Sample records for alters liver glycogen

  1. Acrylamide alters glycogen content and enzyme activities in the liver of juvenile rat. (United States)

    Kovac, Renata; Rajkovic, Vesna; Koledin, Ivana; Matavulj, Milica


    Acrylamide (AA) is spontaneously formed in carbohydrate-rich food during high-temperature processing. It is neurotoxic and potentially cancer causing chemical. Its harmful effects on the liver, especially in a young organism, are still to be elucidated. The study aimed to examine main liver histology, its glycogen content and enzyme activities in juvenile rats treated with 25 or 50mg/kg bw of AA for 3 weeks. Liver samples were fixed in formalin, routinely processed for paraffin embedding, sectioning and histochemical staining. Examination of haematoxylin and eosin (H&E)-stained sections showed an increase in the volume of hepatocytes, their nuclei and cytoplasm in both AA-treated groups compared to the control. In Periodic acid-Schiff (PAS)-stained sections in low-dose group was noticed glycogen reduction, while in high-dose group was present its accumulation compared to the control, respectively. Serum analysis showed increased activity of aspartate aminotransferase (AST), and decreased activity of alanine aminotransferase (ALT) in both AA-treated groups, while the activity of alkaline phosphatase (ALP) was increased in low-dose, but decreased in high-dose group compared to the control, respectively. Present results suggest a prominent hepatotoxic potential of AA which might alter the microstructural features and functional status in hepatocytes of immature liver.

  2. Dysfunctional muscle and liver glycogen metabolism in mdx dystrophic mice.

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    David I Stapleton

    Full Text Available Duchenne muscular dystrophy (DMD is a severe, genetic muscle wasting disorder characterised by progressive muscle weakness. DMD is caused by mutations in the dystrophin (dmd gene resulting in very low levels or a complete absence of the dystrophin protein, a key structural element of muscle fibres which is responsible for the proper transmission of force. In the absence of dystrophin, muscle fibres become damaged easily during contraction resulting in their degeneration. DMD patients and mdx mice (an animal model of DMD exhibit altered metabolic disturbances that cannot be attributed to the loss of dystrophin directly. We tested the hypothesis that glycogen metabolism is defective in mdx dystrophic mice.Dystrophic mdx mice had increased skeletal muscle glycogen (79%, (P<0.01. Skeletal muscle glycogen synthesis is initiated by glycogenin, the expression of which was increased by 50% in mdx mice (P<0.0001. Glycogen synthase activity was 12% higher (P<0.05 but glycogen branching enzyme activity was 70% lower (P<0.01 in mdx compared with wild-type mice. The rate-limiting enzyme for glycogen breakdown, glycogen phosphorylase, had 62% lower activity (P<0.01 in mdx mice resulting from a 24% reduction in PKA activity (P<0.01. In mdx mice glycogen debranching enzyme expression was 50% higher (P<0.001 together with starch-binding domain protein 1 (219% higher; P<0.01. In addition, mdx mice were glucose intolerant (P<0.01 and had 30% less liver glycogen (P<0.05 compared with control mice. Subsequent analysis of the enzymes dysregulated in skeletal muscle glycogen metabolism in mdx mice identified reduced glycogenin protein expression (46% less; P<0.05 as a possible cause of this phenotype.We identified that mdx mice were glucose intolerant, and had increased skeletal muscle glycogen but reduced amounts of liver glycogen.

  3. High liver glycogen in hereditary fructose intolerance. (United States)

    Cain, A R; Ryman, B E


    A case of hereditary fructose intolerance is reported in a girl aged 2 years at the time of her death. She had apparently progressed normally until the age of 14 months. At 19 months she was admitted to hospital with failure to thrive, hepatomegaly, and superficial infections. Investigations revealed hypoglycaemia, persistent acidosis, aminoaciduria, and a high liver glycogen level which suggested that she had glycogen storage disease. There was also some evidence of malabsorption. At necropsy the liver enzyme estimations showed that fructose 1-phosphate aldolase activity was absent and that fructose 1,6-diphosphate aldolase activity was reduced. Hereditary fructose intolerance and glycogen storage disease have been confused in the past on clinical grounds, but a high liver glycogen level has not previously been reported in hereditary fructose intolerance.

  4. Activity of glycogen synthase and glycogen phosphorylase in normal and cirrhotic rat liver during glycogen synthesis from glucose or fructose. (United States)

    Bezborodkina, Natalia N; Chestnova, Anna Yu; Okovity, Sergey V; Kudryavtsev, Boris N


    Cirrhotic patients often demonstrate glucose intolerance, one of the possible causes being a decreased glycogen-synthesizing capacity of the liver. At the same time, information about the rates of glycogen synthesis in the cirrhotic liver is scanty and contradictory. We studied the dynamics of glycogen accumulation and the activity of glycogen synthase (GS) and glycogen phosphorylase (GP) in the course of 120min after per os administration of glucose or fructose to fasted rats with CCl4-cirrhosis or fasted normal rats. Blood serum and liver pieces were sampled for examinations. In the normal rat liver administration of glucose/fructose initiated a fast accumulation of glycogen, while in the cirrhotic liver glycogen was accumulated with a 20min delay and at a lower rate. In the normal liver GS activity rose sharply and GPa activity dropped in the beginning of glycogen synthesis, but 60min later a high synthesis rate was sustained at the background of a high GS and GPa activity. Contrariwise, in the cirrhotic liver glycogen was accumulated at the background of a decreased GS activity and a low GPa activity. Refeeding with fructose resulted in a faster increase in the GS activity in both the normal and the cirrhotic liver than refeeding with glucose. To conclude, the rate of glycogen synthesis in the cirrhotic liver is lower than in the normal one, the difference being probably associated with a low GS activity.

  5. Molecular Structure of Human-Liver Glycogen.

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    Bin Deng

    Full Text Available Glycogen is a highly branched glucose polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets.

  6. Molecular Structure of Human-Liver Glycogen (United States)

    Deng, Bin; Sullivan, Mitchell A.; Chen, Cheng; Li, Jialun; Powell, Prudence O.; Hu, Zhenxia; Gilbert, Robert G.


    Glycogen is a highly branched glucose polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets. PMID:26934359

  7. Reduced-size liver transplantation for glycogen storage disease

    Institute of Scientific and Technical Information of China (English)

    Hao-Feng Ji; Wei-Lin Wang; Yan Shen; Min Zhang; Ting-Bo Liang; Jian Wu; Xiao Xu; Sheng Yan; Shu-Sen Zheng


    BACKGROUND: Glycogen storage disease (GSD) is an inherited metabolic disorder in which the concentration and/or structure of glycogen in tissues is abnormal. Essentially, abnormalities in all known enzymes involved in the synthesis or degradation of glycogen and glucose have been found to cause some type of GSD. Liver and muscle have abundant quantities of glycogen and are the most common and seriously affected tissues. This study was to assess reduced-size liver transplantation for the treatment of GSD. METHODS: The clinical data from one case of GSD typeⅠ with hepatic adenoma was retrospectively analyzed. The clinical manifestations were hepatomegaly, delayed puberty, growth retardation, sexual immaturity, hypoglycemia, and lactic acidosis, which made the young female patient eligible for reduced-size liver transplantation. RESULTS: The patient recovered uneventfully with satisfactory outcome, including 12 cm growth in height and 5 kg increase in weight during 16 months after successful reduced-size liver transplantation. She has been living a normal life for 4 years so far. CONCLUSIONS: Reduced-size liver transplantation is an effective treatment for GSD with hepatomegaly and hepatic adenoma. Delayed puberty, growth retardation, hypoglycemia and lactic acidosis can be cured by surgery.

  8. Acid Hydrolysis and Molecular Density of Phytoglycogen and Liver Glycogen Helps Understand the Bonding in Glycogen α (Composite) Particles (United States)

    Powell, Prudence O.; Sullivan, Mitchell A.; Sheehy, Joshua J.; Schulz, Benjamin L.; Warren, Frederick J.; Gilbert, Robert G.


    Phytoglycogen (from certain mutant plants) and animal glycogen are highly branched glucose polymers with similarities in structural features and molecular size range. Both appear to form composite α particles from smaller β particles. The molecular size distribution of liver glycogen is bimodal, with distinct α and β components, while that of phytoglycogen is monomodal. This study aims to enhance our understanding of the nature of the link between liver-glycogen β particles resulting in the formation of large α particles. It examines the time evolution of the size distribution of these molecules during acid hydrolysis, and the size dependence of the molecular density of both glucans. The monomodal distribution of phytoglycogen decreases uniformly in time with hydrolysis, while with glycogen, the large particles degrade significantly more quickly. The size dependence of the molecular density shows qualitatively different shapes for these two types of molecules. The data, combined with a quantitative model for the evolution of the distribution during degradation, suggest that the bonding between β into α particles is different between phytoglycogen and liver glycogen, with the formation of a glycosidic linkage for phytoglycogen and a covalent or strong non-covalent linkage, most probably involving a protein, for glycogen as most likely. This finding is of importance for diabetes, where α-particle structure is impaired. PMID:25799321

  9. Acid hydrolysis and molecular density of phytoglycogen and liver glycogen helps understand the bonding in glycogen α (composite particles.

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    Prudence O Powell

    Full Text Available Phytoglycogen (from certain mutant plants and animal glycogen are highly branched glucose polymers with similarities in structural features and molecular size range. Both appear to form composite α particles from smaller β particles. The molecular size distribution of liver glycogen is bimodal, with distinct α and β components, while that of phytoglycogen is monomodal. This study aims to enhance our understanding of the nature of the link between liver-glycogen β particles resulting in the formation of large α particles. It examines the time evolution of the size distribution of these molecules during acid hydrolysis, and the size dependence of the molecular density of both glucans. The monomodal distribution of phytoglycogen decreases uniformly in time with hydrolysis, while with glycogen, the large particles degrade significantly more quickly. The size dependence of the molecular density shows qualitatively different shapes for these two types of molecules. The data, combined with a quantitative model for the evolution of the distribution during degradation, suggest that the bonding between β into α particles is different between phytoglycogen and liver glycogen, with the formation of a glycosidic linkage for phytoglycogen and a covalent or strong non-covalent linkage, most probably involving a protein, for glycogen as most likely. This finding is of importance for diabetes, where α-particle structure is impaired.

  10. Quantification of the glycogen cascade system: the ultrasensitive responses of liver glycogen synthase and muscle phosphorylase are due to distinctive regulatory designs

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    Venkatesh KV


    Full Text Available Abstract Background Signaling pathways include intricate networks of reversible covalent modification cycles. Such multicyclic enzyme cascades amplify the input stimulus, cause integration of multiple signals and exhibit sensitive output responses. Regulation of glycogen synthase and phosphorylase by reversible covalent modification cycles exemplifies signal transduction by enzyme cascades. Although this system for regulating glycogen synthesis and breakdown appears similar in all tissues, subtle differences have been identified. For example, phosphatase-1, a dephosphorylating enzyme of the system, is regulated quite differently in muscle and liver. Do these small differences in regulatory architecture affect the overall performance of the glycogen cascade in a specific tissue? We address this question by analyzing the regulatory structure of the glycogen cascade system in liver and muscle cells at steady state. Results The glycogen cascade system in liver and muscle cells was analyzed at steady state and the results were compared with literature data. We found that the cascade system exhibits highly sensitive switch-like responses to changes in cyclic AMP concentration and the outputs are surprisingly different in the two tissues. In muscle, glycogen phosphorylase is more sensitive than glycogen synthase to cyclic AMP, while the opposite is observed in liver. Furthermore, when the liver undergoes a transition from starved to fed-state, the futile cycle of simultaneous glycogen synthesis and degradation switches to reciprocal regulation. Under such a transition, different proportions of active glycogen synthase and phosphorylase can coexist due to the varying inhibition of glycogen-synthase phosphatase by active phosphorylase. Conclusion The highly sensitive responses of glycogen synthase in liver and phosphorylase in muscle to primary stimuli can be attributed to distinctive regulatory designs in the glycogen cascade system. The different

  11. Monitoring of liver glycogen synthesis in diabetic patients using carbon-13 MR spectroscopy

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    Tomiyasu, Moyoko [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba city, Chiba 263-8555 (Japan)], E-mail:; Obata, Takayuki [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba city, Chiba 263-8555 (Japan); Nishi, Yukio; Nakamoto, Hiromitsu [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba city, Chiba 263-8555 (Japan); Pharmaceutical Division, Japan Tobacco Inc., Tokyo (Japan); Nonaka, Hiroi [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba city, Chiba 263-8555 (Japan); Takayama, Yukihisa [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba city, Chiba 263-8555 (Japan); Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Autio, Joonas; Ikehira, Hiroo; Kanno, Iwao [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba city, Chiba 263-8555 (Japan)


    To investigate the relationship between liver glucose, glycogen, and plasma glucose in diabetic patients, in vivo liver carbon-13 magnetic resonance spectroscopy ({sup 13}C MRS) with a clinical 3.0 T MR system was performed. Subjects were healthy male volunteers (n = 5) and male type-2 diabetic patients (n = 5). Pre- and during oral glucose tolerance tests (OGTT), {sup 13}C MR spectra without proton decoupling were acquired in a monitoring period of over 6 h, and in total seven spectra were obtained from each subject. For OGTT, 75 g of glucose, including 5 g of [1-{sup 13}C]glucose, was administered. The MR signals of liver [1-{sup 13}C]glucose and glycogen were detected and their time-course changes were assessed in comparison with the plasma data obtained at screening. The correlations between the fasting plasma glucose level and liver glycogen/glucose rate (Spearman: {rho} = -0.68, p < 0.05, n = 10) and the fasting plasma glucose level and liver glycogen peak/fasting rate (Spearman: {rho} = -0.67, p < 0.05, n = 10) indicated that {sup 13}C MRS can perform noninvasive measurement of glycogen storage/degradation ability in the liver individually and can assist in tailor-made therapy for diabetes. In conclusion, {sup 13}C MRS has a potential to become a powerful tool in diagnosing diabetes multilaterally.

  12. Liver transplantation for glycogen storage disease types I, III, and IV

    NARCIS (Netherlands)

    Matern, D; Starzl, TE; Arnaout, W; Barnard, J; Bynon, JS; Dhawan, A; Emond, J; Haagsma, EB; Hug, G; Lachaux, A; Smit, GPA; Chen, YT


    Glycogen storage disease (GSD) types I, III, and IV can be associated with severe liver disease. The possible development of hepatocellular carcinoma and/or hepatic failure make these GSDs potential candidates for liver transplantation. Early diagnosis and initiation of effective dietary therapy hav

  13. Methodologies of tissue preservation and analysis of the glycogen content of the broiler chick liver. (United States)

    Bennett, L W; Keirs, R W; Peebles, E D; Gerard, P D


    The current study was performed to develop convenient, rapid, reliable, and pragmatic methodologies by which to harvest and preserve liver tissue glycogen and to analyze its levels within reasonable limits of quantification and with extended chromophore stability. Absorbance values decreased by 2 h and again by 24 h after preparation of the iodine-potassium iodide chromophore, whereas absorbance values of the phenol-sulfuric acid chromophore remained constant over the same time period. These absorbance trends for each chromophore followed full color development within 5 min after combining the analyte with the respective chromophore reagent. Use of the phenol-sulfuric acid reagent allowed for a 10-fold reduction in assay limits of detection and quantification when compared with the iodine-potassium iodide reagent. Furthermore, glycogen concentration-absorbance relationships were affected by the source (i.e., rabbit liver vs. bovine liver) of glycogen standards when the iodine-potassium iodide chromophore was used, but the source of the standards had no influence when the phenol-sulfuric acid chromophore was used. The indifference of the phenol-sulfuric acid method to the glycogen source, as exhibited by similar linear regressions of absorbance, may be attributed to actual determination of glucose subunit concentrations after complete glycogen hydrolysis by sulfuric acid. This is in contrast to the actual measurement of whole glycogen, which may exhibit source- or time-related molecular structural differences. The iodine-potassium iodide methodology is a test of whole glycogen concentrations; therefore, it may be influenced by glycogen structural differences. Liver tissue sample weight (between 0.16 and 0.36 g) and processing, which included mincing, immediate freezing, or refrigeration in 10% perchloric acid for 1 wk prior to tissue grinding, had no effect on glycogen concentrations that were analyzed by using the phenol-sulfuric acid reagent. These results

  14. Time sequence of changes in the responsiveness of glycogen breakdown to adrenergic agonists in perfused liver of rats with insulin-induced hypoglycemia

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    Vardanega-Peicher M.


    Full Text Available The time-course changes of the responsiveness of glycogen breakdown to a- and ß-adrenergic agonists during insulin-induced hypoglycemia (IIH were investigated. Blood glucose levels were decreased prior to the alteration in the hepatic responsiveness to adrenergic agonists. The activation of hepatic glucose production and glycogenolysis by phenylephrine (2 µM and isoproterenol (20 µM was decreased in IIH. The changes in the responsiveness of glycogen catabolism were first observed for isoproterenol and later for phenylephrine. Hepatic ß-adrenergic receptors showed a higher degree of adrenergic desensitization than did a-receptors. Liver glycogen synthase activity, glycogen content and the catabolic effect of dibutyryl cyclic AMP (the ß-receptor second messenger were not affected by IIH.

  15. [Noradrenaline and glycogen content and the activity of several enzymes of carbohydrate metabolism in normal, embryonic, and partly denervated livers and in hepatomas of the rat]. (United States)

    Iljin, S V; Shanigina, K I; Sydow, G; Parfhenova, N S


    The noradrenaline and glycogen contents as well as hexokinase, glucokinase and glucose-6-phosphatase activities were determined in normal, embryonic and partially denervated (bilateral dissection of the Nervus splanchnicus or Nervus vagus) rat liver and in two transplantable hepatomas. In embryonic liver and hepatomas a strong decrease or complete loss of noradrenaline and glycogen levels and glucokinase and glucose-6-phosphatase activities is demonstrable as compared to the livers of adult animals, while the hexokinase activity is enhanced. Following bilateral splanchnicotomy the glycogen content and hexokinase activity are enhanced; the glucose-6-phosphatase activity is reduced, and the liver does not contain any noradrenaline. Bilateral vagotomy causes decrease of the glycogen content, of the hexokinase and glucokinase activities and an enhancement of glucose-6-phosphatase activity. The results lend support to the idea of antagonistic action of the sympathetic and parasympathetic nervous systems upon several partial reactions of carbohydrate metabolism of liver. In addition, it can be assumed that the alterations of the carbohydrate metabolism demonstrable in hepatomas as compared to normal liver are not solely attributable to disturbance or breakdown of the nervous regulation.

  16. Lipid and glycogen contents in liver of high-yield dairy cows in peripartal period

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    Đoković Radojica


    Full Text Available Liver tissue samples were taken by biopsy from Holstein cows in advanced stages of gravidity and in early lactation for pathological-histological examinations. Lipid content in hepatocytes was determined using the stereometric method by calculating volume density, and of glycogen using semi-quantitative microscopic examination of sections stained according to the method of Best. Pathological-histological examinations of liver tissue samples in healthy animals, gravid or peripartal cows did not reveal lipid infiltration or cell degeneration, and hepatocytes were completely or partly filled with glycogen. In ketotic cows, pathological-histological examinations of liver tissue samples showed lipid infiltration and hepatocyte degeneration of different intensity. In only one ketotic cow, we determined a slight degree of lipid infiltration, there was a medium degree of lipid infiltration and degeneration in six cows, and three cows were found to have a grave form of fatty liver. The quantity of glycogen in hepatocytes is in negative correlation with the degree of lipid infiltration and degeneration. In severe cases of fatty liver, glycogen is completely absent from hepatocyte cytoplasm.

  17. Posthemorrhage glycogen and lactate metabolism in the liver: an experimental study with postprandial rats

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    Boija, P.O.; Nylander, G.; Suhaili, A.; Ware, J.


    Glycogen and lactate metabolism was studied in livers from three groups of postprandial rats sustaining 70 mm Hg hemorrhagic hypotension for variable periods, 60 min (60H group), 120 min (120H group), and nonbled controls. The donor livers were investigated after completed hemorrhage using an in vitro perfusion system with L-lactate as substrate, together with U-/sup 14/C-lactate. The residual glycogen stores were determined after perfusions. The incorporation of labelled lactate to glucose was increased in the 120H group by 66.7% and 116.8% compared to the 60H group and controls (p less than 0.01), but glycogenolysis was still the main source of glucose released in the 120H group. Glycogen formation from labelled lactate was 46.6% higher in the 120H group compared to controls (p less than 0.05) and lactate oxidation was decreased by 67.5% (p less than 0.05). The data suggest that hepatocytes are capable of rapid change from glycolysis to gluconeogenesis during hemorrhagic hypovolemia. However, energy-sparing glycogen breakdown is given priority over gluconeogenesis as long as glycogen remains available.

  18. Fructose effect to enhance liver glycogen deposition is due to inhibition of glycogenolysis

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    Youn, J.; Kaslow, H.; Bergman, R.


    The effect of fructose on glycogen degradation was examined by measuring flux of (/sup 14/C) from prelabeled glycogen in perfused rat livers. During 2 h refeeding of fasted rats hepatic glycogen was labeled by injection of (U /sup 14/C) galactose (0.1 mg and 0.02 of body weight). Refed livers were perfused for 30 min with glucose only (10 mM) and for 60 min with glucose (10 mM) without (n=5) or with fructose (1, 2, 10 mM; n=5 for each). With fructose, label production immediately declined and remained suppressed through the end of perfusion (P < 0.05). Suppression was dose-dependent: steady state label production was suppressed 45, 64, and 72% by 1, 2, and 10 mM fructose (P < 0.0001), without significant changes in glycogen synthase or phosphorylase. These results suggest the existence of allosteric inhibition of phosphorylase in the presence of fructose. Fructose 1-phosphate (F1P) accumulated in proportion to fructose (0.11 +/- 0.01 without fructose, 0.86 +/- 0.03, 1.81 +/- 0.18, and 8.23 +/- 0.6 of liver with 1, 2, and 10 mM fructose. Maximum inhibition of phosphorylase was 82%; FIP concentration for half inhibition was 0.57 of liver, well within the concentration of F1P attained in refeeding. Fructose enhances net glycogen synthesis in liver by suppressing glycogenolysis and the suppression is presumably caused by allosteric inhibition of phosphorylase by F1P.

  19. Dynamical changing pattems of glycogen and enzyme histochemical activities in rat liver graft undergoing warm ischemia injury

    Institute of Scientific and Technical Information of China (English)

    Xiao-Shun He; Yi Ma; Lin-Wei Wu; Jin-Lang Wu; Rui-De Hu; Gui-Hua Chen; Jie-Fu Huang


    AIM: To investigate the changing patterns of glycogen and enzyme histochemical activities in rat liver graft under a dif ferent warm ischemia time (WIT) and to predict the tolerant time limitation of the liver graft to warm ischemia injury.METHODS: The rats were randomized into five groups, WTT was 0, 15, 30, 45, 60 min, respectively, and histochemical staining of liver graft specimens was observed. The recovery changes of glycogen and enzyme histochemistry activities were measured respectively 6 and 24 h following liver graft implantation.RESULTS: The activities of succinic dehydrogenase, cytochrome oxidase, apyrase (Mg++-ATPase) and content of glycogen were decreased gradually after different WIT in a time-dependent manner. The changes were significant when WIT was over 30 min.CONCLUSION: Hepatic injury is reversible within 30 min of warm ischemia injury. Glycogen and enzyme histochemistry activities of liver grafts and their recovery potency after reperfusion may serve as criteria to evaluate the quality of liver grafts.

  20. Differences in glycogen, lipids, and enzymes in livers from rats flown on Cosmos 2044 (United States)

    Merrill, Alfred H., Jr.; Wang, Elaine; Laroque, Regina; Mullins, Richard E.; Morgan, Edward T.; Hargrove, James L.; Bonkovsky, Herbert L.; Popova, Irina A.


    Livers from rats flown aboard Cosmos 2044 were analyzed for protein, carbohydrate (glycogen), and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. The major differences between the flight group and the synchronous control were elevations in microsomal protein, liver glycogen content, tyrosine aminotransferase, and tryptophan oxygenase and reductions in sphingolipids and the rate-limiting enzyme of heme biosynthesis delta-aminolevulinic acid synthase. These results provide further evidence that spaceflight has pronounced and diverse effects on liver function; however, some of the results with samples from Cosmos 2044 differed notably from those from previous spaceflights. This may be due to conditions of spaceflight and/or the postflight recovery period for Cosmos 2044.

  1. Differences in glycogen, lipids, and enzymes in livers from rats flown on COSMOS 2044. (United States)

    Merrill, A H; Wang, E; LaRocque, R; Mullins, R E; Morgan, E T; Hargrove, J L; Bonkovsky, H L; Popova, I A


    Livers from rats flown aboard COSMOS 2044 were analyzed for protein, carbohydrate (glycogen), and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. The major differences between the flight group and the synchronous control were elevations in microsomal protein, liver glycogen content, tyrosine aminotransferase, and tryptophan oxygenase and reductions in sphingolipids and the rate-limiting enzyme of heme biosynthesis, delta-aminolevulinic acid synthase. These results provide further evidence that spaceflight has pronounced and diverse effects on liver function; however, some of the results with samples from COSMOS 2044 differed notably from those from previous spaceflights. This may be due to conditions of spaceflight and/or the postflight recovery period for COSMOS 2044.

  2. Muscle and liver glycogen, protein, and triglyceride in the rat. Effect of exercise and of the sympatho-adrenal system

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    Richter, E A; Sonne, B; Mikines, K J;


    in skeletal muscle was accompanied by increased breakdown of triglyceride and/or protein. Thus, the effect of exhausting swimming and of running on concentrations of glycogen, protein, and triglyceride in skeletal muscle and liver were studied in rats with and without deficiencies of the sympatho......-adrenal system. In control rats, both swimming and running decreased the concentration of glycogen in fast-twitch red and slow-twitch red muscle whereas concentrations of protein and triglyceride did not decrease. In the liver, swimming depleted glycogen stores but protein and triglyceride concentrations did...... not decrease. In exercising rats, muscle glycogen breakdown was impaired by adrenodemedullation and restored by infusion of epinephrine. However, impaired glycogen breakdown during exercise was not accompanied by a significant net breakdown of protein or triglyceride. Surgical sympathectomy of the muscles did...

  3. Histochemical Effects of “Verita WG” on Glycogen and Lipid Storage in Common Carp (Cyprinus carpio L. Liver

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    Elenka Georgieva


    Full Text Available We aimed in the present work is to study the effects of fosetyl-Al and fenamidone based fungicide (“Verita WG” on glycogen storage and expression of lipid droplets in common carp (Cyprinus carpio, L. liver. Concentrations of the test chemical were 30 mg/L, 38 mg/L and 50 mg/L under laboratory conditions. We used PAS-reaction for detection of glycogen storage and Sudan III staining for detection of lipid droplets in common carp hepatocytes. Hence, we found that the amount of glycogen and the fat storage in the liver increased proportionally with the increased fungicide concentrations. We also found conglomerates of accumulated glycogen in certain hepatocytes at all used concentrations. Overall, the results demonstrated enhanced glyconeogenesis and fat accumulation in the common carp liver, exposed to the test chemical.

  4. Aroclor 1254 disrupts liver glycogen metabolism and enhances acute stressor-mediated glycogenolysis in rainbow trout. (United States)

    Wiseman, Steve; Vijayan, Mathilakath M


    The objective of this study was to investigate the impact of short-term exposure to polychlorinated biphenyls on the acute stress response in rainbow trout. Fish were exposed to dietary Aroclor1254 (10mg kg(-1) body mass/day) for 3 days and then subjected to a 3-min handling disturbance and sampled over a 24h recovery after the stressor exposure. In the pre-stress fish, PCB exposure significantly elevated aryl hydrocarbon receptor (AhR) and cytochrome P4501A1 (Cyp1A1) mRNA abundance and Cyp1A protein expression confirming AhR activation. There was no significant effect of PCB on plasma cortisol and glucose levels, while plasma lactate levels were significantly elevated compared to the sham group. PCB exposure significantly elevated liver glycogen content and hexokinase activity, whereas lactate dehydrogenase activity was depressed. Short-term PCB exposure did not modify the acute stressor-induced plasma cortisol, glucose and lactate responses. Liver glycogen content dropped significantly after stressor exposure in the PCB group but not in the sham group. This was matched by a significantly higher liver LDH activity and a lower HK activity during recovery in the PCB group suggesting enhanced glycolytic capacity to fuel hepatic metabolism. Liver AhR, but not Cyp1A1, transcript levels were significantly reduced during recovery from handling stressor in the Aroclor fed fish. Collectively, this study demonstrates that short-term PCB exposure may impair the liver metabolic performance that is critical to cope with the enhanced energy demand associated with additional stressor exposure in rainbow trout.

  5. Effects of maternal starvation on some blood metabolites, liver glycogen, birth weight and survival of piglets. (United States)

    Ezekwe, M O


    Pregnant crossbred sows were assigned to three treatments during the third trimester of gestation for an evaluation of the effects of maternal starvation on fetal development and piglet survival. Two groups of sows were taken off feed (water and trace mineralized salt only) on days 93 and 107 of gestation, respectively; the third group was fed 1.82 kg of complete sow diet/day and served as the control. Litter size, gestation length and pig birth weight in the 7-day and 21-day starvation groups were not different from those in the control group (P less than .05). Liver weight was depressed (P greater than .05) among the 7-day and 21-day progeny. However, liver glycogen concentrations and total liver glycogen were unaffected. Maternal blood glucose decreased to a fasting but steady level, while free fatty acid (FFA) increased in the two starved groups. Blood glucose and FFA at birth were similar for all treatment groups; however, FFA increased in the progeny of sows in the 7-day (P greater than .05) and 21-day (P greater than .01) starvation groups at 48 hr of age. Blood glucose at 48 hr did not vary (P less than .05), but the control progeny showed a faster glucose utilization, suggesting a greater dependence on carbohydrate metabolism than in the progeny of starved dams. Survival rate at 72 hr of age was higher among 21-day (43.8%) and 7-day (37.5%) progeny than among control progeny (8.5%). The increased plasma FFA level observed with fasting in the progeny of starved dams might indicate a shift toward lipid metabolism, which would account for the improved survival observed among the progeny of treated dams.

  6. Brain glycogen

    DEFF Research Database (Denmark)

    Obel, Linea Lykke Frimodt; Müller, Margit S; Walls, Anne B


    activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms...... underlying glycogen metabolism. Based on (1) the compartmentation of the interconnected second messenger pathways controlling glycogen metabolism (calcium and cAMP), (2) alterations in the subcellular location of glycogen-associated enzymes and proteins induced by the metabolic status and (3) a sequential...

  7. Effect of diabetes on glycogen metabolism in rat retina. (United States)

    Sánchez-Chávez, Gustavo; Hernández-Berrones, Jethro; Luna-Ulloa, Luis Bernardo; Coffe, Víctor; Salceda, Rocío


    Glucose is the main fuel for energy metabolism in retina. The regulatory mechanisms that maintain glucose homeostasis in retina could include hormonal action. Retinopathy is one of the chemical manifestations of long-standing diabetes mellitus. In order to better understand the effect of hyperglycemia in retina, we studied glycogen content as well as glycogen synthase and phosphorylase activities in both normal and streptozotocin-induced diabetic rat retina and compared them with other tissues. Glycogen levels in normal rat retina are low (46 +/- 4.0 nmol glucosyl residues/mg protein). However, high specific activity of glycogen synthase was found in retina, indicating a substantial capacity for glycogen synthesis. In diabetic rats, glycogen synthase activity increased between 50% and 100% in retina, brain cortex and liver of diabetic rats, but only retina exhibited an increase in glycogen content. Although, total and phosphorylated glycogen synthase levels were similar in normal and diabetic retina, activation of glycogen synthase by glucose-6-P was remarkable increased. Glycogen phosphorylase activity decreased 50% in the liver of diabetic animals; it was not modified in the other tissues examined. We conclude that the increase in glycogen levels in diabetic retina was due to alterations in glycogen synthase regulation.

  8. Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887 (United States)

    Merrill, A. H. Jr; Hoel, M.; Wang, E.; Mullins, R. E.; Hargrove, J. L.; Jones, D. P.; Popova, I. A.; Merrill AH, J. r. (Principal Investigator)


    To determine the possible biochemical effects of prolonged weightlessness on liver function, samples of liver from rats that had flown aboard Cosmos 1887 were analyzed for protein, glycogen, and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. Among the parameters measured, the major differences were elevations in the glycogen content and hydroxymethylglutaryl-CoA (HMG-CoA) reductase activities for the rats flown on Cosmos 1887 and decreases in the amount of microsomal cytochrome P-450 and the activities of aniline hydroxylase and ethylmorphine N-demethylase, cytochrome P-450-dependent enzymes. These results support the earlier finding of differences in these parameters and suggest that altered hepatic function could be important during spaceflight and/or the postflight recovery period.

  9. Glutamate cysteine ligase – modulatory subunit knockout mouse shows normal insulin sensitivity but reduced liver glycogen storage.

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    Suzie eLavoie


    Full Text Available Glutathione (GSH deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO for the modulatory subunit of the glutamate cysteine ligase (GCLM, the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilisation following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

  10. Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

    KAUST Repository

    Lavoie, Suzie


    Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

  11. Responsiveness of glycogen breakdown to cyclic AMP in perfused liver from rats with insulin-induced hypoglycemia

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    M. Vardanega-Peicher


    Full Text Available The responsiveness of glycogen breakdown to cAMP was investigated in isolated perfused liver from male Wistar fed rats (200-220 g with insulin-induced hypoglycemia. The activation of glycogenolysis by 3 µM cAMP was decreased (P<0.05 in livers from rats with hypoglycemia induced by the administration of insulin or during the direct infusion of insulin into the isolated liver. The direct effect of insulin on glycogen catabolism promoted by 3 µM cAMP occurred as early as 3 min after starting insulin infusion. In contrast, the cAMP agonists resistant to phosphodiesterases, 8Br-cAMP and 6MB-cAMP, used at the same concentration as cAMP, i.e., 3 µM, did not modify the effect of insulin. The data suggest that the decreased hepatic responsiveness of glycogen breakdown during insulin-induced hypoglycemia is a direct effect of insulin decreasing the intracellular levels of cAMP.

  12. Virtual determination of liver and muscle glycogen obtained from fed rats and from 24-hour fasted rats

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    V.M.T.T. Trindidade et al


    Full Text Available Introduction: Glycogen is the storage polysaccharide of animals, composed by glucoseresidues forming a branched polymer. The liver glycogen metabolism and hepaticgluconeogenesis are important buffer systems of blood glucose in different physiological orpathological situations, such as, during a fast period. Fasting muscle glycogenolysis alsooccurs, however, the release of glucose into the bloodstream is negligible because themuscle doesn’t have the enzyme glucose-6-P phosphatase, which is present in the liver.Objectives: This panel presents a learning object, mediated by computer, which simulatesthe determination of liver and muscle glycogen obtained from fed rats and from 24-hourfasted rats Materials and Methods: At first, cartoons were planned in order to show themethodology procedures and biochemical fundamentals. The most representative imageswere selected, edited, organized in a scene menu and inserted into an animationdeveloped with the aid of the Adobe ® Flash 8 software. The validation of this object wasperformed by the students of Biochemistry I (Pharmacy-UFRGS from the secondsemester of 2009 until the second semester of 2013. Results and Discussion: Theanalysis of students' answers revealed that 83% of them attributed the excellence rate tothe navigation program, to the display format and to the learning help. Conclusion:Therefore, this learning object can be considered an adequate teaching resource as wellas an innovative support in the construction of theoretical and practical knowledge ofBiochemistry. Support: SEAD-UFRGSAvailable at:

  13. Cinnamon increases liver glycogen in an animal model of insulin resistance (United States)

    Cinnamon, and aqueous polyphenol extracts of cinnamon, improve insulin sensitivity in vitro, and in animal and human studies. Given the relationship between the glucose/insulin system and glycogen metabolism, the objective of this study was to determine the effects of cinnamon on glycogen synthesis...

  14. Ingestion of glucose or sucrose prevents liver but not muscle glycogen depletion during prolonged endurance-type exercise in trained cyclists. (United States)

    Gonzalez, Javier T; Fuchs, Cas J; Smith, Fiona E; Thelwall, Pete E; Taylor, Roy; Stevenson, Emma J; Trenell, Michael I; Cermak, Naomi M; van Loon, Luc J C


    The purpose of this study was to define the effect of glucose ingestion compared with sucrose ingestion on liver and muscle glycogen depletion during prolonged endurance-type exercise. Fourteen cyclists completed two 3-h bouts of cycling at 50% of peak power output while ingesting either glucose or sucrose at a rate of 1.7 g/min (102 g/h). Four cyclists performed an additional third test for reference in which only water was consumed. We employed (13)C magnetic resonance spectroscopy to determine liver and muscle glycogen concentrations before and after exercise. Expired breath was sampled during exercise to estimate whole body substrate use. After glucose and sucrose ingestion, liver glycogen levels did not show a significant decline after exercise (from 325 ± 168 to 345 ± 205 and 321 ± 177 to 348 ± 170 mmol/l, respectively; P > 0.05), with no differences between treatments. Muscle glycogen concentrations declined (from 101 ± 49 to 60 ± 34 and 114 ± 48 to 67 ± 34 mmol/l, respectively; P sucrose (2.03 ± 0.43 g/min) vs. glucose (1.66 ± 0.36 g/min; P sucrose ingestion prevent liver glycogen depletion during prolonged endurance-type exercise. Sucrose ingestion does not preserve liver glycogen concentrations more than glucose ingestion. However, sucrose ingestion does increase whole body carbohydrate utilization compared with glucose ingestion. This trial was registered at as NCT02110836.

  15. Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice (United States)

    Udoh, Uduak S.; Swain, Telisha M.; Filiano, Ashley N.; Gamble, Karen L.; Young, Martin E.


    Chronic ethanol consumption has been shown to significantly decrease hepatic glycogen content; however, the mechanisms responsible for this adverse metabolic effect are unknown. In this study, we examined the impact chronic ethanol consumption has on time-of-day-dependent oscillations (rhythms) in glycogen metabolism processes in the liver. For this, male C57BL/6J mice were fed either a control or ethanol-containing liquid diet for 5 wk, and livers were collected every 4 h for 24 h and analyzed for changes in various genes and proteins involved in hepatic glycogen metabolism. Glycogen displayed a robust diurnal rhythm in the livers of mice fed the control diet, with the peak occurring during the active (dark) period of the day. The diurnal glycogen rhythm was significantly altered in livers of ethanol-fed mice, with the glycogen peak shifted into the inactive (light) period and the overall content of glycogen decreased compared with controls. Chronic ethanol consumption further disrupted diurnal rhythms in gene expression (glycogen synthase 1 and 2, glycogenin, glucokinase, protein targeting to glycogen, and pyruvate kinase), total and phosphorylated glycogen synthase protein, and enzyme activities of glycogen synthase and glycogen phosphorylase, the rate-limiting enzymes of glycogen metabolism. In summary, these results show for the first time that chronic ethanol consumption disrupts diurnal rhythms in hepatic glycogen metabolism at the gene and protein level. Chronic ethanol-induced disruption in these daily rhythms likely contributes to glycogen depletion and disruption of hepatic energy homeostasis, a recognized risk factor in the etiology of alcoholic liver disease. PMID:25857999

  16. A metabolic link between mitochondrial ATP synthesis and liver glycogen metabolism: NMR study in rats re-fed with butyrate and/or glucose

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    Beauvieux Marie-Christine


    Full Text Available Abstract Background Butyrate, end-product of intestinal fermentation, is known to impair oxidative phosphorylation in rat liver and could disturb glycogen synthesis depending on the ATP supplied by mitochondrial oxidative phosphorylation and cytosolic glycolysis. Methods In 48 hr-fasting rats, hepatic changes of glycogen and total ATP contents and unidirectional flux of mitochondrial ATP synthesis were evaluated by ex vivo 31P NMR immediately after perfusion and isolation of liver, from 0 to 10 hours after force-feeding with (butyrate 1.90 mg + glucose 14.0 mg.g-1 body weight or isocaloric glucose (18.2 mg.g-1 bw; measurements reflected in vivo situation at each time of liver excision. The contribution of energetic metabolism to glycogen metabolism was estimated. Results A net linear flux of glycogen synthesis (~11.10 ± 0.60 μmol glucosyl units.h-1.g-1 liver wet weight occurred until the 6th hr post-feeding in both groups, whereas butyrate delayed it until the 8th hr. A linear correlation between total ATP and glycogen contents was obtained (r2 = 0.99 only during net glycogen synthesis. Mitochondrial ATP turnover, calculated after specific inhibition of glycolysis, was stable (~0.70 ± 0.25 μmol.min-1.g-1 liver ww during the first two hr whatever the force-feeding, and increased transiently about two-fold at the 3rd hr in glucose. Butyrate delayed the transient increase (1.80 ± 0.33 μmol.min-1.g-1 liver ww to the 6th hr post-feeding. Net glycogenolysis always appeared after the 8th hr, whereas flux of mitochondrial ATP synthesis returned to near basal level (0.91 ± 0.19 μmol.min-1.g-1 liver ww. Conclusion In liver from 48 hr-starved rats, the energy need for net glycogen synthesis from exogenous glucose corresponds to ~50% of basal mitochondrial ATP turnover. The evidence of a late and transient increase in mitochondrial ATP turnover reflects an energetic need, probably linked to a glycogen cycling. Butyrate, known to reduce oxidative

  17. Liver Fibrosis and Altered Matrix Synthesis

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    Katrin Neubauer


    Full Text Available Liver fibrosis represents the uniform response of liver to toxic, infectious or metabolic agents. The process leading to liver fibrosis resembles the process of wound healing, including the three phases following tissue injury: inflammation, synthesis of collagenous and noncollagenous extracellular matrix components, and tissue remodelling (scar formation. While a single liver tissue injury can be followed by an almost complete restitution ad integrum, the persistence of the original damaging noxa results in tissue damage. During the establishment of liver fibrosis, the basement membrane components collagen type IV, entactin and laminin increase and form a basement membrane-like structure within the space of Disse. The number of endothelial fenestrae of the sinusoids decreases. These changes of the sinusoids are called 'capillarization' because the altered structure of the sinusoids resembles that of capillaries. At the cellular level, origin of liver fibrogenesis is initiated by the damage of hepatocytes, resulting in the recruitment of inflammatory cells and platelets, and activation of Kupffer cells, with subsequent release of cytokines and growth factors. The hepatic stellate cells seem to be the primary target cells for these inflammatory stimuli, because during fibrogenesis, they undergo an activation process to a myofibroblast-like cell, which represents the major matrix-producing cell. Based on this pathophysiological mechanism, therapeutic methods are developed to inhibit matrix synthesis or stimulate matrix degradation. A number of substances are currently being tested that either neutralize fibrogenic stimuli and prevent the activation of hepatic stellate cells, or directly modulate the matrix metabolism. However, until now, the elimination of the hepatotoxins has been the sole therapeutic concept available for the treatment of liver fibrogenesis in humans.

  18. Early alterations in soleus GLUT-4, glucose transport, and glycogen in voluntary running rats (United States)

    Henriksen, Erik J.; Halseth, Amy E.


    Voluntary wheel running (WR) by juvenile female rats was used as a noninterventional model of soleus muscle functional overload to study the regulation of insulin-stimulated glucose transport activity by the glucose transporter (GLUT-4 isoform) protein level and glycogen concentration. Soleus total protein content was significantly greater (+18%;P greater than 0.05) than in age-matched controls after 1 wk of WR, and this hypertrophic response continued in weeks 2-4 (+24-32%). GLUT-4 protein was 39% greater than in controls in 1-wk WR soleus, and this adaptation was accompanied by a similar increase in in vitro insulin-stimulated glucose transport activity(+29%). After 2 and 4 wk of WR, however, insulin-stimulated glucose transport activity had returned to control levels, despite a continued elevation (+25-28%) of GLUT-4 protein. At these two time points, glycogen concentration was significantly enhanced in WR soleus (+21-42%), which coincided with significant reductions in glycogen synthase activity ratios (-23 to-41%). These results indicate that, in this model of soleus muscle functional overload, the GLUT-4 protein level may initially regulate insulin-stimulated glucose transport activity in the absence of changes in other modifying factors. However,this regulation of glucose transport activity by GLUT-4 protein may be subsequently overridden by elevated glycogen concentration.

  19. Glycogen levels and energy status of the liver of fasting rats with diabetes types 1 and 2

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    Denise Silva de Oliveira


    Full Text Available Glycogen levels and the energy status of livers from fasting rats with diabetes types 1 and 2 were measured. After a 24 h fast, the hepatic glycogen levels of rats with diabetes1 and diabetes2 were, 18.7 and 2.6 times higher, respectively, than those of livers from the normal rats. In diabetes1 rats, the glycogen levels decreased when the fasting period was extended to 48 and 72 h. The opposite occurred with the control and diabetes2 rats. Consistently, glucose release by the perfused livers from diabetes1 rats was considerably higher during at least 60 minutes after initiating perfusion. The hepatic ATP content of diabetes1 rats was similar to that of the control rats; in diabetes2 rats, the hepatic ATP content was increased. It could be concluded that regulation of glycogen deposition and degradation in rats with diabetes1 differed markedly from that of rats with diabetes2 which, in turn, behaved similarly to normal healthy rats.Teores de glicogênio e os estados energéticos de fígados de ratos com diabete dos tipos 1 e 2 foram medidos. Após um jejum de 24 horas os teores de glicogênio de ratos com diabete1 e diabete2 foram, respectivamente 18,7 e 2,6 vezes superiores àqueles de fígados de animais controle. Em ratos com diabete1 o conteúdo de glicogênio diminuiu quando o período de jejum foi prolongado para 48 e 72 horas. O oposto ocorreu em ratos controle e ratos com diabete2. Consistentemente, a liberação de glicose por fígados em perfusão isolada obtidos de ratos com diabete1 foi consideravelmente maior durante ao menos 60 minutos após o início da perfusão. O conteúdo hepático de ATP de ratos com diabete1 foi similar àquele de ratos controle; em ratos com diabete2 o conteúdo hepático de ATP foi maior. Pode-se concluir que a regulação da deposição e degradação do glicogênio em ratos com diabete1 difere marcadamente daquela de ratos com diabete2, os quais, por seu turno, comportam-se similarmente a ratos normais e

  20. Single valproic acid treatment inhibits glycogen and RNA ribose turnover while disrupting glucose-derived cholesterol synthesis in liver as revealed by the [U-C(6)]-d-glucose tracer in mice. (United States)

    Beger, Richard D; Hansen, Deborah K; Schnackenberg, Laura K; Cross, Brandie M; Fatollahi, Javad J; Lagunero, F Tracy; Sarnyai, Zoltan; Boros, Laszlo G


    Previous genetic and proteomic studies identified altered activity of various enzymes such as those of fatty acid metabolism and glycogen synthesis after a single toxic dose of valproic acid (VPA) in rats. In this study, we demonstrate the effect of VPA on metabolite synthesis flux rates and the possible use of abnormal (13)C labeled glucose-derived metabolites in plasma or urine as early markers of toxicity. Female CD-1 mice were injected subcutaneously with saline or 600 mg/kg) VPA. Twelve hours later, the mice were injected with an intraperitoneal load of 1 g/kg [U-(13)C]-d-glucose. (13)C isotopomers of glycogen glucose and RNA ribose in liver, kidney and brain tissue, as well as glucose disposal via cholesterol and glucose in the plasma and urine were determined. The levels of all of the positional (13)C isotopomers of glucose were similar in plasma, suggesting that a single VPA dose does not disturb glucose absorption, uptake or hepatic glucose metabolism. Three-hour urine samples showed an increase in the injected tracer indicating a decreased glucose re-absorption via kidney tubules. (13)C labeled glucose deposited as liver glycogen or as ribose of RNA were decreased by VPA treatment; incorporation of (13)C via acetyl-CoA into plasma cholesterol was significantly lower at 60 min. The severe decreases in glucose-derived carbon flux into plasma and kidney-bound cholesterol, liver glycogen and RNA ribose synthesis, as well as decreased glucose re-absorption and an increased disposal via urine all serve as early flux markers of VPA-induced adverse metabolic effects in the host.

  1. Intraorgan differences of blood flow, oxygen supply and glycogen content in the multilobular liver of normal and hemorrhagic rats. (United States)

    Metzger, H P; Schywalsky, M


    In order to characterize intraorgan differences in blood supply of the rat liver, hepatic blood flow (HBF), surface oxygen tension (sPO2) and glycogen content of the largest and smallest lobi have been determined for normal and hemorrhagic rats (N = 68) in ketamin-xylazine anesthesia. 1. Mean HBF +/- SD of lobus sinister measured 1.07 +/- 0.23 ml/g min (n = 119 determinations, N = 9 rats); HBF of lob. caudatus dexter showed a left-shifted histogram (mean value = 0.77 ml/g.min, median = 0.72 ml/g.min, modul = 0.63 ml/g.min, p less than 0.005). 2. Mean sPO2 +/- SD of lob. sin. measured 23 +/- 6.8 mm Hg (n = 168, N = 16). The histograms of lob. caudat. dext. and sin. were left-shifted (mean value of l.c.d. = 9 mm Hg, median = 4 mm Hg, modul = 0 mm Hg, mean value of l.c.s. = 16 mm Hg, median = 17 mm Hg, modul = 0 mm Hg). Under hemorrhage sPO2 became almost zero in 91% of the measurements. 3. In response to an arterial bolus of fluorescence stained gamma-globulins, spreading of the dye showed a pronounced front and marked periportal area within lob. sin., while an irregular convective front and a much smaller area were detected within both of the lobi caudati. Under hemorrhage, intersinusoidal staining and undefined, irregular contours were observed within all lobes. 4. Compared with lob. sin. preferential glycogen depletion and partial centrilobular necrosis were detected within both of the lob. caudati while under hemorrhage the glycogen stores were empty and severe group necroses have been observed especially within the small lobi. From the data it is concluded that in comparison to lob. sin. an insufficient supply and pronounced vulnerability against hepatic ischemia exists within the small lobi caudati.

  2. Decreased response to cAMP in the glucose and glycogen catabolism in perfused livers of Walker-256 tumor-bearing rats. (United States)

    de Morais, Hely; Cassola, Priscila; Moreira, Carolina Campos Lima; Bôas, Suéllen Kathiane Fernandes Vilas; Borba-Murad, Glaucia Regina; Bazotte, Roberto Barbosa; de Souza, Helenir Medri


    The hepatic response to cyclic adenosine monophosphate (cAMP) and N6-monobutyryl-cAMP (N6-MB-cAMP) in the glucose and glycogen catabolism and hepatic glycogen levels were evaluated in Walker-256 tumor-bearing rats, on days 5 (WK5), 8 (WK8), and 11 (WK11) after the implantation of tumor. Rats without tumor fed ad libitum (fed control rats) or that received the same daily amount of food ingested by anorexics tumor-bearing rats (pair-fed control rats) or 24 h fasted (fasted control rats) were used as controls. Glucose and glycogen catabolism were measured in perfused liver. Hepatic glycogen levels were lower (p catabolism was lower (p catabolism, under condition of depletion of hepatic glycogen (24 h fast), was lower (p catabolism was lower (p catabolism in various stages of tumor development (days 5, 8 and 11), which was probably not due to the lower hepatic glycogen levels nor due to the increased activity of PDE3B.

  3. Hemorheological Alteration in Patients Clinically Diagnosed with Chronic Liver Diseases. (United States)

    Jang, Bohyun; Han, Ji Won; Sung, Pil Soo; Jang, Jeong Won; Bae, Si Hyun; Choi, Jong Young; Cho, Young I; Yoon, Seung Kew


    Since liver function is changed by chronic liver diseases, chronic liver disease can lead to different hemorheological alterations during the course of the progression. This study aims to compare alterations in whole blood viscosity in patients with chronic liver disease, focusing on the gender effect. Chronic liver diseases were classified into three categories by patient's history, serologic markers, and radiologic findings: nonalcoholic fatty liver disease (NAFLD) (n = 63), chronic viral hepatitis B and C (n = 50), and liver cirrhosis (LC) (n = 35). Whole blood viscosity was measured by automated scanning capillary tube viscometer, while liver stiffness was measured by transient elastography using FibroScan®. Both systolic and diastolic whole blood viscosities were significantly lower in patients with LC than NAFLD and chronic viral hepatitis (P chronic viral hepatitis. Our data suggest that whole blood viscosity test can become a useful tool for classifying chronic liver disease and determining the prognosis for different types of chronic liver diseases.

  4. Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

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    Andrew Specht


    Full Text Available A canine model of Glycogen storage disease type Ia (GSDIa is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

  5. Time-dependent effect of ethanol force-feeding on glycogen repletion: NMR evidence of a link with ATP turnover in rat liver. (United States)

    Beauvieux, Marie-Christine; Gin, Henri; Roumes, Hélène; Kassem, Cendrella; Couzigou, Patrice; Gallis, Jean-Louis


    The purpose was to study the hepatic effects of low-dose ethanol on the links between ATP and glycogen production. Fasted male Wistar rats received a single force-feeding of glucose plus ethanol or isocaloric glucose. At different times after force-feeding (0-10 h), glycogen repletion and ATP characteristics (content, apparent catalytic time constant, mitochondrial turnover) were monitored by (13)C- or (31)P-nuclear magnetic resonance (NMR) in perfused and isolated liver. In vivo glycogen repletion after force-feeding was slower after glucose plus ethanol vs. glucose (12.04 ± 0.68 and 8.50 ± 0.86 μmol/h/g liver wet weight [ww], respectively), reaching a maximum at the 6th hour. From the 3rd to the 8th hour, glycogen content was lower after glucose plus ethanol vs. glucose. After glucose plus ethanol, the correlation between glycogen and ATP contents presented two linear steps: before and after the 3rd hour (30 and 102 μmol glycogen/g ww per μmol ATP/g ww, respectively, the latter being near the single step measured in glucose). After glucose plus ethanol, ATP turnover remained stable for 2 h, was 3-fold higher from the 3rd hour to the 8th hour, and was higher than after glucose (2.59 ± 0.45 and 1.39 ± 0.19 μmol/min/g ww, respectively). In the 1st hour, glucose plus ethanol induced a transient acidosis and an increase in the phosphomonoesters signal. In conclusion, after ethanol consumption, a large part of the ATP production was diverted to redox re-equilibrium during the first 2 h, thereby reducing the glycogen synthesis. Thereafter, the maintenance of a large oxidative phosphorylation allowed the stimulation of glycogen synthesis requiring ATP.

  6. Effect of heavy metals on the level of vitamin E, total lipid and glycogen reserves in the liver of common carp (Cyprinus carpio L.

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    Vinodhini Rajamanickam


    Full Text Available The aim of this study is to examine some changes in the biochemical profile of the liver tissue of common carp (Cyprinus carpio L. exposed to a sublethal concentration of heavy metal mixture (cadmium, chromium, nickel and lead. The biochemical profile, specifically glycogen, total lipid and vitamin E content in the liver tissue was examined and compared to that of the control group. The exposed group showed a marked decline in glycogen and vitamin E reserves. Conversely an increase in total lipid in comparison to control was observed. The result reflects the sensitivity of these biochemical parameters to the effects of sublethal levels of combined heavy metals for this the widely consumed freshwater fish.

  7. Metformin protects the skeletal muscle glycogen stores against alterations inherent to functional limitation

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    Paula Lima Bosi


    Full Text Available The aim of this study was to evaluate the glycogen content (GC of the rat hind limb muscles submitted to joint immobilization, either associated with metformin treatment (M, 1, or not. In the metformin group, there was a significant increase in the GC (soleus - S 65% , white gastrocnemius - WG 30.5%, red gastrocnemius- RG31.7%, extensor digitorum longus - EDL 44%, tibialis anterior- TA 77.4%. The immobilization significantly reduced the GC (S 31.6%, WG 56.6%, RG 39.1%, ELD 41.7%, TA 45.2% and weight (S 34.2% and ELD 27%, whereas in the group immobilized with the metformin, there was an increase in the GC of all the muscles (S 177%, WG 290%, RG 172%,ELD 47%, TA 217%, in addition to minimizing the weight loss of S (29.6% and ELD (27.8%.O objetivo deste estudo foi avaliar o conteúdo de glicogênio (GLI da musculatura da pata posterior de ratos submetidos à imobilização articular, associado ou não ao tratamento com metformina (MET, 1,4 -1 no período de sete dias. No grupo metformina, houve elevação significativa nas RG (65% no sóleo - S, 30.5% no gastrocnêmio branco - GB, 31.7% no gastrocnêmio vermelho - GV , 44% no extensor longo dos dedos - EDL e de 77.4% no tibial anterior - TA . A imobilização reduziu significativamente as RG (S 31,6%, GB 56,6%, GV 39,1%, ELD 41,7%, TA 45,2% e peso (S 34,2% e ELD 27%, já no grupo imobilizado com metformina houve o aumento das RG de todos os músculos (S 177%, GB 290%, GV 172%,EDL 47%, TA 217%, além de minimizar a perda de peso do S (29,6% e ELD (27,8%.

  8. Effects of /sup 45/Ca on murine skeletal muscle. 1. Alterations of glycogen, phosphorylase and phosphohexose isomerase levels

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    Asotra, K.; Katoch, S.S.; Krishan, K.; Malhotra, R.K. (Himachal Pradesh Univ., Simla (India). Dept. of Bio-sciences)


    Adult Swiss albino mice weighing 16+-1 g were injected with 3.7x10/sup 4/ Bq and 7.4x10/sup 4/ Bq/g body weight of /sup 45/Ca. Mice of both dose groups were autopsied on days 1, 3, 5, 7, 14 and 28 after /sup 45/Ca administration. Diaphragm and gastrocnemius in the /sup 45/Ca-treated and normal mice were analyzed for quantitation of glycogen as well as bioassay of phosphorylase and phosphohexose isomerase activities. Internal irradiation with the two doses of /sup 45/Ca resulted in glycogen accumulation in both the muscles. /sup 45/Ca-treated diaphragm showed greater radioresponse but a slower recovery than gastrocnemius with respect to glycogen accumulation. A decline in the rates of glycogenolysis and glycolysis indicated by decreased phosphorylase and phosphohexose isomerase activities appeared to be responsible for glycogen accumulation in skeletal muscle on account of /sup 45/Ca treatment.

  9. Obesity and type 2 diabetes in rats are associated with altered brain glycogen and amino-acid homeostasis

    DEFF Research Database (Denmark)

    Sickmann, Helle M; Waagepetersen, Helle S; Schousboe, Arne


    Obesity and type 2 diabetes have reached epidemic proportions; however, scarce information about how these metabolic syndromes influence brain energy and neurotransmitter homeostasis exist. The objective of this study was to elucidate how brain glycogen and neurotransmitter homeostasis are affect...

  10. Neuroinflammation and neurological alterations in chronic liver diseases

    Directory of Open Access Journals (Sweden)

    Carmina Montoliu


    Full Text Available Several million people with chronic liver diseases (cirrhosis, hepatitis show neurological alterations, named hepatic encephalopathy (HE with cognitive and motor alterations that impair quality of life and reduces life span. Inflammation acts synergistically with hyperammonemia to induce cognitive and motor alterations in patients with chronic liver disease and minimal hepatic encephalopathy (MHE. Previous studies in animal models have suggested that neuroinflammation is a major player in HE. This would also be the case in patients with liver cirrhosis or hepatitis C with HE. Rats with MHE show microglial activation and neuroinflammation that is associated with cognitive impairment and hypokinesia. The anti-inflammatory drug ibuprofen reduces microglial activation and neuroinflammation and restores cognitive and motor functions in rats with MHE. Chronic hyperammonemia per se induces neuroinflammation. Both peripheral inflammation and hyperammonemia would contribute to neuroinflammation in chronic liver failure. Therefore, neuroinflammation may be a key therapeutic target to improve the cognitive and motor alterations in MHE and overt HE. Identifying new targets to reduce neuroinflammation in MHE without inducing secondary effects would serve to develop new therapeutic tools to reverse the cognitive and motor alterations in patients with HE associated with chronic liver diseases.

  11. Quantifying hepatic glycogen synthesis by direct and indirect pathways in rats under normal ad libitum feeding conditions. (United States)

    Soares, Ana F; Viega, Francisco J; Carvalho, Rui A; Jones, John G


    Hepatic glycogen synthesis from intact hexose (direct pathway) relative to that from gluconeogenic precursors (indirect pathway) was quantified in ad libitum-fed rats. Following (2)H(2)O administration and overnight feeding, the livers were removed and glycogen (2)H-enrichment was measured by (2)H NMR. Six controls and six rats rendered hyperglycemic by streptozotocin (STZ; fasting blood glucose = 385 +/- 31 mg/dl) were studied. The indirect pathway contribution, estimated as glycogen hydrogen 5 relative to hydrogen 2 enrichment, was 54% +/- 4% for control rats-similar to values from healthy, meal-fed humans. In STZ-treated rats, the indirect pathway contribution was significantly higher (68% +/- 4%, P diabetic (T1D) patients. In conclusion, sources of hepatic glycogen synthesis in rats during ad libitum nocturnal feeding were quantified by analysis of glycogen enrichment from (2)H(2)O. STZ caused alterations resembling the pathophysiology of hepatic glycogen synthesis in T1D patients.

  12. Individual CLA Isomers, c9t11 and t10c12, Prevent Excess Liver Glycogen Storage and Inhibit Lipogenic Genes Expression Induced by High-Fructose Diet in Rats. (United States)

    Maslak, Edyta; Buczek, Elzbieta; Szumny, Antoni; Szczepnski, Wojciech; Franczyk-Zarow, Magdalena; Kopec, Aneta; Chlopicki, Stefan; Leszczynska, Teresa; Kostogrys, Renata B


    This study assessed the effects of individual conjugated linoleic acid isomers, c9t11-CLA and t10c12-CLA, on nonalcoholic fatty liver disease (NAFLD) and systemic endothelial dysfunction in rats fed for four weeks with control or high-fructose diet. The high-fructose diet hampered body weight gain (without influencing food intake), increased liver weight and glycogen storage in hepatocytes, upregulated expression of fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD-1), and increased saturated fatty acid (SFA) content in the liver. Both CLA isomers prevented excessive accumulation of glycogen in the liver. Specifically, t10c12-CLA decreased concentration of serum triacylglycerols and LDL + VLDL cholesterol, increased HDL cholesterol, and affected liver lipid content and fatty acid composition by downregulation of liver SCD-1 and FAS expression. In turn, the c9t11-CLA decreased LDL+VLDL cholesterol in the control group and downregulated liver expression of FAS without significant effects on liver weight, lipid content, and fatty acid composition. In summary, feeding rats with a high-fructose diet resulted in increased liver glycogen storage, indicating the induction of gluconeogenesis despite simultaneous upregulation of genes involved in de novo lipogenesis. Although both CLA isomers (c9t11 and t10c12) display hepatoprotective activity, the hypolipemic action of the t10c12-CLA isomer proved to be more pronounced than that of c9t11-CLA.

  13. Proteome analysis of fatty liver in feed-deprived dairy cows reveals interaction of fuel sensing, calcium, fatty acid, and glycogen metabolism. (United States)

    Kuhla, Björn; Albrecht, Dirk; Kuhla, Siegfried; Metges, Cornelia C


    The liver of dairy cows is involved in signaling the current hepatic metabolic state to the brain via metabolites and nerval afferents to control and adjust feed intake. Feed deprivation may result in mobilization of body reserves favoring hepatic steatosis. While the overall metabolic changes are well characterized, specific regulatory mechanisms are not readily understood. To identify molecular events associated with metabolic adaptation and the control of energy homeostasis, liver specimens from six ad libitum-fed and six feed-deprived cows were analyzed for selected metabolites, for the activation of AMP kinase, and for regulatory/regulated proteins using two-dimensional gel electrophoresis and MALDI-TOF-MS. Feed deprivation increased total liver fat and the calcium content, as well as augmented AMPK phosphorylation, while it decreased the contents of protein, glucose, glycogen, and cholesterol when expressed as a percentage of dry matter. Among 34 differentially expressed proteins identified, we found downregulation of proteins associated with fatty acid oxidation, glycolysis, electron transfer, protein degradation, and antigen processing, as well as cytoskeletal rearrangement. Proteins upregulated after feed deprivation included enzymes of the urea cycle, fatty acid or cholesterol transport proteins, an inhibitor of glycolysis, and previously unknown changes in calcium signaling network. Direct correlation was found between expression of glycolytic enzymes and glucose/glycogen content, whereas inverse correlation exists between expression of beta-oxidative enzymes and total liver fat content. In conclusion, the regulatory response of identified proteins may help to explain development and consequences of hepatic lipidosis but also offers novel candidates potentially involved in signaling for maintaining energy homeostasis.

  14. Brain glycogen – new perspectives on its metabolic function and regulation at the subcellular level

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    Linea Frimodt Obel


    Full Text Available Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g. liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia. In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies – it is a highly dynamic molecule with versatile implications in brain function, i.e. synaptic activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms underlying glycogen metabolism. Based on i the compartmentation of the interconnected second messenger pathways controlling glycogen metabolism (calcium and cAMP, ii alterations in the subcellular location of glycogen-associated enzymes and proteins induced by the metabolic status and iii a sequential component in the intermolecular mechanisms of glycogen metabolism, we suggest that glycogen metabolism in astrocytes is compartmentalized at the subcellular level. As a consequence, the meaning and importance of conventional terms used to describe glycogen metabolism (e.g. turnover is challenged. Overall, this review represents an overview of contemporary knowledge about brain glycogen and its metabolism and function. However, it also has a sharp focus on what we do not know, which is perhaps even more important for the future quest of uncovering the roles of glycogen in brain physiology and pathology.


    Directory of Open Access Journals (Sweden)

    Petar Batsalov


    Full Text Available The biochemical indexes “glycogen in liver” and “ketones in blood” of 0-72 hours feed deprived (according to methods for balanced experiments Japanese quails with and without energy additives were determined. There were 2 groups of birds- 1-st without energy supplement, 2-nd- fed with 1 g. glucose per os (as 25% solution – twice in 24 hours. The levels of liver glycogen in all the food-deprived quails were signifi cantly lower from -6910 (12-th hour of starving-to 4960mg/kg (72 hour of starving compared to the levels of the same index in fed birds (11990 mg/kg tissue. In the birds receiving energy additive they were higher compared to those deprived of the additive throughout the experimental period. The content of ketones in blood of the control birds was 0.015 mmol/l. The same index increased to 0.027 mmol/l in the feed and energy additive deprived group after the 36 hour of starving, but in the group became energy support, the contents of ketones were lower for the whole period of starving. The energy additive (1g glucose/24 hours helped the maintenance of the energy metabolism during continuous food depriving of the experimental quails.

  16. Alteration of N-glycans and Expression of Their Related Glycogenes in the Epithelial-Mesenchymal Transition of HCV29 Bladder Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Jia Guo


    Full Text Available The epithelial-mesenchymal transition (EMT is an essential step in the proliferation and metastasis of solid tumor cells, and glycosylation plays a crucial role in the EMT process. Certain aberrant glycans have been reported as biomarkers during bladder cancer progression, but global variation of N-glycans in this type of cancer has not been previously studied. We examined the profiles of N-glycan and glycogene expression in transforming growth factor-beta (TGFβ-induced EMT using non-malignant bladder transitional epithelium HCV29 cells. These expression profiles were analyzed by mass spectrometry, lectin microarray analysis, and GlycoV4 oligonucleotide microarray analysis, and confirmed by lectin histochemistry and real-time RT-PCR. The expression of 5 N-glycan-related genes were notably altered in TGFβ-induced EMT. In particular, reduced expression of glycogene man2a1, which encodes α-mannosidase 2, contributed to the decreased proportions of bi-, tri- and tetra-antennary complex N-glycans, and increased expression of hybrid-type N-glycans. Decreased expression of fuca1 gene, which encodes Type 1 α-L-fucosidase, contributed to increased expression of fucosylated N-glycans in TGFβ-induced EMT. Taken together, these findings clearly demonstrate the involvement of aberrant N-glycan synthesis in EMT in these cells. Integrated glycomic techniques as described here will facilitate discovery of glycan markers and development of novel diagnostic and therapeutic approaches to bladder cancer.

  17. Glycogen storage diseases: New perspectives

    Institute of Scientific and Technical Information of China (English)

    Hasan (O)zen


    Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen metabolism. Different hormones,including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. The overall GSD incidence is estimated 1 case per 20 000-43 000 live births. There are over 12 types and they are classified based on the enzyme deficiency and the affected tissue. Disorders of glycogen degradation may affect primarily the liver, the muscle,or both. Type Ⅰ a involves the liver, kidney and intestine (and Ⅰ b also leukocytes), and the clinical manifestations are hepatomegaly, failure to thrive, hypoglycemia,hyperlactatemia, hyperuricemia and hyperlipidemia. Type Ⅲa involves both the liver and muscle, and Ⅲb solely the liver. The liver symptoms generally improve with age.Type Ⅳ usually presents in the first year of life, with hepatomegaly and growth retardation. The disease in general is progressive to cirrhosis. Type Ⅵ and Ⅸ are a heterogeneous group of diseases caused by a deficiency of the liver phosphorylase and phosphorylase kinase system. There is no hyperuricemia or hyperlactatemia.Type Ⅺ is characterized by hepatic glycogenosis and renal Fanconi syndrome. Type Ⅱ is a prototype of inborn lysosomal storage diseases and involves many organs but primarily the muscle. Types Ⅴ and Ⅶ involve only the muscle.

  18. Insulin induces a positive relationship between the rates of ATP and glycogen changes in isolated rat liver in presence of glucose; a 31P and 13C NMR study

    Directory of Open Access Journals (Sweden)

    Gin Henri


    Full Text Available Abstract Background There is an emerging theory suggesting that insulin, which is known to be the predominant postprandial anabolic hormone, is also a major regulator of mitochondrial oxidative phosphorylation in human skeletal muscle. However, little is known about its effects in the liver. Since there is a theoretical relationship between glycogen metabolism and energy status, a simultaneous and continuous investigation of hepatic ATP and glycogen content was performed in intact and isolated perfused liver by 31P and 13C nuclear magnetic resonance (NMR The hepatic rates of ATP and glycogen changes were evaluated with different concentrations of insulin and glucose during continuous and short-term supply. Results Liver from rats fed ad libitum were perfused with Krebs-Henseleit Buffer (KHB(controls or KHB containing 6 mM glucose, 30 mM glucose, insulin alone, insulin + 6 mM glucose, insulin + 30 mM glucose. In the control, glycogenolysis occurred at a rate of -0.53 ± 0.021 %·min-1 and ATP content decreased at a rate of -0.28 ± 0.029 %·min-1. In the absence of insulin, there was a close proportional relationship between the glycogen flux and the glucose concentration, whereas ATP rates never varied. With insulin + glucose, both glycogen and ATP rates were strongly related to the glucose concentration; the magnitude of net glycogen flux was linearly correlated to the magnitude of net ATP flux: fluxglycogen = 72.543(fluxATP + 172.08, R2 = 0.98. Conclusion Only the co-infusion of 30 mM glucose and insulin led to (i a net glycogen synthesis, (ii the maintenance of the hepatic ATP content, and a strong positive correlation between their net fluxes. This has never previously been reported. The specific effect of insulin on ATP change is likely related to a rapid stimulation of the hepatic mitochondrial oxidative phosphorylation. We propose that variations in the correlation between rates of ATP and glycogen changes could be a probe for insulin

  19. Modeling function-perfusion behavior in liver lobules including tissue, blood, glucose, lactate and glycogen by use of a coupled two-scale PDE-ODE approach. (United States)

    Ricken, T; Werner, D; Holzhütter, H G; König, M; Dahmen, U; Dirsch, O


    This study focuses on a two-scale, continuum multicomponent model for the description of blood perfusion and cell metabolism in the liver. The model accounts for a spatial and time depending hydro-diffusion-advection-reaction description. We consider a solid-phase (tissue) containing glycogen and a fluid-phase (blood) containing glucose as well as lactate. The five-component model is enhanced by a two-scale approach including a macroscale (sinusoidal level) and a microscale (cell level). The perfusion on the macroscale within the lobules is described by a homogenized multiphasic approach based on the theory of porous media (mixture theory combined with the concept of volume fraction). On macro level, we recall the basic mixture model, the governing equations as well as the constitutive framework including the solid (tissue) stress, blood pressure and solutes chemical potential. In view of the transport phenomena, we discuss the blood flow including transverse isotropic permeability, as well as the transport of solute concentrations including diffusion and advection. The continuum multicomponent model on the macroscale finally leads to a coupled system of partial differential equations (PDE). In contrast, the hepatic metabolism on the microscale (cell level) was modeled via a coupled system of ordinary differential equations (ODE). Again, we recall the constitutive relations for cell metabolism level. A finite element implementation of this framework is used to provide an illustrative example, describing the spatial and time-depending perfusion-metabolism processes in liver lobules that integrates perfusion and metabolism of the liver.

  20. Implication of altered proteasome function in alcoholic liver injury

    Institute of Scientific and Technical Information of China (English)


    The proteasome is a major protein-degrading enzyme,which catalyzes degradation of oxidized and aged proteins, signal transduction factors and cleaves peptides for antigen presentation. Proteasome exists in the equilibrium of 26S and 20S particles. Proteasome function is altered by ethanol metabolism, depending on oxidative stress levels: low oxidative stress induces proteasome activity, while high oxidative stress reduces it. The proposed mechanisms for modulation of proteasome activity are related to oxidative modification of proteasomal proteins with primary and secondary products derived from ethanol oxidation.Decreased proteolysis by the proteasome results in the accumulation of insoluble protein aggregates, which cannot be degraded by proteasome and which further inhibit proteasome function. Mallory bodies, a common signature of alcoholic liver diseases, are formed by liver cells, when proteasome is unable to remove cytokeratins.Proteasome inhibition by ethanol also promotes the accumulation of pro-apoptotic factors in mitochondria of ethanol-metabolizing liver cells that are normally degraded by proteasome. In addition, decreased proteasome function also induces accumulation of the negative regulators of cytokine signaling (Ⅰ-κB and SOCS), thereby blocking cytokine signal transduction.Finally, ethanol-elicited blockade of interferon type 1 and 2 signaling and decreased proteasome function impairs generation of peptides for MHC class Ⅰ-restricted antigen presentation.

  1. Visceral adiposity influences glucose and glycogen metabolism in control and hyperlipidic-fed animals

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    Danielle Kaiser de Souza


    Full Text Available Introduction: Evidences suggest that fat intake, visceral obesity and intracellular lipids are related to insulin impairment. Objective: The objective of the present paper was correlate visceral obesity and metabolic alterations in control (CTR and hyperlipidic cafeteria diet (CFT fed animals. Methods: After 6 months of diet treatment, liver and muscle of the male rats were utilized to determined glucose uptake and glycogen metabolism after administration of 0.4I U/kg insulin in vivo, and correlate the visceral adiposity to these two parameters. Results: Ample range of physiologic answers to body composition in metabolic profile of the both diets was found. No differences were found in glycemia and triacylglycerol after insulin action in both groups, however CFT group accumulated higher adiposity, mostly visceral fat, and showed lower glycogen content in the liver. We also found an inverse correlation between visceral adiposity and glucose uptake and a decrease of the glycogen synthase active form in the liver. CTR animals demonstrated an inverse correlation between glucose uptake and visceral adiposity in the muscle. Discussion and conclusion: It was observed a variability of metabolic alterations in animals which can be related to degree of accumulation of abdominal adiposity and ingestion of diet fats. Further studies will be required to clarify the reasons for the observed liver alterations in CFT and muscle alterations in CTR animals.


    NARCIS (Netherlands)



    Deficiency of the enzyme glucose-6-phosphatase is the biochemical defect in glycogen storage disease type I (GSD I). Normally this enzyme is present in the liver, intestine and kidneys. The lack of the enzyme in the kidney makes it obvious that glycogen storage will not be restricted to the liver bu

  3. Growth-related alterations during liver carcinogenesis: Effect of promoters

    Energy Technology Data Exchange (ETDEWEB)

    Seglen, P.O.; Gerlyng, P. (Norwegian Radium Hospital, Oslo (Norway))


    Bromodeoxyuridine labeling of DNA, binuclearity counting, and flow cytometric analysis of isolated hepatocytes and hepatocyte nuclei has been used to assess heptocellular growth patterns related to liver carcinogenesis. Three growth patterns can be distinguished. Mononucleating growth is observed during liver regeneration and after treatment with the tumor promoter 2-acetylaminofluorene (2-AAF) and its analogue 4-AAF. In this growth mode binucleation does not occur, resulting in a decrease in the fraction of binucleated cells. Binucleating growth is observed during normal liver development and after treatment with compounds such as phenobarbital, characterized by progressive polyploidization and maintenance of a binucleated cell fraction. Diploid growth is the growth pattern of neoplastic liver hepatocytes. Most of the cells in neoplastic lesions (foci, nodules, and carcinomas) are diploid, in contrast to the normal liver. Diploid tumor cells have a much higher proliferative activity than tetraploid tumor cells, suggesting that the latter may posses a limited growth potential that makes abrogation of binucleation proliferatively advantageous.

  4. Hypoxia and fatty liver


    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito


    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty li...

  5. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)


    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  6. The alterations in the extracellular matrix composition guide the repair of damaged liver tissue. (United States)

    Klaas, Mariliis; Kangur, Triin; Viil, Janeli; Mäemets-Allas, Kristina; Minajeva, Ave; Vadi, Krista; Antsov, Mikk; Lapidus, Natalia; Järvekülg, Martin; Jaks, Viljar


    While the cellular mechanisms of liver regeneration have been thoroughly studied, the role of extracellular matrix (ECM) in liver regeneration is still poorly understood. We utilized a proteomics-based approach to identify the shifts in ECM composition after CCl4 or DDC treatment and studied their effect on the proliferation of liver cells by combining biophysical and cell culture methods. We identified notable alterations in the ECM structural components (eg collagens I, IV, V, fibronectin, elastin) as well as in non-structural proteins (eg olfactomedin-4, thrombospondin-4, armadillo repeat-containing x-linked protein 2 (Armcx2)). Comparable alterations in ECM composition were seen in damaged human livers. The increase in collagen content and decrease in elastic fibers resulted in rearrangement and increased stiffness of damaged liver ECM. Interestingly, the alterations in ECM components were nonhomogenous and differed between periportal and pericentral areas and thus our experiments demonstrated the differential ability of selected ECM components to regulate the proliferation of hepatocytes and biliary cells. We define for the first time the alterations in the ECM composition of livers recovering from damage and present functional evidence for a coordinated ECM remodelling that ensures an efficient restoration of liver tissue.

  7. Alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV. (United States)

    Qin, Yannan; Zhong, Yaogang; Ma, Tianran; Wu, Fei; Wu, Haoxiang; Yu, Hanjie; Huang, Chen; Li, Zheng


    The incidence of hepatocellular carcinoma (HCC) is closely correlated with hepatitis B virus (HBV)-induced liver cirrhosis. Structural changes in the glycans of serum and tissue proteins are reliable indicators of liver damage. However, little is known about the alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV infection. This study compared the differential expression of liver glycopatterns in 7 sets of normal pericarcinomatous tissues (PCTs), cirrhotic, and tumor tissues from patients with liver cirrhosis and HCC induced by HBV using lectin microarrays. Fluorescence-based lectin histochemistry and lectin blotting were further utilized to validate and assess the expression and distribution of certain glycans in 9 sets of corresponding liver tissue sections. Eight lectins (e.g., Jacalin and AAL) revealed significant difference in cirrhotic tissues versus PCTs. Eleven lectins (e.g., EEL and SJA) showed significant alteration during cirrhotic and tumor progression. The expression of Galα1-3(Fucα1-2)Gal (EEL) and fucosyltransferase 1 was mainly increasing in the cytoplasm of hepatocytes during PCTs-cirrhotic-tumor tissues progression, while the expression of T antigen (ACA and PNA) was decreased sharply in cytoplasm of tumor hepatocytes. Understanding the precision alteration of liver glycopatterns related to the development of hepatitis, cirrhosis, and tumor induced by HBV infection may help elucidate the molecular mechanisms underlying the progression of chronic liver diseases and develop new antineoplastic therapeutic strategies.

  8. Liver cell adenoma showing sequential alteration of radiological findings suggestive of well-differentiated hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Takayuki Kogure; Yoshiyuki Ueno; Satoshi Sekiguchi; Kazuyuki Ishida; Takehiko Igarashi; Yuta Wakui; Takao Iwasaki; Tooru Shimosegawa


    A liver tumor 35 mm in diameter was found incidentally in a 40-year-old woman who had no history of liver diseases or the use of oral contraceptives. Radiological diagnostics showed the typical findings of liver cell adenoma (LCA). Dynamic computed tomography revealed that the tumor showed a homogenous enhancement in the arterial phase and almost the same enhancement as the surrounding liver parenchyma in the delayed phase. The tumor was found to contain fat on magnetic resonance imaging. A benign fat containing liver tumor was suggested. However, radiological findings altered, which caused us to suspect that a welldifferentiated hepatocellular carcinoma (HCC) containing fat was becoming dedifferentiated. Partial hepatectomy was performed and the pathological findings showed the typical findings of LCA. This case was an extremely rare LCA, which had no background of risk for LCA and developed the sequential alteration of the radiological findings to suspect well-differentiated HCC.

  9. Psychosine-induced alterations in peroxisomes of Twitcher Mouse Liver (United States)

    Contreras, Miguel Agustin; Haq, Ehtishamul; Uto, Takuhiro; Singh, Inderjit; Singh, Avtar Kaur


    Krabbe’s disease is a neuroinflammatory disorder in which galactosylsphingosine (psychosine) accumulates in nervous tissue. To gain insight into whether the psychosine-induced effects in nervous tissue extend to peripheral organs, we investigated the expression of cytokines and their effects on peroxisomal structure/function in twitcher mouse liver (animal model of Krabbe disease). Immunofluorescence analysis demonstrated TNF-α and IL-6 expression, which was confirmed by mRNAs quantitation. Despite the presence of TNF-α, lipidomic analysis did not indicate a significant decrease in sphingomyelin or an increase in ceramide fractions. Ultrastructural analysis of catalase-dependent staining of liver sections showed reduced reactivity without significant changes in peroxisomal contents. This observation was confirmed by assaying catalase activity and quantitation of its mRNA, both of which were found significantly decreased in twitcher mouse liver. Western blot analysis demonstrated a generalized reduction of peroxisomal matrix and membrane proteins. These observations indicate that twitcher mouse pathobiology extends to the liver, where the induction of TNF-α and IL-6 compromise peroxisomal structure and function. PMID:18602885

  10. Changes in the activity levels of glutamine synthetase, glutaminase and glycogen synthetase in rats subjected to hypoxic stress (United States)

    Vats, P.; Mukherjee, A. K.; Kumria, M. M. L.; Singh, S. N.; Patil, S. K. B.; Rangnathan, S.; Sridharan, K.

    Exposure to high altitude causes loss of body mass and alterations in metabolic processes, especially carbohydrate and protein metabolism. The present study was conducted to elucidate the role of glutamine synthetase, glutaminase and glycogen synthetase under conditions of chronic intermittent hypoxia. Four groups, each consisting of 12 male albino rats (Wistar strain), were exposed to a simulated altitude of 7620 m in a hypobaric chamber for 6 h per day for 1, 7, 14 and 21 days, respectively. Blood haemoglobin, blood glucose, protein levels in the liver, muscle and plasma, glycogen content, and glutaminase, glutamine synthetase and glycogen synthetase activities in liver and muscle were determined in all groups of exposed and in a group of unexposed animals. Food intake and changes in body mass were also monitored. There was a significant reduction in body mass (28-30%) in hypoxia-exposed groups as compared to controls, with a corresponding decrease in food intake. There was rise in blood haemoglobin and plasma protein in response to acclimatisation. Over a three-fold increase in liver glycogen content was observed following 1 day of hypoxic exposure (4.76+/-0.78 mg.g-1 wet tissue in normal unexposed rats; 15.82+/-2.30 mg.g-1 wet tissue in rats exposed to hypoxia for 1 day). This returned to normal in later stages of exposure. However, there was no change in glycogen synthetase activity except for a decrease in the 21-days hypoxia-exposed group. There was a slight increase in muscle glycogen content in the 1-day exposed group which declined significantly by 56.5, 50.6 and 42% following 7, 14, and 21 days of exposure, respectively. Muscle glycogen synthetase activity was also decreased following 21 days of exposure. There was an increase in glutaminase activity in the liver and muscle in the 7-, 14- and 21-day exposed groups. Glutamine synthetase activity was higher in the liver in 7- and 14-day exposed groups; this returned to normal following 21 days of exposure

  11. Deficiency of a Glycogen Synthase-associated Protein, Epm2aip1, Causes Decreased Glycogen Synthesis and Hepatic Insulin Resistance* (United States)

    Turnbull, Julie; Tiberia, Erica; Pereira, Sandra; Zhao, Xiaochu; Pencea, Nela; Wheeler, Anne L.; Yu, Wen Qin; Ivovic, Alexander; Naranian, Taline; Israelian, Nyrie; Draginov, Arman; Piliguian, Mark; Frankland, Paul W.; Wang, Peixiang; Ackerley, Cameron A.; Giacca, Adria; Minassian, Berge A.


    Glycogen synthesis is a major component of the insulin response, and defective glycogen synthesis is a major portion of insulin resistance. Insulin regulates glycogen synthase (GS) through incompletely defined pathways that activate the enzyme through dephosphorylation and, more potently, allosteric activation. We identify Epm2aip1 as a GS-associated protein. We show that the absence of Epm2aip1 in mice impairs allosteric activation of GS by glucose 6-phosphate, decreases hepatic glycogen synthesis, increases liver fat, causes hepatic insulin resistance, and protects against age-related obesity. Our work identifies a novel GS-associated GS activity-modulating component of insulin resistance. PMID:24142699

  12. Altered systemic bile acid homeostasis contributes to liver disease in pediatric patients with intestinal failure (United States)

    Xiao, Yong-Tao; Cao, Yi; Zhou, Ke-Jun; Lu, Li-Na; Cai, Wei


    Intestinal failure (IF)-associated liver disease (IFALD), as a major complication, contributes to significant morbidity in pediatric IF patients. However, the pathogenesis of IFALD is still uncertain. We here investigate the roles of bile acid (BA) dysmetabolism in the unclear pathogenesis of IFALD. It found that the histological evidence of pediatric IF patients exhibited liver injury, which was characterized by liver bile duct proliferation, inflammatory infiltration, hepatocyte apoptosis and different stages of fibrosis. The BA compositions were altered in serum and liver of pediatric IF patients, as reflected by a primary BA dominant composition. In IF patients, the serum FGF19 levels decreased significantly, and were conversely correlated with ileal inflammation grades (r = −0.50, p CYP7A1) increased evidently. In conclusion, ileum inflammation decreases FXR expression corresponding to reduce serum FGF19 concentration, along with increased hepatic bile acid synthesis, leading to liver damages in IF patients. PMID:27976737

  13. Untargeted Metabolomics Analysis of ABCC6-Deficient Mice Discloses an Altered Metabolic Liver Profile

    DEFF Research Database (Denmark)

    Rasmussen, Mie Rostved; Nielsen, Kirstine Lykke; Christensen, Mia Benedicte Lykke Roest


    Loss-of-function mutations in the transmembrane ABCC6 transport protein cause pseudoxanthoma elasticum (PXE), an ectopic, metabolic mineralization disorder that affects the skin, eye, and vessels. ABCC6 is assumed to mediate efflux of one or several small molecule compounds from the liver cytosol...... in acetylation reactions, were accumulated in the liver. None of the identified metabolites seems to explain mineralization in extrahepatic tissues, but the present study now shows that abrogated ABCC6 function does cause alterations in the metabolic profile of the liver in accordance with PXE being a metabolic...

  14. Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis (United States)

    Blaya, Delia; Morales-Ibanez, Oriol; Coll, Mar; Millán, Cristina; Altamirano, José; Arroyo, Vicente; Caballería, Joan; Bataller, Ramón; Ginès, Pere; Sancho-Bru, Pau


    Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis. PMID:26691857

  15. Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis.

    Directory of Open Access Journals (Sweden)

    Silvia Affò

    Full Text Available Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+ and mature dendritic (MHCII+CD11c+ cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis.

  16. Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis. (United States)

    Affò, Silvia; Rodrigo-Torres, Daniel; Blaya, Delia; Morales-Ibanez, Oriol; Coll, Mar; Millán, Cristina; Altamirano, José; Arroyo, Vicente; Caballería, Joan; Bataller, Ramón; Ginès, Pere; Sancho-Bru, Pau


    Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis.

  17. Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jie, E-mail: [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Lu, Yuan-Fu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Zhang, Youcai; Wu, Kai Connie [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Fan, Fang [Cytopathology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Klaassen, Curtis D. [University of Kansas Medical Center, Kansas City, KS 66160 (United States)


    Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential. - Highlights: • Oleanolic acid at higher doses and long-term use may produce liver injury. • Oleanolic acid increased serum ALT, ALP, bilirubin and bile acid concentrations. • OA produced feathery degeneration, inflammation and cell death in the liver. • OA altered bile acid homeostasis, affecting bile acid synthesis and transport.

  18. Hepatocellular alterations and dysregulation of oncogenic pathways in the liver of transgenic mice overexpressing growth hormone. (United States)

    Miquet, Johanna G; Freund, Thomas; Martinez, Carolina S; González, Lorena; Díaz, María E; Micucci, Giannina P; Zotta, Elsa; Boparai, Ravneet K; Bartke, Andrzej; Turyn, Daniel; Sotelo, Ana I


    Growth hormone (GH) overexpression throughout life in transgenic mice is associated with the development of liver tumors at old ages. The preneoplastic pathology observed in the liver of young adult GH-overexpressing mice is similar to that present in humans at high risk of hepatic cancer. To elucidate the molecular pathogenesis underlying the pro-oncogenic liver pathology induced by prolonged exposure to elevated GH levels, the activation and expression of several components of signal transduction pathways that have been implicated in hepatocellular carcinogenesis were evaluated in the liver of young adult GH-transgenic mice. In addition, males and females were analyzed in parallel in order to evaluate sexual dimorphism. Transgenic mice from both sexes exhibited hepatocyte hypertrophy with enlarged nuclear size and exacerbated hepatocellular proliferation, which were higher in males. Dysregulation of several oncogenic pathways was observed in the liver of GH-overexpressing transgenic mice. Many signaling mediators and effectors were upregulated in transgenic mice compared with normal controls, including Akt2, NFκB, GSK3β, β-catenin, cyclin D1, cyclin E, c-myc, c-jun and c-fos. The molecular alterations described did not exhibit sexual dimorphism in transgenic mice except for higher gene expression and nuclear localization of cyclin D1 in males. We conclude that prolonged exposure to GH induces in the liver alterations in signaling pathways involved in cell growth, proliferation and survival that resemble those found in many human tumors.

  19. Hemostatic alterations in liver disease : A review on pathophysiology, clinical consequences, and treatment

    NARCIS (Netherlands)

    Lisman, Ton; Leebeek, Frank W. G.


    In most patients with acute or chronic liver failure, extensive changes in all pathways contributing to hemostasis are found. These hemostatic alterations concern both pro- and antihemostatic pathways, and therefore the net result of the hemostatic dysbalance is unclear. Although it is generally bel

  20. Altered Hepatic Transport by Fetal Arsenite Exposure in Diet-Induced Fatty Liver Disease. (United States)

    Ditzel, Eric J; Li, Hui; Foy, Caroline E; Perrera, Alec B; Parker, Patricia; Renquist, Benjamin J; Cherrington, Nathan J; Camenisch, Todd D


    Non-alcoholic fatty liver disease can result in changes to drug metabolism and disposition potentiating adverse drug reactions. Furthermore, arsenite exposure during development compounds the severity of diet-induced fatty liver disease. This study examines the effects of arsenite potentiated diet-induced fatty liver disease on hepatic transport in male mice. Changes were detected for Mrp2/3/4 hepatic transporter gene expression as well as for Oatp1a4/2b1/1b2. Plasma concentrations of Mrp and Oatp substrates were increased in arsenic exposure groups compared with diet-only controls. In addition, murine embryonic hepatocytes and adult primary hepatocytes show significantly altered transporter expression after exposure to arsenite alone: a previously unreported phenomenon. These data indicate that developmental exposure to arsenite leads to changes in hepatic transport which could increase the risk for ADRs during fatty liver disease.

  1. Glycogen shortage during fasting triggers liver–brain–adipose neurocircuitry to facilitate fat utilization (United States)

    Izumida, Yoshihiko; Yahagi, Naoya; Takeuchi, Yoshinori; Nishi, Makiko; Shikama, Akito; Takarada, Ayako; Masuda, Yukari; Kubota, Midori; Matsuzaka, Takashi; Nakagawa, Yoshimi; Iizuka, Yoko; Itaka, Keiji; Kataoka, Kazunori; Shioda, Seiji; Niijima, Akira; Yamada, Tetsuya; Katagiri, Hideki; Nagai, Ryozo; Yamada, Nobuhiro; Kadowaki, Takashi; Shimano, Hitoshi


    During fasting, animals maintain their energy balance by shifting their energy source from carbohydrates to triglycerides. However, the trigger for this switch has not yet been entirely elucidated. Here we show that a selective hepatic vagotomy slows the speed of fat consumption by attenuating sympathetic nerve-mediated lipolysis in adipose tissue. Hepatic glycogen pre-loading by the adenoviral overexpression of glycogen synthase or the transcription factor TFE3 abolished this liver–brain–adipose axis activation. Moreover, the blockade of glycolysis through the knockdown of the glycogen phosphorylase gene and the resulting elevation in the glycogen content abolished the lipolytic signal from the liver, indicating that glycogen is the key to triggering this neurocircuitry. These results demonstrate that liver glycogen shortage activates a liver–brain–adipose neural axis that has an important role in switching the fuel source from glycogen to triglycerides under prolonged fasting conditions. PMID:23939267

  2. The role of aerobic training and Pistacia atlantica extract on the levels of protein carbonyl, heat shock protein 70, and glycogen in the liver tissue of diabetic rats

    Directory of Open Access Journals (Sweden)

    Fatemeh Mohammadi Karizno


    Conclusion: It was found that aerobic training and Pistacia atlantica extract consumption, either alone or together, led to a significant reduction in PC levels in the liver tissues of diabetic rats. Thus, Pistacia atlantica extract and aerobic training can be good remedies in reducing liver complications resulting from diabetes.

  3. Interplay between viral infections and genetic alterations in liver cancer

    Directory of Open Access Journals (Sweden)

    Pierre Hainaut


    Full Text Available

    With over 500 000 annual deaths, Hepatocellular carcinoma (HCC is the fifth most common cancer worldwide and a leading cause of death in developing countries where about 80% of the cases arise. Risk factors include chronic hepatitis infections (hepatitis B, (HBV and hepatitis C (HCV viruses, alcohol, dietary contaminants such as falatoxins The incidence shows important geographic variations, accor In southern Asia, HCC development is mainly related to the endemic Hepatitis B Virus (HBV infection, cases with hot spot mutation in codon 249 (249ser of TP53 tumor suppressor gene were also described and associated to a low-intermediate exposure rate to Aflatoxin B1 (AFB1. Presence of Hepatitis C Virus (HCV infection was also detected in 12 - 17% of HCC cases. Despite the increasing number of studies identifying viral/host interactions in viro-induced HCC or describing potential pathways for hepatocarcinogenesis, precise mechanism has not been identified so far. HBV was demonstrated to enhance hepatocarcinogenesis by different manners; HBV chronic infection is associated to active hepatitis (CAH and cirrhosis which are hepatic complications considered as early stage for HCC development. These complications mobilise the host immune response, the resulting inflammation initiates and selects the first genetic alteration at the origin of loss of cell control. Moreover, HBV can also promote carcinogenesis through genetic instability generated by its common integration in host DNA. HBV proteins, as HBx, was proven to interact with a variety of targets in the host cell including protein or host transcription factor such as, in particular, the p53 protein or the transcription factor E4F, which is implicated in growth, differenciation and senescence. Specific HBV mutations or distinct HBV genotypes are associated to higher risks factors for HCC or hepatic complications leading

  4. Alterations of the gut microbiome and metabolome in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Wei; Zhong; Zhanxiang; Zhou


    Alcohol consumption is one of the leading causes of liver diseases and liver-related death worldwide. The gut is a habitat for billions of microorganisms which promotes metabolism and digestion in their symbiotic relationship with the host. Alterations of gut microbiome by alcohol consumption are referred to bacterial overgrowth, release of bacteria-derived products, and/or changed microbiota equilibrium. Alcohol consumption also perturbs the function of gastrointestinal mucosa and elicits a pathophysiological condition. These adverse effects caused by alcohol may ultimately result in a broad change of gastrointestinal luminal metabolites such as bile acids, short chain fatty acids, and branched chain amino acids. Gut microbiota alterations, metabolic changes produced in a dysbiotic intestinal environment, and the host factors are all critical contributors to the development and progression of alcoholic liver disease. This review summarizes recent findings of how alcohol-induced alterations of gut microbiota and metabolome, and discusses the mecha-nistic link between gastrointestinal dyshomeostasis and alcoholic liver injury.

  5. Leptin inhibits glycogen catabolism but does not modify acutely the suppressive effect of insulin on glucose production and glycogenolysis stimulated by 8-Br-cAMP in rat liver perfused in situ. (United States)

    Leonardo, Eledir Silveira; Bassoli, Bruna Kempfer; Cassolla, Priscila; Borba-Murad, Glaucia Regina; Bazotte, Roberto Barbosa; De Souza, Helenir Medri


    Leptin, a hormone secreted by the adipocytes, plays a central role in glucose metabolism and the action of insulin. Here we assessed, by means of rat-liver perfusion, the direct influence of physiological (10 ng/ml) and supraphysiological (50 or 100 ng/ml) concentrations of leptin on the suppressive effect of insulin on the glucose production and glycogenolysis stimulated by 8-bromoadenosine-3':5'-monophosphate (8-Br-cAMP). Portal infusion of insulin (20 microU/ml) or leptin (10 ng/ml) reduced (pglycogenolysis induced by 8-Br-cAMP (0.3 microM). However, portal infusion of physiological (10 ng/ml) and supraphysiological (50 or 100 ng/ml) concentrations of leptin together with the insulin did not modify the suppressive effect of the latter on the glucose production and glycogenolysis stimulated by 8-Br-cAMP. Moreover, prolonging the period of leptin infusion from 20 to 40 min also failed to influence the liver response to insulin. Thus, we conclude that: (a) leptin, at physiological levels, has a direct and acute effect, inhibiting the glucose production and glycogenolysis stimulated by 8-Br-cAMP; (b) leptin, at either physiological or supraphysiological concentrations, has no short-term influence on the suppressive effect of insulin on glycogen catabolism stimulated by 8-Br-cAMP.

  6. Alteration of protein profile in rat liver of animals exposed to subacute diazinon: a proteomic approach. (United States)

    Lari, Parisa; Rashedinia, Marzieh; Abnous, Khalil; Hosseinzadeh, Hossein


    Diazinon, an organophosphorus insecticide, is employed to control pests in agriculture. Diazinon may contaminate the environment during the manufacturing process or agricultural application. Previous studies have revealed that diazinon may induce alteration in the protein profile of the liver. Here, a proteomics approach was used to investigate the effects on the protein profile in the liver of rats of subacute oral exposures at 15 mg/kg of diazinon. Liver proteins were separated using 2D-PAGE, and stained by MS-compatible silver staining and/or the fluorescent SYPRO® Ruby protein gel stain. Gels were scanned and analyzed using the Image Master software. Differentially displayed protein species were identified using MALDI-TOF/TOF and MASCOT software. Significantly altered protein species were identified to be involved in apoptosis, cell metabolism, transport, and antioxidant systems. Exposure to diazinon decreased levels of some species of catalase, peroxiredoxin-6, 3-ketoacyl-CoA thiolase, and glucose regulated protein78, whereas the level of protein disulfide-isomerase A3 increased. Our results suggested that diazinon may induce hepatotoxicity through oxidative stress, apoptosis, and metabolic disorders in rat liver.

  7. Postpartal subclinical endometritis alters transcriptome profiles in liver and adipose tissue of dairy cows. (United States)

    Akbar, Haji; Cardoso, Felipe C; Meier, Susanne; Burke, Christopher; McDougall, Scott; Mitchell, Murray; Walker, Caroline; Rodriguez-Zas, Sandra L; Everts, Robin E; Lewin, Harris A; Roche, John R; Loor, Juan J


    Transcriptome alterations in liver and adipose tissue of cows with subclinical endometritis (SCE) at 29 d postpartum were evaluated. Bioinformatics analysis was performed using the Dynamic Impact Approach by means of KEGG and DAVID databases. Milk production, blood metabolites (non-esterified fatty acids, magnesium), and disease biomarkers (albumin, aspartate aminotransferase) did not differ greatly between healthy and SCE cows. In liver tissue of cows with SCE, alterations in gene expression revealed an activation of complement and coagulation cascade, steroid hormone biosynthesis, apoptosis, inflammation, oxidative stress, MAPK signaling, and the formation of fibrinogen complex. Bioinformatics analysis also revealed an inhibition of vitamin B3 and B6 metabolism with SCE. In adipose, the most activated pathways by SCE were nicotinate and nicotinamide metabolism, long-chain fatty acid transport, oxidative phosphorylation, inflammation, T cell and B cell receptor signaling, and mTOR signaling. Results indicate that SCE in dairy cattle during early lactation induces molecular alterations in liver and adipose tissue indicative of immune activation and cellular stress.

  8. Hypoxia and fatty liver. (United States)

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito


    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease.

  9. Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice. (United States)

    Liu, Jie; Lu, Yuan-Fu; Zhang, Youcai; Wu, Kai Connie; Fan, Fang; Klaassen, Curtis D


    Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential.

  10. Brain death induces the alteration of liver protein expression profiles in rabbits. (United States)

    Du, Bing; Li, Ling; Zhong, Zhibiao; Fan, Xiaoli; Qiao, Bingbing; He, Chongxiang; Fu, Zhen; Wang, Yanfeng; Ye, Qifa


    At present, there is no accurate method for evaluating the quality of liver transplant from a brain-dead donor. Proteomics are used to investigate the mechanisms involved in brain death‑induced liver injury and to identify sensitive biomarkers. In the present study, age‑ and gender‑matched rabbits were randomly divided into the brain death and sham groups. The sham served as the control. A brain‑death model was established using an intracranial progressive pressurized method. The differentially expressed proteins extracted from the liver tissues of rabbits that were brain‑dead for 6 h in the two groups were determined by two‑dimensional gel electrophoresis and matrix‑assisted laser desorption ionization time of flight mass spectrometry. Although there was no obvious functional and morphological difference in 2, 4 and 6 h after brain death, results of the proteomics analysis revealed 973±34 and 987±38 protein spots in the control and brain death groups, respectively. Ten proteins exhibited a ≥2‑fold alteration. The downregulated proteins were: aldehyde dehydrogenase, runt‑related transcription factor 1 (RUNX1), inorganic pyrophosphatase, glutamate‑cysteine ligase regulatory subunit and microsomal cytochrome B5. By contrast, the expression of dihydropyrimidinase-related protein 4, peroxiredoxin‑6, 3‑phosphoinositide‑dependent protein kinase‑1, 3-mercaptopyruvate and alcohol dehydrogenase were clearly upregulated. Immunohistochemistry and western blot analysis results revealed that the expression of RUNX1 was gradually increased in a time‑dependent manner in 2, 4, and 6 h after brain death. In conclusion, alteration of the liver protein expression profile induced by brain death indicated the occurrence of complex pathological changes even if no functional or morphological difference was identified. Thus, RUNX1 may be a sensitive predict factor for evaluating the quality of brain death donated liver.

  11. Chronic mild stress alters circadian expressions of molecular clock genes in the liver. (United States)

    Takahashi, Kei; Yamada, Tetsuya; Tsukita, Sohei; Kaneko, Keizo; Shirai, Yuta; Munakata, Yuichiro; Ishigaki, Yasushi; Imai, Junta; Uno, Kenji; Hasegawa, Yutaka; Sawada, Shojiro; Oka, Yoshitomo; Katagiri, Hideki


    Chronic stress is well known to affect metabolic regulation. However, molecular mechanisms interconnecting stress response systems and metabolic regulations have yet to be elucidated. Various physiological processes, including glucose/lipid metabolism, are regulated by the circadian clock, and core clock gene dysregulation reportedly leads to metabolic disorders. Glucocorticoids, acting as end-effectors of the hypothalamus-pituitary-adrenal (HPA) axis, entrain the circadian rhythms of peripheral organs, including the liver, by phase-shifting core clock gene expressions. Therefore, we examined whether chronic stress affects circadian expressions of core clock genes and metabolism-related genes in the liver using the chronic mild stress (CMS) procedure. In BALB/c mice, CMS elevated and phase-shifted serum corticosterone levels, indicating overactivation of the HPA axis. The rhythmic expressions of core clock genes, e.g., Clock, Npas2, Bmal1, Per1, and Cry1, were altered in the liver while being completely preserved in the hypothalamic suprachiasmatic nuculeus (SCN), suggesting that the SCN is not involved in alterations in hepatic core clock gene expressions. In addition, circadian patterns of glucose and lipid metabolism-related genes, e.g., peroxisome proliferator activated receptor (Ppar) α, Pparγ-1, Pparγ-coactivator-1α, and phosphoenolepyruvate carboxykinase, were also disturbed by CMS. In contrast, in C57BL/6 mice, the same CMS procedure altered neither serum corticosterone levels nor rhythmic expressions of hepatic core clock genes and metabolism-related genes. Thus, chronic stress can interfere with the circadian expressions of both core clock genes and metabolism-related genes in the liver possibly involving HPA axis overactivation. This mechanism might contribute to metabolic disorders in stressful modern societies.

  12. Effect of α-Ketoglutarate on Cyanide-induced Biochemical Alterations in Rat Brain and Liver

    Institute of Scientific and Technical Information of China (English)


    Objective To investigate the biochemical changes in rat brain and liver following acute exposure to a lethal dose of cyanide, and its response to treatment of α-ketoglutarate (α-KG) in the absence or presence of sodium thiosulfate (STS). Methods Female rats were administered 2.0 LD50 potassium cyanide (KCN; oral) in the absence or presence of pre-treatment (-10 min), simultaneous treatment (0 min) or post-treatment (+2-3 min) of α-KG (2.0 g/kg, oral) and/or STS (1.0 g/kg,intraperitoneal, -15 min, 0 min or + 2-3 min). At the time of onset of signs and symptoms of KCN toxicity (2-4 min) and at the time of death (5-15 min), various parameters particularly akin to oxidative stress viz. Cytochrome oxidase (CYTOX),superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH) and oxidized glutathione (GSSG) in brain, and CYTOX, sorbitol dehydrogenase (SDH), alkaline phosphatase (ALP), GSH and GSSG in liver homogenate were measured. Results At both time intervals brain CYTOX, SOD, GPx, and GSH significantly reduced (percent inhibition compared to control) to 24%, 56%, 77%, and 65%, and 44%, 46%, 78%, and 57%, respectively. At the corresponding time points liver CYTOX and GSH reduced to 74% and 63%, and 44% and 68%, respectively. The levels of GSSG in the brain and liver, and hepatic ALP and SDH were unchanged. Pre-treatment and simultaneous treatment of α-KG alone or with STS conferred significant protection on above variables. Post-treatment was effective in restoring the changes in liver but failed to normalize the changes in the brain. Conclusions Oral treatment with α-KG alone or in combination with STS has protective effects on cyanide-induced biochemical alterations in rat brain and liver.

  13. The role of skeletal muscle glycogen breakdown for regulation of insulin sensitivity by exercise

    Directory of Open Access Journals (Sweden)

    Jørgen eJensen


    Full Text Available Glycogen is the storage form of carbohydrates in mammals. In humans the majority of glycogen is stored in skeletal muscles (~500 g and the liver (~100 g. Food is supplied in larger meals, but the blood glucose concentration has to be kept within narrow limits to survive and stay healthy. Therefore, the body has to cope with periods of excess carbohydrates and periods without supplementation. Healthy persons remove blood glucose rapidly when glucose is in excess, but insulin-stimulated glucose disposal is reduced in insulin resistant and type 2 diabetic subjects. During a hyperinsulinemic euglycaemic clamp, 70-90 % of glucose disposal will be stored as muscle glycogen in healthy subjects. The glycogen stores in skeletal muscles are limited because an efficient feedback-mediated inhibition of glycogen synthase prevents accumulation. De novo lipid synthesis can contribute to glucose disposal when glycogen stores are filled. Exercise physiologists normally consider glycogen’s main function as energy substrate. Glycogen is the main energy substrate during exercise intensity above 70 % of maximal oxygen uptake (VO2max and fatigue develops when the glycogen stores are depleted in the active muscles. After exercise, the rate of glycogen synthesis is increased to replete glycogen stores, and blood glucose is the substrate. Indeed insulin-stimulated glucose uptake and glycogen synthesis is elevated after exercise, which, from an evolutional point of view, will favour glycogen repletion and preparation for new fight or flight events. In the modern society, the reduced glycogen stores in skeletal muscles after exercise allows carbohydrates to be stored as muscle glycogen and prevents that glucose is channelled to de novo lipid synthesis, which over time will causes ectopic fat accumulation and insulin resistance. The reduction of skeletal muscle glycogen after exercise allows a healthy storage of carbohydrates after meals and prevents development of type

  14. Genetic and histopathological alterations induced by cypermethrin in rat kidney and liver: Protection by sesame oil. (United States)

    Soliman, Mohamed Mohamed; Attia, Hossam F; El-Ella, Ghada A Abou


    Pesticides are widespread synthesized substances used for public health protection and agricultural programs. However, they cause environmental pollution and health hazards. This study aimed to examine the protective effects of sesame oil (SO) on the genetic alterations induced by cypermethrin (CYP) in the liver and kidney of Wistar rats. Male rats were divided into four groups, each containing 10 rats: the control group received vehicle, SO group (5 mL/kg b.w), CYP group (12 mg/kg b.w), and protective group received SO (5 mL/kg b.w) plus CYP (12 mg/kg b.w). Biochemical analysis showed an increase in albumin, urea, creatinine, GPT, GOT, and lipid profiles in the CYP group. Co-administration of SO with CYP normalized such biochemical changes. CYP administration decreased both the activity and mRNA expression of the examined antioxidants. SO co-administration recovered CYP, downregulating the expression of glutathione-S-transferase (GST), catalase, and superoxide dismutase. Additionally, SO co-administration with CYP counteracted the CYP- altering the expression of renal interleukins (IL-1 and IL-6), tumor necrosis factor alpha (TNF-α), heme oxygenase-1 (HO-1), anigotensinogen (AGT), AGT receptors (AT1), and genes of hepatic glucose and fatty acids metabolism. CYP induced degenerative changes in the kidney and liver histology which are ameliorated by SO. In conclusion, SO has a protective effect against alterations and pathological changes induced by CYP in the liver and kidney at genetic and histological levels.

  15. Hepatitis C virus and ethanol alter antigen presentation in liver cells

    Institute of Scientific and Technical Information of China (English)

    Natalia A Osna


    Alcoholic patients have a high incidence of hepatitis Cvirus (HCV) infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCVinduced inability of the immune system to recognizeinfected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex (MHC) classⅠ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC classⅠand class Ⅱ in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 (IL-10) and transforming growth factor beta (TGFβ) predominance,preventing cell maturation and allostimulation capacity.The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC classⅠ-restricted antigen presentation.Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.

  16. Sustained high plasma mannose less sensitive to fluctuating blood glucose in glycogen storage disease type Ia children

    NARCIS (Netherlands)

    Nagasaka, Hironori; Yorifuji, Tohru; Bandsma, Robert H. J.; Takatani, Tomozumi; Asano, Hisaki; Mochizuki, Hiroshi; Takuwa, Mayuko; Tsukahara, Hirokazu; Inui, Ayano; Tsunoda, Tomoyuki; Komatsu, Haruki; Hiejima, Eitaro; Fujisawa, Tomoo; Hirano, Ken-ichi; Miida, Takashi; Ohtake, Akira; Taguchi, Tadao; Miwa, Ichitomo


    Plasma mannose is suggested to be largely generated from liver glycogen-oriented glucose-6-phosphate. This study examined plasma mannose in glycogen storage disease type Ia (GSD Ia) lacking conversion of glucose-6-phosphate to glucose in the liver. We initially examined fasting-and postprandial 2 h-

  17. Glycogenic hepatopathy, an underdiagnosed cause of relapsing hepatitis in uncontrolled type 1 diabetes mellitus (United States)

    Sarkhy, Ahmed A. Al; Zaidi, Zafar A.; Babiker, Amir M.


    Glycogenic hepatopathy is a rare condition that causes significant hepatomegaly and elevated liver enzyme levels in uncontrolled type 1 diabetic patients. It develops due to excessive accumulation of glycogen in the hepatocytes. It is typically reversible with good glycemic control and rarely progresses to mild fibrosis, but not cirrhosis. PMID:28042636

  18. Acoustically Accessible Window Determination for Ultrasound Mediated Treatment of Glycogen Storage Disease Type Ia Patients

    NARCIS (Netherlands)

    Wang, S.; Raju, B.I.; Leyvi, E.; Weinstein, D.; Seip, R.


    Glycogen storage disease type Ia (GSDIa) is caused by an inherited single-gene defect resulting in an impaired glycogen to glucose conversion pathway. Targeted ultrasound mediated delivery (USMD) of plasmid DNA to liver in conjunction with microbubbles may provide a potential treatment for GSDIa pat

  19. Glycogenic hepatopathy in young adults: a case series

    Directory of Open Access Journals (Sweden)

    Marco Silva

    Full Text Available Glycogenic hepatopathy is a rare and underecognized complication in long-standing poorly controlled type 1 diabetes mellitus patients. This is a distinct entity from other causes of hepatomegaly and elevated liver enzymes in diabetics, such as nonalcoholic fatty liver disease. Glycogenic hepatopathy is characterized by the combination of poorly controlled diabetes, acute liver injury with marked elevation in serum aminotransferases, and the characteristic histological features on liver biopsy. It is important to distinguish this entity as it has the potential for resolution following improved glycemic control. In this report, we describe four cases of adult patients presenting elevated serum transaminases and hepatomegaly with a history of poorly controlled type I diabetes mellitus. One of the patients had also elevated amylase and lipase in the serum, without clinical or imagiologic evidence of acute pancreatitis. Liver biopsy was performed in all patients and revealed glycogenic hepatopathy. Clinician's awareness of glycogenic hepatopathy should prevent diagnostic delay or misdiagnosis and will provide better insight and management for this condition.

  20. Chemically-induced alteration of UDP-glucuronic acid concentration in rat liver. (United States)

    Watkins, J B; Klaassen, C D


    Since many xenobiotics alter hepatic UDP-glucuronosyltransferase activity, their effect on UDPGA concentration was determined. Rats were pretreated with: 1) microsomal enzyme inducers (7,8-benzoflavone, benzo(a)pyrene, butylated hydroxyanisole, isosafrole, 3-methylcholanthrene, phenobarbital, pregnenolone-16 alpha-carbonitrile (PCN), 2,3,7,8-tetrachlorodibenzo-p-dioxin, trans-stilbene oxide); 2) inhibitors of microsomal enzymes (cobaltous chloride, piperonyl butoxide, SKF 525-A, borneol, galactosamine); 3) hepatotoxins (allyl alcohol, aflatoxin B1, alpha-naphthylisothiocyanate, bromobenzene, cadmium chloride, carbon tetrachloride, 1,1-dichloroethylene), and 4) commonly used anesthetics (pentobarbital, urethane, diethyl ether, halothane, enflurane, methoxyflurane). Rats were decapitated before removal of the liver. All inducers except PCN and isosafrole increased UDPGA 36-85% above control. Mixed-function oxidase inhibitors had no effect whereas borneol and galactosamine reduced UDPGA 85-90%. Aflatoxin B1 and cadmium produced decreases of 59 and 25%, respectively. Hepatic UDPGA content was diminished 70-95% after exposure to the inhalation anesthetics, whereas the other anesthetics reduced UDPGA about 25%. Thus, numerous xenobiotics alter the concentration of UDPGA in rat liver, which may influence the rate of glucoronidation.

  1. Histological and biochemical alterations in early-stage lobar ischemia-reperfusion in rat liver

    Institute of Scientific and Technical Information of China (English)

    Hossein Ali Arab; Farhang Sasani; Mohammad Hossein Rafiee; Ahmad Fatemi; Abbas Javaheri


    AIM: To investigate the structural and biochemical changes in the early stage of reperfusion in the rat livers exposed to lobar ischemia-reperfusion (IR).METHODS: The median and left lobes of the liver were subjected to 60 min ischemia followed by 5, 10,30, 45, 60 and 120 min reperfusion. Blood samples were taken at different time intervals to test enzyme activities and biochemical alterations induced by reperfusion. At the end of each reperfusion period, the animals were killed by euthanasia and tissue samples were taken for histological examination and immunohistochemistry.RESULTS: Cell vacuolation, bleb formation and focal hepatitis were the most important changes occur during ischemia. While some changes including bleb formation were removed during reperfusion, other alterations including portal hepatitis, inflammation and the induction of apoptosis were seen during this stage. The occurrence of apoptosis, as demonstrated by apoptot i c cel l s and bodies , was the mos t important histological change during reperfusion. The severity of apoptosis was dependent on the time of reperfusion, and by increasing the time of reperfusion,the numbers of apoptotic bodies was significantly enhanced. The amounts of lactate dehydrogenase,alanine aminotransferase, aspartate aminotransferase,creatinine and urea were significantly increased in serum obtained from animals exposed to hepatic IR.

  2. Is glycogen storage disease 1a associated with atherosclerosis?

    NARCIS (Netherlands)

    Ubels, FL; Rake, JP; Slaets, JPJ; Smit, Gerrit; Smit, Andries


    Deficiency of microsomal glucose-6-phosphatase in liver and kidney leads to glycogen storage disease type 1a (GSD 1a). Notwithstanding intensive dietary therapy, moderate to severe dyslipidaemia and microalbuminuria, both known atherosclerotic risk factors, remain present. Although more patients rea

  3. Development of a quantitative 96-well method to image glycogen storage in primary rat hepatocytes. (United States)

    Pilling, James; Garside, Helen; Ainscow, Edward


    Within the liver, hormonal control of glycogen metabolism allows for rapid release and uptake of glucose from the circulation, providing a reserve of glucose that can be utilised by other organs. Traditionally, cellular glycogen storage has been detected using Periodic acid Schiff (PAS) staining of histopathology samples or a biochemical assay. Colorimetric measurement of glycogen content using PAS staining is hard to quantify whilst biochemical techniques give limited information about events such as cytotoxicity or allow analysis of hepatic heterogeneity. Here, we describe the development of an imaging based method to quantify glycogen storage in 96-well cultures of primary rat hepatocytes using the inherent fluorescence properties of the Schiff reagent. PAS-stained hepatocytes were imaged using an automated fluorescent microscope, with the amount of glycogen present in each cell being quantified. Using this technique, we found an increase in glycogen storage in response to insulin (EC50 = 0.31 nM) that was in agreement with that determined using biochemical quantification (EC50 = 0.32 nM). Furthermore, a dose dependent increase in glycogen storage was also seen in response to glycogen synthase kinase inhibitors and glycogen phosphorylase inhibitors. This technique allows rapid assessment of cellular glycogen storage in response to hormones and small molecule inhibitors.

  4. Curcumin prevents bile canalicular alterations in the liver of hamsters infected with Opisthorchis viverrini. (United States)

    Jattujan, Prapaporn; Pinlaor, Somchai; Charoensuk, Lakhanawan; Arunyanart, Channarong; Welbat, Jariya Umka; Chaijaroonkhanarak, Wunnee


    Opisthorchis viverrini infection causes inflammation and liver injury leading to periductal fibrosis. Little is known about the pathological alterations in bile canaliculi in opisthorchiasis. This study aimed to investigate bile canalicular alterations in O. viverrini-infected hamsters and to examine the chemopreventive effects of curcumin on such changes. Hamsters were infected with O. viverrini and one group of animals was fed with 1% dietary curcumin supplement. Animals were examined during the acute infection phase, days 21 and 30 post-infection (PI) and chronic infection phase (day 90 PI). Scanning electron microscopy revealed that in the infected group fed with a normal diet, bile canaliculi became slightly tortuous by 30 day PI and more tortuous at day 90 PI. Transmission electron microscopy showed a reduction in microvilli density of canaliculi starting at day 30 PI, with a marked loss of microvilli at day 90 PI. These ultrastructral changes were slightly seen at day 21 PI, which was similar to that found in infected animals fed with 1% curcumin-supplemented diet. Notably, curcumin treatment prevented the reduction of microvilli density, reduced the dilation of bile canaliculi, and decreased the tortuosity of the bile canaliculi relative to non-infected animals on a normal diet at days 30 and 90 PI. These results suggest that curcumin reduces alteration of bile canaliculi and may be a promising agent to prevent the onset of bile duct abnormalities induced by O. viverrini infection.

  5. Butachlor, a suspected carcinogen, alters growth and transformation characteristics of mouse liver cells. (United States)

    Ou, Y H; Chung, P C; Chang, Y C; Ngo, F Q; Hsu, K Y; Chen, F D


    Butachlor is a widely used herbicide in Asia and South America. Previous investigations have indicated that it is a suspected carcinogen. To understand more about the biological effects of butachlor on cultured cells and the mechanism(s) of its carcinogenicity, we studied the alteration of the growth characteristics that was induced by butachlor in normal mouse liver cells (BNL CL2). This study demonstrates that butachlor decreases the population-doubling time of BNL CL2 cells, suggesting that it stimulates cell proliferation. To support this finding, a thymidine incorporation assay was conducted and a similar result that butachlor stimulates cell proliferation was elucidated. In addition, we show that butachlor increases the saturation density of the BNL CL2 cells. When combined with the tumor initiator N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), butachlor transforms cells efficiently, as demonstrated by loss of contact inhibition. These findings indicate that butachlor alters the growth characteristics of BNL CL2 cells and suggest that butachlor may induce malignant transformation through stimulation of cell proliferation, alteration of cell cycle regulation, and suppression of cell density-dependent inhibition of proliferation.

  6. Liver Disease and Pulmonary Hypertension (United States)

    ... fats, produces several important com- pounds, stores certain vitamins, makes specific amino acids, converts glucose to glycogen, ... liver. This increased pres- sure causes blood to bypass the liver. As a result, the blood is ...

  7. Garlic attenuates histological and histochemical alterations in livers of Schistosoma mansoni infected mice. (United States)

    Mahmoud, Y I; Riad, N H; Taha, H


    Interest in screening for new anti-schistosomal agents is growing because of increased concerns about resistance to and safety of praziquantel. We investigated the anti-schistosomal action of prophylactic and therapeutic doses of garlic on the histological and histochemical alterations caused by Schistosoma mansoni infection. Livers of infected mice were characterized by granulomas, periportal inflammation and fibrosis, hepatocyte vacuolation, fatty degeneration and necrosis, and hypertrophy and pigmentation of Kupffer cells. Significant depletion of carbohydrates and increased lipid vacuoles also were observed. All garlic regimens caused suppression of granuloma formation and amelioration of histological and histochemical changes; the continuous treatment protocol produced the best results. Garlic appears to be a safe and economical anti-schistosomal adjuvant for attenuating the pathogenicity of schistosomiasis.

  8. Alteration in substrate specificity of horse liver alcohol dehydrogenase by an acyclic nicotinamide analog of NAD(+). (United States)

    Malver, Olaf; Sebastian, Mina J; Oppenheimer, Norman J


    A new, acyclic NAD-analog, acycloNAD(+) has been synthesized where the nicotinamide ribosyl moiety has been replaced by the nicotinamide (2-hydroxyethoxy)methyl moiety. The chemical properties of this analog are comparable to those of β-NAD(+) with a redox potential of -324mV and a 341nm λmax for the reduced form. Both yeast alcohol dehydrogenase (YADH) and horse liver alcohol dehydrogenase (HLADH) catalyze the reduction of acycloNAD(+) by primary alcohols. With HLADH 1-butanol has the highest Vmax at 49% that of β-NAD(+). The primary deuterium kinetic isotope effect is greater than 3 indicating a significant contribution to the rate limiting step from cleavage of the carbon-hydrogen bond. The stereochemistry of the hydride transfer in the oxidation of stereospecifically deuterium labeled n-butanol is identical to that for the reaction with β-NAD(+). In contrast to the activity toward primary alcohols there is no detectable reduction of acycloNAD(+) by secondary alcohols with HLADH although these alcohols serve as competitive inhibitors. The net effect is that acycloNAD(+) has converted horse liver ADH from a broad spectrum alcohol dehydrogenase, capable of utilizing either primary or secondary alcohols, into an exclusively primary alcohol dehydrogenase. This is the first example of an NAD analog that alters the substrate specificity of a dehydrogenase and, like site-directed mutagenesis of proteins, establishes that modifications of the coenzyme distance from the active site can be used to alter enzyme function and substrate specificity. These and other results, including the activity with α-NADH, clearly demonstrate the promiscuity of the binding interactions between dehydrogenases and the riboside phosphate of the nicotinamide moiety, thus greatly expanding the possibilities for the design of analogs and inhibitors of specific dehydrogenases.

  9. Muscle glycogen stores and fatigue

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Westerblad, Håkan; Nielsen, Joachim


      Studies performed at the beginning of the last century revealed the importance of carbohydrate as a fuel during exercise, and the importance of muscle glycogen on performance has subsequently been confirmed in numerous studies. However, the link between glycogen depletion and impaired muscle...... function during fatigue is not well understood and a direct cause-and-effect relationship between glycogen and muscle function remains to be established. The use of electron microscopy has revealed that glycogen is not homogeneously distributed in skeletal muscle fibres, but rather localized in distinct...... pools. Furthermore, each glycogen granule has its own metabolic machinery with glycolytic enzymes and regulating proteins. One pool of such glycogenolytic complexes is localized within the myofibrils in close contact with key proteins involved in the excitation-contraction coupling and Ca2+ release from...

  10. The effect of alterations in total coenzyme A on metabolic pathways in the liver and heart

    Energy Technology Data Exchange (ETDEWEB)

    Schlosser, C.A.S.


    The first set of experiments involved in vitro experiments using primary cultures of rat hepatocytes. A range of conditions were developed which resulted in cell cultures with variations in total CoA over a range of 1.3 to 2.9 nmol/mg protein with identical hormonal activation which simulated metabolic stress. Elevations of total CoA levels above that of controls due to preincubation with cyanamide plus pantothenate were correlated with diminished rates of total ketone body production, 3-hydroxybutyrate production and ratios of 3 hydroxybutyrate/acetoactetate with palmitate as substrate. In contrast, cells with elevated total CoA levels had higher rates of ({sup 14}C) CO{sub 2} production from radioactive palmitate which implied greater flux of acetyl CoA units into the TCA cycle and less to the pathway of ketogenesis. The second set of experiments were designed to alter total CoA levels in vivo by maintaining rats on a chronic ethanol diet with or without pantothenate-supplementation. The effect of alterations of CoA on mitochondrial metabolism was evaluated by measuring substrate oxidation rates in liver and heat mitochondria as well as ketone body production with palmitoyl-1-carnitine as substrate.

  11. Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Henriette Kirchner


    Conclusion: Severely obese non-diabetic and type 2 diabetic patients have distinct alterations in the hepatic methylome and transcriptome, with hypomethylation of several genes controlling glucose metabolism within the ATF-motif regulatory site. Obesity appears to shift the epigenetic program of the liver towards increased glycolysis and lipogenesis, which may exacerbate the development of insulin resistance.

  12. A correlated thin section and freeze-fracture study of o-phenylphenol-indued alterations in the rat liver. (United States)

    Robenek, H; Meiss, R; Themann, H; Himmels, S


    The ultrastructural changes in the liver cells of male Wistar rats induced by oral and subcutaneous application of o-phenylphenol were studied electron microscopically using the thin section and freeze-fracture technique. The rats were given the o-phenylphenol once at a dose of 2,500 mg/kg b.w. and were sacrificed 60 h after treatment. In the orally treated animals, alterations in the nuclei and nucleoli of the hepatocytes were the most prominent alterations. Furthermore, an increase in smooth endoplasmic reticulum, lysosomes and microbodies were found. After the subcutaneous injection of o-phenylphenol enlargements of the bile canaliculi, intercellular space and pathological alterations in the mitochondria were seen. A proliferation of the smooth endoplasmic reticulum, an increase of microbodies and a decrease in the rough endoplasmic reticulum could be found. Both groups showed an increase in small intracellular fat droplets in the hepatocytes. In general, the effects of the subcutaneous application on the liver were more pronounced than the effects of the oral application. Freeze-fracture replicas exhibited a disorganization of the zonulae occludentes and an apparent increase in the number and size of gap junctions. These alterations were interpreted as an attempt of the liver cells to counteract the intracanalicular pressure and to increase the mechanical stability of the liver tissue.

  13. Zn(II)-curcumin protects against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism. (United States)

    Yu, Chuan; Mei, Xue-Ting; Zheng, Yan-Ping; Xu, Dong-Hui


    Curcumin can chelate metal ions, forming metallocomplexes. We compared the effects of Zn(II)-curcumin with curcumin against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism. Oral administration of Zn(II)-curcumin dose-dependently prevented the ethanol-induced elevation of serum malondialdehyde (MDA) content and reductions in glutathione level and superoxide dismutase (SOD) activity. Zn(II)-curcumin also inhibited ethanol-induced liver injury. Additionally, Zn(II)-curcumin dose-dependently inhibited hemorheological abnormalities, including the ethanol-induced elevation of whole blood viscosity, plasma viscosity, blood viscosity at corrected hematocrit (45%), erythrocyte aggregation index, erythrocyte rigidity index and hematocrit. Compared to curcumin at the same dose, Zn(II)-curcumin more effectively elevated SOD activity, ameliorated liver injury and improved hemorheological variables. These results suggest that Zn(II)-curcumin protected the rats from ethanol-induced liver injury and hemorheological abnormalities via the synergistic effect of curcumin and zinc.

  14. Refsum disease diagnostic marker phytanic acid alters the physical state of membrane proteins of liver mitochondria. (United States)

    Schönfeld, P; Struy, H


    Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid), a branched chain fatty acid accumulating in Refsum disease to high levels throughout the body, induces uncoupling of rat liver mitochondria similar to non-branched fatty acids (e.g. palmitic acid), but the contribution of the ADP/ATP carrier or the aspartate/glutamate carrier in phytanic acid-induced uncoupling is of minor importance. Possible deleterious effects of phytanic acid on membrane-linked energy coupling processes were studied by ESR spectroscopy using rat liver mitochondria and a membrane preparation labeled with the lipid-specific spin probe 5-doxylstearic acid (5-DSA) or the protein-specific spin probe MAL-TEMPO (4-maleimido-2,2,6, 6-tetramethyl-piperidine-1-oxyl). The effects of phytanic acid on phospholipid molecular dynamics and on the physical state of membrane proteins were quantified by estimation of the order parameter or the ratio of the amplitudes of the weakly to strongly immobilized MAL-TEMPO binding sites (W/S ratio), respectively. It was found, that phytanic acid (1) increased the mobility of phospholipid molecules (indicated by a decrease in the order parameter) and (2) altered the conformational state and/or the segmental mobility of membrane proteins (indicated by a drastic decrease in the W/S ratio). Unsaturated fatty acids with multiple cis-double bonds (e.g. linolenic or arachidonic acid), but not non-branched FFA (ranging from chain length C10:0 to C18:0), also decrease the W/S ratio. It is hypothesized that the interaction of phytanic acid with transmembrane proteins might stimulate the proton permeability through the mitochondrial inner membrane according to a mechanism, different to a protein-supported fatty acid cycling.

  15. Alteration in the fatty acid composition of liver, kidney and plasma from diethylhexyl phthalate-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Okita, J.R.; Okita, R.T. (Medical Coll. of Wisconsin, Milwaukee (United States))


    Cytochromes P-450 are induced in rat liver microsomes by a number of compounds which cause peroxisome proliferation. One such compound, diethylhexyl phthalate (DEHP), induces P-450 IVA1 which catalyzes {omega}- and ({omega}-1)-hydroxylation of fatty acids. In liver of rats fed DEHP, there is a 10-fold induction of {omega}-hydroxylation of laurate and ({omega}-1)-hydroxylation of palmitate, as compared to control rat liver. There is a 3-fold induction of other hydroxylations, such as W-hydroxylation of palmitate and {omega}- ({omega}-1)-hydroxylation of syristate. Despite these increases in hydroxylase activity, the authors have not been able to demonstrate increases in hydroxy fatty acids or dicarboxylic acids in liver or plasma of rats fed DEHP. However, alterations in the fatty acid composition of lipids in liver, kidney cortex and plasma were observed. They consistently observed increases in oleate (expressed as mol% of total fatty acid) in liver (11% in control increased to 24% in DEHP-treated), kidney cortex (12% to 16%) and plasma (13% to 24%). This increase in oleate was quite striking when expressed as ug/gm tissue or ug/al plasma. DEHP treatment resulted in increased oleate in mitochondrial, microsomal and cytosolic fractions of liver.

  16. MRI morphologic alterations after liver SBRT. Direct dose correlation with intermodal matching

    Energy Technology Data Exchange (ETDEWEB)

    Boda-Heggemann, Judit; Jahnke, Anika; Jahnke, Lennart; Vogel, Lena; Simeonova-Chergou, Anna O.; Herskind, Carsten; Wenz, Frederik; Lohr, Frank [University of Heidelberg, Department of Radiation Oncology, University Medical Center Mannheim, Mannheim (Germany); Attenberger, Ulrike; Budjan, Johannes [University of Heidelberg, Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Mannheim (Germany)


    CT morphologic and histopathologic alterations have been reported after SBRT. We analyzed the correlation of MRI morphologic alterations with radiation doses to assess the potential for MRI-based dose-effect correlation in healthy liver tissue. MRI data of 24 patients with liver metastases 7±3 weeks after image-guided SBRT in deep-inspiration breath-hold were retrospectively analyzed. MRI images were intermodally matched to the planning CT and corresponding dose distribution. Absolute doses were converted to EQD{sub 2,α/β=x} with α/β values of 2, 3 for healthy liver tissue, 8 Gy for modelled predamaged liver tissue and 10 Gy for tumor tissue. A central nonenhancing area was observed within the isodose lines of nominally 48.2 ± 15.2 Gy, EQD{sub 2Gy/α/β=10} 92.5 ± 27.7 Gy. Contrast-enhancement around the central nonenhancing area was observed within the isodose lines of nominally 46.9 ± 15.3 Gy, EQD{sub 2Gy/α/β=10} 90.5 ± 28.3 Gy. Outside the high-dose volume, in the beam path, characteristic sharply defined, nonblurred MRI morphologic alterations were observed that corresponded with the following isodose lines: T1-intensity changes occurred at isodose lines of nominally 21.9 ± 6.7 Gy (EQD{sub 2,α/β=2} 42.5 ± 8.7 Gy, EQD{sub 2,α/β=3} 38.5 ± 7.6 Gy, EQD{sub 2,α/β=8} 30.2 ±6.3 Gy). T2-hyper/hypointensity was observed within isodose lines of nominally 22.4 ± 6.6 Gy (EQD{sub 2,α/β=2} 42.7 ± 8.1 Gy, EQD{sub 2,α/β=3} 38.7 ± 7 Gy; EQD{sub 2,α/β=8} 30.5 ± 5.9 Gy). Using deformable matching, direct spatial/dosimetric correlation of SBRT-induced changes in liver tissue was possible. In the PTV high-dose region, a central nonenhancing area and peripheral contrast medium accumulation was observed. Beam path doses of 38-42 Gy (EQD{sub 2,α/β=2-3}) induce characteristic MRI morphologic alterations. (orig.) [German] CT-morphologische Veraenderungen nach SBRT sind beschrieben und korrelieren mit histopathologischen Veraenderungen. Ziel war es, MRT

  17. Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency. (United States)

    Collantes, María; Serrano-Mendioroz, Irantzu; Benito, Marina; Molinet-Dronda, Francisco; Delgado, Mercedes; Vinaixa, María; Sampedro, Ana; Enríquez de Salamanca, Rafael; Prieto, Elena; Pozo, Miguel A; Peñuelas, Iván; Corrales, Fernando J; Barajas, Miguel; Fontanellas, Antonio


    Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver.

  18. Determination of aluminium induced metabolic changes in mice liver: a Fourier transform infrared spectroscopy study. (United States)

    Sivakumar, S; Sivasubramanian, J; Khatiwada, Chandra Prasad; Manivannan, J; Raja, B


    In this study, we made a new approach to evaluate aluminium induced metabolic changes in liver tissue of mice using Fourier transform infrared spectroscopy analysis taking one step further in correlation with strong biochemical evidence. This finding reveals the alterations on the major biochemical constituents, such as lipids, proteins, nucleic acids and glycogen of the liver tissues of mice. The peak area value of amide A significantly decrease from 288.278±3.121 to 189.872±2.012 between control and aluminium treated liver tissue respectively. Amide I and amide II peak area value also decrease from 40.749±2.052 to 21.170±1.311 and 13.167±1.441 to 8.953±0.548 in aluminium treated liver tissue respectively. This result suggests an alteration in the protein profile. The absence of olefinicCH stretching band and CO stretching of triglycerides in aluminium treated liver suggests an altered lipid levels due to aluminium exposure. Significant shift in the peak position of glycogen may be the interruption of aluminium in the calcium metabolism and the reduced level of calcium. The overall findings exhibit that the liver metabolic program is altered through increasing the structural modification in proteins, triglycerides and quantitative alteration in proteins, lipids, and glycogen. All the above mentioned modifications were protected in desferrioxamine treated mice. Histopathological results also revealed impairment of aluminium induced alterations in liver tissue. The results of the FTIR study were found to be in agreement with biochemical studies and which demonstrate FTIR can be used successfully to indicate the molecular level changes.

  19. FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. (United States)

    Kir, Serkan; Beddow, Sara A; Samuel, Varman T; Miller, Paul; Previs, Stephen F; Suino-Powell, Kelly; Xu, H Eric; Shulman, Gerald I; Kliewer, Steven A; Mangelsdorf, David J


    Fibroblast growth factor (FGF) 19 is an enterokine synthesized and released when bile acids are taken up into the ileum. We show that FGF19 stimulates hepatic protein and glycogen synthesis but does not induce lipogenesis. The effects of FGF19 are independent of the activity of either insulin or the protein kinase Akt and, instead, are mediated through a mitogen-activated protein kinase signaling pathway that activates components of the protein translation machinery and stimulates glycogen synthase activity. Mice lacking FGF15 (the mouse FGF19 ortholog) fail to properly maintain blood concentrations of glucose and normal postprandial amounts of liver glycogen. FGF19 treatment restored the loss of glycogen in diabetic animals lacking insulin. Thus, FGF19 activates a physiologically important, insulin-independent endocrine pathway that regulates hepatic protein and glycogen metabolism.

  20. Neither bovine somatotropin nor growth hormone-releasing factor alters expression of thyroid hormone receptors in liver and mammary tissues. (United States)

    Capuco, A V; Binelli, M; Tucker, H A


    Physiological effects of thyroid hormones are mediated primarily by binding of triiodothyronine to specific nuclear receptors. Organ-specific changes in production of triiodothyronine from its prohormone, thyroxine, have been hypothesized to target the action of thyroid hormones on the mammary gland and play a role in mediating or augmenting a galactopoietic response to bovine somatotropin (bST). Additionally, tissue responsiveness to thyroid hormones may be altered by changes in the number or affinity of nuclear receptors for thyroid hormones. In the present study, effects of bST and bovine growth hormone-releasing factor (bGRF) on thyroid hormone receptors in liver and mammary gland were studied. Lactating Holstein cows received continuous infusions of bST or bGRF for 63 d or served as uninfused controls. Nuclei were isolated from harvested mammary and liver tissues and incubated with [(125)I]-triiodothyronine. Treatments did not alter the capacity or affinity of specific binding sites for triiodothyronine in liver or mammary nuclei. Evaluation of transcript abundance for thyroid hormone receptors showed that isoforms of thyroid hormone receptor or retinoid receptor (which may influence thyroid receptor action) expressed in the mammary gland were not altered by bST or bGRF treatment. Data do not support the hypothesis that administration of bST or bGRF alters sensitivity of mammary tissue by changing expression of thyroid hormone receptors.

  1. Assessment of heavy metal (Cu, Ni, Fe, Co, Mn, Cr, Zn) pollution in effluent dominated rivulet water and their effect on glycogen metabolism and histology of Mastacembelus armatus. (United States)

    Javed, Mehjbeen; Usmani, Nazura


    The present study was conducted to examine the contamination of rivulet situated at Kasimpur, Aligarh (27.218° N; 79.378° E). It receives the wastewater of Harduaganj Thermal Power Plant (HTPS) containing fly ash and heavy metals. Among the heavy metals estimated in the rivulet water, Fe (8.71 mgL(-1)) was present in the highest concentration followed by Cu (0.86 mgL(-1)), Zn (0.30 mgL(-1)) Mn (0.21 mgL(-1)), Ni (0.12 mgL(-1)), Co (0.11 mgL(-1)) and Cr (0.10 mgL(-1)). The values for the heavy metals such as Fe, Ni and Mn were beyond the limits set by UNEPGEMS. Bioaccumulation of these heavy metals was detected in tissues such as gills, liver, kidney, muscle and integument of the fish Mastacembelus armatus. Accumulation of Fe (213.29 - 2601.49 mgkg(-1).dw) was highest in all the organs. Liver was the most influenced organ and integument had the least metal load. The accumulation of Fe, Zn, Cu and Mn, observed in the tissues were above the values recommended by FAO/WHO. Biochemical estimation related to blood glucose, liver and muscle glycogen conducted showed significant (p < 0.01) elevation in blood glucose content over control (17.73%), whereas liver glycogen dropped significantly (p < 0.01) over control (-89.83%), and similarly muscle glycogen also decreased significantly (p < 0.05) over control (-71.95%), suggesting enhanced glycolytic capacity to fuel hepatic metabolism. Histopathological alterations were also observed in selected organs (gills, liver and kidney) of Mastacembelus armatus.

  2. Erythrocytes Membrane Alterations Reflecting Liver Damage in CCl₄-Induced Cirrhotic Rats: The Ameliorative Effect of Naltrexone

    Directory of Open Access Journals (Sweden)

    Fatemeh Sarhadi Kholari


    Full Text Available Cirrhosis is the consequence of chronic liver disease. Deleterious effects of oxidative stress on hepatocytes may be reflected in the erythrocyte membrane. Naltrexone (NTX has been shown to attenuate hepatocellular injury in fibrotic animal models. The aim of this study was to investigate the progressive effect of CCl4 on the liver and whether the improvement of liver cirrhosis can be monitored through alterations in the erythrocyte membrane. In this study, 84 male Wistar rats were divided into 4 groups and received reagents (i.p. as follows: 1- CCl₄, 2- NTX + CCl₄, 3- Mineral Oil (M, and 4- NTX + M. After 2, 6 and 8 weeks, the blood and liver tissue samples were collected. Plasma enzyme activities, the content of erythrocyte GSH and some membrane compositions, including protein carbonyl, protein sulfhydryl, and malondialdehyde were assessed. After 6 and 8 weeks, plasma enzyme activities and the content of protein carbonyl were higher in CCl4 group significantly, as compared to other groups (P<0.001. NTX significantly diminished protein carbonyl and plasma enzyme activities (P<0.001. GSH did not change until the 6th week. However, CCl4+NTX increased it significantly as compared to CCl₄ group (P<0.05. Protein sulfhydryl showed changes in NTX+CCl₄ group which indicated a significant increase in protein sulfhydryl content in a 6th week compared to CCl4 group (P<0.05. MDA did not show any significant alteration. CCl₄-induced cirrhosis is accompanied by increased content of oxidative stress markers, especially protein carbonyl of RBC membrane and plasma enzyme activities. This study shows that the progression of liver cirrhosis and the ameliorative effect of NTX can be followed through alterations of these markers.

  3. Dumping syndrome, a cause of acquired glycogenic hepatopathy. (United States)

    Resnick, Jeffrey M; Zador, Ivan; Fish, Daryl L


    A 2-year-old boy, having undergone fundoplication for gastroesophageal reflux disease and fed by gastrostomy, presented with recurrent emesis, syncope with hypoglycemia, and persistently elevated serum liver transaminase levels. Liver biopsy revealed hepatocellular glycogenosis by light and electron microscopy. Further evaluation showed no evidence of diabetes mellitus, glycogen storage disease, or corticosteroid use. Since the hyperglycemic-hyperinsulinemic state of dumping syndrome would provide a mechanism for hepatocellular glycogenosis, the biopsy findings prompted consideration of dumping syndrome. Metabolic evaluation confirmed the diagnosis of dumping syndrome, and appropriate dietary management led to sustained resolution of symptomatology and hypertransaminasemia. Dumping syndrome is proposed to be a cause of hepatocellular glycogenosis, the latter representing a form of acquired glycogenic hepatopathy.

  4. Hormonal control of hepatic glycogen metabolism in food-deprived, continuously swimming coho salmon Oncorhynchus kisutch (United States)

    Vijayan, M.M.; Maule, A.G.; Schreck, C.B.; Moon, T.W.


    The plasma cortisol concentration and liver cytosolic glucocorticoid receptor activities of continuously swimming, food-deprived coho salmon (Oncorhynchus kisutch) did not differ from those of resting, fed fish. Plasma glucose concentration was significantly higher in the exercising, starved fish, but there were no significant differences in either hepatic glycogen concentration or hepatic activities of glycogen phosphorylase, glycogen synthase, pyruvate kinase, or lactate dehydrogenase between the two groups. Total glucose production by hepatocytes did not differ significantly between the two groups; glycogen breakdown accounted for all the glucose produced in the resting, fed fish whereas it explained only 59% of the glucose production in the exercised animals. Epinephrine and glucagon stimulation of glucose production by hepatocytes was decreased in the exercised fish without significantly affecting hepatocyte glycogen breakdown in either group. Insulin prevented glycogen breakdown and enhanced glycogen deposition in exercised fish. The results indicate that food-deprived, continuously swimming coho salmon conserve glycogen by decreasing the responsiveness of hepatocytes to catabolic hormones and by increasing the responsiveness to insulin (anabolic hormone).

  5. Type I Glycogen Storage Disease (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  6. Histopathological alterations in liver anatomy after exposure to chlorpyrifos in zebrafish (Danio rerio)


    Bangeppagari, Manjunatha


    Chlorpyrifos is an organophosphate pesticide widely used in agriculture and aquaculture. This study investigated its effects on histopathology of zebrafish (Danio rerio) liver. For this six adult male and six adult female zebrafish were exposed to 200 ?g/L of chlorpyrifos for 24h, 48h, 72h and 96hrs. Chlorpyrifos toxicity on liver histopathological changes were examined by light microscopy. Structural damage spotted in the liver were vacuolization and presence of sinusoid spaces were observed...

  7. Characterization of a canine model of glycogen storage disease type IIIa

    Directory of Open Access Journals (Sweden)

    Haiqing Yi


    Glycogen storage disease type IIIa (GSD IIIa is an autosomal recessive disease caused by deficiency of glycogen debranching enzyme (GDE in liver and muscle. The disorder is clinically heterogeneous and progressive, and there is no effective treatment. Previously, a naturally occurring dog model for this condition was identified in curly-coated retrievers (CCR. The affected dogs carry a frame-shift mutation in the GDE gene and have no detectable GDE activity in liver and muscle. We characterized in detail the disease expression and progression in eight dogs from age 2 to 16 months. Monthly blood biochemistry revealed elevated and gradually increasing serum alanine transaminase (ALT, aspartate transaminase (AST and alkaline phosphatase (ALP activities; serum creatine phosphokinase (CPK activity exceeded normal range after 12 months. Analysis of tissue biopsy specimens at 4, 12 and 16 months revealed abnormally high glycogen contents in liver and muscle of all dogs. Fasting liver glycogen content increased from 4 months to 12 months, but dropped at 16 months possibly caused by extended fibrosis; muscle glycogen content continually increased with age. Light microscopy revealed significant glycogen accumulation in hepatocytes at all ages. Liver histology showed progressive, age-related fibrosis. In muscle, scattered cytoplasmic glycogen deposits were present in most cells at 4 months, but large, lake-like accumulation developed by 12 and 16 months. Disruption of the contractile apparatus and fraying of myofibrils was observed in muscle at 12 and 16 months by electron microscopy. In conclusion, the CCR dogs are an accurate model of GSD IIIa that will improve our understanding of the disease progression and allow opportunities to investigate treatment interventions.

  8. Sequential alterations in the hepatic content and metabolism of cyclic AMP and cyclic GMP induced by DL-ethionine: evidence for malignant transformation of liver with a sustained increase in cyclic AMP. (United States)

    DeRubertis, F R; Craven, P A


    There is evidence than adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) may have antagonistic actions on cell growth, with cAMP inhibiting and cGMP stimulating this process. However, reductions in cAMP and increases in cGMP are not charactersitic of all neoplastic tissues. Thus, benign and malignant tissues from hepatoma-bearing rats exposed to the hepatic carcinogen DL-ethionine have elevated rather than depressed cAMP, compared to control liver, and parenteral administration of this drug increases hepatic cAMP within hours. In the present study, the effects of ethionine ingestion on the hepatic content and metabolism of both cAMP and cGMP were examined sequentially in rats at 2 and then 6 wk intervals, from the initiation of drug administration until the development of hepatomas. After 2 wk, cAMP content of quick-frozen liver from rats receiving ethionine (E) was significantly increased (826 +/- 91 pmole/g wet weight) above that of liver from pair-fed controls (C, 415 +/- 44), whether calculated by tissue wet weight, protein, or DNA content. In benign tissue from E, higher cAMP was still evident after in vitro incubations of slices with 2 mM 1-methyl-3-iso-butylxanthine (MIX) and was associated with enhanced adenylate cyclase and unchanged high or low Km cAMP-phosphodiesterase activities. These findings are compatible with accelerated cAMP generation in liver from E. Protein kinase activity ratios were significantly increased in frozen liver from E (0.52 +/- 0.04 versus 0.36 +/- 0.03 in C), and the percent glycogen synthetase in the I form was clearly reduced (19% +/- 2% in E versus 47% +/- 5% in c). incubation of hepatic slices from E or C with MIX and/or 10 muM glucagon further increased cAMP and protein kinase activity ratios, data which imply higher effective, as well as total, cellular cAMP in E. Changes in cAMP metabolism and action observed at 2 wk persisted throughout the 38-wk period of drug ingestion. Adenylate cyclase

  9. Dichloroacetate Stimulates Glycogen Accumulation in Primary Hepatocytes through an Insulin-Independent Mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Lingohr, Melissa K.(Washington State University); Bull, Richard J.(SELF-EMPLOYED CONSULTANTS); Kato-Weinstein, Junko (UNIVERSITY PROGRAMS); Thrall, Brian D.(BATTELLE (PACIFIC NW LAB))


    Dichloroacetate (DCA), a by-product of water chlorination, causes liver cancer in B6C3F1 mice. A hallmark response observed in mice exposed to carcinogenic doses of DCA is an accumulation of hepatic glycogen content. To distinguish whether the in vivo glycogenic effect of DCA was dependent on insulin and insulin signaling proteins, experiments were conducted in isolated hepatocytes where insulin concentrations could be controlled. In hepatocytes isolated from male B6C3F1 mice, DCA increased glycogen levels in a dose-related manner, independently of insulin. The accumulation of hepatocellular glycogen induced by DCA was not the result of decreased glycogenolysis, since DCA had no effect on the rate of glucagon-stimulated glycogen breakdown. Glycogen accumulation caused by DCA treatment was not hindered by inhibitors of extracellular-regulated protein kinase kinase (Erk1/2 kinase or MEK) or p70 kDa S6 protein kinase (p70(S6K)), but was completely blocked by the phosphatidylinositol 3-kinase (PI3K) inhibitors, LY294002 and wortmannin. Similarly, insulin-stimulated glycogen deposition was not influenced by the Erk1/2 kinase inhibitor, PD098509, or the p70(S6K) inhibitor, rapamycin. Unlike DCA-stimulated glycogen deposition, PI3K-inhibition only partially blocked the glycogenic effect of insulin. DCA did not cause phosphorylation of the downstream PI3K target protein, protein kinase B (PKB/Akt). The phosphorylation of PKB/Akt did not correlate to insulin-stimulated glycogenesis either. Similar to insulin, DCA in the medium decreased IR expression in isolated hepatocytes. The results indicate DCA increases hepatocellular glycogen accumulation through a PI3K-dependent mechanism that does not involve PKB/Akt and is, at least in part, different from the classical insulin-stimulated glycogenesis pathway. Somewhat surprisingly, insulin-stimulated glycogenesis also appears not to involve PKB/Akt in isolated murine hepatocytes.

  10. Brain Glycogen Decreases During Intense Exercise Without Hypoglycemia: The Possible Involvement of Serotonin. (United States)

    Matsui, Takashi; Soya, Shingo; Kawanaka, Kentaro; Soya, Hideaki


    Brain glycogen stored in astrocytes, a source of lactate as a neuronal energy source, decreases during prolonged exercise with hypoglycemia. However, brain glycogen dynamics during exercise without hypoglycemia remain unknown. Since intense exercise increases brain noradrenaline and serotonin as known inducers for brain glycogenolysis, we hypothesized that brain glycogen decreases with intense exercise not accompanied by hypoglycemia. To test this hypothesis, we employed a well-established acute intense exercise model of swimming in rats. Rats swam for fourteen 20 s bouts with a weight equal to 8 % of their body mass and were sacrificed using high-power (10 kW) microwave irradiation to inactivate brain enzymes for accurate detection of brain glycogen and monoamines. Intense exercise did not alter blood glucose, but did increase blood lactate levels. Immediately after exercise, brain glycogen decreased and brain lactate increased in the hippocampus, cerebellum, cortex, and brainstem. Simultaneously, serotonin turnover in the hippocampus and brainstem mutually increased and were associated with decreased brain glycogen. Intense swimming exercise that does not induce hypoglycemia decreases brain glycogen associated with increased brain lactate, implying an importance of glycogen in brain energetics during intense exercise even without hypoglycemia. Activated serotonergic regulation is a possible underlying mechanism for intense exercise-induced glycogenolysis at least in the hippocampus and brainstem.

  11. Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Sulin Cheng

    Full Text Available Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49 and women (n = 52 with and without NAFLD.Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS. Serum samples were analyzed using a nuclear magnetic resonance (NMR metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot.Increased branched-chain amino acid (BCAA, aromatic amino acid (AAA and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all. Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all, whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all.Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.

  12. Fructose-Drinking Water Induced Nonalcoholic Fatty Liver Disease and Ultrastructural Alteration of Hepatocyte Mitochondria in Male Wistar Rat

    Directory of Open Access Journals (Sweden)

    Norshalizah Mamikutty


    Full Text Available Background. Nonalcoholic fatty liver disease (NAFLD is one of the complications of the metabolic syndrome. It encompasses a wide range of disease spectrum from simple steatosis to liver cirrhosis. Structural alteration of hepatic mitochondria might be involved in the pathogenesis of NAFLD. Aims. In the present study, we used a newly established model of fructose-induced metabolic syndrome in male Wistar rats in order to investigate the ultrastructural changes in hepatic mitochondria that occur with fructose consumption and their association with NAFLD pathogenesis. Methods. The concentration of fructose-drinking water (FDW used in this study was 20%. Six male Wistar rats were supplemented with FDW 20% for eight weeks. Body composition and metabolic parameters were measured before and after 8 weeks of FDW 20%. Histomorphology of the liver was evaluated and ultrastructural changes of mitochondria were assessed with transmission electron micrograph. Results. After 8 weeks of fructose consumption, the animals developed several features of the metabolic syndrome. Moreover, fructose consumption led to the development of macrovesicular hepatic steatosis and mitochondrial ultrastructural changes, such as increase in mitochondrial size, disruption of the cristae, and reduction of matrix density. Conclusion. We conclude that in male Wistar rat 8-week consumption of FDW 20% leads to NAFLD likely via mitochondrial structural alteration.

  13. Altered microRNA expression induced by tumorigenic conazoles in mouse liver. (United States)

    Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants ...

  14. Molecular Mechanism Responsible for Fibronectin-controlled Alterations in Matrix Stiffness in Advanced Chronic Liver Fibrogenesis. (United States)

    Iwasaki, Ayumi; Sakai, Keiko; Moriya, Kei; Sasaki, Takako; Keene, Douglas R; Akhtar, Riaz; Miyazono, Takayoshi; Yasumura, Satoshi; Watanabe, Masatoshi; Morishita, Shin; Sakai, Takao


    Fibrosis is characterized by extracellular matrix (ECM) remodeling and stiffening. However, the functional contribution of tissue stiffening to noncancer pathogenesis remains largely unknown. Fibronectin (Fn) is an ECM glycoprotein substantially expressed during tissue repair. Here we show in advanced chronic liver fibrogenesis using a mouse model lacking Fn that, unexpectedly, Fn-null livers lead to more extensive liver cirrhosis, which is accompanied by increased liver matrix stiffness and deteriorated hepatic functions. Furthermore, Fn-null livers exhibit more myofibroblast phenotypes and accumulate highly disorganized/diffuse collagenous ECM networks composed of thinner and significantly increased number of collagen fibrils during advanced chronic liver damage. Mechanistically, mutant livers show elevated local TGF-β activity and lysyl oxidase expressions. A significant amount of active lysyl oxidase is released in Fn-null hepatic stellate cells in response to TGF-β1 through canonical and noncanonical Smad such as PI3 kinase-mediated pathways. TGF-β1-induced collagen fibril stiffness in Fn-null hepatic stellate cells is significantly higher compared with wild-type cells. Inhibition of lysyl oxidase significantly reduces collagen fibril stiffness, and treatment of Fn recovers collagen fibril stiffness to wild-type levels. Thus, our findings indicate an indispensable role for Fn in chronic liver fibrosis/cirrhosis in negatively regulating TGF-β bioavailability, which in turn modulates ECM remodeling and stiffening and consequently preserves adult organ functions. Furthermore, this regulatory mechanism by Fn could be translated for a potential therapeutic target in a broader variety of chronic fibrotic diseases.

  15. Histological alterations in liver and testis of Astyanax aff. bimaculatus caused by acute exposition to zinc

    Directory of Open Access Journals (Sweden)

    Daiane Cristina Marques dos Santos*


    Full Text Available This study investigated the effect of acute exposition to zinc (Zn on histology of the liver and testes of yellow tail lambari (Astyanax aff. bimaculatus. The exposure consisted of six concentrations of Zn (0, 3, 5, 10, 15, and 20 mg/L for 96 hours of exposure. Fragments of liver and testis were routinely processed and embedded in plastic resin based on glycol methacrylate. Fragments of bones, muscles, liver and testis were dehydrated and digested to quantify the absorption levels of Zn in the tissue. Acute exposure to concentrations above 10mg/L has produced structural changes in the liver and gonads. The changes found in the liver were vascular congestion; decrease of cellular volume; displacement of the hepatocyte nucleus; necrosis; disarrangement of cordon structure; leukocyte infiltrate and vacuolization. The changes found in the gonads were ruptured cyst, delayed development of germ cells, pyknotic nucleus, cell cluster, displacement of cyst wall and vacuolization. The histological changes observed were compatible with the increasing concentration of zinc in environment, compromising liver and reproductive functions, because there was an increase in relative frequency of hepatocytes and reduced sperm production

  16. Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

    Institute of Scientific and Technical Information of China (English)


    AIM: To investigate the effects of resveratrol on liver ischemia/reperfusion (I/R) injury in rats. METHODS: A total of 40 male Sprague-Dawley rats weighing 240-290 g were randomized into four groups often: (1) controls: data from unmanipulated animals; (2) sham group: rats subjected to the surgical procedure, except for liver I/R, and given saline; (3) I/R group: rats underwent liver ischemia for 45 min followed by reperfu-sion for 45 min; (4) I-R/Resveratrol group: rats pretreat-ed with resveratrol (10 μmol/L, iv). Liver tissues were obtained to determine antioxidant enzyme levels and for biochemical and histological evaluation. RESULTS: Plasma aminotransferase activities were higher in the I/R group than in the I-R/Resveratrol group. Malondialdehyde levels and the hepatic injury score decreased, while superoxide dismutase, catalase, and glutathione peroxidase levels increased in group 4 compared to group 3. In group 4, histopathological changes were significantly attenuated in resveratrol-treated livers.CONCLUSION: These results suggest that resveratrol has protective effects against hepatic I/R injury, and is a potential therapeutic drug for ischemia reperfusion-related liver injury.

  17. Protein targeting to glycogen is a master regulator of glycogen synthesis in astrocytes

    KAUST Repository

    Ruchti, E.


    The storage and use of glycogen, the main energy reserve in the brain, is a metabolic feature of astrocytes. Glycogen synthesis is regulated by Protein Targeting to Glycogen (PTG), a member of specific glycogen-binding subunits of protein phosphatase-1 (PPP1). It positively regulates glycogen synthesis through de-phosphorylation of both glycogen synthase (activation) and glycogen phosphorylase (inactivation). In cultured astrocytes, PTG mRNA levels were previously shown to be enhanced by the neurotransmitter noradrenaline. To achieve further insight into the role of PTG in the regulation of astrocytic glycogen, its levels of expression were manipulated in primary cultures of mouse cortical astrocytes using adenovirus-mediated overexpression of tagged-PTG or siRNA to downregulate its expression. Infection of astrocytes with adenovirus led to a strong increase in PTG expression and was associated with massive glycogen accumulation (>100 fold), demonstrating that increased PTG expression is sufficient to induce glycogen synthesis and accumulation. In contrast, siRNA-mediated downregulation of PTG resulted in a 2-fold decrease in glycogen levels. Interestingly, PTG downregulation strongly impaired long-term astrocytic glycogen synthesis induced by insulin or noradrenaline. Finally, these effects of PTG downregulation on glycogen metabolism could also be observed in cultured astrocytes isolated from PTG-KO mice. Collectively, these observations point to a major role of PTG in the regulation of glycogen synthesis in astrocytes and indicate that conditions leading to changes in PTG expression will directly impact glycogen levels in this cell type.

  18. Alteration of Blood Parameters and Histoarchitecture of Liver and Kidney of Silver Barb after Chronic Exposure to Quinalphos

    Directory of Open Access Journals (Sweden)

    Golam Mohammod Mostakim


    Full Text Available Quinalphos (QP is commonly used for pest control in the agricultural fields surrounding freshwater reservoirs. This study was conducted to evaluate the chronic toxicity of this pesticide on blood parameters and some organs of silver barb, Barbonymus gonionotus. Fish were exposed to two sublethal concentrations, 0.47 ppm and 0.94 ppm, of QP for a period of 28 days. All the blood parameters (red blood cell, hematocrit, and hemoglobin and blood glucose except for white blood cells decreased with increasing concentration of toxicant and become significantly lower (p<0.05 at higher concentration when compared with control. The derived hematological indices of mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were equally altered compared to control. Histoarchitectural changes of liver and kidney were observed after exposure to the QP. Hypertrophy of hepatocytes, mild to severe necrosis, ruptured central vein, and vacuolation were observed in the liver of treated groups. Highly degenerated kidney tubules and hematopoietic tissue, degeneration of renal corpuscle, vacuolization, and necrosis were evident in the kidney of treated groups. In conclusion, chronic exposure to QP at sublethal concentrations induced hematological and histological alterations in silver barb and offers a simple tool to evaluate toxicity derived alterations.

  19. Redox state and energy metabolism during liver regeneration: alterations produced by acute ethanol administration. (United States)

    Gutiérrez-Salinas, J; Miranda-Garduño, L; Trejo-Izquierdo, E; Díaz-Muñoz, M; Vidrio, S; Morales-González, J A; Hernández-Muñoz, R


    Ethanol metabolism can induce modifications in liver metabolic pathways that are tightly regulated through the availability of cellular energy and through the redox state. Since partial hepatectomy (PH)-induced liver proliferation requires an oversupply of energy for enhanced syntheses of DNA and proteins, the present study was aimed at evaluating the effect of acute ethanol administration on the PH-induced changes in cellular redox and energy potentials. Ethanol (5 g/kg body weight) was administered to control rats and to two-thirds hepatectomized rats. Quantitation of the liver content of lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, and adenine nucleotides led us to estimate the cytosolic and mitochondrial redox potentials and energy parameters. Specific activities in the liver of alcohol-metabolizing enzymes also were measured in these animals. Liver regeneration had no effect on cellular energy availability, but induced a more reduced cytosolic redox state accompanied by an oxidized mitochondrial redox state during the first 48 hr of treatment; the redox state normalized thereafter. Administration of ethanol did not modify energy parameters in PH rats, but this hepatotoxin readily blocked the PH-induced changes in the cellular redox state. In addition, proliferating liver promoted decreases in the activity of alcohol dehydrogenase (ADH) and of cytochrome P4502E1 (CYP2E1); ethanol treatment prevented the PH-induced diminution of ADH activity. In summary, our data suggest that ethanol could minimize the PH-promoted metabolic adjustments mediated by redox reactions, probably leading to an ineffective preparatory event that culminates in compensatory liver growth after PH in the rat.

  20. Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non-alcoholic Fatty Liver Disease (United States)

    Wang, Baohong; Jiang, Xiangyang; Cao, Min; Ge, Jianping; Bao, Qiongling; Tang, Lingling; Chen, Yu; Li, Lanjuan


    Increasing evidence suggests a role of intestinal dysbiosis in obesity and non-alcoholic fatty liver disease (NAFLD). But it remains unknown in nonobese NAFLD. This prospective, cross-sectional study sought to characterize differences in fecal microbiota between nonobese adult individuals with and without NAFLD and their potential association with metabolic markers of disease progression. A total of 126 nonobese subjects were enrolled: 43 NAFLD and 83 healthy controls (HC). The microbial community was profiled by denaturing gradient gel electrophoresis and examined by 454 pyrosequencing of the 16S ribosomal RNA V3 region. Lower diversity and a phylum-level change in the fecal microbiome were found in NAFLD. Compared with HC, patients had 20% more phylum Bacteroidetes (p = 0.005) and 24% less Firmicutes (p = 0.002). Within Firmicutes, four families and their 8 genera, which were short-chain fatty acids-producing and 7α-dehydroxylating bacteria, were significantly decreased. Moreover, Gram-negative (G−) bacteria were prevalent in NAFLD (p = 0.008). Furthermore, a significant correlation with metabolic markers was revealed for disturbed microbiota in NAFLD. This novel study indicated that intestinal dysbiosis was associated with nonobese NAFLD and might increase the risk of NAFLD progression. PMID:27550547

  1. Glycogen depletion and resynthesis during 14 days of chronic low-frequency stimulation of rabbit muscle

    DEFF Research Database (Denmark)

    Prats, C; Bernal, C; Cadefau, J A;


    Electro-stimulation alters muscle metabolism and the extent of this change depends on application intensity and duration. The effect of 14 days of chronic electro-stimulation on glycogen turnover and on the regulation of glycogen synthase in fast-twitch muscle was studied. The results showed...... synthase was determined during electro-stimulation. The activity of this enzyme was measured at low UDPG concentration with either high or low Glu-6-P content. Western blots were performed against glycogen synthase over a range of stimulation periods. Activation of this enzyme was maximum before the net...

  2. Therapy with bone marrow cells reduces liver alterations in mice chronically infected by Schistosoma mansoni

    Institute of Scientific and Technical Information of China (English)

    Sheilla Andrade Oliveira; Bruno Solano Freitas Souza; Cada Adriana Guimar(a)es-Ferreira; Elton Sá Barreto; Siane Campos Souza; Luiz Antonio Rodrigues Freitas; Ricardo Ribeiro-dos-Santos; Milena Botelho Pereira Soares


    AIM: To investigate the potential of bone marrow mononuclear cells (BM-MCs) in the regeneration of hepatic lesions induced by Schistosoma mansoni (S.mansoni) chronic infection.METHODS: Female mice chronically infected with S.mansoni were treated with BM-MCs obtained from male green fluorescent protein (GFP) transgenic mice by intravenous or intralobular injections. Control mice received injections of saline in similar conditions. Enzyme-linked immunosorbent assay (ELISA) assay for transforming growth factor-beta (TGF-β), polymerase chain reaction (PCR) for GFP DNA, immunofluorescence and morphometric studies were performed.RESULTS: Transplanted GFP+ cells migrated to granuloma areas and reduced the percentage of liver fibrosis. The presence of donor-derived cells was confirmed by Fluorescence in situ hybridization (FISH) analysis for detection of cells bearing Y chromosome and by PCR analysis for detection of GFP DNA. The levels of TGF-β, a cytokine associated with fibrosis deposition, in liver fragments of mice submitted to therapy were reduced. The number of oval cells in liver sections of S.rnansoni-infected mice increased 3-4 fold after transplantation. A partial recovery in albumin expression, which is decreased upon infection with S.mansoni, was found in livers of infected mice after cellular therapy.CONCLUSION: In conclusion, transplanted BMCs migrate to and reduce the damage of chronic fibrotic liver lesions caused by S.mansoni.

  3. Cytomorphological alterations of the thymus, spleen, head-kidney, and liver in cardinal fish (Apogonidae, Teleostei) as bioindicators of stress. (United States)

    Fishelson, Lev


    Morphological and cytological alterations at the light microscope (LM) and transmission electron microscope (TEM) levels were observed in the thymus, spleen, head-kidney, and liver of cardinal fishes (Apogonidae, Teleostei) from the Gulf of Aqaba, Red Sea, sampled from a strongly polluted site at the northern end of the gulf, and compared to similar samples from a clean, reference site. At the polluted site, the most prominent change was the formation of numerous deposits of cells rich in phagosomes with lipofucin, melanin granules, and phagocytosed debris, including a high increase in number and dimensions of Hassall's corpuscles and melano-macrophage centers. The number of Hassall's corpuscles was 20 (+/-8.0)/mm(2) and of melano-macrophage centers 18 (+/-4.0)/mm(2) at the polluted site, and 7.0 (+/-4.0)/m(2) vs. 5.0 (+/-2.0)/mm(2) respectively at the reference site. In numerous instances the head kidney's melano-macrophage centers in fishes from the polluted site were encapsulated by reticulocytes, a phenomenon recognized as a marker of neoplasmosis and possible malignancy. In the spleens of fishes from the polluted site, numerous deposits of cell debris, peroxisomes, and enlarged lysosomes were also observed. The livers (hepatopancreas) of fishes from polluted waters demonstrated very strong hyperlipogeny. Many of their hepatocytes were laden with lipid vesicles, fragmented endoplasmic reticulula, and aberrant mitochondria. Although the observed alterations in the glands and liver do not indicate any immediate threat to the life of the fish, they can become crucial with respect to energy turnover and fecundity trajectories. This study strongly suggests the use of cytological alterations in vital organs, such as were observed, as pathological biomarkers to environmental stress.

  4. In Vivo Acute on Chronic Ethanol Effects in Liver: A Mouse Model Exhibiting Exacerbated Injury, Altered Metabolic and Epigenetic Responses. (United States)

    Shukla, Shivendra D; Aroor, Annayya R; Restrepo, Ricardo; Kharbanda, Kusum K; Ibdah, Jamal A


    Chronic alcoholics who also binge drink (i.e., acute on chronic) are prone to an exacerbated liver injury but its mechanism is not understood. We therefore investigated the in vivo effects of chronic and binge ethanol ingestion and compared to chronic ethanol followed by three repeat binge ethanol on the liver of male C57/BL6 mice fed ethanol in liquid diet (4%) for four weeks followed by binge ethanol (intragastric administration, 3.5 g/kg body weight, three doses, 12h apart). Chronic followed by binge ethanol exacerbated fat accumulation, necrosis, decrease in hepatic SAM and SAM:SAH ratio, increase in adenosine levels, and elevated CYP2E1 levels. Histone H3 lysine acetylation (H3AcK9), dually modified phosphoacetylated histone H3 (H3AcK9/PS10), and phosphorylated H2AX increased after binge whereas phosphorylation of histone H3 ser 10 (H3S10) and H3 ser 28 (H3S28) increased after chronic ethanol-binge. Histone H3 lysine 4 and 9 dimethylation increased with a marked dimethylation in H3K9 in chronic ethanol binge group. Trimethylated histone H3 levels did not change. Nuclear levels of histone acetyl transferase GCN5 and histone deacetylase HDAC3 were elevated whereas phospho-CREB decreased in a distinctive manner. Taken together, acute on chronic ethanol ingestion caused amplification of liver injury and elicited characteristic profiles of histone modifications, metabolic alterations, and changes in nuclear protein levels. These findings demonstrate that chronic ethanol exposure renders liver more susceptible to repeat acute/binge ethanol induced acceleration of alcoholic liver disease.

  5. The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression

    Energy Technology Data Exchange (ETDEWEB)

    Reue, K.; Rehnmark, S.; Cohen, R.D.; Leete, T.H.; Doolittle, M.H. [West Los Angeles VA Medical Center, CA (United States). Lipid Research Lab.]|[Univ. of California, Los Angeles, CA (United States). Dept. of Medicine; Giometti, C.S.; Mishler, K. [Argonne National Lab., IL (United States); Slavin, B.G. [Univ. of Southern California, Los Angeles, CA (United States)


    Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and these droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.

  6. The use of microencapsulated hepatocytes transplantation reduces mortality and liver alterations in Schistosoma mansoni infected hamsters. (United States)

    Sherif, Soad A; Moharib, Mona N; El-Lakkany, Naglaa M; Hammam, Olfat A; Salman, Fatma H; El-Naggar, Mohamed M


    Hepatocyte transplantation is an attractive therapeutic modality for liver disease as an alternative for orthotropic liver transplantation. The goal of this work was to study the adequacy of intrasplenic hepatocyte transplantation (HCTx) in fresh and microencapsulated forms, in a hamster model of liver fibrosis by Schistosoma mansoni infected hamsters were divided into 6 groups; untreated for 11 weeks (GI) and for 15 weeks (GII), treated with praziquantel (PZQ) 7 weeks PI, and killed 4 weeks (GIII) and 8 weeks (GIV) post-treatment. Treated with PZQ 7 weeks PI, and then treated orally with immunosuppressive drug "cyclosporine (4 weeks post PZQ treatment), 24 hr. before interasplenic injection with fresh hepatocytes (V). Treated with PZQ 7 weeks PI, and then injected interasplenically (4 weeks post-treatment) with microencapsulated hepatocytes (GVI). GI & GIII were killed 11 weeks PI for assessment the anti-schistosomal efficacy of PZQ. The other four groups were killed 15 weeks PI for investigation of liver and spleen histology, serum liver enzymes and hepatic oxidative markers before and after HCTx. Freshly isolated hepatocytes with a mean viability 92.97 +/- 1.2% were used for microencapsulation and transplantation. Histological study showed the presence of transplanted hepatocytes in spleen of recipient. PZQ accelerated healing of hepatic granulomatous lesions as evidenced parasitologically by the increase in the percentage of dead eggs and histologically showing more granuloma circumscription with more ova degeneration and less inflammatory cells. The 25-day survival rates in GII, GIV, GV& GVI were 5/15 (33.3%), 8/15 (53.3%), 10/15 (66.7%) and 9/15 (60%) respectively. In addition, there were significantly better outcomes in serum biochemical indexes such as ALT, AST, gamma-GT, ALP, and hepatic SOD and MDA in the fresh and microencapsulated groups than in PZQ-treated group, without great differences between the microencapsulated and the fresh transplanted groups

  7. The extracellular redox state modulates mitochondrial function, gluconeogenesis, and glycogen synthesis in murine hepatocytes.

    Directory of Open Access Journals (Sweden)

    Laura Nocito

    Full Text Available Circulating redox state changes, determined by the ratio of reduced/oxidized pairs of different metabolites, have been associated with metabolic diseases. However, the pathogenic contribution of these changes and whether they modulate normal tissue function is unclear. As alterations in hepatic gluconeogenesis and glycogen metabolism are hallmarks that characterize insulin resistance and type 2 diabetes, we tested whether imposed changes in the extracellular redox state could modulate these processes. Thus, primary hepatocytes were treated with different ratios of the following physiological extracellular redox couples: β-hydroxybutyrate (βOHB/acetoacetate (Acoc, reduced glutathione (GSH/oxidized glutathione (GSSG, and cysteine/cystine. Exposure to a more oxidized ratio via extracellular βOHB/Acoc, GSH/GSSG, and cysteine/cystine in hepatocytes from fed mice increased intracellular hydrogen peroxide without causing oxidative damage. On the other hand, addition of more reduced ratios of extracellular βOHB/Acoc led to increased NAD(PH and maximal mitochondrial respiratory capacity in hepatocytes. Greater βOHB/Acoc ratios were also associated with decreased β-oxidation, as expected with enhanced lipogenesis. In hepatocytes from fasted mice, a more extracellular reduced state of βOHB/Acoc led to increased alanine-stimulated gluconeogenesis and enhanced glycogen synthesis capacity from added glucose. Thus, we demonstrated for the first time that the extracellular redox state regulates the major metabolic functions of the liver and involves changes in intracellular NADH, hydrogen peroxide, and mitochondrial respiration. Because redox state in the blood can be communicated to all metabolically sensitive tissues, this work confirms the hypothesis that circulating redox state may be an important regulator of whole body metabolism and contribute to alterations associated with metabolic diseases.

  8. Association of diabetes and cigarette smoke exposure on the glycemia and liver glycogen of pregnant Wistar rats Associação entre diabetes e exposição à fumaça de cigarro sobre a glicemia e glicogênio hepático de ratas Wistar prenhes

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    Yuri Karen Sinzato


    Full Text Available PURPOSE: To evaluate cigarette smoke exposure and/or diabetes association effects on the glycemia and liver glycogen levels of pregnant Wistar rats. METHODS: 60 adult rats were randomly distributed into (n=10/group: non-diabetic exposed to filtered air (G1; non-diabetic exposed to cigarette smoke only before pregnancy (G2; non-diabetic exposed to cigarette smoke before and during pregnancy (G3; diabetic exposed to filtered air (G4; diabetic exposed to cigarette smoke only before pregnancy (G5, and diabetic exposed to cigarette smoke before and during pregnancy (G6. Glycemia was determined at days 0 and 21 of pregnancy. Liver samples were collected for liver glycogen determinations. RESULTS: At day 21 of pregnancy, glycemia was higher in G5 and G6 compared to G4 group. G2 (2.43±0.43, G3 (3.20±0.49, G4 (2.62±0.34, G5 (2.65±0.27 and G6 groups (1.94±0.35 presented decreased liver glycogen concentrations compared to G1 (4.20±0.18 mg/100mg liver tissue (pOBJETIVO: Avaliar a associação da exposição à fumaça de cigarro e/ou diabete sobre a glicemia e concentrações de glicogênio hepático em ratas Wistar prenhes. MÉTODOS: 60 ratas adultas foram distribuídas aleatoriamente em seis grupos (n=10/grupo: não-diabético exposto ao ar filtrado (G1; não-diabético exposto à fumaça de cigarro antes da prenhez (G2; não-diabético exposto à fumaça de cigarro antes e durante a prenhez (G3; diabético exposto ao ar filtrado (G4; diabético exposto à fumaça de cigarro antes da prenhez (G5; diabético exposto à fumaça de cigarro antes e durante a prenhez (G6. A glicemia foi determinada nos dias 0 e 21 de prenhez. Foram coletadas amostras de fígado para dosagens de glicogênio. RESULTADOS: No 21º dia de prenhez, a glicemia foi maior nos grupos G5 e G6 comparados ao grupo G4. Os grupos G2 (2,43±0,43, G3 (3,20±0,49, G4 (2,62±0,34, G5 (2,65±0,27 e G6 (1,94±0,35 apresentaram concentrações de glicogênio diminuídas comparados ao grupo G1

  9. Multiple Glycogen-binding Sites in Eukaryotic Glycogen Synthase Are Required for High Catalytic Efficiency toward Glycogen

    Energy Technology Data Exchange (ETDEWEB)

    Baskaran, Sulochanadevi; Chikwana, Vimbai M.; Contreras, Christopher J.; Davis, Keri D.; Wilson, Wayne A.; DePaoli-Roach, Anna A.; Roach, Peter J.; Hurley, Thomas D. (Indiana-Med); (Des Moines U)


    Glycogen synthase is a rate-limiting enzyme in the biosynthesis of glycogen and has an essential role in glucose homeostasis. The three-dimensional structures of yeast glycogen synthase (Gsy2p) complexed with maltooctaose identified four conserved maltodextrin-binding sites distributed across the surface of the enzyme. Site-1 is positioned on the N-terminal domain, site-2 and site-3 are present on the C-terminal domain, and site-4 is located in an interdomain cleft adjacent to the active site. Mutation of these surface sites decreased glycogen binding and catalytic efficiency toward glycogen. Mutations within site-1 and site-2 reduced the V{sub max}/S{sub 0.5} for glycogen by 40- and 70-fold, respectively. Combined mutation of site-1 and site-2 decreased the V{sub max}/S{sub 0.5} for glycogen by >3000-fold. Consistent with the in vitro data, glycogen accumulation in glycogen synthase-deficient yeast cells ({Delta}gsy1-gsy2) transformed with the site-1, site-2, combined site-1/site-2, or site-4 mutant form of Gsy2p was decreased by up to 40-fold. In contrast to the glycogen results, the ability to utilize maltooctaose as an in vitro substrate was unaffected in the site-2 mutant, moderately affected in the site-1 mutant, and almost completely abolished in the site-4 mutant. These data show that the ability to utilize maltooctaose as a substrate can be independent of the ability to utilize glycogen. Our data support the hypothesis that site-1 and site-2 provide a 'toehold mechanism,' keeping glycogen synthase tightly associated with the glycogen particle, whereas site-4 is more closely associated with positioning of the nonreducing end during catalysis.

  10. The daily rhythms of mitochondrial gene expression and oxidative stress regulation are altered by aging in the mouse liver. (United States)

    Gong, Changxia; Li, Chengwei; Qi, Xiaoqing; Song, Zhiyin; Wu, Jianguo; Hughes, Michael E; Li, Xiaodong


    The circadian clock regulates many cellular processes, notably including the cell cycle, metabolism and aging. Mitochondria play essential roles in metabolism and are the major sites of reactive oxygen species (ROS) production in the cell. The clock regulates mitochondrial functions by driving daily changes in NAD(+) levels and Sirt3 activity. In addition to this central route, in the present study, we find that the expression of some mitochondrial genes is also rhythmic in the liver, and that there rhythms are disrupted by the Clock(Δ19) mutation in young mice, suggesting that they are regulated by the core circadian oscillator. Related to this observation, we also find that the regulation of oxidative stress is rhythmic in the liver. Since mitochondria and ROS play important roles in aging, and mitochondrial functions are also disturbed by aging, these related observations prompt the compelling hypothesis that circadian oscillators influence aging by regulating ROS in mitochondria. During aging, the expression rhythms of some mitochondrial genes were altered in the liver and the temporal regulation over the dynamics of mitochondrial oxidative stress was disrupted. However, the expression of clock genes was not affected. Our results suggested that mitochondrial functions are combinatorially regulated by the clock and other age-dependent mechanism(s), and that aging disrupts mitochondrial rhythms through mechanisms downstream of the clock.

  11. Ultrastructural and biochemical aspects of liver mitochondria during recovery from ethanol-induced alterations. Experimental evidence of mitochondrial division. (United States)

    Koch, O. R.; Roatta de Conti, L. L.; Bolaños, L. P.; Stoppani, A. O.


    To study the morphologic and biochemical changes occuring in liver mitochondria during recovery from ethanol-induced injury, rats fed a 6-month high-alcohol regimen plus a nutritionally adequate diet which did not induce fatty liver were compared with isocalorically fed controls. After this period the alcohol-fed animals displayed striking ultrastructural changes of liver mitochondria and a decreased respiratory activity with succinate or malate-glutamate as substrate. On the contrary, the respiratory rate with I-glycerophosphate was 50% increased. Regression changes were studied after alcohol was withdrawn from the diet. Enlarged mitochondria rapidly disappeared (in 24 hours), although a few megamitochondria were still present after 8 days of abstinence. A similar recovery was observed for the functional alterations. At the end of the experimental period, only a slight decrease of the maximal respiratory rate using malate-glutamate as a substrate was noted. The ultrastructural findings and the morphometric data suggest that the way in which mitochondrial normalization takes place is based on partition of these organelles. Images Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 1 Figure 2 Figure 13 PMID:623205


    Öz, Gülin; DiNuzzo, Mauro; Kumar, Anjali; Moheet, Amir; Seaquist, Elizabeth R.


    Glycogen provides an important glucose reservoir in the brain since the concentration of glucosyl units stored in glycogen is several fold higher than free glucose available in brain tissue. We have previously reported 3–4 µmol/g brain glycogen content using in vivo 13C magnetic resonance spectroscopy (MRS) in conjunction with [1-13C]glucose administration in healthy humans, while higher levels were reported in the rodent brain. Due to the slow turnover of bulk brain glycogen in humans, complete turnover of the glycogen pool, estimated to take 3–5 days, was not observed in these prior studies. In an attempt to reach complete turnover and thereby steady state 13C labeling in glycogen, here we administered [1-13C]glucose to healthy volunteers for 80 hours. To eliminate any net glycogen synthesis during this period and thereby achieve an accurate estimate of glycogen concentration, volunteers were maintained at euglycemic blood glucose levels during [1-13C]glucose administration and 13C-glycogen levels in the occipital lobe were measured by 13C MRS approximately every 12 hours. Finally, we fitted the data with a biophysical model that was recently developed to take into account the tiered structure of the glycogen molecule and additionally incorporated blood glucose levels and isotopic enrichments as input function in the model. We obtained excellent fits of the model to the 13C-glycogen data, and glycogen content in the healthy human brain tissue was found to be 7.8 ± 0.3 µmol/g, a value substantially higher than previous estimates of glycogen content in the human brain. PMID:26202425

  13. Prenatal arsenic exposure alters gene expression in the adult liver to a proinflammatory state contributing to accelerated atherosclerosis.

    Directory of Open Access Journals (Sweden)

    J Christopher States

    Full Text Available The mechanisms by which environmental toxicants alter developmental processes predisposing individuals to adult onset chronic disease are not well-understood. Transplacental arsenic exposure promotes atherogenesis in apolipoprotein E-knockout (ApoE(-/- mice. Because the liver plays a central role in atherosclerosis, diabetes and metabolic syndrome, we hypothesized that accelerated atherosclerosis may be linked to altered hepatic development. This hypothesis was tested in ApoE(-/- mice exposed to 49 ppm arsenic in utero from gestational day (GD 8 to term. GD18 hepatic arsenic was 1.2 µg/g in dams and 350 ng/g in fetuses. The hepatic transcriptome was evaluated by microarray analysis to assess mRNA and microRNA abundance in control and exposed pups at postnatal day (PND 1 and PND70. Arsenic exposure altered postnatal developmental trajectory of mRNA and microRNA profiles. We identified an arsenic exposure related 51-gene signature at PND1 and PND70 with several hubs of interaction (Hspa8, IgM and Hnf4a. Gene ontology (GO annotation analyses indicated that pathways for gluconeogenesis and glycolysis were suppressed in exposed pups at PND1, and pathways for protein export, ribosome, antigen processing and presentation, and complement and coagulation cascades were induced by PND70. Promoter analysis of differentially-expressed transcripts identified enriched transcription factor binding sites and clustering to common regulatory sites. SREBP1 binding sites were identified in about 16% of PND70 differentially-expressed genes. Western blot analysis confirmed changes in the liver at PND70 that included increases of heat shock protein 70 (Hspa8 and active SREBP1. Plasma AST and ALT levels were increased at PND70. These results suggest that transplacental arsenic exposure alters developmental programming in fetal liver, leading to an enduring stress and proinflammatory response postnatally that may contribute to early onset of atherosclerosis. Genes

  14. Oxidative stress and alteration of biochemical markers in liver and kidney by malathion in rat pups. (United States)

    Selmi, Slimen; El-Fazaa, Saloua; Gharbi, Najoua


    The present study was undertaken to determine the effects of malathion exposure through maternal milk on oxidative stress, functional an metabolic parameters in kidney and liver of rat pups. We found that lactational exposure to malation (200 mg/kg, body weight (bw)) induced an oxidative stress status assessed by an increase in malondialdhyde (MDA) content, reflecting lipoperoxidation, a decrease in thiol groups' content as well as depletion of enzyme activities as a superoxide dismutase (SOD) and catalase (CAT) on postnatal days (Pnds) 21 and 51. Moreover, the current study showed that malathion induced liver and kidney dysfunctions demonstrated by considerable increase in phosphatase alkaline (PAL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as total and direct bilirubin, creatinine urea and acid uric contents. We also observed an increase in triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and a decrease in high-density lipoprotein cholesterol (HDL-C) in the plasma of treated rat pups. These findings evidenced that malathion exposure during lactation through maternal milk of rats pups induced kidney and liver oxidative stress as well as functional and metabolic disorders that play a role in the development of others pathologies as cardiovascular diseases and cancers.

  15. Biochemical and histological alterations in liver following sub chronic exposure of arsenic

    Directory of Open Access Journals (Sweden)

    Madhuri Mehta


    Full Text Available Objective: Contamination of groundwater with arsenic is of global concern. The present work was aimed to evaluate the biochemical and histological changes in liver of female rats induced by sodium arsenite at doses naturally found in groundwater of Punjab. Method: Twenty four female rats were divided into four groups of 6 animals each. Group I animals received distilled water and served as control; Group II-IV received arsenic at the dose of 10, 30 and 50 ppb (μg/L dissolved in distilled water ad libitum for 30 days. At the end of experiment, animals were sacrificed and liver was collected for biochemical and histological evaluation. Results: Biochemical analysis showed an increase in the activity of hepatic marker enzymes including transferases, phosphatases and lactate dehydrogenase (LDH. Also, the levels of antioxidant enzymes (catalase, reduced glutathione and glutathione-S-transferase decreased significantly (P<0.05 in treated animals when compared to control. A significant (P<0.05 dose dependent increase in the levels of lipid peroxidation and arsenic concentration in liver tissue was observed. Histological examination showed the presence of pyknotic bodies (necrosis and sinusoidal dilation in hepatocytes of treated groups. Conclusion: Sub chronic exposure of arsenic at these doses induces hepatotoxicity leading to oxidative stress.

  16. Exercise in muscle glycogen storage diseases

    DEFF Research Database (Denmark)

    Preisler, Nicolai Rasmus; Haller, Ronald G; Vissing, John


    Glycogen storage diseases (GSD) are inborn errors of glycogen or glucose metabolism. In the GSDs that affect muscle, the consequence of a block in skeletal muscle glycogen breakdown or glucose use, is an impairment of muscular performance and exercise intolerance, owing to 1) an increase in glyco......Glycogen storage diseases (GSD) are inborn errors of glycogen or glucose metabolism. In the GSDs that affect muscle, the consequence of a block in skeletal muscle glycogen breakdown or glucose use, is an impairment of muscular performance and exercise intolerance, owing to 1) an increase...... exercise program has the potential to improve general health and fitness and improve quality of life, if executed properly. In this review, we describe skeletal muscle substrate use during exercise in GSDs, and how blocks in metabolic pathways affect exercise tolerance in GSDs. We review the studies...

  17. The Effects of Space Flight on Some Liver Enzymes Concerned with Carbohydrate and Lipid Metabolism in Rats (United States)

    Abraham, S.; Lin, C. Y.; Klein, H. P.; Volkmann, C.


    The activities of about 30 enzymes concerned with carbohydrate and lipid metabolism and the levels of glycogen and of individual fatty acids were measured in livers of rats ex- posed to prolonged space flight (18.5 days) aboard COSMOS 986 Biosatellite. When flight stationary, (FS) and flight centrifuged (FC) rats were compared at recovery (R(sub 0)), decrceases in the activities of glycogen phosphorylase, alpha glycerphosphate, acyl transferase, diglyceride acyl transferase, acconitase and Epsilon-phosphogluconate dehydrogenase were noted in the weightless group (FS). The significance of these findings was strengthened since all activities, showing alterations at R(sub 0), returned to normal 25 days post-flight. Differences were also seen in levels of two liver constituents. When glycogen and total fatty acids of the two groups of flight animals were determined, differences that could be attributed to reduced gravity were observed, the FS group at R(sub 0) contained, on the average, more than twice the amount of glycogen than did controls ad a remarkable shift in the ratio of palmitate to palmitoleate were noted. These metabolic alterations appear to be unique to the weightless condition. Our data justify the conclusion that centrifugation during space flight is equivalent to terrestrial gravity.

  18. 玛咖对一次力竭运动小鼠抗疲劳作用及T-SOD、肝糖原的影响%Influence of Maca on Resist-fatigue and T-SOD, Liver Glycogen of the Mice After Exhaustive Sports

    Institute of Scientific and Technical Information of China (English)

    邱良武; 王路; 王丽; 柏春玲; 保文莉


    Objective To establish the resist-fatigue animal test through using Maca, in order to provide reference for the relevant departments to exploit new sports nutrition . Methods Thirty male KM mice were randomly divided into Quiet control group (A),Exhaustive group (B,high altitude),Maca exhaustive group (C), there were 10 mice in each group. Drinking water containing Maca (Maca =500 mg/L) was supplied in group C. Additional exhaustive group (D,low altitude) was set.Thirty days later, all mice were killed after one exhaustive test, then we tested the exhaustive time, the level of T-SOD and liver glycogen. Results The exhaustive time of group C was significantly longer than group B (P<0.05), the T-SOD level of group C was significantly higher than group A and group B (P<0.05), and the liver glycogen content of group C was significantly higher than group B (P<0.05) . Conclusion Maca can raise T-SOD and liver glycogen level of the mice after exhaustive swimming, and has function of resist-fatigue.%目的:应用玛咖进行抗疲劳动物实验,为相关部门开发新型的运动补剂提供参考.方法将30只SPF昆明种雄性小鼠随机分为安静对照组(A组)、力竭运动组(B组、高海拔)、玛咖+力竭运动组(C组),每组各10只;另加力竭运动组(D组、低海拔)20只.C组在饮用水中溶入玛咖,浓度为5%.30 d后,进行一次力竭实验,测定力竭时间,即刻处死小鼠测试T-SOD、肝糖原等生化指标.结果 C组小鼠力竭游泳时间比B组长且差异有统计学意义(P<0.05),T-SOD比A组和B组高差异有统计学意义(P<0.05),肝糖原含量比B组高且差异有统计学意义(P<0.05).D组小鼠力竭游泳时间比B组长且有统计学意义(P<0.01).结论玛咖能够提高T-SOD活性,提高肝糖原含量,具有较好的抗疲劳作用;低海拔地区小鼠力竭游泳运动时间高于高海拔地区小鼠.

  19. The effect of antenatal administration of solcoseryl on hepatic glycogen synthesis in rat fetuses with intrauterine growth retardation. (United States)

    Takahashi, H; Cheng, K M; Araki, T


    The effect of antenatal solcoseryl administration on hepatic glycogen synthesis and storage was studied in normal developing and intrauterine growth-retarded (IUGR) rat fetuses using biochemical analyses. The maximal effect of solcoseryl occurred 2 hours after administration. The glycogen content of the liver showed a significant increase in normal and IUGR fetuses with antenatal solcoseryl administration compared to their non-solcoseryl counterparts (p solcoseryl administration. Active synthase also increased in normal fetuses with antenatal solcoseryl administration (p solcoseryl administration stimulates hepatic glycogen synthesis and storage in IUGR rat fetuses, and thus might favorably influence the development of neonatal hypoglycemia.

  20. Glycogen storage disease type I: clinical and laboratory profile

    Directory of Open Access Journals (Sweden)

    Berenice L. Santos


    Full Text Available OBJECTIVES: To characterize the clinical, laboratory, and anthropometric profile of a sample of Brazilian patients with glycogen storage disease type I managed at an outpatient referral clinic for inborn errors of metabolism. METHODS: This was a cross-sectional outpatient study based on a convenience sampling strategy. Data on diagnosis, management, anthropometric parameters, and follow-up were assessed. RESULTS: Twenty-one patients were included (median age 10 years, range 1-25 years, all using uncooked cornstarch therapy. Median age at diagnosis was 7 months (range, 1-132 months, and 19 patients underwent liver biopsy for diagnostic confirmation. Overweight, short stature, hepatomegaly, and liver nodules were present in 16 of 21, four of 21, nine of 14, and three of 14 patients, respectively. A correlation was found between height-for-age and BMI-for-age Z-scores (r = 0.561; p = 0.008. CONCLUSIONS: Diagnosis of glycogen storage disease type I is delayed in Brazil. Most patients undergo liver biopsy for diagnostic confirmation, even though the combination of a characteristic clinical presentation and molecular methods can provide a definitive diagnosis in a less invasive manner. Obesity is a side effect of cornstarch therapy, and appears to be associated with growth in these patients.

  1. Histone modifications and alcohol-induced liver disease: Are altered nutrients the missing link?

    Institute of Scientific and Technical Information of China (English)

    Akshata Moghe; Swati Joshi-Barve; Smita Ghare; Leila Gobejishvili; Irina Kirpich; Craig J McClain; Shirish Barve


    Alcoholism is a major health problem in the United States and worldwide, and alcohol remains the single most significant cause of liver-related diseases and deaths. Alcohol is known to influence nutritional status at many levels including nutrient intake, absorption, utilization, and excretion, and can lead to many nutritional disturbances and deficiencies. Nutrients can dramatically affect gene expression and alcohol-induced nutrient imbalance may be a major contributor to pathogenic gene expression in alcohol-induced liver disease (ALD). There is growing interest regarding epigenetic changes, including histone modifications that regulate gene expression during disease pathogenesis. Notably, modifications of core histones in the nucleosome regulate chromatin structure and DNA methylation, and control gene transcription. This review highlights the role of nutrient disturbances brought about during alcohol metabolism and their impact on epigenetic histone modifications that may contribute to ALD. The review is focused on four critical metabolites, namely, acetate, S-adenosylmethionine, nicotinamide adenine dinucleotide and zinc that are particularly relevant to alcohol metabolism and ALD.

  2. A noncanonical, GSK3-independent pathway controls postprandial hepatic glycogen deposition. (United States)

    Wan, Min; Leavens, Karla F; Hunter, Roger W; Koren, Shlomit; von Wilamowitz-Moellendorff, Alexander; Lu, Mingjian; Satapati, Santhosh; Chu, Qingwei; Sakamoto, Kei; Burgess, Shawn C; Birnbaum, Morris J


    Insulin rapidly suppresses hepatic glucose production and slowly decreases expression of genes encoding gluconeogenic proteins. In this study, we show that an immediate effect of insulin is to redirect newly synthesized glucose-6-phosphate to glycogen without changing the rate of gluconeogenesis. This process requires hepatic Akt2, as revealed by blunted insulin-mediated suppression of glycogenolysis in the perfused mouse liver, elevated hepatic glucose production during a euglycemic-hyperinsulinemic clamp, or diminished glycogen accumulation during clamp or refeeding in mice without hepatic Akt2. Surprisingly, the absence of Akt2 disrupted glycogen metabolism independent of GSK3α and GSK3β phosphorylation, which is thought to be an essential step in the pathway by which insulin regulates glycogen synthesis through Akt. These data show that (1) the immediate action of insulin to suppress hepatic glucose production functions via an Akt2-dependent redirection of glucose-6-phosphate to glycogen, and (2) insulin increases glucose phosphorylation and conversion to glycogen independent of GSK3.

  3. Increased hepatic glycogen synthetase and decreased phosphorylase in trained rats

    DEFF Research Database (Denmark)

    Galbo, H; Saugmann, P; Richter, Erik


    Rats were either physically trained by a 12 wk swimming program or were freely eating or weight matched, sedentary controls. Trained rats had a higher relative liver weight and total hepatic glycogen synthetase (EC activity and a lower phosphorylase (EC activity than the other...... groups of rats. These changes may partly explain the demonstrated training-induced increase in glucose tolerance. None of the findings could be ascribed to differences in foold intake or body weight....

  4. Ethanol Metabolism Alters Major Histocompatibility Complex Class I-Restricted Antigen Presentation In Liver Cells (United States)

    Osna, Natalia A.; White, Ronda L.; Thiele, Geoffrey M.; Donohue, Terrence M.


    The proteasome is a major enzyme that cleaves proteins for antigen presentation. Cleaved peptides traffic to the cell surface, where they are presented in the context of MHC class I. Recognition of these complexes by cytotoxic T lymphocytes is crucial for elimination of cells bearing “non-self” proteins. Our previous studies revealed that ethanol suppresses proteasome function in ethanol-metabolizing liver cells. We hypothesized that proteasome suppression reduces the hydrolysis of antigenic peptides, thereby decreasing the presentation of the peptide-MHC class I-complexes on the cell surface. To test this, we used the mouse hepatocyte cell line (CYP2E1/ADH-transfected HepB5 cells) or primary mouse hepatocytes, both derived from livers of C57Bl/6 mice, which present the ovalbumin peptide, SIINFEKL, complexed with H2Kb. To induce H2Kb expression, HepB5 cells were treated with interferon gamma (IFNγ) and then exposed to ethanol. In these cells, ethanol metabolism decreased not only proteasome activity, but also hydrolysis of the C-extended peptide, SIINFEKL-TE and the presentation of SIINFEKL-H2Kb complexes measured after the delivery of SIINFEKL-TE to cytoplasm. The suppressive effects of ethanol were, in part, attributed to ethanol-elicited impairment of IFNγ signaling. However, in primary hepatocytes, even in the absence of IFNγ, we observed a similar decline in proteasome activity and antigen presentation after ethanol exposure. We conclude that proteasome function is directly suppressed by ethanol metabolism and indirectly, by preventing the activating effects of IFNγ. Ethanol-elicited reduction in proteasome activity contributes to the suppression of SIINFEKL-H2Kb presentation on the surface of liver cells. Immune response to viral antigens plays a crucial role in the pathogenesis of hepatitis C or B viral infections (HCV and HBV, respectively). Professional antigen-presenting cells (dendritic cells and macrophages) are responsible for priming the

  5. Hematotesticular barrier is altered from early stages of liver cirrhosis:Effect of insulin-like growth factor 1

    Institute of Scientific and Technical Information of China (English)

    Inma Castilla-Cortázar; Isabel Varela-Nieto; Jesús Prieto; Salvador González-Barón; Nieves Diez; María García-Fernández; Juan Enrique Puche; Fernando Diez-Caballero; Jorge Quiroga; Matías Díaz-Sánchez; Alberto Castilla; Amelia Díaz Casares


    AIM: The pathogenesis of hypogonadism in liver cirrhosis is not well understood. Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis. The administration of IGF-1 for a short period of time reverted the testicular atrophy associated with advanced experimental cirrhosis.The aim of this study was to establish the historical progression of the described alterations in the testes,explore testicular morphology, histopathology, cellular proliferation, integrity of testicular barrier and hypophysogonadal axis in rats with no ascitic cirrhosis.METHODS: Male Wistar rats with histologically-proven cirrhosis induced with carbon tetrachloride (CCl4) for 11 wk,were allocated into two groups (n = 12, each) to receive vehicle. Healthy rats receiving vehicle were used as control group (n = 12).RESULTS: Compared to controls, rats with compensated cirrhosis showed a normal testicular size and weight and very few histopathological testicular abnormalities.However, these animals showed a significant diminution of cellular proliferation and a reduction of testicular transferrin expression. In addition, pituitary-gonadal axis was altered, with significant higher levels of FSH (P<0.001vs controls) and increased levels of LH in untreated cirrhotic animals. Interestingly, IGF-1 treatment normalized testicular transferrin expression and cellular proliferation and reduced serum levels of LH (P = ns vs controls, and P<0.01 vs untreated cirrhotic group).CONCLUSION: The testicular barrier is altered from an early stage of cirrhosis, shown by a reduction of transferrin expression in Sertoli cells, a diminished cellular proliferation and an altered gonadal axis. The treatment with IGF-1 could be also useful in this initial stage of testicular disorder associated with compensated cirrhosis.

  6. Altered UDP-glucuronosyltransferase and sulfotransferase expression and function during progressive stages of human nonalcoholic fatty liver disease. (United States)

    Hardwick, Rhiannon N; Ferreira, Daniel W; More, Vijay R; Lake, April D; Lu, Zhenqiang; Manautou, Jose E; Slitt, Angela L; Cherrington, Nathan J


    The UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) represent major phase II drug-metabolizing enzymes that are also responsible for maintaining cellular homeostasis by metabolism of several endogenous molecules. Perturbations in the expression or function of these enzymes can lead to metabolic disorders and improper management of xenobiotics and endobiotics. Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver damage ranging from steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Because the liver plays a central role in the metabolism of xenobiotics, the purpose of the current study was to determine the effect of human NAFLD progression on the expression and function of UGTs and SULTs in normal, steatosis, NASH (fatty), and NASH (not fatty/cirrhosis) samples. We identified upregulation of UGT1A9, 2B10, and 3A1 and SULT1C4 mRNA in both stages of NASH, whereas UGT2A3, 2B15, and 2B28 and SULT1A1, 2B1, and 4A1 as well as 3'-phosphoadenosine-5'-phosphosulfate synthase 1 were increased in NASH (not fatty/cirrhosis) only. UGT1A9 and 1A6 and SULT1A1 and 2A1 protein levels were decreased in NASH; however, SULT1C4 was increased. Measurement of the glucuronidation and sulfonation of acetaminophen (APAP) revealed no alterations in glucuronidation; however, SULT activity was increased in steatosis compared with normal samples, but then decreased in NASH compared with steatosis. In conclusion, the expression of specific UGT and SULT isoforms appears to be differentially regulated, whereas sulfonation of APAP is disrupted during progression of NAFLD.

  7. Alteration in Haematological and Liver Function Indices during Human Infection with Fasciola spp. Post Treatment with Triclabendazole

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    M.I. Edalatzadeh


    Full Text Available Introduction & Objective: Fascioliasis is a zoonotic parasitic disease, caused by the liver fluke, Fasciola spp.. Human is occasional host when ingesting the metacercaria by eating contaminated aquatic vegetable. In the two past decades, human fasciolasis was emerging as a problem of public health in the Guilan province; in Anzali city. Triclabendazole is a novel anti-helmenthic that during recent years has been used for fascioliasis treatment in this region. The aim of the present work is to study alteration in haematological and liver function indices during human infection with Fasciola spp. pre and post treatment with triclabendazoleMaterials & Methods: The present work is a longitudinal clinical trail. In this regard, fifty confirmed fasciolasis patients, were chosen for parasitological, hematological and biochemical examinations pre-therapy as well as 1 and 6 months post-therapy. Formalin-ether and modified Telemann methods were used for stool examination. For Fasciola antibody detection ELISA technique was employed. Hematological and biochemical tests were performed by standard methods. Results: Results indicated that, triclabendazole efficacy was 74% after usage as one dose of 20mg/kg and reached to 88% after repeating in the next month. Before triclabebdazole therapy the Hb and HCT of the patients were slightly found lower than normal ranges, meanwhile the ESR and eosinophil percentages were higher. However following receiving the drug, in the cured individuals, the indices returned to the normal ranges but in the non-cured individuals were not shifted to the normal. On the other hand liver function indices of the patients mostly were at normal ranges before and following drug therapy.Conclusion: In conclusion haematological indices could be valuable indicator for successful therapy of patients treated with triclabendazole.

  8. A critical role for ceramide synthase 2 in liver homeostasis: I. alterations in lipid metabolic pathways. (United States)

    Pewzner-Jung, Yael; Park, Hyejung; Laviad, Elad L; Silva, Liana C; Lahiri, Sujoy; Stiban, Johnny; Erez-Roman, Racheli; Brügger, Britta; Sachsenheimer, Timo; Wieland, Felix; Prieto, Manuel; Merrill, Alfred H; Futerman, Anthony H


    Ceramide is an important lipid signaling molecule that plays critical roles in regulating cell behavior. Ceramide synthesis is surprisingly complex and is orchestrated by six mammalian ceramide synthases, each of which produces ceramides with restricted acyl chain lengths. We have generated a CerS2 null mouse and characterized the changes in the long chain base and sphingolipid composition of livers from these mice. Ceramide and downstream sphingolipids were devoid of very long (C22-C24) acyl chains, consistent with the substrate specificity of CerS2 toward acyl-CoAs. Unexpectedly, C16-ceramide levels were elevated, and as a result, total ceramide levels were unaltered; however, C16-ceramide synthesis in vitro was not increased. Levels of sphinganine were also significantly elevated, by up to 50-fold, reminiscent of the effect of the ceramide synthase inhibitor, fumonisin B1. With the exceptions of glucosylceramide synthase and neutral sphingomyelinase 2, none of the other enzymes tested in either the sphingolipid biosynthetic or degradative pathways were significantly changed. Total glycerophospholipid and cholesterol levels were unaltered, although there was a marked elevation in C18:1 and C18:2 fatty acids in phosphatidylethanolamine, concomitant with a reduction in C18:0 and C20:4 fatty acids. Finally, differences were observed in the biophysical properties of lipid extracts isolated from liver microsomes, with membranes from CerS2 null mice displaying higher membrane fluidity and showing morphological changes. Together, these results demonstrate novel modes of cross-talk and regulation between the various branches of lipid metabolic pathways upon inhibition of very long acyl chain ceramide synthesis.

  9. Sorafenib metabolism is significantly altered in the liver tumor tissue of hepatocellular carcinoma patient.

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    Ling Ye

    Full Text Available BACKGROUND: Sorafenib, the drug used as first line treatment for hepatocellular carcinoma (HCC, is metabolized by cytochrome P450 (CYP 3A4-mediated oxidation and uridine diphosphate glucuronosyl transferase (UGT 1A9-mediated glucuronidation. Liver diseases are associated with reduced CYP and UGT activities, which can considerably affect drug metabolism, leading to drug toxicity. Thus, understanding the metabolism of therapeutic compounds in patients with liver diseases is necessary. However, the metabolism characteristic of sorafenib has not been systematically determined in HCC patients. METHODS: Sorafenib metabolism was tested in the pooled and individual tumor hepatic microsomes (THLMs and adjacent normal hepatic microsomes (NHLMs of HCC patients (n = 18. Commercial hepatic microsomes (CHLMs were used as a control. In addition, CYP3A4 and UGT1A9 protein expression in different tissues were measured by Western blotting. RESULTS: The mean rates of oxidation and glucuronidation of sorafenib were significantly decreased in the pooled THLMs compared with those in NHLMs and CHLMs. The maximal velocity (Vmax of sorafenib oxidation and glucuronidation were approximately 25-fold and 2-fold decreased in the pooled THLMs, respectively, with unchanged Km values. The oxidation of sorafenib in individual THLMs sample was significantly decreased (ranging from 7 to 67-fold than that in corresponding NHLMs sample. The reduction of glucuronidation in THLMs was observed in 15 out of 18 patients' samples. Additionally, the level of CYP3A4 and UGT1A9 expression were both notably decreased in the pooled THLMs. CONCLUSIONS: Sorafenib metabolism was remarkably decreased in THLMs. This result was associated with the down regulation of the protein expression of CYP3A4 and UGT1A9.

  10. Hepatic glycogen deposition in a patient with anorexia nervosa and persistently abnormal transaminase levels. (United States)

    Kransdorf, Lisa N; Millstine, Denise; Smith, Maxwell L; Aqel, Bashar A


    Anorexia nervosa and other eating disorders characterized by calorie restriction have been associated with a variety of hepatic abnormalities. Fatty steatosis has been described in eating disorder patients. We report the rare finding of glycogen accumulation in the liver in a patient with anorexia nervosa, which to our knowledge is only the second such case reported in the literature. This case highlights the importance of monitoring for liver abnormalities in patients with restrictive eating disorders.

  11. High glycogen levels enhance glycogen breakdown in isolated contracting skeletal muscle

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H


    The influence of supranormal muscle glycogen levels on glycogen breakdown in contracting muscle was investigated. Rats either rested or swam for 3 h and subsequently had their isolated hindquarters perfused after 21 h with access to food. Muscle glycogen concentrations were measured before...... and after 15 min of intermittent electrical muscle stimulation. Before stimulation, glycogen was higher in rats that swam on the preceding day (supercompensated rats) compared with controls. During muscle contractions, glycogen breakdown in fast-twitch red and white fibers was larger in supercompensated...... hindquarters compared with controls. O2 uptake, release of tyrosine and glycerol, and tension development were similar in the two groups. In conclusion, during muscle contractions, increased muscle glycogen levels lead to increased breakdown of glycogen and release of lactate and decreased uptake of glucose...

  12. Brain glycogen supercompensation following exhaustive exercise. (United States)

    Matsui, Takashi; Ishikawa, Taro; Ito, Hitoshi; Okamoto, Masahiro; Inoue, Koshiro; Lee, Min-Chul; Fujikawa, Takahiko; Ichitani, Yukio; Kawanaka, Kentaro; Soya, Hideaki


    Brain glycogen localized in astrocytes, a critical energy source for neurons, decreases during prolonged exhaustive exercise with hypoglycaemia. However, it is uncertain whether exhaustive exercise induces glycogen supercompensation in the brain as in skeletal muscle. To explore this question, we exercised adult male rats to exhaustion at moderate intensity (20 m min(-1)) by treadmill, and quantified glycogen levels in several brain loci and skeletal muscles using a high-power (10 kW) microwave irradiation method as a gold standard. Skeletal muscle glycogen was depleted by 82-90% with exhaustive exercise, and supercompensated by 43-46% at 24 h after exercise. Brain glycogen levels decreased by 50-64% with exhaustive exercise, and supercompensated by 29-63% (whole brain 46%, cortex 60%, hippocampus 33%, hypothalamus 29%, cerebellum 63% and brainstem 49%) at 6 h after exercise. The brain glycogen supercompensation rates after exercise positively correlated with their decrease rates during exercise. We also observed that cortical and hippocampal glycogen supercompensation were sustained until 24 h after exercise (long-lasting supercompensation), and their basal glycogen levels increased with 4 weeks of exercise training (60 min day(-1) at 20 m min(-1)). These results support the hypothesis that, like the effect in skeletal muscles, glycogen supercompensation also occurs in the brain following exhaustive exercise, and the extent of supercompensation is dependent on that of glycogen decrease during exercise across brain regions. However, supercompensation in the brain preceded that of skeletal muscles. Further, the long-lasting supercompensation of the cortex and hippocampus is probably a prerequisite for their training adaptation (increased basal levels), probably to meet the increased energy demands of the brain in exercising animals.

  13. Altered gene and protein expression in liver of the obese spontaneously hypertensive/NDmcr-cp rat

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    Chang Jie


    Full Text Available Abstract Background It is difficult to study the mechanisms of the metabolic syndrome in humans due to the heterogeneous genetic background and lifestyle. The present study investigated changes in the gene and protein profiles in an animal model of the metabolic syndrome to identify the molecular targets associated with the pathogenesis and progression of obesity related to the metabolic syndrome. Methods We extracted mRNAs and proteins from the liver tissues of 6- and 25-week-old spontaneously hypertensive/NIH –corpulent rat SHR/NDmcr-cp (CP, SHR/Lean (Lean and Wistar Kyoto rats (WKY and performed microarray analysis and two-dimensional difference in gel electrophoresis (2D-DIGE linked to a matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS. Results The microarray analysis identified 25 significantly up-regulated genes (P 10 > 1 and 31 significantly down-regulated genes (P 10 P  Conclusion Genes with significant changes in their expression in transcriptomic analysis matched very few of the proteins identified in proteomics analysis. However, annotated functional classifications might provide an important reference resource to understand the pathogenesis of obesity associated with the metabolic syndrome.

  14. Alterations in Arterial Blood Parameters in Patients with Liver Cirrhosis and Ascites

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    Konstantinos Charalabopoulos, Dimitrios Peschos, Leonidas Zoganas, George Bablekos, Christos Golias, Alexander Charalabopoulos, Dimitrios Stagikas, Angi Karakosta, Athanasios Papathanasopoulos, George Karachalios, Anna Batistatou


    Full Text Available In cirrhotic patients, in addition to hepatocytes and Kuppfer cells dysfunction circulatory anatomic shunt and ventilation/perfusion (VA/ Q ratio abnormalities can induce decrease in partial pressure of oxygen in arterial blood (PaO2, in oxygen saturation of hemoglobin (SaO2 as well as various acid-base disturbances. We studied 49 cases of liver cirrhosis (LC with ascites compared to 50 normal controls. Causes were: posthepatic 37 (75.51%, alcoholic 7 (14.24%, cardiac 2 (4.08%, and cryptogenic 3 (6.12%. Complications were: upper gastrointestinal bleeding 24 (48.97, hepatic encephalopathy 20 (40.81%, gastritis 28 (57.14%, hepatoma 5 (10.2%, renal hepatic syndrome 2 (4.01%, HbsAg (+ 24 (48.97%, and hepatic pleural effusions 7 (14.28%. Average PaO2 and SaO2 were 75.2 mmHg and 94.5 mmHg, respectively, compared to 94.2 mmHg and 97.1 mmHg of the control group, respectively (p value in both PaO2 and SaO2 was pA/Q inequality can induce a decrease in PaO2 and SaO2 as well as various acid-base disturbances. As a result, pulmonary resistance is impaired and patients more likely succumb to infections and adult respiratory distress syndrome.

  15. Glycogen metabolism in the rat retina. (United States)

    Coffe, Víctor; Carbajal, Raymundo C; Salceda, Rocío


    It has been reported that glycogen levels in retina vary with retinal vascularization. However, the electrical activity of isolated retina depends on glucose supply, suggesting that it does not contain energetic reserves. We determined glycogen levels and pyruvate and lactate production under various conditions in isolated retina. Ex vivo retinas from light- and dark-adapted rats showed values of 44 +/- 0.3 and 19.5 +/- 0.4 nmol glucosyl residues/mg protein, respectively. The glycogen content of retinas from light-adapted animals was reduced by 50% when they were transferred to darkness. Glycogen levels were low in retinas incubated in glucose-free media and increased in the presence of glucose. The highest glycogen values were found in media containing 20 mm of glucose. A rapid increase in lactate production was observed in the presence of glucose. Surprisingly, glycogen levels were the lowest and lactate production was also very low in the presence of 30 mm glucose. Our results suggest that glycogen can be used as an immediate accessible energy reserve in retina. We speculate on the possibility that gluconeogenesis may play a protective role by removal of lactic acid.

  16. Iron overload alters glucose homeostasis, causes liver steatosis, and increases serum triacylglycerols in rats. (United States)

    Silva, Maísa; Silva, Marcelo E; de Paula, Heberth; Carneiro, Cláudia Martins; Pedrosa, Maria Lucia


    The objective of this study was to investigate the effect of iron overload with a hyperlipidemic diet on the histologic feature of hepatic tissue, the lipid and glycemic serum profiles, and the markers of oxidative damage and stress in a rat model. Twenty-four male Fischer rats, purchased from Experimental Nutrition Laboratory, Federal University of Ouro Preto, were assigned to 4 equal groups, 2 were fed a standard cholesterol-free diet (group C or control and CI or control with iron) containing 8.0% soybean oil and 2 were fed a hyperlipidemic diet (group H or hyperlipidemic and HI or hyperlipidemic with iron) containing 1.0% cholesterol and 25.0% soybean oil. A total of 50 mg of iron was administered to rats in groups CI and HI in 5 equal doses (1 every 3 weeks for a 16-week period) by intraperitoneal injections of 0.1 mL of iron dextran solution (100 g Fe(2+)/L; Sigma, St Louis, Mo). The other rats in groups C and H were treated in a similar manner but with sterile saline (0.1 mL). Irrespective of the diet, iron excess enhanced serum triacylglycerols (P .05) were observed in paraoxonase activities or in serum levels of free or total sulfhydryl radicals, malondialdehyde, or total antioxidants. The findings suggest that iron excess in the rat probably modifies lipid metabolism and, as a consequence, alters glucose homeostasis and increases the level of serum triacylglycerols but not of cholesterol.

  17. Chemotherapy Agents Alter Plasma Lipids in Breast Cancer Patients and Show Differential Effects on Lipid Metabolism Genes in Liver Cells. (United States)

    Sharma, Monika; Tuaine, Jo; McLaren, Blair; Waters, Debra L; Black, Katherine; Jones, Lynnette M; McCormick, Sally P A


    Cardiovascular complications have emerged as a major concern for cancer patients. Many chemotherapy agents are cardiotoxic and some appear to also alter lipid profiles, although the mechanism for this is unknown. We studied plasma lipid levels in 12 breast cancer patients throughout their chemotherapy. Patients received either four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel or three cycles of epirubicin, cyclophosphamide and 5'-fluorouracil followed by three cycles of docetaxel. Patients demonstrated a significant reduction (0.32 mmol/L) in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels (0.18 g/L) and an elevation in apolipoprotein B (apoB) levels (0.15 g/L) after treatment. Investigation of the individual chemotherapy agents for their effect on genes involved in lipoprotein metabolism in liver cells showed that doxorubicin decreased ATP binding cassette transporter A1 (ABCA1) via a downregulation of the peroxisomal proliferator activated receptor γ (PPARγ) and liver X receptor α (LXRα) transcription factors. In contrast, ABCA1 levels were not affected by cyclophosphamide or paclitaxel. Likewise, apoA1 levels were reduced by doxorubicin and remained unaffected by cyclophosphamide and paclitaxel. Doxorubicin and paclitaxel both increased apoB protein levels and paclitaxel also decreased low density lipoprotein receptor (LDLR) protein levels. These findings correlate with the observed reduction in HDL-C and apoA1 and increase in apoB levels seen in these patients. The unfavourable lipid profiles produced by some chemotherapy agents may be detrimental in the longer term to cancer patients, especially those already at risk of cardiovascular disease (CVD). This knowledge may be useful in tailoring effective follow-up care plans for cancer survivors.

  18. The effects of space flight on some rat liver enzymes regulating carbohydrate and lipid metabolism (United States)

    Abraham, S.; Lin, C. Y.; Klein, H. P.; Volkmann, C.


    The effects of space flight conditions on the activities of certain enzymes regulating carbohydrate and lipid metabolism in rat liver are investigated in an attempt to account for the losses in body weight observed during space flight despite preflight caloric consumption. Liver samples were analyzed for the activities of 32 cytosolic and microsomal enzymes as well as hepatic glycogen and individual fatty acid levels for ground control rats and rats flown on board the Cosmos 936 biosatellite under normal space flight conditions and in centrifuges which were sacrificed upon recovery or 25 days after recovery. Significant decreases in the activities of glycogen phosphorylase, alpha-glycerol phosphate acyl transferase, diglyceride acyl transferase, aconitase and 6-phosphogluconate dehydrogenase and an increase in palmitoyl CoA desaturase are found in the flight stationary relative to the flight contrifuged rats upon recovery, with all enzymes showing alterations returning to normal values 25 days postflight. The flight stationary group is also observed to be characterized by more than twice the amount of liver glycogen of the flight centrifuged group as well as a significant increase in the ratio of palmitic to palmitoleic acid. Results thus indicate metabolic changes which may be involved in the mechanism of weight loss during weightlessness, and demonstrate the equivalence of centrifugation during space flight to terrestrial gravity.

  19. Homozygous and heterozygous GH transgenesis alters fatty acid composition and content in the liver of Amago salmon (Oncorhynchus masou ishikawae

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    Manabu Sugiyama


    Growth hormone (GH transgenic Amago (Oncorhynchus masou ishikawae, containing the sockeye GH1 gene fused with metallothionein-B promoter from the same species, were generated and the physiological condition through lipid metabolism compared among homozygous (Tg/Tg and heterozygous GH transgenic (Tg/+ Amago and the wild type control (+/+. Previously, we have reported that the adipose tissue was generally smaller in GH transgenic fish compared to the control, and that the Δ-6 fatty acyl desaturase gene was down-regulated in the Tg/+ fish. However, fatty acid (FA compositions have not been measured previously in these fish. In this study we compared the FAs composition and content in the liver using gas chromatography. Eleven kinds of FA were detected. The composition of saturated and monounsaturated fatty acids (SFA and MUFA such as myristic acid (14:0, palmitoleic acid (16:1n-7, and cis-vaccenic acid (cis-18:1n-7 was significantly (P<0.05 decreased in GH transgenic Amago. On the other hand, the composition of polyunsaturated fatty acids (PUFAs such as linoleic acid (18:2n-6, arachidonic acid (20:4n-6, and docosapentaenoic acid (22:5n-3 was significantly (P<0.05 increased. Levels of serum glucose and triacylglycerol were significantly (P<0.05 decreased in the GH transgenics compared with +/+ fish. Furthermore, 3′-tag digital gene expression profiling was performed using liver tissues from Tg/Tg and +/+ fish, and showed that Mid1 interacting protein 1 (Mid1ip1, which is an important factor to activate Acetyl-CoA carboxylase (ACC, was down-regulated in Tg/Tg fish, while genes involved in FA catabolism were up-regulated, including long-chain-fatty-acid–CoA ligase 1 (ACSL1 and acyl-coenzyme A oxidase 3 (ACOX3. These data suggest that liver tissue from GH transgenic Amago showed starvation by alteration in glucose and lipid metabolism due to GH overexpression. The decrease of serum glucose suppressed Mid1ip1, and caused a decrease of de novo FA synthesis, resulting

  20. Role of liver functions on liver cell mitosis

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    Full Text Available The control mechanism of mitosis in the regenerating rat liver was studied in relation to the cell functions. Partial hepatec· tomy induces a series of changes prior to the initiation of mitosis, i. e. decrease in serum glucose and albumin levels, loss of glycogen from liver cells, and increased lipid mobilization to liver cells. Massive supplies of glucose and fructose suppressed significantly hepatocellu. lar mitosis with suppression of lipid accumulation and preservation of glycogen in the liver cells and of blood sugar level. Homologous serum administration also suppressed the rate of liver cell mitosis after hepatectomy preventing the decrease in serum albumin level, but did not suppress the lipid accumulation in the liver. Starvation, which would relieve the liver cell from the work of detoxication of intesti. nal toxic products, did not show any suppressive effect on the mitotic rate of liver cells after partial hepatectomy in single animals. But starvation induced severe hypoglycemia, moderate hypoalbuminemia and loss of glycogen content in the liver. These changes in metabo. lism by starvation and partial hepatectomy were suppressed by con· jugating the animals with nonhepatectomized by aortic anastomosis, and mitosis was suppressed in the residual liver of the fasting animals in this parabiosis. The results indicate that all the major functions of parenchymal live cells tested, sugar metabolism, serum albumin production, and detoxication, are closely related to the control of liver cell mitosis. Accumulation of lipids in the liver remnant after partial hepatectomy is thought to be for the compensa. tion of reduced glycogen storage and not concerned directly with the liver cell mitosis. Discussion was made briefly on the humoral factor and portal blood factor in relation to excess load of functions on resi. dual liver cells.

  1. Synthesis, screening and docking of small heterocycles as glycogen phosphorylase inhibitors. (United States)

    Schweiker, Stephanie S; Loughlin, Wendy A; Lohning, Anna S; Petersson, Maria J; Jenkins, Ian D


    A series of morpholine substituted amino acids (phenylalanine, leucine, lysine and glutamic acid) was synthesized. A fragment-based screening approach was then used to evaluate a series of small heterocycles, including morpholine, oxazoline, dihydro-1,3-oxazine, tetrahydro-1,3-oxazepine, thiazoline, tetrahydro-1,3-pyrimidine, tetrahydro-1,3-diazepine and hexahydro-1H-benzimidazole, as potential inhibitors of Glycogen Phosphorylase a. Thiazoline 7 displayed an improved potency (IC50 of 25 μM) and had good LE and LELP values, as compared to heterocycles 1, 5, 9-13 and 19 (IC50 values of 1.1 mM-23.9 mM). A docking study using the crystal structure of human liver Glycogen Phosphorylase, provided insight into the interactions of heterocycles 5, 7, 9-13 and 19 with Glycogen Phosphorylase.

  2. Altered distribution of regulatory lymphocytes by oral administration of soy-extracts exerts a hepatoprotective effect alleviating immune mediated liver injury, non-alcoholic steatohepatitis and insulin resistance (United States)

    Khoury, Tawfik; Ben Ya'acov, Ami; Shabat, Yehudit; Zolotarovya, Lidya; Snir, Ram; Ilan, Yaron


    AIM: To determine the immune-modulatory and the hepatoprotective effects of oral administration of two soy extracts in immune mediated liver injury and non-alcoholic steatohepatitis (NASH). METHODS: Two soy extracts, M1 and OS, were orally administered to mice with concanavalin A (ConA) immune-mediated hepatitis, to high-fat diet (HFD) mice and to methionine and choline reduced diet combined with HFD mice. Animals were followed for disease and immune biomarkers. RESULTS: Oral administration of OS and M1 had an additive effect in alleviating ConA hepatitis manifested by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels. Oral administration of the OS and M1 soy derived fractions, ameliorated liver injury in the high fat diet model of NASH, manifested by a decrease in hepatic triglyceride levels, improvement in liver histology, decreased serum cholesterol and triglycerides and improved insulin resistance. In the methionine and choline reduced diet combined with the high fat diet model, we noted a decrease in hepatic triglycerides and improvement in blood glucose levels and liver histology. The effects were associated with reduced serum tumor necrosis factor alpha and alteration of regulatory T cell distribution. CONCLUSION: Oral administration of the combination of OS and M1 soy derived extracts exerted an adjuvant effect in the gut-immune system, altering the distribution of regulatory T cells, and alleviating immune mediated liver injury, hyperlipidemia and insulin resistance. PMID:26139990

  3. Carbohydrates, Muscle Glycogen, and Improved Performance. (United States)

    Sherman, W. Mike


    One way to improve athletic performance without harming the athlete's health is diet manipulation. This article explores the relationship between muscular endurance and muscle glycogen and discusses a diet and training approach to competition. (Author/MT)

  4. Histopathological alterations observed in the liver of Poecilia vivipara (Cyprinodontiformes: Poeciliidae as a tool for the environmental quality assessment of the Cachoeira River, BA

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    DV Paulo

    Full Text Available Histopathological alterations in liver have been widely used as a tool in studies for monitoring environmental quality. To evaluate the environmental quality in the Cachoeira river, five spots were monitored between the municipal districts of Itapé and Ilhéus, using liver histological analysis. The species chosen for analysis was Poecilia vivipara due to the fact that it is one of the most abundant in the sampling. The routine technique of inclusion and impregnation in paraffin was used, and the cuts were stained with Hematoxylin and Eosin (H & E. Histopathological alterations in the liver were evaluated semi-quantitatively and based on the severity of the lesions. The results of the histopathological alteration frequency together with the average taken from the Histopathological Alteration Index from points 1 (Vila de Itapé and 2 (Fazenda Santa Amélia showed that in this area the environment is more threatened because of some stressor agent, possibly contaminants that seem to be acting in the environment and endangering the health of fish. The statistic results demonstrated that there were no significant differences among points 1, 2 and 4, which means they are very similar to one another, and are ecologically endangered.

  5. Refeeding-induced brown adipose tissue glycogen hyper-accumulation in mice is mediated by insulin and catecholamines.

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    Christopher M Carmean

    Full Text Available Brown adipose tissue (BAT generates heat during adaptive thermogenesis through a combination of oxidative metabolism and uncoupling protein 1-mediated electron transport chain uncoupling, using both free-fatty acids and glucose as substrate. Previous rat-based work in 1942 showed that prolonged partial fasting followed by refeeding led to a dramatic, transient increase in glycogen stores in multiple fat depots. In the present study, the protocol was replicated in male CD1 mice, resulting in a 2000-fold increase in interscapular BAT (IBAT glycogen levels within 4-12 hours (hr of refeeding, with IBAT glycogen stores reaching levels comparable to fed liver glycogen. Lesser effects occurred in white adipose tissues (WAT. Over the next 36 hr, glycogen levels dissipated and histological analysis revealed an over-accumulation of lipid droplets, suggesting a potential metabolic connection between glycogenolysis and lipid synthesis. 24 hr of total starvation followed by refeeding induced a robust and consistent glycogen over-accumulation similar in magnitude and time course to the prolonged partial fast. Experimentation demonstrated that hyperglycemia was not sufficient to drive glycogen accumulation in IBAT, but that elevated circulating insulin was sufficient. Additionally, pharmacological inhibition of catecholamine production reduced refeeding-induced IBAT glycogen storage, providing evidence of a contribution from the central nervous system. These findings highlight IBAT as a tissue that integrates both canonically-anabolic and catabolic stimulation for the promotion of glycogen storage during recovery from caloric deficit. The preservation of this robust response through many generations of animals not subjected to food deprivation suggests that the over-accumulation phenomenon plays a critical role in IBAT physiology.

  6. Effects of dimethoate (30% EC), an organophosphate pesticide on liver of common carp, Cyprinus carpio. (United States)

    Singh, Ram Nayan


    Organ histopathology and changes in biochemical parameters in fish are good biomarkers of aquatic pollution. This study is an attempt to assess the effects of dimethoate, an organophosphate insecticide on the liver of common carp (C. carpio). Healthy individual fish were exposed to 0.40 mg l(-1) (25% of 96 hr LC50) concentration of dimethoate, for short term (96 hr). Liver of the exposed fish exhibited alterations like disruption of regular arrangement of hepatocytes, congestion and rupture of vessels; hemorrhage, cytoplasmic vacuolization, pyknotic nuclei and necrosis. Biochemical parameters viz. total liver protein (p < 0.001) and liver glycogen (p < 0.001) registered a significant decrease and blood glucose (p < 0.001) exhibited significant increase throughout exposure.

  7. Distribution of electrophoretically separated serum high density lipoprotein subfraction levels among healthy students and its alteration in patients with liver diseases.

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    Full Text Available In an attempt to evaluate high density lipoprotein (HDL subfraction levels in liver diseases, HDL was separated by a precipitation method with dextran sulfate-Mg2+ from sera of 289 healthy adults and 50 patients with liver diseases. The HDL was subdivided into HDL2e and HDL3e by Utermann's polyacrylamide gel electrophoresis with lauric acid. Ultracentrifugally separated HDL2 and HDL3 roughly corresponded to HDL2e and HDL3e, respectively. Male and female groups had different distributions of HDL2e/HDL3e ratios. Among healthy males, 121 cases had ratios less than 1.0 (mean +/- SD = 0.72 +/- 0.39, n = 150, while among healthy females, the ratios were generally larger than those of males and varied widely from 0.2 to 6.6 (mean +/- SD = 1.77 +/- 1.05, n = 139. Low levels of HDL-cholesterol were found in patients with liver diseases, except those with mild alcoholic liver injury and intrahepatic cholestasis. Apparent decreases in HDL3e, but not in HDL2e, were found in all cases with liver diseases investigated, even in those who did not show decreases in the total HDL level, when male and female patients were analyzed separately. The analysis of HDL subfractions by the present method is simple and useful for the study on altered lipid metabolism in liver diseases.

  8. Dietary Omega-3 Polyunsaturated Fatty Acids Alter Fatty Acid Composition of Lipids and CYP2E1 Expression in Rat Liver Tissue. (United States)

    Maksymchuk, Oksana; Shysh, Angela; Chashchyn, Mykola; Moibenko, Olexyi


    Omega-3 polyunsaturated fatty acids (PUFAs) are used for the treatment and prevention of numerous pathologies in humans. As recently found, PUFAs play significantly protective roles in liver, cardiovascular system and kidney. They also are widely used in total parenteral nutrition. We evaluated the effect of omega-3 PUFA consumption on liver fatty acid composition and the expression of CYP2E1, one of the key enzymes in detoxification and prooxidant systems of liver cells. To estimate the oxidative stress in liver tissue, the antioxidant status and the level of lipid peroxidation were determined in a rodent model. Animals were divided into two groups: control (n = 10) and experimental (n = 10). Epadol-containing omega-3 PUFA fish oil capsules were administered to Wistar rats within 4 weeks (0.1 mL/100 g b.w./day). The consumption of omega-3 PUFAs resulted in changes of fatty acid composition of liver tissue. A significant increase was detected in the α-linolenic, eicosapentaenoic and docosahexaenoic acid content (5.1-, 16-, and 1.3-fold, respectively, p omega-3:omega-6 ratio. Consumption of omega-3 PUFAs led to a 3-fold (p < 0.05) increase in CYP2E1 content, which could entail enhanced Nrf2 expression levels and increases in the HO-1 content in rat liver. The alteration in CYP2E1 expression did not have an impact on the level of lipid peroxidation and on the prooxidant/antioxidant balance.

  9. Characterization of the highly branched glycogen from the thermoacidophilic red microalga Galdieria sulphuraria and comparison with other glycogens. (United States)

    Martinez-Garcia, Marta; Stuart, Marc C A; van der Maarel, Marc J E C


    The thermoacidophilic red microalga Galdieria sulphuraria synthesizes glycogen when growing under heterotrophic conditions. Structural characterization revealed that G. sulphuraria glycogen is the most highly branched glycogen described to date, with 18% of α-(1→6) linkages. Moreover, it differs from other glycogens because it is composed of short chains only and has a substantially smaller molecular weight and particle size. The physiological role of this highly branched glycogen in G. sulphuraria is discussed.

  10. Altered fatty acid profile in the liver and serum of stroke-prone spontaneously hypertensive rats: reduced proportion of cis-vaccenic acid. (United States)

    Tanaka, Shizuyo; Kojiguchi, Chiho; Yamazaki, Tohru; Mitsumoto, Atsushi; Kobayashi, Daisuke; Kudo, Naomi; Kawashima, Yoichi


    Stroke-prone spontaneously hypertensive rats (SHRSP) are utilized as models for study of the pathogenesis of not only stroke and cardiovascular disorders but also atherosclerosis and metabolic syndrome. Basic information on the profiles of fatty acids and lipid classes in the liver is indispensable to use SHRSP as a model of disorder of lipid metabolism; nevertheless, detailed information on the metabolism of triacylglycerols (TAGs) and fatty acids in the liver of SHRSP is lacking. This study aimed to characterize profiles of lipid classes and fatty acids and to explore the mechanism underlying the characteristic alterations in metabolism of TAGs and fatty acids in the liver of SHRSP, in comparison with spontaneously hypertensive rats (SHR). The characteristic changes observed in SHRSP were (1) markedly lower hepatic TAG contents; (2) altered expressions of genes encoding three enzymes responsible for the control of TAG level, namely, adipose triglyceride lipase (for TAG degradation; up-regulated), carnitine palmitoyltransferase 1a (for fatty acid β-oxidation; up-regulated) and long-chain acyl-CoA synthetase 3 (for glycerolipid synthesis; down-regulated); (3) evidently lower contents and proportions of monounsaturated fatty acids, in particular cis-vaccenic acid (18:1n-7), in the liver and serum; and (4) down-regulation of palmitoleoyl-CoA chain elongase, which is necessary for the biosynthesis of 18:1n-7, in the liver. From the above observations, we concluded that there are significant differences in profiles of lipid classes and fatty acids between SHRSP and SHR, and that altered characteristics in SHRSP are likely responsible for increases in TAG hydrolysis and β-oxidation, and decreases in TAG synthesis and 18:1n-7 synthesis.


    Institute of Scientific and Technical Information of China (English)

    徐钢春; 杜富宽; 聂志娟; 殷文健; 徐跑; 顾若波


    time points—before loading (BL), after loading (AL), 2h, 4h, 6h, and 8h after the beginning of transportation, 24h recovery, and 96h recovery. We tested the plasma osmotic pressure, cortisol, glucose and the liver glycogen of these samples. The result showed that after the 96h recovery, the survival rates of the normal stress group and the salt stress group were 20% and 100% re-spectively. The blood osmotic pressure was reduced in the normal stress group after transportation. In contrast it was significantly elevated in the salt stress group, and reached to the peak value [(0.348±0.002) mOsm/kg] 8h after the be-ginning of transportation. The plasma cortisol rapidly climbed to the peak 2h after the beginning of transportation in the normal stress group, whereas, it reached to the peak [(574.71±64.75) ng/mL] 4h after the beginning of transportation in the salt stress group. The level of glucose in the normal stress group was significantly elevated after the transportation, but its change in the salt stress group was much milder and the concentration was stabilized 6h after the beginning of transportation. Moreover, the glucose concentration in the salt stress group was significantly lower than that in the nor-mal stress group. The change in the liver glycogen was consistent with the change in glucose level, so we speculated that the increase in glucose resulted from the glycogenolysis of the liver glycogen. These results suggested that 10‰salinity could significantly improve the level of plasma osmotic pressure, reduce the energy consumption of material, and avoid strong stress reactions such as walling and rawing, therefore effectively raise the survival rate.

  12. Long-Term Selenium-Deficient Diet Induces Liver Damage by Altering Hepatocyte Ultrastructure and MMP1/3 and TIMP1/3 Expression in Growing Rats. (United States)

    Han, Jing; Liang, Hua; Yi, Jianhua; Tan, Wuhong; He, Shulan; Wang, Sen; Li, Feng; Wu, Xiaofang; Ma, Jing; Shi, Xiaowei; Guo, Xiong; Bai, Chuanyi


    The effects of selenium (Se)-deficient diet on the liver were evaluated by using growing rats which were fed with normal and Se-deficient diets, respectively, for 109 days. The results showed that rats fed with Se-deficient diet led to a decrease in Se concentration in the liver, particularly among male rats from the low-Se group. This causes alterations to the ultrastructure of hepatocytes with condensed chromatin and swelling mitochondria observed after low Se intake. Meanwhile, pathological changes and increased fibrosis in hepatic periportal were detected by hematoxylin and eosin and Masson's trichrome staining in low-Se group. Furthermore, through immunohistochemistry (IHC) staining, higher expressions of metalloproteinases (MMP1/3) and their tissue inhibitors of metalloproteinases (TIMP1/3) were observed in the hepatic periportal of rats from the low-Se group. However, higher expressions of MMP1/3 and lower expressions of TIMP1/3 were detected in hepatic central vein and hepatic sinusoid. In addition, upregulated expressions of MMP1/3 and downregulated expressions of TIMP1/3 at the messenger RNA (mRNA) and protein levels also appeared to be relevant to low Se intake. In conclusion, Se-deficient diet could cause low Se concentration in the liver, alterations of hepatocyte ultrastructure, differential expressions of MMP1/3 and TIMP1/3 as well as fibrosis in the liver hepatic periportal.

  13. Ameliorating effect of black tea extract on cadmium chloride-induced alteration of serum lipid profile and liver histopathology in rats. (United States)

    Mantur, Venkappa S; Somannavarib, Manjunath S; Yendigeri, Saeed; Das, Kusal K; Goudar, Shivaprasad S


    Cadmium is one among the most environmental pollutants that affects many organs like kidney, liver and testis. The present study was aimed to assess the simultaneous effects of black tea extracts (BTE) on cadmium chloride induced alterations in lipid profile and liver histology. Adult rats were divided into four groups (n=6/group), group I (normal saline), group II (CdCl2, 1.0 mg/kg, b.wt; i.p), group III (black tea extract, 2.5 gm tea leaf/dl of water that is 2.5% of aqueous BTE) and group IV (cadmium chloride + BTE). Cadmium chloride intoxicated rats showed significant increase in serum total cholesterol, triglycerides, and low density lipoprotein-cholesterol and there is a significant decrease in the serum high density lipoprotein-cholesterol. In the liver, cadmium chloride showed changes in normal architecture, swollen hepatocytes, kupffer cells hyperplasia, dilation and congestion of central vein. Oral administration of black tea extracts with cadmium chloride significantly improves lipid profile and liver architecture as compared to the cadmium chloride group. The results indicate that BTE is beneficial in preventing cadmium-induced lipid alterations and hepatocellular damage.

  14. Butyrate ingestion improves hepatic glycogen storage in the re-fed rat

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    Rigalleau Vincent


    Full Text Available Abstract Background Butyrate naturally produced by intestinal fiber fermentation is the main nutrient for colonocytes, but the metabolic effect of the fraction reaching the liver is not totally known. After glycogen hepatic depletion in the 48-hour fasting rat, we monitored the effect of (butyrate 1.90 mg + glucose 14.0 mg/g body weight versus isocaloric (glucose 18.2 mg/g or isoglucidic (glucose 14.0 mg/g control force-feeding on in vivo changes in hepatic glycogen and ATP contents evaluated ex vivo by NMR in the isolated and perfused liver. Results The change in glycogen was biphasic with (i an initial linear period where presence of butyrate in the diet increased (P = 0.05 the net synthesis rate (0.20 ± 0.01 μmol/min.g-1 liver wet weight, n = 15 versus glucose 14.0 mg/g only (0.16 ± 0.01 μmol/min.g-1 liver ww, n = 14, and (ii a plateau of glycogen store followed by a depletion. Butyrate delayed the establishment of the equilibrium between glycogenosynthetic and glycogenolytic fluxes from the 6th to 8th hour post-feeding. The maximal glycogen content was then 97.27 ± 10.59 μmol/g liver ww (n = 7 at the 8th hour, which was significantly higher than with the isocaloric control diet (64.34 ± 8.49 μmol/g, n = 12, P = 0.03 and the isoglucidic control one (49.11 ± 6.35 μmol/g liver ww, n = 6, P = 0.003. After butyrate ingestion, ATP content increased from 0.95 ± 0.29 to a plateau of 2.14 ± 0.23 μmol/g liver ww at the 8th hour post-feeding (n = 8 [P = 0.04 versus isoglucidic control diet (1.45 ± 0.19 μmol/g, n = 8 but was not different from the isocaloric control diet (1.70 ± 0.18 μmol/g, n = 12]. Conclusion The main hepatic effect of butyrate is a sparing effect on glycogen storage explained (i by competition between butyrate and glucose oxidation, glucose being preferentially directed to glycogenosynthesis during the post-prandial state; and (ii by a likely reduced glycogenolysis from the newly synthesized glycogen. This first

  15. Malarial Infection of Female BWF1 Lupus Mice Alters the Redox State in Kidney and Liver Tissues and Confers Protection against Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    Saleh Al-Quraishy


    Full Text Available Systemic lupus erythematosus (SLE is a prototypic autoimmune disease characterized by an imbalanced redox state and increased apoptosis. Tropical infections, particularly malaria, may confer protection against SLE. Oxidative stress is a hallmark of SLE. We have measured changes in the levels of nitric oxide (NO, hydrogen peroxide (H2O2, malondialdehyde (MDA, and reduced glutathione (GSH in both kidney and liver tissues of female BWF1 lupus mice, an experimental model of SLE, after infection with either live or gamma-irradiated malaria. We observed a decrease in NO, H2O2, and MDA levels in kidney tissues after infection of lupus mice with live malaria. Similarly, the levels of NO and H2O2 were significantly decreased in the liver tissues of lupus mice after infection with live malaria. Conversely, GSH levels were obviously increased in both kidney and liver tissues after infection of lupus mice with either live or gamma-irradiated malaria. Liver and kidney functions were significantly altered after infection of lupus mice with live malaria. We further investigated the ultrastructural changes and detected the number of apoptotic cells in kidney and liver tissues in situ by electron microscopy and TUNEL assays. Our data reveal that infection of lupus mice with malaria confers protection against lupus nephritis.

  16. Patterns of dioxin-altered mRNA expression in livers of dioxin-sensitive versus dioxin-resistant rats

    Energy Technology Data Exchange (ETDEWEB)

    Franc, Monique A. [University of Toronto, Department of Pharmacology and Toxicology, Medical Sciences Building, Toronto, ON (Canada); Johnson and Johnson Pharmaceutical Research and Development, Department of Pharmacogenomics, 1000 Route 202 South, P.O. Box 300, Raritan, NJ (United States); Moffat, Ivy D.; Boutros, Paul C.; Okey, Allan B. [University of Toronto, Department of Pharmacology and Toxicology, Medical Sciences Building, Toronto, ON (Canada); Tuomisto, Jouni T.; Tuomisto, Jouko [National Public Health Institute, Department of Environmental Health, Centre for Environmental Health Risk Analysis, Kuopio (Finland); Pohjanvirta, Raimo [University of Helsinki, Department of Food and Environmental Hygiene, Faculty of Veterinary Medicine, Helsinki (Finland)


    Dioxins exert their major toxicologic effects by binding to the aryl hydrocarbon receptor (AHR) and altering gene transcription. Numerous dioxin-responsive genes previously were identified both by conventional biochemical and molecular techniques and by recent mRNA expression microarray studies. However, of the large set of dioxin-responsive genes the specific genes whose dysregulation leads to death remain unknown. To identify specific genes that may be involved in dioxin lethality we compared changes in liver mRNA levels following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in three strains/lines of dioxin-sensitive rats with changes in three dioxin-resistant rat strains/lines. The three dioxin-resistant strains/lines all harbor a large deletion in the transactivation domain of the aryl hydrocarbon receptor (AHR). Despite this deletion, many genes exhibited a ''Type-I'' response - that is, their responses were similar in dioxin-sensitive and dioxin-resistant rats. Several genes that previously were well established as being dioxin-responsive or under AHR regulation emerged as Type-I responses (e.g. CYP1A1, CYP1A2, CYP1B1 and Gsta3). In contrast, a relatively small number of genes exhibited a Type-II response - defined as a difference in responsiveness between dioxin-sensitive and dioxin-resistant rat strains. Type-II genes include: malic enzyme 1, ubiquitin C, cathepsin L, S-adenosylhomocysteine hydrolase and ferritin light chain 1. In silico searches revealed that AH response elements are conserved in the 5'-flanking regions of several genes that respond to TCDD in both the Type-I and Type-II categories. The vast majority of changes in mRNA levels in response to 100 {mu}g/kg TCDD were strain-specific; over 75% of the dioxin-responsive clones were affected in only one of the six strains/lines. Selected genes were assessed by quantitative RT-PCR in dose-response and time-course experiments and responses of some genes were

  17. Glycogen resynthesis rate following cross-country skiing is closely correlated to skeletal muscle glycogen content

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Nielsen, Joachim; Saltin, Bengt;

    -trial (classic style) on a competition cc track. During the first 4hrs of recovery, skiers received either water or carbohydrate (CHO), after which they all received CHO enriched food (1 g . kg-1 bw . h-1). Muscle biopsies were obtained in both arm and leg muscles before and immediately after the race, as well...... as 4h and 22h after the race and analyzed for glycogen content. Figure 1. Correlation between muscle glycogen resynthesis rate and glycogen content after and in the rocery period after exercise. Line indicate best fit of all the data points (r2 = 0.41, p

  18. Genetics Home Reference: glycogen storage disease type V (United States)

    ... storage disease type V glycogen storage disease type V Enable Javascript to view the expand/collapse boxes. ... All Close All Description Glycogen storage disease type V (also known as GSDV or McArdle disease) is ...

  19. Morphological alterations and acetylcholinesterase and monoamine oxidase inhibition in liver of zebrafish exposed to Aphanizomenon flos-aquae DC-1 aphantoxins

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, De Lu, E-mail: [Department of Lifescience and Biotechnology, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070 (China); Zhang, Jing [College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China); Hu, Chun Xiang, E-mail: [Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China); Wang, Gao Hong; Li, Dun Hai; Liu, Yong Ding [Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China)


    Highlights: • Aphantoxins induced zebrafish hepatic physiological and morphological changes. • AChE and MAO inhibition reflected abnormality of neurotransmitter inactivation. • ROS advance and T-AOC reduction suggested oxidative stress. • ALT, AST, histological and ultrastructural alterations indicated hepatic damage. - Abstract: Aphanizomenon flos-aquae is a cyanobacterium that produces neurotoxins or paralytic shellfish poisons (PSPs) called aphantoxins, which present threats to environmental safety and human health via eutrophication of water bodies worldwide. Although the molecular mechanisms of this neurotoxin have been studied, many questions remain unsolved, including those relating to in vivo hepatic neurotransmitter inactivation, physiological detoxification and histological and ultrastructural alterations. Aphantoxins extracted from the natural strain of A. flos-aquae DC-1 were analyzed by high-performance liquid chromatography. The main components were gonyautoxins 1 and 5 (GTX1, GTX5) and neosaxitoxin (neoSTX), which comprised 34.04%, 21.28%, and 12.77% respectively. Zebrafish (Danio rerio) were exposed intraperitoneally to 5.3 or 7.61 μg STX equivalents (eq)/kg (low and high doses, respectively) of A. flos-aquae DC-1 aphantoxins. Morphological alterations and changes in neurotransmitter conduction functions of acetylcholinesterase (AChE) and monoamine oxidase (MAO) in zebrafish liver were detected at different time points 1–24 h post-exposure. Aphantoxin significantly enhanced hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histological and ultrastructural damage in zebrafish liver at 3–12 h post-exposure. Toxin exposure increased the reactive oxygen species content and reduced total antioxidative capacity in zebrafish liver, suggesting oxidative stress. AChE and MAO activities were significantly inhibited, suggesting neurotransmitter inactivation/conduction function abnormalities in zebrafish

  20. Altered UDP-Glucuronosyltransferase and Sulfotransferase Expression and Function during Progressive Stages of Human Nonalcoholic Fatty Liver Disease


    Hardwick, Rhiannon N.; Ferreira, Daniel W.; More, Vijay R.; Lake, April D.; Lu, Zhenqiang; Manautou, Jose E.; Slitt, Angela L.; Cherrington, Nathan J


    The UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) represent major phase II drug-metabolizing enzymes that are also responsible for maintaining cellular homeostasis by metabolism of several endogenous molecules. Perturbations in the expression or function of these enzymes can lead to metabolic disorders and improper management of xenobiotics and endobiotics. Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver damage ranging from steatosis to nonalcoholic...

  1. Stiffness of hyaluronic acid gels containing liver extracellular matrix supports human hepatocyte function and alters cell morphology. (United States)

    Deegan, Daniel B; Zimmerman, Cynthia; Skardal, Aleksander; Atala, Anthony; Shupe, Thomas D


    Tissue engineering and cell based liver therapies have utilized primary hepatocytes with limited success due to the failure of hepatocytes to maintain their phenotype in vitro. In order to overcome this challenge, hyaluronic acid (HA) cell culture substrates were formulated to closely mimic the composition and stiffness of the normal liver cellular microenvironment. The stiffness of the substrate was modulated by adjusting HA hydrogel crosslinking. Additionally, the repertoire of bioactive molecules within the HA substrate was bolstered by supplementation with normal liver extracellular matrix (ECM). Primary human hepatocyte viability and phenotype were determined over a narrow physiologically relevant range of substrate stiffnesses from 600 to 4600Pa in both the presence and absence of liver ECM. Cell attachment, viability, and organization of the actin cytoskeleton improved with increased stiffness up to 4600Pa. These differences were not evident in earlier time points or substrates containing only HA. However, gene expression for the hepatocyte markers hepatocyte nuclear factor 4 alpha (HNF4α) and albumin significantly decreased on the 4600Pa stiffness at day 7 indicating that cells may not have maintained their phenotype long-term at this stiffness. Function, as measured by albumin secretion, varied with both stiffness and time in culture and peaked at day 7 at the 1200Pa stiffness, slightly below the stiffness of normal liver ECM at 3000Pa. Overall, gel stiffness affected primary human hepatocyte cell adhesion, functional marker expression, and morphological characteristics dependent on both the presence of liver ECM in gel substrates and time in culture.

  2. Gamma-Glutamylcysteine Ethyl Ester Protects against Cyclophosphamide-Induced Liver Injury and Hematologic Alterations via Upregulation of PPARγ and Attenuation of Oxidative Stress, Inflammation, and Apoptosis (United States)

    Alqahtani, Sultan


    Gamma-glutamylcysteine ethyl ester (GCEE) is a precursor of glutathione (GSH) with promising hepatoprotective effects. This investigation aimed to evaluate the hepatoprotective effects of GCEE against cyclophosphamide- (CP-) induced toxicity, pointing to the possible role of peroxisome proliferator activated receptor gamma (PPARγ). Wistar rats were given GCEE two weeks prior to CP. Five days after CP administration, animals were sacrificed and samples were collected. Pretreatment with GCEE significantly alleviated CP-induced liver injury by reducing serum aminotransferases, increasing albumin, and preventing histopathological and hematological alterations. GCEE suppressed lipid peroxidation and nitric oxide production and restored GSH and enzymatic antioxidants in the liver, which were associated with downregulation of COX-2, iNOS, and NF-κB. In addition, CP administration significantly increased serum proinflammatory cytokines and the expression of liver caspase-3 and BAX, an effect that was reversed by GCEE. CP-induced rats showed significant downregulation of PPARγ which was markedly upregulated by GCEE treatment. These data demonstrated that pretreatment with GCEE protected against CP-induced hepatotoxicity, possibly by activating PPARγ, preventing GSH depletion, and attenuating oxidative stress, inflammation, and apoptosis. Our findings point to the role of PPARγ and suggest that GCEE might be a promising agent for the prevention of CP-induced liver injury. PMID:28074115

  3. Regulation of glucose and glycogen metabolism during and after exercise

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Richter, Erik


    Utilization of carbohydrate in the form of intramuscular glycogen stores and glucose delivered from plasma becomes an increasingly important energy substrate to the working muscle with increasing exercise intensity. This review gives an update on the molecular signals by which glucose transport...... in the post-exercise period which can result in an overshoot of intramuscular glycogen resynthesis post exercise (glycogen supercompensation)....

  4. Relationship between single nucleotide polymorphism of glycogen synthase gene of Pacific oyster Crassostrea gigas and its glycogen content (United States)

    Liu, Siwei; Li, Qi; Yu, Hong; Kong, Lingfeng


    Glycogen is important not only for the energy supplementary of oysters, but also for human consumption. High glycogen content can improve the stress survival of oyster. A key enzyme in glycogenesis is glycogen synthase that is encoded by glycogen synthase gene GYS. In this study, the relationship between single nucleotide polymorphisms (SNPs) in coding regions of Crassostrea gigas GYS (Cg-GYS) and individual glycogen content was investigated with 321 individuals from five full-sib families. Single-strand conformation polymorphism (SSCP) procedure was combined with sequencing to confirm individual SNP genotypes of Cg-GYS. Least-square analysis of variance was performed to assess the relationship of variation in glycogen content of C. gigas with single SNP genotype and SNP haplotype. As a consequence, six SNPs were found in coding regions to be significantly associated with glycogen content ( P polymorphism on the glycogen content and provided molecular biological information for the selective breeding of good quality traits of C. gigas.

  5. Glycogen storage disease: report of two cases in the city of Cartagena

    Directory of Open Access Journals (Sweden)

    Ciro C. Alvear


    Full Text Available Objective: to report two cases of children with type Ia glycogen storage disease compatible with Von Gierke disease, suspected in the presence of findings such as hepatomegaly, nephromegaly, hypoglycemia, and stunted growth.Method: Presentation of the clinical records of two patients referred to the diagnostic unit of innate errors of metabolism of the Faculty of Medicine in Universidad de Cartagena.Results: The first case reported was a child who debuted with acute cyanosis without widespread neurological deficit when he was eleven months old, followed by hepatomegaly at two years of age. At 4 years of age, symptoms reappeared with similar characteristics: hypoglycemia, growth failure, and persistent hepatomegaly detected on physical examination. With the precedent that an older brother that presented similar symptoms was suspected of glycogen storage disease, a biopsy was performed and confirmed liver glycogen storage with normal structure. The patient’s treatment was modification of dietary habits (small, frequent feedings during the day and cornstarch. The second event was the older brother who consulted for the first time when he was 18 months old due to prolonged diarrhea. Hepatomegaly was documented by ultrasound study without kidney compromise and no hypoglycemia was found.Recommendations: It is necessary for the entire health team to be trained to detect rare diseases such as glycogen storage disease. If they make early diagnoses and establish support groups for interdisciplinary management of such diseases, they may change the prognosis and quality of life of these children.

  6. Glycogen storage disease: report of two cases in the city of Cartagena

    Directory of Open Access Journals (Sweden)

    Ciro C. Alvear


    Full Text Available Objective: to report two cases of children with type Ia glycogen storage disease compatible with Von Gierke disease, suspected in the presence of findings such as hepatomegaly, nephromegaly, hypoglycemia, and stunted growth. Method: Presentation of the clinical records of two patients referred to the diagnostic unit of innate errors of metabolism of the Faculty of Medicine in Universidad de Cartagena. Results: The first case reported was a child who debuted with acute cyanosis without widespread neurological deficit when he was eleven months old, followed by hepatomegaly at two years of age. At 4 years of age, symptoms reappeared with similar characteristics: hypoglycemia, growth failure, and persistent hepatomegaly detected on physical examination. With the precedent that an older brother that presented similar symptoms was suspected of glycogen storage disease, a biopsy was performed and confirmed liver glycogen storage with normal structure. The patient’s treatment was modification of dietary habits (small, frequent feedings during the day and cornstarch. The second event was the older brother who consulted for the first time when he was 18 months old due to prolonged diarrhea. Hepatomegaly was documented by ultrasound study without kidney compromise and no hypoglycemia was found. Recommendations: It is necessary for the entire health team to be trained to detect rare diseases such as glycogen storage disease. If they make early diagnoses and establish support groups for interdisciplinary management of such diseases, they may change the prognosis and quality of life of these children.

  7. Effects of in ovo injection of carbohydrates on somatic characteristics and liver nutrient profiles of broiler embryos and hatchlings. (United States)

    Zhai, W; Bennett, L W; Gerard, P D; Pulikanti, R; Peebles, E D


    Effects of the in ovo injection of commercial diluent supplemented with dextrin or with dextrin in combination with various other carbohydrates on the somatic characteristics and liver nutrient profiles of Ross × Ross 708 broiler embryos and chicks were investigated. Results include information concerning the gluconeogenic energy status of the liver before and after hatch. Eggs containing live embryos were injected in the amnion on d 18 of incubation using an automated multiple-egg injector for the delivery of the following carbohydrates dissolved in 0.4 mL of commercial diluent: 1) 6.25% glucose and 18.75% dextrin; 2) 6.25% sucrose and 18.75% dextrin; 3) 6.25% maltose and 18.75% dextrin; and 4) 25% dextrin. Also, a noninjected control and a 0.4-mL diluent-injected control were included. Body weight relative to set egg weight on d 19 of incubation (E19) was increased by the injection of all carbohydrate solutions, and on the day of hatch was increased by the injection of diluent, sucrose and dextrin, and maltose and dextrin solutions. Hatchability of the fertilized eggs, residual yolk sac weight, and liver weight were not affected by any injection treatment; however, as compared with the 0.4 mL diluent-injected group, all of the supplementary carbohydrates, except for the glucose and dextrin combination group, increased liver glycogen and glucose concentrations on E19. Furthermore, all carbohydrates, except for the 25% dextrin treatment, decreased liver fat concentration on E19. From E19 to the day of hatch, liver glycogen concentrations dropped dramatically from an average of 3.2 to 0.6%. Despite treatment differences observed on E19 for liver glycogen, glucose, and fat concentrations, these differences were lost by the day of hatch. Nevertheless, liver glycogen and glucose concentrations were positively correlated on the day of hatch. In conclusion, the in ovo injection of various supplemental carbohydrates dissolved in 0.4 mL of commercial diluent altered the

  8. Perioperative management of hemostasis for surgery of benign hepatic adenomas in patients with glycogen storage disease type ia. (United States)

    Mollet-Boudjemline, Alix; Hubert-Buron, Aurélie; Boyer-Neumann, Catherine; Aldea, Roxana; Franco, Dominique; Trioche-Eberschweiller, Pascale; Mas, Anne-Elisabeth; Mabille, Mylène; Labrune, Philippe; Gajdos, Vincent


    The development of hepatocellular adenomas in the liver of patients with glycogen storage disease type I is a well-known complication of the disease. Surgical procedures and perioperative managements described so far have reported persistent and important morbidity. We report here a series of six patients (three males and three females) who underwent hepatic resection, and we propose a new hemostatic management protocol comprising glucose infusion, corticosteroids, desmopressin, and antifibrinolytic drugs, used to prevent efficaciously hepatic hemorrhage due to glycogen storage disease (GSD) platelet dysfunction.

  9. Pregnancies in glycogen storage disease type Ia

    NARCIS (Netherlands)

    Martens, Danielle H. J.; Rake, Jan Peter; Schwarz, Martin; Ullrich, Kurt; Weinstein, David A.; Merkel, Martin; Sauer, Pieter J. J.; Smit, G. Peter A.


    OBJECTIVE: Reports on pregnancies in women with glycogen storage disease type Ia (GSD-Ia) are scarce. Because of improved life expectancy, pregnancy is becoming an important issue. We describe 15 pregnancies by focusing on dietary treatment, biochemical parameters, and GSD-Ia complications. STUDY DE

  10. Histopathological alterations of the gills, liver and kidneys in Anabas Testudineus (Bloch) fish living in an unused lignite mine, Li District, Lamphun Povince, Thailand

    Energy Technology Data Exchange (ETDEWEB)

    Saenphet, S.; Thaworn, W.; Saenphet, K. [Chiang Mai University, Chiang Mai (Thailand). Faculty of Science


    The acidity of mine water generally makes it toxic to most organisms. The gills, kidneys and livers of Anabas testudineus Bloch fish inhabiting the acidic water (pH 2-4) of an unused lignite mine in Li District, Lamphun Province, Thailand were examined and compared to those of farmed fish. Tissue abnormalities were found in all investigated organs. Deterioration and telangiectasia of gill filaments were found. Liver tissue revealed hemorrhages, blood congestion and necrotic cells with mononuclear cell infiltration. In addition, hypertrophy of the epithelial cells of the renal tubules with reduced lumens, aneurisms of the renal tubules, and contractions of the glomeruli in the Bowman's capsule were observed. These histopathological findings suggest the acidic water in this habitat causes severe damage to the internal organs of fish and consequently alter their physiological status. Since the water in this pond is utilized by local people, these findings highlight the need for adequate water treatment.

  11. Characterization of the highly branched glycogen from the thermoacidophilic red microalga Galdieria sulphuraria and comparison with other glycogens

    NARCIS (Netherlands)

    Martinez-Garcia, Marta; Stuart, Marc C A; van der Maarel, Marc J E C


    The thermoacidophilic red microalga Galdieria sulphuraria synthesizes glycogen when growing under heterotrophic conditions. Structural characterization revealed that G. sulphuraria glycogen is the most highly branched glycogen described to date, with 18% of α-(1→6) linkages. Moreover, it differs fro

  12. Different alterations of cytochrome P450 3A4 isoform and its gene expression in livers of patients with chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Li-Qun Yang; Shen-Jing Li; Yun-Fei Cao; Xiao-Bo Man; Wei-Feng Yu; Hong-Yang Wang; Meng-Chao Wu


    AIM: To determine whether parenchymal cells or hepaticcytochrome P450 protein was changed in chronic liverdiseases, and to compare the difference of CYP3A4 enzymeand its gene expression between patients with hepaticcirrhosis and obstructive jaundice, and to investigate thepharmacologic significance behind this difference.METHODS: Liver samples were obtained from patientsundergoing hepatic surgery with hepatic cirrhosis (n=6) andobstructive jaundice (n=6) and hepatic angeioma (controls,n=6). CYP3A4 activity and protein were determined by Nashand western bloting using specific polychonal antibody,respectively. Total hepatic RNA was extracted andCYP3A4cDNA probe was prepared according the methodof random primer marking, and difference of cyp3a4expression was compared among those patients byNorthern blotting.RESULTS: Compared to control group, the CYP3A4 activityand protein in liver tissue among patients with cirrhosis wereevidently reduced. (P<0.01) Northern blot showed the samechange in its mRNA levels. In contrast, the isoenzyme andits gene expression were not changed among patients withobstructive jaundice.CONCLUSION: Hepatic levels of P450s and its CYP3A4isoform activity were selectively changed in different chronicliver diseases. CYP3A4 isoenzyme and its activity declinedamong patients with hepatic cirrhosis as expression of cyp3a4gene was significantly reduced. Liver's ability to eliminatemany clinical therateutic drug substrates would declineconsequently, These findings may have practical implicationsfor the use of drugs in patients with cirrhosis and emphasizethe need to understand the metabolic fate of therapeuticcompounds. Elucidation of the reasons for these differentchanges in hepatic CYP3A4 may provide insight into morefundamental aspects and mechanisms of imparied liverfunction.

  13. Inhibiting Glycogen Synthesis Prevents Lafora Disease in a Mouse Model (United States)

    Pederson, Bartholomew A.; Turnbull, Julie; Epp, Jonathan R.; Weaver, Staci A.; Zhao, Xiaochu; Pencea, Nela; Roach, Peter J.; Frankland, Paul; Ackerley, Cameron A.; Minassian, Berge A.


    Lafora disease (LD) is a fatal progressive myoclonus epilepsy characterized neuropathologically by aggregates of abnormally structured glycogen and proteins (Lafora bodies, LB), and neurodegeneration. Whether LB could be prevented by inhibiting glycogen synthesis and whether they are pathogenic remain uncertain. We genetically eliminated brain glycogen synthesis in LD mice. This resulted in long-term prevention of LB formation, neurodegeneration, and seizure susceptibility. This study establishes that glycogen synthesis is requisite for LB formation and that LB are pathogenic. It opens a therapeutic window for potential treatments in LD with known and future small molecule inhibitors of glycogen synthesis. PMID:23913475

  14. Simultaneous alterations of brain and plasma serotonin concentrations and liver cytochrome P450 in rats fed on a tryptophan-free diet. (United States)

    Kot, Marta; Pilc, Andrzej; Daniel, Władysława A


    Our previous study suggested involvement of the brain serotonergic system in the regulation of liver cytochrome P450 (CYP). The aim of the present study was to demonstrate simultaneous responsiveness of liver CYP and the peripheral and brain serotonergic systems to a tryptophan deficient diet during three days and one or three weeks of ingestion. The concentrations of serotonin, noradrenaline, dopamine and their metabolites were measured in blood plasma, the hypothalamus and brain stem of male rats. The enzyme activity and protein levels in the liver were determined for isoforms CYP1A, CYP2A, CYP2B, CYP2C6, CYP2C11, CYP2D and CYP3A. A three-day tryptophan-free diet increased serotonin content in the hypothalamus (but not in the brain stem or plasma). After one week, the level of serotonin was not changed in the brain, but was markedly increased in the plasma. A three week tryptophan restriction significantly reduced the concentration of serotonin in the brain and plasma. Changes in CYP2C6 and CYP2C11 (an increase and a decrease, respectively) were maintained throughout the experiment, while those found in other CYP isoforms varied, which usually resulted in a gradual increase in the enzyme activity within three weeks. The observed alterations in liver CYPs suggest involvement of both central and peripheral serotonin in the regulation of liver CYP expression whose mechanism is discussed. In conclusion, a deficit in tryptophan in the diet may be responsible for very serious food-cytochrome P450 and food-drug metabolism interactions. Interactions of this type may also refer to drugs acting via serotonergic system.

  15. Alterations of Liver Histomorphology in Relation to Copper Supplementation in Inorganic and Organic Form in Growing Rats

    Directory of Open Access Journals (Sweden)

    Tomaszewska Ewa


    Full Text Available The aim of this study was to define the effects of diet containing the same mineral content of mineral salt or amino acid chelate, and diet containing various levels of Cu amino acid chelate on liver histomorphometry in growing rats. Male Wistar rats were used in the 12th week experiment. The control group (n = 12 was fed standard diet, which provided Cu in an inorganic form at the level required for rats. The experimental animals were divided into four groups (each n = 12 depending on different levels (100%, 75%, 50%, 25% covered daily demand of Cu supplementation in chelated form. Cu content was determined in the liver tissue and blood plasma. Immunohistochemical staining with caspase-3 antibody was performed. Microscopic assessment of the liver structure indicated that Cu supplementation did not change the liver architecture. However, histomorphometric analysis revealed a significant increase in the number of nuclei, total cell number, and multinucleated hepatocytes in rats supplemented with the organic form of Cu at the level of 25% compared with the control group. There was a considerable increase in the number of apoptotic cells and ballooning degeneration of hepatocytes, especially in groups supplemented with organic form of Cu covering the daily demand in 100% and 75%, in comparison to control group. Moreover, there was no Cu deposition in the liver and changes in Cu content in blood. Cu provided in the diet in organic form covering an amount of its minimum daily demand in 25% appears to be the least harmful with regard to the liver. It indicates that there is a need to establish the level of diet supplementation with Cu amino acid chelates.

  16. Glutathione peroxidase 1 expression, malondialdehyde levels and histological alterations in the liver of Acrossocheilus fasciatus exposed to cadmium chloride. (United States)

    Liu, Guo-Di; Sheng, Zhang; Wang, You-Fa; Han, Ying-Li; Zhou, Yang; Zhu, Jun-Quan


    Cadmium (Cd) is known as a widespread pollutant in aquatic environment. The accumulation of reactive oxygen species (ROS) is attributed to Cd exposure, which may affect the growth, development and physiological metabolism of aquatic organisms. In response to these unfavorable damages, antioxidant systems have been developed to protect against oxidative stress. In this study, we investigated the expression pattern of glutathione peroxidase 1 genes (GPx-1a and GPx-1b) in the liver of Acrossocheilus fasciatus after Cd administration. Total RNA extraction, reverse-transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) were performed in order to clone the A. fasciatus GPx-1a and GPx-1b full-length cDNA sequences and partial fragment of β-actin cDNA from the liver for the first time. Tissue-specific expression analysis proved that GPx-1 genes were widely expressed in the liver, kidney, gill, testis, muscle, spleen, heart and brain. The changes of GPx-1 mRNA and malondialdehyde (MDA) levels in the liver treated with Cd were measured. In addition, the acute toxic effects of Cd on the microstructure of the liver were studied using light microscopy. These results suggest that GPx-1, MDA and liver histology which represent molecular, biochemical and histological levels, can be used as potential biomarkers to monitor Cd pollution. The overall findings also highlight the potential use of those three bio-indicators combined together as a multi-level tool (molecular, biochemical and histological levels) when monitoring Cd contamination and other possible exogenetic pollutants in aquatic environment.

  17. Melatonin ameliorates high fat diet-induced diabetes and stimulates glycogen synthesis via a PKCzeta-Akt-GSK3beta pathway in hepatic cells. (United States)

    Shieh, Jiunn-Min; Wu, Hung-Tsung; Cheng, Kai-Chun; Cheng, Juei-Tang


    Low levels of melatonin in circulation had been reported to be related to the development of diabetes. Melatonin administration in animals increases hepatic glycogen content to lower blood glucose. However, the signaling pathway for these effects is still unclear. The present study shows that intraperitoneal injection of 10 mg/kg melatonin ameliorated glucose utilization and insulin sensitivity in high fat diet-induced diabetic mice with an increase in hepatic glycogen and improvement in liver steatosis. We used HepG2 cells to investigate the signaling pathways for the melatonin-stimulated hepatic glycogen increment. Treatment of HepG2 cells with 1 nm melatonin markedly increased glycogen synthesis which was blocked by the melatonin receptor antagonist luzindole. In addition, melatonin increased the phosphorylation of subcellular signals at the level of protein kinase C zeta (PKCzeta), Akt, and glycogen synthase kinase 3beta (GSK3beta) while the increase in glycogen synthesis induced by melatonin was inhibited by PKCzeta pseudo-peptide. However, 3',5'-cyclic adenosine monophosphate-activated protein kinase (AMPK) was not influenced by melatonin treatment. Taken together, melatonin improves glucose intolerance and insulin resistance in high fat diet-induced diabetic mice and stimulates glycogen synthesis via a PKCzeta-Akt-GSK3beta pathway in HepG2 cells.

  18. Functional significance of brain glycogen in sustaining glutamatergic neurotransmission

    DEFF Research Database (Denmark)

    Sickmann, Helle M; Walls, Anne B; Schousboe, Arne


    The involvement of brain glycogen in sustaining neuronal activity has previously been demonstrated. However, to what extent energy derived from glycogen is consumed by astrocytes themselves or is transferred to the neurons in the form of lactate for oxidative metabolism to proceed is at present...... in co-cultures of cerebellar neurons and astrocytes. In the astrocytes it was shown that uptake of the glutamate analogue D-[3H]aspartate was impaired when glycogen degradation was inhibited irrespective of the presence of glucose, signifying that energy derived from glycogen degradation is important...... for the astrocytic compartment. By inhibiting glycogen degradation in co-cultures it was evident that glycogen provides energy to sustain glutamatergic neurotransmission, i.e. release and uptake of glutamate. The relocation of glycogen derived lactate to the neuronal compartment was investigated by employing d...

  19. Effect of fasting on the metabolic response of liver to experimental burn injury.

    Directory of Open Access Journals (Sweden)

    Mehmet A Orman

    Full Text Available Liver metabolism is altered after systemic injuries such as burns and trauma. These changes have been elucidated in rat models of experimental burn injury where the liver was isolated and perfused ex vivo. Because these studies were performed in fasted animals to deplete glycogen stores, thus simplifying quantification of gluconeogenesis, these observations reflect the combined impact of fasting and injury on liver metabolism. Herein we asked whether the metabolic response to experimental burn injury is different in fed vs. fasted animals. Rats were subjected to a cutaneous burn covering 20% of the total body surface area, or to similar procedures without administering the burn, hence a sham-burn. Half of the animals in the burn and sham-burn groups were fasted starting on postburn day 3, and the others allowed to continue ad libitum. On postburn day 4, livers were isolated and perfused for 1 hour in physiological medium supplemented with 10% hematocrit red blood cells. The uptake/release rates of major carbon and nitrogen sources, oxygen, and carbon dioxide were measured during the perfusion and the data fed into a mass balance model to estimate intracellular fluxes. The data show that in fed animals, injury increased glucose output mainly from glycogen breakdown and minimally impacted amino acid metabolism. In fasted animals, injury did not increase glucose output but increased urea production and the uptake of several amino acids, namely glutamine, arginine, glycine, and methionine. Furthermore, sham-burn animals responded to fasting by triggering gluconeogenesis from lactate; however, in burned animals the preferred gluconeogenic substrate was amino acids. Taken together, these results suggest that the fed state prevents the burn-induced increase in hepatic amino acid utilization for gluconeogenesis. The role of glycogen stores and means to increase and/or maintain internal sources of glucose to prevent increased hepatic amino acid

  20. In vitro alterations do not reflect a requirement for host cell cycle progression during Plasmodium liver stage infection. (United States)

    Hanson, Kirsten K; March, Sandra; Ng, Shengyong; Bhatia, Sangeeta N; Mota, Maria M


    Prior to invading nonreplicative erythrocytes, Plasmodium parasites undergo their first obligate step in the mammalian host inside hepatocytes, where each sporozoite replicates to generate thousands of merozoites. While normally quiescent, hepatocytes retain proliferative capacity and can readily reenter the cell cycle in response to diverse stimuli. Many intracellular pathogens, including protozoan parasites, manipulate the cell cycle progression of their host cells for their own benefit, but it is not known whether the hepatocyte cell cycle plays a role during Plasmodium liver stage infection. Here, we show that Plasmodium parasites can be observed in mitotic hepatoma cells throughout liver stage development, where they initially reduce the likelihood of mitosis and ultimately lead to significant acquisition of a binucleate phenotype. However, hepatoma cells pharmacologically arrested in S phase still support robust and complete Plasmodium liver stage development, which thus does not require cell cycle progression in the infected cell in vitro. Furthermore, murine hepatocytes remain quiescent throughout in vivo infection with either Plasmodium berghei or Plasmodium yoelii, as do Plasmodium falciparum-infected primary human hepatocytes, demonstrating that the rapid and prodigious growth of liver stage parasites is accomplished independent of host hepatocyte cell cycle progression during natural infection.

  1. Effect of oat bran on time to exhaustion, glycogen content and serum cytokine profile following exhaustive exercise

    Directory of Open Access Journals (Sweden)

    Frollini Anelena B


    Full Text Available Abstract The aim of this study was to evaluate the effect of oat bran supplementation on time to exhaustion, glycogen stores and cytokines in rats submitted to training. The animals were divided into 3 groups: sedentary control group (C, an exercise group that received a control chow (EX and an exercise group that received a chow supplemented with oat bran (EX-O. Exercised groups were submitted to an eight weeks swimming training protocol. In the last training session, the animals performed exercise to exhaustion, (e.g. incapable to continue the exercise. After the euthanasia of the animals, blood, muscle and hepatic tissue were collected. Plasma cytokines and corticosterone were evaluated. Glycogen concentrations was measured in the soleus and gastrocnemius muscles, and liver. Glycogen synthetase-α gene expression was evaluated in the soleus muscle. Statistical analysis was performed using a factorial ANOVA. Time to exhaustion of the EX-O group was 20% higher (515 ± 3 minutes when compared with EX group (425 ± 3 minutes (p = 0.034. For hepatic glycogen, the EX-O group had a 67% higher concentrations when compared with EX (p = 0.022. In the soleus muscle, EX-O group presented a 59.4% higher glycogen concentrations when compared with EX group (p = 0.021. TNF-α was decreased, IL-6, IL-10 and corticosterone increased after exercise, and EX-O presented lower levels of IL-6, IL-10 and corticosterone levels in comparison with EX group. It was concluded that the chow rich in oat bran increase muscle and hepatic glycogen concentrations. The higher glycogen storage may improve endurance performance during training and competitions, and a lower post-exercise inflammatory response can accelerate recovery.

  2. Epinephrine-stimulated glycogen breakdown activates glycogen synthase and increases insulin-stimulated glucose uptake in epitrochlearis muscles

    DEFF Research Database (Denmark)

    Kolnes, Anders J; Birk, Jesper Bratz; Eilertsen, Einar


    Adrenaline increases glycogen synthase (GS) phosphorylation and decreases GS activity but also stimulates glycogen breakdown and low glycogen content normally activates GS. To test the hypothesis that glycogen content directly regulates GS phosphorylation, glycogen breakdown was stimulated...... in condition with decreased GS activation. Saline or adrenaline (0.02mg/100g rat) was injected subcutaneously in Wistar rats (~130 g) with low (24 h fasted), normal (normal diet) and high glycogen content (fasted-refed) and epitrochlearis muscles were removed after 3 h and incubated ex vivo eliminating...... adrenaline action. Adrenaline injection reduced glycogen content in epitrochlearis muscles with high (120.7±17.8 vs 204.6±14.5 mmol•kg(-1); p

  3. Glycogen Fuels Survival During Hyposmotic-Anoxic Stress in Caenorhabditis elegans. (United States)

    LaMacchia, John C; Frazier, Harold N; Roth, Mark B


    Oxygen is an absolute requirement for multicellular life. Animals that are deprived of oxygen for sufficient periods of time eventually become injured and die. This is largely due to the fact that, without oxygen, animals are unable to generate sufficient quantities of energy. In human diseases triggered by oxygen deprivation, such as heart attack and stroke, hyposmotic stress and cell swelling (edema) arise in affected tissues as a direct result of energetic failure. Edema independently enhances tissue injury in these diseases by incompletely understood mechanisms, resulting in poor clinical outcomes. Here, we present investigations into the effects of osmotic stress during complete oxygen deprivation (anoxia) in the genetically tractable nematode Caenorhabditis elegans. Our findings demonstrate that nematode survival of a hyposmotic environment during anoxia (hyposmotic anoxia) depends on the nematode's ability to engage in glycogen metabolism. We also present results of a genome-wide screen for genes affecting glycogen content and localization in the nematode, showing that nematode survival of hyposmotic anoxia depends on a large number of these genes. Finally, we show that an inability to engage in glycogen synthesis results in suppression of the enhanced survival phenotype observed in daf-2 insulin-like pathway mutants, suggesting that alterations in glycogen metabolism may serve as a basis for these mutants' resistance to hyposmotic anoxia.

  4. In search of proof-of-concept: gene therapy for glycogen storage disease type Ia. (United States)

    Koeberl, Dwight D


    The emergence of life threatening long-term complications in glycogen storage disease type Ia (GSD-Ia) has emphasized the need for new therapies, such as gene therapy, which could achieve biochemical correction of glucose-6-phosphatase deficiency and reverse clinical involvement. We have developed gene therapy with a novel adeno-associated virus (AAV) vector that: 1) prevented mortality and corrected glycogen storage in the liver, 2) corrected hypoglycemia during fasting, and 3) achieved efficacy with a low number of vector particles in G6Pase-deficient mice and dogs. However, the gradual loss of transgene expression from episomal AAV vector genomes eventually necessitated the administration of a different pseudotype of the AAV vector to sustain dogs with GSD-Ia. Further preclinical development of AAV vector-mediated gene therapy is therefore warranted in GSD-Ia.

  5. Gas Chromatography/Mass Spectrometry-Based Metabolomic Profiling Reveals Alterations in Mouse Plasma and Liver in Response to Fava Beans. (United States)

    Xiao, Man; Du, Guankui; Zhong, Guobing; Yan, Dongjing; Zeng, Huazong; Cai, Wangwei


    Favism is a life-threatening hemolytic anemia resulting from the intake of fava beans by susceptible individuals with low erythrocytic glucose 6-phosphate dehydrogenase (G6PD) activity. However, little is known about the metabolomic changes in plasma and liver after the intake of fava beans in G6PD normal and deficient states. In this study, gas chromatography/mass spectrometry was used to analyze the plasma and liver metabolic alterations underlying the effects of fava beans in C3H- and G6PD-deficient (G6PDx) mice, and to find potential biomarkers and metabolic changes associated with favism. Our results showed that fava beans induced oxidative stress in both C3H and G6PDx mice. Significantly, metabolomic differences were observed in plasma and liver between the control and fava bean treated groups of both C3H and G6PDx mice. The levels of 7 and 21 metabolites in plasma showed significant differences between C3H-control (C3H-C)- and C3H fava beans-treated (C3H-FB) mice, and G6PDx-control (G6PDx-C)- and G6PDx fava beans-treated (G6PDx-FB) mice, respectively. Similarly, the levels of 7 and 25 metabolites in the liver showed significant differences between C3H and C3H-FB, and G6PDx and G6PDx-FB, respectively. The levels of oleic acid, linoleic acid, and creatinine were significantly increased in the plasma of both C3H-FB and G6PDx-FB mice. In the liver, more metabolic alterations were observed in G6PDx-FB mice than in C3H-FB mice, and were involved in a sugar, fatty acids, amino acids, cholesterol biosynthesis, the urea cycle, and the nucleotide metabolic pathway. These findings suggest that oleic acid, linoleic acid, and creatinine may be potential biomarkers of the response to fava beans in C3H and G6PDx mice and therefore that oleic acid and linoleic acid may be involved in oxidative stress induced by fava beans. This study demonstrates that G6PD activity in mice can affect their metabolic pathways in response to fava beans.

  6. Effects of cerium dioxide nanoparticles in Oncorhynchus mykiss liver after an acute exposure: assessment of oxidative stress, genotoxicity and histological alterations

    Directory of Open Access Journals (Sweden)

    Ana Cristina Nunes


    Full Text Available At present cerium oxide nanoparticles (CeO2 NP have numerous applications ranging from industry to the household, leading to its wide distribution namely in the aquatic environment. The hereby study aimed to assess the toxic effects of CeO2 NPs in Oncorhynchus mykiss liver following an acute exposure (96h to three different concentrations (0.25, 2.5 and 25 mg/L in terms of the genotoxicity (comet assay, oxidative stress response (Catalase CAT; Glutathione S-Transferases GSTs; Thiobarbituric Acid Reactive Substances TBARS and histopathology. CeO2 NP exposure resulted in genotoxic damage in all exposure treatments, inhibition of CAT in the highest concentration and histopathological changes in all exposure concentrations with predominance of progressive and circulatory alterations. However TBARS and GSTs showed no significant differences comparatively to the control (unexposed group. The results suggest that CeO2 NP are able to cause genotoxicity, biochemical impairment and histological alterations in the liver of rainbow trout.

  7. Glycogen stability and glycogen phosphorylase activities in isolated skeletal muscles from rat and toad. (United States)

    Goodman, C A; Stephenson, G M


    There is increasing evidence that endogenous glycogen depletion may affect excitation-contraction (E-C) coupling events in vertebrate skeletal muscle. One approach employed in physiological investigations of E-C coupling involves the use of mechanically skinned, single fibre preparations obtained from tissues stored under paraffin oil, at room temperature (RT: 20-24 degrees C) and 4 degrees C for several hours. In the present study, we examined the effect of these storage conditions on the glycogen content in three muscles frequently used in research on E-C coupling: rat extensor digitorum longus (EDL) and soleus (SOL) and toad iliofibularis (IF). Glycogen content was determined fluorometrically in homogenates prepared from whole muscles, stored under paraffin oil for up to 6 h at RT or 4 degrees C. Control muscles and muscles stored for 0.5 and 6 h were also analysed for total phosphorylase (Phos(total)) and phosphorylase a (Phos a) activities. No significant change was observed in the glycogen content of EDL and SOL muscles stored at RT for 0.5 h. In rat muscles stored at RT for longer than 0.5 h, the glycogen content decreased to 67.6% (EDL) and 78.7% (SOL) of controls after 3 h and 25.3% (EDL) and 37.4% (SOL) after 6 h. Rat muscles stored at 4 degrees C retained 79.0% (EDL) and 92.5% (SOL) of glycogen after 3 h and 75.2% (EDL) and 61.1% (SOL) after 6 h. The glycogen content of IF muscles stored at RT or 4 degrees C for 6 h was not significantly different from controls. Phos(total) was unchanged in all muscles over the 6 h period, at both temperatures. Phos a was also unchanged in the toad IF muscles, but in rat muscles it decreased rapidly, particularly in EDL (4.1-fold after 0.5 h at RT). Taken together these results indicate that storage under paraffin oil for up to 6 h at RT or 4 degrees C is accompanied by minimal glycogen loss in toad IF muscles and by a time- and temperature-dependent glycogen loss in EDL and SOL muscles of the rat.

  8. Secreted Ectodomain of SIGLEC-9 and MCP-1 Synergistically Improve Acute Liver Failure in Rats by Altering Macrophage Polarity (United States)

    Ito, Takanori; Ishigami, Masatoshi; Matsushita, Yoshihiro; Hirata, Marina; Matsubara, Kohki; Ishikawa, Tetsuya; Hibi, Hideharu; Ueda, Minoru; Hirooka, Yoshiki; Goto, Hidemi; Yamamoto, Akihito


    Effective treatments for acute liver failure (ALF) are still lacking. We recently reported that a single intravenous administration of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) into the D-galactosamine (D-Gal)-induced rat ALF model improves the liver injury. However, the specific factors in SHED-CM that are responsible for resolving ALF remain unclear. Here we found that depleting SHED-CM of two anti-inflammatory M2 macrophage inducers—monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (sSiglec-9)—abolished its ability to resolve rat ALF. Furthermore, treatment with MCP-1/sSiglec-9 alone dramatically improved the survival of ALF rats. This treatment induced anti-inflammatory M2, suppressed hepatocyte apoptosis, and promoted hepatocyte proliferation. Treatment with an M2-depletion reagent (mannosylated clodronate liposomes) suppressed the recovery. In addition, MCP-1 and sSiglec-9 synergistically promoted the M2 differentiation of bone marrow-derived macrophages via CCR2, accompanied by the production of multiple liver-regenerating factors. The conditioned medium from MCP-1/sSiglec-9-activated M2 macrophages, but not from interleukin-4-induced ones, suppressed the D-Gal- and LPS-induced apoptosis of primary hepatocytes and promoted their proliferation in vitro. The unique combination of MCP-1/sSiglec-9 ameliorates rat ALF by inhibiting hepatocellular apoptosis and promoting liver regeneration through the induction of anti-inflammatory/tissue-repairing M2 macrophages. PMID:28272428


    Directory of Open Access Journals (Sweden)

    Teli Parashuram


    Full Text Available Abhrak bhasma, an Ayurvedic drug used against many diseases including hepatitis. In present study various doses of abhrak bhasma (10, 20, 30 and 40 mg/kg body wt were tested for hepatoprotective efficacy against carbon tetrachloride (CCl4 intoxicated liver and kidney functions in male albino rat. Administration of CCl4 to the normal rat increased serum levels of AST, ALT, ALP and bilirubin indicated acute damage. Abhrak bhasma treatment counteracted the action of CCl4 on liver and kidney functions. With the administration of increasing doses of abhrak bhasma all activities were dropped progressively and significantly at 40 mg dose as compared with silicate control. Conjugation metabolism and excretion of bilirubin were improved with increasing doses of abhrak bhasma suggesting dose dependent protection of all metabolic steps in bilirubin metabolism. Also CCl4 induced acute toxicity increased serum urea and creatinine content, which was progressively controlled by increasing abhrak bhasma doses. The findings of this study indicated that abhrak bhasma exert dose dependent protective effects in liver and kidneys functions against CCl4 induced toxicity in albino rat.

  10. Short and Long Term Effects of High-Intensity Interval Training on Hormones, Metabolites, Antioxidant System, Glycogen Concentration, and Aerobic Performance Adaptations in Rats. (United States)

    de Araujo, Gustavo G; Papoti, Marcelo; Dos Reis, Ivan Gustavo Masselli; de Mello, Maria A R; Gobatto, Claudio A


    The purpose of the study was to investigate the effects of short and long term High-Intensity Interval Training (HIIT) on anaerobic and aerobic performance, creatinine, uric acid, urea, creatine kinase, lactate dehydrogenase, catalase, superoxide dismutase, testosterone, corticosterone, and glycogen concentration (liver, soleus, and gastrocnemius). The Wistar rats were separated in two groups: HIIT and sedentary/control (CT). The lactate minimum (LM) was used to evaluate the aerobic and anaerobic performance (AP) (baseline, 6, and 12 weeks). The lactate peak determination consisted of two swim bouts at 13% of body weight (bw): (1) 30 s of effort; (2) 30 s of passive recovery; (3) exercise until exhaustion (AP). Tethered loads equivalent to 3.5, 4.0, 4.5, 5.0, 5.5, and 6.5% bw were performed in incremental phase. The aerobic capacity in HIIT group increased after 12 weeks (5.2 ± 0.2% bw) in relation to baseline (4.4 ± 0.2% bw), but not after 6 weeks (4.5 ± 0.3% bw). The exhaustion time in HIIT group showed higher values than CT after 6 (HIIT = 58 ± 5 s; CT = 40 ± 7 s) and 12 weeks (HIIT = 62 ± 7 s; CT = 49 ± 3 s). Glycogen (mg/100 mg) increased in gastrocnemius for HIIT group after 6 weeks (0.757 ± 0.076) and 12 weeks (1.014 ± 0.157) in comparison to baseline (0.358 ± 0.024). In soleus, the HIIT increased glycogen after 6 weeks (0.738 ± 0.057) and 12 weeks (0.709 ± 0.085) in comparison to baseline (0.417 ± 0.035). The glycogen in liver increased after HIIT 12 weeks (4.079 ± 0.319) in relation to baseline (2.400 ± 0.416). The corticosterone (ng/mL) in HIIT increased after 6 weeks (529.0 ± 30.5) and reduced after 12 weeks (153.6 ± 14.5) in comparison to baseline (370.0 ± 18.3). In conclusion, long term HIIT enhanced the aerobic capacity, but short term was not enough to cause aerobic adaptations. The anaerobic performance increased in HIIT short and long term compared with CT, without differences between HIIT short and long term. Furthermore, the


    Directory of Open Access Journals (Sweden)

    Gustavo Gomes De Araujo


    Full Text Available The purpose of the study was to investigate the effects of short and long term High-Intensity Interval Training (HIIT on anaerobic and aerobic performance, creatinine, uric acid, urea, creatine kinase, lactate dehydrogenase, catalase, superoxide dismutase, testosterone, corticosterone and glycogen concentration (liver, soleus and gastrocnemius. The Wistar were separated in two groups: HIIT and sedentary/control (CT. The lactate minimum (LM was used to evaluate the aerobic and anaerobic performance (AP (baseline, 6 and 12 wk. The lactate peak determination consisted of two swim bouts at 13% of body weight (bw: 1 30 s of effort; 2 30 s of passive recovery; 3 exercise until exhaustion (AP. Tethered loads equivalent to 3.5, 4.0, 4.5, 5.0, 5.5 and 6.5% bw were performed in incremental phase. The aerobic capacity in HIIT group increased after 12 wk (5.2±0.2 % bw in relation to baseline (4.4±0.2 % bw, but not after 6 wk (4.5±0.3 % bw. The exhaustion time in HIIT group showed higher values than CT after 6 (HIIT= 58±5 s; CT=40±7 s and 12 wk (HIIT=62±7 s; CT=49±3 s. Glycogen (mg/100mg increased in gastrocnemius for HIIT group after 6 wk (0.757±0.076 and 12 wk (1.014±0.157 in comparison to baseline (0.358±0.024. In soleus, the HIIT increased glycogen after 6 wk (0.738±0.057 and 12 wk (0.709±0.085 in comparison to baseline (0.417±0.035. The glycogen in liver increased after HIIT 12 wk (4.079±0.319 in relation to baseline (2.400±0.416. The corticosterone (ng/mL in HIIT increased after 6 wk (529.0±30.5 and reduced after 12 wk (153.6±14.5 in comparison to baseline (370.0±18.3. In conclusion, long term HIIT enhanced the aerobic capacity, but short term (6wk was not enough to cause aerobic adaptations. The anaerobic performance increased in HIIT short and long term compared with CT, without differences between HIIT short and long term. Furthermore, the glycogen super-compensantion increased after short and long term HIIT in comparison to

  12. Molecular Mechanisms of Allosteric Inhibition of Brain Glycogen Phosphorylase by Neurotoxic Dithiocarbamate Chemicals. (United States)

    Mathieu, Cécile; Bui, Linh-Chi; Petit, Emile; Haddad, Iman; Agbulut, Onnik; Vinh, Joelle; Dupret, Jean-Marie; Rodrigues-Lima, Fernando


    Dithiocarbamates (DTCs) are important industrial chemicals used extensively as pesticides and in a variety of therapeutic applications. However, they have also been associated with neurotoxic effects and in particular with the development of Parkinson-like neuropathy. Although different pathways and enzymes (such as ubiquitin ligases or the proteasome) have been identified as potential targets of DTCs in the brain, the molecular mechanisms underlying their neurotoxicity remain poorly understood. There is increasing evidence that alteration of glycogen metabolism in the brain contributes to neurodegenerative processes. Interestingly, recent studies with N,N-diethyldithiocarbamate suggest that brain glycogen phosphorylase (bGP) and glycogen metabolism could be altered by DTCs. Here, we provide molecular and mechanistic evidence that bGP is a target of DTCs. To examine this system, we first tested thiram, a DTC pesticide known to display neurotoxic effects, observing that it can react rapidly with bGP and readily inhibits its glycogenolytic activity (kinact = 1.4 × 10(5) m(-1) s(-1)). Using cysteine chemical labeling, mass spectrometry, and site-directed mutagenesis approaches, we show that thiram (and certain of its metabolites) alters the activity of bGP through the formation of an intramolecular disulfide bond (Cys(318)-Cys(326)), known to act as a redox switch that precludes the allosteric activation of bGP by AMP. Given the key role of glycogen metabolism in brain functions and neurodegeneration, impairment of the glycogenolytic activity of bGP by DTCs such as thiram may be a new mechanism by which certain DTCs exert their neurotoxic effects.

  13. Human skeletal muscle glycogen utilization in exhaustive exercise

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Holmberg, Hans-Christer; Schrøder, Henrik Daa


    to be influenced by fibre type prior to exercise, as well as carbohydrate availability during the subsequent period of recovery. These findings provide insight into the significance of fibre type-specific compartmentalization of glycogen metabolism in skeletal muscle during exercise and subsequent recovery. .......Although glycogen is known to be heterogeneously distributed within skeletal muscle cells, there is presently little information available about the role of fibre types, utilization and resynthesis during and after exercise with respect to glycogen localization. Here, we tested the hypothesis...... contained more intramyofibrillar and subsarcolemmal glycogen than the latter. In highly glycogen-depleted fibres, the remaining small intermyofibrillar and subsarcolemmal glycogen particles were often found to cluster in groupings. In the recovery period, when the athletes received either a carbohydrate...

  14. High glycogen levels in the hippocampus of patients with epilepsy

    DEFF Research Database (Denmark)

    Dalsgaard, Mads K; Madsen, Flemming F; Secher, Niels H


    biopsies were obtained from pathologic hippocampus (n=19) and from apparently 'normal' cortical grey and white matter. We determined the in vivo brain glycogen level and the activity of glycogen phosphorylase and synthase. Regional differences in glycogen concentration were examined similarly in healthy...... pigs (n=5). In the patients, the glycogen concentration in 'normal' grey and white matter was 5 to 6 mmol/L, but much higher in the hippocampus, 13.1+/-4.3 mmol/L (mean+/-s.d.; P..., glycogen was similarly higher than in grey and white matter. Consequently, in human grey and white matter and, particularly, in the hippocampus of patients with temporal lope epilepsy, glycogen constitutes a large, active energy reserve, which may be of importance for energy provision during sustained...

  15. The 3T3-L1 adipocyte glycogen proteome


    Stapleton, David; Nelson, Chad; Parsawar, Krishna; Flores-Opazo, Marcelo; McClain, Donald; Parker, Glendon


    Background Glycogen is a branched polysaccharide of glucose residues, consisting of α-1-4 glycosidic linkages with α-1-6 branches that together form multi-layered particles ranging in size from 30 nm to 300 nm. Glycogen spatial conformation and intracellular organization are highly regulated processes. Glycogen particles interact with their metabolizing enzymes and are associated with a variety of proteins that intervene in its biology, controlling its structure, particle size and sub-cellula...

  16. VY6, a β-lactoglobulin-derived peptide, altered metabolic lipid pathways in the zebra fish liver. (United States)

    Mohammed-Geba, K; Arrutia, F; Do-Huu, H; Borrell, Y J; Galal-Khallaf, A; Ardura, A; Riera, Francisco A; Garcia-Vazquez, Eva


    Today enormous research efforts are being focused on alleviating the massive, adverse effects of obesity. Short peptides are key targets for research as they can be generated from natural proteins, like milk. Here we conducted trypsinogen digestion of beta-lactoglobulin (β-lg), the major mammalian milk protein, to release the hexamer VY6. It was assayed in vivo for its activities on lipid metabolism using zebra fish as a vertebrate model. Zebra fish juveniles were injected with two different doses of the peptide: 100 and 800 μg per g fish and left for 5 days before sacrificing. Lipid measurements showed significant reduction in liver triglycerides and free cholesterol, as well as increased liver HDL cholesterol. Dose-dependent increases of the mRNA levels of the genes coding for the enzymes acyl coenzyme A oxidase 1 (acox1) and lipoprotein lipase (lpl) were also found. The complete results suggest significant anti-obesity activity of the β-lg-derived VY6 peptide. Its use as a nutraceutical has been discussed.

  17. Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content

    DEFF Research Database (Denmark)

    Steensberg, A; Febbraio, M A; Osada, T


    1. Prolonged exercise results in a progressive decline in glycogen content and a concomitant increase in the release of the cytokine interleukin-6 (IL-6) from contracting muscle. This study tests the hypothesis that the exercise-induced IL-6 release from contracting muscle is linked...... is associated with alterations in the rate of IL-6 production and release in contracting skeletal muscle....... to the intramuscular glycogen availability. 2. Seven men performed 5 h of a two-legged knee-extensor exercise, with one leg with normal, and one leg with reduced, muscle glycogen content. Muscle biopsies were obtained before (pre-ex), immediately after (end-ex) and 3 h into recovery (3 h rec) from exercise in both...

  18. Intracellular compartmentalization of skeletal muscle glycogen metabolism and insulin signalling

    DEFF Research Database (Denmark)

    Prats Gavalda, Clara; Gomez-Cabello, Alba; Vigelsø Hansen, Andreas


    The interest in skeletal muscle metabolism and insulin signalling has increased exponentially in recent years as a consequence of their role in the development of type 2 diabetes mellitus. Despite this, the exact mechanisms involved in the regulation of skeletal muscle glycogen metabolism...... compartmentalization in the regulation of skeletal muscle glycogen metabolism and insulin signalling. As a result, a hypothetical regulatory mechanism is proposed by which cells could direct glycogen resynthesis towards different pools of glycogen particles depending on the metabolic needs. Furthermore, we discuss...... the role of skeletal muscle transverse tubules as potential modulators of tissue insulin responsiveness....

  19. The modulation of the symbiont/host interaction between Wolbachia pipientis and Aedes fluviatilis embryos by glycogen metabolism.

    Directory of Open Access Journals (Sweden)

    Mariana da Rocha Fernandes

    Full Text Available Wolbachia pipientis, a maternally transmitted bacterium that colonizes arthropods, may affect the general aspects of insect physiology, particularly reproduction. Wolbachia is a natural endosymbiont of Aedes fluviatilis, whose effects in embryogenesis and reproduction have not been addressed so far. In this context, we investigated the correlation between glucose metabolism and morphological alterations during A. fluviatilis embryo development in Wolbachia-positive (W+ and Wolbachia-negative (W- mosquito strains. While both strains do not display significant morphological and larval hatching differences, larger differences were observed in hexokinase activity and glycogen contents during early and mid-stages of embryogenesis, respectively. To investigate if glycogen would be required for parasite-host interaction, we reduced Glycogen Synthase Kinase-3 (GSK-3 levels in adult females and their eggs by RNAi. GSK-3 knock-down leads to embryonic lethality, lower levels of glycogen and total protein and Wolbachia reduction. Therefore, our results suggest that the relationship between A. fluviatilis and Wolbachia may be modulated by glycogen metabolism.

  20. Genome-Wide Screening of Genes Showing Altered Expression in Liver Metastases of Human Colorectal Cancers by cDNA Microarray

    Directory of Open Access Journals (Sweden)

    Rempei Yanagawa


    Full Text Available In spite of intensive and increasingly successful attempts to determine the multiple steps involved in colorectal carcinogenesis, the mechanisms responsible for metastasis of colorectal tumors to the liver remain to be clarified. To identify genes that are candidates for involvement in the metastatic process, we analyzed genome-wide expression profiles of 10 primary colorectal cancers and their corresponding metastatic lesions by means of a cDNA microarray consisting of 9121 human genes. This analysis identified 40 genes whose expression was commonly upregulated in metastatic lesions, and 7 that were commonly downregulated. The upregulated genes encoded proteins involved in cell adhesion, or remodeling of the actin cytoskeleton. Investigation of the functions of more of the altered genes should improve our understanding of metastasis and may identify diagnostic markers and/or novel molecular targets for prevention or therapy of metastatic lesions.

  1. Low-dose, Chronic Exposure to Silver Nanoparticles Causes Mild Mitochondrial Alterations in the Liver of Sprague-Dawley Rat (United States)


    studies proved toxic effects on a panoply of organs, from brain, heart, skin , lungs, bone marrow, to name a few ([12];[13]). However, most of the...measurable alterations. The supplementation of the AgNPs injections with a known antioxidant N-acetyl-L-cysteine (NAC) was effective in preventing most of...mitochondrial dysfunction by increasing reactive oxygen species (ROS) generation and if the antioxidant effects of NAC are responsible for its

  2. Distinct alterations in ATP-binding cassette transporter expression in liver, kidney, small intestine, and brain in adjuvant-induced arthritic rats. (United States)

    Kawase, Atsushi; Norikane, Sari; Okada, Ayaka; Adachi, Mamiko; Kato, Yukio; Iwaki, Masahiro


    Pathophysiological changes of infection or inflammation are associated with alterations in the production of numerous absorption, distribution, metabolism and excretion-related proteins. However, little information is available on the effects of inflammation on the expression levels and activities of ATP-binding cassette (ABC) transporters. We examined the effect of acute (on day 7) and chronic (on day 21) inflammation on the expression of ABC transporters in some major tissues in rat. Adjuvant-induced arthritis (AA) in rats was used as an animal model for inflammation. The mRNA levels of mdr1a and mdr1b encoding P-glycoprotein (P-gp) decreased significantly in livers of AA rats on day 21. Hepatic protein levels of P-gp, Mrp2, and Bcrp decreased significantly in membranes but not homogenates of AA rats after 7 days and after 21 days of treatment with adjuvant. Contrary to liver, protein levels of P-gp and Mrp2, but not Bcrp in kidney, increased significantly in membranes. The biliary excretion of rhodamine 123 was decreased in rats with chronic inflammation owing to decreases in efflux activities of P-gp. Our results showed that the expression of transporters in response to inflammation was organ dependent. In particular, hepatic and renal P-gp and Mrp2 exhibited opposite changes in membrane protein levels.

  3. No effect of glycogen level on glycogen metabolism during high intensity exercise

    DEFF Research Database (Denmark)

    Vandenberghe, Katleen; Hespel, P.; Eynde, Bart Vanden;


    , either for 1 min 45 s (protocol 1; N = 18) or to exhaustion (protocol 2; N = 14). The exercise tests were preceded by either 5 d on a controlled normal (N) diet, or by 2 d of glycogen-depleting exercise accompanied by the normal diet followed by 3 d on a carbohydrate-rich (CHR) diet. In protocol 1...

  4. Altered Liver Proteoglycan/Glycosaminoglycan Structure as a Manifestation of Extracellular Matrix Remodeling upon BCG-induced Granulomatosis in Mice. (United States)

    Kim, L B; Shkurupy, V A; Putyatina, A N


    Experimental BCG-induced granulomatosis in mice was used to study changes in the dynamics of individual liver proteoglycan components reflecting phasic extracellular matrix remodeling, determined by the host-parasite interaction and associated with granuloma development. In the early BCG-granulomatosis period, the increase in individual proteoglycan components promotes granuloma formation, providing conditions for mycobacteria adhesion to host cells, migration of phagocytic cells from circulation, and cell-cell interaction leading to granuloma development and fibrosis. Later, reduced reserve capacity of the extracellular matrix, development of interstitial fibrosis and granuloma fibrosis can lead to trophic shortage for cells within the granulomas, migration of macrophages out of them, and development of spontaneous necrosis and apoptosis typical of tuberculosis.

  5. Prepartal dietary energy alters transcriptional adaptations of the liver and subcutaneous adipose tissue of dairy cows during the transition period. (United States)

    Selim, S; Salin, S; Taponen, J; Vanhatalo, A; Kokkonen, T; Elo, K T


    Overfeeding during the dry period may predispose cows to increased insulin resistance (IR) with enhanced postpartum lipolysis. We studied gene expression in the liver and subcutaneous adipose tissue (SAT) of 16 Finnish Ayrshire dairy cows fed either a controlled energy diet [Con, 99 MJ/day metabolizable energy (ME)] during the last 6 wk of the dry period or high-energy diet (High, 141 MJ/day ME) for the first 3 wk and then gradually decreasing energy allowance during 3 wk to 99 MJ/day ME before the expected parturition. Tissue biopsies were collected at -10, 1, and 9 days, and blood samples at -10, 1, and 7 days relative to parturition. Overfed cows had greater dry matter, crude protein, and ME intakes and ME balance before parturition. Daily milk yield, live weight, and body condition score were not different between treatments. The High cows tended to have greater plasma insulin and lower glucagon/insulin ratio compared with Con cows. No differences in circulating glucose, glucagon, nonesterified fatty acids and β-hydroxybutyrate concentrations, and hepatic triglyceride contents were observed between treatments. Overfeeding compared with Con resulted in lower CPT1A and PCK1 and a tendency for lower G6PC and PC expression in the liver. The High group tended to have lower RETN expression in SAT than Con. No other effects of overfeeding on the expression of genes related to IR in SAT were observed. In conclusion, overfeeding energy prepartum may have compromised hepatic gluconeogenic capacity and slightly affected IR in SAT based on gene expression.

  6. Iminosugars as potential inhibitors of glycogenolysis: structural insights into the molecular basis of glycogen phosphorylase inhibition. (United States)

    Oikonomakos, Nikos G; Tiraidis, Costas; Leonidas, Demetres D; Zographos, Spyros E; Kristiansen, Marit; Jessen, Claus U; Nørskov-Lauritsen, Leif; Agius, Loranne


    Iminosugars DAB (5), isofagomine (9), and several N-substituted derivatives have been identified as potent inhibitors of liver glycogen phosphorylase a (IC(50) = 0.4-1.2 microM) and of basal and glucagon-stimulated glycogenolysis (IC(50) = 1-3 microM). The X-ray structures of 5, 9, and its N-3-phenylpropyl analogue 8 in complex with rabbit muscle glycogen phosphorylase (GPb) shows that iminosugars bind tightly at the catalytic site in the presence of the substrate phosphate and induce conformational changes that characterize the R-state conformation of the enzyme. Charged nitrogen N1 is within hydrogen-bonding distance with the carbonyl oxygen of His377 (5) and in ionic contact with the substrate phosphate oxygen (8 and 9). Our findings suggest that the inhibitors function as oxocarbenium ion transition-state analogues. The conformational change to the R state provides an explanation for previous findings that 5, unlike inhibitors that favor the T state, promotes phosphorylation of GPb in hepatocytes with sequential inactivation of glycogen synthase.

  7. Hepatic mitochondrial dysfunction is a feature of Glycogen Storage Disease Type Ia (GSDIa) (United States)

    Farah, Benjamin L.; Sinha, Rohit A.; Wu, Yajun; Singh, Brijesh K.; Lim, Andrea; Hirayama, Masahiro; Landau, Dustin J.; Bay, Boon Huat; Koeberl, Dwight D.; Yen, Paul M.


    Glycogen storage disease type Ia (GSDIa, von Gierke disease) is the most common glycogen storage disorder. It is caused by the deficiency of glucose-6-phosphatase, an enzyme which catalyses the final step of gluconeogenesis and glycogenolysis. Clinically, GSDIa is characterized by fasting hypoglycaemia and hepatic glycogen and triglyceride overaccumulation. The latter leads to steatohepatitis, cirrhosis, and the formation of hepatic adenomas and carcinomas. Currently, little is known about the function of various organelles and their impact on metabolism in GSDIa. Accordingly, we investigated mitochondrial function in cell culture and mouse models of GSDIa. We found impairments in oxidative phosphorylation and changes in TCA cycle metabolites, as well as decreased mitochondrial membrane potential and deranged mitochondrial ultra-structure in these model systems. Mitochondrial content also was decreased, likely secondary to decreased mitochondrial biogenesis. These deleterious effects culminated in the activation of the mitochondrial apoptosis pathway. Taken together, our results demonstrate a role for mitochondrial dysfunction in the pathogenesis of GSDIa, and identify a new potential target for the treatment of this disease. They also provide new insight into the role of carbohydrate overload on mitochondrial function in other hepatic diseases, such as non-alcoholic fatty liver disease. PMID:28317891

  8. Pathological features of glycogen storage disease type II highlighted in the knockout mouse model. (United States)

    Bijvoet, A G; Van Hirtum, H; Vermey, M; Van Leenen, D; Van Der Ploeg, A T; Mooi, W J; Reuser, A J


    Glycogen storage disease type II (GSDII; Pompe's disease) is an autosomal recessive disease caused by lysosomal alpha-glucosidase deficiency. Skeletal muscle weakness is the most conspicuous clinical symptom of patients suffering from GSDII and skeletal muscle also is prominently involved in the knockout mouse model of this disease. Thus far, however, little detailed information has been published on the pathological changes in other mouse tissues. This paper aims to provide these data and gives a record of the clinical course of the mouse model over a 2-year period. Four-month-old affected mice perform worse in a running wheel than their unaffected littermates, but do not yet display other clear signs of disease. The lysosomal glycogen storage, already evident at birth, becomes more severe in time, leading to muscle wasting by 9-10 months of age and then limb girdle weakness and kyphosis. The disease does not markedly shorten the animal's life span despite the serious tissue pathology, which is not limited to heart and skeletal muscle, but is also seen in the smooth muscle of blood vessels and of the respiratory, digestive, and urogenital tracts. In addition, the mice have lysosomal glycogen storage in the liver, kidney, spleen, and salivary gland; in Schwann cells of the peripheral nerves, and in a subset of neurons in the central nervous system. By pathological criteria, the knockout mouse model parallels the human infantile form of GSDII and is attractive for studying the possible reversal of tissue pathology and symptomatology under different therapeutic regimes.

  9. Amino acid anthranilamide derivatives as a new class of glycogen phosphorylase inhibitors. (United States)

    Evans, Karen A; Li, Yue H; Coppo, Frank T; Graybill, Todd L; Cichy-Knight, Maria; Patel, Mehul; Gale, Jennifer; Li, Hu; Thrall, Sara H; Tew, David; Tavares, Francis; Thomson, Stephen A; Weiel, James E; Boucheron, Joyce A; Clancy, Daphne C; Epperly, Andrea H; Golden, Pamela L


    A series of amino acid anthranilamide derivatives identified from a high-throughput screening campaign as novel, potent, and glucose-sensitive inhibitors of human liver glycogen phosphorylase a are described. A solid-phase synthesis using Wang resin was also developed which provided efficient access to a variety of analogues, and resulted in the identification of key structure-activity relationships, and the discovery of a potent exemplar (IC(50)=80 nM). The SAR scope, synthetic strategy, and in vitro results for this series are presented herein.

  10. Contributions of glycogen to astrocytic energetics during brain activation. (United States)

    Dienel, Gerald A; Cruz, Nancy F


    Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 μmol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K(+) level, oxidative stress management, and memory consolidation; it is a multi-functional compound.

  11. Serum lipoproteins of patients with glycogen storage disease. (United States)

    Rosenfeld, E L; Chibisov, I V; Karmansky, I M; Tabolin, V A; Chistova, L V; Leontiev, A F


    Seventeen patients with different types of glycogen storage disease (GSD) were under observation. The type of the disease was defined from glucaemic and lactotaemic curves obtained in glucose, galactose and adrenaline tolerance tests and by biochemical analysis of liver biopsy specimens. Seven patients were found to have Type I; five patients, Type III; one patient, Type VI; and four patients, the Type IX (or X) of GSD. The serum lipoprotein (LP) content was determined in all patients using analytical ultracentrifugation. Hyperlipoproteinaemia (HLP) was found in virtually all patients. Patients with Type I of GSD were found to have Types 2b and 4 of HLP; and patients with Type III of GSD, 2b Type of HLP. 2a Type of HLP was diagnosed in patients with GSD of VI and IX (X) Types. Patients with Type III GSD, in contrast to those with GSD of other types, had enhanced levels of Sf 12-20 LP. The levels of Sf 100-400 and Sf 20-100 LP were greatly increased only in patients with Type I GSD.

  12. Grape Seed Procyanidins and Cholestyramine Differentially Alter Bile Acid and Cholesterol Homeostatic Gene Expression in Mouse Intestine and Liver.

    Directory of Open Access Journals (Sweden)

    Rebecca M Heidker

    Full Text Available Bile acid (BA sequestrants, lipid-lowering agents, may be prescribed as a monotherapy or combination therapy to reduce the risk of coronary artery disease. Over 33% of adults in the United States use complementary and alternative medicine strategies, and we recently reported that grape seed procyanidin extract (GSPE reduces enterohepatic BA recirculation as a means to reduce serum triglyceride (TG levels. The current study was therefore designed to assess the effects on BA, cholesterol and TG homeostatic gene expression following co-administration with GSPE and the BA sequestrant, cholestyramine (CHY. Eight-week old male C57BL/6 mice were treated for 4 weeks with either a control or 2% CHY-supplemented diet, after which, they were administered vehicle or GSPE for 14 hours. Liver and intestines were harvested and gene expression was analyzed. BA, cholesterol, non-esterified fatty acid and TG levels were also analyzed in serum and feces. Results reveal that GSPE treatment alone, and co-administration with CHY, regulates BA, cholesterol and TG metabolism differently than CHY administration alone. Notably, GSPE decreased intestinal apical sodium-dependent bile acid transporter (Asbt gene expression, while CHY significantly induced expression. Administration with GSPE or CHY robustly induced hepatic BA biosynthetic gene expression, especially cholesterol 7α-hydroxylase (Cyp7a1, compared to control, while co-administration further enhanced expression. Treatment with CHY induced both intestinal and hepatic cholesterologenic gene expression, while co-administration with GSPE attenuated the CHY-induced increase in the liver but not intestine. CHY also induced hepatic lipogenic gene expression, which was attenuated by co-administration with GSPE. Consequently, a 25% decrease in serum TG levels was observed in the CHY+GSPE group, compared to the CHY group. Collectively, this study presents novel evidence demonstrating that GSPE provides additive and

  13. Single fiber analyses of glycogen-related proteins reveal their differential association with glycogen in rat skeletal muscle. (United States)

    Murphy, Robyn M; Xu, Hongyang; Latchman, Heidy; Larkins, Noni T; Gooley, Paul R; Stapleton, David I


    To understand how glycogen affects skeletal muscle physiology, we examined enzymes essential for muscle glycogen synthesis and degradation using single fibers from quiescent and stimulated rat skeletal muscle. Presenting a shift in paradigm, we show these proteins are differentially associated with glycogen granules. Protein diffusibility and/or abundance of glycogenin, glycogen branching enzyme (GBE), debranching enzyme (GDE), phosphorylase (GP), and synthase (GS) were examined in fibers isolated from rat fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscle. GDE and GP proteins were more abundant (~10- to 100-fold) in fibers from EDL compared with SOL muscle. GS and glycogenin proteins were similar between muscles while GBE had an approximately fourfold greater abundance in SOL muscle. Mechanically skinned fibers exposed to physiological buffer for 10 min showed ~70% total pools of GBE and GP were diffusible (nonbound), whereas GDE and GS were considerably less diffusible. Intense in vitro stimulation, sufficient to elicit a ~50% decrease in intracellular glycogen, increased diffusibility of GDE, GP, and GS (~15-60%) and decreased GBE diffusibility (~20%). Amylase treatment, which breaks α-1,4 linkages of glycogen, indicated differential diffusibilities and hence glycogen associations of GDE and GS. Membrane solubilization (1% Triton-X-100) allowed a small additional amount of GDE and GS to diffuse from fibers, suggesting the majority of nonglycogen-associated GDE/GS is associated with myofibrillar/contractile network of muscle rather than membranes. Given differences in enzymes required for glycogen metabolism, the current findings suggest glycogen particles have fiber-type-dependent structures. The greater catabolic potential of glycogen breakdown in fast-twitch fibers may account for different contraction induced rates of glycogen utilization.

  14. Muscle glycogen and cell function - Location, location, location

    DEFF Research Database (Denmark)

    Ørtenblad, N; Nielsen, Joachim


    The importance of glycogen, as a fuel during exercise, is a fundamental concept in exercise physiology. The use of electron microscopy has revealed that glycogen is not evenly distributed in skeletal muscle fibers, but rather localized in distinct pools. In this review, we present the available e...

  15. Glycogen-rich clear cell carcinoma of the breast

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Paulsen, S M


    The light microscopic, immunohistochemical and ultrastructural features of a clear cell carcinoma of the breast have been studied. Both intraductal and invasive components were found. Histochemistry showed large amounts of intracytoplasmic glycogen and sparse neutral mucin in the tumour. The tumour...... was classified as a mucin-containing variant of glycogen-rich, clear cell carcinoma of the breast....

  16. Protective Effect of Ceratonia siliqua L. Against a Dextran Sulfate Sodium-Induced Alterations in Liver and Kidney in Rat. (United States)

    Rtibi, Kaïs; Selmi, Slimen; Jabri, Mohammed-Amine; El-Benna, Jamel; Amri, Mohamed; Marzouki, Lamjed; Sebai, Hichem


    The aim of the present study is to investigate the potential protective role of Ceratonia siliqua L. against dextran sodium sulfate (DSS)-induced oxidative damage and inflammation in liver and kidney of rats. The hepatotoxicity and nephrotoxicity were induced in rats by oral administration of synthetic DSS (5%) in the drinking water for over 7 days. However, carob pods aqueous extract (CPAE; 50 and 100 mg/kg body weight) was given by oral administration for 21 days. Myeloperoxidase (MPO) activity, malondialdehyde, H2O2 content, as well as the levels of antioxidant enzymes in organs were measured to observe the possible mechanisms. As a result, the CPAE counteracted DSS-induced increase of MPO activity, lipoperoxidation, and the activity of antioxidant enzymes, such as superoxide dismutase and catalase (CAT). DSS administration increased also in the organs hydrogen peroxide (H2O2) and free iron levels, whereas the CPAE pretreatment reversed all intracellular mediator perturbations. It was concluded that the CPAE exerted a potential protective effect against DSS-induced inflammation and oxidative stress in the rat organs. Consequently, it is essential that adequate care is taken when we use carob pods for patients with hepatotoxicity and nephrotoxicity.

  17. Cadmium sulfate and CdTe-quantum dots alter DNA repair in zebrafish (Danio rerio) liver cells

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Song; Cai, Qingsong [The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX 79416 (United States); Chibli, Hicham [Department of Biomedical Engineering, McGill University, Montréal, QC H3A 2B4 (Canada); Allagadda, Vinay [The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX 79416 (United States); Nadeau, Jay L. [Department of Biomedical Engineering, McGill University, Montréal, QC H3A 2B4 (Canada); Mayer, Gregory D., E-mail: [The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX 79416 (United States)


    Increasing use of quantum dots (QDs) makes it necessary to evaluate their toxicological impacts on aquatic organisms, since their contamination of surface water is inevitable. This study compares the genotoxic effects of ionic Cd versus CdTe nanocrystals in zebrafish hepatocytes. After 24 h of CdSO{sub 4} or CdTe QD exposure, zebrafish liver (ZFL) cells showed a decreased number of viable cells, an accumulation of Cd, an increased formation of reactive oxygen species (ROS), and an induction of DNA strand breaks. Measured levels of stress defense and DNA repair genes were elevated in both cases. However, removal of bulky DNA adducts by nucleotide excision repair (NER) was inhibited with CdSO{sub 4} but not with CdTe QDs. The adverse effects caused by acute exposure of CdTe QDs might be mediated through differing mechanisms than those resulting from ionic cadmium toxicity, and studying the effects of metallic components may be not enough to explain QD toxicities in aquatic organisms. - Highlights: • Both CdSO{sub 4} and CdTe QDs lead to cell death and Cd accumulation. • Both CdSO{sub 4} and CdTe QDs induce cellular ROS generation and DNA strand breaks. • Both CdSO{sub 4} and CdTe QDs induce the expressions of stress defense and DNA repair genes. • NER repair capacity was inhibited with CdSO{sub 4} but not with CdTe QDs.

  18. Heat and oxidative stress alter the expression of orexin and its related receptors in avian liver cells. (United States)

    Greene, Elizabeth; Khaldi, Stephanie; Ishola, Peter; Bottje, Walter; Ohkubo, Takeshi; Anthony, Nicholas; Dridi, Sami


    Orexins (A and B) or hypocretins (1 and 2) are hypothalamic orexigenic neuropeptides that are involved in the regulation of several physiological processes in mammals. Recently, orexin has been shown to activate the hypothalamic-pituitary-adrenal (HPA) stress axis and emerging evidences identify it as a stress modulator in mammals. However, the regulation of orexin system by stress itself remains unclear. Here, we investigate the effects of heat, 4-Hydroxynonenal (4-HNE) and hydrogen peroxide (H2O2) stress on the hepatic expression of orexin (ORX) and its related receptors (ORXR1/2) in avian species. Using in vivo and in vitro models, we found that heat stress significantly down-regulated ORX and ORXR1/2 mRNA and protein abundances in quail liver and LMH cells. H2O2, however, decreased ORX protein and increased ORX mRNA levels in a dose dependent manner (Porexin mRNA and protein levels suggests that H2O2 treatment modulates post-transcriptional mechanisms. 4-HNE had a biphasic effect on orexin system expression, with a significant up-regulation at low doses (10 and 20μM) and a significant down-regulation at a high dose (30μM). Taken together, our data indicated that hepatic orexin system could be a molecular signature in the heat and oxidative stress response.

  19. [Lipogenesis and gluconeogenesis in the liver of irradiated rats]. (United States)

    Sedlakova, A; Paulikova, E; Diatelinka, I


    The incorporation of 14C from [U-14C] glucose and 3H from 3H2O into the total lipids fatty acids and glycogen of the liver incorporation of 3H from 3H2O into blood glucose was studied in rats totally irradiated in a dose of 14.4 Gy. It is shown that in the liver of irradiated rats glucose is accumulated in considerable amounts as glycogen but it is slightly used as a source of carbon for lipid synthesis. The study of 3H incorporation shows that irradiation stimulates glucogenesis, glyconeogenesis and lipogenesis in the liver.


    NARCIS (Netherlands)



    Although it has never been reported that Bacillus subtilis is capable of accumulating glycogen, we have isolated a region from the chromosome of B. subtilis containing a glycogen operon. The operon is located directly downstream from trnB, which maps at 275 degrees on the B. subtilis chromosome. It

  1. Brain glucagon-like peptide–1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage (United States)

    Knauf, Claude; Cani, Patrice D.; Perrin, Christophe; Iglesias, Miguel A.; Maury, Jean François; Bernard, Elodie; Benhamed, Fadilha; Grémeaux, Thierry; Drucker, Daniel J.; Kahn, C. Ronald; Girard, Jean; Tanti, Jean François; Delzenne, Nathalie M.; Postic, Catherine; Burcelin, Rémy


    Intestinal glucagon-like peptide–1 (GLP-1) is a hormone released into the hepatoportal circulation that stimulates pancreatic insulin secretion. GLP-1 also acts as a neuropeptide to control food intake and cardiovascular functions, but its neural role in glucose homeostasis is unknown. We show that brain GLP-1 controlled whole-body glucose fate during hyperglycemic conditions. In mice undergoing a hyperglycemic hyperinsulinemic clamp, icv administration of the specific GLP-1 receptor antagonist exendin 9–39 (Ex9) increased muscle glucose utilization and glycogen content. This effect did not require muscle insulin action, as it also occurred in muscle insulin receptor KO mice. Conversely, icv infusion of the GLP-1 receptor agonist exendin 4 (Ex4) reduced insulin-stimulated muscle glucose utilization. In hyperglycemia achieved by i.v. infusion of glucose, icv Ex4, but not Ex9, caused a 4-fold increase in insulin secretion and enhanced liver glycogen storage. However, when glucose was infused intragastrically, icv Ex9 infusion lowered insulin secretion and hepatic glycogen levels, whereas no effects of icv Ex4 were observed. In diabetic mice fed a high-fat diet, a 1-month chronic i.p. Ex9 treatment improved glucose tolerance and fasting glycemia. Our data show that during hyperglycemia, brain GLP-1 inhibited muscle glucose utilization and increased insulin secretion to favor hepatic glycogen stores, preparing efficiently for the next fasting state. PMID:16322793

  2. Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage. (United States)

    Knauf, Claude; Cani, Patrice D; Perrin, Christophe; Iglesias, Miguel A; Maury, Jean François; Bernard, Elodie; Benhamed, Fadilha; Grémeaux, Thierry; Drucker, Daniel J; Kahn, C Ronald; Girard, Jean; Tanti, Jean François; Delzenne, Nathalie M; Postic, Catherine; Burcelin, Rémy


    Intestinal glucagon-like peptide-1 (GLP-1) is a hormone released into the hepatoportal circulation that stimulates pancreatic insulin secretion. GLP-1 also acts as a neuropeptide to control food intake and cardiovascular functions, but its neural role in glucose homeostasis is unknown. We show that brain GLP-1 controlled whole-body glucose fate during hyperglycemic conditions. In mice undergoing a hyperglycemic hyperinsulinemic clamp, icv administration of the specific GLP-1 receptor antagonist exendin 9-39 (Ex9) increased muscle glucose utilization and glycogen content. This effect did not require muscle insulin action, as it also occurred in muscle insulin receptor KO mice. Conversely, icv infusion of the GLP-1 receptor agonist exendin 4 (Ex4) reduced insulin-stimulated muscle glucose utilization. In hyperglycemia achieved by i.v. infusion of glucose, icv Ex4, but not Ex9, caused a 4-fold increase in insulin secretion and enhanced liver glycogen storage. However, when glucose was infused intragastrically, icv Ex9 infusion lowered insulin secretion and hepatic glycogen levels, whereas no effects of icv Ex4 were observed. In diabetic mice fed a high-fat diet, a 1-month chronic i.p. Ex9 treatment improved glucose tolerance and fasting glycemia. Our data show that during hyperglycemia, brain GLP-1 inhibited muscle glucose utilization and increased insulin secretion to favor hepatic glycogen stores, preparing efficiently for the next fasting state.

  3. (-)-Hydroxycitric Acid Nourishes Protein Synthesis via Altering Metabolic Directions of Amino Acids in Male Rats. (United States)

    Han, Ningning; Li, Longlong; Peng, Mengling; Ma, Haitian


    (-)-Hydroxycitric acid (HCA), a major active ingredient of Garcinia Cambogia extracts, had shown to suppress body weight gain and fat accumulation in animals and humans. While, the underlying mechanism of (-)-HCA has not fully understood. Thus, this study was aimed to investigate the effects of long-term supplement with (-)-HCA on body weight gain and variances of amino acid content in rats. Results showed that (-)-HCA treatment reduced body weight gain and increased feed conversion ratio in rats. The content of hepatic glycogen, muscle glycogen, and serum T4 , T3 , insulin, and Leptin were increased in (-)-HCA treatment groups. Protein content in liver and muscle were significantly increased in (-)-HCA treatment groups. Amino acid profile analysis indicated that most of amino acid contents in serum and liver, especially aromatic amino acid and branched amino acid, were higher in (-)-HCA treatment groups. However, most of the amino acid contents in muscle, especially aromatic amino acid and branched amino acid, were reduced in (-)-HCA treatment groups. These results indicated that (-)-HCA treatment could reduce body weight gain through promoting energy expenditure via regulation of thyroid hormone levels. In addition, (-)-HCA treatment could promote protein synthesis by altering the metabolic directions of amino acids. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Kalpaamruthaa ameliorates mitochondrial and metabolic alterations in diabetes mellitus induced cardiovascular damage. (United States)

    Latha, Raja; Shanthi, Palanivelu; Sachdanandam, Panchanadham


    Efficacy of Kalpaamruthaa on the activities of lipid and carbohydrate metabolic enzymes, electron transport chain complexes and mitochondrial ATPases were studied in heart and liver of experimental rats. Cardiovascular damage (CVD) was developed in 8 weeks after type 2 diabetes mellitus induction with high fat diet (2 weeks) and low dose of streptozotocin (2 × 35 mg/kg b.w. i.p. in 24 hr interval). In CVD-induced rats, the activities of total lipase, cholesterol ester hydrolase and cholesterol ester synthetase were increased, while lipoprotein lipase and lecithin-cholesterol acyltransferase activities were decreased. The activities of lipid-metabolizing enzymes were altered by Kalpaamruthaa in CVD-induced rats towards normal. Kalpaamruthaa modulated the activities of glycolytic enzymes (hexokinase, phosphogluco-isomerase, aldolase and glucose-6-phosphate dehydrogenase), gluconeogenic enzymes (glucose-6-phosphatase and fructose-1, 6-bisphosphatase) and glycogenolytic enzyme (glycogen phosphorylase) along with increased glycogen content in the liver of CVD-induced rats. The activities of isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, α-ketoglutarate dehydrogenase, Complexes and ATPases (Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase) were decreased in CVD-induced rats, which were ameliorated by the treatment with Kalpaamruthaa. This study ascertained the efficacy of Kalpaamruthaa for the treatment of CVD in diabetes through the modulation of metabolizing enzymes and mitochondrial dysfunction.

  5. Low birth weight and zygosity status is associated with defective muscle glycogen and glycogen synthase regulation in elderly twins

    DEFF Research Database (Denmark)

    Poulsen, Pernille; Wojtaszewski, Jørgen; Richter, Erik;


    AND METHODS: We measured the activities of glycogen synthase (GS), GS kinase (GSK)3 alpha, GS phosphorylation, and glycogen levels in muscle biopsies obtained from 184 young and elderly twins before and after a euglycemic-hyperinsulinemic clamp. RESULTS: Elderly monozygotic twins had significantly lower...... fractional GS activity amidst higher glycogen and GS protein levels compared with dizygotic twins. In addition, we demonstrated strong nongenetic associations between birth weight and defect muscle glycogen metabolism in elderly--but not in younger--twins. Thus, for every 100 g increase in birth weight...... within pairs, GS fractional activity, GS protein level, and glycogen content was increased by 4.2, 8.7, and 4.5%, respectively, in elderly twins. Similarly, for every 100 g increase in birth weight, GSK3 alpha activity and GS phosphorylation at the sites 2, 2+2a, and 3a+3b were decreased by 3.1, 9.0, 10...

  6. Prior Exercise Training Prevent Hyperglycemia in STZ Mice by Increasing Hepatic Glycogen and Mitochondrial Function on Skeletal Muscle. (United States)

    de Carvalho, Afonso Kopczynski; da Silva, Sabrina; Serafini, Edenir; de Souza, Daniela Roxo; Farias, Hemelin Resende; de Bem Silveira, Gustavo; Silveira, Paulo Cesar Lock; de Souza, Claudio Teodoro; Portela, Luis Valmor; Muller, Alexandre Pastoris


    Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. We investigated the effect of a prior 30 days voluntary exercise protocol on STZ-diabetic CF1 mice. Glycemia, and the liver and skeletal muscle glycogen, mitochondrial function, and redox status were analyzed up to 5 days after STZ injection. Animals were engaged in the following groups: Sedentary vehicle (Sed Veh), Sedentary STZ (Sed STZ), Exercise Vehicle (Ex Veh), and Exercise STZ (Ex STZ). Exercise prevented fasting hyperglycemia in the Ex STZ group. In the liver, there was decreased on glycogen level in Sed STZ group but not in EX STZ group. STZ groups showed decreased mitochondrial oxygen consumption compared to vehicle groups, whereas mitochondrial H2 O2 production was not different between groups. Addition of ADP to the medium did not decrease H2 O2 production in Sed STZ mice. Exercise increased GSH level. Sed STZ group increased nitrite levels compared to other groups. In quadriceps muscle, glycogen level was similar between groups. The Sed STZ group displayed decreased O2 consumption, and exercise prevented this reduction. The H2 O2 production was higher in Ex STZ when compared to other groups. Also, GSH level decreased whereas nitrite levels increased in the Sed STZ compared to other groups. The PGC1 α levels increased in Sed STZ, Ex Veh, and Ex STZ groups. In summary, prior exercise training prevents hyperglycemia in STZ-mice diabetic associated with increased liver glycogen storage, and oxygen consumption by the mitochondria of skeletal muscle implying in increased oxidative/biogenesis capacity, and improved redox status of both tissues. J. Cell. Biochem. 118: 678-685, 2017. © 2016 Wiley Periodicals, Inc.

  7. Influence of Ala54Thr polymorphism of fatty acid-binding protein 2 on histological alterations and insulin resistance of non alcoholic fatty liver disease. (United States)

    Aller, R; De Luis, D A; Fernandez, L; Calle, F; Velayos, B; Izaola, O; Gonzalez Sagrado, M; Conde, R; Gonzalez, J M


    A transition G to A at codon 54 of fatty acid binding protein type 2 (FABP2) produces an amino acid substitution (Ala 54 to Thr 54). This amino acid substitution was associated with modifications of insulin resistance, adipokines and insulin concentrations. The aim of this study was to evaluate the influence of Ala54Thr polymorphism in the FABP2 gene on the histological alterations of non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Thirty subjects with the presence of biopsy-proven NAFLD were enrolled for this study. Glucose, Insulin, Insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, resistin, leptin, adiponectin, interleukin-6 and TNF-alfa serum levels were measured at basal time. A tetrapolar bioimpedance, BMI, waist circumference, waist to hip ratio, blood pressure and a prospective serial assessment of nutritional intake with 3 days written food records were examined. Genotype of Ala54Thr FABP2 gene polymorphism was studied. The mean age was 41.6 +/- 11 years and the mean BMI 29.2 +/- 6.6 with 24 males (80%) and 6 females (20%). Fifteen patients (50%) had the genotype Ala54/Ala54 (wild type group) and 15 (50%) patients Ala54/Thr54 (13 patients) or Thr54/Thr54 (2 patients) (mutant type group). Both genotype groups have the similar anthropometric parameters. Serum aspartate aminotransferase and alcaline phosfatase were higher in wild type group than mutant type group, with an unclear explanation. Dietary intake was similar in both groups. A non-statistical significant low levels of adiponectin in mutant group was observed. No differences were detected among other adipokines. There were no differences between genotypes in histological results of inflammation (portal or lobular inflammation) or grade of steatosis or fibrosis. In conclusion, the present study demonstrates that the polymorphism Ala54Thr of FABP in patients with NAFLD doesn't predict liver histological changes, nor both insulin resistance

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

    DEFF Research Database (Denmark)

    Sickmann, Helle M; Waagepetersen, Helle S.


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

  9. 抑制糖原合成酶激酶3活性对Toll样受体4介导肝脏炎症反应的调节作用%Inhibition of glycogen synthase kinase 3β activity regulates Toll-like receptor 4-mediated liver inflammation

    Institute of Scientific and Technical Information of China (English)

    任锋; 张海燕; 朴正福; 郑素军; 陈煜; 陈德喜; 段钟平


    抗炎和促炎因子的表达从而引起肝脏缺血再灌注损伤的改善,随着促炎细胞因子被抑制,使得炎症反应所诱导的肝细胞凋亡也间接地受到有效控制.%Objective To determine the mechanism underlying the therapeutic activities of glycogen synthase kinase 3β (GSK3β) against hepatic ischemia-reperfusion (H-IR) injury by investigating the inhibitive effects of GSK3β on inflammation mediated by Toll-like receptor 4 (TLR4).Methods C57BL/6 male mice were subjected to 90 min of warm liver cephalad lobe ischemia,followed by reperfusion for various lengths of time.The mice were divided into three groups:the H-IR untreated model (control group),and the H-IR inflammation-induced models that received an intraperitoneal injection of purified lipopolysaccharide (LPS) endotoxin alone (inflammation group) or with pretreatment of the SB216763 GSK3β-specific inhibitor (intervention group).To create a parallel isolated cell system for detailed investigations of macrophages,marrow-derived stem cells were isolated from femurs of the H-IR control group of mice and used to derive primary macrophages.The cells were then divided into the same three groups as the whole mouse system:control,LPS-induced inflammation model,and inflammation model with SB216763 intervention.Differential expressions of inflammation-related proteins and genes were detected by Western blotting and real-time quantitative PCR,respectively.Results The phosphorylation levels of ERK,JNK and p38 MAPK were induced in liver at 1 h after reperfusion,but then steadily decreased and returned to baseline levels by 4 h after reperfusion.In addition,the phosphorylation levels of ERK and JNK were induced in macrophages at 15 min after LPS stimulation,while the phosphorylation level of p38 MAPK was induced at 1 h; SB216763 pretreatment suppressed the LPS-stimulated ERK,JNK and p38 phosphorylation in macrophages.In the mouse model,GSK3β activity was found to promote the gene expression of

  10. Liver lipid content and inflammometabolic indices in peripartal dairy cows are altered in response to prepartal energy intake and postpartal intramammary inflammatory challenge. (United States)

    Graugnard, D E; Moyes, K M; Trevisi, E; Khan, M J; Keisler, D; Drackley, J K; Bertoni, G; Loor, J J


    -LPS at 14 and 30 d postpartum. Several inflammation-related genes (TNF, IRAK1, NFKB1, ANGPTL4) showed markedly decreased expression between 7 and 14 d, after which expression remained unchanged. No differences were observed in several genes of the growth-hormone/insulin-like growth factor-1 axis, except for SOCS2, expression of which decreased markedly between 7 and 14 d in OVE-LPS but not in CON-LPS. These data suggest that overfeeding a moderate-energy diet prepartum alters the response of the cow to an intramammary challenge after calving and may predispose it to sustained liver lipidosis.

  11. Treatment of cholestatic fibrosis by altering gene expression of Cthrc1: Implications for autoimmune and non-autoimmune liver disease. (United States)

    Bian, Zhaolian; Miao, Qi; Zhong, Wei; Zhang, Haiyan; Wang, Qixia; Peng, Yanshen; Chen, Xiaoyu; Guo, Canjie; Shen, Li; Yang, Fan; Xu, Jie; Qiu, Dekai; Fang, Jingyuan; Friedman, Scott; Tang, Ruqi; Gershwin, M Eric; Ma, Xiong


    Collagen triple helix repeat containing-1 (Cthrc1) is a documented specific inhibitor of TGF-β signaling. Based on this observation, we developed the hypothesis that knocking in/knocking out the Cthrc1 gene in murine models of cholestasis would alter the natural history of cholestatic fibrosis. To study this thesis, we studied two murine models of fibrosis, first, common bile duct ligation (CBDL) and second, feeding of 3, 5-diethoxy-carbonyl-1, 4-dihydrocollidine (DDC). In both models, we administered well-defined adenoviral vectors that expressed either Cthrc1 or, alternatively, a short hairpin RNA (shRNA)-targeting Cthrc1 either before or after establishment of fibrosis. Importantly, when Cthrc1 gene expression was enhanced, we noted a significant improvement of hepatic fibrosis, both microscopically and by analysis of fibrotic gene expression. In contrast, when Cthrc1 gene expression was deleted, there was a significant exacerbation of fibrosis. To identify the mechanism of action of these significant effects produced by knocking in/knocking out Cthrc gene expression, we thence studied the interaction of Cthrc1 gene expression using hepatic stellate cells (HSCs) and human LX-2 cells. Importantly, we demonstrate that Cthrc1 is induced by TGF-β1 via phospho-Smad3 binding to the promoter with subsequent transcription activation. In addition, we demonstrate that Cthrc1 inhibits TGF-β signaling by accelerating degradation of phospho-Smad3 through a proteosomal pathway. Importantly, the anti-fibrotic effects can be recapitulated with a truncated fragment of Cthrc1. In conclusion, our findings uncover a critical negative feedback regulatory loop in which TGF-β1 induces Cthrc1, which can attenuate fibrosis by accelerating degradation of phospho-Smad3.

  12. Glycogen metabolism and the homeostatic regulation of sleep

    KAUST Repository

    Petit, Jean-Marie


    In 1995 Benington and Heller formulated an energy hypothesis of sleep centered on a key role of glycogen. It was postulated that a major function of sleep is to replenish glycogen stores in the brain that have been depleted during wakefulness which is associated to an increased energy demand. Astrocytic glycogen depletion participates to an increase of extracellular adenosine release which influences sleep homeostasis. Here, we will review some evidence obtained by studies addressing the question of a key role played by glycogen metabolism in sleep regulation as proposed by this hypothesis or by an alternative hypothesis named “glycogenetic” hypothesis as well as the importance of the confounding effect of glucocorticoïds. Even though actual collected data argue in favor of a role of sleep in brain energy balance-homeostasis, they do not support a critical and direct involvement of glycogen metabolism on sleep regulation. For instance, glycogen levels during the sleep-wake cycle are driven by different physiological signals and therefore appear more as a marker-integrator of brain energy status than a direct regulator of sleep homeostasis. In support of this we provide evidence that blockade of glycogen mobilization does not induce more sleep episodes during the active period while locomotor activity is reduced. These observations do not invalidate the energy hypothesis of sleep but indicate that underlying cellular mechanisms are more complex than postulated by Benington and Heller.

  13. Differential effects of fatty acids on glycolysis and glycogen metabolism in vascular smooth muscle. (United States)

    Barron, J T; Kopp, S J; Tow, J P; Parrillo, J E


    The effects of fatty acids of different chain lengths on aerobic glycolysis, lactic acid production, glycogen metabolism and contractile function of vascular smooth muscle were investigated. Porcine carotid artery segments were treated with 50 microM iodoacetate and perchloric acid tissue extracts were then analyzed by 31P-NMR spectroscopy to observe the accumulation of phosphorylated glycolytic intermediates so that the activity of the Embden-Myerhof pathway could be tracked under various experimental paradigms. Aerobic glycolysis and lactate production in resting arteries were almost completely inhibited with 0.5 mM octanoate, partially inhibited with 0.5 mM acetate and unaffected by 0.5 mM palmitate. Inhibition of glycolysis by octanoate was not attributable to inhibition of glucose uptake or glucose phosphorylation. Basal glycogen synthesis was unchanged with palmitate and acetate, but was inhibited by 52% with octanoate incubation. The characteristic glycogenolysis which occurs upon isometric contraction with 80 mM KCl in the absence of fatty acid in the medium was not demonstrable in the presence of any of the fatty acids tested. Glycogen sparing was also demonstrable in norepinephrine contractions with octanoate and acetate, but not with palmitate. Additionally, norepinephrine-stimulated isometric contraction was associated with enhanced synthesis of glycogen amounting to 6-times the basal rate in medium containing octanoate. Contractile responses to norepinephrine were attenuated by 20% in media containing fatty acids. Thus, fatty acids significantly alter metabolism and contractility of vascular smooth muscle. Fatty acids of different chain lengths affect smooth muscle differentially; the pattern of substrate utilization during contraction depends on the contractile agonist and the fatty acid present in the medium.

  14. Infantile Onset Glycogen Storage Disease Type 2: Case Report

    Directory of Open Access Journals (Sweden)

    Serkan Bilge Koca


    Full Text Available Glycogen storage disease type 2 (Pompe’s disease is an autosomal recessive, fatal glycogen storage disease presenting with hypotonia and muscle weakness. It is known that deficiency of lysosomal acid alpha-glucosidase (acid maltase leads to progressive generalised myopathy, cardiomyopathy and death in early infancy because of respiratory muscle weakness. Excessive undegradable intracellular glycogen deposition plays a role in the pathogenesis of the disease. Here we report a 3.5 month-old girl presenting with respiratory failure due to pneumonia and hypotonia, who was later diagnosed as Pompe disease.

  15. Alterations to proteome and tissue recovery responses in fish liver caused by a short-term combination treatment with cadmium and benzo[a]pyrene

    Energy Technology Data Exchange (ETDEWEB)

    Costa, P.M., E-mail: pmcosta@fct.unl.p [IMAR-Instituto do Mar, Departamento de Ciencias e Engenharia do Ambiente, Faculdade de Ciencias e Tecnologia da Universidade Nova de Lisboa, 2829-516 Monte de Caparica (Portugal); Chicano-Galvez, E.; Lopez Barea, J. [Departamento de Bioquimica y Biologia Molecular, Universidad de Cordoba, Campus de Rabanales, Edificio Severo Ochoa, 14071 Cordoba (Spain); DelValls, T.A. [UNESCO/UNITWIN/WiCop Chair-Departamento de Quimica Fisica, Facultad de Ciencias del Mar y Ambientales, Universidad de Cadiz, Poligono rio San Pedro s/n, 11510 Puerto Real, Cadiz (Spain); Costa, M.H. [IMAR-Instituto do Mar, Departamento de Ciencias e Engenharia do Ambiente, Faculdade de Ciencias e Tecnologia da Universidade Nova de Lisboa, 2829-516 Monte de Caparica (Portugal)


    The livers of soles (Solea senegalensis) injected with subacute doses of cadmium (Cd), benzo[a]pyrene (B[a]P), or their combination, were screened for alterations to cytosolic protein expression patterns, complemented by cytological and histological analyses. Cadmium and B[a]P, but not combined, induced hepatocyte apoptosis and Kupfer cell hyperplasia. Proteomics, however, suggested that apoptosis was triggered through distinct pathways. Cadmium and B[a]P caused upregulation of different anti-oxidative enzymes (peroxiredoxin and glutathione peroxidase, respectively) although co-exposure impaired induction. Similarly, apoptosis was inhibited by co-exposure, to which may have contributed a synergistic upregulation of tissue metalloproteinase inhibitor, {beta}-actin and a lipid transport protein. The regulation factors of nine out of eleven identified proteins of different types revealed antagonistic or synergistic effects between Cd and B[a]P at the prospected doses after 24 h of exposure. The results indicate that co-exposure to Cd and B[a]P may enhance toxicity by impairing specific responses and not through cumulative damage. - The interaction between cadmium and benzo[a]pyrene impairs specific responses to toxicity and tissue repair mechanisms.

  16. Role of glycogen availability in sarcoplasmic reticulum Ca2+ kinetics in human skeletal muscle

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Nielsen, Joachim; Saltin, Bengt;


    Glucose is stored as glycogen in skeletal muscle. The importance of glycogen as a fuel during exercise has been recognized since the 1960s; however, little is known about the precise mechanism that relates skeletal muscle glycogen to muscle fatigue. We show that low muscle glycogen is associated ...

  17. Liver transplant (United States)

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  18. Glycogen synthesis is induced in hypoxia by the hypoxia-inducible factor and promotes cancer cell survival

    Directory of Open Access Journals (Sweden)

    Joffrey ePelletier


    Full Text Available The hypoxia-inducible factor 1 (HIF-1, in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumor cells. This transcription factor not only favors cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. In this study we showed that glycogen synthesis is enhanced in non-cancer and cancer cells when exposed to hypoxia, resulting in a large increase in glycogen stores. Furthermore, we demonstrated that the mRNA and protein levels of the first enzyme of glycogenesis, phosphoglucomutase1 (PGM1, were increased in hypoxia. We showed that induction of glycogen storage as well as PGM1 expression were dependent on HIF-1 and HIF-2. We established that hypoxia-induced glycogen stores are rapidly mobilized in cells that are starved of glucose. Glycogenolysis allows these hypoxia-preconditioned cells to confront and survive glucose deprivation. In contrast normoxic control cells exhibit a high rate of cell death following glucose removal. These findings point to the important role of hypoxia and HIF in inducing mechanisms of rapid adaptation and survival in response to a decrease in oxygen tension. We propose that a decrease in pO2 acts as an alarm that prepares the cells to face subsequent nutrient depletion and to survive.

  19. Genetics Home Reference: glycogen storage disease type I (United States)

    ... Wolfsdorf JI, Watson MS; American College of Medical Genetics and Genomics. Diagnosis and management of glycogen storage disease type ... practice guideline of the American College of Medical Genetics and Genomics. Genet Med. 2014 Nov;16(11):e1. Citation ...

  20. Genetics Home Reference: glycogen storage disease type 0 (United States)

    ... PubMed Central Groop L, Orho-Melander M. New insights into impaired muscle glycogen synthesis. PLoS Med. 2008 ... healthcare professional . About Genetics Home Reference Site Map Customer Support Selection Criteria for Links Copyright ...

  1. Histopathological alterations of juvenile green (Acipenser medirostris) and white sturgeon (Acipenser transmontanus) exposed to graded levels of dietary methylmercury. (United States)

    Lee, Jang-Won; Kim, Jae-Won; De Riu, Nicola; Moniello, Giuseppe; Hung, Silas S O


    Triplicate groups of juvenile green and white sturgeon (average weight of 30 ± 2 g) were exposed to one of four concentrations of dietary methylmercury (MeHg; 0, 25, 50, and 100 mg MeHg/kg diet) for 8 weeks to determine and compare the sensitivity of the two sturgeon species from a histopathological perspective. After 4- and 8-week exposure, histological changes were examined in the kidney, liver, gill, skeletal muscle, and heart muscle of both species using light microscopy. Marked abnormalities were observed in the kidney and liver of both sturgeon species after each exposure period; the abnormalities showed progressive histological alterations in severity with increasing doses and duration of exposure. Renal lesions included tubular epithelium degeneration and necrosis, renal corpuscular disintegration, and interstitial tissue degeneration. The changes observed in the livers of both sturgeon species were glycogen depletion and vacuolar degeneration. In the gill and skeletal and heart muscle of green and white sturgeon fed MeHg-added diets, mild histological changes were observed but did not show pronounced difference between the two species. Although the lowest observed effect concentration in both species was the 25 mg MeHg/kg diet, the histological changes in the kidney and liver were more pronounced at all treatments groups of green sturgeon than those of white sturgeon. The current results on structural changes of kidney and liver (i.e., more severe glycogen depletion and tubular epithelium degeneration in green sturgeon) confirmed our previous results, in that green sturgeon exhibited a higher mortality, lower growth rate, and lower protein, lipid, and energy contents in their whole body than white sturgeon under the same MeHg exposures.

  2. Phosphorylation-dependent translocation of glycogen synthase to a novel structure during glycogen resynthesis

    DEFF Research Database (Denmark)

    Prats, Clara; Cadefau, Joan A; Cussó, Roser;


    . Both enzymes are regulated by reversible phosphorylation and by allosteric effectors. However, evidence in the literature indicates that changes in muscle GS and GPh intracellular distribution may constitute a new regulatory mechanism of glycogen metabolism. Already in the 1960s, it was proposed...... structures that were not present in basal muscle, and we present evidence that indicate that they are products of actin cytoskeleton remodeling. Furthermore, for the first time, we show a phosphorylation-dependent intracellular distribution of GS. Here, we present evidence of a new regulatory mechanism...

  3. Trans-10,cis-12-CLA-caused lipodystrophy is associated with profound changes of fatty acid profiles of liver, white adipose tissue and erythrocytes in mice: possible link to tissue-specific alterations of fatty acid desaturation. (United States)

    Jaudszus, Anke; Moeckel, Peter; Hamelmann, Eckard; Jahreis, Gerhard


    Dietary supplementation with conjugated linoleic acid (CLA) has been shown to reduce body fat mass. To investigate the effects of individual CLA isomers on the fatty acid profiles of lipogenic (liver and white adipose) and lipid sensitive (erythrocyte) tissues, BALB/c mice were fed with 1 of 2 diets supplemented with either a c9,t11-CLA-enriched and t10,c12-CLA-free or a CLA-mixture containing both isomers in equal amounts (1% w/w of the diet) for 5 weeks. A control group was fed with a diet enriched in sunflower oil to energy balance the CLA. Compared to the t10,c12-CLA-free and the control diets, we observed a significant reduction of adipose tissue accompanied by fatty livers in the CLA-mix-fed group. These alterations in body fat distribution entailed a conspicuous shift of the fatty acid profiles of adipose tissue and livers. Liver enlargement was mainly caused by accumulation of C18 monoenes that accounted for 67 ± 1% of total fatty acid methyl esters. The significant reduction of the 18:0/18:1 desaturation index in the liver upon CLA-mix diet indicated high stearoyl-CoA desaturase activity. In contrast, reduction in white adipose tissue was largely driven by percental reduction of monounsaturated fatty acids (p ≤ 0.001). 16:0/ 16:1 and 18:0/18:1 desaturation indices for white adipose tissue significantly increased, suggesting an inhibition of stearoyl-CoA desaturase upon CLA-mix diet. The fatty acid profile of the erythrocytes widely reflected that of livers, depending on the supplemented diet. These profound changes in fatty acid composition of lipogenic organs due to t10,c12-CLA intake may be the consequence of functional alterations of lipid metabolism.

  4. Loss of Discoidin Domain Receptor 2 Promotes Hepatic Fibrosis after Chronic Carbon Tetrachloride through Altered Paracrine Interactions between Hepatic Stellate Cells and Liver-Associated Macrophages


    Olaso, Elvira; ARTETA, BEATRIZ; BENEDICTO, AITOR; Crende, Olatz; Friedman, Scott L.


    Hepatic stellate cells (HSCs) interact with fibrillar collagen through the discoidin domain receptor 2 (DDR2) in acute hepatic injury, generating increased fibrosis. However, the contribution of DDR2 signaling to chronic liver fibrosis in vivo is unclear, despite its relevance to chronic human liver disease. We administered carbon tetrachloride (CCl4) to DDR2+/+ and DDR2−/− mice twice weekly, and liver tissues and isolated HSCs were analyzed. In contrast to changes seen in acute injury, after...

  5. Digestion of glycogen by a glucosidase released by Trichomonas vaginalis. (United States)

    Huffman, Ryan D; Nawrocki, Lauren D; Wilson, Wayne A; Brittingham, Andrew


    Trichomonas vaginalis is a protozoan parasite that is the causative agent of trichomoniasis, a widespread sexually transmitted disease. In vitro culture of T. vaginalis typically employs a medium supplemented with either maltose or glucose and carbohydrates are considered essential for growth. Although the nature of the carbohydrates utilized by T. vaginalis in vivo is undefined, the vaginal epithelium is rich in glycogen, which appears to provide a source of carbon for the vaginal microbiota. Here, we show that T. vaginalis grows equally well in growth media supplemented with simple sugars or with glycogen. Analysis of conditioned growth medium by thin layer chromatography indicates that growth on glycogen is accompanied by glycogen breakdown to a mixture of products including maltose, glucose, and oligosaccharides. Enzymatic assays with conditioned growth medium show that glycogen breakdown is accomplished via the release of a glucosidase activity having the properties of an α-amylase into the growth medium. Furthermore, we find that released glucosidase activity increases upon removal of carbohydrate from the growth medium, indicating regulation of synthesis and/or secretion in response to environmental cues. Lastly, we show that addition of T. vaginalis glucosidase activity to a growth medium containing glycogen generates sufficient simple sugar to support the growth of lactobacilli which, themselves, are unable to degrade glycogen. Thus, not only does the glucosidase activity likely play an important role in allowing T. vaginalis to secure simple sugars for its own use, it has the potential to impact the growth of other members of the vaginal microbiome.

  6. Glucose uptake and transport in contracting, perfused rat muscle with different pre-contraction glycogen concentrations

    DEFF Research Database (Denmark)

    Hespel, P; Richter, Erik


    1. Glucose uptake and transport, muscle glycogen, free glucose and glucose-6-phosphate concentrations were studied in perfused resting and contracting rat skeletal muscle with different pre-contraction glycogen concentrations. Rats were pre-conditioned by a combination of swimming exercise and diet......, resulting in either low (glycogen-depleted rats), normal (control rats) or high (supercompensated rats) muscle glycogen concentrations at the time their hindlimbs were perfused. 2. Compared with control rats, pre-contraction muscle glycogen concentration was approximately 40% lower in glycogen-depleted rats......, whereas it was 40% higher in supercompensated rats. Muscle glycogen break-down correlated positively (r = 0.76; P less than 0.001) with pre-contraction muscle glycogen concentration. 3. Glucose uptake during contractions was approximately 50% higher in glycogen-depleted hindquarters than in control...

  7. Quercetin alters energy metabolism in swimming mice. (United States)

    Wu, Jianquan; Gao, Weina; Wei, Jingyu; Yang, Jijun; Pu, Lingling; Guo, Changjiang


    Quercetin has been demonstrated to be effective in increasing physical endurance in mice and humans. However, the mechanisms involved are not fully understood. In this study, male Kunming mice were fed a diet containing 0.1% quercetin for 14 days before swimming for 60 min. The overall serum metabolic profile was investigated by a ¹H nuclear magnetic resonance-based metabolomic approach. Serum glucose, lactate, nonesterified fatty acids (NEFA), and nonprotein nitrogen (NPN), as well as hepatic and muscular glycogen were measured biochemically. The results of metabolomic analysis showed that swimming induced a significant change in serum metabolic profile. Relative increases in the levels of lactate, alanine, low-density lipoprotein-very low-density lipoprotein, and unsaturated fatty acids, and decreases in choline, phosphocholine, and glucose were observed after swimming. With quercetin supplementation, these changes were attenuated. The results of biochemical assays were consistent with the data obtained from metabolomic analysis, in that serum NEFA was increased while lactate and NPN decreased after exposed to quercetin in swimming mice. Similar change in NEFA was also found in liver and gastrocnemius muscle tissues. Our current findings suggest that quercetin alters energy metabolism in swimming mice and increased lipolysis may contribute to the actions of quercetin on physical endurance.

  8. Loss of discoidin domain receptor 2 promotes hepatic fibrosis after chronic carbon tetrachloride through altered paracrine interactions between hepatic stellate cells and liver-associated macrophages. (United States)

    Olaso, Elvira; Arteta, Beatriz; Benedicto, Aitor; Crende, Olatz; Friedman, Scott L


    Hepatic stellate cells (HSCs) interact with fibrillar collagen through the discoidin domain receptor 2 (DDR2) in acute hepatic injury, generating increased fibrosis. However, the contribution of DDR2 signaling to chronic liver fibrosis in vivo is unclear, despite its relevance to chronic human liver disease. We administered carbon tetrachloride (CCl(4)) to DDR2(+/+) and DDR2(-/-) mice twice weekly, and liver tissues and isolated HSCs were analyzed. In contrast to changes seen in acute injury, after chronic CCl(4) administration, DDR2(-/-) livers had increased collagen deposition, gelatinolytic activity, and HSC density. Increased basal gene expression of osteopontin, transforming growth factor-β1, monocyte chemoattractant protein-1, and IL-10 and reduced basal gene expression of matrix metalloproteinase-2, matrix metalloproteinase-13, and collagen type I in quiescent DDR2(-/-) HSCs were amplified further after chronic CCl(4). In concordance, DDR2(-/-) HSCs isolated from chronically injured livers had enhanced in vitro migration and proliferation, but less extracellular matrix degradative activity. Macrophages from chronic CCl(4)-treated DDR2(-/-) livers showed stronger chemoattractive activity toward DDR2(-/-) HSCs than DDR2(+/+) macrophages, increased extracellular matrix degradation, and higher cytokine mRNA expression. In conclusion, loss of DDR2 promotes chronic liver fibrosis after CCl(4) injury. The fibrogenic sinusoidal milieu generated in chronic DDR2(-/-) livers recruits more HSCs to injured regions, which enhances fibrosis. Together, these findings suggest that DDR2 normally orchestrates gene programs and paracrine interactions between HSCs and macrophages that together attenuate chronic hepatic fibrosis.

  9. Obese Mice Fed a Diet Supplemented with Enzyme-Treated Wheat Bran Display Marked Shifts in the Liver Metabolome Concurrent with Altered Gut Bacteria

    DEFF Research Database (Denmark)

    Kieffer, Dorothy A.; Piccolo, Brian D.; Marco, Maria L.


    ) associated with specific microbes may be involved. Objective: The objective of this study was to characterize ETWB-driven shifts in the cecal microbiome and to identify correlates between microbial changes and diet-related differences in liver metabolism in diet-induced obese mice that typically display...... acid; and increased liver and plasma I3-hydroxybutyrate. Liver transcriptomics revealed key metabolic pathways affected by ETWB, especially those related to lipid metabolism and some fed- or fasting-regulated genes. Conclusions: Together, these changes indicate that dietary fibers such as ETWB regulate...... hepatic metabolism concurrently with specific gut bacteria community shifts in C57BL/6J mice. It is proposed that these changes may elicit gut-derived signals that reach the liver via enterohepatic circulation, ultimately affecting host liver metabolism in a manner that mimics, in part, the fasting state....

  10. Altered energetics and parasitism in juvenile northern pike (Esox lucius) inhabiting metal-mining contaminated lakes. (United States)

    Kelly, Jocelyn M; Janz, David M


    The objective of this study was to evaluate possible factors that could be contributing to altered bioenergetics of juvenile northern pike (Esox lucius) living in lakes receiving effluent from the Key Lake uranium mill in northern Saskatchewan, Canada. Although glycogen and triglycerides stores in liver and muscle were significantly greater in pike from exposure lakes compared to the reference, triglycerides stores of aquatic insects and spottail shiners that are prey items of juvenile pike showed no overall differences among lakes. Measures of parasitism, on the other hand, were negatively correlated with pike bioenergetics thereby reflecting a possible energetic cost of parasitism on reference lake fishes. The degree of infection, as measured by the abundance and biomass of intestinal parasites and the abundance of monogeneans on pike gills, was greatest in reference fishes and intermediate in low-exposure pike, whereas high-exposure fishes harbored no parasites.

  11. Period2 gene mutant mice show compromised insulin-mediated endothelial nitric oxide release and altered glucose homeostasis

    Directory of Open Access Journals (Sweden)

    João Miguel Carvas


    Full Text Available Period2 (Per2 is an important component of the circadian clock. Mutation of this gene is associated with vascular endothelial dysfunction and altered glucose metabolism. The aim of this study is to further characterize whole body glucose homeostasis and endothelial NO production in response to insulin in the mPer2Brdm1 mice. We show that mPer2Brdm1 mice exhibit compromised insulin receptor activation and Akt signaling in various tissues including liver, fat, heart, and aortas with a tissue-specific heterogeneous diurnal pattern, and decreased insulin-stimulated endothelial NO release in the aortas in both active and inactive phases of the animals. As compared to wild type mice, the mPer2Brdm1 mice reveal hyperinsulinemia, hypoglycemia with lower fasting hepatic glycogen content and glycogen synthase level, no difference in glucose tolerance and insulin tolerance. The mPer2Brdm1 mice do not show increased predisposition to obesity either on normal chow or high fat diet compared to wild type controls. Thus, mice with Per2 gene mutation show altered glucose homeostasis and compromised insulin-stimulated endothelial NO release, independently of obesity.

  12. Effects of temperature on anoxic submergence: skeletal buffering, lactate distribution, and glycogen utilization in the turtle, Trachemys scripta. (United States)

    Warren, Daniel E; Jackson, Donald C


    To test the hypothesis that submergence temperature affects the distribution of the lactate load and glycogen utilization during anoxia in turtles, we sampled a variety of tissues after 7 days, 24 h, and 4 h of anoxic submergence at 5, 15, and 25 degrees C, respectively. These anoxic durations were chosen because we found that they produced similar decreases in plasma HCO(3)(-) ( approximately 18-22 meq/l). The sampled tissues included ventricle, liver, small intestine, carapace, and the following muscles: flexor digitorum longus, retrahens capitis, iliofibularis, and pectoralis. Shell and skeleton sequestered 41.9, 34.1, and 26.1% of the estimated lactate load at 5, 15, and 25 degrees C. The changes in plasma Ca(2+) and Mg(2+), relative to the estimated lactate load, decreased with increased temperature, indicating greater buffer release from bone at colder temperatures. Tissue lactate contents, relative to plasma lactate, increased with the temperature of the submergence. Glucose mobilization and tissue glycogen utilization were more pronounced at 15 and 25 degrees C than at 5 degrees C. We conclude that, in slider turtles, the ability of the mineralized tissue to participate in the buffering of lactic acid during anoxia is inversely related to temperature, causing the lactate burden to shift to the tissues at warmer temperatures. Muscles utilize glycogen during anoxia more at warmer temperatures.

  13. Effect of fipronil on energy metabolism in the perfused rat liver. (United States)

    de Medeiros, Hyllana Catarine Dias; Constantin, Jorgete; Ishii-Iwamoto, Emy Luiza; Mingatto, Fábio Erminio


    Fipronil is an insecticide used to control pests in animals and plants that can causes hepatotoxicity in animals and humans, and it is hepatically metabolized to fipronil sulfone by cytochrome P-450. The present study aimed to characterize the effects of fipronil (10-50μM) on energy metabolism in isolated perfused rat livers. In fed animals, there was increased glucose and lactate release from glycogen catabolism, indicating the stimulation of glycogenolysis and glycolysis. In the livers of fasted animals, fipronil inhibited glucose and urea production from exogenous l-alanine, whereas ammonia and lactate production were increased. In addition, fipronil at 50μM concentration inhibited the oxygen uptake and increased the cytosolic NADH/NAD⁺ ratio under glycolytic conditions. The metabolic alterations were found both in livers from normal or proadifen-pretreated rats revealing that fipronil and its reactive metabolites contributed for the observed activity. The effects on oxygen uptake indicated that the possible mechanism of toxicity of fipronil involves impairment on mitochondrial respiratory activity, and therefore, interference with energy metabolism. The inhibitory effects on oxygen uptake observed at the highest concentration of 50μM was abolished by pretreatment of the rats with proadifen indicating that the metabolites of fipronil, including fipronil sulfone, acted predominantly as inhibitors of respiratory chain. The hepatoxicity of both the parent compound and its reactive metabolites was corroborated by the increase in the activity of lactate dehydrogenase in the effluent perfusate in livers from normal or proadifen-pretreated rats.

  14. A functional glycogen biosynthesis pathway in Lactobacillus acidophilus: expression and analysis of the glg operon. (United States)

    Goh, Yong Jun; Klaenhammer, Todd R


    Glycogen metabolism contributes to energy storage and various physiological functions in some prokaryotes, including colonization persistence. A role for glycogen metabolism is proposed on the survival and fitness of Lactobacillus acidophilus, a probiotic microbe, in the human gastrointestinal environment. L. acidophilus NCFM possesses a glycogen metabolism (glg) operon consisting of glgBCDAP-amy-pgm genes. Expression of the glg operon and glycogen accumulation were carbon source- and growth phase-dependent, and were repressed by glucose. The highest intracellular glycogen content was observed in early log-phase cells grown on trehalose, which was followed by a drastic decrease of glycogen content prior to entering stationary phase. In raffinose-grown cells, however, glycogen accumulation gradually declined following early log phase and was maintained at stable levels throughout stationary phase. Raffinose also induced an overall higher temporal glg expression throughout growth compared with trehalose. Isogenic ΔglgA (glycogen synthase) and ΔglgB (glycogen-branching enzyme) mutants are glycogen-deficient and exhibited growth defects on raffinose. The latter observation suggests a reciprocal relationship between glycogen synthesis and raffinose metabolism. Deletion of glgB or glgP (glycogen phosphorylase) resulted in defective growth and increased bile sensitivity. The data indicate that glycogen metabolism is involved in growth maintenance, bile tolerance and complex carbohydrate utilization in L. acidophilus.

  15. Liver function test alterations associated with parenteral nutrition in hospitalized adult patients: incidence and risk factors Alteraciones de los parámetros hepáticos asociados con la administración de nutrición parenteral en pacientes adultos hospitalizados: incidencia y factores de riesgo


    M.ª B. Badia-Tahull; E. Leiva-Badosa; J. Llop-Talaverón; A. Figueras-Suriol; A. Quirante-Cremades; M.ª Tubau-Molas; R. Jódar-Masanés


    Background: Parenteral nutrition-associated liver dysfunction can be progressive and irreversible, particularly in children and patients with long-term treatment. This study has assessed the incidence of abnormal liver function tests in hospitalized adults during short term parenteral nutrition (PN) and has investigated risk factors for developing alterations of each parameter. Methods: A prospective cohort study of parenteral nutrition treated patients with preserved liver function at baseli...

  16. Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector.

    LENUS (Irish Health Repository)

    Luo, Xiaoyan


    Glycogen storage disease type Ia (GSD-Ia) is caused by the deficiency of glucose-6-phosphatase (G6Pase). Long-term complications of GSD-Ia include life-threatening hypoglycemia and proteinuria progressing to renal failure. A double-stranded (ds) adeno-associated virus serotype 2 (AAV2) vector encoding human G6Pase was pseudotyped with four serotypes, AAV2, AAV7, AAV8, and AAV9, and we evaluated efficacy in 12-day-old G6pase (-\\/-) mice. Hypoglycemia during fasting (plasma glucose <100 mg\\/dl) was prevented for >6 months by the dsAAV2\\/7, dsAAV2\\/8, and dsAAV2\\/9 vectors. Prolonged fasting for 8 hours revealed normalization of blood glucose following dsAAV2\\/9 vector administration at the higher dose. The glycogen content of kidney was reduced by >65% with both the dsAAV2\\/7 and dsAAV2\\/9 vectors, and renal glycogen content was stably reduced between 7 and 12 months of age for the dsAAV2\\/9 vector-treated mice. Every vector-treated group had significantly reduced glycogen content in the liver, in comparison with untreated G6pase (-\\/-) mice. G6Pase was expressed in many renal epithelial cells of with the dsAAV2\\/9 vector for up to 12 months. Albuminuria and renal fibrosis were reduced by the dsAAV2\\/9 vector. Hepatorenal correction in G6pase (-\\/-) mice demonstrates the potential of AAV vectors for the correction of inherited diseases of metabolism.

  17. Crude extract of cyanobacteria (Radiocystis fernandoi, strain R28) induces liver impairments in fish. (United States)

    Paulino, M G; Tavares, D; Bieczynski, F; Pedrão, P G; Souza, N E S; Sakuragui, M M; Luquet, C M; Terezan, A P; Fernandes, J B; Giani, A; Fernandes, M N


    Radiocystis fernandoi R28 strain is a cyanobacterium which produces mostly the RR and YR microcystin variants (MC-RR and MC-YR, respectively). The effects of crude extract of the R. fernandoi strain R28 were evaluated on the protein phosphatases and on the structure and ultrastructure of the liver of the Neotropical fish, Hoplias malabaricus, after acute and subchronic exposure. Concomitantly, the accumulation of the majority of MCs was determined in the liver and muscle. The fish were exposed to 120.60 MC-RR+MC-LR kg-fish(-1) (=100μg MC-LReq kg-fish(-1)) for 12 and 96h (one single dose, acute exposure) and 30days (one similar dose every 72h, subchronic exposure). MCs did not accumulate in the muscle but, in the liver, MC-YR accumulated after acute exposure and MC-RR and MC-YR accumulation occurred after subchronic exposure. Protein phosphatase 2A (PP2A) activity was inhibited only after subchronic exposure. Acute exposure induced liver hyperemia, hemorrhage, changes in hepatocytes and cord-like disorganization. At the ultrastructural level, the decreasing of glycogen and lipid levels, the swelling of mitochondria and whirling of endoplasmic reticulum suggested hepatocyte necrosis. Subchronic exposure resulted in a complete disarrangement of cord-like hepatocytes, some recovery of mitochondria and whirling endoplasmic reticulum and extensive connective tissues containing fibrous materials in the liver parenchyma. Despite microcystin toxicity and liver alterations, no tumor was induced by MCs. In conclusion, the increased algal mass of R. fernandoi in tropical freshwater, producing mainly MC-RR and MC-YR variants, results in fish liver impairments.

  18. Effects of gestation feeding level on glycogen reserves and blood parameters in the newborn pig. (United States)

    Ojamaa, K M; Elliot, J I; Hartsock, T G


    Ten Yorkshire gilts were fed either 1.36 or .45 kg of a gestation diet per day from day 85 of gestation to farrowing for determination of the effect of feed restriction during late gestation on reproductive performance. All gilts consumed 1.36 kg/day from day of breeding to day 85. Feeding level of affected (P Gestation period tended to be shorter (115.4 vs 113.6 days) and total litter weight tended to be lower (10.6 vs 8.6 kg) in the restricted group although the differences were not statistically significant. Litter size was similar (9.6 vs 9.4 pigs/litter). Restriction of gestation feed significantly reduced individual piglet birth weight (1.1 vs .9 kg), liver weight (32.9 vs 26.0 g) and skeletal muscle weights (8.9 vs 7.1 and 2.1 vs 1.6 g for the longissimus and semitendinosus muscles, respectively). Piglets born to restricted dams also had reduced liver and muscle glycogen concentrations (15.1 vs 13.9, 10.1 vs 9.4 and 9.9 vs 9.4 g/100 g of wet tissue for the liver and longissimus and semitendinosus muscles, respectively), lower (P < .05) blood pH (7.31 vs 7.23) and higher (P < .01) blood lactate levels (43.8 vs 71.3 mg/100 ml).

  19. Total body irradiation of donors can alter the course of tolerance and induce acute rejection in a spontaneous tolerance rat liver transplantation model. (United States)

    Zhang, YeWei; Zhao, HeWei; Bo, Lin; Yang, YinXue; Lu, Xiang; Sun, JingFeng; Wen, JianFei; He, Xia; Yin, GuoWen


    Liver transplantation is an established therapy for end-stage liver diseases. Graft rejection occurs unless the recipient receives immunosuppression after transplantation. This study aimed to explore the mechanism of acute rejection of liver allografts in rats pre-treated with total body irradiation to eliminate passenger lymphocytes and to define the role of CD4(+)CD25(+) regulatory T cells in the induction of immunotolerance in the recipient. Male Lewis rats were used as donors and male DA rats were recipients. Rats were randomly assigned to the following four groups: control group, homogeneity liver transplantation group, idio-immunotolerance group and acute rejection group. After transplantation, the survival time of each group, serum alanine aminotransferase, total bilirubin levels, number of Foxp3(+)CD4(+)CD25(+) regulatory T cells, expression of glucocorticoid-induced tumor necrosis factor receptor on T cell subgroups, histopathology of the hepatic graft and spleen cytotoxic T lymphocyte lytic activity were measured. In the acute rejection group, where donors were preconditioned with total body irradiation before liver transplantation, all recipients died between day 17 and day 21. On day 14, serum alanine aminotransferase increased significantly to (459.2±76.9) U L(-1), total bilirubin increased to (124.1±33.7) μmol L(-1) (Pliver graft, and thus affected the course of tolerance and induced acute rejection after liver transplantation.

  20. Ethanol diversely alters palmitate, stearate and oleate metabolism in the liver and pancreas of rats using the deuterium oxide single tracer (United States)

    Boros, Laszlo G.; Deng, Qinggao; Pandol, Stephen J.; Tsukamoto, Hidekazu; Go, Vay Liang W.; Lee, Wai-Nang Paul


    Objective To determine tissue specific effects of alcohol on fatty acid synthesis and distribution as related to functional changes in triglyceride transport and membrane formation. Methods Tissue fatty acid profile, and de novo lipogenesis were determined in adult male Wistar rats after 5 weeks of ethanol feeding using deuterated water and GC/MS. Liver and pancreas fatty acid profiles and new synthesis fractions were compared with those from control rats on an isocaloric diet. Results Fatty acid ratios in the liver indicated that there was an over two-fold accumulation of stearate to that of palmitate, with an apparent decrease in oleate content. On the other hand, in the pancreas there was a 17% decrease in the stearate to palmitate ratio, while oleate to palmitate ratio was increased by 30%. The fractions of deuterium labeled palmitate and stearate were substantially reduced in the liver and pancreas of the alcohol treated animals. Deuterium labeling of oleate was reduced in the liver but not in the pancreas consistent with the oleate/stearate ratios in these tissues. Conclusions Long-term alcohol exposure results in opposite effects on the desaturase activity in the liver and pancreas limiting fatty acid transport in the liver but promoting the exocrine function of the pancreas. PMID:19248221

  1. Thiamethoxam causes histochemical changes in the liver of Aristichthys nobilis Rich., 1845

    Directory of Open Access Journals (Sweden)



    Full Text Available In the present study, we aimed to investigate the effects of the neonicotinoid insecticide thiamethoxam on the hepatic glycogen in bighead carp (Aristichthys nobilis Rich.. Fish were exposed to 6.6 mg/L, 10 mg/L and 20 mg/L of the insecticide under laboratory conditions for 96 hours. The PAS-reaction was applied to liver cryostat sections in order to indicate the amount of glycogen. The results showed that the hepatic glycogen amount increased with increasing the insecticide concentrations. On the other hand, we observed glycogen conglomerates in certain hepatocytes. Hence, our results demonstrated an enhanced process of glyconeogenesis in the fish liver under the influence of thiamethoxam.

  2. Glycogen availability and skeletal muscle adaptations with endurance and resistance exercise

    NARCIS (Netherlands)

    Knuiman, Pim; Hopman, Maria T.E.; Mensink, Marco


    It is well established that glycogen depletion affects endurance exercise performance negatively. Moreover, numerous studies have demonstrated that post-exercise carbohydrate ingestion improves exercise recovery by increasing glycogen resynthesis. However, recent research into the effects of glyc

  3. Effects of different mitogens on intrasplenic liver tissue transplants in comparison to orthotopic liver. (United States)

    Lupp, Amelie; Lucas, Norma; Tralls, Manuela; Fuchs, Udo; Danz, Manfred


    Ectopic liver cell transplants, when compared to orthotopic liver, can serve as a tool to study topic influences on liver cell differentiation, multiplication, function and responsiveness to xenobiotics. The aim of the present study was to evaluate, if characteristic effects of mitogens are exerted in both liver and intrasplenic liver cell transplants in a similar manner. Fetal liver tissue suspensions were transplanted into the spleens of adult male syngenic rats. Four months later, transplant recipients and controls were treated with fluorene (FEN), fluorenone (FON), 2-acetylaminofluorene (AAF), N-nitrosodibenzylamine (NDBA) or the solvent 48 hours before sacrifice. The following parameters were assessed within livers and spleens: mitotic activity of hepatocytes, glycogen content, cytochrome P450 (P450) isoforms expression, P450 mediated monooxygenase functions, tissue content of lipid peroxides (LPO) and of reduced and oxidized glutathione (GSH; GSSG). In both orthotopic livers and intrasplenic transplants FEN, FON or NDBA administration increased the mitotic activity of the hepatocytes. Treatment with the mitogens caused a distinct and characteristic induction of the P450 isoforms expression and of the respective monooxygenase functions in the livers and (with certain differences) also in the transplants. FEN and FON slightly increased, AAF and NDBA reduced liver glycogen content. The latter effect was also seen in the transplants. NDBA administration caused a slight increase in tissue LPO content in livers, but not in spleens. Additionally, AAF or NDBA treatment led to an elevation of liver (but not of spleen) GSH and GSSG concentrations. The results of the present investigation show that characteristic effects of mitogens on orthotopic liver occur with certain differences also in ectopic liver cell transplants.

  4. Insights into glycogen metabolism in Lactobacillus acidophilus: impact on carbohydrate metabolism, stress tolerance and gut retention. (United States)

    Goh, Yong Jun; Klaenhammer, Todd R


    In prokaryotic species equipped with glycogen metabolism machinery, the co-regulation of glycogen biosynthesis and degradation has been associated with the synthesis of energy storage compounds and various crucial physiological functions, including global cellular processes such as carbon and nitrogen metabolism, energy sensing and production, stress response and cell-cell communication. In addition, the glycogen metabolic pathway was proposed to serve as a carbon capacitor that regulates downstream carbon fluxes, and in some microorganisms the ability to synthesize intracellular glycogen has been implicated in host persistence. Among lactobacilli, complete glycogen metabolic pathway genes are present only in select species predominantly associated with mammalian hosts or natural environments. This observation highlights the potential involvement of glycogen biosynthesis in probiotic activities and persistence of intestinal lactobacilli in the human gastrointestinal tract. In this review, we summarize recent findings on (i) the presence and potential ecological distribution of glycogen metabolic pathways among lactobacilli, (ii) influence of carbon substrates and growth phases on glycogen metabolic gene expression and glycogen accumulation in L. acidophilus, and (iii) the involvement of glycogen metabolism on growth, sugar utilization and bile tolerance. Our present in vivo studies established the significance of glycogen biosynthesis on the competitive retention of L. acidophilus in the mouse intestinal tract, demonstrating for the first time that the ability to synthesize intracellular glycogen contributes to gut fitness and retention among probiotic microorganisms.

  5. Differences between glycogen biogenesis in fast- and slow-twitch rabbit muscle

    DEFF Research Database (Denmark)

    Cussó, R; Lerner, L R; Cadefau, J;


    Skeletal muscle glycogen is an essential energy substrate for muscular activity. The biochemical properties of the enzymes involved in de novo synthesis of glycogen were analysed in two types of rabbit skeletal muscle fiber (fast- and slow-twitch). Glycogen concentration was higher in fast...

  6. Acoustic Accessibility Investigation for Ultrasound Mediated Treatment of Glycogen Storage Disease Type la Patients

    NARCIS (Netherlands)

    Wang, S.; Raju, B.I.; Leyvi, E.; Weinstein, D.A.; Seip, R.


    GSD1a, the most prevalent type among the glycogen storage disease families, is caused by an inherited glycogen-6-phosphatase gene defectresulting in an impaired glycogen to glucose conversion pathway. Strict dietary management continues to be the only treatment for GSD1apatients. Recently, the adven

  7. Partly ordered synthesis and degradation of glycogen in cultured rat myotubes

    DEFF Research Database (Denmark)

    Elsner, Peter; Quistorff, Bjørn; Hansen, Gert H;


    .81 and 1.39 h(-1), respectively. The degradation of glycogen largely followed the last-in-first-out principle, particularly in the initial period. Analysis of the size of the glycogen molecules and the beta-dextrin limit during glycogen accumulation and degradation showed that both synthesis...

  8. Glycogen metabolism in Schistosoma mansoni worms after their isolation from the host

    NARCIS (Netherlands)

    Tiolens, A.G.M.; Bergh, S.G. van den


    Adult Schistosoma mansoni worms rapidly degrade their endogenous glycogen stores immediately after isolation from the host. In NCTC 109 or in a diphasic culture medium the glycogen levels slowly recovered again after the initial decrease. The rapid degradation of glycogen could be prevented, even in

  9. The utilization of glycogen and accumulation of some intermediates during anaerobiosis in Mytilus edulis L.

    NARCIS (Netherlands)

    Zwaan, A.; Zandee, D.I.


    1. 1. Glycogen degradation in the mussel under anaerobic conditions was measured at two temperatures. Glycogen decrease at 6·6°C was about 3 mg and at 20°C about 6 mg/24 hr per mussel. A Pasteur effect was observed. 2. 2. The decrease of glycogen was almost entirely restricted to muscles, including

  10. Humanizing π-class glutathione S-transferase regulation in a mouse model alters liver toxicity in response to acetaminophen overdose.

    Directory of Open Access Journals (Sweden)

    Matthew P Vaughn

    Full Text Available BACKGROUND: Glutathione S-transferases (GSTs metabolize drugs and xenobiotics. Yet despite high protein sequence homology, expression of π-class GSTs, the most abundant of the enzymes, varies significantly between species. In mouse liver, hepatocytes exhibit high mGstp expression, while in human liver, hepatocytes contain little or no hGSTP1 mRNA or hGSTP1 protein. π-class GSTs are known to be critical determinants of liver responses to drugs and toxins: when treated with high doses of acetaminophen, mGstp1/2+/+ mice suffer marked liver damage, while mGstp1/2-/- mice escape liver injury. METHODOLOGY/PRINCIPAL FINDINGS: To more faithfully model the contribution of π-class GSTs to human liver toxicology, we introduced hGSTP1, with its exons, introns, and flanking sequences, into the germline of mice carrying disrupted mGstp genes. In the resultant hGSTP1+mGstp1/2-/- strain, π-class GSTs were regulated differently than in wild-type mice. In the liver, enzyme expression was restricted to bile duct cells, Kupffer cells, macrophages, and endothelial cells, reminiscent of human liver, while in the prostate, enzyme production was limited to basal epithelial cells, reminiscent of human prostate. The human patterns of hGSTP1 transgene regulation were accompanied by human patterns of DNA methylation, with bisulfite genomic sequencing revealing establishment of an unmethylated CpG island sequence encompassing the gene promoter. Unlike wild-type or mGstp1/2-/- mice, when hGSTP1+mGstp1/2-/- mice were overdosed with acetaminophen, liver tissues showed limited centrilobular necrosis, suggesting that π-class GSTs may be critical determinants of toxin-induced hepatocyte injury even when not expressed by hepatocytes. CONCLUSIONS: By recapitulating human π-class GST expression, hGSTP1+mGstp1/2-/- mice may better model human drug and xenobiotic toxicology.

  11. Dietary saturated and monounsaturated fats protect against acute acetaminophen hepatotoxicity by altering fatty acid composition of liver microsomal membrane in rats

    Directory of Open Access Journals (Sweden)

    Shim Eugene


    Full Text Available Abstract Background Dietary polyunsaturated fats increase liver injury in response to ethanol feeding. We evaluated the effect of dietary corn oil (CO, olive oil (OO, and beef tallow (BT on fatty acid composition of liver microsomal membrane and acute acetaminophen hepatotoxicity. Methods Male Sprague-Dawley rats were fed 15% (wt/wt CO, OO or BT for 6 weeks. After treatment with acetaminophen (600 mg/kg, samples of plasma and liver were taken for analyses of the fatty acid composition and toxicity. Results Treatment with acetaminophen significantly elevated levels of plasma GOT and GPT as well as hepatic TBARS but reduced hepatic GSH levels in CO compared to OO and BT groups. Acetaminophen significantly induced protein expression of cytochrome P450 2E1 in the CO group. In comparison with the CO diet, lower levels of linoleic acid, higher levels of oleic acids and therefore much lower ratios of linoleic to oleic acid were detected in rats fed OO and BT diets. Conclusions Dietary OO and BT produces similar liver microsomal fatty acid composition and may account for less severe liver injury after acetaminophen treatment compared to animals fed diets with CO rich in linoleic acid. These findings imply that types of dietary fat may be important in the nutritional management of drug-induced hepatotoxicity.

  12. Alterations of epigenetic signatures in hepatocyte nuclear factor 4α deficient mouse liver determined by improved ChIP-qPCR and (h)MeDIP-qPCR assays. (United States)

    Zhang, Qinghao; Lei, Xiaohong; Lu, Hong


    Hepatocyte nuclear factor 4α (HNF4α) is a liver-enriched transcription factor essential for liver development and function. In hepatocytes, HNF4α regulates a large number of genes important for nutrient/xenobiotic metabolism and cell differentiation and proliferation. Currently, little is known about the epigenetic mechanism of gene regulation by HNF4α. In this study, the global and specific alterations at the selected gene loci of representative histone modifications and DNA methylations were investigated in Hnf4a-deficient female mouse livers using the improved MeDIP-, hMeDIP- and ChIP-qPCR assay. Hnf4a deficiency significantly increased hepatic total IPed DNA fragments for histone H3 lysine-4 dimethylation (H3K4me2), H3K4me3, H3K9me2, H3K27me3 and H3K4 acetylation, but not for H3K9me3, 5-methylcytosine,or 5-hydroxymethylcytosine. At specific gene loci, the relative enrichments of histone and DNA modifications were changed to different degree in Hnf4a-deficient mouse liver. Among the epigenetic signatures investigated, changes in H3K4me3 correlated the best with mRNA expression. Additionally, Hnf4a-deficient livers had increased mRNA expression of histone H1.2 and H3.3 as well as epigenetic modifiers Dnmt1, Tet3, Setd7, Kmt2c, Ehmt2, and Ezh2. In conclusion, the present study provides convenient improved (h)MeDIP- and ChIP-qPCR assays for epigenetic study. Hnf4a deficiency in young-adult mouse liver markedly alters histone methylation and acetylation, with fewer effects on DNA methylation and 5-hydroxymethylation. The underlying mechanism may be the induction of epigenetic enzymes responsible for the addition/removal of the epigenetic signatures, and/or the loss of HNF4α per se as a key coordinator for epigenetic modifiers.

  13. Metabolic alterations and increased liver mTOR expression precede the development of autoimmune disease in a murine model of lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Laia Vilà

    Full Text Available Although metabolic syndrome (MS and systemic lupus erythematosus (SLE are often associated, a common link has not been identified. Using the BWF1 mouse, which develops MS and SLE, we sought a molecular connection to explain the prevalence of these two diseases in the same individuals. We determined SLE- markers (plasma anti-ds-DNA antibodies, splenic regulatory T cells (Tregs and cytokines, proteinuria and renal histology and MS-markers (plasma glucose, non-esterified fatty acids, triglycerides, insulin and leptin, liver triglycerides, visceral adipose tissue, liver and adipose tissue expression of 86 insulin signaling-related genes in 8-, 16-, 24-, and 36-week old BWF1 and control New-Zealand-White female mice. Up to week 16, BWF1 mice showed MS-markers (hyperleptinemia, hyperinsulinemia, fatty liver and visceral adipose tissue that disappeared at week 36, when plasma anti-dsDNA antibodies, lupus nephritis and a pro-autoimmune cytokine profile were detected. BWF1 mice had hyperleptinemia and high splenic Tregs till week 16, thereby pointing to leptin resistance, as confirmed by the lack of increased liver P-Tyr-STAT-3. Hyperinsulinemia was associated with a down-regulation of insulin related-genes only in adipose tissue, whereas expression of liver mammalian target of rapamicyn (mTOR was increased. Although leptin resistance presented early in BWF1 mice can slow-down the progression of autoimmunity, our results suggest that sustained insulin stimulation of organs, such as liver and probably kidneys, facilitates the over-expression and activity of mTOR and the development of SLE.

  14. Pathway-level acceleration of glycogen catabolism by a response regulator in the cyanobacterium Synechocystis species PCC 6803. (United States)

    Osanai, Takashi; Oikawa, Akira; Numata, Keiji; Kuwahara, Ayuko; Iijima, Hiroko; Doi, Yoshiharu; Saito, Kazuki; Hirai, Masami Yokota


    Response regulators of two-component systems play pivotal roles in the transcriptional regulation of responses to environmental signals in bacteria. Rre37, an OmpR-type response regulator, is induced by nitrogen depletion in the unicellular cyanobacterium Synechocystis species PCC 6803. Microarray and quantitative real-time polymerase chain reaction analyses revealed that genes related to sugar catabolism and nitrogen metabolism were up-regulated by rre37 overexpression. Protein levels of GlgP(slr1367), one of the two glycogen phosphorylases, in the rre37-overexpressing strain were higher than those of the parental wild-type strain under both nitrogen-replete and nitrogen-depleted conditions. Glycogen amounts decreased to less than one-tenth by rre37 overexpression under nitrogen-replete conditions. Metabolome analysis revealed that metabolites of the sugar catabolic pathway and amino acids were altered in the rre37-overexpressing strain after nitrogen depletion. These results demonstrate that Rre37 is a pathway-level regulator that activates the metabolic flow from glycogen to polyhydroxybutyrate and the hybrid tricarboxylic acid and ornithine cycle, unraveling the mechanism of the transcriptional regulation of primary metabolism in this unicellular cyanobacterium.

  15. Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme

    Directory of Open Access Journals (Sweden)

    V. Bertone


    Full Text Available Biliary complications often lead to acute and chronic liver injury after orthotopic liver transplantation (OLT. Bile composition and secretion depend on the integrated action of all the components of the biliary tree, starting from hepatocytes. Fatty livers are often discarded as grafts for OLT, since they are extremely vulnerable to conventional cold storage (CS. However, the insufficiency of donors has stimulated research to improve the usage of such marginal organs as well as grafts. Our group has recently developed a machine perfusion system at subnormothermic temperature (20°C; MP20 that allows a marked improvement in preservation of fatty and even of normal rat livers as compared with CS. We sought to evaluate the response of the biliary tree of fatty liver to MP20, and a suitable marker was essential to this purpose. Alkaline phosphatase (AlkP, EC, frequently used as marker of membrane transport in hepatocytes and bile ducts, was our first choice. Since no histochemical data were available on AlkP distribution and activity in fatty liver, we have first settled to investigate AlkP activity in the steatotic liver of fatty Zucker rats (fa/fa, using as controls lean Zucker (fa/+ and normal Wistar rats. The AlkP reaction in Wistar rats was in accordance with the existing data and, in particular, was present in bile canaliculi of hepatocytes in the periportal region and midzone, in the canals of Hering and in small bile ducts but not in large bile ducts. In lean ZR liver the AlkP reaction in Hering canals and small bile ducts was similar to Wistar rat liver but hepatocytes had lower canalicular activity and besides presented moderate basolateral reaction. The difference between lean Zucker and Wistar rats, both phenotypically normal animals, could be related to the fact that lean Zucker rats are genotypically heterozygous for a recessive mutated allele. In fatty liver, the activity in ductules and small bile ducts was unchanged, but

  16. Consensus guidelines for management of glycogen storage disease type 1b - European Study on Glycogen Storage Disease Type 1

    NARCIS (Netherlands)

    Visser, G; Rake, JP; Labrune, P; Leonard, JV; Moses, S; Ullrich, K; Wendel, U; Smit, GPA


    Life expectancy in glycogen storage disease type 1 (GSD-1) has improved considerably. Its relative rarity implies that no metabolic centre has experience of large series of patients and therefore experience with long-term management and follow-up at each centre is limited. There is wide variation in

  17. Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice. (United States)

    Rodríguez, Amaia; Moreno, Natalia R; Balaguer, Inmaculada; Méndez-Giménez, Leire; Becerril, Sara; Catalán, Victoria; Gómez-Ambrosi, Javier; Portincasa, Piero; Calamita, Giuseppe; Soveral, Graça; Malagón, María M; Frühbeck, Gema


    Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue (WAT) and liver. We aimed to investigate whether exogenous administration of leptin improves features of non-alcoholic fatty liver disease (NAFLD) in leptin-deficient ob/ob mice via the regulation of AQP3 and AQP7 (glycerol channels mediating glycerol efflux in adipocytes) and AQP9 (aquaglyceroporin facilitating glycerol influx in hepatocytes). Twelve-week-old male wild type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1 mg/kg/d) and pair-fed. Leptin deficiency was associated with obesity and NAFLD exhibiting an AQP3 and AQP7 increase in WAT, without changes in hepatic AQP9. Adipose Aqp3 and hepatic Aqp9 transcripts positively correlated with markers of adiposity and hepatic steatosis. Chronic leptin administration (4-weeks) was associated with improved body weight, whole-body adiposity, and hepatosteatosis of ob/ob mice and to a down-regulation of AQP3, AQP7 in WAT and an up-regulation of hepatic AQP9. Acute leptin stimulation in vitro (4-h) induced the mobilization of aquaglyceroporins towards lipid droplets (AQP3) and the plasma membrane (AQP7) in murine adipocytes. Our results show that leptin restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, a step which might prevent lipid overaccumulation in WAT and liver in obesity.

  18. Dietary fat source alters hepatic gene expression profile and determines the type of liver pathology in rats overfed via total enteral nutrition (United States)

    This study was designed to determine if the fatty acid composition of the diet affects the development and progression of nonalcoholic fatty liver disease (NAFLD). Male Sprague-Dawley rats (n = 5-6/group) were overfed low (5%) or high (70%) fat diets with different fatty acid sources: olive oil (OO,...

  19. The Liver X Receptor (LXR) and its Target Gene ABCA1 are Regulated Upon Low Oxygen in Human Trophoblast Cells : A Reason for Alterations in Preeclampsia?

    NARCIS (Netherlands)

    Plosch, T.; Gellhaus, A.; van Straten, E. M. E.; Wolf, N.; Huijkman, N. C. A.; Schmidt, M.; Dunk, C. E.; Kuipers, F.; Winterhager, E.


    Objectives: The Liver X receptors (LXR) alpha and beta and their target genes such as the ATP-binding cassette (ABC) transporters have been shown to be crucially involved in the regulation of cellular cholesterol homeostasis. The aim of this study was to characterize the role of LXR alpha/beta in th

  20. Alterations in trace element levels and mRNA expression of Hsps and inflammatory cytokines in livers of duck exposed to molybdenum or/and cadmium. (United States)

    Cao, Huabin; Gao, Feiyan; Xia, Bing; Zhang, Mengmeng; Liao, Yilin; Yang, Zhi; Hu, Guoliang; Zhang, Caiying


    To evaluate the effects of dietary Molybdenum (Mo) or/and Cadmium (Cd) on trace elements and the mRNA expression levels of heat shock proteins (Hsps) and inflammatory cytokines in duck livers. 240 healthy 11-day-old ducks were randomly divided into six groups with 40 ducks in each group, which were treated with Mo or/and Cd at different doses on the basal diet for 120 days. On days 30, 60, 90 and 120, 10 birds in each group were randomly selected and euthanized and then the livers were collected to determine the contents of Mo, Cd, copper (Cu), iron (Fe), zine (Zn), Selenium (Se) and the mRNA expression levels of Hsps, inflammatory cytokines. In addition, liver tissues at 120 days were subjected to histopathological analysis with the optical microscope. The results showed that the mRNA expression of Hsp60, Hsp70, Hsp90, tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and cyclooxygenase-2 (COX-2) were significantly (Pcytokines may play a role in the resistance of liver toxicity induced by Mo and Cd.

  1. In situ metabolic flux analysis to quantify the liver metabolic response to experimental burn injury. (United States)

    Izamis, Maria-Louisa; Sharma, Nripen S; Uygun, Basak; Bieganski, Robert; Saeidi, Nima; Nahmias, Yaakov; Uygun, Korkut; Yarmush, Martin L; Berthiaume, Francois


    Trauma such as burns induces a hypermetabolic response associated with altered central carbon and nitrogen metabolism. The liver plays a key role in these metabolic changes; however, studies to date have evaluated the metabolic state of liver using ex vivo perfusions or isotope labeling techniques targeted to specific pathways. Herein, we developed a unique mass balance approach to characterize the metabolic state of the liver in situ, and used it to quantify the metabolic changes to experimental burn injury in rats. Rats received a sham (control uninjured), 20% or 40% total body surface area (TBSA) scald burn, and were allowed to develop a hypermetabolic response. One day prior to evaluation, all animals were fasted to deplete glycogen stores. Four days post-burn, blood flow rates in major vessels of the liver were measured, and blood samples harvested. We combined measurements of metabolite concentrations and flow rates in the major vessels entering and leaving the liver with a steady-state mass balance model to generate a quantitative picture of the metabolic state of liver. The main findings were: (1) Sham-burned animals exhibited a gluconeogenic pattern, consistent with the fasted state; (2) the 20% TBSA burn inhibited gluconeogenesis and exhibited glycolytic-like features with very few other significant changes; (3) the 40% TBSA burn, by contrast, further enhanced gluconeogenesis and also increased amino acid extraction, urea cycle reactions, and several reactions involved in oxidative phosphorylation. These results suggest that increasing the severity of injury does not lead to a simple dose-dependent metabolic response, but rather leads to qualitatively different responses.

  2. Histopathological alterations of white seabass, Lates calcarifer, in acute and subchronic cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    Thophon, S.; Kruatrachue, M.; Upatham, E.S.; Pokethitiyook, P.; Sahaphong, S.; Jaritkhuan, S


    White seabass responded differently to cadmium at chronic and subchronic levels. - Histopathological alterations to white seabass, Lates calcarifer aged 3 months in acute and subchronic cadmium exposure were studied by light and scanning electron microscopy. The 96-h LC{sub 50} values of cadmium to L. calcarifer was found to be 20.12{+-}0.61 mg/l and the maximum acceptable toxicant concentration (MATC) was 7.79 mg/l. Fish were exposed to 10 and 0.8 mg/l of Cd (as CdCl{sub 2}H{sub 2}O) for 96 h and 90 days, respectively. The study showed that gill lamellae and kidney tubules were the primary target organs for the acute toxic effect of cadmium while in the subchronic exposure, the toxic effect to gills was less than that of kidney and liver. Gill alterations included edema of the epithelial cells with the breakdown of pillar cell system, aneurisms with some ruptures, hypertrophy and hyperplasia of epithelial and chloride cells. The liver showed blood congestion in sinusoids and hydropic swelling of hepatocytes, vacuolation and dark granule accumulation. Lipid droplets and glycogen content were observed in hepatocytes at the second and third month of subchronic exposure. The kidney showed hydropic swelling of tubular cell vacuolation and numerous dark granule accumulation in many tubules. Tubular degeneration and necrosis were seen in some areas.

  3. Liver cancer oncogenomics

    DEFF Research Database (Denmark)

    Marquardt, Jens U; Andersen, Jesper B


    Primary liver cancers are among the most rapidly evolving malignant tumors worldwide. An underlying chronic inflammatory liver disease, which precedes liver cancer development for several decades and frequently creates a pro-oncogenic microenvironment, impairs progress in therapeutic approaches....... Molecular heterogeneity of liver cancer is potentiated by a crosstalk between epithelial tumor and stromal cells that complicate translational efforts to unravel molecular mechanisms of hepatocarcinogenesis with a drugable intend. Next-generation sequencing has greatly advanced our understanding of cancer...... development. With regards to liver cancer, the unprecedented coverage of next-generation sequencing has created a detailed map of genetic alterations and identified key somatic changes such as CTNNB1 and TP53 as well as several previously unrecognized recurrent disease-causing alterations that could...

  4. O-GlcNAc: a bittersweet switch in liver

    Directory of Open Access Journals (Sweden)

    Kaisi eZhang


    Full Text Available The liver is a vital organ responsible for maintaining nutrient homeostasis. After a meal, insulin stimulates glycogen and lipid synthesis in the liver; in the fasted state, glucagon induces gluconeogenesis and ketogenesis, which produce glucose and ketone bodies for other tissues to use as energy sources. These metabolic changes involve spatiotemporally coordinated signaling cascades. O-linked β-N-acetylglucosamine (O-GlcNAc modification has been recognized as a nutrient sensor and regulatory molecular switch. This review highlights mechanistic insights into spatiotemporal regulation of liver metabolism by O-GlcNAc modification and discusses its pathophysiological implications in insulin resistance, non-alcoholic fatty liver disease, and fibrosis.

  5. Insoluble glycogen, a metabolizable internal adsorbent, decreases the lethality of endotoxin shock in rats

    Directory of Open Access Journals (Sweden)

    S. Sipka


    Full Text Available Insoluble glycogen is an enzymatically modified form of naturally occurring soluble glycogen with a great adsorbing capacity. It can be metabolized by phagocytes to glucose. In this study we used insoluble glycogen intravenously in the experimental endotoxin shock of rats. Wistar male rats were sensitized to endotoxin by Pb acetate. The survival of rats were compared in groups of animals endotoxin shock treated and non-treated with insoluble glycogen. Furthermore, we have determined in vitro the binding capacity of insoluble glycogen for endotoxin, tumour necrosis factor alpha, interleukin-1 and secretable phospholipase A2. Use of 10 mg/kg dose of insoluble glycogen could completely prevent the lethality of shock induced by LD50 quantity of endotoxin in rats. All animals treated survived. Insoluble glycogen is a form of ‘metabolizable internal adsorbents’. It can potentially be used for treatment of septic shock.

  6. Technical note: A method for isolating glycogen granules from ruminal protozoa for further characterization. (United States)

    Hall, Mary Beth


    Evaluation of physical, chemical, and enzymatic hydrolysis characteristics of protozoal glycogen is best performed on a pure substrate to avoid interference from other cell components. A method for isolating protozoal glycogen granules without use of detergents or other potentially contaminating chemicals was developed. Rumen inoculum was incubated anerobically in vitro with glucose. Glycogen-laden protozoa produced in the fermentation, primarily isotrichids, were allowed to sediment in a separatory funnel and were dispensed. The protozoa were processed through repeated centrifugations and sonication to isolate glycogen granules largely free of feed and cellular debris. The final water-insoluble lyophilized product analyzed as 98.3% α-glucan with very rare starch granules and 1.9% protein. Observed losses of glycogen granules during the clean-up process indicate that this procedure should not be used for quantitative assessment of protozoal glycogen from fermentations. Further optimization of this procedure to enhance the amount of glycogen obtained per fermentation may be possible.


    Conazoles are fungicides used in crop protection and as pharmaceuticals. Triadimefon and propiconazole are hepatotumorigenic in mice, while myclobutanil is not. Previous toxicogenomic studies suggest that alteration of the retinoic acid metabolism pathway may be a key event in co...

  8. Biochemical aspects of overtraining in endurance sports : the metabolism alteration process syndrome. (United States)

    Petibois, Cyril; Cazorla, Georges; Poortmans, Jacques-Rémi; Déléris, Gérard


    Recent studies have shown that endurance overtraining could result from successive and cumulative alterations in metabolism, which become chronic during training. The onset of this process is a biochemical alteration in carbohydrate (saccharide) metabolism. During endurance exercises, the amount of saccharide chains from two blood glycoproteins (alpha(2)-macroglobulin and alpha(1)-acid glycoprotein) was found to have decreased, i.e. concentrations of these proteins remained unchanged but their quality changed. These saccharide chains were probably used for burning liver glycogen stores during exercise. This step was followed by alterations in lipid metabolism. The most relevant aspect of this step was that the mean chain length of blood fatty acids decreased, i.e. the same amount of fatty acids were found within the blood, but overtrained individuals presented shorter fatty acids than well-trained individuals. This suggests that alterations appeared in the liver synthesis of long-chain fatty acids or that higher peroxidation of blood lipoparticles occurred. For the final step of this overtraining process, it was found that these dysfunctions in carbohydrate/lipid metabolism led to the higher use of amino acids, which probably resulted from protein catabolism. The evolution of three protein concentrations (alpha(1)-acid glycoprotein, alpha(2)-macroglobulin and IgG(3)) correlated with this amino acid concentration increase, suggesting a specific catabolism of these proteins. At this time only, overtraining was clinically diagnosed through conventional symptoms. Therefore, this process described successive alterations in exercise metabolism that shifted from the main energetic stores of exercise (carbohydrates and lipids) towards molecular pools (proteins) normally not substantially used for the energetic supply of skeletal muscles. Now, a general biochemical model of the overtraining process may be proposed which includes most of the previously identified metabolic

  9. [Conditions for preserving glycogen in smears of isolated cells. II. Cytofluorimetric study of the effect of fixation on the glycogen content of cells]. (United States)

    Kudriavtseva, M V; Shalakhmetova, T M


    The influence of fixation on the intensity and specificity of the fluorescence of PAS-reaction (F-PAS) in the rat's liver cells was examined. 1.4 types of fixatives, routinely used in polysacchride cyto- and histochemistry, were tried: 100% metanol, 100% and 80% ethanol, acetone, 10% neutral formalin, buffered neutral formalin, mixtures of various fluids: ethanol : acetone (1 : 1), ethanol : formalin (9 : 1), ethanol : acetic acid (3 : 1), formaline : ethanol : acetic acid (1.0 : 8.5 : 0.5), fixatives of Carnoy, Bouin, Rossman and Shabadash. The cell fluorescence intensity after F-PAS reaction with Schiff's reagent auramine--SO2 and the cell autofluorescence were measured cytofluorometrically. It was shown that all the fixatives, besides Bouin's and Shabadash's fluids provide rather good preservation of the cell glycogen. Results obtained from the cytofluorometry of F-PAS reaction, autofluorescence and from the morphological studies of F-Pas stained cells, suggested that the best fixatives were 100% metanol and 100% ethanol.

  10. L-FABP T94A decreased fatty acid uptake and altered hepatic triglyceride and cholesterol accumulation in Chang liver cells stably transfected with L-FABP. (United States)

    Gao, Na; Qu, Xia; Yan, Jin; Huang, Qi; Yuan, Hao-Yong; Ouyang, Dong-Sheng


    Liver fatty acid-binding protein (L-FABP, FABP1) is a highly conserved key factor in lipid metabolism. This study was undertaken to verify whether the T94A mutation in the L-FABP gene affects fatty acid uptake and intracellular esterification into specific lipid pools. Candidate SNPs were recreated using site-directed mutagenesis and tested for physical function in stably transfected Chang liver cell lines. We found that the T94A mutant of L-FABP lowered FFA uptake but had no effect on FFA efflux. L-FABP T94A-expressing cells showed decreased triglyceride content and increased cholesterol accumulation compared to the wild-type control for cells incubated with an FFA mixture (oleate: palmitate, 2:1 ratio). In conclusion, our study provided additional indications of the functional relevance of the L-FABP T94A SNP in hepatic fatty acid and lipid metabolism in humans.

  11. Liver Transplant (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  12. Exercise intolerance in Glycogen Storage Disease Type III

    DEFF Research Database (Denmark)

    Preisler, Nicolai; Pradel, Agnès; Husu, Edith


    experience exercise intolerance due to insufficient carbohydrate oxidation in skeletal muscle. Six patients aged 17-36-years were studied. We determined VO 2peak (peak oxygen consumption), the response to forearm exercise, and the metabolic and cardiovascular responses to cycle exercise at 70% of VO 2peak......Myopathic symptoms in Glycogen Storage Disease Type IIIa (GSD IIIa) are generally ascribed to the muscle wasting that these patients suffer in adult life, but an inability to debranch glycogen likely also has an impact on muscle energy metabolism. We hypothesized that patients with GSD IIIa can...... caused exercise intolerance with dynamic skeletal muscle symptoms (excessive fatigue and muscle pain), and hypoglycemia in 4 subjects. In this study we combined anaerobic and aerobic exercise to systematically study skeletal muscle metabolism and exercise tolerance in patients with GSD IIIa. Exercise...

  13. Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle

    DEFF Research Database (Denmark)

    Højlund, Kurt; Beck-Nielsen, Henning


    expression analysis and proteomics have pointed to abnormalities in mitochondrial oxidative phosphorylation and cellular stress in muscle of type 2 diabetic subjects, and recent work suggests that impaired mitochondrial activity is another early defect in the pathogenesis of type 2 diabetes. This review...... will discuss the latest advances in the understanding of the molecular mechanisms underlying insulin resistance in human skeletal muscle in type 2 diabetes with focus on possible links between impaired glycogen synthase activity and mitochondrial dysfunction....

  14. Dietary Management of the Ketogenic Glycogen Storage Diseases

    Directory of Open Access Journals (Sweden)

    Kaustuv Bhattacharya MBBS, MRCPCH, FRACP, MD


    Full Text Available The glycogen storage diseases (GSDs comprise a group of rare inherited disorders of glycogen metabolism. The hepatic glycogenolytic forms of these disorders are typically associated with hypoglycemia and hepatomegaly. For GSD I, secondary metabolic disturbances include fasting hyperlactatemia, hyperuricemia, and hyperlipidemia. Glycogen storage disease III is caused by reduced activity of the debrancher enzyme, GSD VI by phosphorylase, and GSD IX by phosphorylase kinase. It has often been reported that the non-GSD I group of disorders have a benign course. However, myopathy, cardiomyopathy, and cirrhosis have been reported significant clinical morbidities associated with GSD III and IX in particular. There have been a range of reports indicating high-protein diets, high-fat diets, medium chain triglyceride (MCT, modified Atkins diet, and therapeutic ketones as rescuing severe phenotypes of GSD III in particular. The etiology of these severe phenotypes has not been defined. Cases presented in this report indicate potential harm from excessive simple sugar use in GSD IX C. Review of the literature indicates that most interventions have reduced the glycemic load and provide alternate substrates for energy in rescue situations. Prevention of complications is most likely to occur with a mixed balanced low glycemic index diet potentially with relative increases in protein.

  15. Mechanisms limiting glycogen storage in muscle during prolonged insulin stimulation

    DEFF Research Database (Denmark)

    Richter, Erik; Hansen, S A; Hansen, B F


    increased muscle glycogen concentrations to maximal values 2, 3, and 3.5 times above normal fed levels in fast-twitch white, slow-twitch red, and fast-twitch red fibers, respectively. Glucose uptake decreased (mean +/- SE) from 34.9 +/- 1.2 mumol.g-1.h-1 at 0 h to 7.5 +/- 0.7 after 7 h of perfusion. During......The extent to which muscle glycogen concentrations can be increased during exposure to maximal insulin concentrations and abundant glucose was investigated in the isolated perfused rat hindquarter preparation. Perfusion for 7 h in the presence of 20,000 microU/ml insulin and 11-13 mM glucose...... the perfusion muscle glycogen synthase activity decreased and free intracellular glucose and glucose 6-phosphate increased indicating that glucose disposal was impaired. However, glucose transport as measured by the uptake of 3-O-[14C]methyl-D-glucose was also markedly decreased after 5 and 7 h of perfusion...

  16. Glycogen synthesis after road cycling in the fed state. (United States)

    Reinert, A; Slivka, D; Cuddy, J; Ruby, B


    The purpose of this study was to determine the effects of a recovery beverage immediately after exercise on rates of muscle glycogen resynthesis in response to road cycling when nutritional supplementation was supplied during exercise and a solid meal was served two hours after exercise. Eight trained male cyclists, (25+/-4 years, 69.3+/-5.2 kg, VO2 peak=4.5+/-0.4 L.min(-1)) performed two 62 km outdoor training rides in a double-blind, randomized cross-over experiment. Subjects received a food bar and a commercial sport drink during each ride. A recovery beverage (40 g CHO+20 g PRO) or a placebo (PL) was administered 30 min post-exercise. At 2 h post-exercise, a solid meal was provided for both trials. There was no difference between trials at any time point for glycogen (140+/-9, 56+/-8, and 70+/-8 wt.(-1).hr.(-1) for pre, post, and 4 h post, respectively). The addition of a supplemental recovery beverage ingested soon after exercise did not significantly increase the rate of muscle glycogen resynthesis after 4 h of recovery when nutritional supplementation is provided during exercise and a meal is consumed 2 h after exercise.

  17. Mice fed a high-fat diet supplemented with resistant starch display marked shifts in the liver metabolome concurrent with altered gut bacteria (United States)

    High-amylose maize resistant starch type 2 (HAMRS2) is a fermentable dietary fiber known to alter the gut milieu, including the gut microbiota, which may explain reported effects of resistant starch to ameliorate obesity-associated metabolic dysfunction. Our working hypothesis is that HAMRS2-induced...

  18. Maternal nutrition during the first 50 days of gestation alters expression of histone and histone modifying genes in bovine fetal liver (United States)

    During the first 50 d of gestation, organogenesis is taking place. Nutritional influences during this time may alter the mammalian phenotype through affecting gene regulatory mechanisms, thus “programming” potential susceptibilities to chronic disease and metabolic issues into the animal’s genome. W...

  19. Protection by pentoxifylline of diazinon-induced toxic stress in rat liver and muscle. (United States)

    Amirkabirian, Nasim; Teimouri, Fatemeh; Esmaily, Hadi; Mohammadirad, Azadeh; Aliahmadi, Atousa; Abdollahi, Mohammad


    ABSTRACT The effects of diazinon, pentoxifylline, and their combination therapy on plasma glucose, the key enzymes of glycogenolysis and gluconeogenesis, and oxidative stress were studied in rat liver and muscle. Oxidative stress was determined by measuring the concentration of lipid peroxides and assessing total antioxidant capacity. Diazinon (60 mg/kg) and pentoxifylline (100 mg/kg) were administrated by gavage. Administration of diazinon increased blood glucose, hepatic glycogen phosphorylase (GP), and phosphoenol pyruvate carboxykinase (PEPCK) by 160.65%, 117.2%, and 93.5%, respectively, while it decreased plasma cholinesterase (ChE) by 53.82%. Diazinon-induced oxidative stress was demonstrated by decreased total antioxidant capacity and enhanced lipid peroxidation by 52.61% and 280% in liver and by 40.02% and 46.6% in muscle, respectively. Pentoxifylline increased plasma glucose, hepatic GP, and PEPCK by 98.65%, 60%, and 79.86%, respectively, while it did not change plasma ChE, liver and muscle lipid peroxides, and total antioxidant capacity. In combination therapy, pentoxifylline did not alter diazinon-induced change in muscle GP activity but restored a diazinon-induced increase in hepatic and muscle lipid peroxides by 39.18% and 42.35%, respectively. Pentoxifylline also recovered a diazinon-induced decrease in liver and muscle total antioxidant capacity and plasma ChE by 122.33%, 56.44%, and 115.62%, respectively. Pentoxifylline did not affect diazinon-induced hyperglycemia and increased hepatic GP and PEPCK or muscle GP activities. It is concluded that pentoxifylline is a good choice for the alleviation of acute toxic stress of diazinon in muscle and liver and ChE in plasma, while it is unable to recover diazinon-induced hyperglycemia.

  20. Altered hepatic gene expression profiles associated with improved fatty liver, insulin resistance, and intestinal permeability after hydroxypropyl methylcellulose (HPMC) supplementation in diet-induced obese mice. (United States)

    Kim, Hyunsook; Bartley, Glenn E; Young, Scott A; Seo, Kun-Ho; Yokoyama, Wallace


    The effect of hydroxypropyl methylcellulose (HPMC) on hepatic gene expression was analyzed by exon microarray and real-time PCR from livers of diet-induced obese (DIO) mice fed a high-fat (HF) diet supplemented with either 6% HPMC or 6% microcrystalline cellulose (MCC). HPMC-fed mice exhibited significantly reduced body weight gain (55% lower compared to MCC), liver weight (13%), plasma LDL-cholesterol concentration (45%), and HF diet-increased intestinal permeability (48%). HPMC significantly reduced areas under the curve for 2 h insulin and glucose responses, indicating enhanced insulin sensitivity and glucose metabolism. HPMC up-regulated hepatic genes related to fatty acid oxidation, cholesterol and bile acid synthesis, and cellular activation of glucocorticoid (bile acid recycling) and down-regulated genes related to oxidative stress, triglyceride synthesis, and polyunsaturated fatty acid elongation. In conclusion, HPMC consumption ameliorates the effects of a HF diet on intestinal permeability, insulin resistance, hepatic lipid accumulation, glucocorticoid-related bile acid recycling, oxidative stress, and weight gain in DIO mice.

  1. Crystal structure of glycogen debranching enzyme and insights into its catalysis and disease-causing mutations. (United States)

    Zhai, Liting; Feng, Lingling; Xia, Lin; Yin, Huiyong; Xiang, Song


    Glycogen is a branched glucose polymer and serves as an important energy store. Its debranching is a critical step in its mobilization. In animals and fungi, the 170 kDa glycogen debranching enzyme (GDE) catalyses this reaction. GDE deficiencies in humans are associated with severe diseases collectively termed glycogen storage disease type III (GSDIII). We report crystal structures of GDE and its complex with oligosaccharides, and structure-guided mutagenesis and biochemical studies to assess the structural observations. These studies reveal that distinct domains in GDE catalyse sequential reactions in glycogen debranching, the mechanism of their catalysis and highly specific substrate recognition. The unique tertiary structure of GDE provides additional contacts to glycogen besides its active sites, and our biochemical experiments indicate that they mediate its recruitment to glycogen and regulate its activity. Combining the understanding of the GDE catalysis and functional characterizations of its disease-causing mutations provides molecular insights into GSDIII.

  2. Hemodynamics alterations during orthotopic liver experimental transplantation in pigs Alterações hemodinâmicas durante transplante hepático ortotópico experimental em suínos

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    Orlando Jorge Martins Torres


    Full Text Available PURPOSE: To describe the hemodynamics alterations during orthotopic liver transplantation in pigs. METHODS: In the period from April 2004 to December 2005, forty-four female Landrace pigs, weighting between 32 and 38 Kg were undergone to orthotopic liver transplantation. The animals were divided into two groups, donor and recipient pairs, which received whole liver grafts. The surgical procedure was divided into four parts: harvested, back-table, hepatectomy of the recipient and implantation. We analyze heart rate, blood gas, mean systemic arterial pressure (MAP-mmHg, central venous pressure, pH, Na-, K+, Cl-, Ca+ and urinary output. RESULTS: The mean anhepatic time was 69 min, cold ischemia was 252.2 min and back-table was 56.6 min. Blood pressure and heart rate dropped significantly during anhepatic phase and after revascularization. Blood gas and electrolytes alterations were observed during anhepatic and reperfusion phases. Although alterations were noted during these phases, the hemodynamic status was recovered and stabilized in the end of the surgery. CONCLUSIONS: Simplified technique of liver transplant was achieved and description of hemodynamic alterations was possible in pigs.OBJETIVO: Descrever as alterações hemodinâmicas que ocorrem durante o transplante hepático ortotópico experimental em suínos. MÉTODOS: No período de abril de 2004 a dezembro de 2005, quarenta porcos da raça Landrace, fêmeas, pesando entre 32 e 38Kg foram submetidos a transplante hepático ortotópico. Os animais foram divididos em dois grupos, doador e receptor, estes receberam enxerto total. O procedimento cirúrgico foi dividido em captação, cirurgia de banco, hepatectomia do receptor e implante do enxerto. Analisamos a freqüência cardíaca, gasometria, pressão arterial média (PAM-mmHg, pressão venosa central, pH, Na-, K+, Cl-, Ca+, e débito urinário. RESULTADOS: O tempo médio de fase anepática foi de 69 minutos, tempo de isquemia fria foi

  3. Alterations of pyrimidine and nucleic acid synthesis during adaptive growth of liver induced by nafenopin, a peroxisome proliferator. An in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Seifert, J.; Mostecka, H. (Institute of Pharmacology, Prague (Czechoslovakia))


    The de novo synthesis of pyrimidine nucleotides in the rat liver after administration of nafenopin (NFP) was studied with the aid of (14C)orotic acid; the utilization of preformed nucleosides (salvage pathways) was followed using the (14C)cytidine and (14C)thymidine. A single dose (400 mg/kg) as well as repeated doses (100 mg/kg/day) of NFP increased the concentration of the cytidine and uridine components of the acid-soluble extract (ASE) of rat liver. Increase in the concentration of the cytidine components preceded the increase in the uridine components. The uptake of (14C)cytidine by the liver of rats that had been given a single dose of NFP was observed 24 h after the administration of the drug and a decrease followed after this period. The specific activity of RNA and DNA cytosine paralleled the changes of the specific activity of ASE. A single dose of NFP had no marked effect on the uptake of (14C)orotic acid. The specific activity of the uridine components of ASE remained unaltered for 2 days. After this period it decreased because of an increase in the amount of the soluble uridine components. A mild drop of the specific activity of cytidine components of ASE occurred on the second day, the total radioactivity of cytidine components increased 24 h after the administration of NFP. The specific activity of DNA pyrimidines was markedly increased 24 h after administration of the drug. On the fourth day the specific activity of DNA cytosine in the experimental group was the same as in the control group, whereas the activity of DNA thymine was lower. Following repeated administration of NFP (100 mg/kg/day) a decreased uptake of (14C)orotic acid was observed; its utilization for the synthesis of the uridine components of ASE, expressed as total radioactivity of soluble uridine components, was continuously suppressed. No changes in the specific activity of cytidine components were observed.

  4. Alterations of pyrimidine and nucleic acid synthesis during adaptive growth of liver induced by nafenopin, a peroxisome proliferator. An in vivo study. (United States)

    Seifert, J; Mostecká, H


    The de novo synthesis of pyrimidine nucleotides in the rat liver after administration of nafenopin (NFP) was studied with the aid of [14C]orotic acid; the utilization of preformed nucleosides (salvage pathways) was followed using the [14C]cytidine and [14C]thymidine. A single dose (400 mg/kg) as well as repeated doses (100 mg/kg/day) of NFP increased the concentration of the cytidine and uridine components of the acid-soluble extract (ASE) of rat liver. Increase in the concentration of the cytidine components preceded the increase in the uridine components. The uptake of [14C]cytidine by the liver of rats that had been given a single dose of NFP was observed 24 h after the administration of the drug and a decrease followed after this period. The specific activity of RNA and DNA cytosine paralleled the changes of the specific activity of ASE. A single dose of NFP had no marked effect on the uptake of [14C]orotic acid. The specific activity of the uridine components of ASE remained unaltered for 2 days. After this period it decreased because of an increase in the amount of the soluble uridine components. A mild drop of the specific activity of cytidine components of ASE occurred on the second day, the total radioactivity of cytidine components increased 24 h after the administration of NFP. The specific activity of DNA pyrimidines was markedly increased 24 h after administration of the drug. On the fourth day the specific activity of DNA cytosine in the experimental group was the same as in the control group, whereas the activity of DNA thymine was lower. Following repeated administration of NFP (100 mg/kg/day) a decreased uptake of [14C]orotic acid was observed; its utilization for the synthesis of the uridine components of ASE, expressed as total radioactivity of soluble uridine components, was continuously suppressed. No changes in the specific activity of cytidine components were observed. The specific activity of DNA cytosine and thymine was distributed unevenly

  5. [Beneficial effect of swimming in thermal waters on muscle glycogen depletion]. (United States)

    D'Amelio, G; Boninsegna, A; Calzavara, M; Bertolini, M


    The effect of swimming in the termal water on muscle glycogen stores was studied. After 30 min the muscle glycogen results in a diminution, but it is not depleted. On the contrary, 30 min of swimming in normal water results in a depletion of muscle glycogene stores. The glycemic homeostasis is well maintained in thermal water, and hypoglicemia occurs only after swimming in normal water.

  6. Free glycogen in vaginal fluids is associated with Lactobacillus colonization and low vaginal pH.

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    Paria Mirmonsef

    Full Text Available Lactobacillus dominates the lower genital tract microbiota of many women, producing a low vaginal pH, and is important for healthy pregnancy outcomes and protection against several sexually transmitted pathogens. Yet, factors that promote Lactobacillus remain poorly understood. We hypothesized that the amount of free glycogen in the lumen of the lower genital tract is an important determinant of Lactobacillus colonization and a low vaginal pH.Free glycogen in lavage samples was quantified. Pyrosequencing of the 16S rRNA gene was used to identify microbiota from 21 African American women collected over 8-11 years.Free glycogen levels varied greatly between women and even in the same woman. Samples with the highest free glycogen had a corresponding median genital pH that was significantly lower (pH 4.4 than those with low glycogen (pH 5.8; p<0.001. The fraction of the microbiota consisting of Lactobacillus was highest in samples with high glycogen versus those with low glycogen (median = 0.97 vs. 0.05, p<0.001. In multivariable analysis, having 1 vs. 0 male sexual partner in the past 6 months was negatively associated, while BMI ≥30 was positively associated with glycogen. High concentrations of glycogen corresponded to higher levels of L. crispatus and L. jensenii, but not L. iners.These findings show that free glycogen in genital fluid is associated with a genital microbiota dominated by Lactobacillus, suggesting glycogen is important for maintaining genital health. Treatments aimed at increasing genital free glycogen might impact Lactobacillus colonization.


    Directory of Open Access Journals (Sweden)

    Nirupama R.


    Full Text Available Acute stress induced alterations in the activity levels of rate limiting enzymes and concentration of intermediates of different pathways of carbohydrate metabolism have been studied. Adult male Wistar rats were restrained (RS for 1 h and after an interval of 4 h they were subjected to forced swimming (FS exercise and appropriate controls were maintained. Five rats were killed before the commencement of the experiment (initial controls, 5 control and equal number of stressed rats were killed 2 h after RS and remaining 5 rats in each group were killed 4 h after FS. There was a significant increase in the adrenal 3β- hydroxy steroid dehydrogenase activity following RS, which showed further increase after FS compared to controls and thereby indicated stress response of rats. There was a significant increase in the blood glucose levels following RS which showed further increase and reached hyperglycemic condition after FS. The hyperglycemic condition due to stress was accompanied by significant increases in the activities of glutamate- pyruvate transaminase, glutamate- oxaloacetate transaminase, glucose -6- phosphatase and lactate dehydrogenase and significant decrease in the glucose -6- phosphate dehydrogenase and pyruvate dehydrogenase activities, whereas pyruvate kinase activity did not show any alteration compared to controls. Further, the glycogen and total protein contents of the liver were decreased whereas those of pyruvate and lactate showed significant increase compared to controls after RS as well as FS.The results put together indicate that acute stress induced hyperglycemia results due to increased gluconeogenesis and glycogenolysis without alteration in glycolysis. The study first time reveals that after first acute stress exposure, the subsequent stressful experience augments metabolic stress response leading to hyperglycemia. The results have relevance to human health as human beings are exposed to several stressors in a day and

  8. Noninvasive measurement of brain glycogen by nuclear magnetic resonance spectroscopy and its application to the study of brain metabolism. (United States)

    Tesfaye, Nolawit; Seaquist, Elizabeth R; Oz, Gülin


    Glycogen is the reservoir for glucose in the brain. Beyond the general agreement that glycogen serves as an energy source in the central nervous system, its exact role in brain energy metabolism has yet to be elucidated. Experiments performed in cell and tissue culture and animals have shown that glycogen content is affected by several factors, including glucose, insulin, neurotransmitters, and neuronal activation. The study of in vivo glycogen metabolism has been hindered by the inability to measure glycogen noninvasively, but, in the past several years, the development of a noninvasive localized (13) C nuclear magnetic resonance (NMR) spectroscopy method has allowed the study of glycogen metabolism in the conscious human. With this technique, (13) C-glucose is administered intravenously, and its incorporation into and washout from brain glycogen is tracked. One application of this method has been to the study of brain glycogen metabolism in humans during hypoglycemia: data have shown that mobilization of brain glycogen is augmented during hypoglycemia, and, after a single episode of hypoglycemia, glycogen synthesis rate is increased, suggesting that glycogen stores rebound to levels greater than baseline. Such studies suggest that glycogen may serve as a potential energy reservoir in hypoglycemia and may participate in the brain's adaptation to recurrent hypoglycemia and eventual development of hypoglycemia unawareness. Beyond this focused area of study, (13) C NMR spectroscopy has a broad potential for application in the study of brain glycogen metabolism and carries the promise of a better understanding of the role of brain glycogen in diabetes and other conditions.

  9. Dietary fat source affects metabolism of fatty acids in pigs as evaluated by altered expression of lipogenic genes in liver and adipose tissues

    DEFF Research Database (Denmark)

    Duran-Montge, P; Theil, Peter Kappel; Lauridsen, Charlotte


    Little is known about pig gene expressions related to dietary fatty acids (FAs) and most work have been conducted in rodents. The aim of this study was to investigate how dietary fats regulate fat metabolism of pigs in different tissues. Fifty-six crossbred gilts (62 ± 5.2 kg BW) were fed one...... differently in liver, fat and muscles tissues....... of seven dietary treatments (eight animals per treatment): a semi-synthetic diet containing a very low level of fat (no fat (NF)) and six fat-supplemented diets (ca. 10%) based on barley and soybean meal. The supplemental fat sources were tallow (T), high-oleic sunflower oil (HOSF), sunflower oil (SFO...

  10. Use of high pressure liquid chromatography to study chemically induced alterations in the pattern of benzo(a)pyrene metabolism. [Rat liver microsomes

    Energy Technology Data Exchange (ETDEWEB)

    Freudenthal, R.I.; Leber, A.P.; Emmerling, D.; Clarke, P.


    The metabolism of radiolabeled benzo(a)pyrene (BP) by control, 3-methylcholanthrene (3-MC) induced and 1,1,1-trichloropropene-2,3-oxide (TCPO)-inhibited rat liver microsomes was measured using fluorescence, radiometric, and high-pressure liquid chromatographic (HPLC) assays. Significant differences in the total measurable metabolism of BP by the three microsomal enzyme incubations resulted from the use of the three assay procedures. Appreciable differences in the concentration of the metabolite fractions after 3-MC induction and TCPO inhibition are clearly demonstrated. NMR analysis revealed that while the 3-hydroxy-BP fraction is greater than 90 percent pure, the 9-hydroxy fraction contains a number of metabolites having essentially identical retention times.

  11. Streptococcus pneumoniae-induced pneumonia and Citrobacter rodentium-induced gut infection differentially alter vitamin A concentrations in the lung and liver of mice. (United States)

    Restori, Katherine H; McDaniel, Kaitlin L; Wray, Amanda E; Cantorna, Margherita T; Ross, A Catharine


    In the developing world, vitamin A (VA) deficiency is endemic in populations that are also at great risk of morbidity and mortality because of pneumococcal pneumonia and enteric infections. To better understand how lung and gastrointestinal pathogens affect VA status, we assessed VA concentrations in serum, lung, and liver during an invasive pneumonia infection induced by Streptococcus pneumoniae serotype 3, and a noninvasive gut infection induced by Citrobacter rodentium, in vitamin A-adequate (VAA) and vitamin A-deficient (VAD) mice. For pneumonia infection, mice were immunized with pneumococcal polysaccharide serotype 3 (PPS3), or not (infected-control), 5 d prior to intranasal inoculation with S. pneumoniae. Two days post-inoculation, immunization was protective against systemic infection regardless of VA status as PPS3 immunization decreased bacteremia compared with infected-control mice (P pneumonia had less effect on VA status than gastrointestinal infection, predominantly owing to reduced hepatic VA storage at the peak of gut infection.

  12. In vivo Alterations in Glutathione-Related Processes, Lipid Peroxidation, and Cholinesterase Enzyme Activities in the Liver of Diazinon-Exposed Oreochromis niloticus. (United States)

    Uner, Nevin; Sevgiler, Yusuf; Durmaz, Hülya; Piner, Petek


    ABSTRACT Although its usage is partially banned in developed countries, organophosphate (OP) pesticide diazinon finds extensive agricultural application in our country (Turkey). This study was conducted to evaluate the effects of diazinon on total glutathione (tGSH), GSH-related enzymes, cholinesterase (ChE) enzyme activities, and lipid peroxidation in the liver of Oreochromis niloticus, a freshwater fish, as a model organism. Fish were exposed to 0.1, 1, and 2 mg/L sublethal concentrations of diazinon for 1, 7, 15, and 30 days. Total GSH levels, GSH-related enzyme and ChE-specific activities, and malondialdehyde (MDA) levels were analyzed using spectrophotometric methods. tGSH levels are decreased at 1 day, while they were increased in the long-term period. GSH-related enzyme activities are affected by diazinon exposure, except glutathione reductase (GR; EC Diazinon displayed an oxidative stress-inducing potential and it increased lipid peroxidation. Similar inhibition levels were observed in acetylcholinesterase (AChE; EC and butyrylcholinesterase (BChE; EC enzyme activities, and these inhibitions were not dose dependent. ChE inhibition-related oxidative stress was observed using its correlation with elevated tGSH levels and increased glutathione S-transferase (GST; EC enzyme activities; that reflects the diazinon-induced oxidative stress in the liver of O. niloticus. According to the results of the present study, tGSH level and GST-specific activity are suitable for reflecting the toxic effects of diazinon in fish.

  13. Keap1-knockdown decreases fasting-induced fatty liver via altered lipid metabolism and decreased fatty acid mobilization from adipose tissue.

    Directory of Open Access Journals (Sweden)

    Jialin Xu

    Full Text Available AIMS: The purpose of this study was to determine whether Nrf2 activation, via Keap1-knockdown (Keap1-KD, regulates lipid metabolism and mobilization induced by food deprivation (e.g. fasting. METHODS AND RESULTS: Male C57BL/6 (WT and Keap1-KD mice were either fed ad libitum or food deprived for 24 hours. After fasting, WT mice exhibited a marked increase in hepatic lipid accumulation, but Keap1-KD mice had an attenuated increase of lipid accumulation, along with reduced expression of lipogenic genes (acetyl-coA carboxylase, stearoyl-CoA desaturase-1, and fatty acid synthase and reduced expression of genes related to fatty acid transport, such as fatty acid translocase/CD36 (CD36 and Fatty acid transport protein (FATP 2, which may attribute to the reduced induction of Peroxisome proliferator-activated receptor (Ppar α signaling in the liver. Additionally, enhanced Nrf2 activity by Keap1-KD increased AMP-activated protein kinase (AMPK phosphorylation in liver. In white adipose tissue, enhanced Nrf2 activity did not change the lipolysis rate by fasting, but reduced expression of fatty acid transporters--CD36 and FATP1, via a PPARα-dependent mechanism, which impaired fatty acid transport from white adipose tissue to periphery circulation system, and resulted in increased white adipose tissue fatty acid content. Moreover, enhanced Nrf2 activity increased glucose tolerance and Akt phosphorylation levels upon insulin administration, suggesting Nrf2 signaling pathway plays a key role in regulating insulin signaling and enhanced insulin sensitivity in skeletal muscle. CONCLUSION: Enhanced Nrf2 activity via Keap1-KD decreased fasting-induced steatosis, pointing to an important function of Nrf2 on lipid metabolism under the condition of nutrient deprivation.

  14. Acute phenanthrene toxicity to juvenile diploid and triploid African catfish (Clarias gariepinus): Molecular, biochemical, and histopathological alterations. (United States)

    Karami, Ali; Romano, Nicholas; Hamzah, Hazilawati; Simpson, Stuart L; Yap, Chee Kong


    Information on the biological responses of polyploid animals towards environmental contaminants is scarce. This study aimed to compare reproductive axis-related gene expressions in the brain, plasma biochemical responses, and the liver and gill histopathological alterations in diploid and triploid full-sibling juvenile African catfish (Clarias gariepinus). Fish were exposed for 96 h to one of the two waterborne phenanthrene (Phe) concentrations [mean measured (SD): 6.2 (2.4) and 76 (4.2) μg/L]. In triploids, exposure to 76 μg/L Phe increased mRNA level of fushi tarazu-factor 1 (ftz-f1). Expression of tryptophan hydroxylase2 (tph2) was also elevated in both ploidies following the exposure to 76 μg/L Phe compared to the solvent control. In triploids, 76 μg/L Phe increased plasma alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels compared to the other Phe-exposed group. It also elevated lactate and glucose contents relative to the other groups. In diploids, however, biochemical biomarkers did not change. Phenanthrene exposures elevated glycogen contents and the prevalence of histopathological lesions in the liver and gills of both ploidies. This study showed substantial differences between diploids and triploids on biochemical and molecular biomarker responses, but similar histopathological alterations following acute Phe exposures.

  15. Fat metabolism is regulated by altered gene expression of lipogenic enzymes and regulatory factors in liver and adipose tissue but not in semimembranosus muscle of pigs during the fattening period. (United States)

    Duran-Montgé, P; Theil, P K; Lauridsen, C; Esteve-Garcia, E


    It has been shown previously that lipid metabolism is regulated by fatty acids (FA) and that thyroid hormones are important regulators of energy metabolism. The effects of weight, dietary fat level and dietary FA profile on thyroid hormone levels and expression of lipogenic genes and tissue FA composition were studied. Sixty-one crossbred gilts weighing 62 ± 5.2 kg BW average were either slaughtered at the beginning of the trial (n = 5) or fed one of seven diets (n = 8 pigs per diet): a semi-synthetic diet formulated to contain a very low level of fat (NF) and six diets based on barley-soybean meal supplemented with approximately 10% fat of different origin and slaughtered at 100 kg BW. The supplemental fats were tallow, high-oleic sunflower oil, sunflower oil (SFO), linseed oil, fat blend (55% tallow, 35% sunflower oil, 10% linseed oil) and fish oil blend (40% fish oil, 60% linseed oil). In general, the dietary FA profiles altered the FA composition of liver, semimembranosus muscle and adipose tissues. Pigs fed the NF diet had the highest free and total triiodothyronine (T3) values followed by pigs fed SFO. Total T3 levels were higher in pigs at 60 kg than in pigs at 100 kg. Correlations between thyroid hormones and genes encoding enzymes of fat synthesis in adipose tissue (acetyl CoA carboxylase (ACACA), fatty acid synthase and stearoyl CoA desaturase (SCD)) and the large differences in expression of lipogenic genes at different weights (60 and 100 kg BW), suggest a role for thyroid hormones and for T3, in particular, in regulating whole animal fat metabolism, with effects brought about by altered expression of lipogenic genes. Liver sterol receptor element binding protein-1 (SREBP1) mRNA content was affected by dietary treatment (P influence on mRNA abundance of genes related with lipid metabolism than diet and tissue FA composition. In the pig, FA synthesis appear to be of greater magnitude in adipose tissue than in the liver as suggested by the higher

  16. Liver biopsy (United States)

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  17. [Enzymology of the liver in hydatidosis]. (United States)

    Stoyanov, G; Yaramov, N; Damianov, N; Bekova, P


    A research has been conducted studying the enzyme system of the liver using biopsy material of the organ taken during the operation from patients with echinococcosis and an experiment with infantile white mice. It is proved reduction of the activity of the alkaline and acid phosphatase as well as of the glycogen along with their progressive reduction during the disease progression. Compared with the other researches--histological and by electronic microscope, etc.--there are proved great hepatic damages due to the echinococcosis that have caused change of the treatment tactics: large preoperative period, including reconstructions of the glycogenic depot in the organ, gentle to the liver anesthesia, exact postoperative reanimation. Very good results have been obtained concerning the postoperative complications and operative mortality: observing the developed acute liver insufficiency--in the past the mortality has been 27.60% throughout 2.49% of the operated patients; after those measures the acute liver insufficiency after this kind of operation is seen just once (0.40% of the patients) and the mortality is 0.


    Directory of Open Access Journals (Sweden)

    Eugênio Gonçalves de Araújo


    Full Text Available Numerous papers report hepatic alterations in ruminants fed with Brachiaria spp. The aim of this study was to verify whether the ingestion of Andropogon gayanus or Brachiaria (B. brizantha and B. decumbens produces microscopic alterations in the liver of cattle. By histological examination was characterized the hepatic injury, and determined the amount and localization of foamy macrophages in the liver and mesenteric and scapular lymphonodes. Those changes were correlated with live weight gains of the animals. Forty bulls divided into two groups of twenty were grazing, from weaning to slaughter, in Brachiaria spp or A. gayanus pastures. In the slaughterhouse, fragments of liver and mesenteric and scapular lymphonodes were collected. Results showed, in both groups, macro and microvacuolar degeneration of hepatocytes, mainly in the periacinar region. The animals fed on Brachiaria spp pastures revealed larger quantity of foamy macrophages in the hepatic parenchyma and mesenteric lymphonodes. There was a negative correlation between the number of foamy macrophages in the liver and in mesenteric lymphonodes with the live weight gain, regardless of the type of ingested grass. In the lymph nodes, the highest macrophage concentrations were in the cortical zone, followed by the paracortical zone. The mesenteric lymphonodes showed a higher amount of foam cells than the liver.

    KEY WORDS: Colangiohepatitis, foamy cells, saponins, sporidesmin, tropical grasses.

    Diversos trabalhos relatam a presença de alterações hepáticas em ruminantes alimentados com Brachiaria spp, em casos espontâneos e/ou induzidos de fotossensibilização hepatógena. O objetivo deste trabalho foi verificar se o tipo de capim ingerido provoca alteração microscópica no fígado de bovinos. Foi caracterizada a lesão hepática, quantificados e localizados os macrófagos espumosos no fígado e linfonodos e as alterações correlacionadas com o peso dos

  19. Sodium valproate increases the brain isoform of glycogen phosphorylase: looking for a compensation mechanism in McArdle disease using a mouse primary skeletal-muscle culture in vitro

    Directory of Open Access Journals (Sweden)

    Noemí de Luna


    Full Text Available McArdle disease, also termed ‘glycogen storage disease type V’, is a disorder of skeletal muscle carbohydrate metabolism caused by inherited deficiency of the muscle-specific isoform of glycogen phosphorylase (GP-MM. It is an autosomic recessive disorder that is caused by mutations in the PYGM gene and typically presents with exercise intolerance, i.e. episodes of early exertional fatigue frequently accompanied by rhabdomyolysis and myoglobinuria. Muscle biopsies from affected individuals contain subsarcolemmal deposits of glycogen. Besides GP-MM, two other GP isoforms have been described: the liver (GP-LL and brain (GP-BB isoforms, which are encoded by the PYGL and PYGB genes, respectively; GP-BB is the main GP isoform found in human and rat foetal tissues, including the muscle, although its postnatal expression is dramatically reduced in the vast majority of differentiated tissues with the exception of brain and heart, where it remains as the major isoform. We developed a cell culture model from knock-in McArdle mice that mimics the glycogen accumulation and GP-MM deficiency observed in skeletal muscle from individuals with McArdle disease. We treated mouse primary skeletal muscle cultures in vitro with sodium valproate (VPA, a histone deacetylase inhibitor. After VPA treatment, myotubes expressed GP-BB and a dose-dependent decrease in glycogen accumulation was also observed. Thus, this in vitro model could be useful for high-throughput screening of new drugs to treat this disease. The immortalization of these primary skeletal muscle cultures could provide a never-ending source of cells for this experimental model. Furthermore, VPA could be considered as a gene-expression modulator, allowing compensatory expression of GP-BB and decreased glycogen accumulation in skeletal muscle of individuals with McArdle disease.

  20. Histopathological alterations in the liver and intestine of Nile tilapia Oreochromis niloticus exposed to long-term sublethal concentrations of cadmium chloride (United States)

    Younis, Elsayed; Abdel-Warith, Abdel-Wahab; Al-Asgah, Nasser; Ebaid, Hossam


    Fingerlings of Nile tilapia Oreochromis niloticus were exposed to 1.68, 3.36, and 5.04 mg/L cadmium (as CdCl2), which represent 10%, 20%, and 30% of their previously determined 96-h LC50. After exposure for 20 days, sections of the liver and intestine of treated fish were examined histologically. Histopathological changes varied from slight to severe structural modification, depending on the exposure concentration. The hepatic tissues of fish exposed to 10% LC50 showed markedly increased vacuolation of the hepatocytes and coarse granulation of their cytoplasm. Abundant erythrocytic infiltration among the hepatocytes was observed in fish exposed to 20% LC50. In the intestinal tissues of fish exposed to all doses, goblet cells proliferated and were greatly increased in size, the longitudinal muscularis mucosa was disturbed and, in the crypts of the sub-mucosal layer, apoptosis increased, indicated by large numbers of degenerated nuclei. Large numbers of inflammatory cells and dilated blood vessels were observed in the intestine of the group treated with 30% LC50.

  1. Pediatric liver transplantation in 31 consecutive children

    Institute of Scientific and Technical Information of China (English)

    SHEN Zhong-yang; WANG Zi-fa; ZHU Zhi-jun; ZANG Yun-jin; ZHENG Hong; DENG Yong-lin; PAN Cheng; CHEN Xin-guo


    Background Although liver transplantation has become a standard therapy for end-stage liver diseases, the experience of pediatric liver transplantation is limited in China. In this article we report our experience in pediatric liver transplantation, and summarize its characters in their indications, surgical techniques, and postoperative managements. Methods Thirty-one children (≤18 years old) underwent liver transplantation in our centers. The mean age at transplantation was 12.4 years old (ranged from 5 months to 18 years) with 7 children being less than 4 years of age at transplantation. The most common diagnosis of patients who underwent liver transplantation were biliary atresia, Wilson's disease, primary biliary cirrhosis, glycogen storage disease, hepatoblastoma, urea cycle defects, fulminant hepatic failure, etc. The surgical procedures included 12 standard (without venovenous bypass), 6 pigyback, 6 reduced-size, 3 split, 3 living donor liver transplantation, and 1 Domino liver transplantation. The triple-drug (FK506, steroid, and mycophenolate mofetil) immunosuppressive regimen was used in most of patients. Patients were followed up for a mean of 21.8 months. Results Five of the 31 patients died during perioperative time; mortality rate was 16.1%. The reasons of death were infections, primary non-function, heart failure, and hypovolemic shock. Postoperative complications in 10 patients included biliary leakage, acute rejection, abdominal infection, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and pulmonary infection. Overall patient cumulative survival rate at 1-, 3-, and 5-year was 78.1%, 62.6%, 62.6%, respectively.Conclusions The most common indications of pediatric liver transplantation were congenital end-stage liver diseases. According to patients' age and body weight, standard, piggyback, reduced-size, split, or living donor liver transplantation should be performed. Pediatric liver transplantation especially requires higher

  2. Reduced glycogen availability is associated with an elevation in HSP72 in contracting human skeletal muscle

    DEFF Research Database (Denmark)

    Febbraio, Mark A; Steensberg, Adam; Walsh, Rory;


    To test the hypothesis that a decrease in intramuscular glycogen availability may stimulate heat shock protein expression, seven men depleted one leg of muscle glycogen the day before performing 4-5 h of exhaustive, two-legged knee extensor exercise at 40 % of leg peak power output. Subjects...

  3. Glycogen accumulation and degradation by the trichomonads Trichomonas vaginalis and Trichomonas tenax. (United States)

    Nielsen, Tyler J; Pradhan, Prajakta; Brittingham, Andrew; Wilson, Wayne A


    Several species of trichomonad have been shown to accumulate significant quantities of glycogen during growth, suggesting an important role for this compound in cell physiology. We provide the first analysis of the changes in glycogen content and glycogen phosphorylase activity that occur during in vitro growth of two trichomonad species: Trichomonas vaginalis and Trichomonas tenax. Both species accumulated glycogen following inoculation into fresh medium and utilized this compound during logarithmic growth. Glycogen phosphorylase activity also varied during growth in a species-specific manner. The expression of phosphorylase genes in T. vaginalis remained constant during growth and thus transcriptional control did not explain the observed fluctuations in phosphorylase activity. After cloning, expression, and purification, two recombinant glycogen phosphorylases from T. vaginalis and one recombinant glycogen phosphorylase from T. tenax had robust activity and, in contrast to many other eukaryotic glycogen phosphorylases, did not appear to be regulated by reversible protein phosphorylation. Furthermore, allosteric regulation, if present, was not mediated by compounds known to impact the activity of better characterized phosphorylases.

  4. Muscle Glycogen Content Modifies SR Ca2 + Release Rate in Elite Endurance Athletes

    DEFF Research Database (Denmark)

    Gejl, Kasper Degn; Hvid, Lars G; Frandsen, Ulrik;


    The aim of the present study was to investigate the influence of muscle glycogen content on sarcoplasmic reticulum (SR) function and peak power output (Wpeak) in elite endurance athletes.......The aim of the present study was to investigate the influence of muscle glycogen content on sarcoplasmic reticulum (SR) function and peak power output (Wpeak) in elite endurance athletes....

  5. Increases in glycogenin and glycogenin mRNA accompany glycogen resynthesis in human skeletal muscle

    DEFF Research Database (Denmark)

    Shearer, Jane; Wilson, Rhonda J.; Battram, Danielle S.


    Glycogenin is the self-glycosylating protein primer that initiates glycogen granule formation. To examine the role of this protein during glycogen resynthesis, eight male subjects exercised to exhaustion on a cycle ergometer at 75% VO2 max followed by five 30-s sprints at maximal capacity to furt...

  6. Isoform-selective regulation of glycogen phosphorylase by energy deprivation and phosphorylation in astrocytes

    DEFF Research Database (Denmark)

    Müller, Margit S; Pedersen, Sofie E; Walls, Anne B;


    by determination of glycogen content showing an increase in glycogen levels following knockdown of either GPMM or GPBB. NE triggered glycogenolysis within 15 min in control cells and after GPBB knockdown. However, astrocytes in which expression of GPMM had been silenced showed a delay in response to NE...

  7. Dual regulation of muscle glycogen synthase during exercise by activation and compartmentalization

    DEFF Research Database (Denmark)

    Prats, Clara; Helge, Jørn W; Nordby, Pernille;


    lateralis muscle of the previously reported mechanism of glycogen metabolism regulation in rabbit tibialis anterior muscle. After overnight low muscle glycogen level and/or in response to exhausting exercise-induced glycogenolysis, GS is associated with spherical structures at the I-band of sarcomeres....

  8. Technical note: A method for isolating glycogen granules from ruminal protozoa for further characterization (United States)

    Evaluation of physical, compositional, and digestion characteristics of protozoal glycogen is best performed on a pure substrate in order to avoid interference from other cell components. A method for isolating protozoal glycogen without use of detergents was developed. Rumen inoculum was incubated ...

  9. Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery. (United States)

    Duarte, João M N; Morgenthaler, Florence D; Gruetter, Rolf


    Patients with diabetes display a progressive decay in the physiological counter-regulatory response to hypoglycemia, resulting in hypoglycemia unawareness. The mechanism through which the brain adapts to hypoglycemia may involve brain glycogen. We tested the hypothesis that brain glycogen supercompensation following hypoglycemia depends on blood glucose levels during recovery. Conscious rats were submitted to hypoglycemia of 2 mmol/L for 90 min and allowed to recover at different glycemia, controlled by means of i.v. glucose infusion. Brain glycogen concentration was elevated above control levels after 24 h of recovery in the cortex, hippocampus and striatum. This glycogen supercompensation was independent of blood glucose levels in the post-hypoglycemia period. In the absence of a preceding hypoglycemia insult, brain glycogen concentrations were unaltered after 24 h under hyperglycemia. In the hypothalamus, which controls peripheral glucose homeostasis, glycogen levels were unaltered. Overall, we conclude that post-hypoglycemia glycogen supercompensation occurs in several brain areas and its magnitude is independent of plasma glucose levels. By supporting brain metabolism during recurrent hypoglycemia periods, glycogen may have a role in the development of hypoglycemia unawareness.

  10. Exercise in rats does not alter hypothalamic AMP-activated protein kinase activity

    DEFF Research Database (Denmark)

    Andersson, Ulrika; Treebak, Jonas Thue; Nielsen, Jakob Nis


    or ran for 30 or 60 min on a treadmill (22 m/min, 10% slope) were sacrificed immediately after exercise or after 60 min recovery either in the fasted state or after oral gavage with glucose (3 g/kg body weight). Exercise decreased muscle and liver glycogen substantially. Hypothalamic total or a2...

  11. Seasonal Variation of the Glycogen Enzyme Activity in Diploid and Triploid Pacific Oyster Gonad During Sexual Maturation

    Institute of Scientific and Technical Information of China (English)


    The glycogen content and the activities of two key enzymes in glycogen metabolism, glycogen phosphorylase and glycogen synthetase, in the gonad of diploid and triploid Pacific oysters (Crassostrea gigas) were compared during maturation. The glycogen content in the gonad of diploids decreased with gametogenesis (by 85.7%), but the glycogen content in the gonad of triploids did not vary significantly. Activity of glycogen phosphorylase (GP) in the gonad of diploids decreased with gametogenesis (by 55.5%), while GP activity of triploids did not vary significantly during maturation. Activity of glycogen synthetase (GS) in the gonad of diploids increased slightly with gametogenesis, reaching a peak in June. Activity of GS declined sharply from June to July, which might be due to gonad spawning. GS activity of triploid oysters in spawning time (July and August) was significantly higher than that

  12. Chronic exposure to ethanol causes steatosis and inflammation in zebrafish liver (United States)

    Schneider, Ana Claudia Reis; Gregório, Cleandra; Uribe-Cruz, Carolina; Guizzo, Ranieli; Malysz, Tais; Faccioni-Heuser, Maria Cristina; Longo, Larisse; da Silveira, Themis Reverbel


    AIM To evaluate the effects of chronic exposure to ethanol in the liver and the expression of inflammatory genes in zebrafish. METHODS Zebrafish (n = 104), wild type, adult, male and female, were divided into two groups: Control and ethanol (0.05 v/v). The ethanol was directly added into water; tanks water were changed every two days and the ethanol replaced. The animals were fed twice a day with fish food until satiety. After two and four weeks of trial, livers were dissected, histological analysis (hematoxilin-eosin and Oil Red staining) and gene expression assessment of adiponectin, adiponectin receptor 2 (adipor2), sirtuin-1 (sirt-1), tumor necrosis factor-alpha (tnf-a), interleukin-1b (il-1b) and interleukin-10 (il-10) were performed. Ultrastructural evaluations were conducted at fourth week. RESULTS Exposing zebrafish to 0.5% ethanol developed intense liver steatosis after four weeks, as demonstrated by oil red staining. In ethanol-treated animals, the main ultrastructural changes were related to cytoplasmic lipid particles and droplets, increased number of rough endoplasmic reticulum cisterns and glycogen particles. Between two and four weeks, hepatic mRNA expression of il-1b, sirt-1 and adipor2 were upregulated, indicating that ethanol triggered signaling molecules which are key elements in both hepatic inflammatory and protective responses. Adiponectin was not detected in the liver of animals exposed and not exposed to ethanol, and il-10 did not show significant difference. CONCLUSION Data suggest that inflammatory signaling and ultrastructural alterations play a significant role during hepatic steatosis in zebrafish chronically exposed to ethanol. PMID:28357029

  13. Restoration of anabolic deficit and muscle glycogen consumption in competitive orienteering. (United States)

    Johansson, C; Tsai, L; Hultman, E; Tegelman, R; Pousette, A


    Consumption and restoration of muscle glycogen and changes in anabolic and catabolic steroid hormones were analyzed in five male elite orienteers during and after an orienteering competition. The magnitude of glycogen consumption and pronounced increase in serum-cortisol during the orienteering race reflect the great muscular output demands during forest running. The free testosterone/cortisol ratio was normalized to the initial level within four hours post-exercise. Synchronously, only 25% of the muscle glycogen loss was restored. Within 24 hours post-exercise all runners showed normalized levels of testosterone, cortisol and free testosterone/cortisol ratio. The glycogen content was also restored except in one of the runners. We conclude that daily orienteering competitions per se do not seem to create risks for developing a state of hormonal imbalance or significant decrease in glycogen when the carbohydrate supply is appropriate.

  14. Astrocyte glycogen metabolism is required for neural activity during aglycemia or intense stimulation in mouse white matter

    DEFF Research Database (Denmark)

    Brown, Angus M; Sickmann, Helle M; Fosgerau, Keld


    We tested the hypothesis that inhibiting glycogen degradation accelerates compound action potential (CAP) failure in mouse optic nerve (MON) during aglycemia or high-intensity stimulation. Axon function was assessed as the evoked CAP, and glycogen content was measured biochemically. Isofagomine...... periods of high-frequency stimulation. The CAP area declined more rapidly when glycogen metabolism was inhibited by isofagomine, explicitly showing an important physiological role for glycogen metabolism during neural activity....

  15. Semecarpus anacardium (Bhallataka Alters the Glucose Metabolism and Energy Production in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Jaya Aseervatham


    Full Text Available Glucose produced by gluconeogenesis and glycogenolysis plays an important role in aggravating hyperglycemia in diabetes, and altered mitochondrial function is associated with impaired energy production. The present study focuses on the effect of Semecarpus anacardium on carbohydrate metabolism and energy production in diabetic rats. Diabetes was induced by the administration of Streptozotocin at a dose of 50 mg/kg.b.wt. Three days after the induction, Semecarpus anacardium at a dose of 300 mg/kg.b.wt was administered for 21 days. After the experimental duration, the activities of the enzymes involved in Glycolysis, TCA cycle, gluconeogenesis, and glycogen were assayed in the liver and kidney of the experimental animals. In addition, to the complexes the protein expression of AKT and PI3K were assayed. The levels of the enzymes involved in Glycolysis and TCA cycle increased, while that of gluconeogensis decreased. The activities of the mitochondrial complexes were also favorably modulated. The expressions of PI3K and AKT also increased in the skeletal muscle. These effects may be attributed to the hypoglycemic and the antioxidative activity of Semecarpus anacardium. The results of the study revealed that Semecarpus anacardium was able to restore the altered activities of the enzymes involved in carbohydrate metabolism and energy production.

  16. Liver regeneration. (United States)

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L


    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review provides an overview of the models of study currently used in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus is placed on clinical applications of current knowledge in liver regeneration, including small-for-size liver transplant. Furthermore, cutting-edge topics in liver regeneration, including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a 3-dimensional scaffold for liver repopulation, are proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration.

  17. 大蒜素促进运动后大鼠糖原合成实验研究%The Experimental Research of Garlicin on Glycogen Synthesis after Exhaustive Exercise

    Institute of Scientific and Technical Information of China (English)

    蔡建光; 易乐; 王立文; 蒋小辉; 朱佩文


      To investigate the effects of garlicin on the content of glycogen in muscle and liver of rats. A total 52 rats were randomly allocated into 5 groups:control, training, training+sugar supplement, training+garlicin supplement and training+sugar+garlicin supplement. The sugar and garlicin were fed on gavage administration. The content of muscle glycogen and liver glycogen were determined by Anthranone method after 2 weeks of swimming exhaustive exercise. The experimental results displayed that, the supplement of garlicin, it was not significant effects on the content of liver glycogen, but the muscle glycogen was significant increased following the supplement of the sugar. It was implied that it was necessay to supplement the sugar to increase the content of glycogen for the swimming exhaustive rats.%  研究大蒜素在大鼠游泳力竭运动后大蒜素对机体糖原合成的影响。52只大鼠分成对照组(4只),训练组(12只),训练组+补糖组(12只),训练组+补大蒜素组(12只)和训练组+补糖+不大蒜素组(12只)后,采用灌胃法对大鼠进行糖和/或大蒜素的补充,进行为期2周游泳力竭训练后用蒽酮法测定大鼠肝糖原和肌糖原的水平。结果表明,补充大蒜素对大鼠肝糖原的影响不显著,但可以显著提高肌糖原的含量,且肌糖原含量的提高有赖于糖的补充。大蒜素促进大鼠游泳力竭运动后糖原的合成应在补糖的基础上才能实现。

  18. Proteoglycans in liver cancer (United States)

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona


    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects. PMID:26755884

  19. Proteoglycans in liver cancer. (United States)

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona


    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects.

  20. Glycogen in honeybee queens, workers and drones (Apis mellifera carnica Pollm.). (United States)

    Crailsheim, K; Panzenböck, U


    Honey bees (Apis mellifera carnica Pollm.) have low glycogen reserves in summer. Upon emergence drones have significantly larger amounts per unit weight when emerging, than workers; perhaps as adaption to the risk of not being fed as intensely as young workers. Maximum content was 0.23mg for workers (28d), and 0.59mg for drones (after emergence). Workers have relatively constant glycogen contents during their life, and very young drones have more glycogen than older ones. Young queens are similar to workers. In workers and queens in summer the greatest amounts of glycogen are found in the thorax. When the bees start flying (6th-8th day of life), drones have the highest amounts in the head (probably to supply their eyes), and upon maturity, drones have the least glycogen in the abdomen.Workers in winter show different glycogen values depending on whether they are active bees from the core area (0.23mg) or inactive ones from the outer surface of the winter cluster (0.37mg). They use glycogen from the thorax and the abdomen for their ongoing energy need.

  1. ORM Promotes Skeletal Muscle Glycogen Accumulation via CCR5-Activated AMPK Pathway in Mice (United States)

    Qin, Zhen; Wan, Jing-Jing; Sun, Yang; Wang, Peng-Yuan; Su, Ding-Feng; Lei, Hong; Liu, Xia


    We found previously that acute phase protein orosomucoid reacts to fatigue and activates C-C chemokine receptor type 5 to increase muscle glycogen storage and enhance muscle endurance (Lei et al., 2016). To explore the underlying molecular mechanisms, we investigated the role of AMP-activated protein kinase, a critical fuel sensor in skeletal muscle, in C-C chemokine receptor type 5-mediated orosomucoid action. It was found orosomucoid increased skeletal muscle AMP-activated protein kinase activation in a time- and dose- dependent manner, which was largely prevented by pharmacological blocking or knockout of C-C chemokine receptor type 5. Administration of orosomucoid also significantly increased the de-phosphorylation and activity of muscle glycogen synthase, the rate-limiting enzyme for glycogen synthesis. The effect was largely absent in mice deficient in C-C chemokine receptor type 5−/− or AMP-activated protein kinase α2−/−, the predominant isoform in skeletal muscle. Moreover, deletion of AMP-activated protein kinase α2 abolished the effect of orosomucoid on fatigue and muscle glycogen. These findings indicate that orosomucoid may promote glycogen storage and enhance muscle function through C-C chemokine receptor type 5-mdiated activation of AMP-activated protein kinase, which in turn activates glycogen synthase and increases muscle glycogen. PMID:27679573

  2. The Effect of Monosodium Glutamate (MSG On Rat Liver And The Ameliorating Effect Of "Guanidino Ethane Sulfonic acid (GES" (Histological, Histochemical and Electron Microscopy Studies

    Directory of Open Access Journals (Sweden)

    Hanaa F. Waer and *Saleh Edress


    Full Text Available Food additives are chemical substances added intentionally to food stuffs to preserve, color, sweeten and flavor food. Monosodium glutamate (MSG is used as a flavor enhancer and found in most soups, salad dressing and processed meat. The use of MSG in food is growing. Irrational fear had increased in the last few years due to the adverse reactions and toxicity of MSG. The present study was designed to investigate the effect of MSG on the rat liver and the ameliorating effect of taurine analog "Guanidinoethane sulfonic acid (GES". Sixty albino rats (2-3 months old were used in the present study. MSG was given orally at a daily dose of 60 mg/1000 g for one month, two months and was given at a daily dose of 100mg/1000gm for one month. The results revealed that the deleterious effects of MSG were dose related and cumulative. In MSG treated rats, the examined sections showed remarkable alterations varied considerably from moderate structural changes to cytoplasmic lysis and signs of degeneration of cellular organelles. The histological changes showed disturbed liver architecture, hemorrhage in the central veins, areas of necrosis, vacuolation and increased inflammatory cells infiltration. The glycogen granules increased as well as the collagen fibers in the liver cells. Ultrastructural changes showed loss of cytoplasmic differentiation, vacuolation, pyknotic nuclei with irregular nuclear membranes and elongated electron dense mitochondria. Conversely, treatment of rats with taurine analog (GES significantly attenuated the cellular toxicity of MSG.

  3. Glycogen content regulates peroxisome proliferator activated receptor-∂ (PPAR-∂) activity in rat skeletal muscle. (United States)

    Philp, Andrew; MacKenzie, Matthew G; Belew, Micah Y; Towler, Mhairi C; Corstorphine, Alan; Papalamprou, Angela; Hardie, D Grahame; Baar, Keith


    Performing exercise in a glycogen depleted state increases skeletal muscle lipid utilization and the transcription of genes regulating mitochondrial β-oxidation. Potential candidates for glycogen-mediated metabolic adaptation are the peroxisome proliferator activated receptor (PPAR) coactivator-1α (PGC-1α) and the transcription factor/nuclear receptor PPAR-∂. It was therefore the aim of the present study to examine whether acute exercise with or without glycogen manipulation affects PGC-1α and PPAR-∂ function in rodent skeletal muscle. Twenty female Wistar rats were randomly assigned to 5 experimental groups (n = 4): control [CON]; normal glycogen control [NG-C]; normal glycogen exercise [NG-E]; low glycogen control [LG-C]; and low glycogen exercise [LG-E]). Gastrocnemius (GTN) muscles were collected immediately following exercise and analyzed for glycogen content, PPAR-∂ activity via chromatin immunoprecipitation (ChIP) assays, AMPK α1/α2 kinase activity, and the localization of AMPK and PGC-1α. Exercise reduced muscle glycogen by 47 and 75% relative to CON in the NG-E and LG-E groups, respectively. Exercise that started with low glycogen (LG-E) finished with higher AMPK-α2 activity (147%, pexercise. Our data would suggest that a factor associated with muscle contraction and/or glycogen depletion activates PPAR-∂ and initiates AMPK translocation in skeletal muscle in response to exercise.

  4. Pathological glycogenesis through glycogen synthase 1 and suppression of excessive AMP kinase activity in myeloid leukemia cells (United States)

    Nonami, Atsushi; Weisberg, Ellen L.; Bonal, Dennis; Kirschmeier, Paul T.; Salgia, Sabrina; Podar, Klaus; Galinsky, Ilene; Chowdary, Tirumala K.; Neuberg, Donna; Tonon, Giovanni; Stone, Richard M.; Asara, John; Griffin, James D.; Sattler, Martin


    The rapid proliferation of myeloid leukemia cells is highly dependent on increased glucose metabolism. Through an unbiased metabolomics analysis of leukemia cells, we found that the glycogenic precursor UDP-D-glucose is pervasively upregulated, despite low glycogen levels. Targeting the rate-limiting glycogen synthase 1 (GYS1) not only decreased glycolytic flux but also increased activation of the glycogen-responsive AMPK (AMP kinase), leading to significant growth suppression. Further, genetic and pharmacological hyper-activation of AMPK was sufficient to induce the changes observed with GYS1 targeting. Cancer genomics data also indicate that elevated levels of the glycogenic enzymes GYS1/2 or GBE1 (glycogen branching enzyme 1) are associated with poor survival in AML. These results suggest a novel mechanism whereby leukemic cells sustain aberrant proliferation by suppressing excess AMPK activity through elevated glycogenic flux and provide a therapeutic entry point for targeting leukemia cell metabolism. PMID:25703587

  5. Liver Disease (United States)

    ... stay still. Liver disease has many causes. Infection Parasites and viruses can infect the liver, causing inflammation ... beyond. National Institute of Diabetes and Digestive and Kidney Diseases. ...

  6. Liver disease (United States)

    ... this page: // Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the ...

  7. Liver Diseases (United States)

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis ...

  8. Loss of glycogen synthase kinase 3 isoforms during murine oocyte growth induces offspring cardiac dysfunction. (United States)

    Monteiro da Rocha, André; Ding, Jun; Slawny, Nicole; Wolf, Amber M; Smith, Gary D


    Glycogen synthase kinase-3 (GSK3) is a constitutively active serine threonine kinase with 1) two isoforms (GSK3A and GSK3B) that have unique and overlapping functions, 2) multiple molecular intracellular mechanisms that involve phosphorylation of diverse substrates, and 3) implications in pathogenesis of many diseases. Insulin causes phosphorylation and inactivation of GSK3 and mammalian oocytes have a functional insulin-signaling pathway whereby prolonged elevated insulin during follicle/oocyte development causes GSK3 hyperphosphorylation, reduced GSK3 activity, and altered oocyte chromatin remodeling. Periconceptional diabetes and chronic hyperinsulinemia are associated with congenital malformations and onset of adult diseases of cardiovascular origin. Objectives were to produce transgenic mice with individual or concomitant loss of GSK3A and/or GSK3B and investigate the in vivo role of oocyte GSK3 on fertility, fetal development, and offspring health. Wild-type males bred to females with individual or concomitant loss of oocyte GSK3 isoforms did not have reduced fertility. However, concomitant loss of GSK3A and GSK3B in the oocyte significantly increased neonatal death rate due to congestive heart failure secondary to ventricular hyperplasia. Individual loss of oocyte GSK3A or GSK3B did not induce this lethal phenotype. In conclusion, absence of oocyte GSK3 in the periconceptional period does not alter fertility yet causes offspring cardiac hyperplasia, cardiovascular defects, and significant neonatal death. These results support a developmental mechanism by which periconceptional hyperinsulinemia associated with maternal metabolic syndrome, obesity, and/or diabetes can act on the oocyte and affect offspring cardiovascular development, function, and congenital heart malformation.

  9. Obesity, inflammation, and liver cancer. (United States)

    Sun, Beicheng; Karin, Michael


    Obesity has become a universal and major public health problem with increasing prevalence in both adults and children in the 21st century, even in developing countries. Extensive epidemiological studies reveal a strong link between obesity and development and progression of various types of cancers. The connection between obesity and liver cancer is particularly strong and obesity often results in liver diseases such as non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH). NASH is characterized by fatty liver inflammation and is believed to cause fibrosis and cirrhosis. The latter is a known liver cancer risk factor. In fact due to its much higher prevalence obesity may be a more substantial contributor to overall hepatocellular carcinoma burden than infection with hepatitis viruses. Here we review and discuss recent advances in elucidation of cellular and molecular alterations and signaling pathways associated with obesity and liver inflammation and their contribution to hepatocarcinogenesis.

  10. Neurological complications after liver retransplantation. (United States)

    Lopez, O L; Estol, C; Colina, I; Quiroga, J; Imvertarza, O C; van Thiel, D H


    Postoperative neurological complications in 185 patients who underwent two or more orthotopic liver transplantations were reviewed. The most common neurological complications were alteration of mental status (84%), seizures (33%) and focal motor deficits (15%). The frequency of neurological complications after a second orthotopic liver transplantation was significantly greater than that after a single orthotopic liver transplantation. However, neurological complications were more frequent after a second orthotopic liver transplantation than after a third transplant. Significantly more neurological complications occurred in patients who did not survive a year than in those who did, regardless of the number of transplants they underwent. These findings indicate that the risk of neurological complications among patients with multiple orthotopic liver transplantations is greater in those who require a second transplant; this risk appears to diminish after a third transplant. Importantly, the presence of neurological complications is associated with increased post-orthotopic liver transplantation mortality rate.

  11. Glycogen synthase kinase-3 facilitates con a-induced IFN-γ-- mediated immune hepatic injury. (United States)

    Tsai, Cheng-Chieh; Huang, Wei-Ching; Chen, Chia-Ling; Hsieh, Chia-Yuan; Lin, Yee-Shin; Chen, Shun-Hua; Yang, Kao-Chi; Lin, Chiou-Feng


    Immune hepatic injury induced by Con A results primarily from IFN-γ-mediated inflammation, followed by hepatic cell death. Glycogen synthase kinase (GSK)-3, which acts proapoptotically and is proinflammatory, is also important for facilitating IFN-γ signaling. We hypothesized a pathogenic role for GSK-3 in Con A hepatic injury. Con A stimulation caused GSK-3 activation in the livers of C57BL/6 mice. Inhibiting GSK-3 reduced Con A hepatic injury, including hepatic necrosis and apoptosis, inflammation, infiltration of T cells and granulocytes, and deregulated expression of adhesion molecule CD54. Con A induced hepatic injury in an IFN-γ receptor 1-dependent manner. Con A/IFN-γ induced activation and expression of STAT1 in a GSK-3-dependent manner. GSK-3 facilitated IFN-γ-induced inducible NO synthase, but had limited effects on CD95 upregulation and CD95-mediated hepatocyte apoptosis in vitro. Notably, inhibiting GSK-3 decreased Con A-induced IFN-γ production in both wild-type and IFN-γ receptor 1-deficient C57BL/6 mice. In Con A-activated NKT cells, GSK-3 was also activated and was required for nuclear translocation of T-box transcription factor Tbx21, a transcription factor of IFN-γ, but it was not required for CD95 ligand expression or activation-induced cell death. These results demonstrate the dual and indispensable role of GSK-3 in Con A hepatic injury by facilitating IFN-γ-induced hepatopathy.

  12. Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Takashige, E-mail:; Yoshimi, Masaki; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya


    The role of endoplasmic reticulum (ER) stress in pregnancy remains largely unknown. Pregnant mice were subcutaneously administered tunicamycin (Tun), an ER stressor, as a single dose [0, 50, and 100 μg Tun/kg/body weight (BW)] on gestation days (GDs) 8.5, 12.5, and 15.5. A high incidence (75%) of preterm delivery was observed only in the group treated with Tun 100 μg/kg BW at GD 15.5, indicating that pregnant mice during late gestation are more susceptible to ER stress on preterm delivery. We further examined whether prolonged in utero exposure to ER stress affects fetal development. Pregnant mice were subcutaneously administered a dose of 0, 20, 40, and 60 μg Tun/kg from GD 12.5 to 16.5. Tun treatment decreased the placental and fetal weights in a dose-dependent manner. Histological evaluation showed the formation of a cluster of spongiotrophoblast cells in the labyrinth zone of the placenta of Tun-treated mice. The glycogen content of the fetal liver and placenta from Tun-treated mice was lower than that from control mice. Tun treatment decreased mRNA expression of Slc2a1/glucose transporter 1 (GLUT1), which is a major transporter for glucose, but increased placental mRNA levels of Slc2a3/GLUT3. Moreover, maternal exposure to Tun resulted in a decrease in vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, and placental growth factor. These results suggest that excessive and exogenous ER stress may induce functional abnormalities in the placenta, at least in part, with altered GLUT and vascular-related gene expression, resulting in low infant birth weight. - Highlights: • Maternal exposure to excessive ER stress induced preterm birth and IUGR. • Prolonged excessive ER stress altered the formation of the placental labyrinth. • ER stress decreased GLUT1 mRNA expression in the placenta, but increased GLUT3. • ER stress-induced IUGR causes decreased glycogen and altered glucose transport.

  13. Capsular glucan and intracellular glycogen of Mycobacterium tuberculosis: biosynthesis and impact on the persistence in mice

    DEFF Research Database (Denmark)

    Sambou, Tounkang; Dinadayala, Premkumar; Stadthagen, Gustavo;


    Mycobacterium tuberculosis and other pathogenic mycobacterial species produce large amounts of a glycogen-like alpha-glucan that represents the major polysaccharide of their outermost capsular layer. To determine the role of the surface-exposed glucan in the physiology and virulence...... of these bacteria, orthologues of the glg genes involved in the biosynthesis of glycogen in Escherichia coli were identified in M. tuberculosis H37Rv and inactivated by allelic replacement. Biochemical analyses of the mutants and complemented strains indicated that the synthesis of glucan and glycogen involves...... the alpha-1,4-glucosyltransferases Rv3032 and GlgA (Rv1212c), the ADP-glucose pyrophosphorylase GlgC (Rv1213) and the branching enzyme GlgB (Rv1326c). Disruption of glgC reduced by half the glucan and glycogen contents of M. tuberculosis, whereas the inactivation of glgA and Rv3032 affected the production...

  14. Adiponectin levels correlate with the severity of hypertriglyceridaemia in glycogen storage disease Ia

    NARCIS (Netherlands)

    Bandsma, R. H. J.; Smit, G. P. A.; Reijngoud, D. -J.; Kuipers, F.


    Glycogen storage disease type Ia (GSD Ia) is characterized by severe hypercholesterolaemia and hypertriglyceridaemia. Little is known about the aetiology of the hyperlipidaemia in GSD Ia. Adipokines play an important regulatory role in lipid metabolism. We investigated whether adipokine concentratio

  15. Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle

    DEFF Research Database (Denmark)

    Hunter, Roger W; Treebak, Jonas Thue; Wojtaszewski, Jørgen


    OBJECTIVE During energy stress, AMP-activated protein kinase (AMPK) promotes glucose transport and glycolysis for ATP production, while it is thought to inhibit anabolic glycogen synthesis by suppressing the activity of glycogen synthase (GS) to maintain the energy balance in muscle. Paradoxically......, chronic activation of AMPK causes an increase in glycogen accumulation in skeletal and cardiac muscles, which in some cases is associated with cardiac dysfunction. The aim of this study was to elucidate the molecular mechanism by which AMPK activation promotes muscle glycogen accumulation. RESEARCH DESIGN...... AND METHODS We recently generated knock-in mice in which wild-type muscle GS was replaced by a mutant (Arg582Ala) that could not be activated by glucose-6-phosphate (G6P), but possessed full catalytic activity and could still be activated normally by dephosphorylation. Muscles from GS knock-in or transgenic...

  16. Identification and Structural Basis of Binding to Host Lung Glycogen by Streptococcal Virulence Factors

    Energy Technology Data Exchange (ETDEWEB)

    Lammerts van Bueren,A.; Higgins, M.; Wang, D.; Burke, R.; Boraston, A.


    The ability of pathogenic bacteria to recognize host glycans is often essential to their virulence. Here we report structure-function studies of previously uncharacterized glycogen-binding modules in the surface-anchored pullulanases from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA). Multivalent binding to glycogen leads to a strong interaction with alveolar type II cells in mouse lung tissue. X-ray crystal structures of the binding modules reveal a novel fusion of tandem modules into single, bivalent functional domains. In addition to indicating a structural basis for multivalent attachment, the structure of the SpuA modules in complex with carbohydrate provides insight into the molecular basis for glycogen specificity. This report provides the first evidence that intracellular lung glycogen may be a novel target of pathogenic streptococci and thus provides a rationale for the identification of the streptococcal {alpha}-glucan-metabolizing machinery as virulence factors.

  17. Glucose balance and muscle glycogen during TPN in the early post-operative phase

    DEFF Research Database (Denmark)

    Henneberg, S; Stjernström, H; Essén-Gustavsson, B


    In order to study how muscle glycogen is influenced by different nutritional regimens in the early post-operative period we took muscle biopsies from 20 patients preoperatively and on the fourth post-operative day after abdominal aortic surgery. Ten patients received 93% of non-protein energy......-production) were performed and from these data glucose balance was calculated as the difference between glucose intake and glucose expenditure. Muscle biopsies were analysed for glycogen, adenosine triphosphate, glucose-6-phosphate, lactate and citrate. We found that it was possible to maintain muscle...... glycogen stores at pre-operative levels with a glucose-insulin regimen. With the fat regimen there was a 31% decrease in muscle glycogen and two patients had a negative glucose balance despite the fact that 150 g of glucose were given. Average glucose balance throughout the study correlated positively...

  18. Lipids in hepatic glycogen storage diseases : pathophysiology, monitoring of dietary management and future directions

    NARCIS (Netherlands)

    Derks, Terry G. J.; van Rijn, Margreet


    Hepatic glycogen storage diseases (GSD) underscore the intimate relationship between carbohydrate and lipid metabolism. The hyperlipidemias in hepatic GSD reflect perturbed intracellular metabolism, providing biomarkers in blood to monitor dietary management. In different types of GSD, hyperlipidemi

  19. [Liver damage caused by drugs]. (United States)

    Strohmeyer, G; Weik, C


    The liver has a central role in the metabolism of many drugs, since this organ is the main site of biotransformation of endo- and xenobiotics. Water-soluble drugs have a small volume of distribution and can be eliminated unchanged in the urine. By contrast, lipid-soluble drugs have a larger volume of distribution and require conversion to water-soluble metabolites for their elimination in urine or bile. The liver with its specific receptors, transporters and enzymes is responsible for the uptake, transformation and excretion of the lipophilic drugs. While most of the drugs are transformed into stable metabolites, other drugs form reactive, potentially toxic, metabolites producing liver cell damage. Liver injury caused by drugs may mimic almost any kind of liver disease. Clinical findings are gastrointestinal symptoms with nausea, vomiting and abdominal pain, cholestatic liver injury with jaundice and pruritus of severe inflammatory and cirrhotic liver damage with signs of liver failure, encephalopathy and cerebral edema. The morphological changes vary from hepatitis, cholestasis, fatty liver, granulomatous hepatitis, peri-/portal inflammation, to fibrosis with cirrhotic alterations and vascular lesions and tumors. The most commonly used drugs causing severe liver injury are discussed in detail. These are anabolics, oral contraceptives, antituberculous and antifungal agents, nonsteroidal anti-inflammatory drugs, ring substituted amphetamins ("designer drugs"), antiarrhythmics and antibiotics.

  20. Glycogen synthesis correlates with androgen-dependent growth arrest in prostate cancer

    Directory of Open Access Journals (Sweden)

    Gorin Frederic A


    Full Text Available Abstract Background Androgen withdrawal in normal prostate or androgen-dependent prostate cancer is associated with the downregulation of several glycolytic enzymes and with reduced glucose uptake. Although glycogen metabolism is known to regulate the intracellular glucose level its involvement in androgen response has not been studied. Methods We investigated the effects of androgen on glycogen phosphorylase (GP, glycogen synthase (GS and on glycogen accumulation in the androgen-receptor (AR reconstituted PC3 cell line containing either an empty vector (PC3-AR-V or vector with HPV-E7 (PC3-AR-E7 and the LNCaP cell line. Results Androgen addition in PC3 cells expressing the AR mimics androgen ablation in androgen-dependent prostate cells. Incubation of PC3-AR-V or PC3-AR-E7 cells with the androgen R1881 induced G1 cell cycle arrest within 24 hours and resulted in a gradual cell number reduction over 5 days thereafter, which was accompanied by a 2 to 5 fold increase in glycogen content. 24 hours after androgen-treatment the level of Glucose-6-P (G-6-P had increased threefold and after 48 hours the GS and GP activities increased twofold. Under this condition inhibition of glycogenolysis with the selective GP inhibitor CP-91149 enhanced the increase in glycogen content and further reduced the cell number. The androgen-dependent LNCaP cells that endogenously express AR responded to androgen withdrawal with growth arrest and increased glycogen content. CP-91149 further increased glycogen content and caused a reduction of cell number. Conclusion Increased glycogenesis is part of the androgen receptor-mediated cellular response and blockage of glycogenolysis by the GP inhibitor CP-91149 further increased glycogenesis. The combined use of a GP inhibitor with hormone therapy may increase the efficacy of hormone treatment by decreasing the survival of prostate cancer cells and thereby reducing the chance of cancer recurrence.

  1. Physiological aspects of the subcellular localization of glycogen in skeletal muscle

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Ørtenblad, Niels


    Glucose is stored in skeletal muscle fibers as glycogen, a branched-chain polymer observed in electron microscopy images as roughly spherical particles (known as β-particles of 10-45 nm in diameter), which are distributed in distinct localizations within the myofibers and are physically associate...... of these phenomena may prove vital in elucidating the mechanisms that integrate basic cellular events with changing glycogen content....

  2. L-alanine supplementation in late infantile glycogen storage disease type II. (United States)

    Bodamer, Olaf A; Haas, Dorothea; Hermans, Monique M; Reuser, Arnold J; Hoffmann, Georg F


    We report a male with late infantile glycogen storage disease type II (Pompe's disease) who presented at 12 months of age with muscular hypotonia and developmental delay. Oral supplementation with L-alanine has been administered for 5 years. Progression of skeletal myopathy was slow, and cardiomyopathy resolved almost completely. L-alanine may be a valuable supplement for infants with glycogen storage disease type II.

  3. 全氟辛烷磺酸促大鼠肝脏 NQO1 甲基化作用%Prenatal exposure to PFOS alters individual genes NQO1 promoter methylation levels of liver in postnatal SD rats

    Institute of Scientific and Technical Information of China (English)

    沈杰; 夏玮; 万延建; 许冰; 李媛媛; 徐顺清


    目的 探讨基因启动子甲基化水平与全氟辛烷磺酸(PFOS)诱导的肝毒性早期过程相关性.方法 在雌性SD大鼠受孕后2~21 d采用PFOS (0.1、0.6、2.0 mg/kg)灌胃染毒;在子鼠出生后21 d收集肝脏组织样本,用亚硫酸氢钠测序聚合酶链式反应法(BSP)结合质粒克隆后测序,检测烟酰胺腺嘌呤二核苷酸:醌氧化还原酶1(NQO1)和肉毒碱棕榈酰转移酶1A(CPT1A)基因启动子区域甲基化状态.结果 与对照组(0%)比较,高剂量PFOS组子鼠肝脏NQO1基因甲基化状态有所上升,-573、-523、-507 3个位点分别升高了10%,而中低剂量组无变化(均为0%);CPT1A基因启动子区域甲基化状态无明显变化.结论 出生前暴露于PFOS的子鼠肝脏中NQO1基因启动子甲基化水平升高.%Objective To examine the possibility of early epigenetic alteration in perfluorooctane sulphonate (PFOS) -exposed rat liver. Methods Pregnant Sprague-Dawley(SD) rats were exposed to PFOS at doses of 0.1,0. 6, and 2. 0 mg/kg/d and 0. 05% Tween 80 as control by gavage from gestation day 2 to 21. The dams were allowed to give birth and liver samples from weaned (postnatal day 21) offspring rats were analyzed for individual genes such as NAD(P)H:quinone oxidoreductase(NQO1) and carnitine palmitoyltransferase 1A(CPT1A) promoter methylation level. Results In PFOS exposed weaned rats, compared to the control, methylation of critical CpG sites in NQO1 promoter was found up to 10% methylated in the livers of treated rats. Conclusion Early induced hypermethylation in critical cytosines within the NQO1 gene promoter region may be a significant biomarker of hepatic PFOS burden, though their direct role in PFOS induced-hepatotoxicity,including its potential carcinogenic action,needs further research.

  4. Hepatic encephalopathy as a complication of liver disease

    Institute of Scientific and Technical Information of China (English)

    Stephan vom Dahl; Gerald Kircheis; Dieter Haussinger


    @@INTRODUCTION Hepatic encephalopathy ( HE) is a frequent complication of chronic liver disease .It is defined as a characteristic functional and reversible alteration of the mental state ,due to impaired liver function and / or increased portosystemic shunting .

  5. Glycogen accumulation in the pars recta of the proximal tubule in Fanconi syndrome. (United States)

    Bendon, R W; Hug, G


    We reviewed the renal pathology in 10 cases of renal Fanconi syndrome. Five cases showed the Armanni-Ebstein lesion, i.e., clear glycogen-filled cells limited to the pars recta of the proximal tubules. The 5 cases included 2 siblings with a unique syndrome characterized by death in infancy, severe Fanconi syndrome, severe rickets, carnitine deficiency, and atrophy of the exocrine pancreas. Two other siblings had glycogen storage disease type XI. One of 4 cases of putative tyrosinemia had the lesion. The ultrastructure was studied in 2 cases. The Armanni-Ebstein lesion in these cases was morphologically indistinguishable from that seen in diabetic patients dying after prolonged hyperglycemia. Glycosuria is the only common factor in both diabetic hyperglycemia and the varied proximal tubular diseases studied. The mechanism of the glycogen accumulation in this short parts recta segment of the proximal renal tubule was further investigated by reviewing the renal histology in cases of glycogen storage disease types I, II, III, and VIII. None showed the Armanni-Ebstein lesion, but type I showed glycogen deposition throughout the proximal tubule. Thus, the Armanni-Ebstein lesion is not the result of an enzymatic deficiency for glycogen synthesis in the convoluted tubules.

  6. Studies on glycogen autophagy: effects of phorbol myristate acetate, ionophore A23187, or phentolamine. (United States)

    Kalamidas, S A; Kotoulas, O B; Hann, A C


    The effects of agents that could manipulate the lysosomal calcium such as phorbol myristate acetate, ionophore A23187, and phentolamine on the lysosomal glycogen degradation were studied by electron microscopy, morphometric analysis, and biochemical assays in newborn rat hepatocytes. Phorbol myristate acetate, which promotes the input of calcium to lysosomes, increased the total volume of autophagic vacuoles and the activity of lysosomal glycogen-hydrolyzing acid alpha 1,4 glucosidase and decreased the fractional volume of undigested glycogen inside the autophagic vacuoles and also decreased the activity of acid mannose 6-phosphatase. Ionophore A23187, which releases lysosomal calcium, produced opposite results in these enzyme activities. Phentolamine, an alpha-adrenergic blocking agent which interferes with the generation of phosphoinositides and may activate the lysosomal calcium uptake pump, increased the total volume of autophagic vacuoles and the activity of lysosomal glycogen-hydrolyzing acid glucosidase and decreased the fractional volume of undigested glycogen inside the autophagic vacuoles. The results of this study constitute evidence that changes in lysosomal calcium may influence certain aspects of autophagy, including the degradation of glycogen inside the autophagic vacuoles. They also support our previous postulate [Kalamidas and Kotoulas (2000a,b) Histol Histopathol 15:29-35, 1011-1018] that stimulation of autophagic mechanisms in newborn rat hepatocytes may be associated with acid mannose 6-phosphatase activity-deficient lysosomes.

  7. Regulation of glycogen breakdown and its consequences for skeletal muscle function after training. (United States)

    Katz, Abram; Westerblad, Håkan


    Repeated bouts of physical exercise, i.e., training, induce mitochondrial biogenesis and result in improved physical performance and attenuation of glycogen breakdown during submaximal exercise. It has been suggested that as a consequence of the increased mitochondrial volume, a smaller degree of metabolic stress (e.g., smaller increases in ADP and Pi) is required to maintain mitochondrial respiration in the trained state during exercise at the same absolute intensity. The lower degree of Pi accumulation is believed to account for the diminished glycogen breakdown, since Pi is a substrate for glycogen phosphorylase, the rate-limiting enzyme for glycogenolysis. However, in this review, we present an alternative explanation for the diminished glycogen breakdown. Thus, the lower degree of metabolic stress after training is also associated with smaller increases in AMP (free concentration during contraction at specific intracellular sites) and this results in less activation of phosphorylase b (the non-phosphorylated form of phosphorylase), resulting in diminished glycogen breakdown. Concomitantly, the smaller accumulation of Pi, which interferes with cross-bridge function and intracellular Ca(2+) handling, contributes to the increased fatigue resistance. The delay in glycogen depletion also contributes to enhanced performance during prolonged exercise by functioning as an energy reserve.

  8. Creatine supplementation spares muscle glycogen during high intensity intermittent exercise in rats

    Directory of Open Access Journals (Sweden)

    Costa André


    Full Text Available Abstract Background The effects of creatine (CR supplementation on glycogen content are still debatable. Thus, due to the current lack of clarity, we investigated the effects of CR supplementation on muscle glycogen content after high intensity intermittent exercise in rats. Methods First, the animals were submitted to a high intensity intermittent maximal swimming exercise protocol to ensure that CR-supplementation was able to delay fatigue (experiment 1. Then, the CR-mediated glycogen sparing effect was examined using a high intensity intermittent sub-maximal exercise test (fixed number of bouts; six bouts of 30-second duration interspersed by two-minute rest interval (experiment 2. For both experiments, male Wistar rats were given either CR supplementation or placebo (Pl for 5 days. Results As expected, CR-supplemented animals were able to exercise for a significant higher number of bouts than Pl. Experiment 2 revealed a higher gastrocnemius glycogen content for the CR vs. the Pl group (33.59%. Additionally, CR animals presented lower blood lactate concentrations throughout the intermittent exercise bouts compared to Pl. No difference was found between groups in soleus glycogen content. Conclusion The major finding of this study is that CR supplementation was able to spare muscle glycogen during a high intensity intermittent exercise in rats.

  9. The Saccharomyces cerevisiae YPR184w gene encodes the glycogen debranching enzyme. (United States)

    Teste, M A; Enjalbert, B; Parrou, J L; François, J M


    The YPR184w gene encodes a 1536-amino acid protein that is 34-39% identical to the mammal, Drosophila melanogaster and Caenorhabditis elegans glycogen debranching enzyme. The N-terminal part of the protein possesses the four conserved sequences of the alpha-amylase superfamily, while the C-terminal part displays 50% similarity with the C-terminal of other eukaryotic glycogen debranching enzymes. Reliable measurement of alpha-1,4-glucanotransferase and alpha-1, 6-glucosidase activity of the yeast debranching enzyme was determined in strains overexpressing YPR184w. The alpha-1, 4-glucanotransferase activity of a partially purified preparation of debranching enzyme preferentially transferred maltosyl units than maltotriosyl. Deletion of YPR184w prevents glycogen degradation, whereas overexpression had no effect on the rate of glycogen breakdown. In response to stress and growth conditions, the transcriptional control of YPR184w gene, renamed GDB1 (for Glycogen DeBranching gene), is strictly identical to that of other genes involved in glycogen metabolism.

  10. Contribution of glycogen in supporting axon conduction in the peripheral and central nervous systems: the role of lactate

    Directory of Open Access Journals (Sweden)

    Angus M Brown


    Full Text Available The role of glycogen in the central nervous system is intimately linked with the glycolytic pathway. Glycogen is synthesized from glucose, the primary substrate for glycolysis, and degraded to glucose-6-phosphate. The metabolic cost of shunting glucose via glycogen exceeds that of simple phosphorylation of glucose to glucose-6-phosphate by hexokinase; thus, there must be a metabolic advantage in utilizing this shunt pathway. The dogmatic view of glycogen as a storage depot persists, based on initial descriptions of glycogen supporting neural function in the face of aglycemia. The variable latency to conduction failure, dependent upon tissue glycogen levels, provided convincing evidence of the role played by glycogen in supporting neural function. Glycogen is located predominantly in astrocytes in the central nervous system, thus for glycogen to benefit neural elements, intercellular metabolic communication must exist in the form of astrocyte to neuron substrate transfer. Experimental evidence supports a model where glycogen is metabolized to lactate in astrocytes, with cellular expression of monocarboxylate transporters and enzymes appropriately located for lactate shuttling between astrocytes and neural elements, where lactate acts as a substrate for oxidative metabolism. Biosensor recordings have demonstrated a significant steady concentration of lactate present on the periphery of both central white matter and peripheral nerve under unstimulated baseline conditions, indicating continuous cellular efflux of lactate to the interstitium. The existence of this lactate pool argues we must reexamine the ‘on demand’ shuttling of lactate between cellular elements, and suggests continuous lactate efflux surplus to immediate neural requirements.

  11. Effects of aging on the recycling via the pentose cycle and on the kinetics of glycogen and protein metabolism in various organs of the rat. (United States)

    Niedermüller, H


    The rate of metabolic kinetics and the frequency of biological cycles may be correlated with the rate of aging and the maximum life-span potential. Therefore, investigations either into changes with age of such parameters within one species or into differences between species may give some information about the genetic programming of the aging process. Male Sprague-Dawley rats aged 3.5, 7, 12, 17, 23 and 33 months (m) were used to determine the changes with age of those metabolic pathways mentioned in the title, using the liver, kidney, brain, heart and the skeletal muscle. The maximum percentage of glucose utilization via the pentose pathway, compared to the total glucose utilization, was calculated after intravenous administration of D-[1-14C]- and D-[6-14C]glucose by the determination of the trioses (as lipids) 3 hours after the application. Glycogen kinetics was determined analogously. Total protein metabolism was observed using the essential amino acid L-[2,5-3H]histidine. The results indicate a decrease in the glucose utilization via the pentose pathway in the course of aging in liver, kidney, heart and skeletal muscle and a decrease from 3.5 months on in brain, a small but not significant change of the kinetics of glycogen metabolism (a lower turnover), and a reduced rate of protein synthesis in liver, kidney, heart and brain through an age of 23 months, followed by an elevated rate. Brain did not show any changes. The reduction of the pentose pathway may possibly be the cause of higher lipofuscin accumulation in the cells of some organs, lacking sufficient reduction equivalents for lipid metabolism. Furthermore, there could exist a connection with the reduced protein turnover, because less riboses are provided for the synthesis of nucleic acids.

  12. What Is Liver Cancer? (United States)

    ... Treatment? Liver Cancer About Liver Cancer What Is Liver Cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  13. Roles of FGF19 in liver metabolism. (United States)

    Kir, S; Kliewer, S A; Mangelsdorf, D J


    Fibroblast growth factor 19 (FGF19) is an ileum-derived postprandial enterokine that governs bile acid and nutrient metabolism. Synthesis of FGF19 is up-regulated by bile acids and, conversely, bile acid synthesis is down-regulated by FGF19. FGF19 also controls gallbladder volume. FGF19 has been shown to have profound effects on glucose and lipid metabolism. Recent studies have described FGF19 as a postprandial regulator of hepatic glucose and protein metabolism. Like insulin, FGF19 induces protein and glycogen synthesis and suppresses gluconeogenesis in liver. However, unlike insulin, FGF19 does not stimulate lipogenesis. A key difference between FGF19 and insulin lies in their use of different cellular signaling pathways. The beneficial effects of FGF19 on liver metabolism raise the question of whether FGF19 and its variants can be used as therapeutic agents in the treatment of diabetes.

  14. Identification of differentially expressed genes in chickens differing in muscle glycogen content and meat quality

    Directory of Open Access Journals (Sweden)

    Marthey Sylvain


    Full Text Available Abstract Background The processing ability of poultry meat is highly related to its ultimate pH, the latter being mainly determined by the amount of glycogen in the muscle at death. The genetic determinism of glycogen and related meat quality traits has been established in the chicken but the molecular mechanisms involved in variations in these traits remain to be fully described. In this study, Chicken Genome Arrays (20 K were used to compare muscle gene expression profiles of chickens from Fat (F and Lean (L lines that exhibited high and low muscle glycogen content, respectively, and of individuals exhibiting extremely high (G+ or low (G- muscle glycogen content originating from the F2 cross between the Fat and Lean lines. Real-time RT-PCR was subsequently performed to validate the differential expression of genes either selected from the microarray analysis or whose function in regulating glycogen metabolism was well known. Results Among the genes found to be expressed in chicken P. major muscle, 197 and 254 transcripts appeared to be differentially expressed on microarrays for the F vs. L and the G+ vs. G- comparisons, respectively. Some involved particularly in lipid and carbohydrate metabolism were selected for further validation studies by real-time RT-PCR. We confirmed that, as in mammals, the down-regulation of CEBPB and RGS2 coincides with a decrease in peripheral adiposity in the chicken, but these genes are also suggested to affect muscle glycogen turnover through their role in the cAMP-dependent signalling pathway. Several other genes were suggested to have roles in the regulation of glycogen storage in chicken muscle. PDK4 may act as a glycogen sensor in muscle, UGDH may compete for glycogen synthesis by using UDP-glucose for glucoronidation, and PRKAB1, PRKAG2, and PHKD may impact on glycogen turnover in muscle, through AMP-activated signalling pathways. Conclusions This study is the first stage in the understanding of molecular

  15. Liver Transplant (United States)

    ... Liver Disease & NASH Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Biliary Atresia Cirrhosis Hemochromatosis Hepatitis A through E (Viral Hepatitis) Hepatitis ...

  16. Differential regulation of glycogenolysis by mutant protein phosphatase-1 glycogen-targeting subunits. (United States)

    Danos, Arpad M; Osmanovic, Senad; Brady, Matthew J


    PTG and G(L) are hepatic protein phosphatase-1 (PP1) glycogen-targeting subunits, which direct PP1 activity against glycogen synthase (GS) and/or phosphorylase (GP). The C-terminal 16 amino residues of G(L) comprise a high affinity binding site for GP that regulates bound PP1 activity against GS. In this study, a truncated G(L) construct lacking the GP-binding site (G(L)tr) and a chimeric PTG molecule containing the C-terminal site (PTG-G(L)) were generated. As expected, GP binding to glutathione S-transferase (GST)-G(L)tr was reduced, whereas GP binding to GST-PTG-G(L) was increased 2- to 3-fold versus GST-PTG. In contrast, PP1 binding to all proteins was equivalent. Primary mouse hepatocytes were infected with adenoviral constructs for each subunit, and their effects on glycogen metabolism were investigated. G(L)tr expression was more effective at promoting GP inactivation, GS activation, and glycogen accumulation than G(L). Removal of the regulatory GP-binding site from G(L)tr completely blocked the inactivation of GS seen in G(L)-expressing cells following a drop in extracellular glucose. As a result, G(L)tr expression prevented glycogen mobilization under 5 mm glucose conditions. In contrast, equivalent overexpression of PTG or PTG-G(L) caused a similar increase in glycogen-targeted PP1 levels and GS dephosphorylation. Surprisingly, GP dephosphorylation was significantly reduced in PTG-G(L)-overexpressing cells. As a result, PTG-G(L) expression permitted glycogenolysis under 5 mm glucose conditions that was prevented in PTG-expressing cells. Thus, expression of constructs that contained the high affinity GP-binding site (G(L) and PTG-G(L)) displayed reduced glycogen accumulation and enhanced glycogenolysis compared with their respective controls, albeit via different mechanisms.

  17. Glycogenotic hepatocellular carcinoma with glycogen-ground-glass hepatocytes: A heuristically highly relevant phenotype

    Institute of Scientific and Technical Information of China (English)

    Peter Bannasch


    Glycogenotic hepatocellular carcinoma (HCC) with glycogen-ground-glass hepatocytes has recently been described as an allegedly "novel variant" of HCC,but neither the historical background nor the heuristic relevance of this observation were put in perspective.In the present contribution,the most important findings in animal models and human beings related to the emergence and further evolution of excessively glycogen storing (glycogenotic) hepatocytes with and without ground glass features during neoplastic development have been summarized.Glycogenotic HCCs with glycogen-ground-glass hepatocytes represent highly differentiated neoplasms which contain subpopulations of cells phenotypically resembling those of certain types of preneoplastic hepatic foci and benign hepatocellular neoplasms.It is questionable whether the occurrence of glycogen-ground-glass hepatocytes in a glycogenotic HCC justifies its classification as a specific entity.The typical appearance of ground-glass hepatocytes is due to a hypertrophy of the smooth endoplasmic reticulum,which is usually associated with an excessive storage of glycogen and frequently also with an expression of the hepatitis B surface antigen.Sequential studies in animal models and observations in humans indicate that glycogen-ground-glass hepatocytes are a facultative,integral part of a characteristic cellular sequence commencing with focal hepatic glycogenosis potentially progressing to benign and malignant neoplasms.During this process highly differentiated glycogenotic cells including ground-glass hepatocytes are gradually transformed via various intermediate stages into poorly differentiated glycogen-poor,basophilic (ribosome-rich) cancer cells.Histochemical,microbiochemical,and molecular biochemical studies on focal hepatic glycogenosis and advanced preneoplastic and neoplastic lesions in tissue sections and laser-dissected specimens in rat and mouse models have provided compelling evidence for an early insulinomimetic

  18. A new diagnostic assay for glycogen storage disease type II in mixed leukocytes. (United States)

    Okumiya, Toshika; Keulemans, Joke L M; Kroos, Marian A; Van der Beek, Nadine M E; Boer, Marijke A; Takeuchi, Hiroaki; Van Diggelen, Otto P; Reuser, Arnold J J


    We have established a new method for the enzymatic diagnosis of glycogen storage disease type II (Pompe disease or acid maltase deficiency) using mixed leukocytes. The method employs glycogen and 4-methylumbelliferyl-alpha-D-glucopyranoside (4MU-alphaGlc) as substrates for measuring the lysosomal acid alpha-glucosidase (acid alphaGlu) activity, and incorporates acarbose to eliminate the interference of unrelated alpha-glucosidases (predominantly maltase-glucoamylase). It is shown that 3.0 micromol/L acarbose completely inhibits the maltase-glucoamylase activity at pH 4.0, but the lysosomal acid alphaGlu activity by less than 5%. With this method, we determined the acid alphaGlu activity in mixed leukocytes from 25 patients with glycogen storage disease type II (2 infantile and 23 late-onset cases), one GAA2/GAA2 homozygote and 30 healthy subjects. In the assay with glycogen as substrate, the addition of acarbose created a clear separation between the patient and the control ranges. In the assay with 4MU-alphaGlc as substrate, the two ranges were fully separated but remained very close despite the use of acarbose. The separation of the patient and normal ranges was improved considerably by taking the ratio of acarbose-inhibited over uninhibited activity. A GAA2/GAA2 homozygote was correctly diagnosed with 4MU-alphaGlc but misdiagnosed as patient when glycogen was used as substrate. We conclude that the inclusion of 3.0 micromol/L acarbose in the assays with glycogen and 4MU-alphaGlc substrates at pH 4.0 allows for the specific measurement of lysosomal acid alphaGlu activity in mixed leukocytes, thus enabling a reliable diagnosis of glycogen storage disease type II in this specimen.

  19. Muscle cramps in liver disease. (United States)

    Mehta, Shivang S; Fallon, Michael B


    Muscle cramps are common in patients with liver disease and adversely influence quality of life. The exact mechanisms by which they occur remain unclear, although a number of pathophysiological events unique to liver disease may contribute. Clinical studies have identified alterations in 3 areas: nerve function, energy metabolism, and plasma volume/electrolytes. Treatments have focused on these particular areas with varied results. This review will focus on the clinical features of muscle cramps in patients with liver disease and review potential mechanisms and current therapies.

  20. Ethanolic Extract of Butea monosperma Leaves Elevate Blood Insulin Level in Type 2 Diabetic Rats, Stimulate Insulin Secretion in Isolated Rat Islets, and Enhance Hepatic Glycogen Formation

    Directory of Open Access Journals (Sweden)

    Mehdi Bin Samad


    Full Text Available We measured a vast range of parameters, in an attempt to further elucidate previously claimed antihyperglycemic activity of Butea monosperma. Our study clearly negates the possibility of antidiabetic activity by inhibited gastrointestinal enzyme action or by reduced glucose absorption. Reduction of fasting and postprandial glucose level was reconfirmed (P<0.05. Improved serum lipid profile via reduced low density lipoprotein (LDL, cholesterol, triglycerides (TG, and increased high density lipoprotein (HDL was also reestablished (P<0.05. Significant insulin secretagogue activity of B. monosperma was found in serum insulin assay of B. monosperma treated type 2 diabetic rats (P<0.01. This was further ascertained by our study on insulin secretion on isolated rat islets (P<0.05. Improved sensitivity of glucose was shown by the significant increase in hepatic glycogen deposition (P<0.05. Hence, we concluded that antihyperglycemic activity of B. monosperma was mediated by enhanced insulin secretion and enhanced glycogen formation in the liver.

  1. [A new case of hepatic adenomatosis treated with orthotopic liver transplantation]. (United States)

    Yunta, P J; Moya, A; San-Juan, F; López-Andújar, R; De Juan, M; Orbis, F; Mir, J


    Hepatic adenomatosis is a rare disease with multiple hepatic adenomas (10 or more), not associated with an history of oral contraceptive use or anabolic steroids use or with glycogen storage disease. A new case is reported in a 23 year-old woman who consulted for an abdominal mass and who had more than 50 adenomas of the liver. The suspicion of malignant transformation by the elevation of the alpha-foetoprotein, and the diffuse affectation of the liver, with minimum free parenchyma, suggested to carry out an orthotopic liver transplantation. The definitive histological examination of the surgical specimen confirmed the existence of local areas of hepatocellular carcinoma.

  2. Human α-amylase present in lower-genital-tract mucosal fluid processes glycogen to support vaginal colonization by Lactobacillus. (United States)

    Spear, Gregory T; French, Audrey L; Gilbert, Douglas; Zariffard, M Reza; Mirmonsef, Paria; Sullivan, Thomas H; Spear, William W; Landay, Alan; Micci, Sandra; Lee, Byung-Hoo; Hamaker, Bruce R


    Lactobacillus colonization of the lower female genital tract provides protection from the acquisition of sexually transmitted diseases, including human immunodeficiency virus, and from adverse pregnancy outcomes. While glycogen in vaginal epithelium is thought to support Lactobacillus colonization in vivo, many Lactobacillus isolates cannot utilize glycogen in vitro. This study investigated how glycogen could be utilized by vaginal lactobacilli in the genital tract. Several Lactobacillus isolates were confirmed to not grow in glycogen, but did grow in glycogen-breakdown products, including maltose, maltotriose, maltopentaose, maltodextrins, and glycogen treated with salivary α-amylase. A temperature-dependent glycogen-degrading activity was detected in genital fluids that correlated with levels of α-amylase. Treatment of glycogen with genital fluids resulted in production of maltose, maltotriose, and maltotetraose, the major products of α-amylase digestion. These studies show that human α-amylase is present in the female lower genital tract and elucidates how epithelial glycogen can support Lactobacillus colonization in the genital tract.

  3. Liver spots (United States)

    Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun or other sources of ultraviolet light, or causes that are not known. Liver spots are very common after age 40. They occur ...

  4. Glycogen content and excitation-contraction coupling in mechanically skinned muscle fibres of the cane toad. (United States)

    Stephenson, D G; Nguyen, L T; Stephenson, G M


    1. Mechanically skinned skeletal muscle fibres from the twitch region of the iliofibularis muscle of cane toads were used to investigate the relationship between fibre glycogen content and fibre capacity to respond to transverse tubular (T-) system depolarization. 2. A large proportion of total fibre glycogen remained in mechanically skinned muscle fibres exposed to aqueous solutions. This glycogen pool (about 80% of total fibre glycogen) was very stable when the preparation was incubated in a rigor solution (pH 7.0) but decreased gradually at a rate of 0.59+/-0.20% min-1 in a relaxing solution (200 nM [Ca2+]). The rate was considerably higher (2.66+/-0.38% min(-1)) when the preparations were exposed to 30 microM [Ca2+]. An even greater rate of glycogen loss was found after T-system depolarization-induced contractions. The Ca2+-dependent loss of fibre glycogen was caused by endogenous glycogenolytic processes. 3. Silver stained SDS gels of components eluted into relaxing solution from single skinned fibres revealed a rapid (2 min) loss of parvalbumin and at least 10 other proteins varying in molecular mass between 10 and 80 kDa but there was essentially no loss of myosin heavy and light chains and actin. Subsequent elution for a further 30 min in either relaxing or maximally Ca2+-activating solution did not result in additional, appreciable detectable loss of fibre protein. 4. Depletion of fibre glycogen was associated with loss of fibre ability to respond to T-system depolarization even though the bathing solutions contained high levels of ATP (8 mM) and creatine phosphate (10 mM). 5. The capacity of mechanically skinned fibres to respond to T-system depolarization was highly positively correlated (Pmuscle to respond to T-system depolarization is related directly or indirectly to the non-washable glycogen pool in fibres, (ii) this relationship holds for conditions where glycogen is not required as a source of energy and (iii) the mechanically skinned fibre

  5. Glycogen phosphorylase is involved in stress endurance and biofilm formation in Azospirillum brasilense Sp7. (United States)

    Lerner, Anat; Castro-Sowinski, Susana; Lerner, Hadas; Okon, Yaacov; Burdman, Saul


    Here we report the identification of a glycogen phosphorylase (glgP) gene in the plant growth-promoting rhizobacterium Azospirillum brasilense, Sp7, and the characterization of a glgP marker exchange mutant of this strain. The glgP mutant showed a twofold reduction of glycogen phosphorylase activity and an increased glycogen accumulation as compared with wild-type Sp7, indicating that the identified gene indeed encodes a protein with glycogen phosphorylase activity. Interestingly, the glgP mutant had higher survival rates than the wild type after exposure to starvation, desiccation and osmotic pressure. The mutant was shown to be compromised in its biofilm formation ability. Analysis of the exopolysaccharide sugar composition of the glgP mutant revealed a decrease in the amount of glucose, accompanied by increases in rhamnose, fucose and ribose, as compared with the Sp7 exopolysaccharide. To the best of our knowledge, this is the first study that demonstrates GlgP activity in A. brasilense, and shows that glycogen accumulation may play an important role in the stress endurance of this bacterium.


    Directory of Open Access Journals (Sweden)

    John L. Ivy


    Full Text Available Recovery from prolonged strenuous exercise requires that depleted fuel stores be replenished, that damaged tissue be repaired and that training adaptations be initiated. Critical to these processes are the type, amount and timing of nutrient intake. Muscle glycogen is an essential fuel for intense exercise, whether the exercise is of an aerobic or anaerobic nature. Glycogen synthesis is a relatively slow process, and therefore the restoration of muscle glycogen requires special considerations when there is limited time between training sessions or competition. To maximize the rate of muscle glycogen synthesis it is important to consume a carbohydrate supplement immediately post exercise, to continue to supplement at frequent intervals and to consume approximately 1.2 g carbohydrate·kg-1 body wt·h-1. Maximizing glycogen synthesis with less frequent supplementation and less carbohydrate can be achieved with the addition of protein to the carbohydrate supplement. This will also promote protein synthesis and reduce protein degradation, thus having the added benefit of stimulating muscle tissue repair and adaptation. Moreover, recent research suggests that consuming a carbohydrate/protein supplement post exercise will have a more positive influence on subsequent exercise performance than a carbohydrate supplement.

  7. Nonlethal evaluation of the physiological health of unionid mussels: Method for biopsy and glycogen analysis (United States)

    Naimo, T.J.; Damschen, E.D.; Rada, R.G.; Monroe, E.M.


    In long-lived unionid mussels, many short-term measures of growth are of limited value. Changes in physiological condition may be an early indication of stress, because the increased energy demand associated with stress often results in a depletion of glycogen reserves, the principal storage form of carbohydrates in unionid mussels. Our goal was to nonlethally extract tissue from freshwater mussels and then to develop a rapid and dependable method for the analysis of glycogen in the tissue extracts. A biopsy technique was developed to remove between 5 and 10 mg of food tissue in Amblema plicata plicata. The survival rate did not differ between biopsied and non-biopsied mussels during a 581-d observation period, demonstrating that the biopsy technique will allow nonlethal evaluation of the physiological condition of individual mussels through measurement of changes in contaminant, genetic, and biochemical indicators in tissue. We also modified the standard alkaline digestion and phenol-sulfuric acid analysis of glycogen for use on the small samples of biopsied tissue and to reduce analysis time and cost. We present quality control data, including method detection limits and estimates of precision and bias. The modified analytical method is rapid and accurate and has a method detection limit of 0.014 mg glycogen. Glycogen content in the biopsied samples was well above the method detection limit; it ranged from 0.09 to 0.36 mg, indicating that the method should be applicable to native mussels.

  8. Homeostasis and the glycogen shunt explains aerobic ethanol production in yeast (United States)

    Shulman, Robert G.; Rothman, Douglas L.


    Aerobic glycolysis in yeast and cancer cells produces pyruvate beyond oxidative needs, a paradox noted by Warburg almost a century ago. To address this question, we reanalyzed extensive measurements from 13C magnetic resonance spectroscopy of yeast glycolysis and the coupled pathways of futile cycling and glycogen and trehalose synthesis (which we refer to as the glycogen shunt). When yeast are given a large glucose load under aerobic conditions, the fluxes of these pathways adapt to maintain homeostasis of glycolytic intermediates and ATP. The glycogen shunt uses glycolytic ATP to store glycolytic intermediates as glycogen and trehalose, generating pyruvate and ethanol as byproducts. This conclusion is supported by studies of yeast with a partial block in the glycogen shunt due to the cif mutation, which found that when challenged with glucose, the yeast cells accumulate glycolytic intermediates and ATP, which ultimately leads to cell death. The control of the relative fluxes, which is critical to maintain homeostasis, is most likely exerted by the enzymes pyruvate kinase and fructose bisphosphatase. The kinetic properties of yeast PK and mammalian PKM2, the isoform found in cancer, are similar, suggesting that the same mechanism may exist in cancer cells, which, under these conditions, could explain their excess lactate generation. The general principle that homeostasis of metabolite and ATP concentrations is a critical requirement for metabolic function suggests that enzymes and pathways that perform this critical role could be effective drug targets in cancer and other diseases. PMID:26283370

  9. Increased Laforin and Laforin Binding to Glycogen Underlie Lafora Body Formation in Malin-deficient Lafora Disease* (United States)

    Tiberia, Erica; Turnbull, Julie; Wang, Tony; Ruggieri, Alessandra; Zhao, Xiao-Chu; Pencea, Nela; Israelian, Johan; Wang, Yin; Ackerley, Cameron A.; Wang, Peixiang; Liu, Yan; Minassian, Berge A.


    The solubility of glycogen, essential to its metabolism, is a property of its shape, a sphere generated through extensive branching during synthesis. Lafora disease (LD) is a severe teenage-onset neurodegenerative epilepsy and results from multiorgan accumulations, termed Lafora bodies (LB), of abnormally structured aggregation-prone and digestion-resistant glycogen. LD is caused by loss-of-function mutations in the EPM2A or EPM2B gene, encoding the interacting laforin phosphatase and malin E3 ubiquitin ligase enzymes, respectively. The substrate and function of malin are unknown; an early counterintuitive observation in cell culture experiments that it targets laforin to proteasomal degradation was not pursued until now. The substrate and function of laforin have recently been elucidated. Laforin dephosphorylates glycogen during synthesis, without which phosphate ions interfere with and distort glycogen construction, leading to LB. We hypothesized that laforin in excess or not removed following its action on glycogen also interferes with glycogen formation. We show in malin-deficient mice that the absence of malin results in massively increased laforin preceding the appearance of LB and that laforin gradually accumulates in glycogen, which corresponds to progressive LB generation. We show that increasing the amounts of laforin in cell culture causes LB formation and that this occurs only with glycogen binding-competent laforin. In summary, malin deficiency causes increased laforin, increased laforin binding to glycogen, and LB formation. Furthermore, increased levels of laforin, when it can bind glycogen, causes LB. We conclude that malin functions to regulate laforin and that malin deficiency at least in part causes LB and LD through increased laforin binding to glycogen. PMID:22669944

  10. Molecular analysis of glycogen storage disease type Ia in Iranian Azeri Turks: identification of a novel mutation

    Indian Academy of Sciences (India)



    Glycogen storage diseases (GSDs) are caused by abnormalities in enzymes that are involved in the regulation of gluconeogenesis and glycogenolysis. GSD I, an autosomal recessive metabolic disorder, is the most common GSD and has four subtypes. Here, we examined GSD Ia caused by the defective glucose-6-phosphatase catalytic (G6PC) gene. We investigated the frequency of GSD Ia and clarified its molecular aspect in patients with the main clinical and biochemical characteristics of GSD, including 37 unrelated patients with a mean age of three years at the time of diagnosis. All patients belonged to the Azeri Turkish population. Hypoglycaemia and hypertriglyceridaemia were the most frequent laboratory findings. Mutations were detected by performing direct sequencing. Mutation analysis of the G6PC gene revealed that GSD Ia accounted for 11%in GSD patients with involvement of liver. Three patients were homozygous for R83C mutation. In addition, a novel stop mutation, Y85X, was identified in a patient with the typical features of GSD Ia.

  11. Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease type 1a

    Energy Technology Data Exchange (ETDEWEB)

    Chou, J.Y.; Lei, K.J.; Shelly, L.L. [National Institutes of Health, Bethesda, MD (United States)


    Glycogen storage disease (GSD) type la (von Gierke disease) is caused by the deficiency of glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. The disease presents with clinical manifestations of severe hypoglycemia, hepatomegaly, growth retardation, lactic acidemia, hyperlipidemia, and hyperuricemia. We have succeeded in isolating a murine G6Pase cDNA from a normal mouse liver cDNA library by differentially screening method. We then isolated the human G6Pase cDNA and gene. To date, we have characterized the G6Pase genes of twelve GSD type la patients and uncovered a total of six different mutations. The mutations are comprised of R83C (an Arg at codon 83 to a Cys), Q347X (a Gly at codon 347 to a stop codon), 459insTA (a two basepair insertion at nucleotide 459 yielding a truncated G6Pase of 129 residues), R295C (an Arg at codon 295 to a Cys), G222R (a Gly at codon 222 to an Arg) and {delta}F327 (a codon deletion for Phe-327 at nucleotides 1058 to 1060). The relative incidences of these mutations are 37.5% (R83C), 33.3% (Q347X), 16.6% (459insTA), 4.2% (G222R), 4.2% (R295C) and 4.2% ({delta}F327). Site-directed mutagenesis and transient expression assays demonstrated that the R83C, Q347X, R295C, and {delta}F327 mutations abolished whereas the G222R mutation greatly reduced G6Pase activity. We further characterized the structure-function requirements of amino acids 83, 222, and 295 in G6Pase catalysis. The identification of mutations in GSD type la patients has unequivocally established the molecular basis of the type la disorder. Knowledge of the mutations may be applied to prenatal diagnosis and opens the way for developing and evaluating new therapeutic approaches.

  12. Genetic alteration in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Chul; Kang, Tae Woong; Lee, Jin Oh [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Seoul (Korea, Republic of)


    Cancer of stomach, colon and liver are a group of the most common cancer in Korea. However, results with current therapeutic modalities are still unsatisfactory. The intensive efforts have been made to understand basic pathogenesis and to find better therapeutic tools for the treatment of this miserable disease. We studied the alteration of tumor suppressor genes and oncogenes in hepatocellular carcinoma in Korea. We found that alteration of Rb gene, APC were 33 %, 13 % respectively. But alterations of oncogenes such as myc, ras and mdm2 were rarely found. Our results suggests that HBV may act as oncogenic role in hepatocarcinogenesis instead of oncogenes. 6 figs, 2 tabs. (Author).

  13. Impaired muscle glycogen resynthesis after a marathon is not caused by decreased muscle GLUT-4 content

    DEFF Research Database (Denmark)

    Asp, S; Rohde, T; Richter, Erik


    -race levels 7 days after the race. We conclude that the total GLUT-4 protein content is unaltered in the lateral gastrocnemius after a competitive marathon and that the slow recovery of muscle glycogen after the race apparently involves factors other than changes in the total content of this protein.......Our purpose was to investigate whether the slow rate of muscle glycogen resynthesis after a competitive marathon is associated with a decrease in the total muscle content of the muscle glucose transporter (GLUT-4). Seven well-trained marathon runners participated in the study, and muscle biopsies...... were obtained from the lateral head of the gastrocnemius muscle before, immediately after, and 1, 2, and 7 days after the marathon, as were venous blood samples. Muscle GLUT-4 content was unaltered over the experimental period. Muscle glycogen concentration was 758 +/- 53 mmol/kg dry weight before...

  14. A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle. (United States)

    Milan, D; Jeon, J T; Looft, C; Amarger, V; Robic, A; Thelander, M; Rogel-Gaillard, C; Paul, S; Iannuccelli, N; Rask, L; Ronne, H; Lundström, K; Reinsch, N; Gellin, J; Kalm, E; Roy, P L; Chardon, P; Andersson, L


    A high proportion of purebred Hampshire pigs carries the dominant RN- mutation, which causes high glycogen content in skeletal muscle. The mutation has beneficial effects on meat content but detrimental effects on processing yield. Here, it is shown that the mutation is a nonconservative substitution (R200Q) in the PRKAG3 gene, which encodes a muscle-specific isoform of the regulatory gamma subunit of adenosine monophosphate-activated protein kinase (AMPK). Loss-of-function mutations in the homologous gene in yeast (SNF4) cause defects in glucose metabolism, including glycogen storage. Further analysis of the PRKAG3 signaling pathway may provide insights into muscle physiology as well as the pathogenesis of noninsulin-dependent diabetes mellitus in humans, a metabolic disorder associated with impaired glycogen synthesis.

  15. Dietary tools to modulate glycogen storage in gilthead seabream muscle: glycerol supplementation. (United States)

    Silva, Tomé S; Matos, Elisabete; Cordeiro, Odete D; Colen, Rita; Wulff, Tune; Sampaio, Eduardo; Sousa, Vera; Valente, Luisa M P; Gonçalves, Amparo; Silva, Joana M G; Bandarra, Narcisa; Nunes, Maria Leonor; Dinis, Maria Teresa; Dias, Jorge; Jessen, Flemming; Rodrigues, Pedro M


    The quality and shelf life of fish meat products depend on the skeletal muscle's energetic state at slaughter, as meat decomposition processes can be exacerbated by energy depletion. In this study, we tested dietary glycerol as a way of replenishing muscle glycogen reserves of farmed gilthead seabream. Two diets were tested in duplicate (n = 42/tank). Results show 5% inclusion of crude glycerol in gilthead seabream diets induces increased muscle glycogen, ATP levels and firmness, with no deleterious effects in terms of growth, proximate composition, fatty acid profile, oxidative state, and organoleptic properties (aroma and color). Proteomic analysis showed a low impact of glycerol-supplementation on muscle metabolism, with most changes probably reflecting increased stress coping capacity in glycerol-fed fish. This suggests inclusion of crude glycerol in gilthead seabream diets (particularly in the finishing phase) seems like a viable strategy to increase glycogen deposition in muscle without negatively impacting fish welfare and quality.

  16. Glucose balance and muscle glycogen during TPN in the early post-operative phase

    DEFF Research Database (Denmark)

    Henneberg, S; Stjernström, H; Essén-Gustavsson, B;


    In order to study how muscle glycogen is influenced by different nutritional regimens in the early post-operative period we took muscle biopsies from 20 patients preoperatively and on the fourth post-operative day after abdominal aortic surgery. Ten patients received 93% of non-protein energy...... as glucose, 7% as fat (Intralipid) and insulin was given to keep the blood glucose below 10 mmol/l. The remaining patients had 80% of non-protein energy as fat (Intralipid). Amino acids constituting 12 g of nitrogen daily were given to both groups. Daily measurements of gas exchange (oxygen uptake, CO2...... glycogen stores at pre-operative levels with a glucose-insulin regimen. With the fat regimen there was a 31% decrease in muscle glycogen and two patients had a negative glucose balance despite the fact that 150 g of glucose were given. Average glucose balance throughout the study correlated positively...

  17. Postexercise Glycogen Recovery and Exercise Performance is Not Significantly Different Between Fast Food and Sport Supplements. (United States)

    Cramer, Michael J; Dumke, Charles L; Hailes, Walter S; Cuddy, John S; Ruby, Brent C


    A variety of dietary choices are marketed to enhance glycogen recovery after physical activity. Past research informs recommendations regarding the timing, dose, and nutrient compositions to facilitate glycogen recovery. This study examined the effects of isoenergetic sport supplements (SS) vs. fast food (FF) on glycogen recovery and exercise performance. Eleven males completed two experimental trials in a randomized, counterbalanced order. Each trial included a 90-min glycogen depletion ride followed by a 4-hr recovery period. Absolute amounts of macronutrients (1.54 ± 0.27 g·kg-1 carbohydrate, 0.24 ± 0.04 g·kg fat-1, and 0.18 ±0.03g·kg protein-1) as either SS or FF were provided at 0 and 2 hr. Muscle biopsies were collected from the vastus lateralis at 0 and 4 hr post exercise. Blood samples were analyzed at 0, 30, 60, 120, 150, 180, and 240 min post exercise for insulin and glucose, with blood lipids analyzed at 0 and 240 min. A 20k time-trial (TT) was completed following the final muscle biopsy. There were no differences in the blood glucose and insulin responses. Similarly, rates of glycogen recovery were not different across the diets (6.9 ± 1.7 and 7.9 ± 2.4 mmol·kg wet weight- 1·hr-1 for SS and FF, respectively). There was also no difference across the diets for TT performance (34.1 ± 1.8 and 34.3 ± 1.7 min for SS and FF, respectively. These data indicate that short-term food options to initiate glycogen resynthesis can include dietary options not typically marketed as sports nutrition products such as fast food menu items.

  18. Structure-Function Analysis of PPP1R3D, a Protein Phosphatase 1 Targeting Subunit, Reveals a Binding Motif for 14-3-3 Proteins which Regulates its Glycogenic Properties


    Rubio-Villena, Carla; Sanz, Pascual; Garcia-Gimeno, Maria Adelaida


    Protein phosphatase 1 (PP1) is one of the major protein phosphatases in eukaryotic cells. It plays a key role in regulating glycogen synthesis, by dephosphorylating crucial enzymes involved in glycogen homeostasis such as glycogen synthase (GS) and glycogen phosphorylase (GP). To play this role, PP1 binds to specific glycogen targeting subunits that, on one hand recognize the substrates to be dephosphorylated and on the other hand recruit PP1 to glycogen particles. In this work we have analyz...

  19. Liver metastases (United States)

    ... no symptoms. When symptoms occur, they may include: Decreased appetite Confusion Fever , sweating Jaundice (yellowing of the skin ... can include: Blockage of the flow of bile Decreased appetite Fever Liver failure (usually only in the late ...

  20. Enlarged Liver (United States)

    ... A blood sample is tested to determine liver enzyme levels. This can give clues about the health ... prescription medications. Limit contact with chemicals. Use aerosol cleaners, insecticides and other toxic chemicals only in well- ...

  1. Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II

    NARCIS (Netherlands)

    A.G.A. Bijvoet (Agnes); A.J.J. Reuser (Arnold); H. van Hirtum (Hans); M.A. Kroos (Marian); E.H. van de Kamp; O. Schoneveld; P. Visser (Pim); J.P. Brakenhoff (Just); M. Weggeman; E.J.J.M. van Corven (Emiel); A.T. van der Ploeg (Ans)


    textabstractPompe's disease or glycogen storage disease type II (GSDII) belongs to the family of inherited lysosomal storage diseases. The underlying deficiency of acid alpha-glucosidase leads in different degrees of severity to glycogen storage in heart, skeletal and s

  2. Role of glycogen-lowering exercise in the change of fat oxidation in response to a high-fat diet.

    NARCIS (Netherlands)

    Schrauwen, P.; van Marken Lichtenbelt, W.D.; Saris, W.H.M.; Westerterp, K.R.


    Department of Human Biology, Maastricht University, The Netherlands. One of the candidate factors for determining the increase of fat oxidation after a switch from a reduced-fat diet to a high-fat diet is the size of the glycogen storage. Therefore, we studied the effect of low glycogen stores on fa

  3. Functional importance of the astrocytic glycogen-shunt and glycolysis for maintenance of an intact intra/extracellular glutamate gradient

    DEFF Research Database (Denmark)

    Schousboe, Arne; Sickmann, Helle M; Walls, Anne B


    It has been proposed that a considerable fraction of glucose metabolism proceeds via the glycogen-shunt consisting of conversion of glucose units to glycogen residues and subsequent production of glucose-1-phosphate to be metabolized in glycolysis after conversion to glucose-6-phosphate...

  4. A whole-body model for glycogen regulation reveals a critical role for substrate cycling in maintaining blood glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    Ke Xu


    Full Text Available Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur during transition from the fed to the fasted state. Analysis of the model reveals a critical role for the inhibition of glycogen synthase phosphatase by glycogen phosphorylase a. This negative regulation leads to high levels of glycogen synthase activity during fasting conditions, which in turn increases substrate (futile cycling, priming the system for a rapid response once an external source of glucose is restored. This work demonstrates that a mechanistic understanding of the design principles used by metabolic control circuits to maintain homeostasis can benefit from the incorporation of mathematical descriptions of these networks into "whole-body" contextual models that mimic in vivo conditions.

  5. Liver function

    Institute of Scientific and Technical Information of China (English)


    2008308 Study on transplantation of induced bone marrow mesenchymal stem cells via a series of the treatment of chronic liver injury. SUN Yan(孙艳), et al. Dept Gastroenterol, 1st Hosp, Jilin Univ, Changchun 130021. Chin J Dig 2008;28(3):171-174.Objective To investigate the efficacy of transplantation of induced bone marrow mesenchymal stem cells(MSCs)via a series of treatment of chronic liver injury.Methods MSCs were isolated and expanded by density

  6. Skeletal muscle glycogen content and particle size of distinct subcellular localizations in the recovery period after a high-level soccer match

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Krustrup, Peter; Nybo, Lars


    Whole muscle glycogen levels remain low for a prolonged period following a soccer match. The present study was conducted to investigate how this relates to glycogen content and particle size in distinct subcellular localizations. Seven high-level male soccer players had a vastus lateralis muscle...... biopsy collected immediately after and 24, 48, 72 and 120 h after a competitive soccer match. Transmission electron microscopy was used to estimate the subcellular distribution of glycogen and individual particle size. During the first day of recovery, glycogen content increased by ~60% in all...... subcellular localizations, but during the subsequent second day of recovery glycogen content located within the myofibrils (Intramyofibrillar glycogen, a minor deposition constituting 10-15% of total glycogen) did not increase further compared with an increase in subsarcolemmal glycogen (-7 vs. +25...

  7. Skeletal muscle glycogen content and particle size of distinct subcellular localizations in the recovery period after a high-level soccer match

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Krustrup, Peter; Nybo, Lars;


    biopsy collected immediately after and 24, 48, 72 and 120 h after a competitive soccer match. Transmission electron microscopy was used to estimate the subcellular distribution of glycogen and individual particle size. During the first day of recovery, glycogen content increased by ~60% in all...... subcellular localizations, but during the subsequent second day of recovery glycogen content located within the myofibrils (Intramyofibrillar glycogen, a minor deposition constituting 10-15% of total glycogen) did not increase further compared with an increase in subsarcolemmal glycogen (-7 vs. +25......%, respectively, P = 0.047). Conversely, from the second to the fifth day of recovery, glycogen content increased (53%) within the myofibrils compared to no change in subsarcolemmal or intermyofibrillar glycogen (P ...

  8. Ameliorating effect of Semecarpus anacardium Linn. nut milk extract on altered glucose metabolism in high fat diet STZ induced type 2 diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Kaladevi Siddhi Vinayagam; Shanthi Palanivelu; Sachdanandam Panchanadham


    Objective: To explore the protective effect of the drug Semecarpus anacardium (S. anacardium) on altered glucose metabolism in diabetic rats. Methods: Type 2 diabetes mellitus was induced by feeding rats with high fat diet followed by single intraperitoneal injection of streptozotocin (STZ) (35 mg/kg b.w.). Seven days after STZ induction, diabetic rats received nut milk extract ofS. anacardium Linn. nut milk extract orally at a dosage of 200 mg/kg daily for 4 weeks. The effect of nut milk extract of S. anacardium on blood glucose, plasma insulin, glucose metabolising enzymes and GSK were studied. Results: Treatment with SA extract showed a significant reduction in blood glucose levels and increase in plasma insulin levels and also increase in HOMA - β and decrease in HOMA -IR. The drug significantly increased the activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase activity and increased the glycogen content in liver of diabetic rats while reducing the activities of gluconeogenic enzymes. The drug also effectively ameliorated the alterations in GSK-3 mRNA expression. Conclusions: Overall, the present study demonstrates the possible mechanism of glucose regulation of S. anacardium suggestive of its therapeutic potential for the management of diabetes mellitus.

  9. Enhanced Glycogen Storage of a Subcellular Hot Spot in Human Skeletal Muscle during Early Recovery from Eccentric Contractions

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Farup, Jean; Rahbek, Stine Klejs


    Unaccustomed eccentric exercise is accompanied by muscle damage and impaired glucose uptake and glycogen synthesis during subsequent recovery. Recently, it was shown that the role and regulation of glycogen in skeletal muscle are dependent on its subcellular localization, and that glycogen...... content during post-exercise recovery from eccentric contractions. Analysis was completed on five male subjects performing an exercise bout consisting of 15 x 10 maximal eccentric contractions. Carbohydrate-rich drinks were subsequently ingested throughout a 48 h recovery period and muscle biopsies...... in both type I and II fibers were lower in the exercise leg compared with the control leg, and this was associated with a smaller size of the glycogen particles. We conclude that in the carbohydrate-supplemented state, the effect of eccentric contractions on glycogen metabolism depends on the subcellular...

  10. Muscle ceramide content in man is higher in type I than type II fibers and not influenced by glycogen content

    DEFF Research Database (Denmark)

    Nordby, P; Prats, C; Kristensen, D;


    Human muscle is studied during glycogen depletion and repletion to understand the influence of exercise and muscle glycogen on total ceramide content. In addition, fiber-type-specific ceramide storage is investigated. Ten healthy males (26.4 +/- 0.9 years, BMI 24.4 +/- 0.7 kg m(-2) and VO2max 57...... +/- 2 mL O2 min(-1) kg(-1)) participated in the study. On the first day, one leg was glycogen-depleted (DL) by exhaustive intermittent exercise followed by low carbohydrate diet. Next day, in the overnight fasted condition, muscle biopsies were excised from vastus lateralis before and after exhaustive...... exercise from both DL and control leg (CL). Muscle glycogen was analyzed biochemically and total muscle ceramide content by 2D quantitative lipidomic approach. Furthermore, fiber-type ceramide content was determined by fluorescence immunohistochemistry. Basal muscle glycogen was decreased (P

  11. Chromosomal mapping and mutational analysis of the coding region of the glycogen synthase kinase-3alpha and beta isoforms in patients with NIDDM

    DEFF Research Database (Denmark)

    Hansen, L; Arden, K C; Rasmussen, S B


    Activation of glycogen synthesis in skeletal muscle in response to insulin results from the combined inactivation of glycogen synthase kinase-3 (GSK-3) and activation of the protein phosphatase-1, changing the ratio between the inactive phosphorylated state of the glycogen synthase to the active ...

  12. Drug –induced liver injury:a review

    Directory of Open Access Journals (Sweden)

    Sreya Kosanam


    Full Text Available The incidence of drug induced liver injury (DILI is about 1/1000 to 1/10000 among patients who receive therapeutic drug doses. Drug induced hepatotoxicity is a major cause of acute and chronic liver disease. The severity of liver damage ranges from nonspecific changes in liver structure to acute liver failure, cirrhosis and liver cancer. Some common agents that can cause liver injury are acetaminophen, antibiotics, statins, INH and herbal drugs.Drug-induced hepatotoxicity can be categorized based on the pattern of liver enzyme alteration (hepatocellular, cholestatic or mixed pattern, the mechanism of hepatotoxicity (direct, immune mediated or idiosyncratic and histologic findings on liver biopsy (steatosis or sinusoidal obstruction syndrome. Treatment options for DILI include discontinuing the drug, conservative measurements and liver transplantation in the case of non-acetaminophen induced hepatotoxicity.

  13. Creatine supplementation does not affect human skeletal muscle glycogen content in the absence of prior exercise. (United States)

    Sewell, Dean A; Robinson, Tristan M; Greenhaff, Paul L


    Due to the current lack of clarity, we examined whether 5 days of dietary creatine (Cr) supplementation per se can influence the glycogen content of human skeletal muscle. Six healthy male volunteers participated in the study, reporting to the laboratory on four occasions to exercise to the point of volitional exhaustion, each after 3 days of a controlled normal habitual dietary intake. After a familiarization visit, participants cycled to exhaustion in the absence of any supplementation (N), and then 2 wk later again they cycled to exhaustion after 5 days of supplementation with simple sugars (CHO). Finally, after a further 2 wk, they again cycled to exhaustion after 5 days of Cr supplementation. Muscle samples were taken at rest before exercise, at the time point of exhaustion in visit 1, and at subsequent visit time of exhaustion. There was a treatment effect on muscle total Cr content in Cr compared with N and CHO supplementation (P exercise. Cr supplementation under conditions of controlled habitual dietary intake had no effect on muscle glycogen content at rest or after exhaustive exercise. We suggest that any Cr-associated increases in muscle glycogen storage are the result of an interaction between Cr supplementation and other mediators of muscle glycogen storage.

  14. GLUT4 and glycogen synthase are key players in bed rest-induced insulin resistance

    DEFF Research Database (Denmark)

    Biensø, Rasmus Sjørup; Jørgensen, Stine Ringholm; Kiilerich, Kristian


    glycogen synthase (GS) was reduced with normal GS site 3 but abnormal GS site 2+2a phosphorylation after bed rest. Exercise enhanced insulin-stimulated leg glucose extraction both before and after bed rest, which was accompanied by higher GS activity in the prior-exercised leg than the rested leg...

  15. Pre- and posttranslational upregulation of muscle-specific glycogen synthase in athletes

    DEFF Research Database (Denmark)

    Vestergaard, H; Andersen, P H; Lund, S


    by insulin. We conclude that athletes have increased whole body insulin-stimulated nonoxidative glucose metabolism associated with both pretranslational (mRNA) and posttranslational (enzyme activity) upregulation of GS. However, the immunoreactive mass of GS is normal, emphasizing that posttranslational...... regulation of the GS protein activity is important for the increased glycogen synthesis rate of muscle in endurance-trained individuals....

  16. Renal Function in Glycogen Storage Disease Type I, Natural Course, and Renopreservative Effects of ACE Inhibition

    NARCIS (Netherlands)

    Martens, Danielle H. J.; Rake, Jan Peter; Navis, Gerjan; Fidler, Vaclav; van Dael, Catharina M. L.; Smit, G. Peter A.


    Background and objectives: Renal failure is a major complication in glycogen storage disease type I (GSD I). We studied the natural course of renal function in GSD I patients. We studied differences between patients in optimal and nonoptimal metabolic control and possible renoprotective effects of a

  17. Thermoregulation during Cold Water Immersion is Unimpaired by Muscle Glycogen Depletion (United States)


    a decrease in plasma glucose oxidation, and a concomitant increase in muscle glycogenolysis as compared to rest (14). Other animal experiments suggest... glycogenolysis . Alternatively, the increased plasma glycerol during cold water immersion in the low-glycogen trial indicates that enhanced lipolysis is

  18. Kinetic analysis of glycogen turnover: relevance to human brain 13C-NMR spectroscopy. (United States)

    DiNuzzo, Mauro


    A biophysical model of the glycogen molecule is developed, which takes into account the points of attack of synthase and phosphorylase at the level of the individual glucose chain. Under the sole assumption of steric effects governing enzyme accessibility to glucosyl residues, the model reproduces the known equilibrium structure of cellular glycogen at steady state. In particular, experimental data are reproduced assuming that synthase (1) operates preferentially on inner chains of the molecule and (2) exhibits a faster mobility than phosphorylase in translocating from an attacked chain to another. The model is then used to examine the turnover of outer versus inner tiers during the labeling process of isotopic enrichment (IE) experiments. Simulated data are fitted to in vivo (13)C nuclear magnetic resonance spectroscopy measurements obtained in the human brain under resting conditions. Within this experimental set-up, analysis of simulated label incorporation and retention shows that 7% to 35% of labeled glucose is lost from the rapidly turning-over surface of the glycogen molecule when stimulation onset is delayed by 7 to 11.5 hours after the end of [1-(13)C]glucose infusion as done in actual procedures. The substantial label washout before stimulation suggests that much of the subsequent activation-induced glycogenolysis could remain undetected. Overall, these results show that the molecular structure significantly affects the patterns of synthesis and degradation of glycogen, which is relevant for appropriate design of labeling experiments aiming at investigating the functional roles of this glucose reserve.

  19. Impact of carbohydrate supplementation during endurance training on glycogen storage and performance

    DEFF Research Database (Denmark)

    Nybo, Lars; Pedersen, K.; Christensen, B.


    ingestion. Methods: In previously untrained males performance and various muscular adaptations were evaluated before and after 8 weeks of supervised endurance training conducted either with (n = 8; CHO group) or without (n = 7; placebo) glucose supplementation. Results: The two groups achieved similar.......05), while resting muscle glycogen increased (P supplementation consumed during exercise training influences various muscular training adaptations, but improvements...

  20. Dietary Tools To Modulate Glycogen Storage In Fish Muscle: A Proteomic Assessment

    DEFF Research Database (Denmark)

    Silva, Tomé S.; Matos, Elisabete; Cordeire, Odete

    Post-mortem flesh deterioration is dependent on the energy reserves present at the time of death. Early depletion of muscle glycogen leads to the buildup of lactate and to the early onset of rigor mortis, resulting in the activation of endogenous proteases and the degradation of myofibrillar prot...

  1. Function of trehalose and glycogen in cell cycle progression and cell viability in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Silljé, H H; Paalman, J W; ter Schure, E G; Olsthoorn, S Q; Verkleij, A J; Boonstra, Johannes; Verrips, C T


    Trehalose and glycogen accumulate in Saccharomyces cerevisiae when growth conditions deteriorate. It has been suggested that aside from functioning as storage factors and stress protectants, these carbohydrates may be required for cell cycle progression at low growth rates under carbon limitation. B

  2. Local depletion of glycogen with supra-maximal exercise in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Gejl, K D; Ørtenblad, N; Andersson, E;


    importance to muscle function. The present study was designed to investigate the depletion of these three sub-cellular glycogen compartments during repeated supra-maximal exercise in elite athletes. Ten elite cross-country skiers (age: 25 ± 4 yrs., VO2 max : 65 ± 4 ml kg(-1) min(-1) , mean ± SD) performed...

  3. Glycogen synthase kinase 3α regulates urine concentrating mechanism in mice

    DEFF Research Database (Denmark)

    Nørregaard, Rikke; Tao, Shixin; Nilsson, Line;


    In mammals, glycogen synthase kinase (GSK)3 comprises GSK3α and GSK3β isoforms. GSK3β has been shown to play a role in the ability of kidneys to concentrate urine by regulating vasopressin-mediated water permeability of collecting ducts, whereas the role of GSK3α has yet to be discerned. To inves...

  4. Advanced glycation end products and the absence of premature atherosclerosis in glycogen storage disease Ia

    NARCIS (Netherlands)

    den Hollander, N. C.; Mulder, Douwe J.; Graaff, R.; Thorpe, S. R.; Baynes, J. W.; Smit, Gerrit; Smit, Andries


    Introducton: Despite their unfavourable cardiovascular risk profile, patients with glycogen storage disease type Ia (GSD Ia) do not develop premature atherosclerosis. We hypothesized that this paradox might be related to a decreased formation of advanced glycation end products (AGEs) resulting from

  5. The effects of glycogen synthase kinase-3beta in serotonin neurons.

    Directory of Open Access Journals (Sweden)

    Wenjun Zhou

    Full Text Available Glycogen synthase kinase-3 (GSK3 is a constitutively active protein kinase in brain. Increasing evidence has shown that GSK3 acts as a modulator in the serotonin neurotransmission system, including direct interaction with serotonin 1B (5-HT1B receptors in a highly selective manner and prominent modulating effect on 5-HT1B receptor activity. In this study, we utilized the serotonin neuron-selective GSK3β knockout (snGSK3β-KO mice to test if GSK3β in serotonin neurons selectively modulates 5-HT1B autoreceptor activity and function. The snGSK3β-KO mice were generated by crossbreeding GSK3β-floxed mice and ePet1-Cre mice. These mice had normal growth and physiological characteristics, similar numbers of tryptophan hydroxylase-2 (TpH2-expressing serotonin neurons, and the same brain serotonin content as in littermate wild type mice. However, the expression of GSK3β in snGSK3β-KO mice was diminished in TpH2-expressing serotonin neurons. Compared to littermate wild type mice, snGSK3β-KO mice had a reduced response to the 5-HT1B receptor agonist anpirtoline in the regulation of serotonergic neuron firing, cAMP production, and serotonin release, whereas these animals displayed a normal response to the 5-HT1A receptor agonist 8-OH-DPAT. The effect of anpirtoline on the horizontal, center, and vertical activities in the open field test was differentially affected by GSK3β depletion in serotonin neurons, wherein vertical activity, but not horizontal activity, was significantly altered in snGSK3β-KO mice. In addition, there was an enhanced anti-immobility response to anpirtoline in the tail suspension test in snGSK3β-KO mice. Therefore, results of this study demonstrated a serotonin neuron-targeting function of GSK3β by regulating 5-HT1B autoreceptors, which impacts serotonergic neuron firing, serotonin release, and serotonin-regulated behaviors.

  6. Alteration in the Expression of Cytochrome P450s (CYP1A1, CYP2E1, and CYP3A11 in the Liver of Mouse Induced by Microcystin-LR

    Directory of Open Access Journals (Sweden)

    Bangjun Zhang


    Full Text Available Microcystins (MCs are cyclic heptapeptide toxins and can accumulate in the liver. Cytochrome P450s (CYPs play an important role in the biotransformation of endogenous substances and xenobiotics in animals. It is unclear if the CYPs are affected by MCs exposure. The objective of this study was to evaluate the effects of microcystin-LR (MCLR on cytochrome P450 isozymes (CYP1A1, CYP2E1, and CYP3A11 at mRNA level, protein content, and enzyme activity in the liver of mice the received daily, intraperitoneally, 2, 4, and 8 µg/kg body weight of MCLR for seven days. The result showed that MCLR significantly decreased ethoxyresorufin-O-deethylase (EROD (CYP1A1 and erythromycin N-demthylase (ERND (CYP3A11 activities and increased aniline hydroxylase (ANH activity (CYP2E1 in the liver of mice during the period of exposure. Our findings suggest that MCLR exposure may disrupt the function of CYPs in liver, which may be partly attributed to the toxicity of MCLR in mice.

  7. Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation (United States)

    Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined abi...

  8. Insulin promotes glycogen storage and cell proliferation in primary human astrocytes.

    Directory of Open Access Journals (Sweden)

    Martin Heni

    Full Text Available INTRODUCTION: In the human brain, there are at least as many astrocytes as neurons. Astrocytes are known to modulate neuronal function in several ways. Thus, they may also contribute to cerebral insulin actions. Therefore, we examined whether primary human astrocytes are insulin-responsive and whether their metabolic functions are affected by the hormone. METHODS: Commercially available Normal Human Astrocytes were grown in the recommended medium. Major players in the insulin signaling pathway were detected by real-time RT-PCR and Western blotting. Phosphorylation events were detected by phospho-specific antibodies. Glucose uptake and glycogen synthesis were assessed using radio-labeled glucose. Glycogen content was assessed by histochemistry. Lactate levels were measured enzymatically. Cell proliferation was assessed by WST-1 assay. RESULTS: We detected expression of key proteins for insulin signaling, such as insulin receptor β-subunit, insulin receptor substrat-1, Akt/protein kinase B and glycogen synthase kinase 3, in human astrocytes. Akt was phosphorylated and PI-3 kinase activity increased following insulin stimulation in a dose-dependent manner. Neither increased glucose uptake nor lactate secretion after insulin stimulation could be evidenced in this cell type. However, we found increased insulin-dependent glucose incorporation into glycogen. Furthermore, cell numbers increased dose-dependently upon insulin treatment. DISCUSSION: This study demonstrated that human astrocytes are insulin-responsive at the molecular level. We identified glycogen synthesis and cell proliferation as biological responses of insulin signaling in these brain cells. Hence, this cell type may contribute to the effects of insulin in the human brain.

  9. High density lipoprotein (HDL promotes glucose uptake in adipocytes and glycogen synthesis in muscle cells.

    Directory of Open Access Journals (Sweden)

    Qichun Zhang

    Full Text Available BACKGROUND: High density lipoprotein (HDL was reported to decrease plasma glucose and promote insulin secretion in type 2 diabetes patients. This investigation was designed to determine the effects and mechanisms of HDL on glucose uptake in adipocytes and glycogen synthesis in muscle cells. METHODS AND RESULTS: Actions of HDL on glucose uptake and GLUT4 translocation were assessed with 1-[(3H]-2-deoxyglucose and plasma membrane lawn, respectively, in 3T3-L1 adipocytes. Glycogen analysis was performed with amyloglucosidase and glucose oxidase-peroxidase methods in normal and palmitate-treated L6 cells. Small interfering RNA was used to observe role of scavenger receptor type I (SR-BI in glucose uptake of HDL. Corresponding signaling molecules were detected by immunoblotting. HDL stimulated glucose uptake in a time- and concentration-dependent manner in 3T3-L1 adipocytes. GLUT4 translocation was significantly increased by HDL. Glycogen deposition got enhanced in L6 muscle cells paralleling with elevated glycogen synthase kinase3 (GSK3 phosphorylation. Meanwhile, increased phosphorylations of Akt-Ser473 and AMP activated protein kinase (AMPK α were detected in 3T3-L1 adipocytes. Glucose uptake and Akt-Ser473 activation but not AMPK-α were diminished in SR-BI knock-down 3T3-L1 cells. CONCLUSIONS: HDL stimulates glucose uptake in 3T3-L1 adipocytes through enhancing GLUT4 translocation by mechanisms involving PI3K/Akt via SR-BI and AMPK signaling pathways, and increases glycogen deposition in L6 muscle cells through promoting GSK3 phosphorylation.

  10. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    Energy Technology Data Exchange (ETDEWEB)

    Manceur, Aziza P. [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Tseng, Michael [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Holowacz, Tamara [Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Witterick, Ian [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Department of Otolaryngology, Head and Neck Surgery, University of Toronto, ON (Canada); Weksberg, Rosanna [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); McCurdy, Richard D. [The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); Warsh, Jerry J. [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Audet, Julie, E-mail: [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada)


    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  11. Variation in glycogen concentrations within mantle and foot tissue in Amblema plicata plicata: Implications for tissue biopsy sampling (United States)

    Naimo, T.J.; Monroe, E.M.


    With the development of techniques to non-lethally biopsy tissue from unionids, a new method is available to measure changes in biochemical, contaminant, and genetic constituents in this imperiled faunal group. However, before its widespread application, information on the variability of biochemical components within and among tissues needs to be evaluated. We measured glycogen concentrations in foot and mantle tissue in Amblema plicata plicata (Say, 1817) to determine if glycogen was evenly distributed within and between tissues and to determine which tissue might be more responsive to the stress associated with relocating mussels. Glycogen was measured in two groups of mussels: those sampled from their native environment (undisturbed mussels) and quickly frozen for analysis and those relocated into an artificial pond (relocated mussels) for 24 months before analysis. In both undisturbed and relocated mussels, glycogen concentrations were evenly distributed within foot, but not within mantle tissue. In mantle tissue, concentrations of glycogen varied about 2-fold among sections. In addition, glycogen varied significantly between tissues in undisturbed mussels, but not in relocated mussels. Twenty-four months after relocation, glycogen concentrations had declined by 80% in mantle tissue and by 56% in foot tissue relative to the undisturbed mussels. These data indicate that representative biopsy samples can be obtained from foot tissue, but not mantle tissue. We hypothesize that mantle tissue could be more responsive to the stress of relocation due to its high metabolic activity associated with shell formation.

  12. Cypermethrin-Induced Toxic Effect on Glycogen Metabolism in Estuarine Clam, Marcia Opima (Gmelin, 1791 of Ratnagiri Coast, Maharashtra

    Directory of Open Access Journals (Sweden)

    Medha Tendulkar


    Full Text Available Cypermethrin is a synthetic pyrethroid class of insecticide. Toxic effects of cypermethrin were studied by selecting Marcia opima as an animal model. Cypermethrins effect on the total glycogen content of mantle, gill, foot, hepatopancreas, male gonad and a female gonad of an estuarine clam, Marcia opima was examined. The clams were exposed to 1.58 ppm cypermethrin for acute and 1/th of that concentration for chronic treatment. It was found that there was a decrease in glycogen content in various tissues as compared to control. In LC0 and LC50 groups, glycogen was decreased in all tissues except in hepatopancreas compared to control. This decrease is greater in mantle, gill, and foot in LC50 group than the decrease in those tissues of LC0 group. In chronic exposure it was found that glycogen was decreased in mantle, foot, male gonad, and female gonad when compared to the control group except in gill and hepatopancreas. Decrease in glycogen content indicates greater utilization of glycogen for metabolic purposes and too combat with cypermethrin stress. The significant increase in glycogen content in gill and hepatopancreas may be a reaction to the increase in energy demand.

  13. Palmitate action to inhibit glycogen synthase and stimulate protein phosphatase 2A increases with risk factors for type 2 diabetes. (United States)

    Mott, David M; Stone, Karen; Gessel, Mary C; Bunt, Joy C; Bogardus, Clifton


    Recent studies have suggested that abnormal regulation of protein phosphatase 2A (PP2A) is associated with Type 2 diabetes in rodent and human tissues. Results with cultured mouse myotubes support a mechanism for palmitate activation of PP2A, leading to activation of glycogen synthase kinase 3. Phosphorylation and inactivation of glycogen synthase by glycogen synthase kinase 3 could be the mechanism for long-chain fatty acid inhibition of insulin-mediated carbohydrate storage in insulin-resistant subjects. Here, we test the effects of palmitic acid on cultured muscle glycogen synthase and PP2A activities. Palmitate inhibition of glycogen synthase fractional activity is increased in subjects with high body mass index compared with subjects with lower body mass index (r = -0.43, P = 0.03). Palmitate action on PP2A varies from inhibition in subjects with decreased 2-h plasma glucose concentration to activation in subjects with increased 2-h plasma glucose concentration (r = 0.45, P < 0.03) during oral glucose tolerance tests. The results do not show an association between palmitate effects on PP2A and glycogen synthase fractional activity. We conclude that subjects at risk for Type 2 diabetes have intrinsic differences in palmitate regulation of at least two enzymes (PP2A and glycogen synthase), contributing to abnormal insulin regulation of glucose metabolism.

  14. Learning to program the liver. (United States)

    Klaassen, Curtis D


    Half a century ago, people were learning to program computers. Similarly, we have been trying to learn how to program the liver to protect us from chemicals. We have given various chemicals that activate transcription factors such as the nuclear receptors: These ligand-activated nuclear receptors enter the nucleus of liver cells (hepatocytes) and bind to their specific motifs in DNA to increase the transcription of various genes that protect against chemical-induced injury. Several examples from our laboratory are given to demonstrate this detoxification process: (a) a steroid chemical that increases the expression of a hepatic transporter to enhance the elimination of other chemicals and thus decrease their toxicity, (b) a metal that decreases its own toxicity by increasing the production of a protein to which it binds, and (c) an herbal chemical that activates a transcription factor that serves as a sensor of oxidative stress and electrophiles to protect against cytotoxicity by increasing the expression of numerous antioxidant proteins. In addition, at the present time, we are investigating which bile acids that are synthesized in the liver and altered by bacteria in the intestine may be used to alter the programming of the liver, as well as how the liver reprograms itself after birth in the transition from a hematopoietic organ to one that decreases the toxicity of chemicals.

  15. Pathological characteristics of liver allografts from donation after brain death followed by cardiac death in pigs. (United States)

    Ye, Hui; Wang, Dong-Ping; Zhang, Chuan-Zhao; Zhang, Long-Juan; Wang, Hao-Chen; Li, Zhuo-Hui; Chen, Zhen; Zhang, Tao; Cai, Chang-Jie; Ju, Wei-Qiang; Ma, Yi; Guo, Zhi-Yong; He, Xiao-Shun


    Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs (25-30 kg) were allocated randomly into donation after brain death (DBD), donation after circulatory death (DCD) and DBCD groups. Brain death was induced by augmenting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were collected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [(0.56±0.30)%] and DBCD [(0.50 ± 0.11)%] groups was much lower than that in DCD group [(3.78±0.33)%] (P0.05)). The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.

  16. Liver Function Tests (United States)

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  17. Benign Liver Tumors (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  18. Liver cancer - hepatocellular carcinoma (United States)

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or ...

  19. Liver Transplant: Nutrition (United States)

    ... ZIP code here Enter ZIP code here Liver Transplant: Nutrition for Veterans and the Public Nutrition Liver ... apply to transplant and liver disease patients. Pre-Transplant Protein Malnutrition -- Many patients with end stage liver ...

  20. Elevated Liver Enzymes (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  1. Glycogen content regulates peroxisome proliferator activated receptor-∂ (PPAR-∂ activity in rat skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Andrew Philp

    Full Text Available Performing exercise in a glycogen depleted state increases skeletal muscle lipid utilization and the transcription of genes regulating mitochondrial β-oxidation. Potential candidates for glycogen-mediated metabolic adaptation are the peroxisome proliferator activated receptor (PPAR coactivator-1α (PGC-1α and the transcription factor/nuclear receptor PPAR-∂. It was therefore the aim of the present study to examine whether acute exercise with or without glycogen manipulation affects PGC-1α and PPAR-∂ function in rodent skeletal muscle. Twenty female Wistar rats were randomly assigned to 5 experimental groups (n = 4: control [CON]; normal glycogen control [NG-C]; normal glycogen exercise [NG-E]; low glycogen control [LG-C]; and low glycogen exercise [LG-E]. Gastrocnemius (GTN muscles were collected immediately following exercise and analyzed for glycogen content, PPAR-∂ activity via chromatin immunoprecipitation (ChIP assays, AMPK α1/α2 kinase activity, and the localization of AMPK and PGC-1α. Exercise reduced muscle glycogen by 47 and 75% relative to CON in the NG-E and LG-E groups, respectively. Exercise that started with low glycogen (LG-E finished with higher AMPK-α2 activity (147%, p<0.05, nuclear AMPK-α2 and PGC-1α, but no difference in AMPK-α1 activity compared to CON. In addition, PPAR-∂ binding to the CPT1 promoter was significantly increased only in the LG-E group. Finally, cell reporter studies in contracting C2C12 myotubes indicated that PPAR-∂ activity following contraction is sensitive to glucose availability, providing mechanistic insight into the association between PPAR-∂ and glycogen content/substrate availability. The present study is the first to examine PPAR-∂ activity in skeletal muscle in response to an acute bout of endurance exercise. Our data would suggest that a factor associated with muscle contraction and/or glycogen depletion activates PPAR-∂ and initiates AMPK translocation in skeletal

  2. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)


    2008447 Identification of gene expression patterns in a rat model of nonalcoholic fatty liver disease. ZHANG Xuequn(张雪群), et al. Dept Gastroenterol, 1st Hosp, Med Coll, Zhejiang Univ, Hangzhou 310003. Chin J Dig 2008;28(5):323-327. Objective To compare and analyze gene expression patterns in a rat model of nonalcoholic fatty liver disease (NAFLD). Methods Twelve male Sprague-Dawley rats were randomly given either general diet (control group) or a high-fat diet (model group) for 4 weeks.

  3. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)


    2008310 Expression of αVβ3 integrin and platelet-endothelial cell adhesion molecule-1 in progressive liver fibrosis: experiment with rats. SONG Zhengji(宋正已), et al. Dept Gastroenterol, Zhongshan Hosp, Fudan Univ, Shanghai 200032. Natl Med J China 2008;88(16):1121-1125.Objective To investigate the expression ofαVβ3 integrin and platelet endothelial cell adhesion molecule-1(CD31)in progressive liver fibrosis of rats.Methods Sixty-four SD rats were randomly divided into 4 equal groups:TAA group,undergoing peritoneal injection of

  4. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)


    2008075 Effect of Jiangzhi granules on expression of leptin receptor mRNA, P-JAK2 and P-STAT3 in rats with non-alcoholic fatty liver disease. MA Zansong(马赞颂), et al. Dept Gastroenterol, Instit Spleen and Stomach Dis, Longhua Hosp. Shanghai TCM Univ, Shanghai 200032.World Chin J Digestol 2007;15(32):3360-3366. Objective To study the effect of Jiangzhi granules on non-alcoholic fatty liver disease in rats, and on the expression of

  5. Seasonal Changes in Glycogen Contents in Various Tissues of the Edible Bivalves, Pen Shell Atrina lischkeana, Ark Shell Scapharca kagoshimensis, and Manila Clam Ruditapes philippinarum in West Japan

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    Tatsuya Yurimoto


    Full Text Available The types of tissues accumulating glycogen and seasonal changes in glycogen content were investigated in the following shell species: pen shell Atrina lischkeana, ark shell Scapharca kagoshimensis, and Manila clam Ruditapes philippinarum. Comparison of the results showed that the adductor muscle or foot was the main glycogen reservoir and the levels varied seasonally. The adductor muscle in the pen shell showed higher glycogen content during spring and lower content during autumn. The ark shell, on the other hand, showed higher content during winter and spring and lower content during summer and autumn, while the Manila clam showed higher glycogen content during spring and summer and lower content during autumn and winter. These results revealed that the adductor muscle in pen shells and the foot in ark shells and Manila clams act as the main storage tissues for glycogen in the three species studied and that these tissues are suitable to analyze glycogen prevalence to estimate individual physiological condition.