang, Lina; Li, Bohan; Jiang, Haowen; Duan, Yanan; Xie, Zhifu; Shuai, Lin; Li, Jia; Li, Jingya

    2018-01-01

    Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic “brown-like” cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood. To illuminate the effect of adipocyte AMPK on energy metabolism, we generated Adiponectin-Cre-driven adipose tissue-specific AMPK α1/α2 KO mice (AKO). These AKO mice were cold intolerant and their inguinal WAT displayed impaired mitochondrial integrity and biogenesis, and reduced expression of thermogenic markers upon cold exposure. High-fat-diet (HFD)-fed AKO mice exhibited increased adiposity and exacerbated hepatic steatosis and fibrosis and impaired glucose tolerance and insulin sensitivity. Meanwhile, energy expenditure and oxygen consumption were markedly decreased in the AKO mice both in basal conditions and after stimulation with a β3-adrenergic receptor agonist, CL 316,243. In contrast, we found that in HFD-fed obese mouse model, chronic AMPK activation by A-769662 protected against obesity and related metabolic dysfunction. A-769662 alleviated HFD-induced glucose intolerance and reduced body weight gain and WAT expansion. Notably, A-769662 increased energy expenditure and cold tolerance in HFD-fed mice. A-769662 treatment also induced the browning process in the inguinal fat depot of HFD-fed mice. Likewise, A-769662 enhanced thermogenesis in differentiated inguinal stromal vascular fraction (SVF) cells via AMPK signaling pathway. In summary, a lack of adipocyte AMPKα induced thermogenic impairment and obesity in response to cold and nutrient-overload, respectively

  4. Energy metabolism and inflammation in brain aging and Alzheimer's disease.

    PubMed

    Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

    2016-11-01

    The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2 , mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Genetic alterations affecting cholesterol metabolism and human fertility.

    PubMed

    DeAngelis, Anthony M; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle

    2014-11-01

    Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. © 2014 by the Society for the Study of Reproduction, Inc.

  6. Free fatty acid receptors and their role in regulation of energy metabolism.

    PubMed

    Hara, Takafumi; Kimura, Ikuo; Inoue, Daisuke; Ichimura, Atsuhiko; Hirasawa, Akira

    2013-01-01

    The free fatty acid receptor (FFAR) is a G protein-coupled receptor (GPCR) activated by free fatty acids (FFAs), which play important roles not only as essential nutritional components but also as signaling molecules in numerous physiological processes. In the last decade, FFARs have been identified by the GPCR deorphanization strategy derived from the human genome database. To date, several FFARs have been identified and characterized as critical components in various physiological processes. FFARs are categorized according to the chain length of FFA ligands that activate each FFAR; FFA2 and FFA3 are activated by short chain FFAs, GPR84 is activated by medium-chain FFAs, whereas FFA1 and GPR120 are activated by medium- or long-chain FFAs. FFARs appear to act as physiological sensors for food-derived FFAs and digestion products in the gastrointestinal tract. Moreover, they are considered to be involved in the regulation of energy metabolism mediated by the secretion of insulin and incretin hormones and by the regulation of the sympathetic nerve systems, taste preferences, and inflammatory responses related to insulin resistance. Therefore, because FFARs can be considered to play important roles in physiological processes and various pathophysiological processes, FFARs have been targeted in therapeutic strategies for the treatment of metabolic disorders including type 2 diabetes and metabolic syndrome. In this review, we present a summary of recent progress regarding the understanding of their physiological roles in the regulation of energy metabolism and their potential as therapeutic targets.

  7. Mitochondrial energy metabolism of rat hippocampus after treatment with the antidepressants desipramine and fluoxetine.

    PubMed

    Villa, Roberto Federico; Ferrari, Federica; Bagini, Laura; Gorini, Antonella; Brunello, Nicoletta; Tascedda, Fabio

    2017-07-15

    Alterations in mitochondrial functions have been hypothesized to participate in the pathogenesis of depression, because brain bioenergetic abnormalities have been detected in depressed patients by neuroimaging in vivo studies. However, this hypothesis is not clearly demonstrated in experimental studies: some suggest that antidepressants are inhibitors of mitochondrial metabolism, while others observe the opposite. In this study, the effects of 21-day treatment with desipramine (15 mg/kg) and fluoxetine (10 mg/kg) were examined on the energy metabolism of rat hippocampus, evaluating the catalytic activity of regulatory enzymes of mitochondrial energy-yielding metabolic pathways. Because of the micro-heterogeneity of brain mitochondria, we have distinguished between (a) non-synaptic mitochondria (FM) of neuronal perikaryon (post-synaptic compartment) and (b) intra-synaptic light (LM) and heavy (HM) mitochondria (pre-synaptic compartment). Desipramine and fluoxetine changed the catalytic activity of specific enzymes in the different types of mitochondria: (a) in FM, both drugs enhanced cytochrome oxidase and glutamate dehydrogenase, (b) in LM, the overall bioenergetics was unaffected and (c) in HM only desipramine increased malate dehydrogenase and decreased the activities of Electron Transport Chain Complexes. These results integrate the pharmacodynamic features of desipramine and fluoxetine at subcellular level, overcoming the previous conflicting data about the effects of antidepressants on brain energy metabolism, mainly referred to whole brain homogenates or to bulk of cerebral mitochondria. With the differentiation in non-synaptic and intra-synaptic mitochondria, this study demonstrates that desipramine and fluoxetine lead to adjustments in the mitochondrial bioenergetics respect to the energy requirements of pre- and post-synaptic compartments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Changes in Energy Metabolism after Continuous Positive Airway Pressure for Obstructive Sleep Apnea.

    PubMed

    Tachikawa, Ryo; Ikeda, Kaori; Minami, Takuma; Matsumoto, Takeshi; Hamada, Satoshi; Murase, Kimihiko; Tanizawa, Kiminobu; Inouchi, Morito; Oga, Toru; Akamizu, Takashi; Mishima, Michiaki; Chin, Kazuo

    2016-09-15

    Disrupted energy homeostasis in obstructive sleep apnea (OSA) may lead to weight gain. Paradoxically, treating OSA with continuous positive airway pressure (CPAP) may also promote weight gain, although the underlying mechanism remains unclear. To explore the underlying mechanism by which patients with OSA gain weight after CPAP. A comprehensive assessment of energy metabolism was performed in 63 newly diagnosed OSA study participants (51 men; 60.8 ± 10.1 yr; apnea-hypopnea index >20 h(-1)) at baseline, CPAP initiation, and at a 3-month follow-up. Measurements included polysomnography, body weight, body composition, basal metabolic rate (BMR), hormones (norepinephrine, cortisol, leptin, ghrelin, insulin-like growth factor-1), dietary intake, eating behavior, and physical activity. BMR significantly decreased after CPAP (1,584 kcal/d at baseline, 1,561 kcal/d at CPAP initiation, and 1,508 kcal/d at follow-up; P < 0.001), whereas physical activity and total caloric intake did not significantly change. In multivariate regression, baseline apnea-hypopnea index, Δurine norepinephrine, and CPAP adherence were significant predictors of ΔBMR. The weight gainers had higher leptin levels, lower ghrelin levels, and higher eating behavior scores than the non-weight gainers, indicating a positive energy balance and disordered eating behavior among the weight gainers. Among the parameters related to energy metabolism, increased caloric intake was a particularly significant predictor of weight gain. Although a reduction in BMR after CPAP predisposes to a positive energy balance, dietary intake and eating behavior had greater impacts on weight change. These findings highlight the importance of lifestyle modifications combined with CPAP. Clinical trial registered with http://www.umin.ac.jp/english/ (UMIN000012639).

  9. 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…

  10. β-Catenin Knockdown Affects Mitochondrial Biogenesis and Lipid Metabolism in Breast Cancer Cells.

    PubMed

    Vergara, Daniele; Stanca, Eleonora; Guerra, Flora; Priore, Paola; Gaballo, Antonio; Franck, Julien; Simeone, Pasquale; Trerotola, Marco; De Domenico, Stefania; Fournier, Isabelle; Bucci, Cecilia; Salzet, Michel; Giudetti, Anna M; Maffia, Michele

    2017-01-01

    β-catenin plays an important role as regulatory hub in several cellular processes including cell adhesion, metabolism, and epithelial mesenchymal transition. This is mainly achieved by its dual role as structural component of cadherin-based adherens junctions, and as a key nuclear effector of the Wnt pathway. For this dual role, different classes of proteins are differentially regulated via β-catenin dependent mechanisms. Here, we applied a liquid chromatography-mass spectrometry (LC-MS/MS) approach to identify proteins modulated after β-catenin knockdown in the breast cancer cell line MCF-7. We used a label free analysis to compare trypsin-digested proteins from CTR (shCTR) and β-catenin knockout cells (shβcat). This led to the identification of 98 differentially expressed proteins, 53 of them were up-regulated and 45 down-regulated. Loss of β-catenin induced morphological changes and a significant modulation of the expression levels of proteins associated with primary metabolic processes. In detail, proteins involved in carbohydrate metabolism and tricarboxylic acid cycle were found to be down-regulated, whereas proteins associated to lipid metabolism were found up-regulated in shβcat compared to shCTR. A loss of mitochondrial mass and membrane potential was also assessed by fluorescent probes in shβcat cells with respect to the controls. These data are consistent with the reduced expression of transcriptional factors regulating mitochondrial biogenesis detected in shβcat cells. β-catenin driven metabolic reprogramming resulted also in a significant modulation of lipogenic enzyme expression and activity. Compared to controls, β-catenin knockout cells showed increased incorporation of [1- 14 C]acetate and decreased utilization of [U- 14 C]glucose for fatty acid synthesis. Our data highlight a role of β-catenin in the regulation of metabolism and energy homeostasis in breast cancer cells.

  11. Impact of Hypoglycemia on Brain Metabolism During Diabetes.

    PubMed

    Rehni, Ashish K; Dave, Kunjan R

    2018-04-10

    Diabetes is a metabolic disease afflicting millions of people worldwide. A substantial fraction of world's total healthcare expenditure is spent on treating diabetes. Hypoglycemia is a serious consequence of anti-diabetic drug therapy, because it induces metabolic alterations in the brain. Metabolic alterations are one of the central mechanisms mediating hypoglycemia-related functional changes in the brain. Acute, chronic, and/or recurrent hypoglycemia modulate multiple metabolic pathways, and exposure to hypoglycemia increases consumption of alternate respiratory substrates such as ketone bodies, glycogen, and monocarboxylates in the brain. The aim of this review is to discuss hypoglycemia-induced metabolic alterations in the brain in glucose counterregulation, uptake, utilization and metabolism, cellular respiration, amino acid and lipid metabolism, and the significance of other sources of energy. The present review summarizes information on hypoglycemia-induced metabolic changes in the brain of diabetic and non-diabetic subjects and the manner in which they may affect brain function.

  12. 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

  13. Neuropeptide Y and peptide YY: important regulators of energy metabolism.

    PubMed

    Nguyen, Amy D; Herzog, Herbert; Sainsbury, Amanda

    2011-02-01

    An overview of recent developments documenting the neuropeptide Y (NPY) family's role in energy metabolism. Specifically focusing on site-specific functions of NPY and increasing evidence of peptide YY (PYY) as a weight loss therapeutic. Studying the NPY family in hypothalamic nuclei, other than the arcuate and paraventricular nuclei, is a recent shift in metabolic research. NPY overexpression in the dorsomedial hypothalamus increases food intake whereas its ablation in this area reduces hyperphagia and obesity. Similarly, NPY exerts orexigenic effects in the ventromedial nucleus. However, specific arcuate Y2 receptor ablation leads to positive energy balance, suggesting the NPY family demonstrates location-specific functions. Peripherally, dual blockade of cannabinoid and NPY pathways has synergistic effects on weight loss, as does combined administration of PYY3-36 and oxyntomodulin in reducing food intake, perhaps due to the recently discovered role of PYY in mediating intestinal Gpr119 activity and controlling glucose tolerance. Conditional Y receptor knockout models have provided deeper insights on NPY's functions according to location. Further study of PYY appears vital, due to recent evidence of its role in intestinal motility, with exercise positively influencing PYY levels.

  14. Plant species affect colonization patterns and metabolic activity of associated endophytes during phytoremediation of crude oil-contaminated soil.

    PubMed

    Fatima, K; Imran, A; Amin, I; Khan, Q M; Afzal, M

    2016-04-01

    Plants coupled with endophytic bacteria hold great potential for the remediation of polluted environment. The colonization patterns and activity of inoculated endophytes in rhizosphere and endosphere of host plant are among the primary factors that may influence the phytoremediation process. However, these colonization patterns and metabolic activity of the inoculated endophytes are in turn controlled by none other than the host plant itself. The present study aims to determine such an interaction specifically for plant-endophyte systems remediating crude oil-contaminated soil. A consortium (AP) of two oil-degrading endophytic bacteria (Acinetobacter sp. strain BRSI56 and Pseudomonas aeruginosa strain BRRI54) was inoculated to two grasses, Brachiaria mutica and Leptochloa fusca, vegetated in crude oil-contaminated soil. Colonization patterns and metabolic activity of the endophytes were monitored in the rhizosphere and endosphere of the plants. Bacterial augmentation enhanced plant growth and crude oil degradation. Maximum crude oil degradation (78%) was achieved with B. mutica plants inoculated with AP consortium. This degradation was significantly higher than those treatments, where plants and bacteria were used individually or L. fusca and endophytes were used in combination. Moreover, colonization and metabolic activity of the endophytes were higher in the rhizosphere and endosphere of B. mutica than L. fusca. The plant species affected not only colonization pattern and biofilm formation of the inoculated bacteria in the rhizosphere and endosphere of the host plant but also affected the expression of alkane hydroxylase gene, alkB. Hence, the investigation revealed that plant species can affect colonization patterns and metabolic activity of inoculated endophytic bacteria and ultimately the phytoremediation process.

  15. Optimal cycling time trial position models: aerodynamics versus power output and metabolic energy.

    PubMed

    Fintelman, D M; Sterling, M; Hemida, H; Li, F-X

    2014-06-03

    The aerodynamic drag of a cyclist in time trial (TT) position is strongly influenced by the torso angle. While decreasing the torso angle reduces the drag, it limits the physiological functioning of the cyclist. Therefore the aims of this study were to predict the optimal TT cycling position as function of the cycling speed and to determine at which speed the aerodynamic power losses start to dominate. Two models were developed to determine the optimal torso angle: a 'Metabolic Energy Model' and a 'Power Output Model'. The Metabolic Energy Model minimised the required cycling energy expenditure, while the Power Output Model maximised the cyclists׳ power output. The input parameters were experimentally collected from 19 TT cyclists at different torso angle positions (0-24°). The results showed that for both models, the optimal torso angle depends strongly on the cycling speed, with decreasing torso angles at increasing speeds. The aerodynamic losses outweigh the power losses at cycling speeds above 46km/h. However, a fully horizontal torso is not optimal. For speeds below 30km/h, it is beneficial to ride in a more upright TT position. The two model outputs were not completely similar, due to the different model approaches. The Metabolic Energy Model could be applied for endurance events, while the Power Output Model is more suitable in sprinting or in variable conditions (wind, undulating course, etc.). It is suggested that despite some limitations, the models give valuable information about improving the cycling performance by optimising the TT cycling position. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Metabolic Inflexibility: When Mitochondrial Indecision Leads to Metabolic Gridlock

    PubMed Central

    Muoio, Deborah M.

    2016-01-01

    Normal energy metabolism is characterized by periodic shifts in glucose and fat oxidation, as the mitochondrial machinery responsible for carbon combustion switches freely between alternative fuels according to physiological and nutritional circumstances. These transitions in fuel choice are orchestrated by an intricate network of metabolic and cell signaling events that enable exquisite crosstalk and cooperation between competing substrates to maintain energy and glucose homeostasis. By contrast, obesity-related cardiometabolic diseases are increasingly recognized as disorders of metabolic inflexibility, in which nutrient overload and heightened substrate competition result in mitochondrial indecision, impaired fuel switching, and energy dysregulation. This Perspective offers a speculative view on the molecular origins and pathophysiological consequences of metabolic inflexibility. PMID:25480291

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

    USDA-ARS?s Scientific Manuscript database

    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. 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.

  19. Factors affecting wood energy consumption by U.S. households

    Treesearch

    Nianfu Song; Francisco X. Aguilar; Stephen R. Shifley; Michael E. Goerndt

    2012-01-01

    About 23% of energy derived from woody sources in the U.S. was consumed by households, of which 70% was used by households in rural areas in 2005. We investigated factors affecting household-level wood energy consumption in the four continental U.S. regions using data from the U.S. Residential Energy Consumption Survey. To account for a large number of zero...

  20. The glycaemic index values of foods containing fructose are affected by metabolic differences between subjects.

    PubMed

    Wolever, T M S; Jenkins, A L; Vuksan, V; Campbell, J

    2009-09-01

    Glycaemic responses are influenced by carbohydrate absorption rate, type of monosaccharide absorbed and the presence of fat; the effect of some of these factors may be modulated by metabolic differences between subjects. We hypothesized that glycaemic index (GI) values are affected by the metabolic differences between subjects for foods containing fructose or fat, but not for starchy foods. The GI values of white bread (WB), fruit leather (FL) and chocolate-chip cookies (CCC) (representing starch, fructose and fat, respectively) were determined in subjects (n=77) recruited to represent all 16 possible combinations of age (< or =40, >40 years), sex (male, female), ethnicity (Caucasian, non-Caucasian) and body mass index (BMI) (< or =25, >25 kg/m2) using glucose as the reference. At screening, fasting insulin, lipids, c-reactive protein (CRP), aspartate transaminase (AST) and waist circumference (WC) were measured. There were no significant main effects of age, sex, BMI or ethnicity on GI, but there were several food x subject-factor interactions. Different factors affected each food's area under the curve (AUC) and GI. The AUC after oral glucose was related to ethnicity, age and triglycerides (r 2=0.27); after WB to ethnicity, age, triglycerides, sex and CRP (r 2=0.43); after CCC to age and weight (r 2=0.18); and after FL to age and CRP (r 2=0.12). GI of WB was related to ethnicity (r 2=0.12) and of FL to AST, insulin and WC (r 2=0.23); but there were no significant correlations for CCC. The GI values of foods containing fructose might be influenced by metabolic differences between -subjects, whereas the GI of starchy foods might be affected by ethnicity. However, the proportion of variation explained by subject factors is small.

  1. Effect of L-carnitine supplementation on the body carnitine pool, skeletal muscle energy metabolism and physical performance in male vegetarians.

    PubMed

    Novakova, Katerina; Kummer, Oliver; Bouitbir, Jamal; Stoffel, Sonja D; Hoerler-Koerner, Ulrike; Bodmer, Michael; Roberts, Paul; Urwyler, Albert; Ehrsam, Rolf; Krähenbühl, Stephan

    2016-02-01

    More than 95% of the body carnitine is located in skeletal muscle, where it is essential for energy metabolism. Vegetarians ingest less carnitine and carnitine precursors and have lower plasma carnitine concentrations than omnivores. Principle aims of the current study were to assess the plasma and skeletal muscle carnitine content and physical performance of male vegetarians and matched omnivores under basal conditions and after L-carnitine supplementation. Sixteen vegetarians and eight omnivores participated in this interventional study with oral supplementation of 2 g L-carnitine for 12 weeks. Before carnitine supplementation, vegetarians had a 10% lower plasma carnitine concentration, but maintained skeletal muscle carnitine stores compared to omnivores. Skeletal muscle phosphocreatine, ATP, glycogen and lactate contents were also not different from omnivores. Maximal oxygen uptake (VO2max) and workload (P max) per bodyweight (bicycle spiroergometry) were not significantly different between vegetarians and omnivores. Sub-maximal exercise (75% VO2max for 1 h) revealed no significant differences between vegetarians and omnivores (respiratory exchange ratio, blood lactate and muscle metabolites). Supplementation with L-carnitine significantly increased the total plasma carnitine concentration (24% in omnivores, 31% in vegetarians) and the muscle carnitine content in vegetarians (13%). Despite this increase, P max and VO2max as well as muscle phosphocreatine, lactate and glycogen were not significantly affected by carnitine administration. Vegetarians have lower plasma carnitine concentrations, but maintained muscle carnitine stores compared to omnivores. Oral L-carnitine supplementation normalizes the plasma carnitine stores and slightly increases the skeletal muscle carnitine content in vegetarians, but without affecting muscle function and energy metabolism.

  2. Effects on Energy Metabolism of Two Guanidine Molecules, (Boc)2 -Creatine and Metformin.

    PubMed

    Garbati, Patrizia; Ravera, Silvia; Scarfì, Sonia; Salis, Annalisa; Rosano, Camillo; Poggi, Alessandro; Damonte, Gianluca; Millo, Enrico; Balestrino, Maurizio

    2017-09-01

    Several enzymes are involved in the energy production, becoming a possible target for new anti-cancer drugs. In this paper, we used biochemical and in silico studies to evaluate the effects of two guanidine molecules, (Boc) 2 -creatine and metformin, on creatine kinase, an enzyme involved in the regulation of intracellular energy levels. Our results show that both drugs inhibit creatine kinase activity; however, (Boc) 2 -creatine displays a competitive inhibition, while metformin acts with a non-competitive mechanism. Moreover, (Boc) 2 -creatine is able to inhibit the activity of hexokinase with a non-competitive mechanism. Considering that creatine kinase and hexokinase are involved in energy metabolism, we evaluated the effects of (Boc) 2 -creatine and metformin on the ATP/AMP ratio and on cellular proliferation in healthy fibroblasts, human breast cancer cells (MDA-MB-468), a human neuroblastoma cell line (SH-SY5Y), a human Hodgkin lymphoma cell line (KMH2). We found that healthy fibroblasts were only partially affected by (Boc) 2 -creatine, while both ATP/AMP ratio and viability of the three cancer cell lines were significantly decreased. By inhibiting both creatine kinase and hexokinase, (Boc) 2 -creatine appears as a promising new agent in anticancer treatment. Further research is needed to understand what types of cancer cells are most suitable to treatment by this new compound. J. Cell. Biochem. 118: 2700-2711, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. High intake of orange juice and cola differently affects metabolic risk in healthy subjects.

    PubMed

    Büsing, Franziska; Hägele, Franziska A; Nas, Alessa; Döbert, Laura-Verena; Fricker, Alena; Dörner, Elisabeth; Podlesny, Daniel; Aschoff, Julian; Pöhnl, Tobias; Schweiggert, Ralf; Fricke, W Florian; Carle, Reinhold; Bosy-Westphal, Anja

    2018-03-03

    Higher consumption of sugar-containing beverages has been associated with an elevated risk of type 2 diabetes and gout. Whether this equally applies to cola with an unhealthy image and orange juice (OJ) having a healthy image remains unknown. In order to investigate whether OJ and cola differently affect metabolic risk 26 healthy adults (24.7 ± 3.2 y; BMI 23.2 ± 3.3 kg/m 2 ) participated in a 2 × 2-wk intervention and consumed either OJ or caffeine-free cola (20% Ereq as sugar from beverages) in-between 3 meals/d at ad libitum energy intake. Glycemic control, uric acid metabolism and gut microbiota were assessed as outcome parameters. Fecal microbiota, body weight, basal and OGTT-derived insulin sensitivity remained unchanged in both intervention periods. Levels of uric acid were normal at baseline and did not change with 2-wk cola consumption (-0.03 ± 0.67 mg/dL; p > 0.05), whereas they decreased with OJ intervention (-0.43 ± 0.56 mg/dL; p < 0.01) due to increased uric acid excretion (+130.2 ± 130.0 mg/d; p < 0.001). Compared to OJ, consumption of cola led to a higher daylong glycemia (ΔiAUC: 36.9 ± 83.2; p < 0.05), an increase in glucose variability (ΔMAGE-Index: 0.29 ± 0.44; p < 0.05), and a lower 24 h-insulin secretion (ΔC-peptide excretion: -31.76 ± 38.61 μg/d; p < 0.001), which may be explained by a decrease in serum potassium levels (-0.11 ± 0.24 mmol/L; p < 0.05). Despite its sugar content, regular consumption of large amounts of OJ do not increase the risk of gout but may even contribute to lower uric acid levels. The etiology of impaired insulin secretion with cola consumption needs to be further investigated. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  4. Mitochondria in Cancer Energy Metabolism

    PubMed Central

    2015-01-01

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

  5. Metabolic inflexibility: when mitochondrial indecision leads to metabolic gridlock.

    PubMed

    Muoio, Deborah M

    2014-12-04

    Normal energy metabolism is characterized by periodic shifts in glucose and fat oxidation, as the mitochondrial machinery responsible for carbon combustion switches freely between alternative fuels according to physiological and nutritional circumstances. These transitions in fuel choice are orchestrated by an intricate network of metabolic and cell signaling events that enable exquisite crosstalk and cooperation between competing substrates to maintain energy and glucose homeostasis. By contrast, obesity-related cardiometabolic diseases are increasingly recognized as disorders of metabolic inflexibility, in which nutrient overload and heightened substrate competition result in mitochondrial indecision, impaired fuel switching, and energy dysregulation. This Perspective offers a speculative view on the molecular origins and pathophysiological consequences of metabolic inflexibility. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. The fungicide triadimefon affects beer flavor and composition by influencing Saccharomyces cerevisiae metabolism

    NASA Astrophysics Data System (ADS)

    Kong, Zhiqiang; Li, Minmin; An, Jingjing; Chen, Jieying; Bao, Yuming; Francis, Frédéric; Dai, Xiaofeng

    2016-09-01

    Despite the fact that beer is produced on a large scale, the effects of pesticide residues on beer have been rarely investigated. In this study, we used micro-brewing settings to determine the effect of triadimefon on the growth of Saccharomyces cerevisiae and beer flavor. The yeast growth in medium was significantly inhibited (45%) at concentrations higher than 5 mg L-1, reaching 80% and 100% inhibition at 10 mg L-1 and 50 mg L-1, respectively. There were significant differences in sensory quality between beer samples fermented with and without triadimefon based on data obtained with an electronic tongue and nose. Such an effect was most likely underlain by changes in yeast fermentation activity, including decreased utilization of maltotriose and most amino acids, reduced production of isobutyl and isoamyl alcohols, and increased ethyl acetate content in the fungicide treated samples. Furthermore, yeast metabolic profiling by phenotype microarray and UPLC/TOF-MS showed that triadimefon caused significant changes in the metabolism of glutathione, phenylalanine and sphingolipids, and in sterol biosynthesis. Thus, triadimefon negatively affects beer sensory qualities by influencing the metabolic activity of S. cerevisiae during fermentation, emphasizing the necessity of stricter control over fungicide residues in brewing by the food industry.

  7. The fungicide triadimefon affects beer flavor and composition by influencing Saccharomyces cerevisiae metabolism

    PubMed Central

    Kong, Zhiqiang; Li, Minmin; An, Jingjing; Chen, Jieying; Bao, Yuming; Francis, Frédéric; Dai, Xiaofeng

    2016-01-01

    Despite the fact that beer is produced on a large scale, the effects of pesticide residues on beer have been rarely investigated. In this study, we used micro-brewing settings to determine the effect of triadimefon on the growth of Saccharomyces cerevisiae and beer flavor. The yeast growth in medium was significantly inhibited (45%) at concentrations higher than 5 mg L−1, reaching 80% and 100% inhibition at 10 mg L−1 and 50 mg L−1, respectively. There were significant differences in sensory quality between beer samples fermented with and without triadimefon based on data obtained with an electronic tongue and nose. Such an effect was most likely underlain by changes in yeast fermentation activity, including decreased utilization of maltotriose and most amino acids, reduced production of isobutyl and isoamyl alcohols, and increased ethyl acetate content in the fungicide treated samples. Furthermore, yeast metabolic profiling by phenotype microarray and UPLC/TOF-MS showed that triadimefon caused significant changes in the metabolism of glutathione, phenylalanine and sphingolipids, and in sterol biosynthesis. Thus, triadimefon negatively affects beer sensory qualities by influencing the metabolic activity of S. cerevisiae during fermentation, emphasizing the necessity of stricter control over fungicide residues in brewing by the food industry. PMID:27629523

  8. Microalgal bioengineering for sustainable energy development: Recent transgenesis and metabolic engineering strategies.

    PubMed

    Banerjee, Chiranjib; Singh, Puneet Kumar; Shukla, Pratyoosh

    2016-03-01

    Exploring the efficiency of algae to produce remarkable products can be directly benefitted by studying its mechanism at systems level. Recent advents in biotechnology like flux balance analysis (FBA), genomics and in silico proteomics minimize the wet lab exertion. It is understood that FBA predicts the metabolic products, metabolic pathways and alternative pathway to maximize the desired product, and these are key components for microalgae bio-engineering. This review encompasses recent transgenesis techniques and metabolic engineering strategies applied to different microalgae for improving different traits. Further it also throws light on RNAi and riboswitch engineering based methods which may be advantageous for high throughput microalgal research. A valid and optimally designed microalga can be developed where every engineering strategies meet each other successfully and will definitely fulfill the market needs. It is also to be noted that Omics (viz. genetic and metabolic manipulation with bioinformatics) should be integrated to develop a strain which could prove to be a futuristic solution for sustainable development for energy. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Ecotypic differentiation matters for latitudinal variation in energy metabolism and flight performance in a butterfly under climate change

    PubMed Central

    Van Dyck, Hans; Holveck, Marie-Jeanne

    2016-01-01

    Life histories of organisms may vary with latitude as they experience different thermal constraints and challenges. This geographic, intraspecific variation could be of significance for range dynamics under climate change beyond edge-core comparisons. In this study, we did a reciprocal transplant experiment between the temperature-regimes of two latitudes with an ectotherm insect, examining the effects on energy metabolism and flight performance. Pararge aegeria expanded its ecological niche from cool woodland (ancestral) to warmer habitat in agricultural landscape (novel ecotype). Northern males had higher standard metabolic rates than southern males, but in females these rates depended on their ecotype. Southern males flew for longer than northern ones. In females, body mass-corrected flight performance depended on latitude and thermal treatment during larval development and in case of the southern females, their interaction. Our experimental study provides evidence for the role of ecological differentiation at the core of the range to modulate ecophysiology and flight performance at different latitudes, which in turn may affect the climatic responsiveness of the species. PMID:27845372

  10. Ecotypic differentiation matters for latitudinal variation in energy metabolism and flight performance in a butterfly under climate change.

    PubMed

    Van Dyck, Hans; Holveck, Marie-Jeanne

    2016-11-15

    Life histories of organisms may vary with latitude as they experience different thermal constraints and challenges. This geographic, intraspecific variation could be of significance for range dynamics under climate change beyond edge-core comparisons. In this study, we did a reciprocal transplant experiment between the temperature-regimes of two latitudes with an ectotherm insect, examining the effects on energy metabolism and flight performance. Pararge aegeria expanded its ecological niche from cool woodland (ancestral) to warmer habitat in agricultural landscape (novel ecotype). Northern males had higher standard metabolic rates than southern males, but in females these rates depended on their ecotype. Southern males flew for longer than northern ones. In females, body mass-corrected flight performance depended on latitude and thermal treatment during larval development and in case of the southern females, their interaction. Our experimental study provides evidence for the role of ecological differentiation at the core of the range to modulate ecophysiology and flight performance at different latitudes, which in turn may affect the climatic responsiveness of the species.

  11. Harvesting biomechanical energy or carrying batteries? An evaluation method based on a comparison of metabolic power.

    PubMed

    Schertzer, Eliran; Riemer, Raziel

    2015-03-20

    Harvesting energy from human motion is an innovative alternative to using batteries as a source of electrical power for portable devices. Yet there are no guidelines as to whether energy harvesting should be preferred over batteries. This paper introduces an approach to determine which source of energy should be preferred. The proposed approach compares the metabolic power while harvesting energy and while using batteries (or any other power supply, e.g., solar panels), which provide equal amount of energy. Energy harvesting is preferred over batteries if the metabolic power required to harvest the energy is lower than that required to carry the batteries. Metabolic power can be experimentally measured. However, for design purposes, it is essential to assess differences in metabolic power as a function of the device parameters. To this end, based on the proposed approach, we develop a mathematical model that considers the following parameters: the device's mass, its location on the human body, the electrical power output, cost of harvesting (COH), walking time, and the specific energy of the battery. We apply the model in two ways. First, we conduct case studies to examine current ankle, knee, and back energy harvesting devices, and assess the walking times that would make these devices preferable over batteries. Second, we conduct a design scenarios analysis, which examines future device developments. The case studies reveal that to be preferred over batteries, current harvesting devices located on the ankle, knee, or back would require walking for 227 hours, 98 hours, or 260 hours, respectively. This would replace batteries weighing 6.81 kg (ankle), 5.88 kg (knee), or 2.6 kg (back). The design scenarios analysis suggests that for harvesting devices to be beneficial with less than 25 walking hours, future development should focus on light harvesting devices (less than 0.2 kg) with low COH (equal or lower than 0). Finally, a comparison with portable

  12. A potential mechanism of energy-metabolism oscillation in an aerobic chemostat culture of the yeast Saccharomyces cerevisiae.

    PubMed

    Xu, Zhaojun; Tsurugi, Kunio

    2006-04-01

    The energy-metabolism oscillation in aerobic chemostat cultures of yeast is a periodic change of the respiro-fermentative and respiratory phase. In the respiro-fermentative phase, the NADH level was kept high and respiration was suppressed, and glucose was anabolized into trehalose and glycogen at a rate comparable to that of catabolism. On the transition to the respiratory phase, cAMP levels increased triggering the breakdown of storage carbohydrates and the increased influx of glucose into the glycolytic pathway activated production of glycerol and ethanol consuming NADH. The resulting increase in the NAD(+)/NADH ratio stimulated respiration in combination with a decrease in the level of ATP, which was consumed mainly in the formation of biomass accompanying budding, and the accumulated ethanol and glycerol were gradually degraded by respiration via NAD(+)-dependent oxidation to acetate and the respiratory phase ceased after the recovery of NADH and ATP levels. However, the mRNA levels of both synthetic and degradative enzymes of storage carbohydrates were increased around the early respiro-fermentative phase, when storage carbohydrates are being synthesized, suggesting that the synthetic enzymes were expressed directly as active forms while the degradative enzymes were activated late by cAMP. In summary, the energy-metabolism oscillation is basically regulated by a feedback loop of oxido-reductive reactions of energy metabolism mediated by metabolites like NADH and ATP, and is modulated by metabolism of storage carbohydrates in combination of post-translational and transcriptional regulation of the related enzymes. A potential mechanism of energy-metabolism oscillation is proposed.

  13. Energy Metabolism Profile in Individuals with Prader-Willi Syndrome and Implications for Clinical Management: A Systematic Review.

    PubMed

    Alsaif, Maha; Elliot, Sarah A; MacKenzie, Michelle L; Prado, Carla M; Field, Catherine J; Haqq, Andrea M

    2017-11-01

    Prader-Willi syndrome (PWS) is a rare genetic disorder associated with excessive weight gain. Hyperphagia associated with PWS may result in higher energy intake, but alterations in energy expenditure may also contribute to energy imbalance. The purpose of this critical literature review is to determine the presence of alterations in energy expenditure in individuals with PWS. Ten studies that measured total energy expenditure (TEE), resting energy expenditure (REE), sleep energy expenditure (SEE), activity energy expenditure (AEE), and diet induced thermogenesis (DIT) were included in this review. The studies provided evidence that absolute TEE, REE, SEE, and AEE are lower in individuals with PWS than in age-, sex-, and body mass index-matched individuals without the syndrome. Alterations in lean body mass and lower physical activity amounts appear to be responsible for the lower energy expenditure in PWS rather than metabolic differences. Regardless of the underlying mechanism for lower TEE, the estimation of energy requirements with the use of equations derived for the general population would result in weight gain in individuals with PWS. The determination of energy requirements for weight management in individuals with PWS requires a more comprehensive understanding of energy metabolism. Future studies should aim to comprehensively profile all specific components of energy expenditure in individuals with PWS with the use of appropriately matched controls and gold standard methods to measure energy metabolism and body composition. One component of energy expenditure that is yet to be explored in detail in PWS is DIT. A reduced DIT (despite differences in fat free mass), secondary to hormonal dysregulation, may be present in PWS individuals, leading to a reduced overall energy expenditure. Further research exploring DIT in PWS needs to be conducted. Dietary energy recommendations for weight management in PWS have not yet been clearly established. © 2017 American

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

    PubMed Central

    2012-01-01

    Background Nitrogen is a principal limiting nutrient in plant growth and development. Among factors that may limit NO3- assimilation, Fe potentially plays a crucial role being a metal cofactor of enzymes of the reductive assimilatory pathway. Very few information is available about the changes of nitrogen metabolism occurring under Fe deficiency in Strategy I plants. The aim of this work was to study how cucumber (Cucumis sativus L.) plants modify their nitrogen metabolism when grown under iron deficiency. Results The activity of enzymes involved in the reductive assimilation of nitrate and the reactions that produce the substrates for the ammonium assimilation both at root and at leaf levels in Fe-deficient cucumber plants were investigated. Under Fe deficiency, only nitrate reductase (EC 1.7.1.1) activity decreased both at the root and leaf level, whilst for glutamine synthetase (EC 6.3.1.2) and glutamate synthase (EC 1.4.1.14) an increase was found. Accordingly, the transcript analysis for these enzymes showed the same behaviour except for root nitrate reductase which increased. Furthermore, it was found that amino acid concentration greatly decreased in Fe-deficient roots, whilst it increased in the corresponding leaves. Moreover, amino acids increased in the xylem sap of Fe-deficient plants. Conclusions The data obtained in this work provided new insights on the responses of plants to Fe deficiency, suggesting that this nutritional disorder differentially affected N metabolism in root and in leaf. Indeed under Fe deficiency, roots respond more efficiently, sustaining the whole plant by furnishing metabolites (i.e. aa, organic acids) to the leaves. PMID:23057967

  15. Molecular Interaction of Bone Marrow Adipose Tissue with Energy Metabolism.

    PubMed

    Suchacki, Karla J; Cawthorn, William P

    2018-01-01

    The last decade has seen a resurgence in the study of bone marrow adipose tissue (BMAT) across diverse fields such as metabolism, haematopoiesis, skeletal biology and cancer. Herein, we review the most recent developments of BMAT research in both humans and rodents, including the distinct nature of BMAT; the autocrine, paracrine and endocrine interactions between BMAT and various tissues, both in physiological and pathological scenarios; how these interactions might impact energy metabolism; and the most recent technological advances to quantify BMAT. Though still dwarfed by research into white and brown adipose tissues, BMAT is now recognised as endocrine organ and is attracting increasing attention from biomedical researchers around the globe. We are beginning to learn the importance of BMAT both within and beyond the bone, allowing us to better appreciate the role of BMAT in normal physiology and disease.

  16. Energy Metabolism and Inflammation in Brain Aging and Alzheimer’s Disease

    PubMed Central

    Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

    2016-01-01

    The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer’s disease. As important cellular sources of H2O2, mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer’s disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer’s disease. Interactions of these systems is reviewed based on basic research and clinical studies. PMID:27154981

  17. 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

  18. Autophagy in tumorigenesis and energy metabolism: friend by day, foe by night.

    PubMed

    Mathew, Robin; White, Eileen

    2011-02-01

    Autophagy is the mechanism by which cells consume parts of themselves to survive starvation and stress. This self-cannibalization limits cell death and tissue inflammation, recycles energy and biosynthetic substrates and removes damaged proteins and organelles, accumulation of which is toxic. In normal tissues, autophagy-mediated damage mitigation may suppress tumorigenesis, while in advanced tumors macromolecular recycling may support survival by buffering metabolic demand under stress. As a result, autophagy-activation in normal cells may suppress tumorigenesis, while autophagy inhibition may be beneficial for the therapy of established tumors. The mechanisms by which autophagy supports cancer cell metabolism are slowly emerging. As cancer is being increasingly recognized as a metabolic disease, how autophagy-mediated catabolism impacts cellular and mammalian metabolism and tumor growth is of great interest. Most cancer therapeutics induce autophagy, either directly by modulating signaling pathways that control autophagy in the case of many targeted therapies, or indirectly in the case of cytotoxic therapy. However, the functional consequence of autophagy induction in the context of cancer therapy is not yet clear. A better understanding of how autophagy modulates cell metabolism under various cellular stresses and the consequences of this on tumorigenesis will help develop better therapeutic strategies against cancer prevention and treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism

    PubMed Central

    Paixão, Laura; Caldas, José; Kloosterman, Tomas G.; Kuipers, Oscar P.; Vinga, Susana; Neves, Ana R.

    2015-01-01

    Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonized by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonization to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological, and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc), and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo 13C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s) was readily consumed and elicited a metabolic shift toward a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence. PMID:26500614

  20. Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism.

    PubMed

    Paixão, Laura; Caldas, José; Kloosterman, Tomas G; Kuipers, Oscar P; Vinga, Susana; Neves, Ana R

    2015-01-01

    Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonized by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonization to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological, and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc), and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo (13)C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s) was readily consumed and elicited a metabolic shift toward a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

  1. Zinc stress affects ionome and metabolome in tea plants.

    PubMed

    Zhang, Yinfei; Wang, Yu; Ding, Zhaotang; Wang, Hui; Song, Lubin; Jia, Sisi; Ma, Dexin

    2017-02-01

    The research of physiological responses to Zn stress in plants has been extensively studied. However, the ionomics and metabolomics responses of plants to Zn stress remain largely unknown. In present study, the nutrient elements were identified involved in ion homeostasis and metabolomics changes related to Zn deficiency or excess in tea plants. Nutrient element analysis demonstrated that the concentrations of Zn affected the ion-uptake in roots and the nutrient element transportation to leaves, leading to the different distribution of P, S, Al, Ca, Fe and Cu in the tea leaves or roots. Metabolomics analysis revealed that Zn deficiency or excess differentially influenced the metabolic pathways in the tea leaves. More specifically, Zn deficiency affected the metabolism of carbohydrates, and Zn excess affected flavonoids metabolism. Additionally, the results showed that both Zn deficiency and Zn excess led to reduced nicotinamide levels, which speeded up NAD + degradation and thus reduced energy metabolism. Furthermore, element-metabolite correlation analysis illustrated that Zn contents in the tea leaves were positively correlated with organic acids, nitrogenous metabolites and some carbohydrate metabolites, and negatively correlated with the metabolites involved in secondary metabolism and some other carbohydrate metabolites. Meanwhile, metabolite-metabolite correlation analysis demonstrated that organic acids, sugars, amino acids and flavonoids played dominant roles in the regulation of the tea leaf metabolism under Zn stress. Therefore, the conclusion should be drawn that the tea plants responded to Zn stress by coordinating ion-uptake and regulation of metabolism of carbohydrates, nitrogenous metabolites, and flavonoids. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

    DOE PAGES

    Rother, Michael; Krzycki, Joseph A.

    2010-01-01

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

  3. Metabolic Energy Demand Is Not Increased during Initial Shell Formation of Bivalves Exposed to Aragonite Undersaturation

    NASA Astrophysics Data System (ADS)

    Pan, F.; Frieder, C.; Applebaum, S.; Manahan, D. T.

    2016-02-01

    The Pacific oyster, Crassostrea gigas, is a major commercial species in global aquaculture. Ocean acidification is having a negative effect on larval production of this species, so the mechanisms of this impact are of considerable interest. Formation of new shell in C. gigas during the first 2-days post-fertilization results in a rapid six-fold increase in total mass. This period of early development has high sensitivity to changes in carbonate chemistry, in particular aragonite saturation state (Ω). An elevated energy cost for calcification at low Ω is often invoked as a mechanism. In this study, we characterized the developmental progression of first shell formation, total metabolic expenditure, and underlying biochemical processes of energy allocation during early development of C. gigas, under control (Ω >> 1) and undersaturated conditions (Ω < 1). While undersaturated conditions delayed the onset of calcification and resulted in decreased shell mass, there was no change in total metabolic energy demand. Furthermore, partitioning of total metabolic energy showed no major re-allocation of ATP to protein synthesis or ion pump activity (Na+, K+-ATPase) between the two treatments. We conclude that early development to the shelled-veliger larval stage does not require more energy at undersaturation. This finding helps constrain potential mechanisms of larval sensitivity to ocean acidification and narrows the focus for possible mitigation strategies for oyster aquaculture production.

  4. A fungal transcription factor essential for starch degradation affects integration of carbon and nitrogen metabolism

    DOE PAGES

    Xiong, Yi; Wu, Vincent W.; Lubbe, Andrea; ...

    2017-05-03

    In Neurospora crassa, the transcription factor COL-26 functions as a regulator of glucose signaling and metabolism. Its loss leads to resistance to carbon catabolite repression. Here, we report that COL-26 is necessary for the expression of amylolytic genes in N. crassa and is required for the utilization of maltose and starch. Additionally, the Δcol-26 mutant shows growth defects on preferred carbon sources, such as glucose, an effect that was alleviated if glutamine replaced ammonium as the primary nitrogen source. This rescue did not occur when maltose was used as a sole carbon source. Transcriptome and metabolic analyses of the Δcol-26more » mutant relative to its wild type parental strain revealed that amino acid and nitrogen metabolism, the TCA cycle and GABA shunt were adversely affected. Phylogenetic analysis showed a single col-26 homolog in Sordariales, Ophilostomatales, and the Magnaporthales, but an expanded number of col-26 homologs in other filamentous fungal species. Deletion of the closest homolog of col-26 in Trichoderma reesei, bglR, resulted in a mutant with similar preferred carbon source growth deficiency, and which was alleviated if glutamine was the sole nitrogen source, suggesting conservation of COL-26 and BglR function. Our finding provides novel insight into the role of COL-26 for utilization of starch and in integrating carbon and nitrogen metabolism for balanced metabolic activities for optimal carbon and nitrogen distribution.« less

  5. A fungal transcription factor essential for starch degradation affects integration of carbon and nitrogen metabolism

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xiong, Yi; Wu, Vincent W.; Lubbe, Andrea

    In Neurospora crassa, the transcription factor COL-26 functions as a regulator of glucose signaling and metabolism. Its loss leads to resistance to carbon catabolite repression. Here, we report that COL-26 is necessary for the expression of amylolytic genes in N. crassa and is required for the utilization of maltose and starch. Additionally, the Δcol-26 mutant shows growth defects on preferred carbon sources, such as glucose, an effect that was alleviated if glutamine replaced ammonium as the primary nitrogen source. This rescue did not occur when maltose was used as a sole carbon source. Transcriptome and metabolic analyses of the Δcol-26more » mutant relative to its wild type parental strain revealed that amino acid and nitrogen metabolism, the TCA cycle and GABA shunt were adversely affected. Phylogenetic analysis showed a single col-26 homolog in Sordariales, Ophilostomatales, and the Magnaporthales, but an expanded number of col-26 homologs in other filamentous fungal species. Deletion of the closest homolog of col-26 in Trichoderma reesei, bglR, resulted in a mutant with similar preferred carbon source growth deficiency, and which was alleviated if glutamine was the sole nitrogen source, suggesting conservation of COL-26 and BglR function. Our finding provides novel insight into the role of COL-26 for utilization of starch and in integrating carbon and nitrogen metabolism for balanced metabolic activities for optimal carbon and nitrogen distribution.« less

  6. A fungal transcription factor essential for starch degradation affects integration of carbon and nitrogen metabolism

    PubMed Central

    Xiong, Yi; Qin, Lina; Kennedy, Megan; Bauer, Diane; Barry, Kerrie; Northen, Trent R.; Grigoriev, Igor V.

    2017-01-01

    In Neurospora crassa, the transcription factor COL-26 functions as a regulator of glucose signaling and metabolism. Its loss leads to resistance to carbon catabolite repression. Here, we report that COL-26 is necessary for the expression of amylolytic genes in N. crassa and is required for the utilization of maltose and starch. Additionally, the Δcol-26 mutant shows growth defects on preferred carbon sources, such as glucose, an effect that was alleviated if glutamine replaced ammonium as the primary nitrogen source. This rescue did not occur when maltose was used as a sole carbon source. Transcriptome and metabolic analyses of the Δcol-26 mutant relative to its wild type parental strain revealed that amino acid and nitrogen metabolism, the TCA cycle and GABA shunt were adversely affected. Phylogenetic analysis showed a single col-26 homolog in Sordariales, Ophilostomatales, and the Magnaporthales, but an expanded number of col-26 homologs in other filamentous fungal species. Deletion of the closest homolog of col-26 in Trichoderma reesei, bglR, resulted in a mutant with similar preferred carbon source growth deficiency, and which was alleviated if glutamine was the sole nitrogen source, suggesting conservation of COL-26 and BglR function. Our finding provides novel insight into the role of COL-26 for utilization of starch and in integrating carbon and nitrogen metabolism for balanced metabolic activities for optimal carbon and nitrogen distribution. PMID:28467421

  7. Restoration of type 1 iodothyronine deiodinase expression in renal cancer cells downregulates oncoproteins and affects key metabolic pathways as well as anti-oxidative system.

    PubMed

    Popławski, Piotr; Wiśniewski, Jacek R; Rijntjes, Eddy; Richards, Keith; Rybicka, Beata; Köhrle, Josef; Piekiełko-Witkowska, Agnieszka

    2017-01-01

    Type 1 iodothyronine deiodinase (DIO1) contributes to deiodination of 3,5,3',5'-tetraiodo-L-thyronine (thyroxine, T4) yielding of 3,5,3'-triiodothyronine (T3), a powerful regulator of cell differentiation, proliferation, and metabolism. Our previous work showed that loss of DIO1 enhances proliferation and migration of renal cancer cells. However, the global effects of DIO1 expression in various tissues affected by cancer remain unknown. Here, the effects of stable DIO1 re-expression were analyzed on the proteome of renal cancer cells, followed by quantitative real-time PCR validation in two renal cancer-derived cell lines. DIO1-induced changes in intracellular concentrations of thyroid hormones were quantified by L-MS/MS and correlations between expression of DIO1 and potential target genes were determined in tissue samples from renal cancer patients. Stable re-expression of DIO1, resulted in 26 downregulated proteins while 59 proteins were overexpressed in renal cancer cells. The 'downregulated' group consisted mainly of oncoproteins (e.g. STAT3, ANPEP, TGFBI, TGM2) that promote proliferation, migration and invasion. Furthermore, DIO1 re-expression enhanced concentrations of two subunits of thyroid hormone transporter (SLC7A5, SLC3A2), enzymes of key pathways of cellular energy metabolism (e.g. TKT, NAMPT, IDH2), sex steroid metabolism and anti-oxidative response (AKR1C2, AKR1B10). DIO1 expression resulted in elevated intracellular concentration of T4. Expression of DIO1-affected genes strongly correlated with DIO1 transcript levels in tissue samples from renal cancer patients as well as with their poor survival. This first study addressing effects of deiodinase re-expression on proteome of cancer cells demonstrates that induced DIO1 re-expression in renal cancer robustly downregulates oncoproteins, affects key metabolic pathways, and triggers proteins involved in anti-oxidative protection. This data supports the notion that suppressed DIO1 expression and changes

  8. Restoration of type 1 iodothyronine deiodinase expression in renal cancer cells downregulates oncoproteins and affects key metabolic pathways as well as anti-oxidative system

    PubMed Central

    Rijntjes, Eddy; Richards, Keith; Rybicka, Beata; Köhrle, Josef

    2017-01-01

    Type 1 iodothyronine deiodinase (DIO1) contributes to deiodination of 3,5,3’,5’-tetraiodo-L-thyronine (thyroxine, T4) yielding of 3,5,3’-triiodothyronine (T3), a powerful regulator of cell differentiation, proliferation, and metabolism. Our previous work showed that loss of DIO1 enhances proliferation and migration of renal cancer cells. However, the global effects of DIO1 expression in various tissues affected by cancer remain unknown. Here, the effects of stable DIO1 re-expression were analyzed on the proteome of renal cancer cells, followed by quantitative real-time PCR validation in two renal cancer-derived cell lines. DIO1-induced changes in intracellular concentrations of thyroid hormones were quantified by L-MS/MS and correlations between expression of DIO1 and potential target genes were determined in tissue samples from renal cancer patients. Stable re-expression of DIO1, resulted in 26 downregulated proteins while 59 proteins were overexpressed in renal cancer cells. The ‘downregulated’ group consisted mainly of oncoproteins (e.g. STAT3, ANPEP, TGFBI, TGM2) that promote proliferation, migration and invasion. Furthermore, DIO1 re-expression enhanced concentrations of two subunits of thyroid hormone transporter (SLC7A5, SLC3A2), enzymes of key pathways of cellular energy metabolism (e.g. TKT, NAMPT, IDH2), sex steroid metabolism and anti-oxidative response (AKR1C2, AKR1B10). DIO1 expression resulted in elevated intracellular concentration of T4. Expression of DIO1-affected genes strongly correlated with DIO1 transcript levels in tissue samples from renal cancer patients as well as with their poor survival. This first study addressing effects of deiodinase re-expression on proteome of cancer cells demonstrates that induced DIO1 re-expression in renal cancer robustly downregulates oncoproteins, affects key metabolic pathways, and triggers proteins involved in anti-oxidative protection. This data supports the notion that suppressed DIO1 expression

  9. Root Transcriptomic Analysis Revealing the Importance of Energy Metabolism to the Development of Deep Roots in Rice (Oryza sativa L.).

    PubMed

    Lou, Qiaojun; Chen, Liang; Mei, Hanwei; Xu, Kai; Wei, Haibin; Feng, Fangjun; Li, Tiemei; Pang, Xiaomeng; Shi, Caiping; Luo, Lijun; Zhong, Yang

    2017-01-01

    Drought is the most serious abiotic stress limiting rice production, and deep root is the key contributor to drought avoidance. However, the genetic mechanism regulating the development of deep roots is largely unknown. In this study, the transcriptomes of 74 root samples from 37 rice varieties, representing the extreme genotypes of shallow or deep rooting, were surveyed by RNA-seq. The 13,242 differentially expressed genes (DEGs) between deep rooting and shallow rooting varieties (H vs. L) were enriched in the pathway of genetic information processing and metabolism, while the 1,052 DEGs between the deep roots and shallow roots from each of the plants (D vs. S) were significantly enriched in metabolic pathways especially energy metabolism. Ten quantitative trait transcripts (QTTs) were identified and some were involved in energy metabolism. Forty-nine candidate DEGs were confirmed by qRT-PCR and microarray. Through weighted gene co-expression network analysis (WGCNA), we found 18 hub genes. Surprisingly, all these hub genes expressed higher in deep roots than in shallow roots, furthermore half of them functioned in energy metabolism. We also estimated that the ATP production in the deep roots was faster than shallow roots. Our results provided a lot of reliable candidate genes to improve deep rooting, and firstly highlight the importance of energy metabolism to the development of deep roots.

  10. Root Transcriptomic Analysis Revealing the Importance of Energy Metabolism to the Development of Deep Roots in Rice (Oryza sativa L.)

    PubMed Central

    Lou, Qiaojun; Chen, Liang; Mei, Hanwei; Xu, Kai; Wei, Haibin; Feng, Fangjun; Li, Tiemei; Pang, Xiaomeng; Shi, Caiping; Luo, Lijun; Zhong, Yang

    2017-01-01

    Drought is the most serious abiotic stress limiting rice production, and deep root is the key contributor to drought avoidance. However, the genetic mechanism regulating the development of deep roots is largely unknown. In this study, the transcriptomes of 74 root samples from 37 rice varieties, representing the extreme genotypes of shallow or deep rooting, were surveyed by RNA-seq. The 13,242 differentially expressed genes (DEGs) between deep rooting and shallow rooting varieties (H vs. L) were enriched in the pathway of genetic information processing and metabolism, while the 1,052 DEGs between the deep roots and shallow roots from each of the plants (D vs. S) were significantly enriched in metabolic pathways especially energy metabolism. Ten quantitative trait transcripts (QTTs) were identified and some were involved in energy metabolism. Forty-nine candidate DEGs were confirmed by qRT-PCR and microarray. Through weighted gene co-expression network analysis (WGCNA), we found 18 hub genes. Surprisingly, all these hub genes expressed higher in deep roots than in shallow roots, furthermore half of them functioned in energy metabolism. We also estimated that the ATP production in the deep roots was faster than shallow roots. Our results provided a lot of reliable candidate genes to improve deep rooting, and firstly highlight the importance of energy metabolism to the development of deep roots. PMID:28798764

  11. Energy metabolism determines the sensitivity of human hepatocellular carcinoma cells to mitochondrial inhibitors and biguanide drugs.

    PubMed

    Hsu, Chia-Chi; Wu, Ling-Chia; Hsia, Cheng-Yuan; Yin, Pen-Hui; Chi, Chin-Wen; Yeh, Tien-Shun; Lee, Hsin-Chen

    2015-09-01

    Human hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide particularly in Asia. Deregulation of cellular energetics was recently included as one of the cancer hallmarks. Compounds that target the mitochondria in cancer cells were proposed to have therapeutic potential. Biguanide drugs which inhibit mitochondrial complex I and repress mTOR signaling are clinically used to treat type 2 diabetes mellitus patients (T2DM) and were recently found to reduce the risk of HCC in T2DM patients. However, whether alteration of energy metabolism is involved in regulating the sensitivity of HCC to biguanide drugs is still unclear. In the present study, we treated four HCC cell lines with mitochondrial inhibitors (rotenone and oligomycin) and biguanide drugs (metformin and phenformin), and found that the HCC cells which had a higher mitochondrial respiration rate were more sensitive to these treatments; whereas the HCC cells which exhibited higher glycolysis were more resistant. When glucose was replaced by galactose in the medium, the altered energy metabolism from glycolysis to mitochondrial respiration in the HCC cells enhanced the cellular sensitivity to mitochondrial inhibitors and biguanides. The energy metabolism change enhanced AMP-activated protein kinase (AMPK) activation, mTOR repression and downregulation of cyclin D1 and Mcl-1 in response to the mitochondrial inhibitors and biguanides. In conclusion, our results suggest that increased mitochondrial oxidative metabolism upregulates the sensitivity of HCC to biguanide drugs. Enhancing the mitochondrial oxidative metabolism in combination with biguanide drugs may be a therapeutic strategy for HCC.

  12. [Coactivators in energy metabolism: peroxisome proliferator-activated receptor-gamma coactivator 1 family].

    PubMed

    Wang, Rui; Chang, Yong-sheng; Fang, Fu-de

    2009-12-01

    Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) family is highly expressed in tissues with high energy metabolism. They coactivate transcription factors in regulating genes engaged in processes such as gluconeogenesis, adipose beta-oxydation, lipoprotein synthesis and secretion, mitochondrial biogenesis, and oxidative metabolism. Protein conformation studies demonstrated that they lack DNA binding domains and act as coactivators through physical interaction with transcription factors. PGC1 activity is regulated at transcription level or by multiple covalent chemical modifications such as phosphorylation, methylation and acetylation/deacetylation. Abnormal expression of PGC1 coactivators usually is closely correlated with diseases such as diabetes, obesity, hyperglycemia, hyperlipemia, and arterial and brain neuron necrosis diseases.

  13. The Energy Metabolism in Caenorhabditis elegans under The Extremely Low-Frequency Electromagnetic Field Exposure

    NASA Astrophysics Data System (ADS)

    Shi, Zhenhua; Yu, Hui; Sun, Yongyan; Yang, Chuanjun; Lian, Huiyong; Cai, Peng

    2015-02-01

    A literal mountain of documentation generated in the past five decades showing unmistakable health hazards associated with extremely low-frequency electromagnetic fields (ELF-EMFs) exposure. However, the relation between energy mechanism and ELF-EMF exposure is poorly understood. In this study, Caenorhabditis elegans was exposed to 50 Hz ELF-EMF at intensities of 0.5, 1, 2, and 3 mT, respectively. Their metabolite variations were analyzed by GC-TOF/MS-based metabolomics. Although minimal metabolic variations and no regular pattern were observed, the contents of energy metabolism-related metabolites such as pyruvic acid, fumaric acid, and L-malic acid were elevated in all the treatments. The expressions of nineteen related genes that encode glycolytic enzymes were analyzed by using quantitative real-time PCR. Only genes encoding GAPDH were significantly upregulated (P < 0.01), and this result was further confirmed by western blot analysis. The enzyme activity of GAPDH was increased (P < 0.01), whereas the total intracellular ATP level was decreased. While no significant difference in lifespan, hatching rate and reproduction, worms exposed to ELF-EMF exhibited less food consumption compared with that of the control (P < 0.01). In conclusion, C. elegans exposed to ELF-EMF have enhanced energy metabolism and restricted dietary, which might contribute to the resistance against exogenous ELF-EMF stress.

  14. Motivation to obtain a food reward of pregnant ewes in negative energy balance: behavioural, metabolic and endocrine considerations.

    PubMed

    Verbeek, E; Waas, J R; Oliver, M H; McLeay, L M; Ferguson, D M; Matthews, L R

    2012-07-01

    Low food availability often coincides with pregnancy in grazing animals. This study investigated how chronic reductions in food intake affected feeding motivation, and metabolic and endocrine parameters in pregnant sheep, which might be indicative of compromised welfare. Ewes with an initial Body Condition Score of 2.7±0.3 (BCS; 0 indicates emaciation and 5 obesity) were fed to attain low (LBC 2.0±0.0,), medium (MBC 2.9±0.1) or high BCS (HBC 3.7±0.1) in the first trimester of pregnancy. A feeding motivation test in which sheep were required to walk a set distance for a palatable food reward was conducted in the second trimester. LBC and MBC ewes consumed more rewards (P=0.001) and displayed a higher expenditure (P=0.02) than HBC ewes, LBC ewes also tended to consume more rewards than MBC ewes (P=0.09). Plasma leptin and glucose concentrations were inversely correlated to expenditure (both P<0.05) and appear to be associated with hunger in sheep. LBC ewes were in negative energy balance, with lower muscle dimensions, plasma glucose, leptin, insulin, cortisol, and insulin-like growth factor-1 concentrations and higher free fatty acids concentrations compared to HBC ewes; metabolic and endocrine parameters of the MBC ewes were intermediate. The high feeding motivation and negative energy balance of low BCS ewes suggested an increased risk of compromised welfare. Imposing even a small cost on a food reward reduced motivation substantially in high BCS ewes (despite high intake when food was freely available). Assessment of a willingness to work for rewards, combined with measures of key metabolic and endocrine parameters, may provide sensitive barometers of welfare in energetically-taxed animals. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Glucagon-receptor Signaling Regulates Energy Metabolism Via Hepatic Farnesoid X Receptor and Fibroblast Growth Factor 21.

    PubMed

    Kim, Teayoun; Nason, Shelly; Holleman, Cassie; Pepin, Mark; Wilson, Landon; Berryhill, Taylor F; Wende, Adam R; Steele, Chad; Young, Martin E; Barnes, Stephen; Drucker, Daniel J; Finan, Brian; DiMarchi, Richard; Perez-Tilve, Diego; Tschoep, Matthias; Habegger, Kirk M

    2018-06-20

    Glucagon, an essential regulator of glucose and lipid metabolism, also promotes weight loss, in part through potentiation of fibroblast-growth factor 21 (FGF21) secretion. However, FGF21 is only a partial mediator of metabolic actions ensuing from GcgR-activation, prompting us to search for additional pathways. Intriguingly, chronic GcgR agonism increases plasma bile acid levels. We hypothesized that GcgR agonism regulates energy metabolism, at least in part, through farnesoid X receptor (FXR). To test this hypothesis, we studied whole body and liver-specific FXR knockout ( Fxr ∆liver ) mice. Chronic GcgR agonist (IUB288) administration in diet-induced obese (DIO) Gcgr , Fgf21 and Fxr whole body or liver-specific knockout ( ∆liver ) mice failed to reduce body weight (BW) when compared to wildtype (WT) mice. IUB288 increased energy expenditure and respiration in DIO WT mice, but not FXR ∆liver mice. GcgR agonism increased [ 14 C]-palmitate oxidation in hepatocytes isolated from WT mice in a dose-dependent manner, an effect blunted in hepatocytes from Fxr ∆liver mice. Our data clearly demonstrate that control of whole body energy expenditure by GcgR agonism requires intact FXR signaling in the liver. This heretofore-unappreciated aspect of glucagon biology has implications for the use of GcgR agonism in the therapy of metabolic disorders. © 2018 by the American Diabetes Association.

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

    PubMed Central

    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-13C 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

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

    PubMed

    Vergara, Fredd; Shino, Amiu; Kikuchi, Jun

    2016-09-02

    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.

  18. [Effects of +Gx load on energy metabolism of brain tissue in rats].

    PubMed

    Wu, Bin; Xie, Bao-sheng; You, Guang-xing; Liu, Xing-hua; Lu, Sheng-qiang; Huang, Wei-fen

    2002-12-01

    Objective. To observe the changes of energy metabolism of brain tissue in rats under +Gx loads, and to explore its possible role in changes of brain function and work efficiency induced by +Gx stress. Method. Forty-five male Wistar rats were randomly divided into control, +5 Gx, +10 Gx, +15 Gx and +20 Gx group. Each group was exposed to the corresponding G value for 3 min. After that, cortical adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and lactic acid (LA) content, lactate dehydrogenase (LDH) activity were measured. Result. Compared with the control group, the cortical (LA) content increased significantly after +5 Gx, +10 Gx, +15 Gx and +20 Gx exposure (P<0.01). Cortical ADP content and ratio of ADP/AMP and AMP/ATP increased significantly after +10 Gx, +15 Gx and +20 Gx exposure (P<0.01), whereas ATP content, energy charge and LDH activity decreased significantly (P<0.05 or 0.01). Cortical AMP content increased significantly after +15 Gx and +20 Gx exposure (P<0.05 and 0.01). Conclusion. It is suggested that +Gx load can result in obvious depression of brain energy metabolism, which could be an important reason for the change of brain function and work efficiency induced by +Gx stress.

  19. The effects of home oxygen therapy on energy metabolism in patients with COPD

    PubMed Central

    Kırıcı Berber, Nurcan; Yetkin, Özkan; Kılıç, Talat; Berber, Ilhami; Özgel, Mehmet

    2018-01-01

    Background COPD is preventable and treatable and is characterized by completely nonreversible airflow obstruction. In this study, we aimed to investigate the effect of long-term oxygen therapy on patients with stage 4 COPD who were followed up and treated at the polyclinic or clinic service. We evaluated the effects of oxygen therapy on energy metabolism and physical activity in patients with COPD. Methods Nineteen patients with COPD (16 male/3 female), treated with oxygen therapy for the first time, were included in this study. Analysis of arterial blood gases and pulmonary function test was performed. Metabolic Holter device (SenseWear® Armband) was placed pre- and post-oxygen therapy on the patients’ arm for at least 3 days. This device captures Holter data in a digitized electronic system, and the daily average value was calculated from the data. Results Post-oxygen treatment showed a significant increase in energy expenditure by patients with COPD (pretreatment, 1,497±596 joule; posttreatment, 2,977±5,985 joule; P=0.044). Moreover, number of steps during walking (pretreatment, 2,056±256; posttreatment, 2,120±195; P=0.03), resting (pretreatment, 6.36±3.31 hours; posttreatment, 3.47±2.19 hours; P<0.03), and sleeping (pretreatment, 4.23±2.13 hours; posttreatment, 2.33±1.42 hours; P<0.00) showed significant differences. Increased daily energy expenditure in patients with respiratory failure was detected with long-term oxygen therapy. In addition, the immobility of patients decreased and duration of physical activity increased in patients with COPD. Conclusion In this study, positive effects of long-term oxygen therapy have been demonstrated with respect to energy metabolism and physical activity of patients with COPD. Thus, we recommend that medication adherence and long-term oxygen therapy should begin early in patients with COPD.

  20. The metabolic ER stress sensor IRE1α suppresses alternative activation of macrophages and impairs energy expenditure in obesity.

    PubMed

    Shan, Bo; Wang, Xiaoxia; Wu, Ying; Xu, Chi; Xia, Zhixiong; Dai, Jianli; Shao, Mengle; Zhao, Feng; He, Shengqi; Yang, Liu; Zhang, Mingliang; Nan, Fajun; Li, Jia; Liu, Jianmiao; Liu, Jianfeng; Jia, Weiping; Qiu, Yifu; Song, Baoliang; Han, Jing-Dong J; Rui, Liangyou; Duan, Sheng-Zhong; Liu, Yong

    2017-05-01

    Obesity is associated with metabolic inflammation and endoplasmic reticulum (ER) stress, both of which promote metabolic disease progression. Adipose tissue macrophages (ATMs) are key players orchestrating metabolic inflammation, and ER stress enhances macrophage activation. However, whether ER stress pathways underlie ATM regulation of energy homeostasis remains unclear. Here, we identified inositol-requiring enzyme 1α (IRE1α) as a critical switch governing M1-M2 macrophage polarization and energy balance. Myeloid-specific IRE1α abrogation in Ern1 f/f ; Lyz2-Cre mice largely reversed high-fat diet (HFD)-induced M1-M2 imbalance in white adipose tissue (WAT) and blocked HFD-induced obesity, insulin resistance, hyperlipidemia and hepatic steatosis. Brown adipose tissue (BAT) activity, WAT browning and energy expenditure were significantly higher in Ern1 f/f ; Lyz2-Cre mice. Furthermore, IRE1α ablation augmented M2 polarization of macrophages in a cell-autonomous manner. Thus, IRE1α senses protein unfolding and metabolic and immunological states, and consequently guides ATM polarization. The macrophage IRE1α pathway drives obesity and metabolic syndrome through impairing BAT activity and WAT browning.

  1. 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 ... Physiology . 14th ed. Hoboken, NJ: John Wiley & Sons; 2014:chap ...

  2. Genetic Alterations Affecting Cholesterol Metabolism and Human Fertility1

    PubMed Central

    DeAngelis, Anthony M.; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle

    2014-01-01

    ABSTRACT Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. PMID:25122065

  3. Comprehensive assessment of variables affecting metabolic control in patients with type 2 diabetes mellitus in Jordan.

    PubMed

    Qteishat, Rola Reyad; Ghananim, Abdel Rahman Al

    2016-01-01

    The aim of the study was to identify variables affecting metabolic control among diabetic patients treated at diabetes and endocrine clinic in Jordan. A total of 200 patients were studied by using a cross sectional study design. Data were collected from patients' medical records, glycemic control tests and prestructured questionnaires about variables that were potentially important based on previous researches and clinical judgment: Adherence evaluation, Patients' knowledge about drug therapy and non-pharmacological therapy, Anxiety and depression, Beliefs about diabetes treatment (benefits and barriers of treatment), Knowledge about treatment goals, Knowledge about diabetes, Self efficacy, and Social support. The mean (±SD) age was 53.5 (±10.38) years and mean HbA1c was 8.4 (±1.95). In the multivariate analysis, education level, and self efficacy found to have significantly independent association with metabolic control (P<0.03). Adequate knowledge and high self efficacy was significant in patients with good metabolic control. Emphasizing the importance of continuous educational programs and improving the self efficacy as well, could warrant achieving good metabolic control. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  4. An expanded view of energy homeostasis: Neural integration of metabolic, cognitive, and emotional drives to eat

    PubMed Central

    Shin, Andrew C.; Zheng, Huiyuan; Berthoud, Hans-Rudolf

    2009-01-01

    The traditional view of neural regulation of body energy homeostasis focuses on internal feedback signals integrated in the hypothalamus and brainstem and in turn leading to balanced activation of behavioral, autonomic, and endocrine effector pathways leading to changes in food intake and energy expenditure. Recent observations have demonstrated that many of these internal signals encoding energy status have much wider effects on the brain, particularly sensory and cortico-limbic systems that process information from the outside world by detecting and interpreting food cues, forming, storing, and recalling representations of experience with food, and assigning hedonic and motivational value to conditioned and unconditioned food stimuli. Thus, part of the metabolic feedback from the internal milieu regulates food intake and energy balance by acting on extrahypothalamic structures, leading to an expanded view of neural control of energy homeostasis taking into account the need to adapt to changing conditions in the environment. The realization that metabolic signals act directly on these non-traditional targets of body energy homeostasis brings opportunities for novel drug targets for the fight against obesity and eating disorders. PMID:19419661

  5. Prosthetic model, but not stiffness or height, affects the metabolic cost of running for athletes with unilateral transtibial amputations.

    PubMed

    Beck, Owen N; Taboga, Paolo; Grabowski, Alena M

    2017-07-01

    Running-specific prostheses enable athletes with lower limb amputations to run by emulating the spring-like function of biological legs. Current prosthetic stiffness and height recommendations aim to mitigate kinematic asymmetries for athletes with unilateral transtibial amputations. However, it is unclear how different prosthetic configurations influence the biomechanics and metabolic cost of running. Consequently, we investigated how prosthetic model, stiffness, and height affect the biomechanics and metabolic cost of running. Ten athletes with unilateral transtibial amputations each performed 15 running trials at 2.5 or 3.0 m/s while we measured ground reaction forces and metabolic rates. Athletes ran using three different prosthetic models with five different stiffness category and height combinations per model. Use of an Ottobock 1E90 Sprinter prosthesis reduced metabolic cost by 4.3 and 3.4% compared with use of Freedom Innovations Catapult [fixed effect (β) = -0.177; P < 0.001] and Össur Flex-Run (β = -0.139; P = 0.002) prostheses, respectively. Neither prosthetic stiffness ( P ≥ 0.180) nor height ( P = 0.062) affected the metabolic cost of running. The metabolic cost of running was related to lower peak (β = 0.649; P = 0.001) and stance average (β = 0.772; P = 0.018) vertical ground reaction forces, prolonged ground contact times (β = -4.349; P = 0.012), and decreased leg stiffness (β = 0.071; P < 0.001) averaged from both legs. Metabolic cost was reduced with more symmetric peak vertical ground reaction forces (β = 0.007; P = 0.003) but was unrelated to stride kinematic symmetry ( P ≥ 0.636). Therefore, prosthetic recommendations based on symmetric stride kinematics do not necessarily minimize the metabolic cost of running. Instead, an optimal prosthetic model, which improves overall biomechanics, minimizes the metabolic cost of running for athletes with unilateral transtibial amputations. NEW & NOTEWORTHY The metabolic cost of running for

  6. (1)H NMR metabolomics analysis of renal cell carcinoma cells: Effect of VHL inactivation on metabolism.

    PubMed

    Cuperlovic-Culf, Miroslava; Cormier, Kevin; Touaibia, Mohamed; Reyjal, Julie; Robichaud, Sarah; Belbraouet, Mehdi; Turcotte, Sandra

    2016-05-15

    Von Hippel-Lindau (VHL) is an onco-suppressor involved in oxygen and energy-dependent promotion of protein ubiquitination and proteosomal degradation. Loss of function mutations of VHL (VHL-cells) result in organ specific cancers with the best studied example in renal cell carcinomas. VHL has a well-established role in deactivation of hypoxia-inducible factor (HIF-1) and in regulation of PI3K/AKT/mTOR activity. Cell culture metabolomics analysis was utilized to determined effect of VHL and HIF-1α or HIF-2α on metabolism of renal cell carcinomas (RCC). RCC cells were stably transfected with VHL or shRNA designed to silence HIF-1α or HIF-2α genes. Obtained metabolic data was analysed qualitatively, searching for overall effects on metabolism as well as quantitatively, using methods developed in our group in order to determine specific metabolic changes. Analysis of the effect of VHL and HIF silencing on cellular metabolic footprints and fingerprints provided information about the metabolic pathways affected by VHL through HIF function as well as independently of HIF. Through correlation network analysis as well as statistical analysis of significant metabolic changes we have determined effects of VHL and HIF on energy production, amino acid metabolism, choline metabolism as well as cell regulation and signaling. VHL was shown to influence cellular metabolism through its effect on HIF proteins as well as by affecting activity of other factors. © 2015 UICC.

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

    PubMed Central

    Hargrove, James L

    2005-01-01

    Hummingbirds and other nectar-feeding, migratory birds possess unusual adaptive traits that offer important lessons concerning obesity, diabetes and the metabolic syndrome. Hummingbirds consume a high sugar diet and have fasting glucose levels that would be severely hyperglycemic in humans, yet these nectar-fed birds recover most glucose that is filtered into the urine. Hummingbirds accumulate over 40% body fat shortly before migrations in the spring and autumn. Despite hyperglycemia and seasonally elevated body fat, the birds are not known to become diabetic in the sense of developing polyuria (glucosuria), polydipsia and polyphagia. The tiny (3–4 g) Ruby-throated hummingbird has among the highest mass-specific metabolic rates known, and loses most of its stored fat in 20 h by flying up to 600 miles across the Gulf of Mexico. During the breeding season, it becomes lean and maintains an extremely accurate energy balance. In addition, hummingbirds can quickly enter torpor and reduce resting metabolic rates by 10-fold. Thus, hummingbirds are wonderful examples of the adaptive nature of fat tissue, and may offer lessons concerning prevention of metabolic syndrome in humans. PMID:16351726

  8. Metabolic remodeling of substrate utilization during heart failure progression.

    PubMed

    Chen, Liang; Song, Jiangping; Hu, Shengshou

    2018-05-23

    Heart failure (HF) is a clinical syndrome caused by a decline in cardiac systolic or diastolic function, which leaves the heart unable to pump enough blood to meet the normal physiological requirements of the human body. It is a serious disease burden worldwide affecting nearly 23 million patients. The concept that heart failure is "an engine out of fuel" has been generally accepted and metabolic remodeling has been recognized as an important aspect of this condition; it is characterized by defects in energy production and changes in metabolic pathways involved in the regulation of essential cellular functions such as the process of substrate utilization, the tricarboxylic acid cycle, oxidative phosphorylation, and high-energy phosphate metabolism. Advances in second-generation sequencing, proteomics, and metabolomics have made it possible to perform comprehensive tests on genes and metabolites that are crucial in the process of HF, thereby providing a clearer and comprehensive understanding of metabolic remodeling during HF. In recent years, new metabolic changes such as ketone bodies and branched-chain amino acids were demonstrated as alternative substrates in end-stage HF. This systematic review focuses on changes in metabolic substrate utilization during the progression of HF and the underlying regulatory mechanisms. Accordingly, the conventional concepts of metabolic remodeling characteristics are reviewed, and the latest developments, particularly multi-omics studies, are compiled.

  9. Myocardial high-energy phosphate metabolism is altered after treatment with anthracycline in childhood.

    PubMed

    Eidenschink, A B; Schröter, G; Müller-Weihrich, S; Stern, H

    2000-11-01

    We aimed to investigate whether changes in high-energy phosphate metabolism after treatment of children and young adults with anthracycline can be demonstrated non-invasively by 31P magnetic resonance spectroscopy. Abnormal myocardial energy metabolism has been suggested as a mechanism for anthracycline-induced cardiotoxicity. Deterioration in such has been shown in animal studies by resonance spectroscopy. We studied 62 patients, with a mean age of 13.5+/-5 years, 3.7+/-4.3 years after a cumulative anthracycline dose of 270+/-137 mg/m2. Normal echocardiographic findings had been elicited in 54 patients. The control group consisted of 28 healthy subjects aged 20+/-7 years. Resonance spectrums of the anterior left ventricular myocardium were obtained at 1.5 Tesla using an image-selected in vivo spectroscopy localization technique. The ratio of phosphocreatine to adenosine triphosphate after blood correction was 1.09+/-0.43 for the patients, and 1.36+/-0.36 (mean+/-SD) for controls (p=0.005), with a significantly reduced mean ratio even in the subgroup of patients with normal echocardiographic results (1.11+/-0.44 versus 1.36+/-0.36, p=0.01). The ratio did not correlate with the cumulative dose of anthracycline. The ratio of phosphodiester to adenosine triphosphate was similar in patients and controls (0.90+/-0.56 versus 0.88+/-0.62). In patients treated with anthracyclines in childhood, myocardial high-energy phosphate metabolism may be impaired even in the absence of cardiomyopathy. Our data support the concept that anthracycline-induced cardiotoxicity is not clearly dose dependent.

  10. Insight into Energy Conservation via Alternative Carbon Monoxide Metabolism in Carboxydothermus pertinax Revealed by Comparative Genome Analysis.

    PubMed

    Fukuyama, Yuto; Omae, Kimiho; Yoneda, Yasuko; Yoshida, Takashi; Sako, Yoshihiko

    2018-05-04

    Carboxydothermus species are some of the most studied thermophilic carboxydotrophs. Their varied carboxydotrophic growth properties suggest distinct strategies for energy conservation via CO metabolism. In this study, we used comparative genome analysis of the genus Carboxydothermus to show variations in the CO dehydrogenase/energy-converting hydrogenase gene cluster, which is responsible for CO metabolism with H 2 production (hydrogenogenic CO metabolism). Indeed, ability or inability to produce H 2 with CO oxidation is explained by the presence or absence of this gene cluster in C. hydrogenoformans , C. islandicus , and C. ferrireducens Interestingly, despite its hydrogenogenic CO metabolism, C. pertinax lacks the Ni-CO dehydrogenase catalytic subunit (CooS-I) and its transcriptional regulator encoding genes in this gene cluster probably due to inversion. Transcriptional analysis in C. pertinax showed that the Ni-CO dehydrogenase gene ( cooS-II ) and distantly encoded energy-converting hydrogenase related genes were remarkably upregulated under 100% CO. In addition, when thiosulfate was available as a terminal electron acceptor under 100% CO, C. pertinax maximum cell density and maximum specific growth rate were 3.1-fold and 1.5-fold higher, respectively, than when thiosulfate was absent. The amount of H 2 produced was only 63% of the consumed CO, less than expected according to hydrogenogenic CO oxidation: CO + H 2 O → CO 2 + H 2 Accordingly, C. pertinax would couple CO oxidation by Ni-CO dehydrogenase-II with simultaneous reduction of not only H 2 O but thiosulfate when grown under 100% CO. IMPORTANCE Anaerobic hydrogenogenic carboxydotrophs are thought to fill a vital niche with scavenging potentially toxic CO and producing H 2 as available energy source for thermophilic microbes. This hydrogenogenic carboxydotrophy relies on a Ni-CO dehydrogenase/energy-converting hydrogenase gene cluster. This feature is thought to be as common to these organisms. However

  11. 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.

  12. 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

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

    PubMed

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

    2014-11-15

    Fasting and glucose shortage activate a metabolic switch that shifts more energy production to mitochondria. This metabolic adaptation ensures energy supply, but also elevates the risk of mitochondrial oxidative damage. Here, we present evidence that metabolically challenged mitochondria undergo active fusion to suppress oxidative stress. In response to glucose starvation, mitofusin 1 (MFN1) becomes associated with the protein deacetylase HDAC6. This interaction leads to MFN1 deacetylation and activation, promoting mitochondrial fusion. Deficiency in HDAC6 or MFN1 prevents mitochondrial fusion induced by glucose deprivation. Unexpectedly, failure to undergo fusion does not acutely affect mitochondrial adaptive energy production; instead, it causes excessive production of mitochondrial reactive oxygen species and oxidative damage, a defect suppressed by an acetylation-resistant MFN1 mutant. In mice subjected to fasting, skeletal muscle mitochondria undergo dramatic fusion. Remarkably, fasting-induced mitochondrial fusion is abrogated in HDAC6-knockout mice, resulting in extensive mitochondrial degeneration. These findings show that adaptive mitochondrial fusion protects metabolically challenged mitochondria. © 2014. Published by The Company of Biologists Ltd.

  14. Metabolic theory predicts whole-ecosystem properties.

    PubMed

    Schramski, John R; Dell, Anthony I; Grady, John M; Sibly, Richard M; Brown, James H

    2015-02-24

    Understanding the effects of individual organisms on material cycles and energy fluxes within ecosystems is central to predicting the impacts of human-caused changes on climate, land use, and biodiversity. Here we present a theory that integrates metabolic (organism-based bottom-up) and systems (ecosystem-based top-down) approaches to characterize how the metabolism of individuals affects the flows and stores of materials and energy in ecosystems. The theory predicts how the average residence time of carbon molecules, total system throughflow (TST), and amount of recycling vary with the body size and temperature of the organisms and with trophic organization. We evaluate the theory by comparing theoretical predictions with outputs of numerical models designed to simulate diverse ecosystem types and with empirical data for real ecosystems. Although residence times within different ecosystems vary by orders of magnitude-from weeks in warm pelagic oceans with minute phytoplankton producers to centuries in cold forests with large tree producers-as predicted, all ecosystems fall along a single line: residence time increases linearly with slope = 1.0 with the ratio of whole-ecosystem biomass to primary productivity (B/P). TST was affected predominantly by primary productivity and recycling by the transfer of energy from microbial decomposers to animal consumers. The theory provides a robust basis for estimating the flux and storage of energy, carbon, and other materials in terrestrial, marine, and freshwater ecosystems and for quantifying the roles of different kinds of organisms and environments at scales from local ecosystems to the biosphere.

  15. Evaluation of the metabolism of high energy phosphates in patients with Chagas' disease.

    PubMed

    Leme, Ana Maria Betim Paes; Salemi, Vera Maria Cury; Parga, José Rodrigues; Ianni, Bárbara Maria; Mady, Charles; Weiss, Robert G; Kalil-Filho, Roberto

    2010-08-01

    Abnormalities in myocardial metabolism have been observed in patients with heart failure of different etiologies. Magnetic resonance spectroscopy (MRS) with phosphorus-31 is a noninvasive technique that allows detection of myocardial metabolic changes. To determine the resting metabolism of high-energy phosphates in patients with Chagas' disease (CD) by MRS with phosphorus-31. We studied 39 patients with CD, 23 with preserved ventricular function (PF Group) and 16 with ventricular dysfunction (VD Group), assessed by Doppler echocardiography. MRS of the anterosseptal region was performed in 39 patients and 8 normal subjects (C Group) through a Phillips 1.5 Tesla device, obtaining the phosphocreatine/beta-adenosine triphosphate myocardial ratio (PCr/β-ATP). The levels of cardiac PCr/β-ATP were reduced in VD Group in relation to PF Group, and the latter presented reduced levels compared to C Group (VD Group: 0.89 ± 0.31 vs PF Group: 1.47 ± 0.34 vs C Group: 1.88 ± 0.08, p < 0.001). A correlation was found between left ventricular ejection fraction and PCr/β-ATP in 39 patients (r = 0.64, p < 0.001). Patients under functional class I (n = 22) presented PCr/β-ATP of 1.45 ± 0.35, and those in functional classes II and III (n = 17), PCr/β-ATP of 0.94 ± 0.36 (p < 0.001). The 31-phosphorus MRS was able to detect non-invasively changes in the rest energy metabolism of patients with Chagas' disease, with and without systolic dysfunction. These changes were related to the severity of heart impairment.

  16. Cellular metabolic energy modulation by tangeretin in 7,12-dimethylbenz(a) anthracene-induced breast cancer.

    PubMed

    Periyasamy, Kuppusamy; Sivabalan, Venkatachalam; Baskaran, Kuppusamy; Kasthuri, Kannayiram; Sakthisekaran, Dhanapal

    2016-03-01

    Breast cancer is the leading cause of death among women worldwide. Chemoprevention and chemotherapy play beneficial roles in reducing the incidence and mortality of cancer. Epidemiological and experimental studies showed that naturally-occurring antioxidants present in the diet may act as anticancer agents. Identifying the abnormalities of cellular energy metabolism facilitates early detection and management of breast cancer. The present study evaluated the effect of tangeretin on cellular metabolic energy fluxes in 7,12-dimethylbenz(a) anthracene (DMBA)-induced proliferative breast cancer. The results showed that the activities of glycolytic enzymes significantly increased in mammary tissues of DMBA-induced breast cancer bearing rats. The gluconeogenic tricarboxylic acid (TCA) cycle and respiratory chain enzyme activities significantly decreased in breast cancer-bearing rats. In addition, proliferating cell nuclear antigen (PCNA) was highly expressed in breast cancer tissues. However, the activities of glycolytic enzymes were significantly normalized in the tangeretin pre- and post-treated rats and the TCA cycle and respiratory chain enzyme activities were significantly increased in tangeretin treated rats. Furthermore, tangeretin down-regulated PCNA expression on breast cancer-bearing rats. Our study demonstrates that tangeretin specifically regulates cellular metabolic energy fluxes in DMBA-induced breast cancer-bearing rats. © 2016 by the Journal of Biomedical Research. All rights reserved.

  17. NMR metabolomics of esca disease-affected Vitis vinifera cv. Alvarinho leaves.

    PubMed

    Lima, Marta R M; Felgueiras, Mafalda L; Graça, Gonçalo; Rodrigues, João E A; Barros, António; Gil, Ana M; Dias, Alberto C P

    2010-09-01

    Esca is a destructive disease that affects vineyards leading to important losses in wine production. Information about the response of Vitis vinifera plants to this disease is scarce, particularly concerning changes in plant metabolism. In order to study the metabolic changes in Vitis plants affected by esca, leaves from both infected and non-affected cordons of V. vinifera cv. Alvarinho (collected in the Vinho Verde region, Portugal) were analysed. The metabolite composition of leaves from infected cordons with visible symptoms [diseased leaves (dl)] and from asymptomatic cordons [healthy leaves (hl)] was evaluated by 1D and 2D (1)H-nuclear magnetic resonance (NMR) spectroscopy. Principal component analysis (PCA) of the NMR spectra showed a clear separation between dl and hl leaves, indicating differential compound production due to the esca disease. NMR/PCA analysis allowed the identification of specific compounds characterizing each group, and the corresponding metabolic pathways are discussed. Altogether, the study revealed a significant increase of phenolic compounds in dl, compared with hl, accompanied by a decrease in carbohydrates, suggesting that dl are rerouting carbon and energy from primary to secondary metabolism. Other metabolic alterations detected comprised increased levels of methanol, alanine, and gamma-aminobutyric acid in dl, which might be the result of the activation of other defence mechanisms.

  18. Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*.

    PubMed

    Carrer, Michele; Liu, Ning; Grueter, Chad E; Williams, Andrew H; Frisard, Madlyn I; Hulver, Matthew W; Bassel-Duby, Rhonda; Olson, Eric N

    2012-09-18

    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.

  19. Altered Achilles tendon function during walking in people with diabetic neuropathy: implications for metabolic energy saving.

    PubMed

    Petrovic, M; Maganaris, C N; Deschamps, K; Verschueren, S M; Bowling, F L; Boulton, A J M; Reeves, N D

    2018-05-01

    The Achilles tendon (AT) has the capacity to store and release elastic energy during walking, contributing to metabolic energy savings. In diabetes patients, it is hypothesized that a stiffer Achilles tendon may reduce the capacity for energy saving through this mechanism, thereby contributing to an increased metabolic cost of walking (CoW). The aim of this study was to investigate the effects of diabetes and diabetic peripheral neuropathy (DPN) on the Achilles tendon and plantarflexor muscle-tendon unit behavior during walking. Twenty-three nondiabetic controls (Ctrl); 20 diabetic patients without peripheral neuropathy (DM), and 13 patients with moderate/severe DPN underwent gait analysis using a motion analysis system, force plates, and ultrasound measurements of the gastrocnemius muscle, using a muscle model to determine Achilles tendon and muscle-tendon length changes. During walking, the DM and particularly the DPN group displayed significantly less Achilles tendon elongation (Ctrl: 1.81; DM: 1.66; and DPN: 1.54 cm), higher tendon stiffness (Ctrl: 210; DM: 231; and DPN: 240 N/mm), and higher tendon hysteresis (Ctrl: 18; DM: 21; and DPN: 24%) compared with controls. The muscle fascicles of the gastrocnemius underwent very small length changes in all groups during walking (~0.43 cm), with the smallest length changes in the DPN group. Achilles tendon forces were significantly lower in the diabetes groups compared with controls (Ctrl: 2666; DM: 2609; and DPN: 2150 N). The results strongly point toward the reduced energy saving capacity of the Achilles tendon during walking in diabetes patients as an important factor contributing to the increased metabolic CoW in these patients. NEW & NOTEWORTHY From measurements taken during walking we observed that the Achilles tendon in people with diabetes and particularly people with diabetic peripheral neuropathy was stiffer, was less elongated, and was subject to lower forces compared with controls without diabetes. These

  20. Hyperthyroidism affects lipid metabolism in lactating and suckling rats.

    PubMed

    Varas, S M; Jahn, G A; Giménez, M S

    2001-08-01

    Two per thousand pregnant women have hyperthyroidism (HT), and although the symptoms are attenuated during pregnancy, they rebound after delivery, affecting infant development. To examine the effects of hyperthyroidism on lactation, we studied lipid metabolism in maternal mammary glands and livers of hyperthyroid rats and their pups. Thyroxine (10 microg/100 g body weight/d) or vehicle-treated rats were made pregnant 2 wk after commencement of treatment and sacrificed on days 7, 14, and 21 of lactation with the litters. Circulating triiodothyronine and tetraiodothyronine concentrations in the HT mothers were increased on all days. Hepatic esterified cholesterol (EC) and free cholesterol (FC) and triglyceride (TG) concentrations were diminished on days 14 and 21. Lipid synthesis, measured by incorporation of [3H]H2O into EC, FC, and TG, fatty acid synthase, and acetyl CoA carboxylase activities increased at day 14, while incorporation into FC and EC decreased at days 7 and 21, respectively. Mammary FC and TG concentrations were diminished at day 14; incorporation of [3H]H2O into TG decreased at days 7 and 21, and incorporation of [3H]H2O into FC increased at day 14. In the HT pups, growth rate was diminished, tetraiodothyronine concentration rose at days 7 and 14 of lactation, and triiodothyronine increased only at day 14. Liver TG concentrations increased at day 7 and fell at day 14, while FC increased at day 14 and only acetyl CoA carboxylase activity fell at day 14. Thus, hyperthyroidism changed maternal liver and mammary lipid metabolism, with decreased lipid concentration in spite of increased liver rate of synthesis and decreases in mammary synthesis. These changes, along with the mild hyperthyroidism of the litters, may have contributed to their reduced growth rate.

  1. Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

    PubMed Central

    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

  2. Food Components Modulate Obesity and Energy Metabolism via the Transcriptional Regulation of Lipid-Sensing Nuclear Receptors.

    PubMed

    Goto, Tsuyoshi; Takahashi, Nobuyuki; Kawada, Teruo

    2015-01-01

    Obesity is a major risk factor for chronic diseases such as diabetes, cardiovascular diseases, and hypertension. Many modern people have a tendency to overeat owing to stress and loosening of self-control. Moreover, energy expenditure varies greatly among individuals. Scientific reduction of obesity is important under these circumstances. Furthermore, recent research on molecular levels has clarified the differentiation of adipocytes, the level of subsequent fat accumulation, and the secretion of the biologically active adipokines by adipocytes. Adipose tissues and obesity have become the most important target for the prevention and treatment of many chronic diseases. We have identified various food-derived compounds modulating nuclear receptors, especially peroxisome proliferators-activated receptor(PPAR), in the regulation of energy metabolism and obesity. In this review, we discuss the PPARs that are most important in obesity and energy metabolism.

  3. Variants in glucose- and circadian rhythm-related genes affect the response of energy expenditure to weight-loss diets: the POUNDS LOST Trial.

    PubMed

    Mirzaei, Khadijeh; Xu, Min; Qi, Qibin; de Jonge, Lilian; Bray, George A; Sacks, Frank; Qi, Lu

    2014-02-01

    Circadian rhythm has been shown to be related to glucose metabolism and risk of diabetes, probably through effects on energy balance. Recent genome-wide association studies identified variants in circadian rhythm-related genes (CRY2 and MTNR1B) associated with glucose homeostasis. We tested whether CRY2 and MTNR1B genotypes affected changes in measures of energy expenditure in response to a weight-loss diet intervention in a 2-y randomized clinical trial, the POUNDS (Preventing Overweight Using Novel Dietary Strategies) LOST Trial. The variants CRY2 rs11605924 (n = 721) and MTNR1B rs10830963 (n = 722) were genotyped in overweight or obese adults who were randomly assigned to 1 of 4 weight-loss diets that differed in their proportions of macronutrients. Respiratory quotient (RQ) and resting metabolic rate (RMR) were measured. By 2 y of diet intervention, the A allele of CRY2 rs11605924 was significantly associated with a greater reduction in RQ (P = 0.03) and a greater increase in RMR and RMR/kg (both P = 0.04). The G allele of MTNR1B rs10830963 was significantly associated with a greater increase in RQ (P = 0.01) but was not related to changes in RMR and RMR/kg. In addition, we found significant gene-diet fat interactions for both CRY2 (P-interaction = 0.02) and MTNR1B (P-interaction < 0.001) in relation to 2-y changes in RQ. Our data indicate that variants in the circadian-related genes CRY2 and MTNR1B may affect long-term changes in energy expenditure, and dietary fat intake may modify the genetic effects. This trial was registered at www.clinicaltrials.gov as NCT00072995.

  4. What is the role of metabolic hormones in taste buds of the tongue.

    PubMed

    Cai, Huan; Maudsley, Stuart; Martin, Bronwen

    2014-01-01

    Gustation is one of the important chemical senses that guides the organism to identify nutrition while avoiding toxic chemicals. An increasing number of metabolic hormones and/or hormone receptors have been identified in the taste buds of the tongue and are involved in modulating taste perception. The gustatory system constitutes an additional endocrine regulatory locus that affects food intake, and in turn whole-body energy homeostasis. Here we provide an overview of the main metabolic hormones known to be present in the taste buds of the tongue; discuss their potential functional roles in taste perception and energy homeostasis and how their functional integrity is altered in the metabolic imbalance status (obesity and diabetes) and aging process. Better understanding of the functional roles of metabolic hormones in flavor perception as well as the link between taste perception and peripheral metabolism may be vital for developing strategies to promote healthier eating and prevent obesity or lifestyle-related disorders. © 2014 S. Karger AG, Basel.

  5. Parametric recursive system identification and self-adaptive modeling of the human energy metabolism for adaptive control of fat weight.

    PubMed

    Őri, Zsolt P

    2017-05-01

    A mathematical model has been developed to facilitate indirect measurements of difficult to measure variables of the human energy metabolism on a daily basis. The model performs recursive system identification of the parameters of the metabolic model of the human energy metabolism using the law of conservation of energy and principle of indirect calorimetry. Self-adaptive models of the utilized energy intake prediction, macronutrient oxidation rates, and daily body composition changes were created utilizing Kalman filter and the nominal trajectory methods. The accuracy of the models was tested in a simulation study utilizing data from the Minnesota starvation and overfeeding study. With biweekly macronutrient intake measurements, the average prediction error of the utilized carbohydrate intake was -23.2 ± 53.8 kcal/day, fat intake was 11.0 ± 72.3 kcal/day, and protein was 3.7 ± 16.3 kcal/day. The fat and fat-free mass changes were estimated with an error of 0.44 ± 1.16 g/day for fat and -2.6 ± 64.98 g/day for fat-free mass. The daily metabolized macronutrient energy intake and/or daily macronutrient oxidation rate and the daily body composition change from directly measured serial data are optimally predicted with a self-adaptive model with Kalman filter that uses recursive system identification.

  6. A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism.

    PubMed

    Shah, Meera; Su, Dan; Scheliga, Judith S; Pluskal, Tomáš; Boronat, Susanna; Motamedchaboki, Khatereh; Campos, Alexandre Rosa; Qi, Feng; Hidalgo, Elena; Yanagida, Mitsuhiro; Wolf, Dieter A

    2016-08-16

    The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Adaptive remodeling of skeletal muscle energy metabolism in high-altitude hypoxia: Lessons from AltitudeOmics.

    PubMed

    Chicco, Adam J; Le, Catherine H; Gnaiger, Erich; Dreyer, Hans C; Muyskens, Jonathan B; D'Alessandro, Angelo; Nemkov, Travis; Hocker, Austin D; Prenni, Jessica E; Wolfe, Lisa M; Sindt, Nathan M; Lovering, Andrew T; Subudhi, Andrew W; Roach, Robert C

    2018-05-04

    Metabolic responses to hypoxia play important roles in cell survival strategies and disease pathogenesis in humans. However, the homeostatic adjustments that balance changes in energy supply and demand to maintain organismal function under chronic low oxygen conditions remain incompletely understood, making it difficult to distinguish adaptive from maladaptive responses in hypoxia-related pathologies. We integrated metabolomic and proteomic profiling with mitochondrial respirometry and blood gas analyses to comprehensively define the physiological responses of skeletal muscle energy metabolism to 16 days of high-altitude hypoxia (5260 m) in healthy volunteers from the AltitudeOmics project. In contrast to the view that hypoxia down-regulates aerobic metabolism, results show that mitochondria play a central role in muscle hypoxia adaptation by supporting higher resting phosphorylation potential and enhancing the efficiency of long-chain acylcarnitine oxidation. This directs increases in muscle glucose toward pentose phosphate and one-carbon metabolism pathways that support cytosolic redox balance and help mitigate the effects of increased protein and purine nucleotide catabolism in hypoxia. Muscle accumulation of free amino acids favor these adjustments by coordinating cytosolic and mitochondrial pathways to rid the cell of excess nitrogen, but might ultimately limit muscle oxidative capacity in vivo Collectively, these studies illustrate how an integration of aerobic and anaerobic metabolism is required for physiological hypoxia adaptation in skeletal muscle, and highlight protein catabolism and allosteric regulation as unexpected orchestrators of metabolic remodeling in this context. These findings have important implications for the management of hypoxia-related diseases and other conditions associated with chronic catabolic stress. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Metabolomics and proteomics technologies to explore the herbal preparation affecting metabolic disorders using high resolution mass spectrometry.

    PubMed

    Zhang, Aihua; Zhou, Xiaohang; Zhao, Hongwei; Zou, Shiyu; Ma, Chung Wah; Liu, Qi; Sun, Hui; Liu, Liang; Wang, Xijun

    2017-01-31

    An integrative metabolomics and proteomics approach can provide novel insights in the understanding of biological systems. We have integrated proteome and metabolome data sets for a holistic view of the molecular mechanisms in disease. Using quantitative iTRAQ-LC-MS/MS proteomics coupled with UPLC-Q-TOF-HDMS based metabolomics, we determined the protein and metabolite expression changes in the kidney-yang deficiency syndrome (KYDS) rat model and further investigated the intervention effects of the Jinkui Shenqi Pill (JSP). The VIP-plot of the orthogonal PLS-DA (OPLS-DA) was used for discovering the potential biomarkers to clarify the therapeutic mechanisms of JSP in treating KYDS. The results showed that JSP can alleviate the kidney impairment induced by KYDS. Sixty potential biomarkers, including 5-l-glutamyl-taurine, phenylacetaldehyde, 4,6-dihydroxyquinoline, and xanthurenic acid etc., were definitely up- or down-regulated. The regulatory effect of JSP on the disturbed metabolic pathways was proved by the established metabonomic method. Using pathway analyses, we identified the disturbed metabolic pathways such as taurine and hypotaurine metabolism, pyrimidine metabolism, tyrosine metabolism, tryptophan metabolism, histidine metabolism, steroid hormone biosynthesis, etc. Furthermore, using iTRAQ-based quantitative proteomics analysis, seventeen differential proteins were identified and significantly altered by the JSP treatment. These proteins appear to be involved in Wnt, chemokine, PPAR, and MAPK signaling pathways, etc. Functional pathway analysis revealed that most of the proteins were found to play a key role in the regulation of metabolism pathways. Bioinformatics analysis with the IPA software found that these differentially-expressed moleculars had a strong correlation with the α-adrenergic signaling, FGF signaling, etc. Our data indicate that high-throughput metabolomics and proteomics can provide an insight on the herbal preparations affecting the

  9. [Effect of biologically active food additives on energy metabolism and human body weight].

    PubMed

    Gapparov, M M

    1999-01-01

    Review is devoted to analysis of human energy requirements depending on age, sex, occupational and living condition. Special attention was paid to importance of strict balance in organism between consumption and expense of energy. Modern views on mechanism of action food supplements as additional instrument of regulation of energy metabolism for correction of surplus body weight is given. Review is the first attempt of systematisation of biologically active food supplements according to their mechanism of action both on nutrition processes and on biochemical mechanisms of assimilation and utilisation of macronutrients, in particular of fats and carbohydrates.

  10. Nuclear localization of metabolic enzymes in immunity and metastasis.

    PubMed

    He, Yuchen; Gao, Menghui; Cao, Yiqu; Tang, Haosheng; Liu, Shuang; Tao, Yongguang

    2017-12-01

    Metabolism is essential to all living organisms that provide cells with energy, regulators, building blocks, enzyme cofactors and signaling molecules, and is in tune with nutritional conditions and the function of cells to make the appropriate developmental decisions or maintain homeostasis. As a fundamental biological process, metabolism state affects the production of multiple metabolites and the activation of various enzymes that participate in regulating gene expression, cell apoptosis, cancer progression and immunoreactions. Previous studies generally focus on the function played by the metabolic enzymes in the cytoplasm and mitochondrion. In this review, we conclude the role of them in the nucleus and their implications for cancer progression, immunity and metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Induction of energy metabolism related enzymes in yeast Saccharomyces cerevisiae exposed to ibogaine is adaptation to acute decrease in ATP energy pool.

    PubMed

    Paskulin, Roman; Jamnik, Polona; Obermajer, Natasa; Slavić, Marija; Strukelj, Borut

    2010-02-10

    Ibogaine has been extensively studied in the last decades in relation to its anti-addictive properties that have been repeatedly reported as being addiction interruptive and craving eliminative. In our previous study we have already demonstrated induction of energy related enzymes in rat brains treated with ibogaine at a dose of 20mg/kg i.p. 24 and 72 h prior to proteomic analysis. In this study a model organism yeast Saccharomyces cerevisiae was cultivated with ibogaine in a concentration of 1mg/l. Energy metabolism cluster enzymes glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, enolase and alcohol dehydrogenase were induced after 5h of exposure. This is a compensation of demonstrated ATP pool decrease after ibogaine. Yeast in a stationary growth phase is an accepted model for studies of housekeeping metabolism of eukaryotes, including humans. Study showed that ibogaine's influence on metabolism is neither species nor tissue specific. Effect is not mediated by binding of ibogaine to receptors, as previously described in literature since they are lacking in this model. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  12. In Vitro Disease Model of Microgravity Conditioning on Human Energy Metabolism

    NASA Technical Reports Server (NTRS)

    Snyder, Jessica; Culbertson, C.; Zhang, Ye; Emami, K.; Wu, H.; Sun, Wei

    2010-01-01

    NASA and its partners are committed to introducing appropriate new technology to enable learning and living safely beyond the Earth for extended periods of time in a sustainable and possibly indefinite manner. In the responsible acquisition of that goal, life sciences is tasked to tune and advance current medical technology to prepare for human health and wellness in the space environment. The space environment affects the condition and function of biological systems from organ level function to shape of individual organelles. The objective of this paper is to study the effect of microgravity on kinetics of drug metabolism. This fundamental characterization is meaningful to (1) scientific understanding of the response of biology to microgravity and (2) clinical dosing requirements and pharmacological thresholds during long term manned space exploration. Metabolism kinetics of the anti-nausea drug promethazine (PMZ) were determined by an in vitro ground model of 3-dimensional aggregates of human hepatocytes conditioned to weightlessness using a rotating wall bioreactor. The authors observed up-regulated PMZ conversion in model microgravity conditions and attribute this to effect to model microgravity conditioning acting on metabolic mechanisms of the cells. Further work is necessary to determine which particular cellular mechanisms are governing the experimental observations, but the authors conclude kinetics of drug metabolism are responsive to gravitational fields and further study of this sensitivity would improve dosing of pharmaceuticals to persons exposed to a microgravity environment.

  13. Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints.

    PubMed

    Bezawork-Geleta, Ayenachew; Wen, He; Dong, LanFeng; Yan, Bing; Vider, Jelena; Boukalova, Stepana; Krobova, Linda; Vanova, Katerina; Zobalova, Renata; Sobol, Margarita; Hozak, Pavel; Novais, Silvia Magalhaes; Caisova, Veronika; Abaffy, Pavel; Naraine, Ravindra; Pang, Ying; Zaw, Thiri; Zhang, Ping; Sindelka, Radek; Kubista, Mikael; Zuryn, Steven; Molloy, Mark P; Berridge, Michael V; Pacak, Karel; Rohlena, Jakub; Park, Sunghyouk; Neuzil, Jiri

    2018-06-07

    Cell growth and survival depend on a delicate balance between energy production and synthesis of metabolites. Here, we provide evidence that an alternative mitochondrial complex II (CII) assembly, designated as CII low , serves as a checkpoint for metabolite biosynthesis under bioenergetic stress, with cells suppressing their energy utilization by modulating DNA synthesis and cell cycle progression. Depletion of CII low leads to an imbalance in energy utilization and metabolite synthesis, as evidenced by recovery of the de novo pyrimidine pathway and unlocking cell cycle arrest from the S-phase. In vitro experiments are further corroborated by analysis of paraganglioma tissues from patients with sporadic, SDHA and SDHB mutations. These findings suggest that CII low is a core complex inside mitochondria that provides homeostatic control of cellular metabolism depending on the availability of energy.

  14. Metabolic adaptation of skeletal muscles to gravitational unloading

    NASA Astrophysics Data System (ADS)

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

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

  15. Loss or Mislocalization of Aquaporin-4 Affects Diffusion Properties and Intermediary Metabolism in Gray Matter of Mice.

    PubMed

    Pavlin, T; Nagelhus, E A; Brekken, C; Eyjolfsson, E M; Thoren, A; Haraldseth, O; Sonnewald, U; Ottersen, O P; Håberg, A K

    2017-01-01

    The first aim of this study was to determine how complete or perivascular loss of aquaporin-4 (AQP4) water channels affects membrane permeability for water in the mouse brain grey matter in the steady state. Time-dependent diffusion magnetic resonance imaging was performed on global Aqp4 knock out (KO) and α-syntrophin (α-syn) KO mice, in the latter perivascular AQP4 are mislocalized, but still functioning. Control animals were corresponding wild type (WT) mice. By combining in vivo diffusion measurements with the effective medium theory and previously measured extra-cellular volume fractions, the effects of membrane permeability and extracellular volume fraction were uncoupled for Aqp4 and α-syn KO. The second aim was to assess the effect of α-syn KO on cortical intermediary metabolism combining in vivo [1- 13 C]glucose and [1,2- 13 C]acetate injection with ex vivo 13 C MR spectroscopy. Aqp4 KO increased the effective diffusion coefficient at long diffusion times by 5%, and a 14% decrease in membrane water permeability was estimated for Aqp4 KO compared with WT mice. α-syn KO did not affect the measured diffusion parameters. In the metabolic analyses, significantly lower amounts of [4- 13 C]glutamate and [4- 13 C]glutamine, and percent enrichment in [4- 13 C]glutamate were detected in the α-syn KO mice. [1,2- 13 C]acetate metabolism was unaffected in α-syn KO, but the contribution of astrocyte derived metabolites to GABA synthesis was significantly increased. Taken together, α-syn KO mice appeared to have decreased neuronal glucose metabolism, partly compensated for by utilization of astrocyte derived metabolites.

  16. 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.

  17. 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

  18. Exercise, Energy Intake, Glucose Homeostasis, and the Brain

    PubMed Central

    van Praag, Henriette; Fleshner, Monika; Schwartz, Michael W.

    2014-01-01

    Here we summarize topics covered in an SFN symposium that considered how and why exercise and energy intake affect neuroplasticity and, conversely, how the brain regulates peripheral energy metabolism. This article is not a comprehensive review of the subject, but rather a view of how the authors' findings fit into a broader context. Emerging findings elucidate cellular and molecular mechanisms by which exercise and energy intake modify the plasticity of neural circuits in ways that affect brain health. By enhancing neurogenesis, synaptic plasticity and neuronal stress robustness, exercise and intermittent energy restriction/fasting may optimize brain function and forestall metabolic and neurodegenerative diseases. Moreover, brain-centered glucoregulatory and immunomodulating systems that mediate peripheral health benefits of intermittent energetic challenges have recently been described. A better understanding of adaptive neural response pathways activated by energetic challenges will enable the development and optimization of interventions to reduce the burden of disease in our communities. PMID:25392482

  19. Exercise, energy intake, glucose homeostasis, and the brain.

    PubMed

    van Praag, Henriette; Fleshner, Monika; Schwartz, Michael W; Mattson, Mark P

    2014-11-12

    Here we summarize topics covered in an SFN symposium that considered how and why exercise and energy intake affect neuroplasticity and, conversely, how the brain regulates peripheral energy metabolism. This article is not a comprehensive review of the subject, but rather a view of how the authors' findings fit into a broader context. Emerging findings elucidate cellular and molecular mechanisms by which exercise and energy intake modify the plasticity of neural circuits in ways that affect brain health. By enhancing neurogenesis, synaptic plasticity and neuronal stress robustness, exercise and intermittent energy restriction/fasting may optimize brain function and forestall metabolic and neurodegenerative diseases. Moreover, brain-centered glucoregulatory and immunomodulating systems that mediate peripheral health benefits of intermittent energetic challenges have recently been described. A better understanding of adaptive neural response pathways activated by energetic challenges will enable the development and optimization of interventions to reduce the burden of disease in our communities. Copyright © 2014 the authors 0270-6474/14/3415139-11$15.00/0.

  20. Mechanisms affecting neuroendocrine and epigenetic regulation of body weight and onset of puberty: potential implications in the child born small for gestational age (SGA).

    PubMed

    Roth, Christian L; Sathyanarayana, Sheela

    2012-06-01

    Signaling peptides produced in peripheral tissues such as gut, adipose tissue, and pancreas communicate with brain centers, such as hypothalamus and hindbrain to manage energy homeostasis. These regulatory mechanisms of energy intake and storage have evolved during long periods of hunger in the evolution of man to protect the species from extinction. It is now clear that these circuitries are influenced by prenatal and postnatal environmental factors including endocrine disruptive chemicals. Hypothalamic appetite regulatory systems develop and mature in utero and early infancy, and involve signaling pathways that are important also for the regulation of puberty onset. Recent studies in humans and animals have shown that metabolic pathways involved in regulation of growth, body weight gain and sexual maturation are largely affected by epigenetic programming that can impact both current and future generations. In particular, intrauterine and early infantile developmental phases of high plasticity are susceptible to factors that affect metabolic programming that therefore, affect metabolic function throughout life. In children born small for gestational age, poor nutritional conditions during gestation can modify metabolic systems to adapt to expectations of chronic undernutrition. These children are potentially poorly equipped to cope with energy-dense diets and are possibly programmed to store as much energy as possible, leading to later obesity, metabolic syndrome, disturbed regulation of normal puberty and early onset of cardiovascular disease. Most cases of disturbed energy balance are likely a result of a combination of genetics, epigenetics and environment. This review will discuss potential mechanisms linking intrauterine growth retardation with changes in growth, energy homeostasis and sexual maturation.

  1. Do stochastic inhomogeneities affect dark-energy precision measurements?

    PubMed

    Ben-Dayan, I; Gasperini, M; Marozzi, G; Nugier, F; Veneziano, G

    2013-01-11

    The effect of a stochastic background of cosmological perturbations on the luminosity-redshift relation is computed to second order through a recently proposed covariant and gauge-invariant light-cone averaging procedure. The resulting expressions are free from both ultraviolet and infrared divergences, implying that such perturbations cannot mimic a sizable fraction of dark energy. Different averages are estimated and depend on the particular function of the luminosity distance being averaged. The energy flux being minimally affected by perturbations at large z is proposed as the best choice for precision estimates of dark-energy parameters. Nonetheless, its irreducible (stochastic) variance induces statistical errors on Ω(Λ)(z) typically lying in the few-percent range.

  2. The role of bile acids in metabolic regulation.

    PubMed

    Vítek, Libor; Haluzík, Martin

    2016-03-01

    Bile acids (BA), long believed to only have lipid-digestive functions, have emerged as novel metabolic modulators. They have important endocrine effects through multiple cytoplasmic as well as nuclear receptors in various organs and tissues. BA affect multiple functions to control energy homeostasis, as well as glucose and lipid metabolism, predominantly by activating the nuclear farnesoid X receptor and the cytoplasmic G protein-coupled BA receptor TGR5 in a variety of tissues. However, BA also are aimed at many other cellular targets in a wide array of organs and cell compartments. Their role in the pathogenesis of diabetes, obesity and other 'diseases of civilization' becomes even more clear. They also interact with the gut microbiome, with important clinical implications, further extending the complexity of their biological functions. Therefore, it is not surprising that BA metabolism is substantially modulated by bariatric surgery, a phenomenon contributing favorably to the therapeutic effects of these surgical procedures. Based on these data, several therapeutic approaches to ameliorate obesity and diabetes have been proposed to affect the cellular targets of BA. © 2016 Society for Endocrinology.

  3. Carbohydrate Metabolism Disorders

    MedlinePlus

    Metabolism is the process your body uses to make energy from the food you eat. Food is ... disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally ...

  4. Metabolic programming of obesity by energy restriction during the perinatal period: different outcomes depending on gender and period, type and severity of restriction

    PubMed Central

    Picó, Catalina; Palou, Mariona; Priego, Teresa; Sánchez, Juana; Palou, Andreu

    2012-01-01

    Epidemiological studies in humans and controlled intervention studies in animals have shown that nutritional programming in early periods of life is a phenomenon that affects metabolic and physiological functions throughout life. The phenotypes of health or disease are hence the result of the interaction between genetic and environmental factors, starting right from conception. In this sense, gestation and lactation are disclosed as critical periods. Continuous food restriction during these stages may lead to permanent adaptations with lasting effects on the metabolism of the offspring and may influence the propensity to develop different chronic diseases associated with obesity. However, the different outcomes of these adaptations on later health may depend on factors such as the type, duration, period, and severity of the exposure to energy restriction conditions, and they are, in part, gender specific. A better understanding of the factors and mechanisms involved in metabolic programming, and their effects, may contribute significantly to the prevention of obesity, which is considered to be one of the major health concerns of our time. Here, the different outcomes of maternal food restriction during gestation and lactation in the metabolic health of offspring, as well as potential mechanisms underlying these effects are reviewed. PMID:23189059

  5. Crosstalk of Signaling and Metabolism Mediated by the NAD(+)/NADH Redox State in Brain Cells.

    PubMed

    Winkler, Ulrike; Hirrlinger, Johannes

    2015-12-01

    The energy metabolism of the brain has to be precisely adjusted to activity to cope with the organ's energy demand, implying that signaling regulates metabolism and metabolic states feedback to signaling. The NAD(+)/NADH redox state constitutes a metabolic node well suited for integration of metabolic and signaling events. It is affected by flux through metabolic pathways within a cell, but also by the metabolic state of neighboring cells, for example by lactate transferred between cells. Furthermore, signaling events both in neurons and astrocytes have been reported to change the NAD(+)/NADH redox state. Vice versa, a number of signaling events like astroglial Ca(2+) signals, neuronal NMDA-receptors as well as the activity of transcription factors are modulated by the NAD(+)/NADH redox state. In this short review, this bidirectional interdependence of signaling and metabolism involving the NAD(+)/NADH redox state as well as its potential relevance for the physiology of the brain and the whole organism in respect to blood glucose regulation and body weight control are discussed.

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

    PubMed Central

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

    2015-01-01

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

  7. Influence of the hypothalamic-pituitary-adrenal axis dysregulation on the metabolic profile of patients affected by diabetes mellitus-associated late onset hypogonadism.

    PubMed

    Tirabassi, G; Chelli, F M; Ciommi, M; Lenzi, A; Balercia, G

    2016-01-01

    Functional hypercortisolism (FH) is generated by clinical states able to chronically activate the hypothalamic-pituitary-adrenal (HPA) axis [e.g. diabetes mellitus (DM)]. No study has evaluated FH influence in worsening the metabolic profile of male patients affected by DM-associated hypogonadism. In this retrospective work, we assess the possible association between HPA axis-dysregulation and cardiovascular risk factors in men simultaneously affected by DM and late-onset hypogonadism (LOH). Fourteen DM and LOH subjects affected by FH (Hypercort-DM-LOH) and fourteen DM and LOH subjects who were not suffering from FH (Normocort-DM-LOH) were retrospectively considered. Clinical, hormonal and metabolic parameters were retrieved. All metabolic parameters, except for systolic blood pressure, were significantly worse in Hypercort-DM-LOH than in Normocort-DM-LOH. After adjustment for body mass index, waist and total testosterone, Hypercort-DM-LOH subjects showed significantly worse metabolic parameters than Normocort-DM-LOH ones. In Normocort-DM-LOH, no significant correlation between general/hormonal parameters and metabolic variables was present. In Hypercort-DM-LOH, positive and significant correlations of cortisol area under the curve (AUC) after corticotropin releasing hormone with glycemia, triglycerides and blood pressure were evident; on the other hand, negative and significant correlation was present between cortisol AUC and high density lipoprotein (HDL) cholesterol. The associations of AUC cortisol with glycemia, HDL cholesterol and diastolic blood pressure (DBP) were further confirmed at quantile regression after adjustment for therapy. FH may determine a worsening of the metabolic profile in DM-associated hypogonadism. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by

  8. NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism.

    PubMed

    Xiao, Wusheng; Wang, Rui-Sheng; Handy, Diane E; Loscalzo, Joseph

    2018-01-20

    The nicotinamide adenine dinucleotide (NAD + )/reduced NAD + (NADH) and NADP + /reduced NADP + (NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has been associated with many pathological disorders. Recent Advances: Newly identified biosynthetic enzymes and newly developed genetically encoded biosensors enable us to understand better how cells maintain compartmentalized NAD(H) and NADP(H) pools. The concept of redox stress (oxidative and reductive stress) reflected by changes in NAD(H)/NADP(H) has increasingly gained attention. The emerging roles of NAD + -consuming proteins in regulating cellular redox and metabolic homeostasis are active research topics. The biosynthesis and distribution of cellular NAD(H) and NADP(H) are highly compartmentalized. It is critical to understand how cells maintain the steady levels of these redox couple pools to ensure their normal functions and simultaneously avoid inducing redox stress. In addition, it is essential to understand how NAD(H)- and NADP(H)-utilizing enzymes interact with other signaling pathways, such as those regulated by hypoxia-inducible factor, to maintain cellular redox homeostasis and energy metabolism. Additional studies are needed to investigate the inter-relationships among compartmentalized NAD(H)/NADP(H) pools and how these two dinucleotide redox couples collaboratively regulate cellular redox states and cellular metabolism under normal and pathological conditions. Furthermore, recent studies suggest the utility of using pharmacological interventions or nutrient-based bioactive NAD + precursors as therapeutic interventions for metabolic diseases. Thus, a better understanding of the cellular functions of NAD(H) and NADP(H) may facilitate efforts to address a host of pathological disorders effectively. Antioxid. Redox Signal. 28, 251-272.

  9. Simultaneous Multiparameter Cellular Energy Metabolism Profiling of Small Populations of Cells.

    PubMed

    Kelbauskas, Laimonas; Ashili, Shashaanka P; Lee, Kristen B; Zhu, Haixin; Tian, Yanqing; Meldrum, Deirdre R

    2018-03-12

    Functional and genomic heterogeneity of individual cells are central players in a broad spectrum of normal and disease states. Our knowledge about the role of cellular heterogeneity in tissue and organism function remains limited due to analytical challenges one encounters when performing single cell studies in the context of cell-cell interactions. Information based on bulk samples represents ensemble averages over populations of cells, while data generated from isolated single cells do not account for intercellular interactions. We describe a new technology and demonstrate two important advantages over existing technologies: first, it enables multiparameter energy metabolism profiling of small cell populations (<100 cells)-a sample size that is at least an order of magnitude smaller than other, commercially available technologies; second, it can perform simultaneous real-time measurements of oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and mitochondrial membrane potential (MMP)-a capability not offered by any other commercially available technology. Our results revealed substantial diversity in response kinetics of the three analytes in dysplastic human epithelial esophageal cells and suggest the existence of varying cellular energy metabolism profiles and their kinetics among small populations of cells. The technology represents a powerful analytical tool for multiparameter studies of cellular function.

  10. Energy metabolism of synaptosomes from different neuronal systems of rat cerebellum during aging: a functional proteomic characterization.

    PubMed

    Ferrari, Federica; Gorini, Antonella; Villa, Roberto Federico

    2015-01-01

    Functional proteomics was used to characterize age-related changes in energy metabolism of different neuronal pathways within the cerebellar cortex of Wistar rats aged 2, 6, 12, 18, and 24 months. The "large" synaptosomes, derived from the glutamatergic mossy fibre endings which make synaptic contact with the granule cells of the granular layer, and the "small" synaptosomes, derived from the pre-synaptic terminals of granule cells making synaptic contact with the dendrites of Purkinje cells, were isolated by a combined differential/gradient centrifugation technique. Because most brain disorders are associated with bioenergetic changes, the maximum rate (Vmax) of selected enzymes of glycolysis, Krebs' cycle, glutamate and amino acids metabolism, and acetylcholine catabolism were evaluated. The results show that "large" and "small" synaptosomes possess specific and independent metabolic features. This study represents a reliable model to study in vivo (1) the physiopathological molecular mechanisms of some brain diseases dependent on energy metabolism, (2) the responsiveness to noxious stimuli, and (3) the effects of drugs, discriminating their action sites at subcellular level on specific neuronal pathways.

  11. 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

  12. Political ideology affects energy-efficiency attitudes and choices.

    PubMed

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

    2013-06-04

    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.

  13. Influence of insulin on glucose metabolism and energy expenditure in septic patients

    PubMed Central

    Rusavy, Zdenek; Sramek, Vladimir; Lacigova, Silvie; Novak, Ivan; Tesinsky, Pavel; Macdonald, Ian A

    2004-01-01

    Introduction It is recognized that administration of insulin with glucose decreases catabolic response in sepsis. The aim of the present study was to compare the effects of two levels of insulinaemia on glucose metabolism and energy expenditure in septic patients and volunteers. Methods Glucose uptake, oxidation and storage, and energy expenditure were measured, using indirect calorimetry, in 20 stable septic patients and 10 volunteers in a two-step hyperinsulinaemic (serum insulin levels 250 and 1250 mIU/l), euglycaemic (blood glucose concentration 5 mmol/l) clamp. Differences between steps of the clamp (from serum insulin 1250 to 250 mIU/l) for all parameters were calculated for each individual, and compared between septic patients and volunteers using the Wilcoxon nonpaired test. Results Differences in glucose uptake and storage were significantly less in septic patients. The differences in glucose oxidation between the groups were not statistically significant. Baseline energy expenditure was significantly higher in septic patients, and there was no significant increase in either step of the clamp in this group; when comparing the two groups, the differences between steps were significantly greater in volunteers. Conclusion A hyperdynamic state of sepsis leads to a decrease in glucose uptake and storage in comparison with healthy volunteers. An increase in insulinaemia leads to an increase in all parameters of glucose metabolism, but the increases in glucose uptake and storage are significantly lower in septic patients. A high level of insulinaemia in sepsis increases glucose uptake and oxidation significantly, but not energy expenditure, in comparison with volunteers. PMID:15312220

  14. Effects of coconut oil consumption on energy metabolism, cardiometabolic risk markers, and appetitive responses in women with excess body fat.

    PubMed

    Valente, Flávia Xavier; Cândido, Flávia Galvão; Lopes, Lílian Lelis; Dias, Desirrê Morais; Carvalho, Samantha Dalbosco Lins; Pereira, Patrícia Feliciano; Bressan, Josefina

    2018-06-01

    Virgin coconut oil (VCO) is a medium-chain fatty acid source with popularly attributed benefits on obesity management. However, its role on obesity requires elucidation due to its saturated nature. In the study herein, we investigated acute effects of VCO consumption on energy metabolism, cardiometabolic risk markers, and appetitive responses in women with excess body fat. Fifteen adult women with excess body fat (37.43 ± 0.83%) participated in this randomized, crossover, controlled study. Two isocaloric mixed breakfasts containing 25 mL of VCO or control (extra-virgin olive oil-C) were evaluated. Resting energy expenditure (REE), fat oxidation rate (FOR), diet induced thermogenesis (DIT) and appetitive subjective responses were assessed at fasting and postprandial periods (up to 240 min). Cardiometabolic risk markers were assessed at fasting and up to 180 min postprandially. VCO did not affect REE, FOR, and DIT compared to C. In addition, VCO did not cause deleterious change in triglycerides, total cholesterol, HDL-c, LDL-c, triglycerides/HDL-c ratio, uric acid, glucose and Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR) (P time×treatment  > 0.05). However, VCO suppressed less hunger (P time×treatment  = 0.003), total satiety (P iAUC  = 0.021) and total fullness (P iAUC  = 0.035) responses than C. VCO consumption did not acutely change energy metabolism and cardiometabolic risk markers when added to a mixed breakfast but promoted less appetitive responses.

  15. Cell proliferation and progesterone synthesis depend on lipid metabolism in bovine granulosa cells.

    PubMed

    Elis, Sebastien; Desmarchais, Alice; Maillard, Virginie; Uzbekova, Svetlana; Monget, Philippe; Dupont, Joëlle

    2015-03-15

    In dairy cows, lipids are essential to support energy supplies for all biological functions, especially during early lactation. Lipid metabolism is crucial for sustaining proper reproductive function. Alteration of lipid metabolism impacts follicular development and affects oocyte developmental competence. Indeed, nonesterified fatty acids are able to decrease granulosa cell (GC) proliferation and affect estradiol synthesis, thus potentially affecting follicular growth and viability. The objective of this study was to assess the impact of lipid metabolism on bovine GCs, through the use of the lipid metabolism inhibitors etomoxir, an inhibitor of fatty acid (FA) oxidation through inhibition of carnitine palmitoyl transferase 1 (CPT1), and C75, an inhibitor of FA synthesis through inhibition of fatty acid synthase. We showed that etomoxir and C75 significantly inhibited DNA synthesis in vitro; C75 also significantly decreased progesterone synthesis. Both inhibitors significantly reduced AMPK (5' adenosine monophosphate-activated protein kinase) and acetyl-CoA carboxylase phosphorylation. Etomoxir also affected the AKT (protein kinase B) signaling pathway. Combined, these data suggest that both FA oxidation and synthesis are important for the bovine GCs to express a proliferative and steroidogenic phenotype and, thus, for sustaining follicular growth. Despite these findings, it is important to note that the changes caused by the inhibitors of FA metabolism on GCs in vitro are globally mild, suggesting that lipid metabolism is not as critical in GCs as was observed in the oocyte-cumulus complex. Further studies are needed to investigate the detailed mechanisms by which lipid metabolism interacts with GC functions. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. 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...

  17. The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial.

    PubMed

    Rijpma, Anne; van der Graaf, Marinette; Lansbergen, Marieke M; Meulenbroek, Olga; Cetinyurek-Yavuz, Aysun; Sijben, John W; Heerschap, Arend; Olde Rikkert, Marcel G M

    2017-07-26

    Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer's disease. Thirty-four drug-naive patients with mild Alzheimer's disease (Mini Mental State Examination score ≥20) were enrolled in this exploratory, double-blind, randomized controlled study. Before and after 4-week intervention with Souvenaid or an isocaloric control product, phosphorus and proton magnetic resonance spectroscopy (MRS) was performed to assess surrogate measures of phospholipid synthesis and breakdown (phosphomonoesters [PME] and phosphodiesters [PDEs]), neural integrity (N-acetyl aspartate), gliosis (myo-inositol), and choline metabolism (choline-containing compounds [tCho]). The main outcome parameters were PME and PDE signal intensities and the PME/PDE ratio. MRS data from 33 patients (60-86 years old; 42% males; Souvenaid arm n = 16; control arm n = 17) were analyzed. PME/PDE and tCho were higher after 4 weeks of Souvenaid compared with control (PME/PDE least squares [LS] mean difference [95% CI] 0.18 [0.06-0.30], p = 0.005; tCho LS mean difference [95% CI] 0.01 [0.00-0.02], p = 0.019). No significant differences were observed in the other MRS outcome parameters. MRS reveals that Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease, in line with findings in preclinical studies. Netherlands Trial Register, NTR3346 . Registered on 13 March 2012.

  18. 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. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  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. Microplastics Affect Energy Balance and Gametogenesis in the Pearl Oyster Pinctada margaritifera.

    PubMed

    Gardon, Tony; Reisser, Céline; Soyez, Claude; Quillien, Virgile; Le Moullac, Gilles

    2018-05-01

    Plastic pollution in the environment is increasing at global scale. Microplastics (MP) are derived from degradation of larger plastic items or directly produced in microparticles form (< 5 mm). Plastics, widely used in structures and equipment of pearl farming, are a source of pollution to the detriment of the lagoon ecosystem. To evaluate the impact of MP on the physiology of Pinctada margaritifera, a species of ecological and commercial interests, adult oysters were exposed to polystyrene microbeads (micro-PS of 6 and 10 μm) for 2 months. Three concentrations, 0.25, 2.5, and 25 μg L -1 , and a control were tested. Ingestion and respiration rate and assimilation efficiency were monitored on a metabolic measurement system to determine the individual energy balance (Scope For Growth, SFG). Effects on reproduction were also assessed. The assimilation efficiency decreased significantly according to micro-PS concentration. The SFG was significantly impacted by a dose-dependent decrease from 0.25 μg L -1 ( p < 0.0001), and a negative SFG was measured in oysters exposed to 25 μg L -1 . Gonads may have provided the missing energy to maintain animals' metabolism through the production of metabolites derived from germ cells phagocytosis. This study shows that micro-PS significantly impact the assimilation efficiency and more broadly the energy balance of P. margaritifera, with negative repercussions on reproduction.

  1. Coupling nutrient sensing to metabolic homoeostasis: the role of the mammalian target of rapamycin complex 1 pathway.

    PubMed

    André, Caroline; Cota, Daniela

    2012-11-01

    The mammalian target of rapamycin complex 1 (mTORC1) pathway is known to couple different environmental cues to the regulation of several energy-demanding functions within the cell, spanning from protein translation to mitochondrial activity. As a result, at the organism level, mTORC1 activity affects energy balance and general metabolic homoeostasis by modulating both the activity of neuronal populations that play key roles in the control of food intake and body weight, as well as by determining storage and use of fuel substrates in peripheral tissues. This review focuses on recent advances made in understanding the role of the mTORC1 pathway in the regulation of energy balance. More particularly, it aims at providing an overview of the status of knowledge regarding the mechanisms underlying the ability of certain amino acids, glucose and fatty acids, to affect mTORC1 activity and in turn illustrates how the mTORC1 pathway couples nutrient sensing to the hypothalamic regulation of the organisms' energy homoeostasis and to the control of intracellular metabolic processes, such as glucose uptake, protein and lipid biosynthesis. The evidence reviewed pinpoints the mTORC1 pathway as an integrator of the actions of nutrients on metabolic health and provides insight into the relevance of this intracellular pathway as a potential target for the therapy of metabolic diseases such as obesity and type-2 diabetes.

  2. ALTERATIONS IN THE ENERGY METABOLISM OF AN ESTUARINE MYSID (MYSIDOPSIS BAHIA) AS INDICATORS OF STRESS FROM CHRONIC PESTICIDE EXPOSURE

    EPA Science Inventory

    Various aspects of the energy metabolism of an estuarine mysid (Mysidopsis bahia) were examined for different life stages during a life-cycle exposure to the organophosphate pesticide fenthion. Dose-response relationships were developed for several metabolic rate functions (oxyge...

  3. Preliminary findings on the role of PLIN1 polymorphisms on body composition and energy metabolism response to energy restriction in obese women.

    PubMed

    Ruiz, J R; Larrarte, E; Margareto, J; Ares, R; Alkorta, P; Labayen, I

    2011-08-01

    The aim of the present study was to investigate the association of PLIN1 11482G>A (rs894160) and PLIN1 13041A>G (rs2304795) polymorphisms with body composition, energy and substrate metabolism, and the metabolic response to a 12-week energy-restricted diet in obese women. The study comprised a total of seventy-eight obese (BMI 34·0 (SD 2·8) kg/m(2)) women (age 36·7 (SD 7) years). We measured weight, height and waist circumference before and after a 12-week controlled energy-restricted diet intervention. Body fat mass and lean mass were measured by dual-energy X-ray absorptiometry. RMR and lipid oxidation rate were measured by indirect calorimetry. We also analysed fasting plasma glucose, insulin, cholesterol and leptin. Women carrying the 11482A allele had a lower reduction in waist circumference than non-A allele carriers (3·2 (SD 0·5) v. 4·6 (SD 0·6) %, respectively, P = 0·047; P for gene-diet interaction = 0·064). Moreover, women with the 11482A allele had a higher decrease in lipid oxidation rate than non-A allele carriers (58·9 (SD 6·7) v. 31·3 (SD 8·2) %, respectively, P = 0·012; P for gene-diet interaction = 0·004). There was no interaction effect between the 13041A>G polymorphism and diet-induced changes on the outcome variables (all P>0·1). These results confirm and extend previous findings suggesting that the PLIN1 11482G>A polymorphism plays a modulating role on diet-induced changes in body fat and energy metabolism in obese women.

  4. Differential effects of lipopolysaccharide on energy metabolism in murine microglial N9 and cholinergic SN56 neuronal cells.

    PubMed

    Klimaszewska-Łata, Joanna; Gul-Hinc, Sylwia; Bielarczyk, Hanna; Ronowska, Anna; Zyśk, Marlena; Grużewska, Katarzyna; Pawełczyk, Tadeusz; Szutowicz, Andrzej

    2015-04-01

    There are significant differences between acetyl-CoA and ATP levels, enzymes of acetyl-CoA metabolism, and toll-like receptor 4 contents in non-activated microglial N9 and non-differentiated cholinergic SN56 neuroblastoma cells. Exposition of N9 cells to lipopolysaccharide caused concentration-dependent several-fold increases of nitrogen oxide synthesis, accompanied by inhibition of pyruvate dehydrogenase complex, aconitase, and α-ketoglutarate dehydrogenase complex activities, and by nearly proportional depletion of acetyl-CoA, but by relatively smaller losses in ATP content and cell viability (about 5%). On the contrary, SN56 cells appeared to be insensitive to direct exposition to high concentration of lipopolysaccharide. However, exogenous nitric oxide resulted in marked inhibition pyruvate dehydrogenase and aconitase activities, depletion of acetyl-CoA, along with respective loss of SN56 cells viability. These data indicate that these two common neurodegenerative signals may differentially affect energy-acetyl-CoA metabolism in microglial and cholinergic neuronal cell compartments in the brain. Moreover, microglial cells appeared to be more resistant than neuronal cells to acetyl-CoA and ATP depletion evoked by these neurodegenerative conditions. Together, these data indicate that differential susceptibility of microglia and cholinergic neuronal cells to neurotoxic signals may result from differences in densities of toll-like receptors and degree of disequilibrium between acetyl-CoA provision in mitochondria and its utilization for energy production and acetylation reactions in each particular group of cells. There are significant differences between acetyl-CoA and ATP levels and enzymes of acetyl-CoA metabolism in non-activated microglial N9 and non-differentiated cholinergic SN56 neuroblastoma cells. Pathological stimulation of microglial toll-like receptors (TLRs) triggered excessive synthesis of microglia-derived nitric oxide (NO)/NOO radicals that

  5. Targeting metabolic pathways for head and neck cancers therapeutics.

    PubMed

    Yamamoto, Masashi; Inohara, Hidenori; Nakagawa, Takashi

    2017-09-01

    Cancer cells have distinctive energy metabolism pathways that support their rapid cell division. The preference for anaerobic glycolysis under the normal oxygen condition is known as the Warburg effect and has been observed in head and neck cancers. These metabolic changes are controlled by cancer-related transcription factors, such as tumor suppressor gene and hypoxia inducible factor 1α. In addition, various metabolic enzymes also actively regulate cancer-specific metabolism including the switch between aerobic and anaerobic glycolysis. For a long time, these metabolic changes in cancer cells have been considered a consequence of transformation required to maintain the high rate of tumor cell replication. However, recent studies indicate that alteration of metabolism is sufficient to initiate tumor transformation. Indeed, oncogenic mutations in the metabolic enzymes, isocitrate dehydrogenase and succinate dehydrogenase, have been increasingly found in various cancers, including head and neck cancers. In the present review, we introduce recent findings regarding the cancer metabolism, including the molecular mechanisms of how they affect cancer pathogenesis and maintenance. We also discuss the current and future perspectives on therapeutics that target metabolic pathways, with an emphasis on head and neck cancer.

  6. Energy Metabolic Adaptation and Cardiometabolic Improvements One Year After Gastric Bypass, Sleeve Gastrectomy, and Gastric Band.

    PubMed

    Tam, Charmaine S; Redman, Leanne M; Greenway, Frank; LeBlanc, Karl A; Haussmann, Mark G; Ravussin, Eric

    2016-10-01

    It is not known whether the magnitude of metabolic adaptation, a greater than expected drop in energy expenditure, depends on the type of bariatric surgery and is associated with cardiometabolic improvements. To compare changes in energy expenditure (metabolic chamber) and circulating cardiometabolic markers 8 weeks and 1 year after Roux-en-y bypass (RYGB), sleeve gastrectomy (SG), laparoscopic adjustable gastric band (LAGB), or a low-calorie diet (LCD). Design, Setting, Participants, and Intervention: This was a parallel-arm, prospective observational study of 30 individuals (27 females; mean age, 46 ± 2 years; body mass index, 47.2 ± 1.5 kg/m 2 ) either self-selecting bariatric surgery (five RYGB, nine SG, seven LAGB) or on a LCD (n = 9) intervention (800 kcal/d for 8 weeks, followed by weight maintenance). After 1 year, the RYGB and SG groups had similar degrees of body weight loss (33-36%), whereas the LAGB and LCD groups had 16 and 4% weight loss, respectively. After adjusting for changes in body composition, 24-hour energy expenditure was significantly decreased in all treatment groups at 8 weeks (-254 to -82 kcal/d), a drop that only persisted in RYGB (-124 ± 42 kcal/d; P = .002) and SG (-155 ± 118 kcal/d; P = .02) groups at 1 year. The degree of metabolic adaptation (24-hour and sleeping energy expenditure) was not significantly different between the treatment groups at either time-point. Plasma high-density lipoprotein and total and high molecular weight adiponectin were increased, and triglycerides and high-sensitivity C-reactive protein levels were reduced 1 year after RYGB or SG. Metabolic adaptation of approximately 150 kcal/d occurs after RYGB and SG surgery. Future studies are required to examine whether these effects remain beyond 1 year.

  7. The Essential Role of Cholesterol Metabolism in the Intracellular Survival of Mycobacterium leprae Is Not Coupled to Central Carbon Metabolism and Energy Production.

    PubMed

    Marques, Maria Angela M; Berrêdo-Pinho, Marcia; Rosa, Thabatta L S A; Pujari, Venugopal; Lemes, Robertha M R; Lery, Leticia M S; Silva, Carlos Adriano M; Guimarães, Ana Carolina R; Atella, Georgia C; Wheat, William H; Brennan, Patrick J; Crick, Dean C; Belisle, John T; Pessolani, Maria Cristina V

    2015-12-01

    Mycobacterium leprae induces the formation of lipid droplets, which are recruited to pathogen-containing phagosomes in infected macrophages and Schwann cells. Cholesterol is among the lipids with increased abundance in M. leprae-infected cells, and intracellular survival relies on cholesterol accumulation. The present study investigated the capacity of M. leprae to acquire and metabolize cholesterol. In silico analyses showed that oxidation of cholesterol to cholest-4-en-3-one (cholestenone), the first step of cholesterol degradation catalyzed by the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD), is apparently the only portion of the cholesterol catabolic pathway seen in Mycobacterium tuberculosis preserved by M. leprae. Incubation of bacteria with radiolabeled cholesterol confirmed the in silico predictions. Radiorespirometry and lipid analyses performed after incubating M. leprae with [4-(14)C]cholesterol or [26-(14)C]cholesterol showed the inability of this pathogen to metabolize the sterol rings or the side chain of cholesterol as a source of energy and carbon. However, the bacteria avidly incorporated cholesterol and, as expected, converted it to cholestenone both in vitro and in vivo. Our data indicate that M. leprae has lost the capacity to degrade and utilize cholesterol as a nutritional source but retains the enzyme responsible for its oxidation to cholestenone. Thus, the essential role of cholesterol metabolism in the intracellular survival of M. leprae is uncoupled from central carbon metabolism and energy production. Further elucidation of cholesterol metabolism in the host cell during M. leprae infection will establish the mechanism by which this lipid supports M. leprae intracellular survival and will open new avenues for novel leprosy therapies. Our study focused on the obligate intracellular pathogen Mycobacterium leprae and its capacity to metabolize cholesterol. The data make an important contribution for those interested in understanding the

  8. The Essential Role of Cholesterol Metabolism in the Intracellular Survival of Mycobacterium leprae Is Not Coupled to Central Carbon Metabolism and Energy Production

    PubMed Central

    Marques, Maria Angela M.; Berrêdo-Pinho, Marcia; Rosa, Thabatta L. S. A.; Pujari, Venugopal; Lemes, Robertha M. R.; Lery, Leticia M. S.; Silva, Carlos Adriano M.; Guimarães, Ana Carolina R.; Atella, Georgia C.; Wheat, William H.; Brennan, Patrick J.; Crick, Dean C.; Belisle, John T.

    2015-01-01

    ABSTRACT Mycobacterium leprae induces the formation of lipid droplets, which are recruited to pathogen-containing phagosomes in infected macrophages and Schwann cells. Cholesterol is among the lipids with increased abundance in M. leprae-infected cells, and intracellular survival relies on cholesterol accumulation. The present study investigated the capacity of M. leprae to acquire and metabolize cholesterol. In silico analyses showed that oxidation of cholesterol to cholest-4-en-3-one (cholestenone), the first step of cholesterol degradation catalyzed by the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD), is apparently the only portion of the cholesterol catabolic pathway seen in Mycobacterium tuberculosis preserved by M. leprae. Incubation of bacteria with radiolabeled cholesterol confirmed the in silico predictions. Radiorespirometry and lipid analyses performed after incubating M. leprae with [4-14C]cholesterol or [26-14C]cholesterol showed the inability of this pathogen to metabolize the sterol rings or the side chain of cholesterol as a source of energy and carbon. However, the bacteria avidly incorporated cholesterol and, as expected, converted it to cholestenone both in vitro and in vivo. Our data indicate that M. leprae has lost the capacity to degrade and utilize cholesterol as a nutritional source but retains the enzyme responsible for its oxidation to cholestenone. Thus, the essential role of cholesterol metabolism in the intracellular survival of M. leprae is uncoupled from central carbon metabolism and energy production. Further elucidation of cholesterol metabolism in the host cell during M. leprae infection will establish the mechanism by which this lipid supports M. leprae intracellular survival and will open new avenues for novel leprosy therapies. IMPORTANCE Our study focused on the obligate intracellular pathogen Mycobacterium leprae and its capacity to metabolize cholesterol. The data make an important contribution for those interested in

  9. Global Profiling of Protein Lysine Malonylation in Escherichia coli Reveals Its Role in Energy Metabolism.

    PubMed

    Qian, Lili; Nie, Litong; Chen, Ming; Liu, Ping; Zhu, Jun; Zhai, Linhui; Tao, Sheng-Ce; Cheng, Zhongyi; Zhao, Yingming; Tan, Minjia

    2016-06-03

    Protein lysine malonylation is a recently identified post-translational modification (PTM), which is evolutionarily conserved from bacteria to mammals. Although analysis of lysine malonylome in mammalians suggested that this modification was related to energy metabolism, the substrates and biological roles of malonylation in prokaryotes are still poorly understood. In this study, we performed qualitative and quantitative analyses to globally identify lysine malonylation substrates in Escherichia coli. We identified 1745 malonylation sites in 594 proteins in E. coli, representing the first and largest malonylome data set in prokaryotes up to date. Bioinformatic analyses showed that lysine malonylation was significantly enriched in protein translation, energy metabolism pathways and fatty acid biosynthesis, implying the potential roles of protein malonylation in bacterial physiology. Quantitative proteomics by fatty acid synthase inhibition in both auxotrophic and prototrophic E. coli strains revealed that lysine malonylation is closely associated with E. coli fatty acid metabolism. Protein structural analysis and mutagenesis experiment suggested malonylation could impact enzymatic activity of citrate synthase, a key enzyme in citric acid (TCA) cycle. Further comparative analysis among lysine malonylome, succinylome and acetylome data showed that these three modifications could participate in some similar enriched metabolism pathways, but they could also possibly play distinct roles such as in fatty acid synthesis. These data expanded our knowledge of lysine malonylation in prokaryotes, providing a resource for functional study of lysine malonylation in bacteria.

  10. Effect of Short-Term Thyroxine Administration on Energy Metabolism and Mitochondrial Efficiency in Humans

    PubMed Central

    Johannsen, Darcy L.; Galgani, Jose E.; Johannsen, Neil M.; Zhang, Zhengyu; Covington, Jeffrey D.; Ravussin, Eric

    2012-01-01

    The physiologic effects of triiodothyronine (T3) on metabolic rate are well-documented; however, the effects of thyroxine (T4) are less clear despite its wide-spread use to treat thyroid-related disorders and other non-thyroidal conditions. Here, we investigated the effects of acute (3-day) T4 supplementation on energy expenditure at rest and during incremental exercise. Furthermore, we used a combination of in situ and in vitro approaches to measure skeletal muscle metabolism before and after T4 treatment. Ten healthy, euthyroid males were given 200 µg T4 (levothyroxine) per day for 3 days. Energy expenditure was measured at rest and during exercise by indirect calorimetry, and skeletal muscle mitochondrial function was assessed by in situ ATP flux (31P MRS) and in vitro respiratory control ratio (RCR, state 3/state 4 rate of oxygen uptake using a Clark-type electrode) before and after acute T4 treatment. Thyroxine had a subtle effect on resting metabolic rate, increasing it by 4% (p = 0.059) without a change in resting ATP demand (i.e., ATP flux) of the vastus lateralis. Exercise efficiency did not change with T4 treatment. The maximal capacity to produce ATP (state 3 respiration) and the coupled state of the mitochondria (RCR) were reduced by approximately 30% with T4 (p = 0.057 and p = 0.04, respectively). Together, the results suggest that T4, although less metabolically active than T3, reduces skeletal muscle efficiency and modestly increases resting metabolism even after short-term supplementation. Our findings may be clinically relevant given the expanding application of T4 to treat non-thyroidal conditions such as obesity and weight loss. PMID:22844412

  11. Variants in glucose- and circadian rhythm–related genes affect the response of energy expenditure to weight-loss diets: the POUNDS LOST Trial123

    PubMed Central

    Mirzaei, Khadijeh; Xu, Min; Qi, Qibin; de Jonge, Lilian; Bray, George A; Sacks, Frank; Qi, Lu

    2014-01-01

    Background: Circadian rhythm has been shown to be related to glucose metabolism and risk of diabetes, probably through effects on energy balance. Recent genome-wide association studies identified variants in circadian rhythm–related genes (CRY2 and MTNR1B) associated with glucose homeostasis. Objective: We tested whether CRY2 and MTNR1B genotypes affected changes in measures of energy expenditure in response to a weight-loss diet intervention in a 2-y randomized clinical trial, the POUNDS (Preventing Overweight Using Novel Dietary Strategies) LOST Trial. Design: The variants CRY2 rs11605924 (n = 721) and MTNR1B rs10830963 (n = 722) were genotyped in overweight or obese adults who were randomly assigned to 1 of 4 weight-loss diets that differed in their proportions of macronutrients. Respiratory quotient (RQ) and resting metabolic rate (RMR) were measured. Results: By 2 y of diet intervention, the A allele of CRY2 rs11605924 was significantly associated with a greater reduction in RQ (P = 0.03) and a greater increase in RMR and RMR/kg (both P = 0.04). The G allele of MTNR1B rs10830963 was significantly associated with a greater increase in RQ (P = 0.01) but was not related to changes in RMR and RMR/kg. In addition, we found significant gene-diet fat interactions for both CRY2 (P-interaction = 0.02) and MTNR1B (P-interaction < 0.001) in relation to 2-y changes in RQ. Conclusions: Our data indicate that variants in the circadian-related genes CRY2 and MTNR1B may affect long-term changes in energy expenditure, and dietary fat intake may modify the genetic effects. This trial was registered at www.clinicaltrials.gov as NCT00072995. PMID:24335056

  12. Energy metabolism of cerebral mitochondria during aging, ischemia and post-ischemic recovery assessed by functional proteomics of enzymes.

    PubMed

    Villa, Roberto Federico; Gorini, Antonella; Ferrari, Federica; Hoyer, Siegfried

    2013-12-01

    Stroke is a leading cause of death and disability, but most of the therapeutic approaches failed in clinical trials. The energy metabolism alterations, due to marked ATP decline, are strongly related to stroke and, at present, their physiopathological roles are not fully understood. Thus, the aim of this study was to evaluate the effects of aging on ischemia-induced changes in energy mitochondrial transduction and the consequences on overall brain energy metabolism in an in vivo experimental model of complete cerebral ischemia of 15min duration and during post-ischemic recirculation after 1, 24, 48, 72 and 96h, in 1year "adult" and 2year-old "aged" rats. The maximum rate (Vmax) of citrate synthase, malate dehydrogenase, succinate dehydrogenase for Krebs' cycle; NADH-cytochrome c reductase and cytochrome oxidase for electron transfer chain (ETC) were assayed in non-synaptic "free" mitochondria and in two populations of intra-synaptic mitochondria, i.e., "light" and "heavy" mitochondria. The catalytic activities of enzymes markedly differ according to: (a) mitochondrial type (non-synaptic, intra-synaptic), (b) age, (c) acute effects of ischemia and (d) post-ischemic recirculation at different times. Enzyme activities changes are injury maturation events and strictly reflect the bioenergetic state of the tissue in each specific experimental condition respect to the energy demand, as shown by the comparative evaluation of the energy-linked metabolites and substrates content. Remarkably, recovery of mitochondrial function was more difficult for intra-synaptic mitochondria in "aged" rats, but enzyme activities of energy metabolism tended to normalize in all mitochondrial populations after 96h of recirculation. This observation is relevant for Therapy, indicating that mitochondrial enzymes may be important metabolic factors for the responsiveness of ischemic penumbra towards the restore of cerebral functions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. 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

  14. 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.

  15. Acetate formation in the energy metabolism of parasitic helminths and protists.

    PubMed

    Tielens, Aloysius G M; van Grinsven, Koen W A; Henze, Katrin; van Hellemond, Jaap J; Martin, William

    2010-03-15

    Formation and excretion of acetate as a metabolic end product of energy metabolism occurs in many protist and helminth parasites, such as the parasitic helminths Fasciola hepatica, Haemonchus contortus and Ascaris suum, and the protist parasites, Giardia lamblia, Entamoeba histolytica, Trichomonas vaginalis as well as Trypanosoma and Leishmania spp. In all of these parasites acetate is a main end product of their energy metabolism, whereas acetate formation does not occur in their mammalian hosts. Acetate production might therefore harbour novel targets for the development of new anti-parasitic drugs. In parasites, acetate is produced from acetyl-CoA by two different reactions, both involving substrate level phosphorylation, that are catalysed by either a cytosolic acetyl-CoA synthetase (ACS) or an organellar acetate:succinate CoA-transferase (ASCT). The ACS reaction is directly coupled to ATP synthesis, whereas the ASCT reaction yields succinyl-CoA for ATP formation via succinyl-CoA synthetase (SCS). Based on recent work on the ASCTs of F. hepatica, T. vaginalis and Trypanosoma brucei we suggest the existence of three subfamilies of enzymes within the CoA-transferase family I. Enzymes of these three subfamilies catalyse the ASCT reaction in eukaryotes via the same mechanism, but the subfamilies share little sequence homology. The CoA-transferases of the three subfamilies are all present inside ATP-producing organelles of parasites, those of subfamily IA in the mitochondria of trypanosomatids, subfamily IB in the mitochondria of parasitic worms and subfamily IC in hydrogenosome-bearing parasites. Together with the recent characterisation among non-parasitic protists of yet a third route of acetate formation involving acetate kinase (ACK) and phosphotransacetylase (PTA) that was previously unknown among eukaryotes, these recent developments provide a good opportunity to have a closer look at eukaryotic acetate formation. (c) 2010 Australian Society for Parasitology

  16. Metabolic and neuroendocrine responses to Roux-en-Y gastric bypass. I: energy balance, metabolic changes, and fat loss.

    PubMed

    Liu, X; Lagoy, A; Discenza, I; Papineau, G; Lewis, E; Braden, G; Romanelli, J; Braun, B; Silva, J E

    2012-08-01

    Obesity is a major health problem. Effective treatment requires understanding the homeostatic responses to caloric restriction. The aim was to study Roux-en-Y gastric bypass patients longitudinally for 6 months after surgery to identify major factors modulating fat loss. We studied 13 patients (11 females and two males) aged 41.2 ± 2 yr. Mean body mass index was 44.6 ± 1.2 kg/m(2), with 50 ± 1% body fat (58.3 kg). Selection excluded patients with confounding comorbidities or treatments. Caloric intake was reduced 742 ± 82 kcal/d by 1 month and 450 kcal/d between 2 and 4 months postoperatively. By 6 months, relative to baseline, body mass index decreased 24.8 ± 1.1%; percentage body fat, 37.3 ± 3.2% (21.7 kg); fat free mass (FFM), 9.7 ± 1.2%; and resting metabolic rate (RMR), 18.1 ± 4.3%. RMR correlated with FFM at all times (r = 0.71; P < 0.0001), but FFM explained no more than 50% of RMR variance. Exercise capacity (treadmill walking, 53 m/min with increasing grade) improved with time. Mean nonexercise physical activity level was low (1.2, or 20% of RMR), with considerable variance among individuals. Fat loss did not correlate with the aggregate energy deficit or its individual components. Resting or postexercise respiratory exchange ratio (RER) was lowest, whereas plasma β-OH-butyrate and glycerol were highest, between 1 and 2 months after surgery. RER increased linearly with mild exercise, and fat loss correlated positively with physical activity level and RER. Although the ultimate cause for weight loss is the energy deficit, the variance in fat loss correlated with glucose oxidation, suggesting that glucose partition between oxidation (muscle) and storage (adipose tissue) is an important factor affecting fat loss in individuals submitted to Roux-en-Y gastric bypass.

  17. Psychological Stress Alters Ultrastructure and Energy Metabolism of Masticatory Muscle in Rats

    PubMed Central

    Chen, Yong-Jin; Huang, Fei; Zhang, Min; Shang, Hai-Yan

    2010-01-01

    To investigate the effects of psychological stress on the masticatory muscles of rats, a communication box was applied to induce the psychological stress (PS) in rats. The successful establishment of psychological stimulation was confirmed by elevated serum levels of adrenocorticotropic hormone (ACTH) and changed behaviors in the elevated plusmaze apparatus. The energy metabolism of the bilateral masseter muscles was tested via chemocolorimetric analysis, whereas muscle ultrastructure was assessed by electron microscopy. In comparison to the control group, the PS group showed evidence of swollen mitochondria with cristae loss and reduced matrix density in the masticatory muscles after three weeks of stimulation; after five weeks of stimulation, severe vacuolar changes to the mitochondria were observed. Increased vascular permeability of the masticatory muscle capillaries was found in the five-week PS rats. In addition, there was decreased activity of Na+-K+ATPase and Ca2+-ATPase and a simultaneous increase in the activity of lactate dehydrogenase and lactic acid in the masticatory muscles of PS rats. Together, these results indicate that psychological stress induces alterations in the ultrastructure and energy metabolism of masticatory muscles in rats. PMID:21052548

  18. Cancer metabolism in space and time: Beyond the Warburg effect.

    PubMed

    Danhier, Pierre; Bański, Piotr; Payen, Valéry L; Grasso, Debora; Ippolito, Luigi; Sonveaux, Pierre; Porporato, Paolo E

    2017-08-01

    Altered metabolism in cancer cells is pivotal for tumor growth, most notably by providing energy, reducing equivalents and building blocks while several metabolites exert a signaling function promoting tumor growth and progression. A cancer tissue cannot be simply reduced to a bulk of proliferating cells. Tumors are indeed complex and dynamic structures where single cells can heterogeneously perform various biological activities with different metabolic requirements. Because tumors are composed of different types of cells with metabolic activities affected by different spatial and temporal contexts, it is important to address metabolism taking into account cellular and biological heterogeneity. In this review, we describe this heterogeneity also in metabolic fluxes, thus showing the relative contribution of different metabolic activities to tumor progression according to the cellular context. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. 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

  20. Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach.

    PubMed

    Lai, Ling; Leone, Teresa C; Keller, Mark P; Martin, Ola J; Broman, Aimee T; Nigro, Jessica; Kapoor, Kapil; Koves, Timothy R; Stevens, Robert; Ilkayeva, Olga R; Vega, Rick B; Attie, Alan D; Muoio, Deborah M; Kelly, Daniel P

    2014-11-01

    An unbiased systems approach was used to define energy metabolic events that occur during the pathological cardiac remodeling en route to heart failure (HF). Combined myocardial transcriptomic and metabolomic profiling were conducted in a well-defined mouse model of HF that allows comparative assessment of compensated and decompensated (HF) forms of cardiac hypertrophy because of pressure overload. The pressure overload data sets were also compared with the myocardial transcriptome and metabolome for an adaptive (physiological) form of cardiac hypertrophy because of endurance exercise training. Comparative analysis of the data sets led to the following conclusions: (1) expression of most genes involved in mitochondrial energy transduction were not significantly changed in the hypertrophied or failing heart, with the notable exception of a progressive downregulation of transcripts encoding proteins and enzymes involved in myocyte fatty acid transport and oxidation during the development of HF; (2) tissue metabolite profiles were more broadly regulated than corresponding metabolic gene regulatory changes, suggesting significant regulation at the post-transcriptional level; (3) metabolomic signatures distinguished pathological and physiological forms of cardiac hypertrophy and served as robust markers for the onset of HF; and (4) the pattern of metabolite derangements in the failing heart suggests bottlenecks of carbon substrate flux into the Krebs cycle. Mitochondrial energy metabolic derangements that occur during the early development of pressure overload-induced HF involve both transcriptional and post-transcriptional events. A subset of the myocardial metabolomic profile robustly distinguished pathological and physiological cardiac remodeling. © 2014 American Heart Association, Inc.

  1. 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

  2. Comparative Physiology of Energy Metabolism: Fishing for Endocrine Signals in the Early Vertebrate Pool

    PubMed Central

    van de Pol, Iris; Flik, Gert; Gorissen, Marnix

    2017-01-01

    Energy is the common currency of life. To guarantee a homeostatic supply of energy, multiple neuro-endocrine systems have evolved in vertebrates; systems that regulate food intake, metabolism, and distribution of energy. Even subtle (lasting) dysregulation of the delicate balance of energy intake and expenditure may result in severe pathologies. Feeding-related pathologies have fueled research on mammals, including of course the human species. The mechanisms regulating food intake and body mass are well-characterized in these vertebrates. The majority of animal life is ectothermic, only birds and mammals are endotherms. What can we learn from a (comparative) study on energy homeostasis in teleostean fishes, ectotherms, with a very different energy budget and expenditure? We present several adaptation strategies in fish. In recent years, the components that regulate food intake in fishes have been identified. Although there is homology of the major genetic machinery with mammals (i.e., there is a vertebrate blueprint), in many cases this does not imply analogy. Although both mammals and fish must gain their energy from food, the expenditure of the energy obtained is different. Mammals need to spend vast amounts of energy to maintain body temperature; fishes seem to utilize a broader metabolic range to their advantage. In this review, we briefly discuss ecto- and endothermy and their consequences for energy balance. Next, we argue that the evolution of endothermy and its (dis-)advantages may explain very different strategies in endocrine regulation of energy homeostasis among vertebrates. We follow a comparative and evolutionary line of thought: we discuss similarities and differences between fish and mammals. Moreover, given the extraordinary radiation of teleostean fishes (with an estimated number of 33,400 contemporary species, or over 50% of vertebrate life forms), we also compare strategies in energy homeostasis between teleostean species. We present recent

  3. Standard Gibbs energy of metabolic reactions: II. Glucose-6-phosphatase reaction and ATP hydrolysis.

    PubMed

    Meurer, Florian; Do, Hoang Tam; Sadowski, Gabriele; Held, Christoph

    2017-04-01

    ATP (adenosine triphosphate) is a key reaction for metabolism. Tools from systems biology require standard reaction data in order to predict metabolic pathways accurately. However, literature values for standard Gibbs energy of ATP hydrolysis are highly uncertain and differ strongly from each other. Further, such data usually neglect the activity coefficients of reacting agents, and published data like this is apparent (condition-dependent) data instead of activity-based standard data. In this work a consistent value for the standard Gibbs energy of ATP hydrolysis was determined. The activity coefficients of reacting agents were modeled with electrolyte Perturbed-Chain Statistical Associating Fluid Theory (ePC-SAFT). The Gibbs energy of ATP hydrolysis was calculated by combining the standard Gibbs energies of hexokinase reaction and of glucose-6-phosphate hydrolysis. While the standard Gibbs energy of hexokinase reaction was taken from previous work, standard Gibbs energy of glucose-6-phosphate hydrolysis reaction was determined in this work. For this purpose, reaction equilibrium molalities of reacting agents were measured at pH7 and pH8 at 298.15K at varying initial reacting agent molalities. The corresponding activity coefficients at experimental equilibrium molalities were predicted with ePC-SAFT yielding the Gibbs energy of glucose-6-phosphate hydrolysis of -13.72±0.75kJ·mol -1 . Combined with the value for hexokinase, the standard Gibbs energy of ATP hydrolysis was finally found to be -31.55±1.27kJ·mol -1 . For both, ATP hydrolysis and glucose-6-phosphate hydrolysis, a good agreement with own and literature values were obtained when influences of pH, temperature, and activity coefficients were explicitly taken into account in order to calculate standard Gibbs energy at pH7, 298.15K and standard state. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin.

    PubMed

    Yuan, Hong; Weng, Chunyan; Yang, Youbo; Huang, Lihua; Xing, Xiaowei

    2013-12-01

    The metabolic syndrome (MS) is a cluster of metabolic disorders arising from insulin resistance, characterized by the presence of central obesity, impaired fasting glucose level, dyslipidemia and hypertension. As the first-line medication, metformin is commonly used for MS to reduce insulin resistance. Comparing with rosiglitazone, metformin does not increase cardiovascular mortality risk in patients with MS. However, metformin is not good enough in improving insulin sensitivity. Its molecular mechanism is still not clear. Recent studies have demonstrated that resistin, an adipokine, could induce IR by both AMPK-dependent and AMPK-independent pathways. Though there were conflicting findings of resistin in metabolic syndrome or type 2 diabetes mellitus in different studies, resistin was significant decreased in the rosiglitazone treated patients than in the metformin-treated patients in most of studies. Here, we hypothesized that resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin. This hypothesis could explain why rosiglitazone is superior to metformin in enhancement of insulin sensitivity. Copyright © 2013. Published by Elsevier Ltd.

  5. Viral affects on metabolism: changes in glucose and glutamine utilization during human cytomegalovirus infection

    PubMed Central

    Yu, Yongjun; Clippinger, Amy J.; Alwine, James C.

    2011-01-01

    Human cytomegalovirus (HCMV) infection causes dramatic alterations of intermediary metabolism, similar to those found in tumor cells. In infected cells, glucose carbon is not completely broken down by the tricarboxylic acid (TCA) cycle for energy; instead it is used biosynthetically. This process requires increased glucose uptake, increased glycolysis and the diversion of glucose carbon, in the form of citrate, from the TCA cycle for use in HCMV-induced fatty acid biosynthesis. The diversion of citrate from the TCA cycle (cataplerosis) requires induction of enzymes to promote glutaminolysis, the conversion of glutamine to -ketoglutarate in order to maintain the TCA cycle (anaplerosis) and ATP production. Such changes could result in heretofore uncharacterized pathogenesis, potentially implicating HCMV as a subtle co-factor in many maladies, including oncogenesis. Recognition of the effects of HCMV, and other viruses, on host cell metabolism will provide new understanding of viral pathogenesis and novel avenues for antiviral therapy. PMID:21570293

  6. Restriction on an energy-dense diet improves markers of metabolic health and cellular aging in mice through decreasing hepatic mTOR activity.

    PubMed

    Schloesser, Anke; Campbell, Graeme; Glüer, Claus-Christian; Rimbach, Gerald; Huebbe, Patricia

    2015-02-01

    Dietary restriction (DR) on a normal low-fat diet improves metabolic health and may prolong life span. However, it is still uncertain whether restriction of an energy-dense, high-fat diet would also be beneficial and mitigate age-related processes. In the present study, we determined biomarkers of metabolic health, energy metabolism, and cellular aging in obesity-prone mice subjected to 30% DR on a high-fat diet for 6 months. Dietary-restricted mice had significantly lower body weights, less adipose tissue, lower energy expenditure, and altered substrate oxidation compared to their ad libitum-fed counterparts. Hepatic major urinary proteins (Mup) expression, which is linked to glucose and energy metabolism, and biomarkers of metabolic health, including insulin, glucose, cholesterol, and leptin/adiponectin ratio, were likewise reduced in high-fat, dietary-restricted mice. Hallmarks of cellular senescence such as Lamp2a and Hsc70 that mediate chaperone-mediated autophagy were induced and mechanistic target of rapamycin (mTOR) signaling mitigated upon high-fat DR. In contrast to DR applied in low-fat diets, anti-oxidant gene expression, proteasome activity, as well as 5'-adenosine monophosphate-activated protein kinase (AMPK) activation were not changed, suggesting that high-fat DR may attenuate some processes associated with cellular aging without the induction of cellular stress response or energy deprivation.

  7. Plasticity in body temperature and metabolic capacity sustains winter activity in a small endotherm (Rattus fuscipes).

    PubMed

    Glanville, Elsa J; Seebacher, Frank

    2010-03-01

    Small mammals that remain active throughout the year at a constant body temperature have a much greater energy and food requirement in winter. Lower body temperatures in winter may offset the increased energetic cost of remaining active in the cold, if cellular metabolism is not constrained by a negative thermodynamic effect. We aimed to determine whether variable body temperatures can be advantageous for small endotherms by testing the hypothesis that body temperature fluctuates seasonally in a wild rat (Rattus fuscipes); conferring an energy saving and reducing food requirements during resource restricted winter. Additionally we tested whether changes in body temperature affected tissue specific metabolic capacity. Winter acclimatized rats had significantly lower body temperatures and thicker fur than summer acclimatized rats. Mitochondrial oxygen consumption and the activity of enzymes that control oxidative (citrate synthase, cytochrome c-oxidase) and anaerobic (lactate dehydrogenase) metabolism were elevated in winter and were not negatively affected by the lower body temperature. Energy transfer modeling showed that lower body temperatures in winter combined with increased fur thickness to confer a 25 kJ day(-1) energy saving, with up to 50% owing to reduced body temperature alone. We show that phenotypic plasticity at multiple levels of organization is an important component of the response of a small endotherm to winter. Mitochondrial function compensates for lower winter body temperatures, buffering metabolic heat production capacity. Copyright 2009 Elsevier Inc. All rights reserved.

  8. Circadian and Metabolic Effects of Light: Implications in Weight Homeostasis and Health

    PubMed Central

    Plano, Santiago A.; Casiraghi, Leandro P.; García Moro, Paula; Paladino, Natalia; Golombek, Diego A.; Chiesa, Juan J.

    2017-01-01

    Daily interactions between the hypothalamic circadian clock at the suprachiasmatic nucleus (SCN) and peripheral circadian oscillators regulate physiology and metabolism to set temporal variations in homeostatic regulation. Phase coherence of these circadian oscillators is achieved by the entrainment of the SCN to the environmental 24-h light:dark (LD) cycle, coupled through downstream neural, neuroendocrine, and autonomic outputs. The SCN coordinate activity and feeding rhythms, thus setting the timing of food intake, energy expenditure, thermogenesis, and active and basal metabolism. In this work, we will discuss evidences exploring the impact of different photic entrainment conditions on energy metabolism. The steady-state interaction between the LD cycle and the SCN is essential for health and wellbeing, as its chronic misalignment disrupts the circadian organization at different levels. For instance, in nocturnal rodents, non-24 h protocols (i.e., LD cycles of different durations, or chronic jet-lag simulations) might generate forced desynchronization of oscillators from the behavioral to the metabolic level. Even seemingly subtle photic manipulations, as the exposure to a “dim light” scotophase, might lead to similar alterations. The daily amount of light integrated by the clock (i.e., the photophase duration) strongly regulates energy metabolism in photoperiodic species. Removing LD cycles under either constant light or darkness, which are routine protocols in chronobiology, can also affect metabolism, and the same happens with disrupted LD cycles (like shiftwork of jetlag) and artificial light at night in humans. A profound knowledge of the photic and metabolic inputs to the clock, as well as its endocrine and autonomic outputs to peripheral oscillators driving energy metabolism, will help us to understand and alleviate circadian health alterations including cardiometabolic diseases, diabetes, and obesity. PMID:29097992

  9. Division of Energy Biosciences annual report and summaries of FY 1996 activities

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1997-04-01

    The mission of the Division of Energy Biosciences is to support research that advances the fundamental knowledge necessary for the future development of biotechnologies related to the Department of Energy`s mission. The departmental civilian objectives include effective and efficient energy production, energy conservation, environmental restoration, and waste management. The Energy Biosciences program emphasizes research in the microbiological and plant sciences, as these understudied areas offer numerous scientific opportunities to dramatically influence environmentally sensible energy production and conservation. The research supported is focused on the basic mechanism affecting plant productivity, conversion of biomass and other organic materials into fuels and chemicalsmore » by microbial systems, and the ability of biological systems to replace energy-intensive or pollutant-producing processes. The Division also addresses the increasing number of new opportunities arising at the interface of biology with other basic energy-related sciences such as biosynthesis of novel materials and the influence of soil organisms on geological processes. This report gives summaries on 225 projects on photosynthesis, membrane or ion transport, plant metabolism and biosynthesis, carbohydrate metabolism lipid metabolism, plant growth and development, plant genetic regulation and genetic mechanisms, plant cell wall development, lignin-polysaccharide breakdown, nitrogen fixation and plant-microbial symbiosis, mechanism for plant adaptation, fermentative microbial metabolism, one and two carbon microbial metabolism, extremophilic microbes, microbial respiration, nutrition and metal metabolism, and materials biosynthesis.« less

  10. Melatonin, mitochondria, and the metabolic syndrome.

    PubMed

    Cardinali, Daniel P; Vigo, Daniel E

    2017-11-01

    A number of risk factors for cardiovascular disease including hyperinsulinemia, glucose intolerance, dyslipidemia, obesity, and elevated blood pressure are collectively known as metabolic syndrome (MS). Since mitochondrial activity is modulated by the availability of energy in cells, the disruption of key regulators of metabolism in MS not only affects the activity of mitochondria but also their dynamics and turnover. Therefore, a link of MS with mitochondrial dysfunction has been suspected since long. As a chronobiotic/cytoprotective agent, melatonin has a special place in prevention and treatment of MS. Melatonin levels are reduced in diseases associated with insulin resistance like MS. Melatonin improves sleep efficiency and has antioxidant and anti-inflammatory properties, partly for its role as a metabolic regulator and mitochondrial protector. We discuss in the present review the several cytoprotective melatonin actions that attenuate inflammatory responses in MS. The clinical data that support the potential therapeutical value of melatonin in human MS are reviewed.

  11. Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients.

    PubMed

    Rolle, A; Paredes, S; Cortínez, L I; Anderson, B J; Quezada, N; Solari, S; Allende, F; Torres, J; Cabrera, D; Contreras, V; Carmona, J; Ramírez, C; Oliveros, A M; Ibacache, M

    2018-05-01

    Obesity has been associated with reduced dexmedetomidine clearance, suggesting impaired hepatic function or reduced hepatic blood flow. The aim of this study was to clarify the effect of obesity in dexmedetomidine metabolic clearance. Forty patients, ASA I-III, 18-60 yr old, weighing 47-126 kg, scheduled for abdominal laparoscopic surgery, were enrolled. Anaesthetic agents (propofol, remifentanil, and dexmedetomidine) were dosed based on lean body weight measured by dual X-ray absorptiometry. Serial venous samples were drawn during and after dexmedetomidine infusion. A pharmacokinetic analysis was undertaken using non-linear mixed-effect models. In the modelling approach, the total body weight, lean body weight, and adjusted body weight were first tested as size descriptors for volumes and clearances. Hepatic blood flow, liver histopathology, liver enzymes, and gene expression of metabolic enzymes (UGT2B10 and UGT1A4) were tested as covariates of dexmedetomidine metabolic clearance. A decrease in NONMEM objective function value (ΔOFV) of 3.84 points, for an added parameter, was considered significant at the 0.05 level. A total of 637 dexmedetomidine serum samples were obtained. A two-compartmental model scaled to measured lean weight adequately described the dexmedetomidine pharmacokinetics. Liver blood flow was a covariate for dexmedetomidine clearance (ΔOFV=-5.878). Other factors, including fat mass, histopathological damage, and differential expression of enzymes, did not affect the dexmedetomidine clearance in the population studied (ΔOFV<3.84). We did not find a negative influence of obesity in dexmedetomidine clearance when doses were adjusted to lean body weight. Liver blood flow showed a significant effect on dexmedetomidine clearance. NCT02557867. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

  12. Oligonucleotide microarray analysis reveals dysregulation of energy-related metabolism in insulin-sensitive tissues of type 2 diabetes patients.

    PubMed

    Wang, M; Wang, X C; Zhao, L; Zhang, Y; Yao, L L; Lin, Y; Peng, Y D; Hu, R M

    2014-06-17

    Impaired insulin action within skeletal muscle, adipose tissue, and the liver is an important characteristic of type 2 diabetes (T2D). In order to identify common underlying defects in insulin-sensitive tissues that may be involved in the pathogenesis of T2D, the gene expression profiles of skeletal muscle, visceral adipose tissue, and liver from autopsy donors with or without T2D were examined using oligonucleotide microarrays and quantitative reverse transcriptase-PCR. Compared with controls, 691 genes were commonly dysregulated in these three insulin-sensitive tissues of humans with T2D. These co-expressed genes were enriched within the mitochondrion, with suggested involvement in energy metabolic processes such as glycolysis and gluconeogenesis, fatty acid beta oxidative, tricarboxylic acid cycle, and electron transport. Genes related to energy metabolism were mostly downregulated in diabetic skeletal muscle and visceral adipose tissue, while they were upregulated in the diabetic liver. This observed dysregulation in energy-related metabolism may be the underlying factor leading to the molecular mechanisms responsible for the insulin resistance of patients with T2D.

  13. A shift in energy metabolism anticipates the onset of sarcopenia in rhesus monkeys

    PubMed Central

    Pugh, Thomas D.; Conklin, Matthew W.; Evans, Trent D.; Polewski, Michael A.; Barbian, Hannah J.; Pass, Rachelle; Anderson, Bradley D.; Colman, Ricki J.; Eliceiri, Kevin W.; Keely, Patricia J.; Weindruch, Richard; Beasley, T. Mark; Anderson, Rozalyn M.

    2013-01-01

    Summary Age-associated skeletal muscle mass loss curtails quality of life and may contribute to defects in metabolic homeostasis in older persons. The onset of sarcopenia occurs in middle age in rhesus macaques although the trigger has yet to be identified. Here we show that a shift in metabolism occurs in advance of the onset of sarcopenia in rhesus vastus lateralis. Multiphoton laser scanning microscopy detects a shift in the kinetics of photon emission from autofluorescent metabolic cofactors NADH and FAD. Lifetime of both fluorophores is shortened at mid-age and this is observed in both free and bound constituent pools. Levels of FAD and free NADH are increased and the NAD/NADH redox ratio is lower. Concomitant with this, expression of fiber type myosin isoforms is altered resulting in a shift in fiber type distribution, activity of cytochrome c oxidase involved in mitochondrial oxidative phosphorylation is significantly lower, and the sub-cellular organization of mitochondria in oxidative fibers is compromised. A regulatory switch involving the transcriptional coactivator PGC-1α directs metabolic fuel utilization and governs the expression of structural proteins. Age did not significantly impact total levels of PGC-1α; however, its sub-cellular localization was disrupted, suggesting that PGC-1α activities may be compromised. Consistent with this, intracellular lipid storage is altered and there is shift to larger lipid droplet size that likely reflect a decline in lipid turnover or a loss in efficiency of lipid metabolism. We suggest that changes in energy metabolism contribute directly to skeletal muscle aging in rhesus monkeys. PMID:23607901

  14. 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

  15. Iron deficiency impairs developing hippocampal neuron gene expression, energy metabolism and dendrite complexity

    PubMed Central

    Bastian, Thomas W.; von Hohenberg, William C.; Mickelson, Daniel J.; Lanier, Lorene M.; Georgieff, Michael K.

    2016-01-01

    Iron deficiency (ID), with and without anemia, affects an estimated 2 billion people worldwide. ID is particularly deleterious during early-life brain development, leading to long-term neurological impairments, including deficits in hippocampus-mediated learning and memory. Neonatal rats with fetal/neonatal ID anemia (IDA) have shorter hippocampal CA1 apical dendrites with disorganized branching. ID-induced dendritic structural abnormalities persist into adulthood despite normalization of iron status. However, the specific developmental effects of neuronal iron loss on hippocampal neuron dendrite growth and branching are unknown. Embryonic hippocampal neuron cultures were chronically treated with deferoxamine (DFO, an iron chelator) beginning at 3 days in vitro (DIV). Levels of mRNA for Tfr1 and Slc11a2, iron-responsive genes involved in iron uptake, were significantly elevated in DFO-treated cultures at 11DIV and 18DIV, indicating a similar degree of neuronal ID as seen in rodent ID models. DFO treatment decreased mRNA levels for genes indexing dendritic and synaptic development (i.e., BdnfVI, Camk2a, Vamp1, Psd95, Cfl1, Pfn1, Pfn2, and Gda) and mitochondrial function (i.e., Ucp2, Pink1, and Cox6a1). At 18DIV, DFO reduced key aspects of energy metabolism including basal respiration, maximal respiration, spare respiratory capacity, ATP production, and glycolytic rate, capacity, and reserve. Sholl analysis revealed a significant decrease in distal dendritic complexity in DFO-treated neurons at both 11DIV and 18DIV. At 11DIV, the length of primary dendrites and the number and length of branches in DFO-treated neurons was reduced. By 18DIV, a partial recovery of dendritic branch number in DFO-treated neurons was counteracted by a significant reduction in the number and length of primary dendrites and length of branches. Our findings suggest that early neuronal iron loss, at least partially driven through altered mitochondrial function and neuronal energy metabolism

  16. Genome-scale estimate of the metabolic turnover of E. Coli from the energy balance analysis

    NASA Astrophysics Data System (ADS)

    De Martino, D.

    2016-02-01

    In this article the notion of metabolic turnover is revisited in the light of recent results of out-of-equilibrium thermodynamics. By means of Monte Carlo methods we perform an exact sampling of the enzymatic fluxes in a genome scale metabolic network of E. Coli in stationary growth conditions from which we infer the metabolites turnover times. However the latter are inferred from net fluxes, and we argue that this approximation is not valid for enzymes working nearby thermodynamic equilibrium. We recalculate turnover times from total fluxes by performing an energy balance analysis of the network and recurring to the fluctuation theorem. We find in many cases values one of order of magnitude lower, implying a faster picture of intermediate metabolism.

  17. Protective effects of magnesium supplementation on metabolic energy derangements in lipopolysaccharide-induced cardiotoxicity in mice.

    PubMed

    Ahmed, Lamiaa A

    2012-11-05

    Metabolic derangements and bioenergetic failure are major contributors to sepsis-induced multiple organ dysfunctions. Due to the well known role of magnesium (Mg) as a cofactor in many enzymatic reactions that involve energy creation and utilization, the present investigation was directed to estimate the cardioprotective effect of Mg supplementation in lipopolysaccharide (LPS)-induced metabolic energy changes in mice. Oral doses of Mg aspartate (20 or 40 mg/kg) were administered once daily for 7 day. Mice were then subjected to a single intraperitoneal injection of LPS (2 mg/kg). Plasma was separated 3 h after LPS injection for determination of creatine kinase-MB activity. Animals were then sacrificed and the hearts were separated for estimation of tissue thiobarbituric acid reactive substances, reduced glutathione, lactate, pyruvate, adenine nucleotides, creatine phosphate and cardiac Na(+),K(+)-ATPase activity. Finally, electron microscopic examination was performed to visualize the protective effects of Mg pretreatment on mitochondrial ultrastructure. In general, the higher dose of Mg was more effective than the lower dose in ameliorating creatine kinase-MB elevation and the state of oxidative stress, lactate accumulation, pyruvate reduction as well as preserving creatine phosphate, adenine nucleotides and Na(+),K(+)-ATPase activity. Moreover, the higher dose of Mg provided a significant cardioprotection against the mitochondrial ultrastructural changes. Mg therapy can afford a significant protection against metabolic energy derangements and mitochondrial ultrastructural changes induced by LPS cardiotoxicity in mice. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Potential hepatic toxicity of buprofezin at sublethal concentrations: ROS-mediated conversion of energy metabolism.

    PubMed

    Ji, Xiaotong; Ku, Tingting; Zhu, Na; Ning, Xia; Wei, Wei; Li, Guangke; Sang, Nan

    2016-12-15

    Buprofezin is known for its broad-spectrum action and environmental safety. The popularity of buprofezin has raised concerns about its potentially adverse effects on human health and risk to the environment. In this study, we first identified the liver as one of the major organs in which buprofezin accumulated, and we detected a severe oxidative stress response. Next, we demonstrated that sublethal concentrations of buprofezin promoted the conversion of energy metabolism from the aerobic tricarboxylic acid (TCA) cycle and oxidative phosphorylation to anaerobic glycolysis. Importantly, reactive oxygen species (ROS) generation partially accounted for the shunting of the energy metabolism through the buprofezin-mediated inhibition of cytochrome c oxidase activity. ROS directly perturbed the activities of several key TCA cycle enzymes, stimulated glycolysis, and indirectly disturbed the activity of the respiratory chain complex by altering mitochondrial DNA (mtDNA). These findings clarify the potential mechanisms of buprofezin toxicity and provide biomarkers for buprofezin-mediated hepatotoxicity at sublethal concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Altered metabolic homeostasis is associated with appetite regulation during and following 48-h of severe energy deprivation in adults.

    PubMed

    Karl, J Philip; Smith, Tracey J; Wilson, Marques A; Bukhari, Asma S; Pasiakos, Stefan M; McClung, Holly L; McClung, James P; Lieberman, Harris R

    2016-04-01

    Military personnel frequently endure intermittent periods of severe energy deficit which can compromise health and performance. Physiologic factors contributing to underconsumption, and the subsequent drive to overeat, are not fully characterized. This study aimed to identify associations between appetite, metabolic homeostasis and endocrine responses during and following severe, short-term energy deprivation. Twenty-three young adults (17M/6F, 21±3years, BMI 25±3kg/m(2)) participated in a randomized, controlled, crossover trial. During separate 48-h periods, participants increased habitual energy expenditure by 1647±345kcal/d (mean±SD) through prescribed exercise at 40-65% VO2peak, and consumed provided isovolumetric diets designed to maintain energy balance at the elevated energy expenditure (EB; 36±93kcal/d energy deficit) or to produce a severe energy deficit (ED; 3681±716kcal/d energy deficit). Appetite, markers of metabolic homeostasis and endocrine mediators of appetite and substrate availability were periodically measured. Ad libitum energy intake was measured over 36h following both experimental periods. Appetite increased during ED and was greater than during EB despite maintenance of diet volume (P=0.004). Ad libitum energy intake was 907kcal/36h [95% CI: 321, 1493kcal/36h, P=0.004] higher following ED compared to following EB. Serum beta-hydroxybutyrate, free fatty acids, branched-chain amino acids, dehydroepiandrosterone-sulfate (DHEA-S) and cortisol concentrations were higher (P<0.001 for all), whereas whole-body protein balance was more negative (P<0.001), and serum glucose, insulin, and leptin concentrations were lower (P<0.001 for all) during ED relative to during EB. Cortisol concentrations, but not any other hormone or metabolic substrate, were inversely associated with satiety during EB (R(2)=0.23, P=0.04). In contrast, serum glucose and DHEA-S concentrations were inversely associated with satiety during ED (R(2)=0.68, P<0.001). No

  20. Obesity, but not metabolic syndrome, negatively affects outcome in bipolar disorder.

    PubMed

    McElroy, S L; Kemp, D E; Friedman, E S; Reilly-Harrington, N A; Sylvia, L G; Calabrese, J R; Rabideau, D J; Ketter, T A; Thase, M E; Singh, V; Tohen, M; Bowden, C L; Bernstein, E E; Brody, B D; Deckersbach, T; Kocsis, J H; Kinrys, G; Bobo, W V; Kamali, M; McInnis, M G; Leon, A C; Faraone, S; Nierenberg, A A; Shelton, R C

    2015-06-26

    Examine the effects of obesity and metabolic syndrome on outcome in bipolar disorder. The Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar Disorder (Bipolar CHOICE) study randomized 482 participants with bipolar disorder in a 6-month trial comparing lithium- and quetiapine-based treatment. Baseline variables were compared between groups with and without obesity, with and without abdominal obesity, and with and without metabolic syndrome respectively. The effects of baseline obesity, abdominal obesity, and metabolic syndrome on outcomes were examined using mixed effects linear regression models. At baseline, 44.4% of participants had obesity, 48.0% had abdominal obesity, and 27.3% had metabolic syndrome; neither obesity, nor abdominal obesity, nor metabolic syndrome were associated with increased global severity, mood symptoms, or suicidality, or with poorer functioning or life satisfaction. Treatment groups did not differ on prevalence of obesity, abdominal obesity, or metabolic syndrome. By contrast, among the entire cohort, obesity was associated with less global improvement and less improvement in total mood and depressive symptoms, suicidality, functioning, and life satisfaction after 6 months of treatment. Abdominal obesity was associated with similar findings. Metabolic syndrome had no effect on outcome. Obesity and abdominal obesity, but not metabolic syndrome, were associated with less improvement after 6 months of lithium- or quetiapine-based treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.