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Sample records for body oxidative metabolism

  1. Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy

    DEFF Research Database (Denmark)

    Magnussen, Line V; Glintborg, Dorte; Hermann, Pernille;

    2016-01-01

    AIMS: To evaluate the effect of testosterone replacement therapy (TRT) on body composition, insulin sensitivity, oxidative metabolism and glycaemic control in aging men with lowered bioavailable testosterone (BioT) levels and type 2 diabetes mellitus (T2D) controlled on metformin monotherapy....... MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled study in 39 men aged 50-70 years with BioT levels testosterone gel (TRT, n = 20) or placebo (n = 19) for 24 weeks. Lean body mass (LBM...

  2. Medical aspects of ketone body metabolism.

    Science.gov (United States)

    Mitchell, G A; Kassovska-Bratinova, S; Boukaftane, Y; Robert, M F; Wang, S P; Ashmarina, L; Lambert, M; Lapierre, P; Potier, E

    1995-06-01

    Ketone bodies are produced in the liver, mainly from the oxidation of fatty acids, and are exported to peripheral tissues for use as an energy source. They are particularly important for the brain, which has no other substantial non-glucose-derived energy source. The 2 main ketone bodies are 3-hydroxybutyrate (3HB) and acetoacetate (AcAc). Biochemically, abnormalities of ketone body metabolism can present in 3 fashions: ketosis, hypoketotic hypoglycemia, and abnormalities of the 3HB/AcAc ratio. Normally, the presence of ketosis implies 2 things: that lipid energy metabolism has been activated and that the entire pathway of lipid degradation is intact. In rare patients, ketosis reflects an inability to utilize ketone bodies. Ketosis is normal during fasting, after prolonged exercise, and when a high-fat diet is consumed. During the neonatal period, infancy and pregnancy, times at which lipid energy metabolism is particularly active, ketosis develops readily. Pathologic causes of ketosis include diabetes, ketotic hypoglycemia of childhood, corticosteroid or growth hormone deficiency, intoxication with alcohol or salicylates, and several inborn errors of metabolism. The absence of ketosis in a patient with hypoglycemia is abnormal and suggests the diagnosis of either hyperinsulinism or an inborn error of fat energy metabolism. An abnormal elevation of the 3HB/AcAc ratio usually implies a non-oxidized state of the hepatocyte mitochondrial matrix resulting from hypoxia-ischemia or other causes. We summarize the differential diagnosis of abnormalities of ketone body metabolism, as well as pertinent recent advances in research.

  3. Ketone body metabolism and its defects.

    Science.gov (United States)

    Fukao, Toshiyuki; Mitchell, Grant; Sass, Jörn Oliver; Hori, Tomohiro; Orii, Kenji; Aoyama, Yuka

    2014-07-01

    Acetoacetate (AcAc) and 3-hydroxybutyrate (3HB), the two main ketone bodies of humans, are important vectors of energy transport from the liver to extrahepatic tissues, especially during fasting, when glucose supply is low. Blood total ketone body (TKB) levels should be evaluated in the context of clinical history, such as fasting time and ketogenic stresses. Blood TKB should also be evaluated in parallel with blood glucose and free fatty acids (FFA). The FFA/TKB ratio is especially useful for evaluation of ketone body metabolism. Defects in ketogenesis include mitochondrial HMG-CoA synthase (mHS) deficiency and HMG-CoA lyase (HL) deficiency. mHS deficiency should be considered in non-ketotic hypoglycemia if a fatty acid beta-oxidation defect is suspected, but cannot be confirmed. Patients with HL deficiency can develop hypoglycemic crises and neurological symptoms even in adolescents and adults. Succinyl-CoA-3-oxoacid CoA transferase (SCOT) deficiency and beta-ketothiolase (T2) deficiency are two defects in ketolysis. Permanent ketosis is pathognomonic for SCOT deficiency. However, patients with "mild" SCOT mutations may have nonketotic periods. T2-deficient patients with "mild" mutations may have normal blood acylcarnitine profiles even in ketoacidotic crises. T2 deficient patients cannot be detected in a reliable manner by newborn screening using acylcarnitines. We review recent data on clinical presentation, metabolite profiles and the course of these diseases in adults, including in pregnancy.

  4. Oxidative refolding from inclusion bodies.

    Science.gov (United States)

    Nelson, Christopher A; Lee, Chung A; Fremont, Daved H

    2014-01-01

    This protocol describes the growth and purification of bacterial inclusion body proteins with an option to selenomethionine label the targeted protein through feedback inhibition of methionine biosynthesis in common (non-auxotrophic) strains of E. coli. The method includes solubilization of inclusion body proteins by chemical denaturation and disulfide reduction, renaturation of the solubilized material through rapid dilution by pulsed injection into refolding buffer containing arginine and a mixture of oxidized and reduced glutathione, recovery of the recombinant protein using a stirred cell concentrator, and removal of the aggregated or misfolded fraction by passage over size-exclusion chromatography. The quality of the resulting protein can be assessed by SDS-PAGE.

  5. Lipid metabolism and body composition in Gclm(-/-) mice

    Energy Technology Data Exchange (ETDEWEB)

    Kendig, Eric L. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Chen, Ying [Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045 (United States); Krishan, Mansi; Johansson, Elisabet; Schneider, Scott N. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Genter, Mary Beth; Nebert, Daniel W. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Shertzer, Howard G., E-mail: shertzhg@ucmail.uc.edu [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States)

    2011-12-15

    In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase modifier subunit gene (Gclm(-/-)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(-/-) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(-/-) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(-/-) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(-/-) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(-/-) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(-/-) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(-/-) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: Black-Right-Pointing-Pointer A high fat diet does not produce body weight and fat gain in Gclm(-/-) mice. Black-Right-Pointing-Pointer A high fat diet does not induce steatosis or insulin resistance in Gclm(-/-) mice. Black-Right-Pointing-Pointer Gclm(-/-) mice have high basal metabolism and mitochondrial

  6. Whole body protein metabolism in chronic hemodialysis

    NARCIS (Netherlands)

    Veeneman, Jorden Marcus

    2004-01-01

    To summarise, evidence suggests that protein-energy malnutrition is associated with mor-bidity and mortality in chronic hemodialysis patients. Urea kinetics are used as a clinical marker for protein intake and oxidation. Chapter 2 focuses on the relation between pro-tein and urea metabolism, which i

  7. Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies.

    Science.gov (United States)

    Rani, Vibha; Deep, Gagan; Singh, Rakesh K; Palle, Komaraiah; Yadav, Umesh C S

    2016-03-01

    Increased body weight and metabolic disorder including insulin resistance, type 2 diabetes and cardiovascular complications together constitute metabolic syndrome. The pathogenesis of metabolic syndrome involves multitude of factors. A number of studies however indicate, with some conformity, that oxidative stress along with chronic inflammatory condition pave the way for the development of metabolic diseases. Oxidative stress, a state of lost balance between the oxidative and anti-oxidative systems of the cells and tissues, results in the over production of oxidative free radicals and reactive oxygen species (ROS). Excessive ROS generated could attack the cellular proteins, lipids and nucleic acids leading to cellular dysfunction including loss of energy metabolism, altered cell signalling and cell cycle control, genetic mutations, altered cellular transport mechanisms and overall decreased biological activity, immune activation and inflammation. In addition, nutritional stress such as that caused by high fat high carbohydrate diet also promotes oxidative stress as evident by increased lipid peroxidation products, protein carbonylation, and decreased antioxidant system and reduced glutathione (GSH) levels. These changes lead to initiation of pathogenic milieu and development of several chronic diseases. Studies suggest that in obese person oxidative stress and chronic inflammation are the important underlying factors that lead to development of pathologies such as carcinogenesis, obesity, diabetes, and cardiovascular diseases through altered cellular and nuclear mechanisms, including impaired DNA damage repair and cell cycle regulation. Here we discuss the aspects of metabolic disorders-induced oxidative stress in major pathological conditions and strategies for their prevention and therapy.

  8. Oxidative stress in metabolic syndrome

    OpenAIRE

    Sharma, Praveen; Mishra, Sandhya; Ajmera, Peeyush; Mathur, Sandeep

    2005-01-01

    As antioxidants play a protective role in the pathophysiology of diabetes and cardiovascular diseases, understanding the physiological status of antioxidant concentration among people at high risk for developing these conditions, such as Metabolic Syndrome, is of interest. In present study out of 187 first degree non-diabetic relatives and 192 non-diabetic spouses, 33.1% and 19.7% were found to have metabolic syndrome respectively. Subjects with metabolic syndrome (≥3 risk factors) had poor a...

  9. Metabolic syndrome and oxidative stress.

    Science.gov (United States)

    Ando, Katsuyuki; Fujita, Toshiro

    2009-08-01

    Metabolic syndrome is an obesity-associated collection of disorders, each of which contributes to cardiovascular risk. Metabolic syndrome is also associated with overproduction of reactive oxygen species (ROS). ROS contribute to the interrelationship between metabolic syndrome and salt-sensitive hypertension, which are both caused by obesity and excess salt consumption and are major threats to health in developed countries. ROS can induce insulin resistance, which is indispensable for the progression of metabolic syndrome, and salt-sensitive hypertension stimulates ROS production, thereby promoting the development of metabolic syndrome. Moreover, ROS activate mineralocorticoid receptors (MRs) and the sympathetic nervous system, which can contribute to the development of metabolic syndrome and salt-sensitive hypertension. Salt-induced progression of cardiovascular disease (CVD) is also accelerated in animal models with metabolic syndrome, probably owing to further stimulation of ROS overproduction and subsequent ROS-induced MR activation and sympathetic excitation. Therefore, ROS contribute to the progression of the metabolic syndrome itself and to the CVD accompanying it, particularly in conjunction with excessive salt consumption.

  10. Magnesium Oxide Induced Metabolic Alkalosis in Cattle

    OpenAIRE

    Ogilvie, T H; Butler, D G; Gartley, C J; Dohoo, I. R.

    1983-01-01

    A study was designed to compare the metabolic alkalosis produced in cattle from the use of an antacid (magnesium oxide) and a saline cathartic (magnesium sulphate). Six, mature, normal cattle were treated orally with a magnesium oxide (MgO) product and one week later given a comparable cathartic dose of magnesium sulphate (MgSO4).

  11. Fipronil insecticide toxicology: oxidative stress and metabolism.

    Science.gov (United States)

    Wang, Xu; Martínez, María Aránzazu; Wu, Qinghua; Ares, Irma; Martínez-Larrañaga, María Rosa; Anadón, Arturo; Yuan, Zonghui

    2016-11-01

    Fipronil (FIP) is widely used across the world as a broad-spectrum phenylpyrazole insecticide and veterinary drug. FIP was the insecticide to act by targeting the γ-aminobutyric acid (GABA) receptor and has favorable selective toxicity towards insects rather than mammals. However, because of accidental exposure, incorrect use of FIP or widespread FIP use leading to the contamination of water and soil, there is increasing evidence that FIP could cause a variety of toxic effects on animals and humans, such as neurotoxic, hepatotoxic, nephrotoxic, reproductive, and cytotoxic effects on vertebrate and invertebrates. In the last decade, oxidative stress has been suggested to be involved in the various toxicities induced by FIP. To date, few reviews have addressed the toxicity of FIP in relation to oxidative stress. The focus of this article is primarily intended to summarize the progress in research associated with oxidative stress as a possible mechanism for FIP-induced toxicity as well as metabolism. The present review reports that studies have been conducted to reveal the generation of reactive oxygen species (ROS) and oxidative stress as a result of FIP treatment and have correlated them with various types of toxicity. Furthermore, the metabolism of FIP was also reviewed, and during this process, various CYP450 enzymes were involved and oxidative stress might occur. The roles of various compounds in protecting against FIP-induced toxicity based on their anti-oxidative effects were also summarized to further understand the role of oxidative stress in FIP-induced toxicity.

  12. Oxidative metabolism in insulin-treated gestational diabetes mellitus.

    Science.gov (United States)

    Hsu, H W; Butte, N F; Wong, W W; Moon, J K; Ellis, K J; Klein, P D; Moise, K J

    1997-06-01

    To investigate whether protein, carbohydrate, and fat metabolism was normalized in insulin-treated gestational diabetes mellitus (GDM), eight Hispanic women with GDM and eight healthy controls were studied at 32-36 wk of gestation and 6 wk postpartum. Net substrate utilization was measured using room respiration calorimetry. Exogenous substrate oxidation was determined by 13C recovered in breath CO2 from 13C-labeled leucine, glucose, and Hiolein. Women with GDM had higher 24-h oxygen consumption, carbon dioxide production, total energy expenditure, and basal metabolic rates than controls due to larger body mass. Adjusted for weight or fat-free mass, total energy expenditure, basal metabolic rate, and basal and 24-h whole body net protein, carbohydrate, and fat utilization did not differ between insulin-treated GDM subjects and controls in pregnancy or postpartum. Oxidation of [13C]leucine and [13C]glucose did not differ by group or pregnancy status. Recovery of exogenously administered [13C]Hiolein, a biosynthetic triglyceride, as breath 13CO2 was significantly lower in the GDM group antepartum and postpartum (P = 0.02), indicating lower oxidation of exogenous triglycerides in GDM.

  13. Body weight regulation and obesity: dietary strategies to improve the metabolic profile.

    Science.gov (United States)

    Munsters, M J M; Saris, W H M

    2014-01-01

    This review discusses dietary strategies that may improve the metabolic profile and body weight regulation in obesity. Recent evidence demonstrated that long-term health effects seem to be more beneficial for low-glycemic index (GI) diets compared to high-protein diets. Still, these results need to be confirmed by other prospective cohort studies and long-term clinical trials, and the discrepancy between these study designs needs to be explored in more detail. Furthermore, the current literature is mixed with regard to the efficacy of increased meal frequency (or snacking) regimens in causing metabolic alterations, particularly in relation to body weight control. In conclusion, a growing body of evidence suggests that dietary strategies with the aim to reduce postprandial insulin response and increase fat oxidation, and that tend to restore metabolic flexibility, have a place in the prevention and treatment of obesity and associated metabolic disorders.

  14. Obesity, body composition and metabolic disturbances in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Svendsen, Pernille Fog; Nilas, Lisbeth; Nørgaard, Kirsten

    2008-01-01

    BACKGROUND: We determined the impact of polycystic ovary syndrome (PCOS) and obesity on glucose and lipid metabolism and beta-cell function in women with PCOS. METHODS: In 35 women with PCOS (17 lean, lean PCOS and 18 obese, obese PCOS) and 25 control women (9 lean, lean controls and 16 obese......-stimulated glucose oxidation (GOX 2) (P metabolism (P

  15. Body composition and risk for metabolic alterations in female adolescents

    OpenAIRE

    Eliane Rodrigues de Faria; Cristiana Araújo Gontijo; Franceschini, Sylvia do Carmo C.; Maria do Carmo G. Peluzio; Silvia Eloiza Priore

    2014-01-01

    OBJECTIVE: To study anthropometrical and body composition variables as predictors of risk for metabolic alterations and metabolic syndrome in female adolescents. METHODS: Biochemical, clinical and corporal composition data of 100 adolescents from 14 to 17 years old, who attended public schools in Viçosa, Southeastern Brazil, were collected. RESULTS: Regarding nutritional status, 83, 11 and 6% showed eutrophia, overweight/obesity and low weight, respectively, and 61% presented high body fat pe...

  16. Role of ketone bodies in perinatal myocardial energy metabolism

    NARCIS (Netherlands)

    Bartelds, B; van der Leij, FR; Kuipers, JRG

    2001-01-01

    Metabolic changes at around the time of birth are crucial for life. Here we review the energy utilization in the myocardium, emphasizing ketone body metabolism. Before birth, glucose and lactate are the major energy substrates for the myocardium. Long-chain fatty acids (LCFA) are normally not availa

  17. Hormonal regulation of ketone-body metabolism in man.

    Science.gov (United States)

    Alberti, K G; Johnston, D G; Gill, A; Barnes, A J; Orskov, H

    1978-01-01

    The main hormones involved in ketone-body metabolism are the anabolic hormone insulin and the primarily catabolic hormones, glucagon, cortisol, catecholamines and growth hormone. These hormones may regulate ketone-body metabolism at three sites: adipose tissue, by regulating fatty acid supply to the liver; the liver itself, by determining the relative activities of the re-esterification and fatty acid oxidation pathways; and the periphery, by influencing the rate of extrahepatic utilization of ketone bodies. The first two are quantitatively the most important. Insulin acts on all three regulatory sites. In adipose tissue lipolysis is inhibited and re-esterification enhanced with consequent decrease of fatty acid release. Both these processes are extremely insulin-sensitive. In the liver insulin increases fatty acid synthesis and esterification. At the same time malonyl-CoA formation is increased, which inhibits the acylcarnitine transferase system and thus decreases the transport of fatty acids into mitochondria and hence fatty acid oxidation and ketogenesis. Insulin also has a small stimulatory effect on extrahepatic ketone-body utilization. The effects of glucagon depend on whether insulin is present. In normal man glucagon stimulates insulin secretion and the predominant effect is that of insulin, i.e. decreased ketogenesis. In insulin deficiency glucagon has a mild stimulatory effect on lipolysis, increasing fatty acid supply to the liver. The main effects of glucagon are, however, on the liver. It activates the carnitine acyltransferase system through inhibition of malonyl-CoA synthesis. Fatty acid oxidation is increased and ketogenesis enhanced. The overall effect on the liver depends on the relative amounts of insulin and glucagon present. Studies with somatostatin show that glucagon can increase ketogenesis acutely when insulin secretion is inhibited in normal man, but the effects are short-lived. Cortisol has similar effects to glucagon. In the presence of

  18. Cajal bodies and plant RNA metabolism

    Science.gov (United States)

    Intracellular location of components associated with RNA metabolism is a key feature of gene expression regulation, although it is often neglected in favor of more direct factors influencing expression. A number of nuclear and subnuclear compartments exist, each carrying out specific functions. Th...

  19. Substrate-energy metabolism and metabolic risk factors for cardiovascular disease in relation to fetal growth and adult body composition.

    Science.gov (United States)

    Kensara, Osama A; Wooton, Steve A; Phillips, David I W; Patel, Mayank; Hoffman, Daniel J; Jackson, Alan A; Elia, Marinos

    2006-08-01

    The effect of fetal programming on intermediary metabolism is uncertain. Therefore, we examined whether fetal programming affects oxidative and nonoxidative macronutrient metabolism and the prevalence of the metabolic syndrome in adult life. Healthy older men, aged 64-72 years, with either a lower birth weight (LBW, or=75th %ile; n = 13) had measurements of 1) net oxidative metabolism using indirect calorimetry before and for 6 h after a mixed meal (3,720 kJ) and 2) postprandial oxidation of exogenous [13C]palmitic acid. Body composition was measured using dual-energy X-ray absorptiometry. After adjustment for current weight and height, the LBW group had a lower resting energy expenditure (REE) in the preprandial (4.01 vs. 4.54 kJ/min, P = 0.015) and postprandial state (4.60 vs. 5.20 kJ/min, P = 0.004), and less fat-free mass than the HBW group. The BW category was a significant, independent, and better predictor of REE than weight plus height. There were no significant differences between groups in net oxidative and nonoxidative macronutrient (protein, fat, carbohydrate) metabolism (or of exogenous [13C]palmitate) or in the prevalence of the metabolic syndrome, which was present almost twice as commonly in the LBW than in the HBW group. The study suggests that fetal programming affects both pre- and postprandial EE in older life by mechanisms that are at least partly related to the mass of the fat-free body. BW was found to be a significant predictor of REE that was independent of adult weight plus height.

  20. DLK1 regulates whole body glucose metabolism

    DEFF Research Database (Denmark)

    Abdallah, Basem; Ditzel, Nicholas; Laborda, Jorge

    2015-01-01

    The endocrine role of the skeleton in regulating energy metabolism is supported by a feed forward loop between circulating osteoblasts (OBs)-derived undercaboxylated osteocalcin (Glu-OCN) and pancreatic β-cell-insulin; in turn insulin favors osteocalcin bioactivity. These data suggest the existence...... cells acts as a negative feedback mechanism to counteract the stimulatory effects of insulin on osteoblast production of Glu-OCN, a potential mechanism preventing OCN-induced hypoglycemia....

  1. Growth hormone enhances effects of endurance training on oxidative muscle metabolism in elderly women

    DEFF Research Database (Denmark)

    Lange, K H; Isaksson, F; Juul, A;

    2000-01-01

    The present study investigated whether recombinant human (rh) growth hormone (GH) combined with endurance training would have a larger effect on oxidative capacity, metabolism, and body fat than endurance training alone. Sixteen healthy, elderly women, aged 75 yr, performed closely monitored...... in the two subjects receiving rhGH. In conclusion, rhGH adds to the effects of endurance training on muscle oxidative enzymes and causes a reduction in body fat in elderly women....

  2. Body composition and risk for metabolic alterations in female adolescents

    Directory of Open Access Journals (Sweden)

    Eliane Rodrigues de Faria

    2014-06-01

    Full Text Available OBJECTIVE: To study anthropometrical and body composition variables as predictors of risk for metabolic alterations and metabolic syndrome in female adolescents.METHODS: Biochemical, clinical and corporal composition data of 100 adolescents from 14 to 17 years old, who attended public schools in Viçosa, Southeastern Brazil, were collected.RESULTS: Regarding nutritional status, 83, 11 and 6% showed eutrophia, overweight/obesity and low weight, respectively, and 61% presented high body fat percent. Total cholesterol presented the highest percentage of inadequacy (57%, followed by high-density lipoprotein (HDL - 50%, low-density lipoprotein (LDL - 47% and triacylglycerol (22%. Inadequacy was observed in 11, 9, 3 and 4% in relation to insulin resistance, fasting insulin, blood pressure and glycemia, respectively. The highest values of the fasting insulin and the Homeostasis Model Assessment-Insulin Resistance(HOMA-IR were verified at the highest quartiles of body mass index (BMI, waist perimeter, waist-to-height ratio and body fat percent. Body mass index, waist perimeter, and waist-to-height ratio were the better predictors for high levels of HOMA-IR, blood glucose and fasting insulin. Waist-to-hip ratio was associated to arterial hypertension diagnosis. All body composition variables were effective in metabolic syndrome diagnosis.CONCLUSIONS: Waist perimeter, BMI and waist-to-height ratio showed to be good predictors for metabolic alterations in female adolescents and then should be used together for the nutritional assessment in this age range.

  3. Integrating cellular metabolism into a multiscale whole-body model.

    Directory of Open Access Journals (Sweden)

    Markus Krauss

    Full Text Available Cellular metabolism continuously processes an enormous range of external compounds into endogenous metabolites and is as such a key element in human physiology. The multifaceted physiological role of the metabolic network fulfilling the catalytic conversions can only be fully understood from a whole-body perspective where the causal interplay of the metabolic states of individual cells, the surrounding tissue and the whole organism are simultaneously considered. We here present an approach relying on dynamic flux balance analysis that allows the integration of metabolic networks at the cellular scale into standardized physiologically-based pharmacokinetic models at the whole-body level. To evaluate our approach we integrated a genome-scale network reconstruction of a human hepatocyte into the liver tissue of a physiologically-based pharmacokinetic model of a human adult. The resulting multiscale model was used to investigate hyperuricemia therapy, ammonia detoxification and paracetamol-induced toxication at a systems level. The specific models simultaneously integrate multiple layers of biological organization and offer mechanistic insights into pathology and medication. The approach presented may in future support a mechanistic understanding in diagnostics and drug development.

  4. Physical activity, body composition and metabolic syndrome in young adults.

    Directory of Open Access Journals (Sweden)

    Minna K Salonen

    Full Text Available Low physical activity (PA is a major risk factor for cardiovascular and metabolic disorders in all age groups. We measured intensity and volume of PA and examined the associations between PA and the metabolic syndrome (MS, its components and body composition among young Finnish adults.The study comprises 991 men and women born 1985-86, who participated in a clinical study during the years 2009-11 which included assessments of metabolism, body composition and PA. Objectively measured (SenseWear Armband five-day PA data was available from 737 participants and was expressed in metabolic equivalents of task (MET.The prevalence of MS ranged between 8-10%. Higher total mean volume (MET-hours or intensity (MET were negatively associated with the risk of MS and separate components of MS, while the time spent at sedentary level of PA was positively associated with MS.MS was prevalent in approximately every tenth of the young adults at the age of 24 years. Higher total mean intensity and volume rates as well as longer duration spent at moderate and vigorous PA level had a beneficial impact on the risk of MS. Longer time spent at the sedentary level of PA increased the risk of MS.

  5. Carotid body, insulin and metabolic diseases: unravelling the links

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    Silvia V Conde

    2014-10-01

    Full Text Available The carotid bodies (CB are peripheral chemoreceptors that sense changes in arterial blood O2, CO2 and pH levels. Hypoxia, hypercapnia and acidosis activate the CB, which respond by increasing the action potential frequency in their sensory nerve, the carotid sinus nerve (CSN. CSN activity is integrated in the brain stem to induce a panoply of cardiorespiratory reflexes aimed, primarily, to normalize the altered blood gases, via hyperventilation, and to regulate blood pressure and cardiac performance, via sympathetic nervous system (SNS activation. Besides its role in the cardiorespiratory control the CB has been proposed as a metabolic sensor implicated in the control of energy homeostasis and, more recently, in the regulation of whole body insulin sensitivity. Hypercaloric diets cause CB overactivation in rats, which seems to be at the origin of the development of insulin resistance and hypertension, core features of metabolic syndrome and type 2 diabetes. Consistent with this notion, CB sensory denervation prevents metabolic and hemodynamic alterations in hypercaloric feed animal. Obstructive sleep apnoea (OSA is another chronic disorder characterized by increased CB activity and intimately related with several metabolic and cardiovascular abnormalities. In this manuscript we review in a concise manner the putative pathways linking CB chemoreceptors deregulation with the pathogenesis of insulin resistance and arterial hypertension. Also, the link between chronic intermittent hypoxia (CIH and insulin resistance is discussed. Then, a final section is devoted to debate strategies to reduce CB activity and its use for prevention and therapeutics of metabolic diseases with an emphasis on new exciting research in the modulation of bioelectronic signals, likely to be central in the future.

  6. Role of Autophagy in the Control of Body Metabolism

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    Wenying Quan

    2013-03-01

    Full Text Available Autophagy plays a crucial role in the maintenance of cellular nutrient balance and the function of organelles such as mitochondria or the endoplasmic reticulum, which are important in intracellular metabolism, insulin release, and insulin sensitivity. In the insulin-producing pancreatic β-cells, autophagy is important in the maintenance of β-cell mass, structure, and function. Mice with deficiencies in β-cell-specific autophagy show reduced β-cell mass and defects in insulin secretion that lead to hypoinsulinemia and hyperglycemia but not diabetes. However, these mice developed diabetes when bred with ob/ob mice, suggesting that autophagy-deficient β-cells have defects in dealing with the increased metabolic stress imposed by obesity. These results also imply that autophagy deficiency in β-cells could be a factor in the progression from obesity to diabetes. Another important function of autophagy is in hypothalamic neurons for the central control of energy expenditure, appetite, and body weight. In addition, mice with autophagy deficiencies in the target tissues of insulin have yielded diverse phenotypes. Taken together, these results suggest that autophagy is important in the control of whole body energy and nutrient homeostasis, and its dysregulation could play a role in the development of metabolic disorders and diabetes.

  7. Regulation of Ketone Body Metabolism and the Role of PPARα

    Science.gov (United States)

    Grabacka, Maja; Pierzchalska, Malgorzata; Dean, Matthew; Reiss, Krzysztof

    2016-01-01

    Ketogenesis and ketolysis are central metabolic processes activated during the response to fasting. Ketogenesis is regulated in multiple stages, and a nuclear receptor peroxisome proliferator activated receptor α (PPARα) is one of the key transcription factors taking part in this regulation. PPARα is an important element in the metabolic network, where it participates in signaling driven by the main nutrient sensors, such as AMP-activated protein kinase (AMPK), PPARγ coactivator 1α (PGC-1α), and mammalian (mechanistic) target of rapamycin (mTOR) and induces hormonal mediators, such as fibroblast growth factor 21 (FGF21). This work describes the regulation of ketogenesis and ketolysis in normal and malignant cells and briefly summarizes the positive effects of ketone bodies in various neuropathologic conditions. PMID:27983603

  8. Regulation of Ketone Body Metabolism and the Role of PPARα.

    Science.gov (United States)

    Grabacka, Maja; Pierzchalska, Malgorzata; Dean, Matthew; Reiss, Krzysztof

    2016-12-13

    Ketogenesis and ketolysis are central metabolic processes activated during the response to fasting. Ketogenesis is regulated in multiple stages, and a nuclear receptor peroxisome proliferator activated receptor α (PPARα) is one of the key transcription factors taking part in this regulation. PPARα is an important element in the metabolic network, where it participates in signaling driven by the main nutrient sensors, such as AMP-activated protein kinase (AMPK), PPARγ coactivator 1α (PGC-1α), and mammalian (mechanistic) target of rapamycin (mTOR) and induces hormonal mediators, such as fibroblast growth factor 21 (FGF21). This work describes the regulation of ketogenesis and ketolysis in normal and malignant cells and briefly summarizes the positive effects of ketone bodies in various neuropathologic conditions.

  9. Regulation of Ketone Body Metabolism and the Role of PPARα

    Directory of Open Access Journals (Sweden)

    Maja Grabacka

    2016-12-01

    Full Text Available Ketogenesis and ketolysis are central metabolic processes activated during the response to fasting. Ketogenesis is regulated in multiple stages, and a nuclear receptor peroxisome proliferator activated receptor α (PPARα is one of the key transcription factors taking part in this regulation. PPARα is an important element in the metabolic network, where it participates in signaling driven by the main nutrient sensors, such as AMP-activated protein kinase (AMPK, PPARγ coactivator 1α (PGC-1α, and mammalian (mechanistic target of rapamycin (mTOR and induces hormonal mediators, such as fibroblast growth factor 21 (FGF21. This work describes the regulation of ketogenesis and ketolysis in normal and malignant cells and briefly summarizes the positive effects of ketone bodies in various neuropathologic conditions.

  10. Ketone body metabolism in the mother and fetus.

    Science.gov (United States)

    Shambaugh, G E

    1985-04-01

    Pregnancy is characterized by a rapid accumulation of lipid stores during the first half of gestation and a utilization of these stores during the latter half of gestation. Lipogenesis results from dietary intake, an exaggerated insulin response, and an intensified inhibition of glucagon release. Increasing levels of placental lactogen and a heightened response of adipose tissue to additional lipolytic hormones balance lipogenesis in the fed state. Maternal starvation in late gestation lowers insulin, and lipolysis supervenes. The continued glucose drain by the conceptus aids in converting the maternal liver to a ketogenic organ, and ketone bodies produced from incoming fatty acids are not only utilized by the mother but cross the placenta where they are utilized in several ways by the fetus: as a fuel in lieu of glucose; as an inhibitor of glucose and lactate oxidation with sparing of glucose for biosynthetic disposition; and for inhibition of branched-chain ketoacid oxidation, thereby maximizing formation of their parent amino acids. Ketone bodies are widely incorporated into several classes of lipids including structural lipids as well as lipids for energy stores in fetal tissues, and may inhibit protein catabolism. Finally, it has recently been shown that ketone bodies inhibit the de novo biosynthesis of pyrimidines in fetal rat brain slices. Thus during maternal starvation ketone bodies may maximize chances for survival both in utero and during neonatal life by restraining cell replication and sustaining protein and lipid stores in fetal tissues.

  11. Lidocaine Oxidation by Electrogenerated Reactive Oxygen Species in the Light of Oxidative Drug Metabolism

    NARCIS (Netherlands)

    Nouri-Nigjeh, Eslam; Permentier, Hjalmar P.; Bischoff, Rainer; Bruins, Andries P.

    2010-01-01

    The study of oxidative drug metabolism by Cytochrome P450s (P450) is important in the earlier stages of drug development. For this purpose, automated analytical techniques are needed for fast and accurate estimation of oxidative drug metabolism. Previous studies have shown that electrochemistry in c

  12. Automotive body panel containing thermally exfoliated graphite oxide

    Science.gov (United States)

    Prud'Homme, Robert K. (Inventor); Aksay, Ilhan A. (Inventor); Adamson, Douglas (Inventor); Abdala, Ahmed (Inventor)

    2011-01-01

    An automotive body panel containing a polymer composite formed of at least one polymer and a modified graphite oxide material, which is a thermally exfoliated graphite oxide with a surface area of from about 300 m.sup.2/g to 2600 m.sup.2/g.

  13. Electrochemical Oxidation by Square-Wave Potential Pulses in the Imitation of Oxidative Drug Metabolism

    NARCIS (Netherlands)

    Nouri-Nigjeh, Eslam; Permentier, Hjalmar P.; Bischoff, Rainer; Bruins, Andries P.

    2011-01-01

    Electrochemistry combined with mass spectrometry (EC-MS) is an emerging analytical technique in the imitation of oxidative drug metabolism at the early stages of new drug development. Here, we present the benefits of electrochemical oxidation by square-wave potential pulses for the oxidation of lido

  14. Oxidant stress and skeletal muscle microvasculopathy in the metabolic syndrome.

    Science.gov (United States)

    Goodwill, Adam G; Frisbee, Jefferson C

    2012-01-01

    The evolution of the metabolic syndrome in afflicted individuals is, in part, characterized by the development of a severely pro-oxidant state within the vasculature. It has been previously demonstrated by many investigators that this increasingly pro-oxidant state can have severe negative implications for many relevant processes within the vasculature, including the coordination of dilator/constrictor tone or reactivity, the structural adaptations of the vascular wall or distal networks, as well as the integrated regulation of perfusion resistance across and throughout the vascular networks. The purpose of this review article is to present the different sources of oxidant stress within the setting of the metabolic syndrome, the available mechanism for attempts at regulation and the vascular outcomes associated with this condition. It is anticipated that this overview will help readers and investigators to more effectively design experiments and interpret their results within the extremely complicated setting of metabolic syndrome.

  15. IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism.

    Science.gov (United States)

    Grassian, Alexandra R; Parker, Seth J; Davidson, Shawn M; Divakaruni, Ajit S; Green, Courtney R; Zhang, Xiamei; Slocum, Kelly L; Pu, Minying; Lin, Fallon; Vickers, Chad; Joud-Caldwell, Carol; Chung, Franklin; Yin, Hong; Handly, Erika D; Straub, Christopher; Growney, Joseph D; Vander Heiden, Matthew G; Murphy, Anne N; Pagliarini, Raymond; Metallo, Christian M

    2014-06-15

    Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed (13)C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells. However, selective inhibition of mutant IDH1 enzyme function could not reverse the defect in reductive carboxylation activity. Furthermore, this metabolic reprogramming increased the sensitivity of IDH1-mutant cells to hypoxia or electron transport chain inhibition in vitro. Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation.

  16. Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice.

    Science.gov (United States)

    Peek, Clara Bien; Affinati, Alison H; Ramsey, Kathryn Moynihan; Kuo, Hsin-Yu; Yu, Wei; Sena, Laura A; Ilkayeva, Olga; Marcheva, Biliana; Kobayashi, Yumiko; Omura, Chiaki; Levine, Daniel C; Bacsik, David J; Gius, David; Newgard, Christopher B; Goetzman, Eric; Chandel, Navdeep S; Denu, John M; Mrksich, Milan; Bass, Joseph

    2013-11-01

    Circadian clocks are self-sustained cellular oscillators that synchronize oxidative and reductive cycles in anticipation of the solar cycle. We found that the clock transcription feedback loop produces cycles of nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, adenosine triphosphate production, and mitochondrial respiration through modulation of mitochondrial protein acetylation to synchronize oxidative metabolic pathways with the 24-hour fasting and feeding cycle. Circadian control of the activity of the NAD(+)-dependent deacetylase sirtuin 3 (SIRT3) generated rhythms in the acetylation and activity of oxidative enzymes and respiration in isolated mitochondria, and NAD(+) supplementation restored protein deacetylation and enhanced oxygen consumption in circadian mutant mice. Thus, circadian control of NAD(+) bioavailability modulates mitochondrial oxidative function and organismal metabolism across the daily cycles of fasting and feeding.

  17. Metabolism and aging: effects of cold exposure on metabolic rate, body composition, and longevity in mice.

    Science.gov (United States)

    Vaanholt, Lobke M; Daan, Serge; Schubert, Kristin A; Visser, G Henk

    2009-01-01

    The proposition that increased energy expenditure shortens life has a long history. The rate-of-living theory (Pearl 1928 ) states that life span and average mass-specific metabolic rate are inversely proportional. Originally based on interspecific allometric comparisons between species of mammals, the theory was later rejected on the basis of comparisons between taxa (e.g., birds have higher metabolic rates than mammals of the same size and yet live longer). It has rarely been experimentally tested within species. Here, we investigated the effects of increased energy expenditure, induced by cold exposure, on longevity in mice. Longevity was measured in groups of 60 male mice maintained at either 22 degrees C (WW) or 10 degrees C (CC) throughout adult life. Forty additional mice were maintained at both of these temperatures to determine metabolic rate (by stable isotope turnover, gas exchange, and food intake) as well as the mass of body and organs of subsets of animals at four different ages. Because energy expenditure might affect longevity by either accumulating damage or by instantaneously affecting mortality rate, we included a third group of mice exposed to 10 degrees C early in life and to 22 degrees C afterward (CW). Exposure to cold increased mean daily energy expenditure by ca. 48% (from 47.8 kJ d(-1) in WW to 70.6 kJ d(-1) in CC mice, with CW intermediate at 59.9 kJ d(-1)). However, we observed no significant differences in median life span among the groups (WW, 832 d; CC, 834 d; CW, 751 d). CC mice had reduced body mass (lifetime mean 30.7 g) compared with WW mice (33.8 g), and hence their lifetime energy potential (LEP) per gram whole-body mass had an even larger excess than per individual. Greenberg ( 1999 ) has pointed out that the size of the energetically costly organs, rather than that of the whole body, may be relevant for the rate-of-living idea. We therefore expressed LEP also in terms of energy expenditure per gram dry lean mass or per gram

  18. Common variants near MC4R in relation to body fat, body fat distribution, metabolic traits and energy expenditure

    DEFF Research Database (Denmark)

    Kring, Sofia Inez Iqbal; Holst, C; Toubro, Søren

    2010-01-01

    Common variants near melanocortin receptor 4 (MC4R) have been related to fatness and type 2 diabetes. We examined the associations of rs17782313 and rs17700633 in relation to body fat, body fat distribution, metabolic traits, weight development and energy expenditure.......Common variants near melanocortin receptor 4 (MC4R) have been related to fatness and type 2 diabetes. We examined the associations of rs17782313 and rs17700633 in relation to body fat, body fat distribution, metabolic traits, weight development and energy expenditure....

  19. Growth hormone enhances effects of endurance training on oxidative muscle metabolism in elderly women

    DEFF Research Database (Denmark)

    Lange, K H; Isaksson, F; Juul, A;

    2000-01-01

    The present study investigated whether recombinant human (rh) growth hormone (GH) combined with endurance training would have a larger effect on oxidative capacity, metabolism, and body fat than endurance training alone. Sixteen healthy, elderly women, aged 75 yr, performed closely monitored...... by approximately 18% in both groups, whereas the marked increase in muscle citrate synthase activity was 50% larger in the GH group compared with the placebo group. In addition, only the GH group revealed an increase in muscle L-3-hydroxyacyl-CoA dehydrogenase activity. Body weight remained unchanged in both...... in the two subjects receiving rhGH. In conclusion, rhGH adds to the effects of endurance training on muscle oxidative enzymes and causes a reduction in body fat in elderly women....

  20. Fat oxidation at rest predicts peak fat oxidation during exercise and metabolic phenotype in overweight men

    DEFF Research Database (Denmark)

    Rosenkilde, M; Nordby, P; Nielsen, L B

    2010-01-01

    OBJECTIVE: To elucidate if fat oxidation at rest predicts peak fat oxidation during exercise and/or metabolic phenotype in moderately overweight, sedentary men. DESIGN: Cross-sectional study.Subjects:We measured respiratory exchange ratio (RER) at rest in 44 moderately overweight, normotensive...... the International Diabetes Federation criteria, we found that there was a lower accumulation of metabolic risk factors in L-RER than in H-RER (1.6 vs 3.5, P=0.028), and no subjects in L-RER and four of eight subjects in H-RER had the metabolic syndrome. Resting RER was positively correlated with plasma...... triglycerides (Pmetabolic...

  1. Body condition score (BCS and metabolic status of shelter dogs

    Directory of Open Access Journals (Sweden)

    I. Andrighetto

    2010-04-01

    Full Text Available A group of 147 shelter dogs were weighted and assigned a body condition score (BCS using a 9 point scale system, in order to evaluate the prevalence of obesity in the kennel. More than 60% of the animals showed a BCS³6 (overweight and obese and this condition was mainly attributed to an excess of carbohydrates and fat in the diet. In 67/147 dogs, a blood sample was drawn and the effects of BCS, age and time spent in the shelter were evaluated on biochemical parameters. Obese dogs showed significantly higher levels of triglycerides (P<0.01, while increasing BCS determined only an increasing non significant trend on cholesterol values. Age influenced creatinine (P<0.05 and the oldest dogs scoring BCS³6 registered significant higher NEFA (P<0.05 and CK (P=0.01 levels. Time spent in the shelter did not affect any parameter. The dogs’ metabolic condition reflects the need of taking more care of the quality of feed administered in the shelters to avoid the negative health effects caused by chronic obesity.

  2. Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis.

    Science.gov (United States)

    Hertz, Leif; Peng, Liang; Dienel, Gerald A

    2007-02-01

    Astrocytic energy demand is stimulated by K(+) and glutamate uptake, signaling processes, responses to neurotransmitters, Ca(2+) fluxes, and filopodial motility. Astrocytes derive energy from glycolytic and oxidative pathways, but respiration, with its high-energy yield, provides most adenosine 5' triphosphate (ATP). The proportion of cortical oxidative metabolism attributed to astrocytes ( approximately 30%) in in vivo nuclear magnetic resonance (NMR) spectroscopic and autoradiographic studies corresponds to their volume fraction, indicating similar oxidation rates in astrocytes and neurons. Astrocyte-selective expression of pyruvate carboxylase (PC) enables synthesis of glutamate from glucose, accounting for two-thirds of astrocytic glucose degradation via combined pyruvate carboxylation and dehydrogenation. Together, glutamate synthesis and oxidation, including neurotransmitter turnover, generate almost as much energy as direct glucose oxidation. Glycolysis and glycogenolysis are essential for astrocytic responses to increasing energy demand because astrocytic filopodial and lamellipodial extensions, which account for 80% of their surface area, are too narrow to accommodate mitochondria; these processes depend on glycolysis, glycogenolysis, and probably diffusion of ATP and phosphocreatine formed via mitochondrial metabolism to satisfy their energy demands. High glycogen turnover in astrocytic processes may stimulate glucose demand and lactate production because less ATP is generated when glucose is metabolized via glycogen, thereby contributing to the decreased oxygen to glucose utilization ratio during brain activation. Generated lactate can spread from activated astrocytes via low-affinity monocarboxylate transporters and gap junctions, but its subsequent fate is unknown. Astrocytic metabolic compartmentation arises from their complex ultrastructure; astrocytes have high oxidative rates plus dependence on glycolysis and glycogenolysis, and their energetics is

  3. Correction factors for 13C-labelled substrate oxidation at whole-body and muscle level

    DEFF Research Database (Denmark)

    Van Hall, Gerrit

    1999-01-01

    The oxidation of fatty acids, carbohydrates and amino acids can be measured by quantifying the rate of excretion of labelled CO2 following administration of 14C- or 13C-labelled substrates at whole-body and tissue level. However, there is a theoretical need to correct the oxidation rates...... for the proportion of labelled CO2 that is produced via oxidation but not excreted. Furthermore, depending on the substrate and position of the C label(s), there may also be a need to correct for labelled C from the metabolized substrate that does not appear as CO2, but rather becomes temporarily fixed in other...... metabolites. The bicarbonate correction factor is used to correct for the labelled CO2 not excreted. Recently, an acetate correction factor has been proposed for the simultaneous correction of CO2 not excreted and label fixed in other metabolites via isotopic exchange reactions, mainly in the tricarboxylic...

  4. Coffee polyphenols modulate whole-body substrate oxidation and suppress postprandial hyperglycaemia, hyperinsulinaemia and hyperlipidaemia.

    Science.gov (United States)

    Murase, Takatoshi; Yokoi, Yuka; Misawa, Koichi; Ominami, Hideo; Suzuki, Yasuto; Shibuya, Yusuke; Hase, Tadashi

    2012-06-01

    Postprandial energy metabolism, including postprandial hyperglycaemia, hyperinsulinaemia and hyperlipidaemia, is related to the risk for developing obesity and CVD. In the present study, we examined the effects of polyphenols purified from coffee (coffee polyphenols (CPP)) on postprandial carbohydrate and lipid metabolism, and whole-body substrate oxidation in C57BL/6J mice. In mice that co-ingested CPP with a lipid-carbohydrate (sucrose or starch)-mixed emulsion, the respiratory quotient determined by indirect calorimetry was significantly lower than that in control mice, whereas there was no difference in VO2 (energy expenditure), indicating that CPP modulates postprandial energy partitioning. CPP also suppressed postprandial increases in plasma glucose, insulin, glucose-dependent insulinotropic polypeptide and TAG levels. Inhibition experiments on digestive enzymes revealed that CPP inhibits maltase and sucrase, and, to a lesser extent, pancreatic lipase in a concentration-dependent manner. Among the nine kinds of polyphenols (caffeoyl quinic acids (CQA), di-CQA, feruloyl quinic acids (FQA)) contained in CPP, di-CQA showed more potent inhibitory activity than CQA or FQA on these digestive enzymes, suggesting a predominant role of di-CQA in the regulation of postprandial energy metabolism. These results suggest that CPP modulates whole-body substrate oxidation by suppressing postprandial hyperglycaemia and hyperinsulinaemia, and these effects are mediated by inhibiting digestive enzymes.

  5. Sucrose Production Mediated by Lipid Metabolism Suppresses the Physical Interaction of Peroxisomes and Oil Bodies during Germination of Arabidopsis thaliana.

    Science.gov (United States)

    Cui, Songkui; Hayashi, Yasuko; Otomo, Masayoshi; Mano, Shoji; Oikawa, Kazusato; Hayashi, Makoto; Nishimura, Mikio

    2016-09-16

    Physical interaction between organelles is a flexible event and essential for cells to adapt rapidly to environmental stimuli. Germinating plants utilize oil bodies and peroxisomes to mobilize storage lipids for the generation of sucrose as the main energy source. Although membrane interaction between oil bodies and peroxisomes has been widely observed, its underlying molecular mechanism is largely unknown. Here we present genetic evidence for control of the physical interaction between oil bodies and peroxisomes. We identified alleles of the sdp1 mutant altered in oil body morphology. This mutant accumulates bigger and more oil body aggregates compared with the wild type and showed defects in lipid mobilization during germination. SUGAR DEPENDENT 1 (SDP1) encodes major triacylglycerol lipase in Arabidopsis Interestingly, sdp1 seedlings show enhanced physical interaction between oil bodies and peroxisomes compared with the wild type, whereas exogenous sucrose supplementation greatly suppresses the interaction. The same phenomenon occurs in the peroxisomal defective 1 (ped1) mutant, defective in lipid mobilization because of impaired peroxisomal β-oxidation, indicating that sucrose production is a key factor for oil body-peroxisomal dissociation. Peroxisomal dissociation and subsequent release from oil bodies is dependent on actin filaments. We also show that a peroxisomal ATP binding cassette transporter, PED3, is the potential anchor protein to the membranes of these organelles. Our results provide novel components linking lipid metabolism and oil body-peroxisome interaction whereby sucrose may act as a negative signal for the interaction of oil bodies and peroxisomes to fine-tune lipolysis.

  6. Total body fat as a possible indicator of metabolic syndrome in adults

    Directory of Open Access Journals (Sweden)

    Edgar Navarro Lechuga

    2016-09-01

    Full Text Available Introduction: The metabolic syndrome is a set of factors related to insulin resistance, which increases the likelihood of coronary events. It is important timely onset identifying to reduce its prevalence. Objective: To explore the percentage of total body fat as indicator of metabolic syndrome in adults from Soledad, Colombia. Material and Methods: Cross-sectional study. n=99 adults (non-pregnant, nor subjects with psychomotor disturbances. Blood samples were taken: total cholesterol, HDL; triglycerides and glucose. Waist circumference, Body Mass Index and body fat by bioimpedance and skinfold thickness were measured. Diagnosis of metabolic syndrome was made according to NHLBI/AHA, ATP III and IDF criteria. Subjects with and without metabolic syndrome according to total body fat averages were compared. Results: The average percentage of body fat was higher (p0.05 in the classification according to ATP III in women, where the average fat percentage was 39.31 % in those with metabolic syndrome and 37.7% in those not suffering. Conclusions: Subjects with metabolic syndrome have higher mean total body fat, significantly, compared with those who did not, so it could be considered the values of total body fat obtained by bioimpedance as future indicators of metabolic syndrome, both as screening and control.

  7. Regulation of myocardial ketone body metabolism by the gut microbiota during nutrient deprivation.

    Science.gov (United States)

    Crawford, Peter A; Crowley, Jan R; Sambandam, Nandakumar; Muegge, Brian D; Costello, Elizabeth K; Hamady, Micah; Knight, Rob; Gordon, Jeffrey I

    2009-07-07

    Studies in mice indicate that the gut microbiota promotes energy harvest and storage from components of the diet when these components are plentiful. Here we examine how the microbiota shapes host metabolic and physiologic adaptations to periods of nutrient deprivation. Germ-free (GF) mice and mice who had received a gut microbiota transplant from conventionally raised donors were compared in the fed and fasted states by using functional genomic, biochemical, and physiologic assays. A 24-h fast produces a marked change in gut microbial ecology. Short-chain fatty acids generated from microbial fermentation of available glycans are maintained at higher levels compared with GF controls. During fasting, a microbiota-dependent, Ppar alpha-regulated increase in hepatic ketogenesis occurs, and myocardial metabolism is directed to ketone body utilization. Analyses of heart rate, hydraulic work, and output, mitochondrial morphology, number, and respiration, plus ketone body, fatty acid, and glucose oxidation in isolated perfused working hearts from GF and colonized animals (combined with in vivo assessments of myocardial physiology) revealed that the fasted GF heart is able to sustain its performance by increasing glucose utilization, but heart weight, measured echocardiographically or as wet mass and normalized to tibial length or lean body weight, is significantly reduced in both fasted and fed mice. This myocardial-mass phenotype is completely reversed in GF mice by consumption of a ketogenic diet. Together, these results illustrate benefits provided by the gut microbiota during periods of nutrient deprivation, and emphasize the importance of further exploring the relationship between gut microbes and cardiovascular health.

  8. Avian basal metabolic rates : their association with body composition and energy expenditure in nature

    NARCIS (Netherlands)

    Daan, Serge; Masman, Dirkjan; Groenewold, Alex

    1990-01-01

    Measurements of basal metabolic rate (BMR), body water, fat, and lean dry mass of different organs were obtained in 22 bird species, ranging from 10.8 to 1,253 g body mass. Residuals of BMR (after subtracting BMR allometrically predicted from body mass) were positively correlated with residuals of l

  9. Body composition and energy metabolism in elderly people.

    NARCIS (Netherlands)

    Visser, M.

    1995-01-01

    This thesis describes several studies related to the three components of energy balance in elderly people: body composition, energy expenditure, and energy intake.Body composition. The applicability of the body mass index, skinfold thickness method, and multi-frequency bioelectrical impedance was te

  10. All-trans retinoic acid increases oxidative metabolism in mature adipocytes

    DEFF Research Database (Denmark)

    Mercader, Josep; Madsen, Lise; Felipe, Francisco;

    2007-01-01

    BACKGROUND/AIMS: In rodents, retinoic acid (RA) treatment favors loss of body fat mass and the acquisition of brown fat features in white fat depots. In this work, we sought to examine to what extent these RA effects are cell autonomous or dependent on systemic factors. METHODS: Parameters of lipid...... metabolism and related gene expression were analyzed in differentiated 3T3-L1 adipocytes after exposure to RA or vehicle. RESULTS: Treatment with RA resulted in decreased cellular triacylglycerol content and increased basal lipolysis and fatty acid oxidation rate. At the mRNA level, RA treatment led......), and to an increased expression of proteins favoring fat oxidation (peroxisome proliferator-activated receptor gamma coactivator-1alpha, uncoupling protein 2, fasting-induced adipose factor, enzymes of mitochondrial fatty acid oxidation). These changes paralleled inactivation of the retinoblastoma protein and were...

  11. Oxidative stress and DNA methylation regulation in the metabolic syndrome.

    Science.gov (United States)

    Yara, Sabrina; Lavoie, Jean-Claude; Levy, Emile

    2015-01-01

    DNA methylation is implicated in tissue-specific gene expression and genomic imprinting. It is modulated by environmental factors, especially nutrition. Modified DNA methylation patterns may contribute to health problems and susceptibility to complex diseases. Current advances have suggested that the metabolic syndrome (MS) is a programmable disease, which is characterized by epigenetic modifications of vital genes when exposed to oxidative stress. Therefore, the main objective of this paper is to critically review the central context of MS while presenting the most recent knowledge related to epigenetic alterations that are promoted by oxidative stress. Potential pro-oxidant mechanisms that orchestrate changes in methylation profiling and are related to obesity, diabetes and hypertension are discussed. It is anticipated that the identification and understanding of the role of DNA methylation marks could be used to uncover early predictors and define drugs or diet-related treatments able to delay or reverse epigenetic changes, thereby combating MS burden.

  12. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism

    DEFF Research Database (Denmark)

    Lerin, Carles; Goldfine, Allison B; Boes, Tanner;

    2016-01-01

    OBJECTIVE: Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. METHODS: To identify pathways related t...... catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D....... methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. RESULTS: Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate...... fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. CONCLUSIONS: Our data indicate that impaired muscle BCAA...

  13. Regulation of Ketone Body Metabolism and the Role of PPARα

    OpenAIRE

    Grabacka, Maja; Pierzchalska, Malgorzata; Dean, Matthew; Reiss, Krzysztof

    2016-01-01

    Ketogenesis and ketolysis are central metabolic processes activated during the response to fasting. Ketogenesis is regulated in multiple stages, and a nuclear receptor peroxisome proliferator activated receptor α (PPARα) is one of the key transcription factors taking part in this regulation. PPARα is an important element in the metabolic network, where it participates in signaling driven by the main nutrient sensors, such as AMP-activated protein kinase (AMPK), PPARγ coactivator 1α (PGC-1α), ...

  14. All-trans retinoic acid increases oxidative metabolism in mature adipocytes

    DEFF Research Database (Denmark)

    Mercader, Josep; Madsen, Lise; Felipe, Francisco;

    2007-01-01

    BACKGROUND/AIMS: In rodents, retinoic acid (RA) treatment favors loss of body fat mass and the acquisition of brown fat features in white fat depots. In this work, we sought to examine to what extent these RA effects are cell autonomous or dependent on systemic factors. METHODS: Parameters of lipid...... preceded by an early RA-induced phosphorylation of p38 mitogen-activated protein kinase. UCP1 expression was not induced. CONCLUSION: The results indicate that RA directly favors remodeling of mature 3T3-L1 adipocytes in culture toward increased oxidative metabolism....

  15. Myocardial Oxidative Metabolism and Protein Synthesis during Mechanical Circulatory Support by Extracorporeal Membrane Oxygenation

    Energy Technology Data Exchange (ETDEWEB)

    Priddy, MD, Colleen M.; Kajimoto, Masaki; Ledee, Dolena; Bouchard, Bertrand; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

    2013-02-01

    Extracorporeal membrane oxygenation (ECMO) provides mechanical circulatory support essential for survival in infants and children with acute cardiac decompensation. However, ECMO also causes metabolic disturbances, which contribute to total body wasting and protein loss. Cardiac stunning can also occur which prevents ECMO weaning, and contributes to high mortality. The heart may specifically undergo metabolic impairments, which influence functional recovery. We tested the hypothesis that ECMO alters oxidative. We focused on the amino acid leucine, and integration with myocardial protein synthesis. We used a translational immature swine model in which we assessed in heart (i) the fractional contribution of leucine (FcLeucine) and pyruvate (FCpyruvate) to mitochondrial acetyl-CoA formation by nuclear magnetic resonance and (ii) global protein fractional synthesis (FSR) by gas chromatography-mass spectrometry. Immature mixed breed Yorkshire male piglets (n = 22) were divided into four groups based on loading status (8 hours of normal circulation or ECMO) and intracoronary infusion [13C6,15N]-L-leucine (3.7 mM) alone or with [2-13C]-pyruvate (7.4 mM). ECMO decreased pulse pressure and correspondingly lowered myocardial oxygen consumption (~ 40%, n = 5), indicating decreased overall mitochondrial oxidative metabolism. However, FcLeucine was maintained and myocardial protein FSR was marginally increased. Pyruvate addition decreased tissue leucine enrichment, FcLeucine, and Fc for endogenous substrates as well as protein FSR. Conclusion: The heart under ECMO shows reduced oxidative metabolism of substrates, including amino acids, while maintaining (i) metabolic flexibility indicated by ability to respond to pyruvate, and (ii) a normal or increased capacity for global protein synthesis, suggesting an improved protein balance.

  16. LSD1 promotes oxidative metabolism of white adipose tissue

    Science.gov (United States)

    Duteil, Delphine; Metzger, Eric; Willmann, Dominica; Karagianni, Panagiota; Friedrichs, Nicolaus; Greschik, Holger; Günther, Thomas; Buettner, Reinhard; Talianidis, Iannis; Metzger, Daniel; Schüle, Roland

    2014-01-01

    Exposure to environmental cues such as cold or nutritional imbalance requires white adipose tissue (WAT) to adapt its metabolism to ensure survival. Metabolic plasticity is prominently exemplified by the enhancement of mitochondrial biogenesis in WAT in response to cold exposure or β3-adrenergic stimulation. Here we show that these stimuli increase the levels of lysine-specific demethylase 1 (LSD1) in WAT of mice and that elevated LSD1 levels induce mitochondrial activity. Genome-wide binding and transcriptome analyses demonstrate that LSD1 directly stimulates the expression of genes involved in oxidative phosphorylation (OXPHOS) in cooperation with nuclear respiratory factor 1 (Nrf1). In transgenic (Tg) mice, increased levels of LSD1 promote in a cell-autonomous manner the formation of islets of metabolically active brown-like adipocytes in WAT. Notably, Tg mice show limited weight gain when fed a high-fat diet. Taken together, our data establish LSD1 as a key regulator of OXPHOS and metabolic adaptation in WAT. PMID:24912735

  17. Altered oxidative stress and carbohydrate metabolism in canine mammary tumors

    Directory of Open Access Journals (Sweden)

    K. Jayasri

    2016-12-01

    Full Text Available Aim: Mammary tumors are the most prevalent type of neoplasms in canines. Even though cancer induced metabolic alterations are well established, the clinical data describing the metabolic profiles of animal tumors is not available. Hence, our present investigation was carried out with the aim of studying changes in carbohydrate metabolism along with the level of oxidative stress in canine mammary tumors. Materials and Methods: Fresh mammary tumor tissues along with the adjacent healthy tissues were collected from the college surgical ward. The levels of thiobarbituric acid reactive substances (TBARS, glutathione, protein, hexose, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and glucose-6-phosphate dehydrogenase (G6PD were analyzed in all the tissues. The results were analyzed statistically. Results: More than two-fold increase in TBARS and three-fold increase in glutathione levels were observed in neoplastic tissues. Hexokinase activity and hexose concentration (175% was found to be increased, whereas glucose-6-phosphatase (33%, fructose-1, 6-bisphosphatase (42%, and G6PD (5 fold activities were reduced in tumor mass compared to control. Conclusion: Finally, it was revealed that lipid peroxidation was increased with differentially altered carbohydrate metabolism in canine mammary tumors.

  18. Body shape shifting during growth permits tests that distinguish between competing geometric theories of metabolic scaling

    DEFF Research Database (Denmark)

    Hirst, Andrew G.; Glazier, Douglas S.; Atkinson, David;

    2014-01-01

    Metabolism fuels all of life’s activities, from biochemical reactions to ecological interactions. According to two intensely debated theories, body size affects metabolism via geometrical influences on the transport of resources and wastes. However, these theories differ crucially in whether...... theory, but contradicting the negative correlations predicted by resource-transport network models. This finding explains strong deviations from predictions of widely adopted theory, and underpins a new explanation for mass-invariant metabolic scaling during ontogeny in animals and plants...

  19. Is higher dairy consumption associated with lower body weight and fewer metabolic disturbances? The Hoorn Study

    NARCIS (Netherlands)

    Snijder, M.B.; Heijden, van der A.A.; Dam, van R.M.; Stehouwer, C.D.A.; Hiddink, G.J.; Nijpels, Giel; Heine, R.J.; Bouter, L.M.; Dekker, J.M.

    2007-01-01

    Objective:The aim of this study was to evaluate the associations of dairy consumption with body weight and other components of the metabolic syndrome. Design:We used cross-sectional data for 2064 men and women aged 50¿75 y who participated in the Hoorn Study. The metabolic syndrome was defined accor

  20. H2S regulation of nitric oxide metabolism

    Science.gov (United States)

    Kolluru, Gopi K.; Yuan, Shuai; Shen, Xinggui; Kevil, Christopher G.

    2015-01-01

    Nitric oxide (NO) and hydrogen sulfide (H2S) are two major gaseous signaling molecules that regulate diverse physiological functions. Recent publications indicate the regulatory role of H2S on NO metabolism. In this chapter, we discuss the latest findings on H2S-NO interactions through formation of novel chemical derivatives, and experimental approaches to study these adducts. This chapter also addresses potential H2S interference on various NO detection techniques, along with precautions for analyzing biological samples from various sources. This information will facilitate critical evaluation and clearer insight into H2S regulation of NO signaling and its influence on various physiological functions. PMID:25725527

  1. Increasing NADH oxidation reduces overflow metabolism in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Vemuri, Goutham; Eiteman, M.A; McEwen, J.E;

    2007-01-01

    Crabtree effect.’’ The yeast Saccharomyces cerevisiae has served as an important model organism for studying the Crabtree effect. When subjected to increasing glycolytic fluxes under aerobic conditions, there is a threshold value of the glucose uptake rate at which the metabolism shifts from purely...... effect is due to limited respiratory capacity or is caused by glucose-mediated repression of respiration. When respiration in S. cerevisiae was increased by introducing a heterologous alternative oxidase, we observed reduced aerobic ethanol formation. In contrast, increasing nonrespiratory NADH oxidation...... NADH dehydrogenases in S. cerevisiae. These results indicate that NADH oxidase localizes in the cytosol, whereas alternative oxidase is directed to the mitochondria....

  2. Exergy efficiency from staple food ingredients to body metabolism

    NARCIS (Netherlands)

    Rodriguez-Illera, Marta; Nikiforidis, Constantinos V.; Goot, van der Atze Jan; Boom, Remko M.

    2017-01-01

    One of the methods to evaluate the efficiency in the production of foods is using exergy, the share of useful energy, and exergy analysis. In this paper, we propose a link between exergy analysis and nutrition to account for the exergy efficiency (exergy of output per exergy of input) in the metabol

  3. Uptake and metabolism of iron oxide nanoparticles in brain cells.

    Science.gov (United States)

    Petters, Charlotte; Irrsack, Ellen; Koch, Michael; Dringen, Ralf

    2014-09-01

    Magnetic iron oxide nanoparticles (IONPs) are used for various applications in biomedicine, for example as contrast agents in magnetic resonance imaging, for cell tracking and for anti-tumor treatment. However, IONPs are also known for their toxic effects on cells and tissues which are at least in part caused by iron-mediated radical formation and oxidative stress. The potential toxicity of IONPs is especially important concerning the use of IONPs for neurobiological applications as alterations in brain iron homeostasis are strongly connected with human neurodegenerative diseases. Since IONPs are able to enter the brain, potential adverse consequences of an exposure of brain cells to IONPs have to be considered. This article describes the pathways that allow IONPs to enter the brain and summarizes the current knowledge on the uptake, the metabolism and the toxicity of IONPs for the different types of brain cells in vitro and in vivo.

  4. Oxidative stress and an altered methionine metabolism in alcoholism.

    Science.gov (United States)

    Bleich, S; Spilker, K; Kurth, C; Degner, D; Quintela-Schneider, M; Javaheripour, K; Rüther, E; Kornhuber, J; Wiltfang, J

    2000-11-03

    The exact mechanism of brain atrophy in patients with chronic alcoholism remains unknown. There is growing evidence that chronic alcoholism is associated with oxidative stress and with a derangement in sulphur amino acid metabolism (e.g. ethanol-induced hyperhomocysteinemia). Furthermore, it has been reported that homocysteine induces neuronal cell death by stimulating N-methyl-D-aspartate receptors as well as by producing free radicals. To further evaluate this latter hypothesis we analysed serum levels of both homocysteine and markers of oxidative stress (malondialdehyde) in alcoholic patients who underwent withdrawal from alcohol. Homocysteine and malondialdehyde were quantified by high performance liquid chromatography (HPLC) in serum samples of 35 patients (active drinkers). There was a significant correlation (Pbrain shrinkage.

  5. Metabolism

    Science.gov (United States)

    ... a particular food provides to the body. A chocolate bar has more calories than an apple, so ... acid phenylalanine, needed for normal growth and protein production). Inborn errors of metabolism can sometimes lead to ...

  6. The Mediterranean diet adoption improves metabolic, oxidative, and inflammatory abnormalities in Algerian metabolic syndrome patients.

    Science.gov (United States)

    Bekkouche, L; Bouchenak, M; Malaisse, W J; Yahia, D Ait

    2014-04-01

    This study was aimed to explore the effects of Mediterranean diet (MD) adoption on insulin resistance, oxidative, and inflammatory status in metabolic syndrome (MS) patients. Eighty four patients with MS were randomly recruited in the medical centers of Oran, Algeria. Eighteen healthy participants were selected as a control group. Among these 84 patients, only 36 patients completed the nutritional advices for 3 months. Patients were instructed to follow a Mediterranean-style diet and received some other selected nutritional and physical activity instructions. Anthropometric measurements were performed and a questionnaire was used to assess dietary intake. Blood samples were drawn at baseline and after 3 months of nutritional intervention from all subjects. At baseline, the MS patients were obese and had altered anthropometric parameters, higher systolic and diastolic blood pressure, plasma lipids, glucose, insulin, HOMA-IR, HbA1c, urea, creatinine, uric acid, and lower albumin compared to healthy subjects. A decrease in plasma, erythrocyte, and platelet antioxidant enzymes, and a rise in lipid and protein oxidation, plasma CRP, and fibrinogen were noted in the MS patients. Moreover, they had an unbalanced dietary pattern when compared to Mediterranean recommendations. Patients following the Mediterranean-style diet had significantly reduced weight, BMI, waist circumference, waist/hip circumference ratio, decreased systolic and diastolic blood pressure, plasma glucose, insulin, HOMA-IR, HbA1c, cholesterol, triacylglycerols, CRP, urea, creatinine, creatinine clearance, lipid and protein oxidation, and higher plasma, erythrocyte, and platelet antioxidant enzymes. In conclusion, a lifestyle intervention based mainly on nutritional advices improves metabolic, oxidative, and inflammatory abnormalities of metabolic syndrome.

  7. Deep body composition phenotyping during weight cycling: relevance to metabolic efficiency and metabolic risk.

    Science.gov (United States)

    Bosy-Westphal, A; Kahlhöfer, J; Lagerpusch, M; Skurk, T; Müller, M J

    2015-02-01

    Weight cycling may lead to adverse effects on metabolic efficiency (i.e. adaptive thermogenesis or 'metabolic slowing') and metabolic risks (e.g. increased risk for insulin resistance and the metabolic syndrome). In order to investigate these topics, the partitioning of fat and lean mass (i.e. the change in the proportion of both compartments) needs to be extended to the organ and tissue level because metabolic risk differs between adipose tissue depots and lean mass is metabolically heterogeneous being composed of organs and tissues differing in metabolic rate. Contrary to data obtained with severe weight loss and regain in lean people, weight cycling most likely has no adverse effects on fat distribution and metabolic risk in obese patients. There is even evidence for an increased ability of fat storage in subcutaneous fat depots (at the trunk in men and at the limbs in women) with weight cycling that may provide a certain protection from ectopic lipid deposition and thus explain the preservation of a favourable metabolic profile despite weight regain. On the other hand, the mass-specific metabolic rate of lean mass may increase with weight gain and decrease with weight loss mainly because of an increase and respective decrease in the proportion (and/or activity) of metabolically active organ mass. Obese people could therefore have a higher slope of the regression line between resting energy expenditure (REE) and fat-free mass that leads to an overestimation of metabolic efficiency when applied to normalize REE data after weight loss. Furthermore, in addressing the impact of macronutrient composition of the diet on partitioning of lean and fat mass, and the old controversy about whether a calorie is a calorie, we discuss recent evidence in support of a low glycaemic weight maintenance diet in countering weight regain and challenge this concept for weight loss by proposing the opposite.

  8. Body composition alterarions, energy expenditure and fat oxidation in elderly males suffering from prostate cancer, pre and post orchiectomy

    Directory of Open Access Journals (Sweden)

    Cristiana Reis

    2009-01-01

    Full Text Available INTRODUCTION: Testosterone is needed for normal male development, muscle strength, bone mineralization, hematopoietic function, and sexual and reproductive functions. The main purpose of androgen deprivation therapy in prostate cancer is to reduce tumor progression, but therapy is often accompanied by significant adverse effects. OBJECTIVE: This study aimed to determine the effects of androgen deprivation therapy on body composition and resting metabolic rate in patients with prostate cancer. PATIENTS AND METHODS: A prospective study was performed to evaluate the body composition of 16 elderly males (aged 63-96; median age 71 with prostate cancer scheduled for orchiectomy, one year before and after surgery. Body composition was measured by DEXA, and energy expenditure, fat and carbohydrate oxidation were measured by indirect calorimetry. RESULTS: Body weight (p=0.01, lean mass (p=0.004, and lipid oxidation (p=0.001 decreased significantly. Carbohydrate oxidation (p=0.02, FSH (p=0.0001 and LH (p=0.0001 levels increased significantly. Changes in fat mass (p=0.06 and bone mineral density (p=0.48 were not significant. CONCLUSIONS: After 12 months of androgen deprivation therapy, elderly men with metastatic prostate cancer exhibit a decline in lean body mass and lipid oxidation, together with increased carbohydrate oxidation.

  9. Ketone Body Metabolic Enzyme OXCT1 Regulates Prostate Cancer Chemoresistance

    Science.gov (United States)

    2015-12-01

    Fig. 8). Taken together, the increased oxygen consumption but decreased ATP and NADH production indicated that OXCT1 knock down induced metabolic... method . shC or shOXCT1 cells without Li-Acetoacetate treatment were set as 100, respectively. Progress and Accomplishments We established OXCT1...Nelson PS, Beer TM. Prostate cancer-associated gene expression alterations determined from needle biopsies. Clin Cancer Res 15 (9): 3135-42, 2009. 2

  10. Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia

    OpenAIRE

    2014-01-01

    Background Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating lev...

  11. The oxidative metabolism of fenbendazole: a comparative study.

    Science.gov (United States)

    Short, C R; Flory, W; Hsieh, L C; Barker, S A

    1988-03-01

    The oxidative metabolism of fenbendazole (FBZ) was studied in hepatic fractions prepared from livers of cattle, sheep, goats, chickens, ducks, turkeys, rats, rabbits and catfish. All species produced the sulfoxide metabolite (oxfendazole; FBZ-SO), and p-hydroxyfenbendazole (FBZ-OH) was produced by all species except sheep. The product of demethoxycarbonylation, fenbendazole amine (FBZ-NH2), was not produced by liver preparations of any species. A fourth metabolite, resulting from the further oxidation of oxfendazole, fenbendazole sulfone (FBZ-SO2), was formed in all species but at highly varying rates. The chicken exhibited the highest overall rate of FBZ metabolism, followed by the duck, goat, sheep, steer, catfish, rat, rabbit, and turkey. Considerable variation was evident among avian species, the duck and turkey produced substantially less of the FBZ-OH and FBZ-SO2 metabolites than the chicken. Catfish liver preparations formed equivalent amounts of metabolite at 25 degrees C and 37 degrees C incubation temperatures. The formation of the sulfone metabolite (FBZ-SO2), however, was practically nonexistent in catfish.

  12. Oxidative metabolism of cocaine: comparison of brain and liver.

    Science.gov (United States)

    Benuck, M; Reith, M E; Sershen, H; Wiener, H L; Lajtha, A

    1989-01-01

    Norcocaine (NC) and N-hydroxynorcocaine (NHNC), products of the oxidative metabolism of cocaine, were examined in plasma, brain, and liver of mice injected intraperitoneally with cocaine. Plasma levels of NHNC were altered in vivo by inhibiting esterase activity with diazinon and chloral hydrate or activating esterase activity with phenobarbital, and activating the microsomal P-450 system with phenobarbital. Changes in plasma concentrations of NHNC resulted in similar changes in brain, which were often different from those in liver. After intracisternal administration of cocaine to mice, no appreciable amount of NC or NHNC could be detected in brain; the same results were obtained upon intracisternal and intraventricular administration to rats. Microsomal preparations from mouse brain were found to be considerably less active than those from liver in converting NC to NHNC. We conclude that the cerebral oxidative metabolism of cocaine is not appreciable and that most of the NC and NHNC found in the brain after systemic cocaine administration is derived from plasma rather than formed centrally by brain microsomal enzymes.

  13. Neonatal cardiomyopathies and metabolic crises due to oxidative phosphorylation defects.

    Science.gov (United States)

    Schiff, Manuel; Ogier de Baulny, Hélène; Lombès, Anne

    2011-08-01

    Neonatal cardiomyopathies due to mitochondrial oxidative phosphorylation (OXPHOS) defects are extremely severe conditions which can be either isolated or included in a multi-organ disease, with or without metabolic crises, of which profound lactic acidosis is the prominent feature. Cardiomyopathy is more often hypertrophic than dilated. Antenatal manifestations such as fetal cardiomyopathy, arrhythmia and/or hydrops have been reported. Pathophysiological mechanisms are complex, going beyond ATP deficiency of the high-energy-consuming neonatal myocardium. Birth is a key metabolic period when the myocardium switches ATP production from anaerobic glycolysis to mitochondrial fatty acid oxidation and OXPHOS. Heart-specificity of the defect may be related to the specific localization of the defect, to the high myocardium dependency on OXPHOS, and/or to interaction between the primary genetic alteration and other factors such as modifier genes. Therapeutic options are limited but standardized diagnostic procedures are mandatory to confirm the OXPHOS defect and to identify its causal mutation, allowing genetic counseling and potential prenatal diagnosis.

  14. Electrochemical and enzymatic synthesis of oxidative drug metabolites for metabolism studies: Exploring selectivity and yield

    OpenAIRE

    Gül, Turan

    2017-01-01

    Metabolism studies of drug molecules play a crucial role in drug discovery and development since the early detection of possibly toxic drug metabolites can save time and money. During the metabolic biotransformation process, oxidation of a drug molecule is catalyzed by specific enzymes which can lead to activation or inactivation of the molecule. Phase I metabolism includes primary oxidation reactions including heteroatom dealkylation/oxidation and aromatic hydroxylation reactions which are m...

  15. Oxidative Inactivation of Liver Mitochondria in High Fructose Diet-Induced Metabolic Syndrome in Rats: Effect of Glycyrrhizin Treatment.

    Science.gov (United States)

    Sil, Rajarshi; Chakraborti, Abhay Sankar

    2016-09-01

    Metabolic syndrome is a serious health problem in the present world. Glycyrrhizin, a triterpenoid saponin of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate the primary complications and hepatocellular damage in rats with the syndrome. In this study, we have explored metabolic syndrome-induced changes in liver mitochondrial function and effect of glycyrrhizin against the changes. Metabolic syndrome was induced in rats by high fructose (60%) diet for 6 weeks. The rats were then treated with glycyrrhizin (50 mg/kg body weight) by single intra-peritoneal injection. After 2 weeks of the treatment, the rats were sacrificed to collect liver tissue. Elevated mitochondrial ROS, lipid peroxidation and protein carbonyl, and decreased reduced glutathione content indicated oxidative stress in metabolic syndrome. Loss of mitochondrial inner membrane cardiolipin was observed. Mitochondrial complex I activity did not change but complex IV activity decreased significantly. Mitochondrial MTT reduction ability, membrane potential, phosphate utilisation and oxygen consumption decreased in metabolic syndrome. Reduced mitochondrial aconitase activity and increased aconitase carbonyl content suggested oxidative damage of the enzyme. Elevated Fe(2+) ion level in mitochondria might be associated with increased ROS generation in metabolic syndrome. Glycyrrhizin effectively attenuated mitochondrial oxidative stress and aconitase degradation, and improved electron transport chain activity. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Gestation length, metabolic rate, and body and brain weights in primates: epigenetic effects.

    Science.gov (United States)

    Little, B B

    1989-10-01

    The relationship of brain and body weights can be expressed in log-log regression: log (brain weight) = log (A) + B log (body weight). To investigate further the weights' similarity, gestation length and brain and body weights were determined from the literature for 46 primate genera. The results of allometric and path regression analyses suggest that the relationship between brain and body weights may not be mainly pleiotropic in the order Primates. The correlation between brain and body weights appears to be due to epigenetic factors in hyperplastic growth related to time constraint by gestation length and to energy utilization limitations imposed by metabolic rate.

  17. Body composition in young adults with inborn errors of protein metabolism--a pilot study.

    Science.gov (United States)

    Wilcox, G; Strauss, B J G; Francis, D E M; Upton, H; Boneh, A

    2005-01-01

    The natural history of inborn errors of protein metabolism and the long-term effects of prescribed semisynthetic therapeutic diets are largely unknown. We assessed body composition, measuring body-fat mass and distribution, fat-free mass, total body protein, total body potassium, bone density and skeletal muscle mass, in young adults (age > 18 years; 6 female, 5 male) with inborn errors of protein metabolism maintained on long-term low-protein diets, compared with controls. Female patients were significantly shorter (159.4 cm vs 169.2 cm, p = 0.013) and had higher BMI (25.3 vs 22.0 kg/m2, p metabolic syndrome and cardiovascular disease in this population.

  18. Chronic oxidative-nitrosative stress impairs coronary vasodilation in metabolic syndrome model rats.

    Science.gov (United States)

    Kagota, Satomi; Maruyama, Kana; Tada, Yukari; Fukushima, Kazuhito; Umetani, Keiji; Wakuda, Hirokazu; Shinozuka, Kazumasa

    2013-07-01

    Metabolic syndrome (MetS) is a combination of clinical disorders that together increase the risk for cardiovascular disease and diabetes. SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP.ZF) rats with MetS show impaired nitric oxide-mediated relaxation in coronary and mesenteric arteries, and angiotensin II receptor type 1 blockers protect against dysfunction and oxidative-nitrosative stress independently of metabolic effects. We hypothesize that superoxide contributes to functional deterioration in SHRSP.ZF rats. To test our hypothesis, we studied effects of treatment with tempol, a membrane-permeable radical scavenger, on impaired vasodilation in SHRSP.ZF rats. Tempol did not alter body weight, high blood pressure, or metabolic abnormalities, but prevented impairment of acetylcholine-induced and nitroprusside-induced vasodilation in the coronary and mesenteric arteries. Furthermore, tempol reduced the levels of serum thiobarbituric acid reactive substance (TBARS) and 3-nitrotyrosine content in mesenteric arteries. Systemic administration of tempol elevated the expression of soluble guanylate cyclase (sGC) above basal levels in mesenteric arteries of SHRSP.ZF rats. However, acute treatment with tempol or ebselen, a peroxynitrite scavenger, did not ameliorate impaired relaxation of isolated mesenteric arteries. No nitration of tyrosine residues in sGC was observed; however, sGC mRNA expression levels in the arteries of SHRSP.ZF rats were lower than those in the arteries of Wistar-Kyoto rats. Levels of Thr(496)- and Ser(1177)-phosphorylated endothelial nitric oxide synthase (eNOS) were lower in arteries of SHRSP.ZF rats, and acetylcholine decreased Thr(496)-phosphorylated eNOS levels. These results indicated that prolonged superoxide production, leading to oxidative-nitrosative stress, was associated with impaired vasodilation in SHRSP.ZF rats with MetS. Down-regulated sGC expression may be linked to dysfunction, while reduced NO bioavailability/eNOS activity and modified s

  19. Hormonal enhancement of insecticide efficacy in Tribolium castaneum: oxidative stress and metabolic aspects.

    Science.gov (United States)

    Plavšin, Ivana; Stašková, Tereza; Šerý, Michal; Smýkal, Vlastimil; Hackenberger, Branimir K; Kodrík, Dalibor

    2015-04-01

    Insect anti-stress responses, including those induced by insecticides, are controlled by adipokinetic hormones (AKHs). We examined the physiological consequences of Pyrap-AKH application on Tribolium castaneum adults (AKH-normal and AKH-deficient prepared by the RNAi technique) treated by two insecticides, pirimiphos-methyl and deltamethrin. Co-application of pirimiphos-methyl and/or deltamethrin with AKH significantly increased beetle mortality compared with application of the insecticides alone. This co-treatment was accompanied by substantial stimulation of general metabolism, as monitored by carbon dioxide production. Further, the insecticide treatment alone affected some basic markers of oxidative stress: it lowered total antioxidative capacity as well as the activity of superoxide dismutase in the beetle body; in addition, it enhanced the activity of catalase and glutathione-S-transferase. However, these discrepancies in oxidative stress markers were eliminated/reduced by co-application with Pyrap-AKH. We suggest that the elevation of metabolism, which is probably accompanied with faster turnover of toxins, might be responsible for the higher mortality that results after AKH and insecticide co-application. Changes in oxidative stress markers are probably not included in the mechanisms responsible for increased mortality.

  20. Effects of α-Tocopherol on Oxidative Status and Metabolic Profile in Overweight Women

    Science.gov (United States)

    Ble-Castillo, J. L.; Cleva-Villanueva, G.; Díaz-Zagoya, J. C.; Medina-Santillán, R.; Rubio-Arias, H. O.; Méndez, J. D.

    2007-01-01

    Despite extensive research, the effects of α-tocopherol supplementation remain controversial. Few studies have been focused on obese and overweight people. We examined the effects of α-tocopherol (AT) on the oxidative status and metabolic profile in overweight women. Sixteen overweight women between the ages of 40–60 years old, received AT, 800 IU/day during 12 weeks, followed by a 6-week washout period. Blood samples were taken at the beginning and then every 6 weeks until the end of the study. AT, retinol, malondialdehyde (MDA), total antioxidant status (TAS), selenium-dependent glutathione peroxidase (GPx) and CuZn-superoxide dismutase (SOD) were quantified to evaluate the oxidative stress. The metabolic profile was estimated by measuring glycated hemoglobin (HbA1c) in erythrocytes and glucose, phosphate, magnesium, lipid and lipoprotein concentrations in serum. Under AT administration HbA1c, serum-MDA levels and erythrocyte GPx activity were markedly reduced. TAS, AT and Mg2+ concentrations in serum and SOD activity in erythrocytes were higher after AT treatment. Body weight; glucose, lipid and retinol concentrations, or blood cells count were unchanged. Lipid peroxidation was considerably reduced in AT treated women and also improved serum antioxidant status was observed, but the imbalanced response between erythrocyte SOD and GPx activities could affect normal response to oxidative stress. PMID:18180536

  1. Parameter estimation for whole-body kinetic model of FDG metabolism

    Institute of Scientific and Technical Information of China (English)

    CUI Yunfeng; BAI Jing; CHEN Yingmao; TIAN Jiahe

    2006-01-01

    Based on the radioactive tracer [18F]2-fluoro-2-deoxy-D-glucose (FDG), positron emission tomography (PET), and compartment model, the tracer kinetic study has become an important method to investigate the glucose metabolic kinetics in human body.In this work, the kinetic parameters of three-compartment and four-parameter model for the FDG metabolism in the tissues of myocardium, lung, liver, stomach, spleen, pancreas, and marrow were estimated through some dynamic FDG-PET experiments. Together with published brain and skeletal muscle parameters, a relatively complete whole-body model was presented. In the liver model, the dual blood supply from the hepatic artery and the portal vein to the liver was considered for parameter estimation, and the more accurate results were obtained using the dual-input rather than the single arterial-input. The established whole-body model provides the functional information of FDG metabolism in human body. It can be used to further investigate the glucose metabolism, and also be used for the simulation and visualization of FDG metabolic process in human body.

  2. Increasing metabolic rate despite declining body weight in an adult parasitoid wasp.

    Science.gov (United States)

    Casas, Jérôme; Body, Mélanie; Gutzwiller, Florence; Giron, David; Lazzari, Claudio R; Pincebourde, Sylvain; Richard, Romain; Llandres, Ana L

    2015-08-01

    Metabolic rate is a positive function of body weight, a rule valid for most organisms and the basis of several theories of metabolic ecology. For adult insects, however, the diversity of relationships between body mass and respiration remains unexplained. The aim of this study is to relate the respiratory metabolism of a parasitoid with body weight and foraging activity. We compared the metabolic rate of groups of starving and host-fed females of the parasitoid Eupelmus vuilleti recorded with respirometry for 7days, corresponding to the mean lifetime of starving females and over half of the lifetime of foraging females. The dynamics of carbohydrate, lipid and protein in the body of foraging females were quantified with biochemical techniques. Body mass and all body nutrients declined sharply from the first day onwards. By contrast, the CO2 produced and the O2 consumed increased steadily. Starving females showed the opposite trend, identifying foraging as the reason for the respiration increase of feeding females. Two complementary physiological processes explain the unexpected relationship between increasing metabolic rate and declining body weight. First, host hemolymph is a highly unbalanced food, and the excess nutrients (protein and carbohydrate) need to be voided, partially through excretion and partially through respiration. Second, a foraging young female produces eggs at an increasing rate during the first half of its lifetime, a process that also increases respiration. We posit that the time-varying metabolic rate contributions of the feeding and reproductive processes supplements the contribution of the structural mass and lead to the observed trend. We extend our explanations to other insect groups and discuss the potential for unification using Dynamic Energy Budget theory.

  3. Association of vegan diet with RMR, body composition and oxidative stress

    Directory of Open Access Journals (Sweden)

    Hoda Nadimi

    2013-09-01

    Full Text Available Background. There is increasing evidence to suggest that a vegetarian diet low in fat and high in complex carbohydrates offers the potential for decreasing the risk of chronic disease. However, there is little information about the effect of vegetarian diets on resting metabolic rate (RMR. The objective of this study was to determine the association of vegan diet with RMR and body composition and oxidative stress. Material and methodology. This research is a cross-sectional descriptive analytic study in which two groups of vegetarians and non vegetarians were compared. RMR was determined by indirect calorimetry, the amount of body fat mass (FM, the percentage of free fat mass (FFM, the markers of oxidative stress (MAD, poteins (PCO and total anti-oxidatant capacity were measured in 20 vegetarians and 20 non-vegetarians. The two groups were matched with regard to body mass index, sex and menstrual cycle. Energy and macronutrient intakes were determined using a 3-day food record and body composition was determined by bioelectric impedance. Results. VEG reported a lower relative intake of protein (40.45 ±19.41 g, 56.96 ±11.94 g, p = 0.04, whereas no differences were observed in daily energy, carbohydrate or fat intakes and body composition. NVEG exhibited a higher absolute RMR (1354.7 ±192.6, 1569.10 ±348.24 Kcal/24 h, p = 0.02. PCO plasma density was seen signifi cantly higher among non-vegetarians (1.09 ±3.6, 0.81 ±0.42, p = 0.02. No signifi cant differences were seen in plasma density of TAC between two groups and MAD was higher amoung vegetarians. Conclusion. These results suggest that the lower RMR observed in VEG is partially mediated by differences in dietary macronutrient composition.

  4. Relationships between inflammation, adiponectin, and oxidative stress in metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Shu-Ju Chen

    Full Text Available Metabolic syndrome (MS represents a cluster of physiological and anthropometric abnormalities. The purpose of this study was to investigate the relationships between the levels of inflammation, adiponectin, and oxidative stress in subjects with MS. The inclusion criteria for MS, according to the Taiwan Bureau of Health Promotion, Department of Health, were applied to the case group (n = 72. The control group (n = 105 comprised healthy individuals with normal blood biochemical values. The levels of inflammatory markers [high sensitivity C-reactive protein (hs-CRP and interleukin-6 (IL-6, adiponectin, an oxidative stress marker (malondialdehyde, and antioxidant enzymes activities [catalase (CAT, superoxide dismutase (SOD, and glutathione peroxidase (GPx] were measured. Subjects with MS had significantly higher concentrations of inflammatory markers and lower adiponectin level, and lower antioxidant enzymes activities than the control subjects. The levels of inflammatory markers and adiponectin were significantly correlated with the components of MS. The level of hs-CRP was significantly correlated with the oxidative stress marker. The IL-6 level was significantly correlated with the SOD and GPx activities, and the adiponectin level was significantly correlated with the GPx activity. A higher level of hs-CRP (≥1.00 mg/L, or IL-6 (≥1.50 pg/mL or a lower level of adiponectin (<7.90 µg/mL were associated with a significantly greater risk of MS. In conclusion, subjects suffering from MS may have a higher inflammation status and a higher level of oxidative stress. A higher inflammation status was significantly correlated with decreases in the levels of antioxidant enzymes and adiponectin and an increase in the risk of MS.

  5. Dietary intakes, resting metabolic rates, and body composition in benign and malignant gastrointestinal disease.

    OpenAIRE

    Burke, M.; Bryson, E I; Kark, A E.

    1980-01-01

    Dietary protein and energy intakes were assessed in 42 patients with cancer and 24 with benign conditions of the gastrointestinal tract. The relations of dietary intake to body composition was examined. Resulting metabolic rate was measured in 51 patients. No significant differences in dietary intake or metabolic rate were found between patients with cancer and those with benign disease. There were significant positive correlations between protein and energy intakes and the ratio of total bod...

  6. The effect of psoriasis treatment on body composition, components of metabolic syndrome and psoriatic arthritis

    OpenAIRE

    Funda Tamer; Mehmet Ali Gürer

    2015-01-01

    Background and Design: Psoriasis is a chronic inflammatory immun mediated skin disorder with unknown etiology. The chronic inflammation in psoriasis have role in the development of metabolic and vascular disorders related with associating comorbidities. Recent studies have suggested a strong association exists between metabolic syndrome, obesity and complexity of the association between psoriasis, body mass index (BMI) and psoriasis tratment. In this study, our aim was to investigate the effe...

  7. [Energy metabolism and body mass ratio in bivalves mollusca (Mollusca: Bivalvia)].

    Science.gov (United States)

    Vladimirova, I G; Kleĭmenov, S Iu; Radzinskaia, L I

    2003-01-01

    On the basis of experimental and published data, the interspecific and intraspecific (ontogenetic) dependence of energy metabolism on body weight in bivalves was calculated. Changes in the parameters of intraspecific allometric dependence under the effect of environmental factors were analyzed. The rate of comparable standard metabolism (coefficient a at k = 0.76) was shown to vary in different taxonomic and zoogeographic groups of bivalves.

  8. Correlation between Body Mass Index and Waist Circumference in Patients with Metabolic Syndrome

    OpenAIRE

    Marcin Gierach; Joanna Gierach; Marlena Ewertowska; Adam Arndt; Roman Junik

    2014-01-01

    Metabolic syndrome is defined as a group of coexisting metabolic risk factors, such as central obesity, lipid disorders, carbohydrate disorders, and arterial hypertension. According to the 2005 IDF criteria, subsequently revised in 2009, abdominal obesity is identified as the waist circumference of ≥80 cm in women and ≥94 cm in men. It is responsible for the development of insulin resistance. The aim of our study was to demonstrate a correlation between waist circumference (WC) and body mass ...

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

    Directory of Open Access Journals (Sweden)

    Andrea W.U. Busch

    2015-04-01

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

  10. The Metabolic Syndrome and Mind-Body Therapies: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Joel G. Anderson

    2011-01-01

    Full Text Available The metabolic syndrome, affecting a substantial and increasing percentage of the worldwide population, is comprised of a cluster of symptoms associated with increased risk of type 2 diabetes, cardiovascular disease, and other chronic conditions. Mind-body modalities based on Eastern philosophy, such as yoga, tai chi, qigong, and meditation, have become increasingly popular worldwide. These complementary therapies have many reported benefits for improving symptoms and physiological measures associated with the metabolic syndrome. However, clinical trial data concerning the effectiveness of these practices on the syndrome as a whole have not been evaluated using a systematic and synthesizing approach. A systematic review was conducted to critically evaluate the data from clinical trials examining the efficacy of mind-body therapies as supportive care modalities for management of the metabolic syndrome. Three clinical trials addressing the use of mind-body therapies for management of the metabolic syndrome were identified. Findings from the studies reviewed support the potential clinical effectiveness of mind-body practices in improving indices of the metabolic syndrome.

  11. Composición corporal y metabolismo energético en mujeres con exceso de peso Body composition and energy metabolism in women with excess body weight

    Directory of Open Access Journals (Sweden)

    E. Lopes Rosado

    2010-08-01

    was no difference in metabolic parameters between groups, but lower nutrient oxidation and increased metabolic efficiency in G1 was suggested. Conclusion. Excess weight was associated with body composition and energy expenditure changes that justify the accumulation of body fat.

  12. Determining the optimal cutoff points for waist circumference and body mass index for identification of metabolic abnormalities and metabolic syndrome in urban Thai population.

    Science.gov (United States)

    Worachartcheewan, Apilak; Dansethakul, Prabhop; Nantasenamat, Chanin; Pidetcha, Phannee; Prachayasittikul, Virapong

    2012-11-01

    This study describes the prevalence and optimal waist circumference (WC) and body mass index (BMI) cutoff point for metabolic abnormalities and metabolic syndrome (MS) from urban Thai population. The optimal BMI/WC cutoff has been used for identifying and evaluating metabolic abnormalities for screening individuals having risk factor of MS.

  13. Assessment of oxidative metabolism in Brown Fat using PET imaging

    Directory of Open Access Journals (Sweden)

    Otto eMuzik

    2012-02-01

    Full Text Available Objective: Although it has been believed that brown adipose tissue (BAT depots disappear shortly after the perinatal period in humans, PET imaging using the glucose analog FDG has shown unequivocally the existence of functional BAT in humans. The objective of this study was to determine, using dynamic oxygen-15 (15O PET imaging, to what extent BAT thermogenesis is activated in adults during cold stress and to establish the relationship between BAT oxidative metabolism and FDG tracer uptake.Methods: Fourteen adult normal subjects (9F/5M, 30+7 years underwent triple oxygen scans (H215O, C15O, 15O2 as well as indirect calorimetric measurements at rest and following exposure to mild cold (60F. Subjects were divided into two groups (BAT+ and BAT- based on the presence or absence of FDG tracer uptake (SUV > 2 in supraclavicular BAT. Blood flow (BF and oxygen extraction fraction (OEF was calculated from dynamic PET scans at the location of BAT, muscle and white adipose tissue (WAT. The metabolic rate of oxygen (MRO2 in BAT was determined and used to calculate the contribution of activated BAT to daily energy expenditure (DEE.Results: The median mass of activated BAT in the BAT+ group (5F, 31+8yrs was 52.4 g (14-68g and was 1.7 g (0-6.3g in the BAT- group (5M/4F, 29+6yrs. SUV values were significantly higher in the BAT+ as compared to the BAT- group (7.4+3.7 vs 1.9+0.9; p=0.03. BF values in BAT were significantly higher in the BAT+ as compared to the BAT- group (13.1+4.4 vs 5.7+1.1 ml/100g/min, p=0.03, but were similar in WAT (4.1+1.6 vs 4.2+1.8 ml/100g/min and muscle (3.7+0.8 vs 3.3+1.2 ml/100g/min. Calculated MRO2 values in BAT increased from 0.95+0.74 to 1.62+0.82 ml/100g/min in the BAT+ group and were significantly higher than those determined in the BAT- group (0.43+0.27 vs 0.56+0.24; p=0.67. The DEE associated with BAT oxidative metabolism was highly variable in the BAT+ group, with an average of 5.5+6.4 kcal/day (range 0.57–15.3 kcal/day.

  14. Metabolism and Aging : Effects of Cold Exposure on Metabolic Rate, Body Composition, and Longevity in Mice

    NARCIS (Netherlands)

    Vaanholt, Lobke M.; Daan, Serge; Schubert, Kristin A.; Visser, G. Henk

    2009-01-01

    The proposition that increased energy expenditure shortens life has a long history. The rate-of-living theory ( Pearl 1928) states that life span and average mass-specific metabolic rate are inversely proportional. Originally based on interspecific allometric comparisons between species of mammals,

  15. The relationship between body mass and field metabolic rate among individual birds and mammals.

    Science.gov (United States)

    Hudson, Lawrence N; Isaac, Nick J B; Reuman, Daniel C

    2013-09-01

    1. The power-law dependence of metabolic rate on body mass has major implications at every level of ecological organization. However, the overwhelming majority of studies examining this relationship have used basal or resting metabolic rates, and/or have used data consisting of species-averaged masses and metabolic rates. Field metabolic rates are more ecologically relevant and are probably more directly subject to natural selection than basal rates. Individual rates might be more important than species-average rates in determining the outcome of ecological interactions, and hence selection. 2. We here provide the first comprehensive database of published field metabolic rates and body masses of individual birds and mammals, containing measurements of 1498 animals of 133 species in 28 orders. We used linear mixed-effects models to answer questions about the body mass scaling of metabolic rate and its taxonomic universality/heterogeneity that have become classic areas of controversy. Our statistical approach allows mean scaling exponents and taxonomic heterogeneity in scaling to be analysed in a unified way while simultaneously accounting for nonindependence in the data due to shared evolutionary history of related species. 3. The mean power-law scaling exponents of metabolic rate vs. body mass relationships were 0.71 [95% confidence intervals (CI) 0.625-0.795] for birds and 0.64 (95% CI 0.564-0.716) for mammals. However, these central tendencies obscured meaningful taxonomic heterogeneity in scaling exponents. The primary taxonomic level at which heterogeneity occurred was the order level. Substantial heterogeneity also occurred at the species level, a fact that cannot be revealed by species-averaged data sets used in prior work. Variability in scaling exponents at both order and species levels was comparable to or exceeded the differences 3/4-2/3 = 1/12 and 0.71-0.64. 4. Results are interpreted in the light of a variety of existing theories. In particular, results

  16. Increased platelet oxidative metabolism, blood oxidative stress and neopterin levels after ultra-endurance exercise.

    Science.gov (United States)

    de Lucas, Ricardo Dantas; Caputo, Fabrizio; Mendes de Souza, Kristopher; Sigwalt, André Roberto; Ghisoni, Karina; Lock Silveira, Paulo Cesar; Remor, Aline Pertile; da Luz Scheffer, Débora; Guglielmo, Luiz Guilherme Antonacci; Latini, Alexandra

    2014-01-01

    The purpose of the present investigation was to identify muscle damage, inflammatory response and oxidative stress blood markers in athletes undertaking the ultra-endurance MultiSport Brazil race. Eleven well-trained male athletes (34.3 ± 3.1 years, 74.0 ± 7.6 kg; 172.2 ± 5.1 cm) participated in the study and performed the race, which consisted of about 90 km of alternating off-road running, mountain biking and kayaking. Twelve hours before and up to 15 minutes after the race a 10 mL blood sample was drawn in order to measure the following parameters: lactate dehydrogenase and creatine kinase activities, lipid peroxidation, catalase activity, protein carbonylation, respiratory chain complexes I, II and IV activities, oxygen consumption and neopterin concentrations. After the race, plasma lactate dehydrogenase and creatine kinase activities were significantly increased. Erythrocyte TBA-RS levels and plasma protein carbonylation were markedly augmented in post-race samples. Additionally, mitochondrial complex II activity and oxygen consumption in post-race platelet-rich plasma were also increased. These altered biochemical parameters were accompanied by increased plasma neopterin levels. The ultra-endurance event provoked systemic inflammation (increased neopterin) accompanied by marked oxidative stress, likely by increasing oxidative metabolism (increased oxidative mitochondrial function). This might be advantageous during prolonged exercise, mainly for efficient substrate oxidation at the mitochondrial level, even when tissue damage is induced.

  17. Resting metabolic rate in Italians : relation with body composition and anthropometric parameters

    NARCIS (Netherlands)

    Lorenzo, de A.; Andreoli, A.; Bertoli, S.; Testolin, G.; Oriani, G.; Deurenberg, P.

    2000-01-01

    The objectives of this study were to obtain values for resting metabolic rate in Italians in relation to parameters of body composition, and to compare them to predicted values using the FAO/WHO/UNU equation. We performed a cross-sectional observational study of 131 healthy subjects (46 males and 85

  18. The effect of psoriasis treatment on body composition, components of metabolic syndrome and psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    Funda Tamer

    2015-03-01

    Full Text Available Background and Design: Psoriasis is a chronic inflammatory immun mediated skin disorder with unknown etiology. The chronic inflammation in psoriasis have role in the development of metabolic and vascular disorders related with associating comorbidities. Recent studies have suggested a strong association exists between metabolic syndrome, obesity and complexity of the association between psoriasis, body mass index (BMI and psoriasis tratment. In this study, our aim was to investigate the effect of psoriasis treatment with methotrexate, cyclosporine and biological agents on body composition, comorbidities and associated laboratory findings. Materials and Methods: Seventy-nine patients treated with methotrexate, cyclosporin and biological agents were included in our study. Demographic characteristics, body composition analysis, psoriasis related comorbidities and laboratory examinations were evaluated before and after 12 weeks of systemic treatment. Results: Comorbidities and metabolic syndrome tended to be more frequent in the anti tumor necrosis factor alpha (anti-TNF-α treated group. Increase in body fat and weight detected in patiens receiving biologic drug therapy. Conclusion: The results of our study showed that severe psoriasis patients with longer disease duration were more likely to have metabolic syndrome because of severe and long term inflammation in pathogenesis of comorbidities.

  19. Improved cerebral energetics and ketone body metabolism in db/db mice

    DEFF Research Database (Denmark)

    Andersen, Jens V; Christensen, Sofie K; Nissen, Jakob D;

    2016-01-01

    It is becoming evident that type 2 diabetes mellitus is affecting brain energy metabolism. The importance of alternative substrates for the brain in type 2 diabetes mellitus is poorly understood. The aim of this study was to investigate whether ketone bodies are relevant candidates to compensate ...

  20. Electrochemistry in the Mimicry of Oxidative Drug Metabolism by Cytochrome P450s

    NARCIS (Netherlands)

    Nouri-Nigjeh, Eslam; Bischoff, Rainer; Bruins, Andries P.; Permentier, Hjalmar P.

    2011-01-01

    Prediction of oxidative drug metabolism at the early stages of drug discovery and development requires fast and accurate analytical techniques to mimic the in vivo oxidation reactions by cytochrome P450s (CYP). Direct electrochemical oxidation combined with mass spectrometry, although limited to the

  1. Does iodine biofortification affect oxidative metabolism in lettuce plants?

    Science.gov (United States)

    Blasco, Begoña; Ríos, Juan Jose; Leyva, Rocío; Cervilla, Luis Miguel; Sánchez-Rodríguez, Eva; Rubio-Wilhelmi, María Mar; Rosales, Miguel Angel; Ruiz, Juan Manuel; Romero, Luis

    2011-09-01

    Plants produce low levels of reactive oxygen species (ROS), which form part of basic cell chemical communication; however, different types of stress can lead to an overexpression of ROS that can damage macromolecules essential for plant growth and development. Iodine is vital to human health, and iodine biofortification programs help improve the human intake through plant consumption. This biofortification process has been shown to influence the antioxidant capacity of lettuce plants, suggesting that the oxidative metabolism of the plant may be affected. The results of this study demonstrate that the response to oxidative stress is variable and depends on the form of iodine applied. Application of iodide (I(-)) to lettuce plants produces a reduction in superoxide dismutase (SOD) activity and an increase in catalase (CAT) and L-galactono dehydrogenase enzyme activities and in the activity of antioxidant compounds such as ascorbate (AA) and glutathione. This did not prove a very effective approach since a dose of 80 μM produced a reduction in the biomass of the plants. For its part, application of iodate (IO (3) (-) ) produced an increase in the activities of SOD, ascorbate peroxidase, and CAT, the main enzymes involved in ROS detoxification; it also increased the concentration of AA and the regenerative activities of the Halliwell-Asada cycle. These data confirm the non-phytotoxicity of IO (3) (-) since there is no lipid peroxidation or biomass reduction. According to our results, the ability of IO (3) (-) to induce the antioxidant system indicates that application of this form of iodine may be an effective strategy to improve the response of plants to different types of stress.

  2. Regulation of egg quality and lipids metabolism by Zinc Oxide Nanoparticles.

    Science.gov (United States)

    Zhao, Yong; Li, Lan; Zhang, Peng-Fei; Liu, Xin-Qi; Zhang, Wei-Dong; Ding, Zhao-Peng; Wang, Shi-Wen; Shen, Wei; Min, Ling-Jiang; Hao, Zhi-Hui

    2016-04-01

    This investigation was designed to explore the effects of Zinc Oxide Nanoparticles (ZnO NP) on egg quality and the mechanism of decreasing of yolk lipids. Different concentration of ZnO NP and ZnSO4 were used to treat hens for 24 weeks. The body weight and egg laying frequency were recorded and analyzed. Albumen height, Haugh unit, and yolk color score were analyzed by an Egg Multi Tester. Breaking strength was determined by an Egg Force Reader. Egg shell thickness was measured using an Egg Shell Thickness Gouge. Shell color was detected by a spectrophotometer. Egg shape index was measured by Egg Form Coefficient Measuring Instrument. Albumen and yolk protein was determined by the Kjeldahl method. Amino acids were determined by an amino acids analyzer. Trace elements Zn, Fe, Cu, and P (mg/kg wet mass) were determined in digested solutions using Inductively Coupled Plasma-Optical Emission Spectrometry. TC and TG were measured using commercial analytical kits. Yolk triglyceride, total cholesterol, pancreatic lipase, and phospholipids were determined by appropriate kits. β-carotene was determined by spectrophotometry. Lipid metabolism was also investigated with liver, plasma, and ovary samples. ZnO NP did not change the body weight of hens during the treatment period. ZnO NP slowed down egg laying frequency at the beginning of egg laying period but not at later time. ZnO NP did not affect egg protein or water contents, slightly decreased egg physical parameters (12 to 30%) and trace elements (20 to 35%) after 24 weeks treatment. However, yolk lipids content were significantly decreased by ZnO NP (20 to 35%). The mechanism of Zinc oxide nanoparticles decreasing yolk lipids was that they decreased the synthesis of lipids and increased lipid digestion. These data suggested ZnO NP affected egg quality and specifically regulated lipids metabolism in hens through altering the function of hen's ovary and liver.

  3. Weight loss is associated with improved endothelial dysfunction via NOX2-generated oxidative stress down-regulation in patients with the metabolic syndrome.

    Science.gov (United States)

    Angelico, Francesco; Loffredo, Lorenzo; Pignatelli, Pasquale; Augelletti, Teresa; Carnevale, Roberto; Pacella, Antonio; Albanese, Fabiana; Mancini, Ilaria; Di Santo, Serena; Del Ben, Maria; Violi, Francesco

    2012-06-01

    The aim of this study was to assess whether adherence to a restricted-calorie, Mediterranean-type diet improves endothelial dysfunction and markers of oxidative stress in patients with metabolic syndrome. A moderately low-calorie (600 calories/day negative energy balance), low-fat, high-carbohydrate diet (syndrome. Participants were divided into two groups according to body weight loss > or syndrome. The coexistent decrease of NOX2 activation suggests a role for oxidative stress in eliciting artery dysfunction.

  4. Metabolic effects of melatonin on oxidative stress and diabetes mellitus.

    Science.gov (United States)

    Nishida, Shigeru

    2005-07-01

    Melatonin, which is synthesized in the pineal gland and other tissues, has a variety of physiological, immunological, and biochemical functions. It is a direct scavenger of free radicals and has indirect antioxidant effects due to its stimulation of the expression and activity of antioxidative enzymes such as glutathione peroxidase, superoxide dismutase and catalase, and NO synthase, in mammalian cells. Melatonin also reduces serum lipid levels in mammalian species, and helps to prevent oxidative stress in diabetic subjects. Long-term melatonin administration to diabetic rats reduced their hyperlipidemia and hyperinsulinemia, and restored their altered ratios of polyunsaturated fatty acid in serum and tissues. It was recently reported that melatonin enhanced insulin-receptor kinase and IRS-1 phosphorylation, suggesting the potential existence of signaling pathway cross-talk between melatonin and insulin. Because TNF-alpha has been shown to impair insulin action by suppressing insulin receptor-tyrosine kinase activity and its IRS-1 tyrosine phosphorylation in peripheral tissues such as skeletal muscle cells, it was speculated that melatonin might counteract TNF-alpha-associated insulin resistance in type 2 diabetes. This review will focus on the physiological and metabolic effects of melatonin and highlight its potential use for the treatment of cholesterol/lipid and carbohydrate disorders.

  5. Changes in bone mineral density, body composition, and lipid metabolism during growth hormone (GH) treatment in children with GH deficiency

    NARCIS (Netherlands)

    A.M. Boot (Annemieke); M.A. Engels (Melanie); G.J.M. Boerma (Geert); E.P. Krenning (Eric); S.M.P.F. de Muinck Keizer-Schrama (Sabine)

    1997-01-01

    textabstractAdults with childhood onset GH deficiency (GHD) have reduced bone mass, increased fat mass, and disorders of lipid metabolism. The aim of the present study was to evaluate bone mineral density (BMD), bone metabolism, body composition, and lipid metabolism in

  6. Effect of Feeding Oxidized Soybean Oil against Antioxidant role of Pomegranate Seed on Physiology and Metabolism of Periparturient Saanen Goats

    Directory of Open Access Journals (Sweden)

    Seyyed Ehsan Ghiasi

    2016-08-01

    Full Text Available Introduction Oxidative stress is metabolic and physiologic status caused by imbalance between free radical production and antioxidant defense of body. In some physiological status such as rapid growth, parturition, disease and high production rate that imbalance would occur. High producing dairy animals are suspected to oxidative stress and require to antioxidant supplementation. Negative energy balance in early lactation force the nutrition specialist to apply oil and high NFC diet to exceed the requirement of high producing dairy animals such as Holstein cows and Saanen goats. In recent years, the attention to the use of herbal or organic antioxidant in animal nutrition has increased. This study was carried out to investigate the effects of feeding oxidized soybean oil (OSO plus pomegranate seed (PS as a natural antioxidant, on metabolism and physiology of Preparturient Saanen Goats. Materials and Methods Eighteen Saanen dairy goats with initial body weight of 47 ± 9 kg were assigned to three dietary treatments in a completely randomized design with repeated measurements for 21 days before anticipated parturition. Experimental treatments including: 1 base diet and 4% fresh soybean oil (FSO, 2 base diet and 4% oxidized soybean oil (DM basis respectively, and 3 base diet plus 4% OSO and 8% Pomegranate seed (OSO-PS. After 2 weeks of feeding trial diets, goats were sampled for blood, rumen liquor, faeces and urine for measuring parameters of blood glucose, BHBA, lipid and nitrogen profile, rumen liquor ammonia nitrogen, urine pH and volume, faeces qualitative and quantitative variables and other responses such as nutrients digestibility. The GLM procedure of SAS software v.9.2 were used for statistical analysis. Initial body weight and metabolic variables were used as covariate in the model. Results and discussion All nutrients digestibility, Ruminal ammonia nitrogen and voluntary feed intake were decreased by OSO (p

  7. Metabolic and body composition changes in first year following traumatic amputation

    Directory of Open Access Journals (Sweden)

    Carly S. Eckard, MS, RD

    2015-09-01

    Full Text Available Body composition and metabolism may change considerably after traumatic amputation because of muscle atrophy and an increase in adiposity. The purpose of this study was to quantify changes in weight, body composition, and metabolic rate during the first year following traumatic amputation in military servicemembers. Servicemembers without amputation were included for comparison. Participants were measured within the first 12 wk after amputation (baseline and at 6, 9, and 12 mo after amputation. Muscle mass, fat mass, weight, and metabolic rate were measured at each time point. There was a significant increase in weight and body mass index in the unilateral group between baseline and all follow-up visits (p < 0.01. Over the 12 mo period, total fat mass and trunk fat mass increased in both unilateral and bilateral groups; however, these changes were not statistically significant over time. Muscle mass increased in both the unilateral and bilateral groups despite percent of lean mass decreasing. No changes in resting metabolism or walking energy expenditure were observed in any group. The results of this study conclude that weight significantly increased because of an increase in both fat mass and muscle mass in the first year following unilateral and bilateral amputation.

  8. Hepatic growth hormone and glucocorticoid receptor signaling in body growth, steatosis and metabolic liver cancer development.

    Science.gov (United States)

    Mueller, Kristina M; Themanns, Madeleine; Friedbichler, Katrin; Kornfeld, Jan-Wilhelm; Esterbauer, Harald; Tuckermann, Jan P; Moriggl, Richard

    2012-09-25

    Growth hormone (GH) and glucocorticoids (GCs) are involved in the control of processes that are essential for the maintenance of vital body functions including energy supply and growth control. GH and GCs have been well characterized to regulate systemic energy homeostasis, particular during certain conditions of physical stress. However, dysfunctional signaling in both pathways is linked to various metabolic disorders associated with aberrant carbohydrate and lipid metabolism. In liver, GH-dependent activation of the transcription factor signal transducer and activator of transcription (STAT) 5 controls a variety of physiologic functions within hepatocytes. Similarly, GCs, through activation of the glucocorticoid receptor (GR), influence many important liver functions such as gluconeogenesis. Studies in hepatic Stat5 or GR knockout mice have revealed that they similarly control liver function on their target gene level and indeed, the GR functions often as a cofactor of STAT5 for GH-induced genes. Gene sets, which require physical STAT5-GR interaction, include those controlling body growth and maturation. More recently, it has become evident that impairment of GH-STAT5 signaling in different experimental models correlates with metabolic liver disease, ranging from hepatic steatosis to hepatocellular carcinoma (HCC). While GH-activated STAT5 has a protective role in chronic liver disease, experimental disruption of GC-GR signaling rather seems to ameliorate metabolic disorders under metabolic challenge. In this review, we focus on the current knowledge about hepatic GH-STAT5 and GC-GR signaling in body growth, metabolism, and protection from fatty liver disease and HCC development.

  9. Associations between body mass index and development of metabolic disorders in fertile women

    DEFF Research Database (Denmark)

    Schmiegelow, Michelle Dalgas; Andersson, Charlotte; Køber, Lars

    2014-01-01

    BACKGROUND: Metabolic disorders are relatively uncommon in young women, but may increase with obesity. The associations between body mass index (BMI) and risks of diabetes, hypertension, and dyslipidemia in apparently healthy, young women have been insufficiently investigated, and are the aims...... of this study. METHODS AND RESULTS: Women giving birth during the years 2004-2009, with no history of cardiovascular disease, renal insufficiency, pregnancy-associated metabolic disorders, diabetes, hypertension, or dyslipidemia were identified in nationwide registers. Women were categorized as underweight (BMI...

  10. Metabolic responses of upper-body accelerometer-controlled video games in adults.

    Science.gov (United States)

    Stroud, Leah C; Amonette, William E; Dupler, Terry L

    2010-10-01

    Historically, video games required little physical exertion, but new systems utilize handheld accelerometers that require upper-body movement. It is not fully understood if the metabolic workload while playing these games is sufficient to replace routine physical activity. The purpose of this study was to quantify metabolic workloads and estimate caloric expenditure while playing upper-body accelerometer-controlled and classic seated video games. Nineteen adults completed a peak oxygen consumption treadmill test followed by an experimental session where exercising metabolism and ventilation were measured while playing 3 video games: control (CON), low activity (LOW) and high activity (HI). Resting metabolic measures (REST) were also acquired. Caloric expenditure was estimated using the Weir equation. Mean oxygen consumption normalized to body weight for HI condition was greater than LOW, CON, and REST. Mean oxygen consumption normalized to body weight for LOW condition was also greater than CON and REST. Mean exercise intensities of oxygen consumption reserve for HI, LOW, and CON were 25.8% ± 5.1%, 6.4% ± 4.8%, and 0.8% ± 2.4%, respectively. Estimated caloric expenditure during the HI was significantly related to aerobic fitness, but not during other conditions. An active video game significantly elevated oxygen consumption and heart rate, but the increase was dependent on the type of game. The mean oxygen consumption reserve during the HI video game was below recommended international standards for moderate and vigorous activity. Although upper-body accelerometer-controlled video games provided a greater exercising stimulus than classic seated video games, these data suggest they should not replace routine moderate or vigorous exercise.

  11. Expanded metabolic versatility of ubiquitous nitrite-oxidizing bacteria from the genus Nitrospira

    OpenAIRE

    Koch, Hanna; Lücker, Sebastian; Albertsen, Mads; Kitzinger, Katharina; Herbold, Craig; Spieck, Eva; Nielsen, Per Halkjaer; Wagner, Michael; Daims, Holger

    2015-01-01

    Nitrification, the sequential aerobic oxidation of ammonia via nitrite to nitrate, is a key process of the biogeochemical nitrogen cycle and catalyzed by two aerobic microbial guilds (nitrifiers): ammonia oxidizers and nitrite-oxidizing bacteria (NOB). NOB are generally considered as metabolically restricted and dependent on ammonia oxidizers. Here, we report that, surprisingly, key NOB of many ecosystems (Nitrospira) convert urea, an important ammonia source in nature, to ammonia and CO2. Th...

  12. Nordic walking training attenuation of oxidative stress in association with a drop in body iron stores in elderly women.

    Science.gov (United States)

    Kortas, Jakub; Kuchta, Agnieszka; Prusik, Krzysztof; Prusik, Katarzyna; Ziemann, Ewa; Labudda, Sandra; Ćwiklińska, Agnieszka; Wieczorek, Ewa; Jankowski, Maciej; Antosiewicz, Jedrzej

    2017-02-22

    Excess body iron accumulation and oxidative stress has been associated with ageing. Regular exercise has been shown to reduce oxidative stress and induce some changes in iron metabolism. However, the effects of exercise on both of these parameters have been poorly investigated. In our study, 35 elderly women participated in 12 weeks of Nordic walking (NW) training (three times a week). We demonstrated that the training caused a significant reduction in malondialdehyde advanced oxidation protein products-markers of oxidative stress but had no effects on paraoxonase 1 activity. These changes were associated with the decrease of blood ferritin (99.4 ± 62.7 vs. 81.4 ± 61.7 ng/ml p < 0.05). Measurement of physical fitness revealed that the training caused a significant improvement in performance and a negative correlation between the blood ferritin and endurance test was recorded (r = -0.34, p = 0.03). In addition, a significant correlation between blood ferritin and fasting glucose level was noted. The training induced a rise of HDL cholesterol from 70.8 ± 19.3-75.3 ± 21.1, p < 0.05, whereas other lipid parameters remained unchanged. In conclusion, NW training reduced body iron stores and it was associated with lower oxidative stress and better endurance.

  13. Electrochemistry in the mimicry of oxidative drug metabolism by cytochrome P450s.

    Science.gov (United States)

    Nouri-Nigjeh, Eslam; Bischoff, Rainer; Bruins, Andries P; Permentier, Hjalmar P

    2011-05-01

    Prediction of oxidative drug metabolism at the early stages of drug discovery and development requires fast and accurate analytical techniques to mimic the in vivo oxidation reactions by cytochrome P450s (CYP). Direct electrochemical oxidation combined with mass spectrometry, although limited to the oxidation reactions initiated by charge transfer, has shown promise in the mimicry of certain CYP-mediated metabolic reactions. The electrochemical approach may further be utilized in an automated manner in microfluidics devices facilitating fast screening of oxidative drug metabolism. A wide range of in vivo oxidation reactions, particularly those initiated by hydrogen atom transfer, can be imitated through the electrochemically-assisted Fenton reaction. This reaction is based on O-O bond activation in hydrogen peroxide and oxidation by hydroxyl radicals, wherein electrochemistry is used for the reduction of molecular oxygen to hydrogen peroxide, as well as the reduction of Fe(3+) to Fe(2+). Metalloporphyrins, as surrogates for the prosthetic group in CYP, utilizing metallo-oxo reactive species, can also be used in combination with electrochemistry. Electrochemical reduction of metalloporphyrins in solution or immobilized on the electrode surface activates molecular oxygen in a manner analogous to the catalytical cycle of CYP and different metalloporphyrins can mimic selective oxidation reactions. Chemoselective, stereoselective, and regioselective oxidation reactions may be mimicked using electrodes that have been modified with immobilized enzymes, especially CYP itself. This review summarizes the recent attempts in utilizing electrochemistry as a versatile analytical and preparative technique in the mimicry of oxidative drug metabolism by CYP.

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

    OpenAIRE

    光冨, 公彦

    2015-01-01

    Objective. 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-in...

  15. Variants in Genes Controlling Oxidative Metabolism Contribute to Lower Hepatic ATP Independent of Liver Fat Content in Type 1 Diabetes.

    Science.gov (United States)

    Gancheva, Sofiya; Bierwagen, Alessandra; Kaul, Kirti; Herder, Christian; Nowotny, Peter; Kahl, Sabine; Giani, Guido; Klueppelholz, Birgit; Knebel, Birgit; Begovatz, Paul; Strassburger, Klaus; Al-Hasani, Hadi; Lundbom, Jesper; Szendroedi, Julia; Roden, Michael

    2016-07-01

    Type 1 diabetes has been recently linked to nonalcoholic fatty liver disease (NAFLD), which is known to associate with insulin resistance, obesity, and type 2 diabetes. However, the role of insulin resistance and hyperglycemia for hepatic energy metabolism is yet unclear. To analyze early abnormalities in hepatic energy metabolism, we examined 55 patients with recently diagnosed type 1 diabetes. They underwent hyperinsulinemic-normoglycemic clamps with [6,6-(2)H2]glucose to assess whole-body and hepatic insulin sensitivity. Hepatic γATP, inorganic phosphate (Pi), and triglyceride concentrations (hepatocellular lipid content [HCL]) were measured with multinuclei magnetic resonance spectroscopy ((31)P/(1)H-MRS). Glucose-tolerant humans served as control (CON) (n = 57). Whole-body insulin sensitivity was 44% lower in patients than in age- and BMI-matched CON. Hepatic γATP was 15% reduced (2.3 ± 0.6 vs. 2.7 ± 0.6 mmol/L, P < 0.001), whereas hepatic Pi and HCL were similar in patients when compared with CON. Across all participants, hepatic γATP correlated negatively with glycemia and oxidized LDL. Carriers of the PPARG G allele (rs1801282) and noncarriers of PPARGC1A A allele (rs8192678) had 21 and 13% lower hepatic ATP concentrations. Variations in genes controlling oxidative metabolism contribute to a reduction in hepatic ATP in the absence of NAFLD, suggesting that alterations in hepatic mitochondrial function may precede diabetes-related liver diseases.

  16. Evidence for hydrogen oxidation and metabolic plasticity in widespread deep-sea sulfur-oxidizing bacteria.

    Science.gov (United States)

    Anantharaman, Karthik; Breier, John A; Sheik, Cody S; Dick, Gregory J

    2013-01-02

    Hydrothermal vents are a well-known source of energy that powers chemosynthesis in the deep sea. Recent work suggests that microbial chemosynthesis is also surprisingly pervasive throughout the dark oceans, serving as a significant CO(2) sink even at sites far removed from vents. Ammonia and sulfur have been identified as potential electron donors for this chemosynthesis, but they do not fully account for measured rates of dark primary production in the pelagic water column. Here we use metagenomic and metatranscriptomic analyses to show that deep-sea populations of the SUP05 group of uncultured sulfur-oxidizing Gammaproteobacteria, which are abundant in widespread and diverse marine environments, contain and highly express genes encoding group 1 Ni, Fe hydrogenase enzymes for H(2) oxidation. Reconstruction of near-complete genomes of two cooccurring SUP05 populations in hydrothermal plumes and deep waters of the Gulf of California enabled detailed population-specific metatranscriptomic analyses, revealing dynamic patterns of gene content and transcript abundance. SUP05 transcripts for genes involved in H(2) and sulfur oxidation are most abundant in hydrothermal plumes where these electron donors are enriched. In contrast, a second hydrogenase has more abundant transcripts in background deep-sea samples. Coupled with results from a bioenergetic model that suggest that H(2) oxidation can contribute significantly to the SUP05 energy budget, these findings reveal the potential importance of H(2) as a key energy source in the deep ocean. This study also highlights the genomic plasticity of SUP05, which enables this widely distributed group to optimize its energy metabolism (electron donor and acceptor) to local geochemical conditions.

  17. Newborn body fat: associations with maternal metabolic state and placental size.

    Directory of Open Access Journals (Sweden)

    Camilla M Friis

    Full Text Available BACKGROUND: Neonatal body composition has implications for the health of the newborn both in short and long term perspective. The objective of the current study was first to explore the association between maternal BMI and metabolic parameters associated with BMI and neonatal percentage body fat and to determine to which extent any associations were modified if adjusting for placental weight. Secondly, we examined the relations between maternal metabolic parameters associated with BMI and placental weight. METHODS: The present work was performed in a subcohort (n = 207 of the STORK study, an observational, prospective study on the determinants of fetal growth and birthweight in healthy pregnancies at Oslo University Hospital, Norway. Fasting glucose, insulin, triglycerides, free fatty acids, HDL- and total cholesterol were measured at week 30-32. Newborn body composition was determined by Dual-Energy X-Ray Absorptiometry (DXA. Placenta was weighed at birth. Linear regression models were used with newborn fat percentage and placental weight as main outcomes. RESULTS: Maternal BMI, fasting glucose and gestational age were independently associated with neonatal fat percentage. However, if placental weight was introduced as a covariate, only placental weight and gestational age remained significant. In the univariate model, the determinants of placenta weight included BMI, insulin, triglycerides, total- and HDL-cholesterol (negatively, gestational weight gain and parity. In the multivariable model, BMI, total cholesterol HDL-cholesterol, gestational weight gain and parity remained independent covariates. CONCLUSION: Maternal BMI and fasting glucose were independently associated with newborn percentage fat. This effect disappeared by introducing placental weight as a covariate. Several metabolic factors associated with maternal BMI were associated with placental weight, but not with neonatal body fat. Our findings are consistent with a concept

  18. Effects of TiO2 nanoparticles on nutrition metabolism in silkworm fat body

    Directory of Open Access Journals (Sweden)

    J. H. Tian

    2016-06-01

    Full Text Available Silkworm (Bombyx mori is an important economic insect with a fat body that plays a crucial role in the storage and transfer of nutrients. It is also known that TiO2 nanoparticles (NPs can improve feed efficiency and promote silk protein synthesis in the silkworm. In this study, we profiled gene expression in the silkworm fat body after TiO2 NP treatment, validated the major RNA-seq findings, and determined the contents of trehalose and triglyceride, the activity of lipase, and the amount of total proteins. RNA-seq analysis revealed that TiO2 NP treatment caused significant expression changes in 341 genes (P≤0.01, 138 of which were upregulated while the other 203 were downregulated. The expression levels of two target genes in the insulin signaling pathway and two protein metabolism-related target genes, three lipid metabolism-associated target genes, two carbohydrate metabolism related target genes and expression levels of seven heat shock protein genes were increased, and that of threonine dehydratase gene and fatty acid transport protein gene were decreased. The RNA-seq results of 16 genes were validated by quantitative real-time PCR. The lipase activity, content of trehalose, and amount of total proteins were elevated by 3.86-fold, 1.34-fold, and 1.21-fold, respectively, and the content of triglyceride was decreased by 0.94-fold after TiO2 NP treatment. These results indicated that TiO2 NPs activated the insulin signaling pathway, promoted the metabolism of protein, fat, and carbohydrate, and improved nutrition metabolism. Our study provides new support for the understanding of the beneficial effect of TiO2 NPs on silkworm nutrient metabolism.

  19. Improved cerebral energetics and ketone body metabolism in db/db mice.

    Science.gov (United States)

    Andersen, Jens V; Christensen, Sofie K; Nissen, Jakob D; Waagepetersen, Helle S

    2017-03-01

    It is becoming evident that type 2 diabetes mellitus is affecting brain energy metabolism. The importance of alternative substrates for the brain in type 2 diabetes mellitus is poorly understood. The aim of this study was to investigate whether ketone bodies are relevant candidates to compensate for cerebral glucose hypometabolism and unravel the functionality of cerebral mitochondria in type 2 diabetes mellitus. Acutely isolated cerebral cortical and hippocampal slices of db/db mice were incubated in media containing [U-(13)C]glucose, [1,2-(13)C]acetate or [U-(13)C]β-hydroxybutyrate and tissue extracts were analysed by mass spectrometry. Oxygen consumption and ATP synthesis of brain mitochondria of db/db mice were assessed by Seahorse XFe96 and luciferin-luciferase assay, respectively. Glucose hypometabolism was observed for both cerebral cortical and hippocampal slices of db/db mice. Significant increased metabolism of [1,2-(13)C]acetate and [U-(13)C]β-hydroxybutyrate was observed for hippocampal slices of db/db mice. Furthermore, brain mitochondria of db/db mice exhibited elevated oxygen consumption and ATP synthesis rate. This study provides evidence of several changes in brain energy metabolism in type 2 diabetes mellitus. The increased hippocampal ketone body utilization and improved mitochondrial function in db/db mice, may act as adaptive mechanisms in order to maintain cerebral energetics during hampered glucose metabolism.

  20. Correlation between Body Mass Index and Waist Circumference in Patients with Metabolic Syndrome.

    Science.gov (United States)

    Gierach, Marcin; Gierach, Joanna; Ewertowska, Marlena; Arndt, Adam; Junik, Roman

    2014-01-01

    Metabolic syndrome is defined as a group of coexisting metabolic risk factors, such as central obesity, lipid disorders, carbohydrate disorders, and arterial hypertension. According to the 2005 IDF criteria, subsequently revised in 2009, abdominal obesity is identified as the waist circumference of ≥80 cm in women and ≥94 cm in men. It is responsible for the development of insulin resistance. The aim of our study was to demonstrate a correlation between waist circumference (WC) and body mass index (BMI) in patients with metabolic syndrome in relation with hypertension, lipid disorders, and carbohydrate disorders. A cross-sectional two-site study was conducted in the Kuyavian-Pomeranian Voivodeship for 24 months. The study group consisted of 839 patients with diagnosed metabolic syndrome: 345 men (41.1%) and 494 women (58.9%) aged 32-80. In the study group, WC was found to be significantly correlated with BMI (R = 0.78, P < 0.01). The presence of overweight in men (BMI 25, 84 kg/m(2)) and even normal body weight in women (BMI 21,62 kg/m(2)) corresponds to an increased volume of visceral tissue in the abdomen. Introduction of primary prophylaxis in those people to limit the development of diabetes mellitus type 2 and cardiovascular diseases should be considered.

  1. In vitro mimicry of metabolic oxidation reactions by electrochemistry/mass spectrometry

    NARCIS (Netherlands)

    Jurva, U; Wikstrom, HV; Bruins, AP

    2000-01-01

    The aim of these studies was to investigate the scope and limitations of electrochemistry on-line with mass spectrometry as a quick and convenient way to mimic phase I:oxidative reactions in drug metabolism. A compound with previously reported in vitro and in vivo metabolism, the dopamine agonist 2-

  2. Electrochemical and enzymatic synthesis of oxidative drug metabolites for metabolism studies : Exploring selectivity and yield

    NARCIS (Netherlands)

    Gül, Turan

    2017-01-01

    Metabolism studies of drug molecules play a crucial role in drug discovery and development since the early detection of possibly toxic drug metabolites can save time and money. During the metabolic biotransformation process, oxidation of a drug molecule is catalyzed by specific enzymes which can lea

  3. Metabolism. Part III: Lipids.

    Science.gov (United States)

    Bodner, George M.

    1986-01-01

    Describes the metabolic processes of complex lipids, including saponification, activation and transport, and the beta-oxidation spiral. Discusses fatty acid degradation in regard to biochemical energy and ketone bodies. (TW)

  4. Detrimental and protective fat: body fat distribution and its relation to metabolic disease.

    Science.gov (United States)

    Booth, Andrea; Magnuson, Aaron; Foster, Michelle

    2014-01-01

    Obesity is linked to numerous comorbidities that include, but are not limited to, glucose intolerance, insulin resistance, dyslipidemia, and cardiovascular disease. Current evidence suggests, however, obesity itself is not an exclusive predictor of metabolic dysregulation but rather adipose tissue distribution. Obesity-related adverse health consequences occur predominately in individuals with upper body fat accumulation, the detrimental distribution, commonly associated with visceral obesity. Increased lower body subcutaneous adipose tissue, however, is associated with a reduced risk of obesity-induced metabolic dysregulation and even enhanced insulin sensitivity, thus, storage in this region is considered protective. The proposed mechanisms that causally relate the differential outcomes of adipose tissue distribution are often attributed to location and/or adipocyte regulation. Visceral adipose tissue effluent to the portal vein drains into the liver where hepatocytes are directly exposed to its metabolites and secretory products, whereas the subcutaneous adipose tissue drains systemically. Adipose depots are also inherently different in numerous ways such as adipokine release, immunity response and regulation, lipid turnover, rate of cell growth and death, and response to stress and sex hormones. Proximal extrinsic factors also play a role in the differential drive between adipose tissue depots. This review focuses on the deleterious mechanisms postulated to drive the differential metabolic response between central and lower body adipose tissue distribution.

  5. Oxidative modifications of glyceraldehyde 3-phosphate dehydrogenase regulate metabolic reprogramming of stored red blood cells.

    Science.gov (United States)

    Reisz, Julie A; Wither, Matthew J; Dzieciatkowska, Monika; Nemkov, Travis; Issaian, Aaron; Yoshida, Tatsuro; Dunham, Andrew J; Hill, Ryan C; Hansen, Kirk C; D'Alessandro, Angelo

    2016-09-22

    Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) plays a key regulatory function in glucose oxidation by mediating fluxes through glycolysis or the pentose phosphate pathway (PPP) in an oxidative stress-dependent fashion. Previous studies documented metabolic reprogramming in stored red blood cells (RBCs) and oxidation of GAPDH at functional residues upon exposure to pro-oxidants diamide and H2O2 Here we hypothesize that routine storage of erythrocyte concentrates promotes metabolic modulation of stored RBCs by targeting functional thiol residues of GAPDH. Progressive increases in PPP/glycolysis ratios were determined via metabolic flux analysis after spiking (13)C1,2,3-glucose in erythrocyte concentrates stored in Additive Solution-3 under blood bank conditions for up to 42 days. Proteomics analyses revealed a storage-dependent oxidation of GAPDH at functional Cys152, 156, 247, and His179. Activity loss by oxidation occurred with increasing storage duration and was progressively irreversible. Irreversibly oxidized GAPDH accumulated in stored erythrocyte membranes and supernatants through storage day 42. By combining state-of-the-art ultra-high-pressure liquid chromatography-mass spectrometry metabolic flux analysis with redox and switch-tag proteomics, we identify for the first time ex vivo functionally relevant reversible and irreversible (sulfinic acid; Cys to dehydroalanine) oxidations of GAPDH without exogenous supplementation of excess pro-oxidant compounds in clinically relevant blood products. Oxidative and metabolic lesions, exacerbated by storage under hyperoxic conditions, were ameliorated by hypoxic storage. Storage-dependent reversible oxidation of GAPDH represents a mechanistic adaptation in stored erythrocytes to promote PPP activation and generate reducing equivalents. Removal of irreversibly oxidized, functionally compromised GAPDH identifies enhanced vesiculation as a self-protective mechanism in ex vivo aging erythrocytes.

  6. Discoidin domain receptor 2 (DDR2) regulates body size and fat metabolism in mice.

    Science.gov (United States)

    Kawai, Ikuma; Matsumura, Hirokazu; Fujii, Wataru; Naito, Kunihiko; Kusakabe, Ken; Kiso, Yasuo; Kano, Kiyoshi

    2014-02-01

    Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase that is activated by fibrillar collagens, which act as its endogenous ligand. DDR2 regulates cell proliferation, cell adhesion, migration, extracellular matrix remodeling and reproductive functions. Both DDR2 null allele mice and mice with a recessive, loss-of-function allele for Ddr2 exhibit dwarfing and a reduction in body weight. However, the detailed mechanisms by which DDR2 exerts its positive systemic regulation of whole body size, local skeletal size and fat tissue volume remain to be clarified. To investigate the systemic role of DDR2 in body size regulation, we produced transgenic mice in which the DDR2 protein is overexpressed, then screened the transgenic mice for abnormalities using systematic mouse abnormality screening. The modified-SHIPRA screen revealed that only the parameter of body size was significantly different among the genotypes. We also discovered that the body length was significantly increased, while the body weight was significantly decreased in transgenic mice compared to their littermate controls. We also found that the epididymal fat pads were significantly decreased in transgenic mice compared to normal littermate mice, which may have been the cause of the leptin decrement in the transgenic mice. The new insight that DDR2 might promote metabolism in adipocyte cells is very interesting, but more experiments will be needed to elucidate the direct relation between DDR2 and adipose-derived hormones. Taken together, our data demonstrated that DDR2 might play a systemic role in the regulation of body size thorough skeletal formation and fat metabolism.

  7. Cardiovascular disease-related parameters and oxidative stress in SHROB rats, a model for metabolic syndrome.

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    Eunice Molinar-Toribio

    Full Text Available SHROB rats have been suggested as a model for metabolic syndrome (MetS as a situation prior to the onset of CVD or type-2 diabetes, but information on descriptive biochemical parameters for this model is limited. Here, we extensively evaluate parameters related to CVD and oxidative stress (OS in SHROB rats. SHROB rats were monitored for 15 weeks and compared to a control group of Wistar rats. Body weight was recorded weekly. At the end of the study, parameters related to CVD and OS were evaluated in plasma, urine and different organs. SHROB rats presented statistically significant differences from Wistar rats in CVD risk factors: total cholesterol, LDL-cholesterol, triglycerides, apoA1, apoB100, abdominal fat, insulin, blood pressure, C-reactive protein, ICAM-1 and PAI-1. In adipose tissue, liver and brain, the endogenous antioxidant systems were activated, yet there was no significant oxidative damage to lipids (MDA or proteins (carbonylation. We conclude that SHROB rats present significant alterations in parameters related to inflammation, endothelial dysfunction, thrombotic activity, insulin resistance and OS measured in plasma as well as enhanced redox defence systems in vital organs that will be useful as markers of MetS and CVD for nutrition interventions.

  8. Turtles (Chelodina longicollis) regulate muscle metabolic enzyme activity in response to seasonal variation in body temperature.

    Science.gov (United States)

    Seebacher, F; Sparrow, J; Thompson, M B

    2004-04-01

    Fluctuations in the thermal environment may elicit different responses in animals: migration to climatically different areas, regulation of body temperature, modification of biochemical reaction rates, or assuming a state of dormancy. Many ectothermic reptiles are active over a range of body temperatures that vary seasonally. Here we test the hypothesis that metabolic enzyme activity acclimatises seasonally in freshwater turtles (Chelodina longicollis) in addition to, or instead of, behavioural regulation of body temperatures. We measured body temperatures in free-ranging turtles (n = 3) by radiotelemetry, and we assayed phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS) and cytochrome c oxidase (CCO) activities in early autumn (March, n = 10 turtles), late autumn (May, n = 7) and mid-winter (July, n = 7) over a range of assay temperatures (10 degrees C, 15 degrees C, 20 degrees C, 25 degrees C). Body temperatures were either not different from, or higher than expected from a theoretical null-distribution of a randomly moving animal. Field body temperatures at any season were lower, however, than expected from animals that maximised their sun exposure. Turtles maintained constant PFK, LDH and CCO activities in different months, despite body temperature differences of nearly 13.0 degrees C between March (average daily body temperature = 24.4 degrees C) and July (average = 11.4 degrees C). CS activity did not vary between March and May (average daily body temperature = 20.2 degrees C), but it decreased in July. Thus C. longicollis use a combination of behavioural thermoregulation and biochemical acclimatisation in response to seasonally changing thermal conditions. Ectothermic reptiles were often thought not to acclimatise biochemically, and our results show that behavioural attainment of a preferred body temperature is not mandatory for activity or physiological performance in turtles.

  9. Supercritical water oxidation of products of human metabolism

    Science.gov (United States)

    Tester, Jefferson W.; Orge A. achelling, Richard K. ADTHOMASSON; Orge A. achelling, Richard K. ADTHOMASSON

    1986-01-01

    Although the efficient destruction of organic material was demonstrated in the supercritical water oxidation process, the reaction kinetics and mechanisms are unknown. The kinetics and mechanisms of carbon monoxide and ammonia oxidation in and reaction with supercritical water were studied experimentally. Experimental oxidation of urine and feces in a microprocessor controlled system was performed. A minaturized supercritical water oxidation process for space applications was design, including preliminary mass and energy balances, power, space and weight requirements.

  10. Whole-body fat oxidation determined by graded exercise and indirect calorimetry: a role for muscle oxidative capacity?

    DEFF Research Database (Denmark)

    Nordby, P; Saltin, B; Helge, J W

    2006-01-01

    subjects were recruited and categorized into an untrained (N=8, VO(2max) 3.5+/-0.1 L/min) and a trained (N=8, VO(2max) 4.6+/-0.2 L/min) group. Subjects performed a graded exercise test commencing at 60 W for 8 min followed by 35 W increments every 3 min. On a separate day, muscle biopsies were obtained...... from vastus lateralis and a 3 h bicycle exercise test was performed at 58% of VO(2max). Whole-body fat oxidation was calculated during prolonged and graded exercise from the respiratory exchange ratio using standard indirect calorimetry equations. Based on the graded exercise test, whole-body peak fat...... oxidation was determined. The body composition was determined by DEXA. Whole-body peak fat oxidation (250+/-25 and 462+/-33 mg/min) was higher (PVO(2max)) in trained compared with untrained subjects, respectively. Muscle...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-10-01

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

  12. Prevalence of Oxidative Stress and Metabolic Syndrome in Adults with Paraplegia and Tetraplegia

    Science.gov (United States)

    Objectives: To investigate the extent of oxidative stress and metabolic syndrome (MetS) in people with spinal cord injuries (SCI) and to identify the major factors associated with oxidative stress and MetS in this population. Methods: 24 subjects with paraplegia (PARA), 26 subjects with tetraplegia ...

  13. Elevated mitochondrial oxidative stress impairs metabolic adaptations to exercise in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Justin D Crane

    Full Text Available Mitochondrial oxidative stress is a complex phenomenon that is inherently tied to energy provision and is implicated in many metabolic disorders. Exercise training increases mitochondrial oxidative capacity in skeletal muscle yet it remains unclear if oxidative stress plays a role in regulating these adaptations. We demonstrate that the chronic elevation in mitochondrial oxidative stress present in Sod2 (+/- mice impairs the functional and biochemical mitochondrial adaptations to exercise. Following exercise training Sod2 (+/- mice fail to increase maximal work capacity, mitochondrial enzyme activity and mtDNA copy number, despite a normal augmentation of mitochondrial proteins. Additionally, exercised Sod2 (+/- mice cannot compensate for their higher amount of basal mitochondrial oxidative damage and exhibit poor electron transport chain complex assembly that accounts for their compromised adaptation. Overall, these results demonstrate that chronic skeletal muscle mitochondrial oxidative stress does not impact exercise induced mitochondrial biogenesis, but impairs the resulting mitochondrial protein function and can limit metabolic plasticity.

  14. RELATION OF BODY WEIGHT AND FOOD CONSUMPTION TO METABOLIC RATE OF JUVENILE JAPANESE SEA BASS,LATEOLABRAX JAPONICUS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The metabolic rate of Japanese sea bass, Lateolabrax japonicus (C & V), was estimated in laboratory at temperature 25.2±0.5℃. The fresh weight of the fish was 4.64-52.28 g (average of 17.81±0.33 g). The routine metabolism was related to body weight by the exponential equation: Rr=14.966W0.74 (r=0.934). The rate of feeding metabolism increased linearly with food consumption. Feeding metabolic rate was 1.8-2.4 times the routine metabolic rate.

  15. A Methionine Deficient Diet Enhances Adipose Tissue Lipid Metabolism and Alters Anti-Oxidant Pathways in Young Growing Pigs.

    Directory of Open Access Journals (Sweden)

    Rosa Castellano

    Full Text Available Methionine is a rate-limiting amino-acid for protein synthesis but non-proteinogenic roles on lipid metabolism and oxidative stress have been demonstrated. Contrary to rodents where a dietary methionine deficiency led to a lower adiposity, an increased lipid accretion rate has been reported in growing pigs fed a methionine deficient diet. This study aimed to clarify the effects of a dietary methionine deficiency on different aspects of tissue lipid metabolism and anti-oxidant pathways in young pigs. Post-weaned pigs (9.8 kg initial body weight were restrictively-fed diets providing either an adequate (CTRL or a deficient methionine supply (MD during 10 days (n=6 per group. At the end of the feeding trial, pigs fed the MD diet had higher lipid content in subcutaneous adipose tissue. Expression levels of genes involved in glucose uptake, lipogenesis but also lipolysis, and activities of NADPH enzyme suppliers were generally higher in subcutaneous and perirenal adipose tissues of MD pigs, suggesting an increased lipid turnover in those pigs. Activities of the anti-oxidant enzymes superoxide dismutase, catalase and glutathione reductase were increased in adipose tissues and muscle of MD pigs. Expression level and activity of the glutathione peroxidase were also higher in liver of MD pigs, but hepatic contents in the reduced and oxidized forms of glutathione and glutathione reductase activity were lower compared with control pigs. In plasma, superoxide dismutase activity was higher but total anti-oxidant power was lower in MD pigs. These results show that a dietary methionine deficiency resulted in increased levels of lipogenesis and lipolytic indicators in porcine adipose tissues. Decreased glutathione content in the liver and coordinated increase of enzymatic antioxidant activities in adipose tissues altered the cellular redox status of young pigs fed a methionine-deficient diet. These findings illustrate that a rapidly growing animal differently

  16. A Methionine Deficient Diet Enhances Adipose Tissue Lipid Metabolism and Alters Anti-Oxidant Pathways in Young Growing Pigs.

    Science.gov (United States)

    Castellano, Rosa; Perruchot, Marie-Hélène; Conde-Aguilera, José Alberto; van Milgen, Jaap; Collin, Anne; Tesseraud, Sophie; Mercier, Yves; Gondret, Florence

    2015-01-01

    Methionine is a rate-limiting amino-acid for protein synthesis but non-proteinogenic roles on lipid metabolism and oxidative stress have been demonstrated. Contrary to rodents where a dietary methionine deficiency led to a lower adiposity, an increased lipid accretion rate has been reported in growing pigs fed a methionine deficient diet. This study aimed to clarify the effects of a dietary methionine deficiency on different aspects of tissue lipid metabolism and anti-oxidant pathways in young pigs. Post-weaned pigs (9.8 kg initial body weight) were restrictively-fed diets providing either an adequate (CTRL) or a deficient methionine supply (MD) during 10 days (n=6 per group). At the end of the feeding trial, pigs fed the MD diet had higher lipid content in subcutaneous adipose tissue. Expression levels of genes involved in glucose uptake, lipogenesis but also lipolysis, and activities of NADPH enzyme suppliers were generally higher in subcutaneous and perirenal adipose tissues of MD pigs, suggesting an increased lipid turnover in those pigs. Activities of the anti-oxidant enzymes superoxide dismutase, catalase and glutathione reductase were increased in adipose tissues and muscle of MD pigs. Expression level and activity of the glutathione peroxidase were also higher in liver of MD pigs, but hepatic contents in the reduced and oxidized forms of glutathione and glutathione reductase activity were lower compared with control pigs. In plasma, superoxide dismutase activity was higher but total anti-oxidant power was lower in MD pigs. These results show that a dietary methionine deficiency resulted in increased levels of lipogenesis and lipolytic indicators in porcine adipose tissues. Decreased glutathione content in the liver and coordinated increase of enzymatic antioxidant activities in adipose tissues altered the cellular redox status of young pigs fed a methionine-deficient diet. These findings illustrate that a rapidly growing animal differently adapts tissue

  17. Oxidative metabolism and muscle biochemical profile of polo horses supplemented with an ADE vitamin complex

    Directory of Open Access Journals (Sweden)

    Rebeca A. Weigel

    2013-12-01

    Full Text Available Horses used for the game of polo experience abrupt and frequent changes in exercise intensity. To meet this variable energy demand, the horses use both aerobic and anaerobic pathways in varying proportions and intensities. In this context, there must be a balance between the formation of reactive oxygen species (ROS and the action of antioxidants to prevent oxidative stress and its consequences. The effect of supplementation with an ADE vitamin complex on oxidative metabolism was evaluated in 18 crossbred horses randomly divided between a treated group (TG and a control group (CG. The TG animals received the ADE vitamin complex (1mL/50 kg of body weight by deep intramuscular injection at 30 and 15 days before the game. The CG horses received 10ml of saline by the same administration route and schedule. During the polo match, the animals played for a total of 7.5 min. Blood samples were collected on the same days as the treatments were administered, and immediately before and at 15, 90 and 180 minutes after the game. The concentrations of creatine phosphokinase (CK, lactate dehydrogenase (LDH, lactate, glucose, aspartate aminotransferase (AST, glutathione (GSH, superoxide dismutase (SOD and malondialdehyde (MDA were measured in the blood samples. After the game, the TG demonstrated higher levels of AST, lactate and glucose than the CG, suggesting more efficient energy use by the treated animals. The higher GSH and lower lactate levels in the TG before the game suggest the presence of a greater antioxidant supply in the treated animals. The maintenance of the MDA levels indicates that neither of the groups exhibited oxidative stress.

  18. Metabolic Profiles and Free Radical Scavenging Activity of Cordyceps bassiana Fruiting Bodies According to Developmental Stage

    Science.gov (United States)

    Hyun, Sun-Hee; Lee, Seok-Young; Sung, Gi-Ho; Kim, Seong Hwan; Choi, Hyung-Kyoon

    2013-01-01

    The metabolic profiles of Cordyceps bassiana according to fruiting body developmental stage were investigated using gas chromatography-mass spectrometry. We were able to detect 62 metabolites, including 48 metabolites from 70% methanol extracts and 14 metabolites from 100% n-hexane extracts. These metabolites were classified as alcohols, amino acids, organic acids, phosphoric acids, purine nucleosides and bases, sugars, saturated fatty acids, unsaturated fatty acids, or fatty amides. Significant changes in metabolite levels were found according to developmental stage. Relative levels of amino acids, purine nucleosides, and sugars were higher in development stage 3 than in the other stages. Among the amino acids, valine, isoleucine, lysine, histidine, glutamine, and aspartic acid, which are associated with ABC transporters and aminoacyl-tRNA biosynthesis, also showed higher levels in stage 3 samples. The free radical scavenging activities, which were significantly higher in stage 3 than in the other stages, showed a positive correlation with purine nucleoside metabolites such as adenosine, guanosine, and inosine. These results not only show metabolic profiles, but also suggest the metabolic pathways associated with fruiting body development stages in cultivated C. bassiana. PMID:24058459

  19. Metabolic profiles and free radical scavenging activity of Cordyceps bassiana fruiting bodies according to developmental stage.

    Directory of Open Access Journals (Sweden)

    Sun-Hee Hyun

    Full Text Available The metabolic profiles of Cordyceps bassiana according to fruiting body developmental stage were investigated using gas chromatography-mass spectrometry. We were able to detect 62 metabolites, including 48 metabolites from 70% methanol extracts and 14 metabolites from 100% n-hexane extracts. These metabolites were classified as alcohols, amino acids, organic acids, phosphoric acids, purine nucleosides and bases, sugars, saturated fatty acids, unsaturated fatty acids, or fatty amides. Significant changes in metabolite levels were found according to developmental stage. Relative levels of amino acids, purine nucleosides, and sugars were higher in development stage 3 than in the other stages. Among the amino acids, valine, isoleucine, lysine, histidine, glutamine, and aspartic acid, which are associated with ABC transporters and aminoacyl-tRNA biosynthesis, also showed higher levels in stage 3 samples. The free radical scavenging activities, which were significantly higher in stage 3 than in the other stages, showed a positive correlation with purine nucleoside metabolites such as adenosine, guanosine, and inosine. These results not only show metabolic profiles, but also suggest the metabolic pathways associated with fruiting body development stages in cultivated C. bassiana.

  20. Metabolic profile of santa inês ewes whith low body condition score during peripartum

    Directory of Open Access Journals (Sweden)

    Nayara Resende Nasciutti

    2012-02-01

    Full Text Available The objective of this study was to analyse the variations in the metabolic profile of protein, energy enzyme and mineral of Santa Inês ewes with low body condition score (BCS during peripartum. Blood samples were collected from 12 animals by jugular venipuncture to determine the serum biochemical profiles of protein, energy, mineral and enzyme metabolisms. Samples were collected on the following days: days 28, 21, 14, and 7 before lambing, at birth and, at days 2, 4, 7, 14, 21, and 28 postpartum (dpp. The samples were centrifuged and the serum analysed by Automated-Analyser. There was no alteration of the BCS during the 28 dpp, between 0.6 and 2.1 ± 2.4 ± 0.5, and was considered, as lean. The values of the total serum protein, globulin, albumin, and albumin/globulin ratio were reduced effective from the period before birth until 28dpp. The values of beta-hydroxybutyrate, calcium, phosphorus and magnesium remained below those of reference values. The concentrations of alanin aminotransferase (ALT were decreased particularly during the weeks before delivery. It was concluded that Santa Inês sheep with low body condition score demonstrated a reduction in the metabolism of proteins, energy, mineral and enzyme during peripartum.

  1. Metabolic features of Protochlamydia amoebophila elementary bodies--a link between activity and infectivity in Chlamydiae.

    Directory of Open Access Journals (Sweden)

    Barbara S Sixt

    Full Text Available The Chlamydiae are a highly successful group of obligate intracellular bacteria, whose members are remarkably diverse, ranging from major pathogens of humans and animals to symbionts of ubiquitous protozoa. While their infective developmental stage, the elementary body (EB, has long been accepted to be completely metabolically inert, it has recently been shown to sustain some activities, including uptake of amino acids and protein biosynthesis. In the current study, we performed an in-depth characterization of the metabolic capabilities of EBs of the amoeba symbiont Protochlamydia amoebophila. A combined metabolomics approach, including fluorescence microscopy-based assays, isotope-ratio mass spectrometry (IRMS, ion cyclotron resonance Fourier transform mass spectrometry (ICR/FT-MS, and ultra-performance liquid chromatography mass spectrometry (UPLC-MS was conducted, with a particular focus on the central carbon metabolism. In addition, the effect of nutrient deprivation on chlamydial infectivity was analyzed. Our investigations revealed that host-free P. amoebophila EBs maintain respiratory activity and metabolize D-glucose, including substrate uptake as well as host-free synthesis of labeled metabolites and release of labeled CO2 from (13C-labeled D-glucose. The pentose phosphate pathway was identified as major route of D-glucose catabolism and host-independent activity of the tricarboxylic acid (TCA cycle was observed. Our data strongly suggest anabolic reactions in P. amoebophila EBs and demonstrate that under the applied conditions D-glucose availability is essential to sustain metabolic activity. Replacement of this substrate by L-glucose, a non-metabolizable sugar, led to a rapid decline in the number of infectious particles. Likewise, infectivity of Chlamydia trachomatis, a major human pathogen, also declined more rapidly in the absence of nutrients. Collectively, these findings demonstrate that D-glucose is utilized by P. amoebophila

  2. Carnitine supplementation alleviates lipid metabolism derangements and protects against oxidative stress in non-obese hereditary hypertriglyceridemic rats.

    Science.gov (United States)

    Cahova, Monika; Chrastina, Petr; Hansikova, Hana; Drahota, Zdenek; Trnovska, Jaroslava; Skop, Vojtech; Spacilova, Jana; Malinska, Hana; Oliyarnyk, Olena; Papackova, Zuzana; Palenickova, Eliska; Kazdova, Ludmila

    2015-03-01

    The aim of this study was to estimate the effect of carnitine supplementation on lipid disorders and peripheral tissue insulin sensitivity in a non-obese animal model of insulin resistance, the hereditary hypertriglyceridemic (HHTg) rat. Male HHTg rats were fed a standard diet, and half of them received daily doses of carnitine (500 mg·kg(-1) body weight) for 8 weeks. Rats of the original Wistar strain were used for comparison. HHTg rats exhibited increased urinary excretion of free carnitine and reduced carnitine content in the liver and blood. Carnitine supplementation compensated for this shortage and promoted urinary excretion of acetylcarnitine without any signs of (acyl)carnitine accumulation in skeletal muscle. Compared with their untreated littermates, carnitine-treated HHTg rats exhibited lower weight gain, reduced liver steatosis, lower fasting triglyceridemia, and greater reduction of serum free fatty acid content after glucose load. Carnitine treatment was associated with increased mitochondrial biogenesis and oxidative capacity for fatty acids, amelioration of oxidative stress, and restored substrate switching in the liver. In skeletal muscle (diaphragm), carnitine supplementation was associated with significantly higher palmitate oxidation and a more favorable complete to incomplete oxidation products ratio. Carnitine supplementation further enhanced insulin sensitivity ex vivo. No effects on whole-body glucose tolerance were observed. Our data suggest that some metabolic syndrome-related disorders, particularly fatty acid oxidation, steatosis, and oxidative stress in the liver, could be attenuated by carnitine supplementation. The effect of carnitine could be explained, at least partly, by enhanced substrate oxidation and increased fatty acid transport from tissues in the form of short-chain acylcarnitines.

  3. A review on effects of conjugated linoleic fatty acid (CLA) upon body composition and energetic metabolism.

    Science.gov (United States)

    Lehnen, Tatiana Ederich; da Silva, Marcondes Ramos; Camacho, Augusto; Marcadenti, Aline; Lehnen, Alexandre Machado

    2015-01-01

    Conjugated linoleic acid (CLA) is highly found in fats from ruminants and it appears to favorably modify the body composition and cardiometabolic risk factors. The capacity of CLA to reduce the body fat levels as well as its benefic actions on glycemic profile, atherosclerosis and cancer has already been proved in experimental models. Furthermore, CLA supplementation may modulate the immune function, help re-synthetize of glycogen and potentiate the bone mineralization. CLA supplementation also could increase the lipolysis and reduce the accumulation of fatty acids on the adipose tissue; the putative mechanisms involved may be its action in reducing the lipase lipoprotein activity and to increase the carnitine-palmitoil-transferase-1 (CAT-1) activity, its interaction with PPARγ, and to raise the expression of UCP-1. Although studies made in human have shown some benefits of CLA supplementation as the weight loss, the results are still discordant. Moreover, some have shown adverse effects, such as negative effects on glucose metabolism and lipid profile. The purpose of this article is to review the available data regarding the benefits of CLA on the energetic metabolism and body composition, emphasizing action mechanisms.

  4. The phytochemical glaucarubinone promotes mitochondrial metabolism, reduces body fat, and extends lifespan of Caenorhabditis elegans.

    Science.gov (United States)

    Zarse, K; Bossecker, A; Müller-Kuhrt, L; Siems, K; Hernandez, M A; Berendsohn, W G; Birringer, M; Ristow, M

    2011-04-01

    Naturally occurring compounds that promote energy expenditure and delay aging in model organisms may be of significant interest, since these substances potentially provide pharmaceutical approaches to tackle obesity and promote healthy lifespan in humans. We aimed to test whether pharmaceutical concentrations of glaucarubinone, a cytotoxic and antimalarial quassinoid known from different species of the plant family Simaroubaceae, are capable of affecting metabolism and/or extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Adult C. elegans roundworms, maintained on agar plates, were fed with E. coli strain OP50 bacteria, and glaucarubinone was applied to the agar to test (i) whether it alters respiration rates and mitochondrial activity, (ii) whether it affects body fat content, and (iii) whether it may promote longevity by quantifying survival in the presence and absence of the compound. We have found that glaucarubinone induces oxygen consumption and reduces body fat content of C. elegans. Moreover and consistent with the concept of mitohormesis, glaucarubinone extends C. elegans lifespan when applied at a concentration of 1 or 10 nanomolar. Taken together, glaucarubinone is capable of reducing body fat and promoting longevity in C. elegans, tentatively suggesting that this compound may promote metabolic health and lifespan in mammals and possibly humans.

  5. Predictors of Metabolic Syndrome in the Iranian Population: Waist Circumference, Body Mass Index, or Waist to Hip Ratio?

    OpenAIRE

    Mojgan Gharipour; Nizal Sarrafzadegan; Masoumeh Sadeghi; Elham Andalib; Mohammad Talaie; Davood Shafie; Esmaiel Aghababaie

    2013-01-01

    This study aimed to investigate whether body mass index (BMI), waist circumference (WC), or waist to hip ratio (WHR) could be a better predictor of metabolic syndrome and, if so, what would be the cutoff points for these surrogates to appropriately differentiate metabolic syndrome in different age and sex subgroups. Methods. The present cross-sectional study was conducted on a sample of Isfahan Cohort Study (ICS). In total, 468 individuals (194 with and 274 subjects without metabolic syndrome...

  6. Basal metabolic rate and body composition of elite Japanese male athletes.

    Science.gov (United States)

    Koshimizu, Takako; Matsushima, Yoshiko; Yokota, Yukari; Yanagisawa, Kae; Nagai, Satsuki; Okamura, Koji; Komatsu, Yutaka; Kawahara, Takashi

    2012-01-01

    The estimated energy requirement is important for adequate nutritional management in athletes. The energy requirement can be estimated from the basal metabolic rate (BMR). However, there is little data regarding the BMR of Japanese athletes. This study measured the BMR and body composition of 81 elite Japanese male athletes in different sports categories: endurance (E), strength, power and sprint (S) and ball game (B). The factors influencing the BMR were also investigated. The BMR and body composition were measured by indirect calorimetry and an air-displacement plentysmograph device (the BOD POD), respectively. The BMR per lean body mass (LBM) differed significantly among the three groups. The BMR was significantly correlated with the body weight (BW) and LBM in all groups. A multiple-regression analysis showed that the LBM was the most powerful predictor in the E and S groups, whereas the BW was the most powerful predictor in the B group. The BW appears to become an important predictor as the BW of athletes increases. Additionally, height was the second explanatory variable in the S and B groups, thus suggesting that height needs to be considered for the BMR in these groups. Therefore, the BMR in elite athletes needs to be estimated according to their body composition.

  7. Metabolism of polychaete Neanthes japonica Izuka: relations to temperature, salinity and body weight

    Institute of Scientific and Technical Information of China (English)

    LIU Yong; XIAN Weiwei; SUN Shichun

    2009-01-01

    Polychaete Neanthesjaponica is a species geographically specific in China and Japan with important scientific implication and commercial value. In this study, the relations of body weight, salinity and temperature to oxygen consumption and ammonia excretion of N. japonica were determined. Threedifferent groups in body weight (large: 2.34±0.36 g, middle: 1.50±0.21 g and small: 0.62±0.12 g) were set for all experiments. Results show that the body weight is negatively related to the rates of oxygen consumption and ammonia excretion; and the relationship is significant. The oxygen consumption and ammonia excretion at 24℃ decreased at salinity from 5 to 30 and increased above 30, indicating that both lower and higher salinity are adverse and certain degree of salinity stress is necessary for enhancing the energy demand. At salinity 30, rising temperature from 18℃ to 30℃, the oxygen consumption increased before 27℃ and then decreased. However, the relation of ammonia excretion and temperature seems more complex. Two-way ANOVA shows that salinity, temperature and body weight all have a significant effect on the oxygen consumption and ammonia excretion of the worm. Moreover, interaction between salinity/temperature and body weight is also significant. O:N (oxygen/nitrogen) ratio varies greatly in this case from 5.97 to 463.22, indicating that N. japonica can regulate the type of metabolic substrate against environment changes.

  8. The Relation of Standard Metabolic Rate to Water Temperature and Body Weight of Schlegels Black Rockfish (Sebastodes Fuscescens)

    Institute of Scientific and Technical Information of China (English)

    马志敏; 孙耀; 张波; 唐启升

    2004-01-01

    Standard metabolic rates of Schlegels black rockfish with different body weights are determined in laboratory by using the flow-through respirometer at 11.2 ℃, 14.7 ℃, 18.0℃ and 23.6 ℃. The results indicate that the standard metabolic rates increase with the increase of body weight at different temperatures. Relationship between them could be described as Rs = a InW b. The mean of standard metabolic rate is significantly different among groups, but the b values are not. The standard metabolic rates of amended standard body weights decrease with the increase of temperature, and the mean of standard metabolic rate is also significantly different among groups when the standard body weights are 48.6 g, 147.9 g, and 243.1 g.Relationship between them could be described as Rsw = me-bT . The relations of standard metabolic rate ( Rs ) or relative metabolic rate ( Rs ) to body weight and temperature yield the following equations: Rs = 1.160 W0.752 e-9.494/7 and Rs1= 1.160 W0.254e-9.494/7.

  9. The effect of temperature and body size on metabolic scope of activity in juvenile Atlantic cod Gadus morhua L

    DEFF Research Database (Denmark)

    Tirsgaard, Bjørn; Behrens, Jane; Steffensen, John Fleng

    2015-01-01

    Changes in ambient temperature affect the physiology and metabolism and thus the distribution of fish. In this study we used intermittent flow respirometry to determine the effect of temperature (2, 5, 10, 15 and 20 °C) and wet body mass (BM) (~30–460 g) on standard metabolic rate (SMR, mg O2 h−1...

  10. Permethrin-induced oxidative stress and toxicity and metabolism. A review.

    Science.gov (United States)

    Wang, Xu; Martínez, María-Aránzazu; Dai, Menghong; Chen, Dongmei; Ares, Irma; Romero, Alejandro; Castellano, Victor; Martínez, Marta; Rodríguez, José Luis; Martínez-Larrañaga, María-Rosa; Anadón, Arturo; Yuan, Zonghui

    2016-08-01

    Permethrin (PER), the most frequently used synthetic Type I pyrethroid insecticide, is widely used in the world because of its high activity as an insecticide and its low mammalian toxicity. It was originally believed that PER exhibited low toxicity on untargeted animals. However, as its use became more extensive worldwide, increasing evidence suggested that PER might have a variety of toxic effects on animals and humans alike, such as neurotoxicity, immunotoxicity, cardiotoxicity, hepatotoxicity, reproductive, genotoxic, and haematotoxic effects, digestive system toxicity, and cytotoxicity. A growing number of studies indicate that oxidative stress played critical roles in the various toxicities associated with PER. To date, almost no review has addressed the toxicity of PER correlated with oxidative stress. The focus of this article is primarily to summarise advances in the research associated with oxidative stress as a potential mechanism for PER-induced toxicity as well as its metabolism. This review summarises the research conducted over the past decade into the reactive oxygen species (ROS) generation and oxidative stress as a consequence of PER treatments, and ultimately their correlation with the toxicity and the metabolism of PER. The metabolism of PER involves various CYP450 enzymes, alcohol or aldehyde dehydrogenases for oxidation and the carboxylesterases for hydrolysis, through which oxidative stress might occur, and such metabolic factors are also reviewed. The protection of a variety of antioxidants against PER-induced toxicity is also discussed, in order to further understand the role of oxidative stress in PER-induced toxicity. This review will throw new light on the critical roles of oxidative stress in PER-induced toxicity, as well as on the blind spots that still exist in the understanding of PER metabolism, the cellular effects in terms of apoptosis and cell signaling pathways, and finally strategies to help to protect against its oxidative

  11. Electrocatalytic oxidation of hydrogen peroxide on a platinum electrode in the imitation of oxidative drug metabolism of lidocaine

    NARCIS (Netherlands)

    Nouri-Nigjeh, Eslam; Bruins, Andries P.; Bischoff, Rainer; Permentier, Hjalmar P.

    2012-01-01

    Electrochemistry in combination with mass spectrometry has shown promise as a versatile technique not only in the analytical assessment of oxidative drug metabolism, but also for small-scale synthesis of drug metabolites. However, electrochemistry is generally limited to reactions initiated by direc

  12. Major facilitator superfamily domain-containing protein 2a (MFSD2A has roles in body growth, motor function, and lipid metabolism.

    Directory of Open Access Journals (Sweden)

    Justin H Berger

    Full Text Available The metabolic adaptations to fasting in the liver are largely controlled by the nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARα, where PPARα upregulates genes encoding the biochemical pathway for β-oxidation of fatty acids and ketogenesis. As part of an effort to identify and characterize nutritionally regulated genes that play physiological roles in the adaptation to fasting, we identified Major facilitator superfamily domain-containing protein 2a (Mfsd2a as a fasting-induced gene regulated by both PPARα and glucagon signaling in the liver. MFSD2A is a cell-surface protein homologous to bacterial sodium-melibiose transporters. Hepatic expression and turnover of MFSD2A is acutely regulated by fasting/refeeding, but expression in the brain is constitutive. Relative to wildtype mice, gene-targeted Mfsd2a knockout mice are smaller, leaner, and have decreased serum, liver and brown adipose triglycerides. Mfsd2a knockout mice have normal liver lipid metabolism but increased whole body energy expenditure, likely due to increased β-oxidation in brown adipose tissue and significantly increased voluntary movement, but surprisingly exhibited a form of ataxia. Together, these results indicate that MFSD2A is a nutritionally regulated gene that plays myriad roles in body growth and development, motor function, and lipid metabolism. Moreover, these data suggest that the ligand(s that are transported by MFSD2A play important roles in these physiological processes and await future identification.

  13. Emerging concepts in bioenergetics and cancer research: metabolic flexibility, coupling, symbiosis, switch, oxidative tumors, metabolic remodeling, signaling and bioenergetic therapy.

    Science.gov (United States)

    Obre, Emilie; Rossignol, Rodrigue

    2015-02-01

    The field of energy metabolism dramatically progressed in the last decade, owing to a large number of cancer studies, as well as fundamental investigations on related transcriptional networks and cellular interactions with the microenvironment. The concept of metabolic flexibility was clarified in studies showing the ability of cancer cells to remodel the biochemical pathways of energy transduction and linked anabolism in response to glucose, glutamine or oxygen deprivation. A clearer understanding of the large-scale bioenergetic impact of C-MYC, MYCN, KRAS and P53 was obtained, along with its modification during the course of tumor development. The metabolic dialog between different types of cancer cells, but also with the stroma, also complexified the understanding of bioenergetics and raised the concepts of metabolic symbiosis and reverse Warburg effect. Signaling studies revealed the role of respiratory chain-derived reactive oxygen species for metabolic remodeling and metastasis development. The discovery of oxidative tumors in human and mice models related to chemoresistance also changed the prevalent view of dysfunctional mitochondria in cancer cells. Likewise, the influence of energy metabolism-derived oncometabolites emerged as a new means of tumor genetic regulation. The knowledge obtained on the multi-site regulation of energy metabolism in tumors was translated to cancer preclinical studies, supported by genetic proof of concept studies targeting LDHA, HK2, PGAM1, or ACLY. Here, we review those different facets of metabolic remodeling in cancer, from its diversity in physiology and pathology, to the search of the genetic determinants, the microenvironmental regulators and pharmacological modulators.

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

    Directory of Open Access Journals (Sweden)

    Jordan Katherine W

    2010-05-01

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

  15. Silent information regulator 1 modulator resveratrol increases brain lactate production and inhibits mitochondrial metabolism, whereas SRT1720 increases oxidative metabolism.

    Science.gov (United States)

    Rowlands, Benjamin D; Lau, Chew Ling; Ryall, James G; Thomas, Donald S; Klugmann, Matthias; Beart, Philip M; Rae, Caroline D

    2015-07-01

    Silent information regulators (SIRTs) have been shown to deacetylate a range of metabolic enzymes, including those in glycolysis and the Krebs cycle, and thus alter their activity. SIRTs require NAD(+) for their activity, linking cellular energy status to enzyme activity. To examine the impact of SIRT1 modulation on oxidative metabolism, this study tests the effect of ligands that are either SIRT-activating compounds (resveratrol and SRT1720) or SIRT inhibitors (EX527) on the metabolism of (13)C-enriched substrates by guinea pig brain cortical tissue slices with (13)C and (1)H nuclear magnetic resonance spectroscopy. Resveratrol increased lactate labeling but decreased incorporation of (13)C into Krebs cycle intermediates, consistent with effects on AMPK and inhibition of the F0/F1-ATPase. By testing with resveratrol that was directly applied to astrocytes with a Seahorse analyzer, increased glycolytic shift and increased mitochondrial proton leak resulting from interactions of resveratrol with the mitochondrial electron transport chain were revealed. SRT1720, by contrast, stimulated incorporation of (13)C into Krebs cycle intermediates and reduced incorporation into lactate, although the inhibitor EX527 paradoxically also increased Krebs cycle (13)C incorporation. In summary, the various SIRT1 modulators show distinct acute effects on oxidative metabolism. The strong effects of resveratrol on the mitochondrial respiratory chain and on glycolysis suggest that caution should be used in attempts to increase bioavailability of this compound in the CNS.

  16. Cerebral blood flow and oxidative metabolism during human endotoxemia

    DEFF Research Database (Denmark)

    Møller, Kirsten; Strauss, Gitte Irene; Qvist, Jesper;

    2002-01-01

    The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been suggested to mediate septic encephalopathy through an effect on cerebral blood flow (CBF) and metabolism. The effect of an intravenous bolus of endotoxin on global CBF, metabolism, and net flux of cytokines...... and catecholamines was investigated in eight healthy young volunteers. Cerebral blood flow was measured by the Kety-Schmidt technique at baseline (during normocapnia and voluntary hyperventilation for calculation of subject-specific cerebrovascular CO reactivity), and 90 minutes after an intravenous bolus...

  17. Metabolism of fatty acids and lipid hydroperoxides in human body monitoring with Fourier transform Infrared Spectroscopy

    Directory of Open Access Journals (Sweden)

    Zhang Qin-Zeng

    2009-07-01

    Full Text Available Abstract Background The metabolism of dietary fatty acids in human has been measured so far using human blood cells and stable-isotope labeled fatty acids, however, no direct data was available for human peripheral tissues and other major organs. To realize the role of dietary fatty acids in human health and diseases, it would be eager to develop convenient and suitable method to monitor fatty acid metabolism in human. Results We have developed the measurement system in situ for human lip surface lipids using the Fourier transform infrared spectroscopy (FTIR – attenuated total reflection (ATR detection system with special adaptor to monitor metabolic changes of lipids in human body. As human lip surface lipids may not be much affected by skin sebum constituents and may be affected directly by the lipid constituents of diet, we could detect changes of FTIR-ATR spectra, especially at 3005~3015 cm-1, of lip surface polyunsaturated fatty acids in a duration time-dependent manner after intake of the docosahexaenoic acid (DHA-containing triglyceride diet. The ingested DHA appeared on the lip surface and was detected by FTIR-ATR directly and non-invasively. It was found that the metabolic rates of DHA for male volunteer subjects with age 60s were much lower than those with age 20s. Lipid hydroperoxides were found in lip lipids which were extracted from the lip surface using a mixture of ethanol/ethylpropionate/iso-octane solvents, and were the highest in the content just before noon. The changes of lipid hydroperoxides were detected also in situ with FTIR-ATR at 968 cm-1. Conclusion The measurements of lip surface lipids with FTIR-ATR technique may advance the investigation of human lipid metabolism in situ non-invasively.

  18. Mechanisms and evolution of oxidative sulfur metabolism in green sulfur bacteria

    DEFF Research Database (Denmark)

    Gregersen, Lea Haarup; Bryant, Donald A.; Frigaard, Niels-Ulrik

    2011-01-01

    Green sulfur bacteria (GSB) constitute a closely related group of photoautotrophic and thiotrophic bacteria with limited phenotypic variation. They typically oxidize sulfide and thiosulfate to sulfate with sulfur globules as an intermediate. Based on genome sequence information from 15 strains......, the distribution and phylogeny of enzymes involved in their oxidative sulfur metabolism was investigated. At least one homolog of sulfide:quinone oxidoreductase (SQR) is present in all strains. In all sulfur-oxidizing GSB strains except the earliest diverging Chloroherpeton thalassium, the sulfide oxidation...... and SOX systems. Finally, based upon structural, biochemical, and phylogenetic analyses, a uniform nomenclature is suggested for sqr genes in prokaryotes....

  19. Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications

    Directory of Open Access Journals (Sweden)

    Oluwafeyisetan O. Adebiyi

    2015-12-01

    Full Text Available Nucleoside Reverse Transcriptase Inhibitors (NRTIs have not only improved therapeutic outcomes in the treatment of HIV infection but have also led to an increase in associated metabolic complications of NRTIs. Naringin’s effects in mitigating NRTI-induced complications were investigated in this study. Wistar rats, randomly allotted into seven groups (n = 7 were orally treated daily for 56 days with 100 mg/kg zidovudine (AZT (groups I, II III, 50 mg/kg stavudine (d4T (groups IV, V, VI and 3 mL/kg of distilled water (group VII. Additionally, rats in groups II and V were similarly treated with 50 mg/kg naringin, while groups III and VI were treated with 45 mg/kg vitamin E. AZT or d4T treatment significantly reduced body weight and plasma high density lipoprotein concentrations but increased liver weights, plasma triglycerides and total cholesterol compared to controls, respectively. Furthermore, AZT or d4T treatment significantly increased oxidative stress, adiposity index and expression of Bax protein, but reduced Bcl-2 protein expression compared to controls, respectively. However, either naringin or vitamin E significantly mitigated AZT- or d4T-induced weight loss, dyslipidemia, oxidative stress and hepatocyte apoptosis compared to AZT- or d4T-only treated rats. Our results suggest that naringin reverses metabolic complications associated with NRTIs by ameliorating oxidative stress and apoptosis. This implies that naringin supplements could mitigate lipodystrophy and dyslipidemia associated with NRTI therapy.

  20. Estrous cycle and sex as regulating factors of baseline brain oxidative metabolism and behavior

    Directory of Open Access Journals (Sweden)

    Héctor González-Pardo

    2010-01-01

    Full Text Available The existence of sex differences in brain function is still today a controversial issue, and contradictory results are reported in the scientific literature. Part of this controversy would be solved by taken into consideration the rhythmic changes in the levels of circulating gonadal steroids during the menstrual or estrous cycle in females as compared to males. The aim of this study was to evaluate the changes in oxidative metabolism of limbic brain regions in male and female rats at two different stages of estral cycle (estrous and diestrous. Cytochrome oxidase activity was used as a reliable marker of neuronal oxidative metabolism. We found the highest levels of oxidative metabolism during the diestrous phase in several brain regions, when estrogen levels are high. Males displayed similar cytochrome oxidase activity as compared to females in estrous phase. Our results support behavioral and neurobiological studies reporting sex differences in rodents and humans.

  1. Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

    DEFF Research Database (Denmark)

    Assies, Johanna; Mocking, Roel J T; Lok, Christianne A;

    2014-01-01

    membrane peroxidizability and fluidity, eicosanoid synthesis, neuroprotection and epigenetics. CONCLUSION: While oxidative-stress-induced alterations in FA and 1-C metabolism may initially enhance oxidative stress resistance, persisting chronically, they may cause damage possibly underlying (co...

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

    Science.gov (United States)

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

    2014-02-01

    Dietary lysine restriction may differentially affect body growth and lipid and nitrogen metabolism, depending on the degree of lysine restriction. This study was conducted to examine the effect of dietary lysine restriction on growth and lipid and nitrogen metabolism with two different degree of lysine restriction. Isocaloric amino acid-defined diets containing 1.4% lysine (adequate), 0.70% lysine (50% moderate lysine restriction) and 0.35% lysine (75% severe lysine restriction) were fed from the age of 52 to 77 days for 25 days in male Sprague-Dawley rats. The 75% severe lysine restriction increased (p muscle lipid contents and abdominal fat accumulation, increased (p  0.05) affect body growth and lipid and nitrogen metabolism. Our results demonstrate that severe 75% lysine restriction has detrimental effects on body growth and deregulate lipid and nitrogen metabolism.

  3. Increased fat oxidation and regulation of metabolic genes with ultraendurance exercise

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Rehrer, N J; Pilegaard, H

    2007-01-01

    AIM: Regular endurance exercise stimulates muscle metabolic capacity, but effects of very prolonged endurance exercise are largely unknown. This study examined muscle substrate availability and utilization during prolonged endurance exercise, and associated metabolic genes. METHODS: Data were...... exercise markedly increases plasma fatty acid availability and fat utilization during exercise. Exercise-induced regulation of genes encoding proteins involved in fatty acid recruitment and oxidation may contribute to these changes....

  4. Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain.

    Science.gov (United States)

    Lin, Ai-Ling; Zhang, Wei; Gao, Xiaoli; Watts, Lora

    2015-07-01

    Caloric restriction (CR) has been shown to increase the life span and health span of a broad range of species. However, CR effects on in vivo brain functions are far from explored. In this study, we used multimetric neuroimaging methods to characterize the CR-induced changes of brain metabolic and vascular functions in aging rats. We found that old rats (24 months of age) with CR diet had reduced glucose uptake and lactate concentration, but increased ketone bodies level, compared with the age-matched and young (5 months of age) controls. The shifted metabolism was associated with preserved vascular function: old CR rats also had maintained cerebral blood flow relative to the age-matched controls. When investigating the metabolites in mitochondrial tricarboxylic acid cycle, we found that citrate and α-ketoglutarate were preserved in the old CR rats. We suggest that CR is neuroprotective; ketone bodies, cerebral blood flow, and α-ketoglutarate may play important roles in preserving brain physiology in aging.

  5. Effects of a recreational physical activity summer camp on body composition, metabolic syndrome and physical fitness in obese children.

    Science.gov (United States)

    Roriz DE Oliveira, Mafalda S; Teixeira Seabra, André F; Ribeiro Maia, José A

    2016-01-01

    This study sought to examine the effects of a recreational physical activity summer camp on body composition, metabolic syndrome, and physical fitness in obese children. Forty-eight children (8-10 years; Body Mass Index ≥85th percentile) completed 4-weeks of a structured recreational physical activity program summer camp (5 hours/day, 5 days/week). Over the 4-weeks, significant reductions (Psummer camp yields several body-composition, metabolic-syndrome, and physical fitness benefits in obese children and should represent an effective support for their health development.

  6. Interrelation between compensation of carbohydrate metabolism and severity of manifestations of oxidative stress in type II diabetes mellitus.

    Science.gov (United States)

    Nedosugova, L V; Lankin, V Z; Balabolkin, M I; Konovalova, G G; Lisina, M O; Antonova, K V; Tikhaze, A K; Belenkov, Yu N

    2003-08-01

    Glycosylation end-products formed during diabetes mellitus promoted atherogenic oxidative modification of low-density lipoproteins. We evaluated the effects of compensation of carbohydrate metabolism and therapy with antioxidant probucol on parameters of free radical oxidation in patients with type II diabetes mellitus. Compensation of carbohydrate metabolism reduced manifestations of oxidative stress, which was manifested in accelerated enzymatic utilization of reactive oxygen species and lipid peroxides and decreased content of free radical oxidation products in low-density lipoproteins. In patients with type II diabetes mellitus combination therapy with antioxidant probucol decreased the severity of oxidative stress and stabilized carbohydrate metabolism without increasing the dose of hypoglycemic preparations.

  7. Some aspects of the mitochondrial oxidative metabolism in human atrial tissue during cardiopulmonary by-pass.

    Science.gov (United States)

    Corbucci, G G; Gasparetto, A; Antonelli, M; Bufi, M; De Blasi, R A

    1987-01-01

    Following previous research on the hypoxic cell in human circulatory shock, the present work has investigated some mitochondrial oxidative aspects in atrial biopsies taken during cardiopulmonary by-pass. Cardioplegic solution and hypothermia were administered to 10 patients and the atrial samples were collected before and after aortic clamping. The results show a cellular protective effect of cardioplegia and hypothermia on the electron-transport chain, even if the enzymes with high KmO2 appear to be more sensitive to ischaemia. The results suggest a metabolic injury rather than an oxidative damage due to the induced ischaemia, alterations to fatty-acid beta-oxidation being especially notable. Because of the unchanged oxidative capacities, the oxyradical generation and the peroxidative damage appear to be irrelevant in the ischaemic period and during the course of reperfusion. Further studies are needed to elucidate the metabolic damage and the therapeutic implications due to the induced ischaemia in the myocardial cell during the aortic clamping.

  8. Topographical body fat distribution links to amino acid and lipid metabolism in healthy obese women [corrected].

    Directory of Open Access Journals (Sweden)

    Francois-Pierre J Martin

    Full Text Available Visceral adiposity is increasingly recognized as a key condition for the development of obesity related disorders, with the ratio between visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT reported as the best correlate of cardiometabolic risk. In this study, using a cohort of 40 obese females (age: 25-45 y, BMI: 28-40 kg/m(2 under healthy clinical conditions and monitored over a 2 weeks period we examined the relationships between different body composition parameters, estimates of visceral adiposity and blood/urine metabolic profiles. Metabonomics and lipidomics analysis of blood plasma and urine were employed in combination with in vivo quantitation of body composition and abdominal fat distribution using iDXA and computerized tomography. Of the various visceral fat estimates, VAT/SAT and VAT/total abdominal fat ratios exhibited significant associations with regio-specific body lean and fat composition. The integration of these visceral fat estimates with metabolic profiles of blood and urine described a distinct amino acid, diacyl and ether phospholipid phenotype in women with higher visceral fat. Metabolites important in predicting visceral fat adiposity as assessed by Random forest analysis highlighted 7 most robust markers, including tyrosine, glutamine, PC-O 44∶6, PC-O 44∶4, PC-O 42∶4, PC-O 40∶4, and PC-O 40∶3 lipid species. Unexpectedly, the visceral fat associated inflammatory profiles were shown to be highly influenced by inter-days and between-subject variations. Nevertheless, the visceral fat associated amino acid and lipid signature is proposed to be further validated for future patient stratification and cardiometabolic health diagnostics.

  9. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer.

    Science.gov (United States)

    Seyfried, T N; Sanderson, T M; El-Abbadi, M M; McGowan, R; Mukherjee, P

    2003-10-06

    Brain tumours lack metabolic versatility and are dependent largely on glucose for energy. This contrasts with normal brain tissue that can derive energy from both glucose and ketone bodies. We examined for the first time the potential efficacy of dietary therapies that reduce plasma glucose and elevate ketone bodies in the CT-2A syngeneic malignant mouse astrocytoma. C57BL/6J mice were fed either a standard diet unrestricted (SD-UR), a ketogenic diet unrestricted (KD-UR), the SD restricted to 40% (SD-R), or the KD restricted to 40% of the control standard diet (KD-R). Body weights, tumour weights, plasma glucose, beta-hydroxybutyrate (beta-OHB), and insulin-like growth factor 1 (IGF-1) were measured 13 days after tumour implantation. CT-2A growth was rapid in both the SD-UR and KD-UR groups, but was significantly reduced in both the SD-R and KD-R groups by about 80%. The results indicate that plasma glucose predicts CT-2A growth and that growth is dependent more on the amount than on the origin of dietary calories. Also, restriction of either diet significantly reduced the plasma levels of IGF-1, a biomarker for angiogenesis and tumour progression. Owing to a dependence on plasma glucose, IGF-1 was also predictive of CT-2A growth. Ketone bodies are proposed to reduce stromal inflammatory activities, while providing normal brain cells with a nonglycolytic high-energy substrate. Our results in a mouse astrocytoma suggest that malignant brain tumours are potentially manageable with dietary therapies that reduce glucose and elevate ketone bodies.

  10. Oxidative metabolism drives inflammation-induced platinum resistance in human ovarian cancer.

    Science.gov (United States)

    Matassa, D S; Amoroso, M R; Lu, H; Avolio, R; Arzeni, D; Procaccini, C; Faicchia, D; Maddalena, F; Simeon, V; Agliarulo, I; Zanini, E; Mazzoccoli, C; Recchi, C; Stronach, E; Marone, G; Gabra, H; Matarese, G; Landriscina, M; Esposito, F

    2016-09-01

    Tumour cells have long been considered defective in mitochondrial respiration and mostly dependent on glycolytic metabolism. However, this assumption is currently challenged by several lines of evidence in a growing number of tumours. Ovarian cancer (OC) is one of the most lethal cancers worldwide, but it continues to be a poorly understood disease and its metabolic features are far to be elucidated. In this context, we investigated the role of tumour necrosis factor receptor-associated protein 1 (TRAP1), which is found upregulated in several cancer types and is a key modulator of tumour cell metabolism. Surprisingly, we found that TRAP1 expression inversely correlated with grade, stage and lower survival in a large cohort of OC patients. Accordingly, TRAP1 silencing induced resistance to cisplatin, resistant cells showed increased oxidative metabolism compared with their sensitive counterpart, and the bioenergetics cellular index of higher grade tumours indicated increased mitochondrial respiration. Strikingly, cisplatin resistance was reversible upon pharmacological inhibition of mitochondrial oxidative phosphorylation by metformin/oligomycin. At molecular level, increased oxidative metabolism in low TRAP1-expressing OC cells and tissues enhanced production of inflammatory mediators such as interleukin (IL)-6 and IL-8. Mechanistically, we identified members of the multidrug resistance complex (MDR) as key mediators of such metabolism-driven, inflammation-induced process. Indeed, treatment of OC cell lines with TNFα and IL6 induced a selective increase in the expression of TAP1 and multidrug resistance protein 1, whereas TAP1 silencing sensitized cells to cisplatin-induced apoptosis. Our results unveil a novel role for TRAP1 and oxidative metabolism in cancer progression and suggest the targeting of mitochondrial bioenergetics to increase cisplatin efficacy in human OC.

  11. Body mass, Thermogenesis and energy metabolism in Tupaia belangeri during cold acclimation

    Directory of Open Access Journals (Sweden)

    Wan-long Zhu

    2012-05-01

    Full Text Available In order to study the relationship between energy strategies and environmental temperature, basal metabolic rate (BMR, nonshivering thermogenesis (NST, the total protein contents, mitochondrial protein contents, state and state respiratory ability, cytochrome C oxidase activity Ⅲ Ⅳ of liver, heart, diaphragm, gastrocnemius and brown adipose tissue (BAT, serum leptin level and serum thyroid hormone levels were measured in tree shrews (Tupaia belangeri during cold exposure (5±1oC for 1 day, 7 days,14days,21 days. The results showed that body mass increased, BMR and NST increased, the change of liver mitochondrial protein content was more acutely than total protein. The mitochondrial protein content of heart and BAT were significantly increased during cold-exposed, however the skeletal muscle more moderate reaction. The state Ⅲ and state Ⅳ mitochondrial respiration of these tissues were enhanced significantly than the control. The cytochrome C oxidase activity with cold acclimation also significantly increased except the gastrocnemius. Liver, muscle, BAT, heart and other organs were concerned with thermoregulation during the thermal regulation process above cold-exposed. There is a negative correlation between leptin level and body mass. These results suggested that T. belangeri enhanced thermogenic capacity during cold acclimation, and leptin participated in the regulation of energy balance and body weight in T. belangeri.

  12. Metabolic constraint imposes tradeoff between body size and number of brain neurons in human evolution.

    Science.gov (United States)

    Fonseca-Azevedo, Karina; Herculano-Houzel, Suzana

    2012-11-06

    Despite a general trend for larger mammals to have larger brains, humans are the primates with the largest brain and number of neurons, but not the largest body mass. Why are great apes, the largest primates, not also those endowed with the largest brains? Recently, we showed that the energetic cost of the brain is a linear function of its numbers of neurons. Here we show that metabolic limitations that result from the number of hours available for feeding and the low caloric yield of raw foods impose a tradeoff between body size and number of brain neurons, which explains the small brain size of great apes compared with their large body size. This limitation was probably overcome in Homo erectus with the shift to a cooked diet. Absent the requirement to spend most available hours of the day feeding, the combination of newly freed time and a large number of brain neurons affordable on a cooked diet may thus have been a major positive driving force to the rapid increased in brain size in human evolution.

  13. Basal metabolic rate and body fatness of adult men in northern Mexico.

    Science.gov (United States)

    Valencia, M E; Moya, S Y; McNeill, G; Haggarty, P

    1994-03-01

    To investigate the possibility that overprediction of basal metabolic rate (BMR) of tropical populations is related to differences in fatness between tropical and temperate populations, 32 Mexican men aged 18-40 years underwent measurements of BMR and body fat content. The men were divided into four body mass index (BMI) groups (FAO/WHO/UNU (1985) equations. The FAO/WHO/UNU equations overestimated measured BMR by 9.8%, 9.6%, 7.8% and 5.5% in the four groups. The overall difference was 8.2%, which was statistically significant (P < 0.001). The intercepts of the two equations were significantly different (P < 0.001) by 532 kJ/day, but there was no significant difference between the slopes of the two regression equations. There was no significant difference between BMR/kg fat-free mass in the four BMI groups. The results therefore do not support the possibility that the overprediction of BMR in tropical populations by international prediction equations based on body weight is accounted for by differences in fatness between tropical and temperate populations.

  14. A RAPID THIN-LAYER CHROMATOGRAPHIC PROCEDURE TO IDENTIFY POOR AND EXTENSIVE OXIDATIVE DRUG METABOLIZERS IN MAN USING DEXTROMETHORPHAN

    NARCIS (Netherlands)

    DEZEEUW, RA; EIKEMA, D; FRANKE, JP; JONKMAN, JHG

    1992-01-01

    A rapid TLC method is presented to distinguish poor oxidative drug metabolizers from extensive oxidative drug metabolizers. Dextromethorphan (1) is used as test probe because it is safe, well characterized, generally available and easy to measure. The method is based on the extraction of 1 and its m

  15. Menopause is associated with decreased whole body fat oxidation during exercise

    DEFF Research Database (Denmark)

    Abildgaard, J; Pedersen, A T; Green, C J

    2013-01-01

    ), and postmenopausal (n = 14)]. Estimated insulin sensitivity was obtained from an oral glucose tolerance test. Body composition was measured by dual-energy X-ray absorptiometry and magnetic resonance imaging. Fat oxidation and energy expenditure were measured during an acute exercise bout of 45 min of ergometer...... biking at 50% of maximal oxygen consumption (Vo2 max). Muscle biopsies from the vastus lateralis of the quadriceps muscle were obtained before and immediately after the exercise bout. Postmenopausal women had 33% [confidence interval (CI) 95%: 12-55] lower whole body fat oxidation (P = 0.005) and 19% (CI...... 95%: 9-22) lower energy expenditure (P = 0.02) during exercise, as well as 4.28 kg lower lean body mass (LBM) than premenopausal women. Correction for LBM reduced differences in fat oxidation to 23% (P = 0.05), whereas differences in energy expenditure disappeared (P = 0.22). No differences between...

  16. Differential oxidative metabolism and 5-ketoclomazone accumulation are involved in Echinochloa phyllopogon resistance to clomazone.

    Science.gov (United States)

    Yasuor, Hagai; Zou, Wei; Tolstikov, Vladimir V; Tjeerdema, Ronald S; Fischer, Albert J

    2010-05-01

    Echinochloa phyllopogon (late watergrass) is a major weed of California rice (Oryza sativa) that has evolved cytochrome P450-mediated metabolic resistance to different herbicides with multiple modes of action. E. phyllopogon populations from Sacramento Valley rice fields have also recently shown resistance to the herbicide clomazone. Clomazone is a proherbicide that must be metabolized to 5-ketoclomazone, which is the active compound that inhibits deoxyxylulose 5-phosphate synthase, a key enzyme of the nonmevalonate isoprenoid pathway. This study evaluated the differential clomazone metabolism within strains of the same species to investigate whether enhanced oxidative metabolism also confers clomazone resistance in E. phyllopogon. Using reverse-phase liquid chromatography-tandem mass spectrometry techniques in the multireaction monitoring mode, we elucidated that oxidative biotransformations are involved as a mechanism of clomazone resistance in this species. E. phyllopogon plants hydroxylated mostly the isoxazolidinone ring of clomazone, and clomazone hydroxylation activity was greater in resistant than in susceptible plants. The major clomazone metabolites resulted from monohydroxylation and dihydroxylation of the isoxazolidinone ring. Resistant plants accumulated 6- to 12-fold more of the monohydroxylated metabolite than susceptible plants, while susceptible plants accumulated 2.5-fold more of the phytotoxic metabolite of clomazone, 5-ketoclomazone. Our results demonstrate that oxidative metabolism endows multiple-herbicide-resistant E. phyllopogon with cross-resistance to clomazone through enhanced herbicide degradation and lower accumulation of the toxic metabolite in resistant versus susceptible plants.

  17. Mutant Huntingtin and Elusive Defects in Oxidative Metabolism and Mitochondrial Calcium Handling.

    Science.gov (United States)

    Brustovetsky, Nickolay

    2016-07-01

    Elongation of a polyglutamine (polyQ) stretch in huntingtin protein (Htt) is linked to Huntington's disease (HD) pathogenesis. The mutation in Htt correlates with neuronal dysfunction in the striatum and cerebral cortex and eventually leads to neuronal cell death. The exact mechanisms of the injurious effect of mutant Htt (mHtt) on neurons are not completely understood but might include aberrant gene transcription, defective autophagy, abnormal mitochondrial biogenesis, anomalous mitochondrial dynamics, and trafficking. In addition, deficiency in oxidative metabolism and defects in mitochondrial Ca(2+) handling are considered essential contributing factors to neuronal dysfunction in HD and, consequently, in HD pathogenesis. Since the discovery of the mutation in Htt, the questions whether mHtt affects oxidative metabolism and mitochondrial Ca(2+) handling and, if it does, what mechanisms could be involved were in focus of numerous investigations. However, despite significant research efforts, the detrimental effect of mHtt and the mechanisms by which mHtt might impair oxidative metabolism and mitochondrial Ca(2+) handling remain elusive. In this paper, I will briefly review studies aimed at clarifying the consequences of mHtt interaction with mitochondria and discuss experimental results supporting or arguing against the mHtt effects on oxidative metabolism and mitochondrial Ca(2+) handling.

  18. Age and metabolic risk factors associated with oxidatively damaged DNA in human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Løhr, Mille; Jensen, Annie; Eriksen, Louise;

    2015-01-01

    Aging is associated with oxidative stress-generated damage to DNA and this could be related to metabolic disturbances. This study investigated the association between levels of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs) and metabolic risk factors in 1,019 subjects, aged...... metabolic syndrome criteria. In summary, positive associations between age and levels of oxidatively damaged DNA appeared mediated by age-related increases in metabolic risk factors....... 18-93 years. DNA damage was analyzed as strand breaks by the comet assay and levels of formamidopyrimidine (FPG-) and human 8-oxoguanine DNA glycosylase 1 (hOGG1)-sensitive sites There was an association between age and levels of FPG-sensitive sites for women, but not for men. The same tendency...... was observed for the level of hOGG1-sensitive sites, whereas there was no association with the level of strand breaks. The effect of age on oxidatively damaged DNA in women disappeared in multivariate models, which showed robust positive associations between DNA damage and plasma levels of triglycerides...

  19. Beta-carbolines, psychoactive compounds in the mammalian body. Part I: Occurrence, origin and metabolism.

    Science.gov (United States)

    Airaksinen, M M; Kari, I

    1981-02-01

    We review the occurrence in nature and the formation and biotransformation in mammals of beta-carbolines, the condensation products of tryptophan and indolealkylamines with aldehydes, with special reference to their possible role in man. They are found in many plants, some of which have been used as hallucinogens and drugs. They also occur as minor constituents in tobacco smoke. In man tetrahydro-beta-carboline (tetrahydronorharman), formed from tryptamine condensed with formaldehyde, occurs normally in plasma and is highly concentrated in platelets. The corresponding products from 5-hydroxytryptamine and 5-methoxytryptamine have been identified in rats but their concentrations in man have not yet been assessed. 1-Methyltetrahydro-beta-carboline (tetrahydroharman) is formed in the body as the acetaldehyde condensate after alcohol intake and its concentration is usually greatest at the time of hang-over. Its oxidation product, 1-methyl-beta-carboline (harman), has also been found in human urine and platelets. Tetrahydro-beta-carbolines may be oxidized to corresponding dihydro-beta-carbolines and beta-carbolines, at least in vitro. Due to the interesting biochemical and pharmacological effects (see part II) of beta-carbolines, several hypotheses about their role in the body can be made. The concentrations and roles of beta-carbolines in different neuropsychiatric diseases, however, remain to be determined, as suitable evaluation methods have only been developed in recent years.

  20. Therapeutic Strategies for Mitochondrial Dysfunction and Oxidative Stress in Age-Related Metabolic Disorders.

    Science.gov (United States)

    Bhatti, J S; Kumar, S; Vijayan, M; Bhatti, G K; Reddy, P H

    2017-01-01

    Mitochondria are complex, intercellular organelles present in the cells and are involved in multiple roles including ATP formation, free radicals generation and scavenging, calcium homeostasis, cellular differentiation, and cell death. Many studies depicted the involvement of mitochondrial dysfunction and oxidative damage in aging and pathogenesis of age-related metabolic disorders and neurodegenerative diseases. Remarkable advancements have been made in understanding the structure, function, and physiology of mitochondria in metabolic disorders such as diabetes, obesity, cardiovascular diseases, and stroke. Further, much progress has been done in the improvement of therapeutic strategies, including lifestyle interventions, pharmacological, and mitochondria-targeted therapeutic approaches. These strategies were mainly focused to reduce the mitochondrial dysfunction caused by oxidative stress and to retain the mitochondrial health in various diseases. In this chapter, we have highlighted the involvement of mitochondrial dysfunction in the pathophysiology of various disorders and recent progress in the development of mitochondria-targeted molecules as therapeutic measures for metabolic disorders.

  1. Effects of pistachios on body weight in Chinese subjects with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Wang Xin

    2012-04-01

    Full Text Available Abstract Background Studies have shown that pistachios can improve blood lipid profiles in subjects with moderate hypercholesterolemia which could reduce the risk of cardiovascular disease. However, there is also a widely perceived view that eating nuts can lead to body weight gain due to their high fat content. Purpose To investigate the impact of different dosages of pistachios on body weight, blood pressure, blood lipids, blood glucose and insulin in subjects with metabolic syndrome. Methods Ninety subjects with metabolic syndrome (consistent with 2005 International Diabetes Federation metabolic syndrome standard without diabetes were enrolled in three endocrinology outpatient clinics in Beijing. All subjects received dietary counseling according to the guidelines of the American Heart Association Step I diet. After a 4 week run-in, subjects were randomized to consume either the recommended daily serving of 42 g pistachios (RSG, a higher daily serving of 70 g pistachio (HSG or no pistachios (DCG for 12 weeks. Results Subjects in all three groups were matched at baseline for BMI: DCG 28.03 ± 4.3; RSG 28.12 ± 3.22; and HSG 28.01 ± 4.51 kg/m2. There were no significant changes in body weight or BMI in any groups during the study nor any change from baseline at any time point in any group. During the entire study, there were no significant differences in waist-to-hip ratio among the groups or any change from baseline in any group (DCG -0.00 ± 0.03, RSG -0.01 ± 0.02 and HSG 0.01 ± 0.04. There were no significant differences detected among groups in triglycerides, fasting glucose and 2 hour postprandial glucose following a 75 gram glucose challenge. Exploratory analyses demonstrated that glucose values 2 h after a 75 gm glucose challenge were significantly lower at week 12 compared with baseline values in the HSG group (-1.13 ± 2.58 mmol/L, p = 0.02, and a similar trend was noted in the RSG group (-0.77 ± 2.07 mmol/L, p = 0.06, while no

  2. The Metabolic Syndrome, Oxidative Stress, Environment, and Cardiovascular Disease: The Great Exploration

    Directory of Open Access Journals (Sweden)

    Rebecca Hutcheson

    2012-01-01

    Full Text Available The metabolic syndrome affects 30% of the US population with increasing prevalence. In this paper, we explore the relationship between the metabolic syndrome and the incidence and severity of cardiovascular disease in general and coronary artery disease (CAD in particular. Furthermore, we look at the impact of metabolic syndrome on outcomes of coronary revascularization therapies including CABG, PTCA, and coronary collateral development. We also examine the association between the metabolic syndrome and its individual component pathologies and oxidative stress. Related, we explore the interaction between the main external sources of oxidative stress, cigarette smoke and air pollution, and metabolic syndrome and the effect of this interaction on CAD. We discuss the apparent lack of positive effect of antioxidants on cardiovascular outcomes in large clinical trials with emphasis on some of the limitations of these trials. Finally, we present evidence for successful use of antioxidant properties of pharmacological agents, including metformin, statins, angiotensin II type I receptor blockers (ARBs, and angiotensin II converting enzyme (ACE inhibitors, for prevention and treatment of the cardiovascular complications of the metabolic syndrome.

  3. Tumor glucose metabolism imaged in vivo in small animals with whole-body photoacoustic computed tomography

    Science.gov (United States)

    Chatni, Muhammad Rameez; Xia, Jun; Sohn, Rebecca; Maslov, Konstantin; Guo, Zijian; Zhang, Yu; Wang, Kun; Xia, Younan; Anastasio, Mark; Arbeit, Jeffrey; Wang, Lihong V.

    2012-07-01

    With the increasing use of small animals for human disease studies, small-animal whole-body molecular imaging plays an important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose molecular information, leading to higher costs of building dual-modality systems. Even with image co-registration, the spatial resolution of the molecular imaging modality is not improved. Utilizing a ring-shaped confocal photoacoustic computed tomography system, we demonstrate, for the first time, that both anatomy and glucose uptake can be imaged in a single modality. Anatomy was imaged with the endogenous hemoglobin contrast, and glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose.

  4. Offspring body size and metabolic profile - effects of lifestyle intervention in obese pregnant women

    DEFF Research Database (Denmark)

    Tanvig, Mette; Jensen, Dorte Møller

    2014-01-01

    of normal weight mothers all outcomes were similar. We speculate that obese mothers entering a lifestyle intervention RCT regardless of the intervention have a high motivation to focus on healthy lifestyle during pregnancy, which makes it difficult to determine the effects of the randomized lifestyle....... The obesity epidemic is not simply a consequence of poor diet or sedentary lifestyles. Obesity is a multifactorial condition in which environmental, biological and genetic factors all play essential roles. The Developmental Origins of Health and Disease (DoHaD) hypothesis has highlighted the link between...... disturbances in the offspring. Pregnancy offers the opportunity to modify the intrauterine environment, and maternal lifestyle changes during gestation may confer health benefits to the child. The overall aim with this PhD thesis was to study the effects of maternal obesity on offspring body size and metabolic...

  5. Gestational heat stress alters postnatal offspring body composition indices and metabolic parameters in pigs.

    Directory of Open Access Journals (Sweden)

    Rebecca L Boddicker

    Full Text Available The study objectives were to test the hypothesis that heat stress (HS during gestational development alters postnatal growth, body composition, and biological response to HS conditions in pigs. To investigate this, 14 first parity crossbred gilts were exposed to one of four environmental treatments (TNTN, TNHS, HSTN, or HSHS during gestation. TNTN and HSHS dams were exposed to thermal neutral (TN, cyclical 18-22°C or HS conditions (cyclical 28-34°C during the entire gestation, respectively. Dams assigned to HSTN and TNHS treatments were heat-stressed for the first or second half of gestation, respectively. Postnatal offspring were exposed to one of two thermal environments for an acute (24 h or chronic (five weeks duration in either constant TN (21°C or HS (35°C environment. Exposure to chronic HS during their growth phase resulted in decreased longissimus dorsi cross-sectional area (LDA in offspring from HSHS and HSTN treated dams whereas LDA was larger in offspring from dams in TNTN and TNHS conditions. Irrespective of HS during prepubertal postnatal growth, pigs from dams that experienced HS during the first half of gestation (HSHS and HSTN had increased (13.9% subcutaneous fat thickness compared to pigs from dams exposed to TN conditions during the first half of gestation. This metabolic repartitioning towards increased fat deposition in pigs from dams heat-stressed during the first half of gestation was accompanied by elevated blood insulin concentrations (33%; P = 0.01. Together, these results demonstrate HS during the first half of gestation altered metabolic and body composition parameters during future development and in biological responses to a subsequent HS challenge.

  6. Gestational heat stress alters postnatal offspring body composition indices and metabolic parameters in pigs.

    Science.gov (United States)

    Boddicker, Rebecca L; Seibert, Jacob T; Johnson, Jay S; Pearce, Sarah C; Selsby, Joshua T; Gabler, Nicholas K; Lucy, Matthew C; Safranski, Timothy J; Rhoads, Robert P; Baumgard, Lance H; Ross, Jason W

    2014-01-01

    The study objectives were to test the hypothesis that heat stress (HS) during gestational development alters postnatal growth, body composition, and biological response to HS conditions in pigs. To investigate this, 14 first parity crossbred gilts were exposed to one of four environmental treatments (TNTN, TNHS, HSTN, or HSHS) during gestation. TNTN and HSHS dams were exposed to thermal neutral (TN, cyclical 18-22°C) or HS conditions (cyclical 28-34°C) during the entire gestation, respectively. Dams assigned to HSTN and TNHS treatments were heat-stressed for the first or second half of gestation, respectively. Postnatal offspring were exposed to one of two thermal environments for an acute (24 h) or chronic (five weeks) duration in either constant TN (21°C) or HS (35°C) environment. Exposure to chronic HS during their growth phase resulted in decreased longissimus dorsi cross-sectional area (LDA) in offspring from HSHS and HSTN treated dams whereas LDA was larger in offspring from dams in TNTN and TNHS conditions. Irrespective of HS during prepubertal postnatal growth, pigs from dams that experienced HS during the first half of gestation (HSHS and HSTN) had increased (13.9%) subcutaneous fat thickness compared to pigs from dams exposed to TN conditions during the first half of gestation. This metabolic repartitioning towards increased fat deposition in pigs from dams heat-stressed during the first half of gestation was accompanied by elevated blood insulin concentrations (33%; P = 0.01). Together, these results demonstrate HS during the first half of gestation altered metabolic and body composition parameters during future development and in biological responses to a subsequent HS challenge.

  7. Impact of Orexin-A Treatment on Food Intake, Energy Metabolism and Body Weight in Mice

    Science.gov (United States)

    Blais, Anne; Drouin, Gaëtan; Chaumontet, Catherine; Voisin, Thierry; Couvelard, Anne; Even, Patrick Christian; Couvineau, Alain

    2017-01-01

    Orexin-A and -B are hypothalamic neuropeptides of 33 and 28-amino acids, which regulate many homeostatic systems including sleep/wakefulness states, energy balance, energy homeostasis, reward seeking and drug addiction. Orexin-A treatment was also shown to reduce tumor development in xenografted nude mice and is thus a potential treatment for carcinogenesis. The aim of this work was to explore in healthy mice the consequences on energy expenditure components of an orexin-A treatment at a dose previously shown to be efficient to reduce tumor development. Physiological approaches were used to evaluate the effect of orexin-A on food intake pattern, energy metabolism body weight and body adiposity. Modulation of the expression of brain neuropeptides and receptors including NPY, POMC, AgRP, cocaine- and amphetamine related transcript (CART), corticotropin-releasing hormone (CRH) and prepro-orexin (HCRT), and Y2 and Y5 neuropeptide Y, MC4 (melanocortin), OX1 and OX2 orexin receptors (Y2R, Y5R, MC4R, OX1R and OX2R, respectively) was also explored. Our results show that orexin-A treatment does not significantly affect the components of energy expenditure, and glucose metabolism but reduces intraperitoneal fat deposit, adiposity and the expression of several brain neuropeptide receptors suggesting that peripheral orexin-A was able to reach the central nervous system. These findings establish that orexin-A treatment which is known for its activity as an inducer of tumor cell death, do have minor parallel consequence on energy homeostasis control. PMID:28085909

  8. How hydrogen peroxide is metabolized by oxidized cytochrome c oxidase.

    Science.gov (United States)

    Jancura, Daniel; Stanicova, Jana; Palmer, Graham; Fabian, Marian

    2014-06-10

    In the absence of external electron donors, oxidized bovine cytochrome c oxidase (CcO) exhibits the ability to decompose excess H2O2. Depending on the concentration of peroxide, two mechanisms of degradation were identified. At submillimolar peroxide concentrations, decomposition proceeds with virtually no production of superoxide and oxygen. In contrast, in the millimolar H2O2 concentration range, CcO generates superoxide from peroxide. At submillimolar concentrations, the decomposition of H2O2 occurs at least at two sites. One is the catalytic heme a3-CuB center where H2O2 is reduced to water. During the interaction of the enzyme with H2O2, this center cycles back to oxidized CcO via the intermediate presence of two oxoferryl states. We show that at pH 8.0 two molecules of H2O2 react with the catalytic center accomplishing one cycle. In addition, the reactions at the heme a3-CuB center generate the surface-exposed lipid-based radical(s) that participates in the decomposition of peroxide. It is also found that the irreversible decline of the catalytic activity of the enzyme treated with submillimolar H2O2 concentrations results specifically from the decrease in the rate of electron transfer from heme a to the heme a3-CuB center during the reductive phase of the catalytic cycle. The rates of electron transfer from ferrocytochrome c to heme a and the kinetics of the oxidation of the fully reduced CcO with O2 were not affected in the peroxide-modified CcO.

  9. A pilot study on the impact of body composition on bone and mineral metabolism in Parkinson's disease.

    Science.gov (United States)

    Fernández, María C; Parisi, Muriel S; Díaz, Sergio P; Mastaglia, Silvina R; Deferrari, Juan M; Seijo, Mariana; Bagur, Alicia; Micheli, Federico; Oliveri, Beatriz

    2007-08-01

    The impact of body composition on bone and mineral metabolism in Parkinson's disease (PD) was evaluated. Body fat mass, lean mass, bone mineral content, and bone mineral density (BMD) were measured by DXA in 22 PD patients and 104 controls. Female patients exhibited reduced body mass index, fat mass, and BMD compared to controls (p<0.05). Significant positive correlation was found between 25 OHD levels and BMC. Diminished bone mass in women with PD was found to be associated with alterations in body composition and low 25 OHD levels.

  10. Metabolic characteristics and oxidative damage to skeletal muscle in broiler chickens exposed to chronic heat stress.

    Science.gov (United States)

    Azad, M A K; Kikusato, M; Maekawa, T; Shirakawa, H; Toyomizu, M

    2010-03-01

    Emerging evidence has shown that acute heat exposure affects metabolic characteristics and causes oxidative damage to skeletal muscle in birds. Little is known, however, about such phenomena under chronic heat stress conditions. To address this, we designed the present study to determine the influence of cyclic (32 to 24 to 32 degrees C: 32 degrees C for 8 h/d, 32-24-32HS ), and constant (32 and 34 degrees C, 32HS and 34HS, respectively) heat exposure on the metabolic and peroxide status in skeletal muscle of 4-wk-old male broiler chickens. Heat stress, particularly in the 32HS and 34HS groups, depressed feed intake and growth, while cyclic high temperature gave rise to a less severe stress response in performance terms. Malondialdehyde (MDA) levels in skeletal muscle were enhanced (Pstress model. The 3HADH (3-hydroxyacyl CoA dehydrogenase related to fatty acid oxidation) and CS (citrate synthase) enzyme activities were lowered (Pchickens. On exposure to chronic heat stress, GPx activity remained relatively constant, though a temperature-dependent elevation in Cu/Zn-SOD activity was observed, implying that anti-oxidation ability was disturbed by the chronic stress condition. From these results it can be concluded that chronic heat stress did not induce oxidative damage to a major extent. This may probably be due to a decrease in metabolic oxidation capacity or due to a self-propagating scavenging system, though the system was not fully activated.

  11. Value of waist circumference, body mass index and hyperinsulinaemia in identifying metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    Hui TIAN; Jingfang SUN; Changyu PAN; Juming LU; Jingtao DOU; Fangling MA; Xiaoman ZHOU; Fusheng FANG; Yinghong SHAO; Chunlin LI; Jian LI; Xiutang CAO; Shuangtong YAN; Wenwen ZHONG; Yanyan LI

    2008-01-01

    To investigate the significance of waist circum-ference (WC), body mass index (BMI) and hyperinsuli-naemia A (Hlns) in evaluating metabolic syndrome (MS). Clinical data from middle-aged and senile indivi-duals (middle-senile group) who received glucose tol-erance test after diabetes mellitus screening and a group of subjects who received annual oral glucose tolerance test (OGTT) for diabetes mellitus screening (adult group) were collected. Data were collected by use of special mes-sengers, input into a computer data base and analyzed using SAS 5.0 software by expert staff. Abnormal WC and BMI were determined according to International Diabetes Federation (IDF) and Chinese Diabetes Society (CDS) criteria. Hlns was ascertained if fasting insulin (Fins)≥15 mU/L, and/or 2-hour insulin after a glucose challenge was (2hPIns)≥80 mU/L. Abnorma-lities in WC, BMI and Hlns were all found to be risk factors for abnormal glucose metabolism, hypertension and dyslipidemia. In the middle-senile group, the abnor-mality rate of WC and Hlns as well as the overall insulin level were significantly higher than those in the adult group. The abnormality rate of BMI was higher in the adult group, and HIns was mostly seen in impaired glu-cose test (IGT) and normal glucose test (NGT). The con-cordance rate of WC and BMI diagnostic criteria for evaluating obesity in the middle-senile and adult groups were 77.5% and 74.3%, respectively. When only the WC criterion was used for evaluating the existence of insulin resistance, there was a 28.2% missed diagnosis rate for MS patients. WC, BMI and Hlns were all risk factors for abnormal glucose metabolism, hypertension and dyslipi-demia. There was differing prevalence in the different populations. The combination of WC, BMI and Hlnsmight be more helpful in identifying MS at early stage.

  12. Cerebral blood flow and oxygen metabolism in dementia with Lewy bodies

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Yoshitomo; Takahashi, Satoshi; Yonezawa, Hisashi [Iwate Medical Univ., Morioka (Japan). School of Medicine

    2000-06-01

    Regional cerebral blood flow (rCBF), oxygen metabolism (rCMRO{sub 2}) and the oxygen extraction fraction (rOEF) were measured using the steady-state {sup 15}O technique and positron emission tomography (PET) in six patients with dementia with Lewy bodies (DLB), and compared with ten patients with Alzheimer disease (AD) and six normal controls. In the AD patients, rCBF and rCMRO{sub 2} were significantly decreased in the frontal, parietal, and temporal cortices compared with controls. In DLB patients, rCBF and rCMRO{sub 2} were decreased in the frontal, parietal, temporal, and occipital cortices compared with controls, and were decreased more diffusely than in AD patients. rCBF and rCMRO{sub 2} were significantly decreased in occipital cortex compared with AD patients. rOEF was significantly increased in the parieto-temporal cortex in AD patients compared with controls. In DLB patients, rOEF was significantly increased not only in the parieto-temporal cortex but also in the occipital and frontal cortices compared with controls, and was significantly increased in the occipital cortex compared with AD patients. The diffuse reduction of cerebral blood flow and oxygen metabolism including the occipital cortex may be related to visual hallucination and other visuospatial deficits frequently seen in DLB patients. The increase in rOEF may be mainly due to the reduction in the vascular bed associated with decreased activity in the vasodilatory cholinergic system. (author)

  13. Effects of whole body exposure to electromagnetic field on normal and osteoporotic bone metabolism in rats

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, S.; Iida, H. [National Inst. of Radiological Sciences, Chiba (Japan)

    2000-05-01

    The biological effects of the exposure to the electromagnetic field particularly on bone metabolism in growing rats that were ovariectomized (OVX) and fed different calcium diets were determined. Female Wistar rats, 8 weeks old, were divided into four groups; OVX fed standardized (1.2%) calcium diet (StCa), OVX fed low (0.02%) Ca diet (LCa), no-OVX+StCa and no-OVX+LCa groups. Half of rats in each group were exposed to electromagnetic field (100 mG, 50 Hz). Rats (n=5) in each group were sacrificed 1, 2, and 3 month after the exposure. Analyses of bone and serum were performed. Compared to the corresponding control groups, the body weights in the exposure groups, decreased at each measured point. The bone mineral density in the total and trabecular bone in the tibia and femur decreased 2 month after the exposure. In the histomorphometric measurement using the tibial proximal metaphysis at 3 months later, the decreases in bone volume, bone formation rate, eroded surface and depth, and the increases in trabecular separation were observed in the exposure groups. The bone fragility (femur) also was observed. Simultaneously the decreases in the weights of adrenal gland and skeletal muscles, and value in serum rat-PTH and BGP were observed. The results indicate that the bone growth and metabolism in the growth process are inhibited and enlarged with low Ca intakes by the long-term exposure in an electromagnetic field in rats. (author)

  14. Biphasic effect of melanocortin agonists on metabolic rate and body temperature.

    Science.gov (United States)

    Lute, Beth; Jou, William; Lateef, Dalya M; Goldgof, Margalit; Xiao, Cuiying; Piñol, Ramón A; Kravitz, Alexxai V; Miller, Nicole R; Huang, Yuning George; Girardet, Clemence; Butler, Andrew A; Gavrilova, Oksana; Reitman, Marc L

    2014-08-01

    The melanocortin system regulates metabolic homeostasis and inflammation. Melanocortin agonists have contradictorily been reported to both increase and decrease metabolic rate and body temperature. We find two distinct physiologic responses occurring at similar doses. Intraperitoneal administration of the nonselective melanocortin agonist MTII causes a melanocortin-4 receptor (Mc4r)-mediated hypermetabolism/hyperthermia. This is preceded by a profound, transient hypometabolism/hypothermia that is preserved in mice lacking any one of Mc1r, Mc3r, Mc4r, or Mc5r. Three other melanocortin agonists also caused hypothermia, which is actively achieved via seeking a cool environment, vasodilation, and inhibition of brown adipose tissue thermogenesis. These results suggest that the hypometabolic/hypothermic effect of MTII is not due to a failure of thermoregulation. The hypometabolism/hypothermia was prevented by dopamine antagonists, and MTII selectively activated arcuate nucleus dopaminergic neurons, suggesting that these neurons may contribute to the hypometabolism/hypothermia. We propose that the hypometabolism/hypothermia is a regulated response, potentially beneficial during extreme physiologic stress.

  15. Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure.

    Science.gov (United States)

    Díaz-Flores, Margarita; Cruz, Miguel; Duran-Reyes, Genoveva; Munguia-Miranda, Catarina; Loza-Rodríguez, Hilda; Pulido-Casas, Evelyn; Torres-Ramírez, Nayeli; Gaja-Rodriguez, Olga; Kumate, Jesus; Baiza-Gutman, Luis Arturo; Hernández-Saavedra, Daniel

    2013-10-01

    Reactive oxygen species derived from abdominal fat and uncontrolled glucose metabolism are contributing factors to both oxidative stress and the development of metabolic syndrome (MetS). This study was designed to evaluate the effects of daily administration of an oral glycine supplement on antioxidant enzymes and lipid peroxidation in MetS patients. The study included 60 volunteers: 30 individuals that were supplemented with glycine (15 g/day) and 30 that were given a placebo for 3 months. We analysed thiobarbituric acid reactive substances (TBARS) and S-nitrosohemoglobin (SNO-Hb) in plasma; the enzymatic activities of glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) in erythrocytes; and the expression of CAT, GPX, and SOD2 in leukocytes. Individuals treated with glycine showed a 25% decrease in TBARS compared with the placebo-treated group. Furthermore, there was a 20% reduction in SOD-specific activity in the glycine-treated group, which correlated with SOD2 expression. G6PD activity and SNO-Hb levels increased in the glycine-treated male group. Systolic blood pressure (SBP) also showed a significant decrease in the glycine-treated men (p = 0.043). Glycine plays an important role in balancing the redox reactions in the human body, thus protecting against oxidative damage in MetS patients.

  16. The potential for mitochondrial fat oxidation in human skeletal muscle influences whole body fat oxidation during low-intensity exercise.

    Science.gov (United States)

    Sahlin, K; Mogensen, M; Bagger, M; Fernström, M; Pedersen, P K

    2007-01-01

    The purpose of this study was to investigate fatty acid (FA) oxidation in isolated mitochondrial vesicles (mit) and its relation to training status, fiber type composition, and whole body FA oxidation. Trained (Vo(2 peak) 60.7 +/- 1.6, n = 8) and untrained subjects (39.5 +/- 2.0 ml.min(-1).kg(-1), n = 5) cycled at 40, 80, and 120 W, and whole body relative FA oxidation was assessed from respiratory exchange ratio (RER). Mit were isolated from muscle biopsies, and maximal ADP stimulated respiration was measured with carbohydrate-derived substrate [pyruvate + malate (Pyr)] and FA-derived substrate [palmitoyl-l-carnitine + malate (PC)]. Fiber type composition was determined from analysis of myosin heavy-chain (MHC) composition. The rate of mit oxidation was lower with PC than with Pyr, and the ratio between PC and Pyr oxidation (MFO) varied greatly between subjects (49-93%). MFO was significantly correlated to muscle fiber type distribution, i.e., %MHC I (r = 0.62, P = 0.03), but was not different between trained (62 +/- 5%) and untrained subjects (72 +/- 2%). MFO was correlated to RER during submaximal exercise at 80 (r = -0.62, P = 0.02) and 120 W (r = -0.71, P = 0.007) and interpolated 35% Vo(2 peak) (r = -0.74, P = 0.004). ADP sensitivity of mit respiration was significantly higher with PC than with Pyr. It is concluded that MFO is influenced by fiber type composition but not by training status. The inverse correlation between RER and MFO implies that intrinsic mit characteristics are of importance for whole body FA oxidation during low-intensity exercise. The higher ADP sensitivity with PC than that with Pyr may influence fuel utilization at low rate of respiration.

  17. Iron metabolism and oxidative profile of dogs naturally infected by Ehrlichia canis: Acute and subclinical disease.

    Science.gov (United States)

    Bottari, Nathieli B; Crivellenti, Leandro Z; Borin-Crivellenti, Sofia; Oliveira, Jéssica R; Coelho, Stefanie B; Contin, Catarina M; Tatsch, Etiane; Moresco, Rafael N; Santana, Aureo E; Tonin, Alexandre A; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

    2016-03-01

    The aim of this study was to evaluate the oxidant profile and iron metabolism in serum of dogs infected by Ehrlichia canis. Banked sera samples of dogs were divided into two groups: negative control (n = 17) and infected by E. canis on acute (n = 24), and subclinical (n = 18) phases of the disease. The eritrogram, leucogram, and platelet counts were evaluate as well as iron, ferritin, and transferrin levels, latent iron binding capacity (LIBC), and transferrin saturation index (TSI) concentration. In addition, the advanced oxidation protein products (AOPP) and ferric reducing ability of plasma (FRAP) in sera were also analyzed. Blood samples were examined for the presence of E. canis by PCR techniques. History and clinical signals were recorded for each dog. During the acute phase of the disease, infected animals showed thrombocytopenia and anemia when compared to healthy animals (P canis showed changes in the iron metabolism and developed an oxidant status in consequence of disease pathophysiology.

  18. Effect of abomasal glucose infusion on splanchnic and whole-body glucose metabolism in periparturient dairy cows

    DEFF Research Database (Denmark)

    Larsen, Mogens; Kristensen, Niels Bastian

    2009-01-01

    Six periparturient Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the hepatic portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic and whole-body glucose metabolism.......Six periparturient Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the hepatic portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic and whole-body glucose metabolism....

  19. A multi-tissue type genome-scale metabolic network for analysis of whole-body systems physiology

    Directory of Open Access Journals (Sweden)

    Feist Adam M

    2011-10-01

    Full Text Available Abstract Background Genome-scale metabolic reconstructions provide a biologically meaningful mechanistic basis for the genotype-phenotype relationship. The global human metabolic network, termed Recon 1, has recently been reconstructed allowing the systems analysis of human metabolic physiology and pathology. Utilizing high-throughput data, Recon 1 has recently been tailored to different cells and tissues, including the liver, kidney, brain, and alveolar macrophage. These models have shown utility in the study of systems medicine. However, no integrated analysis between human tissues has been done. Results To describe tissue-specific functions, Recon 1 was tailored to describe metabolism in three human cells: adipocytes, hepatocytes, and myocytes. These cell-specific networks were manually curated and validated based on known cellular metabolic functions. To study intercellular interactions, a novel multi-tissue type modeling approach was developed to integrate the metabolic functions for the three cell types, and subsequently used to simulate known integrated metabolic cycles. In addition, the multi-tissue model was used to study diabetes: a pathology with systemic properties. High-throughput data was integrated with the network to determine differential metabolic activity between obese and type II obese gastric bypass patients in a whole-body context. Conclusion The multi-tissue type modeling approach presented provides a platform to study integrated metabolic states. As more cell and tissue-specific models are released, it is critical to develop a framework in which to study their interdependencies.

  20. The Effects Of Two Fitness Programs With Different Metabolic Demands On Oxidative Stress In The Blood Of Young Females

    Directory of Open Access Journals (Sweden)

    Djordjevic Dusica

    2015-06-01

    Full Text Available The aim of the present study was to assess the effects of two metabolically different exercise programs on the redox state of women who were physically inactive before the beginning of the study. For this purpose, participants (women 25±5 years old chose one of two popular fitness programs, Pilates or Tae Bo, and attended it 3 times a week for 12 weeks. At the beginning and end of the study, body composition analysis and venous blood sampling were performed. The levels of superoxide anion radical, hydrogen peroxide, nitric oxide and lipid peroxidation were measured in plasma, and the levels of reduced glutathione and the activity of superoxide dismutase and catalase were measured in erythrocytes. Only the Tae Bo program induced changes (positive in body composition, whereas both exercise programs induced slight oxidative stress in exercisers. In the Tae Bo group, the levels of hydrogen peroxide were significantly increased, whereas the levels of reduced glutathione were decreased after three months of training. In the Pilates group, hydrogen peroxide and catalase activity were increased, and nitrites decreased. However, at the end of the study, those two groups had no significantly different values for any pro/antioxidant compared with the subjects who served as controls. This finding suggests that moderate physical activity, such as recreational fitness programs, may induce the increased production of reactive oxygen species but do not lead to a serious disturbance of the redox homeostasis of exercisers.

  1. Body size and metabolic differences in Maine Coon cats with and without hypertrophic cardiomyopathy.

    Science.gov (United States)

    Freeman, Lisa M; Rush, John E; Meurs, Kathryn M; Bulmer, Barret J; Cunningham, Suzanne M

    2013-02-01

    An interplay between growth, glucose regulation and hypertrophic cardiomyopathy (HCM) may exist, but has not been studied in detail. The purpose of this study was to characterize morphometric features, insulin-like growth factor-1 (IGF-1) and glucose metabolism in Maine Coon cats with HCM. Body weight, body condition score (BCS), head length and width, and abdominal circumference were measured in Maine Coon cats >2 years of age. Echocardiography and thoracic radiography (for measurement of humerus length, and fourth and twelfth vertebrae length) were also performed. Blood was collected for biochemistry profile, DNA testing, insulin and IGF-1. Sixteen of 63 cats had HCM [myosin binding protein C (MYBPC)+, n = 3 and MYBPC-, n = 13] and 47/63 were echocardiographically normal (MYBPC+, n = 17 and MYBPC-, n = 30). There were no significant differences in any measured parameter between MYBPC+ and MYBPC- cats. Cats with HCM were significantly older (P <0.001), heavier (P = 0.006), more obese (P = 0.008), and had longer humeri (P = 0.02) compared with the HCM- group. Cats with HCM also had higher serum glucose (P = 0.01), homeostasis model assessment (HOMA) and IGF-1 (P = 0.01) concentrations, were from smaller litters (P = 0.04), and were larger at 6 months (P = 0.02) and at 1 year of age (P = 0.03). Multivariate analysis revealed that age (P <0.001), BCS (P = 0.03) and HOMA (P = 0.047) remained significantly associated with HCM. These results support the hypothesis that early growth and nutrition, larger body size and obesity may be environmental modifiers of genetic predisposition to HCM. Further studies are warranted to evaluate the effects of early nutrition on the phenotypic expression of HCM.

  2. Study of Body Composition and Metabolic Parameters in HIV-1 Male Patients

    Directory of Open Access Journals (Sweden)

    Gurudath Gundurao Sreekantamurthy

    2014-01-01

    Full Text Available Background. HIV patients on highly active antiretroviral therapy (HAART containing protease inhibitors (PIs had been often associated with lipodystrophy. However, there are only few studies on association of nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI and NNRTI with lipodystrophy. Study Design. One hundred and one HIV male patients were categorised into ART naïve (n=22, zidovudine (n=22, stavudine (n=18, tenofovir (n=15, and PIs (n=24 based HAART. Their clinicoepidemiological data had been entered in preformed pro forma. The body composition, using TANITA machine and metabolic parameters like lipid profile, blood sugars was analysed. Results. Clinically, lipoatrophy of face was most prevalent in HIV patients on stavudine (15 patients, 83.3% and PIs (20 patients, 83.3% based HAART. The mean BMI among study population was in normal range. Excess visceral fat was most prevalent among patients on PIs, 4 patients (16.7%. The waist-hip ratio was significantly higher in PIs (P=0.01 based HAART. There was no significant difference among different study populations in terms of BMI (P=0.917, body water (P=0.318, body fat (P=0.172, bone mass (P=0.200, and muscle mass (P=0.070. Hypertriglyceridiemia was found in stavudine, tenofovir, and protease inhibitors regimens. Low levels of high density lipoprotein (HDL was found zidovudine, stavudine, and PIs regimens. Fasting and postprandial hyperglycaemia was found PIs and impaired glucose tolerance in stavudine regimen. Conclusion. Patients on PIs were associated with truncal obesity and lipoatrophy of face, along with dyslipidemia and hyperglycaemia. Stavudine based regimen is associated with hypertriglyceridiemia and low HDL along with lipoatrophy of face.

  3. Methionine Metabolism Alters Oxidative Stress Resistance via the Pentose Phosphate Pathway.

    Science.gov (United States)

    Campbell, Kate; Vowinckel, Jakob; Keller, Markus A; Ralser, Markus

    2016-04-01

    Nutrient uptake and metabolism have a significant impact on the way cells respond to stress. The amino acid methionine is, in particular, a key player in the oxidative stress response, and acting as a reactive oxygen species scavenger, methionine is implicated in caloric restriction phenotypes and aging. We here provide evidence that some effects of methionine in stress situations are indirect and caused by altered activity of the nicotinamide adenine dinucleotide phosphate (NADPH) producing oxidative part of the pentose phosphate pathway (PPP). In Saccharomyces cerevisiae, both methionine prototrophic (MET15) and auxotrophic (met15Δ) cells supplemented with methionine showed an increase in PPP metabolite concentrations downstream of the NADPH producing enzyme, 6-phosphogluconate dehydrogenase. Proteomics revealed this enzyme to also increase in expression compared to methionine self-synthesizing cells. Oxidant tolerance was increased in cells preincubated with methionine; however, this effect was abolished when flux through the oxidative PPP was prevented by deletion of its rate limiting enzyme, ZWF1. Stress resistance phenotypes that follow methionine supplementation hence involve the oxidative PPP. Effects of methionine on oxidative metabolism, stress signaling, and aging have thus to be seen in the context of an altered activity of this NADP reducing pathway.

  4. Oxidative Stress and Metabolic Syndrome: Cause or Consequence of Alzheimer's Disease?

    Directory of Open Access Journals (Sweden)

    Diana Luque-Contreras

    2014-01-01

    Full Text Available Alzheimer’s disease (AD is a major neurodegenerative disease affecting the elderly. Clinically, it is characterized by a progressive loss of memory and cognitive function. Neuropathologically, it is characterized by the presence of extracellular β-amyloid (Aβ deposited as neuritic plaques (NP and neurofibrillary tangles (NFT made of abnormal and hyperphosphorylated tau protein. These lesions are capable of generating the neuronal damage that leads to cell death and cognitive failure through the generation of reactive oxygen species (ROS. Evidence indicates the critical role of Aβ metabolism in prompting the oxidative stress observed in AD patients. However, it has also been proposed that oxidative damage precedes the onset of clinical and pathological AD symptoms, including amyloid-β deposition, neurofibrillary tangle formation, vascular malfunction, metabolic syndrome, and cognitive decline. This paper provides a brief description of the three main proteins associated with the development of the disease (Aβ, tau, and ApoE and describes their role in the generation of oxidative stress. Finally, we describe the mitochondrial alterations that are generated by Aβ and examine the relationship of vascular damage which is a potential prognostic tool of metabolic syndrome. In addition, new therapeutic approaches targeting ROS sources and metabolic support were reported.

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

    Science.gov (United States)

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

    2013-10-01

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

  6. Metabolic acidosis

    Science.gov (United States)

    Acidosis - metabolic ... Metabolic acidosis occurs when the body produces too much acid. It can also occur when the kidneys are not ... the body. There are several types of metabolic acidosis. Diabetic acidosis develops when acidic substances, known as ...

  7. Oxidative stress indicators and metabolic adaptations in response to the omission of the dry period in dairy cows.

    Science.gov (United States)

    Mantovani, Roberto; Sgorlon, Sandy; Marinelli, Lieta; Bailoni, Lucia; Bittante, Giovanni; Gabai, Gianfranco

    2010-08-01

    The effects of dry period omission on oxidative stress and metabolic indicators around calving were studied. Seventeen Italian Friesian cows were randomly assigned to two groups, homogeneous for milk yield and parity, and managed either with a traditional 55-d dry off period (n=8) or continuously milked till parturition (n=9). Between 60 d before expected calving and 90 d after calving, body condition (BCS) was recorded and blood samples were collected to measure cortisol, urea, cholesterol, glucose, NEFA, triglycerides, insulin, malondialdehyde (MDA), total glutathione (GSH) and glutathione peroxidase (GPx) activity. BCS changes after calving were not different between the two groups. The normally dried group showed lower (Pmilked cows after calving (Pmilking up to parturition (Pmilk secretion. The differences in plasma GSH observed after calving may depend upon sulphur amino acid sparing in continuously milked cows.

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

    Science.gov (United States)

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

    2013-01-27

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

  9. The effect of body weight changes and endurance training on 24h substrate oxidation

    NARCIS (Netherlands)

    Pasman, W.J.; Westerterp-Plantenga, M.S.; Saris, W.H.M.

    1999-01-01

    The effect of body weight changes and endurance training on 24h substrate oxidation. Pasman WJ, Westerterp MS, Saris WH. Maastricht University, Department of Human Biology, The Netherlands. Pasman@voeding.tno.nl OBJECTIVE: To investigate the effect of exercise training and dietary macronutrient comp

  10. Metabolism evaluation of the anticancer candidate AC04 by biomimetic oxidative model and rat liver microsomes.

    Science.gov (United States)

    Pigatto, Maiara Cássia; Alves de Lima, Maria do Carmo; Galdino, Suely Lins; Pitta, Ivan da Rocha; Vessecchi, Ricardo; Assis, Marilda das Dores; dos Santos, Joicy Santamalvina; Dalla Costa, Teresa; Lopes, Norberto Peporine

    2011-09-01

    Jacobsen reagents, in the presence of monooxygen donors, appear as an alternative to produce metabolites from biological active compounds. This reaction may mimic the oxidation and oxygenation reactions of cytochrome P450 (CYP450) enzymes upon various drugs and biologically active compounds. Acridines represent a well-known group of polyaromatic compounds capable of acting as DNA intercalating agents. Viewing to search for new anticancer agents, one promising new acridine, the 5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-thiazolidine-2,4-dione (AC04) (2), has been studied by our group and the in vitro metabolism was investigated in this work, aiming to advance in the pre-clinical pharmacokinetic investigation. A systematic investigation of the gas-phase reaction, supported by computational chemistry, of the AC04 (2) was studied to help the structure elucidation of possible in vivo metabolites. To confirm the methodology, the oxidized product was obtained in large scale for NMR analysis and the data confirmed the structure. In addition, AC04 (2) was submitted to an in vitro metabolism assay employing rat liver microsomes and also, a pilot study was conducted in rats after AC04 intravenous (i.v.) dosing of 1.5 mg/kg. A single oxidized product was obtained from microsomal metabolism and detected in rat plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis corresponding to the same product formed by Jacobsen-catalyzed reaction. These results indicate that Jacobsen oxidation reactions, combined with in vitro metabolism assays employing isolated microsomes, might replace some in vivo metabolism studies, thus reducing the use of animals in new chemical entities pre-clinical investigation.

  11. Multiple controls of oxidative metabolism in living tissues as studied by phosphorus magnetic resonance.

    Science.gov (United States)

    Chance, B; Leigh, J S; Kent, J; McCully, K; Nioka, S; Clark, B J; Maris, J M; Graham, T

    1986-12-01

    Three types of metabolic control of oxidative metabolism are observed in the various tissues that have been studied by phosphorous magnetic resonance spectroscopy. The principal control of oxidative metabolism in skeletal muscle is by ADP (or Pi/phosphocreatine). This conclusion is based upon studies of arm muscles of humans during steady-state exercise. A work-cost (Vm vs. Pi/phosphocreatine) relationship follows a Michaelis-Menten rectangular hyperbola, where Km values from 0.5 to 0.6 and Vmax values from 50 to 200 (at nearly constant pH) are found in linearized plots of the equation V/Vmax = 1/(1 + 0.6 phosphocreatine/Pi) where V is work level (which is equal to the velocity of the enzymatic reaction) and Vmax is the maximal work capacity that is a measure of the enzyme activity (E) of oxidative metabolism. Adaptation to exercise enhances the slope of the work-cost relationship and causes large changes in Vmax or E. A second metabolic control may enhance the slope of the work-cost relationship but not Vmax. For example, the initiation of exercise can lead to an improved characteristic that can be explained by 2-fold increased substrate delivery, for example, increased oxygen delivery by microcirculatory control. Cardiac tissue of the adult dog affords an example of optimal endurance performance adaptation and exhibits the steepest work-cost relationship observed and is attributed to a coordinated control of substrate delivery that may involve Ca2+ and inorganic phosphate control of NADH; control of O2 delivery may also be involved. The calculated work-cost relationship is similar to that observed in the beagle heart. The theoretical curve illustrates that the liability of multiple controls is a sharp break point in metabolic control at the end of the multiple control range--a possible cause of instability of cardiac performance at high V/Vmax.

  12. Selective Impairment of Glucose but Not Fatty Acid or Oxidative Metabolism in Brown Adipose Tissue of Subjects With Type 2 Diabetes.

    Science.gov (United States)

    Blondin, Denis P; Labbé, Sébastien M; Noll, Christophe; Kunach, Margaret; Phoenix, Serge; Guérin, Brigitte; Turcotte, Éric E; Haman, François; Richard, Denis; Carpentier, André C

    2015-07-01

    Spontaneous glucose uptake by brown adipose tissue (BAT) is lower in overweight or obese individuals and in diabetes. However, BAT metabolism has not been previously investigated in patients with type 2 diabetes during controlled cold exposure. Using positron emission tomography with (11)C-acetate, (18)F-fluoro-deoxyglucose ((18)FDG), and (18)F-fluoro-thiaheptadecanoic acid ((18)FTHA), a fatty acid tracer, BAT oxidative metabolism and perfusion and glucose and nonesterified fatty acid (NEFA) turnover were determined in men with well-controlled type 2 diabetes and age-matched control subjects under experimental cold exposure designed to minimize shivering. Despite smaller volumes of (18)FDG-positive BAT and lower glucose uptake per volume of BAT compared with young healthy control subjects, cold-induced oxidative metabolism and NEFA uptake per BAT volume and an increase in total body energy expenditure did not differ in patients with type 2 diabetes or their age-matched control subjects. The reduction in (18)FDG-positive BAT volume and BAT glucose clearance were associated with a reduction in BAT radiodensity and perfusion. (18)FDG-positive BAT volume and the cold-induced increase in BAT radiodensity were associated with an increase in systemic NEFA turnover. These results show that cold-induced NEFA uptake and oxidative metabolism are not defective in type 2 diabetes despite reduced glucose uptake per BAT volume and BAT "whitening."

  13. Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets.

    Science.gov (United States)

    Apontes, Pasha; Liu, Zhongbo; Su, Kai; Benard, Outhiriaradjou; Youn, Dou Y; Li, Xisong; Li, Wei; Mirza, Raihan H; Bastie, Claire C; Jelicks, Linda A; Pessin, Jeffrey E; Muzumdar, Radhika H; Sauve, Anthony A; Chi, Yuling

    2014-11-01

    Excessive dietary fat intake causes systemic metabolic toxicity, manifested in weight gain, hyperglycemia, and insulin resistance. In addition, carbohydrate utilization as a fuel is substantially inhibited. Correction or reversal of these effects during high-fat diet (HFD) intake is of exceptional interest in light of widespread occurrence of diet-associated metabolic disorders in global human populations. Here we report that mangiferin (MGF), a natural compound (the predominant constituent of Mangifera indica extract from the plant that produces mango), protected against HFD-induced weight gain, increased aerobic mitochondrial capacity and thermogenesis, and improved glucose and insulin profiles. To obtain mechanistic insight into the basis for these effects, we determined that mice exposed to an HFD combined with MGF exhibited a substantial shift in respiratory quotient from fatty acid toward carbohydrate utilization. MGF treatment significantly increased glucose oxidation in muscle of HFD-fed mice without changing fatty acid oxidation. These results indicate that MGF redirects fuel utilization toward carbohydrates. In cultured C2C12 myotubes, MGF increased glucose and pyruvate oxidation and ATP production without affecting fatty acid oxidation, confirming in vivo and ex vivo effects. Furthermore, MGF inhibited anaerobic metabolism of pyruvate to lactate but enhanced pyruvate oxidation. A key target of MGF appears to be pyruvate dehydrogenase, determined to be activated by MGF in a variety of assays. These findings underscore the therapeutic potential of activation of carbohydrate utilization in correction of metabolic syndrome and highlight the potential of MGF to serve as a model compound that can elicit fuel-switching effects.

  14. A many-body potential approach to modelling the thermomechanical properties of actinide oxides.

    Science.gov (United States)

    Cooper, M W D; Rushton, M J D; Grimes, R W

    2014-03-12

    A many-body potential model for the description of actinide oxide systems, which is robust at high temperatures, is reported for the first time. The embedded atom method is used to describe many-body interactions ensuring good reproduction of a range of thermophysical properties (lattice parameter, bulk modulus, enthalpy and specific heat) between 300 and 3000 K for AmO2, CeO2, CmO2, NpO2, ThO2, PuO2 and UO2. Additionally, the model predicts a melting point for UO2 between 3000 and 3100 K, in close agreement with experiment. Oxygen-oxygen interactions are fixed across the actinide oxide series because it facilitates the modelling of oxide solid solutions. The new potential is also used to predict the energies of Schottky and Frenkel pair disorder processes.

  15. Mechanisms of formation and function of eosinophil lipid bodies: inducible intracellular sites involved in arachidonic acid metabolism

    Directory of Open Access Journals (Sweden)

    Bozza Patricia T

    1997-01-01

    Full Text Available Lipid bodies, inducible lipid-rich cytoplasmic inclusions, are characteristically abundant in cells associated with inflammation, including eosinophils. Here we reviewed the formation and function of lipid bodies in human eosinophils. We now have evidence that the formation of lipid bodies is not attributable to adverse mechanisms, but is centrally mediated by specific signal transduction pathways. Arachidonic acid and other cis fatty acids by an NSAID-inhibitable process, diglycerides, and PAF by a 5-lipoxygenase dependent pathway are potent stimulators of lipid body induction. Lipid body formation develops rapidly by processes that involve PKC, PLC, and de novo mRNA and protein synthesis. These structures clearly serve as repositoires of arachidonyl-phospholipids and are more than inert depots. Specific enzymes, including cytosolic phospholipase A2, MAP kinases, lipoxygenases and cyclooxygenases, associate with lipid bodies. Lipid bodies appear to be dynamic, organelle-like structures involved in intracellular pathways of lipid mobilization and metabolism. Indeed, increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. We hypothesize that lipid bodies are distinct inducible sites for generating eicosanoids as paracrine mediators with varied activities in inflammation. The capacity of lipid body formation to be specifically and rapidly induced in leukocytes enhances eicosanoid mediator formation, and conversely pharmacologic inhibition of lipid body induction represents a potential novel and specific target for anti-inflammatory therapy.

  16. Oxidative bioelectrocatalysis: From natural metabolic pathways to synthetic metabolons and minimal enzyme cascades.

    Science.gov (United States)

    Minteer, Shelley D

    2016-05-01

    Anodic bioelectrodes for biofuel cells are more complex than cathodic bioelectrodes for biofuel cells, because laccase and bilirubin oxidase can individually catalyze four electron reduction of oxygen to water, whereas most anodic enzymes only do a single two electron oxidation of a complex fuel (i.e. glucose oxidase oxidizing glucose to gluconolactone while generating 2 electrons of the total 24 electrons), so enzyme cascades are typically needed for complete oxidation of the fuel. This review article will discuss the lessons learned from natural metabolic pathways about multi-step oxidation and how those lessons have been applied to minimal or artificial enzyme cascades. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson.

  17. FTO gene associated fatness in relation to body fat distribution and metabolic traits throughout a broad range of fatness

    DEFF Research Database (Denmark)

    Kring, Sofia I I; Holst, Claus; Zimmermann, Esther;

    2008-01-01

    A common single nucleotide polymorphism (SNP) of FTO (rs9939609, T/A) is associated with total body fatness. We investigated the association of this SNP with abdominal and peripheral fatness and obesity-related metabolic traits in middle-aged men through a broad range of fatness present already...

  18. IMPACT OF GENETIC STRAIN ON BODY FAT LOSS, FOOD CONSUMPTION, METABOLISM, VENTILATION, AND MOTOR ACTIVITY IN FREE RUNNING FEMALE RATS

    Science.gov (United States)

    Physiologic data associated with different strains of common laboratory rat strains.This dataset is associated with the following publication:Gordon , C., P. Phillips , and A. Johnstone. Impact of Genetic Strain on Body Fat Loss, Food Consumption, Metabolism, Ventilation, and Motor Activity in Free Running Female Rats. PHYSIOLOGY AND BEHAVIOR. Elsevier Science Ltd, New York, NY, USA, 153: 56-63, (2016).

  19. Abomasal amino acid infusion in postpartum dairy cows: Effect on whole-body, splanchnic, and mammary glucose metabolism

    DEFF Research Database (Denmark)

    Galindo, C; Larsen, Mogens; Ouellet, D R

    2015-01-01

    Nine Holstein cows fitted with rumen cannulas and indwelling catheters in splanchnic blood vessels were used to study the effects of supplementing AA on milk lactose secretion, whole-body rate of appearance (WB-Ra) of glucose, and tissue metabolism of glucose, lactate, glycerol, and β-OH-butyrate...

  20. Polycyclic Aromatic Hydrocarbon Metabolism by White Rot Fungi and Oxidation by Coriolopsis gallica UAMH 8260 Laccase

    Science.gov (United States)

    Pickard, Michael A.; Roman, Rosa; Tinoco, Raunel; Vazquez-Duhalt, Rafael

    1999-01-01

    We studied the metabolism of polycyclic aromatic hydrocarbons (PAHs) by using white rot fungi previously identified as organisms that metabolize polychlorinated biphenyls. Bran flakes medium, which has been shown to support production of high levels of laccase and manganese peroxidase, was used as the growth medium. Ten fungi grown for 5 days in this medium in the presence of anthracene, pyrene, or phenanthrene, each at a concentration of 5 μg/ml could metabolize these PAHs. We studied the oxidation of 10 PAHs by using laccase purified from Coriolopsis gallica. The reaction mixtures contained 20 μM PAH, 15% acetonitrile in 60 mM phosphate buffer (pH 6), 1 mM 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS), and 5 U of laccase. Laccase exhibited 91% of its maximum activity in the absence of acetonitrile. The following seven PAHs were oxidized by laccase: benzo[a]pyrene, 9-methylanthracene, 2-methylanthracene, anthracene, biphenylene, acenaphthene, and phenanthrene. There was no clear relationship between the ionization potential of the substrate and the first-order rate constant (k) for substrate loss in vitro in the presence of ABTS. The effects of mediating substrates were examined further by using anthracene as the substrate. Hydroxybenzotriazole (HBT) (1 mM) supported approximately one-half the anthracene oxidation rate (k = 2.4 h−1) that ABTS (1 mM) supported (k = 5.2 h−1), but 1 mM HBT plus 1 mM ABTS increased the oxidation rate ninefold compared with the oxidation rate in the presence of ABTS, to 45 h−1. Laccase purified from Pleurotus ostreatus had an activity similar to that of C. gallica laccase with HBT alone, with ABTS alone, and with 1 mM HBT plus 1 mM ABTS. Mass spectra of products obtained from oxidation of anthracene and acenaphthene revealed that the dione derivatives of these compounds were present. PMID:10473379

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

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Kayo [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Education and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Hartman, Philip S. [Biology Department, Texas Christian University, Fort Worth, TX 76129 (United States); Ishii, Takamasa [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Suda, Hitoshi [School of High-Technology for Human Welfare, Tokai University, Nishino 317, Numazu, Shizuoka 410-0395 (Japan); Akatsuka, Akira [Education and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Shoyama, Tetsuji [School of High-Technology for Human Welfare, Tokai University, Nishino 317, Numazu, Shizuoka 410-0395 (Japan); Miyazawa, Masaki [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Ishii, Naoaki, E-mail: nishii@is.icc.u-tokai.ac.jp [Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan)

    2011-01-21

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

  2. The Emerging Nexus of Active DNA Demethylation and Mitochondrial Oxidative Metabolism in Post-Mitotic Neurons

    Directory of Open Access Journals (Sweden)

    Huan Meng

    2014-12-01

    Full Text Available The variable patterns of DNA methylation in mammals have been linked to a number of physiological processes, including normal embryonic development and disease pathogenesis. Active removal of DNA methylation, which potentially regulates neuronal gene expression both globally and gene specifically, has been recently implicated in neuronal plasticity, learning and memory processes. Model pathways of active DNA demethylation involve ten-eleven translocation (TET methylcytosine dioxygenases that are dependent on oxidative metabolites. In addition, reactive oxygen species (ROS and oxidizing agents generate oxidative modifications of DNA bases that can be removed by base excision repair proteins. These potentially link the two processes of active DNA demethylation and mitochondrial oxidative metabolism in post-mitotic neurons. We review the current biochemical understanding of the DNA demethylation process and discuss its potential interaction with oxidative metabolism. We then summarise the emerging roles of both processes and their interaction in neural plasticity and memory formation and the pathophysiology of neurodegeneration. Finally, possible therapeutic approaches for neurodegenerative diseases are proposed, including reprogramming therapy by global DNA demethylation and mitohormesis therapy for locus-specific DNA demethylation in post-mitotic neurons.

  3. Developmental Ethanol Exposure Leads to Dysregulation of Lipid Metabolism and Oxidative Stress in Drosophila

    Science.gov (United States)

    Logan-Garbisch, Theresa; Bortolazzo, Anthony; Luu, Peter; Ford, Audrey; Do, David; Khodabakhshi, Payam; French, Rachael L.

    2014-01-01

    Ethanol exposure during development causes an array of developmental abnormalities, both physiological and behavioral. In mammals, these abnormalities are collectively known as fetal alcohol effects (FAE) or fetal alcohol spectrum disorder (FASD). We have established a Drosophila melanogaster model of FASD and have previously shown that developmental ethanol exposure in flies leads to reduced expression of insulin-like peptides (dILPs) and their receptor. In this work, we link that observation to dysregulation of fatty acid metabolism and lipid accumulation. Further, we show that developmental ethanol exposure in Drosophila causes oxidative stress, that this stress is a primary cause of the developmental lethality and delay associated with ethanol exposure, and, finally, that one of the mechanisms by which ethanol increases oxidative stress is through abnormal fatty acid metabolism. These data suggest a previously uncharacterized mechanism by which ethanol causes the symptoms associated with FASD. PMID:25387828

  4. The effect of normobaric hypoxic confinement on metabolism, gut hormones and body composition

    Directory of Open Access Journals (Sweden)

    Igor B. Mekjavic

    2016-06-01

    Full Text Available To assess the effect of normobaric hypoxia on metabolism, gut hormones and body composition, eleven normal weight, aerobically trained ( O2peak: 60.6±9.5 ml·kg-1·min-1 men (73.0±7.7 kg; 23.7±4.0 yrs, BMI 22.2±2.4 kg·m-2 were confined to a normobaric (altitude⋍940m normoxic (NORMOXIA; PIO2⋍133.2 mmHg or normobaric hypoxic (HYPOXIA; PIO was reduced from 105.6 to 97.7 mmHg over 10 days environment for 10 days in a randomized cross-over design. The wash-out period between confinements was 3 weeks. During each 10-day period, subjects avoided strenuous physical activity and were under continuous nutritional control. Before, and at the end of each exposure, subjects completed a meal tolerance test, during which blood glucose, insulin, GLP-1, ghrelin, peptide-YY, adrenaline, noradrenaline, leptin, and gastro-intestinal blood flow and appetite sensations were measured. There was no significant change in body weight in either of the confinements (NORMOXIA: -0.7±0.2 kg; HYPOXIA: -0.9±0.2 kg, but a significant increase in fat mass in NORMOXIA (0.23±0.45 kg, but not in HYPOXIA (0.08±0.08 kg. HYPOXIA confinement increased fasting noradrenaline and decreased energy intake, the latter most likely associated with increased fasting leptin. The majority of all other measured variables/responses were similar in NORMOXIA and HYPOXIA. To conclude, normobaric hypoxic confinement without exercise training results in negative energy balance due to primarily reduced energy intake.

  5. Computer-aided prediction of xenobiotic metabolism in the human body

    Science.gov (United States)

    Bezhentsev, V. M.; Tarasova, O. A.; Dmitriev, A. V.; Rudik, A. V.; Lagunin, A. A.; Filimonov, D. A.; Poroikov, V. V.

    2016-08-01

    The review describes the major databases containing information about the metabolism of xenobiotics, including data on drug metabolism, metabolic enzymes, schemes of biotransformation and the structures of some substrates and metabolites. Computational approaches used to predict the interaction of xenobiotics with metabolic enzymes, prediction of metabolic sites in the molecule, generation of structures of potential metabolites for subsequent evaluation of their properties are considered. The advantages and limitations of various computational methods for metabolism prediction and the prospects for their applications to improve the safety and efficacy of new drugs are discussed. Bibliography — 165 references.

  6. Obesity and oxidative stress: potential roles of melatonin as antioxidant and metabolic regulator.

    Science.gov (United States)

    Bonnefont-Rousselot, Dominique

    2014-01-01

    Obesity is associated with an oxidative stress status, defined as an excessive production of reactive oxygen species (ROS) compared to the level of antioxidants acting in the natural defence systems. Several sources of ROS can be identified in obesity (e.g., mitochondrial respiratory chain, or NADPH oxidase) and could contribute to the pathogenesis of obesity. Indeed, these conditions favour the development of insulin resistance and metabolic syndrome through deregulation of adipokines and pro-inflammatory cytokines, so that it could be of interest to associate antioxidant therapeutic strategies with strategies of weight loss. Among antioxidants, melatonin holds a special place, on the one hand for its antioxidant and anti-inflammatory properties, and on the other hand for its role as a metabolic regulator. As melatonin modulates several processes involved in obesity and its related metabolic alterations, it could have a therapeutic interest in the treatment of obesity.

  7. Purine metabolism and oxidative stress in children with autistic spectrum disorders

    Directory of Open Access Journals (Sweden)

    Faisal Gh. Al-Rubaye

    2013-08-01

    Results: Serum ADA and SOD were significantly lower in boys with autism accompanied by significant higher serum MDA levels when compared with controls. Conclusion: Patients with ASD have impaired purine metabolism and increased oxidative stress which was supported by low levels of ADA and SOD, and high level of MDA. Further biochemical or genetic studies are required to explore the nature of autism. [J Exp Integr Med 2013; 3(4.000: 293-297

  8. Creatine Supplementation Increases Total Body Water in Soccer Players: a Deuterium Oxide Dilution Study.

    Science.gov (United States)

    Deminice, R; Rosa, F T; Pfrimer, K; Ferrioli, E; Jordao, A A; Freitas, E

    2016-02-01

    This study aimed to evaluate changes in total body water (TBW) in soccer athletes using a deuterium oxide dilution method and bioelectrical impedance (BIA) formulas after 7 days of creatine supplementation. In a double-blind controlled manner, 13 healthy (under-20) soccer players were divided randomly in 2 supplementation groups: Placebo (Pla, n=6) and creatine supplementation (CR, n=7). Before and after the supplementation period (0.3 g/kg/d during 7 days), TBW was determined by deuterium oxide dilution and BIA methods. 7 days of creatine supplementation lead to a large increase in TBW (2.3±1.0 L) determined by deuterium oxide dilution, and a small but significant increase in total body weight (1.0±0.4 kg) in Cr group compared to Pla. The Pla group did not experience any significant changes in TBW or body weight. Although 5 of 6 BIA equations were sensitive to determine TBW changes induced by creatine supplementation, the Kushner et al. 16 method presented the best concordance levels when compared to deuterium dilution method. In conclusion, 7-days of creatine supplementation increased TBW determined by deuterium oxide dilution or BIA formulas. BIA can be useful to determine TBW changes promoted by creatine supplementation in soccer athletes, with special concern for formula choice.

  9. Soil carbon dioxide emissions controlled by an extracellular oxidative metabolism identifiable by its isotope signature

    Science.gov (United States)

    Kéraval, Benoit; Lehours, Anne Catherine; Colombet, Jonathan; Amblard, Christian; Alvarez, Gaël; Fontaine, Sébastien

    2016-11-01

    Soil heterotrophic respiration is a major determinant of the carbon (C) cycle and its interactions with climate. Given the complexity of the respiratory machinery, it is traditionally considered that oxidation of organic C into carbon dioxide (CO2) strictly results from intracellular metabolic processes. Here we show that C mineralization can operate in soils deprived of all observable cellular forms. Moreover, the process responsible for CO2 emissions in sterilized soils induced a strong C isotope fractionation (up to 50 ‰) incompatible with respiration of cellular origin. The supply of 13C glucose in sterilized soil led to the release of 13CO2 suggesting the presence of respiratory-like metabolism (glycolysis, decarboxylation reaction, chain of electron transfer) carried out by soil-stabilized enzymes, and by soil mineral and metal catalysts. These findings indicate that CO2 emissions from soils can have two origins: (1) from the well-known respiration of soil heterotrophic microorganisms and (2) from an extracellular oxidative metabolism (EXOMET) or, at least, catabolism. These two metabolisms should be considered separately when studying effects of environmental factors on the C cycle because the likelihood is that they do not obey the same laws and they respond differently to abiotic factors.

  10. Increasing NAD synthesis in muscle via nicotinamide phosphoribosyltransferase is not sufficient to promote oxidative metabolism.

    Science.gov (United States)

    Frederick, David W; Davis, James G; Dávila, Antonio; Agarwal, Beamon; Michan, Shaday; Puchowicz, Michelle A; Nakamaru-Ogiso, Eiko; Baur, Joseph A

    2015-01-16

    The NAD biosynthetic precursors nicotinamide mononucleotide and nicotinamide riboside are reported to confer resistance to metabolic defects induced by high fat feeding in part by promoting oxidative metabolism in skeletal muscle. Similar effects are obtained by germ line deletion of major NAD-consuming enzymes, suggesting that the bioavailability of NAD is limiting for maximal oxidative capacity. However, because of their systemic nature, the degree to which these interventions exert cell- or tissue-autonomous effects is unclear. Here, we report a tissue-specific approach to increase NAD biosynthesis only in muscle by overexpressing nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway that converts nicotinamide to NAD (mNAMPT mice). These mice display a ∼50% increase in skeletal muscle NAD levels, comparable with the effects of dietary NAD precursors, exercise regimens, or loss of poly(ADP-ribose) polymerases yet surprisingly do not exhibit changes in muscle mitochondrial biogenesis or mitochondrial function and are equally susceptible to the metabolic consequences of high fat feeding. We further report that chronic elevation of muscle NAD in vivo does not perturb the NAD/NADH redox ratio. These studies reveal for the first time the metabolic effects of tissue-specific increases in NAD synthesis and suggest that critical sites of action for supplemental NAD precursors reside outside of the heart and skeletal muscle.

  11. Metabolic and oxidative status of Saanen goats of different parity during the peripartum period.

    Science.gov (United States)

    Radin, Lada; Šimpraga, Miljenko; Vince, Silvijo; Kostelić, Antun; Milinković-Tur, Suzana

    2015-11-01

    The aim of this study was to research changes in metabolic and antioxidative status of Saanen goats of different parity occurring during the peripartum period. Blood samples were taken on 10-7 and 3-1 d prepartally and 1-3, 14 and 28 d postpartally from goats allocated in three groups according to their parity: primiparous (PRIM), goats that kidded the 2nd or 3rd time (MID), and goats that kidded 4 or more times (MULTI)). Metabolic profile parameters (non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), glucose, triglycerides, albumin and urea) and indicators of oxidative stress ((superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA)) were determined. Intense metabolic changes associated with late pregnancy and onset of lactation were pronounced the most in MULTI goats that also had the biggest litter per goat. Significant differences were found in metabolic parameters NEFA, BHB, glucose, triglycerides within groups during peripartum period, as well as between them (the effect of parity). MDA concentrations were indicative of increased lipid peroxidation around parturition, especially pronounced in MULTI group 1-3 d prepartally, when the highest GSH-Px/SOD ratio was also found. Postpartally, antioxidant enzymes ratio in MID and MULTI group decreased while MDA concentrations remained high, suggesting antioxidant system inefficiency. Significant time × group interaction was observed for most of the parameters. The obtained results show that the goats of higher parity display higher levels of metabolism intensity and consequently, varying levels of oxidative stress during the peripartum period. Further studies should determine applicability of NEFA and BHB in periparturient metabolic profiling in dairy goats as well as establish normal ranges and cut-off levels for these biomarkers.

  12. Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism

    DEFF Research Database (Denmark)

    Mourtzakis, M.; Graham, T.E.; Gonzalez-Alonso, J.;

    2008-01-01

    Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops approximately 40-80% with the onset of exercise and 2-oxoglutarate...... declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70......% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (VO2peak) in the T thigh was greater than that in the UT thigh (Pglutamate infusion. Peak...

  13. The role of oxidative stress on the pathophysiology of metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Fabiane Valentini Francisqueti

    Full Text Available Summary Metabolic syndrome (MetS has a high prevalence around the world. Considering the components used to classify MetS, it is clear that it is closely related to obesity. These two conditions begin with an increase in abdominal adipose tissue, which is metabolically more active, containing a greater amount of resident macrophages compared to other fat deposits. Abdominal adiposity promotes inflammation and oxidative stress, which are precursors of various complications involving MetS components, namely insulin resistance, hypertension and hyperlipidemia. One way to block the effects of oxidative stress would be through the antioxidant defense system, which offsets the excess free radicals. It is known that individuals with metabolic syndrome and obesity have high consumption of fats and sugars originated from processed foods containing high levels of sodium as well as low intake of fruits and vegetables, thus maintaining a state of oxidative stress, that can speed up the onset of MetS. Healthy eating habits could prevent or delay MetS by adding antioxidant-rich foods into the diet.

  14. HPLC analysis of in vivo intestinal absorption and oxidative metabolism of salicylic acid in the rat.

    Science.gov (United States)

    Kuzma, Mónika; Nyúl, Eszter; Mayer, Mátyás; Fischer, Emil; Perjési, Pál

    2016-12-01

    In vivo absorption and oxidative metabolism of salicylic acid in rat small intestine was studied by luminal perfusion experiment. Perfusion through the lumen of proximal jejunum with isotonic medium containing 250 μm sodium salicylate was carried out. Absorption of salicylate was measured by a validated HPLC-DAD method which was evaluated for a number of validation characteristics (specificity, repeatability and intermediate precision, limit of detection, limit of quantification, linearity and accuracy). The method was linear over the concentration range 0.5-50 μg/mL. After liquid-liquid extraction of the perfusion samples oxidative biotransformation of salicylate was also investigated by HPLC-MS. The method was linear over the concentration range 0.25-5.0 μg/mL. Two hydroxylated metabolites of salicylic acid (2,5-dihydroxybenzoic acid and 2,3-dihydroxybenzoic acid) were detected and identified. The mean recovery of extraction was 72.4% for 2,3-DHB, 72.5% for 2,5-DHB and 50.1% for salicylic acid, respectively. The methods were successfully applied to investigate jejunal absorption and oxidative metabolism of sodium salicylate in experimental animals. The methods provide analytical background for further metabolic studies of salycilates under modified physiological conditions.

  15. OPTIMIZATION OF THE HUMAN DIET TO MAINTAIN BODY WEIGHT, TAKING INTO ACCOUNT DIFFERENT TYPES OF METABOLISM

    Directory of Open Access Journals (Sweden)

    Sidorko N. K.

    2015-01-01

    Full Text Available A diet of a modern man affects the formation of a healthy lifestyle very highly. It supplies the body with the main and irreplaceable nutrients, mineral components and energy. The Russian Federation population surveys, which were carried out by government agencies of the country show us that there is a lack of many nutrients with high nutritional value. Russian market is gradually stuffed with food products which have high nutritional value. For the maintenance of health, active longevity, and for improving their performance, people must consume their organism with all the necessary nutrients. That's why achieving an optimal balance among the nutrients is one of the important question of vital activity. In this article, there were considered optimization approaches to human diet with considering different types of metabolism and maintain weight with using economic and mathematical methods. Also in this article you can find the calculated values of the daily values depending on your calorie eating plan, anthropometric parameters and energy expenditure. We obtained daily value of calories and distributed basic food components- carbohydrates, proteins and fats, and also we calculate the optimal diet for the results of each type of physique - ectomorph, endomorph and mesomorph

  16. Whole Body Vibration Exercises and the Improvement of the Flexibility in Patient with Metabolic Syndrome

    Science.gov (United States)

    Sá-Caputo, Danúbia da Cunha; Ronikeili-Costa, Pedro; Carvalho-Lima, Rafaelle Pacheco; Bernardo, Luciana Camargo; Bravo-Monteiro, Milena Oliveira; Costa, Rebeca; de Moraes-Silva, Janaina; Paiva, Dulciane Nunes; Machado, Christiano Bittencourt; Mantilla-Giehl, Paula; Arnobio, Adriano; Marin, Pedro Jesus; Bernardo-Filho, Mario

    2014-01-01

    Vibrations produced in oscillating/vibratory platform generate whole body vibration (WBV) exercises, which are important in sports, as well as in treating diseases, promoting rehabilitation, and improving the quality of life. WBV exercises relevantly increase the muscle strength, muscle power, and the bone mineral density, as well as improving the postural control, the balance, and the gait. An important number of publications are found in the PubMed database with the keyword “flexibility” and eight of the analyzed papers involving WBV and flexibility reached a level of evidence II. The biggest distance between the third finger of the hand to the floor (DBTFF) of a patient with metabolic syndrome (MS) was found before the first session and was considered to be 100%. The percentages to the other measurements in the different sessions were determined to be related to the 100%. It is possible to see an immediate improvement after each session with a decrease of the %DBTFF. As the presence of MS is associated with poorer physical performance, a simple and safe protocol using WBV exercises promoted an improvement of the flexibility in a patient with MS. PMID:25276434

  17. Whole Body Vibration Exercises and the Improvement of the Flexibility in Patient with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Danúbia da Cunha Sá-Caputo

    2014-01-01

    Full Text Available Vibrations produced in oscillating/vibratory platform generate whole body vibration (WBV exercises, which are important in sports, as well as in treating diseases, promoting rehabilitation, and improving the quality of life. WBV exercises relevantly increase the muscle strength, muscle power, and the bone mineral density, as well as improving the postural control, the balance, and the gait. An important number of publications are found in the PubMed database with the keyword “flexibility” and eight of the analyzed papers involving WBV and flexibility reached a level of evidence II. The biggest distance between the third finger of the hand to the floor (DBTFF of a patient with metabolic syndrome (MS was found before the first session and was considered to be 100%. The percentages to the other measurements in the different sessions were determined to be related to the 100%. It is possible to see an immediate improvement after each session with a decrease of the %DBTFF. As the presence of MS is associated with poorer physical performance, a simple and safe protocol using WBV exercises promoted an improvement of the flexibility in a patient with MS.

  18. Downregulation of nuclear-encoded genes of oxidative metabolism in dialyzed chronic kidney disease patients.

    Directory of Open Access Journals (Sweden)

    Gianluigi Zaza

    Full Text Available BACKGROUND: Mitochondria, essential eukaryotic cells organelles defined as the "powerhouse of the cell" because of their ability to produce the vast majority of energy necessary for cellular metabolism, may have a primary role in the oxidative stress-related intracellular machinery associated to chronic kidney disease (CKD. METHODS: To better assess this research assumption, we decided to study the key factors regulating mitochondrial oxidative metabolism in CKD patients in peritoneal dialysis (PD, n = 15 using several bio-molecular methodologies. RESULTS: RT-PCR experiments demonstrate that the expression level of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α and nuclear respiratory factor-1 (NRF-1, two genes primarily involved in mitochondrial biogenesis and functions, were significantly hypo-expressed in peripheral blood mononuclear cells of PD patients compared to healthy subjects (HS, n = 15. Additionally, mRNA levels of several PGC1-α downstream target genes (TFAM, COX6C,COX7C, UQCRH and MCAD were profoundly down-regulated in PD cells. TFAM protein analysis confirmed gene-expression results. High plasmatic concentration of Malondialdehyde found in PD patients, confirmed the contribution of the oxidative stress to these biological effects. Finally, Nuclear factor erythroid-derived 2-like 2 (NRF2 or NFE2L2, a transcription factor for numerous antioxidant/detoxifying enzymes and one of its target genes, superoxide dismutase-2 mitochondrial (SOD2 were up-regulated in PD compared to HS. CONCLUSIONS: Our results revealed, for the first time, that CKD-PD patients' PBMC, through a complex intracellular biochemical machinery, are able to modulate their mitochondrial functions probably in the attempt to reduce oxidative metabolic damage and to turn on a valuable defense cellular strategy against oxidative stress.

  19. AMP-Activated Protein Kinase Regulates Oxidative Metabolism in Caenorhabditis elegans through the NHR-49 and MDT-15 Transcriptional Regulators.

    Science.gov (United States)

    Moreno-Arriola, Elizabeth; El Hafidi, Mohammed; Ortega-Cuéllar, Daniel; Carvajal, Karla

    2016-01-01

    Cellular energy regulation relies on complex signaling pathways that respond to fuel availability and metabolic demands. Dysregulation of these networks is implicated in the development of human metabolic diseases such as obesity and metabolic syndrome. In Caenorhabditis elegans the AMP-activated protein kinase, AAK, has been associated with longevity and stress resistance; nevertheless its precise role in energy metabolism remains elusive. In the present study, we find an evolutionary conserved role of AAK in oxidative metabolism. Similar to mammals, AAK is activated by AICAR and metformin and leads to increased glycolytic and oxidative metabolic fluxes evidenced by an increase in lactate levels and mitochondrial oxygen consumption and a decrease in total fatty acids and lipid storage, whereas augmented glucose availability has the opposite effects. We found that these changes were largely dependent on the catalytic subunit AAK-2, since the aak-2 null strain lost the observed metabolic actions. Further results demonstrate that the effects due to AAK activation are associated to SBP-1 and NHR-49 transcriptional factors and MDT-15 transcriptional co-activator, suggesting a regulatory pathway that controls oxidative metabolism. Our findings establish C. elegans as a tractable model system to dissect the relationship between distinct molecules that play a critical role in the regulation of energy metabolism in human metabolic diseases.

  20. Beneficial effects of the RESMENA dietary pattern on oxidative stress in patients suffering from metabolic syndrome with hyperglycemia are associated to dietary TAC and fruit consumption.

    Science.gov (United States)

    de la Iglesia, Rocio; Lopez-Legarrea, Patricia; Celada, Paloma; Sánchez-Muniz, Francisco J; Martinez, J Alfredo; Zulet, M Angeles

    2013-01-01

    Hyperglycemia and oxidative stress are conditions directly related to the metabolic syndrome (MetS), whose prevalence is increasing worldwide. This study aimed to evaluate the effectiveness of a new weight-loss dietary pattern on improving the oxidative stress status on patients suffering MetS with hyperglycemia. Seventy-nine volunteers were randomly assigned to two low-calorie diets (-30% Energy): the control diet based on the American Health Association criteria and the RESMENA diet based on a different macronutrient distribution (30% proteins, 30% lipids, 40% carbohydrates), which was characterized by an increase of the meal frequency (seven-times/day), low glycemic load, high antioxidant capacity (TAC) and high n-3 fatty acids content. Dietary records, anthropometrical measurements, biochemical parameters and oxidative stress biomarkers were analyzed before and after the six-month-long study. The RESMENA (Metabolic Syndrome Reduction in Navarra) diet specifically reduced the android fat mass and demonstrated more effectiveness on improving general oxidative stress through a greater decrease of oxidized LDL (oxLDL) values and protection against arylesterase depletion. Interestingly, oxLDL values were associated with dietary TAC and fruit consumption and with changes on body mass index (BMI), waist circumference, fat mass and triacilglyceride (TG) levels. In conclusion, the antioxidant properties of the RESMENA diet provide further benefits to those attributable to weight loss on patients suffering Mets with hyperglycemia.

  1. Corrosion behavior of plasma electrolytically oxidized gamma titanium aluminide alloy in simulated body fluid.

    Science.gov (United States)

    Lara Rodriguez, L; Sundaram, P A

    2016-09-15

    Plasma electrolytic oxidized (PEO) γTiAl alloy samples were electrochemically characterized by open circuit potential (OCP), cyclic polarization and electrochemical impedance spectroscopy (EIS) to evaluate their corrosion resistance in simulated body fluid (SBF) in order to gauge their potential for biomedical applications. Experimental results through OCP and cyclic polarization studies demonstrated the protective nature and the beneficial effect of the PEO coatings on γTiAl. The PEO surface increased corrosion resistance of these surface modified alloys. EIS data indicated the presence of an underlying compact oxide layer with surface pores represented by two domes in the Nyquist plots. Electrical equivalent circuits to describe the EIS results are proposed.

  2. Plasma pH does not influence the cerebral metabolic ratio during maximal whole body exercise

    DEFF Research Database (Denmark)

    Volianitis, Stefanos; Rasmussen, Peter; Seifert, Thomas;

    2011-01-01

    Exercise lowers the cerebral metabolic ratio of O2 to carbohydrate (glucose + 1/2 lactate) and metabolic acidosis appears to promote cerebral lactate uptake. However, the influence of pH on cerebral lactate uptake and, in turn, on the cerebral metabolic ratio during exercise is not known. Sodium.......05) following the Sal and Bicarb trials, respectively. Accordingly, the cerebral metabolic ratio decreased equally during the Sal and Bicarb trials: from 5.8 ± 0.6 at rest to 1.7 ± 0.1 and 1.8 ± 0.2, respectively. The enlarged blood-buffering capacity after infusion of Bicarb eliminated metabolic acidosis...

  3. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

    Directory of Open Access Journals (Sweden)

    Elena Lima-Cabello

    2016-01-01

    Full Text Available Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.

  4. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

    Science.gov (United States)

    Lima-Cabello, Elena; Garcia-Guirado, Francisco; Calvo-Medina, Rocio; el Bekay, Rajaa; Perez-Costillas, Lucia; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes

    2016-01-01

    Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome. PMID:26788253

  5. Abnormal Reactions of Free Radicals and Oxidative Damages in the Bodies of Patients With Chronic Glomerulonephritis

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To study the abnormal reactions of a series of free radicals and the oxidative damages induced by free radical abnormal reactions in the bodies of patients with chronic glomerulonephritis. Methods Eighty chronic glomerulonephritis patients (CGNP) and eighty healthy adult volunteers (HAV) were enrolled in a random control study, in which concentrations of nitric oxide (NO) in plasma, lipoperoxides (LPO) in plasma and in erythrocytes, and vitamin C (VC),vitamin E (VE) and beta-carotene (β-CAR) in plasma as well as activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in erythrocytes were determined with spectrophotometric assays. Results Compared with the average values of the above biochemical parameters in the HAV group, the average values of NO in plasma, and LPO in plasma and erythrocytes in the CGNP group were significantly increased (P = 0.0001), while those of VC, VE and β-CAR in plasma as well as those of SOD, CAT and GPX in erythrocytes in the CGNP group were significantly decreased (P = 0.0001). Pearson product-moment correlation analysis showed that with increase of the concentration of blood creatinine as well as prolongation of the course of disease in the CGNP, the concentrations of NO in plasma, and LPO in plasma and erythrocytes in the CGNP increased gradually, while the concentrations of VC, VE and β-CAR in plasma as well as the activities of SOD, CAT and GPX in erythrocytes in the CGNP decreased gradually (P = 0.002454 - 0.000001).The relative risk ratio (RR) of the above biochemical parameters reflecting oxidative damages in the bodies of CGNP ranged from 6.061 to 72.429. The reliability coefficient (alpha) that the above biochemical parameters were used to reflect the oxidative damages of the CGNP was 0.8137,standardized item alpha = 0.9728, Hotelling's T-Squared = 1135680.191, F = 53274.6478, P =0.000001. Conclusions The findings irt this study show that in the bodies of CGNP a series of free

  6. Oxidative state and oxidative metabolism in the brain of rats with adjuvant-induced arthritis.

    Science.gov (United States)

    Wendt, Mariana Marques Nogueira; de Sá-Nakanishi, Anacharis Babeto; de Castro Ghizoni, Cristiane Vizioli; Bersani Amado, Ciomar Aparecida; Peralta, Rosane Marina; Bracht, Adelar; Comar, Jurandir Fernando

    2015-06-01

    The purpose of the present study was to evaluate the oxidative status of the brain of arthritic rats, based mainly on the observation that arthritis induces a pronounced oxidative stress in the liver of arthritis rats and that morphological alterations have been reported to occur in patients with rheumatoid arthritis. Rats with adjuvant-induced arthritis were used. These animals presented higher levels of reactive oxygen species (ROS) in the total brain homogenate (25% higher) and in the mitochondria (+55%) when compared to healthy rats. The nitrite plus nitrate contents, nitric oxide (NO) markers, were also increased in both mitochondria (+27%) and cytosol (+14%). Arthritic rats also presented higher levels of protein carbonyl groups in the total homogenate (+43%), mitochondria (+69%) and cytosol (+145%). Arthritis caused a diminution of oxygen consumption in isolated brain mitochondria only when ascorbate was the electron donor. The disease diminished the mitochondrial cytochrome c oxidase activity by 55%, but increased the transmembrane potential by 16%. The pro-oxidant enzyme xanthine oxidase was 150%, 110% and 283% higher, respectively, in the brain homogenate, mitochondria and cytosol of arthritic animals. The same occurred with the calcium-independent NO-synthase activity that was higher in the brain homogenate (90%) and cytosol (122%) of arthritic rats. The catalase activity, on the other hand, was diminished by arthritis in all cellular fractions (between 30 and 40%). It is apparent that the brain of rats with adjuvant-induced arthritis presents a pronounced oxidative stress and a significant injury to lipids and proteins, a situation that possibly contributes to the brain symptoms of the arthritis disease.

  7. Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men

    DEFF Research Database (Denmark)

    van der Beek, Christina M; Canfora, Emanuel E; Lenaerts, Kaatje

    2016-01-01

    Gut microbial-derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men...

  8. Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages

    Directory of Open Access Journals (Sweden)

    Meera eRath

    2014-10-01

    Full Text Available Macrophages play a major role in the immune system, both as antimicrobial effector cells and as immunoregulatory cells, which induce, suppress or modulate adaptive immune responses. These key aspects of macrophage biology are fundamentally driven by the phenotype of macrophage arginine metabolism that is prevalent in an evolving or ongoing immune response. M1 macrophages express the enzyme nitric oxide synthase (NOS, which metabolizes arginine to nitric oxide (NO and citrulline. NO can be metabolized to further downstream reactive nitrogen species, while citrulline might be reused for efficient NO synthesis via the citrulline-NO cycle. M2 macrophages are characterized by expression of the enzyme arginase, which hydrolyzes arginine to ornithine and urea. The arginase pathway limits arginine availability for NO synthesis and ornithine itself can further feed into the important downstream pathways of polyamine and proline syntheses, which are important for cellular proliferation and tissue repair. M1 versus M2 polarization leads to opposing outcomes of inflammatory reactions, but depending on the context, M1 and M2 macrophages can be both pro- and antiinflammatory. Notably, M1/M2 macrophage polarization can be driven by microbial infection or innate danger signals without any influence of adaptive immune cells, secondarily driving the T helper (Th1/Th2 polarization of the evolving adaptive immune response. Since both arginine metabolic pathways cross-inhibit each other on the level of the respective arginine break-down products and Th1 and Th2 lymphocytes can drive or amplify macrophage M1/M2 dichotomy via cytokine activation, this forms the basis of a self-sustaining M1/M2 polarization of the whole immune response. Understanding the arginine metabolism of M1/M2 macrophage phenotypes is therefore central to find new possibilities to manipulate immune responses in infection, autoimmune diseases, chronic inflammatory conditions and cancer.

  9. Metabolism of (-)-cis- and (-)-trans-rose oxide by cytochrome P450 enzymes in human liver microsomes.

    Science.gov (United States)

    Nakahashi, Hiroshi; Yamamura, Yuuki; Usami, Atsushi; Rangsunvigit, Pramoch; Malakul, Pomthong; Miyazawa, Mitsuo

    2015-12-01

    The in vitro metabolism of (-)-cis- and (-)-trans-rose oxide was investigated using human liver microsomes and recombinant cytochrome P450 (P450 or CYP) enzymes for the first time. Both isomers of rose oxide were incubated with human liver microsomes, and the formation of the respective 9-oxidized metabolite were determined using gas chromatography-mass spectrometry (GC-MS). Of 11 different recombinant human P450 enzymes used, CYP2B6 and CYP2C19 were the primary enzymes catalysing the metabolism of (-)-cis- and (-)-trans-rose oxide. CYP1A2 also efficiently oxidized (-)-cis-rose oxide at the 9-position but not (-)-trans-rose oxide. α-Naphthoflavone (a selective CYP1A2 inhibitor), thioTEPA (a CYP2B6 inhibitor) and anti-CYP2B6 antibody inhibited (-)-cis-rose oxide 9-hydroxylation catalysed by human liver microsomes. On the other hand, the metabolism of (-)-trans-rose oxide was suppressed by thioTEPA and anti-CYP2B6 at a significant level in human liver microsomes. However, omeprazole (a CYP2C19 inhibitor) had no significant effects on the metabolism of both isomers of rose oxide. Using microsomal preparations from nine different human liver samples, (-)-9-hydroxy-cis- and (-)-9-hydroxy-trans-rose oxide formations correlated with (S)-mephenytoin N-demethylase activity (CYP2B6 marker activity). These results suggest that CYP2B6 plays important roles in the metabolism of (-)-cis- and (-)-trans-rose oxide in human liver microsomes.

  10. Metabolism

    Science.gov (United States)

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

  11. Metabolism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008255 Serum adiponectin level declines in the elderly with metabolic syndrome.WU Xiaoyan(吴晓琰),et al.Dept Geriatr,Huashan Hosp,Fudan UnivShanghai200040.Chin J Geriatr2008;27(3):164-167.Objective To investigate the correlation between ser-um adiponectin level and metabolic syndrome in the elderly·Methods Sixty-one subjects with metabolic syndrome and140age matched subjects without metabolic

  12. Impaired cross-talk between mesolimbic food reward processing and metabolic signaling predicts body mass index

    Directory of Open Access Journals (Sweden)

    Joe J Simon

    2014-10-01

    Full Text Available The anticipation of the pleasure derived from food intake drives the motivation to eat, and hence facilitate overconsumption of food which ultimately results in obesity. Brain imaging studies provide evidence that mesolimbic brain regions underlie both general as well as food related anticipatory reward processing. In light of this knowledge, the present study examined the neural responsiveness of the ventral striatum in participants with a broad BMI spectrum. The study differentiated between general (i.e. monetary and food related anticipatory reward processing. We recruited a sample of volunteers with greatly varying body weights, ranging from a low BMI (below 20 kg/m² over a normal (20 to 25 kg/m² and overweight (25 to 30 kg/m² BMI, to class I (30 to 35 kg/m² and class II (35 to 40 kg/m² obesity. A total of 24 participants underwent functional magnetic resonance imaging whilst performing both a food and monetary incentive delay task, which allows to measure neural activation during the anticipation of rewards. After the presentation of a cue indicating the amount of food or money to be won, participants had to react correctly in order to earn snack points or money coins which could then be exchanged for real food or money, respectively, at the end of the experiment. During the anticipation of both types of rewards, participants displayed activity in the ventral striatum, a region that plays a pivotal role in the anticipation of rewards. Additionally, we observed that specifically anticipatory food reward processing predicted the individual BMI (current and maximum lifetime. This relation was found to be mediated by impaired hormonal satiety signaling, i.e. increased leptin levels and insulin resistance. These findings suggest that heightened food reward motivation contributes to obesity through impaired metabolic signaling.

  13. Hydroxylated bisabolol oxides: evidence for secondary oxidative metabolism in Matricaria chamomilla.

    Science.gov (United States)

    Avonto, Cristina; Wang, Mei; Chittiboyina, Amar G; Avula, Bharathi; Zhao, Jianping; Khan, Ikhlas A

    2013-10-25

    German chamomile (Matricaria chamomilla) is one of the most popular medicinal plants used in Western herbal medicine. Among the various phytochemicals present in the essential oil of the flowers of German chamomile, bisabolol and its oxidized metabolites are considered as marker compounds for distinguishing different chemotypes. These compounds are influential in mediating the aroma of the essential oil of M. chamomilla and contribute to the therapeutic properties (anti-inflammatory, antibacterial, insecticidal, and antiulcer) of this species. In order to find other possible bisabolol derivatives as marker compounds for authentication of German chamomile in botanical and commercial products, an in-depth investigation using a GC-assisted fractionation procedure was performed on nonpolar fractions. As a result of this approach, three new hydroxylated derivatives of bisabolol oxides A and B (1-3) have been isolated from M. chamomilla. Plausible biogenetic pathways are presented.

  14. Development of Dietary Patterns Spanning Infancy and Toddlerhood: Relation to Body Size, Composition and Metabolic Risk Markers at Three Years

    DEFF Research Database (Denmark)

    Andersen, Louise B. B.; Mølgaard, Christian; Ejlerskov, Katrine Tschentscher;

    2015-01-01

    Little is known about the development of dietary patterns during toddlerhood and the relation to growth and health. The study objective was to characterise the development of dietary patterns from 9-36 mo of age and investigate the association to body size, body composition and metabolic risk...... higher BMI z-scores at 36 mo. Similar trend was identified for higher fat mass indices. Children with lower adherence to the Healthy Food pattern than average at all three ages compared to children with higher adherence to the Healthy Food pattern at the first two registrations, 9 and 18 mo had higher...

  15. Metabolic Rather Than Body Composition Measurements Are Associated With Lower Serum Natriuretic Peptide Concentrations in Normal Weight and Obese Men

    DEFF Research Database (Denmark)

    Asferg, Camilla L; Nielsen, Søren J; Andersen, Ulrik B

    2014-01-01

    men (BMI ≥ 30kg/m(2)), we determined body composition (total, android, and gynoid fat mass) by dual energy x-ray absorptiometry scanning, and we measured fasting serum concentrations of midregional proatrial NP (MR-proANP) and insulin, as well as fasting plasma glucose concentrations. RESULTS: Mean.......0001) and plasma glucose concentrations (β = -0.21; P = 0.02) but not with total (β = 0.00), android (β = -0.01), or gynoid (β = 0.03) fat mass percentage (P > 0.76). No significant interaction effects between metabolic measurements or body composition measurements and weight status on MR-proANP concentrations...

  16. Metabolic, Thermal and Cardiovascular Adjustments to Cold Exposure with Special Reference to Physical Work and Body Composition.

    Science.gov (United States)

    1982-06-01

    frame of reference for the metabolic demands of the arm-leg work task, peak i021 on the cycle ergometer was determined on a separate day by means of a...andE identify by block numbr) Cold exposure; water exposure; temperature regulation; rectal temperature; lean, average and obese body fatness; body...at 36W (8.2 kcal.miLn- ) in air and water at,20, 24 and 280C. At rest, in all water conditions, the obese men (> 222 fat) maintained Tre at levels

  17. Metabolic Abnormalities Are Common among South American Hispanics Subjects with Normal Weight or Excess Body Weight: The CRONICAS Cohort Study.

    Directory of Open Access Journals (Sweden)

    Catherine P Benziger

    Full Text Available We aimed to characterize metabolic status by body mass index (BMI status.The CRONICAS longitudinal study was performed in an age-and-sex stratified random sample of participants aged 35 years or older in four Peruvian settings: Lima (Peru's capital, costal urban, highly urbanized, urban and rural Puno (both high-altitude, and Tumbes (costal semirural. Data from the baseline study, conducted in 2010, was used. Individuals were classified by BMI as normal weight (18.5-24.9 kg/m2, overweight (25.0-29.9 kg/m2, and obese (≥30 kg/m2, and as metabolically healthy (0-1 metabolic abnormality or metabolically unhealthy (≥2 abnormalities. Abnormalities included individual components of the metabolic syndrome, high-sensitivity C-reactive protein, and insulin resistance.A total of 3088 (age 55.6±12.6 years, 51.3% females had all measurements. Of these, 890 (28.8%, 1361 (44.1% and 837 (27.1% were normal weight, overweight and obese, respectively. Overall, 19.0% of normal weight in contrast to 54.9% of overweight and 77.7% of obese individuals had ≥3 risk factors (p<0.001. Among normal weight individuals, 43.1% were metabolically unhealthy, and age ≥65 years, female, and highest socioeconomic groups were more likely to have this pattern. In contrast, only 16.4% of overweight and 3.9% of obese individuals were metabolically healthy and, compared to Lima, the rural and urban sites in Puno were more likely to have a metabolically healthier profile.Most Peruvians with overweight and obesity have additional risk factors for cardiovascular disease, as well as a majority of those with a healthy weight. Prevention programs aimed at individuals with a normal BMI, and those who are overweight and obese, are urgently needed, such as screening for elevated fasting cholesterol and glucose.

  18. Menopause is associated with decreased whole body fat oxidation during exercise.

    Science.gov (United States)

    Abildgaard, J; Pedersen, A T; Green, C J; Harder-Lauridsen, N M; Solomon, T P; Thomsen, C; Juul, A; Pedersen, M; Pedersen, J T; Mortensen, O H; Pilegaard, H; Pedersen, B K; Lindegaard, B

    2013-06-01

    The purpose of this study was to examine if fat oxidation was affected by menopausal status and to investigate if this could be related to the oxidative capacity of skeletal muscle. Forty-one healthy women were enrolled in this cross-sectional study [premenopausal (n = 19), perimenopausal (n = 8), and postmenopausal (n = 14)]. Estimated insulin sensitivity was obtained from an oral glucose tolerance test. Body composition was measured by dual-energy X-ray absorptiometry and magnetic resonance imaging. Fat oxidation and energy expenditure were measured during an acute exercise bout of 45 min of ergometer biking at 50% of maximal oxygen consumption (Vo2 max). Muscle biopsies from the vastus lateralis of the quadriceps muscle were obtained before and immediately after the exercise bout. Postmenopausal women had 33% [confidence interval (CI) 95%: 12-55] lower whole body fat oxidation (P = 0.005) and 19% (CI 95%: 9-22) lower energy expenditure (P = 0.02) during exercise, as well as 4.28 kg lower lean body mass (LBM) than premenopausal women. Correction for LBM reduced differences in fat oxidation to 23% (P = 0.05), whereas differences in energy expenditure disappeared (P = 0.22). No differences between groups were found in mRNA [carnitine palmitoyltransferase I, β-hydroxyacyl-CoA dehydrogenase (β-HAD), peroxisome proliferator-activated receptor-α, citrate synthase (CS), pyruvate dehydrogenase kinase 4, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)], protein [phosphorylated AMP-activated protein kinase (AMPK), vascular endothelial growth factor, pyruvate dehydrogenase-1Eα, cytochrome oxidase I], or enzyme activities (β-HAD, CS) in resting skeletal muscle, except for an increased protein level of cytochrome c in the post- and perimenopausal women relative to premenopausal women. Postmenopausal women demonstrated a trend to a blunted exercise-induced increase in phosphorylation of AMPK compared with premenopausal women (P = 0.06). We conclude

  19. Prevalence of metabolic syndrome and its components among Chinese professional athletes of strength sports with different body weight categories.

    Directory of Open Access Journals (Sweden)

    Jianjun Guo

    Full Text Available BACKGROUND: There is an increasing concern on cardiometabolic health in young professional athletes at heavy-weight class. OBJECTIVE: Our cross-sectional survey aimed to evaluate the prevalence of metabolic syndrome and clustering of metabolic risk factors in a population of young and active professional athletes of strength sports in China. METHODS: From July 2006 to December 2008, a total of 131 male and 130 female athletes of strength sports were enrolled. We used two criteria provided by the Chinese Diabetes Society (2004 and the National Cholesterol Education Program's Adult Treatment Panel III (2002 to define the metabolic syndrome and its individual components, respectively. RESULTS: Regardless of their similar ages (mean: 21 years and exercise levels, athletes in the heaviest-weight-class with unlimited maximum body weight (UBW boundaries (mean weight and BMI: 130 kg and 38 kg/m(2 for men, 110 kg and 37 kg/m(2 for women had significantly higher prevalence of metabolic syndrome than did those in all other body-weight-class with limited body weight (LBW boundaries (mean weight and BMI: 105 kg and 32 kg/m(2 for men, 70 kg and 26 kg/m(2 for women. Prevalence of metabolic syndrome using CDS criteria (UBW vs. LBW: 89% vs. 18% for men, 47% vs. 0% for women and its individual components, including central obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein-cholesterol levels, and impaired fasting glucose, were all significantly higher in athletes at the heaviest weight group with UBW than all other weight groups with LBW. CONCLUSIONS: Our study suggests that professional athletes of strength sports at the heaviest-weight-class are at a significant increased risk of cardiometabolic disease compared with those at all other weight categories. The findings support the importance of developing and implementing the strategy of early screening, awareness, and interventions for weight-related health among young athletes.

  20. Quantitative lipidomics reveals age-dependent perturbations of whole-body lipid metabolism in ACBP deficient mice

    DEFF Research Database (Denmark)

    Gallego, Sandra F; Sprenger, Richard R; Neess, Ditte

    2017-01-01

    and delayed weaning, the physiological process where newborns transit from a fat-based milk diet to a carbohydrate-rich diet. To gain insights into how ACBP impinges on weaning and the concomitant remodeling of whole-body lipid metabolism we performed a comparative lipidomics analysis charting the absolute......The acyl-CoA binding protein (ACBP) plays a key role in chaperoning long-chain acyl-CoAs into lipid metabolic processes and acts as an important regulatory hub in mammalian physiology. This is highlighted by the recent finding that mice devoid of ACBP suffer from a compromised epidermal barrier...... abundance of 613 lipid molecules in liver, muscle and plasma from weaning and adult Acbp knockout and wild type mice. Our results reveal that ACBP deficiency affects primarily lipid metabolism of liver and plasma during weaning. Specifically, we show that ACBP deficient mice have elevated levels of hepatic...

  1. Quantitative lipidomics reveals age-dependent perturbations of whole-body lipid metabolism in ACBP deficient mice

    DEFF Research Database (Denmark)

    Gallego, Sandra Fernandez; Sprenger, Richard; Neess, Ditte;

    2016-01-01

    The acyl-CoA binding protein (ACBP) plays a key role in chaperoning long-chain acyl-CoAs into lipid metabolic processes and acts as an important regulatory hub in mammalian physiology. This is highlighted by the recent finding that mice devoid of ACBP suffer from a compromised epidermal barrier...... and delayed weaning, the physiological process where newborns transit from a fat-based milk diet to a carbohydrate-rich diet. To gain insights into how ACBP impinges on weaning and the concomitant remodeling of whole-body lipid metabolism we performed a comparative lipidomics analysis charting the absolute...... abundance of 613 lipid molecules in liver, muscle and plasma from weaning and adult Acbp knockout and wild type mice. Our results reveal that ACBP deficiency affects primarily lipid metabolism of liver and plasma during weaning. Specifically, we show that ACBP deficient mice have elevated levels of hepatic...

  2. COPPER AND COPPER-CONTAINING PESTICIDES: METABOLISM, TOXICITY AND OXIDATIVE STRESS

    Directory of Open Access Journals (Sweden)

    Viktor Husak

    2015-05-01

    Full Text Available The purpose of this paper is to provide a brief review of the current knowledge regarding metabolism and toxicity of copper and copper-based pesticides in living organisms. Copper is an essential trace element in all living organisms (bacteria, fungi, plants, and animals, because it participates in different metabolic processes and maintain functions of organisms. The transport and metabolism of copper in living organisms is currently the subject of many studies. Copper is absorbed, transported, distributed, stored, and excreted in the body via the complex of homeostatic processes, which provide organisms with a needed constant level of this micronutrient and avoid excessive amounts. Many aspects of copper homeostasis were studied at the molecular level. Copper based-pesticides, in particularly fungicides, bacteriocides and herbicides, are widely used in agricultural practice throughout the world. Copper is an integral part of antioxidant enzymes, particularly copper-zinc superoxide dismutase (Cu,Zn-SOD, and plays prominent roles in iron homeostasis. On the other hand, excess of copper in organism has deleterious effect, because it stimulates free radical production in the cell, induces lipid peroxidation, and disturbs the total antioxidant capacity of the body. The mechanisms of copper toxicity are discussed in this review also.

  3. Microencapsulated conjugated linoleic acid associated with hypocaloric diet reduces body fat in sedentary women with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Carvalho RF

    2012-12-01

    Full Text Available Roberta F Carvalho,1 Sofia K Uehara,2 Glorimar Rosa1,21Medicine Department, Federal University of Rio de Janeiro, Brazil; 2Nutrition and Dietetic Department, Josué de Castro Institute of Nutrition, Federal University of Rio de Janeiro, BrazilBackground: Animal studies have suggested beneficial effects of conjugated linoleic acid (CLA in reducing body fat mass and improvement in the serum lipid profile and glycemia. However, these effects are controversial in humans. The purpose of this study was to investigate the effects of microencapsulated CLA supplementation on body composition, body mass index, waist circumference, and blood pressure in sedentary women with metabolic syndrome.Methods: This study was a placebo-controlled and randomized clinical trial. Fourteen women diagnosed with metabolic syndrome received light strawberry jam enriched or not with microencapsulated CLA (3 g/day as a mixture of 38.57% cis-9, trans-11, and 39.76% trans-10, cis-12 CLA isomers associated with a hypocaloric diet for 90 days. The subjects were monitored to assess variables associated with the metabolic syndrome, in addition to assessing adherence with the intervention.Results: There were no significant effects of microencapsulated CLA on the lipid profile or blood pressure. Mean plasma insulin concentrations were significantly lower in women supplemented with microencapsulated CLA (Δ T90 – T0 = −12.87 ± 4.26 µU/mL, P = 0.02. Microencapsulated CLA supplementation did not alter the waist circumference, but there was a reduction in body fat mass detected after 30 days (Δ = −2.68% ± 0.82%, P = 0.02, which was maintained until the 90-day intervention period (Δ = −3.32% ± 1.41%, P = 0.02 in the microencapsulated CLA group. The placebo group showed this effect only after 90 days (Δ = −1.97% ± 0.60%, P = 0.02, but had a reduced waist circumference (Δ T90 – T0 = −4.25 ± 1.31 cm, P = 0.03.Conclusion: Supplementation with mixed

  4. Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability.

    Science.gov (United States)

    Patella, Francesca; Schug, Zachary T; Persi, Erez; Neilson, Lisa J; Erami, Zahra; Avanzato, Daniele; Maione, Federica; Hernandez-Fernaud, Juan R; Mackay, Gillian; Zheng, Liang; Reid, Steven; Frezza, Christian; Giraudo, Enrico; Fiorio Pla, Alessandra; Anderson, Kurt; Ruppin, Eytan; Gottlieb, Eyal; Zanivan, Sara

    2015-03-01

    Endothelial cells (ECs) play a key role to maintain the functionality of blood vessels. Altered EC permeability causes severe impairment in vessel stability and is a hallmark of pathologies such as cancer and thrombosis. Integrating label-free quantitative proteomics data into genome-wide metabolic modeling, we built up a model that predicts the metabolic fluxes in ECs when cultured on a tridimensional matrix and organize into a vascular-like network. We discovered how fatty acid oxidation increases when ECs are assembled into a fully formed network that can be disrupted by inhibiting CPT1A, the fatty acid oxidation rate-limiting enzyme. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which are restored by replenishing the tricarboxylic acid cycle. Remarkably, global phosphoproteomic changes measured upon acute CPT1A inhibition pinpointed altered calcium signaling. Indeed, CPT1A inhibition increases intracellular calcium oscillations. Finally, inhibiting CPT1A induces hyperpermeability in vitro and leakage of blood vessel in vivo, which were restored blocking calcium influx or replenishing the tricarboxylic acid cycle. Fatty acid oxidation emerges as central regulator of endothelial functions and blood vessel stability and druggable pathway to control pathological vascular permeability.

  5. Iron-dependent changes in cellular energy metabolism: influence on citric acid cycle and oxidative phosphorylation.

    Science.gov (United States)

    Oexle, H; Gnaiger, E; Weiss, G

    1999-11-10

    Iron modulates the expression of the critical citric acid cycle enzyme aconitase via a translational mechanism involving iron regulatory proteins. Thus, the present study was undertaken to investigate the consequences of iron perturbation on citric acid cycle activity, oxidative phosphorylation and mitochondrial respiration in the human cell line K-562. In agreement with previous data iron increases the activity of mitochondrial aconitase while it is reduced upon addition of the iron chelator desferrioxamine (DFO). Interestingly, iron also positively affects three other citric acid cycle enzymes, namely citrate synthase, isocitric dehydrogenase, and succinate dehydrogenase, while DFO decreases the activity of these enzymes. Consequently, iron supplementation results in increased formation of reducing equivalents (NADH) by the citric acid cycle, and thus in increased mitochondrial oxygen consumption and ATP formation via oxidative phosphorylation as shown herein. This in turn leads to downregulation of glucose utilization. In contrast, all these metabolic pathways are reduced upon iron depletion, and thus glycolysis and lactate formation are significantly increased in order to compensate for the decrease in ATP production via oxidative phosphorylation in the presence of DFO. Our results point to a complex interaction between iron homeostasis, oxygen supply and cellular energy metabolism in human cells.

  6. Proteomics-Based Metabolic Modeling Reveals That Fatty Acid Oxidation (FAO) Controls Endothelial Cell (EC) Permeability*

    Science.gov (United States)

    Patella, Francesca; Schug, Zachary T.; Persi, Erez; Neilson, Lisa J.; Erami, Zahra; Avanzato, Daniele; Maione, Federica; Hernandez-Fernaud, Juan R.; Mackay, Gillian; Zheng, Liang; Reid, Steven; Frezza, Christian; Giraudo, Enrico; Fiorio Pla, Alessandra; Anderson, Kurt; Ruppin, Eytan; Gottlieb, Eyal; Zanivan, Sara

    2015-01-01

    Endothelial cells (ECs) play a key role to maintain the functionality of blood vessels. Altered EC permeability causes severe impairment in vessel stability and is a hallmark of pathologies such as cancer and thrombosis. Integrating label-free quantitative proteomics data into genome-wide metabolic modeling, we built up a model that predicts the metabolic fluxes in ECs when cultured on a tridimensional matrix and organize into a vascular-like network. We discovered how fatty acid oxidation increases when ECs are assembled into a fully formed network that can be disrupted by inhibiting CPT1A, the fatty acid oxidation rate-limiting enzyme. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which are restored by replenishing the tricarboxylic acid cycle. Remarkably, global phosphoproteomic changes measured upon acute CPT1A inhibition pinpointed altered calcium signaling. Indeed, CPT1A inhibition increases intracellular calcium oscillations. Finally, inhibiting CPT1A induces hyperpermeability in vitro and leakage of blood vessel in vivo, which were restored blocking calcium influx or replenishing the tricarboxylic acid cycle. Fatty acid oxidation emerges as central regulator of endothelial functions and blood vessel stability and druggable pathway to control pathological vascular permeability. PMID:25573745

  7. Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation

    Science.gov (United States)

    Zheng, Xinde; Boyer, Leah; Jin, Mingji; Mertens, Jerome; Kim, Yongsung; Ma, Li; Ma, Li; Hamm, Michael; Gage, Fred H; Hunter, Tony

    2016-01-01

    How metabolism is reprogrammed during neuronal differentiation is unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation. The protein levels of c-MYC and N-MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically. Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death, indicating that the shut-off aerobic glycolysis is essential for neuronal survival. The metabolic regulators PGC-1α and ERRγ increase significantly upon neuronal differentiation to sustain the transcription of metabolic and mitochondrial genes, whose levels are unchanged compared to NPCs, revealing distinct transcriptional regulation of metabolic genes in the proliferation and post-mitotic differentiation states. Mitochondrial mass increases proportionally with neuronal mass growth, indicating an unknown mechanism linking mitochondrial biogenesis to cell size. DOI: http://dx.doi.org/10.7554/eLife.13374.001 PMID:27282387

  8. Oxidative status imbalance in patients with metabolic syndrome: role of the myeloperoxidase/hydrogen peroxide axis.

    Science.gov (United States)

    da Fonseca, Lucas José Sá; Nunes-Souza, Valéria; Guedes, Glaucevane da Silva; Schettino-Silva, Glauber; Mota-Gomes, Marco Antônio; Rabelo, Luíza Antas

    2014-01-01

    The present study evaluated the cardiometabolic and redox balance profiles in patients with Metabolic Syndrome compared to apparently healthy individuals, and the participation of the myeloperoxidase/hydrogen peroxide axis in systemic lipid peroxidation. Twenty-four patients with Metabolic Syndrome and eighteen controls underwent a full clinical assessment. Venous blood samples were collected for general biochemical dosages, as well as for the oxidative stress analyses (superoxide dismutase, catalase, and arginase activities; and lipid peroxidation, myeloperoxidase activity, nitrite, and hydrogen peroxide concentrations in plasma). Arterial stiffness was assessed by radial artery applanation tonometry. Plasma lipid peroxidation, erythrocyte superoxide dismutase activity, myeloperoxidase activity, and hydrogen peroxide concentrations were shown to be increased in Metabolic Syndrome patients, without significant differences for the other enzymes, plasma nitrite concentrations, and arterial stiffness. Linear regression analysis revealed a positive and significant correlation between lipid peroxidation and myeloperoxidase and also between this enzyme and hydrogen peroxide. In contrast, such correlation was not observed between lipid peroxidation and hydrogen peroxide. In summary, Metabolic Syndrome patients exhibited evident systemic redox imbalance compared to controls, with the possible participation of the myeloperoxidase/hydrogen peroxide axis as a contributor in lipid peroxidation.

  9. Suppression of PGC-1α is critical for reprogramming oxidative metabolism in renal cell carcinoma

    Science.gov (United States)

    LaGory, Edward L.; Wu, Colleen; Taniguchi, Cullen M.; Ding, Chien-Kuang Cornelia; Chi, Jen-Tsan; von Eyben, Rie; Scott, David A.; Richardson, Adam D.; Giaccia, Amato J.

    2015-01-01

    Summary Long believed to be a byproduct of malignant transformation, reprogramming of cellular metabolism is now recognized as a driving force in tumorigenesis. In clear cell renal cell carcinoma (ccRCC) frequent activation of HIF-signaling induces a metabolic switch that promotes tumorigenesis. Here we demonstrate that PGC-1α, a central regulator of energy metabolism, is suppressed in VHL-deficient ccRCC by a HIF/Dec1-dependent mechanism. In VHL wild type cells, PGC-1α suppression leads to decreased expression of the mitochondrial transcription factor Tfam and impaired mitochondrial respiration. Conversely, PGC-1α expression in VHL-deficient cells restores mitochondrial function and induces oxidative stress. ccRCC cells expressing PGC-1α exhibit impaired tumor growth and enhanced sensitivity to cytotoxic therapies. In patients, low levels of PGC-1α expression are associated with poor outcome. These studies demonstrate that suppression of PGC-1α recapitulates key metabolic phenotypes of ccRCC and highlight the potential of targeting PGC-1α expression as a therapeutic modality for the treatment of ccRCC. PMID:26119730

  10. Suppression of PGC-1α Is Critical for Reprogramming Oxidative Metabolism in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Edward L. LaGory

    2015-07-01

    Full Text Available Long believed to be a byproduct of malignant transformation, reprogramming of cellular metabolism is now recognized as a driving force in tumorigenesis. In clear cell renal cell carcinoma (ccRCC, frequent activation of HIF signaling induces a metabolic switch that promotes tumorigenesis. Here, we demonstrate that PGC-1α, a central regulator of energy metabolism, is suppressed in VHL-deficient ccRCC by a HIF/Dec1-dependent mechanism. In VHL wild-type cells, PGC-1α suppression leads to decreased expression of the mitochondrial transcription factor Tfam and impaired mitochondrial respiration. Conversely, PGC-1α expression in VHL-deficient cells restores mitochondrial function and induces oxidative stress. ccRCC cells expressing PGC-1α exhibit impaired tumor growth and enhanced sensitivity to cytotoxic therapies. In patients, low levels of PGC-1α expression are associated with poor outcome. These studies demonstrate that suppression of PGC-1α recapitulates key metabolic phenotypes of ccRCC and highlight the potential of targeting PGC-1α expression as a therapeutic modality for the treatment of ccRCC.

  11. EFFECTS OF CORDYCEPS SINENSIS PREPARATION ON BODY PROTEIN AND AMINO ACID METABOLISM IN PATIENTS AND RATS WITH CHRONIC RENAL FAILURE

    Institute of Scientific and Technical Information of China (English)

    朱淳; 刘强; 左静南; 朱汉威; 马济民

    2002-01-01

    Objective To study the effects of Cordyceps sinensis (CS) on the metabolism of body protein and intra-extracellular amino acids in patients with chronic renal failure( CRF) , and on the rates of protein synthesis in rats with CRF. Methods In patients with CRF, free amino acid concentrations in plasma and skeletal muscle before and after CS treatment were measured by the LKB-4400 amino acid automatic analytical instrument and the changes of body protein metabolism were observed by the method of 15 N-labeled glycine.Meanwhile, the rates of protein synthesis in liver ( SL % /d ) and muscle (SM%/d) of rats with CRF were determinedd by 3f-phenylalanine radioactive tracer. Results After patients with CRF were treated by CS, the Leu, lie, Thr , Lys, Cys, Tyr concentrations in plasma approached the normal levels. In one sample of skeletal muscle the Thr and Lys concentrations approached the normal, whereas both the intracellular and extracellular Val concentrations were still remarkably decreased as compared with the normal controls. Moreover, the nitrogen flow rate (Q) , rates of protein synthesis (S) and catabolism ( C) , and amino nitrogen utilization ratio (S/Q) in patients with CRF and the SL % /d and SM%/d in rats with CRF were significantly increased as compared with those before CS treatment. Conclusion CS can notably improve the amino acid metabolism, promote the body protein synthesis in patients with CRF , and increase the rates of SL % /d and SM%/d in rats with CRF.

  12. Distinct developmental profile of lower-body adipose tissue defines resistance against obesity-associated metabolic complications.

    Science.gov (United States)

    Pinnick, Katherine E; Nicholson, George; Manolopoulos, Konstantinos N; McQuaid, Siobhán E; Valet, Philippe; Frayn, Keith N; Denton, Nathan; Min, Josine L; Zondervan, Krina T; Fleckner, Jan; McCarthy, Mark I; Holmes, Chris C; Karpe, Fredrik

    2014-11-01

    Upper- and lower-body fat depots exhibit opposing associations with obesity-related metabolic disease. We defined the relationship between DEXA-quantified fat depots and diabetes/cardiovascular risk factors in a healthy population-based cohort (n = 3,399). Gynoid fat mass correlated negatively with insulin resistance after total fat mass adjustment, whereas the opposite was seen for abdominal fat. Paired transcriptomic analysis of gluteal subcutaneous adipose tissue (GSAT) and abdominal subcutaneous adipose tissue (ASAT) was performed across the BMI spectrum (n = 49; 21.4-45.5 kg/m(2)). In both depots, energy-generating metabolic genes were negatively associated and inflammatory genes were positively associated with obesity. However, associations were significantly weaker in GSAT. At the systemic level, arteriovenous release of the proinflammatory cytokine interleukin-6 (n = 34) was lower from GSAT than ASAT. Isolated preadipocytes retained a depot-specific transcriptional "memory" of embryonic developmental genes and exhibited differential promoter DNA methylation of selected genes (HOTAIR, TBX5) between GSAT and ASAT. Short hairpin RNA-mediated silencing identified TBX5 as a regulator of preadipocyte proliferation and adipogenic differentiation in ASAT. In conclusion, intrinsic differences in the expression of developmental genes in regional adipocytes provide a mechanistic basis for diversity in adipose tissue (AT) function. The less inflammatory nature of lower-body AT offers insight into the opposing metabolic disease risk associations between upper- and lower-body obesity.

  13. Vest Chest Physiotherapy Airway Clearance is Associated with Nitric Oxide Metabolism

    Directory of Open Access Journals (Sweden)

    Joseph H. Sisson

    2013-01-01

    Full Text Available Background. Vest chest physiotherapy (VCPT enhances airway clearance in cystic fibrosis (CF by an unknown mechanism. Because cilia are sensitive to nitric oxide (NO, we hypothesized that VCPT enhances clearance by changing NO metabolism. Methods. Both normal subjects and stable CF subjects had pre- and post-VCPT airway clearance assessed using nasal saccharin transit time (NSTT followed by a collection of exhaled breath condensate (EBC analyzed for NO metabolites (. Results. VCPT shorted NSTT by 35% in normal and stable CF subjects with no difference observed between the groups. EBC concentrations decreased 68% in control subjects after VCPT (before = 115 ± 32 μM versus after = 37 ± 17 μM; . CF subjects had a trend toward lower EBC . Conclusion. We found an association between VCPT-stimulated clearance and exhaled levels in human subjects. We speculate that VCPT stimulates clearance via increased NO metabolism.

  14. Highly proliferative primitive fetal liver hematopoietic stem cells are fueled by oxidative metabolic pathways

    Directory of Open Access Journals (Sweden)

    Javed K. Manesia

    2015-11-01

    Full Text Available Hematopoietic stem cells (HSCs in the fetal liver (FL unlike adult bone marrow (BM proliferate extensively, posing different metabolic demands. However, metabolic pathways responsible for the production of energy and cellular building blocks in FL HSCs have not been described. Here, we report that FL HSCs use oxygen dependent energy generating pathways significantly more than their BM counterparts. RNA-Seq analysis of E14.5 FL versus BM derived HSCs identified increased expression levels of genes involved in oxidative phosphorylation (OxPhos and the citric acid cycle (TCA. We demonstrated that FL HSCs contain more mitochondria than BM HSCs, which resulted in increased levels of oxygen consumption and reactive oxygen species (ROS production. Higher levels of DNA repair and antioxidant pathway gene expression may prevent ROS-mediated (genotoxicity in FL HSCs. Thus, we here for the first time highlight the underestimated importance of oxygen dependent pathways for generating energy and building blocks in FL HSCs.

  15. Highly proliferative primitive fetal liver hematopoietic stem cells are fueled by oxidative metabolic pathways.

    Science.gov (United States)

    Manesia, Javed K; Xu, Zhuofei; Broekaert, Dorien; Boon, Ruben; van Vliet, Alex; Eelen, Guy; Vanwelden, Thomas; Stegen, Steve; Van Gastel, Nick; Pascual-Montano, Alberto; Fendt, Sarah-Maria; Carmeliet, Geert; Carmeliet, Peter; Khurana, Satish; Verfaillie, Catherine M

    2015-11-01

    Hematopoietic stem cells (HSCs) in the fetal liver (FL) unlike adult bone marrow (BM) proliferate extensively, posing different metabolic demands. However, metabolic pathways responsible for the production of energy and cellular building blocks in FL HSCs have not been described. Here, we report that FL HSCs use oxygen dependent energy generating pathways significantly more than their BM counterparts. RNA-Seq analysis of E14.5 FL versus BM derived HSCs identified increased expression levels of genes involved in oxidative phosphorylation (OxPhos) and the citric acid cycle (TCA). We demonstrated that FL HSCs contain more mitochondria than BM HSCs, which resulted in increased levels of oxygen consumption and reactive oxygen species (ROS) production. Higher levels of DNA repair and antioxidant pathway gene expression may prevent ROS-mediated (geno)toxicity in FL HSCs. Thus, we here for the first time highlight the underestimated importance of oxygen dependent pathways for generating energy and building blocks in FL HSCs.

  16. Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication

    Institute of Scientific and Technical Information of China (English)

    Minjong; Lee; Jung-Hwan; Yoon

    2015-01-01

    Aerobic glycolysis, i.e., the Warburg effect, may contribute to the aggressive phenotype of hepatocellular carcinoma. However, increasing evidence highlights the limitations of the Warburg effect, such as high mitochondrial respiration and low glycolysis rates in cancer cells. To explain such contradictory phenomena with regard to the Warburg effect, a metabolic interplay between glycolytic and oxidative cells was proposed, i.e., the "reverse Warburg effect". Aerobic glycolysis may also occur in the stromal compartment that surrounds the tumor; thus, the stromal cells feed the cancer cells with lactate and this interaction prevents the creation of an acidic condition in the tumor microenvironment. This concept provides great heterogeneity in tumors, which makes the disease difficult to cure using a single agent. Understanding metabolic flexibility by lactate shuttles offers new perspectives to develop treatments that target the hypoxic tumor microenvironment and overcome the limitations of glycolytic inhibitors.

  17. Imitation of phase I oxidative metabolism of anabolic steroids by titanium dioxide photocatalysis.

    Science.gov (United States)

    Ruokolainen, Miina; Valkonen, Minna; Sikanen, Tiina; Kotiaho, Tapio; Kostiainen, Risto

    2014-12-18

    The aim of this study was to investigate the feasibility of titanium dioxide (TiO2) photocatalysis for oxidation of anabolic steroids and for imitation of their phase I metabolism. The photocatalytic reaction products of five anabolic steroids were compared to their phase I in vitro metabolites produced by human liver microsomes (HLM). The same main reaction types - hydroxylation, dehydrogenation and combination of these two - were observed both in TiO2 photocatalysis and in microsomal incubations. Several isomers of each product type were formed in both systems. Based on the same mass, retention time and similarity of the product ion spectra, many of the products observed in HLM reactions were also formed in TiO2 photocatalytic reactions. However, products characteristic to only either one of the systems were also formed. In conclusion, TiO2 photocatalysis is a rapid, simple and inexpensive method for imitation of phase I metabolism of anabolic steroids and production of metabolite standards.

  18. Synergistic effects between catalase inhibitors and modulators of nitric oxide metabolism on tumor cell apoptosis.

    Science.gov (United States)

    Scheit, Katrin; Bauer, Georg

    2014-10-01

    Inhibitors of catalase (such as ascorbate, methyldopa, salicylic acid and neutralizing antibodies) synergize with modulators of nitric oxide (NO) metabolism (such as arginine, arginase inhibitor, NO synthase-inducing interferons and NO dioxygenase inhibitors) in the singlet oxygen-mediated inactivation of tumor cell protective catalase. This is followed by reactive oxygen species (ROS)-dependent apoptosis induction. TGF-beta, NADPH oxidase-1, NO synthase, dual oxidase-1 and caspase-9 are characterized as essential catalysts in this process. The FAS receptor and caspase-8 are required for amplification of ROS signaling triggered by individual compounds, but are dispensable when the synergistic effect is established. Our findings explain the antitumor effects of catalase inhibitors and of compounds that target NO metabolism, as well as their synergy. These data may have an impact on epidemiological studies related to secondary plant compounds and open new perspectives for the establishment of novel antitumor drugs and for the improvement of established chemotherapeutics.

  19. Mechanisms and evolution of oxidative sulfur metabolism in green sulfur bacteria

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    Lea Haarup Gregersen

    2011-05-01

    Full Text Available Green sulfur bacteria (GSB constitute a closely related group of photoautotrophic and thiotrophic bacteria with limited phenotypic variation. They typically oxidize sulfide and thiosulfate to sulfate with sulfur globules as an intermediate. Based on genome sequence information from 15 strains, the distribution and phylogeny of enzymes involved in their oxidative sulfur metabolism was investigated. At least one homolog of sulfide:quinone oxidoreductase (SQR is present in all strains. In all sulfur-oxidizing GSB strains except the earliest diverging Chloroherpeton thalassium, the sulfide oxidation product is further oxidized to sulfite by the dissimilatory sulfite reductase (DSR system. This system consists of components horizontally acquired partly from sulfide-oxidizing and partly from sulfate-reducing bacteria. Depending on the strain, the sulfite is probably oxidized to sulfate by one of two different mechanisms that have different evolutionary origins: adenosine-5’-phosphosulfate reductase (APR or polysulfide reductase-like complex 3 (PSRLC3. Thiosulfate utilization by the SOX system in GSB has apparently been acquired horizontally from proteobacteria. SoxCD does not occur in GSB, and its function in sulfate formation in other bacteria has been replaced by the DSR system in GSB. Sequence analyses suggested that the conserved soxJXYZAKBW gene cluster was horizontally acquired by Chlorobium phaeovibrioides DSM 265 from the Chlorobaculum lineage and that this acquisition was mediated by a mobile genetic element. Thus, the last common ancestor of currently known GSB was probably photoautotrophic, hydrogenotrophic, and contained SQR but not DSR or SOX. In addition, the predominance of the Chlorobium-Chlorobaculum-Prosthecochloris lineage among cultured GSB could be due to the horizontally acquired DSR and SOX systems. Finally, based upon structural, biochemical, and phylogenetic analyses, a uniform nomenclature is suggested for sqr genes in

  20. Relation of Oxidative Stress and Impaired Fibrinolysis with HDL Biogenesis in Indonesian Men with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Ida Paulina Sormin

    2010-04-01

    Full Text Available BACKGROUND: Biogenesis of HDL involves factors that regulate the synthesis, intravascular remodeling, and catabolism of HDL. Disturbance of these factors can lead to low concentration of HDL-C. Metabolic syndrome (MetS is characterized by low concentration of high-density lipoprotein cholesterol (HDL-C. In MetS occur several pathological conditions including oxidative stress and impaired fibrinolysis, which contribute to the risk of atherosclerosis process. The correlation between oxidative stress and impaired fibrinolysis with HDL biogenesis dysfunction and its correlation with low concentration of HDL-C has not been well understood and therefore needs to be further investigated. METHODS: This study was an observational study with crosssectional design, involving 163 adult men, aged 25-60 years with metabolic syndrome. Concentration of apoA-1, prebeta-1 HDL, CETP, F2-isoprostan, PAI-1, and HDL-C were measured. The apo A1/HDL ratio indicated HDL maturation, whereas the CETP/HDL-C and CETP/TG ratios indicated HDL catabolism. RESULTS: The study showed that there were a positive correlation between PAI-1 with apoA1/HDL-C ratios (r=0.226, p=0.005 and a negative correlation with the CETP/TG ratios (r=-0.215, p=0.007, whereas F2-isoprostan did not have correlation with HDL biogenesis factors. CONCLUSIONS: We concluded that there was correlation between impaired fibrinolysis with decreased HDL maturation and there was increased HDL catabolism leading to low HDL-C concentration in men with metabolic syndrome. KEYWORDS: F2-isoprostan, PAI-1, apoA-1, prebeta-1 HDL, CETP, metabolic syndrome.

  1. Expression of nitric oxide synthase and guanylate cyclase in the human ciliary body and trabecular meshwork

    Institute of Scientific and Technical Information of China (English)

    WU Ren-yi; MA Ning

    2012-01-01

    Background The role played by the nitric oxide (NO) signaling pathway in the aqueous humor dynamics is still unclear.This study was designed to investigate the expression and distribution of NO synthase (NOS) isoforms and guanylate cyclase (GC) in human ciliary body,trabecular meshwork and the Schlemm's canal.Methods Twelve eyes after corneal transplantation were used.Expression of three NOS isoforms (i.e.neuronal NOS (nNOS),inducible NOS (iNOS) and endothelial NOS (eNOS)) and GC were assessed in 10 eyes by immunohistochemical staining using monoclonal or polyclonal antibody of NOS and GC.Ciliary bodies were dissected free and the total proteins were extracted.Western blotting was performed to confirm the protein expression of 3 NOS isoforms and GC.Results Expression of 3 NOS isoforms and GC were observed in the ciliary epithelium,ciliary muscle,trabecular meshwork and the endothelium of the Schlemm's canal.Immunoreactivity of nNOS was detected mainly along the apical cytoplasmic junction of the non-pigmented epithelium (NPE) and pigmented epithelial (PE) cells.Protein expressions of 3 NOS isoforms and GC were confirmed in isolated human ciliary body by Western blotting.Conclusions The expression of NOS isoforms and GC in human ciliary body suggest the possible involvement of NO and cyclic guanosine monophosphate (cyclic GMP,cGMP) signaling pathway in the ciliary body,and may play a role in both processes of aqueous humor formation and drainage.

  2. A metabolic and body-size scaling framework for parasite within-host abundance, biomass, and energy flux.

    Science.gov (United States)

    Hechinger, Ryan F

    2013-08-01

    Energetics may provide a useful currency for studying the ecology of parasite assemblages within individual hosts. Parasite assemblages may also provide powerful models to study general principles of ecological energetics. Yet there has been little ecological research on parasite-host energetics, probably due to methodological difficulties. However, the scaling relationships of individual metabolic rate with body or cell size and temperature may permit us to tackle the energetics of parasite assemblages in hosts. This article offers the foundations and initial testing of a metabolic theory of ecology (MTE) framework for parasites in hosts. I first provide equations to estimate energetic flux through observed parasite assemblages. I then develop metabolic scaling theory for parasite abundance, energetics, and biomass in individual hosts. In contrast to previous efforts, the theory factors in both host and parasite metabolic scaling, how parasites use host space, and whether energy or space dictates carrying capacity. Empirical tests indicate that host energetic flux can set parasite carrying capacity, which decreases as predicted considering the scaling of host and parasite metabolic rates. The theory and results also highlight that the phenomenon of "energetic equivalence" is not an assumption of MTE but a possible outcome contingent on how species partition resources. Hence, applying MTE to parasites can lend mechanistic, quantitative, predictive insight into the nature of parasitism and can inform general ecological theory.

  3. Quantitative lipidomics reveals age-dependent perturbations of whole-body lipid metabolism in ACBP deficient mice.

    Science.gov (United States)

    Gallego, Sandra F; Sprenger, Richard R; Neess, Ditte; Pauling, Josch K; Færgeman, Nils J; Ejsing, Christer S

    2017-02-01

    The acyl-CoA binding protein (ACBP) plays a key role in chaperoning long-chain acyl-CoAs into lipid metabolic processes and acts as an important regulatory hub in mammalian physiology. This is highlighted by the recent finding that mice devoid of ACBP suffer from a compromised epidermal barrier and delayed weaning, the physiological process where newborns transit from a fat-based milk diet to a carbohydrate-rich diet. To gain insights into how ACBP impinges on weaning and the concomitant remodeling of whole-body lipid metabolism we performed a comparative lipidomics analysis charting the absolute abundance of 613 lipid molecules in liver, muscle and plasma from weaning and adult Acbp knockout and wild type mice. Our results reveal that ACBP deficiency affects primarily lipid metabolism of liver and plasma during weaning. Specifically, we show that ACBP deficient mice have elevated levels of hepatic cholesteryl esters, and that lipids featuring an 18:1 fatty acid moiety are increased in Acbp depleted mice across all tissues investigated. Our results also show that the perturbation of systemic lipid metabolism in Acbp knockout mice is transient and becomes normalized and similar to that of wild type as mice grow older. These findings demonstrate that ACBP serves crucial functions in maintaining lipid metabolic homeostasis in mice during weaning.

  4. Predictors of metabolic syndrome in the Iranian population: waist circumference, body mass index, or waist to hip ratio?

    Science.gov (United States)

    Gharipour, Mojgan; Sarrafzadegan, Nizal; Sadeghi, Masoumeh; Andalib, Elham; Talaie, Mohammad; Shafie, Davood; Aghababaie, Esmaiel

    2013-01-01

    This study aimed to investigate whether body mass index (BMI), waist circumference (WC), or waist to hip ratio (WHR) could be a better predictor of metabolic syndrome and, if so, what would be the cutoff points for these surrogates to appropriately differentiate metabolic syndrome in different age and sex subgroups. Methods. The present cross-sectional study was conducted on a sample of Isfahan Cohort Study (ICS). In total, 468 individuals (194 with and 274 subjects without metabolic syndrome) according to the National Cholesterol Education Program's Adult Treatment Panel III (ATP-III) criteria were selected. Anthropometric indices were measured and plotted using receiver-operating characteristic (ROC) curves. Results. According to ROC curve analysis, WC and WHR parameters were better indicators of metabolic syndrome compared to BMI in women, whereas in men WHR had a lower discriminating value compared to the other two parameters. Among these three anthropometric parameters, BMI had a lower sensitivity and WC and WHR both had a higher sensitivity for predicting metabolic syndrome in women compared with in men. The cut points for WC were nearly equal in men and women, 90.3 versus 90.0, respectively. Women had higher cut points for BMI (28.5 kg/m(2)) compared to men (26.0 kg/m(2)). Our results showed the highest sensitivity and specificity for WC cut points specially in women. To predict metabolic syndrome, we looked into optimal age-specific cut points for BMI, WC, and WHR. The results indicated that WC had the highest discriminating value compared to other indicators in the different age subgroups. The optimal cut points for all three parameters gradually increased with age. Conclusion. Our results demonstrated that regardless of gender and age variables, WC could be a preferred parameter for predicting metabolic syndrome compared to BMI and WHR in Iranian population.

  5. Effects of an 8-weeks erythropoietin treatment on mitochondrial and Whole body fat oxidation capacity during exercise in healthy males

    DEFF Research Database (Denmark)

    Guadalupe Grau, Amelia; Plenge, Ulla; Bønding, Signe Helbo

    2015-01-01

    Abstract The present investigation was performed to elucidate if the non-erythropoietic ergogenic effect of a recombinant erythropoietin treatment results in an impact on skeletal muscle mitochondrial and whole body fatty acid oxidation capacity during exercise, myoglobin concentration and angiog......Abstract The present investigation was performed to elucidate if the non-erythropoietic ergogenic effect of a recombinant erythropoietin treatment results in an impact on skeletal muscle mitochondrial and whole body fatty acid oxidation capacity during exercise, myoglobin concentration......, pyruvate, succinate) with additional electron input from β-oxidation (octanoylcarnitine) (from 60 ± 13 to 87 ± 24 pmol · s(-1) · mg(-1) P ... of recombinant erythropoietin treatment increases mitochondrial fatty acid oxidation capacity and myoglobin concentration without any effect on whole body maximal fat oxidation....

  6. The effect of seasonality on oxidative metabolism in Nacella (Patinigera) magellanica.

    Science.gov (United States)

    Malanga, Gabriela; Estevez, María Susana; Calvo, Jorge; Abele, Doris; Puntarulo, Susana

    2007-04-01

    We studied the seasonal variation on aerobic metabolism and the response of oxidative stress parameters in the digestive glands of the subpolar limpet Nacella (P.) magellanica. Sampling was carried out from July (winter) 2002 to July 2003 in Beagle Channel, Tierra del Fuego, Argentina. Whole animal respiration rates increased in early spring as the animals spawned and remained elevated throughout summer and fall (winter: 0.09+/-0.02 micromol O2 h-1 g-1; summer: 0.31+/-0.06 micromol O2 h-1 g-1). Oxidative stress was assessed at the hydrophilic level as the ascorbyl radical content/ascorbate content ratio (A./AH-). The A./AH- ratio showed minimum values in winter (3.7+/-0.2 10(-5)AU) and increased in summer (18+/-5 10(-5) AU). A similar pattern was observed for lipid radical content (122+/-29 pmol mg-1 fresh mass [FW] in winter and 314+/-45 pmol mg-1 FW in summer), iron content (0.99+/-0.07 and 2.7+/-0.6 nmol mg-1 FW in winter and summer, respectively) and catalase activity (2.9+/-0.2 and 7+/-1 U mg-1 FW in winter and summer, respectively). Since nitrogen derived radicals are thought to be critically involved in oxidative metabolism in cells, nitric oxide content was measured and a significant difference in the content of the Fe-MGD-NO adduct in digestive glands from winter and summer animals was observed. Together, the data indicate that both oxygen and nitrogen radical generation rates in N. (P.) magellanica are strongly dependent on season.

  7. Three-body system metaphor for the two-slit experiment and Escherichia coli lactose-glucose metabolism.

    Science.gov (United States)

    Asano, Masanari; Khrennikov, Andrei; Ohya, Masanori; Tanaka, Yoshiharu; Yamato, Ichiro

    2016-05-28

    We compare the contextual probabilistic structures of the seminal two-slit experiment (quantum interference experiment), the system of three interacting bodies andEscherichia colilactose-glucose metabolism. We show that they have the same non-Kolmogorov probabilistic structure resulting from multi-contextuality. There are plenty of statistical data with non-Kolmogorov features; in particular, the probabilistic behaviour of neither quantum nor biological systems can be described classically. Biological systems (even cells and proteins) are macroscopic systems and one may try to present a more detailed model of interactions in such systems that lead to quantum-like probabilistic behaviour. The system of interactions between three bodies is one of the simplest metaphoric examples for such interactions. By proceeding further in this way (by playing withn-body systems) we shall be able to find metaphoric mechanical models for complex bio-interactions, e.g. signalling between cells, leading to non-Kolmogorov probabilistic data.

  8. Nitric oxide metabolism and indole acetic acid biosynthesis cross-talk in Azospirillum brasilense SM.

    Science.gov (United States)

    Koul, Vatsala; Tripathi, Chandrakant; Adholeya, Alok; Kochar, Mandira

    2015-04-01

    Production of nitric oxide (NO) and the presence of NO metabolism genes, nitrous oxide reductase (nosZ), nitrous oxide reductase regulator (nosR) and nitric oxide reductase (norB) were identified in the plant-associated bacterium (PAB) Azospirillum brasilense SM. NO presence was confirmed in all overexpressing strains, while improvement in the plant growth response of these strains was mediated by increased NO and indole-3-acetic acid (IAA) levels in the strains. Electron microscopy showed random distribution to biofilm, with surface colonization of pleiomorphic Azospirilla. Quantitative IAA estimation highlighted a crucial role of nosR and norBC in regulating IAA biosynthesis. The NO quencher and donor reduced/blocked IAA biosynthesis by all strains, indicating their common regulatory role in IAA biosynthesis. Tryptophan (Trp) and l-Arginine (Arg) showed higher expression of NO genes tested, while in the case of ipdC, only Trp and IAA increased expression, while Arg had no significant effect. The highest nosR expression in SMnosR in the presence of IAA and Trp, along with its 2-fold IAA level, confirmed the relationship of nosR overexpression with Trp in increasing IAA. These results indicate a strong correlation between IAA and NO in A. brasilense SM and suggest the existence of cross-talk or shared signaling mechanisms in these two growth regulators.

  9. Metabolic and Nutritional Needs to Normalize Body Mass Index by Doubling the Admission Body Weight in Severe Anorexia Nervosa

    Science.gov (United States)

    Gentile, Maria Gabriella; Lessa, Chiara; Cattaneo, Marina

    2013-01-01

    Anorexia nervosa exhibits one of the highest death rates among psychiatric patients and a relevant fraction of it is derived from undernutrition. Nutritional and medical treatment of extreme undernutrition present two very complex and conflicting tasks: (1) to avoid “refeeding syndrome” caused by a too fast correction of malnutrition; and (2) to avoid “underfeeding” caused by a too cautious refeeding. To obtain optimal treatment results, the caloric intake should be planned starting with indirect calorimetry measurements and electrolyte abnormalities accurately controlled and treated. This article reports the case of an anorexia nervosa young female affected by extreme undernutrition (BMI 9.6 kg/m2) who doubled her admission body weight (from 22.5 kg to 44 kg) in a reasonable time with the use of enteral tube feeding for gradual correction of undernutrition. Refeeding syndrome was avoided through a specialized and flexible program according to clinical, laboratory, and physiological findings. PMID:23645991

  10. Metabolic Disorders

    Science.gov (United States)

    ... as your liver, muscles, and body fat. A metabolic disorder occurs when abnormal chemical reactions in your body ... that produce the energy. You can develop a metabolic disorder when some organs, such as your liver or ...

  11. Circulating oxidized low-density lipoproteins and arterial elasticity: comparison between men with metabolic syndrome and physically active counterparts

    Directory of Open Access Journals (Sweden)

    Pohjantähti-Maaroos Hanna

    2010-08-01

    Full Text Available Abstract Background Accumulation of oxidized low-density lipoproteins in the intimae of arteries and endothelial dysfunction are key events in the development of atherosclerosis. Patients with metabolic syndrome are at high risk for cardiovascular diseases but the linkage between metabolic syndrome and atherosclerosis is incompletely understood. We studied whether the levels of oxidized LDL and arterial elasticity differ between metabolic syndrome patients and physically active controls. Methods 40 men with metabolic syndrome and 40 physically active controls participated in this cross-sectional study. None of the study subjects had been diagnosed with cardiovascular disease. Levels of oxidized LDL were assessed by a two-site ELISA immunoassay. Arterial elasticity was assessed non-invasively by the HDI/PulseWave™ CR-2000 arterial tonometer. Results Levels of oxidized LDL were 89.6 ± 33.1 U/L for metabolic syndrome subjects and 68.5 ± 23.6 U/L for controls (p = 0.007. The difference remained significant after adjustment for LDL cholesterol. Large artery elasticity index (C1 was 16.2 ± 4.1 mL/mmHgx10 for metabolic syndrome subjects and 19.4 ± 3.7 mL/mmHgx10 for controls (p = 0.001, small artery indices (C2 were 7.0 ± 3.2 mL/mmHgx100 and 6.5 ± 2.9 mL/mmHgx100 (NS, respectively. Conclusions Subjects with metabolic syndrome had elevated levels of oxidized LDL and reduced large arterial elasticity compared to controls. This finding may partly explain the increased risk for cardiovascular diseases among metabolic syndrome patients. Trial registration ClinicalTrials.gov NCT01114763

  12. The critical role of oxidative stress in the toxicity and metabolism of quinoxaline 1,4-di-N-oxides in vitro and in vivo.

    Science.gov (United States)

    Wang, Xu; Martínez, María-Aránzazu; Cheng, Guyue; Liu, Zhaoying; Huang, Lingli; Dai, Menghong; Chen, Dongmei; Martínez-Larrañaga, María-Rosa; Anadón, Arturo; Yuan, Zonghui

    2016-05-01

    Quinoxaline 1,4-dioxide derivatives (QdNOs) have been widely used as growth promoters and antibacterial agents. Carbadox (CBX), olaquindox (OLA), quinocetone (QCT), cyadox (CYA) and mequindox (MEQ) are the classical members of QdNOs. Some members of QdNOs are known to cause a variety of toxic effects. To date, however, almost no review has addressed the toxicity and metabolism of QdNOs in relation to oxidative stress. This review focused on the research progress associated with oxidative stress as a plausible mechanism for QdNO-induced toxicity and metabolism. The present review documented that the studies were performed over the past 10 years to interpret the generation of reactive oxygen species (ROS) and oxidative stress as the results of QdNO treatment and have correlated them with various types of QdNO toxicity, suggesting that oxidative stress plays critical roles in their toxicities. The major metabolic pathways of QdNOs are N→O group reduction and hydroxylation. Xanthine oxidoreductase (XOR), aldehyde oxidase (SsAOX1), carbonyl reductase (CBR1) and cytochrome P450 (CYP) enzymes were involved in the QdNOs metabolism. Further understanding the role of oxidative stress in QdNOs-induced toxicity will throw new light onto the use of antioxidants and scavengers of ROS as well as onto the blind spots of metabolism and the metabolizing enzymes of QdNOs. The present review might contribute to revealing the QdNOs toxicity, protecting against oxidative damage and helping to improve the rational use of concurrent drugs, while developing novel QdNO compounds with more efficient potentials and less toxic effects.

  13. Long-term vegetarians have low oxidative stress, body fat, and cholesterol levels.

    Science.gov (United States)

    Kim, Mi Kyung; Cho, Sang Woon; Park, Yoo Kyoung

    2012-04-01

    Excessive oxidative stress and abnormal blood lipids may cause chronic diseases. This risk can be reduced by consuming an antioxidant- and fiber-rich vegetarian diet. We compared biomarkers of oxidative stress, antioxidant capacity, and lipid profiles of sex- and age-matched long-term vegetarians and omnivores in Korea. Forty-five vegetarians (23 men and 22 women; mean age, 49.5 ± 5.3 years), who had maintained a vegetarian diet for a minimum of 15 years, and 30 omnivores (15 men and 15 women; mean age, 48.9 ± 3.6 years) participated in this study. Their 1-day, 24-h recall, and 2-day dietary records were analyzed. Oxidative stress was measured by the levels of diacron reactive oxygen metabolites (d-ROM). Antioxidant status was determined by the biological antioxidant potential (BAP) and levels of endogenous antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. We observed that vegetarians had a significantly lower body fat percentage (21.6 ± 6.4%) than that of omnivores (25.4 ± 4.6%; P vegetarians than those in omnivores (331.82 ± 77.96 and 375.80 ± 67.26 Carratelli units; P vegetarians and omnivores were 173.73 ± 31.42 mg/dL and 193.17 ± 37.89 mg/dL, respectively (P vegetarians and omnivores, respectively, indicating that vegetarians had significantly lower lipid levels. Thus, oxidative stress, body fat, and cholesterol levels were lower in long-term vegetarians than those in omnivores.

  14. The Impact of Rapid Weight Loss on Oxidative Stress Markers and the Expression of the Metabolic Syndrome in Obese Individuals

    Directory of Open Access Journals (Sweden)

    Eva Tumova

    2013-01-01

    Full Text Available Objective. Obesity is linked with a state of increased oxidative stress, which plays an important role in the etiology of atherosclerosis and type 2 diabetes mellitus. The aim of our study was to evaluate the effect of rapid weight loss on oxidative stress markers in obese individuals with metabolic syndrome (MetS. Design and Methods. We measured oxidative stress markers in 40 obese subjects with metabolic syndrome (MetS+, 40 obese subjects without metabolic syndrome (MetS−, and 20 lean controls (LC at baseline and after three months of very low caloric diet. Results. Oxidized low density lipoprotein (ox-LDL levels decreased by 12% in MetS+ subjects, associated with a reduction in total cholesterol (TC, even after adjustment for age and sex. Lipoprotein associated phospholipase A2 (Lp-PLA2 activity decreased by 4.7% in MetS+ subjects, associated with a drop in LDL-cholesterol (LDL-C, TC, and insulin levels. Multivariate logistic regression analysis showed that a model including ox-LDL, LpPLA2 activity, and myeloperoxidase (MPO improved prediction of MetS status among obese individuals compared to each oxidative stress marker alone. Conclusions. Oxidative stress markers were predictive of MetS in obese subjects, suggesting a higher oxidative stress. Rapid weight loss resulted in a decline in oxidative stress markers, especially in MetS+ patients.

  15. Xanthine Oxidase Activity Is Associated with Risk Factors for Cardiovascular Disease and Inflammatory and Oxidative Status Markers in Metabolic Syndrome: Effects of a Single Exercise Session

    Directory of Open Access Journals (Sweden)

    Ana Maria Pandolfo Feoli

    2014-01-01

    Full Text Available Objective. The main goal of the present study was to investigate the xanthine oxidase (XO activity in metabolic syndrome in subjects submitted to a single exercise session. We also investigated parameters of oxidative and inflammatory status. Materials/Methods. A case-control study (9 healthy and 8 MS volunteers was performed to measure XO, superoxide dismutase (SOD, glutathione peroxidase activities, lipid peroxidation, high-sensitivity C-reactive protein (hsCRP content, glucose levels, and lipid profile. Body mass indices, abdominal circumference, systolic and diastolic blood pressure, and TG levels were also determined. The exercise session consisted of 3 minutes of stretching, 3 minutes of warm-up, 30 minutes at a constant dynamic workload at a moderate intensity, and 3 minutes at a low speed. The blood samples were collected before and 15 minutes after the exercise session. Results. Serum XO activity was higher in MS group compared to control group. SOD activity was lower in MS subjects. XO activity was correlated with SOD, abdominal circumference, body mass indices, and hsCRP. The single exercise session reduced the SOD activity in the control group. Conclusions. Our data support the association between oxidative stress and risk factors for cardiovascular diseases and suggest XO is present in the pathogenesis of metabolic syndrome.

  16. The role of glutamine synthetase in energy production and glutamine metabolism during oxidative stress.

    Science.gov (United States)

    Aldarini, Nohaiah; Alhasawi, Azhar A; Thomas, Sean C; Appanna, Vasu D

    2017-01-17

    Oxidative stress is known to severely impede aerobic adenosine triphosphate (ATP) synthesis. However, the metabolically-versatile Pseudomonas fluorescens survives this challenge by invoking alternative ATP-generating networks. When grown in a medium with glutamine as the sole organic nutrient in the presence of H2O2, the microbe utilizes glutamine synthetase (GS) to modulate its energy budget. The activity of this enzyme that mediates the release of energy stored in glutamine was sharply increased in the stressed cells compared to the controls. The enhanced activities of such enzymes as acetate kinase, adenylate kinase and nucleotide diphosphate kinase ensured the efficacy of this ATP producing-machine by transferring the high energy phosphate. The elevated amounts of phosphoenol pyruvate carboxylase and pyruvate orthophosphate dikinase recorded in the H2O2 exposed cells provided another route to ATP independent of the reduction of O2. This is the first demonstration of a metabolic pathway involving GS dedicated to ATP synthesis. The phospho-transfer network that is pivotal to the survival of the microorganism under oxidative stress may reveal therapeutic targets against infectious microbes reliant on glutamine for their proliferation.

  17. Differential response of oxidative stress and thiol metabolism in contrasting rice genotypes for arsenic tolerance.

    Science.gov (United States)

    Tripathi, Preeti; Mishra, Aradhana; Dwivedi, Sanjay; Chakrabarty, Debasis; Trivedi, Prabodh K; Singh, Rana Pratap; Tripathi, Rudra Deo

    2012-05-01

    The mechanism of arsenic (As) tolerance was investigated on two contrasting rice (Oryza sativa L.) genotypes, selected for As tolerance and accumulation. One tolerant (Triguna) and one sensitive (IET-4786) variety were exposed to various arsenate (0-50 μM) levels for 7 d for biochemical analyses. Arsenic induced oxidative stress was more pronounced in IET-4786 than Triguna especially in terms of reactive oxygen species, lipid peroxidation, EC and pro-oxidant enzymes (NADPH oxidase and ascorbate oxidase). However, Triguna tolerated As stress through the enhanced enzymes activities particularly pertaining to thiol metabolism such as serine acetyl transferase (SAT), cysteine synthase (CS), γ-glutamyl cysteine synthase (γ-ECS), γ-glutamyl transpeptidase (γ-GT), and glutathione-S-transferase (GST) as well as arsenate reductase (AR). Besides maintaining the ratio of redox couples GSH/GSSG and ASC/DHA, the level of phytochelatins (PCs) and phytochelatin synthase (PCS) activity were more pronounced in Triguna, in which harmonized responses of thiol metabolism was responsible for As tolerance in contrast to IET-4786 showing its susceptible nature towards As exposure.

  18. Antioxidant defenses and metabolic depression. The hypothesis of preparation for oxidative stress in land snails.

    Science.gov (United States)

    Hermes-Lima, M; Storey, J M; Storey, K B

    1998-07-01

    The roles of enzymatic antioxidant defenses in the natural tolerance of environmental stresses that impose changes in oxygen availability and oxygen consumption on animals is discussed with a particular focus on the biochemistry of estivation and metabolic depression in pulmonate land snails. Despite reduced oxygen consumption and PO2 during estivation, which should also mean reduced production of oxyradicals, the activities of antioxidant enzymes, such as superoxide dismutase and catalase, increased in 30 day-estivating snails. This appears to be an adaptation that allows the snails to deal with oxidative stress that takes place during arousal when PO2 and oxygen consumption rise rapidly. Indeed, oxidative stress was indicated by increased levels of lipid peroxidation damage products accumulating in hepatopancreas within minutes after arousal was initiated. The various metabolic sites responsible for free radical generation during arousal are still unknown but it seems unlikely that the enzyme xanthine oxidase plays any substantial role in this despite being implicated in oxidative stress in mammalian models of ischemia/reperfusion. We propose that the activation of antioxidant defenses in the organs of Otala lactea during estivation is a preparative mechanism against oxidative stress during arousal. Increased activities of antioxidant enzymes have also observed under other stress situations in which the actual production of oxyradicals should decrease. For example, antioxidant defenses are enhanced during anoxia exposure in garter snakes Thamnophis sirtalis parietalis (10 h at 5 degrees C) and leopard frogs Rana pipiens (30 h at 5 degrees C) and during freezing exposure (an ischemic condition due to plasma freezing) in T. sirtalis parietalis and wood frogs Rana sylvatica. It seems that enhancement of antioxidant enzymes during either anoxia or freezing is used as a preparatory mechanism to deal with a physiological oxidative stress that occurs rapidly within the

  19. Associations between γ-glutamyl transferase, metabolic abnormalities and inflammation in healthy subjects from a population-based cohort: A possible implication for oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Simona Bo; Roberto Gambino; Marilena Durazzo; Sabrina Guidi; Elisa Tiozzo; Federica Ghione; Luigi Gentile; Maurizio Cassader; Gian Franco Pagano

    2005-01-01

    AIM: To examine the relationships between γ -glutamyltransferase (GGT), alanine-aminotransferase (ALT),aspartate-aminotransferase (AST) and various metabolic parameters, C-reactive protein (CRP) and an oxidative stress marker (nitrotyrosine, NT) in subjects without any metabolic abnormalities from a population-based sample.METHODS: Two hundred and five subjects with normal body mass index (BMI), glucose tolerance, and without any metabolic abnormality were studied out of 1339subjects, without known liver diseases, alcohol abuse or use of hepatotoxic drugs, who are representative of the 45-64 aged population of Asti (north-western Italy).RESULTS: In all patients metabolic parameters and hs-CRP levels linearly increase from the lowest to the highest ALT and GGT tertiles, while in subjects without metabolic abnormalities, there is a significant association between fasting glucose, uric acid, waist circumference,hs-CRP, triglyceride values, and GGT levels. In these subjects, male sex, higher hs-CRP and glucose levels are associated with GGT levels in a multiple regression model, after adjustments for multiple confounders.In the same model, median NT levels are significantly associated with the increasing GGT tertile (β = 1.06;95%CI 0.67-1.45), but not with the AST and ALT tertiles.In a multiple regression model, after adjusting for age,sex, BMI, waist, smoking, and alcohol consumption, both NT (β = 0.05; 95%CI 0.02-0.08) and hs-CRP levels (β =0.09; 95%CI 0.03-0.15) are significantly associated with fasting glycemia.CONCLUSION: GGT, an easy, universally standardized and available measurement, could represent an early marker of sub-clinical inflammation and oxidative stress in otherwise healthy individuals. Prospective studies are needed to establish if GGT could predict future diabetes in these subjects.

  20. High-fat diet induces metabolic changes and reduces oxidative stress in female mouse hearts.

    Science.gov (United States)

    Barba, Ignasi; Miró-Casas, Elisabet; Torrecilla, José L; Pladevall, Eulàlia; Tejedor, Sergi; Sebastián-Pérez, Rubén; Ruiz-Meana, Marisol; Berrendero, José R; Cuevas, Antonio; García-Dorado, David

    2017-02-01

    After an acute myocardial infarction, obese patients generally have a better prognosis than their leaner counterparts, known as the "obesity paradox". In addition, female sex is associated with a lower risk of cardiac ischemic events and smaller infarct size compared to males. The objective of the present work was to study the metabolic phenotype and mitochondrial function associated to female sex and short-term high-fat diet. (1)H NMR spectra of mice heart extracts were analysed by mRMR variable selection and linear discriminant analysis was used to evaluate metabolic changes. In separate experiments, O2 consumption and H2O2 production were measured from isolated mitochondria as well as serum oxidation susceptibility. Fingerprinting showed that male hearts contained more myo-inositol, taurine and glutamate than female hearts. HFD reduced the levels of creatine, taurine citrate and acetate. Profiling showed increased alanine and fumarate in HFD suggesting altered glycolitic and Krebs cycle pathways. Female mice contained less glucose than males. Female sex nor HFD altered mitochondria oxygen consumption but both conditions reduced the amount of H2O2 produced in an additive manner. Serum of females had lower oxidation susceptibility than serum from males but there were no differences associated with HFD. In conclusion, female sex and short-term HFD have an effect on the myocardial metabolic pattern and reduce the amount of H2O2 produced by mitochondria in an additive manner suggesting different mechanisms of action. This could explain, at least in part, the protection afforded by female sex and the "obesity paradox".

  1. Nitric oxide and reactive oxygen species mediate metabolic changes in barley seed embryo during germination

    Directory of Open Access Journals (Sweden)

    Zhenguo eMa

    2016-02-01

    Full Text Available The levels of nitric oxide (NO and reactive oxygen species (ROS, ATP/ADP ratios, reduction levels of ascorbate and glutathione, expression of the genes encoding proteins involved in metabolism of NO and activities of the enzymes involved in fermentation and in metabolism of NO and ROS were studied in the embryos of germinating seeds of two barley (Hordeum vulgare L. cultivars differing in dormancy level. The level of NO production continuously increased after imbibition while the level of nitrosylated SH-groups in proteins increased. This corresponded to the decrease of free SH-groups in proteins. At early stage of germination (0-48 h postimbibition the genes encoding class 1 phytoglobin (the protein scavenging NO and S-nitrosoglutathione reductase (scavenging S-nitrosoglutathione were markedly expressed. More dormant cultivar exhibited lower ATP/ADP and ascorbate/dehydroascorbate ratios and lower lactate and alcohol dehydrogenase activities, while the production of NO and nitrosylation of proteins was higher as compared to the non-dormant cultivar. The obtained data indicate that at the onset of germination NO is actively generated causing nitrosylation of SH-groups and a switch from respiration to fermentation. After radicle protrusion the metabolism changes in a more reducing type as recorded by ratio of reduced and oxidized glutathione and ascorbate. The turnover of NO by the scavenging systems (phytoglobin, S-nitrosoglutathione reductase and interaction with ROS might contribute to the maintenance of redox and energy balance of germinating seeds and lead to alleviation of dormancy.

  2. Effect of high-fat diets on body composition, lipid metabolism and insulin sensitivity, and the role of exercise on these parameters

    Directory of Open Access Journals (Sweden)

    D.F. Coelho

    2011-10-01

    Full Text Available Dietary fat composition can interfere in the development of obesity due to the specific roles of some fatty acids that have different metabolic activities, which can alter both fat oxidation and deposition rates, resulting in changes in body weight and/or composition. High-fat diets in general are associated with hyperphagia, but the type of dietary fat seems to be more important since saturated fats are linked to a positive fat balance and omental adipose tissue accumulation when compared to other types of fat, while polyunsaturated fats, omega-3 and omega-6, seem to increase energy expenditure and decrease energy intake by specific mechanisms involving hormone-sensitive lipase, activation of peroxisome proliferator-activated receptor α (PPARα and others. Saturated fat intake can also impair insulin sensitivity compared to omega-3 fat, which has the opposite effect due to alterations in cell membranes. Obesity is also associated with impaired mitochondrial function. Fat excess favors the production of malonyl-CoA, which reduces GLUT4 efficiency. The tricarboxylic acid cycle and beta-oxidation are temporarily uncoupled, forming metabolite byproducts that augment reactive oxygen species production. Exercise can restore mitochondrial function and insulin sensitivity, which may be crucial for a better prognosis in treating or preventing obesity.

  3. Metabolic engineering of β-oxidation in Penicillium chrysogenum for improved semi-synthetic cephalosporin biosynthesis.

    Science.gov (United States)

    Veiga, Tânia; Gombert, Andreas K; Landes, Nils; Verhoeven, Maarten D; Kiel, Jan A K W; Krikken, Arjen M; Nijland, Jeroen G; Touw, Hesselien; Luttik, Marijke A H; van der Toorn, John C; Driessen, Arnold J M; Bovenberg, Roel A L; van den Berg, Marco A; van der Klei, Ida J; Pronk, Jack T; Daran, Jean-Marc

    2012-07-01

    Industrial production of semi-synthetic cephalosporins by Penicillium chrysogenum requires supplementation of the growth media with the side-chain precursor adipic acid. In glucose-limited chemostat cultures of P. chrysogenum, up to 88% of the consumed adipic acid was not recovered in cephalosporin-related products, but used as an additional carbon and energy source for growth. This low efficiency of side-chain precursor incorporation provides an economic incentive for studying and engineering the metabolism of adipic acid in P. chrysogenum. Chemostat-based transcriptome analysis in the presence and absence of adipic acid confirmed that adipic acid metabolism in this fungus occurs via β-oxidation. A set of 52 adipate-responsive genes included six putative genes for acyl-CoA oxidases and dehydrogenases, enzymes responsible for the first step of β-oxidation. Subcellular localization of the differentially expressed acyl-CoA oxidases and dehydrogenases revealed that the oxidases were exclusively targeted to peroxisomes, while the dehydrogenases were found either in peroxisomes or in mitochondria. Deletion of the genes encoding the peroxisomal acyl-CoA oxidase Pc20g01800 and the mitochondrial acyl-CoA dehydrogenase Pc20g07920 resulted in a 1.6- and 3.7-fold increase in the production of the semi-synthetic cephalosporin intermediate adipoyl-6-APA, respectively. The deletion strains also showed reduced adipate consumption compared to the reference strain, indicating that engineering of the first step of β-oxidation successfully redirected a larger fraction of adipic acid towards cephalosporin biosynthesis.

  4. Fine Astrocyte Processes Contain Very Small Mitochondria: Glial Oxidative Capability May Fuel Transmitter Metabolism.

    Science.gov (United States)

    Derouiche, Amin; Haseleu, Julia; Korf, Horst-Werner

    2015-12-01

    The peripheral astrocyte process (PAP) is the glial compartment largely handling inactivation of transmitter glutamate, and supplying glutamate to the axon terminal. It is not clear how these energy demanding processes are fueled, and whether the PAP exhibits oxidative capability. Whereas the GFAP-positive perinuclear cytoplasm and stem process are rich in mitochondria, the PAP is often considered too narrow to contain mitochondria and might thus not rely on oxidative metabolism. Applying high resolution light microscopy, we investigate here the presence of mitochondria in the PAPs of freshly dissociated, isolated astrocytes. We provide an overview of the subcellular distribution and the approximate size of astrocytic mitochondria. A substantial proportion of the astrocyte's mitochondria are contained in the PAPs and, on the average, they are smaller there than in the stem processes. The majority of mitochondria in the stem and peripheral processes are surprisingly small (0.2-0.4 µm), spherical and not elongate, or tubular, which is supported by electron microscopy. The density of mitochondria is two to several times lower in the PAPs than in the stem processes. Thus, PAPs do not constitute a mitochondria free glial compartment but contain mitochondria in large numbers. No juxtaposition of mitochondria-containing PAPs and glutamatergic synapses has been reported. However, the issue of sufficient ATP concentrations in perisynaptic PAPs can be seen in the light of (1) the rapid, activity dependent PAP motility, and (2) the recently reported activity-dependent mitochondrial transport and immobilization leading to spatial, subcellular organisation of glutamate uptake and oxidative metabolism.

  5. Can body mass index, waist circumference, waist-hip ratio and waist-height ratio predict the presence of multiple metabolic risk factors in Chinese subjects?

    OpenAIRE

    Lu Liping; Tong Weiwei; Tong Guanghui; Liu Yong; Qin Xiaosong

    2011-01-01

    Abstract Background Obesity is associated with metabolic risk factors. Body mass index (BMI), waist circumference, waist-hip ratio (WHR) and waist-height ratio (WHtR) are used to predict the risk of obesity related diseases. However, it has not been examined whether these four indicators can detect the clustering of metabolic risk factors in Chinese subjects. Methods There are 772 Chinese subjects in the present study. Metabolic risk factors including high blood pressure, dyslipidemia, and gl...

  6. Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse, human glioblastomas in the mouse brain in vivo

    Science.gov (United States)

    Marin-Valencia, Isaac; Yang, Chendong; Mashimo, Tomoyuki; Cho, Steve; Baek, Hyeonman; Yang, Xiao-Li; Rajagopalan, Kartik N.; Maddie, Melissa; Vemireddy, Vamsidhara; Zhao, Zhenze; Cai, Ling; Good, Levi; Tu, Benjamin P.; Hatanpaa, Kimmo J.; Mickey, Bruce E.; Matés, José M.; Pascual, Juan M.; Maher, Elizabeth A.; Malloy, Craig R.; DeBerardinis, Ralph J.; Bachoo, Robert M.

    2012-01-01

    SUMMARY Dysregulated metabolism is a hallmark of cancer cell lines, but little is known about the fate of glucose and other nutrients in tumors growing in their native microenvironment. To study tumor metabolism in vivo, we used an orthotopic mouse model of primary human glioblastoma (GBM). We infused 13C-labeled nutrients into mice bearing three independent GBM lines, each with a distinct set of mutations. All three lines displayed glycolysis, as expected for aggressive tumors. They also displayed unexpected metabolic complexity, oxidizing glucose via pyruvate dehydrogenase and the citric acid cycle, and using glucose to supply anaplerosis and other biosynthetic activities. Comparing the tumors to surrounding brain revealed obvious metabolic differences, notably the accumulation of a large glutamine pool within the tumors. Many of these same activities were conserved in cells cultured ex vivo from the tumors. Thus GBM cells utilize mitochondrial glucose oxidation during aggressive tumor growth in vivo. PMID:22682223

  7. Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress.

    Science.gov (United States)

    Liu, Dong; Chan, Sic L; de Souza-Pinto, Nadja C; Slevin, John R; Wersto, Robert P; Zhan, Ming; Mustafa, Khadija; de Cabo, Rafael; Mattson, Mark P

    2006-01-01

    The high-metabolic demand of neurons and their reliance on glucose as an energy source places them at risk for dysfunction and death under conditions of metabolic and oxidative stress. Uncoupling proteins (UCPs) are mitochondrial inner membrane proteins implicated in the regulation of mitochondrial membrane potential (Deltapsim) and cellular energy metabolism. The authors cloned UCP4 cDNA from mouse and rat brain, and demonstrate that UCP4 mRNA is expressed abundantly in brain and at particularly high levels in populations of neurons believed to have high-energy requirements. Neural cells with increased levels of UCP4 exhibit decreased Deltapsim, reduced reactive oxygen species (ROS) production and decreased mitochondrial calcium accumulation. UCP4 expressing cells also exhibited changes of oxygen-consumption rate, GDP sensitivity, and response of Deltapsim to oligomycin that were consistent with mitochondrial uncoupling. UCP4 modulates neuronal energy metabolism by increasing glucose uptake and shifting the mode of ATP production from mitochondrial respiration to glycolysis, thereby maintaining cellular ATP levels. The UCP4-mediated shift in energy metabolism reduces ROS production and increases the resistance of neurons to oxidative and mitochondrial stress. Knockdown of UCP4 expression by RNA interference in primary hippocampal neurons results in mitochondrial calcium overload and cell death. UCP4-mRNA expression is increased in neurons exposed to cold temperatures and in brain cells of rats maintained on caloric restriction, suggesting a role for UCP4 in the previously reported antiageing and neuroprotective effects of caloric restriction. By shifting energy metabolism to reduce ROS production and cellular reliance on mitochondrial respiration, UCP4 can protect neurons against oxidative stress and calcium overload.

  8. Physiological mechanisms by which non-nutritive sweeteners may impact body weight and metabolism.

    Science.gov (United States)

    Burke, Mary V; Small, Dana M

    2015-12-01

    Evidence linking sugar-sweetened beverage (SSB) consumption to weight gain and other negative health outcomes has prompted many individuals to resort to artificial, non-nutritive sweetener (NNS) substitutes as a means of reducing SSB intake. However, there is a great deal of controversy regarding the biological consequences of NNS use, with accumulating evidence suggesting that NNS consumption may influence feeding and metabolism via a variety of peripheral and central mechanisms. Here we argue that NNSs are not physiologically inert compounds and consider the potential biological mechanisms by which NNS consumption may impact energy balance and metabolic function, including actions on oral and extra-oral sweet taste receptors, and effects on metabolic hormone secretion, cognitive processes (e.g. reward learning, memory, and taste perception), and gut microbiota.

  9. Acetylation control of cardiac fatty acid β-oxidation and energy metabolism in obesity, diabetes, and heart failure.

    Science.gov (United States)

    Fukushima, Arata; Lopaschuk, Gary D

    2016-12-01

    Alterations in cardiac energy metabolism are an important contributor to the cardiac pathology associated with obesity, diabetes, and heart failure. High rates of fatty acid β-oxidation with cardiac insulin resistance represent a cardiac metabolic hallmark of diabetes and obesity, while a marginal decrease in fatty acid oxidation and a prominent decrease in insulin-stimulated glucose oxidation are commonly seen in the early stages of heart failure. Alterations in post-translational control of energy metabolic processes have recently been identified as an important contributor to these metabolic changes. In particular, lysine acetylation of non-histone proteins, which controls a diverse family of mitochondrial metabolic pathways, contributes to the cardiac energy derangements seen in obesity, diabetes, and heart failure. Lysine acetylation is controlled both via acetyltransferases and deacetylases (sirtuins), as well as by non-enzymatic lysine acetylation due to increased acetyl CoA pool size or dysregulated nicotinamide adenine dinucleotide (NAD(+)) metabolism (which stimulates sirtuin activity). One of the important mitochondrial acetylation targets are the fatty acid β-oxidation enzymes, which contributes to alterations in cardiac substrate preference during the course of obesity, diabetes, and heart failure, and can ultimately lead to cardiac dysfunction in these disease states. This review will summarize the role of lysine acetylation and its regulatory control in the context of mitochondrial fatty acid β-oxidation. The functional contribution of cardiac protein lysine acetylation to the shift in cardiac energy substrate preference that occurs in obesity, diabetes, and especially in the early stages of heart failure will also be reviewed. This article is part of a Special Issue entitled: The role of post-translational protein modifications on heart and vascular metabolism edited by Jason R.B. Dyck & Jan F.C. Glatz.

  10. Differential impact of nutrition on developmental and metabolic gene expression during fruiting body development in Neurospora crassa.

    Science.gov (United States)

    Wang, Zheng; Lehr, Nina; Trail, Frances; Townsend, Jeffrey P

    2012-05-01

    Fungal fruiting body size and form are influenced by the ecology of the species, including diverse environmental stimuli. Accordingly, nutritional resources available to the fungus during development can be vital to successful production of fruiting bodies. To investigate the effect of nutrition, perithecial development of Neurospora crassa was induced on two different media, a chemically sparsely nutritive Synthetic Crossing Medium (SCM) and a natural Carrot Agar (CA). Protoperithecia were collected before crossing, and perithecia were collected at 2, 24, 48, 72, 96, 120, and at full maturity 144 h after crossing. No differences in fruiting body morphology were observed between the two media at any time point. A circuit of microarray hybridizations comparing cDNA from all neighboring stages was performed. For a majority of differentially expressed genes, expression was higher in SCM than in CA, and expression of core metabolic genes was particularly affected. Effects of nutrition were highest in magnitude before crossing, lowering in magnitude during early perithecial development. Interestingly, metabolic effects of the media were also large in magnitude during late perithecial development, at which stage the lower expression in CA presumably reflected the continued intake of diverse complex initial compounds, diminishing the need for expression of anabolic pathways. However, for genes with key regulatory roles in sexual development, including pheromone precursor ccg-4 and poi2, expression patterns were similar between treatments. When possible, a common nutritional environment is ideal for comparing transcriptional profiles between different fungi. Nevertheless, the observed consistency of the developmental program across media, despite considerable metabolic differentiation is reassuring. This result facilitates comparative studies that will require different nutritional resources for sexual development in different fungi.

  11. Metabolism

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    4.1 Nutrition imbalance 2006024 Effect of multiple micronutrients supplementation on anti - oxidative activity and oxidized DNA damage of lymphocytes in children ZHANG Ming ( 张明), Nutrit Dept, Weifang People Hosp, Weifang 261041. Chin J Epidemiol 2005 ;26(4) :268 -272. Objective:To examine the effect of multiple micronutrients supplementation on anti - oxidative activity and decreasing oxidized DNA damage of lymphocytes in Chinese children. Methods:82 healthy children in rural areas, aged 9-11 years, were selected and randomized into group receiving supplements and control group with 41 in

  12. Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats

    Science.gov (United States)

    Tokubuchi, Ichiro; Tajiri, Yuji; Iwata, Shimpei; Hara, Kento; Wada, Nobuhiko; Hashinaga, Toshihiko; Nakayama, Hitomi; Mifune, Hiroharu; Yamada, Kentaro

    2017-01-01

    Objective Metformin is known to have a beneficial effect on body weight and body composition, although the precise mechanism has not been elucidated yet. The aim of this study is to investigate the effects of metformin on energy metabolism and anthropometric factors in both human subjects and rats. Methods In human studies, metformin (1500mg/day) was administered to 23 healthy subjects and 18 patients with type 2 diabetes for 2 weeks. Metabolic parameters and energy metabolism were measured during a meal tolerance test in the morning before and after the treatment of metformin. In animal studies, 13 weeks old SD rats were fed 25–26 g of standard chow only during 12-hours dark phase with either treated by metformin (2.5mg/ml in drinking water) or not for 2 weeks, and metabolic parameters, anthropometric factors and energy metabolism together with expressions related to fat oxidation and adaptive thermogenesis were measured either in fasting or post-prandial state at 15 weeks old. Results Post-prandial plasma lactate concentration was significantly increased after the metformin treatment in both healthy subjects and diabetic patients. Although energy expenditure (EE) did not change, baseline respiratory quotient (RQ) was significantly decreased and post-prandial RQ was significantly increased vice versa following the metformin treatment in both groups. By the administration of metformin to SD rats for 2 weeks, plasma levels of lactate and pyruvate were significantly increased in both fasting and post-prandial states. RQ during a fasting state was significantly decreased in metformin-treated rats compared to controls with no effect on EE. Metformin treatment brought about a significant reduction of visceral fat mass compared to controls accompanied by an up-regulation of fat oxidation-related enzyme in the liver, UCP-1 in the brown adipose tissue and UCP-3 in the skeletal muscle. Conclusion From the results obtained, beneficial effects of metformin on visceral fat

  13. Mediating effects of dietary intake on associations of TV viewing, body mass index and metabolic syndrome in adolescents

    OpenAIRE

    Fletcher, E. A.; McNaughton, S. A.; Lacy, K E; Dunstan, D.W.; Carson, V.; Salmon, J.

    2016-01-01

    Summary Objective Evidence suggests that TV viewing is associated with body mass index (BMI) and metabolic syndrome (MetS) in adolescents. However, it is unclear whether dietary intake mediates these relationships. Methods A cross‐sectional analysis was conducted in adolescents (12–19 years) participating in the 2003–2006 United States National Health and Nutrition Examination Survey. BMI z scores (zBMI) (n = 3,161) and MetS (n = 1,379) were calculated using age‐ and sex‐specific criteria for...

  14. Presymptomatic alterations in energy metabolism and oxidative stress in the APP23 mouse model of Alzheimer disease.

    Science.gov (United States)

    Hartl, Daniela; Schuldt, Victoria; Forler, Stephanie; Zabel, Claus; Klose, Joachim; Rohe, Michael

    2012-06-01

    Glucose hypometabolism is the earliest symptom observed in the brains of Alzheimer disease (AD) patients. In a former study, we analyzed the cortical proteome of the APP23 mouse model of AD at presymptomatic age (1 month) using a 2-D electrophoresis-based approach. Interestingly, long before amyloidosis can be observed in APP23 mice, proteins associated with energy metabolism were predominantly altered in transgenic as compared to wild-type mice indicating presymptomatic changes in energy metabolism. In the study presented here, we analyzed whether the observed changes were associated with oxidative stress and confirmed our previous findings in primary cortical neurons, which exhibited altered ADP/ATP levels if transgenic APP was expressed. Reactive oxygen species produced during energy metabolism have important roles in cell signaling and homeostasis as they modify proteins. We observed an overall up-regulation of protein oxidation status as shown by increased protein carbonylation in the cortex of presymptomatic APP23 mice. Interestingly, many carbonylated proteins, such as Vilip1 and Syntaxin were associated to synaptic plasticity. This demonstrates an important link between energy metabolism and synaptic function, which is altered in AD. In summary, we demonstrate that changes in cortical energy metabolism and increased protein oxidation precede the amyloidogenic phenotype in a mouse model for AD. These changes might contribute to synaptic failure observed in later disease stages, as synaptic transmission is particularly dependent on energy metabolism.

  15. [The correlations between aging of the human body, oxidative stress and reduced efficiency of repair systems].

    Science.gov (United States)

    Michalak, Aleksandra; Krzeszowiak, Jakub; Markiewicz-Górka, Iwona

    2014-12-15

    The article presents an current knowledge overview about the importance of oxidative stress and reduced efficiency of repair processes during the aging process of the human body. Oxidative damage to cellular macromolecules (proteins, lipids, nucleic acids), are formed under the influence of reactive oxygen species (ROS). They are the part of important mechanism which is responsible for the process of aging and the development of many diseases. The most important effects result from DNA damage, due to the mutations formation, which can lead to the development of tumors. However, a well-functioning repair systems (i.a. homologous recombination) remove the damage and prevent harmful changes in the cells. Lipid peroxidation products also cause oxidative modification of nucleic acids (and proteins). Proteins and fats also have repair systems, but much simpler than those responsible for the repair of nucleic acids. Unfortunately, with increasing age, they are more weakened, which contributes to increase numbers of cell damage, and consequently development of diseases specific to old age: cancer, neurodegenerative diseases or atherosclerosis.

  16. Hypothalamic sensing of ketone bodies after prolonged cerebral exposure leads to metabolic control dysregulation

    Science.gov (United States)

    Carneiro, Lionel; Geller, Sarah; Hébert, Audrey; Repond, Cendrine; Fioramonti, Xavier; Leloup, Corinne; Pellerin, Luc

    2016-01-01

    Ketone bodies have been shown to transiently stimulate food intake and modify energy homeostasis regulatory systems following cerebral infusion for a moderate period of time (neuropeptides. Moreover, insulinemia was increased and caused a decrease in glucose production despite an increased resistance to insulin. The present study confirms that ketone bodies reaching the brain stimulates food intake. Moreover, we provide evidence that a prolonged hyperketonemia leads to a dysregulation of energy homeostasis control mechanisms. Finally, this study shows that brain exposure to ketone bodies alters insulin signaling and consequently glucose homeostasis. PMID:27708432

  17. Oxidative metabolism of the anti-cancer agent mitoxantrone by horseradish, lacto-and lignin peroxidase.

    Science.gov (United States)

    Brück, Thomas B; Brück, Dieter W

    2011-02-01

    Mitoxantrone (MH(2)X), an anthraquinone-type anti-cancer agent used clinically in the treatment of human malignancies, is oxidatively activated by the peroxidase/H(2)O(2) enzyme system. In contrast to the enzymatic mechanisms of drug oxidation, the chemical transformations of MH(2)X are not well described. In this study, MH(2)X metabolites, produced by the horseradish, lacto- or lignin peroxidase (respectively HRP, LPO and LIP)/H(2)O(2) system, were investigated by steady-state spectrokinetic and HPLC-MS methods. At an equimolar mitoxantrone/H(2)O(2) ratio, the efficacy of the enzyme-catalyzed oxidation of mitoxantrone decreased in the following order: LPO > HRP > LIP, which accorded with the decreasing size of the substrate access channel in the enzyme panel examined. In all cases, the central drug oxidation product was the redox-active cyclic metabolite, hexahydronaphtho-[2,3-f]-quinoxaline-7,12-dione (MH(2)), previously identified in the urine of mitoxantrone-treated patients. As the reaction progressed, data gathered in this study suggests that further oxidation of the MH(2) side-chains occurred, yielding the mono- and dicarboxylic acid derivatives respectively. Based on the available data a further MH(2) derivative is proposed, in which the amino-alkyl side-chain(s) are cyclised. With increasing H(2)O(2) concentrations, these novel MH(2) derivatives were oxidised to additional metabolites, whose spectral properties and MS data indicated a stepwise destruction of the MH(2) chromophore due to an oxidative cleavage of the 9,10-anthracenedione moiety. The novel metabolites extend the known sequence of peroxidase-induced mitoxantrone metabolism, and may contribute to the cytotoxic effects of the drug in vivo. Based on the structural features of the proposed MH(2) oxidation products we elaborate on various biochemical mechanisms, which extend the understanding of mitoxantrone's pharmaceutical action and its clinical effectiveness with a particular focus on

  18. Assessing the cost of helping: the roles of body condition and oxidative balance in the Seychelles warbler (Acrocephalus sechellensis.

    Directory of Open Access Journals (Sweden)

    Janske van de Crommenacker

    Full Text Available In cooperatively breeding species, helping close relatives may provide important fitness benefits. However, helping can be energetically expensive and may result in increased generation of reactive oxygen species. Consequently, an oxidant/antioxidant imbalance can lead to higher oxidative stress susceptibility. Given the potential costs of helping, it may be that only individuals with a sufficiently good body condition and/or stable oxidative balance can afford to help. Knowledge about relationships between social status and oxidative balance in cooperatively breeding systems is still limited. Studying these relationships is important for understanding the costs of helping and physiological pressures of reproduction. Here we evaluate the relationship between helping behaviour, body condition and oxidative balance in a wild population of the cooperatively breeding Seychelles warbler (Acrocephalus sechellensis. In this species, some subordinate individuals help dominant birds with the rearing of young, while others refrain from any assistance. We assessed body condition and oxidative parameters of birds of different social status caught during different breeding stages. We found that, prior to breeding, female subordinates that did not subsequently help (non-helpers had significantly lower body condition and higher ROMs (reactive oxygen metabolites than helpers and dominants. During the later stages of breeding, body condition was low in dominants and helpers, but high in non-helpers. Differences in oxidative balance between individuals of different social status were found only during nest care: Dominant males occupied with guarding behaviours tended to have relatively high oxidative stress susceptibility. Furthermore, dominant and helper females showed elevated antioxidant capacity (measured as OXY in the weeks just prior to egg-laying, possibly representing a change in their reproductive physiology. The results imply that an individuals

  19. The metabolic syndrome in black hypertensive women - Waist circumference more strongly related than body mass index

    NARCIS (Netherlands)

    Rheeder, P; Stolk, RP; Veenhouwer, JF; Grobbee, DE

    2002-01-01

    Objective. To examine the association between measures of. obesity and features of the metabolic syndrome in treated. black female hypertensive subjects. Design. Cross-sectional study. Setting. An urban primary health care centre in Mamelodi, Pretoria. Subjects. Women with hypertension and without k

  20. Effect of growth rate and body mass on resting metabolic rate in galliform chicks

    NARCIS (Netherlands)

    Dietz, MW; Drent, RH

    1997-01-01

    In this study, we asked whether within-species variation in chick resting metabolic rate was related to variation in growth and whether this relationship changed during development in three galliform species (turkey, Meleagris gallopavo, guinea fowl, Numida meleagris, and Japanese quail, Coturnix co

  1. Overexpression of Jazf1 reduces body weight gain and regulates lipid metabolism in high fat diet

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Woo Young; Bae, Ki Beom; Kim, Sung Hyun; Yu, Dong Hun; Kim, Hei Jung; Ji, Young Rae; Park, Seo Jin; Park, Si Jun; Kang, Min-Cheol; Jeong, Ja In [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Park, Sang-Joon [College of Veterinary Medicine, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Lee, Sang Gyu [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Lee, Inkyu [School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 700-842 (Korea, Republic of); Kim, Myoung Ok [School of Animal BT Sciences, Sangju Campus, Kyungpook National University, 386 Gajang-dong, Sangju, Gyeongsangbuk-do 742-211 (Korea, Republic of); Yoon, Duhak, E-mail: dhyoon@knu.ac.kr [School of Animal BT Sciences, Sangju Campus, Kyungpook National University, 386 Gajang-dong, Sangju, Gyeongsangbuk-do 742-211 (Korea, Republic of); Ryoo, Zae Young, E-mail: jaewoong64@hanmail.net [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of)

    2014-02-14

    Highlights: • The expression of Jazf1 in the liver suppressed lipid accumulation. • Jazf1 significantly increases transcription of fatty acid synthase. • Jazf1 plays a critical role in the regulation of energy and lipid homeostasis. • Jazf1 associates the development of metabolic disorder. • Jazf1 may provide a new therapeutic target in the management of metabolic disorder. - Abstract: Jazf1 is a 27 kDa nuclear protein containing three putative zinc finger motifs that is associated with diabetes mellitus and prostate cancer; however, little is known about the role that this gene plays in regulation of metabolism. Recent evidence indicates that Jazf1 transcription factors bind to the nuclear orphan receptor TR4. This receptor regulates PEPCK, the key enzyme involved in gluconeogenesis. To elucidate Jazf1’s role in metabolism, we fed a 60% fat diet for up to 15 weeks. In Jazf1 overexpression mice, weight gain was found to be significantly decreased. The expression of Jazf1 in the liver also suppressed lipid accumulation and decreased droplet size. These results suggest that Jazf1 plays a critical role in the regulation of lipid homeostasis. Finally, Jazf1 may provide a new therapeutic target in the management of obesity and diabetes.

  2. Basal metabolic rate, food intake, and body mass in cold- and warm-acclimated Garden Warblers

    NARCIS (Netherlands)

    Klaassen, M.R.J.; Oltrogge, M.; Trost, L.

    2004-01-01

    We address the question of whether physiological flexibility in relation to climate is a general feature of the metabolic properties of birds. We tested this hypothesis in hand-raised Garden Warblers (Sylvia borin), long-distance migrants, which normally do not experience great temperature differenc

  3. Exercising for Life? Energy Metabolism, Body Composition, and Longevity in Mice Exercising at Different Intensities

    NARCIS (Netherlands)

    Vaanholt, Lobke M.; Daan, Serge; Garland, Theodore; Visser, G. Henk; Garland Jr., Theodore

    2010-01-01

    Studies that have found a positive influence of moderate, non-exhaustive exercise on life expectancy contradict the rate-of-living theory, which predicts that high energy expenditure in exercising animals should shorten life. We investigated effects of exercise on energy metabolism and life span in

  4. Exposure to lead in water and cysteine non-oxidative metabolism in Pelophylax ridibundus tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kaczor, Marta [Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Sura, Piotr [Department of Human Developmental Biology, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Bronowicka-Adamska, Patrycja [Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Wrobel, Maria, E-mail: mbwrobel@cyf-kr.edu.pl [Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland)

    2013-02-15

    Chronic, low-level exposure to metals is an increasing global problem. Lead is an environmentally persistent toxin that causes many lead-related pathologies, directly affects tissues and cellular components or exerts an effect of the generation of reactive oxygen species causing a diminished level of available sulfhydryl antioxidant reserves. Cysteine is one of substrates in the synthesis of glutathione - the most important cellular antioxidant, and it may also undergo non-oxidative desulfuration that produces compounds containing sulfane sulfur atoms. The aim of the experiment was to examine changes of the non-oxidative metabolism of cysteine and the levels of cysteine and glutathione in the kidneys, heart, brain, liver and muscle of Marsh frogs (Pelophylax ridibundus) exposed to 28 mg/L Pb(NO{sub 3}){sub 2} for 10 days. The activities of sulfurtransferases, enzymes related to the sulfane sulfur metabolism - 3-mercaptopyruvate sulfurtransfearse, {gamma}-cystathionase and rhodanese - were detected in tissue homogenates. The activity of sulfurtransferases was much higher in the kidneys of frogs exposed to lead in comparison to control frogs, not exposed to lead. The level of sulfane sulfur remained unchanged. Similarly, the total level of cysteine did not change significantly. The total levels of glutathione and the cysteine/cystine and GSH/GSSG ratios were elevated. Thus, it seems that the exposure to lead intensified the metabolism of sulfane sulfur and glutathione synthesis in the kidneys. The results presented in this work not only confirm the participation of GSH in the detoxification of lead ions and/or products appearing in response to their presence, such as reactive oxygen species, but also indicate the involvement of sulfane sulfur and rhodanese in this process (e.g. brain). As long as the expression of enzymatic proteins (rhodanese, MPST and CST) is not examined, no answer will be provided to the question whether changes in their activity are due to

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-15

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

  6. Metabolic adaptations in the adipose tissue that underlie the body fat mass gain in middle-aged rats.

    Science.gov (United States)

    Sertié, Rogério Antonio Laurato; Caminhotto, Rennan de Oliveira; Andreotti, Sandra; Campaña, Amanda Baron; de Proença, André Ricardo Gomes; de Castro, Natalie Carolina; Lima, Fábio Bessa

    2015-10-01

    Little is known about adipocyte metabolism during aging process and whether this can influence body fat redistribution and systemic metabolism. To better understand this phenomenon, two animal groups were studied: young-14 weeks old-and middle-aged-16 months old. Periepididymal (PE) and subcutaneous (SC) adipocytes were isolated and tested for their capacities to perform lipolysis and to incorporate D-[U-(14)C]-glucose, D-[U-(14)C]-lactate, and [9,10(n)-(3)H]-oleic acid into lipids. Additionally, the morphometric characteristics of the adipose tissues, glucose tolerance tests, and biochemical determinations (fasting glucose, triglycerides, insulin) in blood were performed. The middle-aged rats showed adipocyte (PE and SC) hypertrophy and glucose intolerance, although there were no significant changes in fasting glycemia and insulin. Furthermore, PE tissue revealed elevated rates (+50 %) of lipolysis during beta-adrenergic-stimulation. There was also an increase (+62 %) in the baseline rate of glucose incorporation into lipids in the PE adipocytes, while these PE cells were almost unresponsive to insulin stimulation and less responsive (a 34 % decrease) in the SC tissue. Also, the capacity of oleic acid esterification was elevated in baseline state and with insulin stimulus in the PE tissue (+90 and 82 %, respectively). Likewise, spontaneous incorporation of lactate into lipids in the PE and SC tissues was higher (+100 and 11 %, respectively) in middle-aged rats. We concluded that adipocyte metabolism of middle-aged animals seems to strongly favor cellular hypertrophy and increased adipose mass, particularly the intra-abdominal PE fat pad. In discussion, we have interpreted all these results as a metabolic adaptations to avoid the spreading of fat that can reach tissues beyond adipose protecting them against ectopic fat accumulation. However, these adaptations may have the potential to lead to future metabolic dysfunctions seen in the senescence.

  7. Effects of aerobic exercise training on body composition and metabolic syndrome factors in obese male college student

    Directory of Open Access Journals (Sweden)

    RASTEGAR HOSEINI

    2014-10-01

    Full Text Available Metabolic syndrome (Ms is emerging as a serious public health problem in Iran. The purpose of this study was to examine the effects of 8 weeks of aerobic exercise training on body composition and Ms factors in obese Iran male college students. subjects were randomly assigned to exercise (n = 19 and control (n = 19 groups. The exercise group trained for 50 min/day, for 3 day/week for 8 weeks. each exercise session comprised 3 phases: warm-up for 10 min, aerobic exercise for 30 min (the exercise intensity for aerobic exercise was 60–80% of the heart rate reserve (HRR for 30 min and cool down for 10 min. The paired and unpaired t-test in 0.05. A 8-week aerobic exercise program could effectively reduce tgs, tc, LDL, percent body fat, Wc, sBP, DBP and in- crease HDL in a sample population of obese Iran male college students.

  8. Development of Dietary Patterns Spanning Infancy and Toddlerhood: Relation to Body Size, Composition and Metabolic Risk Markers at Three Years

    DEFF Research Database (Denmark)

    Andersen, Louise B. B.; Mølgaard, Christian; Ejlerskov, Katrine Tschentscher;

    2015-01-01

    Little is known about the development of dietary patterns during toddlerhood and the relation to growth and health. The study objective was to characterise the development of dietary patterns from 9-36 mo of age and investigate the association to body size, body composition and metabolic risk...... markers at 36 mo. Food records were filled out at 9, 18 and 36 mo of age (n = 229). Dietary patterns were identified by principal component analysis (PCA). Three dietary patterns were identified: Transition Food, Healthy Food and Traditional Food. The course of development in dietary patterns from 9-36 mo...... total cholesterol and LDL. Hence, this could represent undesirable development of dietary patterns in toddlers. In conclusion, development of dietary patterns can be exploratory characterised by PCA and related to potential cardiovascular risk markers in toddlers even within a relatively homogeneous...

  9. Increased intake of fruits and vegetables in overweight subjects: effects on body weight, body composition, metabolic risk factors and dietary intake.

    Science.gov (United States)

    Järvi, A; Karlström, B; Vessby, B; Becker, W

    2016-05-28

    A diet rich in fruits and vegetables has been associated with several health benefits. However, the effects on body weight (BW) and metabolic markers are not fully known. The present study investigated the effects of increased intake of fruits and vegetables in overweight and obese men and women on dietary habits, anthropometry and metabolic control. In a 16-week controlled intervention, thirty-four men and thirty-four women aged 35-65 years (BMI>27 kg/m2) were randomised to an intervention (IN) or a reference (RG) group. All participants received general dietary advice, and subjects in the IN group received fruits and vegetables for free, of which ≥500 g had to be eaten daily. BW, waist circumference (WC), sagittal abdominal diameter (SAD), plasma insulin, blood glucose, glycated Hb (HbA1c), serum lipids, blood pressure, plasminogen activator inhibitor-1 activity, urinary isoprostane (iso-8-PGF 2α) and serum carotenoids were measured. Diet was assessed using 3-d weighed food records. In all, thirty subjects in the IN group and thirty-two in the RG group completed the intervention. Intake of fruits and vegetables doubled in the IN group, whereas intake of fruits increased in the RG group. Serum α- and β-carotene concentrations and intakes of folate and vitamin C increased significantly in the IN group. Energy intake, BW, WC and SAD decreased significantly in both groups. Supine systolic blood pressure decreased significantly in the IN group, with no between-group differences. No significant changes were observed for other metabolic markers. Provision of fruits and vegetables led to substantially increased intakes, with subsequent favourable changes in anthropometry and insulin levels, which tended to be more pronounced in the IN group. The observed improvements may, in combination with improved nutritional markers, have health benefits in the long term.

  10. A review on effects of conjugated linoleic fatty acid (CLA) upon body composition and energetic metabolism

    OpenAIRE

    Lehnen, Tatiana Ederich; da Silva, Marcondes Ramos; Camacho, Augusto; Marcadenti, Aline; Lehnen, Alexandre Machado

    2015-01-01

    Conjugated linoleic acid (CLA) is highly found in fats from ruminants and it appears to favorably modify the body composition and cardiometabolic risk factors. The capacity of CLA to reduce the body fat levels as well as its benefic actions on glycemic profile, atherosclerosis and cancer has already been proved in experimental models. Furthermore, CLA supplementation may modulate the immune function, help re-synthetize of glycogen and potentiate the bone mineralization. CLA supplementation al...

  11. Cognitive impairment and Alzheimer’s disease: Links with oxidative stress and cholesterol metabolism

    Science.gov (United States)

    Sekler, Alejandra; Jiménez, José M; Rojo, Leonel; Pastene, Edgard; Fuentes, Patricio; Slachevsky, Andrea; Maccioni, Ricardo B

    2008-01-01

    Oxidative stress has been implicated in the progression of a number of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease and amyotrophic lateral sclerosis. We carried out an in-depth study of cognitive impairment and its relationships with oxidative stress markers such as ferric-reducing ability of plasma (FRAP), plasma malondialdehyde and total antioxidative capacity (TAC), as well as cholesterol parameters, in two subsets of subjects, AD patients (n = 59) and a control group of neurologically normal subjects (n = 29), attending the University Hospital Salvador in Santiago, Chile. Cognitive impairment was assessed by a set of neuropsychological tests (Mini-Mental State Examination, Boston Naming Test, Ideomotor Praxia by imitation, Semantic Verbal Fluency of animals or words with initial A, Test of Memory Alteration, Frontal Assessment Battery), while the levels of those oxidative stress markers and cholesterol metabolism parameters were determined according with standard bioassays in fresh plasma samples of the two subgroups of patients. No significant differences were observed when the cholesterol parameters (low-, high-density lipoprotein, total cholesterol) of the AD group were compared with normal controls. Interestingly, a correlation was evidenced when the levels of cognitive impairment were analyzed with respect to the plasma antioxidant capacity (AOC) of patients. In this context, the subset of subjects exhibiting cognitive impairment were divided into two subgroups according with their Global Dementia Scale performance: a subgroup with mild AD and a subgroup with moderate to severe AD. Significant differences in AOC were found between subgroups. The different correlations between cognitive impairment of subgroups of subjects with the oxidative stress profile are discussed in the context of AD pathogenesis. PMID:19043515

  12. Some aspects of oxidative metabolism in human endometrium after long time of applying the intrauterine contraceptive device.

    Science.gov (United States)

    Bausic, V; Ionescu, N

    1996-01-01

    The paper intends to study the variation of oxidative metabolism of human endometrium (all the components) after applying the intrauterine contraceptive device for a long period of time. The results of the study show that modifications "in situ" of the oxidative enzymes vary according to the: type of the enzymes (NADH2-cytochrome-c-reductase, Lactatdehydrogenase), the hormonal cyclic stage (proliferative phase, or luteal phase), epithelial or connective tissue structures, time of resting the intrauterine contraceptive device (DIU) in uterus.

  13. Low dose/low fluence ionizing radiation-induced biological effects: The role of intercellular communication and oxidative metabolism

    Science.gov (United States)

    Azzam, Edouard

    Mechanistic investigations have been considered critical to understanding the health risks of exposure to ionizing radiation. To gain greater insight in the biological effects of exposure to low dose/low fluence space radiations with different linear energy transfer (LET) properties, we examined short and long-term biological responses to energetic protons and high charge (Z) and high energy (E) ions (HZE particles) in human cells maintained in culture and in targeted and non-targeted tissues of irradiated rodents. Particular focus of the studies has been on mod-ulation of gene expression, proliferative capacity, induction of DNA damage and perturbations in oxidative metabolism. Exposure to mean doses of 1000 MeV/nucleon iron ions, by which a small to moderate proportion of cells in an exposed population is targeted through the nucleus by an HZE particle, induced stressful effects in the irradiated and non-irradiated cells in the population. Direct intercellular communication via gap-junctions was a primary mediator of the propagation of stressful effects from irradiated to non-irradiated cells. Compromised prolif-erative capacity, elevated level of DNA damage and oxidative stress evaluated by measurements of protein carbonylation, lipid peroxidation and activity of metabolic enzymes persisted in the progeny of irradiated and non-irradiated cells. In contrast, progeny of cells exposed to high or low doses from 150-1000 MeV protons retained the ability to form colonies and harbored similar levels of micronuclei, a surrogate form of DNA damage, as control, which correlated with normal reactive oxygen species (ROS) levels. Importantly, a significant increase in the spontaneous neoplastic transformation frequency was observed in progeny of bystander mouse embryo fibroblasts (MEFs) co-cultured with MEFs irradiated with energetic iron ions but not protons. Of particular significance, stressful effects were detected in non-targeted tissues of rats that received partial

  14. Dissimilatory metabolism of nitrogen oxides in bacteria: comparative reconstruction of transcriptional networks.

    Directory of Open Access Journals (Sweden)

    2005-10-01

    Full Text Available Bacterial response to nitric oxide (NO is of major importance since NO is an obligatory intermediate of the nitrogen cycle. Transcriptional regulation of the dissimilatory nitric oxides metabolism in bacteria is diverse and involves FNR-like transcription factors HcpR, DNR, and NnrR; two-component systems NarXL and NarQP; NO-responsive activator NorR; and nitrite-sensitive repressor NsrR. Using comparative genomics approaches, we predict DNA-binding motifs for these transcriptional factors and describe corresponding regulons in available bacterial genomes. Within the FNR family of regulators, we observed a correlation of two specificity-determining amino acids and contacting bases in corresponding DNA recognition motif. Highly conserved regulon HcpR for the hybrid cluster protein and some other redox enzymes is present in diverse anaerobic bacteria, including Clostridia, Thermotogales, and delta-proteobacteria. NnrR and DNR control denitrification in alpha- and beta-proteobacteria, respectively. Sigma-54-dependent NorR regulon found in some gamma- and beta-proteobacteria contains various enzymes involved in the NO detoxification. Repressor NsrR, which was previously known to control only nitrite reductase operon in Nitrosomonas spp., appears to be the master regulator of the nitric oxides' metabolism, not only in most gamma- and beta-proteobacteria (including well-studied species such as Escherichia coli, but also in Gram-positive Bacillus and Streptomyces species. Positional analysis and comparison of regulatory regions of NO detoxification genes allows us to propose the candidate NsrR-binding motif. The most conserved member of the predicted NsrR regulon is the NO-detoxifying flavohemoglobin Hmp. In enterobacteria, the regulon also includes two nitrite-responsive loci, nipAB (hcp-hcr and nipC (dnrN, thus confirming the identity of the effector, i.e. nitrite. The proposed NsrR regulons in Neisseria and some other species are extended to include

  15. Dissimilatory Metabolism of Nitrogen Oxides in Bacteria:Comparative Reconstruction of Transcriptional Networks

    Energy Technology Data Exchange (ETDEWEB)

    Rodionov, Dmitry A.; Dubchak, Inna L.; Arkin, Adam P.; Alm, EricJ.; Gelfand, Mikhail S.

    2005-09-01

    Bacterial response to nitric oxide (NO) is of major importance since NO is an obligatory intermediate of the nitrogen cycle. Transcriptional regulation of the dissimilatory nitric oxides metabolism in bacteria is diverse and involves FNR-like transcription factors HcpR, DNR and NnrR, two-component systems NarXL and NarQP, NO-responsive activator NorR, and nitrite sensitive repressor NsrR. Using comparative genomics approaches we predict DNA-binding signals for these transcriptional factors and describe corresponding regulons in available bacterial genomes. Within the FNR family of regulators, we observed a correlation of two specificity-determining amino acids and contacting bases in corresponding DNA signal. Highly conserved regulon HcpR for the hybrid cluster protein and some other redox enzymes is present in diverse anaerobic bacteria including Clostridia, Thermotogales and delta-proteobacteria. NnrR and DNR control denitrification in alpha- and beta-proteobacteria, respectively. Sigma-54-dependent NorR regulon found in some gamma- and beta-proteobacteria contains various enzymes involved in the NO detoxification. Repressor NsrR, which was previously known to control only nitrite reductase operon in Nitrosomonas spp., appears to be the master regulator of the nitric oxides metabolism not only in most gamma- and beta-proteobacteria (including well-studied species like Escherichia coli), but also in Gram-positive Bacillus and Streptomyces species. Positional analysis and comparison of regulatory regions of NO detoxification genes allows us to propose the candidate NsrR-binding signal. The most conserved member of the predicted NsrR regulon is the NO-detoxifying flavohemoglobin Hmp. In enterobacteria, the regulon includes also two nitrite-responsive loci, nipAB (hcp-hcr) and nipC(dnrN), thus confirming the identity of the effector, i.e., nitrite. The proposed NsrR regulons in Neisseria and some other species are extended to include denitrification genes. As the

  16. Dissimilatory metabolism of nitrogen oxides in bacteria: comparative reconstruction of transcriptional networks.

    Directory of Open Access Journals (Sweden)

    Dmitry A Rodionov

    2005-10-01

    Full Text Available Bacterial response to nitric oxide (NO is of major importance since NO is an obligatory intermediate of the nitrogen cycle. Transcriptional regulation of the dissimilatory nitric oxides metabolism in bacteria is diverse and involves FNR-like transcription factors HcpR, DNR, and NnrR; two-component systems NarXL and NarQP; NO-responsive activator NorR; and nitrite-sensitive repressor NsrR. Using comparative genomics approaches, we predict DNA-binding motifs for these transcriptional factors and describe corresponding regulons in available bacterial genomes. Within the FNR family of regulators, we observed a correlation of two specificity-determining amino acids and contacting bases in corresponding DNA recognition motif. Highly conserved regulon HcpR for the hybrid cluster protein and some other redox enzymes is present in diverse anaerobic bacteria, including Clostridia, Thermotogales, and delta-proteobacteria. NnrR and DNR control denitrification in alpha- and beta-proteobacteria, respectively. Sigma-54-dependent NorR regulon found in some gamma- and beta-proteobacteria contains various enzymes involved in the NO detoxification. Repressor NsrR, which was previously known to control only nitrite reductase operon in Nitrosomonas spp., appears to be the master regulator of the nitric oxides' metabolism, not only in most gamma- and beta-proteobacteria (including well-studied species such as Escherichia coli, but also in gram-positive Bacillus and Streptomyces species. Positional analysis and comparison of regulatory regions of NO detoxification genes allows us to propose the candidate NsrR-binding motif. The most conserved member of the predicted NsrR regulon is the NO-detoxifying flavohemoglobin Hmp. In enterobacteria, the regulon also includes two nitrite-responsive loci, nipAB (hcp-hcr and nipC (dnrN, thus confirming the identity of the effector, i.e. nitrite. The proposed NsrR regulons in Neisseria and some other species are extended to include

  17. Glucagon-Like Peptide-1 as Predictor of Body Mass Index and Dentate Gyrus Neurogenesis: Neuroplasticity and the Metabolic Milieu

    Directory of Open Access Journals (Sweden)

    Jeremy D. Coplan

    2014-01-01

    Full Text Available Glucagon-like peptide-1 (GLP-1 regulates carbohydrate metabolism and promotes neurogenesis. We reported an inverse correlation between adult body mass and neurogenesis in nonhuman primates. Here we examine relationships between physiological levels of the neurotrophic incretin, plasma GLP-1 (pGLP-1, and body mass index (BMI in adolescence to adult neurogenesis and associations with a diabesity diathesis and infant stress. Morphometry, fasting pGLP-1, insulin resistance, and lipid profiles were measured in early adolescence in 10 stressed and 4 unstressed male bonnet macaques. As adults, dentate gyrus neurogenesis was assessed by doublecortin staining. High pGLP-1, low body weight, and low central adiposity, yet peripheral insulin resistance and high plasma lipids, during adolescence were associated with relatively high adult neurogenesis rates. High pGLP-1 also predicted low body weight with, paradoxically, insulin resistance and high plasma lipids. No rearing effects for neurogenesis rates were observed. We replicated an inverse relationship between BMI and neurogenesis. Adolescent pGLP-1 directly predicted adult neurogenesis. Two divergent processes relevant to human diabesity emerge—high BMI, low pGLP-1, and low neurogenesis and low BMI, high pGLP-1, high neurogenesis, insulin resistance, and lipid elevations. Diabesity markers putatively reflect high nutrient levels necessary for neurogenesis at the expense of peripheral tissues.

  18. [Difference of acute ketone body metabolism between insulin-dependent diabetic and non-insulin-dependent diabetic individuals].

    Science.gov (United States)

    Mayumi, K; Suzuki, S; Takuma, T; Gomi, Y; Kondo, Y; Sakamaki, T; Kokei, S; Inoue, T; Iino, S

    1992-10-20

    The difference in the acute metabolic change in ketone bodies between patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) was investigated in this study. The subjects employed were 7 patients with IDDM losing residual insulin secretion and 7 patients with NIDDM matched to the former patients for age, body mass index, duration of diabetes, daily insulin dosage, fasting plasma glucose and HbA1c. Blood samples were drawn at 3A.M. and 7A.M. on the same day, and plasma glucose, acetoacetic acid (AcAc), 3-beta-hydroxybutylic acid (3-OHBA), free fatty acid (FFA), glycerol, cortisol and growth hormone (GH) concentrations were determined. Plasma total ketone bodies (AcAc and 3-OHBA), 3-OHBA and FFA concentrations at 7A.M. were significantly higher in the patients with IDDM than in those with NIDDM (p ketone bodies, AcAc and 3-OHBA concentrations were also more significantly elevated in the patients with IDDM than in those with NIDDM. It was observed that the ratio of 3-OHBA was more than 2.0 in all of the patients with IDDM and less than 2.0 in all of the patients with NIDDM, the difference being significant with p < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Nrf2-mediated antioxidant response by ethanolic extract of Sida cordifolia provides protection against alcohol-induced oxidative stress in liver by upregulation of glutathione metabolism.

    Science.gov (United States)

    Rejitha, S; Prathibha, P; Indira, M

    2015-03-01

    Objective The study aimed to evaluate the antioxidant property of ethanolic extract of Sida cordifolia (SAE) on alcohol-induced oxidative stress and to elucidate its mechanism of action. Methods Male albino rats of the Sprague-Dawley strain were grouped into four: (1) control, (2) alcohol (4 g/kg body weight), (3) SAE (50 mg/100 g body weight), and (4) alcohol (4 g/kg body weight) + SAE (50 mg/100 g body weight). Alcohol and SAE were given orally each day by gastric intubation. The duration of treatment was 90 days. Results The activities of toxicity markers in liver and serum increased significantly in alcohol-treated rats and to a lesser extent in the group administered SAE + alcohol. The activity of alcohol dehydrogenase and the reactive oxygen species level were increased significantly in alcohol-treated rats but attenuated in the SAE co-administered group. Oxidative stress was increased in alcohol-treated rats as evidenced by the lowered activities of antioxidant enzymes, decreased level of reduced glutathione (GSH), increased lipid peroxidation products, and decreased expression of γ-glutamyl cysteine synthase in liver. The co-administration of SAE with alcohol almost reversed these changes. The activity of glutathione-S-transferase and translocation of Nrf2 from cytosol to nucleus in the liver was increased in both the alcohol and alcohol + SAE groups, but the maximum changes were observed in the latter group. Discussion The SAE most likely elicits its antioxidant potential by reducing oxidative stress, enhancing the translocation of Nrf2 to nucleus and thereby regulating glutathione metabolism, leading to enhanced GSH content.

  20. The combination of conjugated linoleic acid (CLA) and extra virgin olive oil increases mitochondrial and body metabolism and prevents CLA-associated insulin resistance and liver hypertrophy in C57Bl/6 mice.

    Science.gov (United States)

    Baraldi, Flávia G; Vicentini, Tatiane M; Teodoro, Bruno G; Dalalio, Felipe M; Dechandt, Carlos R P; Prado, Ieda M R; Curti, Carlos; Cardoso, Fernanda C; Uyemura, Sergio A; Alberici, Luciane C

    2016-02-01

    Clinical conditions associated with obesity can be improved by daily intake of conjugated linoleic acid (CLA) or extra virgin olive oil (EVOO). Here we investigated whether dietary supplementation with CLA and EVOO, either alone or in combination, changes body metabolism associated with mitochondrial energetics. Male C57Bl/6 mice were divided into one of four groups: CLA (1:1 cis-9, trans-11:trans-10, cis-12; 18:2 isomers), EVOO, CLA plus EVOO or control (linoleic acid). Each mouse received 3 g/kg body weight of the stated oil by gavage on alternating days for 60 days. Dietary supplementation with CLA, alone or in combination with EVOO: (a) reduced the white adipose tissue gain; (b) increased body VO2 consumption, VCO2 production and energy expenditure; (c) elevated uncoupling protein (UCP)-2 expression and UCP activity in isolated liver mitochondria. This organelle, when energized with NAD(+)-linked substrates, produced high amounts of H2O2 without inducing oxidative damage. Dietary supplementation with EVOO alone did not change any metabolic parameter, but supplementation with CLA itself promoted insulin resistance and elevated weight, lipid content and acetyl-CoA carboxylase-1 expression in liver. Interestingly, the in vivo antioxidant therapy with N-acetylcysteine abolished the CLA-induced rise of body metabolism and liver UCP expression and activity, while the in vitro antioxidant treatment with catalase mitigated the CLA-dependent UCP-2 expression in hepatocytes; these findings suggest the participation of an oxidative-dependent pathway. Therefore, this study clarifies the mechanisms by which CLA induces liver UCP expression and activity, and demonstrates for the first time the beneficial effects of combined CLA and EVOO supplementation.

  1. Long-term exercise in mice has sex-dependent benefits on body composition and metabolism during aging.

    Science.gov (United States)

    McMullan, Rachel C; Kelly, Scott A; Hua, Kunjie; Buckley, Brian K; Faber, James E; Pardo-Manuel de Villena, Fernando; Pomp, Daniel

    2016-11-01

    Aging is associated with declining exercise and unhealthy changes in body composition. Exercise ameliorates certain adverse age-related physiological changes and protects against many chronic diseases. Despite these benefits, willingness to exercise and physiological responses to exercise vary widely, and long-term exercise and its benefits are difficult and costly to measure in humans. Furthermore, physiological effects of aging in humans are confounded with changes in lifestyle and environment. We used C57BL/6J mice to examine long-term patterns of exercise during aging and its physiological effects in a well-controlled environment. One-year-old male (n = 30) and female (n = 30) mice were divided into equal size cohorts and aged for an additional year. One cohort was given access to voluntary running wheels while another was denied exercise other than home cage movement. Body mass, composition, and metabolic traits were measured before, throughout, and after 1 year of treatment. Long-term exercise significantly prevented gains in body mass and body fat, while preventing loss of lean mass. We observed sex-dependent differences in body mass and composition trajectories during aging. Wheel running (distance, speed, duration) was greater in females than males and declined with age. We conclude that long-term exercise may serve as a preventive measure against age-related weight gain and body composition changes, and that mouse inbred strains can be used to characterize effects of long-term exercise and factors (e.g. sex, age) modulating these effects. These findings will facilitate studies on relationships between exercise and health in aging populations, including genetic predisposition and genotype-by-environment interactions.

  2. Ethanol metabolism and oxidative stress are required for unfolded protein response activation and steatosis in zebrafish with alcoholic liver disease

    Science.gov (United States)

    Tsedensodnom, Orkhontuya; Vacaru, Ana M.; Howarth, Deanna L.; Yin, Chunyue; Sadler, Kirsten C.

    2013-01-01

    SUMMARY Secretory pathway dysfunction and lipid accumulation (steatosis) are the two most common responses of hepatocytes to ethanol exposure and are major factors in the pathophysiology of alcoholic liver disease (ALD). However, the mechanisms by which ethanol elicits these cellular responses are not fully understood. Recent data indicates that activation of the unfolded protein response (UPR) in response to secretory pathway dysfunction can cause steatosis. Here, we examined the relationship between alcohol metabolism, oxidative stress, secretory pathway stress and steatosis using zebrafish larvae. We found that ethanol was immediately internalized and metabolized by larvae, such that the internal ethanol concentration in 4-day-old larvae equilibrated to 160 mM after 1 hour of exposure to 350 mM ethanol, with an average ethanol metabolism rate of 56 μmol/larva/hour over 32 hours. Blocking alcohol dehydrogenase 1 (Adh1) and cytochrome P450 2E1 (Cyp2e1), the major enzymes that metabolize ethanol, prevented alcohol-induced steatosis and reduced induction of the UPR in the liver. Thus, we conclude that ethanol metabolism causes ALD in zebrafish. Oxidative stress generated by Cyp2e1-mediated ethanol metabolism is proposed to be a major culprit in ALD pathology. We found that production of reactive oxygen species (ROS) increased in larvae exposed to ethanol, whereas inhibition of the zebrafish CYP2E1 homolog or administration of antioxidants reduced ROS levels. Importantly, these treatments also blocked ethanol-induced steatosis and reduced UPR activation, whereas hydrogen peroxide (H2O2) acted as a pro-oxidant that synergized with low doses of ethanol to induce the UPR. Collectively, these data demonstrate that ethanol metabolism and oxidative stress are conserved mechanisms required for the development of steatosis and hepatic dysfunction in ALD, and that these processes contribute to ethanol-induced UPR activation and secretory pathway stress in hepatocytes. PMID

  3. Improvement of oxidized glutathione fermentation by thiol redox metabolism engineering in Saccharomyces cerevisiae.

    Science.gov (United States)

    Hara, Kiyotaka Y; Aoki, Naoko; Kobayashi, Jyumpei; Kiriyama, Kentaro; Nishida, Keiji; Araki, Michihiro; Kondo, Akihiko

    2015-11-01

    Glutathione is a valuable tripeptide widely used in the pharmaceutical, food, and cosmetic industries. In industrial fermentation, glutathione is currently produced primarily using the yeast Saccharomyces cerevisiae. Intracellular glutathione exists in two forms; the majority is present as reduced glutathione (GSH) and a small amount is present as oxidized glutathione (GSSG). However, GSSG is more stable than GSH and is a more attractive form for the storage of glutathione extracted from yeast cells after fermentation. In this study, intracellular GSSG content was improved by engineering thiol oxidization metabolism in yeast. An engineered strain producing high amounts of glutathione from over-expression of glutathione synthases and lacking glutathione reductase was used as a platform strain. Additional over-expression of thiol oxidase (1.8.3.2) genes ERV1 or ERO1 increased the GSSG content by 2.9-fold and 2.0-fold, respectively, compared with the platform strain, without decreasing cell growth. However, over-expression of thiol oxidase gene ERV2 showed almost no effect on the GSSG content. Interestingly, ERO1 over-expression did not decrease the GSH content, raising the total glutathione content of the cell, but ERV1 over-expression decreased the GSH content, balancing the increase in the GSSG content. Furthermore, the increase in the GSSG content due to ERO1 over-expression was enhanced by additional over-expression of the gene encoding Pdi1, whose reduced form activates Ero1 in the endoplasmic reticulum. These results indicate that engineering the thiol redox metabolism of S. cerevisiae improves GSSG and is critical to increasing the total productivity and stability of glutathione.

  4. Effect of nitric oxide synthase inhibitor on proteoglycan metabolism in repaired articular cartilage in rabbits

    Institute of Scientific and Technical Information of China (English)

    孙炜; 金大地; 王吉兴; 秦立赟; 刘晓霞

    2003-01-01

    Objective: To study the effect of nitric oxide synthase inhibitor, S-methyl thiocarbamate (SMT), on proteoglycan metabolism in repaired articular cartilage in rabbits. Methods: Twenty-four male New Zealand white rabbits, aged 8 months and weighing 2.5 kg±0.2 kg, were used in this study. Cartilage defects in full thickness were created on the intercondylar articular surface of bilateral femurs of all the rabbits. Then the rabbits were randomly divided into 3 groups (n=8 in each group). The defects in one group were filled with fibrin glue impregnated with recombinant human bone morphogenetic protein-2 (rhBMP-2, BMP group), in one group with fibrin glue impregnated with rhBMP-2 and hypodermic injection with SMT (SMT group) and in the other group with nothing (control group). All the animals were killed at one year postoperatively. The tissue sections were stained with safranine O-fast green and analyzed by Quantiment 500 system to determine the content of glycosaminoglycan through measuring the percentage of safranine O-stained area, the thickness of cartilages and the mean gray scale (average stain intensity). Radiolabelled sodium sulphate (Na235SO4) was used to assess the proteoglycan synthesis. Results: At one year postoperatively, the percentage of safranine O-stained area, the mean gray scale and the cartilage thickness of the repaired tissues in SMT group were significantly higher than those of BMP group (P<0.01) and the control group (P<0.05). Result of incorporation of Na235SO4 showed that the proteoglycan synthesis in SMT group was higher than those of BMP group and the control group (P<0.01). Conclusions: SMT, a nitric oxide synthase inhibitor, can significantly increase the content of glycosaminoglycan and proteoglycan synthesis, and computer-based image analysis is a reliable method for evaluating proteoglycan metabolism.

  5. Physiological mechanisms by which non-nutritive sweeteners may impact body weight and metabolism

    OpenAIRE

    Burke, Mary V.; Small, Dana M

    2015-01-01

    Evidence linking sugar-sweetened beverage (SSB) consumption to weight gain and other negative health outcomes has prompted many individuals to resort to artificial, non-nutritive sugar (NNS) substitutes as a means of reducing SSB intake. However, there is a great deal of controversy regarding the biological consequences of NNS use, with accumulating evidence suggesting that NNS consumption may influence feeding and metabolism via a variety of peripheral and central mechanisms. Here we argue t...

  6. Anatomical and metabolic small-animal whole-body imaging using ring-shaped confocal photoacoustic computed tomography

    Science.gov (United States)

    Xia, Jun; Chatni, Muhammad; Maslov, Konstantin; Wang, Lihong V.

    2013-03-01

    Due to the wide use of animals for human disease studies, small animal whole-body imaging plays an increasingly important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose metabolic information, leading to higher costs of building dual-modality systems. Even with image coregistration, the spatial resolution of the metabolic imaging modality is not improved. We present a ring-shaped confocal photoacoustic computed tomography (RC-PACT) system that can provide both assessments in a single modality. Utilizing the novel design of confocal full-ring light delivery and ultrasound transducer array detection, RC-PACT provides full-view cross-sectional imaging with high spatial resolution. Scanning along the orthogonal direction provides three-dimensional imaging. While the mouse anatomy was imaged with endogenous hemoglobin contrast, the glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose. Through mouse tumor models, we demonstrate that RC-PACT may be a paradigm shifting imaging method for preclinical research.

  7. Oxidative Stress and Metabolic Perturbations in Wooden Breast Disorder in Chickens.

    Science.gov (United States)

    Abasht, Behnam; Mutryn, Marie F; Michalek, Ryan D; Lee, William R

    2016-01-01

    This study was conducted to characterize metabolic features of the breast muscle (pectoralis major) in chickens affected with the Wooden Breast myopathy. Live birds from two purebred chicken lines and one crossbred commercial broiler population were clinically examined by manual palpation of the breast muscle (pectoralis major) at 47-48 days of age. Metabolite abundance was determined by gas chromatography/mass spectrometry (GC/MS) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) using breast muscle tissue samples from 16 affected and 16 unaffected chickens. Muscle glycogen content was also quantified in breast muscle tissue samples from affected and unaffected chickens. In total, levels of 140 biochemicals were significantly different (FDR1.3 or chickens. Glycogen content measurements were considerably lower (1.7-fold) in samples taken from Wooden Breast affected birds when compared with samples from unaffected birds. Affected tissues exhibited biomarkers related to increased oxidative stress, elevated protein levels, muscle degradation, and altered glucose utilization. Affected muscle also showed elevated levels of hypoxanthine, xanthine, and urate molecules, the generation of which can contribute to altered redox homeostasis. In conclusion, our findings show that Wooden Breast affected tissues possess a unique metabolic signature. This unique profile may identify candidate biomarkers for diagnostic utilization and provide mechanistic insight into altered biochemical processes contributing to tissue hardening associated with the Wooden Breast myopathy in commercial chickens.

  8. Effects of nitrous oxide on cerebral haemodynamics and metabolism during isoflurane anaesthesia in man

    Energy Technology Data Exchange (ETDEWEB)

    Algotsson, L.; Messeter, K. (Department of Anaesthesiology, University Hospital, Lund (Sweden)); Rosen, I. (Department of Clinical Neurophysiology, University Hospital, Lund (Sweden)); Holmin, T. (Department of Surgery, University Hospital, Lund (Sweden))

    1992-01-01

    Seven normoventilated and five hyperventilated healthy adults undergoing cholecystectomy and anaesthetized with methohexitone, fentanyl and pancuronium were studied with measurement of cerebral blood flow (CBF), cereal metabolic rate of oxygen (CMRo[sub 2]), and quantified electroencephalography (EEG) under two sets of conditions: (1) 1.7% end-tidal concentration of isoflurane in air/oxygen: (2) 0.85% end-tidal concentration of isoflurane in nitrous oxide (N[sub 2]O)/oxygen. The object was to study the effects of N[sub 2]O during isoflurane anaesthesia on cerebral circulation, metabolism and neuroelectric activity. N[sub 2]O in the anaesthetic gas mixture caused a 43% (P<0.05) increase in CBF during normocarbic conditions but no significant change during hypocapnia. CMRo[sub 2] was not significantly altered by N[sub 2]O. EEG demonstrated an activated pattern with decreased low frequency activity and increased high frequency activity. The results confirm that N[sub 2]O is a potent cerebral vasodilator in man, although the mechanisms underlying the effects on CBF are still unclear. (au).

  9. Mammalian Tissue Response to Low Dose Ionizing Radiation: The Role of Oxidative Metabolism and Intercellular Communication

    Energy Technology Data Exchange (ETDEWEB)

    Azzam, Edouard I

    2013-01-16

    The objective of the project was to elucidate the mechanisms underlying the biological effects of low dose/low dose rate ionizing radiation in organs/tissues of irradiated mice that differ in their susceptibility to ionizing radiation, and in human cells grown under conditions that mimic the natural in vivo environment. The focus was on the effects of sparsely ionizing cesium-137 gamma rays and the role of oxidative metabolism and intercellular communication in these effects. Four Specific Aims were proposed. The integrated outcome of the experiments performed to investigate these aims has been significant towards developing a scientific basis to more accurately estimate human health risks from exposures to low doses ionizing radiation. By understanding the biochemical and molecular changes induced by low dose radiation, several novel markers associated with mitochondrial functions were identified, which has opened new avenues to investigate metabolic processes that may be affected by such exposure. In particular, a sensitive biomarker that is differentially modulated by low and high dose gamma rays was discovered.

  10. Monoacylglycerol Lipases Act as Evolutionarily Conserved Regulators of Non-oxidative Ethanol Metabolism*

    Science.gov (United States)

    Heier, Christoph; Taschler, Ulrike; Radulovic, Maja; Aschauer, Philip; Eichmann, Thomas O.; Grond, Susanne; Wolinski, Heimo; Oberer, Monika; Zechner, Rudolf; Kohlwein, Sepp D.; Zimmermann, Robert

    2016-01-01

    Fatty acid ethyl esters (FAEEs) are non-oxidative metabolites of ethanol that accumulate in human tissues upon ethanol intake. Although FAEEs are considered as toxic metabolites causing cellular dysfunction and tissue damage, the enzymology of FAEE metabolism remains poorly understood. In this study, we used a biochemical screen in Saccharomyces cerevisiae to identify and characterize putative hydrolases involved in FAEE catabolism. We found that Yju3p, the functional orthologue of mammalian monoacylglycerol lipase (MGL), contributes >90% of cellular FAEE hydrolase activity, and its loss leads to the accumulation of FAEE. Heterologous expression of mammalian MGL in yju3Δ mutants restored cellular FAEE hydrolase activity and FAEE catabolism. Moreover, overexpression or pharmacological inhibition of MGL in mouse AML-12 hepatocytes decreased or increased FAEE levels, respectively. FAEEs were transiently incorporated into lipid droplets (LDs) and both Yju3p and MGL co-localized with these organelles. We conclude that the storage of FAEE in inert LDs and their mobilization by LD-resident FAEE hydrolases facilitate a controlled metabolism of these potentially toxic lipid metabolites. PMID:27036938

  11. Toxicity of graphene oxide on growth and metabolism of Pseudomonas putida.

    Science.gov (United States)

    Combarros, R G; Collado, S; Díaz, M

    2016-06-05

    The increasing consumption of graphene derivatives leads to greater presence of these materials in wastewater treatment plants and ecological systems. The toxicity effect of graphene oxide (GO) on the microbial functions involved in the biological wastewater treatment process is studied, using Pseudomonas putida and salicylic acid (SA) as bacterial and pollutant models. A multiparametric flow cytometry (FC) method has been developed to measure the metabolic activity and viability of P. putida in contact with GO. A continuous reduction in the percentages of viable cells and a slight increase, lower than 5%, in the percentages of damaged and dead cells, suggest that P. putida in contact with GO loses the membrane integrity but preserves metabolic activity. The growth of P. putida was strongly inhibited by GO, since 0.05mgmL(-1) of GO reduced the maximum growth by a third, and the inhibition was considerably greater for GO concentrations higher than 0.1mgmL(-1). The specific SA removal rate decreased with GO concentration up to 0.1mgmL(-1) indicating that while GO always reduces the growth of P. putida, for concentrations higher than 0.1mgmL(-1), it also reduces its activity. Similar behaviour is observed using simulated urban and industrial wastewaters, the observed effects being more acute in the industrial wastewaters.

  12. Effect of Centella asiatica on Oxidative Stress and Lipid Metabolism in Hyperlipidemic Animal Models

    Directory of Open Access Journals (Sweden)

    Yun Zhao

    2014-01-01

    Full Text Available Hyperlipidemia and many other metabolic diseases are related to oxidative stress. Centella asiatica is a traditional Chinese medicine whose antioxidant effect in vitro has been reported. We are interested in whether it possesses this effect in vivo and hence modulates lipid metabolism. Therefore, experiments were carried out on mice and golden hamsters regarding its antioxidant and hypolipidemic effect. We observed that a fraction (CAF3 of the ethanol extract (CAE of Centella asiatica had a cholesterol decrease of 79% and a triglyceride decrease of 95% in acute mice model, so CAF3 was further investigated in high-fat-fed hamster model. It was shown that CAF3 increased SOD and GSH-Px activities and decreased MDA level, and it also improved TC, TG, LDL-C, HDL-C, AST, and ALT levels. L-CAT and SR-BI gene expression in hamsters were increased. Taken together, our data suggest that the CAF3 fraction of Centella asiatica has antioxidant and hypolipidemic properties.

  13. Galactose enhances oxidative metabolism and reveals mitochondrial dysfunction in human primary muscle cells.

    Directory of Open Access Journals (Sweden)

    Céline Aguer

    Full Text Available BACKGROUND: Human primary myotubes are highly glycolytic when cultured in high glucose medium rendering it difficult to study mitochondrial dysfunction. Galactose is known to enhance mitochondrial metabolism and could be an excellent model to study mitochondrial dysfunction in human primary myotubes. The aim of the present study was to 1 characterize the effect of differentiating healthy human myoblasts in galactose on oxidative metabolism and 2 determine whether galactose can pinpoint a mitochondrial malfunction in post-diabetic myotubes. METHODOLOGY/PRINCIPAL FINDINGS: Oxygen consumption rate (OCR, lactate levels, mitochondrial content, citrate synthase and cytochrome C oxidase activities, and AMPK phosphorylation were determined in healthy myotubes differentiated in different sources/concentrations of carbohydrates: 25 mM glucose (high glucose (HG, 5 mM glucose (low glucose (LG or 10 mM galactose (GAL. Effect of carbohydrates on OCR was also determined in myotubes derived from post-diabetic patients and matched obese non-diabetic subjects. OCR was significantly increased whereas anaerobic glycolysis was significantly decreased in GAL myotubes compared to LG or HG myotubes. This increased OCR in GAL myotubes occurred in conjunction with increased cytochrome C oxidase activity and expression, as well as increased AMPK phosphorylation. OCR of post-diabetic myotubes was not different than that of obese non-diabetic myotubes when differentiated in LG or HG. However, whereas GAL increased OCR in obese non-diabetic myotubes, it did not affect OCR in post-diabetic myotubes, leading to a significant difference in OCR between groups. The lack of an increase in OCR in post-diabetic myotubes differentiated in GAL was in relation with unaltered cytochrome C oxidase activity levels or AMPK phosphorylation. CONCLUSIONS/SIGNIFICANCE: Our results indicate that differentiating human primary myoblasts in GAL enhances aerobic metabolism. Because this cell

  14. Signal transduction pathways in erythrocyte nitric oxide metabolism under high fibrinogen levels

    Science.gov (United States)

    Saldanha, Carlota; Freitas, T.; Lopez de Almeida, J. P.; Silva-Herdade, A.

    2014-05-01

    Previous studies show that the fibrinogen molecule modulates the metabolism of nitric oxide (NO) in erythrocyte. The in vitro induced hiperfibrinogenemia interferes in the metabolism of the NO in the erythrocyte in dependence of the phosphorylation degree of the band 3. The soluble form of fibrinogen binds into CD47 protein present in the erythrocyte membrane. The soluble thrombomodulin is an inflammatory marker that binds to the erythrocyte CD47 in a site with a sequence peptide known as 4N1K. A study done in vitro shows that when hiperfibrinogenemia was induced in the presence of the peptide 4N1K agonist of CD47 it were observed variations in the efflux of NO from erythrocyte and an increase in the concentrations of GSNO, peroxinitrite, nitrite and nitrate of the erythrocytes. The aim of this work was to study the influence of the peptide 4N1K, on the metabolism of NO in the erythrocyte under high fibrinogen concentration and in the presence of inhibitors of the status of phosphorylation of protein band 3. In this in vitro study, whole blood samples were harvested from healthy subjects and NO, peroxynitrite, nitrite, nitrate and S-nitro-glutathione (GSNO) were determined in presence of 4N1K, calpeptine, Syk inhibitor and under high fibrinogen concentrations. The results obtained in erythrocytes under high fibrinogen levels when 4N1K is present with the Syk inhibitor or with calpeptine, showed in relation to the control samples increased significant concentrations of efflux of NO and of peroxynitrite, nitrite, nitrate and GSNO. In conclusion it was verified that in the in vitro model of hiperfibrinogenemia the peptide 4N1K, agonist of CD47, induces mobilization of NO in the erythrocyte in dependence of the status of phosphorylation of protein band 3.

  15. Effects of whole-body electromyostimulation on resting metabolic rate, body composition, and maximum strength in postmenopausal women: the Training and ElectroStimulation Trial.

    Science.gov (United States)

    Kemmler, Wolfgang; Schliffka, Rebecca; Mayhew, Jerry L; von Stengel, Simon

    2010-07-01

    We evaluated the effect of whole-body electromyostimulation (WB-EMS) during dynamic exercises over 14 weeks on anthropometric, physiological, and muscular parameters in postmenopausal women. Thirty women (64.5 +/- 5.5 years) with experience in physical training (>3 years) were randomly assigned either to a control group (CON, n = 15) that maintained their general training program (2 x 60 min.wk of endurance and dynamic strength exercise) or to an electromyostimulation group (WB-EMS, n = 15) that additionally performed a 20-minute WB-EMS training (2 x 20 min.10 d). Resting metabolic rate (RMR) determined from spirometry was selected to indicate muscle mass. In addition, body circumferences, subcutaneous skinfolds, strength, power, and dropout and adherence values. Resting metabolic rate was maintained in WB-EMS (-0.1 +/- 4.8 kcal.h) and decreased in CON (-3.2+/-5.2 kcal.h, p = 0.038); although group differences were not significant (p = 0.095), there was a moderately strong effect size (ES = 0.62). Sum of skinfolds (28.6%) and waist circumference (22.3%) significantly decreased in WB-EMS whereas both parameters (1.4 and 0.1%, respectively) increased in CON (p = 0.001, ES = 1.37 and 1.64, respectively), whereas both parameters increased in CON (1.4 and 0.1%, respectively). Isometric strength changes of the trunk extensors and leg extensors differed significantly (p < or = 0.006) between WB-EMS and CON (9.9% vs. -6.4%, ES = 1.53; 9.6% vs. -4.5%, ES = 1.43, respectively). In summary, adjunct WB-EMS training significantly exceeds the effect of isolated endurance and resistance type exercise on fitness and fatness parameters. Further, we conclude that for elderly subjects unable or unwilling to perform dynamic strength exercises, electromyostimulation may be a smooth alternative to maintain lean body mass, strength, and power.

  16. Asiatic Acid Alleviates Hemodynamic and Metabolic Alterations via Restoring eNOS/iNOS Expression, Oxidative Stress, and Inflammation in Diet-Induced Metabolic Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Poungrat Pakdeechote

    2014-01-01

    Full Text Available Asiatic acid is a triterpenoid isolated from Centella asiatica. The present study aimed to investigate whether asiatic acid could lessen the metabolic, cardiovascular complications in rats with metabolic syndrome (MS induced by a high-carbohydrate, high-fat (HCHF diet. Male Sprague-Dawley rats were fed with HCHF diet with 15% fructose in drinking water for 12 weeks to induce MS. MS rats were treated with asiatic acid (10 or 20 mg/kg/day or vehicle for a further three weeks. MS rats had an impairment of oral glucose tolerance, increases in fasting blood glucose, serum insulin, total cholesterol, triglycerides, mean arterial blood pressure, heart rate, and hindlimb vascular resistance; these were related to the augmentation of vascular superoxide anion production, plasma malondialdehyde and tumor necrosis factor-alpha (TNF-α levels (p < 0.05. Plasma nitrate and nitrite (NOx were markedly high with upregulation of inducible nitric oxide synthase (iNOS expression, but dowregulation of endothelial nitric oxide synthase (eNOS expression (p < 0.05. Asiatic acid significantly improved insulin sensitivity, lipid profiles, hemodynamic parameters, oxidative stress markers, plasma TNF-α, NOx, and recovered abnormality of eNOS/iNOS expressions in MS rats (p < 0.05. In conclusion, asiatic acid improved metabolic, hemodynamic abnormalities in MS rats that could be associated with its antioxidant, anti-inflammatory effects and recovering regulation of eNOS/iNOS expression.

  17. Adult onset global loss of the fto gene alters body composition and metabolism in the mouse.

    Directory of Open Access Journals (Sweden)

    Fiona McMurray

    Full Text Available The strongest BMI-associated GWAS locus in humans is the FTO gene. Rodent studies demonstrate a role for FTO in energy homeostasis and body composition. The phenotypes observed in loss of expression studies are complex with perinatal lethality, stunted growth from weaning, and significant alterations in body composition. Thus understanding how and where Fto regulates food intake, energy expenditure, and body composition is a challenge. To address this we generated a series of mice with distinct temporal and spatial loss of Fto expression. Global germline loss of Fto resulted in high perinatal lethality and a reduction in body length, fat mass, and lean mass. When ratio corrected for lean mass, mice had a significant increase in energy expenditure, but more appropriate multiple linear regression normalisation showed no difference in energy expenditure. Global deletion of Fto after the in utero and perinatal period, at 6 weeks of age, removed the high lethality of germline loss. However, there was a reduction in weight by 9 weeks, primarily as loss of lean mass. Over the subsequent 10 weeks, weight converged, driven by an increase in fat mass. There was a switch to a lower RER with no overall change in food intake or energy expenditure. To test if the phenotype can be explained by loss of Fto in the mediobasal hypothalamus, we sterotactically injected adeno-associated viral vectors encoding Cre recombinase to cause regional deletion. We observed a small reduction in food intake and weight gain with no effect on energy expenditure or body composition. Thus, although hypothalamic Fto can impact feeding, the effect of loss of Fto on body composition is brought about by its actions at sites elsewhere. Our data suggest that Fto may have a critical role in the control of lean mass, independent of its effect on food intake.

  18. Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems.

    Science.gov (United States)

    Thevenet, Jonathan; De Marchi, Umberto; Domingo, Jaime Santo; Christinat, Nicolas; Bultot, Laurent; Lefebvre, Gregory; Sakamoto, Kei; Descombes, Patrick; Masoodi, Mojgan; Wiederkehr, Andreas

    2016-05-01

    Medium-chain triglycerides have been used as part of a ketogenic diet effective in reducing epileptic episodes. The health benefits of the derived medium-chain fatty acids (MCFAs) are thought to result from the stimulation of liver ketogenesis providing fuel for the brain. We tested whether MCFAs have direct effects on energy metabolism in induced pluripotent stem cell-derived human astrocytes and neurons. Using single-cell imaging, we observed an acute pronounced reduction of the mitochondrial electrical potential and a concomitant drop of the NAD(P)H signal in astrocytes, but not in neurons. Despite the observed effects on mitochondrial function, MCFAs did not lower intracellular ATP levels or activate the energy sensor AMP-activated protein kinase. ATP concentrations in astrocytes were unaltered, even when blocking the respiratory chain, suggesting compensation through accelerated glycolysis. The MCFA decanoic acid (300 μM) promoted glycolysis and augmented lactate formation by 49.6%. The shorter fatty acid octanoic acid (300 μM) did not affect glycolysis but increased the rates of astrocyte ketogenesis 2.17-fold compared with that of control cells. MCFAs may have brain health benefits through the modulation of astrocyte metabolism leading to activation of shuttle systems that provide fuel to neighboring neurons in the form of lactate and ketone bodies.-Thevenet, J., De Marchi, U., Santo Domingo, J., Christinat, N., Bultot, L., Lefebvre, G., Sakamoto, K., Descombes, P., Masoodi, M., Wiederkehr, A. Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems.

  19. METABOLISM

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Objective: To determine the allele frequencies of genetic variants 373 Ala→Pro and 451 Arg→Gln of cholesteryl ester transfer protein (CETP) and to explore their potential impacts on serum lipid metabolism. Methods: The genotypes in CETP codon 373 and 451 in 91 German healthy students and 409 an-

  20. Differential Oxidative Metabolism and 5-Ketoclomazone Accumulation Are Involved in Echinochloa phyllopogon Resistance to Clomazone1[C][W][OA

    Science.gov (United States)

    Yasuor, Hagai; Zou, Wei; Tolstikov, Vladimir V.; Tjeerdema, Ronald S.; Fischer, Albert J.

    2010-01-01

    Echinochloa phyllopogon (late watergrass) is a major weed of California rice (Oryza sativa) that has evolved cytochrome P450-mediated metabolic resistance to different herbicides with multiple modes of action. E. phyllopogon populations from Sacramento Valley rice fields have also recently shown resistance to the herbicide clomazone. Clomazone is a proherbicide that must be metabolized to 5-ketoclomazone, which is the active compound that inhibits deoxyxylulose 5-phosphate synthase, a key enzyme of the nonmevalonate isoprenoid pathway. This study evaluated the differential clomazone metabolism within strains of the same species to investigate whether enhanced oxidative metabolism also confers clomazone resistance in E. phyllopogon. Using reverse-phase liquid chromatography-tandem mass spectrometry techniques in the multireaction monitoring mode, we elucidated that oxidative biotransformations are involved as a mechanism of clomazone resistance in this species. E. phyllopogon plants hydroxylated mostly the isoxazolidinone ring of clomazone, and clomazone hydroxylation activity was greater in resistant than in susceptible plants. The major clomazone metabolites resulted from monohydroxylation and dihydroxylation of the isoxazolidinone ring. Resistant plants accumulated 6- to 12-fold more of the monohydroxylated metabolite than susceptible plants, while susceptible plants accumulated 2.5-fold more of the phytotoxic metabolite of clomazone, 5-ketoclomazone. Our results demonstrate that oxidative metabolism endows multiple-herbicide-resistant E. phyllopogon with cross-resistance to clomazone through enhanced herbicide degradation and lower accumulation of the toxic metabolite in resistant versus susceptible plants. PMID:20207709

  1. Chloroguanide metabolism in relation to the efficacy in malaria prophylaxis and the S-mephenytoin oxidation in Tanzanians

    DEFF Research Database (Denmark)

    Skjelbo, E; Mutabingwa, T K; Bygbjerg, Ib Christian;

    1996-01-01

    S-Mephenytoin and chloroguanide (proguanil) oxidation was studied in 216 tanzanians. The mephenytoin S/R ratio in urine ranged from 0.9, were arbitrarily defined as poor metabolizers of mephenytoin. The chloroguanide/cycloguanil ratio ranged from 0.82 to 249. There was a significant correlation b...

  2. Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

    NARCIS (Netherlands)

    Assies, J.; Mocking, R.J.; Lok, A.; Ruhe, H.G.; Pouwer, F.; Schene, A.H.

    2014-01-01

    OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive respons

  3. An antiinflammatory dietary mix modulates inflammation and oxidative and metabolic stress in overweight men: A nutrigenomics approach

    NARCIS (Netherlands)

    Bakker, G.C.M.; Erk, M.J. van; Pellis, L.; Wopereis, S.; Rubingh, C.M.; Cnubben, N.H.P.; Kooistra, T.; Ommen, B. van; Hendriks, H.F.J.

    2010-01-01

    Background: Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Objective: It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. Design: Dietary products

  4. Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

    NARCIS (Netherlands)

    Assies, J.; Mocking, R. J. T.; Lok, A.; Ruhe, H. G.; Pouwer, F.; Schene, A. H.

    2014-01-01

    Objective: Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive respons

  5. Oxidative Damage and Energy Metabolism Disorder Contribute to the Hemolytic Effect of Amorphous Silica Nanoparticles

    Science.gov (United States)

    Jiang, Lizhen; Yu, Yongbo; Li, Yang; Yu, Yang; Duan, Junchao; Zou, Yang; Li, Qiuling; Sun, Zhiwei

    2016-02-01

    Amorphous silica nanoparticles (SiNPs) have been extensively used in biomedical applications due to their particular characteristics. The increased environmental and iatrogenic exposure of SiNPs gained great concerns on the biocompatibility and hematotoxicity of SiNPs. However, the studies on the hemolytic effects of amorphous SiNPs in human erythrocytes are still limited. In this study, amorphous SiNPs with 58 nm were selected and incubated with human erythrocytes for different times (30 min and 2 h) at various concentrations (0, 10, 20, 50, and 100 μg/mL). SiNPs induced a dose-dependent increase in percent hemolysis and significantly increased the malondialdehyde (MDA) content and decreased the superoxide dismutase (SOD) activity, leading to oxidative damage in erythrocytes. Hydroxyl radical (·OH) levels were detected by electron spin resonance (ESR), and the decreased elimination rates of ·OH showed SiNPs induced low antioxidant ability in human erythrocytes. Na+-K+ ATPase activity and Ca2+-Mg2+ ATPase activity were found remarkably inhibited after SiNP treatment, possibly causing energy sufficient in erythrocytes. Percent hemolysis of SiNPs was significantly decreased in the presence of N-acetyl-cysteine (NAC) and adenosine diphosphate (ADP). It was concluded that amorphous SiNPs caused dose-dependent hemolytic effects in human erythrocytes. Oxidative damage and energy metabolism disorder contributed to the hemolytic effects of SiNPs in vitro.

  6. Association of Inflammatory and Oxidative Stress Markers with Metabolic Syndrome in Asian Indians in India

    Directory of Open Access Journals (Sweden)

    Veena S. Rao

    2011-01-01

    Full Text Available Metabolic syndrome (MetS is a primary risk factor for cardiovascular disease and is associated with a proinflammatory state. Here, we assessed the contribution of inflammatory and oxidative stress markers towards prediction of MetS. A total of 2316 individuals were recruited in Phase I of the Indian Atherosclerosis Research Study (IARS. Modified ATPIII guidelines were used for classification of subjects with MetS. Among the inflammatory and oxidative stress markers studied, levels of hsCRP (P<.0001, Neopterin (P=.036, and oxLDL (P<.0001 were significantly higher among subjects with MetS. Among the markers we tested, oxLDL stood out as a robust predictor of MetS in the IARS population (OR 4.956 95% CI 2.504–9.810; P<.0001 followed by hsCRP (OR 1.324 95% CI 1.070–1.638; P=.010. In conclusion, oxLDL is a candidate predictor for MetS in the Asian Indian population.

  7. Redox Modulation of Cellular Signaling and Metabolism Through Reversible Oxidation of Methionine Sensors in Calcium Regulatory Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Bigelow, Diana J.; Squier, Thomas C.

    2005-01-17

    Adaptive responses associated with environmental stressors are critical to cell survival. These involve the modulation of central signaling protein functions through site-specific and enzymatically reversible oxidative modifications of methionines to coordinate cellular metabolism, energy utilization, and calcium signaling. Under conditions when cellular redox and antioxidant defenses are overwhelmed, the selective oxidation of critical methionines within selected protein sensors functions to down-regulate energy metabolism and the further generation of reactive oxygen species (ROS). Mechanistically, these functional changes within protein sensors take advantage of the helix-breaking character of methionine sulfoxide. Thus, depending on either the ecological niche of the organism or the cellular milieu of different organ systems, cellular metabolism can be fine-tuned to maintain optimal function in the face of variable amounts of collateral oxidative damage. The sensitivity of several calcium regulatory proteins to oxidative modification provides cellular sensors that link oxidative stress to cellular response and recovery. Calmodulin (CaM) is one such critical calcium regulatory protein, which is functionally sensitive to methionine oxidation. Helix destabilization resulting from the oxidation of either Met{sup 144} or Met{sup 145} results in the nonproductive association between CaM and target proteins. The ability of oxidized CaM to stabilize its target proteins in an inhibited state with an affinity similar to that of native (unoxidized) CaM permits this central regulatory protein to function as a cellular rheostat that down-regulates energy metabolism in response to oxidative stress. Likewise, oxidation of a methionine within a critical switch region of the regulatory protein phospholamban is expected to destabilize the phosphorylationdependent helix formation necessary for the release of enzyme inhibition, resulting in a down-regulation of the Ca-ATPase in

  8. Cinnamon improves insulin sensitivity and alters body composition in an animal model of the metabolic syndrome

    Science.gov (United States)

    Polyphenols from cinnamon (CN) have been described recently as insulin sensitizers and antioxidants, but their effects on the glucose/insulin system in vivo have not been totally investigated. The aim of this study was to determine the effects of CN on insulin resistance and body composition, using ...

  9. Bone metabolism biomarkers, body weight, and bone age in healthy Brazilian male adolescents.

    Science.gov (United States)

    da Silva, Carla Cristiane; Kurokawa, Cilmery Suemi; Nga, Hong Si; Moretto, Maria Regina; Dalmas, José Carlos; Goldberg, Tamara Beres Lederer

    2012-01-01

    Eighty-seven male volunteers were grouped according to bone age (BA): 10-12 years (n=25), 13-15 years (n=36), and 16-18 years (n=26), and the following were recorded for each: weight (kg), height (m), BMI (kg/m(2)), calcium intake from three 24-h food recalls (mg/day), puberty evaluation by Tanner stages, bone biomarker (BB) evaluation, serum osteocalcin (OC), bone alkaline phosphatase (BAP), carboxyterminal telopeptide (S-CTx), and bone mineral density (BMD) evaluations by dual-energy X-ray absorptiometry (g x cm(2)) in the lumbar spine, proximal femur, and the whole body. BBs showed similar behaviors, and very high median values were observed for individuals aged 13-15 years (BAP = 155.50 IU/L, OC = 41.63 ng/mL, S-CT x =2.09 ng/mL). Lower median BB values were observed with advancing BA between 16 and 18 years (BA P =79.80 IU/L, O C =27.80 ng/mL, S-CT x =1.65 ng/mL). Stepwise multiple regression analysis showed body weight associated with BA as independent variables with greater determination power for S-CTx (r(2) = 0.40) and OC (r(2)=0.21). For BAP, stepwise analysis showed body weight and whole-body BMD (r(2) = 0.34). All predictive models showed significance ( p Weight and BA were significant in determining predictive equations of OC and of S-CTx, whereas for BAP, weight and BMD of full body were selected.

  10. Effect of the Combination of Gelam Honey and Ginger on Oxidative Stress and Metabolic Profile in Streptozotocin-Induced Diabetic Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Nur Fathiah Abdul Sani

    2014-01-01

    Full Text Available Diabetic complications occur as a result of increased reactive oxygen species (ROS due to long term hyperglycaemia. Honey and ginger have been shown to exhibit antioxidant activity which can scavenge ROS. The main aim of this study was to evaluate the antioxidant and antidiabetic effects of gelam honey, ginger, and their combination. Sprague-Dawley rats were divided into 2 major groups which consisted of diabetic and nondiabetic rats. Diabetes was induced with streptozotocin intramuscularly (55 mg/kg body weight. Each group was further divided into 4 smaller groups according to the supplements administered: distilled water, honey (2 g/kg body weight, ginger (60 mg/kg body weight, and honey + ginger. Body weight and glucose levels were recorded weekly, while blood from the orbital sinus was obtained after 3 weeks of supplementation for the estimation of metabolic profile: glucose, triglyceride (TG, superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx, reduced glutathione (GSH: oxidized glutathione (GSSG, and malondialdehyde (MDA. The combination of gelam honey and ginger did not show hypoglycaemic potential; however, the combination treatment reduced significantly (P<0.05 SOD and CAT activities as well as MDA level, while GSH level and GSH/GSSG ratio were significantly elevated (P<0.05 in STZ-induced diabetic rats compared to diabetic control rats.

  11. Effect of the combination of gelam honey and ginger on oxidative stress and metabolic profile in streptozotocin-induced diabetic Sprague-Dawley rats.

    Science.gov (United States)

    Sani, Nur Fathiah Abdul; Belani, Levin Kesu; Sin, Chong Pui; Rahman, Siti Nor Amilah Abdul; Das, Srijit; Chi, Thent Zar; Makpol, Suzana; Yusof, Yasmin Anum Mohd

    2014-01-01

    Diabetic complications occur as a result of increased reactive oxygen species (ROS) due to long term hyperglycaemia. Honey and ginger have been shown to exhibit antioxidant activity which can scavenge ROS. The main aim of this study was to evaluate the antioxidant and antidiabetic effects of gelam honey, ginger, and their combination. Sprague-Dawley rats were divided into 2 major groups which consisted of diabetic and nondiabetic rats. Diabetes was induced with streptozotocin intramuscularly (55 mg/kg body weight). Each group was further divided into 4 smaller groups according to the supplements administered: distilled water, honey (2 g/kg body weight), ginger (60 mg/kg body weight), and honey + ginger. Body weight and glucose levels were recorded weekly, while blood from the orbital sinus was obtained after 3 weeks of supplementation for the estimation of metabolic profile: glucose, triglyceride (TG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH): oxidized glutathione (GSSG), and malondialdehyde (MDA). The combination of gelam honey and ginger did not show hypoglycaemic potential; however, the combination treatment reduced significantly (P diabetic rats compared to diabetic control rats.

  12. Cognitive impairment and Alzheimer’s disease: Links with oxidative stress and cholesterol metabolism

    Directory of Open Access Journals (Sweden)

    Alejandra Sekler

    2008-08-01

    Full Text Available Alejandra Sekler1,2, José M Jiménez2, Leonel Rojo2, Edgard Pastene3, Patricio Fuentes4, Andrea Slachevsky4, Ricardo B Maccioni1,21Center of Cognitive Neurosciences, International Center for Biomedicine (ICC, Santiago, Chile; 2Laboratory of Cellular, Molecular Biology and Neurosciences, Faculty of Sciences, Universidad de Chile, Santiago, Chile; 3Department of Pharmacy, Faculty of Pharmacy, University of Concepcion, Concepción, Chile; 4Unidad de Neurología Cognitiva y Demencias, Servicio de Neurología, Hospital del Salvador, Santiago, ChileAbstract: Oxidative stress has been implicated in the progression of a number of neurodegenerative diseases, including Alzheimer’s disease (AD, Parkinson’s disease and amyotrophic lateral sclerosis. We carried out an in-depth study of cognitive impairment and its relationships with oxidative stress markers such as ferric-reducing ability of plasma (FRAP, plasma malondialdehyde and total antioxidative capacity (TAC, as well as cholesterol parameters, in two subsets of subjects, AD patients (n = 59 and a control group of neurologically normal subjects (n = 29, attending the University Hospital Salvador in Santiago, Chile. Cognitive impairment was assessed by a set of neuropsychological tests (Mini-Mental State Examination, Boston Naming Test, Ideomotor Praxia by imitation, Semantic Verbal Fluency of animals or words with initial A, Test of Memory Alteration, Frontal Assessment Battery, while the levels of those oxidative stress markers and cholesterol metabolism parameters were determined according with standard bioassays in fresh plasma samples of the two subgroups of patients. No significant differences were observed when the cholesterol parameters (low-, high-density lipoprotein, total cholesterol of the AD group were compared with normal controls. Interestingly, a correlation was evidenced when the levels of cognitive impairment were analyzed with respect to the plasma antioxidant capacity (AOC of

  13. Caenorhabditis elegans: A Useful Model for Studying Metabolic Disorders in Which Oxidative Stress Is a Contributing Factor

    Science.gov (United States)

    Moreno-Arriola, Elizabeth; Cárdenas-Rodríguez, Noemí; Coballase-Urrutia, Elvia; Pedraza-Chaverri, José; Carmona-Aparicio, Liliana; Ortega-Cuellar, Daniel

    2014-01-01

    Caenorhabditis elegans is a powerful model organism that is invaluable for experimental research because it can be used to recapitulate most human diseases at either the metabolic or genomic level in vivo. This organism contains many key components related to metabolic and oxidative stress networks that could conceivably allow us to increase and integrate information to understand the causes and mechanisms of complex diseases. Oxidative stress is an etiological factor that influences numerous human diseases, including diabetes. C. elegans displays remarkably similar molecular bases and cellular pathways to those of mammals. Defects in the insulin/insulin-like growth factor-1 signaling pathway or increased ROS levels induce the conserved phase II detoxification response via the SKN-1 pathway to fight against oxidative stress. However, it is noteworthy that, aside from the detrimental effects of ROS, they have been proposed as second messengers that trigger the mitohormetic response to attenuate the adverse effects of oxidative stress. Herein, we briefly describe the importance of C. elegans as an experimental model system for studying metabolic disorders related to oxidative stress and the molecular mechanisms that underlie their pathophysiology. PMID:24955209

  14. Caenorhabditis elegans: A Useful Model for Studying Metabolic Disorders in Which Oxidative Stress Is a Contributing Factor

    Directory of Open Access Journals (Sweden)

    Elizabeth Moreno-Arriola

    2014-01-01

    Full Text Available Caenorhabditis elegans is a powerful model organism that is invaluable for experimental research because it can be used to recapitulate most human diseases at either the metabolic or genomic level in vivo. This organism contains many key components related to metabolic and oxidative stress networks that could conceivably allow us to increase and integrate information to understand the causes and mechanisms of complex diseases. Oxidative stress is an etiological factor that influences numerous human diseases, including diabetes. C. elegans displays remarkably similar molecular bases and cellular pathways to those of mammals. Defects in the insulin/insulin-like growth factor-1 signaling pathway or increased ROS levels induce the conserved phase II detoxification response via the SKN-1 pathway to fight against oxidative stress. However, it is noteworthy that, aside from the detrimental effects of ROS, they have been proposed as second messengers that trigger the mitohormetic response to attenuate the adverse effects of oxidative stress. Herein, we briefly describe the importance of C. elegans as an experimental model system for studying metabolic disorders related to oxidative stress and the molecular mechanisms that underlie their pathophysiology.

  15. Contributions Of Adipocyte Lipid Metabolism To Body Fat Content And Implications For The Treatment Of Obesity

    OpenAIRE

    Marcelin, Genevieve; Chua, Streamson

    2010-01-01

    Obesity is a chronic disease that increases susceptibility to various diseases, particularly cardiovascular dysfunction, type 2 diabetes and some types of cancer. In this review, we highlighted recent evidence in mouse models that support a potential benefit of increasing adipose lipid utilization through stimulating lipolysis in adipose tissue and fatty acid oxidation. Brown adipocyte development within white adipose tissue of humans suggests that mouse models may be applicable to human obes...

  16. Weight loss on stimulant medication: how does it affect body composition and bone metabolism? – A prospective longitudinal study

    Directory of Open Access Journals (Sweden)

    Poulton Alison

    2012-12-01

    Full Text Available Abstract Objective Children treated with stimulant medication for attention deficit hyperactivity disorder (ADHD often lose weight. It is important to understand the implications of this during growth. This prospective study was designed to quantify the changes in body composition and markers of bone metabolism on starting treatment. Methods 34 children (29 boys aged 4.7 to 9.1 years newly diagnosed with ADHD were treated with dexamphetamine or methylphenidate, titrating the dose to optimise the therapeutic response. Medication was continued for as long as clinically indicated. Body composition and bone density (dual-energy X-ray absorptiometry were measured at baseline, 6 months and 3 years; changes were analysed in Z-scores based on data from 241 healthy, local children. Markers of bone turnover were measured at baseline, 3 months and 3 years. Results Fat loss of 1.4±0.96kg (total fat 5.7±3.6 to 4.3±3.1kg, p Conclusions Stimulant medication was associated with early fat loss and reduced bone turnover. Lean tissue including bone increased more slowly over 3 years of continuous treatment than would be expected for growth in height. There was long-term improvement in the proportion of central fat for height. This study shows that relatively minor reductions in weight on stimulant medication can be associated with long-term changes in body composition. Further study is required to determine the effects of these changes on adult health.

  17. Coordinated FA-MS and SIFT-MS analyses of breath following ingestion of D2O and ethanol: total body water, dispersal kinetics and ethanol metabolism.

    Science.gov (United States)

    Spanel, Patrik; Wang, Tianshu; Smith, David

    2005-08-01

    A coordinated study of the dispersal of water between the various body compartments (stomach and gut, blood stream and tissue) and the similar dispersal kinetics of ethanol and its metabolism has been carried out involving two healthy volunteers using flowing afterglow mass spectrometry, FA-MS, and selected ion flow tube mass spectrometry, SIFT-MS. Thus, using these techniques, the variations of HDO and ethanol in breath, measured in successive single exhalations, were followed in real time after the ingestion of measured quantities of D2O and ethanol in proportion to the body weights of the subjects at the dose rates D2O approximately 0.283 g kg-1, ethanol approximately 0.067 g kg-1. During the FA-MS experimental periods (about 2 h), the dispersion of HDO into the body water and finally its equilibration in the total body water is observed from which total body water for each subject was determined. In the SIFT-MS measurements, the dispersion of ethanol into the body water and its loss via metabolism was observed until the physiological (pre-dose) breath level of ethanol for each individual was restored. A simple linear transformation is used to derive the time variations of the blood levels of HDO and ethanol. This has allowed a comparison of the fractions of the ingested ethanol that are metabolized during first-pass metabolism for the two subjects. Thus, in one subject 30% and in the other subject 40% of the ingested alcohol is metabolized in the first 20 min following ingestion. The good time resolution allowed by non-invasive breath analysis ensures that the rates of processes such as ethanol metabolism can be accurately measured. Simultaneous measurements of breath acetaldehyde (largely formed via the ethanol metabolism) and acetone were also performed during the SIFT-MS single breath exhalations.

  18. [Oxygen metabolism in the body during substitution of nitrogen by helium in the air].

    Science.gov (United States)

    Troshikhin, G V; Isaakian, L A; Bekirova, G G

    1975-01-01

    The total gas exchange, body temperature, content of free oxygen in the quadriceps muscle and its changes upon oxygen inhalation of a known dosage (oxygen test) were measured in the Wistar rats during their one-hour exposure to a helium-oxygen atmosphere (21%) at 25 degrees C. In this atmosphere the animals displayed a 1.8 degrees decline in the body temperature, a 20.5% increase in the gas exchange and a 26% decrease of oxygen in the muscular tissue as compared with the respective parameters in the air. After the experiment during the first 20 min exposure to the normal atmosphere oxygen tests were 10-15% lower than before the experiment. These findings give evidence for an increase of oxygen exchange in the muscles of animals exposed to the helium-oxygen atmosphere at a temperature below the comfortable level.

  19. Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats

    Energy Technology Data Exchange (ETDEWEB)

    Lubaczeuski, C.; Balbo, S.L. [Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, PR (Brazil); Ribeiro, R.A. [Universidade Federal do Rio de Janeiro, Macaé, RJ (Brazil); Vettorazzi, J.F.; Santos-Silva, J.C.; Carneiro, E.M. [Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP (Brazil); Bonfleur, M.L. [Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, PR (Brazil)

    2015-02-24

    The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic β-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca{sup 2+} mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and β-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and β-cell area/pancreas section, respectively. Also, the β-cell number per β-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca{sup 2+} mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater β-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats.

  20. Metabolic stability of new anticonvulsants in body fluids and organ homogenates.

    Science.gov (United States)

    Marszałek, Dorota; Goldnik, Anna; Pluciński, Franciszek; Mazurek, Aleksander P; Jakubiak, Anna; Lis, Ewa; Tazbir, Piotr; Koziorowska, Agnieszka

    2012-01-01

    The stability as a function of time of compounds with established anticonvulsant activity: picolinic acid benzylamide (Pic-BZA), picolinic acid 2-fluorobenzylamide (Pic-2-F-BZA), picolinic acid 3-fluorobenzylamide (Pic-3-F-BZA), picolinic acid 4-fluorobenzylamide (Pic-4-F-BZA) and picolinic acid 2-methylbenzylamide (Pic-2-Me-BZA) in body fluids and homogenates of body organs were determined after incubation. It was found that they decompose relatively rapidly in liver and kidney and are stable against enzymes present in body fluids and some organs. These results are consistent with the bond strength expressed as total energy of amide bonds (calculated by quantum chemical methods) in the studied anticonvulsants. The calculated values of the amide bond energy are: 199.4 kcal/mol, 200.2 kcal/mol, 207.5 kcal/mol, 208.4 kcal/mol and 198.2 kcal/mol, respectively. The strength of the amide bonds in the studied anticonvulsants correctly reflects their stability in liver or kidney.

  1. Body mass, cardiovascular risk and metabolic characteristics of young persons presenting for mental healthcare in Sydney, Australia

    Science.gov (United States)

    Scott, Elizabeth M; Hermens, Daniel F; White, Django; Naismith, Sharon L; GeHue, Jeanne; Whitwell, Bradley G; Glozier, Nick; Hickie, Ian B

    2015-01-01

    Objectives To determine the body mass, cardiovascular and metabolic characteristics of young people presenting for mental healthcare. Design Cross-sectional assessments of body mass, cardiovascular and metabolic risk factors. Setting Two primary-care based sites in Sydney, Australia for young people in the early stages of mental disorders. Participants A clinical sample of young people (12–30 years) with mental health problems. Outcome measures Daily smoking rates, body mass index (BMI), blood glucose and lipids, blood pressure (BP) and pulse rate. Results Of 1005 young people who had their BMI determined (62% female; 19.0±3.5 years), three quarters (739/1005) also had BP recordings and one-third (298/1005) had blood sampling. Clinically, 775 were assigned to one of three diagnostic categories (anxious-depression: n=541; mania-fatigue, n=104; developmental-psychotic n=130). The profile of BMI categories approximated that of the comparable segments of the Australian population. Older age, lower levels of social functioning and higher systolic BP were all associated with high BMI. In a subset (n=129), current use of any psychotropic medication was associated (p<0.05) with increased BMI. Almost one-third of cases were current daily smokers (compared to population rate of 11%). Males had a higher proportion of raised glucose and high-density lipoprotein (HDL) compared to females (9.3% and 34.1% vs 2.1% and 5.9%, respectively). Overall, there was no relationship between BMI and fasting glucose but significant relationships with triglycerides and HDL were noted. Furthermore, there were no significant relationships between diagnostic subgroup and metabolic profiles. Conclusions Daily smoking rates are increased among young people presenting for mental healthcare. However, these young people do not demonstrate adverse cardiometabolic profiles. The high levels of smoking, and association of BMI with adverse social circumstances, suggest that risk factors for chronic

  2. Influence of glutathione-S-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism.

    Science.gov (United States)

    Fletcher, Marianne E; Boshier, Piers R; Wakabayashi, Kenji; Keun, Hector C; Smolenski, Ryszard T; Kirkham, Paul A; Adcock, Ian M; Barton, Paul J; Takata, Masao; Marczin, Nandor

    2015-06-15

    Oxidant-mediated tissue injury is key to the pathogenesis of acute lung injury. Glutathione-S-transferases (GSTs) are important detoxifying enzymes that catalyze the conjugation of glutathione with toxic oxidant compounds and are associated with acute and chronic inflammatory lung diseases. We hypothesized that attenuation of cellular GST enzymes would augment intracellular oxidative and metabolic stress and induce lung cell injury. Treatment of murine lung epithelial cells with GST inhibitors, ethacrynic acid (EA), and caffeic acid compromised lung epithelial cell viability in a concentration-dependent manner. These inhibitors also potentiated cell injury induced by hydrogen peroxide (H2O2), tert-butyl-hydroperoxide, and hypoxia and reoxygenation (HR). SiRNA-mediated attenuation of GST-π but not GST-μ expression reduced cell viability and significantly enhanced stress (H2O2/HR)-induced injury. GST inhibitors also induced intracellular oxidative stress (measured by dihydrorhodamine 123 and dichlorofluorescein fluorescence), caused alterations in overall intracellular redox status (as evidenced by NAD(+)/NADH ratios), and increased protein carbonyl formation. Furthermore, the antioxidant N-acetylcysteine completely prevented EA-induced oxidative stress and cytotoxicity. Whereas EA had no effect on mitochondrial energetics, it significantly altered cellular metabolic profile. To explore the physiological impact of these cellular events, we used an ex vivo mouse-isolated perfused lung model. Supplementation of perfusate with EA markedly affected lung mechanics and significantly increased lung permeability. The results of our combined genetic, pharmacological, and metabolic studies on multiple platforms suggest the importance of GST enzymes, specifically GST-π, in the cellular and whole lung response to acute oxidative and metabolic stress. These may have important clinical implications.

  3. Assessment of right ventricular oxidative metabolism by PET in patients with idiopathic dilated cardiomyopathy undergoing cardiac resynchronisation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Knuuti, Juhani; Naum, Alexandru; Stolen, Kira Q.; Kalliokoski, Riikka [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); Sundell, Jan [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); University of Turku, Department of Medicine, Turku (Finland); Engblom, Erik; Koistinen, Juhani; Airaksinen, K.E. Juhani [University of Turku, Department of Medicine, Turku (Finland); Ylitalo, Antti [Satakunta Central Hospital, Department of Medicine, Pori (Finland); Nekolla, Stephan G. [Klinikum rechts der Isar der Technischen Universitaet Muenchen, Klinik und Poliklinik fuer Nuklearmedizin, Munich (Germany); Bax, K.E. Jeroen J. [Leiden University, Department of Cardiology, Leiden (Netherlands)

    2004-12-01

    Right ventricular (RV) performance is known to have prognostic value in patients with congestive heart failure (CHF). Cardiac resynchronisation therapy (CRT) has been found to enhance left ventricular (LV) energetics and metabolic reserve in patients with heart failure. The interplay between the LV and RV may play an important role in CRT response. The purpose of the study was to investigate RV oxidative metabolism, metabolic reserve and the effects of CRT in patients with CHF and left bundle brach block. In addition, the role of the RV in the response to CRT was evaluated. Ten patients with idiopathic dilated cardiomyopathy who had undergone implantation of a biventricular pacemaker 8{+-}5 months earlier were studied under two conditions: CRT ON and after CRT had been switched OFF for 24 h. Oxidative metabolism was measured using [{sup 11}C]acetate positron emission tomography (K{sub mono}). The measurements were performed at rest and during dobutamine-induced stress (5 {mu}g/kg per minute). LV performance and interventricular mechanical delay (interventricular asynchrony) were measured using echocardiography. CRT had no effect on RV K{sub mono} at rest (ON: 0.052{+-}0.014, OFF: 0.047{+-}0.018, NS). Dobutamine-induced stress increased RV K{sub mono} significantly under both conditions but oxidative metabolism was more enhanced when CRT was ON (0.076{+-}0.026 vs 0.065{+-}0.027, p=0.003). CRT shortened interventricular delay significantly (45{+-}33 vs 19{+-}35 ms, p=0.05). In five patients the response to CRT was striking (32% increase in mean LV stroke volume, range 18-36%), while in the other five patients no response was observed (mean change +2%, range -6% to +4%). RV K{sub mono} and LV stroke volume response to CRT correlated inversely (r=-0.66, p=0.034). None of the other measured parameters, including all LV parameters and electromechanical parameters, were associated with the response to CRT. In responders, RV K{sub mono} with CRT OFF was significantly lower

  4. Dietary Caffeine and Polyphenol Supplementation Enhances Overall Metabolic Rate and Lipid Oxidation at Rest and After a Bout of Sprint Interval Exercise.

    Science.gov (United States)

    Jo, Edward; Lewis, Kiana L; Higuera, Daniel; Hernandez, Joshua; Osmond, Adam D; Directo, Dean J; Wong, Michael

    2016-07-01

    Jo, E, Lewis, KL, Higuera, D, Hernandez, J, Osmond, AD, Directo, DJ, and Wong, M. Dietary caffeine and polyphenol supplementation enhances overall metabolic rate and lipid oxidation at rest and after a bout of sprint interval exercise. J Strength Cond Res 30(7): 1871-1879, 2016-The purpose of this study was to investigate the effects of a caffeine-polyphenolic supplement on (a) metabolic rate and fat oxidation at rest and after a bout of sprint interval exercise (SIE) and (b) SIE performance. In a double-blind, randomized, placebo-controlled, crossover study and after an initial familiarization visit, 12 subjects (male: n = 11; female: n = 1) (body mass = 76.1 ± 2.2 kg; height = 169.8 ± 1.6 cm; body mass index = 22.7 ± 3.0 kg·m; body fat % = 21.6 ± 2.0%) underwent 2 testing sessions during which time they consumed either a caffeine-polyphenol supplement or placebo. After supplementation, resting energy expenditure, heart rate (HR), and blood pressure (BP) were assessed. Subsequently, subjects performed 30 minutes of SIE while researchers collected performance data. Subjects were then tested for post-SIE energy expenditure, HR, and BP. The caffeine-polyphenol treatment resulted in significantly (p ≤ 0.05) greater energy expenditure (+7.99% rest; +10.16% post-SIE), V[Combining Dot Above]O2 (+9.64% rest; +12.10% post-SIE), and fat oxidation rate (+10.60% rest; +9.76% post-SIE) vs. placebo at rest and post-SIE. No significant differences were detected for peak and average power at all sprint intervals between treatments. Post-SIE HR was significantly (p ≤ 0.05) greater with caffeine-polyphenol supplementation vs. placebo (90.8 ± 3.5 vs. 85.1 ± 3.6 b·min). There were no significant between-treatment differences for BP. It may be concluded that the observed thermogenic response after SIE was directly attributable to caffeine-polyphenol supplementation as opposed to an indirect manifestation of enhanced performance and work output. Collectively, these results

  5. Nitric oxide alleviated arsenic toxicity by modulation of antioxidants and thiol metabolism in rice (Oryza sativa L..

    Directory of Open Access Journals (Sweden)

    Amit Pal Singh

    2016-01-01

    Full Text Available Nitric oxide is a gaseous signalling molecule and has a profound impact on plant growth and development. It is reported to serve as pro oxidant as well as antioxidant in plant system. In present study, we evaluated the protective role of nitric oxide against AsV toxicity in rice plants. Arsenate exposure has hampered the plant growth, reduced the chlorophyll content and enhanced the oxidative stress while the exogenous NO supplementation has reverted these symptoms. Nitric oxide supplementation has reduced the As accumulation in root as well as shoot. Nitric oxide supplementation to AsV exposed plants has reduced the gene expression level of OsLsi1 and OsLsi2. Arsenate stress significantly impacted thiol metabolism, it reduced GSH content and GSH/GSSG ratio and enhanced the level of PCs. Nitric oxide supplementation maintained the GSH/GSSG ratio and reduced the level of PCs. Nitric oxide supplementation reverted AsV induced iron deficiency in shoot and had significant impact of gene expression level of various iron transporters (OsYSL2, OsFRDL1, OsIRT1 and OsIRO2. Conclusively, exogenous application of nitric oxide could be advantageous against AsV toxicity and could confer the tolerance to AsV stress in rice.

  6. Effect of Ambient Temperature on Body Temperature and Rest Metabolic Rate in Apodemus chevrieri During Postnatal Development

    Directory of Open Access Journals (Sweden)

    Zhu Wan-long

    2014-05-01

    Full Text Available In order to investigate the ability of constant temperature and thermoregulation in Apodemus chevrieri, body temperature and rest metabolic rate (RMR were measured during postnatal development (1~42 day when the A. chevrieri exposed different ambient temperature. The result showed that: body temperature and RMR of pups in A. chevrieri increased according to the increase of ambient temperature during 1 day to 7 day, showed character of poikilotherms; body temperature of pups were lower in low temperature(5oC and 10oC, relatively and RMR significant increased when day age is 14 day, it indicated that the pups showed a certain degree of thermoregulation in this phase. Its thermoregulation ability developed quickly during 7 day to 14 day. RMR of pups was extreme significantly higher in low temperature than that in other temperature when day age was 21 day, it showed that the pups had some thermoregulation to low temperature stimulation. The RMR of pups was showed increasing trend in high temperature(35oC when 28 day; when day age was 35 day and 42 day, the thermal neutral zone were 22.5 to 30oC and approaching its adult level. All of these results indicated that pups of A. chevrieri in the different growing period had different thermogenesis and energy allocation to maintain stable to body temperature, thermogenesis was weaker in the early phase of postnatal development, most of energy is used to its growth. After pups were weaned, the ability of constant temperature and thermoregulation developed quickly to adjust variations of environment during postnatal development.

  7. Several statins increase body and liver fat accumulation in a model of metabolic syndrome.

    Science.gov (United States)

    Aguirre, L; Hijona, E; Macarulla, M T; Gracia, A; Larrechi, I; Bujanda, L; Hijona, L; Portillo, M P

    2013-06-01

    Statins are a family of drugs used in hypercholesterolemia. The aim of this study was to analyze the effect of statins on body and liver fat accumulation in obese Zucker rats. Seventy Zucker (fa/fa) rats were divided into seven groups. Rats from six statin groups were treated with pravastatin, simvastatin, atorvastatin, rosuvastatin, fluvastatin and lovastatin respectively, at a dose of 0.6 mg/kg body weight/day. After 6 weeks, liver and white adipose tissue from intra-abdominal and subcutaneous locations were dissected and weighed. Subcutaneous adipose tissue from rosuvastatin, atorvastatin, fluvastatin and lovastatin treated rats was significantly increased. Fatty acid synthase (FAS) activity was increased by the administration of fluvastatin and lovastatin, as was glucose-6-P dehydrogenase (G6PDH) by the administration of atorvastatin and lovastatin. No changes were observed in malic enzyme (ME) activity. Furthermore, heparin-releasable lipoprotein lipase (HR-LPL) was increased in all groups where the subcutaneous depot was increased, and total LPL increased only in rosuvastatin and fluvastatin-treated groups. With regard to liver, there were no changes in weight but the amount of triacylglycerols was increased in rosuvastatin group, as well as its liver damage was higher. In this group FAS and G6PDH activities were increased and no changes were observed in ME, acyl CoA oxidase (ACO) and carnitine palmitoyltransferase-1a (CPT-1a) activities. All statins, with the exception of simvastatin, worsen insulin resistance. These results show that statins have different effects on body fat accumulation. Moreover, rosuvastatin also shows a prosteatotic effect. These results should be taken into account for statin choice in prescription.

  8. Fe biomineralization mirrors individual metabolic activity in a nitrate-dependent Fe(II-oxidizer

    Directory of Open Access Journals (Sweden)

    Jennyfer eMIOT

    2015-09-01

    Full Text Available Microbial biomineralization sometimes leads to periplasmic encrustation, which is predicted to enhance microorganism preservation in the fossil record. Mineral precipitation within the periplasm is however thought to induce death, as a result of permeability loss preventing nutrient and waste transit across the cell wall. This hypothesis had however never been investigated down to the single cell level. Here, we cultured the nitrate reducing Fe(II oxidizing bacteria Acidovorax sp. strain BoFeN1 that have been previously shown to promote the precipitation of a diversity of Fe minerals (lepidocrocite, goethite, Fe phosphate encrusting the periplasm. We investigated the connection of Fe biomineralization with carbon assimilation at the single cell level, using a combination of electron microscopy and Nano-Secondary Ion Mass Spectrometry (NanoSIMS. Our analyses revealed strong individual heterogeneities of Fe biomineralization. Noteworthy, a small proportion of cells remaining free of any precipitate persisted even at advanced stages of biomineralization. Using pulse chase experiments with 13C-acetate, we provide evidences of individual phenotypic heterogeneities of carbon assimilation, correlated with the level of Fe biomineralization. Whereas non- and moderately encrusted cells were able to assimilate acetate, higher levels of periplasm encrustation prevented any carbon incorporation. Carbon assimilation only depended on the level of Fe encrustation and not on the nature of Fe minerals precipitated in the cell wall. Carbon assimilation decreased exponentially with increasing cell-associated Fe content. Persistence of a small proportion of non-mineralized and metabolically active cells might constitute a strategy of survival in highly ferruginous environments. Eventually, our results suggest that periplasmic Fe biomineralization may provide a signature of individual metabolic status, which could be looked for in the fossil record and in modern

  9. Correlation of serum homocysteine metabolism and oxidative stress level with peripheral nerve damage in patients with Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Wei-Xia Gu; Zhi-Qing Zhuang; Mo-Lan Wang; Jun Zhu

    2016-01-01

    Objective:To analyze the correlation of serum homocysteine metabolism and oxidative stress level with peripheral nerve damage in patients with Parkinson's disease.Methods:A total of 58 patients with Parkinson's disease and 67 normal human beings were included in the study, levels of plasma homocysteine (Hcy) as well as superoxide dismutase (SOD), GSH, malondialdehyde (MDA) and other oxidative stress indexes were detected, and common peroneal nerve motor conduction velocity (MCV), latent period (LP) and amplitude (Amp) were determined.Results: Serum Hcy level of observation group was higher than that of control group while folic acid and vitamin B6 levels were lower than those of control group; serum oxidative indexes LHP, H2O2, AOPP and MDA levels were higher than those of control group while antioxidant indexes SOD T, SOD Mn, SOD Cu-Zn, GSH-PX, T-AOC and CAT levels were lower than those of control group; common peroneal nerve MCV and Amp values were lower than those of control group while LP value was higher than that of control group. Peripheral nerve damage parameter values in patients with Parkinson's disease were directly correlated with serum levels of Hcy metabolism indexes and oxidative stress indexes. Conclusions: Peripheral nerve damage in patients with Parkinson's disease is associated with hyperhomocysteinemia and oxidative stress disorder, and intervention in serum levels of Hcy and oxidative stress indexes is expected to become a new way for treatment of Parkinson's disease.

  10. Genetic regulation of life span, metabolism, and body weight in Pohn, a new wild-derived mouse strain.

    Science.gov (United States)

    Yuan, Rong; Flurkey, Kevin; Meng, Qingying; Astle, Mike C; Harrison, David E

    2013-01-01

    Quantitative trait loci (QTL) of longevity identified in human and mouse are significantly colocalized, suggesting that common mechanisms are involved. However, the limited number of strains that have been used in mouse longevity studies undermines the ability to identify longevity genes. We crossed C57BL/6J mice with a new wild-derived strain, Pohn, and identified two life span QTL-Ls1 and Ls2. Interestingly, homologous human longevity QTL colocalize with Ls1. We also defined new QTL for metabolic heat production and body weight. Both phenotypes are significantly correlated with life span. We found that large clone ratio, an in vitro indicator for cellular senescence, is not correlated with life span, suggesting that cell senescence and intrinsic aging are not always associated. Overall, by using Pohn mice, we identified new QTL for longevity-related traits, thus facilitating the exploration of the genetic regulation of aging.

  11. Understanding the determinants of selectivity in drug metabolism through modeling of dextromethorphan oxidation by cytochrome P450

    Science.gov (United States)

    Oláh, Julianna; Mulholland, Adrian J.; Harvey, Jeremy N.

    2011-01-01

    Cytochrome P450 enzymes play key roles in the metabolism of the majority of drugs. Improved models for prediction of likely metabolites will contribute to drug development. In this work, two possible metabolic routes (aromatic carbon oxidation and O-demethylation) of dextromethorphan are compared using molecular dynamics (MD) simulations and density functional theory (DFT). The DFT results on a small active site model suggest that both reactions might occur competitively. Docking and MD studies of dextromethorphan in the active site of P450 2D6 show that the dextromethorphan is located close to heme oxygen in a geometry apparently consistent with competitive metabolism. In contrast, calculations of the reaction path in a large protein model [using a hybrid quantum mechanical–molecular mechanics (QM/MM) method] show a very strong preference for O-demethylation, in accordance with experimental results. The aromatic carbon oxidation reaction is predicted to have a high activation energy, due to the active site preventing formation of a favorable transition-state structure. Hence, the QM/MM calculations demonstrate a crucial role of many active site residues in determining reactivity of dextromethorphan in P450 2D6. Beyond substrate binding orientation and reactivity of Compound I, successful metabolite predictions must take into account the detailed mechanism of oxidation in the protein. These results demonstrate the potential of QM/MM methods to investigate specificity in drug metabolism. PMID:21444768

  12. Effect of Breathwalk on body composition, metabolic and mood state in chronic hepatitis C patients with insulin resistance syndrome

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To identify the anthropometric, metabolic and mood state in hepatitis C virus (HCV)-infected patients from the west of Mexico and to evaluate the effect of Breathwalk (BW), a combination of walking, synchronized breathing and focussed attention, on those patients.METHODS: In an experimental study, 17 patients with serological and molecular diagnosis of HCV, not receiving pharmacological treatment, were studied. One hour sessions of BW were practiced 3 times at week for six months. Body composition was assessed by electric impedance. Biochemical profiles and insulin resistance (IR) risk was assessed by conventional methods. Mood state was evaluated with specific and open questions at the beginning and at the end of the program.RESULTS: Seventy percent of patients were overweight or obese, and 77% of the patients presented with IR at the beginning of the study. Improvements were observed at the 3rd mo, and statistically significant differences were recorded at the 6th mo using the fitness score (76 vs 83, P < 0.01), in alanine aminotransferase (ALT)(106 ± 93 U/L vs 59 ± 32 U/L, P < 0.01), total bilirubin (0.09 ± 1 mg/dL vs 0.62 ± 0.2 mg/dL, P < 0.01), ALT/AST ratio (1.04 vs 0.70, P < 0.01), triglycerides (165 ±86 mg/dL vs 124±49 mg/dL, P < 0.01) and the IR risk (4.0 vs 2.7). Most patients (88%) indicated to feel better at the end of BW (P < 0.01).CONCLUSION: Breathwalk has an important effect on body composition, lipid profile and liver enzymes. It is also easy, inexpensive and has a beneficial effect on metabolic and mood state in HCV patients.

  13. Prevalence of cachexia in chronic heart failure and characteristics of body composition and metabolic status

    DEFF Research Database (Denmark)

    Christensen, Heidi Marie; Kistorp, Caroline Michaela Nervil; Schou, Morten;

    2012-01-01

    The prevalence of cardiac cachexia has previously been estimated to 8-42 %. However, novel treatment strategies for chronic heart failure (CHF) have improved and decreased morbidity and mortality. Therefore, we aimed to reassess the prevalence of cachexia in an outpatient CHF clinic...... and to characterize a CHF population with and without cachexia with respect to body composition and related biomarkers. From 2008 to 2011, we screened 238 optimally treated, non-diabetic CHF patients for cardiac cachexia, defined as unintentional non-oedematous weight loss of >5 % over ≥6 months. CHF patients (LVEF...... 45 % (n = 19). The groups were matched for age, sex, and kidney function. Body composition was assessed by dual energy X-ray absorptiometry. The prevalence of cachexia was 10.5 %. Abdominal fat ± SD (%) was reduced in cachectic CHF: 27.4 ± 10.0 versus 37.5 ± 10.6 % (CHF, no cachexia) and 40...

  14. Acute effects of growth hormone on metabolism of pancreatic hormones, glucose and ketone bodies.

    Science.gov (United States)

    Okuda, Y; Peña, J; Chou, J; Field, J B

    2001-07-01

    Controversy exists as to whether acute administration of growth hormone has insulin-like effects. In conscious dogs, acute effects on plasma flows, plasma glucose, hepatic glucose output, free fatty acids, ketone bodies, insulin, and glucagon were determined following intravenous injection of 1 mg of growth hormone extracted from the canine pituitary gland. The following results were obtained: (1) Plasma flows in the portal vein, hepatic artery and hepatic vein were significantly increased 20 min after growth hormone administration. (2) By 40 min after growth hormone, the glucose concentration in these three vessels was significantly increased. (3) Hepatic glucose output was significantly increased 60 min after growth hormone administration. (4) Free fatty acids levels were significantly but transiently increased at 20 min, while ketone body concentrations were elevated at 120-180 min. (5) The insulin levels in the three vessels demonstrated a biphasic response. In the portal vein, they were significantly higher 20 min after growth hormone and again at 150-180 min. Glucagon concentrations were increased in all three vessels by 20 min and remained elevated for the remainder of the experiment. These results do not support an acute insulin-like action of growth hormone in normal dogs.

  15. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity.

    Science.gov (United States)

    Cantó, Carles; Houtkooper, Riekelt H; Pirinen, Eija; Youn, Dou Y; Oosterveer, Maaike H; Cen, Yana; Fernandez-Marcos, Pablo J; Yamamoto, Hiroyasu; Andreux, Pénélope A; Cettour-Rose, Philippe; Gademann, Karl; Rinsch, Chris; Schoonjans, Kristina; Sauve, Anthony A; Auwerx, Johan

    2012-06-06

    As NAD(+) is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38-both NAD(+) consumers-increases NAD(+) bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD(+) precursor with the ability to increase NAD(+) levels, Sir2-dependent gene silencing, and replicative life span in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD(+) levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high-fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin NR could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function.

  16. Rice protein improves adiposity, body weight and reduces lipids level in rats through modification of triglyceride metabolism

    Directory of Open Access Journals (Sweden)

    Yang Lin

    2012-02-01

    Full Text Available Abstract Background To elucidate whether rice protein can possess a vital function in improving lipids level and adiposity, the effects of rice proteins extracted by alkaline (RP-A and α-amylase (RP-E on triglyceride metabolism were investigated in 7-week-old male Wistar rats fed cholesterol-enriched diets for 2 weeks, as compared with casein (CAS. Results Compared with CAS, plasma concentrations of glucose and lipids were significantly reduced by RP-feeding (P P P P P > 0.05. There was a significant positive correlation between protein digestibility and deposit fat (r = 0.8567, P P Conclusions The present study demonstrates that rice protein can modify triglyceride metabolism, leading to an improvement of body weight and adiposity. Results suggest that the triglyceride-lowering action as well as the potential of anti-adiposity induced by rice protein is attributed to upregulation of lipolysis and downregulation of lipogenesis, and the lower digestibility of rice protein may be the main modulator responsible for the lipid-lowering action.

  17. MicroRNA-Mediated Regulation of Dp53 in the Drosophila Fat Body Contributes to Metabolic Adaptation to Nutrient Deprivation

    Directory of Open Access Journals (Sweden)

    Lara Barrio

    2014-07-01

    Full Text Available Multiple conserved mechanisms sense nutritional conditions and coordinate metabolic changes in the whole organism. We unravel a role for the Drosophila homolog of p53 (Dp53 in the fat body (FB; a functional analog of vertebrate adipose and hepatic tissues in starvation adaptation. Under nutrient deprivation, FB-specific depletion of Dp53 accelerates consumption of major energy stores and reduces survival rates of adult flies. We show that Dp53 is regulated by the microRNA (miRNA machinery and miR-305 in a nutrition-dependent manner. In well-fed animals, TOR signaling contributes to miR-305-mediated inhibition of Dp53. Nutrient deprivation reduces the levels of miRNA machinery components and leads to Dp53 derepression. Our results uncover an organism-wide role for Dp53 in nutrient sensing and metabolic adaptation and open up avenues toward understanding the molecular mechanisms underlying p53 activation under nutrient deprivation.

  18. Fetal Programming of Body Composition, Obesity, and Metabolic Function: The Role of Intrauterine Stress and Stress Biology

    Directory of Open Access Journals (Sweden)

    Sonja Entringer

    2012-01-01

    Full Text Available Epidemiological, clinical, physiological, cellular, and molecular evidence suggests that the origins of obesity and metabolic dysfunction can be traced back to intrauterine life and supports an important role for maternal nutrition prior to and during gestation in fetal programming. The elucidation of underlying mechanisms is an area of interest and intense investigation. In this perspectives paper we propose that in addition to maternal nutrition-related processes it may be important to concurrently consider the potential role of intrauterine stress and stress biology. We frame our arguments in the larger context of an evolutionary-developmental perspective that supports roles for both nutrition and stress as key environmental conditions driving natural selection and developmental plasticity. We suggest that intrauterine stress exposure may interact with the nutritional milieu, and that stress biology may represent an underlying mechanism mediating the effects of diverse intrauterine perturbations, including but not limited to maternal nutritional insults (undernutrition and overnutrition, on brain and peripheral targets of programming of body composition, energy balance homeostasis, and metabolic function. We discuss putative maternal-placental-fetal endocrine and immune/inflammatory candidate mechanisms that may underlie the long-term effects of intrauterine stress. We conclude with a commentary of the implications for future research and clinical practice.

  19. Compilation of basal metabolic and blood perfusion rates in various multi-compartment, whole-body thermoregulation models

    Science.gov (United States)

    Shitzer, Avraham; Arens, Edward; Zhang, Hui

    2016-07-01

    The assignments of basal metabolic rates (BMR), basal cardiac output (BCO), and basal blood perfusion rates (BBPR) were compared in nine multi-compartment, whole-body thermoregulation models. The data are presented at three levels of detail: total body, specific body regions, and regional body tissue layers. Differences in the assignment of these quantities among the compared models increased with the level of detail, in the above order. The ranges of variability in the total body BMR was 6.5 % relative to the lowest value, with a mean of 84.3 ± 2 W, and in the BCO, it was 8 % with a mean of 4.70 ± 0.13 l/min. The least variability among the body regions is seen in the combined torso (shoulders, thorax, and abdomen: ±7.8 % BMR and ±5.9 % BBPR) and in the combined head (head, face, and neck ±9.9 % BMR and ±10.9 % BBPR), determined by the ratio of the standard deviation to the mean. Much more variability is apparent in the extremities with the most showing in the BMR of the feet (±117 %), followed by the BBPR in the arms (±61.3 %). In the tissue layers, most of the bone layers were assigned zero BMR and BBPR, except in the shoulders and in the extremities that were assigned non-zero values in a number of models. The next lowest values were assigned to the fat layers, with occasional zero values. Skin basal values were invariably non-zero but involved very low values in certain models, e.g., BBPR in the feet and the hands. Muscle layers were invariably assigned high values with the highest found in the thorax, abdomen, and legs. The brain, lung, and viscera layers were assigned the highest of all values of both basal quantities with those of the brain layers showing rather tight ranges of variability in both basal quantities. Average basal values of the "time-seasoned" models presented in this study could be useful as a first step in future modeling efforts subject to appropriate adjustment of values to conform to most recently available and reliable data.

  20. Effects of supplemental fish oil on resting metabolic rate, body composition, and salivary cortisol in healthy adults

    Directory of Open Access Journals (Sweden)

    Pabon Vanessa A

    2010-10-01

    Full Text Available Abstract Background To determine the effects of supplemental fish oil (FO on resting metabolic rate (RMR, body composition, and cortisol production in healthy adults. Methods A total of 44 men and women (34 ± 13y, mean+SD participated in the study. All testing was performed first thing in the morning following an overnight fast. Baseline measurements of RMR were measured using indirect calorimetry using a facemask, and body composition was measured using air displacement plethysmography. Saliva was collected via passive drool and analyzed for cortisol concentration using ELISA. Following baseline testing, subjects were randomly assigned in a double blind manner to one of two groups: 4 g/d of Safflower Oil (SO; or 4 g/d of FO supplying 1,600 mg/d eicosapentaenoic acid (EPA and 800 mg/d docosahexaenoic acid (DHA. All tests were repeated following 6 wk of treatment. Pre to post differences were analyzed using a treatment X time repeated measures ANOVA, and correlations were analyzed using Pearson's r. Results Compared to the SO group, there was a significant increase in fat free mass following treatment with FO (FO = +0.5 ± 0.5 kg, SO = -0.1 ± 1.2 kg, p = 0.03, a significant reduction in fat mass (FO = -0.5 ± 1.3 kg, SO = +0.2 ± 1.2 kg, p = 0.04, and a tendency for a decrease in body fat percentage (FO = -0.4 ± 1.3% body fat, SO = +0. 3 ± 1.5% body fat, p = 0.08. No significant differences were observed for body mass (FO = 0.0 ± 0.9 kg, SO = +0.2 ± 0.8 kg, RMR (FO = +17 ± 260 kcal, SO = -62 ± 184 kcal or respiratory exchange ratio (FO = -0.02 ± 0.09, SO = +0.02 ± 0.05. There was a tendency for salivary cortisol to decrease in the FO group (FO = -0.064 ± 0.142 μg/dL, SO = +0.016 ± 0.272 μg/dL, p = 0.11. There was a significant correlation in the FO group between change in cortisol and change in fat free mass (r = -0.504, p = 0.02 and fat mass (r = 0.661, p = 0.001. Conclusion 6 wk of supplementation with FO significantly increased

  1. 24-hour energy expenditure and substrate oxidation rates are unaffected by body fat distribution in obese women.

    Science.gov (United States)

    Buemann, B; Astrup, A; Quaade, F; Madsen, J

    1994-01-01

    Twenty-four-hour energy expenditure (EE) and nonprotein respiratory quotient (RQnp) were measured by indirect calorimetry in 19 upper-body-obese (UBO) and 15 lower-body-obese (LBO) women with similar body mass index (BMI) and body fat percent. The measurements were performed in a respiration chamber on a predetermined physical activity program and a controlled diet. No differences between the UBO and LBO groups were found in 24-hour, daytime, and sleeping EE after adjustment for differences in fat-free mass (FFM). Furthermore, no group effect was observed in RQnp, but a positive correlation was found between RQnp and age. Despite the fact that an increased free fatty acid (FFA) turnover has been found in UBO subjects, the present study does not support the contention that upper-body obesity is accompanied by an increased lipid oxidation.

  2. Metabolic expenditures of lunge feeding rorquals across scale: implications for the evolution of filter feeding and the limits to maximum body size.

    Directory of Open Access Journals (Sweden)

    Jean Potvin

    Full Text Available Bulk-filter feeding is an energetically efficient strategy for resource acquisition and assimilation, and facilitates the maintenance of extreme body size as exemplified by baleen whales (Mysticeti and multiple lineages of bony and cartilaginous fishes. Among mysticetes, rorqual whales (Balaenopteridae exhibit an intermittent ram filter feeding mode, lunge feeding, which requires the abandonment of body-streamlining in favor of a high-drag, mouth-open configuration aimed at engulfing a very large amount of prey-laden water. Particularly while lunge feeding on krill (the most widespread prey preference among rorquals, the effort required during engulfment involve short bouts of high-intensity muscle activity that demand high metabolic output. We used computational modeling together with morphological and kinematic data on humpback (Megaptera noveaangliae, fin (Balaenoptera physalus, blue (Balaenoptera musculus and minke (Balaenoptera acutorostrata whales to estimate engulfment power output in comparison with standard metrics of metabolic rate. The simulations reveal that engulfment metabolism increases across the full body size of the larger rorqual species to nearly 50 times the basal metabolic rate of terrestrial mammals of the same body mass. Moreover, they suggest that the metabolism of the largest body sizes runs with significant oxygen deficits during mouth opening, namely, 20% over maximum VO2 at the size of the largest blue whales, thus requiring significant contributions from anaerobic catabolism during a lunge and significant recovery after a lunge. Our analyses show that engulfment metabolism is also significantly lower for smaller adults, typically one-tenth to one-half VO2|max. These results not only point to a physiological limit on maximum body size in this lineage, but also have major implications for the ontogeny of extant rorquals as well as the evolutionary pathways used by ancestral toothed whales to transition from hunting

  3. Metabolic expenditures of lunge feeding rorquals across scale: implications for the evolution of filter feeding and the limits to maximum body size.

    Science.gov (United States)

    Potvin, Jean; Goldbogen, Jeremy A; Shadwick, Robert E

    2012-01-01

    Bulk-filter feeding is an energetically efficient strategy for resource acquisition and assimilation, and facilitates the maintenance of extreme body size as exemplified by baleen whales (Mysticeti) and multiple lineages of bony and cartilaginous fishes. Among mysticetes, rorqual whales (Balaenopteridae) exhibit an intermittent ram filter feeding mode, lunge feeding, which requires the abandonment of body-streamlining in favor of a high-drag, mouth-open configuration aimed at engulfing a very large amount of prey-laden water. Particularly while lunge feeding on krill (the most widespread prey preference among rorquals), the effort required during engulfment involve short bouts of high-intensity muscle activity that demand high metabolic output. We used computational modeling together with morphological and kinematic data on humpback (Megaptera noveaangliae), fin (Balaenoptera physalus), blue (Balaenoptera musculus) and minke (Balaenoptera acutorostrata) whales to estimate engulfment power output in comparison with standard metrics of metabolic rate. The simulations reveal that engulfment metabolism increases across the full body size of the larger rorqual species to nearly 50 times the basal metabolic rate of terrestrial mammals of the same body mass. Moreover, they suggest that the metabolism of the largest body sizes runs with significant oxygen deficits during mouth opening, namely, 20% over maximum VO2 at the size of the largest blue whales, thus requiring significant contributions from anaerobic catabolism during a lunge and significant recovery after a lunge. Our analyses show that engulfment metabolism is also significantly lower for smaller adults, typically one-tenth to one-half VO2|max. These results not only point to a physiological limit on maximum body size in this lineage, but also have major implications for the ontogeny of extant rorquals as well as the evolutionary pathways used by ancestral toothed whales to transition from hunting individual prey

  4. Sea urchins in a high-CO2 world: partitioned effects of body size, ocean warming and acidification on metabolic rate.

    Science.gov (United States)

    Carey, Nicholas; Harianto, Januar; Byrne, Maria

    2016-04-15

    Body size and temperature are the major factors explaining metabolic rate, and the additional factor of pH is a major driver at the biochemical level. These three factors have frequently been found to interact, complicating the formulation of broad models predicting metabolic rates and hence ecological functioning. In this first study of the effects of warming and ocean acidification, and their potential interaction, on metabolic rate across a broad range in body size (two to three orders of magnitude difference in body mass), we addressed the impact of climate change on the sea urchin ITALIC! Heliocidaris erythrogrammain context with climate projections for southeast Australia, an ocean warming hotspot. Urchins were gradually introduced to two temperatures (18 and 23°C) and two pH levels (7.5 and 8.0), at which they were maintained for 2 months. Identical experimental trials separated by several weeks validated the fact that a new physiological steady state had been reached, otherwise known as acclimation. The relationship between body size, temperature and acidification on the metabolic rate of ITALIC! H. erythrogrammawas strikingly stable. Both stressors caused increases in metabolic rate: 20% for temperature and 19% for pH. Combined effects were additive: a 44% increase in metabolism. Body size had a highly stable relationship with metabolic rate regardless of temperature or pH. None of these diverse drivers of metabolism interacted or modulated the effects of the others, highlighting the partitioned nature of how each influences metabolic rate, and the importance of achieving a full acclimation state. Despite these increases in energetic demand there was very limited capacity for compensatory modulating of feeding rate; food consumption increased only in the very smallest specimens, and only in response to temperature, and not pH. Our data show that warming, acidification and body size all substantially affect metabolism and are highly consistent and

  5. Endothelial nitric oxide synthase uncoupling and perivascular adipose oxidative stress and inflammation contribute to vascular dysfunction in a rodent model of metabolic syndrome.

    Science.gov (United States)

    Marchesi, Chiara; Ebrahimian, Talin; Angulo, Orlando; Paradis, Pierre; Schiffrin, Ernesto L

    2009-12-01

    The metabolic syndrome represents a constellation of cardiovascular risk factors that promote the development of cardiovascular disease. Oxidative stress is a mediator of endothelial dysfunction and vascular remodeling. We investigated vascular dysfunction in the metabolic syndrome and the oxidant mechanisms involved. New Zealand obese (NZO) mice with metabolic syndrome and New Zealand black control mice were studied. NZO mice showed insulin resistance and increased visceral fat and blood pressure compared with New Zealand black mice. Mesenteric resistance arteries from NZO mice exhibited increased media:lumen ratio and media cross-sectional area, demonstrating hypertrophic vascular remodeling. Endothelium-dependent relaxation to acetylcholine, assessed by pressurized myography, was impaired in NZO mice, not affected by N(G)-nitro-l-arginine methyl ester, inhibitor of endothelial NO synthase, and improved by the antioxidant Tempol, suggesting reduced NO bioavailability and increased oxidative stress. Dimer:monomer ratio of endothelial NO synthase was decreased in NZO mice compared with New Zealand black mice, suggesting endothelial NO synthase uncoupling. Furthermore, vascular superoxide and peroxynitrite production was increased, as well as adhesion molecule expression. Perivascular adipose tissue of NZO mice showed increased superoxide production and NADPH oxidase activity, as well as adipocyte hypertrophy, associated with inflammatory Mac-3-positive cell infiltration. Vasoconstriction to norepinephrine decreased in the presence of perivascular adipose tissue in New Zealand black mice but was unaffected by perivascular adipose tissue in NZO mice, suggesting loss of perivascular adipose tissue anticontractile properties. Our data suggest that this rodent model of metabolic syndrome is associated with perivascular adipose inflammation and oxidative stress, hypertrophic resistance artery remodeling, and endothelial dysfunction, the latter a result of decreased NO

  6. Artificial light at night affects body mass but not oxidative status in free-living nestling songbirds: an experimental study

    Science.gov (United States)

    Raap, Thomas; Casasole, Giulia; Costantini, David; Abdelgawad, Hamada; Asard, Han; Pinxten, Rianne; Eens, Marcel

    2016-10-01

    Artificial light at night (ALAN), termed light pollution, is an increasingly important anthropogenic environmental pressure on wildlife. Exposure to unnatural lighting environments may have profound effects on animal physiology, particularly during early life. Here, we experimentally investigated for the first time the impact of ALAN on body mass and oxidative status during development, using nestlings of a free-living songbird, the great tit (Parus major), an important model species. Body mass and blood oxidative status were determined at baseline (=13 days after hatching) and again after a two night exposure to ALAN. Because it is very difficult to generalise the oxidative status from one or two measures we relied on a multi-biomarker approach. We determined multiple metrics of both antioxidant defences and oxidative damage: molecular antioxidants GSH, GSSG; antioxidant enzymes GPX, SOD, CAT; total non-enzymatic antioxidant capacity and damage markers protein carbonyls and TBARS. Light exposed nestlings showed no increase in body mass, in contrast to unexposed individuals. None of the metrics of oxidative status were affected. Nonetheless, our study provides experimental field evidence that ALAN may negatively affect free-living nestlings’ development and hence may have adverse consequences lasting throughout adulthood.

  7. Two-body wear of dental porcelain and substructure oxide ceramics.

    Science.gov (United States)

    Rosentritt, Martin; Preis, Verena; Behr, Michael; Hahnel, Sebastian; Handel, Gerhard; Kolbeck, Carola

    2012-06-01

    The aim of this in vitro study was to investigate the two-body wear of different ceramics. Two-body wear tests were performed in a chewing simulator with steatite and enamel antagonists, respectively. Specimens were loaded in a pin-on-block design with a vertical load of 50 N for 1.2 × 10(5) cycles; (f = 1.6 Hz; lateral movement, 1 mm; mouth opening: 2 mm). Human enamel was used as a reference. Three zirconia ceramics, three veneering porcelains, two glass-infiltrated and one lithium disilicate ceramic were investigated. Veneering and lithium disilicate ceramics were glazed before testing. Surface roughness Ra (SP6, Perthen-Feinprüf, G) and wear depth were determined using a 3D scanner (Laserscan 3D, Willytec, G). SEM (Quanta FEG 400, FEI, USA) pictures of the worn specimens and antagonists were made for evaluating wear performance. Veneering porcelain provided wear traces between 71.2 and 124.1 μm (enamel antagonist) and 117.4 and 274.1 μm (steatite). Wear of the steatite antagonists varied between 0.618 and 2.85 mm². No wear was found for zirconia and glass-infiltrated substructure ceramics. Also, no wear was found for the corresponding antagonists. Wear of specimens and antagonists was strongly material dependent. No visible wear was found on zirconia and glass-infiltrated ceramics. Porcelain and lithium disilicate ceramic showed a comparable or lower wear than the enamel reference. Antagonist wear was found to be lower when specimens were made of substructure oxide ceramics instead of veneering porcelain. From the point of wear testing, zirconia may be used for the fabrication of fixed dental prosthesis without veneering.

  8. Effects of supplements of folic acid, vitamin B12, and rumen-protected methionine on whole body metabolism of methionine and glucose in lactating dairy cows.

    Science.gov (United States)

    Preynat, A; Lapierre, H; Thivierge, M C; Palin, M F; Matte, J J; Desrochers, A; Girard, C L

    2009-02-01

    The present experiment was undertaken to determine the effects of dietary supplements of rumen-protected methionine and intramuscular injections of folic acid and vitamin B(12), given 3 wk before to 16 wk after calving, on glucose and methionine metabolism of lactating dairy cows. Twenty-four multiparous Holstein cows were assigned to 6 blocks of 4 cows each according to their previous milk production. Within each block, 2 cows were fed a diet estimated to supply methionine as 1.83% metabolizable protein, equivalent to 76% of methionine requirement, whereas the 2 other cows were fed the same diet supplemented daily with 18 g of rumen-protected methionine. Within each diet, the cows were administrated either no vitamin supplement or weekly intramuscular injections of 160 mg of folic acid plus 10 mg of vitamin B(12.) To investigate metabolic changes at 12 wk of lactation, glucose and methionine kinetics were measured by isotope dilution using infusions of 3[U-(13)C]glucose, [(13)C]NaHCO(3) and 3[1-(13)C,(2)H(3)] methionine. Milk and plasma concentrations of folic acid and vitamin B(12) increased with vitamin injections. Supplementary B-vitamins increased milk production from 34.7 to 38.9 +/- 1.0 kg/d and increased milk lactose, protein, and total solids yields. Whole-body glucose flux tended to increase with vitamin supplementation with a similar quantitative magnitude as the milk lactose yield increase. Vitamin supplementation increased methionine utilization for protein synthesis through increased protein turnover when methionine was deficient and through decreased methionine oxidation when rumen-protected methionine was fed. Vitamin supplementation decreased plasma concentrations of homocysteine independently of rumen-protected methionine feeding, although no effect of vitamin supplementation was measured on methionine remethylation, but this could be due to the limitation of the technique used. Therefore, the effects of these B-vitamins on lactation performance

  9. TIPE2 negatively regulates inflammation by switching arginine metabolism from nitric oxide synthase to arginase.

    Directory of Open Access Journals (Sweden)

    Yunwei Lou

    Full Text Available TIPE2, the tumor necrosis factor (TNF-alpha-induced protein 8-like 2 (TNFAIP8L2, plays an essential role in maintaining immune homeostasis. It is highly expressed in macrophages and negatively regulates inflammation through inhibiting Toll-like receptor signaling. In this paper, we utilized RAW264.7 cells stably transfected with a TIPE2 expression plasmid, as well as TIPE2-deficient macrophages to study the roles of TIPE2 in LPS-induced nitric oxide (NO and urea production. The results showed that TIPE2-deficiency significantly upregulated the levels of iNOS expression and NO production in LPS-stimulated macrophages, but decreased mRNA levels of arginase I and urea production. However, TIPE2 overexpression in macrophages was capable of downregulating protein levels of LPS-induced iNOS and NO, but generated greater levels of arginase I and urea production. Furthermore, TIPE2-/- mice had higher iNOS protein levels in lung and liver and higher plasma NO concentrations, but lower levels of liver arginase I compared to LPS-treated WT controls. Interestingly, significant increases in IκB degradation and phosphorylation of JNK, p38, and IκB were observed in TIPE2-deficient macrophages following LPS challenge. These results strongly suggest that TIPE2 plays an important role in shifting L-arginase metabolism from production of NO to urea, during host inflammatory response.

  10. Lipid Peroxidation, Nitric Oxide Metabolites, and Their Ratio in a Group of Subjects with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Gregorio Caimi

    2014-01-01

    Full Text Available Our aim was to evaluate lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS, nitric oxide metabolites (nitrite + nitrate expressed as NOx, and TBARS/NOx ratio in a group of subjects with metabolic syndrome (MS. In this regard we enrolled 106 subjects with MS defined according to the IDF criteria, subsequently subdivided into diabetic (DMS and nondiabetic (NDMS and also into subjects with a low triglycerides/HDL-cholesterol (TG/HDL-C index or with a high TG/HDL-C index. In the entire group and in the four subgroups of MS subjects we found an increase in TBARS and NOx levels and a decrease in TBARS/NOx ratio in comparison with normal controls. Regarding all these parameters no statistical difference between DMS and NDMS was evident, but a significant increase in NOx was present in subjects with a high TG/HDL-C index in comparison with those with a low index. In MS subjects we also found a negative correlation between TBARS/NOx ratio and TG/HDL-C index. Considering the hyperactivity of the inducible NO synthase in MS, these data confirm the altered redox and inflammatory status that characterizes the MS and suggest a link between lipid peroxidation, inflammation, and insulin resistance, evaluated as TG/HDL-C index.

  11. Effects of Hormone Therapy on Oxidative Stress in Postmenopausal Women with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Martha A. Sánchez-Rodríguez

    2016-08-01

    Full Text Available The aim of this study was to determine the effect of oral hormone therapy (HT on oxidative stress (OS in postmenopausal women with metabolic syndrome (MetS. A randomized, double blind, placebo-controlled trial was carried out. We formed four groups of 25 women each; healthy (HW and MetS women (MSW were assigned to HT (1 mg/day of estradiol valerate plus 5 mg/10 day of medroxiprogesterone or placebo. We measured plasma lipoperoxides, erythrocyte superoxide dismutase and glutathione peroxidase, total plasma antioxidant status and uric acid, as OS markers. Alternative cut-off values of each parameter were defined and a stress score (SS ranging from 0 to 7 was used as total OS. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII criteria. Participants were seen at baseline, 3 and 6 months. After 6 months, MetS decreased in MSW-HT (48%, their triglycerides and high-density lipoprotein cholesterol (HDL-c improved; in the other groups no difference was found. SS in MSW-HT decreased (3.8 ± 0.3 to 1.7 ± 0.3, p < 0.05 and OS was also reduced (44%, this effect was evident since 3 mo. HW-HT with high OS also decreased (40%. In placebo groups there was no change. Our findings suggest that HT improve lipids and OS associated to MetS in postmenopausal women.

  12. Effects of Hormone Therapy on Oxidative Stress in Postmenopausal Women with Metabolic Syndrome

    Science.gov (United States)

    Sánchez-Rodríguez, Martha A.; Zacarías-Flores, Mariano; Castrejón-Delgado, Lizett; Ruiz-Rodríguez, Ana Karen; Mendoza-Núñez, Víctor Manuel

    2016-01-01

    The aim of this study was to determine the effect of oral hormone therapy (HT) on oxidative stress (OS) in postmenopausal women with metabolic syndrome (MetS). A randomized, double blind, placebo-controlled trial was carried out. We formed four groups of 25 women each; healthy (HW) and MetS women (MSW) were assigned to HT (1 mg/day of estradiol valerate plus 5 mg/10 day of medroxiprogesterone) or placebo. We measured plasma lipoperoxides, erythrocyte superoxide dismutase and glutathione peroxidase, total plasma antioxidant status and uric acid, as OS markers. Alternative cut-off values of each parameter were defined and a stress score (SS) ranging from 0 to 7 was used as total OS. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria. Participants were seen at baseline, 3 and 6 months. After 6 months, MetS decreased in MSW-HT (48%), their triglycerides and high-density lipoprotein cholesterol (HDL-c) improved; in the other groups no difference was found. SS in MSW-HT decreased (3.8 ± 0.3 to 1.7 ± 0.3, p < 0.05) and OS was also reduced (44%), this effect was evident since 3 mo. HW-HT with high OS also decreased (40%). In placebo groups there was no change. Our findings suggest that HT improve lipids and OS associated to MetS in postmenopausal women. PMID:27563883

  13. Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis.

    Science.gov (United States)

    Cassano, Paolo; Petrie, Samuel R; Hamblin, Michael R; Henderson, Theodore A; Iosifescu, Dan V

    2016-07-01

    We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: "near-infrared radiation," "NIR," "low-level light therapy," "low-level laser therapy," or "LLLT" plus "depression." We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD.

  14. Oxidative stress disturbs energy metabolism of mitochondria in ethanol-induced gastric mucosa injury

    Institute of Scientific and Technical Information of China (English)

    Jin-Shui Pan; Shao-Zhen He; Hong-Zhi Xu; Xiao-Juan Zhan; Xiao-Ning Yang; Hong-Min Xiao; Hua-Xiu Shi; Jian-Lin Ren

    2008-01-01

    AIM: To study the role of mitochondrial energy disorder in the pathogenesis of ethanol-induced gastric mucosa injury.METHODS: Wistar rats were used in this study. A gastric mucosal injury model was established by giving the rats alcohol. Gross and microscopic appearance of gastric mucosa and ultrastructure of mitochondria were evaluated. Malondiadehyde (MDA) in gastric mucosa was measured with thiobarbituric acid. Expression of ATP synthase (ATPase) subunits 6 and 8 in mitochondrial DNA (mtDNA) was determined by reverse transcription polymerase chain reaction (RT-PCR).RESULTS: The gastric mucosal lesion index was correlated with the MDA content in gastric mucosa. As the concentration of ethanol was elevated and the exposure time to ethanol was extended, the content of MDA in gastric mucosa increased and the extent of damage aggravated. The ultrastructure of mitochondria was positively related to the ethanol concentration and exposure time. The expression of mtDNA ATPase subunits 6 and 8 mRNA declined with the increasing MDA content in gastric mucosa after gavage with ethanol.CONCLUSION: Ethanol-induced gastric mucosa injury is related to oxidative stress, which disturbs energy metabolism of mitochondria and plays a critical role in the pathogenesis of ethanol-induced gastric mucosa injury.

  15. Oxidative stress disturbs energy metabolism of mitochondria in ethanol-induced gastric mucosa injury

    Science.gov (United States)

    Pan, Jin-Shui; He, Shao-Zhen; Xu, Hong-Zhi; Zhan, Xiao-Juan; Yang, Xiao-Ning; Xiao, Hong-Min; Shi, Hua-Xiu; Ren, Jian-Lin

    2008-01-01

    AIM: To study the role of mitochondrial energy disorder in the pathogenesis of ethanol-induced gastric mucosa injury. METHODS: Wistar rats were used in this study. A gastric mucosal injury model was established by giving the rats alcohol. Gross and microscopic appearance of gastric mucosa and ultrastructure of mitochondria were evaluated. Malondiadehyde (MDA) in gastric mucosa was measured with thiobarbituric acid. Expression of ATP synthase (ATPase) subunits 6 and 8 in mitochondrial DNA (mtDNA) was determined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The gastric mucosal lesion index was correlated with the MDA content in gastric mucosa. As the concentration of ethanol was elevated and the exposure time to ethanol was extended, the content of MDA in gastric mucosa increased and the extent of damage aggravated. The ultrastructure of mitochondria was positively related to the ethanol concentration and exposure time. The expression of mtDNA ATPase subunits 6 and 8 mRNA declined with the increasing MDA content in gastric mucosa after gavage with ethanol. CONCLUSION: Ethanol-induced gastric mucosa injury is related to oxidative stress, which disturbs energy metabolism of mitochondria and plays a critical role in the pathogenesis of ethanol-induced gastric mucosa injury. PMID:18855985

  16. Total body water estimations in healthy men and women using bioimpedance spectroscopy: a deuterium oxide comparison

    Directory of Open Access Journals (Sweden)

    Bemben Michael G

    2008-03-01

    Full Text Available Abstract Background Total body water (TBW estimations have been used to estimate body composition, particularly fat-free mass, to aid in nutritional interventions, and to monitor hydration status. In the past, bioimpedance spectroscopy (BIS devices have been used to estimate TBW. Previous investigations have examined the validity of the XiTRON 4000B (XiTRON Technologies BIS device for estimating TBW. Recently, a new BIS device (Imp™ SFB7 has become available, claiming greater precision when estimating TBW. The Imp™ SFB7 (SFB7 is based on similar BIS principles, while offering increased portability and a greater range of frequencies when compared to older devices, such as the XiTRON 4000B (4000B. The purpose of this study was to examine the validity of the SFB7 for estimating total body water in healthy college-age men and women compared to the 4000B and deuterium oxide (D2O. Methods Twenty-eight Caucasian men and women (14 men, 14 women; 24 ± 4 yrs; 174.6 ± 8.7 cm; 72.80 ± 17.58 kg had their TBW estimated by the SFB7, the 4000B, and D2O. Results Both BIS devices produced similar standard error of estimate (SEE and r values (SFB7, SEE = 2.12L, r = 0.98; 4000B, SEE = 2.99L, r = 0.96 when compared to D2O, though a significant constant error (CE was detected for the 4000B (2.26L, p ≤ 0.025. The 4000B produced a larger total error (TE and CE (TE = 3.81L, CE = 2.26L when compared to the SFB7 (TE = 2.21L, CE = -0.09L. Additionally, the limits of agreement were larger for the 4000B (-3.88 to 8.39L than the SFB7 (-4.50 to 4.31L. These results were consistent when sex was analyzed separately, though women produced lower SEE and TE values for both devices. Conclusion The 4000B and SFB7 are valid BIS devices when compared to D2O to estimate TBW in college-age Caucasian men and women. Furthermore, the new SFB7 device displayed greater precision in comparison to the 4000B, which may decrease the error when estimating TBW on an individual basis.

  17. SH2B1 regulation of energy balance, body weight, and glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    Liangyou; Rui

    2014-01-01

    The Src homology 2B(SH2B)family members(SH2B1,SH2B2 and SH2B3)are adaptor signaling proteins containing characteristic SH2 and PH domains.SH2B1(also called SH2-B and PSM)and SH2B2(also called APS)are able to form homo-or hetero-dimers via their N-terminal dimerization domains.Their C-terminal SH2 domains bind to tyrosyl phosphorylated proteins,including Janus kinase 2(JAK2),TrkA,insulin receptors,insulin-like growth factor-1 receptors,insulin receptor substrate-1(IRS1),and IRS2.SH2B1 enhances leptin signaling by both stimulating JAK2 activity and assembling a JAK2/IRS1/2 signaling complex.SH2B1 promotes insulin signaling by both enhancing insulin receptor catalytic activity and protecting against dephosphorylation of IRS proteins.Accordingly,genetic deletion of SH2B1 results in severe leptin resistance,insulin resistance,hyperphagia,obesity,and type 2 diabetes in mice.Neuronspecific overexpression of SH2B1βtransgenes protects against diet-induced obesity and insulin resistance.SH2B1 in pancreaticβcells promotesβcell expansion and insulin secretion to counteract insulin resistance in obesity.Moreover,numerous SH2B1 mutations are genetically linked to leptin resistance,insulin resistance,obesity,and type 2 diabetes in humans.Unlike SH2B1,SH2B2 and SH2B3 are not required for the maintenance of normal energy and glucose homeostasis.The metabolic function of the SH2B family is conserved from insects to humans.

  18. Metabolic responses of Beauveria bassiana to hydrogen peroxide-induced oxidative stress using an LC-MS-based metabolomics approach.

    Science.gov (United States)

    Zhang, Chen; Wang, Wei; Lu, Ruili; Jin, Song; Chen, Yihui; Fan, Meizhen; Huang, Bo; Li, Zengzhi; Hu, Fenglin

    2016-06-01

    The entomopathogenic fungus, Beauveria bassiana, is commonly used as a biological agent for pest control. Environmental and biological factors expose the fungus to oxidative stress; as a result, B. bassiana has adopted a number of anti-oxidant mechanisms. In this study, we investigated metabolites of B. bassiana that are formed in response to oxidative stress from hydrogen peroxide (H2O2) by using a liquid chromatography mass spectrometry (LC-MS) approach. Partial least-squares discriminant analysis (PLS-DA) revealed differences between the control and the H2O2-treated groups. Hierarchical cluster analysis (HCA) showed 18 up-regulated metabolites and 25 down-regulated metabolites in the H2O2-treated fungus. Pathway analysis indicated that B. bassiana may be able to alleviate oxidative stress by enhancing lipid catabolism and glycometabolism, thus decreasing membrane polarity and preventing polar H2O2 or ROS from permeating into fungal cells and protecting cells against oxidative injury. Meanwhile, most of the unsaturated fatty acids that are derived from glycerophospholipids hydrolysis can convert into oxylipins through autoxidation, which can prevent the reactive oxygen of H2O2 from attacking important macromolecules of the fungus. Results showed also that H2O2 treatment can enhance mycotoxins production which implies that oxidative stress may be able to increase the virulence of the fungus. In comparison to the control group, citric acid and UDP-N-acetylglucosamine were down-regulated, which suggested that metabolic flux was occurring to the TCA cycle and enhancing carbohydrate metabolism. The findings from this study will contribute to the understanding of how the molecular mechanisms of fungus respond to environmental and biological stress factors as well as how the manipulation of such metabolisms may lead to selection of more effective fungal strains for pest control.

  19. Metabolic control of resting hemispheric cerebral blood flow is oxidative, not glycolytic

    OpenAIRE

    Powers, William. J.; Videen, Tom O.; Markham, Joanne; Walter, Vonn; Perlmutter, Joel S.

    2011-01-01

    Although the close regional coupling of resting cerebral blood flow (CBF) with both cerebral metabolic rate of oxygen (CMRO2) and cerebral metabolic rate of glucose (CMRglc) within individuals is well documented, there are few data regarding the coupling between whole brain flow and metabolism among different subjects. To investigate the metabolic control of resting whole brain CBF, we performed multivariate analysis of hemispheric CMRO2, CMRglc, and other covariates as predictors of resting ...

  20. Session III: Mechanisms of age-related cognitive change and targets for intervention: inflammatory, oxidative, and metabolic processes.

    Science.gov (United States)

    Craft, Suzanne; Foster, Thomas C; Landfield, Philip W; Maier, Steven F; Resnick, Susan M; Yaffe, Kristine

    2012-06-01

    There is increasing evidence from basic science and human epidemiological studies that inflammation, oxidative stress, and metabolic abnormalities are associated with age-related cognitive decline and impairment. This article summarizes selected research on these topics presented at the Cognitive Aging Summit II. Speakers in this session presented evidence highlighting the roles of these processes and pathways on age-related cognitive decline, pointing to possible targets for intervention in nondemented older adults. Specific areas discussed included age differences in the production of cytokines following injury or infection, mechanisms underlying oxidative stress-induced changes in memory consolidation, insulin effects on brain signaling and memory, and the association between metabolic syndrome and cognitive decline in older adults. These presentations emphasize advances in our understanding of mechanisms and modifiers of age-related cognitive decline and provide insights into potential targets to promote cognitive health in older adults.

  1. Proteomic analysis of mitochondria reveals a metabolic switch from fatty acid oxidation to glycolysis in the failing heart

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    This work characterizes the mitochondrial proteomic profile in the failing heart and elucidates the molecular basis of mitochondria in heart failure. Heart failure was induced in rats by myocardial infarction, and mitochondria were isolated from hearts by differential centrifugation. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry, a system biology approach was employed to investigate differences in mitochondrial proteins between normal and failing hearts. Mass spectrometry identified 27 proteins differentially expressed that involved in energy metabolism. Among those, the up-regulated proteins included tricarboxylic acid cycle enzymes and pyruvate dehydrogenase complex subunits while the down-regulated proteins were involved in fatty acid oxidation and the OXPHOS complex. These results suggest a substantial metabolic switch from free fatty acid oxidation to glycolysis in heart failure and provide molecular evidence for alterations in the structural and functional parameters of mitochondria that may contribute to cardiac dysfunction during ischemic injury.

  2. Caveolin-1 is necessary for hepatic oxidative lipid metabolism: evidence for crosstalk between caveolin-1 and bile acid signaling.

    Science.gov (United States)

    Fernández-Rojo, Manuel A; Gongora, Milena; Fitzsimmons, Rebecca L; Martel, Nick; Martin, Sheree D; Nixon, Susan J; Brooks, Andrew J; Ikonomopoulou, Maria P; Martin, Sally; Lo, Harriet P; Myers, Stephen A; Restall, Christina; Ferguson, Charles; Pilch, Paul F; McGee, Sean L; Anderson, Robin L; Waters, Michael J; Hancock, John F; Grimmond, Sean M; Muscat, George E O; Parton, Robert G

    2013-07-25

    Caveolae and caveolin-1 (CAV1) have been linked to several cellular functions. However, a model explaining their roles in mammalian tissues in vivo is lacking. Unbiased expression profiling in several tissues and cell types identified lipid metabolism as the main target affected by CAV1 deficiency. CAV1-/- mice exhibited impaired hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent oxidative fatty acid metabolism and ketogenesis. Similar results were recapitulated in CAV1-deficient AML12 hepatocytes, suggesting at least a partial cell-autonomous role of hepatocyte CAV1 in metabolic adaptation to fasting. Finally, our experiments suggest that the hepatic phenotypes observed in CAV1-/- mice involve impaired PPARα ligand signaling and attenuated bile acid and FXRα signaling. These results demonstrate the significance of CAV1 in (1) hepatic lipid homeostasis and (2) nuclear hormone receptor (PPARα, FXRα, and SHP) and bile acid signaling.

  3. Caveolin-1 Is Necessary for Hepatic Oxidative Lipid Metabolism: Evidence for Crosstalk between Caveolin-1 and Bile Acid Signaling

    Directory of Open Access Journals (Sweden)

    Manuel A. Fernández-Rojo

    2013-07-01

    Full Text Available Caveolae and caveolin-1 (CAV1 have been linked to several cellular functions. However, a model explaining their roles in mammalian tissues in vivo is lacking. Unbiased expression profiling in several tissues and cell types identified lipid metabolism as the main target affected by CAV1 deficiency. CAV1−/− mice exhibited impaired hepatic peroxisome proliferator-activated receptor α (PPARα-dependent oxidative fatty acid metabolism and ketogenesis. Similar results were recapitulated in CAV1-deficient AML12 hepatocytes, suggesting at least a partial cell-autonomous role of hepatocyte CAV1 in metabolic adaptation to fasting. Finally, our experiments suggest that the hepatic phenotypes observed in CAV1−/− mice involve impaired PPARα ligand signaling and attenuated bile acid and FXRα signaling. These results demonstrate the significance of CAV1 in (1 hepatic lipid homeostasis and (2 nuclear hormone receptor (PPARα, FXRα, and SHP and bile acid signaling.

  4. Myc and Ras oncogenes engage different energy metabolism programs and evoke distinct patterns of oxidative and DNA replication stress.

    Science.gov (United States)

    Maya-Mendoza, Apolinar; Ostrakova, Jitka; Kosar, Martin; Hall, Arnaldur; Duskova, Pavlina; Mistrik, Martin; Merchut-Maya, Joanna Maria; Hodny, Zdenek; Bartkova, Jirina; Christensen, Claus; Bartek, Jiri

    2015-03-01

    Both Myc and Ras oncogenes impact cellular metabolism, deregulate redox homeostasis and trigger DNA replication stress (RS) that compromises genomic integrity. However, how are such oncogene-induced effects evoked and temporally related, to what extent are these kinetic parameters shared by Myc and Ras, and how are these cellular changes linked with oncogene-induced cellular senescence in different cell context(s) remain poorly understood. Here, we addressed the above-mentioned open questions by multifaceted comparative analyses of human cellular models with inducible expression of c-Myc and H-RasV12 (Ras), two commonly deregulated oncoproteins operating in a functionally connected signaling network. Our study of DNA replication parameters using the DNA fiber approach and time-course assessment of perturbations in glycolytic flux, oxygen consumption and production of reactive oxygen species (ROS) revealed the following results. First, overabundance of nuclear Myc triggered RS promptly, already after one day of Myc induction, causing slow replication fork progression and fork asymmetry, even before any metabolic changes occurred. In contrast, Ras overexpression initially induced a burst of cell proliferation and increased the speed of replication fork progression. However, after several days of induction Ras caused bioenergetic metabolic changes that correlated with slower DNA replication fork progression and the ensuing cell cycle arrest, gradually leading to senescence. Second, the observed oncogene-induced RS and metabolic alterations were cell-type/context dependent, as shown by comparative analyses of normal human BJ fibroblasts versus U2-OS sarcoma cells. Third, the energy metabolic reprogramming triggered by Ras was more robust compared to impact of Myc. Fourth, the detected oncogene-induced oxidative stress was due to ROS (superoxide) of non-mitochondrial origin and mitochondrial OXPHOS was reduced (Crabtree effect). Overall, our study provides novel

  5. Effects of olive leave extract on metabolic disorders and oxidative stress induced by 2.45 GHz WIFI signals.

    Science.gov (United States)

    Salah, Myriam Ben; Abdelmelek, Hafedh; Abderraba, Manef

    2013-11-01

    We investigated the effect of olive leaves extract administration on glucose metabolism and oxidative response in liver and kidneys of rats exposed to radio frequency (RF). The exposure of rats to RF (2.45 GHz, 1h/day during 21 consecutive days) induced a diabetes-like status. Moreover, RF decreased the activities of glutathione peroxidase (GPx, -33.33% and -49.40%) catalase (CAT, -43.39% and -39.62%) and the superoxide dismutase (SOD, -59.29% and -68.53%) and groups thiol amount (-62.68% and -34.85%), respectively in liver and kidneys. Indeed, exposure to RF increased the malondialdehyde (MDA, 29.69% and 51.35%) concentration respectively in liver and kidneys. Olive leaves extract administration (100 mg/kg, ip) in RF-exposed rats prevented glucose metabolism disruption and restored the activities of GPx, CAT and SOD and thiol group amount in liver and kidneys. Moreover, olive leave extract administration was able to bring down the elevated levels of MDA in liver but not in kidneys. Our investigations suggested that RF exposure induced a diabetes-like status through alteration of oxidative response. Olive leaves extract was able to correct glucose metabolism disorder by minimizing oxidative stress induced by RF in rat tissues.

  6. Biofluid metabotyping of occupationally exposed subjects to air pollution demonstrates high oxidative stress and deregulated amino acid metabolism

    Science.gov (United States)

    Pradhan, Surya Narayan; Das, Aleena; Meena, Ramovatar; Nanda, Ranjan Kumar; Rajamani, Paulraj

    2016-01-01

    Occupational exposure to air pollution induces oxidative stress and prolonged exposure increases susceptibility to cardiovascular and respiratory diseases in several working groups. Biofluid of these subjects may reflect perturbed metabolic phenotypes. In this study we carried out a comparative molecular profiling study using parallel biofluids collected from subjects (n = 85) belonging to auto rickshaw drivers (ARD), traffic cops (TC) and office workers (OW). Higher levels of oxidative stress and inflammation markers in serum of ARD subjects were observed as compared to OW and TC. Uni and multivariate analyses of metabolites identified in urine by 1H NMR revealed 11 deregulated molecules in ARD subjects and involved in phenylalanine, histidine, arginine and proline metabolism. Despite contribution of confounding factors like exposure period, dietary factors including smoking and alcohol status, our results demonstrate existence of exposure specific metabotypes in biofluids of ARD, OW and TC groups. Monitoring serum oxidative stress and inflammation markers and urine metabolites by NMR may be useful to characterize perturbed metabolic phenotypes in populations exposed to urban traffic air pollution. PMID:27767182

  7. Oxidative stress and metabolic perturbations in Escherichia coli exposed to sublethal levels of 2,4-dichlorophenoxyacetic acid.

    Science.gov (United States)

    Bhat, Supriya V; Booth, Sean C; Vantomme, Erik A N; Afroj, Shirin; Yost, Christopher K; Dahms, Tanya E S

    2015-09-01

    The chlorophenoxy herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is used extensively worldwide despite its known toxicity and our limited understanding of how it affects non-target organisms. Escherichia coli is a suitable model organism to investigate toxicity and adaptation mechanisms in bacteria exposed to xenobiotic chemicals. We developed a methodical platform that uses atomic force microscopy, metabolomics and biochemical assays to quantify the response of E. coli exposed to sublethal levels of 2,4-D. This herbicide induced a filamentous phenotype in E. coli BL21 and a similar phenotype was observed in a selection of genotypically diverse E. coli strains (A0, A1, B1, and D) isolated from the environment. The filamentous phenotype was observed at concentrations 1000 times below field levels and was reversible upon supplementation with polyamines. Cells treated with 2,4-D had more compliant envelopes, significantly remodeled surfaces that were rougher and altered vital metabolic pathways including oxidative phosphorylation, the ABC transport system, peptidoglycan biosynthesis, amino acid, nucleotide and sugar metabolism. Most of the observed effects could be attributed to oxidative stress, consistent with increases in reactive oxygen species as a function of 2,4-D exposure. This study provides direct evidence that 2,4-D at sublethal levels induces oxidative stress and identifies the associated metabolic changes in E. coli.

  8. Biofluid metabotyping of occupationally exposed subjects to air pollution demonstrates high oxidative stress and deregulated amino acid metabolism

    Science.gov (United States)

    Pradhan, Surya Narayan; Das, Aleena; Meena, Ramovatar; Nanda, Ranjan Kumar; Rajamani, Paulraj

    2016-10-01

    Occupational exposure to air pollution induces oxidative stress and prolonged exposure increases susceptibility to cardiovascular and respiratory diseases in several working groups. Biofluid of these subjects may reflect perturbed metabolic phenotypes. In this study we carried out a comparative molecular profiling study using parallel biofluids collected from subjects (n = 85) belonging to auto rickshaw drivers (ARD), traffic cops (TC) and office workers (OW). Higher levels of oxidative stress and inflammation markers in serum of ARD subjects were observed as compared to OW and TC. Uni and multivariate analyses of metabolites identified in urine by 1H NMR revealed 11 deregulated molecules in ARD subjects and involved in phenylalanine, histidine, arginine and proline metabolism. Despite contribution of confounding factors like exposure period, dietary factors including smoking and alcohol status, our results demonstrate existence of exposure specific metabotypes in biofluids of ARD, OW and TC groups. Monitoring serum oxidative stress and inflammation markers and urine metabolites by NMR may be useful to characterize perturbed metabolic phenotypes in populations exposed to urban traffic air pollution.

  9. The role of fatty acid oxidation in the metabolic reprogramming of activated T cells

    Directory of Open Access Journals (Sweden)

    Craig Alan Byersdorfer

    2014-12-01

    Full Text Available Activation represents a significant bioenergetic challenge for T cells, which must undergo metabolic reprogramming to keep pace with increased energetic demands. This review focuses on the role of fatty acid metabolism, both in vitro and in vivo, following T cell activation. Based upon previous studies in the literature, as well as accumulating evidence in allogeneic cells, I propose a multi-step model of in vivo metabolic reprogramming. In this model, a primary determinant of metabolic phenotype is the ubiquity and duration of antigen exposure. The implications of this model, as well as the future challenges and opportunities in studying T cell metabolism, will be discussed.

  10. Black Beans, Fiber, and Antioxidant Capacity Pilot Study: Examination of Whole Foods vs. Functional Components on Postprandial Metabolic, Oxidative Stress, and Inflammation in Adults with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Elizabeth J. Reverri

    2015-07-01

    Full Text Available Beans (Phaseolus vulgaris contain bioactive components with functional properties that may modify cardiovascular risk. The aims of this pilot study were to evaluate the ability of black beans to attenuate postprandial metabolic, oxidative stress, and inflammatory responses and determine relative contribution of dietary fiber and antioxidant capacity of beans to the overall effect. In this randomized, controlled, crossover trial, 12 adults with metabolic syndrome (MetS consumed one of three meals (black bean (BB, fiber matched (FM, and antioxidant capacity matched (AM on three occasions that included blood collection before (fasting and five hours postprandially. Insulin was lower after the BB meal, compared to the FM or AM meals (p < 0.0001. A significant meal × time interaction was observed for plasma antioxidant capacity (p = 0.002 revealing differences over time: AM > BB > FM. Oxidized LDL (oxLDL was not different by meal, although a trend for declining oxLDL was observed after the BB and AM meals at five hours compared to the FM meal. Triglycerides and interleukin-6 (IL-6 increased in response to meals (p < 0.0001. Inclusion of black beans with a typical Western-style meal attenuates postprandial insulin and moderately enhances postprandial antioxidant endpoints in adults with MetS, which could only be partly explained by fiber content and properties of antioxidant capacity.

  11. Black Beans, Fiber, and Antioxidant Capacity Pilot Study: Examination of Whole Foods vs. Functional Components on Postprandial Metabolic, Oxidative Stress, and Inflammation in Adults with Metabolic Syndrome.

    Science.gov (United States)

    Reverri, Elizabeth J; Randolph, Jody M; Steinberg, Francene M; Kappagoda, C Tissa; Edirisinghe, Indika; Burton-Freeman, Britt M

    2015-07-27

    Beans (Phaseolus vulgaris) contain bioactive components with functional properties that may modify cardiovascular risk. The aims of this pilot study were to evaluate the ability of black beans to attenuate postprandial metabolic, oxidative stress, and inflammatory responses and determine relative contribution of dietary fiber and antioxidant capacity of beans to the overall effect. In this randomized, controlled, crossover trial, 12 adults with metabolic syndrome (MetS) consumed one of three meals (black bean (BB), fiber matched (FM), and antioxidant capacity matched (AM)) on three occasions that included blood collection before (fasting) and five hours postprandially. Insulin was lower after the BB meal, compared to the FM or AM meals (p differences over time: AM > BB > FM. Oxidized LDL (oxLDL) was not different by meal, although a trend for declining oxLDL was observed after the BB and AM meals at five hours compared to the FM meal. Triglycerides and interleukin-6 (IL-6) increased in response to meals (p < 0.0001). Inclusion of black beans with a typical Western-style meal attenuates postprandial insulin and moderately enhances postprandial antioxidant endpoints in adults with MetS, which could only be partly explained by fiber content and properties of antioxidant capacity.

  12. Waist-to-height ratio, body mass index and waist circumference for screening paediatric cardio-metabolic risk factors: a meta-analysis.

    Science.gov (United States)

    Lo, K; Wong, M; Khalechelvam, P; Tam, W

    2016-12-01

    Waist-to-height ratio (WHtR) is superior to body mass index and waist circumference for measuring adult cardio-metabolic risk factors. However, there is no meta-analysis to evaluate its discriminatory power in children and adolescents. A meta-analysis was conducted using multiple databases, including Embase and Medline. Studies were included that utilized receiver-operating characteristics curve analysis and published area under the receiver-operating characteristics curves (AUC) for adiposity indicators with hyperglycaemia, elevated blood pressure, dyslipidemia, metabolic syndrome and other cardio-metabolic outcomes. Thirty-four studies met the inclusion criteria. AUC values were extracted and pooled using a random-effects model and were weighted using the inverse variance method. The mean AUC values for each index were greater than 0.6 for most outcomes including hypertension. The values were the highest when screening for metabolic syndrome (AUC > 0.8). WHtR did not have significantly better screening power than other two indexes in most outcomes, except for elevated triglycerides when compared with body mass index and high metabolic risk score when compared with waist circumference. Although not being superior in discriminatory power, WHtR is convenient in terms of measurement and interpretation, which is advantageous in practice and allows for the quick identification of children with cardio-metabolic risk factors at an early age.

  13. [Oxidative metabolism of main and accessory olfactory bulbs, limpic system and hypothalamus during the estral cycle of the rat (author's transl)].

    Science.gov (United States)

    Sánchez-Criado, J E

    1979-06-01

    The in vitro oxidative metabolism of hypothalamus, olfactory and limbic systems from female rats in the estrous cycle have been measured. The accessory olfactory bulb becomes most active during diestrous when the hypothalamus reaches its lowest values.

  14. Peroxisome proliferator-activated receptor γ (PPARγ) mediates a Ski oncogene-induced shift from glycolysis to oxidative energy metabolism.

    Science.gov (United States)

    Ye, Fang; Lemieux, Hélène; Hoppel, Charles L; Hanson, Richard W; Hakimi, Parvin; Croniger, Colleen M; Puchowicz, Michelle; Anderson, Vernon E; Fujioka, Hisashi; Stavnezer, Ed

    2011-11-18

    Overexpression of the Ski oncogene induces oncogenic transformation of chicken embryo fibroblasts (CEFs). However, unlike most other oncogene-transformed cells, Ski-transformed CEFs (Ski-CEFs) do not display the classical Warburg effect. On the contrary, Ski transformation reduced lactate production and glucose utilization in CEFs. Compared with CEFs, Ski-CEFs exhibited enhanced TCA cycle activity, fatty acid catabolism through β-oxidation, glutamate oxidation, oxygen consumption, as well as increased numbers and mass of mitochondria. Interestingly, expression of PPARγ, a key transcription factor that regulates adipogenesis and lipid metabolism, was dramatically elevated at both the mRNA and protein levels in Ski-CEFs. Accordingly, PPARγ target genes that are involved in lipid uptake, transport, and oxidation were also markedly up-regulated by Ski. Knocking down PPARγ in Ski-CEFs by RNA interference reversed the elevated expression of these PPARγ target genes, as well as the shift to oxidative metabolism and the increased mitochondrial biogenesis. Moreover, we found that Ski co-immunoprecipitates with PPARγ and co-activates PPARγ-driven transcription.

  15. Effect of Tiaoxin Recipe (调心方) on Spatial Memory and Energy Metabolism of Oxidation Injured Alzheimer's Disease Rats

    Institute of Scientific and Technical Information of China (English)

    邱宏; 金国琴; 赵伟康; 张学礼

    2003-01-01

    Objective: To observe the effect of Tiaoxin Recipe (TXR) on the spatial memory, brain mitochondrial energy metabolism of oxidation injured Alzheimer's disease (AD) rats, and to explore the mechanism of TXR in treating AD. Methods: Eighty-eight SD rats were randomly divided into five groups (normal group, operative group, "AD" model group,TXR group and Aricept group). An oxygen free radical generation system (dihydroxy fumaric acid-trichloroferric-adenosine diphosphate, DHF-FeCl3-ADP) was used to create oxidation injured rat models mimic to AD; spatial learning and memory impairment (Morris water maze method), the activity of Succinate-oxidase, NADH-oxidase, CytC-oxidase (Clark oxygen electrode method) and the expression of cytochrome oxidase (CO)ⅡmRNA (in situ hybridization method) were observed. Results: Compared with the normal group, the spatial memory, activity of CytC-oxidase and COⅡmRNA expression of oxidation injured "AD" rats were obviously decreased; TXR, however, could improve these functions in "AD" rat models obviously. Conclusion: The mechanism of the action of TXR in treating AD was partly related to its effect on anti-oxidation which could improve brain mitochondrial energy metabolism.

  16. Development of Dietary Patterns Spanning Infancy and Toddlerhood: Relation to Body Size, Composition and Metabolic Risk Markers at Three Years

    Directory of Open Access Journals (Sweden)

    Louise BB Andersen

    2015-07-01

    Full Text Available Little is known about the development of dietary patterns during toddlerhood and the relation to growth and health. The study objective was to characterise the development of dietary patterns from 9-36 mo of age and investigate the association to body size, body composition and metabolic risk markers at 36 mo. Food records were filled out at 9, 18 and 36 mo of age (n = 229. Dietary patterns were identified by principal component analysis (PCA. Three dietary patterns were identified: Transition Food, Healthy Food and Traditional Food. The course of development in dietary patterns from 9-36 mo indicated tracking for a relatively large group of participants in the three patterns. Transition Food and Healthy Food were associated with some of the investigated outcomes. Children with lower adherence to the Transition Food pattern than average at 18 and 36 mo irrespectively of intake at 9 mo had higher BMI z-scores at 36 mo. Similar trend was identified for higher fat mass indices. Children with lower adherence to the Healthy Food pattern than average at all three ages compared to children with higher adherence to the Healthy Food pattern at the first two registrations, 9 and 18 mo had higher total cholesterol and LDL. Hence, this could represent undesirable development of dietary patterns in toddlers. In conclusion, development of dietary patterns can be exploratory characterised by PCA and related to potential cardiovascular risk markers in toddlers even within a relatively homogeneous population with a high socioeconomic status. The tracking of dietary patterns from 9 mo of age indicates a need for early and sustained promotion of healthy diets.

  17. Paraoxonase-1 inhibits oxidized low-density lipoprotein-induced metabolic alterations and apoptosis in endothelial cells: a nondirected metabolomic study.

    Science.gov (United States)

    García-Heredia, Anabel; Marsillach, Judit; Rull, Anna; Triguero, Iris; Fort, Isabel; Mackness, Bharti; Mackness, Michael; Shih, Diana M; Joven, Jorge; Camps, Jordi

    2013-01-01

    We studied the influence of PON1 on metabolic alterations induced by oxidized LDL when incubated with endothelial cells. HUVEC cells were incubated with native LDL, oxidized LDL, oxidized LDL plus HDL from wild type mice, and oxidized LDL plus HDL from PON1-deficient mice. Results showed alterations in carbohydrate and phospholipid metabolism and increased apoptosis in cells incubated with oxidized LDL. These changes were partially prevented by wild type mouse HDL, but the effects were less effective with HDL from PON1-deficient mice. Our results suggest that PON1 may play a significant role in endothelial cell survival by protecting cells from alterations in the respiratory chain induced by oxidized LDL. These results extend current knowledge on the protective role of HDL and PON1 against oxidation and apoptosis in endothelial cells.

  18. Effects of 2 different prior endurance exercises on whole-body fat oxidation kinetics: light vs. heavy exercise.

    Science.gov (United States)

    Chenevière, Xavier; Borrani, Fabio; Droz, David; Gojanovic, Boris; Malatesta, Davide

    2012-10-01

    This study aimed to compare the effects of 2 different prior endurance exercises on subsequent whole-body fat oxidation kinetics. Fifteen men performed 2 identical submaximal incremental tests (Incr2) on a cycle ergometer after (i) a ∼40-min submaximal incremental test (Incr1) followed by a 90-min continuous exercise performed at 50% of maximal aerobic power-output and a 1-h rest period (Heavy); and (ii) Incr1 followed by a 2.5-h rest period (Light). Fat oxidation was measured using indirect calorimetry and plotted as a function of exercise intensity during Incr1 and Incr2. A sinusoidal equation, including 3 independent variables (dilatation, symmetry and translation), was used to characterize the fat oxidation kinetics and to determine the intensity (Fat(max)) that elicited the maximal fat oxidation (MFO) during Incr. After the Heavy and Light trials, Fat(max), MFO, and fat oxidation rates were significantly greater during Incr2 than Incr1 (p < 0.001). However, Δ (i.e., Incr2-Incr1) Fat(max), MFO, and fat oxidation rates were greater in the Heavy compared with the Light trial (p < 0.05). The fat oxidation kinetics during Incr2(Heavy) showed a greater dilatation and rightward asymmetry than Incr1(Heavy), whereas only a greater dilatation was observed in Incr2(Light) (p < 0.05). This study showed that although to a lesser extent in the Light trial, both prior exercise sessions led to an increase in Fat(max), MFO, and absolute fat oxidation rates during Incr2, inducing significant changes in the shape of the fat oxidation kinetics.

  19. Metabolic changes in serum steroids induced by total-body irradiation of female C57B/6 mice.

    Science.gov (United States)

    Moon, Ju-Yeon; Shin, Hee-June; Son, Hyun-Hwa; Lee, Jeongae; Jung, Uhee; Jo, Sung-Kee; Kim, Hyun Sik; Kwon, Kyung-Hoon; Park, Kyu Hwan; Chung, Bong Chul; Choi, Man Ho

    2014-05-01

    The short- and long-term effects of a single exposure to gamma radiation on steroid metabolism were investigated in mice. Gas chromatography-mass spectrometry was used to generate quantitative profiles of serum steroid levels in mice that had undergone total-body irradiation (TBI) at doses of 0Gy, 1Gy, and 4Gy. Following TBI, serum samples were collected at the pre-dose time point and 1, 3, 6, and 9 months after TBI. Serum levels of progestins, progesterone, 5β-DHP, 5α-DHP, and 20α-DHP showed a significant down-regulation following short-term exposure to 4Gy, with the exception of 20α-DHP, which was significantly decreased at each of the time points measured. The corticosteroids 5α-THDOC and 5α-DHB were significantly elevated at each of the time points measured after exposure to either 1 or 4Gy. Among the sterols, 24S-OH-cholestoerol showed a dose-related elevation after irradiation that reached significance in the high dose group at the 6- and 9-month time points.

  20. Assessment of nitric oxide (NO) redox reactions contribution to nitrous oxide (N2 O) formation during nitrification using a multispecies metabolic network model.

    Science.gov (United States)

    Perez-Garcia, Octavio; Chandran, Kartik; Villas-Boas, Silas G; Singhal, Naresh

    2016-05-01

    Over the coming decades nitrous oxide (N2O) is expected to become a dominant greenhouse gas and atmospheric ozone depleting substance. In wastewater treatment systems, N2O is majorly produced by nitrifying microbes through biochemical reduction of nitrite (NO2(-)) and nitric oxide (NO). However it is unknown if the amount of N2O formed is affected by alternative NO redox reactions catalyzed by oxidative nitrite oxidoreductase (NirK), cytochromes (i.e., P460 [CytP460] and 554 [Cyt554 ]) and flavohemoglobins (Hmp) in ammonia- and nitrite-oxidizing bacteria (AOB and NOB, respectively). In this study, a mathematical model is developed to assess how N2O formation is affected by such alternative nitrogen redox transformations. The developed multispecies metabolic network model captures the nitrogen respiratory pathways inferred from genomes of eight AOB and NOB species. The performance of model variants, obtained as different combinations of active NO redox reactions, was assessed against nine experimental datasets for nitrifying cultures producing N2O at different concentration of electron donor and acceptor. Model predicted metabolic fluxes show that only variants that included NO oxidation to NO2(-) by CytP460 and Hmp in AOB gave statistically similar estimates to observed production rates of N2O, NO, NO2(-) and nitrate (NO3(-)), together with fractions of AOB and NOB species in biomass. Simulations showed that NO oxidation to NO2(-) decreased N2O formation by 60% without changing culture's NO2(-) production rate. Model variants including NO reduction to N2O by Cyt554 and cNor in NOB did not improve the accuracy of experimental datasets estimates, suggesting null N2O production by NOB during nitrification. Finally, the analysis shows that in nitrifying cultures transitioning from dissolved oxygen levels above 3.8 ± 0.38 to <1.5 ± 0.8 mg/L, NOB cells can oxidize the NO produced by AOB through reactions catalyzed by oxidative NirK.

  1. Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria.

    Science.gov (United States)

    Filipović, Dragana; Costina, Victor; Perić, Ivana; Stanisavljević, Andrijana; Findeisen, Peter

    2017-03-15

    Fluoxetine (Flx) is the principal treatment for depression; however, the precise mechanisms of its actions remain elusive. Our aim was to identify protein expression changes within rat hippocampus regulated by chronic Flx treatment versus vehicle-controls using proteomics. Fluoxetine-hydrohloride (15mg/kg) was administered daily to adult male Wistar rats for 3weeks, and cytosolic and nonsynaptic mitochondrial hippocampal proteomes were analyzed. All differentially expressed proteins were functionally annotated according to biological process and molecular function using Uniprot and Blast2GO. Our comparative study revealed that in cytosolic and nonsynaptic mitochondrial fractions, 60 and 3 proteins respectively, were down-regulated, and 23 and 60 proteins, respectively, were up-regulated. Proteins differentially regulated in cytosolic and nonsynaptic mitochondrial fractions were primarily related to cellular and metabolic processes. Of the identified proteins, the expressions of calretinin and parvalbumine were confirmed. The predominant molecular functions of differentially expressed proteins in both cell hippocampal fractions were binding and catalytic activity. Most differentially expressed proteins in nonsynaptic mitochondria were catalytic enzymes involved in the pyruvate metabolism, citric acid cycle, oxidative phosphorylation, ATP synthesis, ATP transduction and glutamate metabolism. Results indicate that chronic Flx treatment may influence proteins involved in calcium signaling, cytoskeletal structure, chaperone system and stimulates energy metabolism via the upregulation of GAPDH expression in cytoplasm, as well as directing energy metabolism toward the citric acid cycle and oxidative phosphorylation in nonsynaptic mitochondria. This approach provides new insight into the chronic effects of Flx treatment on protein expression in a key brain region associated with stress response and memory.

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

    Directory of Open Access Journals (Sweden)

    Indika Edirisinghe

    2012-12-01

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

  3. Modeling the metabolic fate of dietary phosphorus and calcium and the dynamics of body ash content in growing pigs.

    Science.gov (United States)

    Létourneau-Montminy, M P; Narcy, A; Dourmad, J Y; Crenshaw, T D; Pomar, C

    2015-03-01

    A better understanding of the fate of dietary P use by growing pigs will allow an optimization of P use and enhance sustainable practices. The optimization of P utilization is complicated by the multiple criteria, such as growth performance, bone mineralization, and manure P used for assessment of needs. Mathematical modeling is a useful tool to describe relevant biological mechanisms and predict relationships that describe the whole system behavior. Modeling allows development of robust multicriteria approaches to optimize P utilization, feeding cost, and manure application cost. This paper describes and evaluates a model developed to simulate the fate of dietary P, that is, to simulate its digestive and metabolic utilization through digestion, soft tissue, and ash modules. The digestion module takes into account the varied sources of dietary minerals including responses to microbial and plant phytase and Ca and P interactions and predicts absorption and fecal excretion. The soft tissue module simulates the growth of the protein and is based on InraPorc model principles. The ash module simulates the partitioning of absorbed Ca and P into the bone, protein, and lipid compartments as well as urinary excretion. Model behavior showed that the model was able to accurately represent the impact of Lys deficiency on P retention, of Ca and P imbalances, and of Ca and P depletion and repletion sequences. The model's prediction capabilities in simulating whole-body protein, Ca, P, and ash based on published data showed high accuracy, with a slope and intercept that did not differ from 1 and 0, respectively, and an error due to disturbance (ED; variance not accounted for by regression of observed on predicted values). The model's prediction capabilities in simulating balance trial data showed good accuracy for apparent total tract digestibility (ATTD) of P (observed = -0.77 + 1.06 predicted) and P retention coefficient (observed = -4.5 + 1.15 predicted) with an ED of 89% for

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

    NARCIS (Netherlands)

    Bisschop, PH; de Sain-van der Velden, MGM; Stellaard, F; Kuipers, F; Meijer, AJ; Sauerwein, HP; Romijn, JA

    2003-01-01

    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

  5. Energy Expenditure and Substrate Oxidation in Response to Side-Alternating Whole Body Vibration across Three Commonly-Used Vibration Frequencies.

    Directory of Open Access Journals (Sweden)

    Elie-Jacques Fares

    Full Text Available There is increasing recognition about the importance of enhancing energy expenditure (EE for weight control through increases in low-intensity physical activities comparable with daily life (1.5-4 METS. Whole-body vibration (WBV increases EE modestly and could present both a useful adjuvant for obesity management and tool for metabolic phenotyping. However, it is unclear whether a "dose-response" exists between commonly-used vibration frequencies (VF and EE, nor if WBV influences respiratory quotient (RQ, and hence substrate oxidation. We aimed to investigate the EE-VF and RQ-VF relationships across three different frequencies (30, 40, and 50Hz.EE and RQ were measured in 8 healthy young adults by indirect calorimetry at rest, and subsequently during side-alternating WBV at one of 3 VFs (30, 40, and 50 Hz. Each frequency was assessed over 5 cycles of intermittent WBV (30s vibration/30s rest, separated by 5 min seated rest. During the WBV participants stood on the platform with knees flexed sufficiently to maintain comfort, prevent transmission of vibration to the upper body, and minimise voluntary physical exertion. Repeatability was assessed across 3 separate days in a subset of 4 individuals. In order to assess any sequence/habituation effect, an additional group of 6 men underwent 5 cycles of intermittent WBV (30s vibration/30s rest at 40 Hz, separated by 5 min seated rest.Side-alternating WBV increased EE relative to standing, non-vibration levels (+36%, p<0.001. However, no differences in EE were observed across VFs. Similarly, no effect of VF on RQ was found, nor did WBV alter RQ relative to standing without vibration.No relationship could be demonstrated between EE and VF in the range of 30-50Hz, and substrate oxidation did not change in response to WBV. Furthermore, the thermogenic effect of intermittent WBV, whilst robust, was quantitatively small (<2 METS.

  6. Single-leg cycle training is superior to double-leg cycling in improving the oxidative potential and metabolic profile of trained skeletal muscle.

    Science.gov (United States)

    Abbiss, Chris R; Karagounis, Leonidas G; Laursen, Paul B; Peiffer, Jeremiah J; Martin, David T; Hawley, John A; Fatehee, Naeem N; Martin, James C

    2011-05-01

    Single-leg cycling may enhance the peripheral adaptations of skeletal muscle to a greater extent than double-leg cycling. The purpose of the current study was to determine the influence of 3 wk of high-intensity single- and double-leg cycle training on markers of oxidative potential and muscle metabolism and exercise performance. In a crossover design, nine trained cyclists (78 ± 7 kg body wt, 59 ± 5 ml·kg(-1)·min(-1) maximal O(2) consumption) performed an incremental cycling test and a 16-km cycling time trial before and after 3 wk of double-leg and counterweighted single-leg cycle training (2 training sessions per week). Training involved three (double) or six (single) maximal 4-min intervals with 6 min of recovery. Mean power output during the single-leg intervals was more than half that during the double-leg intervals (198 ± 29 vs. 344 ± 38 W, P < 0.05). Skeletal muscle biopsy samples from the vastus lateralis revealed a training-induced increase in Thr(172)-phosphorylated 5'-AMP-activated protein kinase α-subunit for both groups (P < 0.05). However, the increase in cytochrome c oxidase subunits II and IV and GLUT-4 protein concentration was greater following single- than double-leg cycling (P < 0.05). Training-induced improvements in maximal O(2) consumption (3.9 ± 6.2% vs. 0.6 ± 3.6%) and time-trial performance (1.3 ± 0.5% vs. 2.3 ± 4.2%) were similar following both interventions. We conclude that short-term high-intensity single-leg cycle training can elicit greater enhancement in the metabolic and oxidative potential of skeletal muscle than traditional double-leg cycling. Single-leg cycling may therefore provide a valuable training stimulus for trained and clinical populations.

  7. Dose-dependent effects of dietary zinc oxide on bacterial communities and metabolic profiles in the ileum of weaned pigs.

    Science.gov (United States)

    Pieper, R; Vahjen, W; Neumann, K; Van Kessel, A G; Zentek, J

    2012-10-01

    Pharmacological levels of zinc oxide (ZnO) can improve the health of weaning piglets and influence the intestinal microbiota. This experiment aimed at studying the dose-response effect of five dietary concentrations of ZnO on small intestinal bacteria and metabolite profiles. Fifteen piglets, weaned at 25 ± 1 days of age, were allocated into five groups according to body weight and litter. Diets were formulated to contain 50 (basal diet), 150, 250, 1000 and 2500 mg zinc/kg by adding analytical-grade (>98% purity) ZnO to the basal diet and fed ad libitum for 14 days after a 7-day adaptation period on the basal diet. Ileal bacterial community profiles were analysed by denaturing gradient gel electrophoresis and selected bacterial groups quantified by real-time PCR. Concentrations of ileal volatile fatty acids (VFA), D- and L-lactate and ammonia were determined. Species richness, Shannon diversity and evenness were significantly higher at high ZnO levels. Quantitative PCR revealed lowest total bacterial counts in the 50 mg/kg group. Increasing ZnO levels led to an increase (p = 0.017) in enterobacteria from log 4.0 cfu/g digesta (50 mg/kg) to log 6.7 cfu/g digesta (2500 mg/kg). Lactic acid bacteria were not influenced (p = 0.687) and clostridial cluster XIVa declined (p = 0.035) at highest ZnO level. Concentration of total, D- and L-lactate and propionate was not affected (p = 0.736, p = 0.290 and p = 0.630), but concentrations of ileal total VFA, acetate and butyrate increased markedly from 50 to 150 mg/kg and decreased with further increasing zinc levels and reached low levels again at 2500 mg/kg (p = 0.048, p = 0.048 and p = 0.097). Ammonia decreased (p < 0.006) with increasing dietary ZnO level. In conclusion, increasing levels of dietary ZnO had strong and dose-dependent effects on ileal bacterial community composition and activity, suggesting taxonomic variation in metabolic response to ZnO.

  8. Safety implications of high-field MRI: actuation of endogenous magnetic iron oxides in the human body.

    Directory of Open Access Journals (Sweden)

    Jon Dobson

    Full Text Available BACKGROUND: Magnetic Resonance Imaging scanners have become ubiquitous in hospitals and high-field systems (greater than 3 Tesla are becoming increasingly common. In light of recent European Union moves to limit high-field exposure for those working with MRI scanners, we have evaluated the potential for detrimental cellular effects via nanomagnetic actuation of endogenous iron oxides in the body. METHODOLOGY: Theoretical models and experimental data on the composition and magnetic properties of endogenous iron oxides in human tissue were used to analyze the forces on iron oxide particles. PRINCIPAL FINDING AND CONCLUSIONS: Results show that, even at 9.4 Tesla, forces on these particles are unlikely to disrupt normal cellular function via nanomagnetic actuation.

  9. Oxidative phosphorylation efficiency, proton conductance and reactive oxygen species production of liver mitochondria correlates with body mass in frogs.

    Science.gov (United States)

    Roussel, Damien; Salin, Karine; Dumet, Adeline; Romestaing, Caroline; Rey, Benjamin; Voituron, Yann

    2015-10-01

    Body size is a central biological parameter affecting most biological processes (especially energetics) and the mitochondrion is a key organelle controlling metabolism and is also the cell's main source of chemical energy. However, the link between body size and mitochondrial function is still unclear, especially in ectotherms. In this study, we investigated several parameters of mitochondrial bioenergetics in the liver of three closely related species of frog (the common frog Rana temporaria, the marsh frog Pelophylax ridibundus and the bull frog Lithobates catesbeiana). These particular species were chosen because of their differences in adult body mass. We found that mitochondrial coupling efficiency was markedly increased with animal size, which led to a higher ATP production (+70%) in the larger frogs (L. catesbeiana) compared with the smaller frogs (R. temporaria). This was essentially driven by a strong negative dependence of mitochondrial proton conductance on body mass. Liver mitochondria from the larger frogs (L. catesbeiana) displayed 50% of the proton conductance of mitochondria from the smaller frogs (R. temporaria). Contrary to our prediction, the low mitochondrial proton conductance measured in L. catesbeiana was not associated with higher reactive oxygen species production. Instead, liver mitochondria from the larger individuals produced significantly lower levels of radical oxygen species than those from the smaller frogs. Collectively, the data show that key bioenergetics parameters of mitochondria (proton leak, ATP production efficiency and radical oxygen species production) are correlated with body mass in frogs. This research expands our understanding of the relationship between mitochondrial function and the evolution of allometric scaling in ectotherms.

  10. Energy metabolism and nutrient oxidation in young pigs and rats during feeding, starvation and re-feeding

    DEFF Research Database (Denmark)

    Chwalibog, A; Jakobsen, Kirsten; Tauson, A -H

    2005-01-01

    -4 days of starvation and 4 days of re-feeding. O2 consumption and CO2 production were measured by open-air-circuit respiration units. In the feeding period, protein retention in relation to metabolic live mass (kg(0.75)) was identical for pigs and rats, while there was a tendency of a higher fat......The investigation included individual measurements of energy metabolism and oxidation of nutrients in 12 castrated male pigs (Sus scrofa) (20-40 kg) and 12 male rats (Rattus norvegicus) (65-105 g). Measurements were carried out in 5-6 days balance periods with ad libitum feeding, followed by 3...... retention in pigs than in rats. A substantial part of digested carbohydrate was not oxidized, but transferred to fat metabolism without significant differences (P > 0.05) between pigs and rats (18% vs. 22%). During starvation, nitrogen excretion in urine decreased to 226 mg/kg(0.75) in pigs and to 429 mg...

  11. Ozone Emitted During Copying Process -A Potential Cause of Pathological Oxidative Stress and Potential Oxidative Damage in the Bodies of Operators

    Institute of Scientific and Technical Information of China (English)

    JUN-FU ZHOU; WEI-WEI CHEN; GUI-ZHONG TONG

    2003-01-01

    Objective To estimate the impact of copying on the indoor air quality, and to investigatewhether ozone emitted during such a process induces pathological oxidative stress and potentialoxidative damage in the bodies of operators. Methods 67 copying operators (CO) and 67 healthyvolunteers (HV) were enrolled in a random control study, in which levels of lipoperoxide (LPO) inplasma and erythrocytes, and levels of vitamin C (VC), vitamin E (VE) and β-carotene (β-CAR) inplasma as well as activities of superoxide dismutase (SOD), catalase (CAT) and glutathioneperoxidase (GPX) in erythrocytes were determined by spectrophotometric methods. ResultsCompared with the HV group, the average values of LPO in plasma and erythrocytes in the CO groupwere significantly increased (P<0.0001), while those of VC, VE and β-CAR in plasma as well asthose of SOD, CAT and GPX in erythrocytes in the CO group were significantly decreased(P<0.0001). Pearson product-moment correlation analysis showed that with increase of ozone level incopying sites and duration of exposure to ozone, the values of LPO in plasma and erythrocytes in thebodies of operators were gradually increased,while those of VC, VE, β-CAR, SOD, CAT and GPXwere decreased in the same manner. Odds ratio (OR) of risk of biochemical parameters reflectingpotential oxidative damage of the copying operators ranged from 4.440 to 13.516, and 95 % CI of ORwas from 2.113 to 34.061. Reliability coefficient (α) of the biochemical parameters used to reflect thepotential oxidative damage of the operators was 0.8156, standardized item α=0.9929, P<0.0001.Conclusion Findings in the present study suggest that there exist a series of free radical chainreactions and pathological oxidative stress induced by high dose ozone in the operators, therebycausing potential oxidative and lipoperoxidative damages in their bodies.

  12. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism

    Directory of Open Access Journals (Sweden)

    Carles Lerin

    2016-10-01

    Conclusions: Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D.

  13. High-fat diet-induced reduction of peroxisome proliferator-activated receptor-γ coactivator-1α messenger RNA levels and oxidative capacity in the soleus muscle of rats with metabolic syndrome.

    Science.gov (United States)

    Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Takeda, Isao; Tsuda, Kinsuke; Ishihara, Akihiko

    2012-02-01

    Animal models of type 2 diabetes exhibit reduced peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) messenger RNA (mRNA) levels, which are associated with decreased oxidative capacity, in skeletal muscles. In contrast, animal models with metabolic syndrome show normal PGC-1α mRNA levels. We hypothesized that a high-fat diet decreases PGC-1α mRNA levels in skeletal muscles of rats with metabolic syndrome, reducing muscle oxidative capacity and accelerating metabolic syndrome or inducing type 2 diabetes. We examined mRNA levels and fiber profiles in the soleus muscles of rats with metabolic syndrome (SHR/NDmcr-cp [cp/cp]; CP) fed a high-fat diet. Five-week-old CP rats were assigned to a sedentary group (CP-N) that was fed a standard diet (15.1 kJ/g, 23.6% protein, 5.3% fat, and 54.4% carbohydrates) or a sedentary group (CP-H) that was fed a high-fat diet (21.6 kJ/g, 23.6% protein, 34.9% fat, and 25.9% carbohydrates) and were housed for 10 weeks. Body weight, energy intake, and systolic blood pressure were higher in the CP-H group than in the CP-N group. Nonfasting glucose, triglyceride, total cholesterol, and leptin levels were higher in the CP-H group than in the CP-N group. There was no difference in insulin levels between the CP-N and CP-H groups. Muscle PGC-1α mRNA levels and succinate dehydrogenase activity were lower in the CP-H group than in the CP-N group. We concluded that a high-fat diet reduces PGC-1α mRNA levels and oxidative capacity in skeletal muscles and accelerates metabolic syndrome.

  14. Tamoxifen affects glucose and lipid metabolism parameters, causes browning of subcutaneous adipose tissue and transient body composition changes in C57BL/6NTac mice.

    Science.gov (United States)

    Hesselbarth, Nico; Pettinelli, Chiara; Gericke, Martin; Berger, Claudia; Kunath, Anne; Stumvoll, Michael; Blüher, Matthias; Klöting, Nora

    2015-08-28

    Tamoxifen is a selective estrogen receptor (ER) modulator which is widely used to generate inducible conditional transgenic mouse models. Activation of ER signaling plays an important role in the regulation of adipose tissue (AT) metabolism. We therefore tested the hypothesis that tamoxifen administration causes changes in AT biology in vivo. 12 weeks old male C57BL/6NTac mice were treated with either tamoxifen (n = 18) or vehicle (n = 18) for 5 consecutive days. Tamoxifen treatment effects on body composition, energy homeostasis, parameters of AT biology, glucose and lipid metabolism were investigated up to an age of 18 weeks. We found that tamoxifen treatment causes: I) significantly increased HbA1c, triglyceride and free fatty acid serum concentrations (p body composition changes. Tamoxifen may induce changes in body composition, whole body glucose and lipid metabolism and has significant effects on AT biology, which need to be considered when using Tamoxifen as a tool to induce conditional transgenic mouse models. Our data further suggest that tamoxifen-treated wildtype mice should be characterized in parallel to experimental transgenic models to control for tamoxifen administration effects.

  15. A PGC-1α- and muscle fibre type-related decrease in markers of mitochondrial oxidative metabolism in skeletal muscle of humans with inherited insulin resistance

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Skov, Vibe; Petersson, Stine Juhl;

    2014-01-01

    Insulin resistance in obesity and type 2 diabetes is related to abnormalities in mitochondrial oxidative phosphorylation (OxPhos) in skeletal muscle. We tested the hypothesis that mitochondrial oxidative metabolism is impaired in muscle of patients with inherited insulin resistance and defective...... insulin signalling....

  16. Role of nitric oxide synthase uncoupling at rostral ventrolateral medulla in redox-sensitive hypertension associated with metabolic syndrome.

    Science.gov (United States)

    Wu, Kay L H; Chao, Yung-Mei; Tsay, Shiow-Jen; Chen, Chen Hsiu; Chan, Samuel H H; Dovinova, Ima; Chan, Julie Y H

    2014-10-01

    Metabolic syndrome (MetS), which is rapidly becoming prevalent worldwide, is long known to be associated with hypertension and recently with oxidative stress. Of note is that oxidative stress in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons reside, contributes to sympathoexcitation and hypertension. This study sought to identify the source of tissue oxidative stress in RVLM and their roles in neural mechanism of hypertension associated with MetS. Adult normotensive rats subjected to a high-fructose diet for 8 weeks developed metabolic traits of MetS, alongside increases in sympathetic vasomotor activity and blood pressure. In RVLM of these MetS rats, the tissue level of reactive oxygen species was increased, nitric oxide (NO) was decreased, and mitochondrial electron transport capacity was reduced. Whereas the protein expression of neuronal NO synthase (nNOS) or protein inhibitor of nNOS was increased, the ratio of nNOS dimer/monomer was significantly decreased. Oral intake of pioglitazone or intracisternal infusion of tempol or coenzyme Q10 significantly abrogated all those molecular events in high-fructose diet-fed rats and ameliorated sympathoexcitation and hypertension. Gene silencing of protein inhibitor of nNOS mRNA in RVLM using lentivirus carrying small hairpin RNA inhibited protein inhibitor of nNOS expression, increased the ratio of nNOS dimer/monomer, restored NO content, and alleviated oxidative stress in RVLM of high-fructose diet-fed rats, alongside significantly reduced sympathoexcitation and hypertension. These results suggest that redox-sensitive and protein inhibitor of nNOS-mediated nNOS uncoupling is engaged in a vicious cycle that sustains the production of reactive oxygen species in RVLM, resulting in sympathoexcitation and hypertension associated with MetS.

  17. Suppression of nitric oxide production from nasal fibroblasts by metabolized clarithromycin in vitro

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    Hirano Kojiro

    2010-11-01

    Full Text Available Abstract Background Low-dose and long-term administration of 14-membered macrolide antibiotics, so called macrolide therapy, has been reported to favorably modify the clinical conditions of chronic airway diseases. Since there is growing evidence that macrolide antibiotic-resistant bacteria's spreaders in the populations received macrolide therapy, it is strongly desired to develop macrolide antibiotics, which showed only anti-inflammatory action. The present study was designed to examine the influence of clarithromycin (CAM and its metabolized materials, M-1, M-4 and M-5, on free radical generation from nasal polyp fibroblasts (NPFs through the choice of nitric oxide (NO, which is one of important effector molecule in the development of airway inflammatory disease in vitro. Methods NPFs (5 × 105 cells/ml were stimulated with 1.0 μg/ml lipopolysaccharide (LPS in the presence of agents for 24 hours. NO levels in culture supernatants were examined by the Griess method. We also examined the influence of agents on the phosphorylation of MAPKs, NF-κB activation, iNOS mRNA expression and iNOS production in NPFs cultured for 2, 4, 8, and 12 hours, respectively. Results The addition of CAM (> 0.4 μg/ml and M-4 (> 0.04 μg/ml could suppress NO production from NPFs after LPS stimulation through the suppression of iNOS mRNA expression and NF-κB activation. CAM and M-4 also suppressed phosphorylation of MAPKs, ERK and p38 MAPK, but not JNK, which are increased LPS stimulation. On the other hand, M-1 and M-5 could not inhibit the NO generation, even when 0.1 μg/ml of the agent was added to cell cultures. Conclusion The present results may suggest that M-4 will be a good candidate for the agent in the treatment of chronic airway inflammatory diseases, since M-4 did not have antimicribiological effects on gram positive and negative bacteria.

  18. Metabolic potential of fatty acid oxidation and anaerobic respiration by abundant members of Thaumarchaeota and Thermoplasmata in deep anoxic peat

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Xueju [Georgia Inst. of Technology, Atlanta, GA (United States); Handley, Kim M. [Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States); Gilbert, Jack A. [Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States); Marine Biological Lab., Woods Hole, MA (United States); Zhejiang Univ., Hangzhou (China); Kostka, Joel E. [Georgia Inst. of Technology, Atlanta, GA (United States)

    2015-05-22

    To probe the metabolic potential of abundant Archaea in boreal peats, we reconstructed two near-complete archaeal genomes, affiliated with Thaumarchaeota group 1.1c (bin Fn1, 8% abundance), which was a genomically unrepresented group, and Thermoplasmata (bin Bg1, 26% abundance), from metagenomic data acquired from deep anoxic peat layers. Each of the near-complete genomes encodes the potential to degrade long-chain fatty acids (LCFA) via β-oxidation. Fn1 has the potential to oxidize LCFA either by syntrophic interaction with methanogens or by coupling oxidation with anaerobic respiration using fumarate as a terminal electron acceptor (TEA). Fn1 is the first Thaumarchaeota genome without an identifiable carbon fixation pathway, indicating that this mesophilic phylum encompasses more diverse metabolisms than previously thought. Furthermore, we report genetic evidence suggestive of sulfite and/or organosulfonate reduction by Thermoplasmata Bg1. In deep peat, inorganic TEAs are often depleted to extremely low levels, yet the anaerobic respiration predicted for two abundant archaeal members suggests organic electron acceptors such as fumarate and organosulfonate (enriched in humic substances) may be important for respiration and C mineralization in peatlands.

  19. Metabolic encephalopathy and lipid storage myopathy associated with a presumptive mitochondrial fatty acid oxidation defect in a dog

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    Vanessa R Biegen

    2015-11-01

    Full Text Available A 1-year-old spayed female Shih Tzu presented for episodic abnormalities of posture and mentation. Neurologic examination was consistent with a bilaterally symmetric multifocal encephalopathy. The dog had a waxing-and-waning hyperlactemia and hypoglycemia. Magnetic resonance imaging revealed bilaterally symmetric cavitated lesions of the caudate nuclei with less severe abnormalities in the cerebellar nuclei. Empirical therapy was unsuccessful and the patient was euthanized. Post-mortem histopathology revealed bilaterally symmetric necrotic lesions of the caudate and cerebellar nuclei and multi-organ lipid accumulation, including a lipid storage myopathy. Malonic aciduria and ketonuria were found on urinary organic acid screen. Plasma acylcarnitine analysis suggested a fatty acid oxidation defect. Fatty acid oxidation disorders are inborn errors of metabolism documented in humans, but poorly described in dogs. Although neurologic signs have been described in humans with this group of diseases, descriptions of advanced imaging and histopathology are severely lacking. This report suggests that abnormalities of fatty acid metabolism may cause severe, bilateral gray matter necrosis and lipid accumulation in multiple organs including the skeletal muscles, liver, and kidneys. Veterinarians should be aware that fatty acid oxidation disorders, although potentially fatal, may be treatable. A timely definitive diagnosis is essential in guiding therapy.

  20. K-rasG12V transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis

    Institute of Scientific and Technical Information of China (English)

    Yumin Hu; Helene Pelicano; Paul J Chiao; Michael J Keating; Guillermo Garcia-Manero; Peng Huang; Weiqin Lu; Gang Chen; Peng Wang; Zhao Chen; Yan Zhou; Marcia Ogasawara; Dunyaporn Trachootham; Li Feng

    2012-01-01

    Increased aerobic glycolysis and oxidative stress are important features of cancer cell metabolism,but the underlying biochemical and molecular mechanisms remain elusive.Using a tetracycline inducible model,we show that activation of K-rasG12V causes mitochondrial dysfunction,leading to decreased respiration,elevated glycolysis,and increased generation of reactive oxygen species.The K-RAS protein is associated with mitochondria,and induces a rapid suppression of respiratory chain complex-I and a decrease in mitochondrial transmembrane potential by affecting the cyclosporin-sensitive permeability transition pore.Furthermore,pre-induction of K-rasG12V expression in vitro to allow metabolic adaptation to high glycolytic metabolism enhances the ability of the transformed cells to form tumor in vivo.Our study suggests that induction of mitochondrial dysfunction is an important mechanism by which K-rasG12V causes metabolic changes and ROS stress in cancer cells,and promotes tumor development.

  1. Metabolic control of resting hemispheric cerebral blood flow is oxidative, not glycolytic.

    Science.gov (United States)

    Powers, William J; Videen, Tom O; Markham, Joanne; Walter, Vonn; Perlmutter, Joel S

    2011-05-01

    Although the close regional coupling of resting cerebral blood flow (CBF) with both cerebral metabolic rate of oxygen (CMRO(2)) and cerebral metabolic rate of glucose (CMRglc) within individuals is well documented, there are few data regarding the coupling between whole brain flow and metabolism among different subjects. To investigate the metabolic control of resting whole brain CBF, we performed multivariate analysis of hemispheric CMRO(2), CMRglc, and other covariates as predictors of resting CBF among 23 normal humans. The univariate analysis showed that only CMRO(2) was a significant predictor of CBF. The final multivariate model contained two additional terms in addition to CMRO(2): arterial oxygen content and oxygen extraction fraction. Notably, arterial plasma glucose concentration and CMRglc were not included in the final model. Our data demonstrate that the metabolic factor controlling hemispheric CBF in the normal resting brain is CMRO(2) and that CMRglc does not make a contribution. Our findings provide evidence for compartmentalization of brain metabolism into a basal component in which CBF is coupled to oxygen metabolism and an activation component in which CBF is controlled by another mechanism.

  2. Effectiveness of exercise and protein supplementation intervention on body composition, functional fitness, and oxidative stress among elderly Malays with sarcopenia

    Directory of Open Access Journals (Sweden)

    Shahar S

    2013-10-01

    Full Text Available Suzana Shahar,1 Norshafarina Shari Kamaruddin,2 Manal Badrasawi,1 Noor Ibrahim Mohamed Sakian,3 Zahara Abd Manaf,1 Zaitun Yassin,4 Leonard Joseph51Dietetic Programme, 2Biomedical Programme, 3Occupational Therapy Programme, School of Healthcare Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, 4Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, 5Department of Physiotherapy, School of Healthcare Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, MalaysiaAbstract: Sarcopenia, characterized as muscle loss that occurs with aging, is a major health problem in an aging population, due to its implications on mobility, quality of life, and fall risk. Protein supplementation could improve the physical fitness by increasing protein anabolism, and exercise has a documented evidence of positive effect on functional status among the elderly. However, the combined effect of both protein supplementation and exercise has not been investigated among sarcopenic elderly in the Asian population. Thus, this study aimed to determine the effectiveness of exercise intervention and protein supplementation either alone or in combination for 12 weeks, on body composition, functional fitness, and oxidative stress among elderly Malays with sarcopenia. Sixty five sarcopenic elderly Malays aged 60-74 years were assigned to the control group, exercise group (ExG, protein supplementation group (PrG, or the combination of exercise and protein supplementation group. A significant interaction effect between body weight and body mass index (BMI was observed, with the PrG (-2.1% body weight, -1.8% BMI showing the highest reductions. Further, there was a decrease in % body fat (-4.5% and an increase in fat-free mass (kg (+5.7% in the ExG after 12 weeks (P < 0.05. The highest increments in lower and upper body strength were observed in the Pr

  3. Effects of long-term football training on the expression profile of genes involved in muscle oxidative metabolism.

    Science.gov (United States)

    Alfieri, A; Martone, D; Randers, M B; Labruna, G; Mancini, A; Nielsen, J J; Bangsbo, J; Krustrup, P; Buono, P

    2015-02-01

    We investigated whether long-term recreational football training affects the expression of health-related biochemical and molecular markers in healthy untrained subjects. Five untrained healthy men trained for 1 h 2.4 times/week for 12 weeks and 1.3 times/week for another 52 weeks. Blood samples and a muscle biopsy from the vastus lateralis were collected at T0 (pre intervention) and at T1 (post intervention). Gene expression was measured by RTqPCR on RNA extracted from muscle biopsies. The expression levels of the genes principally involved in energy metabolism (PPARγ, adiponectin, AMPKα1/α2, TFAM, NAMPT, PGC1α and SIRT1) were measured at T0 and T1. Up-regulation of PPARγ (p football training could be a useful tool to improve the expression of muscle molecular biomarkers that are correlated to oxidative metabolism in healthy males.

  4. Metabolic remodeling in chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    Jing WANG; Tao GUO

    2013-01-01

    Although the management of chronic heart failure (CHF) has made enormous progress over the past decades,CHF is still a tremendous medical and societal burden.Metabolic remodeling might play a crucial role in the pathophysiology of CHF.The characteristics and mechanisms of metabolic remodeling remained unclear,and the main hypothesis might include the changes in the availability of metabolic substrate and the decline of metabolic capability.In the early phases of the disease,metabolism shifts toward carbohydrate utilization from fatty acids (FAs) oxidation.Along with the progress of the disease,the increasing level of the hyperadrenergic state and insulin resistance cause the changes that shift back to a greater FA uptake and oxidation.In addition,a growing body of experimental and clinical evidence suggests that the improvement in the metabolic capability is likely to be more significant than the selection of the substrate.

  5. Metagenomic and biochemical characterizations of sulfur oxidation metabolism in uncultured large sausage-shaped bacterium in hot spring microbial mats.

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    Satoshi Tamazawa

    Full Text Available So-called "sulfur-turf" microbial mats in sulfide containing hot springs (55-70°C, pH 7.3-8.3 in Japan were dominated by a large sausage-shaped bacterium (LSSB that is closely related to the genus Sulfurihydrogenibium. Several previous reports proposed that the LSSB would be involved in sulfide oxidation in hot spring. However, the LSSB has not been isolated yet, thus there has been no clear evidence showing whether it possesses any genes and enzymes responsible for sulfide oxidation. To verify this, we investigated sulfide oxidation potential in the LSSB using a metagenomic approach and subsequent biochemical analysis. Genome fragments of the LSSB (a total of 3.7 Mb sequence including overlapping fragments were obtained from the metagenomic fosmid library constructed from genomic DNA of the sulfur-turf mats. The sequence annotation clearly revealed that the LSSB possesses sulfur oxidation-related genes coding sulfide dehydrogenase (SD, sulfide-quinone reductase and sulfite dehydrogenase. The gene encoding SD, the key enzyme for sulfide oxidation, was successfully cloned and heterologously expressed in Escherichia coli. The purified recombinant enzyme clearly showed SD activity with optimum temperature and pH of 60°C and 8.0, respectively, which were consistent with the environmental conditions in the hot spring where the sulfur-turf thrives. Furthermore, the affinity of SD to sulfide was relatively high, which also reflected the environment where the sulfide could be continuously supplied. This is the first report showing that the LSSB harbors sulfide oxidizing metabolism adapted to the hot spring environment and can be involved in sulfide oxidation in the sulfur-turf microbial mats.

  6. Evaluation of metabolic risk markers in polycystic ovary syndrome (PCOS). Adiponectin, ghrelin, leptin and body composition in hirsute PCOS patients and controls

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Andersen, Marianne; Hagen, Claus

    2006-01-01

    .4 to 1.7) microg/l, Pwaist circumference and BMI. During multiple regression analysis, testosterone correlated positively with adiponectin and negatively with ghrelin independent of BMI, WHR and total fat mass. CONCLUSION......OBJECTIVE: Polycystic ovary syndrome (PCOS) patients are abdominally obese and are at increased risk of developing the metabolic syndrome. Low adiponectin and ghrelin levels in PCOS patients could be caused by insulin resistance as well as high testosterone levels. DESIGN: Adiponectin and ghrelin...... of body composition including waist-hip-ratio (WHR), body mass index (BMI) and whole body dual-energy X-ray absorptiometry scan measures of body fat mass. Measurements of fasting levels of adiponectin, ghrelin, leptin, androgen status, oestradiol, lipid variables and insulin during follicular phase...

  7. Obesity Index That Better Predict Metabolic Syndrome: Body Mass Index, Waist Circumference, Waist Hip Ratio, or Waist Height Ratio

    Directory of Open Access Journals (Sweden)

    Abdulbari Bener

    2013-01-01

    Full Text Available Aim. The aim was to compare body mass index (BM