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Sample records for affects protein metabolism

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

    NARCIS (Netherlands)

    Bisschop, PH; de Sain-van der Velden, MGM; Stellaard, F; Kuipers, F; Meijer, AJ; Sauerwein, HP; Romijn, JA

    Because insulin is an important regulator of protein metabolism, we hypothesized that physiological modulation of insulin secretion, by means of extreme variations in dietary carbohydrate content, affects postabsorptive protein metabolism. Therefore, we studied the effects of three isocaloric diets

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

    NARCIS (Netherlands)

    Bisschop, P. H.; de Sain-van der Velden, M. G. M.; Stellaard, F.; Kuipers, F.; Meijer, A. J.; Sauerwein, H. P.; Romijn, J. A.

    2003-01-01

    Because insulin is an important regulator of protein metabolism, we hypothesized that physiological modulation of insulin secretion, by means of extreme variations in dietary carbohydrate content, affects postabsorptive protein metabolism. Therefore, we studied the effects of three isocaloric diets

  3. Glucagon-Like Peptide 2 Stimulates Postresection Intestinal Adaptation in Preterm Pigs by Affecting Proteins Related to Protein, Carbohydrate, and Sulphur Metabolism

    DEFF Research Database (Denmark)

    Jiang, Pingping; Vegge, Andreas; Thymann, Thomas

    2017-01-01

    cellular structural proteins, while the added GLP-2 treatment affected proteins involved in protein processing and the metabolism of protein, carbohydrate, and sulphur. CONCLUSION: In the first days following resection, proteins affected by resection plus GLP-2 treatment differed markedly from those...

  4. Casein and soy protein meals differentially affect whole-body and splanchnic protein metabolism in healthy humans.

    Science.gov (United States)

    Luiking, Yvette C; Deutz, Nicolaas E P; Jäkel, Martin; Soeters, Peter B

    2005-05-01

    Dietary protein quality is considered to be dependent on the degree and velocity with which protein is digested, absorbed as amino acids, and retained in the gut as newly synthesized protein. Metabolic animal studies suggest that the quality of soy protein is inferior to that of casein protein, but confirmatory studies in humans are lacking. The study objective was to assess the quality of casein and soy protein by comparing their metabolic effects in healthy human subjects. Whole-body protein kinetics, splanchnic leucine extraction, and urea production rates were measured in the postabsorptive state and during 8-h enteral intakes of isonitrogenous [0.42 g protein/(kg body weight . 8 h)] protein-based test meals, which contained either casein (CAPM; n = 12) or soy protein (SOPM; n = 10) in 2 separate groups. Stable isotope techniques were used to study metabolic effects. With enteral food intake, protein metabolism changed from net protein breakdown to net protein synthesis. Net protein synthesis was greater in the CAPM group than in the SOPM group [52 +/- 14 and 17 +/- 14 nmol/(kg fat-free mass (FFM) . min), respectively; P CAPM (P = 0.07). Absolute splanchnic extraction of leucine was higher in the subjects that consumed CAPM [306 +/- 31 nmol/(kg FFM . min)] vs. those that consumed SOPM [235 +/- 29 nmol/(kg FFM . min); P < 0.01]. In conclusion, a significantly larger portion of soy protein is degraded to urea, whereas casein protein likely contributes to splanchnic utilization (probably protein synthesis) to a greater extent. The biological value of soy protein must be considered inferior to that of casein protein in humans.

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

    Science.gov (United States)

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

    1990-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

  7. Intermittent fasting does not affect whole-body glucose, lipid, or protein metabolism

    NARCIS (Netherlands)

    Soeters, Maarten R.; Lammers, Nicolette M.; Dubbelhuis, Peter F.; Ackermans, Mariëtte T.; Jonkers-Schuitema, Cora F.; Fliers, Eric; Sauerwein, Hans P.; Aerts, Johannes M.; Serlie, Mireille J.

    2009-01-01

    Background: Intermittent fasting (IF) was shown to increase whole-body insulin sensitivity, but it is uncertain whether IF selectively influences intermediary metabolism. Such selectivity might be advantageous when adapting to periods of food abundance and food shortage. Objective: The objective was

  8. Membrane biocompatibility does not affect whole body protein metabolism during dialysis

    NARCIS (Netherlands)

    Veeneman, JM; Kingma, HA; Stellaard, F; de Jong, PE; Reijngoud, DJ; Huisman, RM

    2005-01-01

    Background: Protein-calorie malnutrition is present in 30-50% of dialysis patients. The lack of biocompatibility of the dialysis membrane, which results in low-grade inflammation, could be responsible for this malnutrition. We investigated whether protein-energy malnutrition could be partly due to

  9. Nutrient Fortification of Human Donor Milk Affects Intestinal Function and Protein Metabolism in Preterm Pigs

    DEFF Research Database (Denmark)

    Sun, Jing; Li, Yanqi; Nguyen, Duc Ninh

    2018-01-01

    (BC) may be an alternative nutrient fortifier, considering its high content of protein and milk bioactive factors. Objective: We investigated whether BC was superior to an FF product based on processed bovine milk and vegetable oil to fortify donor human milk (DHM) for preterm pigs, used as a model......) and DHM with or without FF or BC fortification (+4.6 g protein ⋅ kg-1 ⋅ d-1). Results: DPM-fed pigs showed higher growth (10-fold), protein synthesis (+15-30%), villus heights, lactase and peptidase activities (+30%), and reduced intestinal cytokines (-50%) relative to DHM pigs (all P ....05). Fortification increased protein synthesis (+20-30%), but with higher weight gain and lower urea and cortisol concentrations for DHM+BC compared with DHM+FF pigs (2- to 3-fold differences, all P ≤ 0.06). DHM+FF pigs showed more diarrhea and reduced lactase and peptidase activities, hexose uptake, and villus...

  10. Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner

    Directory of Open Access Journals (Sweden)

    Jessica M. V. Pino

    2017-05-01

    Full Text Available Iron is an essential micronutrient for several physiological functions, including the regulation of dopaminergic neurotransmission. On the other hand, both iron, and dopamine can affect the folding and aggregation of proteins related with neurodegenerative diseases, such as cellular prion protein (PrPC and α-synuclein, suggesting that deregulation of iron homeostasis and the consequential disturbance of dopamine metabolism can be a risk factor for conformational diseases. These proteins, in turn, are known to participate in the regulation of iron and dopamine metabolism. In this study, we evaluated the effects of dietary iron restriction on brain ferritin levels, dopamine metabolism, and the expression levels of PrPC and α-synuclein. To achieve this goal, C57BL/6 mice were fed with iron restricted diet (IR or with normal diet (CTL for 1 month. IR reduced iron and ferritin levels in liver. Ferritin reduction was also observed in the hippocampus. However, in the striatum of IR group, ferritin level was increased, suggesting that under iron-deficient condition, each brain area might acquire distinct capacity to store iron. Increased lipid peroxidation was observed only in hippocampus of IR group, where ferritin level was reduced. IR also generated discrete results regarding dopamine metabolism of distinct brain regions: in striatum, the level of dopamine metabolites (DOPAC and HVA was reduced; in prefrontal cortex, only HVA was increased along with the enhanced MAO-A activity; in hippocampus, no alterations were observed. PrPC levels were increased only in the striatum of IR group, where ferritin level was also increased. PrPC is known to play roles in iron uptake. Thus, the increase of PrPC in striatum of IR group might be related to the increased ferritin level. α-synuclein was not altered in any regions. Abnormal accumulation of ferritin, increased MAO-A activity or lipid peroxidation are molecular features observed in several neurological

  11. Energy metabolism in young mink kits (Neovison vison) affected by protein and carbohydrate level in the diet

    DEFF Research Database (Denmark)

    Hellwing, Anne Louise Frydendahl; Hansen, Niels Enggaard; Tauson, Anne-Helene

    2010-01-01

    The mink is a strict carnivore and mink diets usually have a high content of protein. The energy metabolism in young minks in the transition period from milk to solid food is not investigated in detail, and the protein requirement is poorly defined. The substrate oxidation can give useful...

  12. Protein metabolism in the rat cerebral cortex in vivo and in vitro as affected by the acquisition enhancing drug piracetam

    NARCIS (Netherlands)

    Nickolson, V.J.; Wolthuis, O.L.

    1976-01-01

    The effect of Piracetam on rat cerebral protein metabolism in vivo and in vitro was studied. It was found that the drug stimulates the uptake of labelled leucine by cerebral cortex slices, has no effect on the incorporation of leucine into cerebral protein, neither in slices nor in vivo, but

  13. Arginine depletion by arginine deiminase does not affect whole protein metabolism or muscle fractional protein synthesis rate in mice

    Science.gov (United States)

    Due to the absolute need for arginine that certain cancer cells have, arginine depletion is a therapy in clinical trials to treat several types of cancers. Arginine is an amino acids utilized not only as a precursor for other important molecules, but also for protein synthesis. Because arginine depl...

  14. Does methamphetamine affect bone metabolism?

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  15. Peroxisome protein transportation affects metabolism of branched-chain fatty acids that critically impact growth and development of C. elegans.

    Directory of Open Access Journals (Sweden)

    Rencheng Wang

    Full Text Available The impact of specific lipid molecules, including fatty acid variants, on cellular and developmental regulation is an important research subject that remains under studied. Monomethyl branched-chain fatty acids (mmBCFAs are commonly present in multiple organisms including mammals, however our understanding of mmBCFA functions is very limited. C. elegans has been the premier model system to study the functions of mmBCFAs and their derived lipids, as mmBCFAs have been shown to play essential roles in post-embryonic development in this organism. To understand more about the metabolism of mmBCFAs in C. elegans, we performed a genetic screen for suppressors of the L1 developmental arrest phenotype caused by mmBCFA depletion. Extensive characterization of one suppressor mutation identified prx-5, which encodes an ortholog of the human receptor for the type-1 peroxisomal targeting signal protein. Our study showed that inactivating prx-5 function compromised the peroxisome protein import, resulting in an increased level of branched-chain fatty acid C17ISO in animals lacking normal mmBCFA synthesis, thereby restoring wild-type growth and development. This work reveals a novel connection between peroxisomal functions and mmBCFA metabolism.

  16. Does methamphetamine affect bone metabolism?

    Science.gov (United States)

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

    2014-05-07

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

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

    Science.gov (United States)

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

    2016-08-01

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

  18. Long-Term Intake of a High-Protein Diet Affects Body Phenotype, Metabolism, and Plasma Hormones in Mice.

    Science.gov (United States)

    Vu, John P; Luong, Leon; Parsons, William F; Oh, Suwan; Sanford, Daniel; Gabalski, Arielle; Lighton, John Rb; Pisegna, Joseph R; Germano, Patrizia M

    2017-12-01

    Background: High-protein diets (HPDs) recently have been used to obtain body weight and fat mass loss and expand muscle mass. Several studies have documented that HPDs reduce appetite and food intake. Objective: Our goal was to determine the long-term effects of an HPD on body weight, energy intake and expenditure, and metabolic hormones. Methods: Male C57BL/6 mice (8 wk old) were fed either an HPD (60% of energy as protein) or a control diet (CD; 20% of energy as protein) for 12 wk. Body composition and food intakes were determined, and plasma hormone concentrations were measured in mice after being fed and after overnight feed deprivation at several time points. Results: HPD mice had significantly lower body weight (in means ± SEMs; 25.73 ± 1.49 compared with 32.5 ± 1.31 g; P = 0.003) and fat mass (9.55% ± 1.24% compared with 15.78% ± 2.07%; P = 0.05) during the first 6 wk compared with CD mice, and higher lean mass throughout the study starting at week 2 (85.45% ± 2.25% compared with 75.29% ± 1.90%; P = 0.0001). Energy intake, total energy expenditure, and respiratory quotient were significantly lower in HPD compared with CD mice as shown by cumulative energy intake and eating rate. Water vapor was significantly higher in HPD mice during both dark and light phases. In HPD mice, concentrations of leptin [feed-deprived: 41.31 ± 11.60 compared with 3041 ± 683 pg/mL ( P = 0.0004); postprandial: 112.5 ± 102.0 compared with 8273 ± 1415 pg/mL ( P < 0.0001)] and glucagon-like peptide 1 (GLP-1) [feed-deprived: 5.664 ± 1.44 compared with 21.31 ± 1.26 pg/mL ( P = <0.0001); postprandial: 6.54 ± 2.13 compared with 50.62 ± 11.93 pg/mL ( P = 0.0037)] were significantly lower, whereas postprandial glucagon concentrations were higher than in CD-fed mice. Conclusions: In male mice, the 12-wk HPD resulted in short-term body weight and fat mass loss, but throughout the study preserved body lean mass and significantly reduced energy intake and expenditure as well as

  19. [Low-molecular-weight regulators of biogenic polyamine metabolism affect cytokine production and expression of hepatitis С virus proteins in Huh7.5 human hepatocarcinoma cells].

    Science.gov (United States)

    Masalova, O V; Lesnova, E I; Samokhvalov, E I; Permyakova, K Yu; Ivanov, A V; Kochetkov, S N; Kushch, A A

    2017-01-01

    Hepatitis C virus (HCV) induces the expression of the genes of proinflammatory cytokines, the excessive production of which may cause cell death, and contribute to development of liver fibrosis and hepatocarcinoma. The relationship between cytokine production and metabolic disorders in HCV-infected cells remains obscure. The levels of biogenic polyamines, spermine, spermidine, and their precursor putrescine, may be a potential regulator of these processes. The purpose of the present work was to study the effects of the compounds which modulate biogenic polyamines metabolism on cytokine production and HCV proteins expression. Human hepatocarcinoma Huh7.5 cells have been transfected with the plasmids that encode HCV proteins and further incubated with the following low-molecular compounds that affect different stages of polyamine metabolism: (1) difluoromethylornithine (DFMO), the inhibitor of ornithine decarboxylase, the enzyme that catalyzes the biosynthesis of polyamines; (2) N,N'-bis(2,3-butane dienyl)-1,4-diaminobutane (MDL72.527), the inhibitor of proteins involved in polyamine degradation; and (3) synthetic polyamine analog N^(I),N^(II)-diethylnorspermine (DENSpm), an inducer of polyamine degradation enzyme. The intracellular accumulation and secretion of cytokines (IL-6, IL-1β, TNF-α, and TGF-β) was assessed by immunocytochemistry and in the immunoenzyme assay, while the cytokine gene expression was studied using reverse transcription and PCR. The effects of the compounds under analysis on the expression of HCV proteins were analyzed using the indirect immunofluorescence with anti-HCV monoclonal antibodies. It has been demonstrated that, in cells transfected with HCV genes, DFMO reduces the production of three out of four tested cytokines, namely, TNF-α and TGF-β in cells that express HCV core, Е1Е2, NS3, NS5A, and NS5B proteins, and IL-1β in the cells that express HCV core, Е1Е2, and NS3 proteins. MDL72527 and DENSpm decreased cytokine production

  20. Diet-induced hyperinsulinemia differentially affects glucose and protein metabolism: a high-throughput metabolomic approach in rats.

    Science.gov (United States)

    Etxeberria, U; de la Garza, A L; Martínez, J A; Milagro, F I

    2013-09-01

    Metabolomics is a high-throughput tool that quantifies and identifies the complete set of biofluid metabolites. This "omics" science is playing an increasing role in understanding the mechanisms involved in disease progression. The aim of this study was to determine whether a nontargeted metabolomic approach could be applied to investigate metabolic differences between obese rats fed a high-fat sucrose (HFS) diet for 9 weeks and control diet-fed rats. Animals fed with the HFS diet became obese, hyperleptinemic, hyperglycemic, hyperinsulinemic, and resistant to insulin. Serum samples of overnight-fasted animals were analyzed by (1)H NMR technique, and 49 metabolites were identified and quantified. The biochemical changes observed suggest that major metabolic processes like carbohydrate metabolism, β-oxidation, tricarboxylic acid cycle, Kennedy pathway, and folate-mediated one-carbon metabolism were altered in obese rats. The circulating levels of most amino acids were lower in obese animals. Serum levels of docosahexaenoic acid, linoleic acid, unsaturated n-6 fatty acids, and total polyunsaturated fatty acids also decreased in HFS-fed rats. The circulating levels of urea, six water-soluble metabolites (creatine, creatinine, choline, acetyl carnitine, formate, and allantoin), and two lipid compounds (phosphatidylcholines and sphingomyelin) were also significantly reduced by the HFS diet intake. This study offers further insight of the possible mechanisms implicated in the development of diet-induced obesity. It suggests that the HFS diet-induced hyperinsulinemia is responsible for the decrease in the circulating levels of urea, creatinine, and many amino acids, despite an increase in serum glucose levels.

  1. Perturbations of Amino Acid Metabolism Associated with Glyphosate-Dependent Inhibition of Shikimic Acid Metabolism Affect Cellular Redox Homeostasis and Alter the Abundance of Proteins Involved in Photosynthesis and Photorespiration1[W][OA

    Science.gov (United States)

    Vivancos, Pedro Diaz; Driscoll, Simon P.; Bulman, Christopher A.; Ying, Liu; Emami, Kaveh; Treumann, Achim; Mauve, Caroline; Noctor, Graham; Foyer, Christine H.

    2011-01-01

    The herbicide glyphosate inhibits the shikimate pathway of the synthesis of amino acids such as phenylalanine, tyrosine, and tryptophan. However, much uncertainty remains concerning precisely how glyphosate kills plants or affects cellular redox homeostasis and related processes in glyphosate-sensitive and glyphosate-resistant crop plants. To address this issue, we performed an integrated study of photosynthesis, leaf proteomes, amino acid profiles, and redox profiles in the glyphosate-sensitive soybean (Glycine max) genotype PAN809 and glyphosate-resistant Roundup Ready Soybean (RRS). RRS leaves accumulated much more glyphosate than the sensitive line but showed relatively few changes in amino acid metabolism. Photosynthesis was unaffected by glyphosate in RRS leaves, but decreased abundance of photosynthesis/photorespiratory pathway proteins was observed together with oxidation of major redox pools. While treatment of a sensitive genotype with glyphosate rapidly inhibited photosynthesis and triggered the appearance of a nitrogen-rich amino acid profile, there was no evidence of oxidation of the redox pools. There was, however, an increase in starvation-associated and defense proteins. We conclude that glyphosate-dependent inhibition of soybean leaf metabolism leads to the induction of defense proteins without sustained oxidation. Conversely, the accumulation of high levels of glyphosate in RRS enhances cellular oxidation, possibly through mechanisms involving stimulation of the photorespiratory pathway. PMID:21757634

  2. Perturbations of amino acid metabolism associated with glyphosate-dependent inhibition of shikimic acid metabolism affect cellular redox homeostasis and alter the abundance of proteins involved in photosynthesis and photorespiration.

    Science.gov (United States)

    Vivancos, Pedro Diaz; Driscoll, Simon P; Bulman, Christopher A; Ying, Liu; Emami, Kaveh; Treumann, Achim; Mauve, Caroline; Noctor, Graham; Foyer, Christine H

    2011-09-01

    The herbicide glyphosate inhibits the shikimate pathway of the synthesis of amino acids such as phenylalanine, tyrosine, and tryptophan. However, much uncertainty remains concerning precisely how glyphosate kills plants or affects cellular redox homeostasis and related processes in glyphosate-sensitive and glyphosate-resistant crop plants. To address this issue, we performed an integrated study of photosynthesis, leaf proteomes, amino acid profiles, and redox profiles in the glyphosate-sensitive soybean (Glycine max) genotype PAN809 and glyphosate-resistant Roundup Ready Soybean (RRS). RRS leaves accumulated much more glyphosate than the sensitive line but showed relatively few changes in amino acid metabolism. Photosynthesis was unaffected by glyphosate in RRS leaves, but decreased abundance of photosynthesis/photorespiratory pathway proteins was observed together with oxidation of major redox pools. While treatment of a sensitive genotype with glyphosate rapidly inhibited photosynthesis and triggered the appearance of a nitrogen-rich amino acid profile, there was no evidence of oxidation of the redox pools. There was, however, an increase in starvation-associated and defense proteins. We conclude that glyphosate-dependent inhibition of soybean leaf metabolism leads to the induction of defense proteins without sustained oxidation. Conversely, the accumulation of high levels of glyphosate in RRS enhances cellular oxidation, possibly through mechanisms involving stimulation of the photorespiratory pathway.

  3. Protein metabolism in marine animals: the underlying mechanism of growth.

    Science.gov (United States)

    Fraser, Keiron P P; Rogers, Alex D

    2007-01-01

    Growth is a fundamental process within all marine organisms. In soft tissues, growth is primarily achieved by the synthesis and retention of proteins as protein growth. The protein pool (all the protein within the organism) is highly dynamic, with proteins constantly entering the pool via protein synthesis or being removed from the pool via protein degradation. Any net change in the size of the protein pool, positive or negative, is termed protein growth. The three inter-related processes of protein synthesis, degradation and growth are together termed protein metabolism. Measurement of protein metabolism is vital in helping us understand how biotic and abiotic factors affect growth and growth efficiency in marine animals. Recently, the developing fields of transcriptomics and proteomics have started to offer us a means of greatly increasing our knowledge of the underlying molecular control of protein metabolism. Transcriptomics may also allow us to detect subtle changes in gene expression associated with protein synthesis and degradation, which cannot be detected using classical methods. A large literature exists on protein metabolism in animals; however, this chapter concentrates on what we know of marine ectotherms; data from non-marine ectotherms and endotherms are only discussed when the data are of particular relevance. We first consider the techniques available to measure protein metabolism, their problems and what validation is required. Protein metabolism in marine organisms is highly sensitive to a wide variety of factors, including temperature, pollution, seasonality, nutrition, developmental stage, genetics, sexual maturation and moulting. We examine how these abiotic and biotic factors affect protein metabolism at the level of whole-animal (adult and larval), tissue and cellular protein metabolism. Available gene expression data, which help us understand the underlying control of protein metabolism, are also discussed. As protein metabolism appears to

  4. Dietary sardine protein lowers insulin resistance, leptin and TNF-α and beneficially affects adipose tissue oxidative stress in rats with fructose-induced metabolic syndrome.

    Science.gov (United States)

    Madani, Zohra; Louchami, Karim; Sener, Abdullah; Malaisse, Willy J; Ait Yahia, Dalila

    2012-02-01

    The present study aims at exploring the effects of sardine protein on insulin resistance, plasma lipid profile, as well as oxidative and inflammatory status in rats with fructose-induced metabolic syndrome. Rats were fed sardine protein (S) or casein (C) diets supplemented or not with high-fructose (HF) for 2 months. Rats fed the HF diets had greater body weight and adiposity and lower food intake as compared to control rats. Increased plasma glucose, insulin, HbA1C, triacylglycerols, free fatty acids and impaired glucose tolerance and insulin resistance was observed in HF-fed rats. Moreover, a decline in adipose tissues antioxidant status and a rise in lipid peroxidation and plasma TNF-α and fibrinogen were noted. Rats fed sardine protein diets exhibited lower food intake and fat mass than those fed casein diets. Sardine protein diets diminished plasma insulin and insulin resistance. Plasma triacylglycerol and free fatty acids were also lower, while those of α-tocopherol, taurine and calcium were enhanced as compared to casein diets. Moreover, S-HF diet significantly decreased plasma glucose and HbA1C. Sardine protein consumption lowered hydroperoxide levels in perirenal and brown adipose tissues. The S-HF diet, as compared to C-HF diet decreased epididymal hydroperoxides. Feeding sardine protein diets decreased brown adipose tissue carbonyls and increased glutathione peroxidase activity. Perirenal and epididymal superoxide dismutase and catalase activities and brown catalase activity were significantly greater in S-HF group than in C-HF group. Sardine protein diets also prevented hyperleptinemia and reduced inflammatory status in comparison with rats fed casein diets. Taken together, these results support the beneficial effect of sardine protein in fructose-induced metabolic syndrome on such variables as hyperglycemia, insulin resistance, hyperlipidemia and oxidative and inflammatory status, suggesting the possible use of sardine protein as a protective

  5. AMPK Activation Affects Glutamate Metabolism in Astrocytes

    DEFF Research Database (Denmark)

    Voss, Caroline Marie; Pajęcka, Kamilla; Stridh, Malin H

    2015-01-01

    acid (TCA) cycle was studied using high-performance liquid chromatography analysis supplemented with gas chromatography-mass spectrometry technology. It was found that AMPK activation had profound effects on the pathways involved in glutamate metabolism since the entrance of the glutamate carbon...... on glutamate metabolism in astrocytes was studied using primary cultures of these cells from mouse cerebral cortex during incubation in media containing 2.5 mM glucose and 100 µM [U-(13)C]glutamate. The metabolism of glutamate including a detailed analysis of its metabolic pathways involving the tricarboxylic...... skeleton into the TCA cycle was reduced. On the other hand, glutamate uptake into the astrocytes as well as its conversion to glutamine catalyzed by glutamine synthetase was not affected by AMPK activation. Interestingly, synthesis and release of citrate, which are hallmarks of astrocytic function, were...

  6. Leucine and protein metabolism in obese zucker rats

    Science.gov (United States)

    Branched-chain amino acids (BCAAs) are circulating nutrient signals for protein accretion, however they increase in obesity and appear to prognosticate diabetes onset. To understand the mechanisms whereby obesity affects BCAAs and protein metabolism, we employed metabolomics and measured rates of [1...

  7. Tissue protein metabolism in parasitized animals

    International Nuclear Information System (INIS)

    Symons, L.E.A.; Steel, J.W.; Jones, W.O.

    1981-01-01

    The effects of gastrointestinal nematode infection of mammals, particularly of the small intestine of the sheep, on protein metabolism of skeletal muscle, liver, the gastrointestinal tract and wool are described. These changes have been integrated to explain poor growth and production in the sheep heavily infected with Trichostrongylus colubriformis. The rates of both synthesis and catabolism of muscle protein are depressed, but nitrogen is lost from this tissue because the depression of synthesis exceeds that of catabolism. Anorexia is the major cause of these changes. Although the effect on liver protein synthesis is unclear, it is probable that the leakage of plasma proteins into the gastrointestinal tract stimulates an early increase in the rate of synthesis of these proteins, but this eventually declines and is insufficient to correct developing hypoalbuminaemia. Changes in the intestinal tract are complex. Exogenous nitrogen is reduced by anorexia, but the flow of nitrogen through the tract from abomasum to faeces is above normal because of the increase of endogenous protein from leakage of plasma protein and, presumably, from exfoliated epithelial cells. There is evidence that protein metabolism of intestinal tissue, particularly in the uninfected distal two-thirds, is increased. Synthesis of wool protein is decreased. As the result of anorexia, intestinal loss of endogenous protein and an increased rate of intestinal protein metabolism there is a net movement of amino nitrogen from muscle, liver and possibly skin to the intestine of the heavily infected sheep. Thus, the availability of amino nitrogen for growth and wool production is reduced. (author)

  8. High dietary fat-induced obesity in Wistar rats and type 2 diabetes in nonobese Goto-Kakizaki rats differentially affect retinol binding protein 4 expression and vitamin A metabolism.

    Science.gov (United States)

    Shirai, Tomomi; Shichi, Yuta; Sato, Miyuki; Tanioka, Yuri; Furusho, Tadasu; Ota, Toru; Tadokoro, Tadahiro; Suzuki, Tsukasa; Kobayashi, Ken-Ichi; Yamamoto, Yuji

    2016-03-01

    Obesity is a major risk factor for type 2 diabetes, which is caused mainly by insulin resistance. Retinol binding protein 4 (RBP4) is the only specific transport protein for retinol in the serum. RBP4 level is increased in the diabetic state and high-fat condition, indicating that retinol metabolism may be affected under these conditions. However, the precise effect of diabetes and high fat-induced obesity on retinol metabolism is unknown. In this study, we examined differences in retinol metabolite levels in rat models of diet-induced obesity and type 2 diabetes (Goto-Kakizaki [GK] rat). Four-week-old male Wistar and GK rats were given either a control diet (AIN-93G) or a high-fat diet (HFD, 40% fat kJ). After 15 weeks of feeding, the RBP4 levels increased by 2-fold in the serum of GK rats but not HFD-fed rats. The hepatic retinol concentration of HFD-fed rats was approximately 50% that of the controls (P type 2 diabetes mellitus. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Cytokines: muscle protein and amino acid metabolism

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2012-01-01

    raises TNF-α and IL-6 to moderate levels, has only identified IL-6 as a potent cytokine, decreasing systemic amino acid levels and muscle protein metabolism. The marked decrease in circulatory and muscle amino acid concentrations was observed with a concomitant reduction in both the rates of muscle...... of IL-6 on the regulation of muscle protein metabolism but indirectly via IL-6 reducing amino acid availability. SUMMARY: Recent studies suggest that the best described cytokines TNF-α and IL-6 are unlikely to be the major direct mediators of muscle protein loss in inflammatory diseases. However...

  10. Higher Total Protein Intake and Change in Total Protein Intake Affect Body Composition but Not Metabolic Syndrome Indexes in Middle-Aged Overweight and Obese Adults Who Perform Resistance and Aerobic Exercise for 36 Weeks.

    Science.gov (United States)

    Campbell, Wayne W; Kim, Jung Eun; Amankwaah, Akua F; Gordon, Susannah L; Weinheimer-Haus, Eileen M

    2015-09-01

    Studies assessing the effects of protein supplementation on changes in body composition (BC) and health rarely consider the impact of total protein intake (TPro) or the change in TPro (CTPro) from participants' usual diets. This secondary data analysis assessed the impact of TPro and CTPro on changes in BC and metabolic syndrome (MetS) indexes in overweight and obese middle-aged adults who participated in an exercise training program. Men and women [n = 117; age: 50 ± 0.7 y, body mass index (BMI; in kg/m(2)): 30.1 ± 0.3; means ± SEs] performed resistance exercise 2 d/wk and aerobic exercise 1 d/wk and consumed an unrestricted diet along with 200-kcal supplements (0, 10, 20, or 30 g whey protein) twice daily for 36 wk. Protein intake was assessed via 4-d food records. Multiple linear regression model and stratified analysis were applied for data analyses. Among all subjects, TPro and CTPro were inversely associated (P exercise training, higher TPro promoted positive changes in BC but not in MetS indexes in overweight and obese middle-aged adults. Changes in TPro from before to during the intervention also influenced BC responses and should be considered in future research when different TPro is achieved via diet or supplements. This trial was registered at clinicaltrials.gov as NCT00812409. © 2015 American Society for Nutrition.

  11. Amino acid metabolism conflicts with protein diversity

    OpenAIRE

    Krick, Teresa; Shub, David A.; Verstraete, Nina; Ferreiro, Diego U.; Alonso, Leonardo G.; Shub, Michael; Sanchez, Ignacio E.

    2014-01-01

    The 20 protein-coding amino acids are found in proteomes with different relative abundances. The most abundant amino acid, leucine, is nearly an order of magnitude more prevalent than the least abundant amino acid, cysteine. Amino acid metabolic costs differ similarly, constraining their incorporation into proteins. On the other hand, a diverse set of protein sequences is necessary to build functional proteomes. Here, we present a simple model for a cost-diversity trade-off postulating that n...

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

    NARCIS (Netherlands)

    Margalef, M.; Pons, Z.; Iglesias-Carres, L.; Bravo, F.I.; Muguerza, B.; Arola-Arnal, A.

    2017-01-01

    Flavanols, which exert several health benefits, are metabolized after ingestion. Factors such as the host physiological condition could affect the metabolism and bioavailability of flavanols, influencing their bioactivities. This study aimed to qualitatively evaluate whether a pathological state

  13. Mitochondrial uncoupling proteins and energy metabolism

    Directory of Open Access Journals (Sweden)

    Rosa Anna Busiello

    2015-02-01

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

  14. Nicotine affects protein complex rearrangement in Caenorhabditis elegans cells.

    Science.gov (United States)

    Sobkowiak, Robert; Zielezinski, Andrzej; Karlowski, Wojciech M; Lesicki, Andrzej

    2017-10-01

    Nicotine may affect cell function by rearranging protein complexes. We aimed to determine nicotine-induced alterations of protein complexes in Caenorhabditis elegans (C. elegans) cells, thereby revealing links between nicotine exposure and protein complex modulation. We compared the proteomic alterations induced by low and high nicotine concentrations (0.01 mM and 1 mM) with the control (no nicotine) in vivo by using mass spectrometry (MS)-based techniques, specifically the cetyltrimethylammonium bromide (CTAB) discontinuous gel electrophoresis coupled with liquid chromatography (LC)-MS/MS and spectral counting. As a result, we identified dozens of C. elegans proteins that are present exclusively or in higher abundance in either nicotine-treated or untreated worms. Based on these results, we report a possible network that captures the key protein components of nicotine-induced protein complexes and speculate how the different protein modules relate to their distinct physiological roles. Using functional annotation of detected proteins, we hypothesize that the identified complexes can modulate the energy metabolism and level of oxidative stress. These proteins can also be involved in modulation of gene expression and may be crucial in Alzheimer's disease. The findings reported in our study reveal putative intracellular interactions of many proteins with the cytoskeleton and may contribute to the understanding of the mechanisms of nicotinic acetylcholine receptor (nAChR) signaling and trafficking in cells.

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

    Science.gov (United States)

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

    2018-01-01

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

  16. Early postnatal feed restriction reduces liver connective tissue levels and affects H3K9 acetylation state of regulated genes associated with protein metabolism in low birth weight pigs.

    Science.gov (United States)

    Nebendahl, Constance; Görs, Solvig; Albrecht, Elke; Krüger, Ricarda; Martens, Karen; Giller, Katrin; Hammon, Harald M; Rimbach, Gerald; Metges, Cornelia C

    2016-03-01

    Intrauterine growth retardation is associated with metabolic consequences in adulthood. Since our previous data indicate birth weight-dependent effects of feed restriction (R) on protein degradation processes in the liver, it should be investigated whether effects on connective tissue turnover are obvious and could be explained by global changes of histone H3K9me3 and H3K9ac states in regulated genes. For this purpose, female littermate pigs with low (U) or normal (N) birth weight were subjected to 3-week R (60% of ad libitum fed controls) with subsequent refeeding (REF) for further 5 weeks. The 3-week R-period induced a significant reduction of connective tissue area by 43% in the liver of U animals at 98 d of age, which was not found in age-matched N animals. Of note, after REF at 131 d of age, in previously feed-restricted U animals (UR), the percentage of mean connective tissue was only 53% of ad libitum fed controls (UK), indicating a persistent effect. In U animals, R induced H3K9 acetylation of regulated genes (e.g. XBP1, ERLEC1, GALNT2, PTRH2), which were inter alia associated with protein metabolism. In contrast, REF was mostly accompanied by deacetylation in U and N animals. Thus, our epigenetic data may give a first explanation for the observed birth weight-dependent differences in this connective tissue phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Protein design in systems metabolic engineering for industrial strain development.

    Science.gov (United States)

    Chen, Zhen; Zeng, An-Ping

    2013-05-01

    Accelerating the process of industrial bacterial host strain development, aimed at increasing productivity, generating new bio-products or utilizing alternative feedstocks, requires the integration of complementary approaches to manipulate cellular metabolism and regulatory networks. Systems metabolic engineering extends the concept of classical metabolic engineering to the systems level by incorporating the techniques used in systems biology and synthetic biology, and offers a framework for the development of the next generation of industrial strains. As one of the most useful tools of systems metabolic engineering, protein design allows us to design and optimize cellular metabolism at a molecular level. Here, we review the current strategies of protein design for engineering cellular synthetic pathways, metabolic control systems and signaling pathways, and highlight the challenges of this subfield within the context of systems metabolic engineering. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Leucine and protein metabolism in obese Zucker rats.

    Directory of Open Access Journals (Sweden)

    Pengxiang She

    Full Text Available Branched-chain amino acids (BCAAs are circulating nutrient signals for protein accretion, however, they increase in obesity and elevations appear to be prognostic of diabetes. To understand the mechanisms whereby obesity affects BCAAs and protein metabolism, we employed metabolomics and measured rates of [1-(14C]-leucine metabolism, tissue-specific protein synthesis and branched-chain keto-acid (BCKA dehydrogenase complex (BCKDC activities. Male obese Zucker rats (11-weeks old had increased body weight (BW, 53%, liver (107% and fat (∼300%, but lower plantaris and gastrocnemius masses (-21-24%. Plasma BCAAs and BCKAs were elevated 45-69% and ∼100%, respectively, in obese rats. Processes facilitating these rises appeared to include increased dietary intake (23%, leucine (Leu turnover and proteolysis [35% per g fat free mass (FFM, urinary markers of proteolysis: 3-methylhistidine (183% and 4-hydroxyproline (766%] and decreased BCKDC per g kidney, heart, gastrocnemius and liver (-47-66%. A process disposing of circulating BCAAs, protein synthesis, was increased 23-29% by obesity in whole-body (FFM corrected, gastrocnemius and liver. Despite the observed decreases in BCKDC activities per gm tissue, rates of whole-body Leu oxidation in obese rats were 22% and 59% higher normalized to BW and FFM, respectively. Consistently, urinary concentrations of eight BCAA catabolism-derived acylcarnitines were also elevated. The unexpected increase in BCAA oxidation may be due to a substrate effect in liver. Supporting this idea, BCKAs were elevated more in liver (193-418% than plasma or muscle, and per g losses of hepatic BCKDC activities were completely offset by increased liver mass, in contrast to other tissues. In summary, our results indicate that plasma BCKAs may represent a more sensitive metabolic signature for obesity than BCAAs. Processes supporting elevated BCAA]BCKAs in the obese Zucker rat include increased dietary intake, Leu and protein

  19. Protein Molecular Structures, Protein SubFractions, and Protein Availability Affected by Heat Processing: A Review

    International Nuclear Information System (INIS)

    Yu, P.

    2007-01-01

    The utilization and availability of protein depended on the types of protein and their specific susceptibility to enzymatic hydrolysis (inhibitory activities) in the gastrointestine and was highly associated with protein molecular structures. Studying internal protein structure and protein subfraction profiles leaded to an understanding of the components that make up a whole protein. An understanding of the molecular structure of the whole protein was often vital to understanding its digestive behavior and nutritive value in animals. In this review, recently obtained information on protein molecular structural effects of heat processing was reviewed, in relation to protein characteristics affecting digestive behavior and nutrient utilization and availability. The emphasis of this review was on (1) using the newly advanced synchrotron technology (S-FTIR) as a novel approach to reveal protein molecular chemistry affected by heat processing within intact plant tissues; (2) revealing the effects of heat processing on the profile changes of protein subfractions associated with digestive behaviors and kinetics manipulated by heat processing; (3) prediction of the changes of protein availability and supply after heat processing, using the advanced DVE/OEB and NRC-2001 models, and (4) obtaining information on optimal processing conditions of protein as intestinal protein source to achieve target values for potential high net absorbable protein in the small intestine. The information described in this article may give better insight in the mechanisms involved and the intrinsic protein molecular structural changes occurring upon processing.

  20. Metabolic and affective consequences of fatherhood in male California mice.

    Science.gov (United States)

    Zhao, Meng; Garland, Theodore; Chappell, Mark A; Andrew, Jacob R; Saltzman, Wendy

    2017-08-01

    Physiological and affective condition can be modulated by the social environment and parental state in mammals. However, in species in which males assist with rearing offspring, the metabolic and affective effects of pair bonding and fatherhood on males have rarely been explored. In this study we tested the hypothesis that fathers, like mothers, experience energetic costs as well as behavioral and affective changes (e.g., depression, anxiety) associated with parenthood. We tested this hypothesis in the monogamous, biparental California mouse (Peromyscus californicus). Food intake, blood glucose and lipid levels, blood insulin and leptin levels, body composition, pain sensitivity, and depression-like behavior were compared in males from three reproductive groups: virgin males (VM, housed with another male), non-breeding males (NB, housed with a tubally ligated female), and breeding males (BM, housed with a female and their first litter). We found statistically significant (Pfatherhood influences several metabolic, morphological, and affective measures in male California mice. Overall, the changes we observed in breeding males were minor, but stronger effects might occur in long-term breeding males and/or under more challenging environmental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Risk factors that affect metabolic health status in obese children.

    Science.gov (United States)

    Elmaogullari, Selin; Demirel, Fatma; Hatipoglu, Nihal

    2017-01-01

    While some obese children are metabolically healthy (MHO), some have additional health problems, such as hypertension, dyslipidemia, insulin resistance, and hepatosteatosis, which increase mortality and morbidity related to cardiovascular diseases (CVD) during adulthood. These children are metabolically unhealthy obese (MUO) children. In this study we assessed the factors that affect metabolic health in obesity and the clinical and laboratory findings that distinguish between MHO and MUO children. In total, 1085 patients aged 6-18 years, with age- and sex-matched BMI exceeding the 95th percentile were included in the study (mean 11.1±2.9 years, 57.6% female, 59.7% pubertal). Patients without dyslipidemia, insulin resistance, hepatosteatosis, or hypertension were considered as MHO. Dyslipidemia was defined as total cholesterol level over 200 mg/dL, triglyceride over 150 mg/dL, LDL over 130 mg/dL, or HDL under 40 mg/dL. Insulin resistance was calculated using the homeostasis model of assesment for insulin resistance (HOMA-IR) index. Hepatosteatosis was evaluated with abdominal ultrasound. Duration of obesity, physical activity and nutritional habits, screen time, and parental obesity were questioned. Thyroid and liver function tests were performed. Six hundred and forty-two cases (59.2%) were MUO. Older age, male sex, increased BMI-SDS, and sedentary lifestyle were associated with MUO. Excessive junk food consumption was associated with MUO particularly among the prepubertal obese patients. Our results revealed that the most important factors that affect metabolic health in obesity are age and BMI. Positive effects of an active lifestyle and healthy eating habits are prominent in the prepubertal period and these habits should be formed earlier in life.

  2. Radioactive Lysine in Protein Metabolism Studies

    Science.gov (United States)

    Miller, L. L.; Bale, W. F.; Yuile, C. L.; Masters, R. E.; Tishkoff, G. H.; Whipple,, G. H.

    1950-01-09

    Studies of incorporation of DL-lysine in various body proteins of the dog; the time course of labeled blood proteins; and apparent rate of disappearance of labeled plasma proteins for comparison of behavior of the plasma albumin and globulin fractions; shows more rapid turn over of globulin fraction.

  3. Metabolic behavior of cell surface biotinylated proteins

    International Nuclear Information System (INIS)

    Hare, J.F.; Lee, E.

    1989-01-01

    The turnover of proteins on the surface of cultured mammalian cells was measured by a new approach. Reactive free amino or sulfhydryl groups on surface-accessible proteins were derivatized with biotinyl reagents and the proteins solubilized from culture dishes with detergent. Solubilized, biotinylated proteins were then adsorbed onto streptavidin-agarose, released with sodium dodecyl sulfate and mercaptoethanol, and separated on polyacrylamide gels. Biotin-epsilon-aminocaproic acid N-hydroxysuccinimide ester (BNHS) or N-biotinoyl-N'-(maleimidohexanoyl)hydrazine (BM) were the derivatizing agents. Only 10-12 bands were adsorbed onto streptavidin-agarose from undervatized cells or from derivatized cells treated with free avidin at 4 degrees C. Two-dimensional isoelectric focusing-sodium dodecyl sulfate gel electrophoresis resolved greater than 100 BNHS-derivatized proteins and greater than 40 BM-derivatized proteins. There appeared to be little overlap between the two groups of derivatized proteins. Short-term pulse-chase studies showed an accumulation of label into both groups of biotinylated proteins up until 1-2 h of chase and a rapid decrease over the next 1-5 h. Delayed appearance of labeled protein at the cell surface was attributed to transit time from site of synthesis. The unexpected and unexplained rapid disappearance of pulse-labeled proteins from the cell surface was invariant for all two-dimensionally resolved proteins and was sensitive to temperature reduction to 18 degrees C. Long-term pulse-chase experiments beginning 4-8 h after the initiation of chase showed the disappearance of derivatized proteins to be a simple first-order process having a half-life of 115 h in the case of BNHS-derivatized proteins and 30 h in the case of BM-derivatized proteins

  4. Effect of dietary protein restriction on renal ammonia metabolism

    Science.gov (United States)

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Guo, Hui; Verlander, Jill W.

    2015-01-01

    Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during protein restriction. Ammonia is the primary component of net acid excretion, and inappropriate ammonia excretion can lead to negative nitrogen balance. Accordingly, we examined ammonia excretion in response to protein restriction and then we determined the molecular mechanism of the changes observed. Wild-type C57Bl/6 mice fed a 20% protein diet and then changed to 6% protein developed an 85% reduction in ammonia excretion within 2 days, which persisted during a 10-day study. The expression of multiple proteins involved in renal ammonia metabolism was altered, including the ammonia-generating enzymes phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase (PEPCK) and the ammonia-metabolizing enzyme glutamine synthetase. Rhbg, an ammonia transporter, increased in expression in the inner stripe of outer medullary collecting duct intercalated cell (OMCDis-IC). However, collecting duct-specific Rhbg deletion did not alter the response to protein restriction. Rhcg deletion did not alter ammonia excretion in response to dietary protein restriction. These results indicate 1) dietary protein restriction decreases renal ammonia excretion through coordinated regulation of multiple components of ammonia metabolism; 2) increased Rhbg expression in the OMCDis-IC may indicate a biological role in addition to ammonia transport; and 3) Rhcg expression is not necessary to decrease ammonia excretion during dietary protein restriction. PMID:25925252

  5. DROUGHT AFFECTS PROTEIN AND PHENOLIC CONTENT IN ...

    African Journals Online (AJOL)

    userpc

    ABSTRACT. Bambara groundnut (Vigna subterranea L. Verdc.) is a legume crop, which has long been recognised as a protein-rich and drought-tolerant crop, used extensively in sub-Saharan. Africa. This study evaluates the effect of experimental water deficit stress on total protein concentration, secondary protein structure ...

  6. Effect of long-term refeeding on protein metabolism in patients with cirrhosis of the liver

    DEFF Research Database (Denmark)

    Kondrup, J; Nielsen, K; Juul, A

    1997-01-01

    , protein requirement and protein utilization were investigated further by measuring protein synthesis and degradation. In two separate studies, five or six patients with cirrhosis of the liver were refed on a balanced diet for an average of 2 or 4 weeks. Protein and energy intakes were doubled in both...... studies. Initial and final whole-body protein metabolism was measured in the fed state by primed continuous [15N]glycine infusion. Refeeding caused a statistically significant increase of about 30% in protein synthesis in both studies while protein degradation was only slightly affected. The increase...... in protein synthesis was associated with significant increases in plasma concentrations of total amino acids (25%), leucine (58%), isoleucine (82%), valine (72%), proline (48%) and triiodothyronine (27%) while insulin, growth hormone, insulin-like growth factor (IGF)-I and IGF-binding protein-3 were...

  7. Analysis of soybean root proteins affected by gibberellic acid treatment under flooding stress.

    Science.gov (United States)

    Oh, Myeong Won; Nanjo, Yohei; Komatsu, Setsuko

    2014-01-01

    Flooding is a serious abiotic stress for soybean because it restricts growth and reduces grain yields. To investigate the effect of gibberellic acid (GA) on soybean under flooding stress, root proteins were analyzed using a gel-free proteomic technique. Proteins were extracted from the roots of 4-days-old soybean seedlings exposed to flooding stress in the presence and absence of exogenous GA3 for 2 days. A total of 307, 324, and 250 proteins were identified from untreated, and flooding-treated soybean seedlings without or with GA3, respectively. Secondary metabolism- and cell-related proteins, and proteins involved in protein degradation/synthesis were decreased by flooding stress; however, the levels of these proteins were restored by GA3 supplementation under flooding. Fermentation- and cell wall-related proteins were not affected by GA3 supplementation. Furthermore, putative GA-responsive proteins, which were identified by the presence of a GA-responsive element in the promoter region, were less abundant by flooding stress; however, these proteins were more abundant by GA3 supplementation under flooding. Taken together, these results suggest that GA3 affects the abundance of proteins involved in secondary metabolism, cell cycle, and protein degradation/synthesis in soybeans under flooding stress.

  8. Effect of supplemental protein source during the winter on pre- and postpartum glucose metabolism

    Science.gov (United States)

    Circulating serum glucose concentrations as well as glucose utilization have been shown to be affected by forage quality. Supplemental protein provided to grazing range cows while consuming low quality forage may improve glucose metabolism. The objective of our study was to determine the effects of ...

  9. Liver and muscle protein metabolism in cachexia

    NARCIS (Netherlands)

    Peters, J.A.C.

    2009-01-01

    Up to 50% of cancer patients suffer from progressive weight loss (cachexia). Cachexia is induced by proinflammatory mediators (cytokines), induced by the tumor’s presence. These cytokines induce so-called acute phase protein synthesis by the liver, followed by skeletal muscle protein breakdown.

  10. Differential metabolic effects of casein and soy protein meals on skeletal muscle in healthy volunteers.

    Science.gov (United States)

    Luiking, Yvette C; Engelen, Mariëlle P K J; Soeters, Peter B; Boirie, Yves; Deutz, Nicolaas E P

    2011-02-01

    Dietary protein intake is known to affect whole body and interorgan protein turnover. We examined if moderate-nitrogen and carbohydrate casein and soy meals have a different effect on skeletal muscle protein and amino acid kinetics in healthy young subjects. Muscle protein and amino acid kinetics were measured in the postabsorptive state and during 4-h enteral intake of isonitrogenous [0.21 g protein/(kg body weight. 4 h)] protein-based test meals, which contained either casein (CAPM; n = 12) or soy protein (SOPM; n = 10) in 2 separate groups. Stable isotope and muscle biopsy techniques were used to study metabolic effects. The net uptake of glutamate, serine, histidine, and lysine across the leg was larger during CAPM than during SOPM intake. Muscle concentrations of glutamate, serine, histidine, glutamine, isoleucine and BCAA changed differently after CAPM and SOPM (P CAPM and SOPM, but differences in their (net) breakdown rates were not significant. Muscle protein synthesis was not different between CAPM and SOPM. Moderate-nitrogen casein and soy protein meals differently alter leg amino acid uptake without a significant difference in influencing acute muscle protein metabolism. Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  11. Adjustments of Protein Metabolism in Fasting Arctic Charr, Salvelinus alpinus.

    Directory of Open Access Journals (Sweden)

    Alicia A Cassidy

    Full Text Available Protein metabolism, including the interrelated processes of synthesis and degradation, mediates the growth of an animal. In ectothermic animals, protein metabolism is responsive to changes in both biotic and abiotic conditions. This study aimed to characterise responses of protein metabolism to food deprivation that occur in the coldwater salmonid, Arctic charr, Salvelinus alpinus. We compared two groups of Arctic charr: one fed continuously and the other deprived of food for 36 days. We measured the fractional rate of protein synthesis (KS in individuals from the fed and fasted groups using a flooding dose technique modified for the use of deuterium-labelled phenylalanine. The enzyme activities of the three major protein degradation pathways (ubiquitin proteasome, lysosomal cathepsins and the calpain systems were measured in the same fish. This study is the first to measure both KS and the enzymatic activity of protein degradation in the same fish, allowing us to examine the apparent contribution of different protein degradation pathways to protein turnover in various tissues (red and white muscle, liver, heart and gills. KS was lower in the white muscle and in liver of the fasted fish compared to the fed fish. There were no observable effects of food deprivation on the protease activities in any of the tissues with the exception of liver, where the ubiquitin proteasome pathway seemed to be activated during fasting conditions. Lysosomal proteolysis appears to be the primary degradation pathway for muscle protein, while the ubiquitin proteasome pathway seems to predominate in the liver. We speculate that Arctic charr regulate protein metabolism during food deprivation to conserve proteins.

  12. Influence on bone metabolism of dietary trace elements, protein, fat, carbohydrates, and vitamins.

    Science.gov (United States)

    Sarazin, M; Alexandre, C; Thomas, T

    2000-01-01

    Osteoporosis is a multifactorial disease driven primarily by the genetic factors that control bone metabolism. Among environmental factors, diet may play a key role, affording a target for low-cost intervention. Calcium and vitamin D are well known to affect bone metabolism. Other nutrients may influence bone mass changes; for instance, a number of trace elements and vitamins other than vitamin D are essential to many of the steps of bone metabolism. A wide variety of foods provide these nutrients, and in industrialized countries deficiencies are more often due to idiosyncratic eating habits than to cultural influences. Both culture and vogue influence the amount of carbohydrate, fat, and protein in the typical diet. In children, the current trend is to reduce protein and to increase carbohydrate and fat. Data from epidemiological and animal studies suggest that this may adversely affect bone mass and the fracture risk.

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

    Science.gov (United States)

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

    2013-06-12

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

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

    Science.gov (United States)

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

    2017-08-01

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

  15. Protein nutrition and metabolism during early development of the chick embryo

    International Nuclear Information System (INIS)

    Klein, N.W.

    1976-01-01

    Cultures of intact early chick embryos have been used as a model system in which to study the nutrition and metabolism of proteins during early embryonic development. Previous studies have shown that these embryos require nutrient proteins for growth and development. The protein requirement was found to be specific in that at least two proteins were essential; one a transferrin (either conalbumin or yolk transferrin) and the other either ovalbumin or lipovitellin. Variations in the quantity or type of protein provided in the medium altered the growth of embryo regions through regionally specific changes in protein breakdown. This was confirmed through protein synthetic studies with isolated polyribosomes. More recently such variations in protein nutrition have been shown also to affect the actual patterns of proteins synthesized by regions of the embryo. These observed responses to protein nutrition have been difficult to reconcile with our observation that proteins as such did not reach the embryo proper but were first degraded to amine acids within the yolk-sac membrane. Studies on the synthesis of serum proteins by the yolk-sac membrane have provided a possible explanation in that the relative synthesis of individual serum proteins was dramatically influenced by the protein composition of the culture medium. We are currently attempting to demonstrate that serum proteins are indeed the mediators of the response of embryos to protein nutrition. (author)

  16. Regulation of intestinal protein metabolism by amino acids.

    Science.gov (United States)

    Bertrand, Julien; Goichon, Alexis; Déchelotte, Pierre; Coëffier, Moïse

    2013-09-01

    Gut homeostasis plays a major role in health and may be regulated by quantitative and qualitative food intake. In the intestinal mucosa, an intense renewal of proteins occurs, at approximately 50% per day in humans. In some pathophysiological conditions, protein turnover is altered and may contribute to intestinal or systemic diseases. Amino acids are key effectors of gut protein turnover, both as constituents of proteins and as regulatory molecules limiting intestinal injury and maintaining intestinal functions. Many studies have focused on two amino acids: glutamine, known as the preferential substrate of rapidly dividing cells, and arginine, another conditionally essential amino acid. The effects of glutamine and arginine on protein synthesis appear to be model and condition dependent, as are the involved signaling pathways. The regulation of gut protein degradation by amino acids has been minimally documented until now. This review will examine recent data, helping to better understand how amino acids regulate intestinal protein metabolism, and will explore perspectives for future studies.

  17. Efficient protein production by yeast requires global tuning of metabolism

    DEFF Research Database (Denmark)

    Huang, Mingtao; Bao, Jichen; Hallstrom, Bjorn M.

    2017-01-01

    The biotech industry relies on cell factories for production of pharmaceutical proteins, of which several are among the top-selling medicines. There is, therefore, considerable interest in improving the efficiency of protein production by cell factories. Protein secretion involves numerous...... intracellular processes with many underlying mechanisms still remaining unclear. Here, we use RNA-seq to study the genome-wide transcriptional response to protein secretion in mutant yeast strains. We find that many cellular processes have to be attuned to support efficient protein secretion. In particular...... that by tuning metabolism cells are able to efficiently secrete recombinant proteins. Our findings provide increased understanding of which cellular regulations and pathways are associated with efficient protein secretion....

  18. Inactivation of Tor proteins affects the dynamics of endocytic proteins ...

    Indian Academy of Sciences (India)

    Tor2 is an activator of the Rom2/Rho1 pathway that regulates -factor internalization. Since the recruitment of endocytic proteins such as actin-binding proteins and the amphiphysins precedes the internalization of -factor, we hypothesized that loss of Tor function leads to an alteration in the dynamics of the endocytic ...

  19. Hyperthyroidism affects lipid metabolism in lactating and suckling rats.

    Science.gov (United States)

    Varas, S M; Jahn, G A; Giménez, M S

    2001-08-01

    Two per thousand pregnant women have hyperthyroidism (HT), and although the symptoms are attenuated during pregnancy, they rebound after delivery, affecting infant development. To examine the effects of hyperthyroidism on lactation, we studied lipid metabolism in maternal mammary glands and livers of hyperthyroid rats and their pups. Thyroxine (10 microg/100 g body weight/d) or vehicle-treated rats were made pregnant 2 wk after commencement of treatment and sacrificed on days 7, 14, and 21 of lactation with the litters. Circulating triiodothyronine and tetraiodothyronine concentrations in the HT mothers were increased on all days. Hepatic esterified cholesterol (EC) and free cholesterol (FC) and triglyceride (TG) concentrations were diminished on days 14 and 21. Lipid synthesis, measured by incorporation of [3H]H2O into EC, FC, and TG, fatty acid synthase, and acetyl CoA carboxylase activities increased at day 14, while incorporation into FC and EC decreased at days 7 and 21, respectively. Mammary FC and TG concentrations were diminished at day 14; incorporation of [3H]H2O into TG decreased at days 7 and 21, and incorporation of [3H]H2O into FC increased at day 14. In the HT pups, growth rate was diminished, tetraiodothyronine concentration rose at days 7 and 14 of lactation, and triiodothyronine increased only at day 14. Liver TG concentrations increased at day 7 and fell at day 14, while FC increased at day 14 and only acetyl CoA carboxylase activity fell at day 14. Thus, hyperthyroidism changed maternal liver and mammary lipid metabolism, with decreased lipid concentration in spite of increased liver rate of synthesis and decreases in mammary synthesis. These changes, along with the mild hyperthyroidism of the litters, may have contributed to their reduced growth rate.

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

    Directory of Open Access Journals (Sweden)

    Jia Li

    2016-01-01

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

  1. Does vitamin D affects components of the metabolic syndrome?

    OpenAIRE

    Sevil Karahan Yılmaz; Aylin Ayaz

    2015-01-01

    Metabolic syndrome is a major public health problem which has become increasingly common worlwide with cardiometabolic complications and have high morbidity and mortality. In addition to some genetical features, environmental factors such sedentary lifestyle, improper eating habits constitutes a risk factor for metabolic syndrome. Important components of the metabolic syndrome are dyslipidemia (low HDL levels, high triglycerides level), hyperglycemia, elevated blood...

  2. Spastin binds to lipid droplets and affects lipid metabolism.

    Directory of Open Access Journals (Sweden)

    Chrisovalantis Papadopoulos

    2015-04-01

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

  3. Protein metabolism in Turner syndrome and the impact of hormone replacement therapy.

    Science.gov (United States)

    Gravholt, Claus Højbjerg; Riis, Anne Lene; Møller, Niels; Christiansen, Jens Sandahl

    2007-09-01

    Studies have documented an altered body composition in Turner syndrome (TS). Body fat is increased and muscle mass is decreased. Ovarian failure necessitates substitution with female hormone replacement therapy (HRT), and HRT induces favourable changes in body composition. It is unknown how HRT affects protein metabolism. To test whether alterations in body composition before and after HRT in TS are a result of altered protein metabolism. We performed a randomized crossover study with active treatment (HRT in TS and oral contraceptives in controls) or no treatment. We studied eight women (age 29.7 +/- 5.6 (mean +/- SD) years) with TS, verified by karyotype, and eight age-matched controls (age 27.3 +/- 4.9 years). All subjects underwent a 3-h study in the postabsorptive state. Protein dynamics of the whole body and of the forearm muscles were measured by an amino acid tracer dilution technique using [(15)N]phenylalanine and [(2)H(4)]tyrosine. Substrate metabolism was examined by indirect calorimetry. Energy expenditure was comparable among TS and controls, and did not change during active treatment. Whole-body phenylalanine and tyrosine fluxes were similar in the untreated situations, and did not change during active treatment. Amino acid degradation and protein synthesis were similar in all situations. Muscle protein breakdown was similar among groups, and was not affected by treatment. Muscle protein synthesis rate and forearm blood flow did not differ among groups or due to treatment. Protein metabolism in TS is comparable to controls, and is not affected by HRT.

  4. Maternal protein intake in pregnancy and offspring metabolic health at age 9-16 y

    DEFF Research Database (Denmark)

    Maslova, Ekaterina; Hansen, Susanne; Grunnet, Louise Groth

    2017-01-01

    in free-living populations remains limited. Objective: We examined the association of protein intake in pregnancy with offspring metabolic health at age 9-16 y in a longitudinal cohort that oversampled pregnancies with gestational diabetes mellitus (GDM). Design: Six hundred eight women with an index...... provide little support for an association of maternal protein intake in pregnancy with measures of offspring metabolic health. Further studies in larger cohorts are needed to determine whether low maternal protein intake in pregnancy may improve glucose homeostasis in GDM-exposed and male offspring....... pregnancy affected by gestational diabetes mellitus and 626 controls enrolled in the Danish National Birth Cohort were used for the analysis. Protein (total, animal, vegetable) intake was assessed by using a foodfrequency questionnaire in gestational week 25. The offspring underwent a clinical examination...

  5. Effects of reducing dietary crude protein and metabolic energy in ...

    African Journals Online (AJOL)

    The objective of this experiment was to determine the effects of a pure reduction in the dietary crude protein (CP) and metabolic energy (ME) contents on growth performance, nutrient digestibility, blood profile, faecal microflora and odour gas emission in weaned pigs. A total of 80 weaned piglets ((Landrace × Yorkshire) ...

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

    Science.gov (United States)

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

    2016-06-01

    We have recently demonstrated that specific overexpression of DEP-domain containing mTOR-interacting protein (DEPTOR) in the mediobasal hypothalamus (MBH) protects mice against high-fat diet-induced obesity, revealing DEPTOR as a significant contributor to energy balance regulation. On the basis of evidence that DEPTOR is expressed in the proopiomelanocortin (POMC) neurons of the MBH, the present study aimed to investigate whether these neurons mediate the metabolic effects of DEPTOR. Here, we report that specific DEPTOR overexpression in POMC neurons does not recapitulate any of the phenotypes observed when the protein was overexpressed in the MBH. Unlike the previous model, mice overexpressing DEPTOR only in POMC neurons 1) did not show differences in feeding behavior, 2) did not exhibit changes in locomotion activity and oxygen consumption, 3) did not show an improvement in systemic glucose metabolism, and 4) were not resistant to high-fat diet-induced obesity. These results support the idea that other neuronal populations are responsible for these phenotypes. Nonetheless, we observed a mild elevation in fasting blood glucose, insulin resistance, and alterations in liver glucose and lipid homeostasis in mice overexpressing DEPTOR in POMC neurons. Taken together, these results show that DEPTOR overexpression in POMC neurons does not affect energy balance regulation but could modulate metabolism through a brain-liver connection. Copyright © 2016 the American Physiological Society.

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

    Science.gov (United States)

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

    2014-01-01

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

  8. Altered sterol metabolism in budding yeast affects mitochondrial iron-sulfur (Fe-S) cluster synthesis.

    Science.gov (United States)

    Ward, Diane M; Chen, Opal S; Li, Liangtao; Kaplan, Jerry; Bhuiyan, Shah Alam; Natarajan, Selvamuthu K; Bard, Martin; Cox, James E

    2018-05-17

    Ergosterol synthesis is essential for cellular growth and viability of the budding yeast Saccharomyces cerevisiae, and intracellular sterol distribution and homeostasis are therefore highly regulated in this species. Erg25 is an iron-containing C4-methyl sterol oxidase that contributes to the conversion of 4,4-dimethylzymosterol to zymosterol, a precursor of ergosterol. The ERG29 gene encodes an endoplasmic reticulum (ER)-associated protein, and here we identified a role for Erg29 in the methyl sterol oxidase step of ergosterol synthesis. ERG29 deletion resulted in lethality in respiring cells, but respiration-incompetent (Rho- or Rho0) cells survived, suggesting that Erg29 loss leads to accumulation of oxidized sterol metabolites that affect cell viability. Down-regulation of ERG29 expression in Δerg29 cells indeed led to accumulation of methyl sterol metabolites, resulting in increased mitochondrial oxidants and a decreased ability of mitochondria to synthesize iron-sulfur (Fe-S) clusters due to reduced levels of Yfh1, the mammalian frataxin homolog, which is involved in mitochondrial Fe metabolism. Using a high-copy genomic library, we identified suppressor genes that permitted growth of Δerg29 cells on respiratory substrates, and these included genes encoding the mitochondrial proteins Yfh1, Mmt1, Mmt2, and Pet20, which reversed all phenotypes associated with loss of ERG29. Of note, loss of Erg25 also resulted in accumulation of methyl sterol metabolites and also increased mitochondrial oxidants and degradation of Yfh1. We propose that accumulation of toxic intermediates of the methyl sterol oxidase reaction increase mitochondrial oxidants, which affect Yfh1 protein stability. These results indicate an interaction between sterols generated by ER proteins and mitochondrial iron metabolism. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Effect of protein provision via milk replacer or solid feed on protein metabolism in veal calves.

    Science.gov (United States)

    Berends, H; van den Borne, J J G C; Røjen, B A; Hendriks, W H; Gerrits, W J J

    2015-02-01

    The current study evaluated the effects of protein provision to calves fed a combination of solid feed (SF) and milk replacer (MR) at equal total N intake on urea recycling and N retention. Nitrogen balance traits and [(15)N2]urea kinetics were measured in 30 calves (23 wk of age, 180±3.7kg of body weight), after being exposed to the following experimental treatments for 11 wk: a low level of SF with a low N content (SF providing 12% of total N intake), a high level of SF with a low N content (SF providing 22% of total N intake), or a high level of SF with a high N content (SF providing 36% of total N intake). The SF mixture consisted of 50% concentrates, 25% corn silage, and 25% straw on a dry matter basis. Total N intake was equalized to 1.8g of N·kg of BW(-0.75)·d(-1) by adjusting N intake via MR. All calves were housed individually on metabolic cages to allow for quantification of a N balance of calves for 5 d, and for the assessment of urea recycling from [(15)N2]urea kinetics. Increasing low-N SF intake at equal total N intake resulted in a shift from urinary to fecal N excretion but did not affect protein retention (0.71g of N·kg of BW(-0.75)·d(-1)). Increasing low-N SF intake increased urea recycling but urea reused for anabolism remained unaffected. Total-tract neutral detergent fiber digestibility decreased (-9%) with increasing low-N SF intake, indicating reduced rumen fermentation. Increasing the N content of SF at equal total N intake resulted in decreased urea production, excretion, and return to ornithine cycle, and increased protein retention by 17%. This increase was likely related to an effect of energy availability on protein retention due to an increase in total-tract neutral detergent fiber digestion (>10%) and due to an increased energy supply via the MR. In conclusion, increasing low-N SF intake at the expense of N intake from MR, did not affect protein retention efficiency in calves. Increasing the N content of SF at equal total N

  10. Protein and leucine metabolism in maple syrup urine disease

    International Nuclear Information System (INIS)

    Thompson, G.N.; Bresson, J.L.; Pacy, P.J.; Bonnefont, J.P.; Walter, J.H.; Leonard, J.V.; Saudubray, J.M.; Halliday, D.

    1990-01-01

    Constant infusions of [13C]leucine and [2H5]phenylalanine were used to trace leucine and protein kinetics, respectively, in seven children with maple syrup urine disease (MSUD) and eleven controls matched for age and dietary protein intake. Despite significant elevations of plasma leucine (mean 351 mumol/l, range 224-477) in MSUD subjects, mean whole body protein synthesis [3.78 +/- 0.42 (SD) g.kg-1. 24 h-1] and catabolism (4.07 +/- 0.46) were similar to control values (3.69 +/- 0.50 and 4.09 +/- 0.50, respectively). The relationship between phenylalanine and leucine fluxes was also similar in MSUD subjects (mean phenylalanine-leucine flux ratio 0.35 +/- 0.07) and previously reported adult controls (0.33 +/- 0.02). Leucine oxidation was undetectable in four of the MSUD subjects and very low in the other three (less than 4 mumol.kg-1.h-1; controls 13-20). These results show that persistent elevation in leucine concentration has no effect on protein synthesis. The marked disturbance in leucine metabolism in MSUD did not alter the relationship between rates of catabolism of protein to phenylalanine and leucine, which provides further support for the validity of the use of a single amino acid to trace whole body protein metabolism. The minimal leucine oxidation in MSUD differs from findings in other inborn metabolic errors and indicates that in patients with classical MSUD there is no significant route of leucine disposal other than through protein synthesis

  11. Insulin Stimulates S100B Secretion and These Proteins Antagonistically Modulate Brain Glucose Metabolism.

    Science.gov (United States)

    Wartchow, Krista Minéia; Tramontina, Ana Carolina; de Souza, Daniela F; Biasibetti, Regina; Bobermin, Larissa D; Gonçalves, Carlos-Alberto

    2016-06-01

    Brain metabolism is highly dependent on glucose, which is derived from the blood circulation and metabolized by the astrocytes and other neural cells via several pathways. Glucose uptake in the brain does not involve insulin-dependent glucose transporters; however, this hormone affects the glucose influx to the brain. Changes in cerebrospinal fluid levels of S100B (an astrocyte-derived protein) have been associated with alterations in glucose metabolism; however, there is no evidence whether insulin modulates glucose metabolism and S100B secretion. Herein, we investigated the effect of S100B on glucose metabolism, measuring D-(3)H-glucose incorporation in two preparations, C6 glioma cells and acute hippocampal slices, and we also investigated the effect of insulin on S100B secretion. Our results showed that: (a) S100B at physiological levels decreases glucose uptake, through the multiligand receptor RAGE and mitogen-activated protein kinase/ERK signaling, and (b) insulin stimulated S100B secretion via PI3K signaling. Our findings indicate the existence of insulin-S100B modulation of glucose utilization in the brain tissue, and may improve our understanding of glucose metabolism in several conditions such as ketosis, streptozotocin-induced dementia and pharmacological exposure to antipsychotics, situations that lead to changes in insulin signaling and extracellular levels of S100B.

  12. Hypolipidemic effect of dietary pea proteins: Impact on genes regulating hepatic lipid metabolism.

    Science.gov (United States)

    Rigamonti, Elena; Parolini, Cinzia; Marchesi, Marta; Diani, Erika; Brambilla, Stefano; Sirtori, Cesare R; Chiesa, Giulia

    2010-05-01

    Controversial data on the lipid-lowering effect of dietary pea proteins have been provided and the mechanisms behind this effect are not completely understood. The aim of the study was to evaluate a possible hypolipidemic activity of a pea protein isolate and to determine whether pea proteins could affect the hepatic lipid metabolism through regulation of genes involved in cholesterol and fatty acid homeostasis. Rats were fed Nath's hypercholesterolemic diets for 28 days, the protein sources being casein or a pea protein isolate from Pisum sativum. After 14 and 28 days of dietary treatment, rats fed pea proteins had markedly lower plasma cholesterol and triglyceride levels than rats fed casein (pPea protein-fed rats displayed higher hepatic mRNA levels of LDL receptor versus those fed casein (ppea protein-fed rats than in rats fed casein (ppea proteins in rats. Moreover, pea proteins appear to affect cellular lipid homeostasis by upregulating genes involved in hepatic cholesterol uptake and by downregulating fatty acid synthesis genes.

  13. miR-122 targets pyruvate kinase M2 and affects metabolism of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Angela M Liu

    Full Text Available In contrast to normal differentiated cells that depend on mitochondrial oxidative phosphorylation for energy production, cancer cells have evolved to utilize aerobic glycolysis (Warburg's effect, with benefit of providing intermediates for biomass production. MicroRNA-122 (miR-122 is highly expressed in normal liver tissue regulating a wide variety of biological processes including cellular metabolism, but is reduced in hepatocellular carcinoma (HCC. Overexpression of miR-122 was shown to inhibit cancer cell proliferation, metastasis, and increase chemosensitivity, but its functions in cancer metabolism remains unknown. The present study aims to identify the miR-122 targeted genes and to investigate the associated regulatory mechanisms in HCC metabolism. We found the ectopic overexpression of miR-122 affected metabolic activities of HCC cells, evidenced by the reduced lactate production and increased oxygen consumption. Integrated gene expression analysis in a cohort of 94 HCC tissues revealed miR-122 level tightly associated with a battery of glycolytic genes, in which pyruvate kinase (PK gene showed the strongest anti-correlation coefficient (Pearson r = -0.6938, p = <0.0001. In addition, reduced PK level was significantly associated with poor clinical outcomes of HCC patients. We found isoform M2 (PKM2 is the dominant form highly expressed in HCC and is a direct target of miR-122, as overexpression of miR-122 reduced both the mRNA and protein levels of PKM2, whereas PKM2 re-expression abrogated the miR-122-mediated glycolytic activities. The present study demonstrated the regulatory role of miR-122 on PKM2 in HCC, having an implication of therapeutic intervention targeting cancer metabolic pathways.

  14. Effect of bacterial protein meal on protein and energy metabolism in growing chickens

    DEFF Research Database (Denmark)

    Hellwing, Anne Louise Frydendahl; Tauson, Anne-Helene; Skrede, Anders

    2006-01-01

    This experiment investigates the effect of increasing the dietary content of bacterial protein meal (BPM) on the protein and energy metabolism, and carcass chemical composition of growing chickens. Seventy-two Ross male chickens were allocated to four diets, each in three replicates with 0% (D0), 2...... (period 1), 5 chickens (period 2), and one chicken (periods 3-5). After each balance period, one chicken in each cage was killed and the carcass weight was recorded. Chemical Analyses were performed on the carcasses from periods, 1, 3, and 5. Weight gain, feed intake, and feed conversion rate were found...... to be similar for all diets. Chickens on D0 retained 1.59 g N·kg-°75·d-¹, respectively. This was probably caused by the higher nitrogen content of D0. Neither the HE (p=0.92) nor the retention of energy (P=0.88) were affected by diet. Carcass composition was similar between diets, in line with the values...

  15. Isotopic labeling affects 1,25-dihydroxyvitamin D metabolism

    International Nuclear Information System (INIS)

    Halloran, B.P.; Bikle, D.D.; Castro, M.E.; Gee, E.

    1989-01-01

    Isotope substitution can change the biochemical properties of vitamin D. To determine the effect of substituting 3H for 1H on the metabolism of 1,25(OH)2D3, we measured the metabolic clearance rate and renal metabolism of unlabeled and 3H-labeled 1,25(OH)2D3. Substitution of 3H for 1H on carbons 26 and 27 [1,25(OH)2[26,27(n)-3H]D3] or on carbons 23 and 24 [1,25(OH)2[23,24(n)-3H]D3] reduced the in vivo metabolic clearance rate of 1,25(OH)2D3 by 36% and 37%, respectively, and reduced the in vitro renal catabolism of 1,25(OH)2D3 by 11% and 54%, respectively. Substitutions of 3H for 1H on carbons 23 and 24 as opposed to carbons 26 and 27 reduced conversion of [3H]1,25(OH)2D3 to [3H]1,24,25(OH)2D3 by 25% and to putative 24-oxo-1,23,25-dihydroxyvitamin D3 by 1600%. These results indicate that substitution of 3H for 1H on carbons 26 and 27 or on carbons 23 and 24 can reduce the metabolic clearance rate and in vitro metabolism of 1,25(OH)2D3 and quantitatively alter the pattern of metabolic products produced

  16. Radioisotope techniques in the study of protein metabolism

    International Nuclear Information System (INIS)

    1965-01-01

    The International Atomic Energy Agency (IAEA) held a panel meeting on June 1-5, 1964. The purpose of the panel was to discuss the present status of radioactive tracer techniques for the study of protein metabolism and to suggest ways of extending an co-ordinating the Agency's research programme in this field. The meeting was attended by 13 invited experts from ten different countries, and three representatives of the World Health Organization (WHO). Sessions of the panel were devoted to methods of preparation of labelled proteins and protein-like substances, to techniques of measurement of gastro-intestinal protein absorption and loss and to the clinical applications of these techniques. At each session, working papers were presented by various participants and then discussed in detail. This report gives the full texts of the working papers together with extensive summaries of the discussions and provides a detailed picture of the present situation and likely future developments in this field of work. It is hoped that its publication will be of interest to all concerned with problems of protein metabolism, whether in clinical medicine or the basic medical sciences. 349 refs, figs and tabs

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

    Science.gov (United States)

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

    2009-09-01

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

  18. 5' adenosine monophosphate-activated protein kinase, metabolism and exercise.

    Science.gov (United States)

    Aschenbach, William G; Sakamoto, Kei; Goodyear, Laurie J

    2004-01-01

    The 5' adenosine monophosphate-activated protein kinase (AMPK) is a member of a metabolite-sensing protein kinase family that functions as a metabolic 'fuel gauge' in skeletal muscle. AMPK is a ubiquitous heterotrimeric protein, consisting of an alpha catalytic, and beta and gamma regulatory subunits that exist in multiple isoforms and are all required for full enzymatic activity. During exercise, AMPK becomes activated in skeletal muscle in response to changes in cellular energy status (e.g. increased adenosine monophosphate [AMP]/adenosine triphosphate [ATP] and creatine/phosphocreatine ratios) in an intensity-dependent manner, and serves to inhibit ATP-consuming pathways, and activate pathways involved in carbohydrate and fatty-acid metabolism to restore ATP levels. Recent evidence shows that although AMPK plays this key metabolic role during acute bouts of exercise, it is also an important component of the adaptive response of skeletal muscles to endurance exercise training because of its ability to alter muscle fuel reserves and expression of several exercise-responsive genes. This review discusses the putative roles of AMPK in acute and chronic exercise responses, and suggests avenues for future AMPK research in exercise physiology and biochemistry.

  19. Genetic alterations affecting cholesterol metabolism and human fertility.

    Science.gov (United States)

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

    2014-11-01

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

  20. How coffee affects metabolic syndrome and its components.

    Science.gov (United States)

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

    2017-06-21

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

  1. Regulation of Lipid and Glucose Metabolism by Phosphatidylcholine Transfer Protein

    Science.gov (United States)

    Kang, Hye Won; Wei, Jie; Cohen, David E.

    2010-01-01

    Phosphatidylcholine transfer protein (PC-TP, a.k.a. StARD2) binds phosphatidylcholines and catalyzes their intermembrane transfer and exchange in vitro. The structure of PC-TP comprises a hydrophobic pocket and a well-defined head-group binding site, and its gene expression is regulated by peroxisome proliferator activated receptor α. Recent studies have revealed key regulatory roles for PC-TP in lipid and glucose metabolism. Notably, Pctp−/− mice are sensitized to insulin action and exhibit more efficient brown fat-mediated thermogenesis. PC-TP appears to limit access of fatty acids to mitochondria by stimulating the activity of thioesterase superfamily member 2, a newly characterized long-chain fatty acyl-CoA thioesterase. Because PC-TP discriminates among phosphatidylcholines within lipid bilayers, it may function as a sensor that links metabolic regulation to membrane composition. PMID:20338778

  2. Xenobiotic-contaminated diets affect hepatic lipid metabolism: Implications for liver steatosis in Sparus aurata juveniles

    Energy Technology Data Exchange (ETDEWEB)

    Maradonna, F.; Nozzi, V. [Dipartimento di Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, 60131 Ancona (Italy); Santangeli, S. [Dipartimento di Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, 60131 Ancona (Italy); INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy); Traversi, I. [Dipartimento di Scienze della Terra, dell’Ambiente e della Vita, Università di Genova, 16132 Genova (Italy); Gallo, P. [INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy); Dipartimento di Chimica, Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Napoli (Italy); Fattore, E. [Dipartimento Ambiente e Salute, IRCCS–Istituto di Ricerche Farmacologiche “Mario Negri”, 20156 Milano (Italy); Mita, D.G. [INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy); Mandich, A. [INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy); Dipartimento di Scienze della Terra, dell’Ambiente e della Vita, Università di Genova, 16132 Genova (Italy); Carnevali, O., E-mail: o.carnevali@univpm.it [Dipartimento di Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, 60131 Ancona (Italy); INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy)

    2015-10-15

    Highlights: • Diets contaminated with NP, BPA, or t-OP affect lipid metabolism. • Xenobiotic-contaminated diets induce metabolic disorders. • Hepatic metabolic disorders may be related to environmental pollution. - Abstract: The metabolic effects induced by feed contaminated with a lower or a higher concentration of -nonylpnenol (NP), 4-tert-octylphenol (t-OP) or bisphenol A (BPA), three environmental endocrine disruptors, were assessed in juvenile sea bream liver. Histological analysis demonstrated that all these three xenobiotics induced hepatic lipid accumulation and steatosis. These findings prompted analysis of the expression of the major molecules involved in lipid metabolism: peroxisome proliferator activated receptors (which is encoded by ppars), fatty acid synthase (encoded by fas), lipoprotein lipase (encoded by lpl) and hormone-sensitive lipase (encoded by hsl). The enzymes encoded by ppars and fas are in fact responsible for lipid accumulation, whereas lpl- and hsl- encoded proteins play a pivotal role in fat mobilization. The three xenobiotics modulated ppar mRNA expression: pparα mRNA expression was induced by the higher dose of each contaminant; pparβ mRNA expression was upregulated by the lower doses and in BPA2 fish ppary mRNA overexpression was induced by all pollutants. These data agreed with the lipid accumulation profiles documented by histology. Fas mRNA levels were modulated by the two NP doses and the higher BPA concentration. Lpl mRNA was significantly upregulated in all experimental groups except for BPA1 fish while hsl mRNA was significantly downregulated in all groups except for t-OP2 and BPA1 fish. The plasma concentrations of cortisol, the primary stress biomarker, were correlated with the levels of pepck mRNA level. This gene encodes phosphoenolpyruvate carboxykinase which is one of the key enzymes of gluconeogenesis. Pepck mRNA was significantly overexpressed in fish exposed to NP2 and both t-OP doses. Finally, the genes

  3. Xenobiotic-contaminated diets affect hepatic lipid metabolism: Implications for liver steatosis in Sparus aurata juveniles

    International Nuclear Information System (INIS)

    Maradonna, F.; Nozzi, V.; Santangeli, S.; Traversi, I.; Gallo, P.; Fattore, E.; Mita, D.G.; Mandich, A.; Carnevali, O.

    2015-01-01

    Highlights: • Diets contaminated with NP, BPA, or t-OP affect lipid metabolism. • Xenobiotic-contaminated diets induce metabolic disorders. • Hepatic metabolic disorders may be related to environmental pollution. - Abstract: The metabolic effects induced by feed contaminated with a lower or a higher concentration of -nonylpnenol (NP), 4-tert-octylphenol (t-OP) or bisphenol A (BPA), three environmental endocrine disruptors, were assessed in juvenile sea bream liver. Histological analysis demonstrated that all these three xenobiotics induced hepatic lipid accumulation and steatosis. These findings prompted analysis of the expression of the major molecules involved in lipid metabolism: peroxisome proliferator activated receptors (which is encoded by ppars), fatty acid synthase (encoded by fas), lipoprotein lipase (encoded by lpl) and hormone-sensitive lipase (encoded by hsl). The enzymes encoded by ppars and fas are in fact responsible for lipid accumulation, whereas lpl- and hsl- encoded proteins play a pivotal role in fat mobilization. The three xenobiotics modulated ppar mRNA expression: pparα mRNA expression was induced by the higher dose of each contaminant; pparβ mRNA expression was upregulated by the lower doses and in BPA2 fish ppary mRNA overexpression was induced by all pollutants. These data agreed with the lipid accumulation profiles documented by histology. Fas mRNA levels were modulated by the two NP doses and the higher BPA concentration. Lpl mRNA was significantly upregulated in all experimental groups except for BPA1 fish while hsl mRNA was significantly downregulated in all groups except for t-OP2 and BPA1 fish. The plasma concentrations of cortisol, the primary stress biomarker, were correlated with the levels of pepck mRNA level. This gene encodes phosphoenolpyruvate carboxykinase which is one of the key enzymes of gluconeogenesis. Pepck mRNA was significantly overexpressed in fish exposed to NP2 and both t-OP doses. Finally, the genes

  4. Do diabetes and obesity affect the metabolic response to exercise?

    Science.gov (United States)

    Plomgaard, Peter; Weigert, Cora

    2017-07-01

    Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. Poor glycemic control before an intervention can be a risk factor of reduced therapeutic benefit from exercise. But the acute metabolic response to exercise and the transcriptional profile of the working muscle is similar in healthy controls and type 2 diabetic patients, including but not limited to intact activation of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent on the glucagon/insulin ratio and the exercise-induced increase in hepatokines such as fibroblast growth factor 21 and follistatin is impaired in type 2 diabetes and obesity, but consequences for the benefit from exercise are unknown yet. Severe metabolic dysregulation can reduce the benefit from exercise, but the intact response of key metabolic regulators in exercising skeletal muscle of diabetic patients demonstrates the effectiveness of exercise programs to treat the disease.

  5. Early postnatal low-protein nutrition, metabolic programming and the autonomic nervous system in adult life

    OpenAIRE

    de Oliveira, Júlio Cezar; Grassiolli, Sabrina; Gravena, Clarice; de Mathias, Paulo Cezar Freitas

    2012-01-01

    Abstract Protein restriction during lactation has been used as a rat model of metabolic programming to study the impact of perinatal malnutrition on adult metabolism. In contrast to protein restriction during fetal life, protein restriction during lactation did not appear to cause either obesity or the hallmarks of metabolic syndrome, such as hyperinsulinemia, when individuals reached adulthood. However, protein restriction provokes body underweight and hypoinsulinemia. This review is focused...

  6. Levetiracetam Affects Differentially Presynaptic Proteins in Rat Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Daniele Marcotulli

    2017-12-01

    Full Text Available Presynaptic proteins are potential therapeutic targets for epilepsy and other neurological diseases. We tested the hypothesis that chronic treatment with the SV2A ligand levetiracetam affects the expression of other presynaptic proteins. Results showed that in rat neocortex no significant difference was detected in SV2A protein levels in levetiracetam treated animals compared to controls, whereas levetiracetam post-transcriptionally decreased several vesicular proteins and increased LRRK2, without any change in mRNA levels. Analysis of SV2A interactome indicates that the presynaptic proteins regulation induced by levetiracetam reported here is mediated by this interactome, and suggests that LRRK2 plays a role in forging the pattern of effects.

  7. Amino acid metabolism and whole-body protein turnover in lambs ...

    African Journals Online (AJOL)

    The effect of protein supplementation of a wheat straw diet on the metabolism of lysine, leucine, methionine and urea, and on whole-body protein turnover rate was investigated in lambs. The metabolism of lysine and leucine is reported elsewhere (Cronje et aI., 1992); in this paper methionine metabolism is discussed, and ...

  8. The Effect of Protein Restriction in the In Vitro Metabolism of Albendazole in Rats.

    Science.gov (United States)

    Belaz, Kátia Roberta A; de O Cardoso, Josiane; da Silva, Carlos Alberto; Oliveira, Regina V

    2015-01-01

    This work presents an in vitro investigation of the effect of protein restriction on the metabolism of albendazole (ABZ). This study was conducted using liver microsomal fractions obtained from Wistar rats. For the quantitative analysis, a multidimensional High Performance Liquid Chromatography (2D HPLC) method was fully validated for the determination of the ABZ metabolites: albendazole sulfoxide, albendazole sulfone and albendazole 2-aminesulfone. The target compounds were directly extracted using a C8-RAM-BSA column (5.0x0.46 cm i.d.) and analyzed on a chromatographic chiral column containing amylose tris(3,5-dimethylphenylcarbamate) (150x4.6 mm i.d.). The in vitro biotransformation results showed that the protein restriction influenced the oxidative metabolism of ABZ. The production of R-(+)-ABZ-SO (1309 nmol/L) and S-(-)-ABZ-SO (1456 nmol/L) was higher in the control animals than in the animals fed with a diet containing 6% protein, which produced 778.7 nmol/L and 709.5 nmol/L for R-(+) and S-(-)-ABZ-SO enantiomers, respectively. These results were statistically inspected by Student´s t test and the results showed a significant difference between the two means (p0.05). Furthermore, animal nutritional condition could affect the pattern of ABZ sulphoxidation indicating that the protein nutrition affect primarily the formation of R-(+)-ABZSO and S-(-)-ABZ-SO enantiomers.

  9. Production of biopharmaceutical proteins by yeast: Advances through metabolic engineering

    DEFF Research Database (Denmark)

    Nielsen, Jens

    2013-01-01

    Production of recombinant proteins for use as pharmaceuticals, so-called biopharmaceuticals, is a multi-billion dollar industry. Many different cell factories are used for the production of biopharmaceuticals, but the yeast Saccharomyces cerevisiae is an important cell factory as it is used for p...... production. The involvement of directed metabolic engineering through the integration of tools from genetic engineering, systems biology and mathematical modeling, is also discussed....... by yeast are human serum albumin, hepatitis vaccines and virus like particles used for vaccination against human papillomavirus. Here is given a brief overview of biopharmaceutical production by yeast and it is discussed how the secretory pathway can be engineered to ensure more efficient protein...

  10. Effect of altitude on the protein metabolism of Bolivian children

    International Nuclear Information System (INIS)

    San Miguel Simron, J.L.; Berger, J.; Spielvogel, H.; Tellez Castellon, W.; Lujan Medina, C.; Caceres, E.

    1996-01-01

    The malnutrition is prevalent and is a major problem among Bolivian children. It is caused by several interacting factors: (1) inadequate protein energy intake due to low socio-economic status; (ii) exposure to acute, repeated and chronic bacterial infections; (iii) exposure to multiple and chronic parasitic infections; (iv) high altitude of the capital, La Paz, 3600 m, with a numerous populations compared to the rest of the country. The research objectives in the first phase are: (i) determination of protein utilization with a non-invasive method using stable isotope tracer among children living at high and low altitude; (ii) determination of protein metabolism among eutrophic children without parasitic or acute bacterial infections at both altitudes; (iii) determination of protein requirement among these children. Two groups of 10 pubertal children, matched for age and sex, of same socio-economic status, eutrophic, without malnutrition, infections or intestinal parasites will be studied; the different status being arrived by anthropometric, nutritional intake, biochemical and pediatrical evaluation. For the metabolic study, stable isotopes L-[1-13C] leucine labelled casein will be used and 13 CO 2 excreted will be measured. All the basic nutritional assessment and VCO 2 measurements will be performed in Bolivia, while the samples of expired gas will be stored in Vacutainers for further analysis by isotope radio mass spectrometer (IRMS), in Clermont-Ferrand, France. The plans for future work is based on the study of the effects of the different variables and their interactions. The following will be evaluated: (i) the socio-economic status; (ii) the bacterial infections: (iii) the parasitic infections; (iv) the altitude. As published by Obert, et al., the socio-economic variable is more connected with the nutritional status than with the altitude. 12 refs, 1 fig., 1 tab

  11. Effect of altitude on the protein metabolism of Bolivian children

    Energy Technology Data Exchange (ETDEWEB)

    San Miguel Simron, J L; Berger, J; Spielvogel, H; Tellez Castellon, W; Lujan Medina, C; Caceres, E [Instituto Boliviano de Boliviano de Biologia de Altura, La Paz (Bolivia). Dept. de Nutricion; Beaufrere, B; Gachons, P; Coudert, J [Laboratoire de Nutrition Humaine, Clermont-Ferrand (France)

    1997-12-31

    The malnutrition is prevalent and is a major problem among Bolivian children. It is caused by several interacting factors: (1) inadequate protein energy intake due to low socio-economic status; (ii) exposure to acute, repeated and chronic bacterial infections; (iii) exposure to multiple and chronic parasitic infections; (iv) high altitude of the capital, La Paz, 3600 m, with a numerous populations compared to the rest of the country. The research objectives in the first phase are: (i) determination of protein utilization with a non-invasive method using stable isotope tracer among children living at high and low altitude; (ii) determination of protein metabolism among eutrophic children without parasitic or acute bacterial infections at both altitudes; (iii) determination of protein requirement among these children. Two groups of 10 pubertal children, matched for age and sex, of same socio-economic status, eutrophic, without malnutrition, infections or intestinal parasites will be studied; the different status being arrived by anthropometric, nutritional intake, biochemical and pediatrical evaluation. For the metabolic study, stable isotopes L-[1-13C] leucine labelled casein will be used and {sup 13}CO{sub 2} excreted will be measured. All the basic nutritional assessment and VCO{sub 2} measurements will be performed in Bolivia, while the samples of expired gas will be stored in Vacutainers for further analysis by isotope radio mass spectrometer (IRMS), in Clermont-Ferrand, France. The plans for future work is based on the study of the effects of the different variables and their interactions. The following will be evaluated: (i) the socio-economic status; (ii) the bacterial infections: (iii) the parasitic infections; (iv) the altitude. As published by Obert, et al., the socio-economic variable is more connected with the nutritional status than with the altitude. 12 refs, 1 fig., 1 tab.

  12. Protein metabolism in malnourished children with acute lower respiratory infection

    International Nuclear Information System (INIS)

    Manary, M.; Broadhead, R.

    1996-01-01

    We studied 19 subjects and 15 controls from November 1994 to February 1995. HIV infection is common among this population and HIV testing was done by ELISA of most subjects and controls in the course of their routine clinical care. To determine how HIV infection effects protein metabolism all HIV infected subjects and controls were grouped into a third category and compared to the subjects and controls. After the HIV subgrouping we were left with 13 subjects, 13 controls, and 8 HIV positive patients. KIC enrichments were used to calculate protein synthesis and breakdown, as KIC is believed to reflect intracellular leucine concentrations. Of note in Table 2 is the KIC/Leucine ratio is consistently greater than 1, averaging 1.3 over 16 samples. This is an unexpected finding as the KIC/Leucine ratio has been shown to be constant with a value of about 0.75 over a wide range of conditions. Samples for these eight patients have been evaluated under six different GCMS conditions to verify this unexpected observation. This ratio > 1.0 has been consistently found under all of these conditions. We are not certain what biological phenomenon can explain this, but it calls into question the validity of the four compartment model upon which these calculations are based. It is not unreasonable to expect that children with kwashiorkor metabolize ketoacids differently, and this difference could account for the increased KIC/Leucine ratio. 19 refs, 4 tabs

  13. Changes in contralateral protein metabolism following unilateral sciatic nerve section

    International Nuclear Information System (INIS)

    Menendez, J.A.; Cubas, S.C.

    1990-01-01

    Changes in nerve biochemistry, anatomy, and function following injuries to the contralateral nerve have been repeatedly reported, though their significance is unknown. The most likely mechanisms for their development are either substances carried by axoplasmic flow or electrically transmitted signals. This study analyzes which mechanism underlies the development of a contralateral change in protein metabolism. The incorporation of labelled amino acids (AA) into proteins of both sciatic nerves was assessed by liquid scintillation after an unilateral section. AA were offered locally for 30 min to the distal stump of the sectioned nerves and at homologous levels of the intact contralateral nerves. At various times, from 1 to 24 h, both sciatic nerves were removed and the proteins extracted with trichloroacetic acid (TCA). An increase in incorporation was found in both nerves 14-24 h after section. No difference existed between sectioned and intact nerves, which is consistent with the contralateral effect. Lidocaine, but not colchicine, when applied previously to the nerves midway between the sectioning site and the spinal cord, inhibited the contralateral increase in AA incorporation. It is concluded that electrical signals, crossing through the spinal cord, are responsible for the development of the contralateral effect. Both the nature of the proteins and the significance of the contralateral effect are matters for speculation

  14. Kinetic parameters of protein metabolism in rats during protein-free feeding

    International Nuclear Information System (INIS)

    Krawielitzki, K.; Schadereit, R.; Wuensche, J.

    1987-01-01

    16 male rats of 100 g live weight were given 50 mg of a mixture containing 15 N-labelled amino acids as a single dose within a protein-free feeding period. Following this the 15 N excretion in feces and urine as well as the development of the 15 N excess in different organs and tissues were estimated over 3 days by slaughtering the animals within given 7 time intervals. Using a 3 pool model and the computer program for the interpretation of 15 N tracer experiments by Toewe et al. (1984), kinetic parameters such as the rate of protein synthesis, protein breakdown and the rate of reutilization were calculated. Despite a negative N balance (- 41.8 mg N/d) under protein-free conditions the protein metabolism of the rat shows high dynamics characterized by a high flux rate (225 mg N/d) and a high rate of body protein synthesis (181 mg/d). The reutilization was 85 %. Depending on time the 15 N excess in the tested organs and tissues showed significant differences and seems to demonstrate that under these conditions protein synthesis mainly takes place in the most important organs (e.g. intestinal tract, liver). Under protein-free feeding conditions protein synthesis and protein breakdown of the whole body seems to be slightly increased in comparison to N balanced feeding conditions. (author)

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

    Science.gov (United States)

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

    2016-01-26

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

  16. Effect of beta-hydroxy-beta-methylbutyrate (HMB) on protein metabolism in whole body and in selected tissues.

    Science.gov (United States)

    Holecek, M; Muthny, T; Kovarik, M; Sispera, L

    2009-01-01

    Beta-hydroxy-beta-methylbutyrate (HMB) is a leucine metabolite with protein anabolic effect. The aim of the study was to examine the role of exogenous HMB on leucine and protein metabolism in whole body and selected tissues. Rats were administered by HMB (0.1 g/kg b.w.) or by saline. The parameters of whole-body protein metabolism were evaluated 24 h later using L-[1-14C]leucine and L-[3,4,5-3H]phenylalanine. Changes in proteasome dependent proteolysis and protein synthesis were determined according the "chymotrypsin-like" enzyme activity and labeled leucine and phenylalanine incorporation into the protein. A decrease in leucine clearance and whole-body protein turnover (i.e., a decrease in whole-body proteolysis and protein synthesis) was observed in HMB treated rats. Proteasome-dependent proteolysis decreased significantly in skeletal muscle, changes in heart, liver, jejunum, colon, kidney, and spleen were insignificant. Decrease in protein synthesis was observed in the heart, colon, kidney, and spleen, while an increase was observed in the liver. There were no significant changes in leucine oxidation. We conclude that protein anabolic effect of HMB in skeletal muscle is related to inhibition of proteolysis in proteasome. Alterations in protein synthesis in visceral tissues may affect several important functions and the metabolic status of the whole body.

  17. Protein and amino acid metabolism in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Guoyao.

    1989-01-01

    Isolated chick extensor digitorum communis (EDC) muscles and, in some experiments, rat skeletal muscles were used to study a number of aspects of protein and amino acid metabolism. (1) Chick EDC muscles synthesize and release large amounts of alanine and glutamine, which indirectly obtain their amino groups from branched-chain amino acids (BCAA). (2) Acetoacetate or DL-{beta}-hydroxybutyrate (4 mM) decrease (P < 0.01) alanine synthesis and BCAA transamination in EDC muscles from 24-h fasted chicks by decreasing (P < 0.01) intracellular concentrations of pyruvate due to inhibition of glycolysis. (3) Glutamine is extensively degraded in skeletal muscles from both chicks and rats, thus challenging the traditional view that glutamine oxidation is negligible in skeletal muscle. The cytosolic glutamine aminotransferases L and K in the rat and the mitochondrial phosphate-activated glutaminase in the chick play important roles in the conversion of glutamine to {alpha}-ketoglutarate for further oxidation. (4) Although methionine has been reported to be extensively transaminated in rat skeletal muscle preparations in the absence of other amino acids, transamination of methionine is absent or negligible in chick and rat skeletal muscles in the presence of physiological concentrations of amino acids. (5) Glutamine at 1.0-15 mM increases (P < 0.01) protein synthesis ({sup 3}H-phenylalanine incorporation), and at 10.0-15.0 mM decreases (P < 0.05) protein degradation ({sup 3}H-phenylalanine release from prelabelled protein in vivo) in EDC muscles from fed chicks as compared to muscles incubated in the absence of glutamine. (6) Acetoacetate or DL-{beta}-hydroxybutyrate (4 mM) has a small but significant inhibitory effect (P < 0.05) on the rate of protein synthesis, but has no effect (P > 0.05) on the rate of protein degradation in EDC muscles from fed chicks.

  18. The Roles of Vitamin A in the Regulation of Carbohydrate, Lipid, and Protein Metabolism

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2014-05-01

    Full Text Available Currently, two-thirds of American adults are overweight or obese. This high prevalence of overweight/obesity negatively affects the health of the population, as obese individuals tend to develop several chronic diseases, such as type 2 diabetes and cardiovascular diseases. Due to obesity’s impact on health, medical costs, and longevity, the rise in the number of obese people has become a public health concern. Both genetic and environmental/dietary factors play a role in the development of metabolic diseases. Intuitively, it seems to be obvious to link over-nutrition to the development of obesity and other metabolic diseases. However, the underlying mechanisms are still unclear. Dietary nutrients not only provide energy derived from macronutrients, but also factors such as micronutrients with regulatory roles. How micronutrients, such as vitamin A (VA; retinol, regulate macronutrient homeostasis is still an ongoing research topic. As an essential micronutrient, VA plays a key role in the general health of an individual. This review summarizes recent research progress regarding VA’s role in carbohydrate, lipid, and protein metabolism. Due to the large amount of information regarding VA functions, this review focusses on metabolism in metabolic active organs and tissues. Additionally, some perspectives for future studies will be provided.

  19. Matrix rigidity regulates cancer cell growth by modulating cellular metabolism and protein synthesis.

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    Robert W Tilghman

    Full Text Available Tumor cells in vivo encounter diverse types of microenvironments both at the site of the primary tumor and at sites of distant metastases. Understanding how the various mechanical properties of these microenvironments affect the biology of tumor cells during disease progression is critical in identifying molecular targets for cancer therapy.This study uses flexible polyacrylamide gels as substrates for cell growth in conjunction with a novel proteomic approach to identify the properties of rigidity-dependent cancer cell lines that contribute to their differential growth on soft and rigid substrates. Compared to cells growing on more rigid/stiff substrates (>10,000 Pa, cells on soft substrates (150-300 Pa exhibited a longer cell cycle, due predominantly to an extension of the G1 phase of the cell cycle, and were metabolically less active, showing decreased levels of intracellular ATP and a marked reduction in protein synthesis. Using stable isotope labeling of amino acids in culture (SILAC and mass spectrometry, we measured the rates of protein synthesis of over 1200 cellular proteins under growth conditions on soft and rigid/stiff substrates. We identified cellular proteins whose syntheses were either preferentially inhibited or preserved on soft matrices. The former category included proteins that regulate cytoskeletal structures (e.g., tubulins and glycolysis (e.g., phosphofructokinase-1, whereas the latter category included proteins that regulate key metabolic pathways required for survival, e.g., nicotinamide phosphoribosyltransferase, a regulator of the NAD salvage pathway.The cellular properties of rigidity-dependent cancer cells growing on soft matrices are reminiscent of the properties of dormant cancer cells, e.g., slow growth rate and reduced metabolism. We suggest that the use of relatively soft gels as cell culture substrates would allow molecular pathways to be studied under conditions that reflect the different mechanical

  20. Dietary protein and carbohydrate affect feeding behavior and metabolic regulation in hummingbirds (Melanotrochilus fuscus Las proteínas y carbohidratos dietarios afectan la conducta de alimentación y la regulación metabólica en picaflores (Melanotrochilus fuscus

    Directory of Open Access Journals (Sweden)

    FLAVIA P. ZANOTTO

    2005-06-01

    Full Text Available The objective of this work was to link hummingbird feeding behavior with metabolic regulation and in addition to assess whether dietary composition would affect entrance into torpor. Hummingbirds were fed a combination of diets with contrasting amounts of protein and carbohydrate. The diets were composed of the following: 2.4 % protein (P - 12 % sucrose (S and 0.8 % protein (P - 36 % sucrose (S. The main findings showed that periods of feeding on each of the diets could be distinguished as separate bouts or feeding events. Hummingbirds presented to high protein-low carbohydrate diets (2.4P-12S ingested a larger volume of diet, fed for longer (both around 1.7x and increased the interval between feedings compared with hummingbirds fed diets 0.8P-36S. Physiological regulation between feeding events, on the other hand, was achieved through an increase in metabolic rate for low protein-high sugar diets (0.8P-36S. This response could probably be related to high sucrose assimilation rates through the digestive system of hummingbirds, a process already known to be very efficient in these birds. Additionally, there was a steeper decrease in oxygen consumption for hummingbirds fed diets 2.4P-12S during fasting and a suggestion of a higher torpor incidence in birds fed these dietsEl objetivo de este trabajo fue unir la conducta de alimentación de picaflores con su regulación metabólica y además determinar como la composición dietaria podría afectar la entrada en sopor. Los picaflores fueron alimentados con una combinación de dietas con cantidades contrastantes de proteínas y carbohidratos. La composición dietaria fue: 2,4 % proteína (P - 12 % sacarosa (S y 0.8 % proteína (P - 36 % (sacarosa (S. Se observó que para cada dieta, los períodos de alimentación se pueden distinguir como eventos separados de alimentación. Cuando se enfrentan a dietas de alta proteína-bajo carbohidratos (2,4P-12S, los picaflores ingieren grandes volúmenes de

  1. Do diabetes and obesity affect the metabolic response to exercise?

    DEFF Research Database (Denmark)

    Plomgaard, Peter; Weigert, Cora

    2017-01-01

    control before an intervention can be a risk factor of reduced therapeutic benefit from exercise. But the acute metabolic response to exercise and the transcriptional profile of the working muscle is similar in healthy controls and type 2 diabetic patients, including but not limited to intact activation...... of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent......PURPOSE OF REVIEW: Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. RECENT FINDINGS: Poor glycemic...

  2. Combined metabonomic and quantitative real-time PCR analyses reveal systems metabolic changes in Jurkat T-cells treated with HIV-1 Tat protein.

    Science.gov (United States)

    Liao, Wenting; Tan, Guangguo; Zhu, Zhenyu; Chen, Qiuli; Lou, Ziyang; Dong, Xin; Zhang, Wei; Pan, Wei; Chai, Yifeng

    2012-11-02

    HIV-1 Tat protein is released by infected cells and can affect bystander uninfected T cells and induce numerous biological responses which contribute to its pathogenesis. To elucidate the complex pathogenic mechanism, we conducted a comprehensive investigation on Tat protein-related extracellular and intracellular metabolic changes in Jurkat T-cells using combined gas chromatography-mass spectrometry (GC-MS), reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) and a hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS)-based metabonomics approach. Quantitative real-time PCR (qRT-PCR) analyses were further employed to measure expressions of several relevant enzymes together with perturbed metabolic pathways. Combined metabonomic and qRT-PCR analyses revealed that HIV-1 Tat caused significant and comprehensive metabolic changes, as represented by significant changes of 37 metabolites and 10 relevant enzymes in HIV-1 Tat-treated cells. Using MetaboAnalyst 2.0, it was found that 11 pathways (Impact-value >0.10) among the regulated pathways were acutely perturbed, including sphingolipid metabolism, glycine, serine and threonine metabolism, pyruvate metabolism, inositol phosphate metabolism, arginine and proline metabolism, citrate cycle, phenylalanine metabolism, tryptophan metabolism, pentose phosphate pathway, glycerophospholipid metabolism, glycolysis or gluconeogenesis. These results provide metabolic evidence of the complex pathogenic mechanism of HIV-1 Tat protein as a "viral toxin", and would help obligate Tat protein as "an important target" for therapeutic intervention and vaccine development.

  3. Short communication: Proteins from circulating exosomes represent metabolic state in transition dairy cows.

    Science.gov (United States)

    Crookenden, M A; Walker, C G; Peiris, H; Koh, Y; Heiser, A; Loor, J J; Moyes, K M; Murray, A; Dukkipati, V S R; Kay, J K; Meier, S; Roche, J R; Mitchell, M D

    2016-09-01

    Biomarkers that identify prepathological disease could enhance preventive management, improve animal health and productivity, and reduce costs. Circulating extracellular vesicles, particularly exosomes, are considered to be long-distance, intercellular communication systems in human medicine. Exosomes provide tissue-specific messages of functional state and can alter the cellular activity of recipient tissues through their protein and microRNA content. We hypothesized that exosomes circulating in the blood of cows during early lactation would contain proteins representative of the metabolic state of important tissues, such as liver, which play integral roles in regulating the physiology of cows postpartum. From a total of 150 cows of known metabolic phenotype, 10 cows were selected with high (n=5; high risk) and low (n=5; low risk) concentrations of nonesterified fatty acids, β-hydroxybutyrate, and liver triacylglycerol during wk 1 and 2 after calving. Exosomes were extracted from blood on the day of calving (d 0) and postcalving at wk 1 and wk 4, and their protein composition was determined by mass spectroscopy. Extracellular vesicle protein concentration and the number of exosome vesicles were not affected by risk category; however, the exosome protein cargo differed between the groups, with proteins at each time point identified as being unique to the high- and low-risk groups. The proteins α-2 macroglobulin, fibrinogen, and oncoprotein-induced transcript 3 were unique to the high-risk cows on d 0 and have been associated with metabolic syndrome and liver function in humans. Their presence may indicate a more severe inflammatory state and a greater degree of liver dysfunction in the high-risk cows than in the low-risk cows, consistent with the high-risk cows' greater plasma β-hydroxybutyrate and liver triacylglycerol concentrations. The commonly shared proteins and those unique to the low-risk category indicate a role for exosomes in immune function. The data

  4. Alternative splicing affects the targeting sequence of peroxisome proteins in Arabidopsis.

    Science.gov (United States)

    An, Chuanjing; Gao, Yuefang; Li, Jinyu; Liu, Xiaomin; Gao, Fuli; Gao, Hongbo

    2017-07-01

    A systematic analysis of the Arabidopsis genome in combination with localization experiments indicates that alternative splicing affects the peroxisomal targeting sequence of at least 71 genes in Arabidopsis. Peroxisomes are ubiquitous eukaryotic cellular organelles that play a key role in diverse metabolic functions. All peroxisome proteins are encoded by nuclear genes and target to peroxisomes mainly through two types of targeting signals: peroxisomal targeting signal type 1 (PTS1) and PTS2. Alternative splicing (AS) is a process occurring in all eukaryotes by which a single pre-mRNA can generate multiple mRNA variants, often encoding proteins with functional differences. However, the effects of AS on the PTS1 or PTS2 and the targeting of the protein were rarely studied, especially in plants. Here, we systematically analyzed the genome of Arabidopsis, and found that the C-terminal targeting sequence PTS1 of 66 genes and the N-terminal targeting sequence PTS2 of 5 genes are affected by AS. Experimental determination of the targeting of selected protein isoforms further demonstrated that AS at both the 5' and 3' region of a gene can affect the inclusion of PTS2 and PTS1, respectively. This work underscores the importance of AS on the global regulation of peroxisome protein targeting.

  5. Kinetic variation of protein metabolism in pregnant rats

    International Nuclear Information System (INIS)

    Kubo, Katsuharu

    1980-01-01

    Kinetic variation of nitrogen metabolism in the skeletal muscle and liver of rats during the course of pregnancy was studied by the use of 15 N-amino nitrogen during acclimatization on a protein-free diet. 15 N from 15 N-glycine given on day 1 of pregnancy decreased from the 1st to 2nd trimester in the liver, suggesting contribution to the N metabolic pool. In the muscle, the rate of 15 N showed a marked decrease in the 2nd trimester, indicating, along with an increased accumulation of the total muscular N content, N accumulation in muscle protein in the 2nd trimester and promoted decomposition of mobiler muscular protein in the 2nd trimester. The marked decrease in the muscle 15 N content from the 2nd trimester and the decrease in the total N content in the 3rd trimester support the serious involvement of muscular N in fetal growth. The level of 15 N from 15 N-ammonium during the course of pregnancy was significantly high in the 2nd trimester and low in the 3rd. The 2nd trimester showed amino N accumulation in the muscle, and the 3rd, a decrease in N accumulation and amino N release. In regard to the kinetics of 15 N-lysine in the cell fraction, the muscular microsomes showed a high 15 N accumulation in the 2nd trimester and a voluminous release in the 3rd trimester. In contrast, the liver microsomes showed a linear decrease of 15 N up to 2nd trimester, followed by no change. (Chiba, N.)

  6. Acute Phase Proteins and Variables of Protein Metabolism in Dairy Cows during the Pre- and Postpartal Period

    Directory of Open Access Journals (Sweden)

    Cs. Tóthová

    2008-01-01

    Full Text Available The objective of the present study was to compare the concentrations of acute phase proteins and selected variables of protein metabolism in dairy cows of the Slovak Spotted breed from 4 weeks before parturition to 10 weeks after parturition. Acute phase proteins - haptoglobin (Hp and serum amyloid A (SAA - and variables of protein metabolism - total proteins, albumin, urea, creatinine, total immunoglobulins - were evaluated in blood serum. Significant differences were found in average values of the Hp and SAA concentrations in several groups during the monitored period (P P P P P P P P P < 0.001. The above mentioned results indicate that in the time around parturition there are significant changes in concentrations of acute phase proteins, as well as in the whole protein metabolism of dairy cows. These facts suggest that the postparturient period is a critical biological phase, throughout which there is the highest incidence of metabolic disorders.

  7. Comparative proteome analysis of metabolic proteins from seeds of durum wheat (cv. Svevo) subjected to heat stress

    DEFF Research Database (Denmark)

    Laino, Paolo; Shelton, Dale; Finnie, Christine

    2010-01-01

    of nonprolamin proteins were monitored to identify polypeptides affected by heat stress during grain fill. This study shows that heat stress alters significantly the durum wheat seed proteome, although the changes range is only between 1.2- and 2.2-fold. This analysis revealed 132 differentially expressed...... include proteins with metabolic activity or structural function. In order to investigate the consequences of heat stress on the accumulation of nonprolamin proteins in mature durum wheat kernels, the Italian cultivar Svevo was subjected to two thermal regimes (heat stress versus control). The 2-D patterns...... polypeptides, 47 of which were identified by MALDI-TOF and MALDI-TOF-TOF MS and included HSPs, proteins involved in the glycolysis and carbohydrate metabolism, as well as stress-related proteins. Many of the heat-induced polypeptides are considered to be allergenic for sensitive individuals....

  8. Protein kinase N2 regulates AMP kinase signaling and insulin responsiveness of glucose metabolism in skeletal muscle.

    Science.gov (United States)

    Ruby, Maxwell A; Riedl, Isabelle; Massart, Julie; Åhlin, Marcus; Zierath, Juleen R

    2017-10-01

    Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. Because skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. Although Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anterior muscle in vivo. PKN2 knockdown in vitro decreased insulin-stimulated glucose uptake, incorporation into glycogen, and oxidation. PKN2 siRNA increased 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling while stimulating fatty acid oxidation and incorporation into triglycerides and decreasing protein synthesis. At the transcriptional level, PKN2 knockdown increased expression of PGC-1α and SREBP-1c and their target genes. In mature skeletal muscle, in vivo PKN2 knockdown decreased glucose uptake and increased AMPK phosphorylation. Thus, PKN2 alters key signaling pathways and transcriptional networks to regulate glucose and lipid metabolism. Identification of PKN2 as a novel regulator of insulin and AMPK signaling may provide an avenue for manipulation of skeletal muscle metabolism. Copyright © 2017 the American Physiological Society.

  9. A role for 12/15 lipoxygenase in the amyloid beta precursor protein metabolism.

    Science.gov (United States)

    Succol, Francesca; Praticò, Domenico

    2007-10-01

    12/15 Lipoxygenase (12/15LO) protein levels and activity are increased in pathologically affected regions of Alzheimer's disease (AD) brains, compared with controls. Its metabolic products are elevated in cerebrospinal fluid of patients with AD and individuals with mild cognitive impairment, suggesting that this enzyme may be involved early in AD pathogenesis. Herein, we investigate the effect of pharmacologic inhibition of 12/15LO on the amyloid beta precursor protein (APP) metabolism. To this end, we used CHO and N2A cells stably expressing human APP with the Swedish mutant, and two structurally distinct and selective 12/15LO inhibitors, PD146176 and CDC. Our results demonstrated that both drugs dose-dependently reduced Abeta formation without affecting total APP levels. Interestingly, in the same cells we observed a significant reduction in secreted (s)APPbeta and beta-secretase (BACE), but not sAPPalpha and ADAM10 protein levels. Together, these data show for the first time that this enzymatic pathway influences Abeta formation whereby modulating the BACE proteolytic cascade. We conclude that specific pharmacologic inhibition of 12/15LO could represent a novel therapeutic target for treating or preventing AD pathology in humans.

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

    Science.gov (United States)

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

    2006-09-01

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

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

    Science.gov (United States)

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-01-01

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

  12. A Systematic Review of the Effects of Plant Compared with Animal Protein Sources on Features of Metabolic Syndrome.

    Science.gov (United States)

    Chalvon-Demersay, Tristan; Azzout-Marniche, Dalila; Arfsten, Judith; Egli, Léonie; Gaudichon, Claire; Karagounis, Leonidas G; Tomé, Daniel

    2017-03-01

    Dietary protein may play an important role in the prevention of metabolic dysfunctions. However, the way in which the protein source affects these dysfunctions has not been clearly established. The aim of the current systematic review was to compare the impact of plant- and animal-sourced dietary proteins on several features of metabolic syndrome in humans. The PubMed database was searched for both chronic and acute interventional studies, as well as observational studies, in healthy humans or those with metabolic dysfunctions, in which the impact of animal and plant protein intake was compared while using the following variables: cholesterolemia and triglyceridemia, blood pressure, glucose homeostasis, and body composition. Based on data extraction, we observed that soy protein consumption (with isoflavones), but not soy protein alone (without isoflavones) or other plant proteins (pea and lupine proteins, wheat gluten), leads to a 3% greater decrease in both total and LDL cholesterol compared with animal-sourced protein ingestion, especially in individuals with high fasting cholesterol concentrations. This observation was made when animal proteins were provided as a whole diet rather than given supplementally. Some observational studies reported an inverse association between plant protein intake and systolic and diastolic blood pressure, but this was not confirmed by intervention studies. Moreover, plant protein (wheat gluten, soy protein) intake as part of a mixed meal resulted in a lower postprandial insulin response than did whey. This systematic review provides some evidence that the intake of soy protein associated with isoflavones may prevent the onset of risk factors associated with cardiovascular disease, i.e., hypercholesterolemia and hypertension, in humans. However, we were not able to draw any further conclusions from the present work on the positive effects of plant proteins relating to glucose homeostasis and body composition. © 2017 American

  13. Dietary live yeast alters metabolic profiles, protein biosynthesis and thermal stress tolerance of Drosophila melanogaster.

    Science.gov (United States)

    Colinet, Hervé; Renault, David

    2014-04-01

    The impact of nutritional factors on insect's life-history traits such as reproduction and lifespan has been excessively examined; however, nutritional determinant of insect's thermal tolerance has not received a lot of attention. Dietary live yeast represents a prominent source of proteins and amino acids for laboratory-reared drosophilids. In this study, Drosophila melanogaster adults were fed on diets supplemented or not with live yeast. We hypothesized that manipulating nutritional conditions through live yeast supplementation would translate into altered physiology and stress tolerance. We verified how live yeast supplementation affected body mass characteristics, total lipids and proteins, metabolic profiles and cold tolerance (acute and chronic stress). Females fed with live yeast had increased body mass and contained more lipids and proteins. Using GC/MS profiling, we found distinct metabolic fingerprints according to nutritional conditions. Metabolite pathway enrichment analysis corroborated that live yeast supplementation was associated with amino acid and protein biosyntheses. The cold assays revealed that the presence of dietary live yeast greatly promoted cold tolerance. Hence, this study conclusively demonstrates a significant interaction between nutritional conditions and thermal tolerance. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Childhood obesity affects adult metabolic syndrome and diabetes.

    Science.gov (United States)

    Liang, Yajun; Hou, Dongqing; Zhao, Xiaoyuan; Wang, Liang; Hu, Yuehua; Liu, Junting; Cheng, Hong; Yang, Ping; Shan, Xinying; Yan, Yinkun; Cruickshank, J Kennedy; Mi, Jie

    2015-09-01

    We seek to observe the association between childhood obesity by different measures and adult obesity, metabolic syndrome (MetS), and diabetes. Thousand two hundred and nine subjects from "Beijing Blood Pressure Cohort Study" were followed 22.9 ± 0.5 years in average from childhood to adulthood. We defined childhood obesity using body mass index (BMI) or left subscapular skinfold (LSSF), and adult obesity as BMI ≥ 28 kg/m(2). MetS was defined according to the joint statement of International Diabetes Federation and American Heart Association with modified waist circumference (≥ 90/85 cm for men/women). Diabetes was defined as fasting plasma glucose ≥ 7.0 mmol/L or blood glucose 2 h after oral glucose tolerance test ≥ 11.1 mmol/L or currently using blood glucose-lowering agents. Multiple linear and logistic regression models were used to assess the association. The incidence of adult obesity was 13.4, 60.0, 48.3, and 65.1 % for children without obesity, having obesity by BMI only, by LSSF only, and by both, respectively. Compared to children without obesity, children obese by LSSF only or by both had higher risk of diabetes. After controlling for adult obesity, childhood obesity predicted independently long-term risks of diabetes (odds ratio 2.8, 95 % confidence interval 1.2-6.3) or abdominal obesity (2.7, 1.6-4.7) other than MetS as a whole (1.2, 0.6-2.4). Childhood obesity predicts long-term risk of adult diabetes, and the effect is independent of adult obesity. LSSF is better than BMI in predicting adult diabetes.

  15. Central regulation of metabolism by protein tyrosine phosphatases

    Directory of Open Access Journals (Sweden)

    Ryan eTsou

    2013-01-01

    Full Text Available Protein tyrosine phosphatases (PTPs are important regulators of intracellular signaling pathways via the dephosphorylation of phosphotyrosyl residues on various receptor and non-receptor substrates. The phosphorylation state of central nervous system (CNS signaling components underlies the molecular mechanisms of a variety of physiological functions including the control of energy balance and glucose homeostasis. In this review, we summarize the current evidence implicating PTPs as central regulators of metabolism, specifically highlighting their interactions with the neuronal leptin and insulin signaling pathways. We discuss the role of a number of PTPs (PTP1B, SHP2, TCPTP, RPTPe, and PTEN, reviewing the findings from genetic mouse models and in vitro studies which highlight these phosphatases as key central regulators of energy homeostasis.

  16. Metabolic factors affecting enhanced phosphorus uptake by activated sludge.

    Science.gov (United States)

    Boughton, W H; Gottfried, R J; Sinclair, N A; Yall, I

    1971-10-01

    Activated sludges obtained from the Rilling Road plant located at San Antonio, Tex., and from the Hyperion treatment plant located at Los Angeles, Calif., have the ability to remove all of the orthophosphate normally present in Tucson sewage within 3 hr after being added to the waste water. Phosphorus removal was independent of externally supplied sources of energy and ions, since orthophosphate and (32)P radioactivity were readily removed from tap water, glass-distilled water, and deionized water. Phosphorus uptake by Rilling sludge in the laboratory appears to be wholly biological, as it has an optimum pH range (7.7 to 9.7) and an optimum temperature range (24 to 37 C). It was inhibited by HgCl(2), iodoacetic acid, p-chloromercuribenzoic acid, NaN(3), and 2, 4-dinitrophenol (compounds that affect bacterial membrane permeability, sulfhydryl enzymes, and adenosine triphosphate synthesis). Uptake was inhibited by 1% NaCl but was not affected by 10(-3)m ethylenediaminetetraacetic acid disodium salt (a chelating agent for many metallic ions).

  17. Uncoupling proteins, dietary fat and the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Warden Craig H

    2006-09-01

    Full Text Available Abstract There has been intense interest in defining the functions of UCP2 and UCP3 during the nine years since the cloning of these UCP1 homologues. Current data suggest that both UCP2 and UCP3 proteins share some features with UCP1, such as the ability to reduce mitochondrial membrane potential, but they also have distinctly different physiological roles. Human genetic studies consistently demonstrate the effect of UCP2 alleles on type-2 diabetes. Less clear is whether UCP2 alleles influence body weight or body mass index (BMI with many studies showing a positive effect while others do not. There is strong evidence that both UCP2 and UCP3 protect against mitochondrial oxidative damage by reducing the production of reactive oxygen species. The evidence that UCP2 protein is a negative regulator of insulin secretion by pancreatic β-cells is also strong: increased UCP2 decreases glucose stimulated insulin secretion ultimately leading to β-cell dysfunction. UCP2 is also neuroprotective, reducing oxidative stress in neurons. UCP3 may also transport fatty acids out of mitochondria thereby protecting the mitochondria from fatty acid anions or peroxides. Current data suggest that UCP2 plays a role in the metabolic syndrome through down-regulation of insulin secretion and development of type-2 diabetes. However, UCP2 may protect against atherosclerosis through reduction of oxidative stress and both UCP2 and UCP3 may protect against obesity. Thus, these UCP1 homologues may both contribute to and protect from the markers of the metabolic syndrome.

  18. Metabolic syndrome and C-reactive protein in bank employees

    Directory of Open Access Journals (Sweden)

    Cattafesta M

    2016-05-01

    Full Text Available Monica Cattafesta,1 Nazaré Souza Bissoli,2 Luciane Bresciani Salaroli,1,31Postgraduate Program in Nutrition and Health, 2Postgraduate Program in Physiological Sciences, 3Postgraduate Program in Public Health, Department of Health Integrated Education, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil Background: The ultrasensitive C-reactive protein (us-CRP is used for the diagnosis of cardiovascular disease, but it is not well described as a marker for the diagnosis of metabolic syndrome (MS. Methods: An observational and transversal study of bank employees evaluated anthropometric, hemodynamic, and biochemical data. CRP values were determined using commercial kits from Roche Diagnostics Ltd, and MS criteria were analyzed according to National Cholesterol Education Program’s – Adult Treatment Panel III (NCEP/ATP III. Results: A total of 88 individuals had MS, and 77.3% (n=68 of these showed alterations of us-CRP (P=0.0001, confidence interval [CI] 0.11–0.34. Individuals with MS had higher mean values of us-CRP in global measures (P=0.0001 and stratified by sex (P=0.004 than individuals without the syndrome. This marker exhibited significant differences with varying criteria for MS, such as waist circumference (P=0.0001, triglycerides (P=0.002, and diastolic blood pressure (P=0.007, and the highest levels of us-CRP were found in individuals with more MS criteria. Conclusion: us-CRP was strongly associated with the presence of MS and MS criteria in this group of workers. us-CRP is a useful and effective marker for identifying the development of MS and may be used as a reference in routine care. Keywords: C-reactive protein, bank employees, metabolic syndrome, inflammation mediators, occupational health

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

    International Nuclear Information System (INIS)

    Kodavanti, Prasada Rao S.; Osorio, Cristina; Royland, Joyce E.; Ramabhadran, Ram; Alzate, Oscar

    2011-01-01

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

  20. Does family history of metabolic syndrome affect the metabolic profile phenotype in young healthy individuals?

    Science.gov (United States)

    Lipińska, Anna; Koczaj-Bremer, Magdalena; Jankowski, Krzysztof; Kaźmierczak, Agnieszka; Ciurzyński, Michał; Ou-Pokrzewińska, Aisha; Mikocka, Ewelina; Lewandowski, Zbigniew; Demkow, Urszula; Pruszczyk, Piotr

    2014-01-01

    Early identification of high-risk individuals is key for the prevention of cardiovascular disease (CVD). The aim of this study was to assess the potential impact of a family history of metabolic syndrome (fhMetS) on the risk of metabolic disorders (abnormal body mass, lipid profile, glucose metabolism, insulin resistance, and blood pressure) in healthy young individuals. We studied CVD risk factors in 90 healthy volunteers, aged 27-39 years; of these, 78 had fhMetS and 12 were without fhMetS (control group). Fasting serum lipids, glucose, and insulin levels were assayed, and anthropometric parameters and blood pressure using, an ambulatory blood pressure monitoring system, were measured. Nutritional and physical activity habits were assessed. Despite similar nutritional and physical activity habits, abnormal body mass was found in 53.2% of the fhMetS participants and 46.1% of the control participants (p = 0.54). The occurrence of obesity was 19.4% and 0%, respectively (p = 0.69). Compared to the control participants, fhMetS was associated with significantly higher total cholesterol (5.46 mmol/L vs. 4.69 mmol/L, p family history of MetS.

  1. Study of protein and metabolic profile of sugarcane workers

    Energy Technology Data Exchange (ETDEWEB)

    Polachini, G.M.; Tajara, E.H. [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil); Santos, U.P. [Universidade de Sao Paulo (USP), SP (Brazil); Zeri, A.C.M.; Paes Leme, A.F. [Laboratorio Nacional de Luz Sincrotron (LNLS), Campinas, SP (Brazil)

    2012-07-01

    Full text: The National Alcohol Program (Proalcool) is a successful Brazilian renewable fuel initiative aiming to reduce the country's oil dependence. Producing ethanol from sugar cane, the program has shown positive results although accompanied by potential damage. The environmental impact mainly derives from the particulate matter emissions due to sugarcane burning, which is potentially harmful to human health. The physical activity of sugarcane workers is repetitive and exhaustive and is carried out in presence of dust, smoke and soot. The efforts by the sugarcane workers during the labor process result in increased risks of nervous, respiratory and cardiovascular system diseases and also in premature death. The aim of the present study was to investigate the effect of occupational stress on protein and metabolic profile of sugarcane workers. Forty serum samples were analyzed by 1-DE and LC MS/MS proteomic shotgun strategy and nuclear magnetic resonance (NMR). A set of proteins was found to be altered in workers after crops when compared with controls. The analysis of NMR spectra by Chenomx also showed differences in the expression of metabolites. For example, lactate displayed higher levels in control subjects than in sugarcane workers, and vice versa for the acetate. The concentrations of the two metabolites were lower after the crop, except in the case of acetate, which remained uniform in the control subjects before and after the crop. The present findings can have important application for rational designs of preventive measures and early disease detection in sugarcane workers. (author)

  2. Study of protein and metabolic profile of sugarcane workers

    International Nuclear Information System (INIS)

    Polachini, G.M.; Tajara, E.H.; Santos, U.P.; Zeri, A.C.M.; Paes Leme, A.F.

    2012-01-01

    Full text: The National Alcohol Program (Proalcool) is a successful Brazilian renewable fuel initiative aiming to reduce the country's oil dependence. Producing ethanol from sugar cane, the program has shown positive results although accompanied by potential damage. The environmental impact mainly derives from the particulate matter emissions due to sugarcane burning, which is potentially harmful to human health. The physical activity of sugarcane workers is repetitive and exhaustive and is carried out in presence of dust, smoke and soot. The efforts by the sugarcane workers during the labor process result in increased risks of nervous, respiratory and cardiovascular system diseases and also in premature death. The aim of the present study was to investigate the effect of occupational stress on protein and metabolic profile of sugarcane workers. Forty serum samples were analyzed by 1-DE and LC MS/MS proteomic shotgun strategy and nuclear magnetic resonance (NMR). A set of proteins was found to be altered in workers after crops when compared with controls. The analysis of NMR spectra by Chenomx also showed differences in the expression of metabolites. For example, lactate displayed higher levels in control subjects than in sugarcane workers, and vice versa for the acetate. The concentrations of the two metabolites were lower after the crop, except in the case of acetate, which remained uniform in the control subjects before and after the crop. The present findings can have important application for rational designs of preventive measures and early disease detection in sugarcane workers. (author)

  3. High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age.

    Science.gov (United States)

    Bedarida, Tatiana; Baron, Stephanie; Vessieres, Emilie; Vibert, Francoise; Ayer, Audrey; Marchiol-Fournigault, Carmen; Henrion, Daniel; Paul, Jean-Louis; Noble, Florence; Golmard, Jean-Louis; Beaudeux, Jean-Louis; Cottart, Charles-Henry; Nivet-Antoine, Valerie

    2014-09-01

    High-protein-low-carbohydrate (HP-LC) diets have become widespread. Yet their deleterious consequences, especially on glucose metabolism and arteries, have already been underlined. Our previous study (2) has already shown glucose intolerance with major arterial dysfunction in very old mice subjected to an HP-LC diet. The hypothesis of this work was that this diet had an age-dependent deleterious metabolic and cardiovascular outcome. Two groups of mice, young and adult (3 and 6 mo old), were subjected for 12 wk to a standard or to an HP-LC diet. Glucose and lipid metabolism was studied. The cardiovascular system was explored from the functional stage with Doppler-echography to the molecular stage (arterial reactivity, mRNA, immunohistochemistry). Young mice did not exhibit any significant metabolic modification, whereas adult mice presented marked glucose intolerance associated with an increase in resistin and triglyceride levels. These metabolic disturbances were responsible for cardiovascular damages only in adult mice, with decreased aortic distensibility and left ventricle dysfunction. These seemed to be the consequence of arterial dysfunctions. Mesenteric arteries were the worst affected with a major oxidative stress, whereas aorta function seemed to be maintained with an appreciable role of cyclooxygenase-2 to preserve endothelial function. This study highlights for the first time the age-dependent deleterious effects of an HP-LC diet on metabolism, with glucose intolerance and lipid disorders and vascular (especially microvessels) and cardiac functions. This work shows that HP-LC lead to equivalent cardiovascular alterations, as observed in very old age, and underlines the danger of such diet. Copyright © 2014 the American Physiological Society.

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

    Science.gov (United States)

    Connysson, M; Muhonen, S; Jansson, A

    2017-11-01

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

  5. The adverse effect of 4-tert-octylphenol on fat metabolism in pregnant rats via regulation of lipogenic proteins.

    Science.gov (United States)

    Kim, Jun; Kang, Eun-Jin; Park, Mee-Na; Kim, Ji-Eun; Kim, Seung-Chul; Jeung, Eui-Bae; Lee, Geun-Shik; Hwang, Dae-Youn; An, Beum-Soo

    2015-07-01

    Alkylphenols such as 4-tert-octylphenol (OP), nonylphenol, and bisphenol A are classified as endocrine-disrupting chemicals (EDCs). Digestion and metabolism of food are controlled by many endocrine factors, including insulin, glucagon, and estrogen. These factors are differentially regulated during pregnancy. The alteration of nutritional intake and fat metabolism may affect the maintenance of pregnancy and supplementation of nutrients to the fetus, and therefore can cause severe metabolic diseases such as ketosis, marasmus and diabetes mellitus in pregnant individuals. In this study, we examined the effects of OP on fat metabolism in pregnant rats. Ethinyl estradiol (EE) was also administered as an estrogenic positive control. In our results, rats treated with OP showed significantly reduced body weights compared to the control group. In addition, histological analysis showed that the amount of fat deposited in adipocytes was reduced by OP treatment. To study the mechanism of action of OP in fat metabolism, we examined the expression levels of fat metabolism-associated genes in rat adipose tissue and liver by real-time PCR. OP and EE negatively regulated the expression of lipogenic enzymes, including FAS (fatty acid synthase), ACC-1 (acetyl-CoA carboxylase-1), and SCD-1 (stearoyl-CoA desaturase-1). The levels of lipogenic enzyme-associated transcription factors such as C/EBP-α (CAAT enhancer binding protein alpha) and SREBP-1c (sterol regulatory element binding protein-1c) were also reduced in both liver and adipose tissue. In summary, these findings suggest that OP has adverse effects on fat metabolism in pregnant rats and inhibits fat deposition via regulating lipogenic genes in the liver and adipose tissue. The altered fat metabolism by OP may affect the nutrition balance during pregnancy and can cause metabolism-related diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Protein and energy metabolism in two lines of chickens selected for growth on high or low protein diets

    DEFF Research Database (Denmark)

    Chwalibog, André; Eggum, B O; Sørensen, Peter

    1983-01-01

    Genetic adaptation was investigated in broilers selected for seven generations on a normal (A) or a low (B) protein diet. Protein and energy metabolism were studied in males from these selected lines fed on a diet of intermediate protein content. All selected birds retained more nitrogen than those...

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

    Science.gov (United States)

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

    2017-01-01

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

  8. The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial

    NARCIS (Netherlands)

    Rijpma, A.; Graaf, M. van der; Lansbergen, M.M.; Meulenbroek, O.V.; Cetinyurek-Yavuz, A.; Sijben, J.W.; Heerschap, A.; Olde Rikkert, M.G.M.

    2017-01-01

    BACKGROUND: Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients

  9. Influence of some simulated factors of cosmic flight on mineral and protein metabolism in the maxillodental system of rats

    International Nuclear Information System (INIS)

    Khristova, M.N.

    1985-01-01

    Mineral and protein metabolic changes in hard tissues of the maxillodental system, as opposed to skeletal bone, were studied in model experiments simulating space flight, with extreme factors given solely or combined: hypergravitation, ionizing radiation, magnetically activated water. Alterations occurring in protein synthesis proved to be the key events, whereas those in individual mineral components were either insignificant or of secondary nature. Long-term ingestion of magnetically activated water reduced radiation susceptibility of metabolic processes in mineralized tissues, but affected unfavorably the complex of signs resulting from combined exposure to extreme factors. Administration of a radioprotective drug, Adeturone, in treatments involving acceleration plus radiation led to normalization or partial balancing of metabolic processes in the mineral and organic components of maxillodental hard tissues and skeletal bone. The evidence obtained adds thus an anti-osteolathyrogenic feature to the radioprotective characteristics of Adeturone

  10. Protein metabolism in slow- and fast-twitch skeletal muscle during turpentine-induced inflammation.

    Science.gov (United States)

    Muthny, Tomas; Kovarik, Miroslav; Sispera, Ludek; Tilser, Ivan; Holecek, Milan

    2008-02-01

    The aim of our study was to evaluate the differences in protein and amino acid metabolism after subcutaneous turpentine administration in the soleus muscle (SOL), predominantly composed of red fibres, and the extensor digitorum longus muscle (EDL) composed of white fibres. Young rats (40-60 g) were injected subcutaneously with 0.2 ml of turpentine oil/100 g body weight (inflammation) or with the same volume of saline solution (control). Twenty-four hours later SOL and EDL were dissected and incubated in modified Krebs-Heinseleit buffer to estimate total and myofibrillar proteolysis, chymotrypsin-like activity of proteasome (CHTLA), leucine oxidation, protein synthesis and amino acid release into the medium. The data obtained demonstrate that in intact rats, all parameters measured except protein synthesis are significantly higher in SOL than in EDL. In turpentine treated animals, CHTLA increased and protein synthesis decreased significantly more in EDL. Release of leucine was inhibited significantly more in SOL. We conclude that turpentine-induced inflammation affects more CHTLA, protein synthesis and leucine release in EDL compared to SOL.

  11. Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates: a systematic review.

    Science.gov (United States)

    Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

    2011-09-01

    Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as acetyl cholinesterase (AChE) inhibitors that affect lots of organs such as peripheral and central nervous systems, muscles, liver, pancreas, and brain, whereas OC are neurotoxic involved in alteration of ion channels. There are several reports about metabolic disorders, hyperglycemia, and also oxidative stress in acute and chronic exposures to pesticides that are linked with diabetes and other metabolic disorders. In this respect, there are several in vitro and in vivo but few clinical studies about mechanism underlying these effects. Bibliographic databases were searched for the years 1963-2010 and resulted in 1652 articles. After elimination of duplicates or irrelevant papers, 204 papers were included and reviewed. Results indicated that OP and CB impair the enzymatic pathways involved in metabolism of carbohydrates, fats and protein within cytoplasm, mitochondria, and proxisomes. It is believed that OP and CB show this effect through inhibition of AChE or affecting target organs directly. OC mostly affect lipid metabolism in the adipose tissues and change glucose pathway in other cells. As a shared mechanism, all OP, CB and OC induce cellular oxidative stress via affecting mitochondrial function and therefore disrupt neuronal and hormonal status of the body. Establishing proper epidemiological studies to explore exact relationships between exposure levels to these pesticides and rate of resulted metabolic disorders in human will be helpful.

  12. Impact of Dietary Carbohydrate and Protein Levels on Carbohydrate Metabolism

    Science.gov (United States)

    Lasker, Denise Ann

    2009-01-01

    The goal of this dissertation was to investigate the impact of changing dietary carbohydrate (CARB) intakes within recommended dietary guidelines on metabolic outcomes specifically associated with glycemic regulations and carbohydrate metabolism. This research utilized both human and animal studies to examine changes in metabolism across a wide…

  13. Foliar nitrogen metabolism of adult Douglas-fir trees is affected by soil water availability and varies little among provenances.

    Science.gov (United States)

    Du, Baoguo; Kreuzwieser, Jürgen; Dannenmann, Michael; Junker, Laura Verena; Kleiber, Anita; Hess, Moritz; Jansen, Kirstin; Eiblmeier, Monika; Gessler, Arthur; Kohnle, Ulrich; Ensminger, Ingo; Rennenberg, Heinz; Wildhagen, Henning

    2018-01-01

    The coniferous forest tree Douglas-fir (Pseudotsuga menziesii) is native to the pacific North America, and is increasingly planted in temperate regions worldwide. Nitrogen (N) metabolism is of great importance for growth, resistance and resilience of trees. In the present study, foliar N metabolism of adult trees of three coastal and one interior provenance of Douglas-fir grown at two common gardens in southwestern Germany (Wiesloch, W; Schluchsee, S) were characterized in two subsequent years. Both the native North American habitats of the seed sources and the common garden sites in Germany differ in climate conditions. Total and mineral soil N as well as soil water content were higher in S compared to W. We hypothesized that i) provenances differ constitutively in N pool sizes and composition, ii) N pools are affected by environmental conditions, and iii) that effects of environmental factors on N pools differ among interior and coastal provenances. Soil water content strongly affected the concentrations of total N, soluble protein, total amino acids (TAA), arginine and glutamate. Foliar concentrations of total N, soluble protein, structural N and TAA of trees grown at W were much higher than in trees at S. Provenance effects were small but significant for total N and soluble protein content (interior provenance showed lowest concentrations), as well as arginine, asparagine and glutamate. Our data suggest that needle N status of adult Douglas-fir is independent from soil N availability and that low soil water availability induces a re-allocation of N from structural N to metabolic N pools. Small provenance effects on N pools suggest that local adaptation of Douglas-fir is not dominated by N conditions at the native habitats.

  14. Regulation of Brain Glucose Metabolic Patterns by Protein Phosphorlyation and Drug Therapy

    Science.gov (United States)

    2007-03-30

    Tymoczko et al. 2002). Both cardiac muscle and brain contain the necessary enzymes to metabolize either glucose or ketone bodies . The enzymes... metabolic phenotype of astrocytes and neurons in vitro; and to determine whether antipsychotic drug administration affects glucose metabolites in...Cortical Astrocytes and Neurons 20 Abstract 21 v Introduction ~ 22 Results 24 Enriched Astrocyte and Neuronal Cultures Display Unique Metabolic

  15. Plant protein and animal proteins: do they differentially affect cardiovascular disease risk?

    Science.gov (United States)

    Richter, Chesney K; Skulas-Ray, Ann C; Champagne, Catherine M; Kris-Etherton, Penny M

    2015-11-01

    Proteins from plant-based compared with animal-based food sources may have different effects on cardiovascular disease (CVD) risk factors. Numerous epidemiologic and intervention studies have evaluated their respective health benefits; however, it is difficult to isolate the role of plant or animal protein on CVD risk. This review evaluates the current evidence from observational and intervention studies, focusing on the specific protein-providing foods and populations studied. Dietary protein is derived from many food sources, and each provides a different composite of nonprotein compounds that can also affect CVD risk factors. Increasing the consumption of protein-rich foods also typically results in lower intakes of other nutrients, which may simultaneously influence outcomes. Given these complexities, blanket statements about plant or animal protein may be too general, and greater consideration of the specific protein food sources and the background diet is required. The potential mechanisms responsible for any specific effects of plant and animal protein are similarly multifaceted and include the amino acid content of particular foods, contributions from other nonprotein compounds provided concomitantly by the whole food, and interactions with the gut microbiome. Evidence to date is inconclusive, and additional studies are needed to further advance our understanding of the complexity of plant protein vs. animal protein comparisons. Nonetheless, current evidence supports the idea that CVD risk can be reduced by a dietary pattern that provides more plant sources of protein compared with the typical American diet and also includes animal-based protein foods that are unprocessed and low in saturated fat. © 2015 American Society for Nutrition.

  16. Chlamydia pneumoniae acute liver infection affects hepatic cholesterol and triglyceride metabolism in mice.

    Science.gov (United States)

    Marangoni, Antonella; Fiorino, Erika; Gilardi, Federica; Aldini, Rita; Scotti, Elena; Nardini, Paola; Foschi, Claudio; Donati, Manuela; Montagnani, Marco; Cevenini, Monica; Franco, Placido; Roda, Aldo; Crestani, Maurizio; Cevenini, Roberto

    2015-08-01

    Chlamydia pneumoniae has been linked to atherosclerosis, strictly associated with hyperlipidemia. The liver plays a central role in the regulation of lipid metabolism. Since in animal models C. pneumoniae can be found at hepatic level, this study aims to elucidate whether C. pneumoniae infection accelerates atherosclerosis by affecting lipid metabolism. Thirty Balb/c mice were challenged intra-peritoneally with C. pneumoniae elementary bodies and thirty with Chlamydia trachomatis, serovar D. Thirty mice were injected with sucrose-phosphate-glutamate buffer, as negative controls. Seven days after infection, liver samples were examined both for presence of chlamydia and expression of genes involved in inflammation and lipid metabolism. C. pneumoniae was isolated from 26 liver homogenates, whereas C. trachomatis was never re-cultivated (P triglycerides levels compared both with negative controls (P metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. The Effect of Oral Leucine on Protein Metabolism in Adolescents with Type 1 Diabetes Mellitus

    OpenAIRE

    Vardhini Desikan; Izolda Mileva; Jeremy Garlick; Andrew H. Lane; Thomas A. Wilson; Margaret A. McNurlan

    2010-01-01

    Lack of insulin results in a catabolic state in subjects with insulin-dependent diabetes mellitus which is reversed by insulin treatment. Amino acid supply, especially branched chain amino acids such as leucine, enhances protein synthesis in both animal and human studies. This small study was undertaken to assess the acute effect of supplemental leucine on protein metabolism in adolescents with type 1 diabetes. L-[1-13C] Leucine was used to assess whole-body protein metabolism in six adolesc...

  18. Metabolic responses to high protein diet in Korean elite bodybuilders with high-intensity resistance exercise

    OpenAIRE

    Kim, Hyerang; Lee, Saningun; Choue, Ryowon

    2011-01-01

    Abstract Background High protein diet has been known to cause metabolic acidosis, which is manifested by increased urinary excretion of nitrogen and calcium. Bodybuilders habitually consumed excessive dietary protein over the amounts recommended for them to promote muscle mass accretion. This study investigated the metabolic response to high protein consumption in the elite bodybuilders. Methods Eight elite Korean bodybuilders within the age from 18 to 25, mean age 21.5 ± 2.6. For data collec...

  19. Differential glucose metabolism in mice and humans affected by McArdle disease

    DEFF Research Database (Denmark)

    Krag, Thomas O; Pinós, Tomàs; Nielsen, Tue L

    2016-01-01

    McArdle disease (muscle glycogenosis type V) is a disease caused by myophosphorylase deficiency leading to "blocked" glycogen breakdown. A significant but varying glycogen accumulation in especially distal hind limb muscles of mice affected by McArdle disease has recently been demonstrated......, which could lead to lower glycogen accumulation. In comparison, tibialis anterior, extensor digitorum longus, and soleus had massive glycogen accumulation, but few, if any, changes or adaptations in glucose metabolism compared with wild-type mice. The findings suggest plasticity in glycogen metabolism....... In this study, we investigated how myophosphorylase deficiency affects glucose metabolism in hind limb muscle of 20-wk-old McArdle mice and vastus lateralis muscles from patients with McArdle disease. Western blot analysis and activity assay demonstrated that glycogen synthase was inhibited in glycolytic muscle...

  20. Cell-free protein synthesis enabled rapid prototyping for metabolic engineering and synthetic biology

    Directory of Open Access Journals (Sweden)

    Lihong Jiang

    2018-06-01

    Full Text Available Advances in metabolic engineering and synthetic biology have facilitated the manufacturing of many valuable-added compounds and commodity chemicals using microbial cell factories in the past decade. However, due to complexity of cellular metabolism, the optimization of metabolic pathways for maximal production represents a grand challenge and an unavoidable barrier for metabolic engineering. Recently, cell-free protein synthesis system (CFPS has been emerging as an enabling alternative to address challenges in biomanufacturing. This review summarizes the recent progresses of CFPS in rapid prototyping of biosynthetic pathways and genetic circuits (biosensors to speed up design-build-test (DBT cycles of metabolic engineering and synthetic biology. Keywords: Cell-free protein synthesis, Metabolic pathway optimization, Genetic circuits, Metabolic engineering, Synthetic biology

  1. Exposure to atrazine affects the expression of key genes in metabolic pathways integral to energy homeostasis in Xenopus laevis tadpoles.

    Science.gov (United States)

    Zaya, Renee M; Amini, Zakariya; Whitaker, Ashley S; Ide, Charles F

    2011-08-01

    In our laboratory, Xenopus laevis tadpoles exposed throughout development to 200 or 400 μg/L atrazine, concentrations reported to periodically occur in puddles, vernal ponds and runoff soon after application, were smaller and had smaller fat bodies (the tadpole's lipid storage organ) than controls. It was hypothesized that these changes were due to atrazine-related perturbations of energy homeostasis. To investigate this hypothesis, selected metabolic responses to exposure at the transcriptional and biochemical levels in atrazine-exposed tadpoles were measured. DNA microarray technology was used to determine which metabolic pathways were affected after developmental exposure to 400 μg/L atrazine. From these data, genes representative of the affected pathways were selected for assay using quantitative real time polymerase chain reaction (qRT-PCR) to measure changes in expression during a 2-week exposure to 400 μg/L. Finally, ATP levels were measured from tadpoles both early in and at termination of exposure to 200 and 400 μg/L. Microarray analysis revealed significant differential gene expression in metabolic pathways involved with energy homeostasis. Pathways with increased transcription were associated with the conversion of lipids and proteins into energy. Pathways with decreased transcription were associated with carbohydrate metabolism, fat storage, and protein synthesis. Using qRT-PCR, changes in gene expression indicative of an early stress response to atrazine were noted. Exposed tadpoles had significant decreases in acyl-CoA dehydrogenase (AD) and glucocorticoid receptor protein (GR) mRNA after 24 h of exposure, and near-significant (p=0.07) increases in peroxisome proliferator-activated receptor β (PPAR-β) mRNA by 72 h. Decreases in AD suggested decreases in fatty acid β-oxidation while decreases in GR may have been a receptor desensitization response to a glucocorticoid surge. Involvement of PPAR-β, an energy homeostasis regulatory molecule, also

  2. Exposure to atrazine affects the expression of key genes in metabolic pathways integral to energy homeostasis in Xenopus laevis tadpoles

    International Nuclear Information System (INIS)

    Zaya, Renee M.; Amini, Zakariya; Whitaker, Ashley S.; Ide, Charles F.

    2011-01-01

    In our laboratory, Xenopus laevis tadpoles exposed throughout development to 200 or 400 μg/L atrazine, concentrations reported to periodically occur in puddles, vernal ponds and runoff soon after application, were smaller and had smaller fat bodies (the tadpole's lipid storage organ) than controls. It was hypothesized that these changes were due to atrazine-related perturbations of energy homeostasis. To investigate this hypothesis, selected metabolic responses to exposure at the transcriptional and biochemical levels in atrazine-exposed tadpoles were measured. DNA microarray technology was used to determine which metabolic pathways were affected after developmental exposure to 400 μg/L atrazine. From these data, genes representative of the affected pathways were selected for assay using quantitative real time polymerase chain reaction (qRT-PCR) to measure changes in expression during a 2-week exposure to 400 μg/L. Finally, ATP levels were measured from tadpoles both early in and at termination of exposure to 200 and 400 μg/L. Microarray analysis revealed significant differential gene expression in metabolic pathways involved with energy homeostasis. Pathways with increased transcription were associated with the conversion of lipids and proteins into energy. Pathways with decreased transcription were associated with carbohydrate metabolism, fat storage, and protein synthesis. Using qRT-PCR, changes in gene expression indicative of an early stress response to atrazine were noted. Exposed tadpoles had significant decreases in acyl-CoA dehydrogenase (AD) and glucocorticoid receptor protein (GR) mRNA after 24 h of exposure, and near-significant (p = 0.07) increases in peroxisome proliferator-activated receptor β (PPAR-β) mRNA by 72 h. Decreases in AD suggested decreases in fatty acid β-oxidation while decreases in GR may have been a receptor desensitization response to a glucocorticoid surge. Involvement of PPAR-β, an energy homeostasis regulatory molecule

  3. Exposure to atrazine affects the expression of key genes in metabolic pathways integral to energy homeostasis in Xenopus laevis tadpoles

    Energy Technology Data Exchange (ETDEWEB)

    Zaya, Renee M., E-mail: renee.zaya@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Amini, Zakariya, E-mail: zakariya.amini@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Whitaker, Ashley S., E-mail: ashley.s.whitaker@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Ide, Charles F., E-mail: charles.ide@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States)

    2011-08-15

    In our laboratory, Xenopus laevis tadpoles exposed throughout development to 200 or 400 {mu}g/L atrazine, concentrations reported to periodically occur in puddles, vernal ponds and runoff soon after application, were smaller and had smaller fat bodies (the tadpole's lipid storage organ) than controls. It was hypothesized that these changes were due to atrazine-related perturbations of energy homeostasis. To investigate this hypothesis, selected metabolic responses to exposure at the transcriptional and biochemical levels in atrazine-exposed tadpoles were measured. DNA microarray technology was used to determine which metabolic pathways were affected after developmental exposure to 400 {mu}g/L atrazine. From these data, genes representative of the affected pathways were selected for assay using quantitative real time polymerase chain reaction (qRT-PCR) to measure changes in expression during a 2-week exposure to 400 {mu}g/L. Finally, ATP levels were measured from tadpoles both early in and at termination of exposure to 200 and 400 {mu}g/L. Microarray analysis revealed significant differential gene expression in metabolic pathways involved with energy homeostasis. Pathways with increased transcription were associated with the conversion of lipids and proteins into energy. Pathways with decreased transcription were associated with carbohydrate metabolism, fat storage, and protein synthesis. Using qRT-PCR, changes in gene expression indicative of an early stress response to atrazine were noted. Exposed tadpoles had significant decreases in acyl-CoA dehydrogenase (AD) and glucocorticoid receptor protein (GR) mRNA after 24 h of exposure, and near-significant (p = 0.07) increases in peroxisome proliferator-activated receptor {beta} (PPAR-{beta}) mRNA by 72 h. Decreases in AD suggested decreases in fatty acid {beta}-oxidation while decreases in GR may have been a receptor desensitization response to a glucocorticoid surge. Involvement of PPAR-{beta}, an energy

  4. Role of the Irr protein in the regulation of iron metabolism in Rhodobacter sphaeroides.

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    Verena Peuser

    Full Text Available In Rhizobia the Irr protein is an important regulator for iron-dependent gene expression. We studied the role of the Irr homolog RSP_3179 in the photosynthetic alpha-proteobacterium Rhodobacter sphaeroides. While Irr had little effect on growth under iron-limiting or non-limiting conditions its deletion resulted in increased resistance to hydrogen peroxide and singlet oxygen. This correlates with an elevated expression of katE for catalase in the Irr mutant compared to the wild type under non-stress conditions. Transcriptome studies revealed that Irr affects the expression of genes for iron metabolism, but also has some influence on genes involved in stress response, citric acid cycle, oxidative phosphorylation, transport, and photosynthesis. Most genes showed higher expression levels in the wild type than in the mutant under normal growth conditions indicating an activator function of Irr. Irr was however not required to activate genes of the iron metabolism in response to iron limitation, which showed even stronger induction in the absence of Irr. This was also true for genes mbfA and ccpA, which were verified as direct targets for Irr. Our results suggest that in R. sphaeroides Irr diminishes the strong induction of genes for iron metabolism under iron starvation.

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

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

    2018-02-01

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

  6. Metabolic Turnover of Synaptic Proteins: Kinetics, Interdependencies and Implications for Synaptic Maintenance

    Science.gov (United States)

    Cohen, Laurie D.; Zuchman, Rina; Sorokina, Oksana; Müller, Anke; Dieterich, Daniela C.; Armstrong, J. Douglas; Ziv, Tamar; Ziv, Noam E.

    2013-01-01

    Chemical synapses contain multitudes of proteins, which in common with all proteins, have finite lifetimes and therefore need to be continuously replaced. Given the huge numbers of synaptic connections typical neurons form, the demand to maintain the protein contents of these connections might be expected to place considerable metabolic demands on each neuron. Moreover, synaptic proteostasis might differ according to distance from global protein synthesis sites, the availability of distributed protein synthesis facilities, trafficking rates and synaptic protein dynamics. To date, the turnover kinetics of synaptic proteins have not been studied or analyzed systematically, and thus metabolic demands or the aforementioned relationships remain largely unknown. In the current study we used dynamic Stable Isotope Labeling with Amino acids in Cell culture (SILAC), mass spectrometry (MS), Fluorescent Non–Canonical Amino acid Tagging (FUNCAT), quantitative immunohistochemistry and bioinformatics to systematically measure the metabolic half-lives of hundreds of synaptic proteins, examine how these depend on their pre/postsynaptic affiliation or their association with particular molecular complexes, and assess the metabolic load of synaptic proteostasis. We found that nearly all synaptic proteins identified here exhibited half-lifetimes in the range of 2–5 days. Unexpectedly, metabolic turnover rates were not significantly different for presynaptic and postsynaptic proteins, or for proteins for which mRNAs are consistently found in dendrites. Some functionally or structurally related proteins exhibited very similar turnover rates, indicating that their biogenesis and degradation might be coupled, a possibility further supported by bioinformatics-based analyses. The relatively low turnover rates measured here (∼0.7% of synaptic protein content per hour) are in good agreement with imaging-based studies of synaptic protein trafficking, yet indicate that the metabolic load

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

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    Thais de Castro Barbosa

    2016-03-01

    Conclusion: Our results provide insight into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations.

  8. Effects of Radiation and Dietary Iron on Expression of Genes and Proteins Involved in Drug Metabolism

    Science.gov (United States)

    Faust, K. M.; Wotring, V. E.

    2014-01-01

    + rad group. Metallothionein is involved in the regulation of physiological metals and also has antioxidant activities. Among the drug metabolism genes examined, ATP binding cassette subfamily B (Abcb1b) gene expression increased more than 10-fold in both groups that received radiation treatments. This increased expression was also seen at the protein level. This ABC transporter carries many different compounds across cell membranes, including administered medications. The cytochrome P450 2E1 enzyme, a mixed-function oxidase that deactivates some medications and activates others, showed about a 2-fold increase in gene expression in both radiation-treated groups, with a trend toward increased expression at the protein level. Expression of epoxide hydrolase, which detoxifies polycyclic aromatic hydrocarbons, showed similar 2-fold increases. Among the DNA repair genes examined, expression of RAD51 was significantly down regulated (1.5 fold) in the radiation treated group. RAD51 is involved in repair of double-stranded DNA breaks. CONCLUSION This experiment used 2 different sources of physiological oxidative stress, administered separately and together, and examined their impacts on liver gene and protein expression. It is clear that significant changes occurred in expression of several genes and proteins in the radiation-treated animals. If the results from this ground analog of portions of the spaceflight environment hold true for the spaceflight environment itself, the physiological roles of the affected enzymes (drug transport and metabolism, redox homeostasis) could mean consequences in redox homeostasis or the pharmacokinetics of administered medications

  9. Deep Proteomics of Mouse Skeletal Muscle Enables Quantitation of Protein Isoforms, Metabolic Pathways, and Transcription Factors*

    Science.gov (United States)

    Deshmukh, Atul S.; Murgia, Marta; Nagaraj, Nagarjuna; Treebak, Jonas T.; Cox, Jürgen; Mann, Matthias

    2015-01-01

    Skeletal muscle constitutes 40% of individual body mass and plays vital roles in locomotion and whole-body metabolism. Proteomics of skeletal muscle is challenging because of highly abundant contractile proteins that interfere with detection of regulatory proteins. Using a state-of-the art MS workflow and a strategy to map identifications from the C2C12 cell line model to tissues, we identified a total of 10,218 proteins, including skeletal muscle specific transcription factors like myod1 and myogenin and circadian clock proteins. We obtain absolute abundances for proteins expressed in a muscle cell line and skeletal muscle, which should serve as a valuable resource. Quantitation of protein isoforms of glucose uptake signaling pathways and in glucose and lipid metabolic pathways provides a detailed metabolic map of the cell line compared with tissue. This revealed unexpectedly complex regulation of AMP-activated protein kinase and insulin signaling in muscle tissue at the level of enzyme isoforms. PMID:25616865

  10. Protein engineering for metabolic engineering: current and next-generation tools

    Science.gov (United States)

    Marcheschi, Ryan J.; Gronenberg, Luisa S.; Liao, James C.

    2014-01-01

    Protein engineering in the context of metabolic engineering is increasingly important to the field of industrial biotechnology. As the demand for biologically-produced food, fuels, chemicals, food additives, and pharmaceuticals continues to grow, the ability to design and modify proteins to accomplish new functions will be required to meet the high productivity demands for the metabolism of engineered organisms. This article reviews advances of selecting, modeling, and engineering proteins to improve or alter their activity. Some of the methods have only recently been developed for general use and are just beginning to find greater application in the metabolic engineering community. We also discuss methods of generating random and targeted diversity in proteins to generate mutant libraries for analysis. Recent uses of these techniques to alter cofactor use, produce non-natural amino acids, alcohols, and carboxylic acids, and alter organism phenotypes are presented and discussed as examples of the successful engineering of proteins for metabolic engineering purposes. PMID:23589443

  11. A review of some metabolic changes in protein-energy malnutrition.

    Science.gov (United States)

    Akuyam, S A

    2007-06-01

    Protein-energy malnutrition (PEM) is a major public health problem in the tropical and subtropical regions of the world and often arises during protein and / or energy deficit due to nutritional inadequacy, infections and poor socio-economic and environmental conditions. It is the most common nutritional disorder affecting children in developing countries and the third most common disease of childhood in such countries. PEM has a lasting effect on immune functions, growth and development of children, learning ability, social adjustment, work efficiency and productivity of labour. It seems that many deaths from PEM occur as a result of outdated clinical practices and that improving these practices reduces the rate of morbidity and mortality. This paper reviews various metabolic changes in protein-energy malnutrition (PEM). It gives an overview of the theoretical basis for the understanding of the biochemical derangements in PEM. It aims at stimulating the paediatricians and clinical chemists to read more on the recent advances in this broad subject with the view to improving the understanding of the current laboratory investigation of PEM. This review demonstrates that the metabolic changes in PEM include water and electrolytes imbalance, amino acids and proteins deficiencies, carbohydrates and energy deficiencies, hypolipidaemias, hypolipoproteinaemias, hormonal imbalance, deficiency of anti-oxidant vitamins and enzymes, depression of cell-mediated immune complexes and decrease in amino acids and trace elements in skin and hair. The review therefore suggests that assessment of these conditions in PEM patients could improve the management of this group of patients and hence reduce the rate of morbidity and mortality from PEM.

  12. Identifying molecular effects of diet through systems biology: influence of herring diet on sterol metabolism and protein turnover in mice.

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    Intawat Nookaew

    Full Text Available BACKGROUND: Changes in lifestyle have resulted in an epidemic development of obesity-related diseases that challenge the healthcare systems worldwide. To develop strategies to tackle this problem the focus is on diet to prevent the development of obesity-associated diseases such as cardiovascular disease (CVD. This will require methods for linking nutrient intake with specific metabolic processes in different tissues. METHODOLOGY/PRINCIPAL FINDING: Low-density lipoprotein receptor-deficient (Ldlr -/- mice were fed a high fat/high sugar diet to mimic a westernized diet, being a major reason for development of obesity and atherosclerosis. The diets were supplemented with either beef or herring, and matched in macronutrient contents. Body composition, plasma lipids and aortic lesion areas were measured. Transcriptomes of metabolically important tissues, e.g. liver, muscle and adipose tissue were analyzed by an integrated approach with metabolic networks to directly map the metabolic effects of diet in these different tissues. Our analysis revealed a reduction in sterol metabolism and protein turnover at the transcriptional level in herring-fed mice. CONCLUSION: This study shows that an integrated analysis of transcriptome data using metabolic networks resulted in the identification of signature pathways. This could not have been achieved using standard clustering methods. In particular, this systems biology analysis could enrich the information content of biomedical or nutritional data where subtle changes in several tissues together affects body metabolism or disease progression. This could be applied to improve diets for subjects exposed to health risks associated with obesity.

  13. Comparative proteomic analyses reveal that the regulators of G-protein signaling proteins regulate amino acid metabolism of the rice blast fungus Magnaporthe oryzae.

    Science.gov (United States)

    Zhang, Haifeng; Ma, Hongyu; Xie, Xin; Ji, Jun; Dong, Yanhan; Du, Yan; Tang, Wei; Zheng, Xiaobo; Wang, Ping; Zhang, Zhengguang

    2014-11-01

    The rice blast fungus Magnaporthe oryzae encodes eight regulators of G-protein (GTP-binding protein) signaling (RGS) proteins MoRgs1-MoRgs8 that orchestrate the growth, asexual/sexual production, appressorium differentiation, and pathogenicity. To address the mechanisms by which MoRgs proteins function, we conducted a 2DE proteome study and identified 82 differentially expressed proteins by comparing five ∆Morgs mutants with wild-type Guy11 strain. We found that the abundances of eight amino acid (AA) biosynthesis or degradation associated proteins were markedly altered in five ∆Morgs mutants, indicating one of the main collective roles for the MoRgs proteins is to influence AA metabolism. We showed that MoRgs proteins have distinct roles in AA metabolism and nutrient responses from growth assays. In addition, we characterized MoLys20 (Lys is lysine), a homocitrate synthase, whose abundance was significantly decreased in the ∆Morgs mutants. The ∆Molys20 mutant is auxotrophic for lys and exogenous lys could partially rescue its auxotrophic defects. Deletion of MoLYS20 resulted in defects in conidiation and infection, as well as pathogenicity on rice. Overall, our results indicate that one of the critical roles for MoRgs proteins is to regulate AA metabolism, and that MoLys20 may be directly or indirectly regulated by MoRgs and participated in lys biosynthesis, thereby affecting fungal development and pathogenicity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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    Thomas K Uchida

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

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

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    Motoi Tamura

    2013-12-01

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

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

    Science.gov (United States)

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-12-10

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

  17. Metabolic Syndrome as a Factor Affecting Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Rubinsztajn, R; Przybyłowski, T; Maskey-Warzęchowska, M; Paplińska-Goryca, M; Nejman-Gryz, P; Karwat, K; Chazan, R

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is a systemic disease which may be associated with other comorbidities. The aim of the study was to estimate the incidence of metabolic syndrome (MS) in COPD patients and to assess its impact on systemic inflammation and lung function. MS was diagnosed in accordance with the recommendations of the Polish Forum for the Prevention of Cardiovascular Diseases. The study group consisted of 267 patients with stable COPD in all stages of severity. All patients underwent spirometry with bronchial reversibility testing and 6 min walk test (6MWT). The following blood tests were evaluated: lipid profile, glucose and C-reactive protein as well as serum concentration of IL-6, leptin, adiponectin, and endothelin. MS was diagnosed in 93 patients (35.8%). No differences were observed in the incidence of MS in relation to airflow limitation severity (mild; moderate; severe and very severe: 38.9; 36.3; 35.2 and 25.0%, respectively). FEV 1 (% predicted), FVC (% predicted), 6MWT distance (6MWD), age, and the number of pack-years were similar in patients with and without MS. MS was more frequent in males than females (38.7 vs. 28.4%, p > 0.05). Serum concentrations of IL-6, endothelin, leptin, and CRP were higher in the MS group, contrary to adiponectin concentration which was lower (p < 0.01). MS was more frequent in male COPD patients, but there were no differences in its frequency between patients with different severity of airflow limitation. We conclude that MS, as a comorbidity, occurs in all COPD stages and affects systemic inflammation. MS incidence does not depend on COPD severity.

  18. Lengths of Orthologous Prokaryotic Proteins Are Affected by Evolutionary Factors

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    Tatiana Tatarinova

    2015-01-01

    Full Text Available Proteins of the same functional family (for example, kinases may have significantly different lengths. It is an open question whether such variation in length is random or it appears as a response to some unknown evolutionary driving factors. The main purpose of this paper is to demonstrate existence of factors affecting prokaryotic gene lengths. We believe that the ranking of genomes according to lengths of their genes, followed by the calculation of coefficients of association between genome rank and genome property, is a reasonable approach in revealing such evolutionary driving factors. As we demonstrated earlier, our chosen approach, Bubble-sort, combines stability, accuracy, and computational efficiency as compared to other ranking methods. Application of Bubble Sort to the set of 1390 prokaryotic genomes confirmed that genes of Archaeal species are generally shorter than Bacterial ones. We observed that gene lengths are affected by various factors: within each domain, different phyla have preferences for short or long genes; thermophiles tend to have shorter genes than the soil-dwellers; halophiles tend to have longer genes. We also found that species with overrepresentation of cytosines and guanines in the third position of the codon (GC3 content tend to have longer genes than species with low GC3 content.

  19. Lengths of Orthologous Prokaryotic Proteins Are Affected by Evolutionary Factors.

    Science.gov (United States)

    Tatarinova, Tatiana; Salih, Bilal; Dien Bard, Jennifer; Cohen, Irit; Bolshoy, Alexander

    2015-01-01

    Proteins of the same functional family (for example, kinases) may have significantly different lengths. It is an open question whether such variation in length is random or it appears as a response to some unknown evolutionary driving factors. The main purpose of this paper is to demonstrate existence of factors affecting prokaryotic gene lengths. We believe that the ranking of genomes according to lengths of their genes, followed by the calculation of coefficients of association between genome rank and genome property, is a reasonable approach in revealing such evolutionary driving factors. As we demonstrated earlier, our chosen approach, Bubble-sort, combines stability, accuracy, and computational efficiency as compared to other ranking methods. Application of Bubble Sort to the set of 1390 prokaryotic genomes confirmed that genes of Archaeal species are generally shorter than Bacterial ones. We observed that gene lengths are affected by various factors: within each domain, different phyla have preferences for short or long genes; thermophiles tend to have shorter genes than the soil-dwellers; halophiles tend to have longer genes. We also found that species with overrepresentation of cytosines and guanines in the third position of the codon (GC3 content) tend to have longer genes than species with low GC3 content.

  20. A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.

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    Michael Oster

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

  1. The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture.

    Science.gov (United States)

    Caetano-Anollés, Gustavo; Kim, Hee Shin; Mittenthal, Jay E

    2007-05-29

    Metabolism represents a complex collection of enzymatic reactions and transport processes that convert metabolites into molecules capable of supporting cellular life. Here we explore the origins and evolution of modern metabolism. Using phylogenomic information linked to the structure of metabolic enzymes, we sort out recruitment processes and discover that most enzymatic activities were associated with the nine most ancient and widely distributed protein fold architectures. An analysis of newly discovered functions showed enzymatic diversification occurred early, during the onset of the modern protein world. Most importantly, phylogenetic reconstruction exercises and other evidence suggest strongly that metabolism originated in enzymes with the P-loop hydrolase fold in nucleotide metabolism, probably in pathways linked to the purine metabolic subnetwork. Consequently, the first enzymatic takeover of an ancient biochemistry or prebiotic chemistry was related to the synthesis of nucleotides for the RNA world.

  2. Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

    International Nuclear Information System (INIS)

    Keith, Dove; Finlay, Liam; Butler, Judy; Gómez, Luis; Smith, Eric; Moreau, Régis; Hagen, Tory

    2014-01-01

    Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks

  3. Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

    Energy Technology Data Exchange (ETDEWEB)

    Keith, Dove; Finlay, Liam; Butler, Judy [Linus Pauling Institute, Oregon State University (United States); Gómez, Luis; Smith, Eric [Linus Pauling Institute, Oregon State University (United States); Biochemistry Biophysics Department, Oregon State University (United States); Moreau, Régis [Linus Pauling Institute, Oregon State University (United States); Hagen, Tory [Linus Pauling Institute, Oregon State University (United States); Biochemistry Biophysics Department, Oregon State University (United States)

    2014-07-18

    Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks.

  4. Study of Stationary Phase Metabolism Via Isotopomer Analysis of Amino Acids from an Isolated Protein

    Energy Technology Data Exchange (ETDEWEB)

    Shaikh, AfshanS.; Tang, YinjieJ.; Mukhopadhyay, Aindrila; Martin, Hector Garcia; Gin, Jennifer; Benke, Peter; Keasling, Jay D.

    2009-09-14

    Microbial production of many commercially important secondary metabolites occurs during stationary phase, and methods to measure metabolic flux during this growth phase would be valuable. Metabolic flux analysis is often based on isotopomer information from proteinogenic amino acids. As such, flux analysis primarily reflects the metabolism pertinent to the growth phase during which most proteins are synthesized. To investigate central metabolism and amino acids synthesis activity during stationary phase, addition of fully 13C-labeled glucose followed by induction of green fluorescent protein (GFP) expression during stationary phase was used. Our results indicate that Escherichia coli was able to produce new proteins (i.e., GFP) in the stationary phase, and the amino acids in GFP were mostly from degraded proteins synthesized during the exponential growth phase. Among amino acid biosynthetic pathways, only those for serine, alanine, glutamate/glutamine, and aspartate/asparagine had significant activity during the stationary phase.

  5. Evaluation of the protein metabolism during hepatic coma evidenced by 15N tracer data

    International Nuclear Information System (INIS)

    Matkowitz, R.; Hartig, W.; Junghans, P.; Jung, K.; Hirschberg, K.; Bornhak, H.

    1983-01-01

    In patients in coma hepaticum as well as in pigs with experimental hepatic coma the protein metabolism was studied under conditions of parenteral application of an amino acid diet using 15 N-glycine as tracer

  6. The choice of label and measurement technique in tracer studies of body protein metabolism in man

    International Nuclear Information System (INIS)

    James, W.P.T.; Sender, P.M.; Garlick, P.J.; Waterlow, J.C.

    1975-01-01

    The turnover of non-serum proteins in man has had limited study despite the physiological importance of maintaining the balance between synthesis and breakdown of body proteins. Body protein is usually considered as a single pool and breakdown rates are often measured by monitoring excreted label at intervals after pulse labelling with radioactive or 15 N amino acids. No label has yet been used for measuring tissue protein breakdown in man which is free from the major problem of label re-utilization. All measurements of breakdown rates, eg. with 75 Se-selenomethionine, 15 N- or 14 C-glycine, give rate constants which are too low. The heterogeneity of body proteins also means that an estimate of the weighted average breakdown rate can only be obtained after following the excretion of isotope for a long period, perhaps of the order of 3-4 half-lives which, for man, would be 100 days after labelling. We therefore use infusions with either 14 C- or 15 N-labelled amino acids to measure breakdown and synthesis rates: these values are less affected by problems of protein heterogeneity. Single injection techniques are subject to more error than constant infusions of label because of the difficulty of defining the precursor activity. 15 N labelling need not be confined to essential amino acids if total protein rather than amino acid turnover is studied: the latter involves measurements of the labelled amino acid itself which is difficult with 15 N because of the small amounts of free amino acid nitrogen available. Carbon labelling of non-essential amino acids is unsuitable for studies of protein turnover and the choice of the position of the label on the molecule is important when labelled essential amino acids are employed. Short-term changes in protein metabolism are evaluated better with amino acids with a small pool size; the equilibration time in the excretory bicarbonate pool is also shorter than in the urea pool so that 15 N is less useful than carbon labelling. We

  7. Circulating adipocyte fatty acid-binding protein, juvenile obesity, and metabolic syndrome

    NARCIS (Netherlands)

    Krzystek-Korpacka, Malgorzata; Patryn, Eliza; Bednarz-Misa, Iwona; Mierzchala, Magdalena; Hotowy, Katarzyna; Czapinska, Elzbieta; Kustrzeba-Wojcicka, Irena; Gamian, Andrzej; Noczynska, Anna

    2011-01-01

    Adipocyte fatty acid-binding protein (A-FABP) links obesity and metabolic syndrome (MetS) and might be targeted in future therapies. Its utility as a MetS biomarker has been suggested in adults but has not been examined in children/adolescents. Our objectives were to identify metabolic parameters

  8. Effects of Quercetin Supplementation on Lipid and Protein Metabolism after Classic Boxing Training

    Science.gov (United States)

    Demirci, Nevzat

    2017-01-01

    The metabolic fitness (MF) is a component of athletes' physical conditioning. This study aims to investigate the effects of quercetin supplementation on Turkish Junior athletes' lipid and protein metabolism relating to MF after one month classic boxing training. Totally 20 voluntary junior male athletes were separated into two equal groups as the…

  9. Factors affecting high-sensitivity cardiac troponin T elevation in Japanese metabolic syndrome patients

    Directory of Open Access Journals (Sweden)

    Hitsumoto T

    2015-03-01

    Full Text Available Takashi Hitsumoto,1 Kohji Shirai2 1Hitsumoto Medical Clinic, Yamaguchi, Japan; 2Department of Vascular Function (donated, Sakura Hospital, Toho University School of Medicine, Chiba, Japan Purpose: The blood concentration of cardiac troponin T (ie, high-sensitivity cardiac troponin T [hs-cTnT], measured using a highly sensitive assay, represents a useful biomarker for evaluating the pathogenesis of heart failure or predicting cardiovascular events. However, little is known about the clinical significance of hs-cTnT in metabolic syndrome. The aim of this study was to examine the factors affecting hs-cTnT elevation in Japanese metabolic syndrome patients. Patients and methods: We enrolled 258 metabolic syndrome patients who were middle-aged males without a history of cardiovascular events. We examined relationships between hs-cTnT and various clinical parameters, including diagnostic parameters of metabolic syndrome. Results: There were no significant correlations between hs-cTnT and diagnostic parameters of metabolic syndrome. However, hs-cTnT was significantly correlated with age (P<0.01, blood concentrations of brain natriuretic peptide (P<0.01, reactive oxygen metabolites (markers of oxidative stress, P<0.001, and the cardio–ankle vascular index (marker of arterial function, P<0.01. Furthermore, multiple regression analysis revealed that these factors were independent variables for hs-cTnT as a subordinate factor. Conclusion: The findings of this study indicate that in vivo oxidative stress and abnormality of arterial function are closely associated with an increase in hs-cTnT concentrations in Japanese metabolic syndrome patients. Keywords: troponin, metabolic syndrome, risk factor, oxidative stress, cardio–ankle vascular index

  10. Combined enteral infusion of glutamine, carbohydrates, and antioxidants modulates gut protein metabolism in humans.

    Science.gov (United States)

    Coëffier, Moïse; Claeyssens, Sophie; Lecleire, Stéphane; Leblond, Jonathan; Coquard, Aude; Bôle-Feysot, Christine; Lavoinne, Alain; Ducrotté, Philippe; Déchelotte, Pierre

    2008-11-01

    Available data suggest that nutrients can affect intestinal protein metabolism, which contributes to the regulation of gut barrier function. We aimed to assess whether an oral nutritional supplement (ONS) containing glutamine (as the dipeptide Ala-Gln), carbohydrates, and antioxidants would modulate duodenal protein metabolism in healthy humans. Thirty healthy control subjects were included and, over a period of 5 h, received by nasogastric tube either saline or ONS providing 11.7 kcal/kg as 0.877 g Ala-Gln/kg, 3.9 g carbohydrates/kg, and antioxidants (29.25 mg vitamin C/kg, 9.75 mg vitamin E/kg, 195 microg beta-carotene/kg, 5.85 mg Se/kg, and 390 microg Zn/kg) or glutamine (0.585 g/kg, 2.34 kcal/kg). Simultaneously, a continuous intravenous infusion of l-[1-(13)C]-leucine was done until endoscopy. Leucine enrichment was assessed by using gas chromatography-mass spectrometric analysis, and mucosal fractional synthesis rate was calculated by using intracellular amino acid enrichment as precursor. Mucosal proteolytic pathways were also evaluated. ONS infusion resulted in a doubling increase (P < 0.01) of duodenal fractional synthesis rate and a significant (P < 0.05) decrease in cathepsin D-mediated proteolysis compared with saline, whereas proteasome and Ca(2+)-dependent activities were unaffected. ONS infusion significantly (P < 0.01) decreased duodenal glutathione but not glutathione disulfide concentrations or the ratio of glutathione to glutathione disulfide. Insulinemia increased after ONS infusion, whereas plasma essential amino acids decreased. Infusion of glutamine alone did not reproduce ONS effects. ONS infusion improves duodenal protein balance in healthy humans. Further investigations are needed to study the origin of these effects and to evaluate ONS supply in stressed persons.

  11. The effect of simvastatin treatment on the amyloid precursor protein and brain cholesterol metabolism in patients with Alzheimer's disease

    DEFF Research Database (Denmark)

    Hoglund, K; Thelen, K M; Syversen, S

    2005-01-01

    During the last years, several clinical studies have been published trying to elucidate the effect of statin treatment on amyloid precursor protein (APP) processing and metabolism of brain cholesterol in Alzheimer's disease (AD) in humans. We present an open biochemical study where 19 patients...... with AD have been treated with simvastatin (20 mg/day) for 12 months. The aim was to further investigate the effect of simvastatin treatment on cerebrospinal fluid (CSF) biomarkers of APP processing, AD biomarkers as total tau and tau phosphorylated at threonine 181, brain cholesterol metabolism as well...... as on cognitive decline in patients with AD. Despite biochemical data suggesting that treatment with 20 mg/day of simvastatin for 12 months does affect the brain cholesterol metabolism, we did not find any change in CSF or plasma levels of beta-amyloid (Abeta)(1-42). However, by analysis of APP isoforms, we found...

  12. Effects of immobilization and aerobic training on proteins related to intramuscular substrate storage and metabolism in young and older men.

    Science.gov (United States)

    Vigelsø, Andreas; Gram, Martin; Wiuff, Caroline; Hansen, Christina Neigaard; Prats, Clara; Dela, Flemming; Helge, Jørn Wulff

    2016-03-01

    Aging and inactivity lead to skeletal muscle metabolic inflexibility, but the underlying molecular mechanisms are not entirely elucidated. Therefore, we investigated how muscle lipid and glycogen stores and major regulatory proteins were affected by short-term immobilization followed by aerobic training in young and older men. 17 young (23 ± 1 years, 24 ± 1 kg m(-2), and 20 ± 2% body fat) and 15 older men (68 ± 1 years; 27 ± 1 kg m(-2), and 29 ± 2% body fat) underwent 2 weeks' one leg immobilization followed by 6 weeks' cycle training. Biopsies were obtained from m. vastus lateralis just before immobilization (at inclusion), after immobilization, and the after 6 weeks' training. The biopsies were analyzed for muscle substrates; muscle perilipin protein (PLIN), glycogen synthase (GS), synaptosomal-associated protein of 23 kDa (SNAP23) protein content, and muscle 3-hydroxyacyl-CoA dehydrogenase (HAD) activity The older men had higher intramuscular triglyceride (IMTG) (73 %) and Glycogen (16%) levels compared to the young men, and IMTG tended to increase with immobilization. PLIN2 and 3 protein content increased with immobilization in the older men only. The young men had higher GS (74%) protein compared to the older men. Immobilization decreased and training restored HAD activity, GS and SNAP23 protein content in young and older men. Evidence of age-related metabolic inflexibility is presented, seen as body fat and IMTG accumulation. The question arises as to whether IMTG accumulation in the older men is caused by or leading to the increase in PLIN2 and 3 protein content. Training decreased body fat and IMTG levels in both young and older men; hence, training should be prioritized to reduce the detrimental effect of aging on metabolism.

  13. Functional analysis of thermostable proteins involved in carbohydrate metabolism

    NARCIS (Netherlands)

    Akerboom, A.P.

    2007-01-01

    Thermostable proteins can resist temperature stress whilst keeping their integrity and functionality. In many cases, thermostable proteins originate from hyperthermophilic microorganisms that thrive in extreme environments. These systems are generally located close to geothermal (volcanic) activity,

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

    Science.gov (United States)

    Vancampfort, Davy; Stubbs, Brendon

    2017-12-15

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

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

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Sulek, Karolina; Skov, Kasper

    2014-01-01

    (NCFM) on the intestinal metabolome (jejunum, caecum, and colon) in mice by comparing NCFM mono-colonized (MC) mice with GF mice using liquid chromatography coupled to mass-spectrometry (LC-MS). The study adds to existing evidence that NCFM in vivo affects the bile acid signature of mice...... by deconjugation and dehydroxylation of bile acids. Furthermore, we confirmed that carbohydrate metabolism is affected by NCFM in the mouse intestine. Especially, the digestion of larger carbohydrates (penta- and tetrasaccharides) was increased in MC mice. Interestingly, we also found vitamin E (α...

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

    Energy Technology Data Exchange (ETDEWEB)

    Kodavanti, Prasada Rao S., E-mail: kodavanti.prasada@epa.gov [Neurotoxicology Branch, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina (United States); Osorio, Cristina [Systems Proteomics Center, University of North Carolina at Chapel Hill, North Carolina (United States); Program on Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, North Carolina (United States); Royland, Joyce E.; Ramabhadran, Ram [Genetic and Cellular Toxicology Branch, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina (United States); Alzate, Oscar [Department of Cellular and Developmental Biology, University of North Carolina at Chapel Hill, North Carolina (United States); Systems Proteomics Center, University of North Carolina at Chapel Hill, North Carolina (United States); Program on Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, North Carolina (United States)

    2011-11-15

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

  17. Effect of altitude on protein metabolism in Bolivian children

    International Nuclear Information System (INIS)

    Beaufrere, B.; Gachon, P.; Boirie, Y.; San Miguel, J.L.; Maubois, J.L.; Coudert, J.

    1994-01-01

    Protein utilization during feeding is difficult to assess by classical tracer methodology, particularly under field conditions. We propose a new approach using the measurement of tracer recovery (expired 13 CO 2 ) after the ingestion of a single oral dose of a 13 C-leucine labelled milk protein. Protein will be obtained by infusing a cow with 13 C-leucine. The difference between the amounts of tracer given and recovered should be an index of protein utilization. Since altitude might influence protein absorption, this non-invasive method will be used in Bolivian children, living either at 3600 m (La Paz) or at sea level. (author). 14 refs

  18. Partial sequence determination of metabolically labeled radioactive proteins and peptides

    International Nuclear Information System (INIS)

    Anderson, C.W.

    1982-01-01

    The author has used the sequence analysis of radioactive proteins and peptides to approach several problems during the past few years. They, in collaboration with others, have mapped precisely several adenovirus proteins with respect to the nucleotide sequence of the adenovirus genome; identified hitherto missed proteins encoded by bacteriophage MS2 and by simian virus 40; analyzed the aminoterminal maturation of several virus proteins; determined the cleavage sites for processing of the poliovirus polyprotein; and analyzed the mechanism of frameshifting by excess normal tRNAs during cell-free protein synthesis. This chapter is designed to aid those without prior experience at protein sequence determinations. It is based primarily on the experience gained in the studies cited above, which made use of the Beckman 890 series automated protein sequencers

  19. Studies on the sulfur metabolism of cows on protein-free and low-protein feed

    Directory of Open Access Journals (Sweden)

    Eino Matikkala

    1977-09-01

    Full Text Available The influence of purified, protein-free feed with urea and ammonium salts as nitrogen sources (0-feed and of non-purified, urea-rich, low-protein feeds (ULP-feed on the sulfur metabolism of cows has been studied by determining the contents of sulfur fractions in faeces, urine, milk, blood and rumen fluid. The sulfur of 0-feed was composed entirely of inorganic sulfate. During balance trials the N:S ratio in the feed varied from 6.1 to 9.5, and the sulfur content from 0.22 to 0.31 % of the dry matter. In every trial (seven with 0-feed and two with ULP-feed, of five or seven days duration, the cows were in high-positive sulfur balance. The 0-cows excreted a greater proportion of their total sulfur output via urine than the ULP-cows. The excretion of inorganic sulfate sulfur, as a proportion of the urinary and faecal sulfur, was greater for 0-cows than for ULP- or NorP-cows (cows on normal, protein-rich feed; the opposite was the case with regard to the excretion of ester sulfate sulfur and neutral sulfur. The sulfur contents of milk and blood showed only minor inter-feed differences. The sulfate content in the rumen fluid of the 0-cow rose rapidly after the commencement of feeding and then fell quite rapidly. We conclude tentatively that in the rumen of the 0-cow hydrogen sulfide is generated so quickly that the whole of it cannot be used for the synthesis of sulfur-containing compounds, a considerable proportion of it being lost in eructations or excreted as inorganic sulfates in the urine.

  20. Thioacetamide effects on protein metabolism in the liver: lessons from isolated hepatocytes

    International Nuclear Information System (INIS)

    Cajone, F.; Bernelli-Zazzera, A.

    1984-01-01

    The effects of a short-term treatment with thioacetamide have been studied in isolated hepatocytes obtained from intoxicated rats. A technique has been developed which utilizes leucine alternatively labeled with either [ 14 C] or [ 3 H] and permits the simultaneous evaluation of protein synthesis, catabolism and secretion in the same cell during the same incubation period. The results indicate that short-term thioacetamide treatment causes an overall slowing-down of protein metabolism. Protein synthesis, however, decreases less than protein degradation and total protein secretion; albumin secretion, which is also less than normal, seems to be less compromised than total protein secretion

  1. A diet containing whey protein, glutamine, and TGFbeta modulates gut protein metabolism during chemotherapy-induced mucositis in rats.

    Science.gov (United States)

    Boukhettala, Nabile; Ibrahim, Ayman; Claeyssens, Sophie; Faure, Magali; Le Pessot, Florence; Vuichoud, Jacques; Lavoinne, Alain; Breuillé, Denis; Déchelotte, Pierre; Coëffier, Moïse

    2010-08-01

    Mucositis, a common side effect of chemotherapy, is characterized by compromised digestive function, barrier integrity and immune competence. Our aim was to evaluate the impact of a specifically designed diet Clinutren Protect (CP), which contains whey proteins, TGFbeta-rich casein, and free glutamine, on mucositis in rats. Mucositis was induced by three consecutive injections (day 0, day 1, day 2) of methotrexate (2.5 mg/kg). Rats had free access to CP or placebo diets from days -7 to 9. In the placebo diet, whey proteins and TGFbeta-rich casein were replaced by TGFbeta-free casein and glutamine by alanine. Intestinal parameters were assessed at day 3 and 9. Values, expressed as mean +/- SEM, were compared using two-way ANOVA. At day 3, villus height was markedly decreased in the placebo (296 +/- 11 microm) and CP groups (360 +/- 10 microm) compared with controls (464 +/- 27 microm), but more markedly in the placebo as compared to CP group. The intestinal damage score was also reduced in the CP compared with the placebo group. Glutathione content increased in the CP compared with the placebo group (2.2 +/- 0.2 vs. 1.7 +/- 0.2 micromol/g tissue). Gut protein metabolism was more affected in the placebo than in the CP group. The fractional synthesis rate was decreased in the placebo group (93.8 +/- 4.9%/day) compared with controls (121.5 +/- 12.1, P < 0.05), but not in the CP group (106.0 +/- 13.1). In addition, at day 9, rats exhibited improved body weight and food intake recovery in the CP compared to the placebo group. Clinutren Protect feeding reduces intestinal injury in the acute phase of methotrexate-induced mucositis in rats and improves recovery.

  2. Integrating the protein and metabolic engineering toolkits for next-generation chemical biosynthesis.

    Science.gov (United States)

    Pirie, Christopher M; De Mey, Marjan; Jones Prather, Kristala L; Ajikumar, Parayil Kumaran

    2013-04-19

    Through microbial engineering, biosynthesis has the potential to produce thousands of chemicals used in everyday life. Metabolic engineering and synthetic biology are fields driven by the manipulation of genes, genetic regulatory systems, and enzymatic pathways for developing highly productive microbial strains. Fundamentally, it is the biochemical characteristics of the enzymes themselves that dictate flux through a biosynthetic pathway toward the product of interest. As metabolic engineers target sophisticated secondary metabolites, there has been little recognition of the reduced catalytic activity and increased substrate/product promiscuity of the corresponding enzymes compared to those of central metabolism. Thus, fine-tuning these enzymatic characteristics through protein engineering is paramount for developing high-productivity microbial strains for secondary metabolites. Here, we describe the importance of protein engineering for advancing metabolic engineering of secondary metabolism pathways. This pathway integrated enzyme optimization can enhance the collective toolkit of microbial engineering to shape the future of chemical manufacturing.

  3. Genome-scale metabolic model of Pichia pastoris with native and humanized glycosylation of recombinant proteins.

    Science.gov (United States)

    Irani, Zahra Azimzadeh; Kerkhoven, Eduard J; Shojaosadati, Seyed Abbas; Nielsen, Jens

    2016-05-01

    Pichia pastoris is used for commercial production of human therapeutic proteins, and genome-scale models of P. pastoris metabolism have been generated in the past to study the metabolism and associated protein production by this yeast. A major challenge with clinical usage of recombinant proteins produced by P. pastoris is the difference in N-glycosylation of proteins produced by humans and this yeast. However, through metabolic engineering, a P. pastoris strain capable of producing humanized N-glycosylated proteins was constructed. The current genome-scale models of P. pastoris do not address native nor humanized N-glycosylation, and we therefore developed ihGlycopastoris, an extension to the iLC915 model with both native and humanized N-glycosylation for recombinant protein production, but also an estimation of N-glycosylation of P. pastoris native proteins. This new model gives a better prediction of protein yield, demonstrates the effect of the different types of N-glycosylation of protein yield, and can be used to predict potential targets for strain improvement. The model represents a step towards a more complete description of protein production in P. pastoris, which is required for using these models to understand and optimize protein production processes. © 2015 Wiley Periodicals, Inc.

  4. Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins

    Directory of Open Access Journals (Sweden)

    Khanichi N. Charles

    2017-10-01

    Full Text Available Summary: Deterioration of metabolic health is a hallmark of aging and generally assumed to be detrimental to longevity. Exposure to a high-calorie diet impairs metabolism and accelerates aging; conversely, calorie restriction (CR prevents age-related metabolic diseases and extends lifespan. However, it is unclear whether preservation of metabolic health is sufficient to extend lifespan. We utilized a genetic mouse model lacking Fabp4/5 that confers protection against metabolic diseases and shares molecular and lipidomic features with CR to address this question. Fabp-deficient mice exhibit extended metabolic healthspan, with protection against insulin resistance and glucose intolerance, inflammation, deterioration of adipose tissue integrity, and fatty liver disease. Surprisingly, however, Fabp-deficient mice did not exhibit any extension of lifespan. These data indicate that extension of metabolic healthspan in the absence of CR can be uncoupled from lifespan, indicating the potential for independent drivers of these pathways, at least in laboratory mice. : Deterioration of metabolic health is a hallmark of aging and generally thought to be detrimental to longevity. Charles et al. utilize FABP-deficient mice as a model to demonstrate that the preservation of metabolic health in this model persists throughout life, even under metabolic stress, but does not increase longevity. Keywords: fatty acid binding protein, aging, calorie restriction, metabolic health, inflammation, metaflammation, diabetes, obesity, de novo lipogenesis

  5. Perinatal exposure to perfluorooctane sulfonate affects glucose metabolism in adult offspring.

    Directory of Open Access Journals (Sweden)

    Hin T Wan

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

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

    Science.gov (United States)

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

    2017-08-01

    Adseverin is an actin-severing/capping protein that may contribute to osteoclast differentiation in vitro but its role in bone remodeling of healthy animals is not defined. We analyzed bone and osteoclast structure in adseverin conditional null mice at alveolar and long bone sites. In wild-type and adseverin null mice, as measured by dual-energy X-ray absorptiometry, there were no differences of bone mineral content or bone mineral density, indicating no change of bone metabolism. In tibiae, TRAcP + osteoclasts were formed in comparable numbers in adseverin null and wild-type mice. Ultrastructural analysis showed normal and similar abundance of ruffled borders, sealing zones, and mitochondria, and with no difference of osteoclast nuclear numbers. In contrast, analyses of long bone showed that in the absence of adseverin osteoclasts were smaller (120 ± 13 vs. 274 ± 19 µm 2 ; p structure but not to bone metabolism in vivo.

  7. Drought affects protein and phenolic content in bambara groundnut ...

    African Journals Online (AJOL)

    Bambara groundnut (Vigna subterranea L. Verdc.) is a legume crop, which has long been recognised as a protein-rich and drought-tolerant crop, used extensively in sub-Saharan Africa. This study evaluates the effect of experimental water deficit stress on total protein concentration, secondary protein structure and the total ...

  8. Metabolic flux profiling of recombinant protein secreting Pichia pastoris growing on glucose:methanol mixtures

    Science.gov (United States)

    2012-01-01

    Background The methylotrophic yeast Pichia pastoris has emerged as one of the most promising yeast hosts for the production of heterologous proteins. Mixed feeds of methanol and a multicarbon source instead of methanol as sole carbon source have been shown to improve product productivities and alleviate metabolic burden derived from protein production. Nevertheless, systematic quantitative studies on the relationships between the central metabolism and recombinant protein production in P. pastoris are still rather limited, particularly when growing this yeast on mixed carbon sources, thus hampering future metabolic network engineering strategies for improved protein production. Results The metabolic flux distribution in the central metabolism of P. pastoris growing on a mixed feed of glucose and methanol was analyzed by Metabolic Flux Analysis (MFA) using 13C-NMR-derived constraints. For this purpose, we defined new flux ratios for methanol assimilation pathways in P. pastoris cells growing on glucose:methanol mixtures. By using this experimental approach, the metabolic burden caused by the overexpression and secretion of a Rhizopus oryzae lipase (Rol) in P. pastoris was further analyzed. This protein has been previously shown to trigger the unfolded protein response in P. pastoris. A series of 13C-tracer experiments were performed on aerobic chemostat cultivations with a control and two different Rol producing strains growing at a dilution rate of 0.09 h−1 using a glucose:methanol 80:20 (w/w) mix as carbon source. The MFA performed in this study reveals a significant redistristribution of carbon fluxes in the central carbon metabolism when comparing the two recombinant strains vs the control strain, reflected in increased glycolytic, TCA cycle and NADH regeneration fluxes, as well as higher methanol dissimilation rates. Conclusions Overall, a further 13C-based MFA development to characterise the central metabolism of methylotrophic yeasts when growing on mixed

  9. Metabolic flux profiling of recombinant protein secreting Pichia pastoris growing on glucose:methanol mixtures

    Directory of Open Access Journals (Sweden)

    Jordà Joel

    2012-05-01

    Full Text Available Abstract Background The methylotrophic yeast Pichia pastoris has emerged as one of the most promising yeast hosts for the production of heterologous proteins. Mixed feeds of methanol and a multicarbon source instead of methanol as sole carbon source have been shown to improve product productivities and alleviate metabolic burden derived from protein production. Nevertheless, systematic quantitative studies on the relationships between the central metabolism and recombinant protein production in P. pastoris are still rather limited, particularly when growing this yeast on mixed carbon sources, thus hampering future metabolic network engineering strategies for improved protein production. Results The metabolic flux distribution in the central metabolism of P. pastoris growing on a mixed feed of glucose and methanol was analyzed by Metabolic Flux Analysis (MFA using 13C-NMR-derived constraints. For this purpose, we defined new flux ratios for methanol assimilation pathways in P. pastoris cells growing on glucose:methanol mixtures. By using this experimental approach, the metabolic burden caused by the overexpression and secretion of a Rhizopus oryzae lipase (Rol in P. pastoris was further analyzed. This protein has been previously shown to trigger the unfolded protein response in P. pastoris. A series of 13C-tracer experiments were performed on aerobic chemostat cultivations with a control and two different Rol producing strains growing at a dilution rate of 0.09 h−1 using a glucose:methanol 80:20 (w/w mix as carbon source. The MFA performed in this study reveals a significant redistristribution of carbon fluxes in the central carbon metabolism when comparing the two recombinant strains vs the control strain, reflected in increased glycolytic, TCA cycle and NADH regeneration fluxes, as well as higher methanol dissimilation rates. Conclusions Overall, a further 13C-based MFA development to characterise the central metabolism of methylotrophic

  10. Protein metabolism of prolific ewes during late gestation and early lactation

    NARCIS (Netherlands)

    Sebek, L.B.J.

    2001-01-01

    Subject headings: protein / metabolism / ewes

    Introduction of prolific crossbred ewes and a new protein evaluation system for ruminants, the DVE/OEB system, necessitate a reconsideration of ewe feeding strategies. The objective of this thesis is to investigate the amount

  11. Deep proteomics of mouse skeletal muscle enables quantitation of protein isoforms, metabolic pathways and transcription factors

    DEFF Research Database (Denmark)

    Deshmukh, Atul S; Murgia, Marta; Nagaraja, Nagarjuna

    2015-01-01

    Skeletal muscle constitutes 40% of individual body mass and plays vital roles in locomotion and whole-body metabolism. Proteomics of skeletal muscle is challenging due to highly abundant contractile proteins that interfere with detection of regulatory proteins. Using a state-of-the art mass...

  12. Adenylate kinase I does not affect cellular growth characteristics under normal and metabolic stress conditions.

    Science.gov (United States)

    de Bruin, Wieke; Oerlemans, Frank; Wieringa, Bé

    2004-07-01

    Adenylate kinase (AK)-catalyzed phosphotransfer is essential in the maintenance of cellular energetic economy in cells of fully differentiated tissues with highly variable energy demand, such as muscle and brain. To investigate if AK isoenzymes have a comparable function in the energy-demand management of proliferating cells, AK1 and AK1beta were expressed in mouse neuroblastoma N2a cells and in human colon carcinoma SW480 cells. Glucose deprivation, galactose feeding, and metabolic inhibitor tests revealed a differential energy dependency for these two cell lines. N2a cells showed a faster proliferation rate and strongest coupling to mitochondrial activity, SW480 proliferation was more dependent on glycolysis. Despite these differences, ectopic expression of AK1 or AK1beta did not affect their growth characteristics under normal conditions. Also, no differential effects were seen under metabolic stress upon treatment with mitochondrial and glycolytic inhibitors in in vitro culture or in solid tumors grown in vivo. Although many intimate connections have been revealed between cell death and metabolism, our results suggest that AK1- or AK1beta-mediated high-energy phosphoryl transfer is not a modulating factor in the survival of tumor cells during episodes of metabolic crisis.

  13. Comprehensive assessment of variables affecting metabolic control in patients with type 2 diabetes mellitus in Jordan.

    Science.gov (United States)

    Qteishat, Rola Reyad; Ghananim, Abdel Rahman Al

    2016-01-01

    The aim of the study was to identify variables affecting metabolic control among diabetic patients treated at diabetes and endocrine clinic in Jordan. A total of 200 patients were studied by using a cross sectional study design. Data were collected from patients' medical records, glycemic control tests and prestructured questionnaires about variables that were potentially important based on previous researches and clinical judgment: Adherence evaluation, Patients' knowledge about drug therapy and non-pharmacological therapy, Anxiety and depression, Beliefs about diabetes treatment (benefits and barriers of treatment), Knowledge about treatment goals, Knowledge about diabetes, Self efficacy, and Social support. The mean (±SD) age was 53.5 (±10.38) years and mean HbA1c was 8.4 (±1.95). In the multivariate analysis, education level, and self efficacy found to have significantly independent association with metabolic control (Pknowledge and high self efficacy was significant in patients with good metabolic control. Emphasizing the importance of continuous educational programs and improving the self efficacy as well, could warrant achieving good metabolic control. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Enise Bagci

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

  15. Synergizing metabolic flux analysis and nucleotide sugar metabolism to understand the control of glycosylation of recombinant protein in CHO cells

    LENUS (Irish Health Repository)

    Burleigh, Susan C

    2011-10-18

    Abstract Background The glycosylation of recombinant proteins can be altered by a range of parameters including cellular metabolism, metabolic flux and the efficiency of the glycosylation process. We present an experimental set-up that allows determination of these key processes associated with the control of N-linked glycosylation of recombinant proteins. Results Chinese hamster ovary cells (CHO) were cultivated in shake flasks at 0 mM glutamine and displayed a reduced growth rate, glucose metabolism and a slower decrease in pH, when compared to other glutamine-supplemented cultures. The N-linked glycosylation of recombinant human chorionic gonadotrophin (HCG) was also altered under these conditions; the sialylation, fucosylation and antennarity decreased, while the proportion of neutral structures increased. A continuous culture set-up was subsequently used to understand the control of HCG glycosylation in the presence of varied glutamine concentrations; when glycolytic flux was reduced in the absence of glutamine, the glycosylation changes that were observed in shake flask culture were similarly detected. The intracellular content of UDP-GlcNAc was also reduced, which correlated with a decrease in sialylation and antennarity of the N-linked glycans attached to HCG. Conclusions The use of metabolic flux analysis illustrated a case of steady state multiplicity, where use of the same operating conditions at each steady state resulted in altered flux through glycolysis and the TCA cycle. This study clearly demonstrated that the control of glycoprotein microheterogeneity may be examined by use of a continuous culture system, metabolic flux analysis and assay of intracellular nucleotides. This system advances our knowledge of the relationship between metabolic flux and the glycosylation of biotherapeutics in CHO cells and will be of benefit to the bioprocessing industry.

  16. Fibroblast activation protein (FAP as a novel metabolic target

    Directory of Open Access Journals (Sweden)

    Miguel Angel Sánchez-Garrido

    2016-10-01

    Conclusions: We conclude that pharmacological inhibition of FAP enhances levels of FGF21 in obese mice to provide robust metabolic benefits not observed in lean animals, thus validating this enzyme as a novel drug target for the treatment of obesity and diabetes.

  17. Metabolic Models of Protein Allocation Call for the Kinetome

    DEFF Research Database (Denmark)

    Nilsson, Avlant; Nielsen, Jens; Palsson, Bernhard

    2017-01-01

    The flux of metabolites in the living cell depend on enzyme activities. Recently, many metabolic phenotypes have been explained by computer models that incorporate enzyme activity data. To move further, the scientific community needs to measure the kinetics of all enzymes in a systematic way....

  18. The influence of a steroid hormone and of physical exercise on protein metabolism in rats

    International Nuclear Information System (INIS)

    Menschikowski, M.; Jung, K.; Junghans, P.; Petzke, K.J.; Albrecht, V.; Akademie der Wissenschaften der DDR, Potsdam

    1989-01-01

    The influence of an anabolic steroid hormone preparation and of a physical exercise training program was studied on the nitrogen and protein metabolism in rats with the help of the 15 N tracer technique and the emission spectrometric 15 N isotope analysis. For the determination of the dynamic parameters of the protein metabolism graphic (stochastic) and computer-aided compartmental methods wer compared. Using the area method as a stochastic approach the animals showed significant differences in the protein turnover parameters under the influence of hormone treatment and (or) physical stress by swimming exercise in comparison to the controls. (author)

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

    Science.gov (United States)

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

    2004-01-30

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

  20. The Gustatory Signaling Pathway and Bitter Taste Receptors Affect the Development of Obesity and Adipocyte Metabolism in Mice.

    Directory of Open Access Journals (Sweden)

    Bert Avau

    Full Text Available Intestinal chemosensory signaling pathways involving the gustatory G-protein, gustducin, and bitter taste receptors (TAS2R have been implicated in gut hormone release. Alterations in gut hormone profiles may contribute to the success of bariatric surgery. This study investigated the involvement of the gustatory signaling pathway in the development of diet-induced obesity and the therapeutic potential of targeting TAS2Rs to induce body weight loss. α-gustducin-deficient (α-gust-/- mice became less obese than wild type (WT mice when fed a high-fat diet (HFD. White adipose tissue (WAT mass was lower in α-gust-/- mice due to increased heat production as a result of increases in brown adipose tissue (BAT thermogenic activity, involving increased protein expression of uncoupling protein 1. Intra-gastric treatment of obese WT and α-gust-/- mice with the bitter agonists denatonium benzoate (DB or quinine (Q during 4 weeks resulted in an α-gustducin-dependent decrease in body weight gain associated with a decrease in food intake (DB, but not involving major changes in gut peptide release. Both WAT and 3T3-F442A pre-adipocytes express TAS2Rs. Treatment of pre-adipocytes with DB or Q decreased differentiation into mature adipocytes. In conclusion, interfering with the gustatory signaling pathway protects against the development of HFD-induced obesity presumably through promoting BAT activity. Intra-gastric bitter treatment inhibits weight gain, possibly by directly affecting adipocyte metabolism.

  1. Protein and lipid oxidation affect the viscoelasticity of whey protein layers at the oil-water interface

    NARCIS (Netherlands)

    Berton-Carabin, Claire C.; Schroder, Anja; Rovalino-Cordova, Ana; Schroën, Karin; Sagis, Leonard

    2016-01-01

    Protein and lipid oxidation are prevailing issues that negatively affect the nutritional and sensory quality of food emulsions. It is probable that such oxidative modifications affect the functional properties of proteins, and in particular their ability to form densely packed, interconnected

  2. Phytosterol supplementation does not affect plasma antioxidant capacity in patients with metabolic syndrome.

    Science.gov (United States)

    Sialvera, Theodora-Eirini; Koutelidakis, Antonios E; Richter, Dimitris J; Yfanti, Georgia; Kapsokefalou, Maria; Micha, Renata; Goumas, Giorgos; Diamantopoulos, Emmanouil; Zampelas, Antonis

    2013-02-01

    Several studies have observed decreased levels of lipophilic antioxidants after supplementation with phytosterols and stanols. The aim of this study was to examine the effect of phytosterol supplementation on plasma total antioxidant capacity in patients with metabolic syndrome. In a parallel arm, randomized placebo-controlled design, 108 patients with metabolic syndrome were assigned to consume yogurt beverage which provided 4 g of phytosterols per day or yogurt beverage without phytosterols. The duration of the study was 2 months and the patients in both groups followed their habitual westernized type diet. Blood samples were drawn at baseline and after 2 months, and the total antioxidant capacity of plasma was measured using the ferric reducing antioxidant power of plasma and oxygen radical absorbance capacity assays. After 2 months of intervention, plasma total antioxidant capacity did not differ between and within the intervention and the control groups. Phytosterol supplementation does not affect plasma antioxidant status.

  3. Investigation of protein and lipid metabolism in thyroid pathology using whole-body radiometry

    International Nuclear Information System (INIS)

    Gorobets, V.F.; Matveenko, E.G.

    1987-01-01

    Radiometry of the whole body and its organs was employed to study certain aspects of protein-aminoacid and lipid metabolism in patients with thyroid diseases. Metabolism of human serum 131 I-albumin was studied in 12 patients with neurocirculatory dystonia, in 13 patients with diffuse toxic goiter (in 10 before and after drug therapy) and in 9 controls. 75 Se-methionine aminoacid metabolism was investigated in 9 patients with toxic thyroid adenoma and in 13 controls. The body cell mass was determined in 82 patients with thyrotoxicosis by a measurable amount of 40 K. These data were compared with those of 249 healthy persons. An increase in catabolism of labeled albumin, intensification of labeled methionine metabolism at the tissue level, signs of a decrease in the total amount of metabolic albumin in the body were revealed. Intensification of protein metabolism resulted in a decrease in the body cell mass of these patients. After adequate therapy the above indices of protein metabolism in patients with thyrotoxicosis returned to normal. The assimilation of fatty acids and neutral fat was disturbed both in thyrotoxicosis and hypothyroidism

  4. Nitrogen metabolism and protozoa production rate in cattle fed on diet containing protected protein

    International Nuclear Information System (INIS)

    Singh, G.P.; Gupta, B.N.

    1992-01-01

    Nitrogen metabolism and protozoa production rate using 14 C-choline as marker were studied on 9 adult male crossbred (Tharparker x Brown Swiss) rumen fistulated animals divided into 3 groups (A, B and C). All the animals were fed concentrate mixture and wheatstraw. However, groundnut cake (GNC) in concentrate mixture was untreated in group A, 50 per cent formaldehyde treated in group B and 100 per cent formaldehyde treated in group C. Although, DM intake was similar in these groups but water intake was significantly (P<0.05) higher in control group. Total-N, ammonia-N and blood urea were significantly lower in group B and C as compared to group A. Apparent CP digestibility was not affected by addition of formaldehyde treated GNC at 50 and 100 per cent levels. However, N balances increased significantly (P<0.05) due to addition of protected protein in diet. Protozoal pool as well as production rate were significantly (P<0.01) decreased due to formaldehyde treatment of GNC protein. Thus addition of formaldehyde treated GNC in diets decreased ammonia and protozoa production but increased N retention in groups B and C. (author). 27 refs., 3 tabs., 2 figs

  5. The Protein Cost of Metabolic Fluxes: Prediction from Enzymatic Rate Laws and Cost Minimization.

    Directory of Open Access Journals (Sweden)

    Elad Noor

    2016-11-01

    Full Text Available Bacterial growth depends crucially on metabolic fluxes, which are limited by the cell's capacity to maintain metabolic enzymes. The necessary enzyme amount per unit flux is a major determinant of metabolic strategies both in evolution and bioengineering. It depends on enzyme parameters (such as kcat and KM constants, but also on metabolite concentrations. Moreover, similar amounts of different enzymes might incur different costs for the cell, depending on enzyme-specific properties such as protein size and half-life. Here, we developed enzyme cost minimization (ECM, a scalable method for computing enzyme amounts that support a given metabolic flux at a minimal protein cost. The complex interplay of enzyme and metabolite concentrations, e.g. through thermodynamic driving forces and enzyme saturation, would make it hard to solve this optimization problem directly. By treating enzyme cost as a function of metabolite levels, we formulated ECM as a numerically tractable, convex optimization problem. Its tiered approach allows for building models at different levels of detail, depending on the amount of available data. Validating our method with measured metabolite and protein levels in E. coli central metabolism, we found typical prediction fold errors of 4.1 and 2.6, respectively, for the two kinds of data. This result from the cost-optimized metabolic state is significantly better than randomly sampled metabolite profiles, supporting the hypothesis that enzyme cost is important for the fitness of E. coli. ECM can be used to predict enzyme levels and protein cost in natural and engineered pathways, and could be a valuable computational tool to assist metabolic engineering projects. Furthermore, it establishes a direct connection between protein cost and thermodynamics, and provides a physically plausible and computationally tractable way to include enzyme kinetics into constraint-based metabolic models, where kinetics have usually been ignored or

  6. Early postnatal low-protein nutrition, metabolic programming and the autonomic nervous system in adult life

    Directory of Open Access Journals (Sweden)

    de Oliveira Júlio

    2012-09-01

    Full Text Available Abstract Protein restriction during lactation has been used as a rat model of metabolic programming to study the impact of perinatal malnutrition on adult metabolism. In contrast to protein restriction during fetal life, protein restriction during lactation did not appear to cause either obesity or the hallmarks of metabolic syndrome, such as hyperinsulinemia, when individuals reached adulthood. However, protein restriction provokes body underweight and hypoinsulinemia. This review is focused on the regulation of insulin secretion and the influence of the autonomic nervous system (ANS in adult rats that were protein-malnourished during lactation. The data available on the topic suggest that the perinatal phase of lactation, when insulted by protein deficit, imprints the adult metabolism and thereby alters the glycemic control. Although hypoinsulinemia programs adult rats to maintain normoglycemia, pancreatic β-cells are less sensitive to secretion stimuli, such as glucose and cholinergic agents. These pancreatic dysfunctions may be attributed to an imbalance of ANS activity recorded in adult rats that experienced maternal protein restriction.

  7. Fibroblast activation protein (FAP) as a novel metabolic target

    DEFF Research Database (Denmark)

    Sánchez-Garrido, Miguel Angel; Habegger, Kirk M; Clemmensen, Christoffer

    2016-01-01

    to block FAP enzymatic activity. RESULTS: TB administration to diet-induced obese (DIO) animals led to profound decreases in body weight, reduced food consumption and adiposity, increased energy expenditure, improved glucose tolerance and insulin sensitivity, and lowered cholesterol levels. Total...... (TB), we explored the impact of FAP inhibition on metabolic regulation in mice. METHODS: To address this question we evaluated the pharmacology of TB in various mouse models including those deficient in FGF21, GLP1 and GIP signaling. We also studied the ability of FAP to process FGF21 in vitro and TB...... and intact plasma FGF21 were observed to be elevated in TB-treated DIO mice but not lean animals where the metabolic impact of TB was significantly attenuated. Furthermore, and in stark contrast to naïve DIO mice, the administration of TB to obese FGF21 knockout animals demonstrated no appreciable effect...

  8. Dim Light at Night Disrupts Molecular Circadian Rhythms and Affects Metabolism

    Science.gov (United States)

    Fonken, Laura K.; Aubrecht, Taryn G.; Meléndez-Fernández, O. Hecmarie; Weil, Zachary M.; Nelson, Randy J.

    2014-01-01

    With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms which are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electrical lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to nighttime light and investigated changes in the circadian system and body weight. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night attenuate core circadian clock rhythms in the SCN at both the gene and protein level. Moreover, circadian clock rhythms were perturbed in the liver by nighttime light exposure. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide mechanistic evidence for how mild changes in environmental lighting can alter circadian and metabolic function. PMID:23929553

  9. YEAST A SINGLE CELL PROTEIN: CHARACTERISTICS and METABOLISM

    OpenAIRE

    AMATA, I.A

    2013-01-01

    Most of the developing countries of the world are facing a major problem of malnutrition. Due to rapid growth in the population, food and feed scarcity are prevalent leading to a deficiency of protein and essential nutrients amongst human beings and livestock. It is therefore important to take necessary measures to stem this trend by increasing protein production and making it available and more affordable to the population by utilizing methods available for the production of alternative sour...

  10. Engineered proteins with PUF scaffold to manipulate RNA metabolism

    Science.gov (United States)

    Wang, Yang; Wang, Zefeng; Tanaka Hall, Traci M.

    2013-01-01

    Pumilio/fem-3 mRNA binding factor (FBF) proteins are characterized by a sequence-specific RNA-binding domain. This unique single-stranded RNA recognition module, whose sequence specificity can be reprogrammed, has been fused with functional modules to engineer protein factors with various functions. Here we summarize the advancement in developing RNA regulatory tools and opportunities for the future. PMID:23731364

  11. GlmS and NagB regulate amino sugar metabolism in opposing directions and affect Streptococcus mutans virulence.

    Directory of Open Access Journals (Sweden)

    Miki Kawada-Matsuo

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

  12. A novel family of small proteins that affect plant development

    Energy Technology Data Exchange (ETDEWEB)

    John Charles Walker

    2011-04-29

    The DVL genes represent a new group of plant proteins that influence plant growth and development. Overexpression of DVL1, and other members of the DVL family, causes striking phenotypic changes. The DVL proteins share sequence homology in their C-terminal half. Point mutations in the C-terminal domain show it is necessary and deletion studies demonstrate the C-terminal domain is sufficient to confer the overexpression phenotypes. The phenotypes observed, and the conservation of the protein sequence in the plant kingdom, does suggest the DVL proteins have a role in modulating plant growth and development. Our working hypothesis is the DVL proteins function as regulators of cellular signaling pathways that control growth and development.

  13. Lipid Bilayer Composition Affects Transmembrane Protein Orientation and Function

    Directory of Open Access Journals (Sweden)

    Katie D. Hickey

    2011-01-01

    Full Text Available Sperm membranes change in structure and composition upon ejaculation to undergo capacitation, a molecular transformation which enables spermatozoa to undergo the acrosome reaction and be capable of fertilization. Changes to the membrane environment including lipid composition, specifically lipid microdomains, may be responsible for enabling capacitation. To study the effect of lipid environment on proteins, liposomes were created using lipids extracted from bull sperm membranes, with or without a protein (Na+ K+-ATPase or -amylase. Protein incorporation, function, and orientation were determined. Fluorescence resonance energy transfer (FRET confirmed protein inclusion in the lipid bilayer, and protein function was confirmed using a colourometric assay of phosphate production from ATP cleavage. In the native lipid liposomes, ATPase was oriented with the subunit facing the outer leaflet, while changing the lipid composition to 50% native lipids and 50% exogenous lipids significantly altered this orientation of Na+ K+-ATPase within the membranes.

  14. Deletion of GPR40 Impairs Glucose-Induced Insulin Secretion In Vivo in Mice Without Affecting Intracellular Fuel Metabolism in Islets

    Energy Technology Data Exchange (ETDEWEB)

    Alquier, Thierry; Peyot, Marie-Line; Latour, M. G.; Kebede, Melkam; Sorensen, Christina M.; Gesta, Stephane; Kahn, C. R.; Smith, Richard D.; Jetton, Thomas L.; Metz, Thomas O.; Prentki, Marc; Poitout, Vincent J.

    2009-11-01

    The G protein-coupled receptor GPR40 mediates fatty-acid potentiation of glucose-stimulated insulin secretion, but its contribution to insulin secretion in vivo and mechanisms of action remain uncertain. This study was aimed to ascertain whether GPR40 controls insulin secretion in vivo and modulates intracellular fuel metabolism in islets. We observed that glucose- and arginine-stimulated insulin secretion, assessed by hyperglycemic clamps, was decreased by approximately 60% in GPR40 knock-out (KO) fasted and fed mice, without changes in insulin sensitivity assessed by hyperinsulinemic-euglycemic clamps. Glucose and palmitate metabolism were not affected by GPR40 deletion. Lipid profiling revealed a similar increase in triglyceride and decrease in lysophosphatidylethanolamine species in WT and KO islets in response to palmitate. These results demonstrate that GPR40 regulates insulin secretion in vivo not only in response to fatty acids but also to glucose and arginine, without altering intracellular fuel metabolism.

  15. Testosterone affects hormone-sensitive lipase (HSL) activity and lipid metabolism in the left ventricle

    DEFF Research Database (Denmark)

    Langfort, Jozef; Jagsz, Slawomir; Dobrzyn, Pawel

    2010-01-01

    Fatty acids, which are the major cardiac fuel, are derived from lipid droplets stored in cardiomyocytes, among other sources. The heart expresses hormone-sensitive lipase (HSL), which regulates triglycerides (TG) breakdown, and the enzyme is under hormonal control. Evidence obtained from adipose...... levels, caused an inhibitory effect on carbohydrate metabolism in the heart, and elevated left ventricular phosphocreatine and ATP levels as compared to control rats. These data indicate that testosterone is involved in cardiac HSL activity regulation which, in turn, may affect cardiac lipid...

  16. Proteins involved in flor yeast carbon metabolism under biofilm formation conditions.

    Science.gov (United States)

    Moreno-García, Jaime; García-Martínez, Teresa; Moreno, Juan; Mauricio, Juan Carlos

    2015-04-01

    A lack of sugars during the production of biologically aged wines after fermentation of grape must causes flor yeasts to metabolize other carbon molecules formed during fermentation (ethanol and glycerol, mainly). In this work, a proteome analysis involving OFFGEL fractionation prior to LC/MS detection was used to elucidate the carbon metabolism of a flor yeast strain under biofilm formation conditions (BFC). The results were compared with those obtained under non-biofilm formation conditions (NBFC). Proteins associated to processes such as non-fermentable carbon uptake, the glyoxylate and TCA cycles, cellular respiration and inositol metabolism were detected at higher concentrations under BFC than under the reference conditions (NBFC). This study constitutes the first attempt at identifying the flor yeast proteins responsible for the peculiar sensory profile of biologically aged wines. A better metabolic knowledge of flor yeasts might facilitate the development of effective strategies for improved production of these special wines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Toxicokinetics of the food-toxin IQ in human placental perfusion is not affected by ABCG2 or xenobiotic metabolism

    DEFF Research Database (Denmark)

    Immonen, E; Kummu, M; Petsalo, A

    2010-01-01

    Metabolizing enzymes and transporters affect toxicokinetics of foreign compounds (e.g. drugs and carcinogens) in human placenta. The heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a food-borne carcinogen being metabolically activated by cytochrome P450 (CYP) enzymes, especial...

  18. The Endocannabinoid System Affects Myocardial Glucose Metabolism in the DOCA-Salt Model of Hypertension

    Directory of Open Access Journals (Sweden)

    Agnieszka Polak

    2018-03-01

    Full Text Available Background/Aims: Recent interest in the use of cannabinoids as therapeutic agents has revealed the involvement of the endogenous cannabinoid system (ECS in the regulation of the cardiovascular system in hypertension. Abnormalities in glucose metabolism and insulin action are commonly detected in hypertensive animals. Thus, potential antihypertensive drugs should be investigated with respect to modulation of glucose homeostasis. Therefore, the aim of the present study was to evaluate the effects of the ECS activation after chronic fatty acid amide hydrolase inhibitor (URB597 administration on plasma glucose and insulin concentrations as well as parameters of myocardial glucose metabolism in the deoxycorticosterone acetate (DOCA-salt hypertensive rats, an animal model of secondary hypertension. Methods: Hypertension was induced by DOCA (25mg/kg injections and addition of 1% NaCl in the drinking water for six weeks. Chronic activation of the ECS was performed by URB597 (1mg/kg injections for two weeks. We examined fasting plasma levels of insulin (ELISA, glucose and intramyocardial glycogen (colorimetric method. Expressions of glucose transporters (GLUT1, 4 and selected proteins engaged in GLUT translocation as well as glucose metabolism were determined using Western blotting. Results: Hypertension induced hypoinsulinemia with concomitant lack of significant changes in glycemia, reduced intramyocardial glycogen content and increased pyruvate dehydrogenase (PDH expression in the cardiac muscle. Importantly, chronic URB597 administration in the hypertensive rats increased insulin concentration, elevated plasmalemmal GLUT1 and GLUT4 expression and concomitantly improved myocardial glycogen storage. Conclusion: Chronic administration of fatty acid amide hydrolase (FAAH inhibitor has potential protective properties on myocardial glucose metabolism in hypertension.

  19. Effect of Prolonged Simulated Microgravity on Metabolic Proteins in Rat Hippocampus: Steps toward Safe Space Travel.

    Science.gov (United States)

    Wang, Yun; Javed, Iqbal; Liu, Yahui; Lu, Song; Peng, Guang; Zhang, Yongqian; Qing, Hong; Deng, Yulin

    2016-01-04

    Mitochondria are not only the main source of energy in cells but also produce reactive oxygen species (ROS), which result in oxidative stress when in space. This oxidative stress is responsible for energy imbalances and cellular damage. In this study, a rat tail suspension model was used in individual experiments for 7 and 21 days to explore the effect of simulated microgravity (SM) on metabolic proteins in the hippocampus, a vital brain region involved in learning, memory, and navigation. A comparative (18)O-labeled quantitative proteomic strategy was used to observe the differential expression of metabolic proteins. Forty-two and sixty-seven mitochondrial metabolic proteins were differentially expressed after 21 and 7 days of SM, respectively. Mitochondrial Complex I, III, and IV, isocitrate dehydrogenase and malate dehydrogenase were down-regulated. Moreover, DJ-1 and peroxiredoxin 6, which defend against oxidative damage, were up-regulated in the hippocampus. Western blot analysis of proteins DJ-1 and COX 5A confirmed the mass spectrometry results. Despite these changes in mitochondrial protein expression, no obvious cell apoptosis was observed after 21 days of SM. The results of this study indicate that the oxidative stress induced by SM has profound effects on metabolic proteins.

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

    Science.gov (United States)

    Mourtzakis, M; Graham, T E; González-Alonso, J; Saltin, B

    2008-08-01

    Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops approximately 40-80% with the onset of exercise and 2-oxoglutarate declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (VO2peak) in the T thigh was greater than that in the UT thigh (PTCA cycle intermediates. In the UT thigh, peak exercise (vs. rest) induced an increase in fumarate (0.33+/-0.07 vs. 0.02+/-0.01 mmol/kg dry wt (dw), PTCA cycle, glutamate and TCA cycle intermediates do not directly affect VO2peak in either trained or untrained muscle.

  1. The TIM Barrel Architecture Facilitated the Early Evolution of Protein-Mediated Metabolism.

    Science.gov (United States)

    Goldman, Aaron David; Beatty, Joshua T; Landweber, Laura F

    2016-01-01

    The triosephosphate isomerase (TIM) barrel protein fold is a structurally repetitive architecture that is present in approximately 10% of all enzymes. It is generally assumed that this ubiquity in modern proteomes reflects an essential historical role in early protein-mediated metabolism. Here, we provide quantitative and comparative analyses to support several hypotheses about the early importance of the TIM barrel architecture. An information theoretical analysis of protein structures supports the hypothesis that the TIM barrel architecture could arise more easily by duplication and recombination compared to other mixed α/β structures. We show that TIM barrel enzymes corresponding to the most taxonomically broad superfamilies also have the broadest range of functions, often aided by metal and nucleotide-derived cofactors that are thought to reflect an earlier stage of metabolic evolution. By comparison to other putatively ancient protein architectures, we find that the functional diversity of TIM barrel proteins cannot be explained simply by their antiquity. Instead, the breadth of TIM barrel functions can be explained, in part, by the incorporation of a broad range of cofactors, a trend that does not appear to be shared by proteins in general. These results support the hypothesis that the simple and functionally general TIM barrel architecture may have arisen early in the evolution of protein biosynthesis and provided an ideal scaffold to facilitate the metabolic transition from ribozymes, peptides, and geochemical catalysts to modern protein enzymes.

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

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    Lucie Šedová

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

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

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

    2016-05-11

    Flight is an essential biological ability of many insects, but is energetically costly. Environments under rapid human-induced change are characterized by habitat fragmentation and may impose constraints on the energy income budget of organisms. This may, in turn, affect locomotor performance and willingness to fly. We tested flight performance and metabolic rates in meadow brown butterflies (Maniola jurtina) of two contrasted agricultural landscapes: intensively managed, nectar-poor (IL) versus extensively managed, nectar-rich landscapes (EL). Young female adults were submitted to four nectar treatments (i.e. nectar quality and quantity) in outdoor flight cages. IL individuals had better flight capacities in a flight mill and had lower resting metabolic rates (RMR) than EL individuals, except under the severest treatment. Under this treatment, RMR increased in IL individuals, but decreased in EL individuals; flight performance was maintained by IL individuals, but dropped by a factor 2.5 in EL individuals. IL individuals had more canalized (i.e. less plastic) responses relative to the nectar treatments than EL individuals. Our results show significant intraspecific variation in the locomotor and metabolic response of a butterfly to different energy income regimes relative to the landscape of origin. Ecophysiological studies help to improve our mechanistic understanding of the eco-evolutionary impact of anthropogenic environments on rare and widespread species. © 2016 The Author(s).

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

    Science.gov (United States)

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

    2012-01-01

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

  6. Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease.

    Science.gov (United States)

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

    2015-01-01

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

  7. Effect of protein provision via milk replacer or solid feed on protein metabolism in veal calves

    DEFF Research Database (Denmark)

    Berends, H.; van den Borne, J. J G C; Røjen, B. A.

    2015-01-01

    recycling but urea reused for anabolism remained unaffected. Total-tract neutral detergent fiber digestibility decreased (-9%) with increasing low-N SF intake, indicating reduced rumen fermentation. Increasing the N content of SF at equal total N intake resulted in decreased urea production, excretion......The current study evaluated the effects of protein provision to calves fed a combination of solid feed (SF) and milk replacer (MR) at equal total N intake on urea recycling and N retention. Nitrogen balance traits and [15N2]urea kinetics were measured in 30 calves (23 wk of age, 180±3.7kg of body...... of calves for 5 d, and for the assessment of urea recycling from [15N2]urea kinetics. Increasing low-N SF intake at equal total N intake resulted in a shift from urinary to fecal N excretion but did not affect protein retention (0.71g of N·kg of BW-0.75·d-1). Increasing low-N SF intake increased urea...

  8. Pathophysiological changes that affect drug disposition in protein-energy malnourished children

    Directory of Open Access Journals (Sweden)

    Oshikoya Kazeem A

    2009-12-01

    Full Text Available Abstract Protein-energy malnutrition (PEM is a major public health problem affecting a high proportion of infants and older children world-wide and accounts for a high childhood morbidity and mortality in the developing countries. The epidemiology of PEM has been extensively studied globally and management guidelines formulated by the World Health Organization (WHO. A wide spectrum of infections such as measles, malaria, acute respiratory tract infection, intestinal parasitosis, tuberculosis and HIV/AIDS may complicate PEM with two or more infections co-existing. Thus, numerous drugs may be required to treat the patients. In-spite of abundant literature on the epidemiology and management of PEM, focus on metabolism and therapeutic drug monitoring is lacking. A sound knowledge of pathophysiology of PEM and pharmacology of the drugs frequently used for their treatment is required for safe and rational treatment. In this review, we discuss the pathophysiological changes in children with PEM that may affect the disposition of drugs frequently used for their treatment. This review has established abnormal disposition of drugs in children with PEM that may require dosage modification. However, the relevance of these abnormalities to the clinical management of PEM remains inconclusive. At present, there are no good indications for drug dosage modification in PEM; but for drug safety purposes, further studies are required to accurately determine dosages of drugs frequently used for children with PEM.

  9. Role of Heme and Heme-Proteins in Trypanosomatid Essential Metabolic Pathways

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    Karina E. J. Tripodi

    2011-01-01

    Full Text Available Around the world, trypanosomatids are known for being etiological agents of several highly disabling and often fatal diseases like Chagas disease (Trypanosoma cruzi, leishmaniasis (Leishmania spp., and African trypanosomiasis (Trypanosoma brucei. Throughout their life cycle, they must cope with diverse environmental conditions, and the mechanisms involved in these processes are crucial for their survival. In this review, we describe the role of heme in several essential metabolic pathways of these protozoans. Notwithstanding trypanosomatids lack of the complete heme biosynthetic pathway, we focus our discussion in the metabolic role played for important heme-proteins, like cytochromes. Although several genes for different types of cytochromes, involved in mitochondrial respiration, polyunsaturated fatty acid metabolism, and sterol biosynthesis, are annotated at the Tritryp Genome Project, the encoded proteins have not yet been deeply studied. We pointed our attention into relevant aspects of these protein functions that are amenable to be considered for rational design of trypanocidal agents.

  10. Association between C-reactive protein and features of the metabolic syndrome

    DEFF Research Database (Denmark)

    Fröhlich, M; Imhof, A; Berg, Gabriele

    2000-01-01

    OBJECTIVE: To assess the association of circulating levels of C-reactive protein, a sensitive systemic marker of inflammation, with different components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: Total cholesterol (TC), HDL cholesterol, triglycerides, uric acid, BMI , and prevalence...... concentrations in subjects grouped according to the presence of 0-1, 2-3, and > or =4 features of the metabolic syndrome were 1.11, 1.27, and 2.16 mg/l, respectively, with a statistically highly significant trend (P metabolic syndrome...

  11. The effects of wet cupping on serum high-sensitivity C-reactive protein and heat shock protein 27 antibody titers in patients with metabolic syndrome.

    Science.gov (United States)

    Farahmand, Seyed Kazem; Gang, Li Zhi; Saghebi, Seyed Ahmad; Mohammadi, Maryam; Mohammadi, Shabnam; Mohammadi, Ghazaleh; Ferns, Gordan A; Ghanbarzadeh, Majid; Razmgah, Gholamreza Ghayour; Ramazani, Zahra; Ghayour-Mobarhan, Majid; Esmaily, Habibollah; Bahrami Taghanaki, Hamidreza; Azizi, Hoda

    2014-08-01

    It has previously been reported that increased level of serum heat shock proteins (Hsps) antibody in patients with metabolic syndrome. It is possible that the expression of Hsp and inflammatory markers can be affected by cupping and traditional Chinese medicine. There is a little data investigating the effects of cupping on markers of inflammation and Hsp proteins, hence, the objective of this study was evaluation of the effects of wet cupping on serum high-sensitivity C-reactive protein (hs-CRP) and Hsp27 antibody titers in patients with metabolic syndrome. Serum Hs-CRP and Hsp27 antibody titers were assessed in samples from 126 patients with metabolic syndrome (18-65 years of age) at baseline, and after 6 and 12 weeks after treatment. One hundred and twenty-six patients were randomly divided into the experimental group treated with wet cupping combined with dietary advice, and the control group treated with dietary advice alone using a random number table. Eight patients in case group and five subjects in control groups were excluded from the study. Data were analyzed using SPSS 15.0 software and a repeated measure ANCOVA. Serum hs-CRP titers did not change significantly between groups (p>0.05) and times (p=0.27). The same result was found for Hsp27 titers (p>0.05). Wet-cupping on the interscapular region has no effect on serum hs-CRP and Hsp27 patients with metabolic syndrome. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Metabolic responses to high protein diet in Korean elite bodybuilders with high-intensity resistance exercise

    Directory of Open Access Journals (Sweden)

    Choue Ryowon

    2011-07-01

    Full Text Available Abstract Background High protein diet has been known to cause metabolic acidosis, which is manifested by increased urinary excretion of nitrogen and calcium. Bodybuilders habitually consumed excessive dietary protein over the amounts recommended for them to promote muscle mass accretion. This study investigated the metabolic response to high protein consumption in the elite bodybuilders. Methods Eight elite Korean bodybuilders within the age from 18 to 25, mean age 21.5 ± 2.6. For data collection, anthropometry, blood and urinary analysis, and dietary assessment were conducted. Results They consumed large amounts of protein (4.3 ± 1.2 g/kg BW/day and calories (5,621.7 ± 1,354.7 kcal/day, as well as more than the recommended amounts of vitamins and minerals, including potassium and calcium. Serum creatinine (1.3 ± 0.1 mg/dl and potassium (5.9 ± 0.8 mmol/L, and urinary urea nitrogen (24.7 ± 9.5 mg/dl and creatinine (2.3 ± 0.7 mg/dl were observed to be higher than the normal reference ranges. Urinary calcium (0.3 ± 0.1 mg/dl, and phosphorus (1.3 ± 0.4 mg/dl were on the border of upper limit of the reference range and the urine pH was in normal range. Conclusions Increased urinary excretion of urea nitrogen and creatinine might be due to the high rates of protein metabolism that follow high protein intake and muscle turnover. The obvious evidence of metabolic acidosis in response to high protein diet in the subjects with high potassium intake and intensive resistance exercise were not shown in this study results. However, this study implied that resistance exercise with adequate mineral supplementation, such as potassium and calcium, could reduce or offset the negative effects of protein-generated metabolic changes. This study provides preliminary information of metabolic response to high protein intake in bodybuilders who engaged in high-intensity resistance exercise. Further studies will be needed to determine the effects of the intensity

  13. Metabolism of homologous and heterologous serum proteins in garter snakes (Thamnophis ordinoides)

    International Nuclear Information System (INIS)

    Leong, D.; Coe, J.E.

    1978-01-01

    The half-life (Tsub(1/2) of serum immunoglobulin (Ig) and albumin from snakes and mammals were determined in both garter snakes (Thamnophis ordinoides) and mice (Mus musculus). Metabolism of serum proteins in snakes was similar to mammalian protein metabolism in that homologous serum albumin had shorter Tsub(1/2) (16 days) than IgG (38 days). Also, reptilian and mammalian serum proteins had a relatively longer Tsub(1/2) when injected into closely related species. Thus mammalian serum Ig (rabbit gamma globulin (RGG)) had a shorter Tsub(1/2) (6.3 days) in snake than did homologous snake IgG (38 days), whereas in mice, RGG had a longer Tsub(1/2) (3.8 days) than snake Ig (0.9 days). Differences between metabolism of homologous and heterologous albumins were apparent only in snakes in which the Tsub(1/2) of homologous albumin was approximately 8-fold greater than mammalian albumin. These results indicate that metabolism of both Ig and albumin in snakes is regulated by specific receptors whereas albumin receptors have been difficult to demonstrate in mammals. The results of this study suggest that one of the factors determining the metabolism of a protein is its foreignness to the host perhaps because of receptor cross reactions. (author)

  14. The Role of Maternal Dietary Proteins in Development of Metabolic Syndrome in Offspring

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    Alireza Jahan-Mihan

    2015-11-01

    Full Text Available The prevalence of metabolic syndrome and obesity has been increasing. Pre-natal environment has been suggested as a factor influencing the risk of metabolic syndrome in adulthood. Both observational and experimental studies showed that maternal diet is a major modifier of the development of regulatory systems in the offspring in utero and post-natally. Both protein content and source in maternal diet influence pre- and early post-natal development. High and low protein dams’ diets have detrimental effect on body weight, blood pressure191 and metabolic and intake regulatory systems in the offspring. Moreover, the role of the source of protein in a nutritionally adequate maternal diet in programming of food intake regulatory system, body weight, glucose metabolism and blood pressure in offspring is studied. However, underlying mechanisms are still elusive. The purpose of this review is to examine the current literature related to the role of proteins in maternal diets in development of characteristics of the metabolic syndrome in offspring.

  15. Female hormones: do they influence muscle and tendon protein metabolism?

    DEFF Research Database (Denmark)

    Hansen, Mette

    2018-01-01

    (or lack of female hormones) on skeletal muscle protein turnover at rest and in response to exercise. This review is primarily based on data from human trials. Many elderly post-menopausal women experience physical disabilities and loss of independence related to sarcopenia, which reduces life quality...

  16. Effects of atorvastatin on human c reactive protein metabolism

    Science.gov (United States)

    Statins are known to reduce plasma C-reactive protein (CRP) concentrations. Our goals were to define the mechanisms by which CRP was reduced by maximal dose atorvastatin. Eight subjects with combined hyperlipidemia (5 men and 3 postmenopausal women) were enrolled in a randomized, placebo-controlled...

  17. Regulation of triglyceride metabolism by angiopoietin-like proteins

    NARCIS (Netherlands)

    Mattijssen, F.B.J.; Kersten, A.H.

    2012-01-01

    asma triglyceride concentrations are determined by the balance between production of the triglyceride-rich lipoproteins VLDL and chylomicrons in liver and intestine, and their lipoprotein lipase-mediated clearance in peripheral tissues. In the last decade, the group of Angiopoietin-like proteins has

  18. Control of Secreted Protein Gene Expression and the Mammalian Secretome by the Metabolic Regulator PGC-1α.

    Science.gov (United States)

    Minsky, Neri; Roeder, Robert G

    2017-01-06

    Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes, and signal molecules. However, how the secretome is regulated remains incompletely understood. Here we demonstrate, unexpectedly, that peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate the expression of diverse genes encoding secreted molecules and extracellular matrix components to modulate the secretome. Using cell lines, primary cells, and mice, we show that both endogenous and exogenous PGC-1α down-regulate the expression of numerous genes encoding secreted molecules. Mechanistically, results obtained using mRNA stability measurements as well as intronic RNA expression analysis are consistent with a transcriptional effect of PGC-1α on the expression of genes encoding secreted proteins. Interestingly, PGC-1α requires the central heat shock response regulator heat shock factor protein 1 (HSF1) to affect some of its targets, and both factors co-reside on several target genes encoding secreted molecules in cells. Finally, using a mass spectrometric analysis of secreted proteins, we demonstrate that PGC-1α modulates the secretome of mouse embryonic fibroblasts. Our results define a link between a key pathway controlling metabolic regulation and the regulation of the mammalian secretome. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Litter environment affects behavior and brain metabolic activity of adult knockout mice

    Directory of Open Access Journals (Sweden)

    David Crews

    2009-08-01

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

  20. Nonsense mutations in the human β-globin gene affect mRNA metabolism

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  1. Factors affecting the separation performance of proteins in capillary electrophoresis.

    Science.gov (United States)

    Zhu, Yueping; Li, Zhenqing; Wang, Ping; Shen, Lisong; Zhang, Dawei; Yamaguchi, Yoshinori

    2018-04-15

    Capillary electrophoresis (CE) is an effective tool for protein separation and analysis. Compared with capillary gel electrophoresis (CGE), non-gel sieving capillary electrophoresis (NGSCE) processes the superiority on operation, repeatability and automaticity. Herein, we investigated the effect of polymer molecular weight and concentration, electric field strength, and the effective length of the capillary on the separation performance of proteins, and find that (1) polymer with high molecular weight and concentration favors the separation of proteins, although concentrated polymer hinders its injection into the channel of the capillary due to its high viscosity. (2) The resolution between the adjacent proteins decreases with the increase of electric field strength. (3) When the effective length of the capillary is long, the separation performance improves at the cost of separation time. (4) 1.4% (w/v) hydroxyethyl cellulose (HEC), 100 V/cm voltage and 12 cm effective length offers the best separation for the proteins with molecular weight from 14,400 Da to 97,400 Da. Finally, we employed the optimal electrophoretic conditions to resolve Lysozyme, Ovalbumin, BSA and their mixtures, and found that they were baseline resolved within 15 min. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Deep proteomics of mouse skeletal muscle enables quantitation of protein isoforms, metabolic pathways, and transcription factors.

    Science.gov (United States)

    Deshmukh, Atul S; Murgia, Marta; Nagaraj, Nagarjuna; Treebak, Jonas T; Cox, Jürgen; Mann, Matthias

    2015-04-01

    Skeletal muscle constitutes 40% of individual body mass and plays vital roles in locomotion and whole-body metabolism. Proteomics of skeletal muscle is challenging because of highly abundant contractile proteins that interfere with detection of regulatory proteins. Using a state-of-the art MS workflow and a strategy to map identifications from the C2C12 cell line model to tissues, we identified a total of 10,218 proteins, including skeletal muscle specific transcription factors like myod1 and myogenin and circadian clock proteins. We obtain absolute abundances for proteins expressed in a muscle cell line and skeletal muscle, which should serve as a valuable resource. Quantitation of protein isoforms of glucose uptake signaling pathways and in glucose and lipid metabolic pathways provides a detailed metabolic map of the cell line compared with tissue. This revealed unexpectedly complex regulation of AMP-activated protein kinase and insulin signaling in muscle tissue at the level of enzyme isoforms. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Motile hepatocellular carcinoma cells preferentially secret sugar metabolism regulatory proteins via exosomes.

    Science.gov (United States)

    Zhang, Jing; Lu, Shaohua; Zhou, Ye; Meng, Kun; Chen, Zhipeng; Cui, Yizhi; Shi, Yunfeng; Wang, Tong; He, Qing-Yu

    2017-07-01

    Exosomes are deliverers of critically functional proteins, capable of transforming target cells in numerous cancers, including hepatocellular carcinoma (HCC). We hypothesize that the motility of HCC cells can be featured by comparative proteome of exosomes. Hence, we performed the super-SILAC-based MS analysis on the exosomes secreted by three human HCC cell lines, including the non-motile Hep3B cell, and the motile 97H and LM3 cells. More than 1400 exosomal proteins were confidently quantified in each MS analysis with highly biological reproducibility. We justified that 469 and 443 exosomal proteins represented differentially expressed proteins (DEPs) in the 97H/Hep3B and LM3/Hep3B comparisons, respectively. These DEPs focused on sugar metabolism-centric canonical pathways per ingenuity pathway analysis, which was consistent with the gene ontology analysis on biological process enrichment. These pathways included glycolysis I, gluconeogenesis I and pentose phosphate pathways; and the DEPs enriched in these pathways could form a tightly connected network. By analyzing the relative abundance of proteins and translating mRNAs, we found significantly positive correlation between exosomes and cells. The involved exosomal proteins were again focusing on sugar metabolism. In conclusion, motile HCC cells tend to preferentially export more sugar metabolism-associated proteins via exosomes that differentiate them from non-motile HCC cells. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-02-01

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

  5. Methodical investigation of the protein metabolism and of the bioenergetics of the protein retention in growing animals. 2

    International Nuclear Information System (INIS)

    Voelker, T.; Krawielitzki, K.; Klein, M.; Keller, J.

    1983-01-01

    The amino acid composition of the proteins in selected body fractions of chickens and the 15 N -excess of amino acids isolated from them resulting from a feeding experiment with long-term 15 NH 4 -acetate labelling were determined. The amino acid spectra of feathers, breast and leg muscles are characterized by differences in the content of individual amino acids specific for the organs, the composition of the proteins, however, is independent of the protein content of the ration and the age of the animals. The sarcoplasmatic and myofibrillar proteins also have typical amino acid patterns, which-with the exception of the histidine content-are neither influenced by the extraction of the proteins from the breast or leg muscles nor by the energy level of the feeding or the age of the animals. There are no significant differences in the metabolization of the main protein fraction of the breast and leg muscles. The oral supply of 15 N-ammonium acetate to broilers predominantly labels the non-essential amino acids so that the derived kinetic data chiefly represent the metabolism of the non-essential amino acids. (author)

  6. Digestion and microbial protein synthesis in sheep as affected by ...

    African Journals Online (AJOL)

    Useni , Alain

    enzyme (EFE) on the in vitro gas production (GP) and ANKOM digestion systems on the mixture of milled ... determine the EFE effect on the DM, CP and NDF digestion of a mixture of lucerne hay and wheat straw .... and the microbial protein synthesis (MPS) measured as purine derivates (RNA equivalent in µg/DM g) on.

  7. Factors affecting yeast growth and protein yield production from ...

    African Journals Online (AJOL)

    SERVER

    2008-02-05

    Feb 5, 2008 ... microbial protein which in turn can be used to upgrade both human and animal feeds. Studies to ... In many of the ... These include carbon and energy source .... The Candida sp. used for this study produced discrete colonies ...

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

    DEFF Research Database (Denmark)

    Li, C.B.; Li, J.; Zhou, G.H.

    2012-01-01

    The objective of this study was to investigate the response of sarcoplasmic proteins in bovine longissimus muscle to low-voltage electrical stimulation (ES, 80 V, 35 s) after dressing and its contribution to meat tenderization at early postmortem time. Proteome analysis showed that ES resulted...... muscles up to 24 h. Immunohistochemistry and transmission electron microscopy further indicated that lysosomal enzymes were released at early postmortem time. ES also induced ultrastructural disruption of sarcomeres. In addition, ES accelerated (P ..., as well as pH decline and more preferred pH/temperature decline mode. Finally, ES accelerated meat tenderization with lower (P time. A possible relationship was suggested between change in phosphorylation level of energy metabolic enzymes and postmortem...

  9. Programming of intermediate metabolism in young lambs affected by late gestational maternal undernourishment

    DEFF Research Database (Denmark)

    Husted, Sanne; Nielsen, Mette Olaf; Tygesen, Malin Plumhoff

    2007-01-01

    Effects of moderate maternal undernourishment during late gestation on the intermediary metabolism and maturational changes in young lambs were investigated. 20 twin-bearing sheep, bred to two different rams, were randomly allocated the last 6 wk of gestation to either a NORM diet [barley, protein...... supplement, and silage ad libitum ˜ 15 MJ metabolizable energy (ME/day] or a LOW diet (50% of ME intake in NORM, offered exclusively as silage ¨7 MJ ME/day). Post partum, ewes were fed to requirement. After weaning, lambs were fed concentrate and hay ad libitum. At 10 and 19 wk of age, lambs wee subjected...... to an intravenous glucose tolerance test (IGTT) followed by 24 h of fasting. Heat energy (HE) was determined in a respiration chamber at 9 or 20 wk of age. LOW lambs had a lower birth weight and continued to be lighter throughout the experiment. Glucose tolerance did not differ between groups. However, 19-wk...

  10. Identification of Proteins Involved in Carbohydrate Metabolism and Energy Metabolism Pathways and Their Regulation of Cytoplasmic Male Sterility in Wheat

    Directory of Open Access Journals (Sweden)

    Xingxia Geng

    2018-01-01

    Full Text Available Cytoplasmic male sterility (CMS where no functional pollen is produced has important roles in wheat breeding. The anther is a unique organ for male gametogenesis and its abnormal development can cause male sterility. However, the mechanisms and regulatory networks related to plant male sterility are poorly understood. In this study, we conducted comparative analyses using isobaric tags for relative and absolute quantification (iTRAQ of the pollen proteins in a CMS line and its wheat maintainer. Differentially abundant proteins (DAPs were analyzed based on Gene Ontology classifications, metabolic pathways and transcriptional regulation networks using Blast2GO. We identified 5570 proteins based on 23,277 peptides, which matched with 73,688 spectra, including proteins in key pathways such as glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase and 6-phosphofructokinase 1 in the glycolysis pathway, isocitrate dehydrogenase and citrate synthase in the tricarboxylic acid cycle and nicotinamide adenine dinucleotide (NADH-dehydrogenase and adenosine-triphosphate (ATP synthases in the oxidative phosphorylation pathway. These proteins may comprise a network that regulates male sterility in wheat. Quantitative real time polymerase chain reaction (qRT-PCR analysis, ATP assays and total sugar assays validated the iTRAQ results. These DAPs could be associated with abnormal pollen grain formation and male sterility. Our findings provide insights into the molecular mechanism related to male sterility in wheat.

  11. Identification of Proteins Involved in Carbohydrate Metabolism and Energy Metabolism Pathways and Their Regulation of Cytoplasmic Male Sterility in Wheat.

    Science.gov (United States)

    Geng, Xingxia; Ye, Jiali; Yang, Xuetong; Li, Sha; Zhang, Lingli; Song, Xiyue

    2018-01-23

    Cytoplasmic male sterility (CMS) where no functional pollen is produced has important roles in wheat breeding. The anther is a unique organ for male gametogenesis and its abnormal development can cause male sterility. However, the mechanisms and regulatory networks related to plant male sterility are poorly understood. In this study, we conducted comparative analyses using isobaric tags for relative and absolute quantification (iTRAQ) of the pollen proteins in a CMS line and its wheat maintainer. Differentially abundant proteins (DAPs) were analyzed based on Gene Ontology classifications, metabolic pathways and transcriptional regulation networks using Blast2GO. We identified 5570 proteins based on 23,277 peptides, which matched with 73,688 spectra, including proteins in key pathways such as glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase and 6-phosphofructokinase 1 in the glycolysis pathway, isocitrate dehydrogenase and citrate synthase in the tricarboxylic acid cycle and nicotinamide adenine dinucleotide (NADH)-dehydrogenase and adenosine-triphosphate (ATP) synthases in the oxidative phosphorylation pathway. These proteins may comprise a network that regulates male sterility in wheat. Quantitative real time polymerase chain reaction (qRT-PCR) analysis, ATP assays and total sugar assays validated the iTRAQ results. These DAPs could be associated with abnormal pollen grain formation and male sterility. Our findings provide insights into the molecular mechanism related to male sterility in wheat.

  12. Influence of culture conditions on growth and protein metabolism in chlorella pyranosides

    International Nuclear Information System (INIS)

    Mazon Matanzo, M. P.; Fernandez Gonzalez, J.; Batuecas Suarez, B.

    1981-01-01

    Growth and protein metabolism of Chlorella pyranoside under different conditions of temperature, photo period and CO 2 concentration was studied. The optimum of biomass production was observed at 25 degree centigree, 40.000 ppm of CO 2 in air and a 20 h. light period, followed of 4 h. of darkness. Some variations in free aminoacids content was observed under different conditions but no change did occur in protein. (Author) 68 refs

  13. Influence of culture conditions on growth and protein metabolism in chlorella pyrenoidosa

    International Nuclear Information System (INIS)

    Fernandez Gonzalez, J.; Mazon, M.P.; Batuecas, B.

    1981-01-01

    Growth and protein metabolism of chlorella pyrenoidosa under differents conditions of temperature, photoperiod and CO 2 concentration was studied. The optimum of biomas production was observed at 25 deg C, 40.000 ppm of CO 2 in air and a 20 h. light period, followed of 4 h. of darkness. Some variations in free aminoacids content was observed under differents conditions but no change did occur in protein. (author)

  14. Association between C-reactive protein and features of the metabolic syndrome

    DEFF Research Database (Denmark)

    Fröhlich, M; Imhof, A; Berg, Gabriele

    2000-01-01

    OBJECTIVE: To assess the association of circulating levels of C-reactive protein, a sensitive systemic marker of inflammation, with different components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: Total cholesterol (TC), HDL cholesterol, triglycerides, uric acid, BMI , and prevalence...... C-reactive protein and TC (R = 0.19), TG (R = 0.29), BMI (R = 0.32), glucose (R = 0.11), and uric acid (R = 0.14) (all P

  15. Effects of Dairy Protein and Fat on the Metabolic Syndrome and Type 2 Diabetes

    OpenAIRE

    Bjørnshave, Ann; Hermansen, Kjeld

    2014-01-01

    The incidence of the metabolic syndrome (MetS) and type 2 diabetes (T2D) is increasing worldwide. Evidence supports a negative relationship between the consumption of dairy products and risk of MetS and T2D. Dairy proteins are known to have a directly beneficial effect on hypertension, dyslipidemia, and hyperglycemia, but a detailed understanding of the underlying mechanisms is missing. It has been confirmed by observations that the insulinotropic effect of dairy proteins is associated with t...

  16. Perinatal protein malnutrition affects mitochondrial function in adult and results in a resistance to high fat diet-induced obesity.

    Science.gov (United States)

    Jousse, Céline; Muranishi, Yuki; Parry, Laurent; Montaurier, Christophe; Even, Patrick; Launay, Jean-Marie; Carraro, Valérie; Maurin, Anne-Catherine; Averous, Julien; Chaveroux, Cédric; Bruhat, Alain; Mallet, Jacques; Morio, Béatrice; Fafournoux, Pierre

    2014-01-01

    Epidemiological findings indicate that transient environmental influences during perinatal life, especially nutrition, may have deleterious heritable health effects lasting for the entire life. Indeed, the fetal organism develops specific adaptations that permanently change its physiology/metabolism and that persist even in the absence of the stimulus that initiated them. This process is termed "nutritional programming". We previously demonstrated that mothers fed a Low-Protein-Diet (LPD) during gestation and lactation give birth to F1-LPD animals presenting metabolic consequences that are different from those observed when the nutritional stress is applied during gestation only. Compared to control mice, adult F1-LPD animals have a lower body weight and exhibit a higher food intake suggesting that maternal protein under-nutrition during gestation and lactation affects the energy metabolism of F1-LPD offspring. In this study, we investigated the origin of this apparent energy wasting process in F1-LPD and demonstrated that minimal energy expenditure is increased, due to both an increased mitochondrial function in skeletal muscle and an increased mitochondrial density in White Adipose Tissue. Importantly, F1-LPD mice are protected against high-fat-diet-induced obesity. Clearly, different paradigms of exposure to malnutrition may be associated with differences in energy expenditure, food intake, weight and different susceptibilities to various symptoms associated with metabolic syndrome. Taken together these results demonstrate that intra-uterine environment is a major contributor to the future of individuals and disturbance at a critical period of development may compromise their health. Consequently, understanding the molecular mechanisms may give access to useful knowledge regarding the onset of metabolic diseases.

  17. Perinatal protein malnutrition affects mitochondrial function in adult and results in a resistance to high fat diet-induced obesity.

    Directory of Open Access Journals (Sweden)

    Céline Jousse

    Full Text Available Epidemiological findings indicate that transient environmental influences during perinatal life, especially nutrition, may have deleterious heritable health effects lasting for the entire life. Indeed, the fetal organism develops specific adaptations that permanently change its physiology/metabolism and that persist even in the absence of the stimulus that initiated them. This process is termed "nutritional programming". We previously demonstrated that mothers fed a Low-Protein-Diet (LPD during gestation and lactation give birth to F1-LPD animals presenting metabolic consequences that are different from those observed when the nutritional stress is applied during gestation only. Compared to control mice, adult F1-LPD animals have a lower body weight and exhibit a higher food intake suggesting that maternal protein under-nutrition during gestation and lactation affects the energy metabolism of F1-LPD offspring. In this study, we investigated the origin of this apparent energy wasting process in F1-LPD and demonstrated that minimal energy expenditure is increased, due to both an increased mitochondrial function in skeletal muscle and an increased mitochondrial density in White Adipose Tissue. Importantly, F1-LPD mice are protected against high-fat-diet-induced obesity. Clearly, different paradigms of exposure to malnutrition may be associated with differences in energy expenditure, food intake, weight and different susceptibilities to various symptoms associated with metabolic syndrome. Taken together these results demonstrate that intra-uterine environment is a major contributor to the future of individuals and disturbance at a critical period of development may compromise their health. Consequently, understanding the molecular mechanisms may give access to useful knowledge regarding the onset of metabolic diseases.

  18. Molecular events in matrix protein metabolism in the aging kidney

    Science.gov (United States)

    Sataranatarajan, Kavithalakshmi; Feliers, Denis; Mariappan, Meenalakshmi M.; Lee, Hak Joo; Lee, Myung Ja; Day, Robert T.; Yalamanchili, Hima Bindu; Choudhury, Goutam G.; Barnes, Jeffrey L.; Van Remmen, Holly; Richardson, Arlan; Kasinath, Balakuntalam S.

    2018-01-01

    Summary We explored molecular events associated with aging-induced matrix changes in the kidney. C57BL6 mice were studied in youth, middle age, and old age. Albuminuria and serum cystatin C level (an index of glomerular filtration) increased with aging. Renal hypertrophy was evident in middle-aged and old mice and was associated with glomerulomegaly and increase in mesangial fraction occupied by extracellular matrix. Content of collagen types I and III and fibronectin was increased with aging; increment in their mRNA varied with the phase of aging. The content of ZEB1 and ZEB2, collagen type I transcription inhibitors, and their binding to the collagen type Iα2 promoter by ChIP assay also showed age-phase-specific changes. Lack of increase in mRNA and data from polysome assay suggested decreased degradation as a potential mechanism for kidney collagen type I accumulation in the middle-aged mice. These changes occurred with increment in TGFβ mRNA and protein and activation of its SMAD3 pathway; SMAD3 binding to the collagen type Iα2 promoter was also increased. TGFβ-regulated microRNAs (miRs) exhibited selective regulation. The renal cortical content of miR-21 and miR-200c, but not miR-192, miR-200a, or miR-200b, was increased with aging. Increased miR-21 and miR-200c contents were associated with reduced expression of their targets, Sprouty-1 and ZEB2, respectively. These data show that aging is associated with complex molecular events in the kidney that are already evident in the middle age and progress to old age. Agephase-specific regulation of matrix protein synthesis occurs and involves matrix protein-specific transcriptional and post-transcriptional mechanisms. PMID:23020145

  19. Cre-Mediated Stress Affects Sirtuin Expression Levels, Peroxisome Biogenesis and Metabolism, Antioxidant and Proinflammatory Signaling Pathways

    Science.gov (United States)

    Xiao, Yu; Karnati, Srikanth; Qian, Guofeng; Nenicu, Anca; Fan, Wei; Tchatalbachev, Svetlin; Höland, Anita; Hossain, Hamid; Guillou, Florian; Lüers, Georg H.; Baumgart-Vogt, Eveline

    2012-01-01

    Cre-mediated excision of loxP sites is widely used in mice to manipulate gene function in a tissue-specific manner. To analyze phenotypic alterations related to Cre-expression, we have used AMH-Cre-transgenic mice as a model system. Different Cre expression levels were obtained by investigation of C57BL/6J wild type as well as heterozygous and homozygous AMH-Cre-mice. Our results indicate that Cre-expression itself in Sertoli cells already has led to oxidative stress and lipid peroxidation (4-HNE lysine adducts), inducing PPARα/γ, peroxisome proliferation and alterations of peroxisome biogenesis (PEX5, PEX13 and PEX14) as well as metabolic proteins (ABCD1, ABCD3, MFP1, thiolase B, catalase). In addition to the strong catalase increase, a NRF2- and FOXO3-mediated antioxidative response (HMOX1 of the endoplasmic reticulum and mitochondrial SOD2) and a NF-κB activation were noted. TGFβ1 and proinflammatory cytokines like IL1, IL6 and TNFα were upregulated and stress-related signaling pathways were induced. Sertoli cell mRNA-microarray analysis revealed an increase of TNFR2-signaling components. 53BP1 recruitment and expression levels for DNA repair genes as well as for p53 were elevated and the ones for related sirtuin deacetylases affected (SIRT 1, 3-7) in Sertoli cells. Under chronic Cre-mediated DNA damage conditions a strong downregulation of Sirt1 was observed, suggesting that the decrease of this important coordinator between DNA repair and metabolic signaling might induce the repression release of major transcription factors regulating metabolic and cytokine-mediated stress pathways. Indeed, caspase-3 was activated and increased germ cell apoptosis was observed, suggesting paracrine effects. In conclusion, the observed wide stress-induced effects and metabolic alterations suggest that it is essential to use the correct control animals (Cre/Wt) with matched Cre expression levels to differentiate between Cre-mediated and specific gene-knock out

  20. Cre-mediated stress affects sirtuin expression levels, peroxisome biogenesis and metabolism, antioxidant and proinflammatory signaling pathways.

    Directory of Open Access Journals (Sweden)

    Yu Xiao

    Full Text Available Cre-mediated excision of loxP sites is widely used in mice to manipulate gene function in a tissue-specific manner. To analyze phenotypic alterations related to Cre-expression, we have used AMH-Cre-transgenic mice as a model system. Different Cre expression levels were obtained by investigation of C57BL/6J wild type as well as heterozygous and homozygous AMH-Cre-mice. Our results indicate that Cre-expression itself in Sertoli cells already has led to oxidative stress and lipid peroxidation (4-HNE lysine adducts, inducing PPARα/γ, peroxisome proliferation and alterations of peroxisome biogenesis (PEX5, PEX13 and PEX14 as well as metabolic proteins (ABCD1, ABCD3, MFP1, thiolase B, catalase. In addition to the strong catalase increase, a NRF2- and FOXO3-mediated antioxidative response (HMOX1 of the endoplasmic reticulum and mitochondrial SOD2 and a NF-κB activation were noted. TGFβ1 and proinflammatory cytokines like IL1, IL6 and TNFα were upregulated and stress-related signaling pathways were induced. Sertoli cell mRNA-microarray analysis revealed an increase of TNFR2-signaling components. 53BP1 recruitment and expression levels for DNA repair genes as well as for p53 were elevated and the ones for related sirtuin deacetylases affected (SIRT 1, 3-7 in Sertoli cells. Under chronic Cre-mediated DNA damage conditions a strong downregulation of Sirt1 was observed, suggesting that the decrease of this important coordinator between DNA repair and metabolic signaling might induce the repression release of major transcription factors regulating metabolic and cytokine-mediated stress pathways. Indeed, caspase-3 was activated and increased germ cell apoptosis was observed, suggesting paracrine effects. In conclusion, the observed wide stress-induced effects and metabolic alterations suggest that it is essential to use the correct control animals (Cre/Wt with matched Cre expression levels to differentiate between Cre-mediated and specific gene-knock out

  1. Effects of a combined intervention with a lentil protein hydrolysate and a mixed training protocol on the lipid metabolism and hepatic markers of NAFLD in Zucker rats.

    Science.gov (United States)

    Martínez, Rosario; Kapravelou, Garyfallia; Donaire, Ana; Lopez-Chaves, Carlos; Arrebola, Francisco; Galisteo, Milagros; Cantarero, Samuel; Aranda, Pilar; Porres, Jesus M; López-Jurado, María

    2018-02-21

    Metabolic syndrome is a cluster of metabolic alterations characterized by central obesity, dyslipidemia, elevated plasma glucose, insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). In this study, a combined intervention of a lentil protein hydrolysate and a mixed training protocol was assessed in an animal experimental model of genetic obesity and metabolic syndrome. Thirty-two male obese and 32 lean Zucker rats were divided into eight different experimental groups. Rats performed a mixed exercise protocol or had a sedentary lifestyle and were administered a lentil protein hydrolysate or placebo. Daily food intake, weekly body weight gain, plasma parameters of glucose and lipid metabolisms, body composition, hepatic weight, total fat content and fatty acid profile, as well as gene expression of lipogenic and lipolytic nuclear transcription factors and their target genes were measured. Obese Zucker rats exhibited higher body and liver weight and fat content than did their lean counterparts. Such alterations were related to modifications in aerobic capacity, plasma biochemical parameters of glucose and lipid metabolisms, hepatic fatty acid profile and gene expression of nuclear transcription factors SREBP1c, PPARα, LXR and associated lipogenic and lipolytic enzymes. The interventions tested did not affect body weight gain but improved aerobic capacity, reduced hepatomegalia and steatosis associated with NAFLD and relieved the adverse effects produced by this condition in glucose and lipid metabolisms through the modulation in the expression of different genes involved in diverse metabolic pathways.

  2. The effect of milk and milk proteins on risk factors of metabolic syndrome in overweight adolecents

    DEFF Research Database (Denmark)

    Arnberg, Karina

    This PhD is based on data from an intervention study with milk and milk proteins conducted in Danish adolescents with overweight. There is a high prevalence of overweight in Danish adolescents. Metabolic syndrome is a cluster of risk factors related to overweight and believed to increase the risk...... of type-2 diabetes and atherosclerotic cardiovascular diseases. Overweight children have higher concentrations of the metabolic syndrome risk factors than normal weight children and the pathological condition underlying cardiovascular diseases, called atherosclerosis, seems to start in childhood. A well...... skimmed milk, whey, casein or water for three months. The background for the intervention is that milk is an important source of protein in the Western diet and epidemiological studies in children have shown that children drinking low amounts of milk have higher concentrations of the metabolic risk...

  3. Role of the Mixed-Lineage Protein Kinase Pathway in the Metabolic Stress Response to Obesity

    Directory of Open Access Journals (Sweden)

    Shashi Kant

    2013-08-01

    Full Text Available Saturated free fatty acid (FFA is implicated in the metabolic response to obesity. In vitro studies indicate that FFA signaling may be mediated by the mixed-lineage protein kinase (MLK pathway that activates cJun NH2-terminal kinase (JNK. Here, we examined the role of the MLK pathway in vivo using a mouse model of diet-induced obesity. The ubiquitously expressed MLK2 and MLK3 protein kinases have partially redundant functions. We therefore compared wild-type and compound mutant mice that lack expression of MLK2 and MLK3. MLK deficiency protected mice against high-fat-diet-induced insulin resistance and obesity. Reduced JNK activation and increased energy expenditure contribute to the metabolic effects of MLK deficiency. These data confirm that the MLK pathway plays a critical role in the metabolic response to obesity.

  4. Metabolic Regulation of CaMKII Protein and Caspases in Xenopus laevis Egg Extracts*

    Science.gov (United States)

    McCoy, Francis; Darbandi, Rashid; Chen, Si-Ing; Eckard, Laura; Dodd, Keela; Jones, Kelly; Baucum, Anthony J.; Gibbons, Jennifer A.; Lin, Sue-Hwa; Colbran, Roger J.; Nutt, Leta K.

    2013-01-01

    The metabolism of the Xenopus laevis egg provides a cell survival signal. We found previously that increased carbon flux from glucose-6-phosphate (G6P) through the pentose phosphate pathway in egg extracts maintains NADPH levels and calcium/calmodulin regulated protein kinase II (CaMKII) activity to phosphorylate caspase 2 and suppress cell death pathways. Here we show that the addition of G6P to oocyte extracts inhibits the dephosphorylation/inactivation of CaMKII bound to caspase 2 by protein phosphatase 1. Thus, G6P sustains the phosphorylation of caspase 2 by CaMKII at Ser-135, preventing the induction of caspase 2-mediated apoptotic pathways. These findings expand our understanding of oocyte biology and clarify mechanisms underlying the metabolic regulation of CaMKII and apoptosis. Furthermore, these findings suggest novel approaches to disrupt the suppressive effects of the abnormal metabolism on cell death pathways. PMID:23400775

  5. Chronic contamination with 137Cesium affects Vitamin D3 metabolism in rats

    International Nuclear Information System (INIS)

    Tissandie, E.; Gueguen, Y.; Lobaccaro, J.M.A.; Aigueperse, J.; Gourmelon, P.; Paquet, F.; Souidi, M.

    2006-01-01

    Twenty years after Chernobyl disaster, many people are still chronically exposed to low dose of 137 Cs, mainly through the food consumption. A large variety of diseases have been described in highly exposed people with 137 Cs, which include bone disorders. The aim of this work was to investigate the biological effects of a chronic exposure to 137 Cs on Vitamin D 3 metabolism, a hormone essential in bone homeostasis. Rats were exposed to 137 Cs in their drinking water for 3 months at a dose of 6500 Bq/l (approximately 150 Bq/rat/day), a similar concentration ingested by the population living in contaminated territories in the former USSR countries. Cytochromes P450 enzymes involved in Vitamin D 3 metabolism, related nuclear receptors and Vitamin D 3 target genes were assessed by real time PCR in liver, kidney and brain. Vitamin D, PTH, calcium and phosphate levels were measured in plasma. An increase in the expression level of cyp2r1 (40%, p 137 Cs-exposed rats. However a significant decrease of Vitamin D (1,25(OH)D 3 ) plasma level (53%, p = 0.02) was observed. In brain, cyp2r1 mRNA level was decreased by 20% (p 137 Cs contamination. In conclusion, this study showed for the first time that chronic exposure with post-accidental doses of 137 Cs affects Vitamin D 3 active form level and induces molecular modifications of CYPs enzymes involved its metabolism in liver and brain, without leading to mineral homeostasis disorders

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

    Directory of Open Access Journals (Sweden)

    Stephanie P Cartwright

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

  7. Effects of antenatal steroids on protein metabolism in preterm infants on the first day of life

    NARCIS (Netherlands)

    de Pipaon, M.S.; Vanbeek, R.H.T.; Zimmermann, L.J.J.; Wattimena, D.J.L.; Quero, J.; Sauer, P. J. J.

    Objective To analyze, in an existing cohort of infants, whether antenatal administered corticosteroids influence protein metabolism in preterm infants on the first day of life. Study design Three groups of infants were studied. The mothers of 25 infants had received 2 or more doses of

  8. Heme metabolism in stress regulation and protein production: from Cinderella to a key player

    DEFF Research Database (Denmark)

    Martinez Ruiz, José Luis; Petranovic, D.; Nielsen, Jens

    2016-01-01

    Heme biosynthesis is a highly conserved pathway which is present in all kingdoms, from Archaea to higher organisms such as plants and mammals. The heme molecule acts as a prosthetic group for different proteins and enzymes involved in energy metabolism and reactions involved in electron transfer....

  9. Riboflavin carrier protein-targeted fluorescent USPIO for the assessment of vascular metabolism in tumors

    NARCIS (Netherlands)

    Jayapaul, J.; Arns, S.; Lederle, W.; Lammers, Twan Gerardus Gertudis Maria; Comba, P.; Gätjens, J.; Kiessling, F.

    2012-01-01

    Abstract Riboflavin (Rf) and its metabolic analogs flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are essential for normal cellular growth and function. Their intracellular transport is regulated by the riboflavin carrier protein (RCP), which has been shown to be over-expressed by

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Fernando Norambuena

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

  12. Myostatin promotes distinct responses on protein metabolism of skeletal and cardiac muscle fibers of rodents.

    Science.gov (United States)

    Manfredi, L H; Paula-Gomes, S; Zanon, N M; Kettelhut, I C

    2017-10-19

    Myostatin is a novel negative regulator of skeletal muscle mass. Myostatin expression is also found in heart in a much less extent, but it can be upregulated in pathological conditions, such as heart failure. Myostatin may be involved in inhibiting protein synthesis and/or increasing protein degradation in skeletal and cardiac muscles. Herein, we used cell cultures and isolated muscles from rats to determine protein degradation and synthesis. Muscles incubated with myostatin exhibited an increase in proteolysis with an increase of Atrogin-1, MuRF1 and LC3 genes. Extensor digitorum longus muscles and C2C12 myotubes exhibited a reduction in protein turnover. Cardiomyocytes showed an increase in proteolysis by activating autophagy and the ubiquitin proteasome system, and a decrease in protein synthesis by decreasing P70S6K. The effect of myostatin on protein metabolism is related to fiber type composition, which may be associated to the extent of atrophy mediated effect of myostatin on muscle.

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

    Science.gov (United States)

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

    2015-08-01

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

  14. Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk.

    Directory of Open Access Journals (Sweden)

    Cathy Slack

    2010-03-01

    Full Text Available Drosophila Lnk is the single ancestral orthologue of a highly conserved family of structurally-related intracellular adaptor proteins, the SH2B proteins. As adaptors, they lack catalytic activity but contain several protein-protein interaction domains, thus playing a critical role in signal transduction from receptor tyrosine kinases to form protein networks. Physiological studies of SH2B function in mammals have produced conflicting data. However, a recent study in Drosophila has shown that Lnk is an important regulator of the insulin/insulin-like growth factor (IGF-1 signaling (IIS pathway during growth, functioning in parallel to the insulin receptor substrate, Chico. As this pathway also has an evolutionary conserved role in the determination of organism lifespan, we investigated whether Lnk is required for normal lifespan in Drosophila. Phenotypic analysis of mutants for Lnk revealed that loss of Lnk function results in increased lifespan and improved survival under conditions of oxidative stress and starvation. Starvation resistance was found to be associated with increased metabolic stores of carbohydrates and lipids indicative of impaired metabolism. Biochemical and genetic data suggest that Lnk functions in both the IIS and Ras/Mitogen activated protein Kinase (MapK signaling pathways. Microarray studies support this model, showing transcriptional feedback onto genes in both pathways as well as indicating global changes in both lipid and carbohydrate metabolism. Finally, our data also suggest that Lnk itself may be a direct target of the IIS responsive transcription factor, dFoxo, and that dFoxo may repress Lnk expression. We therefore describe novel functions for a member of the SH2B protein family and provide the first evidence for potential mechanisms of SH2B regulation. Our findings suggest that IIS signaling in Drosophila may require the activity of a second intracellular adaptor, thereby yielding fundamental new insights into the

  15. Genomic analysis of an attenuated Chlamydia abortus live vaccine strain reveals defects in central metabolism and surface proteins.

    Science.gov (United States)

    Burall, L S; Rodolakis, A; Rekiki, A; Myers, G S A; Bavoil, P M

    2009-09-01

    Comparative genomic analysis of a wild-type strain of the ovine pathogen Chlamydia abortus and its nitrosoguanidine-induced, temperature-sensitive, virulence-attenuated live vaccine derivative identified 22 single nucleotide polymorphisms unique to the mutant, including nine nonsynonymous mutations, one leading to a truncation of pmpG, which encodes a polymorphic membrane protein, and two intergenic mutations potentially affecting promoter sequences. Other nonsynonymous mutations mapped to a pmpG pseudogene and to predicted coding sequences encoding a putative lipoprotein, a sigma-54-dependent response regulator, a PhoH-like protein, a putative export protein, two tRNA synthetases, and a putative serine hydroxymethyltransferase. One of the intergenic mutations putatively affects transcription of two divergent genes encoding pyruvate kinase and a putative SOS response nuclease, respectively. These observations suggest that the temperature-sensitive phenotype and associated virulence attenuation of the vaccine strain result from disrupted metabolic activity due to altered pyruvate kinase expression and/or alteration in the function of one or more membrane proteins, most notably PmpG and a putative lipoprotein.

  16. Testosterone affects hormone-sensitive lipase (HSL) activity and lipid metabolism in the left ventricle

    DEFF Research Database (Denmark)

    Langfort, Jozef; Jagsz, Slawomir; Dobrzyn, Pawel

    2010-01-01

    tissue suggests that testosterone regulates HSL activity. To test whether this is also true in the heart, we measured HSL activity in the left ventricle of sedentary male rats that had been treated with testosterone supplementation or orchidectomy with or without testosterone substitution. Left ventricle...... HSL activity against TG was significantly elevated in intact rats supplemented with testosterone. HSL activity against both TG and diacylglyceride was reduced by orchidectomy, whereas testosterone replacement fully reversed this effect. Moreover, testosterone increased left ventricle free fatty acid...... levels, caused an inhibitory effect on carbohydrate metabolism in the heart, and elevated left ventricular phosphocreatine and ATP levels as compared to control rats. These data indicate that testosterone is involved in cardiac HSL activity regulation which, in turn, may affect cardiac lipid...

  17. Impact of weight loss and maintenance with ad libitum diets varying in protein and glycemic index content on metabolic syndrome

    DEFF Research Database (Denmark)

    Papadaki, Angeliki; Linardakis, Manolis; Plada, Maria

    2014-01-01

    We investigated the effects of weight loss and maintenance with diets that varied with regard to protein content and glycemic index (GI) on metabolic syndrome (MetSyn) status.......We investigated the effects of weight loss and maintenance with diets that varied with regard to protein content and glycemic index (GI) on metabolic syndrome (MetSyn) status....

  18. New method for the quality check of food proteins of the maintenance metabolism. 4

    International Nuclear Information System (INIS)

    Simon, O.; Hernandez, M.; Bergner, H.

    1981-01-01

    Male adult rats (370 g body weight) were fed on maintenance level (460 kJ ME/kgsup(0,75). In a 10 days preliminary period they received a casein/methionine (95/5) diet supplemented with 10 mg 15 N excess per 0.178 kg metabolic body weight in form of ammonium acetate. Thereafter the animals were put on 8 isonitrogenous diets containing as protein sources casein, soya protein, gelatine, whole-egg, fish meal, pea, wheat and yeast. The 15 N excretion via urine and feces was used to evaluate the dietary proteins for maintenance. 15 N in urine was lowest in animals fed on wheat diet and highest after feeding whole-egg diet. From these data a so called ' 15 N excretion biological valence (BV)' was calculated, which indicated the highest quality for wheat and soy protein in meeting the needs of the intermediary maintenance metabolism. On the other hand, dietary protein sources influence the loss of endogenous nitrogen as metabolic fecal nitrogen (MFN). It was found to be lowest in animals fed on diets containing isolated proteins (6 mg MFN/100 g body weight) and highest after feeding protein sources of plant origin with a high content in crude fibre (10 mg MFN/100 g). Both, losses of 15 N via urine and via feces were combined in a parameter called 'total BV'. According to this parameter the differences in quality for maintenance were only little between the protein sources tested (casein 100, soy protein 100, pea 99, wheat 99, whole egg 92, fish meal 89, gelatin 89). It was concluded that in the state of maintenance the supply with essential amino acids is not critical and that the supply with dispensable amino acids (or nonspecific nitrogen) is of great importance. (author)

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    Highlights: •Molybdenum (Mo) is a key micronutrient for nitrogen and redox metabolism in many microalgae. •Molybdate and (more abundant) sulfate anions compete for uptake, although proper mechanism is still obscure. •Higher concentrations of molybdate in culture medium diminish sulfur content in L. polyedrum. •Mo toxicity was monitored as a function of [Mo]:[sulfate] ratios in L. polyedrum and was linked to oxidative stress. •Induction of xanthine oxidase activity and/or depletion of thiol-dependent antioxidants are suggested as plausible mechanisms to explain Mo toxicity in dinoflagellates. -- Abstract: Molybdenum is a transition metal used primarily (90% or more) as an additive to steel and corrosion-resistant alloys in metallurgical industries and its release into the environment is a growing problem. As a catalytic center of some redox enzymes, molybdenum is an essential element for inorganic nitrogen assimilation/fixation, phytohormone synthesis, and free radical metabolism in photosynthesizing species. In oceanic and estuarine waters, microalgae absorb molybdenum as the water-soluble molybdate anion (MoO 4 2− ), although MoO 4 2− uptake is thought to compete with uptake of the much more abundant sulfate anion (SO 4 2− , approximately 25 mM in seawater). Thus, those aspects of microalgal biology impacted by molybdenum would be better explained by considering both MoO 4 2− and SO 4 2− concentrations in the aquatic milieu. This work examines toxicological, physiological and redox imbalances in the dinoflagellate Lingulodinium polyedrum that have been induced by changes in the molybdate:sulfate ratios. We prepared cultures of Lingulodinium polyedrum grown in artificial seawater containing eight different MoO 4 2− concentrations (from 0 to 200 μM) and three different SO 4 2− concentrations (3.5 mM, 9.6 mM and 25 mM). We measured sulfur content in cells, the activities of the three major antioxidant enzymes (superoxide dismutase, catalase

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

    Energy Technology Data Exchange (ETDEWEB)

    Barros, M.P., E-mail: marcelo.barros@cruzeirodosul.edu.br [Postgraduate Program in Health Science (Environmental Chemistry), CBS, Universidade Cruzeiro do Sul, 08060070 São Paulo, SP (Brazil); Hollnagel, H.C. [Pós-Graduação, Faculdade Mario Schenberg, 06710500 Cotia, SP (Brazil); Glavina, A.B. [Postgraduate Program in Health Science (Environmental Chemistry), CBS, Universidade Cruzeiro do Sul, 08060070 São Paulo, SP (Brazil); Soares, C.O. [Postgraduate Program in Health Science (Environmental Chemistry), CBS, Universidade Cruzeiro do Sul, 08060070 São Paulo, SP (Brazil); Department of Biochemistry, Instituto de Química, Universidade de São Paulo (IQ-USP), São Paulo (Brazil); Ganini, D. [Postgraduate Program in Health Science (Environmental Chemistry), CBS, Universidade Cruzeiro do Sul, 08060070 São Paulo, SP (Brazil); Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709 (United States); Dagenais-Bellefeuille, S.; Morse, D. [Departement de Sciences Biologiques, Institut de Recherche en Biologie Végétale, Université de Montréal, Montreal, QC H1X 2B2 (Canada); Colepicolo, P. [Department of Biochemistry, Instituto de Química, Universidade de São Paulo (IQ-USP), São Paulo (Brazil)

    2013-10-15

    Highlights: •Molybdenum (Mo) is a key micronutrient for nitrogen and redox metabolism in many microalgae. •Molybdate and (more abundant) sulfate anions compete for uptake, although proper mechanism is still obscure. •Higher concentrations of molybdate in culture medium diminish sulfur content in L. polyedrum. •Mo toxicity was monitored as a function of [Mo]:[sulfate] ratios in L. polyedrum and was linked to oxidative stress. •Induction of xanthine oxidase activity and/or depletion of thiol-dependent antioxidants are suggested as plausible mechanisms to explain Mo toxicity in dinoflagellates. -- Abstract: Molybdenum is a transition metal used primarily (90% or more) as an additive to steel and corrosion-resistant alloys in metallurgical industries and its release into the environment is a growing problem. As a catalytic center of some redox enzymes, molybdenum is an essential element for inorganic nitrogen assimilation/fixation, phytohormone synthesis, and free radical metabolism in photosynthesizing species. In oceanic and estuarine waters, microalgae absorb molybdenum as the water-soluble molybdate anion (MoO{sub 4}{sup 2−}), although MoO{sub 4}{sup 2−} uptake is thought to compete with uptake of the much more abundant sulfate anion (SO{sub 4}{sup 2−}, approximately 25 mM in seawater). Thus, those aspects of microalgal biology impacted by molybdenum would be better explained by considering both MoO{sub 4}{sup 2−} and SO{sub 4}{sup 2−} concentrations in the aquatic milieu. This work examines toxicological, physiological and redox imbalances in the dinoflagellate Lingulodinium polyedrum that have been induced by changes in the molybdate:sulfate ratios. We prepared cultures of Lingulodinium polyedrum grown in artificial seawater containing eight different MoO{sub 4}{sup 2−} concentrations (from 0 to 200 μM) and three different SO{sub 4}{sup 2−} concentrations (3.5 mM, 9.6 mM and 25 mM). We measured sulfur content in cells, the activities of

  1. A palatable hyperlipidic diet causes obesity and affects brain glucose metabolism in rats

    Directory of Open Access Journals (Sweden)

    Motoyama Caio SM

    2011-09-01

    Full Text Available Abstract Background We have previously shown that either the continuous intake of a palatable hyperlipidic diet (H or the alternation of chow (C and an H diet (CH regimen induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism. Methods Male Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids. Results The relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups. Conclusion These findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age.

  2. Effect of protein malnutrition on the metabolism of bone collagen in albino rats

    Energy Technology Data Exchange (ETDEWEB)

    Rao, J S; Rao, V H [Central Leather Research Inst., Madras (India)

    1981-01-01

    The effect of protein malnutrition on the metabolism of collagen in bone was studied in young female albino rats after a single injection of /sup 3/H-proline. Both specific and total radioactivities of hydroxyproline in the total collagen of the bone were found to decrease in the protein-deficient animals, indicating decreased rate of collagen synthesis. In the urine the amount of hydroxyproline excreted and total radioactivity of /sup 3/H-hydroxyproline were greatly decreased. The results of the present investigation therefore clearly indicate decreased synthesis and catabolism of collagen in bones of protein deficient animals compared to controls.

  3. Endocrine and metabolic changes in transition dairy cows are affected by prepartum infusions of a serotonin precursor

    DEFF Research Database (Denmark)

    Hernandez Castellano, Lorenzo E; Hernandez, Laura L.; Sauerwein, Helga

    2017-01-01

    Serotonin (5-HT) has been shown to be involved in calcium homeostasis, modulating calcium concentration in blood. In addition, 5-HT participates in a variety of metabolic pathways, mainly through the modulation of glucose and lipid metabolism. The hypothesis of the present study...... was that the prepartum administration of 5-hydroxy-l-tryptophan (5-HTP), a 5-HT precursor, would affect endocrine systems related to calcium homeostasis, and interact with other endocrine and metabolic pathways during the transition period. In this study, 20 Holstein dairy cows were randomly assigned to 2 experimental...... homeostasis independent of PTH. The lack of treatment effects on IgG and on other hormones and metabolites indicates that 5-HTP did not affect these other metabolic pathways and the IgG concentration during the transition period....

  4. Insulin resistance and protein energy metabolism in patients with advanced chronic kidney disease.

    Science.gov (United States)

    Siew, Edward D; Ikizler, Talat Alp

    2010-01-01

    Insulin resistance (IR), the reciprocal of insulin sensitivity is a known complication of advanced chronic kidney disease (CKD) and is associated with a number of metabolic derangements. The complex metabolic abnormalities observed in CKD such as vitamin D deficiency, obesity, metabolic acidosis, inflammation, and accumulation of "uremic toxins" are believed to contribute to the etiology of IR and acquired defects in the insulin-receptor signaling pathway in this patient population. Only a few investigations have explored the validity of commonly used assessment methods in comparison to gold standard hyperinsulinemic hyperglycemic clamp technique in CKD patients. An important consequence of insulin resistance is its role in the pathogenesis of protein energy wasting, a state of metabolic derangement characterized by loss of somatic and visceral protein stores not entirely accounted for by inadequate nutrient intake. In the general population, insulin resistance has been associated with accelerated protein catabolism. Among end-stage renal disease (ESRD) patients, enhanced muscle protein breakdown has been observed in patients with Type II diabetes compared to ESRD patients without diabetes. In the absence of diabetes mellitus (DM) or severe obesity, insulin resistance is detectable in dialysis patients and strongly associated with increased muscle protein breakdown, primarily mediated by the ubiquitin-proteasome pathway. Recent epidemiological data indicate a survival advantage and better nutritional status in insulin-free Type II DM patients treated with insulin sensitizer thiazolidinediones. Given the high prevalence of protein energy wasting in ESRD and its unequivocal association with adverse clinical outcomes, insulin resistance may represent an important modifiable target for intervention in the ESRD population.

  5. Metabolism

    Science.gov (United States)

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

  6. The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial

    OpenAIRE

    Rijpma, A.; Graaf, M. van der; Lansbergen, M.M.; Meulenbroek, O.V.; Cetinyurek-Yavuz, A.; Sijben, J.W.; Heerschap, A.; Olde Rikkert, M.G.M.

    2017-01-01

    Background Synaptic dysfunction contributes to cognitive impairment in Alzheimer?s disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer?s disease. Methods Thirty-four drug-naive patients with mild Alzheimer?s disease (Mini Mental State Examination score ?20) were enrolled in this exploratory, double-blind, randomized...

  7. Prioritizing Popular Proteins in Liver Cancer: Remodelling One-Carbon Metabolism.

    Science.gov (United States)

    Mora, María Isabel; Molina, Manuela; Odriozola, Leticia; Elortza, Félix; Mato, José María; Sitek, Barbara; Zhang, Pumin; He, Fuchu; Latasa, María Uxue; Ávila, Matías Antonio; Corrales, Fernando José

    2017-12-01

    Primary liver cancer (HCC) is recognized as the fifth most common neoplasm and the second leading cause of cancer death worldwide. Most risk factors are known, and the molecular pathogenesis has been widely studied in the past decade; however, the underlying molecular mechanisms remain to be unveiled, as they will facilitate the definition of novel biomarkers and clinical targets for more effective patient management. We utilize the B/D-HPP popular protein strategy. We report a list of popular proteins that have been highly cocited with the expression "liver cancer". Several enzymes highlight the known metabolic remodeling of liver cancer cells, four of which participate in one-carbon metabolism. This pathway is central to the maintenance of differentiated hepatocytes, as it is considered the connection between intermediate metabolism and epigenetic regulation. We designed a targeted selective reaction monitoring (SRM) method to follow up one-carbon metabolism adaptation in mouse HCC and in regenerating liver following exposure to CCl 4 . This method allows systematic monitoring of one-carbon metabolism and could prove useful in the follow-up of HCC and of chronically liver-diseased patients (cirrhosis) at risk of HCC. The SRM data are available via ProteomeXchange in PASSEL (PASS01060).

  8. Protein metabolism in obese patients during very low-calorie mixed diets containing different amounts of proteins and carbohydrates.

    Science.gov (United States)

    Pasquali, R; Casimirri, F; Melchionda, N

    1987-12-01

    To assess long-term nitrogen sparing capacity of very low-calorie mixed diets, we administered two isoenergetic (2092KJ) liquid formula regimens of different composition for 8 weeks to two matched groups of massively obese patients (group 1: proteins 60 g, carbohydrate 54 g; group 2: proteins 41 g, carbohydrates 81 g). Weight loss was similar in both groups. Daily nitrogen balance (g) during the second month resulted more a negative in group 2 with respect to group 1. However, within the groups individual nitrogen sparing capacity varied markedly; only a few in group 1 and one in group 2 were able to attain nitrogen equilibrium throughout the study. Daily urine excretion of 3-methylhistidine fell significantly in group 1 but did not change in group 2. Unlike total proteins, albumins, and transferrin, serum levels of retinol-binding protein, thyroxin-binding globulin, and complement-C3 fell significantly in both groups but per cent variations of complement-C3 were more pronounced in the first group. Prealbumin levels fell persistently in group 1 and transiently in group 2. The results indicate that even with this type of diet an adequate amount of dietary protein represents the most important factor in minimizing whole body protein catabolism during long-term semistarvation in massively obese patients. Moreover, they confirm the possible role of dietary carbohydrates in the regulation of some visceral protein metabolism.

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

    DEFF Research Database (Denmark)

    Shaik, Shahnoor S.; Obata, Toshihiro; Hebelstrup, Kim H

    2016-01-01

    in starch granule morphology at maturity. The results demonstrate that decreasing the storage starch branching resulted in metabolic adjustments and re-directions, tuning to evade deleterious effects on caryopsis physiology and plant performance while only little effect was evident by increasing starch......Starch is of fundamental importance for plant development and reproduction and its optimized molecular assembly is potentially necessary for correct starch metabolism. Re-structuring of starch granules in-planta can therefore potentially affect plant metabolism. Modulation of granule micro...

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

    DEFF Research Database (Denmark)

    Shaik, Shahnoor S.; Obata, Toshihiro; Hebelstrup, Kim H

    2016-01-01

    Starch is of fundamental importance for plant development and reproduction and its optimized molecular assembly is potentially necessary for correct starch metabolism. Re-structuring of starch granules in-planta can therefore potentially affect plant metabolism. Modulation of granule micro...... in starch granule morphology at maturity. The results demonstrate that decreasing the storage starch branching resulted in metabolic adjustments and re-directions, tuning to evade deleterious effects on caryopsis physiology and plant performance while only little effect was evident by increasing starch...

  11. Prion protein polymorphisms affect chronic wasting disease progression.

    Directory of Open Access Journals (Sweden)

    Chad J Johnson

    Full Text Available Analysis of the PRNP gene in cervids naturally infected with chronic wasting disease (CWD suggested that PRNP polymorphisms affect the susceptibility of deer to infection. To test this effect, we orally inoculated 12 white-tailed deer with CWD agent. Three different PRNP alleles, wild-type (wt; glutamine at amino acid 95 and glycine at 96, Q95H (glutamine to histidine at amino acid position 95 and G96S (glycine to serine at position 96 were represented in the study cohort with 5 wt/wt, 3 wt/G96S, and 1 each wt/Q95H and Q95H/G96S. Two animals were lost to follow-up due to intercurrent disease. The inoculum was prepared from Wisconsin hunter-harvested homozygous wt/wt animals. All infected deer presented with clinical signs of CWD; the orally infected wt/wt had an average survival period of 693 days post inoculation (dpi and G96S/wt deer had an average survival period of 956 dpi. The Q95H/wt and Q95H/G96S deer succumbed to CWD at 1,508 and 1,596 dpi respectively. These data show that polymorphisms in the PRNP gene affect CWD incubation period. Deer heterozygous for the PRNP alleles had extended incubation periods with the Q95H allele having the greatest effect.

  12. [The effect of copper on the metabolism of iodine, carbohydrates and proteins in rats].

    Science.gov (United States)

    Esipenko, B E; Marsakova, N V

    1990-01-01

    Experiments on 156 rats maintained at ration with copper deficiency have demonstrated a decrease in the values of iodine metabolism in organs and tissues excluding the liver where a sharp increase in the concentration and content of inorganic iodine was observed. A disturbance in indices of carbohydrate and proteins metabolism in the organism of animals is marked. A direct relationship with a correlation coefficient equaling 0.87-1.00 is determined between changes in the concentration of protein-bound iodine in blood and concentration of glycogen in the liver, skeletal muscles, albumins, alpha 1-, alpha 2-globulins, urea concentration; an inverse relationship with glucose, activity of blood lipo-dehydrogenase and liver mitochondria, aldolase, concentration of pyruvic and lactic acids is established as well. It is concluded that copper deficiency can exert both a direct effect on metabolic processes (as data from literature testify) and an indirect one disturbing iodine metabolism, i. e. sharply decreasing protein-bound iodine production by the thyroid gland.

  13. Assessment of chitosan-affected metabolic response by peroxisome proliferator-activated receptor bioluminescent imaging-guided transcriptomic analysis.

    Directory of Open Access Journals (Sweden)

    Chia-Hung Kao

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

  14. The protein type within a hypocaloric diet affects obesity-related inflammation: the RESMENA project.

    Science.gov (United States)

    Lopez-Legarrea, Patricia; de la Iglesia, Rocio; Abete, Itziar; Navas-Carretero, Santiago; Martinez, J Alfredo; Zulet, M Angeles

    2014-04-01

    The aim of this study was to compare the effect of two energy-restricted, differing with regard to protein content, on the inflammation state of obese individuals with features of metabolic syndrome. Ninety-six participants completed an 8-wk randomized intervention trial that compared the RESMENA diet (-30% energy, with 30% energy from protein) with a control diet (-30% energy, with 15% energy from protein) that was based on American Heart Association criteria. The mean body weight losses were 7.09 ± 0.82 kg and 6.73 ± 0.71 kg, respectively, with no differences seen between the groups. The endpoint inflammation score-which was based on high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, and plasminogen activator inhibitor-1 levels-was significantly lower (P = 0.012) in the low-protein group (6.81 ± 2.32 versus 7.94 ± 1.94). The linear regression analyses revealed that total protein intake was positively associated with inflammation (P = 0.007) as well as with animal protein (P = 0.025) and meat protein (P = 0.015), but neither vegetable- nor fish-derived proteins were found to influence inflammatory status. Our results suggest that the type of protein consumed (more than the total protein consumed) within an energy-restricted diet influences the inflammation status associated with obesity-related comorbidities. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Exposure to gemfibrozil and atorvastatin affects cholesterol metabolism and steroid production in zebrafish (Danio rerio).

    Science.gov (United States)

    Al-Habsi, Aziz A; Massarsky, Andrey; Moon, Thomas W

    2016-09-01

    The commonly used lipid-lowering pharmaceuticals gemfibrozil (GEM) and atorvastatin (ATV) are detected in the aquatic environment; however, their potential effects on non-target fish species are yet to be fully understood. This study examined the effects of GEM and/or ATV on female and male adult zebrafish after a 30d dietary exposure. The exposure led to changes in several biochemical parameters, including reduction in cholesterol, triglycerides, cortisol, testosterone, and estradiol. Changes in cholesterol and triglycerides were also associated with changes in transcript levels of key genes involved with cholesterol and lipid regulation, including SREBP2, HMGCR1, PPARα, and SREBP1. We also noted higher CYP3A65 and atrogin1 mRNA levels in drug-treated male fish. Sex differences were apparent in some of the examined parameters at both biochemical and molecular levels. This study supports these drugs affecting cholesterol metabolism and steroid production in adult zebrafish. We conclude that the reduction in cortisol may impair the ability of these fish to mount a suitable stress response, whereas the reduction of sex steroids may negatively affect reproduction. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Proteomic analysis of Arabidopsis thaliana leaves in response to acute boron deficiency and toxicity reveals effects on photosynthesis, carbohydrate metabolism, and protein synthesis.

    Science.gov (United States)

    Chen, Mei; Mishra, Sasmita; Heckathorn, Scott A; Frantz, Jonathan M; Krause, Charles

    2014-02-15

    Boron (B) stress (deficiency and toxicity) is common in plants, but as the functions of this essential micronutrient are incompletely understood, so too are the effects of B stress. To investigate mechanisms underlying B stress, we examined protein profiles in leaves of Arabidopsis thaliana plants grown under normal B (30 μM), compared to plants transferred for 60 and 84 h (i.e., before and after initial visible symptoms) in deficient (0 μM) or toxic (3 mM) levels of B. B-responsive polypeptides were sequenced by mass spectrometry, following 2D gel electrophoresis, and 1D gels and immunoblotting were used to confirm the B-responsiveness of some of these proteins. Fourteen B-responsive proteins were identified, including: 9 chloroplast proteins, 6 proteins of photosynthetic/carbohydrate metabolism (rubisco activase, OEC23, photosystem I reaction center subunit II-1, ATPase δ-subunit, glycolate oxidase, fructose bisphosphate aldolase), 6 stress proteins, and 3 proteins involved in protein synthesis (note that the 14 proteins may fall into multiple categories). Most (8) of the B-responsive proteins decreased under both B deficiency and toxicity; only 3 increased with B stress. Boron stress decreased, or had no effect on, 3 of 4 oxidative stress proteins examined, and did not affect total protein. Hence, our results indicate relatively early specific effects of B stress on chloroplasts and protein synthesis. Copyright © 2013 Elsevier GmbH. All rights reserved.

  17. Whey Protein Supplementation Enhances Whole Body Protein Metabolism and Performance Recovery after Resistance Exercise: A Double-Blind Crossover Study.

    Science.gov (United States)

    West, Daniel W D; Abou Sawan, Sidney; Mazzulla, Michael; Williamson, Eric; Moore, Daniel R

    2017-07-11

    No study has concurrently measured changes in free-living whole body protein metabolism and exercise performance during recovery from an acute bout of resistance exercise. We aimed to determine if whey protein ingestion enhances whole body net protein balance and recovery of exercise performance during overnight (10 h) and 24 h recovery after whole body resistance exercise in trained men. In a double-blind crossover design, 12 trained men (76 ± 8 kg, 24 ± 4 years old, 14% ± 5% body fat; means ± standard deviation (SD)) performed resistance exercise in the evening prior to consuming either 25 g of whey protein (PRO; MuscleTech 100% Whey) or an energy-matched placebo (CHO) immediately post-exercise (0 h), and again the following morning (~10 h of recovery). A third randomized trial, completed by the same participants, involving no exercise and no supplement served as a rested control trial (Rest). Participants ingested [ 15 N]glycine to determine whole body protein kinetics and net protein balance over 10 and 24 h of recovery. Performance was assessed pre-exercise and at 0, 10, and 24 h of recovery using a battery of tests. Net protein balance tended to improve in PRO ( P = 0.064; effect size (ES) = 0.61, PRO vs. CHO) during overnight recovery. Over 24 h, net balance was enhanced in PRO ( P = 0.036) but not in CHO ( P = 0.84; ES = 0.69, PRO vs. CHO), which was mediated primarily by a reduction in protein breakdown (PRO protein supplementation improved MVC (ES = 0.76), REP (ES = 0.44), and peak power (ES = 0.55). In conclusion, whey protein supplementation enhances whole body anabolism, and may improve acute recovery of exercise performance after a strenuous bout of resistance exercise.

  18. Effects of Human C-Reactive Protein on Pathogenesis of Features of the Metabolic Syndrome

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Kajiya, T.; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šimáková, Miroslava; Šilhavý, Jan; Malínská, H.; Oliyarnyk, O.; Kazdová, L.; Fan, J.; Wang, J.; Kurtz, T. W.

    2011-01-01

    Roč. 57, č. 4 (2011), s. 731-737 ISSN 0194-911X R&D Projects: GA MZd(CZ) NS9759; GA MŠk(CZ) ME08006; GA MŠk(CZ) 1M0520; GA ČR(CZ) GAP301/10/0290; GA ČR GAP303/10/0505; GA AV ČR(CZ) IAA500110805 Grant - others:EC(XE) HEALTH-F4-2010-241504 Institutional research plan: CEZ:AV0Z50110509 Keywords : C-reactive protein * metabolic syndrome * transgenic rat Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 6.207, year: 2011

  19. Putative drug and vaccine target protein identification using comparative genomic analysis of KEGG annotated metabolic pathways of Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Damte, Dereje; Suh, Joo-Won; Lee, Seung-Jin; Yohannes, Sileshi Belew; Hossain, Md Akil; Park, Seung-Chun

    2013-07-01

    In the present study, a computational comparative and subtractive genomic/proteomic analysis aimed at the identification of putative therapeutic target and vaccine candidate proteins from Kyoto Encyclopedia of Genes and Genomes (KEGG) annotated metabolic pathways of Mycoplasma hyopneumoniae was performed for drug design and vaccine production pipelines against M.hyopneumoniae. The employed comparative genomic and metabolic pathway analysis with a predefined computational systemic workflow extracted a total of 41 annotated metabolic pathways from KEGG among which five were unique to M. hyopneumoniae. A total of 234 proteins were identified to be involved in these metabolic pathways. Although 125 non homologous and predicted essential proteins were found from the total that could serve as potential drug targets and vaccine candidates, additional prioritizing parameters characterize 21 proteins as vaccine candidate while druggability of each of the identified proteins evaluated by the DrugBank database prioritized 42 proteins suitable for drug targets. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Expression of Lipid Metabolism-Related Proteins Differs between Invasive Lobular Carcinoma and Invasive Ductal Carcinoma.

    Science.gov (United States)

    Cha, Yoon Jin; Kim, Hye Min; Koo, Ja Seung

    2017-01-23

    We comparatively investigated the expression and clinical implications of lipid metabolism-related proteins in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) of the breast. A total of 584 breast cancers (108 ILC and 476 IDC) were subjected to tissue microarray and immunohistochemical analysis for lipid metabolism-related proteins including hormone-sensitive lipase (HSL), perilipin A, fatty acid binding protein (FABP)4, carnitine palmitoyltransferase (CPT)-1, acyl-CoA oxidase 1, and fatty acid synthetase (FASN). HSL, perilipin A, and FABP4 expression (all p invasive cancers, HSL and FABP4 were highly expressed in luminal A-type ILC ( p cancers, HSL and FABP4 were more highly expressed in ILC ( p < 0.001). Univariate analysis found associations of shorter disease-free survival with CPT-1 positivity ( p = 0.004) and acyl-CoA oxidase 1 positivity ( p = 0.032) and of shorter overall survival with acyl-CoA oxidase 1 positivity ( p = 0.027). In conclusion, ILC and IDC exhibited different immunohistochemical lipid metabolism-related protein expression profiles. Notably, ILC exhibited high HSL and FABP4 and low perilipin A expression.

  1. Expression of Lipid Metabolism-Related Proteins Differs between Invasive Lobular Carcinoma and Invasive Ductal Carcinoma

    Directory of Open Access Journals (Sweden)

    Yoon Jin Cha

    2017-01-01

    Full Text Available We comparatively investigated the expression and clinical implications of lipid metabolism-related proteins in invasive lobular carcinoma (ILC and invasive ductal carcinoma (IDC of the breast. A total of 584 breast cancers (108 ILC and 476 IDC were subjected to tissue microarray and immunohistochemical analysis for lipid metabolism-related proteins including hormone-sensitive lipase (HSL, perilipin A, fatty acid binding protein (FABP4, carnitine palmitoyltransferase (CPT-1, acyl-CoA oxidase 1, and fatty acid synthetase (FASN. HSL, perilipin A, and FABP4 expression (all p < 0.001 differed significantly: HSL and FABP4 were more frequently present in ILC, whereas perilipin A was more frequently detected in IDC. Among all invasive cancers, HSL and FABP4 were highly expressed in luminal A-type ILC (p < 0.001 and perilipin A in luminal A-type IDC (p = 0.007. Among luminal B-type cancers, HSL and FABP4 were more highly expressed in ILC (p < 0.001. Univariate analysis found associations of shorter disease-free survival with CPT-1 positivity (p = 0.004 and acyl-CoA oxidase 1 positivity (p = 0.032 and of shorter overall survival with acyl-CoA oxidase 1 positivity (p = 0.027. In conclusion, ILC and IDC exhibited different immunohistochemical lipid metabolism-related protein expression profiles. Notably, ILC exhibited high HSL and FABP4 and low perilipin A expression.

  2. [L-arginine metabolism enzyme activities in rat liver subcellular fractions under condition of protein deprivation].

    Science.gov (United States)

    Kopyl'chuk, G P; Buchkovskaia, I M

    2014-01-01

    The features of arginase and NO-synthase pathways of arginine's metabolism have been studied in rat liver subcellular fractions under condition of protein deprivation. During the experimental period (28 days) albino male rats were kept on semi synthetic casein diet AIN-93. The protein deprivation conditions were designed as total absence of protein in the diet and consumption of the diet partially deprived with 1/2 of the casein amount compared to in the regular diet. Daily diet consumption was regulated according to the pair feeding approach. It has been shown that the changes of enzyme activities, involved in L-arginine metabolism, were characterized by 1.4-1.7 fold decrease in arginase activity, accompanied with unchanged NO-synthase activity in cytosol. In mitochondrial fraction the unchanged arginase activity was accompanied by 3-5 fold increase of NO-synthase activity. At the terminal stages of the experiment the monodirectional dynamics in the studied activities have been observed in the mitochondrial and cytosolfractions in both experimental groups. In the studied subcellular fractions arginase activity decreased (2.4-2.7 fold with no protein in the diet and 1.5 fold with partly supplied protein) and was accompanied by NO-synthase activity increase by 3.8 fold in cytosole fraction, by 7.2 fold in mitochondrial fraction in the group with no protein in the diet and by 2.2 and 3.5 fold in the group partialy supplied with protein respectively. The observed tendency is presumably caused by the switch of L-arginine metabolism from arginase into oxidizing NO-synthase parthway.

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

    Science.gov (United States)

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

    2017-09-01

    This study aimed to determine the effect of preexercise metabolic acidosis and alkalosis on power output (PO) and aerobic and anaerobic energy expenditure during a 4-km cycling time trial (TT). Eleven recreationally trained cyclists (V˙O2peak 54.1 ± 9.3 mL·kg·min) performed a 4-km TT 100 min after ingesting in a double-blind matter 0.15 g·kg of body mass of ammonium chloride (NH4Cl, acidosis), 0.3 g·kg of sodium bicarbonate (NaHCO3, alkalosis), or 0.15 g·kg of CaCO3 (placebo). A preliminary study (n = 7) was conducted to establish the optimal doses to promote the desirable preexercise blood pH alterations without gastrointestinal distress. Data for PO, aerobic and anaerobic energy expenditure, and blood and respiratory parameters were averaged for each 1 km and compared between conditions using two-way repeated-measures ANOVA (condition and distance factors). Gastrointestinal discomfort was analyzed qualitatively. Compared with placebo (pH 7.37 ± 0.02, [HCO3]: 27.5 ± 2.6 mmol·L), the NaHCO3 ingestion resulted in a preexercise blood alkalosis (pH +0.06 ± 0.04, [HCO3]: +4.4 ± 2.0 mmol·L, P 0.05). Minimal gastrointestinal distress was noted in all conditions. Preexercise acidosis, but not alkalosis, affects anaerobic metabolism and PO during a 4-km cycling TT.

  4. FANCM-FAAP24 and FANCJ: FA proteins that metabolize DNA

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Abdullah Mahmood; Singh, Thiyam Ramsing [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH 45229 (United States); Meetei, Amom Ruhikanta, E-mail: Ruhikanta.Meetei@cchmc.org [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH 45229 (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 (United States)

    2009-07-31

    Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder characterized by aplastic anemia, cancer susceptibility and cellular sensitivity to DNA-crosslinking agents. Eight FA proteins (FANCA, -B, -C, -E, -F, -G, -L and -M) and three non-FA proteins (FAAP100, FAAP24 and HES1) form the FA nuclear core complex that is required for monoubiquitination of the FANCD2-FANCI dimer upon DNA damage. The other three FA proteins, FANCD1/BRCA2, FANCJ/BACH1/BRIP1 and FANCN/PALB2, act in parallel or downstream of the FANCD2-FANCI dimer. Despite the isolation and characterization of several FA proteins, the mechanism by which these proteins protect cells from DNA interstrand crosslinking agents has been unclear. This is because a majority of the FA proteins lack any recognizable functional domains that can provide insight into their function. The recently discovered FANCM (Hef) and FANCJ (BRIP1/BACH1) proteins contain helicase domains, providing potential insight into the role of FA proteins in DNA repair. FANCM with its partner, FAAP24, and FANCJ bind and metabolize a variety of DNA substrates. In this review, we focus on the discovery, structure, and function of the FANCM-FAAP24 and FANCJ proteins.

  5. FANCM-FAAP24 and FANCJ: FA proteins that metabolize DNA

    International Nuclear Information System (INIS)

    Ali, Abdullah Mahmood; Singh, Thiyam Ramsing; Meetei, Amom Ruhikanta

    2009-01-01

    Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder characterized by aplastic anemia, cancer susceptibility and cellular sensitivity to DNA-crosslinking agents. Eight FA proteins (FANCA, -B, -C, -E, -F, -G, -L and -M) and three non-FA proteins (FAAP100, FAAP24 and HES1) form the FA nuclear core complex that is required for monoubiquitination of the FANCD2-FANCI dimer upon DNA damage. The other three FA proteins, FANCD1/BRCA2, FANCJ/BACH1/BRIP1 and FANCN/PALB2, act in parallel or downstream of the FANCD2-FANCI dimer. Despite the isolation and characterization of several FA proteins, the mechanism by which these proteins protect cells from DNA interstrand crosslinking agents has been unclear. This is because a majority of the FA proteins lack any recognizable functional domains that can provide insight into their function. The recently discovered FANCM (Hef) and FANCJ (BRIP1/BACH1) proteins contain helicase domains, providing potential insight into the role of FA proteins in DNA repair. FANCM with its partner, FAAP24, and FANCJ bind and metabolize a variety of DNA substrates. In this review, we focus on the discovery, structure, and function of the FANCM-FAAP24 and FANCJ proteins.

  6. Protein carbonylation associated to high-fat, high-sucrose diet and its metabolic effects.

    Science.gov (United States)

    Méndez, Lucía; Pazos, Manuel; Molinar-Toribio, Eunice; Sánchez-Martos, Vanesa; Gallardo, José M; Rosa Nogués, M; Torres, Josep L; Medina, Isabel

    2014-12-01

    The present research draws a map of the characteristic carbonylation of proteins in rats fed high-caloric diets with the aim of providing a new insight of the pathogenesis of metabolic diseases derived from the high consumption of fat and refined carbohydrates. Protein carbonylation was analyzed in plasma, liver and skeletal muscle of Sprague-Dawley rats fed a high-fat, high-sucrose (HFHS) diet by a proteomics approach based on carbonyl-specific fluorescence-labeling, gel electrophoresis and mass spectrometry. Oxidized proteins along with specific sites of oxidative damage were identified and discussed to illustrate the consequences of protein oxidation. The results indicated that long-term HFHS consumption increased protein oxidation in plasma and liver; meanwhile, protein carbonyls from skeletal muscle did not change. The increment of carbonylation by HFHS diet was singularly selective on specific target proteins: albumin from plasma and liver, and hepatic proteins such as mitochondrial carbamoyl-phosphate synthase (ammonia), mitochondrial aldehyde dehydrogenase, argininosuccinate synthetase, regucalcin, mitochondrial adenosine triphosphate synthase subunit beta, actin cytoplasmic 1 and mitochondrial glutamate dehydrogenase 1. The possible consequences that these specific protein carbonylations have on the excessive weight gain, insulin resistance and nonalcoholic fatty liver disease resulting from HFHS diet consumption are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Ying Wang

    2012-06-01

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

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

    Science.gov (United States)

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

    2012-06-01

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

  9. L-Alanylglutamine inhibits signaling proteins that activate protein degradation, but does not affect proteins that activate protein synthesis after an acute resistance exercise.

    Science.gov (United States)

    Wang, Wanyi; Choi, Ran Hee; Solares, Geoffrey J; Tseng, Hung-Min; Ding, Zhenping; Kim, Kyoungrae; Ivy, John L

    2015-07-01

    Sustamine™ (SUS) is a dipeptide composed of alanine and glutamine (AlaGln). Glutamine has been suggested to increase muscle protein accretion; however, the underlying molecular mechanisms of glutamine on muscle protein metabolism following resistance exercise have not been fully addressed. In the present study, 2-month-old rats climbed a ladder 10 times with a weight equal to 75 % of their body mass attached at the tail. Rats were then orally administered one of four solutions: placebo (PLA-glycine = 0.52 g/kg), whey protein (WP = 0.4 g/kg), low dose of SUS (LSUS = 0.1 g/kg), or high dose of SUS (HSUS = 0.5 g/kg). An additional group of sedentary (SED) rats was intubated with glycine (0.52 g/kg) at the same time as the ladder-climbing rats. Blood samples were collected immediately after exercise and at either 20 or 40 min after recovery. The flexor hallucis longus (FHL), a muscle used for climbing, was excised at 20 or 40 min post exercise and analyzed for proteins regulating protein synthesis and degradation. All supplements elevated the phosphorylation of FOXO3A above SED at 20 min post exercise, but only the SUS supplements significantly reduced the phosphorylation of AMPK and NF-kB p65. SUS supplements had no effect on mTOR signaling, but WP supplementation yielded a greater phosphorylation of mTOR, p70S6k, and rpS6 compared with PLA at 20 min post exercise. However, by 40 min post exercise, phosphorylation of mTOR and rpS6 in PLA had risen to levels not different than WP. These results suggest that SUS blocks the activation of intracellular signals for MPB, whereas WP accelerates mRNA translation.

  10. The Copper Metabolism MURR1 Domain protein 1 (COMMD1) modulates the aggregation of misfolded protein species in a client-specific manner

    NARCIS (Netherlands)

    W.I.M. Vonk (Willianne I.); V. Kakkar (Vaishali); P. Bartuzi (Paulina); D. Jaarsma (Dick); R. Berger (Ruud); M.A. Hofker (Marten); L.W.J. Klomp (Leo W.); C. Wijmenga (Cisca); H. Kampinga (Harm); B. van de Sluis (Bart)

    2014-01-01

    textabstractThe Copper Metabolism MURR1 domain protein 1 (COMMD1) is a protein involved in multiple cellular pathways, including copper homeostasis, NF-κB and hypoxia signalling. Acting as a scaffold protein, COMMD1 mediates the levels, stability and proteolysis of its substrates (e.g. the

  11. [Metabolism of thyroid gland cells as affected by prolactin and emotional-physical stress].

    Science.gov (United States)

    Strizhkov, V V

    1991-01-01

    A study was made of the role of prolactin (PRL) in the regulation of thyroid function in intact animals and in those exposed to stress (swimming was used as physical exercise). A single daily dose of 125 micrograms of PRL per 100 g of body mass was injected subcutaneously in 0.5 ml of saline solution during a week to male rats (control: intact rats; injection of 0.5 ml of saline solution subcutaneously). Redox enzymes; succinate dehydrogenase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, NAD.H2 and NADP.H2, ATPase and monoamine oxidase, total protein, RNA and glycogen in glandular cells were investigated histochemically 24 h after the last injection of PRL or saline, 30 min., 1, 2, 3, 5 and 7 hours after swimming or right after complete fatigue (in the presence of experimental hyperprolactinemia). A conclusion has been made that one of the most important mechanisms of the adaptive effect of PRL is its ability to suppress thyroid function, thus decreasing the metabolism level, which results in reduction of oxygen consumption and improves body tolerance to stress.

  12. Protein turnover in lactating mink (Mustela vison) is not affected by dietary protein supply

    DEFF Research Database (Denmark)

    Tauson, Anne-Helene; Fink, Rikke; Chwalibog, André

    2006-01-01

    The mink is a strict carnivore and may therefore serve as a model for the cat. Current recommendations for protein supply for lactating mink are based on production experiments with preweaning kit growth as a measure of dietary adequacy (1,2). Recently, nitrogen balance and substrate oxidation have...... in humans (7), growing pigs (8), and growing rats (9). In adult cats, both protein synthesis and breakdown were lower when feeding a low- than when feeding a high-protein diet [20 vs. 70% of metabolizable energy (ME)5 from protein] (10). The objectives of this study were therefore to develop a ¹5N...

  13. Metabolism and Whole-Body Fat Oxidation Following Post-Exercise Carbohydrate or Protein Intake

    DEFF Research Database (Denmark)

    Hall, Ulrika Andersson; Pettersson, Stefan; Edin, Fredrik

    2018-01-01

    : Protein supplementation immediately post-exercise did not affect the doubling in whole body fat oxidation seen during a subsequent exercise trial 2 hours later. Neither did it affect resting fat oxidation during the post-exercise period despite increased insulin levels and attenuated ketosis. Carbohydrate...

  14. Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.

    Science.gov (United States)

    Bedarida, Tatiana; Domingues, Alison; Baron, Stephanie; Ferreira, Chrystophe; Vibert, Francoise; Cottart, Charles-Henry; Paul, Jean-Louis; Escriou, Virginie; Bigey, Pascal; Gaussem, Pascale; Leguillier, Teddy; Nivet-Antoine, Valerie

    2018-06-01

    Although thioredoxin-interacting protein (TXNIP) is involved in a variety of biologic functions, the contribution of endothelial TXNIP has not been well defined. To investigate the endothelial function of TXNIP, we generated a TXNIP knockout mouse on the Cdh5-cre background (TXNIP fl/fl cdh5 cre ). Control (TXNIP fl/fl ) and TXNIP fl/fl cdh5 cre mice were fed a high protein-low carbohydrate (HP-LC) diet for 3 mo to induce metabolic stress. We found that TXNIP fl/fl and TXNIP fl/fl cdh5 cre mice on an HP-LC diet displayed impaired glucose tolerance and dyslipidemia concretizing the metabolic stress induced. We evaluated the impact of this metabolic stress on mice with reduced endothelial TXNIP expression with regard to arterial structure and function. TXNIP fl/fl cdh5 cre mice on an HP-LC diet exhibited less endothelial dysfunction than littermate mice on an HP-LC diet. These mice were protected from decreased aortic medial cell content, impaired aortic distensibility, and increased plasminogen activator inhibitor 1 secretion. This protective effect came with lower oxidative stress and lower inflammation, with a reduced NLRP3 inflammasome expression, leading to a decrease in cleaved IL-1β. We also show the major role of TXNIP in inflammation with a knockdown model, using a TXNIP-specific, small interfering RNA included in a lipoplex. These findings demonstrate a key role for endothelial TXNIP in arterial impairments induced by metabolic stress, making endothelial TXNIP a potential therapeutic target.-Bedarida, T., Domingues, A., Baron, S., Ferreira, C., Vibert, F., Cottart, C.-H., Paul, J.-L., Escriou, V., Bigey, P., Gaussem, P., Leguillier, T., Nivet-Antoine, V. Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.

  15. The Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism

    DEFF Research Database (Denmark)

    Szekeres, Ferenc; Chadt, Alexandra; Tom, Robby Z

    2012-01-01

    The Rab-GTPase-activating protein TBC1D1 has emerged as a novel candidate involved in metabolic regulation. Our aim was to determine whether TBC1D1 is involved in insulin as well as energy-sensing signals controlling skeletal muscle metabolism. TBC1D1-deficient congenic B6.SJL-Nob1.10 (Nob1.10(SJL...... be explained partly by a 50% reduction in GLUT4 protein, since proximal signaling at the level of Akt, AMPK, and acetyl-CoA carboxylase (ACC) was unaltered. Paradoxically, in vivo insulin-stimulated 2-deoxyglucose uptake was increased in EDL and tibialis anterior muscle from TBC1D1-deficient mice......)) and wild-type littermates were studied. Glucose and insulin tolerance, glucose utilization, hepatic glucose production, and tissue-specific insulin-mediated glucose uptake were determined. The effect of insulin, AICAR, or contraction on glucose transport was studied in isolated skeletal muscle. Glucose...

  16. A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution

    DEFF Research Database (Denmark)

    Maida, Adriano; Zota, Annika; Sjøberg, Kim Anker

    2016-01-01

    of impaired glucose homeostasis independently of obesity and food intake. DPD-mediated metabolic inefficiency and improvement of glucose homeostasis were independent of uncoupling protein 1 (UCP1), but required expression of liver-derived fibroblast growth factor 21 (FGF21) in both lean and obese mice. FGF21...... expression and secretion as well as the associated metabolic remodeling induced by DPD also required induction of liver-integrated stress response-driven nuclear protein 1 (NUPR1). Insufficiency of select nonessential amino acids (NEAAs) was necessary and adequate for NUPR1 and subsequent FGF21 induction...... and secretion in hepatocytes in vitro and in vivo. Taken together, these data indicate that DPD promotes improved glucose homeostasis through an NEAA insufficiency-induced liver NUPR1/FGF21 axis....

  17. High Temperature During Rice Grain Filling Enhances Aspartate Metabolism in Grains and Results in Accumulation of Aspartate-Family Amino Acids and Protein Components

    Directory of Open Access Journals (Sweden)

    Cheng-gang LIANG

    2013-09-01

    Full Text Available Global warming causes the exacerbation of rice growing environment, which seriously affects rice growth and reproduction, and finally results in the decrease of rice yield and quality. We investigated the activities of aspartate metabolism enzymes in grains, and the contents of Aspartate-family amino acids and protein components to further understand the effects of high temperature (HT on rice nutritional quality during rice grain filling. Under HT, the average activities of aspartate aminotransferase (AAT and aspartokinase (AK in grains significantly increased, the amino acid contents of aspartate (Asp, lysine (Lys, threonine (Thr, methionine (Met and isoleucine (Ile and the protein contents of albumin, globulin, prolamin and glutelin also significantly increased. The results indicated that HT enhanced Asp metabolism during rice grain filling and the enhancement of Asp metabolism might play an important role in the increase of Asp-family amino acids and protein components in grains. In case of the partial appraisal of the change of Asp-family amino acids and protein components under HT, we introduced eight indicators (amino acid or protein content, ratio of amino acid or protein, amino acid or protein content per grain and amino acid or protein content per panicle to estimate the effects of HT. It is suggested that HT during rice grain filling was benefit for the accumulation of Asp-family amino acids and protein components. Combined with the improvement of Asp-family amino acid ratio in grains under HT, it is suggested that HT during grain filling may improve the rice nutritional quality. However, the yields of parts of Asp-family amino acids and protein components were decreased under HT during rice grain filling.

  18. REPRODUCTIVE AND METABOLIC RESPONSES IN EWES TO DIETARY PROTEIN SUPPLEMENT DURING MATING PERIOD IN DRY SEASON OF NORTHEAST BRAZIL

    Directory of Open Access Journals (Sweden)

    Magda Rodrigues

    2015-01-01

    Full Text Available This study evaluated the effect of food supplements with different levels of protein on reproductive and metabolic response of ewes during the mating period. Forty-one ewes were supplemented during 43 days with amount protein to meet 1.0 (diet I; n = 14, 1.7 (diet II; n = 13 and 2.1 (diet III; n = 14 times the maintenance requirements. Dry matter (DM intake was higher (P < 0.01 in diet III when compared to diets I and II. Orts were lesser in diets II and III (P < 0.05 when compared to diet I. Intake of organic matter (OM, crude protein (CP and ether extract (EE was higher in diet III (P < 0.05, but NDF and ADF intake was superior in diet I (P < 0.05. In diet III, a higher frequency of female mated was observed (P < 0.05. The prolificity and twinning rate was higher in ewes of diet II (P < 0.05. Greater birth weight of lambs (P < 0.05 was verified in diet III. The progesterone levels were affected by diets II and III (P < 0.05. In conclusion, the supplementation of ewes with intermediate level of protein improves their reproductive response.

  19. Muscle protein degradation and amino acid metabolism during prolonged knee-extensor exercise in humans

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Saltin, B; Wagenmakers, A J

    1999-01-01

    to a substantial increase in net muscle protein degradation, and that a lowering of the starting muscle glycogen content leads to a further increase. The carbon atoms of the branched-chain amino acids (BCAA), glutamate, aspartate and asparagine, liberated by protein degradation, and the BCAA and glutamate......The aim of this study was to investigate whether prolonged one-leg knee-extensor exercise enhances net protein degradation in muscle with a normal or low glycogen content. Net amino acid production, as a measure of net protein degradation, was estimated from leg exchange and from changes...... in the concentrations of amino acids that are not metabolized in skeletal muscle. Experiments were performed at rest and during one-leg knee-extensor exercise in six subjects having one leg with a normal glycogen content and the other with a low glycogen content. Exercise was performed for 90 min at a workload of 60...

  20. Role of the mixed-lineage protein kinase pathway in the metabolic stress response to obesity

    OpenAIRE

    Kant, Shashi; Barrett, Tamera; Vertii, Anastassiia; Noh, Yun Hee; Jung, Dae Young; Kim, Jason K.; Davis, Roger J.

    2013-01-01

    Saturated free fatty acid (FFA) is implicated in the metabolic response to obesity. In vitro studies indicate that FFA signaling may be mediated by the mixed-lineage protein kinase (MLK) pathway that activates cJun NH2-terminal kinase (JNK). Here, we examined the role of the MLK pathway in vivo using a mouse model of diet-induced obesity. The ubiquitously expressed MLK2 and MLK3 protein kinases have partially redundant functions. We therefore compared wild-type and compound mutant mice that l...

  1. Intrinsically Disordered Segments Affect Protein Half-Life in the Cell and during Evolution

    Directory of Open Access Journals (Sweden)

    Robin van der Lee

    2014-09-01

    Full Text Available Precise control of protein turnover is essential for cellular homeostasis. The ubiquitin-proteasome system is well established as a major regulator of protein degradation, but an understanding of how inherent structural features influence the lifetimes of proteins is lacking. We report that yeast, mouse, and human proteins with terminal or internal intrinsically disordered segments have significantly shorter half-lives than proteins without these features. The lengths of the disordered segments that affect protein half-life are compatible with the structure of the proteasome. Divergence in terminal and internal disordered segments in yeast proteins originating from gene duplication leads to significantly altered half-life. Many paralogs that are affected by such changes participate in signaling, where altered protein half-life will directly impact cellular processes and function. Thus, natural variation in the length and position of disordered segments may affect protein half-life and could serve as an underappreciated source of genetic variation with important phenotypic consequences.

  2. Altered Mitochondria, Protein Synthesis Machinery, and Purine Metabolism Are Molecular Contributors to the Pathogenesis of Creutzfeldt-Jakob Disease.

    Science.gov (United States)

    Ansoleaga, Belén; Garcia-Esparcia, Paula; Llorens, Franc; Hernández-Ortega, Karina; Carmona Tech, Margarita; Antonio Del Rio, José; Zerr, Inga; Ferrer, Isidro

    2016-06-12

    Neuron loss, synaptic decline, and spongiform change are the hallmarks of sporadic Creutzfeldt-Jakob disease (sCJD), and may be related to deficiencies in mitochondria, energy metabolism, and protein synthesis. To investigate these relationships, we determined the expression levels of genes encoding subunits of the 5 protein complexes of the electron transport chain, proteins involved in energy metabolism, nucleolar and ribosomal proteins, and enzymes of purine metabolism in frontal cortex samples from 15 cases of sCJD MM1 and age-matched controls. We also assessed the protein expression levels of subunits of the respiratory chain, initiation and elongation translation factors of protein synthesis, and localization of selected mitochondrial components. We identified marked, generalized alterations of mRNA and protein expression of most subunits of all 5 mitochondrial respiratory chain complexes in sCJD cases. Expression of molecules involved in protein synthesis and purine metabolism were also altered in sCJD. These findings point to altered mRNA and protein expression of components of mitochondria, protein synthesis machinery, and purine metabolism as components of the pathogenesis of CJD. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

    de Castro Barbosa, Thais; Ingerslev, Lars R; Alm, Petter S

    2016-01-01

    OBJECTIVES: Chronic and high consumption of fat constitutes an environmental stress that leads to metabolic diseases. We hypothesized that high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa and metabolism of the offspring. METHODS: F0-male rats fed either HFD or chow diet......1 male offspring showed common DNA methylation and small non-coding RNA expression signatures. Altered expression of sperm miRNA let-7c was passed down to metabolic tissues of the offspring, inducing a transcriptomic shift of the let-7c predicted targets. CONCLUSION: Our results provide insight...... into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations....

  4. Metabolic and mitochondrial dysfunction in early mouse embryos following maternal dietary protein intervention.

    Science.gov (United States)

    Mitchell, Megan; Schulz, Samantha L; Armstrong, David T; Lane, Michelle

    2009-04-01

    Dietary supply of nutrients, both periconception and during pregnancy, influence the growth and development of the fetus and offspring and their health into adult life. Despite the importance of research efforts surrounding the developmental origins of health and disease hypothesis, the biological mechanisms involved remain elusive. Mitochondria are of major importance in the oocyte and early embryo, particularly as a source of ATP generation, and perturbations in their function have been related to reduced embryo quality. The present study examined embryo development following periconception exposure of females to a high-protein diet (HPD) or a low-protein diet (LPD) relative to a medium-protein diet (MPD; control), and we hypothesized that perturbed mitochondrial metabolism in the mouse embryo may be responsible for the impaired embryo and fetal development reported by others. Although the rate of development to the blastocyst stage did not differ between diets, both the HPD and LPD reduced the number of inner cell mass cells in the blastocyst-stage embryo. Furthermore, mitochondrial membrane potential was reduced and mitochondrial calcium levels increased in the 2-cell embryo. Embryos from HPD females had elevated levels of reactive oxygen species and ADP concentrations, indicative of metabolic stress and, potentially, the uncoupling of oxidative phosphorylation, whereas embryos from LPD females had reduced mitochondrial clustering around the nucleus, suggestive of an overall quietening of metabolism. Thus, although periconception dietary supply of different levels of protein is permissive of development, mitochondrial metabolism is altered in the early embryo, and the nature of the perturbation differs between HPD and LPD exposure.

  5. Importance of the cyanobacterial Gun4 protein for chlorophyll metabolism and assembly of photosynthetic complexes

    Czech Academy of Sciences Publication Activity Database

    Sobotka, Roman; Dühring, U.; Komenda, Josef; Peter, E.; Gardian, Zdenko; Tichý, Martin; Grimm, D.; Wilde, A.

    2008-01-01

    Roč. 283, č. 38 (2008), s. 25794-25802 ISSN 0021-9258 R&D Projects: GA AV ČR IAA500200713 Grant - others:DE(DE) SFB429; DE(DE) TPA8 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z50510513 Keywords : gun4 protein * chlorophyll metabolism * photosystem II Subject RIV: EE - Microbiology, Virology Impact factor: 5.520, year: 2008

  6. Effect of hyperbaric oxygenation on carbohydrate metabolism protein synthesis in the myocardium during sustained hypodynamia

    Science.gov (United States)

    Makarov, G. A.

    1980-01-01

    Glycolysis and the intensity of protein synthesis were studied in 140 white male rats in subcellular fractions of the myocardium during 45 day hypodynamia and hyperbaric oxygenation. Hypodynamia increased: (1) the amount of lactic acids; (2) the amount of pyruvic acid; (3) the lactate/pyruvate coefficient; and (4) the activities of aldolase and lactate dehydrogenase. Hyperbaric oxygenation was found to have a favorable metabolic effect on the animals with hypodynamia.

  7. Metabolism of serine in growing rats and chicks at various dietary protein levels

    International Nuclear Information System (INIS)

    Tanaka, Hideyuki; Yamaguchi, Michio; Kametaka, Masao

    1976-01-01

    The metabolic fate of the carbon skeleton of L-serine-U- 14 C has been investigated, in vivo and in vitro, in growing rats and chicks fed the diets with various protein calories percents (C %) at 410 kcal of metabolizable energy. The incorporation of 14 C into body protein at 12 hr after the injection of serine- 14 C was about 49% of the injected dose in rats fed the 10 or 15 PC% diet, though the value was reduced in rats fed lower and higher protein diets. The 14 CO 2 production was smaller in rats fed the 10 and 15 PC% diet, and it showed an inverse pattern to that of the 14 C incorporation into body protein. Urinary excretion of 14 C was higher in rats fed 10 and higher PC% diets, whose growth rate and net body protein retention were maximum. In contrast to the case of rats, the incorporation of 14 C into body protein of chicks at 6 hr after the injection was rather reduced in the 15 PC% group. The proportion of 14 C excreted as uric acid was remarkably increased above the 10 PC% group, and about 19% of the injected dose was recovered in the 50 PC% group. The catabolic rate of serine in the liver slices of rats and chicks was increased by high protein diets. These results support the concept that the nutritional significance of metabolism of the carbon skeleton of serine in growing rats and chicks is different from each other, especially at high protein diets. (auth.)

  8. Dietary fatty acids early in life affect lipid metabolism and adiposity in young rats.

    Science.gov (United States)

    Silva, Ana Paula S; Guimarães, Daniella E D; Mizurini, Daniella M; Maia, Ingrid C; Ortiz-Costa, Susana; Sardinha, Fátima L; do Carmo, Maria G Tavares

    2006-06-01

    The purpose of this study was to evaluate the effects of four isoenergetic diets of differing fat composition on blood lipid profile and adiposity in young rats. Diets containing different lipid sources--partially hydrogenated vegetable oil (PHVO), palm oil (PO), canola oil (CO), and soy oil (SO)--were fed to lactating rats during the 21 days of lactation, and then fed to young males following weaning until the 45th day of life. In vivo lipogenesis rate (LR), lipid content (LC), relative level of FA, and the activity of lipoprotein lipase (LPL) enzyme were measured in epididymal adipose tissue (EPI). Fasting blood lipoproteins and LC in the carcass were also appraised. Body weight of PO and PHVO groups was significantly higher than CO and SO groups from day 14 of lactation to day 45, despite the lower food intake in the PHVO group. PO and PHVO groups presented higher LR and LC in EPI than SO and CO groups. Carcass fat content was significantly higher in PHVO and PO groups than in CO and SO groups. The LPL activity in EPI was unaffected by dietary lipids. PHVO group had increased total cholesterol and TAG concentrations in comparison with the PO group, and significantly lower HDL level compared with the other groups. These results show that the kind of FA in the dietary lipid offered early in life can affect lipid metabolism and adiposity.

  9. Metabolic syndrome prevalence in different affective temperament profiles in bipolar-I disorder

    Directory of Open Access Journals (Sweden)

    Kursat Altinbas

    2013-06-01

    Full Text Available Objective: Temperament originates in the brain structure, and individual differences are attributable to neural and physiological function differences. It has been suggested that temperament is associated with metabolic syndrome (MetS markers, which may be partly mediated by lifestyle and socioeconomic status. Therefore, we aim to compare MetS prevalence between different affective temperamental profiles for each season in bipolar patients. Methods: Twenty-six bipolar type-I patients of a specialized outpatient mood disorder unit were evaluated for MetS according to new definition proposed by the International Diabetes Federation in the four seasons of a year. Temperament was assessed using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego - autoquestionnaire version (TEMPS-A. Results: The proportions of MetS were 19.2, 23.1, 34.6, and 38.5% in the summer, fall, spring, and winter, respectively. Only depressive temperament scores were higher (p = 0.002 during the winter in patients with MetS. Conclusion: These data suggest that depressive temperament profiles may predispose an individual to the development of MetS in the winter.

  10. Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

    Directory of Open Access Journals (Sweden)

    Anastasia V. Ponasenko

    2017-01-01

    Full Text Available Infective endocarditis (IE is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE.

  11. Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

    Science.gov (United States)

    Rutkovskaya, Natalia V.; Kondyukova, Natalia V.; Odarenko, Yuri N.; Kazachek, Yana V.; Tsepokina, Anna V.; Barbarash, Leonid S.

    2017-01-01

    Infective endocarditis (IE) is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE. PMID:28659664

  12. Acute Consumption of Flavan-3-ol-Enriched Dark Chocolate Affects Human Endogenous Metabolism.

    Science.gov (United States)

    Ostertag, Luisa M; Philo, Mark; Colquhoun, Ian J; Tapp, Henri S; Saha, Shikha; Duthie, Garry G; Kemsley, E Kate; de Roos, Baukje; Kroon, Paul A; Le Gall, Gwénaëlle

    2017-07-07

    Flavan-3-ols and methylxanthines have potential beneficial effects on human health including reducing cardiovascular risk. We performed a randomized controlled crossover intervention trial to assess the acute effects of consumption of flavan-3-ol-enriched dark chocolate, compared with standard dark chocolate and white chocolate, on the human metabolome. We assessed the metabolome in urine and blood plasma samples collected before and at 2 and 6 h after consumption of chocolates in 42 healthy volunteers using a nontargeted metabolomics approach. Plasma samples were assessed and showed differentiation between time points with no further separation among the three chocolate treatments. Multivariate statistics applied to urine samples could readily separate the postprandial time points and distinguish between the treatments. Most of the markers responsible for the multivariate discrimination between the chocolates were of dietary origin. Interestingly, small but significant level changes were also observed for a subset of endogenous metabolites. 1 H NMR revealed that flavan-3-ol-enriched dark chocolate and standard dark chocolate reduced urinary levels of creatinine, lactate, some amino acids, and related degradation products and increased the levels of pyruvate and 4-hydroxyphenylacetate, a phenolic compound of bacterial origin. This study demonstrates that an acute chocolate intervention can significantly affect human metabolism.

  13. The LDL Receptor-Related Protein 1: At the Crossroads of Lipoprotein Metabolism and Insulin Signaling

    Directory of Open Access Journals (Sweden)

    Dianaly T. Au

    2017-01-01

    Full Text Available The metabolic syndrome is an escalating worldwide public health concern. Defined by a combination of physiological, metabolic, and biochemical factors, the metabolic syndrome is used as a clinical guideline to identify individuals with a higher risk for type 2 diabetes and cardiovascular disease. Although risk factors for type 2 diabetes and cardiovascular disease have been known for decades, the molecular mechanisms involved in the pathophysiology of these diseases and their interrelationship remain unclear. The LDL receptor-related protein 1 (LRP1 is a large endocytic and signaling receptor that is widely expressed in several tissues. As a member of the LDL receptor family, LRP1 is involved in the clearance of chylomicron remnants from the circulation and has been demonstrated to be atheroprotective. Recently, studies have shown that LRP1 is involved in insulin receptor trafficking and regulation and glucose metabolism. This review summarizes the role of tissue-specific LRP1 in insulin signaling and its potential role as a link between lipoprotein and glucose metabolism in diabetes.

  14. Relationship of C-reactive protein, metabolic syndrome and diabetes mellitus: potential role of statins.

    Science.gov (United States)

    Nash, David T

    2005-12-01

    Atherosclerosis and the metabolic derangements of insulin resistance, metabolic syndrome and diabetes mellitus are all associated with underlying inflammatory processes. C-reactive protein (CRP), a marker of inflammation, has been shown to be a strong independent predictor of vascular events. It adds to cardiovascular disease risk at all levels of low-density-lipoprotein cholesterol and Framingham risk scores, and elevated levels are also associated with increasing severity of the metabolic syndrome. The development of a simple, stable, noninvasive test to measure high-sensitivity CRP has provided a clinical tool that may have an important role in the identification and assessment of individuals likely to develop cardiovascular or metabolic disease. The role of CRP in predicting cardiovascular risk is less clear in African Americans, however, than in white populations. Statins and thiazolidinediones are being investigated for their potential role in the prevention and treatment of the inflammatory processes involved in the metabolic syndrome and cardiovascular disease. In the future, assessment of CRP levels may contribute importantly to clinical decision-making in reducing cardiovascular risk.

  15. The Role of Carbohydrate Response Element Binding Protein in Intestinal and Hepatic Fructose Metabolism

    Directory of Open Access Journals (Sweden)

    Katsumi Iizuka

    2017-02-01

    Full Text Available Many articles have discussed the relationship between fructose consumption and the incidence of obesity and related diseases. Fructose is absorbed in the intestine and metabolized in the liver to glucose, lactate, glycogen, and, to a lesser extent, lipids. Unabsorbed fructose causes bacterial fermentation, resulting in irritable bowl syndrome. Therefore, understanding the mechanisms underlying intestinal and hepatic fructose metabolism is important for the treatment of metabolic syndrome and fructose malabsorption. Carbohydrate response element binding protein (ChREBP is a glucose-activated transcription factor that controls approximately 50% of de novo lipogenesis in the liver. ChREBP target genes are involved in glycolysis (Glut2, liver pyruvate kinase, fructolysis (Glut5, ketohexokinase, and lipogenesis (acetyl CoA carboxylase, fatty acid synthase. ChREBP gene deletion protects against high sucrose diet-induced and leptin-deficient obesity, because Chrebp−/− mice cannot consume fructose or sucrose. Moreover, ChREBP contributes to some of the physiological effects of fructose on sweet taste preference and glucose production through regulation of ChREBP target genes, such as fibroblast growth factor-21 and glucose-6-phosphatase catalytic subunits. Thus, ChREBP might play roles in fructose metabolism. Restriction of excess fructose intake will be beneficial for preventing not only metabolic syndrome but also irritable bowl syndrome.

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

    Science.gov (United States)

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

  17. Uteroplacental insufficiency down regulates insulin receptor and affects expression of key enzymes of long-chain fatty acid (LCFA metabolism in skeletal muscle at birth

    Directory of Open Access Journals (Sweden)

    Puglianiello Antonella

    2008-05-01

    Full Text Available Abstract Background Epidemiological studies have revealed a relationship between early growth restriction and the subsequent development of insulin resistance and type 2 diabetes. Ligation of the uterine arteries in rats mimics uteroplacental insufficiency and serves as a model of intrauterine growth restriction (IUGR and subsequent developmental programming of impaired glucose tolerance, hyperinsulinemia and adiposity in the offspring. The objective of this study was to investigate the effects of uterine artery ligation on the skeletal muscle expression of insulin receptor and key enzymes of LCFA metabolism. Methods Bilateral uterine artery ligation was performed on day 19 of gestation in Sprague-Dawley pregnant rats. Muscle of the posterior limb was dissected at birth and processed by real-time RT-PCR to analyze the expression of insulin receptor, ACCα, ACCβ (acetyl-CoA carboxylase alpha and beta subunits, ACS (acyl-CoA synthase, AMPK (AMP-activated protein kinase, alpha2 catalytic subunit, CPT1B (carnitine palmitoyltransferase-1 beta subunit, MCD (malonyl-CoA decarboxylase in 14 sham and 8 IUGR pups. Muscle tissue was treated with lysis buffer and Western immunoblotting was performed to assay the protein content of insulin receptor and ACC. Results A significant down regulation of insulin receptor protein (p Conclusion Our data suggest that uteroplacental insufficiency may affect skeletal muscle metabolism down regulating insulin receptor and reducing the expression of key enzymes involved in LCFA formation and oxidation.

  18. Metabolism

    Science.gov (United States)

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  19. Metabolism of early-lactation dairy cows as affected by dietary starch and monensin supplementation.

    Science.gov (United States)

    McCarthy, M M; Yasui, T; Ryan, C M; Pelton, S H; Mechor, G D; Overton, T R

    2015-05-01

    The objective of this study was to evaluate the effect of dietary starch content and monensin (MON) on metabolism of dairy cows during early lactation. Before parturition, primiparous (n=21) and multiparous (n=49) Holstein cows were fed a common controlled-energy close-up diet with a daily topdress of either 0 or 400mg/d monensin. From d 1 to 21 postpartum, cows were fed a high-starch (HS; 26.2% starch, 34.3% neutral detergent fiber, 22.7% acid detergent fiber, 15.5% crude protein) or low-starch (LS; 21.5% starch, 36.9% neutral detergent fiber, 25.2% acid detergent fiber, 15.4% crude protein) total mixed ration with a daily topdress of either 0mg/d monensin (CON) or 450mg/d monensin (MON), continuing with prepartum topdress assignment. From d 22 through 63 postpartum, all cows were fed HS and continued with the assigned topdress treatment until d 63. Cows fed HS had higher plasma glucose and insulin and lower nonesterified fatty acids (NEFA) than cows fed LS during d 1 to 21 postpartum. Cows fed LS had elevated early-lactation β-hydroxybutyrate (BHBA) compared with cows fed HS. Cows fed HS had greater insulin resistance and increased plasma haptoglobin in the early lactation period. There was no effect of MON on postpartum plasma NEFA. Cows fed MON had higher plasma glucose compared with CON cows, which was driven by a MON × parity interaction in which primiparous cows fed MON had greater plasma glucose concentrations than cows fed CON. Cows fed MON had lower plasma BHBA compared with CON, which was contributed to by a MON × parity interaction in which primiparous cows fed MON had lower BHBA concentrations than CON. Starch treatment had no effect on overall liver triglyceride content. Primiparous cows fed MON had increased liver triglyceride content compared with CON primiparous cows, and multiparous cows fed MON had decreased liver triglyceride content compared with CON cows. Multiparous cows fed LS with MON had higher liver glycogen content than multiparous

  20. Restoration of type 1 iodothyronine deiodinase expression in renal cancer cells downregulates oncoproteins and affects key metabolic pathways as well as anti-oxidative system.

    Science.gov (United States)

    Popławski, Piotr; Wiśniewski, Jacek R; Rijntjes, Eddy; Richards, Keith; Rybicka, Beata; Köhrle, Josef; Piekiełko-Witkowska, Agnieszka

    2017-01-01

    Type 1 iodothyronine deiodinase (DIO1) contributes to deiodination of 3,5,3',5'-tetraiodo-L-thyronine (thyroxine, T4) yielding of 3,5,3'-triiodothyronine (T3), a powerful regulator of cell differentiation, proliferation, and metabolism. Our previous work showed that loss of DIO1 enhances proliferation and migration of renal cancer cells. However, the global effects of DIO1 expression in various tissues affected by cancer remain unknown. Here, the effects of stable DIO1 re-expression were analyzed on the proteome of renal cancer cells, followed by quantitative real-time PCR validation in two renal cancer-derived cell lines. DIO1-induced changes in intracellular concentrations of thyroid hormones were quantified by L-MS/MS and correlations between expression of DIO1 and potential target genes were determined in tissue samples from renal cancer patients. Stable re-expression of DIO1, resulted in 26 downregulated proteins while 59 proteins were overexpressed in renal cancer cells. The 'downregulated' group consisted mainly of oncoproteins (e.g. STAT3, ANPEP, TGFBI, TGM2) that promote proliferation, migration and invasion. Furthermore, DIO1 re-expression enhanced concentrations of two subunits of thyroid hormone transporter (SLC7A5, SLC3A2), enzymes of key pathways of cellular energy metabolism (e.g. TKT, NAMPT, IDH2), sex steroid metabolism and anti-oxidative response (AKR1C2, AKR1B10). DIO1 expression resulted in elevated intracellular concentration of T4. Expression of DIO1-affected genes strongly correlated with DIO1 transcript levels in tissue samples from renal cancer patients as well as with their poor survival. This first study addressing effects of deiodinase re-expression on proteome of cancer cells demonstrates that induced DIO1 re-expression in renal cancer robustly downregulates oncoproteins, affects key metabolic pathways, and triggers proteins involved in anti-oxidative protection. This data supports the notion that suppressed DIO1 expression and changes

  1. Restoration of type 1 iodothyronine deiodinase expression in renal cancer cells downregulates oncoproteins and affects key metabolic pathways as well as anti-oxidative system.

    Directory of Open Access Journals (Sweden)

    Piotr Popławski

    Full Text Available Type 1 iodothyronine deiodinase (DIO1 contributes to deiodination of 3,5,3',5'-tetraiodo-L-thyronine (thyroxine, T4 yielding of 3,5,3'-triiodothyronine (T3, a powerful regulator of cell differentiation, proliferation, and metabolism. Our previous work showed that loss of DIO1 enhances proliferation and migration of renal cancer cells. However, the global effects of DIO1 expression in various tissues affected by cancer remain unknown. Here, the effects of stable DIO1 re-expression were analyzed on the proteome of renal cancer cells, followed by quantitative real-time PCR validation in two renal cancer-derived cell lines. DIO1-induced changes in intracellular concentrations of thyroid hormones were quantified by L-MS/MS and correlations between expression of DIO1 and potential target genes were determined in tissue samples from renal cancer patients. Stable re-expression of DIO1, resulted in 26 downregulated proteins while 59 proteins were overexpressed in renal cancer cells. The 'downregulated' group consisted mainly of oncoproteins (e.g. STAT3, ANPEP, TGFBI, TGM2 that promote proliferation, migration and invasion. Furthermore, DIO1 re-expression enhanced concentrations of two subunits of thyroid hormone transporter (SLC7A5, SLC3A2, enzymes of key pathways of cellular energy metabolism (e.g. TKT, NAMPT, IDH2, sex steroid metabolism and anti-oxidative response (AKR1C2, AKR1B10. DIO1 expression resulted in elevated intracellular concentration of T4. Expression of DIO1-affected genes strongly correlated with DIO1 transcript levels in tissue samples from renal cancer patients as well as with their poor survival. This first study addressing effects of deiodinase re-expression on proteome of cancer cells demonstrates that induced DIO1 re-expression in renal cancer robustly downregulates oncoproteins, affects key metabolic pathways, and triggers proteins involved in anti-oxidative protection. This data supports the notion that suppressed DIO1 expression

  2. Metabolism of histones and nonhistone proteins of the nuclei and chromatin of liver cells in rats of different ages

    International Nuclear Information System (INIS)

    Klimenko, A.I.; Malyshev, A.B.; Kulachenko, B.V.

    1986-01-01

    The metabolism of various classes of histones and nonhistone proteins in whole nuclei and liver chromatin of albino Wistar rats 1, 3, 12, and 24 months of age was studied. It was shown that in the course of postnatal ontogenesis, the metabolism of nonhistone proteins, extractable by a 0.14 M solution of NaCl, is increased in the animals. The incorporation of labeled precursors into the HMG 14 and HMG 17 proteins decreases with age of the animals; a higher level of specific radioactivity was established for the HMG 1+2 proteins in the 3- and 24-month old animals. The intensity of the metabolism of nonhistone proteins and histones is higher in the chromatin complex than in the whole nucleus at all stages of postnatal development of the animals. Among the histone proteins, H1 histones possess a higher level of specific radioactivity in animals of all age groups

  3. Effect of protein provision via milk replacer or solid feed on protein metabolism in veal calves

    NARCIS (Netherlands)

    Berends, H.; Borne, van den J.J.G.C.; Røjen, B.A.; Hendriks, W.H.; Gerrits, W.J.J.

    2015-01-01

    The current study evaluated the effects of protein provision to calves fed a combination of solid feed (SF) and milk replacer (MR) at equal total N intake on urea recycling and N retention. Nitrogen balance traits and [15N2]urea kinetics were measured in 30 calves (23 wk of age, 180 ± 3.7 kg of body

  4. The Effect of Oral Leucine on Protein Metabolism in Adolescents with Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Wilson ThomasA

    2010-11-01

    Full Text Available Lack of insulin results in a catabolic state in subjects with insulin-dependent diabetes mellitus which is reversed by insulin treatment. Amino acid supply, especially branched chain amino acids such as leucine, enhances protein synthesis in both animal and human studies. This small study was undertaken to assess the acute effect of supplemental leucine on protein metabolism in adolescents with type 1 diabetes. L-[1-13C] Leucine was used to assess whole-body protein metabolism in six adolescent females (16–18 yrs with type 1 diabetes during consumption of a basal diet (containing 58 μmoles leucine/kg/h and the basal diet with supplemental leucine (232 μmoles leucine/kg/h. Net leucine balance was significantly higher with supplemental leucine ( μmoles leucine/kg body weight/hr than with the basal diet (, due to reduced protein degradation ( μmoles leucine/kg body weight/hr compared to the basal diet (, .

  5. Does altered protein metabolism interfere with postmortem degradation analysis for PMI estimation?

    Science.gov (United States)

    Zissler, A; Ehrenfellner, B; Foditsch, E E; Monticelli, F C; Pittner, S

    2018-03-02

    An accurate estimation of the postmortem interval (PMI) is a central aspect in forensic routine. Recently, a novel approach based on the analysis of postmortem muscle protein degradation has been proposed. However, a number of questions remain to be answered until sensible application of this method to a broad variety of forensic cases is possible. To evaluate whether altered in vivo protein metabolism interferes with postmortem degradation patterns, we conducted a comparative study. We developed a standardized animal degradation model in rats, and collected additional muscle samples from animals recovering from muscle injury and from rats with developed disuse muscle atrophy after induced spinal cord injury. All samples were analyzed by SDS-PAGE and Western blot, labeling well-characterized muscle proteins. Tropomyosin was found to be stable throughout the investigated PMI and no alterations were detected in regenerating and atrophic muscles. In contrast, significant predictable postmortem changes occurred in desmin and vinculin protein band patterns. While no significant deviations from native patterns were detected in at-death samples of disuse muscle atrophy, interestingly, samples of rats recovering from muscle injury revealed additional desmin and vinculin degradation bands that did not occur in this form in any of the examined postmortem samples regardless of PMI. It remains to be investigated whether in vivo-altered metabolism influences postmortem degradation kinetics or if such muscle samples undergo postmortem degradation in a regular fashion.

  6. Whey Protein Supplementation Enhances Whole Body Protein Metabolism and Performance Recovery after Resistance Exercise: A Double-Blind Crossover Study

    Directory of Open Access Journals (Sweden)

    Daniel W. D. West

    2017-07-01

    Full Text Available No study has concurrently measured changes in free-living whole body protein metabolism and exercise performance during recovery from an acute bout of resistance exercise. We aimed to determine if whey protein ingestion enhances whole body net protein balance and recovery of exercise performance during overnight (10 h and 24 h recovery after whole body resistance exercise in trained men. In a double-blind crossover design, 12 trained men (76 ± 8 kg, 24 ± 4 years old, 14% ± 5% body fat; means ± standard deviation (SD performed resistance exercise in the evening prior to consuming either 25 g of whey protein (PRO; MuscleTech 100% Whey or an energy-matched placebo (CHO immediately post-exercise (0 h, and again the following morning (~10 h of recovery. A third randomized trial, completed by the same participants, involving no exercise and no supplement served as a rested control trial (Rest. Participants ingested [15N]glycine to determine whole body protein kinetics and net protein balance over 10 and 24 h of recovery. Performance was assessed pre-exercise and at 0, 10, and 24 h of recovery using a battery of tests. Net protein balance tended to improve in PRO (P = 0.064; effect size (ES = 0.61, PRO vs. CHO during overnight recovery. Over 24 h, net balance was enhanced in PRO (P = 0.036 but not in CHO (P = 0.84; ES = 0.69, PRO vs. CHO, which was mediated primarily by a reduction in protein breakdown (PRO < CHO; P < 0.01. Exercise decreased repetitions to failure (REP, maximal strength (MVC, peak and mean power, and countermovement jump performance (CMJ at 0 h (all P < 0.05 vs. Pre. At 10 h, there were small-to-moderate effects for enhanced recovery of the MVC (ES = 0.56, mean power (ES = 0.49, and CMJ variables (ES: 0.27–0.49 in PRO. At 24 h, protein supplementation improved MVC (ES = 0.76, REP (ES = 0.44, and peak power (ES = 0.55. In conclusion, whey protein supplementation enhances whole body anabolism, and may improve acute recovery of

  7. Free fatty acids and their metabolism affect function and survival of podocytes

    Directory of Open Access Journals (Sweden)

    Jonas eSieber

    2014-10-01

    Full Text Available Podocyte injury and loss critically contribute to the pathogenesis of proteinuric kidney diseases including diabetic nephropathy. Deregulated lipid metabolism with disturbed free fatty acid (FFA metabolism is a characteristic of metabolically unhealthy obesity and type 2 diabetes and likely contributes to end-stage kidney disease irrespective of the underlying kidney disease. In the current review we summarize recent findings related to FFAs and altered renal FFA metabolism with a special focus on podocytes. We will outline the opposing effects of saturated and monounsaturated FFAs and a particular emphasis will be given to the underlying molecular mechanisms involving insulin resistance and endoplasmic reticulum homeostasis. Finally, recent data suggesting a critical role of renal FFA metabolism to adapt to an altered lipid environment will be discussed.

  8. Mild hypothermic culture conditions affect residual host cell protein composition post-Protein A chromatography.

    Science.gov (United States)

    Goey, Cher Hui; Bell, David; Kontoravdi, Cleo

    2018-04-01

    Host cell proteins (HCPs) are endogenous impurities, and their proteolytic and binding properties can compromise the integrity, and, hence, the stability and efficacy of recombinant therapeutic proteins such as monoclonal antibodies (mAbs). Nonetheless, purification of mAbs currently presents a challenge because they often co-elute with certain HCP species during the capture step of protein A affinity chromatography. A Quality-by-Design (QbD) strategy to overcome this challenge involves identifying residual HCPs and tracing their source to the harvested cell culture fluid (HCCF) and the corresponding cell culture operating parameters. Then, problematic HCPs in HCCF may be reduced by cell engineering or culture process optimization. Here, we present experimental results linking cell culture temperature and post-protein A residual HCP profile. We had previously reported that Chinese hamster ovary cell cultures conducted at standard physiological temperature and with a shift to mild hypothermia on day 5 produced HCCF of comparable product titer and HCP concentration, but with considerably different HCP composition. In this study, we show that differences in HCP variety at harvest cascaded to downstream purification where different residual HCPs were present in the two sets of samples post-protein A purification. To detect low-abundant residual HCPs, we designed a looping liquid chromatography-mass spectrometry method with continuous expansion of a preferred, exclude, and targeted peptide list. Mild hypothermic cultures produced 20% more residual HCP species, especially cell membrane proteins, distinct from the control. Critically, we identified that half of the potentially immunogenic residual HCP species were different between the two sets of samples.

  9. Sugar Allocation to Metabolic Pathways is Tightly Regulated and Affects the Virulence of Streptococcus mutans

    Directory of Open Access Journals (Sweden)

    Miki Kawada-Matsuo

    2016-12-01

    Full Text Available Bacteria take up and metabolize sugar as a carbohydrate source for survival. Most bacteria can utilize many sugars, including glucose, sucrose, and galactose, as well as amino sugars, such as glucosamine and N-acetylglucosamine. After entering the cytoplasm, the sugars are mainly allocated to the glycolysis pathway (energy production and to various bacterial component biosynthesis pathways, including the cell wall, nucleic acids and amino acids. Sugars are also utilized to produce several virulence factors, such as capsule and lipoteichoic acid. Glutamine-fructose-6-phosphate aminotransferase (GlmS and glucosamine-6-phosphate deaminase (NagB have crucial roles in sugar distribution to the glycolysis pathway and to cell wall biosynthesis. In Streptococcus mutans, a cariogenic pathogen, the expression levels of glmS and nagB are coordinately regulated in response to the presence or absence of amino sugars. In addition, the disruption of this regulation affects the virulence of S. mutans. The expression of nagB and glmS is regulated by NagR in S. mutans, but the precise mechanism underlying glmS regulation is not clear. In Staphylococcus aureus and Bacillus subtilis, the mRNA of glmS has ribozyme activity and undergoes self-degradation at the mRNA level. However, there is no ribozyme activity region on glmS mRNA in S. mutans. In this review article, we summarize the sugar distribution, particularly the coordinated regulation of GlmS and NagB expression, and its relationship with the virulence of S. mutans.

  10. Bole girdling affects metabolic properties and root, trunk and branch hydraulics of young ponderosa pine trees.

    Science.gov (United States)

    Domec, Jean-Christophe; Pruyn, Michele L

    2008-10-01

    Effects of trunk girdling on seasonal patterns of xylem water status, water transport and woody tissue metabolic properties were investigated in ponderosa pine (Pinus ponderosa Dougl. ex P. Laws.) trees. At the onset of summer, there was a sharp decrease in stomatal conductance (g(s)) in girdled trees followed by a full recovery after the first major rainfall in September. Eliminating the root as a carbohydrate sink by girdling induced a rapid reversible reduction in g(s). Respiratory potential (a laboratory measure of tissue-level respiration) increased above the girdle (branches and upper trunk) and decreased below the girdle (lower trunk and roots) relative to control trees during the growing season, but the effect was reversed after the first major rainfall. The increase in branch respiratory potential induced by girdling suggests that the decrease in g(s) was caused by the accumulation of carbohydrates above the girdle, which is consistent with an observed increase in leaf mass per area in the girdled trees. Trunk girdling did not affect native xylem embolism or xylem conductivity. Both treated and control trunks experienced loss of xylem conductivity ranging from 10% in spring to 30% in summer. Girdling reduced xylem growth and sapwood to leaf area ratio, which in turn reduced branch leaf specific conductivity (LSC). The girdling-induced reductions in g(s) and transpiration were associated with a decrease in leaf hydraulic conductance. Two years after girdling, when root-to-shoot phloem continuity had been restored, girdled trees had a reduced density of new wood, which increased xylem conductivity and whole-tree LSC, but also vulnerability to embolism.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  12. SVD identifies transcript length distribution functions from DNA microarray data and reveals evolutionary forces globally affecting GBM metabolism.

    Directory of Open Access Journals (Sweden)

    Nicolas M Bertagnolli

    Full Text Available To search for evolutionary forces that might act upon transcript length, we use the singular value decomposition (SVD to identify the length distribution functions of sets and subsets of human and yeast transcripts from profiles of mRNA abundance levels across gel electrophoresis migration distances that were previously measured by DNA microarrays. We show that the SVD identifies the transcript length distribution functions as "asymmetric generalized coherent states" from the DNA microarray data and with no a-priori assumptions. Comparing subsets of human and yeast transcripts of the same gene ontology annotations, we find that in both disparate eukaryotes, transcripts involved in protein synthesis or mitochondrial metabolism are significantly shorter than typical, and in particular, significantly shorter than those involved in glucose metabolism. Comparing the subsets of human transcripts that are overexpressed in glioblastoma multiforme (GBM or normal brain tissue samples from The Cancer Genome Atlas, we find that GBM maintains normal brain overexpression of significantly short transcripts, enriched in transcripts that are involved in protein synthesis or mitochondrial metabolism, but suppresses normal overexpression of significantly longer transcripts, enriched in transcripts that are involved in glucose metabolism and brain activity. These global relations among transcript length, cellular metabolism and tumor development suggest a previously unrecognized physical mode for tumor and normal cells to differentially regulate metabolism in a transcript length-dependent manner. The identified distribution functions support a previous hypothesis from mathematical modeling of evolutionary forces that act upon transcript length in the manner of the restoring force of the harmonic oscillator.

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Deluc Laurent G

    2009-05-01

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

  15. Liver carbohydrates metabolism: A new islet-neogenesis associated protein peptide (INGAP-PP) target.

    Science.gov (United States)

    Villagarcía, Hernán Gonzalo; Román, Carolina Lisi; Castro, María Cecilia; González, Luisa Arbeláez; Ronco, María Teresa; Francés, Daniel Eleazar; Massa, María Laura; Maiztegui, Bárbara; Flores, Luis Emilio; Gagliardino, Juan José; Francini, Flavio

    2018-03-01

    Islet-Neogenesis Associated Protein-Pentadecapeptide (INGAP-PP) increases β-cell mass and enhances glucose and amino acids-induced insulin secretion. Our aim was to demonstrate its effect on liver metabolism. For that purpose, adult male Wistar rats were injected twice-daily (10 days) with saline solution or INGAP-PP (250 μg). Thereafter, serum glucose, triglyceride and insulin levels were measured and homeostasis model assessment (HOMA-IR) and hepatic insulin sensitivity (HIS) were determined. Liver glucokinase and glucose-6-phosphatase (G-6-Pase) expression and activity, phosphoenolpyruvate carboxykinase (PEPCK) expression, phosphofructokinase-2 (PFK-2) protein content, P-Akt/Akt and glycogen synthase kinase-3β (P-GSK3/GSK3) protein ratios and glycogen deposit were also determined. Additionally, glucokinase activity and G-6-Pase and PEPCK gene expression were also determined in isolated hepatocytes from normal rats incubated with INGAP-PP (5 μg/ml). INGAP-PP administration did not modify any of the serum parameters tested but significantly increased activity of liver glucokinase and the protein level of its cytosolic activator, PFK-2. Conversely, INGAP-PP treated rats decreased gene expression and enzyme activity of gluconeogenic enzymes, G-6-Pase and PEPCK. They also showed a higher glycogen deposit and P-GSK3/GSK3 and P-Akt/Akt ratio. In isolated hepatocytes, INGAP-PP increased GK activity and decreased G-6-Pase and PEPCK expression. These results demonstrate a direct effect of INGAP-PP on the liver acting through P-Akt signaling pathway. INGAP-PP enhances liver glucose metabolism and deposit and reduces its production/output, thereby contributing to maintain normal glucose homeostasis. These results reinforce the concept that INGAP-PP might become a useful tool to treat people with impaired islet/liver glucose metabolism as it occurs in T2D. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. The role of mitochondria in cellular iron-sulfur protein biogenesis and iron metabolism.

    Science.gov (United States)

    Lill, Roland; Hoffmann, Bastian; Molik, Sabine; Pierik, Antonio J; Rietzschel, Nicole; Stehling, Oliver; Uzarska, Marta A; Webert, Holger; Wilbrecht, Claudia; Mühlenhoff, Ulrich

    2012-09-01

    Mitochondria play a key role in iron metabolism in that they synthesize heme, assemble iron-sulfur (Fe/S) proteins, and participate in cellular iron regulation. Here, we review the latter two topics and their intimate connection. The mitochondrial Fe/S cluster (ISC) assembly machinery consists of 17 proteins that operate in three major steps of the maturation process. First, the cysteine desulfurase complex Nfs1-Isd11 as the sulfur donor cooperates with ferredoxin-ferredoxin reductase acting as an electron transfer chain, and frataxin to synthesize an [2Fe-2S] cluster on the scaffold protein Isu1. Second, the cluster is released from Isu1 and transferred toward apoproteins with the help of a dedicated Hsp70 chaperone system and the glutaredoxin Grx5. Finally, various specialized ISC components assist in the generation of [4Fe-4S] clusters and cluster insertion into specific target apoproteins. Functional defects of the core ISC assembly machinery are signaled to cytosolic or nuclear iron regulatory systems resulting in increased cellular iron acquisition and mitochondrial iron accumulation. In fungi, regulation is achieved by iron-responsive transcription factors controlling the expression of genes involved in iron uptake and intracellular distribution. They are assisted by cytosolic multidomain glutaredoxins which use a bound Fe/S cluster as iron sensor and additionally perform an essential role in intracellular iron delivery to target metalloproteins. In mammalian cells, the iron regulatory proteins IRP1, an Fe/S protein, and IRP2 act in a post-transcriptional fashion to adjust the cellular needs for iron. Thus, Fe/S protein biogenesis and cellular iron metabolism are tightly linked to coordinate iron supply and utilization. This article is part of a Special Issue entitled: Cell Biology of Metals. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Historical and contemporary stable isotope tracer approaches to studying mammalian protein metabolism

    Science.gov (United States)

    2016-01-01

    Over a century ago, Frederick Soddy provided the first evidence for the existence of isotopes; elements that occupy the same position in the periodic table are essentially chemically identical but differ in mass due to a different number of neutrons within the atomic nucleus. Allied to the discovery of isotopes was the development of some of the first forms of mass spectrometers, driven forward by the Nobel laureates JJ Thomson and FW Aston, enabling the accurate separation, identification, and quantification of the relative abundance of these isotopes. As a result, within a few years, the number of known isotopes both stable and radioactive had greatly increased and there are now over 300 stable or radioisotopes presently known. Unknown at the time, however, was the potential utility of these isotopes within biological disciplines, it was soon discovered that these stable isotopes, particularly those of carbon (13C), nitrogen (15N), oxygen (18O), and hydrogen (2H) could be chemically introduced into organic compounds, such as fatty acids, amino acids, and sugars, and used to “trace” the metabolic fate of these compounds within biological systems. From this important breakthrough, the age of the isotope tracer was born. Over the following 80 yrs, stable isotopes would become a vital tool in not only the biological sciences, but also areas as diverse as forensics, geology, and art. This progress has been almost exclusively driven through the development of new and innovative mass spectrometry equipment from IRMS to GC‐MS to LC‐MS, which has allowed for the accurate quantitation of isotopic abundance within samples of complex matrices. This historical review details the development of stable isotope tracers as metabolic tools, with particular reference to their use in monitoring protein metabolism, highlighting the unique array of tools that are now available for the investigation of protein metabolism in vivo at a whole body down to a single protein level

  18. The Ablation of Mitochondrial Protein Phosphatase Pgam5 Confers Resistance Against Metabolic Stress.

    Science.gov (United States)

    Sekine, Shiori; Yao, Akari; Hattori, Kazuki; Sugawara, Sho; Naguro, Isao; Koike, Masato; Uchiyama, Yasuo; Takeda, Kohsuke; Ichijo, Hidenori

    2016-03-01

    Phosphoglycerate mutase family member 5 (PGAM5) is a mitochondrial protein phosphatase that has been reported to be involved in various stress responses from mitochondrial quality control to cell death. However, its roles in vivo are largely unknown. Here, we show that Pgam5-deficient mice are resistant to several metabolic insults. Under cold stress combined with fasting, Pgam5-deficient mice better maintained body temperature than wild-type mice and showed an extended survival rate. Serum triglycerides and lipid content in brown adipose tissue (BAT), a center of adaptive thermogenesis, were severely reduced in Pgam5-deficient mice. Moreover, although Pgam5 deficiency failed to maintain proper mitochondrial integrity in BAT, it reciprocally resulted in the dramatic induction of fibroblast growth factor 21 (FGF21) that activates various functions of BAT including thermogenesis. Thus, the enhancement of lipid metabolism and FGF21 may contribute to the cold resistance of Pgam5-deficient mice under fasting condition. Finally, we also found that Pgam5-deficient mice are resistant to high-fat-diet-induced obesity. Our study uncovered that PGAM5 is involved in the whole-body metabolism in response to stresses that impose metabolic challenges on mitochondria.

  19. The Ablation of Mitochondrial Protein Phosphatase Pgam5 Confers Resistance Against Metabolic Stress

    Directory of Open Access Journals (Sweden)

    Shiori Sekine

    2016-03-01

    Full Text Available Phosphoglycerate mutase family member 5 (PGAM5 is a mitochondrial protein phosphatase that has been reported to be involved in various stress responses from mitochondrial quality control to cell death. However, its roles in vivo are largely unknown. Here, we show that Pgam5-deficient mice are resistant to several metabolic insults. Under cold stress combined with fasting, Pgam5-deficient mice better maintained body temperature than wild-type mice and showed an extended survival rate. Serum triglycerides and lipid content in brown adipose tissue (BAT, a center of adaptive thermogenesis, were severely reduced in Pgam5-deficient mice. Moreover, although Pgam5 deficiency failed to maintain proper mitochondrial integrity in BAT, it reciprocally resulted in the dramatic induction of fibroblast growth factor 21 (FGF21 that activates various functions of BAT including thermogenesis. Thus, the enhancement of lipid metabolism and FGF21 may contribute to the cold resistance of Pgam5-deficient mice under fasting condition. Finally, we also found that Pgam5-deficient mice are resistant to high-fat-diet-induced obesity. Our study uncovered that PGAM5 is involved in the whole-body metabolism in response to stresses that impose metabolic challenges on mitochondria.

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

    OpenAIRE

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

    2012-01-01

    Honey bees (Apis mellifera) provide a system for studying social and food-related behavior. A caste of workers performs age-related tasks: young bees (nurses) usually feed the brood and other adult bees inside the nest, while older bees (foragers) forage outside for pollen, a protein/lipid source, or nectar, a carbohydrate source. The workers' transition from nursing to foraging and their foraging preferences correlate with differences in gustatory perception, metabolic gene expression, and e...

  1. Myostatin promotes distinct responses on protein metabolism of skeletal and cardiac muscle fibers of rodents

    Directory of Open Access Journals (Sweden)

    L.H. Manfredi

    2017-10-01

    Full Text Available Myostatin is a novel negative regulator of skeletal muscle mass. Myostatin expression is also found in heart in a much less extent, but it can be upregulated in pathological conditions, such as heart failure. Myostatin may be involved in inhibiting protein synthesis and/or increasing protein degradation in skeletal and cardiac muscles. Herein, we used cell cultures and isolated muscles from rats to determine protein degradation and synthesis. Muscles incubated with myostatin exhibited an increase in proteolysis with an increase of Atrogin-1, MuRF1 and LC3 genes. Extensor digitorum longus muscles and C2C12 myotubes exhibited a reduction in protein turnover. Cardiomyocytes showed an increase in proteolysis by activating autophagy and the ubiquitin proteasome system, and a decrease in protein synthesis by decreasing P70S6K. The effect of myostatin on protein metabolism is related to fiber type composition, which may be associated to the extent of atrophy mediated effect of myostatin on muscle.

  2. Effects of a high protein diet on cognition and brain metabolism in cirrhotic rats.

    Science.gov (United States)

    Méndez-López, M; Méndez, M; Arias, J; Arias, J L

    2015-10-01

    Hepatic encephalopathy (HE) is a neurological complication observed in patients with liver disease. Patients who suffer from HE present neuropsychiatric, neuromuscular and behavioral symptoms. Animal models proposed to study HE resulting from cirrhosis mimic the clinical characteristics of cirrhosis and portal hypertension, and require the administration of hepatotoxins such as thioacetamide (TAA). The aim of this study was to assess the effects of a high protein diet on motor function, anxiety and memory processes in a model of cirrhosis induced by TAA administration. In addition, we used cytochrome c-oxidase (COx) histochemistry to assess the metabolic activity of the limbic system regions. Male rats were distributed into groups: control, animals with cirrhosis, Control rats receiving a high protein diet, and animals with cirrhosis receiving a high protein diet. Results showed preserved motor function and normal anxiety levels in all the groups. The animals with cirrhosis showed an impairment in active avoidance behavior and spatial memory, regardless of the diet they received. However, the animals with cirrhosis and a high protein diet showed longer escape latencies on the spatial memory task. The model of cirrhosis presented an under-activation of the dentate gyrus and CA3 hippocampal subfields and the medial part of the medial mammillary nucleus. The results suggest that a high protein intake worsens spatial memory deficits shown by the TAA-induced model of cirrhosis. However, high protein ingestion has no influence on the COx hypoactivity associated with the model. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. [Indicators of protein metabolism in infants with intrauterine dystrophy red various dietary mixtures].

    Science.gov (United States)

    Krukowa, A; Symonowicz, H; Wachnik, Z; Koziej, M

    1979-01-01

    In the previous work published in No 7 of "Development Period Medicine" ( Problemy Medycyny Wieku Rozwojowego ) the results of nitrogen balance studies in S-f-D infants fed different milk formulas were described. The present study concerns other protein metabolism indices in the same infants. The infants were divided into four groups according to the formula they were fed. The composition of formulas is shown in table I. In the infants besides the balance study, serum urea nitrogen, protein and albumin level, were estimated once a month. Also urea, creatine and creatinine, and hydroxyproline in 24-hours urine collections were examined. Excretion of creatine, creatinine and hydroxyproline was summarized in 5 boys from the group of 38 investigated infants in the first five months of life when meat-free diet was fed. The above mentioned indices permit for better assessment of the effect of the diet on protein metabolism and the requirement of protein for S-f-D infants. The results of protein metabolism indices were compared with the indices obtained in F.S. infants similarly fed. Group S of S-f-D infants was compared with group A of F.S. infants and the other groups of S-f-D infants were compared with each other. In S-f-D infants fed formula S, a lower level of serum urea nitrogen was observed in comparison with F.S. infants of group A in spite of greater protein intake in S-f-D infants. This should prove a greater protein requirement in S-f-D infants. Decreased protein content and cow's milk fat modification also had profitable influence on protein utilization because serum urea nitrogen and nitrogen in urine were low in S-f-D infants fed this formula. Urine urea nitrogen as a part of total urine nitrogen is bigger in group S and C infants, and the lowest in group G infants (formula with lower fat and total protein content). Serum protein and albumin level was generally higher in S-f-D infants than in FS ones. Particularly high level of these parameters was observed

  4. Adherence issues in inherited metabolic disorders treated by low natural protein diets

    DEFF Research Database (Denmark)

    MaCdonald, A; van Rijn, M; Feillet, F

    2012-01-01

    Common inborn errors of metabolism treated by low natural protein diets [amino acid (AA) disorders, organic acidemias and urea cycle disorders] are responsible for a collection of diverse clinical symptoms, each condition presenting at different ages with variable severity. Precursor......-free or essential L-AAs are important in all these conditions. Optimal long-term outcome depends on early diagnosis and good metabolic control, but because of the rarity and severity of conditions, randomized controlled trials are scarce. In all of these disorders, it is commonly described that dietary adherence...... on their neuropsychological profile. There are little data about their ability to self-manage their own diet or the success of any formal educational programs that may have been implemented. Trials conducted in non-phenylketonuria (PKU) patients are rare, and the development of specialist L-AAs for non-PKU AA disorders has...

  5. Lipo-protein emulsion structure in the diet affects protein digestion kinetics, intestinal mucosa parameters and microbiota composition

    OpenAIRE

    Oberli, Marion; Douard, Véronique; Beaumont, Martin; Jaoui, Daphné; Devime, Fabienne; Laurent, Sandy; Chaumontet, Catherine; Mat, Damien; Le Feunteun, Steven; Michon, Camille; Davila, Anne-Marie; Fromentin, Gilles; Tomé, Daniel; Souchon, Isabelle; Leclerc, Marion

    2017-01-01

    SCOPE: Food structure is a key factor controlling digestion and nutrient absorption. We tested the hypothesis that protein emulsion structure in the diet may affect digestive and absorptive processes. METHODS & RESULTS: Rats (n = 40) were fed for 3 weeks two diets chemically identical but based on lipid-protein liquid-fine (LFE) or gelled-coarse (GCE) emulsions that differ at the macro- and micro-structure levels. After an overnight fasting, they ingested a 15 N-labeled LFE or GCE te...

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

    Science.gov (United States)

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

    2013-12-01

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

  7. Respiratory muscle strength and muscle endurance are not affected by acute metabolic acidemia.

    NARCIS (Netherlands)

    Nizet, T.A.C.; Heijdra, Y.F.; Elshout, F.J.J. van den; Ven, M.J.T. van de; Bosch, F.H.; Mulder, P.H.M. de; Folgering, H.T.M.

    2009-01-01

    Respiratory muscle fatigue in asthma and chronic obstructive lung disease (COPD) contributes to respiratory failure with hypercapnia, and subsequent respiratory acidosis. Therapeutic induction of acute metabolic acidosis further increases the respiratory drive and, therefore, may diminish

  8. Trehalose Alters Subcellular Trafficking and the Metabolism of the Alzheimer-associated Amyloid Precursor Protein.

    Science.gov (United States)

    Tien, Nguyen T; Karaca, Ilker; Tamboli, Irfan Y; Walter, Jochen

    2016-05-13

    The disaccharide trehalose is commonly considered to stimulate autophagy. Cell treatment with trehalose could decrease cytosolic aggregates of potentially pathogenic proteins, including mutant huntingtin, α-synuclein, and phosphorylated tau that are associated with neurodegenerative diseases. Here, we demonstrate that trehalose also alters the metabolism of the Alzheimer disease-related amyloid precursor protein (APP). Cell treatment with trehalose decreased the degradation of full-length APP and its C-terminal fragments. Trehalose also reduced the secretion of the amyloid-β peptide. Biochemical and cell biological experiments revealed that trehalose alters the subcellular distribution and decreases the degradation of APP C-terminal fragments in endolysosomal compartments. Trehalose also led to strong accumulation of the autophagic marker proteins LC3-II and p62, and decreased the proteolytic activation of the lysosomal hydrolase cathepsin D. The combined data indicate that trehalose decreases the lysosomal metabolism of APP by altering its endocytic vesicular transport. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Protein metabolism in the small intestine during cancer cachexia and chemotherapy in mice.

    Science.gov (United States)

    Samuels, S E; Knowles, A L; Tilignac, T; Debiton, E; Madelmont, J C; Attaix, D

    2000-09-01

    The impact of cancer cachexia and chemotherapy on small intestinal protein metabolism and its subsequent recovery was investigated. Cancer cachexia was induced in mice with colon 26 adenocarcinoma, which is a small and slow-growing tumor characteristic of the human condition, and can be cured with 100% efficacy using an experimental nitrosourea, cystemustine (C6H12ClN3O4S). Both healthy mice and tumor-bearing mice were given a single i.p. injection of cystemustine (20 mg/kg) 3 days after the onset of cachexia. Cancer cachexia led to a reduced in vivo rate of protein synthesis in the small intestine relative to healthy mice (-13 to -34%; P synthesis compared with healthy mice (23-34%; P < 0.05). Northern hybridizations of mRNA encoding components of the major proteolytic systems suggested that proteolysis may not have mediated intestinal wasting or recovery. A major clinical goal should be to design methods to improve small intestinal protein metabolism before the initiation of chemotherapy.

  10. Effects of rumen undegradable protein supplementation on productive performance and indicators of protein and energy metabolism in Holstein fresh cows.

    Science.gov (United States)

    Amanlou, H; Farahani, T Amirabadi; Farsuni, N Eslamian

    2017-05-01

    The objective of this study was to determine the effects of feeding increased dietary crude protein (CP) on productive performance and indicators of protein and energy metabolism during 21 d postpartum. Thirty multiparous Holstein dairy cows were balanced by previous lactation milk yield, body condition score (BCS) at calving, and parity and randomly allocated to 1 of 3 dietary treatments from calving until 21 d postpartum. Dietary treatments were 16.0% CP with 5.0% rumen undegradable protein (RUP) based on dry matter (DM) (16CP), 18.7% CP with 7.0% RUP based on DM (19CP), and 21.4% CP with 9.0% RUP based on DM (21CP). Diets were similar in net energy for lactation (approximately 1.7 Mcal/kg of DM) and CP levels were increased with corn gluten meal and fish meal. Dry matter intake (DMI) was increased by increasing dietary CP levels from 16.0 to 19.0% of DM, but dietary CP beyond 19.0% had no effect on DMI. Milk yields were 4.7 and 6.5 kg/d greater in cows fed the 19CP and 21CP diets versus those fed the 16CP diet, whereas 4% fat-corrected milk was greater for cows fed the 21CP than the 16CP diet (36.0 vs. 31.4 kg/d). Milk protein content and yield, lactose yield, and milk urea nitrogen were elevated by increased dietary CP. Milk lactose content and fat yield were not different among dietary treatments, but milk fat content tended to decline with increasing content of CP in diets. High CP levels increased milk N secretion but decreased milk N efficiency. Apparent digestibility of DM, CP, and neutral detergent fiber was greater on the 19CP and 21CP diets compared with the 16CP diet. Cows fed the 19CP and 21CP diets lost less body condition relative to those fed the 16CP diet over 21 d postpartum. Feeding higher CP levels increased the concentrations of serum albumin, albumin to globulin ratio, and urea nitrogen and decreased aspartate aminotransferase, nonesterified fatty acids, and β-hydroxybutyrate, but had no effect on globulin, glucose, cholesterol, or

  11. Prosthetic model, but not stiffness or height, affects the metabolic cost of running for athletes with unilateral transtibial amputations.

    Science.gov (United States)

    Beck, Owen N; Taboga, Paolo; Grabowski, Alena M

    2017-07-01

    Running-specific prostheses enable athletes with lower limb amputations to run by emulating the spring-like function of biological legs. Current prosthetic stiffness and height recommendations aim to mitigate kinematic asymmetries for athletes with unilateral transtibial amputations. However, it is unclear how different prosthetic configurations influence the biomechanics and metabolic cost of running. Consequently, we investigated how prosthetic model, stiffness, and height affect the biomechanics and metabolic cost of running. Ten athletes with unilateral transtibial amputations each performed 15 running trials at 2.5 or 3.0 m/s while we measured ground reaction forces and metabolic rates. Athletes ran using three different prosthetic models with five different stiffness category and height combinations per model. Use of an Ottobock 1E90 Sprinter prosthesis reduced metabolic cost by 4.3 and 3.4% compared with use of Freedom Innovations Catapult [fixed effect (β) = -0.177; P Run (β = -0.139; P = 0.002) prostheses, respectively. Neither prosthetic stiffness ( P ≥ 0.180) nor height ( P = 0.062) affected the metabolic cost of running. The metabolic cost of running was related to lower peak (β = 0.649; P = 0.001) and stance average (β = 0.772; P = 0.018) vertical ground reaction forces, prolonged ground contact times (β = -4.349; P = 0.012), and decreased leg stiffness (β = 0.071; P running. Instead, an optimal prosthetic model, which improves overall biomechanics, minimizes the metabolic cost of running for athletes with unilateral transtibial amputations. NEW & NOTEWORTHY The metabolic cost of running for athletes with unilateral transtibial amputations depends on prosthetic model and is associated with lower peak and stance average vertical ground reaction forces, longer contact times, and reduced leg stiffness. Metabolic cost is unrelated to prosthetic stiffness, height, and stride kinematic symmetry. Unlike nonamputees who decrease leg stiffness with

  12. Activity of carbohydrate metabolism enzymes of bone marrow cells of rats affected by radiation

    International Nuclear Information System (INIS)

    Sukhomlinov, B.F.; Grinyuk, Yu.S.; Sibirnaya, N.A.; Starikovich, L.S.; Khmil', M.V.

    1990-01-01

    The influence of ionizing radiation (154.8 mC/kg on activity of some carbohydrate metabolism dehydrogenases in cells of the whole and fractionated rat bone marrow has been investigated. Different glucose metabolism units differently responded to radiation, the highest radiation response being exhibited by pentosophosphate cycle processes. The pattern of changes in the enzyme activity of different myelocaryocyte populations was shown to depend directly on the functional specilization of cells and the energy exchange types predominated in them

  13. Quantitative proteome and phosphoproteome analyses of Streptomyces coelicolor reveal proteins and phosphoproteins modulating differentiation and secondary metabolism

    DEFF Research Database (Denmark)

    Rioseras, Beatriz; Sliaha, Pavel V; Gorshkov, Vladimir

    2018-01-01

    identified and quantified 3461 proteins corresponding to 44.3% of the S. coelicolor proteome across three developmental stages: vegetative hypha (MI); secondary metabolite producing hyphae (MII); and sporulating hyphae. A total of 1350 proteins exhibited more than 2-fold expression changes during....../Thr/Tyr kinases, making this genus an outstanding model for the study of bacterial protein phosphorylation events. We used mass spectrometry based quantitative proteomics and phosphoproteomics to characterize bacterial differentiation and activation of secondary metabolism of Streptomyces coelicolor. We...... the bacterial differentiation process. These proteins include 136 regulators (transcriptional regulators, transducers, Ser/Thr/Tyr kinases, signalling proteins), as well as 542 putative proteins with no clear homology to known proteins which are likely to play a role in differentiation and secondary metabolism...

  14. Protein restriction does not affect body temperature pattern in female mice.

    Science.gov (United States)

    Kato, Goro A; Shichijo, Hiroki; Takahashi, Toshihiro; Shinohara, Akio; Morita, Tetsuo; Koshimoto, Chihiro

    2017-10-30

    Daily torpor is a physiological adaptation in mammals and birds characterized by a controlled reduction of metabolic rate and body temperature during the resting phase of circadian rhythms. In laboratory mice, daily torpor is induced by dietary caloric restriction. However, it is not known which nutrients are related to daily torpor expression. To determine whether dietary protein is a key factor in inducing daily torpor in mice, we fed mice a protein-restricted (PR) diet that included only one-quarter of the amount of protein but the same caloric level as a control (C) diet. We assigned six non-pregnant female ICR mice to each group and recorded their body weights and core body temperatures for 4 weeks. Body weights in the C group increased, but those in the PR group remained steady or decreased. Mice in both groups did not show daily torpor, but most mice in a food-restricted group (n=6) supplied with 80% of the calories given to the C group exhibited decreased body weights and frequently displayed daily torpor. This suggests that protein restriction is not a trigger of daily torpor; torpid animals can conserve their internal energy, but torpor may not play a significant role in conserving internal protein. Thus, opportunistic daily torpor in mice may function in energy conservation rather than protein saving.

  15. Plasma metabolic profiling of dairy cows affected with clinical ketosis using LC/MS technology.

    Science.gov (United States)

    Li, Y; Xu, C; Xia, C; Zhang, Hy; Sun, Lw; Gao, Y

    2014-01-01

    Ketosis in dairy cattle is an important metabolic disorder. Currently, the plasma metabolic profile of ketosis as determined using liquid chromatography-mass spectrometry (LC/MS) has not been reported. To investigate plasma metabolic profiles from cows with clinical ketosis in comparison to control cows. Twenty Holstein dairy cows were divided into two groups based on clinical signs and plasma β-hydroxybutyric acid and glucose concentrations 7-21 days postpartum: clinical ketosis and control cows. Plasma metabolic profiles were analyzed using LC/MS. Data were processed using principal component analysis and orthogonal partial least-squares discriminant analysis. Compared to control cows, the levels of valine, glycine, glycocholic, tetradecenoic acid, and palmitoleic acid increased significantly in clinical ketosis. On the other hand, the levels of arginine, aminobutyric acid, leucine/isoleucine, tryptophan, creatinine, lysine, norcotinine, and undecanoic acid decreased markedly. Our results showed that the metabolic changes in cows with clinical ketosis involve complex metabolic networks and signal transduction. These results are important for future studies elucidating the pathogenesis, diagnosis, and prevention of clinical ketosis in dairy cows.

  16. Hypoxia Pathway Proteins As Central Mediators of Metabolism in the Tumor Cells and Their Microenvironment

    Directory of Open Access Journals (Sweden)

    Sundary Sormendi

    2018-01-01

    Full Text Available Low oxygen tension or hypoxia is a determining factor in the course of many different processes in animals, including when tissue expansion and cellular metabolism result in high oxygen demands that exceed its supply. This is mainly happening when cells actively proliferate and the proliferating mass becomes distant from the blood vessels, such as in growing tumors. Metabolic alterations in response to hypoxia can be triggered in a direct manner, such as the switch from oxidative phosphorylation to glycolysis or inhibition of fatty acid desaturation. However, as the modulated action of hypoxia-inducible factors or the oxygen sensors (prolyl hydroxylase domain-containing enzymes can also lead to changes in enzyme expression, these metabolic changes can also be indirect. With this review, we want to summarize our current knowledge of the hypoxia-induced changes in metabolism during cancer development, how they are affected in the tumor cells and in the cells of the microenvironment, most prominently in immune cells.

  17. DsSWEET17, a Tonoplast-Localized Sugar Transporter from Dianthus spiculifolius, Affects Sugar Metabolism and Confers Multiple Stress Tolerance in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Aimin Zhou

    2018-05-01

    Full Text Available Plant SWEETs (Sugars Will Eventually be Exported Transporters affect the growth of plants by regulating the transport of sugar from source to sink and its intracellular transport between different organelles. In this study, DsSWEET17 from Dianthus spiculifolius was identified and characterized. Real-time quantitative PCR analysis revealed that the expression of DsSWEET17 was affected by exogenous application of fructose and glucose as well as under salt, osmotic, and oxidation stress. Colocalization experiments showed that the DsSWEET17-GFP (green fluorescent protein fusion protein was localized to the FM4-64-labeled tonoplasts in Arabidopsis. Compared to the wild type, the transgenic Arabidopsis seedlings overexpressing DsSWEET17 had longer roots, greater fresh weight, and a faster root growth upon exogenous application of fructose. Furthermore, transgenic Arabidopsis seedlings had significantly higher fructose accumulation than was observed for the wild-type seedlings. The analysis of root length revealed that transgenic Arabidopsis had higher tolerance to salt, osmotic, and oxidative stresses. Taken together, our results suggest that DsSWEET17 may be a tonoplast sugar transporter, and its overexpression affects sugar metabolism and confers multiple stress tolerance in Arabidopsis.

  18. DsSWEET17, a Tonoplast-Localized Sugar Transporter from Dianthus spiculifolius, Affects Sugar Metabolism and Confers Multiple Stress Tolerance in Arabidopsis.

    Science.gov (United States)

    Zhou, Aimin; Ma, Hongping; Feng, Shuang; Gong, Shufang; Wang, Jingang

    2018-05-24

    Plant SWEETs (Sugars Will Eventually be Exported Transporters) affect the growth of plants by regulating the transport of sugar from source to sink and its intracellular transport between different organelles. In this study, DsSWEET17 from Dianthus spiculifolius was identified and characterized. Real-time quantitative PCR analysis revealed that the expression of DsSWEET17 was affected by exogenous application of fructose and glucose as well as under salt, osmotic, and oxidation stress. Colocalization experiments showed that the DsSWEET17-GFP (green fluorescent protein) fusion protein was localized to the FM4-64-labeled tonoplasts in Arabidopsis . Compared to the wild type, the transgenic Arabidopsis seedlings overexpressing DsSWEET17 had longer roots, greater fresh weight, and a faster root growth upon exogenous application of fructose. Furthermore, transgenic Arabidopsis seedlings had significantly higher fructose accumulation than was observed for the wild-type seedlings. The analysis of root length revealed that transgenic Arabidopsis had higher tolerance to salt, osmotic, and oxidative stresses. Taken together, our results suggest that DsSWEET17 may be a tonoplast sugar transporter, and its overexpression affects sugar metabolism and confers multiple stress tolerance in Arabidopsis .

  19. Lipo-Protein Emulsion Structure in the Diet Affects Protein Digestion Kinetics, Intestinal Mucosa Parameters and Microbiota Composition.

    Science.gov (United States)

    Oberli, Marion; Douard, Véronique; Beaumont, Martin; Jaoui, Daphné; Devime, Fabienne; Laurent, Sandy; Chaumontet, Catherine; Mat, Damien; Le Feunteun, Steven; Michon, Camille; Davila, Anne-Marie; Fromentin, Gilles; Tomé, Daniel; Souchon, Isabelle; Leclerc, Marion; Gaudichon, Claire; Blachier, François

    2018-01-01

    Food structure is a key factor controlling digestion and nutrient absorption. We test the hypothesis that protein emulsion structure in the diet may affect digestive and absorptive processes. Rats (n = 40) are fed for 3 weeks with two diets chemically identical but based on lipid-protein liquid-fine (LFE) or gelled-coarse (GCE) emulsions that differ at the macro- and microstructure levels. After an overnight fasting, they ingest a 15 N-labeled LFE or GCE test meal and are euthanized 0, 15 min, 1 h, and 5 h later. 15 N enrichment in intestinal contents and blood are measured. Gastric emptying, protein digestion kinetics, 15 N absorption, and incorporation in blood protein and urea are faster with LFE than GCE. At 15 min time point, LFE group shows higher increase in GIP portal levels than GCE. Three weeks of dietary adaptation leads to higher expression of cationic amino acid transporters in ileum of LFE compared to GCE. LFE diet raises cecal butyrate and isovalerate proportion relative to GCE, suggesting increased protein fermentation. LFE diet increases fecal Parabacteroides relative abundance but decreases Bifidobacterium, Sutterella, Parasutterella genera, and Clostridium cluster XIV abundance. Protein emulsion structure regulates digestion kinetics and gastrointestinal physiology, and could be targeted to improve food health value. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Clofazimine modulates the expression of lipid metabolism proteins in Mycobacterium leprae-infected macrophages.

    Science.gov (United States)

    Degang, Yang; Akama, Takeshi; Hara, Takeshi; Tanigawa, Kazunari; Ishido, Yuko; Gidoh, Masaichi; Makino, Masahiko; Ishii, Norihisa; Suzuki, Koichi

    2012-01-01

    Mycobacterium leprae (M. leprae) lives and replicates within macrophages in a foamy, lipid-laden phagosome. The lipids provide essential nutrition for the mycobacteria, and M. leprae infection modulates expression of important host proteins related to lipid metabolism. Thus, M. leprae infection increases the expression of adipophilin/adipose differentiation-related protein (ADRP) and decreases hormone-sensitive lipase (HSL), facilitating the accumulation and maintenance of lipid-rich environments suitable for the intracellular survival of M. leprae. HSL levels are not detectable in skin smear specimens taken from leprosy patients, but re-appear shortly after multidrug therapy (MDT). This study examined the effect of MDT components on host lipid metabolism in vitro, and the outcome of rifampicin, dapsone and clofazimine treatment on ADRP and HSL expression in THP-1 cells. Clofazimine attenuated the mRNA and protein levels of ADRP in M. leprae-infected cells, while those of HSL were increased. Rifampicin and dapsone did not show any significant effects on ADRP and HSL expression levels. A transient increase of interferon (IFN)-β and IFN-γ mRNA was also observed in cells infected with M. leprae and treated with clofazimine. Lipid droplets accumulated by M. leprae-infection were significantly decreased 48 h after clofazimine treatment. Such effects were not evident in cells without M. leprae infection. In clinical samples, ADRP expression was decreased and HSL expression was increased after treatment. These results suggest that clofazimine modulates lipid metabolism in M. leprae-infected macrophages by modulating the expression of ADRP and HSL. It also induces IFN production in M. leprae-infected cells. The resultant decrease in lipid accumulation, increase in lipolysis, and activation of innate immunity may be some of the key actions of clofazimine.

  1. Respiratory and metabolic acidosis differentially affect the respiratory neuronal network in the ventral medulla of neonatal rats.

    Science.gov (United States)

    Okada, Yasumasa; Masumiya, Haruko; Tamura, Yoshiyasu; Oku, Yoshitaka

    2007-11-01

    Two respiratory-related areas, the para-facial respiratory group/retrotrapezoid nucleus (pFRG/RTN) and the pre-Bötzinger complex/ventral respiratory group (preBötC/VRG), are thought to play key roles in respiratory rhythm. Because respiratory output patterns in response to respiratory and metabolic acidosis differ, we hypothesized that the responses of the medullary respiratory neuronal network to respiratory and metabolic acidosis are different. To test these hypotheses, we analysed respiratory-related activity in the pFRG/RTN and preBötC/VRG of the neonatal rat brainstem-spinal cord in vitro by optical imaging using a voltage-sensitive dye, and compared the effects of respiratory and metabolic acidosis on these two populations. We found that the spatiotemporal responses of respiratory-related regional activities to respiratory and metabolic acidosis are fundamentally different, although both acidosis similarly augmented respiratory output by increasing respiratory frequency. PreBötC/VRG activity, which is mainly inspiratory, was augmented by respiratory acidosis. Respiratory-modulated pixels increased in the preBötC/VRG area in response to respiratory acidosis. Metabolic acidosis shifted the respiratory phase in the pFRG/RTN; the pre-inspiratory dominant pattern shifted to inspiratory dominant. The responses of the pFRG/RTN activity to respiratory and metabolic acidosis are complex, and involve either augmentation or reduction in the size of respiratory-related areas. Furthermore, the activation pattern in the pFRG/RTN switched bi-directionally between pre-inspiratory/inspiratory and post-inspiratory. Electrophysiological study supported the results of our optical imaging study. We conclude that respiratory and metabolic acidosis differentially affect activities of the pFRG/RTN and preBötC/VRG, inducing switching and shifts of the respiratory phase. We suggest that they differently influence the coupling states between the pFRG/RTN and preBötC/VRG.

  2. Dietary protein content affects evolution for body size, body fat and viability in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Kristensen, Torsten N; Overgaard, Johannes; Loeschcke, Volker

    2011-01-01

    The ability to use different food sources is likely to be under strong selection if organisms are faced with natural variation in macro-nutrient (protein, carbohydrate and lipid) availabilities. Here, we use experimental evolution to study how variable dietary protein content affects adult body...... composition and developmental success in Drosophila melanogaster. We reared flies on either a standard diet or a protein-enriched diet for 17 generations before testing them on both diet types. Flies from lines selected on protein-rich diet produced phenotypes with higher total body mass and relative lipid...... content when compared with those selected on a standard diet, irrespective of which of the two diets they were tested on. However, selection on protein-rich diet incurred a cost as flies reared on this diet had markedly lower developmental success in terms of egg-to-adult viability on both medium types...

  3. Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown.

    Science.gov (United States)

    Riis, Anne Lene Dalkjaer; Jørgensen, Jens Otto Lunde; Gjedde, Signe; Nørrelund, Helene; Jurik, Anne Grethe; Nair, K S; Ivarsen, Per; Weeke, Jørgen; Møller, Niels

    2005-06-01

    Thyroid hormones have significant metabolic effects, and muscle wasting and weakness are prominent clinical features of chronic hyperthyroidism. To assess the underlying mechanisms, we examined seven hyperthyroid women with Graves' disease before (Ht) and after (Eut) medical treatment and seven control subjects (Ctr). All subjects underwent a 3-h study in the postabsorptive state. After regional catheterization, protein dynamics of the whole body and of the forearm muscles were measured by amino acid tracer dilution technique using [15N]phenylalanine and [2H4]tyrosine. Before treatment, triiodothyronine was elevated (6.6 nmol/l) and whole body protein breakdown was increased 40%. The net forearm release of phenylalanine was increased in hyperthyroidism (microg.100 ml(-1).min(-1)): -7.0 +/- 1.2 Ht vs. -3.8 +/- 0.8 Eut (P = 0.04), -4.2 +/- 0.3 Ctr (P = 0.048). Muscle protein breakdown, assessed by phenylalanine rate of appearance, was increased (microg.100 ml(-1).min(-1)): 15.5 +/- 2.0 Ht vs. 9.6 +/- 1.4 Eut (P = 0.03), 9.9 +/- 0.6 Ctr (P = 0.02). Muscle protein synthesis rate did not differ significantly. Muscle mass and muscle function were decreased 10-20% before treatment. All abnormalities were normalized after therapy. In conclusion, our results show that hyperthyroidism is associated with increased muscle amino acid release resulting from increased muscle protein breakdown. These abnormalities can explain the clinical manifestations of sarcopenia and myopathy.

  4. Soy Germ Protein With or Without-Zn Improve Plasma Lipid Profile in Metabolic Syndrome Women

    Directory of Open Access Journals (Sweden)

    SIWI PRAMATAMA MARS WIJAYANTI

    2012-03-01

    Full Text Available The aim of this research was to determine the effect of soy germ protein on lipid profile of metabolic syndrome (MetS patients. Respondents were 30 women with criteria, i.e. blood glucose level > normal, body mass index > 25 kg/m2, hypertriglyceridemia, low cholesterol-HDL level, 40-65 years old, living in Purwokerto, and signed the informed consent. The project was approved by the ethics committee of the Medical Faculty from Gadjah Mada University-Yogyakarta. Respondents were divided into three randomly chosen groups consisting of ten women each. The first, second, and third groups were treated, respectively, with milk enriched soy germ protein plus Zn, milk enriched soy germ protein (without Zn, and placebo for two months. Blood samples were taken at baseline, one and two months after observation. Two months after observation the groups consuming milk enriched with soy germ protein, both with or without Zn, had their level of cholesterol-total decrease from 215.8 to 180.2 mg/dl (P = 0.03, triglyceride from 240.2 to 162.5 mg/dl (P = 0.02, and LDL from 154.01 to 93.85 mg/dl (P = 0.03. In contrast, HDL increased from 38.91 to 49.49 mg/dl (P = 0.0008. In conclusion, soy germ protein can improve lipid profile, thus it can inhibit atherosclerosis incident.

  5. Changes in protein metabolism after gastric resection studied by 125I-albumin

    International Nuclear Information System (INIS)

    Beno, I.; Cerven, J.

    1976-01-01

    The changes were studied in the metabolism of protein using albumin- 125 I in seven patients with benign conditions of the stomach or duodenum before gastrectomy and starting with the second week after the surgery. In the postoperative period body weight was found to be significantly reduced, there was a drop in erythrocyte count, and blood hemoglobin and plasma albumin concentration were decreased. There was a significant rise of plasma volume during this period. Compared with the preoperative findings, the intravascular albumin pool was diminished by 11%, the extravascular albumin pool by 19.%, so that the overall albumin pool was postoperatively found to be reduced by 1/6. (author)

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

    Science.gov (United States)

    Petersen, Ann M; Gleeson, Todd T

    2011-09-01

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

  7. Investigation of carbohydrate and protein metabolism in the digestive organs of the rabbit under the combined influence of vibration, acceleration and irradiation

    Science.gov (United States)

    Yuy, R. I.

    1975-01-01

    During spaceflight, the organism is subjected to the influence of various extremal factors such as acceleration, vibration, irradiation, etc. The study of the influence of these factors on metabolism, especially carbohydrate and protein metabolism, in young rabbits is of great significance in simulation experiments. Dynamic factors and irradiation, depending on dose and duration, lead to reduced RNA and protein metabolism.

  8. Hepatic expression of the GH/JAK/STAT/IGF pathway, acute-phase response signalling and complement system are affected in mouse offspring by prenatal and early postnatal exposure to maternal high-protein diet.

    Science.gov (United States)

    Vanselow, Jens; Kucia, Marzena; Langhammer, Martina; Koczan, Dirk; Rehfeldt, Charlotte; Metges, Cornelia C

    2011-12-01

    Effects of pre- and early postnatal exposure to maternal high-protein diets are not well understood. Transcription profiling was performed in male mouse offspring exposed to maternal high-protein diet during pregnancy and/or lactation to identify affected hepatic molecular pathways. Dams were fed isoenergetic diets with control (20% w/w) or high protein levels (40%). The hepatic expression profiles were evaluated by differential microarray analysis 3 days (d3) and 3 weeks (d21) after birth. Offspring from three different high-protein dietary groups, HP (d3, high-protein diet during pregnancy), HPHP (d21, high-protein diet during pregnancy and lactation) and CHP (d21, control diet during pregnancy and high-protein diet during lactation), were compared with age-matched offspring from dams fed control diet. Offspring body and liver mass of all high-protein groups were decreased. Prenatal high-protein diet affected hepatic expression of genes mapping to the acute response/complement system and the GH/JAK/STAT/IGF signalling pathways. Maternal exposure to high-protein diet during lactation affected hepatic gene expression of the same pathways but additionally affected genes mapping to protein, fatty acid, hexose and pyruvate metabolism. (1) Genes of the acute response/complement system and GH/JAK/STAT/IGF pathways were down-regulated in offspring of dams exposed to high-protein diets during pregnancy and/or lactation. (2) Genes related to nutrient and energy metabolism, however, were only affected when high-protein diet was administered during lactation. (3) Modulation of the GH/JAK/STAT/IGF pathway might be responsible for reduced body and liver masses by maternal high-protein diet.

  9. Multi-omic profiling of EPO-producing Chinese hamster ovary cell panel reveals metabolic adaptation to heterologous protein production

    DEFF Research Database (Denmark)

    Ley, Daniel; Kazemi Seresht, Ali; Engmark, Mikael

    2015-01-01

    Chinese hamster ovary (CHO) cells are the preferred production host for many therapeutic proteins. The production of heterologous proteins in CHO cells imposes a burden on the host cell metabolism and impact cellular physiology on a global scale. In this work, a multi-omics approach was applied...

  10. Intracerebroventricular ghrelin treatment affects lipid metabolism in liver of rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Velasco, Cristina; Librán-Pérez, Marta; Otero-Rodiño, Cristina; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

    2016-03-01

    We aimed to elucidate in rainbow trout (Oncorhynchus mykiss) the effects of central ghrelin (GHRL) treatment on the regulation of liver lipid metabolism, and the possible modulatory effect of central GHRL treatment on the simultaneous effects of raised levels of oleate. Thus, we injected intracerebroventricularly (ICV) rainbow trout GHRL in the presence or absence of oleate and evaluated in liver variables related to lipid metabolism. Oleate treatment elicited in liver of rainbow trout decreased lipogenesis and increased oxidative capacity in agreement with previous studies. Moreover, as demonstrated for the first time in fish in the present study, GHRL also acts centrally modulating lipid metabolism in liver, resulting in increased potential for lipogenesis and decreased potential for fatty acid oxidation, i.e. the converse effects to those elicited by central oleate treatment. The simultaneous treatment of GHRL and oleate confirmed these counteractive effects. Thus, the nutrient sensing mechanisms present in hypothalamus, particularly those involved in sensing of fatty acid, are involved in the control of liver energy metabolism in fish, and this control is modulated by the central action of GHRL. These results give support to the notion of hypothalamus as an integrative place for the regulation of peripheral energy metabolism in fish. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. An increase level of acylation stimulating protein is correlated with metabolic risk markers in North Indian obese women.

    Science.gov (United States)

    Mishra, Supriya; Gupta, Vani; Mishra, Sameeksha; Gupta, Vandana; Mahdi, Abbas Ali; Sachan, Rekha

    2017-12-01

    The present study was to investigate the association between serum acylation stimulating protein (ASP) level with metabolic risk factors in North Indian obese women. This is a case control study, total n=322 women aged between 20 and 45 years (n=162 with metabolic syndrome & n=160 without metabolic syndrome) were recruited for the study according to National Cholesterol Education Program Treatment Panel (NCEPATP) guidelines. Serum ASP level were determined by enzyme linked immunosorbent assay. Results indicated that circulating ASP and other metabolic risk factors (waist circumference, triglycerides, fasting plasma glucose etc) were significantly higher in women with metabolic syndrome (WmetS) than in women without syndrome (WometS) (pwomen with metabolic syndrome. Conclusively circulating ASP was found to be significantly associated with hyperlipidemia, obesity and obesity related disorders in North Indian obese women. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  12. Abomasal protein infusion in postpartum transition dairy cows: Effect on performance and mammary metabolism

    DEFF Research Database (Denmark)

    Larsen, Mogens; Lapierre, H; Kristensen, Niels Bastian

    2014-01-01

    The effect of increasing the postpartum metabolizable protein (MP) supply on performance and mammary metabolism was studied using 8 Holstein cows in a complete randomized design. At parturition, cows were assigned to abomasal infusion of water (CTRL) or casein (CAS). Arterial and epigastric venous....../d for CTRL, but did not differ at 29 DIM (1,383 ± 48 g/d). The ratio of MP total supply to requirement was numerically greater at 4 DIM for CAS compared with CTRL, indicating less postpartum protein deficiency. In contrast, a greater net energy deficiency tended to be induced with CAS, but the greater milk...... of glucose, lactate, and β-hydroxybutyrate, whereas uptakes of volatile fatty acids were unaffected. Despite similar MP supply by 29 DIM, milk and lactose yields were greater with CAS indicating a persistent response to increased postpartum MP supply. In conclusion, the postpartum MP deficiency can have...

  13. Cytosolic fatty acid-binding proteins: subjects and tools in metabolic research

    Energy Technology Data Exchange (ETDEWEB)

    Binas, B. [Max Delbrueck Center for Molecular Medicine, Berlin-Buch (Germany)

    1998-12-31

    Fatty acid-binding proteins (FABPs) are major targets for specific binding of fatty acids in vivo. They constitute a widely expressed family of genetically related, small cytosolic proteins which very likely mediate intracellular transport of free long chain fatty acids. Genetic inhibition of FABP expression in vivo should therefore provide a useful tool to investigate and engineer fatty acid metabolism. (orig.) [Deutsch] Fettsaeurebindungsproteine (FABPs) sind wichtige Bindungsstellen fuer Fettsaeuren in vivo; sie bilden eine breit exprimierte Familie genetisch verwandter kleiner Zytosoleiweisse, die sehr wahrscheinlich den intrazellulaeren Transport unveresterter langkettiger Fettsaeuren vermitteln. Die genetische Hemmung der FABP-Expanssion in vivo bietet sich deshalb als Werkzeug zur Erforschung und gezielten Veraenderung des Fettsaeurestoffwechsels an. (orig.)

  14. Anesthesia with halothane and nitrous oxide alters protein and amino acid metabolism in dogs

    International Nuclear Information System (INIS)

    Horber, F.F.; Krayer, S.; Rehder, K.; Haymond, M.W.

    1988-01-01

    General anesthesia in combination with surgery is known to result in negative nitrogen balance. To determine whether general anesthesia without concomitant surgery decreases whole body protein synthesis and/or increases whole body protein breakdown, two groups of dogs were studied: Group 1 (n = 6) in the conscious state and Group 2 (n = 8) during general anesthesia employing halothane (1.5 MAC) in 50% nitrous oxide and oxygen. Changes in protein metabolism were estimated by isotope dilution techniques employing simultaneous infusions of [4,53H]leucine and alpha-[1-14C]-ketoisocaproate (KIC). Total leucine carbon flux was unchanged or slightly increased in the anesthetized animals when compared to the conscious controls, indicating only a slight increase in the rate of proteolysis. However, leucine oxidation was increased (P less than 0.001) by more than 80% in the anesthetized animals when compared with their conscious controls, whereas whole body nonoxidative leucine disappearance, an indicator of whole body protein synthesis, was decreased. The ratio of leucine oxidation to the nonoxidative rate of leucine disappearance, which provides an index of the catabolism of at least one essential amino acid in the postabsorptive state, was more than twofold increased (P less than 0.001) in the anesthetized animals regardless of the tracer employed. These studies suggest that the administration of anesthesia alone, without concomitant surgery, is associated with a decreased rate of whole body protein synthesis and increased leucine oxidation, resulting in increased leucine and protein catabolism, which may be underlying or initiating some of the protein wasting known to occur in patients undergoing surgery

  15. The impact of visual media to encourage low protein cooking in inherited metabolic disorders.

    Science.gov (United States)

    Evans, S; Daly, A; Hopkins, V; Davies, P; MacDonald, A

    2009-10-01

    The use of educational visual aids is one way to help children with inherited metabolic disorders (IMD) understand and develop a positive attitude towards their low protein diet. However, it is difficult to establish their effectiveness in the clinical setting. The present study aimed to evaluate the impact of a low protein recipe book and accompanying DVD for children with IMD. One hundred and five children (53% female; median age = 6-8 years) with IMD on low protein diets were each given a low protein recipe book and DVD. After 6 months, children and carers were posted a questionnaire asking whether they used these resources; identifying any change in frequency of low protein cooking; and the outcome when preparing recipes. One hundred and two questionnaires were returned, representing 105 patients. Seventy percent (n = 71) of questionnaires were from carers. Ninety-three percent (n = 66) of carers acknowledged receipt of the resource; one-third (n = 22) had not watched the DVD and 23% (n = 15) had not opened the recipe book; 55% (n = 36) had tried the recipes; and 71% (n = 47) said the recipe book and/or DVD motivated them to try new recipes. Children were more likely to have watched the DVD (75%; n = 21/28) and read the recipe book (86%; n = 24/28) than carers. Although a helpful educational tool, just over one-half of respondents had used the resource. Identifying visual media that, by itself, will motivate most families of children with IMD to prepare low protein recipes may be unrealistic. The combined approach of visual aids and 'hands-on' practical experience, such as low protein cooking workshops and individual counselling, may be more beneficial.

  16. Designing and determining validity and reliability of a questionnaire to identify factors affecting nutritional behavior among patients with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Naseh Esmaeili

    2017-06-01

    Full Text Available Background : A number of studies have shown a clear relationship between diet and component of metabolic syndrome. Based on the Theory of Reasoned Action (TRA, attitude and subjective norm are factors affecting behavioral intention and subsequently behavior. The aim of the present study is to design a valid questionnaire identifying factors affecting nutritional behavior among patients with metabolic syndrome. Materials and Methods: Via literature review, six focus group discussion and interview with nutrition specialists were performed to develop an instrument based on the theory of reasoned action. To determine validity of the instrument, content and face validity analyses with 15 expert panels conducted and also to determine reliability, Cronbach’s Alpha coefficient performed. Results: A draft of 100 items questionnaire was developed and after evaluation of validity and reliability, final questionnaire included 46 items: 17 items for attitude, 13 items for subjective norms and 16 items for behavioral intention. For the final questionnaire average of content validity index was 0/92 and Cronbach’s Alpha coefficient was 0/85. Conclusion: Based on the results of the current study the developed questionnaire is a valid and reliable instrument and it can be used to identify factors affecting nutritional behavior among people with metabolic syndrome based on the theory of reasoned action.

  17. The non-psychoactive plant cannabinoid, cannabidiol affects cholesterol metabolism-related genes in microglial cells.

    Science.gov (United States)

    Rimmerman, Neta; Juknat, Ana; Kozela, Ewa; Levy, Rivka; Bradshaw, Heather B; Vogel, Zvi

    2011-08-01

    Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that is clinically used in a 1:1 mixture with the psychoactive cannabinoid Δ(9)-tetrahydrocannabinol (THC) for the treatment of neuropathic pain and spasticity in multiple sclerosis. Our group previously reported that CBD exerts anti-inflammatory effects on microglial cells. In addition, we found that CBD treatment increases the accumulation of the endocannabinoid N-arachidonoyl ethanolamine (AEA), thus enhancing endocannabinoid signaling. Here we proceeded to investigate the effects of CBD on the modulation of lipid-related genes in microglial cells. Cell viability was tested using FACS analysis, AEA levels were measured using LC/MS/MS, gene array analysis was validated with real-time qPCR, and cytokine release was measured using ELISA. We report that CBD significantly upregulated the mRNAs of the enzymes sterol-O-acyl transferase (Soat2), which synthesizes cholesteryl esters, and of sterol 27-hydroxylase (Cyp27a1). In addition, CBD increased the mRNA of the lipid droplet-associated protein, perilipin2 (Plin2). Moreover, we found that pretreatment of the cells with the cholesterol chelating agent, methyl-β-cyclodextrin (MBCD), reversed the CBD-induced increase in Soat2 mRNA but not in Plin2 mRNA. Incubation with AEA increased the level of Plin2, but not of Soat2 mRNA. Furthermore, MBCD treatment did not affect the reduction by CBD of the LPS-induced release of the proinflammatory cytokine IL-1β. CBD treatment modulates cholesterol homeostasis in microglial cells, and pretreatment with MBCD reverses this effect without interfering with CBD's anti-inflammatory effects. The effects of the CBD-induced increase in AEA accumulation on lipid-gene expression are discussed.

  18. Clinical and protein metabolic efficacy of glutamine granules-supplemented enteral nutrition in severely burned patients.

    Science.gov (United States)

    Peng, Xi; Yan, Hong; You, Zhongyi; Wang, Pei; Wang, Shiliang

    2005-05-01

    As an abundant amino acid in the human body, glutamine has many important metabolic roles that may protect or promote tissue integrity and enhance the immune system. A relative deficiency of glutamine in such patients could compromise recovery and result in prolonged illness and an increase in late mortality. The purpose of this clinical study is to observe the effects of enteral supplement with glutamine granules on protein metabolism in severely burned patients. Forty-eight severe burn patients (total burn surface area 30-75%, full thickness burn area 20-58%) who met the requirements of the protocol joined this double-blind randomized controlled clinical trial. Patients were randomly divided into two groups: burn control group (B group, 23 patients) and glutamine treated group (Gln group, 25 patients). There was isonitrogenous and isocaloric intake in both groups, glutamine and B group patents were supplemented with glutamine granules or placebo (glycine) at 0.5 g/kg per day for 14 days with oral feeding or tube feeding, respectively. The level of plasma glutamine, plasma protein content, urine nitrogen and urine 3-methylhistidine (3-MTH) excretion were determined, wound healing rate of the burned area and hospital stay were recorded. The results showed that there were significant reductions in plasma glutamine level and abnormal protein metabolism. After supplement with glutamine granules for 14 days, the plasma glutamine concentration was significantly higher than that in B group (607.86+/-147.25 micromol/L versus 447.63+/-132.38 micromol/L, P0.05). On the other hand, the amount of urine nitrogen and 3-MTH excreted in Gln group were significantly lower than that in B group. In addition, wound healing was faster and hospital stay days were shorter in Gln group than B group (46.59+/-12.98 days versus 55.68+/-17.36 days, P<0.05). These indicated that supplement glutamine granules with oral feeding or tube feeding could abate the degree of glutamine depletion

  19. A new fluorescence-based method identifies protein phosphatases regulating lipid droplet metabolism.

    Directory of Open Access Journals (Sweden)

    Bruno L Bozaquel-Morais

    Full Text Available In virtually every cell, neutral lipids are stored in cytoplasmic structures called lipid droplets (LDs and also referred to as lipid bodies or lipid particles. We developed a rapid high-throughput assay based on the recovery of quenched BODIPY-fluorescence that allows to quantify lipid droplets. The method was validated by monitoring lipid droplet turnover during growth of a yeast culture and by screening a group of strains deleted in genes known to be involved in lipid metabolism. In both tests, the fluorimetric assay showed high sensitivity and good agreement with previously reported data using microscopy. We used this method for high-throughput identification of protein phosphatases involved in lipid droplet metabolism. From 65 yeast knockout strains encoding protein phosphatases and its regulatory subunits, 13 strains revealed to have abnormal levels of lipid droplets, 10 of them having high lipid droplet content. Strains deleted for type I protein phosphatases and related regulators (ppz2, gac1, bni4, type 2A phosphatase and its related regulator (pph21 and sap185, type 2C protein phosphatases (ptc1, ptc4, ptc7 and dual phosphatases (pps1, msg5 were catalogued as high-lipid droplet content strains. Only reg1, a targeting subunit of the type 1 phosphatase Glc7p, and members of the nutrient-sensitive TOR pathway (sit4 and the regulatory subunit sap190 were catalogued as low-lipid droplet content strains, which were studied further. We show that Snf1, the homologue of the mammalian AMP-activated kinase, is constitutively phosphorylated (hyperactive in sit4 and sap190 strains leading to a reduction of acetyl-CoA carboxylase activity. In conclusion, our fast and highly sensitive method permitted us to catalogue protein phosphatases involved in the regulation of LD metabolism and present evidence indicating that the TOR pathway and the SNF1/AMPK pathway are connected through the Sit4p-Sap190p pair in the control of lipid droplet biogenesis.

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

    Science.gov (United States)

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

    2014-01-01

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

  1. Thyroid hormone affects secretory activity and uncoupling protein-3 expression in rat harderian gland.

    Science.gov (United States)

    Chieffi Baccari, Gabriella; Monteforte, Rossella; de Lange, Pieter; Raucci, Franca; Farina, Paola; Lanni, Antonia

    2004-07-01

    The effects of T(3) administration on the rat Harderian gland were examined at morphological, biochemical, and molecular levels. T(3) induced hypertrophy of the two cell types (A and B) present in the glandular epithelium. In type A cells, the hypertrophy was mainly due to an increase in the size of the lipid compartment. The acinar lumina were filled with lipoproteic substances, and the cells often showed an olocrine secretory pattern. In type B cells, the hypertrophy largely consisted of a marked proliferation of mitochondria endowed with tightly packed cristae, the mitochondrial number being nearly doubled (from 62 to 101/100 microm(2)). Although the average area of individual mitochondria decreased by about 50%, the total area of the mitochondrial compartment increased by about 80% (from 11 to 19/100 microm(2)). This could be ascribed to T(3)-induced mitochondrial proliferation. The morphological and morphometric data correlated well with our biochemical results, which indicated that mitochondrial respiratory activity is increased in hyperthyroid rats. T(3), by influencing the metabolic function of the mitochondrial compartment, induces lipogenesis and the release of secretory product by type A cells. Mitochondrial uncoupling proteins 2 and 3 were expressed at both mRNA and protein levels in the euthyroid rat Harderian gland. T(3) treatment increased the mRNA levels of both uncoupling protein 2 (UCP2) and UCP3, but the protein level only of UCP3. A possible role for these proteins in the Harderian gland is discussed.

  2. Dissociation of the effects of epinephrine and insulin on glucose and protein metabolism

    International Nuclear Information System (INIS)

    Castellino, P.; Luzi, L.; Del Prato, S.; DeFronzo, R.A.

    1990-01-01

    The separate and combined effects of insulin and epinephrine on leucine metabolism were examined in healthy young volunteers. Subjects participated in four experimental protocols: (1) euglycemic insulin clamp (+80 microU/ml), (2) epinephrine infusion (50 ng.kg-1.min-1) plus somatostatin with basal replacement of insulin and glucagon, (3) combined epinephrine (50 ng.kg-1.min-1) plus insulin (+80 microU/ml) infusion, and (4) epinephrine and somatostatin as in study 2 plus basal amino acid replacement. Studies were performed with a prime-continuous infusion of [1-14C]leucine and indirect calorimetry. Our results indicate that (1) hyperinsulinemia causes a generalized decrease in plasma amino acid concentrations, including leucine; (2) the reduction in plasma leucine concentration is primarily due to an inhibition of endogenous leucine flux; nonoxidative leucine disposal decreases after insulin infusion; (3) epinephrine, without change in plasma insulin concentration, reduces plasma amino acid levels; (4) combined epinephrine-insulin infusion causes a greater decrease in plasma amino levels than observed with either hormone alone; this is because of a greater inhibition of endogenous leucine flux; and (5) when basal amino acid concentrations are maintained constant with a balanced amino acid infusion, epinephrine inhibits the endogenous leucine flux. In conclusion, the present results do not provide support for the concept that epinephrine is a catabolic hormone with respect to amino acid-protein metabolism. In contrast, epinephrine markedly inhibits insulin-mediated glucose metabolism

  3. Heterogeneity of elderly depression: increased risk of Alzheimer's disease and Aβ protein metabolism.

    Science.gov (United States)

    Namekawa, Yuki; Baba, Hajime; Maeshima, Hitoshi; Nakano, Yoshiyuki; Satomura, Emi; Takebayashi, Naoko; Nomoto, Hiroshi; Suzuki, Toshihito; Arai, Heii

    2013-06-03

    Epidemiological studies have proposed that depression may increase the risk for Alzheimer's disease (AD), even in patients with early-onset depression. Although metabolism of amyloid β protein (Aβ) in elderly depression received attention in terms of their correlation, there is a serious heterogeneity in elderly depression in terms of age at onset of depression. Moreover, it is unknown whether early-onset major depressive disorder (MDD) has a long-term effect on the involvement of Aβ metabolism and later development of AD. Thus, we evaluated serum Aβ40 and Aβ42 levels, the Aβ40/Aβ42 ratio in 89 elderly (≥60 years of age) inpatients with MDD and 81 age-matched healthy controls, and compared them among patients with early-onset (great interest that the serum Aβ40/Aβ42 ratio was negatively correlated with the age at MDD onset (R=-0.201, p=0.032). These results suggest that an earlier onset of MDD may have a more serious abnormality in Aβ metabolism, possibly explaining a biological mechanism underlying the link between depression and AD. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Prenatal dietary load of Maillard reaction products combined with postnatal Coca-Cola drinking affects metabolic status of female Wistar rats.

    Science.gov (United States)

    Gurecká, Radana; Koborová, Ivana; Janšáková, Katarína; Tábi, Tamás; Szökő, Éva; Somoza, Veronika; Šebeková, Katarína; Celec, Peter

    2015-04-01

    To assess the impact of prenatal exposure to Maillard reaction products (MRPs) -rich diet and postnatal Coca-Cola consumption on metabolic status of female rats. Diet rich in MRPs and consumption of saccharose/fructose sweetened soft drinks is presumed to impose increased risk of development of cardiometabolic afflictions, such as obesity or insulin resistance. At the first day of pregnancy, 9 female Wistar rats were randomized into two groups, pair-fed either with standard rat chow (MRP-) or MRPs-rich diet (MRP+). Offspring from each group of mothers was divided into two groups and given either water (Cola-) or Coca-Cola (Cola+) for drinking ad libitum for 18 days. Oral glucose tolerance test was performed, and circulating markers of inflammation, oxidative stress, glucose and lipid metabolism were assessed. MRP+ groups had higher weight gain, significantly so in the MRP+/Cola- vs MRP-/Cola-. Both prenatal and postnatal intervention increased carboxymethyllysine levels and semicarbazide-sensitive amine oxidase activity, both significantly higher in MRP+/Cola + than in MRP-/Cola-. Total antioxidant capacity was lower in MRP+ groups, with significant decrease in MRP+/Cola + vs MRP-/Cola+. Rats drinking Coca-Cola had higher insulin, homeostatic model assessment of insulin resistance, heart rate, advanced oxidation of protein products, triacylglycerols, and oxidative stress markers measured as thiobarbituric acid reactive substances compared to rats drinking water, with no visible effect of MRPs-rich diet. Metabolic status of rats was affected both by prenatal and postnatal dietary intervention. Our results suggest that combined effect of prenatal MRPs load and postnatal Coca-Cola drinking may play a role in development of metabolic disorders in later life.

  5. Synthetic protein scaffolds based on peptide motifs and cognate adaptor domains for improving metabolic productivity

    Directory of Open Access Journals (Sweden)

    Anselm H.C. Horn

    2015-11-01

    Full Text Available The efficiency of many cellular processes relies on the defined interaction among different proteins within the same metabolic or signaling pathway. Consequently, a spatial colocalization of functionally interacting proteins has frequently emerged during evolution. This concept has been adapted within the synthetic biology community for the purpose of creating artificial scaffolds. A recent advancement of this concept is the use of peptide motifs and their cognate adaptor domains. SH2, SH3, GBD, and PDZ domains have been used most often in research studies to date. The approach has been successfully applied to the synthesis of a variety of target molecules including catechin, D-glucaric acid, H2, hydrochinone, resveratrol, butyrate, gamma-aminobutyric acid, and mevalonate. Increased production levels of up to 77-fold have been observed compared to non-scaffolded systems. A recent extension of this concept is the creation of a covalent linkage between peptide motifs and adaptor domains, which leads to a more stable association of the scaffolded systems and thus bears the potential to further enhance metabolic productivity.

  6. Lack of the Lysosomal Membrane Protein, GLMP, in Mice Results in Metabolic Dysregulation in Liver.

    Directory of Open Access Journals (Sweden)

    Xiang Yi Kong

    Full Text Available Ablation of glycosylated lysosomal membrane protein (GLMP, formerly known as NCU-G1 has been shown to cause chronic liver injury which progresses into liver fibrosis in mice. Both lysosomal dysfunction and chronic liver injury can cause metabolic dysregulation. Glmp gt/gt mice (formerly known as Ncu-g1gt/gt mice were studied between 3 weeks and 9 months of age. Body weight gain and feed efficiency of Glmp gt/gt mice were comparable to wild type siblings, only at the age of 9 months the Glmp gt/gt siblings had significantly reduced body weight. Reduced size of epididymal fat pads was accompanied by hepatosplenomegaly in Glmp gt/gt mice. Blood analysis revealed reduced levels of blood glucose, circulating triacylglycerol and non-esterified fatty acids in Glmp gt/gt mice. Increased flux of glucose, increased de novo lipogenesis and lipid accumulation were detected in Glmp gt/gt primary hepatocytes, as well as elevated triacylglycerol levels in Glmp gt/gt liver homogenates, compared to hepatocytes and liver from wild type mice. Gene expression analysis showed an increased expression of genes involved in fatty acid uptake and lipogenesis in Glmp gt/gt liver compared to wild type. Our findings are in agreement with the metabolic alterations observed in other mouse models lacking lysosomal proteins, and with alterations characteristic for advanced chronic liver injury.

  7. Impaired mitochondrial metabolism and protein synthesis in streptozotocin diabetic rat hepatocytes

    International Nuclear Information System (INIS)

    Memon, R.A.; Bessman, S.P.; Mohan, C.

    1990-01-01

    Isolated hepatocytes prepared from control, streptozotocin diabetic rats were incubated at 30 degrees C in Krebs-Henseleit bicarbonate buffer, pH 7.4, containing 0.5 mM concentration of each of the 20 natural amino acids. Effect of insulin on the oxidation of 2,3- 14 C and 1,4- 14 C succinate (suc) carbons and their incorporation into hepatocyte protein, lipid and various metabolic intermediates was studied. Mitochondrial oxidation of suc carbons and their incorporation into protein and lipid was significantly lower in diabetic and insulin treated diabetic rats. Diabetic rats failed to exhibit any significant insulin effect on the oxidation of either 2,3 or 1,4- 14 C suc carbons. Amphibolic channeling of 2,3- 14 C suc carbons into amino acids was significantly reduced in hepatocytes of diabetic rats, however, more of these carbons were diverted into the gluconeogenesis pathway. Diabetes caused a far greater decrease in the oxidation of 2,3- 14 C suc carbons as compared to 1,4- 14 C suc. Based on an earlier report that insulin stimulates only the intramitochondrial Krebs cycle reactions, the authors conclude that the diminished level of anabolic activities in the diabetic rat hepatocytes is due to the subsequent reduction in amphibolic channeling of metabolic intermediates

  8. A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress.

    Science.gov (United States)

    Kant, Shashi; Standen, Claire L; Morel, Caroline; Jung, Dae Young; Kim, Jason K; Swat, Wojciech; Flavell, Richard A; Davis, Roger J

    2017-09-19

    Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH 2 -terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin

    Directory of Open Access Journals (Sweden)

    Julia Ring

    2017-11-01

    Full Text Available Hereditary spastic paraplegias, a group of neurodegenerative disorders, can be caused by loss-of-function mutations in the protein spartin. However, the physiological role of spartin remains largely elusive. Here we show that heterologous expression of human or Drosophila spartin extends chronological lifespan of yeast, reducing age-associated ROS production, apoptosis, and necrosis. We demonstrate that spartin localizes to the proximity of mitochondria and physically interacts with proteins related to mitochondrial and respiratory metabolism. Interestingly, Nde1, the mitochondrial external NADH dehydrogenase, and Pda1, the core enzyme of the pyruvate dehydrogenase complex, are required for spartin-mediated cytoprotection. Furthermore, spartin interacts with the glycolysis enhancer phospo-fructo-kinase-2,6 (Pfk26 and is sufficient to complement for PFK26-deficiency at least in early aging. We conclude that mitochondria-related energy metabolism is crucial for spartin’s vital function during aging and uncover a network of specific interactors required for this function.

  10. Energy dense, protein restricted diet increases adiposity and perturbs metabolism in young, genetically lean pigs.

    Science.gov (United States)

    Fisher, Kimberly D; Scheffler, Tracy L; Kasten, Steven C; Reinholt, Brad M; van Eyk, Gregory R; Escobar, Jeffery; Scheffler, Jason M; Gerrard, David E

    2013-01-01

    Animal models of obesity and metabolic dysregulation during growth (or childhood) are lacking. Our objective was to increase adiposity and induce metabolic syndrome in young, genetically lean pigs. Pre-pubertal female pigs, age 35 d, were fed a high-energy diet (HED; n = 12), containing 15% tallow, 35% refined sugars and 9.1-12.9% crude protein, or a control corn-based diet (n = 11) with 12.2-19.2% crude protein for 16 wk. Initially, HED pigs self-regulated energy intake similar to controls, but by wk 5, consumed more (Pblood glucose increased (Pblood glucose did not return to baseline (P = 0.01), even 4 h post-challenge. During OGTT, glucose area under the curve (AUC) was higher and insulin AUC was lower in HED pigs compared to controls (P = 0.001). Chronic HED intake increased (PAUC and insulin AUC did not improve, supporting that dietary intervention was not sufficient to recover glucose tolerance or insulin production. These data suggest a HED may be used to increase adiposity and disrupt glucose homeostasis in young, growing pigs.

  11. A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress

    Directory of Open Access Journals (Sweden)

    Shashi Kant

    2017-09-01

    Full Text Available Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA activation of a non-receptor tyrosine kinase (SRC-dependent cJun NH2-terminal kinase (JNK signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway.

  12. Osteocalcin: The extra-skeletal role of a vitamin K-dependent protein in glucose metabolism

    Directory of Open Access Journals (Sweden)

    Eibhlís M. O'Connor

    2017-03-01

    Full Text Available The role of vitamin K in the body has long been associated with blood clotting and coagulation. In more recent times, its role in a range of physiological processes has been described including the regulation of bone and soft tissue calcification, cell growth and proliferation, cognition, inflammation, various oxidative processes and fertility, where osteocalcin is thought to up-regulate the synthesis of the enzymes needed for the biosynthesis of testosterone thereby increasing male fertility. Vitamin K dependent proteins (VKDP contain γ-carboxyglutamic acid residues which require post-translational, gamma-glutamyl carboxylation by the vitamin K-dependent (VKD gamma-glutamyl carboxylase enzyme for full functionality. These proteins are present both hepatically and extrahepatically. The role of bone-derived osteocalcin has many physiological roles including, maintenance of bone mass with more recent links to energy metabolism due to the role of the skeleton as an endocrine organ. It has been proposed that insulin binds to bone forming cells (osteoblasts promoting osteocalcin production which in turn promotes β-cell proliferation, insulin secretion and glucose control. However much of this research has been conducted in animal models with equivocal findings in human studies. This review will discuss the role of osteocalcin in relation to its role in human health, focusing specifically on glucose metabolism.

  13. Protein O-linked ß-N-acetylglucosamine: A novel effector of cardiomyocyte metabolism and function

    Science.gov (United States)

    Darley-Usmar, Victor M.; Ball, Lauren E.; Chatham, John C.

    2014-01-01

    The post-translational modification of serine and threonine residues of nuclear and cytoplasmic proteins by the O-linked attachment of the monosaccharide ß-N-acetyl-glucosamine (O-GlcNAc) is emerging as an important mechanism for the regulation of numerous biological processes critical for normal cell function. Active synthesis of O-GlcNAc is essential for cell viability and acute activation of pathways resulting in increased protein O-GlcNAc levels improves the tolerance of cells to a wide range of stress stimuli. Conversely sustained increases in O-GlcNAc levels have been implicated in numerous chronic disease states, especially as a pathogenic contributor to diabetic complications. There has been increasing interest in the role of O-GlcNAc in the heart and vascular system and acute activation of O-GlcNAc levels have been shown to reduce ischemia/reperfusion injury attenuate vascular injury responses as well mediate some of the detrimental effects of diabetes and hypertension on cardiac and vascular function. Here we provide an overview of our current understanding of pathways regulating protein O-GlcNAcylation, summarize the different methodologies for identifying and characterizing O-GlcNAcylated proteins and subsequently focus on two emerging areas: 1) the role of O-GlcNAc as a potential regulator of cardiac metabolism and 2) the cross talk between O-GlcNAc and reactive oxygen species. PMID:21878340

  14. Metabolic Characterization of Intact Cells Reveals Intracellular Amyloid Beta but Not Its Precursor Protein to Reduce Mitochondrial Respiration

    Science.gov (United States)

    Schaefer, Patrick M.; von Einem, Bjoern; Walther, Paul; Calzia, Enrico; von Arnim, Christine A. F.

    2016-01-01

    One hallmark of Alzheimer´s disease are senile plaques consisting of amyloid beta (Aβ), which derives from the processing of the amyloid precursor protein (APP). Mitochondrial dysfunction has been linked to the pathogenesis of Alzheimer´s disease and both Aβ and APP have been reported to affect mitochondrial function in isolated systems. However, in intact cells, considering a physiological localization of APP and Aβ, it is pending what triggers the mitochondrial defect. Thus, the aim of this study was to dissect the impact of APP versus Aβ in inducing mitochondrial alterations with respect to their subcellular localization. We performed an overexpression of APP or beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), increasing APP and Aβ levels or Aβ alone, respectively. Conducting a comprehensive metabolic characterization we demonstrate that only APP overexpression reduced mitochondrial respiration, despite lower extracellular Aβ levels compared to BACE overexpression. Surprisingly, this could be rescued by a gamma secretase inhibitor, oppositionally indicating an Aβ-mediated mitochondrial toxicity. Analyzing Aβ localization revealed that intracellular levels of Aβ and an increased spatial association of APP/Aβ with mitochondria are associated with reduced mitochondrial respiration. Thus, our data provide marked evidence for a prominent role of intracellular Aβ accumulation in Alzheimer´s disease associated mitochondrial dysfunction. Thereby it highlights the importance of the localization of APP processing and intracellular transport as a decisive factor for mitochondrial function, linking two prominent hallmarks of neurodegenerative diseases. PMID:28005987

  15. Recent Advance in Division of Carbohydrate and Protein Fractions of Ruminant Feed and Their Metabolism in Digestive Tract

    Institute of Scientific and Technical Information of China (English)

    Xiaohua; PAN; Liang; YANG; Hairui; XIN; Benhai; XIONG

    2016-01-01

    Accurate assessment of feed’s Carbohydrate( CHO) and protein nutritional values and rumen metabolism are significant for dairy production. Cornell Net Carbohydrate and Protein System( CNCPS) as an important method to evaluate feedstuff nutritional values,hasn’t been widely used in China. In order to illustrate updates of CNCPS systems deeply,the following sections were reviewed:( i) CHO and protein fractions were updated,CA was subdivided into CA1,CA2,CA3 and CA4 in CNCPS v6. 1,protein was reclassified into PA1,PA2,PB1,PB2 and PC after CNCPS v6. 1. Content of CHO and protein fractions vary in different feedstuff and affected by feed processing;( ii) Degradation rates( Kd) values for the new CA expanded scheme were updated to 0,7,5,40- 60 % h-1respectively,Kd for PA and PB1 decreased to 200 % h-1and 10- 40 % h-1;( iii) Equations for passage rate( Kp) initially includes Kpf( Kp of forages) and Kpc( Kp of concentrates),and adjusted by effective NDF( e NDF),while in CNCPS v5. 0,Kpl( Kp of liquids) equation was added and e NDF was replaced by physically effective NDF( pe NDF). In CNCPS v6. 1,Fp BW and Cp BW were integrated into Kp equations and pe NDF was abandoned.( iv)The relationship and difference among Weende system of proximate analysis,Van Soest fiber analysis[35],NRC( 2001)[28]and CNCPS were analyzed. The first two systems laid the foundation for NRC( 2001) and CNCPS system. The latter two systems are different in CHO and protein division,also NRC( 2001) developed separate Kp equations for wet and dry forages but no equation for Kpl. CNCPS developed a Kp equation that work for wet and dry forages,and Kpl equation was established. In conclusion,the division and development of CHO and protein fractions,the update of Kd and Kp equation were reviewed systematically.

  16. Dietary protein level affects iridescent coloration in Anna's hummingbirds, Calypte anna.

    Science.gov (United States)

    Meadows, Melissa G; Roudybush, Thomas E; McGraw, Kevin J

    2012-08-15

    Many animal displays involve colorful ornamental traits that signal an individual's quality as a mate or rival. Brilliant iridescent ornaments are common, but little is currently known about their production cost and signaling value. One potential cost of colorful ornaments is the acquisition of limited dietary resources that may be involved, directly or indirectly, in their production. Protein, the primary component of bird feathers and of many nanostructural components of iridescent traits, is naturally restricted in hummingbird diets (comprised mostly of sugars), suggesting that iridescent coloration may be especially challenging to produce in these animals. In this study, we experimentally investigated the effect of dietary protein availability during molt on iridescent color expression in male Anna's hummingbirds (Calypte anna). We fed captive birds either a 6% (high) or a 3% (low) protein diet and stimulated molt by plucking half the gorget and crown ornaments on each bird as well as the non-ornamental iridescent green tail feathers. We found that birds receiving more protein grew significantly more colorful crown feathers (higher red chroma and redder hue) than those fed the low-protein diet. Diet did not affect gorget coloration, but regrowth of feathers in captivity affected both gorget and crown coloration. Additionally, birds on the high-protein diet grew yellower (higher hue) green tail feathers than birds on the low-protein diet. These results indicate that iridescent ornamental feathers are sensitive to diet quality and may serve as honest signals of nutrition to mates or rivals. Further, because both ornamental and non-ornamental iridescent coloration were affected by conditions during their growth, iridescent color in these birds appears to be generally condition dependent.

  17. Metabolic syndrome in a cohort of affectively ill patients, a naturalistic study

    DEFF Research Database (Denmark)

    Vinberg, Maj; Madsen, Maiken; Breum, Leif

    2012-01-01

    at a Mood Disorder Clinic. Methods: Patients were evaluated for the presence of metabolic syndrome (MeS) according to modified NCEP ATP III criteria. Results: Of the 143 patients eligible for participation, 100 patients participated in the study (32% male, mean age 43.6 ± 14.2); the prevalence of MeS was 26...

  18. Eucalypt plants are physiologically and metabolically affected by infection with Ceratocystis fimbriata.

    Science.gov (United States)

    da Silva, André Costa; de Oliveira Silva, Franklin Magnum; Milagre, Jocimar Caiafa; Omena-Garcia, Rebeca Patricia; Abreu, Mário Castro; Mafia, Reginaldo Gonçalves; Nunes-Nesi, Adriano; Alfenas, Acelino Couto

    2018-02-01

    Ceratocystis wilt, caused by Ceratocystis fimbriata, is currently one of the most important disease in eucalypt plantations. Plants infected by C. fimbriata have lower volumetric growth, lower pulp yields and reduced timber values. The physiological bases of infection induced by this pathogen in eucalypt plant are not known. Therefore, this study aims to assess the physiological and metabolic changes in eucalypt clones that are resistant and susceptible to C. fimbriata. Once, we evaluated in detail their leaf gas exchange, chlorophyll a fluorescence, water potential, metabolite profiling and growth-related parameters. When inoculated, the susceptible clone displayed reduced water potential, CO 2 assimilation rate, stomatal conductance, transpiration rate, photochemical quenching coefficient, electron transport rate, and root biomass. Inoculated resistant and susceptible clones both presented higher respiration rates than healthy plants. Many compounds of primary and secondary metabolism were significantly altered after fungal infection in both clones. These results suggest that, C. fimbriata interferes in the primary and secondary metabolism of plants that may be linked to the induction of defense mechanisms and that, due to water restrictions caused by the fungus in susceptible plants, there is a partial closure of the stomata to prevent water loss and a consequent reduction in photosynthesis and the transpiration rate, which in turn, leads to a decrease in the plant's growth-related. These results combined, allowed for a better understanding of the physiological and metabolic changes following the infectious process of C. fimbriata, which limit eucalypt plant growth. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Does acute tryptophan depletion affect peripheral serotonin metabolism in the intestine?

    NARCIS (Netherlands)

    Keszthelyi, D.; Troost, F.J.; Jonkers, D.M.; Donkelaar, van E.L.; Dekker, J.; Buurman, W.A.; Masclee, A.A.

    2012-01-01

    Background: Serotonin (5-hydroxytryptamine; 5-HT), a tryptophan metabolite, plays an important regulatory role in the human central nervous system and in the gastrointestinal tract. Acute tryptophan depletion (ATD) is currently the most widely established method to investigate 5-HT metabolism.

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

    Science.gov (United States)

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

    2017-03-07

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

  1. Embryonic protein undernutrition by albumen removal programs the hepatic amino acid and glucose metabolism during the perinatal period in an avian model.

    Directory of Open Access Journals (Sweden)

    Els Willems

    Full Text Available Different animal models have been used to study the effects of prenatal protein undernutrition and the mechanisms by which these occur. In mammals, the maternal diet is manipulated, exerting both direct nutritional and indirect hormonal effects. Chicken embryos develop independent from the hen in the egg. Therefore, in the chicken, the direct effects of protein deficiency by albumen removal early during incubation can be examined. Prenatal protein undernutrition was established in layer-type eggs by the partial replacement of albumen by saline at embryonic day 1 (albumen-deprived group, compared to a mock-treated sham and a non-treated control group. At hatch, survival of the albumen-deprived group was lower compared to the control and sham group due to increased early mortality by the manipulation. No treatment differences in yolk-free body weight or yolk weight could be detected. The water content of the yolk was reduced, whereas the water content of the carcass was increased in the albumen-deprived group, compared to the control group, indicating less uptake of nutrients from the yolk. At embryonic day 16, 20 and at hatch, plasma triiodothyronine (T3, corticosterone, lactate or glucose concentrations and hepatic glycogen content were not affected by treatment. At embryonic day 20, the plasma thyroxine (T4 concentrations of the albumen-deprived embryos was reduced compared to the control group, indicating a decreased metabolic rate. Screening for differential protein expression in the liver at hatch using two-dimensional difference gel electrophoresis revealed not only changed abundance of proteins important for amino acid metabolism, but also of enzymes related to energy and glucose metabolism. Interestingly, GLUT1, a glucose transporter, and PCK2 and FBP1, two out of three regulatory enzymes of the gluconeogenesis were dysregulated. No parallel differences in gene expressions causing the differences in protein abundance could be detected

  2. Resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin.

    Science.gov (United States)

    Yuan, Hong; Weng, Chunyan; Yang, Youbo; Huang, Lihua; Xing, Xiaowei

    2013-12-01

    The metabolic syndrome (MS) is a cluster of metabolic disorders arising from insulin resistance, characterized by the presence of central obesity, impaired fasting glucose level, dyslipidemia and hypertension. As the first-line medication, metformin is commonly used for MS to reduce insulin resistance. Comparing with rosiglitazone, metformin does not increase cardiovascular mortality risk in patients with MS. However, metformin is not good enough in improving insulin sensitivity. Its molecular mechanism is still not clear. Recent studies have demonstrated that resistin, an adipokine, could induce IR by both AMPK-dependent and AMPK-independent pathways. Though there were conflicting findings of resistin in metabolic syndrome or type 2 diabetes mellitus in different studies, resistin was significant decreased in the rosiglitazone treated patients than in the metformin-treated patients in most of studies. Here, we hypothesized that resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin. This hypothesis could explain why rosiglitazone is superior to metformin in enhancement of insulin sensitivity. Copyright © 2013. Published by Elsevier Ltd.

  3. Association of cancer metabolism-related proteins with oral carcinogenesis – indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?

    Science.gov (United States)

    2014-01-01

    Background Tumor metabolism is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). Methods Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, PFK-1, LDHA, TKTL1), mitochondrial enzymes (SDHA, SDHB, ATP synthase) were analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry and real-time polymerase chain reaction (qPCR) analysis in OSCC cell lines. Metabolism-related proteins were correlated with proliferation activity (Ki-67) and apoptotic properties (TUNEL assay) in OSCC. Specificity of antibodies was confirmed by western blotting in cancer cell lines. Results Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, LDHA, TKTL1), and mitochondrial enzymes (SDHA, SDHB, ATP synthase) were significantly increased in the carcinogenesis of OSCC. Metabolic active regions of OSCC were strongly correlated with proliferating cancer (Ki-67+) cells without detection of apoptosis (TUNEL assay). Conclusions This study provides the first evidence of the expression of IGF-R1, glycolysis-related proteins GLUT-1, HK 2, PFK-1, LDHA, and TKTL1, as well as mitochondrial enzymes SDHA, SDHB, and ATP synthase in the multi-step carcinogenesis of OSCC. Both, hypoxia-related glucose metabolism and mitochondrial oxidative phosphorylation characteristics are associated with the carcinogenesis of OSCC. Acidosis and OXPHOS may drive a metabolic shift towards the pentose phosphate pathway (PPP). Therefore, inhibition of the PPP, glycolysis, and targeted anti-mitochondrial therapies (ROS generation) by natural compounds or synthetic vitamin derivatives may act as sensitizer for apoptosis in cancer cells mediated by adjuvant therapies in OSCC. PMID:25048361

  4. Is there an optimal topographical surface in nano-scale affecting protein adsorption and cell behaviors? Part II

    Energy Technology Data Exchange (ETDEWEB)

    Wang Huajie, E-mail: wanghuajie972001@163.com; Sun Yuanyuan; Cao Ying, E-mail: caoying1130@sina.com; Wang Kui; Yang Lin [Henan Normal University, College of Chemistry and Environmental Science (China); Zhang Yidong; Zheng Zhi [Xuchang University, Institute of Surface Micro and Nano Materials (China)

    2012-05-15

    Although nano-structured surfaces exhibit superior biological activities to the smooth or micro-structured surfaces, whether there is an optimal topographical surface in nano-scale affecting protein adsorption and cell behaviors is still controversial. In this study, porous aluminum oxide membranes with different pore sizes ranging from 25 to 120 nm were prepared by the anodic oxidation technique. The surface morphology, topography and wettability were analyzed by scanning electron microscope, atomic force microscope and water contact angle measurement, respectively. The results indicated that the synergistic action of the nano-topography structure and hydrophilic/hydrophobic properties resulted in a highest protein adsorption on the aluminum oxide membrane with 80 nm pore size. Additionally, the morphological, metabolic and cell counting methods showed that cells had different sensitivity to porous aluminum oxide membranes with different surface features. Furthermore, this sensitivity was cell type dependent. The optimal pore size of aluminum oxide membranes for cell growth was 80 nm for PC12 cells and 50 nm for NIH 3T3 cells.

  5. Radiolabeled hydroxamate-based matrix metalloproteinase inhibitors: How chemical modifications affect pharmacokinetics and metabolic stability

    International Nuclear Information System (INIS)

    Hugenberg, Verena; Hermann, Sven; Galla, Fabian; Schäfers, Michael

    2016-01-01

    Introduction: Dysregulated MMP expression or activation is associated with several diseases. To study MMP activity in vivo by means of PET a radiolabeled MMP inhibitor (MMPI) functioning as radiotracer has been developed by our group based on the lead structure CGS 25966. Materials and methods: Aiming at the modification of the pharmacokinetics of this lipophilic model tracer a new class of MMPIs has been discovered, consisting of additional fluorinated hydrophilic substructures, such as mini-PEG and/or 1,2,3-triazole units. To identify the best candidate for further clinical applications, radiofluorinated compounds of each subgroup have been (radio) synthesized and evaluated regarding their biodistribution behavior and their metabolic stability. Results: Radiosyntheses of different triazole based MMPIs could be realized using two step “click chemistry” procedures. Compared to lead structure [ 18 F]FEtO-CGS 25966 ([ 18 F]1e, log D(exp) = 2.02, IC 50 = 2–50 nM) all selected candidates showed increased hydrophilicities and inhibition potencies (log D(exp) = 0.23–1.25, IC 50 = 0.006–6 nM). Interestingly, despite different hydrophilicities most triazole based MMPIs showed no significant differences in their in vivo biodistribution behavior and were cleared predominantly via the hepatobiliary excretion route. Biostability and metabolism studies in vitro and in vivo revealed significant higher metabolic stability for the triazole moiety compared to the benzyl ring in the lead structure. Cleavage of ethylene glycol subunits of the mini-PEG chain led to a faster metabolism of mini-PEG containing MMPIs. Conclusion: The introduction of hydrophilic groups such as mini-PEG and 1,2,3-triazole units did not lead to a significant shift of the hepatobiliary elimination towards renal clearance. Particularly the introduction of mini-PEG chains led to an intense metabolic decomposition. Substitution of the benzyl moiety in lead structure 1e by a 1,2,3-trizole ring resulted

  6. Uncoupling protein homologs may provide a link between mitochondria, metabolism and lifespan.

    Science.gov (United States)

    Wolkow, Catherine A; Iser, Wendy B

    2006-05-01

    Uncoupling proteins (UCPs), which dissipate the mitochondrial proton gradient, have the ability to decouple mitochodrial respiration from ATP production. Since mitochondrial electron transport is a major source of free radical production, it is possible that UCP activity might impact free radical production. Free radicals can react with and damage cellular proteins, DNA and lipids. Accumulated damage from oxidative stress is believed to be a major contributor to cellular decline during aging. If UCP function were to impact mitochondrial free radical production, then one would expect to find a link between UCP activity and aging. This theory has recently been tested in a handful of organisms whose genomes contain UCP1 homologs. Interestingly, these experiments indicate that UCP homologs can affect lifespan, although they do not support a simple relationship between UCP activity and aging. Instead, UCP-like proteins appear to have a variety of effects on lifespan, and on pathways implicated in lifespan regulation. One possible explanation for this complex picture is that UCP homologs may have tissue-specific effects that complicate their effects on aging. Furthermore, the functional analysis of UCP1 homologs is incomplete. Thus, these proteins may perform functions in addition to, or instead of, mitochondrial uncoupling. Although these studies have not revealed a clear picture of UCP effects on aging, they have contributed to the growing knowledge base for these interesting proteins. Future biochemical and genetic investigation of UCP-like proteins will do much to clarify their functions and to identify the regulatory networks in which they are involved.

  7. A 7-day high protein hypocaloric diet promotes cellular metabolic adaptations and attenuates lean mass loss in healthy males

    OpenAIRE

    Matthew Furber; Ana Anton-Solanas; Emma Koppe; Charlotte Ashby; Michael Roberts; Justin Roberts

    2017-01-01

    Mitochondrial quantity and density are associated with increased oxidative metabolism. It has been demonstrated that a hypocaloric high fat/low carbohydrate (HF/LC) diet can up-regulate transcriptional markers of mitochondrial biogenesis; this was yet to be explored in vivo subsequent to a high protein/low carbohydrate (HP/LC) diet. Thus the aims of the study were to explore such diets on transcriptional markers or mitochondrial biogenesis, body composition and resting metabolic rate (RMR). F...

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

    Science.gov (United States)

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

    2016-02-01

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

  9. Increasing protein intake modulates lipid metabolism in healthy young men and women consuming a high-fat hypercaloric diet.

    Science.gov (United States)

    Rietman, Annemarie; Schwarz, Jessica; Blokker, Britt A; Siebelink, Els; Kok, Frans J; Afman, Lydia A; Tomé, Daniel; Mensink, Marco

    2014-08-01

    The objective of this study was to evaluate the effect of increasing protein intake, at the expense of carbohydrates, on intrahepatic lipids (IHLs), circulating triglycerides (TGs), and body composition in healthy humans consuming a high-fat, hypercaloric diet. A crossover randomized trial with a parallel control group was performed. After a 2-wk run-in period, participants were assigned to either the control diet [n = 10; 27.8 energy percent (en%) fat, 16.9 en% protein, 55.3 en% carbohydrates] for 4 wk or a high-fat, hypercaloric diet (n = 17; >2 MJ/d) crossover trial with 2 periods of 2 wk, with either high-protein (HP) (37.7 en% fat, 25.7 en% protein, 36.6 en% carbohydrates) or normal-protein (NP) (39.4 en% fat, 15.4 en% protein, 45.2 en% carbohydrates) content. Measurements were performed after 2 wk of run-in (baseline), 2 wk of intervention (period 1), and 4 wk of intervention (period 2). A trend toward lower IHL and plasma TG concentrations during the HP condition compared with the NP condition was observed (IHL: 0.35 ± 0.04% vs. 0.51 ± 0.08%, P = 0.08; TG: 0.65 ± 0.03 vs. 0.77 ± 0.05 mmol/L, P = 0.07, for HP and NP, respectively). Fat mass was significantly lower (10.6 ± 1.72 vs. 10.9 ± 1.73 kg; P = 0.02) with the HP diet than with the NP diet, whereas fat-free mass was higher (55.7 ± 2.79 vs. 55.2 ± 2.80 kg; P = 0.003). This study indicated that an HP, high-fat, hypercaloric diet affects lipid metabolism. It tends to lower the IHL and circulating TG concentrations and significantly lowers fat mass and increases fat-free mass compared with an NP, high-fat, hypercaloric diet. This trail was registered at www.clinicaltrials.gov as NCT01354626. © 2014 American Society for Nutrition.

  10. Protein level affects the relative lysine requirement of growing rainbow trout (Oncorhynchus mykiss) fry.

    Science.gov (United States)

    Bodin, Noelie; Govaerts, Bernadette; Abboudi, Tarik; Detavernier, Christel; De Saeger, Sarah; Larondelle, Yvan; Rollin, Xavier

    2009-07-01

    The effect of two digestible protein levels (310 and 469 g/kg DM) on the relative lysine (Lys; g Lys/kg DM or g Lys/100 g protein) and the absolute Lys (g Lys intake/kg 0.75 per d) requirements was studied in rainbow trout fry using a dose-response trial. At each protein level, sixteen isoenergetic (22-23 MJ digestible energy/kg DM) diets were tested, involving a full range (2-70 g/kg DM) of sixteen Lys levels. Each diet was given to one group of sixty rainbow trout fry (mean initial body weight 0.78 g) reared at 15 degrees C for 31 feeding d. The Lys requirements were estimated based on the relationships between weight, protein, and Lys gains (g/kg 0.75 per d) and Lys concentration (g/kg DM or g/100 g protein) or Lys intake (g/kg 0.75 per d), using the broken-line model (BLM) and the non-linear four-parameter saturation kinetics model (SKM-4). Both the model and the response criterion chosen markedly impacted the relative Lys requirement. The relative Lys requirement for Lys gain of rainbow trout estimated with the BLM (and SKM-4 at 90 % of the maximum response) increased from 16.8 (19.6) g/kg DM at a low protein level to 23.4 (24.5) g/kg DM at a high protein level. However, the dietary protein content affected neither the absolute Lys requirement nor the relative Lys requirement expressed as g Lys/100 g protein nor the Lys requirement for maintenance (21 mg Lys/kg 0.75 per d).

  11. Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis.

    Directory of Open Access Journals (Sweden)

    Vladimir López

    2016-03-01

    Full Text Available Mycobacteria of the Mycobacterium tuberculosis complex (MTBC greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB. In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB- and M. bovis-infected young (TB+ and adult animals with different infection status [TB lesions localized in the head (TB+ or affecting multiple organs (TB++]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to

  12. Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis.

    Science.gov (United States)

    López, Vladimir; Villar, Margarita; Queirós, João; Vicente, Joaquín; Mateos-Hernández, Lourdes; Díez-Delgado, Iratxe; Contreras, Marinela; Alves, Paulo C; Alberdi, Pilar; Gortázar, Christian; de la Fuente, José

    2016-03-01

    Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to limit pathogen

  13. The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial.

    Science.gov (United States)

    Rijpma, Anne; van der Graaf, Marinette; Lansbergen, Marieke M; Meulenbroek, Olga; Cetinyurek-Yavuz, Aysun; Sijben, John W; Heerschap, Arend; Olde Rikkert, Marcel G M

    2017-07-26

    Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer's disease. Thirty-four drug-naive patients with mild Alzheimer's disease (Mini Mental State Examination score ≥20) were enrolled in this exploratory, double-blind, randomized controlled study. Before and after 4-week intervention with Souvenaid or an isocaloric control product, phosphorus and proton magnetic resonance spectroscopy (MRS) was performed to assess surrogate measures of phospholipid synthesis and breakdown (phosphomonoesters [PME] and phosphodiesters [PDEs]), neural integrity (N-acetyl aspartate), gliosis (myo-inositol), and choline metabolism (choline-containing compounds [tCho]). The main outcome parameters were PME and PDE signal intensities and the PME/PDE ratio. MRS data from 33 patients (60-86 years old; 42% males; Souvenaid arm n = 16; control arm n = 17) were analyzed. PME/PDE and tCho were higher after 4 weeks of Souvenaid compared with control (PME/PDE least squares [LS] mean difference [95% CI] 0.18 [0.06-0.30], p = 0.005; tCho LS mean difference [95% CI] 0.01 [0.00-0.02], p = 0.019). No significant differences were observed in the other MRS outcome parameters. MRS reveals that Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease, in line with findings in preclinical studies. Netherlands Trial Register, NTR3346 . Registered on 13 March 2012.

  14. Hibiscus chlorotic ringspot virus coat protein upregulates sulfur metabolism genes for enhanced pathogen defense.

    Science.gov (United States)

    Gao, Ruimin; Ng, Florence Kai Lin; Liu, Peng; Wong, Sek-Man

    2012-12-01

    In both Hibiscus chlorotic ringspot virus (HCRSV)-infected and HCRSV coat protein (CP) agroinfiltrated plant leaves, we showed that sulfur metabolism pathway related genes-namely, sulfite oxidase (SO), sulfite reductase, and adenosine 5'-phosphosulfate kinase-were upregulated. It led us to examine a plausible relationship between sulfur-enhanced resistance (SED) and HCRSV infection. We broadened an established method to include different concentrations of sulfur (0S, 1S, 2S, and 3S) to correlate them to symptom development of HCRSV-infected plants. We treated plants with glutathione and its inhibitor to verify the SED effect. Disease resistance was induced through elevated glutathione contents during HCRSV infection. The upregulation of SO was related to suppression of symptom development induced by sulfur treatment. In this study, we established that HCRSV-CP interacts with SO which, in turn, triggers SED and leads to enhanced plant resistance. Thus, we have discovered a new function of SO in the SED pathway. This is the first report to demonstrate that the interaction of a viral protein and host protein trigger SED in plants. It will be interesting if such interaction applies generally to other host-pathogen interactions that will lead to enhanced pathogen defense.

  15. Sorbitol dehydrogenase is a cytosolic protein required for sorbitol metabolism in Arabidopsis thaliana.

    Science.gov (United States)

    Aguayo, María Francisca; Ampuero, Diego; Mandujano, Patricio; Parada, Roberto; Muñoz, Rodrigo; Gallart, Marta; Altabella, Teresa; Cabrera, Ricardo; Stange, Claudia; Handford, Michael

    2013-05-01

    Sorbitol is converted to fructose in Rosaceae species by SORBITOL DEHYDROGENASE (SDH, EC 1.1.1.14), especially in sink organs. SDH has also been found in non-Rosaceae species and here we show that the protein encoded by At5g51970 in Arabidopsis thaliana (L.) Heynh. possesses the molecular characteristics of an SDH. Using a green fluorescent protein-tagged version and anti-SDH antisera, we determined that SDH is cytosolically localized, consistent with bioinformatic predictions. We also show that SDH is widely expressed, and that SDH protein accumulates in both source and sink organs. In the presence of NAD+, recombinant SDH exhibited greatest oxidative activity with sorbitol, ribitol and xylitol as substrates; other sugar alcohols were oxidized to a lesser extent. Under standard growth conditions, three independent sdh- mutants developed as wild-type. Nevertheless, all three exhibited reduced dry weight and primary root length compared to wild-type when grown in the presence of sorbitol. Additionally, under short-day conditions, the mutants were more resistant to dehydration stress, as shown by a reduced loss of leaf water content when watering was withheld, and a greater survival rate on re-watering. This evidence suggests that limitations in the metabolism of sugar alcohols alter the growth of Arabidopsis and its response to drought. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Deoxynivalenol affects in vitro intestinal epithelial cell barrier integrity through inhibition of protein synthesis

    International Nuclear Information System (INIS)

    Van De Walle, Jacqueline; Sergent, Therese; Piront, Neil; Toussaint, Olivier; Schneider, Yves-Jacques; Larondelle, Yvan

    2010-01-01

    Deoxynivalenol (DON), one of the most common mycotoxin contaminants of raw and processed cereal food, adversely affects the gastrointestinal tract. Since DON acts as a protein synthesis inhibitor, the constantly renewing intestinal epithelium could be particularly sensitive to DON. We analyzed the toxicological effects of DON on intestinal epithelial protein synthesis and barrier integrity. Differentiated Caco-2 cells, as a widely used model of the human intestinal barrier, were exposed to realistic intestinal concentrations of DON (50, 500 and 5000 ng/ml) during 24 h. DON caused a concentration-dependent decrease in total protein content associated with a reduction in the incorporation of [ 3 H]-leucine, demonstrating its inhibitory effect on protein synthesis. DON simultaneously increased the paracellular permeability of the monolayer as reflected through a decreased transepithelial electrical resistance associated with an increased paracellular flux of the tracer [ 3 H]-mannitol. A concentration-dependent reduction in the expression level of the tight junction constituent claudin-4 was demonstrated by Western blot, which was not due to diminished transcription, increased degradation, or NF-κB, ERK or JNK activation, and was also observed for a tight junction independent protein, i.e. intestinal alkaline phosphatase. These results demonstrate a dual toxicological effect of DON on differentiated Caco-2 cells consisting in an inhibition of protein synthesis as well as an increase in monolayer permeability, and moreover suggest a possible link between them through diminished synthesis of the tight junction constituent claudin-4.

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

    Directory of Open Access Journals (Sweden)

    Milene L. Brownlow

    2017-05-01

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

  18. SpirPro: A Spirulina proteome database and web-based tools for the analysis of protein-protein interactions at the metabolic level in Spirulina (Arthrospira) platensis C1.

    Science.gov (United States)

    Senachak, Jittisak; Cheevadhanarak, Supapon; Hongsthong, Apiradee

    2015-07-29

    Spirulina (Arthrospira) platensis is the only cyanobacterium that in addition to being studied at the molecular level and subjected to gene manipulation, can also be mass cultivated in outdoor ponds for commercial use as a food supplement. Thus, encountering environmental changes, including temperature stresses, is common during the mass production of Spirulina. The use of cyanobacteria as an experimental platform, especially for photosynthetic gene manipulation in plants and bacteria, is becoming increasingly important. Understanding the mechanisms and protein-protein interaction networks that underlie low- and high-temperature responses is relevant to Spirulina mass production. To accomplish this goal, high-throughput techniques such as OMICs analyses are used. Thus, large datasets must be collected, managed and subjected to information extraction. Therefore, databases including (i) proteomic analysis and protein-protein interaction (PPI) data and (ii) domain/motif visualization tools are required for potential use in temperature response models for plant chloroplasts and photosynthetic bacteria. A web-based repository was developed including an embedded database, SpirPro, and tools for network visualization. Proteome data were analyzed integrated with protein-protein interactions and/or metabolic pathways from KEGG. The repository provides various information, ranging from raw data (2D-gel images) to associated results, such as data from interaction and/or pathway analyses. This integration allows in silico analyses of protein-protein interactions affected at the metabolic level and, particularly, analyses of interactions between and within the affected metabolic pathways under temperature stresses for comparative proteomic analysis. The developed tool, which is coded in HTML with CSS/JavaScript and depicted in Scalable Vector Graphics (SVG), is designed for interactive analysis and exploration of the constructed network. SpirPro is publicly available on the web

  19. MiR-27a suppresses triglyceride accumulation and affects gene mRNA expression associated with fat metabolism in dairy goat mammary gland epithelial cells.

    Science.gov (United States)

    Lin, Xian-Zi; Luo, Jun; Zhang, Li-Ping; Wang, Wei; Shi, Heng-Bo; Zhu, Jiang-Jiang

    2013-05-25

    MicroRNAs (miRNAs), a well-defined group of small RNAs containing about 22 nucleotides, participate in various biological metabolic processes. miR-27a is a miRNA that is known to regulate fat synthesis and differentiation in preadipocyte cells. However, little is known regarding the role that miR-27a plays in regulating goat milk fat synthesis. In this study, we determined the miR-27a expression profile in goat mammary gland and found that miR-27a expression was correlated with the lactation cycle. Additionally, prolactin promoted miR-27a expression in goat mammary gland epithelial cells. Further functional analysis showed that over-expression of miR-27a down-regulated triglyceride accumulation and decreased the ratio of unsaturated/saturated fatty acid in mammary gland epithelial cells. miR-27a also significantly affected mRNA expression related to milk fat metabolism. Specifically, over-expression of miR-27a reduced gene mRNA expression associated with triglyceride synthesis by suppressing PPARγ protein levels. This study provides the first experimental evidence that miR-27a regulates triglyceride synthesis in goat mammary gland epithelial cells and improves our understanding about the importance of miRNAs in milk fat synthesis. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  20. Does vagal nerve stimulation affect body composition and metabolism? Experimental study of a new potential technique in bariatric surgery.

    Science.gov (United States)

    Sobocki, Jacek; Fourtanier, Gilles; Estany, Joan; Otal, Phillipe

    2006-02-01

    It has been shown that vagal nerve stimulation (VNS) can affect body mass. The aim of this study was to evaluate effect of VNS on body mass, body composition, metabolic rate, and plasma leptin and IGF-I levels. Eight female pigs were included in the study. Under general anesthesia, a bipolar electrode was implanted on the anterior vagal nerve by laparoscopy. Group A was treated by VNS, and group B was the control. After 4 weeks, stimulation was discontinued in group A and started in group B. The following parameters were evaluated: body mass, body composition, metabolic rate, plasma leptin and IGF-1 levels and intramuscular fat content (IMF). VNS attenuated body weight gain (2.28 +/- 3.47 kg vs 14.04 +/- 6.75 kg; P = .0112, for stimulation and nonstimulation periods, respectively), backfat gain (0.04 +/- 0.26 mm vs 2.31 +/- 1.12 mm) and IMF gain (-3.76 +/- 6.06 mg/g MS vs 7.24 +/- 12.90 mg/g MS; P = .0281). VNS resulted in lower backfat depth/loin muscle area ratio (0.33 +/- 0.017 vs 0.38 +/- 0.35; P = .0476). Lower plasma IGF-I concentration was found after VNS (-3.67 +/- -11.55 ng/mL vs 9.86 +/- 10.74 ng/mL; P = .0312). No significant changes in other parameters were observed. VNS affects body weight mainly at the expense of body fat resources; however, metabolic rate is not affected.

  1. [Relationship between high-sensitivity C-reactive protein and obesity/metabolic syndrome in children].

    Science.gov (United States)

    Chen, Fangfang; Wang, Wenpeng; Teng, Yue; Hou, Dongqing; Zhao, Xiaoyuan; Yang, Ping; Yan, Yinkun; Mi, Jie

    2014-06-01

    To explore the relationship between high-sensitivity C-reactive protein (hsCRP) and obesity/metabolic syndrome (MetS) related factors in children. 403 children aged 10-14 and born in Beijing were involved in this study. Height, weight, waist circumference, fat mass percentage (Fat%), blood pressure (BP), hsCRP, triglyceride (TG), total cholesterol (TC), fasting plasma glucose (FPG), high and low density lipoprotein cholesterol (HDL-C, LDL-C) were observed among these children. hsCRP was transformed with base 10 logarithm (lgCRP). MetS was defined according to the International Diabetes Federation 2007 definition. Associations between MetS related components and hsCRP were tested using partial correlation analysis, analysis of covariance and linear regression models. 1) lgCRP was positively correlated with BMI, waist circumference, Fat%,BP, FPG, LDL-C and TC while negatively correlated with HDL-C. With BMI under control, the relationships disappeared, but LDL-C (r = 0.102). 2) The distributions of lgCRP showed obvious differences in all the metabolic indices, in most groups, respectively. With BMI under control, close relationships between lgCRP and high blood pressure/high TG disappeared and the relationship with MetS weakened. 3) Through linear regression models, factors as waist circumference, BMI, Fat% were the strongest factors related to hsCRP, followed by systolic BP, HDL-C, diastolic BP, TG and LDL-C. With BMI under control, the relationships disappeared, but LDL-C(β = 0.045). hsCRP was correlated with child obesity, lipid metabolism and MetS. Waist circumference was the strongest factors related with hsCRP. Obesity was the strongest and the independent influencing factor of hsCRP.

  2. Relative Abundance of Integral Plasma Membrane Proteins in Arabidopsis Leaf and Root Tissue Determined by Metabolic Labeling and Mass Spectrometry

    Science.gov (United States)

    Bernfur, Katja; Larsson, Olaf; Larsson, Christer; Gustavsson, Niklas

    2013-01-01

    Metabolic labeling of proteins with a stable isotope (15N) in intact Arabidopsis plants was used for accurate determination by mass spectrometry of differences in protein abundance between plasma membranes isolated from leaves and roots. In total, 703 proteins were identified, of which 188 were predicted to be integral membrane proteins. Major classes were transporters, receptors, proteins involved in membrane trafficking and cell wall-related proteins. Forty-one of the integral proteins, including nine of the 13 isoforms of the PIP (plasma membrane intrinsic protein) aquaporin subfamily, could be identified by peptides unique to these proteins, which made it possible to determine their relative abundance in leaf and root tissue. In addition, peptides shared between isoforms gave information on the proportions of these isoforms. A comparison between our data for protein levels and corresponding data for mRNA levels in the widely used database Genevestigator showed an agreement for only about two thirds of the proteins. By contrast, localization data available in the literature for 21 of the 41 proteins show a much better agreement with our data, in particular data based on immunostaining of proteins and GUS-staining of promoter activity. Thus, although mRNA levels may provide a useful approximation for protein levels, detection and quantification of isoform-specific peptides by proteomics should generate the most reliable data for the proteome. PMID:23990937

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

    Directory of Open Access Journals (Sweden)

    Patrick Lyn

    2009-10-01

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

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

    Science.gov (United States)

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

    2012-05-01

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

  5. Phenobarbital and neonatal seizures affect cerebral oxygen metabolism: a near-infrared spectroscopy study.

    Science.gov (United States)

    Sokoloff, Max D; Plegue, Melissa A; Chervin, Ronald D; Barks, John D E; Shellhaas, Renée A

    2015-07-01

    Near-infrared spectroscopy (NIRS) measures oxygen metabolism and is increasingly used for monitoring critically ill neonates. The implications of NIRS-recorded data in this population are poorly understood. We evaluated NIRS monitoring for neonates with seizures. In neonates monitored with video-electroencephalography, NIRS-measured cerebral regional oxygen saturation (rSO2) and systemic O2 saturation were recorded every 5 s. Mean rSO2 was extracted for 1-h blocks before, during, and after phenobarbital doses. For each electrographic seizure, mean rSO2 was extracted for a period of three times the duration of the seizure before and after the ictal pattern, as well as during the seizure. Linear mixed models were developed to assess the impact of phenobarbital administration and of seizures on rSO2 and fractional tissue oxygen extraction. For 20 neonates (estimated gestational age: 39.6 ± 1.5 wk), 61 phenobarbital doses and 40 seizures were analyzed. Cerebral rSO2 rose (P = 0.005), and fractional tissue oxygen extraction declined (P = 0.018) with increasing phenobarbital doses. rSO2 declined during seizures, compared with baseline and postictal phases (baseline 81.2 vs. ictal 77.7 vs. postictal 79.4; P = 0.004). Fractional tissue oxygen extraction was highest during seizures (P = 0.002). Cerebral oxygen metabolism decreases after phenobarbital administration and increases during seizures. These small, but clear, changes in cerebral oxygen metabolism merit assessment for potential clinical impact.

  6. Nitrogen Metabolism in Lactating Goats Fed with Diets Containing Different Protein Sources

    Directory of Open Access Journals (Sweden)

    A. B. Santos

    2014-05-01

    Full Text Available This study aimed to evaluate urea excretion, nitrogen balance and microbial protein synthesis in lactating goats fed with diets containing different protein sources in the concentrate (soybean meal, cottonseed meal, aerial part of cassava hay and leucaena hay. Four Alpine goats whose mean body weight was 42.6±6.1 kg at the beginning of the experiment, a mean lactation period of 94.0±9.0 days and a production of 1.7±0.4 kg of milk were distributed in a 4×4 Latin square with four periods of 15 days. Diets were formulated to be isonitrogenous, containing 103.0 g/kg of CP, 400 g/kg of Tifton 85 hay and 600 g/kg of concentrate. Diet containing cottonseed meal provided (p<0.05 increased excretion of urea and urea nitrogen in the urine (g/d and mg/kg of BW when compared with leucaena hay. The diets affected the concentrations of urea nitrogen in plasma (p<0.05 and excretion of urea nitrogen in milk, being that soybean meal and cottonseed meal showed (p<0.05 higher than the average aerial part of the cassava hay. The use of diets with cottonseed meal as protein source in the concentrate in feeding of lactating goats provides greater nitrogen excretion in urine and negative nitrogen balance, while the concentrate with leucaena hay as a source of protein, provides greater ruminal microbial protein synthesis.

  7. Salmonella Typhimurium metabolism affects virulence in the host – A mini-review

    DEFF Research Database (Denmark)

    Herrero-fresno, Ana; Olsen, John Elmerdhahl

    2018-01-01

    Salmonella enterica remains an important food borne pathogen in all regions of the world with S. Typhimurium as one of the most frequent serovars causing food borne disease. Since the majority of human cases are caused by food of animal origin, there has been a high interest in understanding how S....... Typhimurium interacts with the animal host, mostly focusing on factors that allow it to breach host barriers and to manipulate host cells to the benefit of itself. Up to recently, such studies have ignored the metabolic factors that allow the bacteria to multiply in the host, but this is changing rapidly...

  8. AMP-activated protein kinase: Role in metabolism and therapeutic implications.

    Science.gov (United States)

    Schimmack, Greg; Defronzo, Ralph A; Musi, Nicolas

    2006-11-01

    AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge which becomes activated in situations of energy consumption. AMPK functions to restore cellular ATP levels by modifying diverse metabolic and cellular pathways. In the skeletal muscle, AMPK is activated during exercise and is involved in contraction-stimulated glucose transport and fatty acid oxidation. In the heart, AMPK activity increases during ischaemia and functions to sustain ATP, cardiac function and myocardial viability. In the liver, AMPK inhibits the production of glucose, cholesterol and triglycerides and stimulates fatty acid oxidation. Recent studies have shown that AMPK is involved in the mechanism of action of metformin and thiazolidinediones, and the adipocytokines leptin and adiponectin. These data, along with evidence that pharmacological activation of AMPK in vivo improves blood glucose homeostasis, cholesterol concentrations and blood pressure in insulin-resistant rodents, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes, ischaemic heart disease and other metabolic diseases.

  9. Saliva C-reactive protein as a biomarker of metabolic syndrome in diabetic patients.

    Science.gov (United States)

    Dezayee, Zhian Mahmood Ibrahim; Al-Nimer, Marwan Salih Mohamad

    2016-01-01

    Human C-reactive protein (CRP) has been used in the risk assessment of coronary events. Human saliva mirrors the body's health and well-being and is noninvasive, easy to collect, and ideal for third-world countries as well as for large patient screening. This study aimed to screen the saliva CRP qualitatively in patients with diabetes (Type 1 and 2) taking in considerations, the diagnostic criteria of metabolic syndrome. Center for diabetes mellitus, prospective study. A total number of 50 Type 2 diabetes (T2D) patients, 25 Type 1 diabetes (T1D) patients, and 25 healthy subjects were recruited from the center for diabetes mellitus. Each patient was assessed clinically, and the anthropometric measures, glycemic status, and lipid profiles were determined. Stimulated salivary flow rate and saliva CRP were determined. All calculations analysis was made using Excel 2003 program for Windows. The results showed that the salivary flow rate in T1D was less than healthy subjects and T2D and CRP was found positive (6 mg/L) in 36% and 56% of patients with T1D and T2D, respectively. Saliva CRP was found to be related to the anthropometric measurement, blood pressure, and glycemic control. We conclude that saliva CRP may be used as a biomarker for metabolic syndrome and its value is obvious in T2D rather than in T1D.

  10. Influence of multidrug resistance and drug transport proteins on chemotherapy drug metabolism.

    Science.gov (United States)

    Joyce, Helena; McCann, Andrew; Clynes, Martin; Larkin, Annemarie

    2015-05-01

    Chemotherapy involving the use of anticancer drugs remains an important strategy in the overall management of patients with metastatic cancer. Acquisition of multidrug resistance remains a major impediment to successful chemotherapy. Drug transporters in cell membranes and intracellular drug metabolizing enzymes contribute to the resistance phenotype and determine the pharmacokinetics of anticancer drugs in the body. ATP-binding cassette (ABC) transporters mediate the transport of endogenous metabolites and xenobiotics including cytotoxic drugs out of cells. Solute carrier (SLC) transporters mediate the influx of cytotoxic drugs into cells. This review focuses on the substrate interaction of these transporters, on their biology and what role they play together with drug metabolizing enzymes in eliminating therapeutic drugs from cells. The majority of anticancer drugs are substrates for the ABC transporter and SLC transporter families. Together, these proteins have the ability to control the influx and the efflux of structurally unrelated chemotherapeutic drugs, thereby modulating the intracellular drug concentration. These interactions have important clinical implications for chemotherapy because ultimately they determine therapeutic efficacy, disease progression/relapse and the success or failure of patient treatment.

  11. [The study on metabolic difference of human body affected by active stress and passive stress under special events].

    Science.gov (United States)

    Guo, Guang-hong; Gu, Feng; Dong, Zhen-nan; Yuan, Xin-hong; Wang, Ling; Tian, Ya-ping

    2010-05-01

    To study the metabolic difference of body influenced by active stress and passive stress under special events. To detect serum multiple biochemistry index of 57 earthquake rescue medical team and 13 victims of a natural calamity in Wenchuan earthquake by using Hitachi 7600 automatic analyzer. Stress affected biochemistry index deeply. To compared with rescue medical team, the serum ADA, ALP and TG of victims increased obviously and TP, ALB, MAO, Cr, UA, K, Na, Cl, Ca, ApoA1 and HDL decreased obviously. Many biochemistry index have been changed under stress and it relate with stress extent. The human body function status was better in active stress than in passive stress.

  12. Proteome-Level Analysis of Metabolism- and Stress-Related Proteins during Seed Dormancy and Germination in Gnetum parvifolium.

    Science.gov (United States)

    Chang, Ermei; Deng, Nan; Zhang, Jin; Liu, Jianfeng; Chen, Lanzhen; Zhao, Xiulian; Abbas, M; Jiang, Zeping; Shi, Shengqing

    2018-03-21

    Gnetum parvifolium is a rich source of materials for traditional medicines, food, and oil, but little is known about the mechanism underlying its seed dormancy and germination. In this study, we analyzed the proteome-level changes in its seeds during germination using isobaric tags for relative and absolute quantitation. In total, 1,040 differentially expressed proteins were identified, and cluster analysis revealed the distinct time points during which signal transduction and oxidation-reduction activity changed. Gene Ontology analysis showed that "carbohydrate metabolic process" and "response to oxidative stress" were the main enriched terms. Proteins associated with starch degradation and antioxidant enzymes were important for dormancy-release, while proteins associated with energy metabolism and protein synthesis were up-regulated during germination. Moreover, protein-interaction networks were mainly associated with heat-shock proteins. Furthermore, in accord with changes in the energy metabolism- and antioxidant-related proteins, indole-3-acetic acid, Peroxidase, and soluble sugar content increased, and the starch content decreased in almost all six stages of dormancy and germination analyzed (S1-S6). The activity of superoxide dismutase, abscisic acid, and malondialdehyde content increased in the dormancy stages (S1-S3) and then decreased in the germination stages (S4-S6). Our results provide new insights into G. parvifolium seed dormancy and germination at the proteome and physiological levels, with implications for improving seed propagation.

  13. A putative ATP/GTP binding protein affects Leishmania mexicana growth in insect vectors and vertebrate hosts

    Science.gov (United States)

    Hlaváčová, Jana; Zimmer, Sara L.; Butenko, Anzhelika; Podešvová, Lucie; Leštinová, Tereza; Lukeš, Julius; Kostygov, Alexei; Votýpka, Jan; Volf, Petr

    2017-01-01

    Background Leishmania virulence factors responsible for the complicated epidemiology of the various leishmaniases remain mainly unidentified. This study is a characterization of a gene previously identified as upregulated in two of three overlapping datasets containing putative factors important for Leishmania’s ability to establish mammalian intracellular infection and to colonize the gut of an insect vector. Methodology/Principal findings The investigated gene encodes ATP/GTP binding motif-containing protein related to Leishmania development 1 (ALD1), a cytosolic protein that contains a cryptic ATP/GTP binding P-loop. We compared differentiation, growth rates, and infective abilities of wild-type and ALD1 null mutant cell lines of L. mexicana. Loss of ALD1 results in retarded growth kinetics but not defects in differentiation in axenic culture. Similarly, when mice and the sand fly vector were infected with the ALD1 null mutant, the primary difference in infection and colonization phenotype relative to wild type was an inability to achieve maximal host pathogenicity. While ability of the ALD1 null mutant cells to infect macrophages in vitro was not affected, replication within macrophages was clearly curtailed. Conclusions/Significance L. mexicana ALD1, encoding a protein with no assigned functional domains or motifs, was identified utilizing multiple comparative analyses with the related and often experimentally overlooked monoxenous flagellates. We found that it plays a role in Leishmania infection and colonization in vitro and in vivo. Results suggest that ALD1 functions in L. mexicana’s general metabolic network, rather than function in specific aspect of virulence as anticipated from the compared datasets. This result validates our comparative genomics approach for finding relevant factors, yet highlights the importance of quality laboratory-based analysis of genes tagged by these methods. PMID:28742133

  14. Energy dense, protein restricted diet increases adiposity and perturbs metabolism in young, genetically lean pigs.

    Directory of Open Access Journals (Sweden)

    Kimberly D Fisher

    Full Text Available Animal models of obesity and metabolic dysregulation during growth (or childhood are lacking. Our objective was to increase adiposity and induce metabolic syndrome in young, genetically lean pigs. Pre-pubertal female pigs, age 35 d, were fed a high-energy diet (HED; n = 12, containing 15% tallow, 35% refined sugars and 9.1-12.9% crude protein, or a control corn-based diet (n = 11 with 12.2-19.2% crude protein for 16 wk. Initially, HED pigs self-regulated energy intake similar to controls, but by wk 5, consumed more (P<0.001 energy per kg body weight. At wk 15, pigs were subjected to an oral glucose tolerance test (OGTT; blood glucose increased (P<0.05 in control pigs and returned to baseline levels within 60 min. HED pigs were hyperglycemic at time 0, and blood glucose did not return to baseline (P = 0.01, even 4 h post-challenge. During OGTT, glucose area under the curve (AUC was higher and insulin AUC was lower in HED pigs compared to controls (P = 0.001. Chronic HED intake increased (P<0.05 subcutaneous, intramuscular, and perirenal fat deposition, and induced hyperglycemia, hypoinsulinemia, and low-density lipoprotein hypercholesterolemia. A subset of HED pigs (n = 7 was transitioned back to a control diet for an additional six weeks. These pigs were subjected to an additional OGTT at 22 wk. Glucose AUC and insulin AUC did not improve, supporting that dietary intervention was not sufficient to recover glucose tolerance or insulin production. These data suggest a HED may be used to increase adiposity and disrupt glucose homeostasis in young, growing pigs.

  15. A recruiting protein of geranylgeranyl diphosphate synthase controls metabolic flux toward chlorophyll biosynthesis in rice.

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    Zhou, Fei; Wang, Cheng-Yuan; Gutensohn, Michael; Jiang, Ling; Zhang, Peng; Zhang, Dabing; Dudareva, Natalia; Lu, Shan

    2017-06-27

    In plants, geranylgeranyl diphosphate (GGPP) is produced by plastidic GGPP synthase (GGPPS) and serves as a precursor for vital metabolic branches, including chlorophyll, carotenoid, and gibberellin biosynthesis. However, molecular mechanisms regulating GGPP allocation among these biosynthetic pathways localized in the same subcellular compartment are largely unknown. We found that rice contains only one functionally active GGPPS, OsGGPPS1, in chloroplasts. A functionally active homodimeric enzyme composed of two OsGGPPS1 subunits is located in the stroma. In thylakoid membranes, however, the GGPPS activity resides in a heterodimeric enzyme composed of one OsGGPPS1 subunit and GGPPS recruiting protein (OsGRP). OsGRP is structurally most similar to members of the geranyl diphosphate synthase small subunit type II subfamily. In contrast to members of this subfamily, OsGRP enhances OsGGPPS1 catalytic efficiency and specificity of GGPP production on interaction with OsGGPPS1. Structural biology and protein interaction analyses demonstrate that affinity between OsGRP and OsGGPPS1 is stronger than between two OsGGPPS1 molecules in homodimers. OsGRP determines OsGGPPS1 suborganellar localization and directs it to a large protein complex in thylakoid membranes, consisting of geranylgeranyl reductase (OsGGR), light-harvesting-like protein 3 (OsLIL3), protochlorophyllide oxidoreductase (OsPORB), and chlorophyll synthase (OsCHLG). Taken together, genetic and biochemical analyses suggest OsGRP functions in recruiting OsGGPPS1 from the stroma toward thylakoid membranes, thus providing a mechanism to control GGPP flux toward chlorophyll biosynthesis.

  16. Affect

    NARCIS (Netherlands)

    Cetinic, M.; Diamanti, J.; Szeman, I.; Blacker, S.; Sully, J.

    2017-01-01

    This chapter historicizes four divergent but historically contemporaneous genres of affect theory – romantic, realist, speculative, and materialist. While critics credited with the turn to affect in the 1990s wrote largely in the wake of poststructuralism from the perspective of gender and queer

  17. Alteration of Fatty-Acid-Metabolizing Enzymes Affects Mitochondrial Form and Function in Hereditary Spastic Paraplegia

    Science.gov (United States)

    Tesson, Christelle; Nawara, Magdalena; Salih, Mustafa A.M.; Rossignol, Rodrigue; Zaki, Maha S.; Al Balwi, Mohammed; Schule, Rebecca; Mignot, Cyril; Obre, Emilie; Bouhouche, Ahmed; Santorelli, Filippo M.; Durand, Christelle M.; Oteyza, Andrés Caballero; El-Hachimi, Khalid H.; Al Drees, Abdulmajeed; Bouslam, Naima; Lamari, Foudil; Elmalik, Salah A.; Kabiraj, Mohammad M.; Seidahmed, Mohammed Z.; Esteves, Typhaine; Gaussen, Marion; Monin, Marie-Lorraine; Gyapay, Gabor; Lechner, Doris; Gonzalez, Michael; Depienne, Christel; Mochel, Fanny; Lavie, Julie; Schols, Ludger; Lacombe, Didier; Yahyaoui, Mohamed; Al Abdulkareem, Ibrahim; Zuchner, Stephan; Yamashita, Atsushi; Benomar, Ali; Goizet, Cyril; Durr, Alexandra; Gleeson, Joseph G.; Darios, Frederic; Brice, Alexis; Stevanin, Giovanni

    2012-01-01

    Hereditary spastic paraplegia (HSP) is considered one of the most heterogeneous groups of neurological disorders, both clinically and genetically. The disease comprises pure and complex forms that clinically include slowly progressive lower-limb spasticity resulting from degeneration of the corticospinal tract. At least 48 loci accounting for these diseases have been mapped to date, and mutations have been identified in 22 genes, most of which play a role in intracellular trafficking. Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing. Interestingly, three subjects with CYP2U1 mutations presented with a thin corpus callosum, white-matter abnormalities, and/or calcification of the basal ganglia. These genes code for two enzymes involved in fatty-acid metabolism, and we have demonstrated in human cells that the HSP pathophysiology includes alteration of mitochondrial architecture and bioenergetics with increased oxidative stress. Our combined results focus attention on lipid metabolism as a critical HSP pathway with a deleterious impact on mitochondrial bioenergetic function. PMID:23176821

  18. BIOCHEMICAL PARAMETERS OF LIPID METABOLISM IN ANIMALS AFFECTED BY HEAVY METAL SALTS AND TREATED WITH CARNITINE CHLORIDE AND SODIUM ALGINATE

    Directory of Open Access Journals (Sweden)

    I. R. Bekus

    2017-02-01

    Full Text Available Background. Lipid metabolism disorders in the organism affected by environmental pollutants, including poisoning with cadmium and lead salts are of topical matter nowadays. Objective. The study was aimed to examine biochemical features of lipid metabolism in rats subjected to toxic damage by lead and cadmium salts and treated with carnitine chloride and Algigel. Methods. Experiments were carried out on white mature outbred male rats weighing 180-200 g. To cause the toxic damage the animals were administered with aqueous solution of cadmium chloride and lead acetate daily for the period of 30 days using intra-gastric lavage. The indices of lipid metabolism were detected by biochemical methods. Results. In animals treated with cadmium chloride and lead acetate the following changes were observed: HDL-cholesterol concentrations significantly decreased, resulting in 87% of the levels in the intact animals on the third day, 84% on the fifth and 80% on the seventh day. Conversely, concentrations of HDL-cholesterol and VLDL-cholesterol significantly increased during the experiment. Respectively, the ratios for HDL-cholesterol are 240%, 352%, and 388%; and for VLDL-cholesterol 108%, 116%, and 132%. Conclusions. Lipids profile of the rats displayed changes in the levels of cholesterol, triglycerides and lipoproteins of low, high and very low density.

  19. SIRT1 stimulation by polyphenols is affected by their stability and metabolism

    NARCIS (Netherlands)

    Boer, de V.C.J.; Goffau, de L.; Arts, I.C.W.; Hollman, P.C.H.; Keijer, J.

    2006-01-01

    Silent information regulator two ortholog 1 (SIRT1) is the human ortholog of the yeast sir2 protein; one of the most important regulators of lifespan extension by caloric restriction in several organisms. Dietary polyphenols, abundant in vegetables, fruits, cereals, wine and tea, were reported to

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

    NARCIS (Netherlands)

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

    2017-01-01

    Adseverin is an actin-severing/capping protein that may contribute to osteoclast differentiation in vitro but its role in bone remodeling of healthy animals is not defined. We analyzed bone and osteoclast structure in adseverin conditional null mice at alveolar and long bone sites. In wild-type and

  1. Metabolic syndrome, C-reactive protein and cardiovascular risk in psoriasis patients: a cross-sectional study*

    Science.gov (United States)

    Paschoal, Renato Soriani; Silva, Daniela Antoniali; Cardili, Renata Nahas; Souza, Cacilda da Silva

    2018-01-01

    Background Psoriasis has been associated with co-morbidities and elevated cardiovascular risk. Objectives To analyze the relationships among metabolic syndrome, cardiovascular risk, C-reactive protein, gender, and Psoriasis severity. Methods In this cross-sectional study, plaque Psoriasis patients (n=90), distributed equally in gender, were analyzed according to: Psoriasis Area and Severity Index, cardiovascular risk determined by the Framingham risk score and global risk assessment, C-reactive protein and metabolic syndrome criteria (NCEPT-ATP III). Results Metabolic syndrome frequency was 43.3% overall, without significance between genders (P=0.14); but women had higher risk for obesity (OR 2.56, 95%CI 1.02-6.41; P=0.04) and systemic arterial hypertension (OR 3.29, 95%CI 1.39-7.81; P=0.006). The increase in the Psoriasis Area and Severity Index also increased the risk for metabolic syndrome (OR 1.060, 95%CI 1.006-1.117; P=0.03). Absolute 10-year cardiovascular risk was higher in males (P=0.002), but after global risk assessment, 51.1% patients, 52.2% women, were re-classified as high-intermediate cardiovascular risk; without significance between genders (P=0.83). C-reactive protein level was elevated nearly six-fold overall, higher in metabolic syndrome (P=0.05), systemic arterial hypertension (P=0.004)