Quantitative diagnosis of breast tumors by morphometric classification of microenvironmental myoepithelial cells using a machine learning approach

OpenAIRE

Yamamoto, Yoichiro; Saito, Akira; Tateishi, Ayako; Shimojo, Hisashi; Kanno, Hiroyuki; Tsuchiya, Shinichi; Ito, Ken-ichi; Cosatto, Eric; Graf, Hans Peter; Moraleda, Rodrigo R.; Eils, Roland; Grabe, Niels

2017-01-01

Machine learning systems have recently received increased attention for their broad applications in several fields. In this study, we show for the first time that histological types of breast tumors can be classified using subtle morphological differences of microenvironmental myoepithelial cell nuclei without any direct information about neoplastic tumor cells. We quantitatively measured 11661 nuclei on the four histological types: normal cases, usual ductal hyperplasia and low/high grade du...

Engineering of metabolic control

Science.gov (United States)

Liao, James C.

2004-03-16

The invention features a method of producing heterologous molecules in cells under the regulatory control of a metabolite and metabolic flux. The method can enhance the synthesis of heterologous polypeptides and metabolites.

Genetic variance in micro-environmental sensitivity for milk and milk quality in Walloon Holstein cattle.

Science.gov (United States)

Vandenplas, J; Bastin, C; Gengler, N; Mulder, H A

2013-09-01

Animals that are robust to environmental changes are desirable in the current dairy industry. Genetic differences in micro-environmental sensitivity can be studied through heterogeneity of residual variance between animals. However, residual variance between animals is usually assumed to be homogeneous in traditional genetic evaluations. The aim of this study was to investigate genetic heterogeneity of residual variance by estimating variance components in residual variance for milk yield, somatic cell score, contents in milk (g/dL) of 2 groups of milk fatty acids (i.e., saturated and unsaturated fatty acids), and the content in milk of one individual fatty acid (i.e., oleic acid, C18:1 cis-9), for first-parity Holstein cows in the Walloon Region of Belgium. A total of 146,027 test-day records from 26,887 cows in 747 herds were available. All cows had at least 3 records and a known sire. These sires had at least 10 cows with records and each herd × test-day had at least 5 cows. The 5 traits were analyzed separately based on fixed lactation curve and random regression test-day models for the mean. Estimation of variance components was performed by running iteratively expectation maximization-REML algorithm by the implementation of double hierarchical generalized linear models. Based on fixed lactation curve test-day mean models, heritability for residual variances ranged between 1.01×10(-3) and 4.17×10(-3) for all traits. The genetic standard deviation in residual variance (i.e., approximately the genetic coefficient of variation of residual variance) ranged between 0.12 and 0.17. Therefore, some genetic variance in micro-environmental sensitivity existed in the Walloon Holstein dairy cattle for the 5 studied traits. The standard deviations due to herd × test-day and permanent environment in residual variance ranged between 0.36 and 0.45 for herd × test-day effect and between 0.55 and 0.97 for permanent environmental effect. Therefore, nongenetic effects also

Stem Cell Metabolism in Cancer and Healthy Tissues: Pyruvate in the Limelight

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Cyril Corbet

2018-01-01

Full Text Available Normal and cancer stem cells (CSCs share the remarkable potential to self-renew and differentiate into many distinct cell types. Although most of the stem cells remain under quiescence to maintain their undifferentiated state, they can also undergo cell divisions as required to regulate tissue homeostasis. There is now a growing evidence that cell fate determination from stem cells implies a fine-tuned regulation of their energy balance and metabolic status. Stem cells can shift their metabolic substrate utilization, between glycolysis and mitochondrial oxidative metabolism, during specification and/or differentiation, as well as in order to adapt their microenvironmental niche. Pyruvate appears as a key metabolite since it is at the crossroads of cytoplasmic glycolysis and mitochondrial oxidative phosphorylation. This Review describes how metabolic reprogramming, focusing on pyruvate utilization, drives the fate of normal and CSCs by modulating their capacity for self-renewal, clonal expansion/differentiation, as well as metastatic potential and treatment resistance in cancer. This Review also explores potential therapeutic strategies to restore or manipulate stem cell function through the use of small molecules targeting the pyruvate metabolism.

Cytokine Regulation of Microenvironmental Cells in Myeloproliferative Neoplasms

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Gregor Hoermann

2015-01-01

Full Text Available The term myeloproliferative neoplasms (MPN refers to a heterogeneous group of diseases including not only polycythemia vera (PV, essential thrombocythemia (ET, and primary myelofibrosis (PMF, but also chronic myeloid leukemia (CML, and systemic mastocytosis (SM. Despite the clinical and biological differences between these diseases, common pathophysiological mechanisms have been identified in MPN. First, aberrant tyrosine kinase signaling due to somatic mutations in certain driver genes is common to these MPN. Second, alterations of the bone marrow microenvironment are found in all MPN types and have been implicated in the pathogenesis of the diseases. Finally, elevated levels of proinflammatory and microenvironment-regulating cytokines are commonly found in all MPN-variants. In this paper, we review the effects of MPN-related oncogenes on cytokine expression and release and describe common as well as distinct pathogenetic mechanisms underlying microenvironmental changes in various MPN. Furthermore, targeting of the microenvironment in MPN is discussed. Such novel therapies may enhance the efficacy and may overcome resistance to established tyrosine kinase inhibitor treatment in these patients. Nevertheless, additional basic studies on the complex interplay of neoplastic and stromal cells are required in order to optimize targeting strategies and to translate these concepts into clinical application.

Microenvironmental characteristics important for personal exposures to aldehydes in Sacramento, CA, and Milwaukee, WI

Science.gov (United States)

Raymer, J. H.; Akland, G.; Johnson, T. R.; Long, T.; Michael, L.; Cauble, L.; McCombs, M.

Oxygenated additives in gasoline are designed to decrease the ozone-forming hydrocarbons and total air toxics, yet they can increase the emissions of aldehydes and thus increase human exposure to these toxic compounds. This paper describes a study conducted to characterize targeted aldehydes in microenvironments in Sacramento, CA, and Milwaukee, WI, and to improve our understanding of the impact of the urban environment on human exposure to air toxics. Data were obtained from microenvironmental concentration measurements, integrated, 24-h personal measurements, indoor and outdoor pollutant monitors at the participants' residences, from ambient pollutant monitors at fixed-site locations in each city, and from real-time diaries and questionnaires completed by the technicians and participants. As part of this study, a model to predict personal exposures based on individual time/activity data was developed for comparison to measured concentrations. Predicted concentrations were generally within 25% of the measured concentrations. The microenvironments that people encounter daily provide for widely varying exposures to aldehydes. The activities that occur in those microenvironments can modulate the aldehyde concentrations dramatically, especially for environments such as "indoor at home." By considering personal activity, location (microenvironment), duration in the microenvironment, and a knowledge of the general concentrations of aldehydes in the various microenvironments, a simple model can do a reasonably good job of predicting the time-averaged personal exposures to aldehydes, even in the absence of monitoring data. Although concentrations of aldehydes measured indoors at the participants' homes tracked well with personal exposure, there were instances where personal exposures and indoor concentrations differed significantly. Key to the ability to predict exposure based on time/activity data is the quality and completeness of the microenvironmental

Precision metabolic engineering: The design of responsive, selective, and controllable metabolic systems.

Science.gov (United States)

McNerney, Monica P; Watstein, Daniel M; Styczynski, Mark P

2015-09-01

Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed "precision metabolic engineering," involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Modeling microenvironmental regulation of glioblastoma stem cells: a biomaterials perspective

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Heffernan, John M.; Sirianni, Rachael W.

2018-02-01

Following diagnosis of a glioblastoma (GBM) brain tumor, surgical resection, chemotherapy and radiation together yield a median patient survival of only 15 months. Importantly, standard treatments fail to address the dynamic regulation of the brain tumor microenvironment that actively supports tumor progression and treatment resistance. It is becoming increasingly recognized that specialized niches within the tumor microenvironment maintain a population of highly malignant glioblastoma stem-like cells (GSCs). GSCs are resistant to traditional chemotherapy and radiation therapy, suggesting that they may be responsible for the near universal rates of tumor recurrence and associated morbidity in GBM. Thus, disrupting microenvironmental support for GSCs could be critical to developing more effective GBM therapies. Three-dimensional (3D) culture models of the tumor microenvironment are powerful tools for identifying key biochemical and biophysical inputs that impact malignant behaviors. Such systems have been used effectively to identify conditions that regulate GSC proliferation, invasion, stem-specific phenotypes, and treatment resistance. Considering the significant role that GSC microenvironments play in regulating this tumorigenic sub-population, these models may be essential for uncovering mechanisms that limit GSCs malignancy.

Thermodynamics of the control of metabolism

NARCIS (Netherlands)

Westerhoff, H. V.; Plomp, P. J.; Groen, A. K.; Wanders, R. J.

1987-01-01

A theory is presented, describing the control analysis of metabolic systems in terms of Gibbs free energies, extending earlier work of Kacser and Burns (25), and Heinrich and Rapoport (29). It is shown that relationships exist between flux control coefficients (the degree to which enzymes control

Slave nodes and the controllability of metabolic networks

International Nuclear Information System (INIS)

Kim, Dong-Hee; Motter, Adilson E

2009-01-01

Recent work on synthetic rescues has shown that the targeted deletion of specific metabolic genes can often be used to rescue otherwise non-viable mutants. This raises a fundamental biophysical question: to what extent can the whole-cell behavior of a large metabolic network be controlled by constraining the flux of one or more reactions in the network? This touches upon the issue of the number of degrees of freedom contained by one such network. Using the metabolic network of Escherichia coli as a model system, here we address this question theoretically by exploring not only reaction deletions, but also a continuum of all possible reaction expression levels. We show that the behavior of the metabolic network can be largely manipulated by the pinned expression of a single reaction. In particular, a relevant fraction of the metabolic reactions exhibits canalizing interactions, in that the specification of one reaction flux determines cellular growth as well as the fluxes of most other reactions in optimal steady states. The activity of individual reactions can thus be used as surrogates to monitor and possibly control cellular growth and other whole-cell behaviors. In addition to its implications for the study of control processes, our methodology provides a new approach to study how the integrated dynamics of the entire metabolic network emerges from the coordinated behavior of its component parts.

TORCing up metabolic control in the brain.

Science.gov (United States)

Hietakangas, Ville; Cohen, Stephen M

2008-05-01

Transducer of regulated CREB activity 2 (TORC2) is a coactivator of CREB and an important regulator of energy balance in mammals through control of gluconeogenesis in the liver. In this issue of Cell Metabolism, Wang and coworkers (2008) report an intriguing role for Drosophila TORC in the neuronal regulation of metabolism.

Metabolic control of female puberty: potential therapeutic targets.

Science.gov (United States)

Castellano, Juan M; Tena-Sempere, Manuel

2016-10-01

The onset of puberty in females is highly sensitive to the nutritional status and the amount of energy reserves of the organism. This metabolic information is sensed and transmitted to hypothalamic GnRH neurons, considered to be ultimately responsible for triggering puberty through the coordinated action of different peripheral hormones, central neurotransmitters, and molecular mediators. This article will review and discuss (i) the relevant actions of the adipose hormone leptin, as a stimulatory/permissive signal, and the gut hormone ghrelin, as an inhibitory factor, in the metabolic control of female puberty; (ii) the crucial role of the hypothalamic kisspeptin neurons, recently emerged as essential gatekeepers of puberty, in transmitting this metabolic information to GnRH neurons; and (iii) the potential involvement of key cellular energy sensors, such as mTOR, as molecular mediators in this setting. The thorough characterization of the physiological roles of the above elements in the metabolic control of female puberty, along with the discovery of novel factors, pathways, and mechanisms involved, will promote our understanding of the complex networks connecting metabolism and puberty and, ultimately, will aid in the design of target-specific treatments for female pubertal disorders linked to conditions of metabolic stress.

Micro-environmental mechanical stress controls tumor spheroid size and morphology by suppressing proliferation and inducing apoptosis in cancer cells.

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Gang Cheng

Full Text Available Compressive mechanical stress produced during growth in a confining matrix limits the size of tumor spheroids, but little is known about the dynamics of stress accumulation, how the stress affects cancer cell phenotype, or the molecular pathways involved.We co-embedded single cancer cells with fluorescent micro-beads in agarose gels and, using confocal microscopy, recorded the 3D distribution of micro-beads surrounding growing spheroids. The change in micro-bead density was then converted to strain in the gel, from which we estimated the spatial distribution of compressive stress around the spheroids. We found a strong correlation between the peri-spheroid solid stress distribution and spheroid shape, a result of the suppression of cell proliferation and induction of apoptotic cell death in regions of high mechanical stress. By compressing spheroids consisting of cancer cells overexpressing anti-apoptotic genes, we demonstrate that mechanical stress-induced apoptosis occurs via the mitochondrial pathway.Our results provide detailed, quantitative insight into the role of micro-environmental mechanical stress in tumor spheroid growth dynamics, and suggest how tumors grow in confined locations where the level of solid stress becomes high. An important implication is that apoptosis via the mitochondrial pathway, induced by compressive stress, may be involved in tumor dormancy, in which tumor growth is held in check by a balance of apoptosis and proliferation.

Role of metabolic control on diabetic nephropathy

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Macedo Célia Sperandéo

2002-01-01

Full Text Available OBJECTIVE: The aim of this investigation was studying the influence of glucose metabolic control on diabetic nephropathy. The authors observed the effect of acarbose, insulin, and both drugs on the metabolic control and development of mesangial enlargement of kidney glomeruli in alloxan-diabetic rats. METHODS: Five groups of Wistar rats were used: normal rats (N, non-treated alloxan-diabetic rats (D, alloxan-diabetic rats treated with acarbose (AD, alloxan-diabetic rats treated with insulin (ID, and alloxan-diabetic rats treated with insulin plus acarbose (IAD. The following parameters were evaluated: body weight; water and food intake; diuresis; blood and urine glucose levels; and the kidney lesions: mesangial enlargement and tubule cell vacuolization. Renal lesions were analysed using a semi-quantitative score 1, 3, 6, 9, and 12 months after diabetes induction. RESULTS: Diabetic rats showed a marked increase of glycemia, urinary glucose levels, diuresis, water and food intake, and weight loss, while the treated diabetic rats showed significant decreased levels of these parameters. The most satisfactory metabolic control was that of diabetic rats treated with acarbose + insulin. There was a significant mesangial enlargement in diabetic rats compared to normal rats from the third up to the 12th month after diabetes induction, with a significant difference between the animals treated with acarbose + insulin and non-treated diabetic rats. A difference between the animals treated with acarbose or insulin alone and non-treated diabetics rats was not seen. CONCLUSIONS: The authors discuss the results stressing the role of diabetic metabolic control in the prevention of diabetic nephropathy.

Controlling cell-free metabolism through physiochemical perturbations.

Science.gov (United States)

Karim, Ashty S; Heggestad, Jacob T; Crowe, Samantha A; Jewett, Michael C

2018-01-01

Building biosynthetic pathways and engineering metabolic reactions in cells can be time-consuming due to complexities in cellular metabolism. These complexities often convolute the combinatorial testing of biosynthetic pathway designs needed to define an optimal biosynthetic system. To simplify the optimization of biosynthetic systems, we recently reported a new cell-free framework for pathway construction and testing. In this framework, multiple crude-cell extracts are selectively enriched with individual pathway enzymes, which are then mixed to construct full biosynthetic pathways on the time scale of a day. This rapid approach to building pathways aids in the study of metabolic pathway performance by providing a unique freedom of design to modify and control biological systems for both fundamental and applied biotechnology. The goal of this work was to demonstrate the ability to probe biosynthetic pathway performance in our cell-free framework by perturbing physiochemical conditions, using n-butanol synthesis as a model. We carried out three unique case studies. First, we demonstrated the power of our cell-free approach to maximize biosynthesis yields by mapping physiochemical landscapes using a robotic liquid-handler. This allowed us to determine that NAD and CoA are the most important factors that govern cell-free n-butanol metabolism. Second, we compared metabolic profile differences between two different approaches for building pathways from enriched lysates, heterologous expression and cell-free protein synthesis. We discover that phosphate from PEP utilization, along with other physiochemical reagents, during cell-free protein synthesis-coupled, crude-lysate metabolic system operation inhibits optimal cell-free n-butanol metabolism. Third, we show that non-phosphorylated secondary energy substrates can be used to fuel cell-free protein synthesis and n-butanol biosynthesis. Taken together, our work highlights the ease of using cell-free systems to explore

Sleep and metabolic control: waking to a problem?

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Trenell, Michael I; Marshall, Nathaniel S; Rogers, Naomi L

2007-01-01

1. The aim of the present review is to outline: (i) the association between sleep and metabolism; (ii) how sleep duration influences the development of disease; and (iii) how sex differences, ageing and obesity may potentially influence the relationship between sleep, metabolic control and subsequent disease. 2. Sleep is associated with a number of endocrine changes, including a change in insulin action in healthy young individuals. Sleep duration shows a prospective U-shaped relationship with all-cause mortality, cardiovascular disease and Type 2 diabetes. 3. Chronic sleep restriction is becoming more common. Experimental sleep restriction impedes daytime glucose control and increases appetite. 4. The sex hormones oestrogen and testosterone influence sleep duration and quality and may account for sex differences in the prevalence of sleep-related disorders. 5. Ageing is associated with a decreased sleep duration, decreased muscle mass and impaired insulin action. 6. Obesity impairs insulin action and is associated with the incidence and severity of obstructive sleep apnoea. 7. Sleep plays an integral role in metabolic control. Consequently, insufficient sleep may represent a modifiable risk factor for the development of Type 2 diabetes. The challenge ahead is to identify how sex differences, ageing and obesity could potentially influence the relationship between sleep and metabolism.

Adherence to two methods of education and metabolic control in ...

African Journals Online (AJOL)

BACKGROUND: Education in diabetes optimizes metabolic control, prevents acute and chronic complications, and improves quality of life. Our main objective was to evaluate if a better metabolic control is achieved in diabetic patients undergoing a program of intensive interactive care than in those with traditional care and ...

Molecular and Microenvironmental Determinants of Glioma Stem-Like Cell Survival and Invasion

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Alison Roos

2017-06-01

Full Text Available Glioblastoma multiforme (GBM is the most frequent primary brain tumor in adults with a 5-year survival rate of 5% despite intensive research efforts. The poor prognosis is due, in part, to aggressive invasion into the surrounding brain parenchyma. Invasion is a complex process mediated by cell-intrinsic pathways, extrinsic microenvironmental cues, and biophysical cues from the peritumoral stromal matrix. Recent data have attributed GBM invasion to the glioma stem-like cell (GSC subpopulation. GSCs are slowly dividing, highly invasive, therapy resistant, and are considered to give rise to tumor recurrence. GSCs are localized in a heterogeneous cellular niche, and cross talk between stromal cells and GSCs cultivates a fertile environment that promotes GSC invasion. Pro-migratory soluble factors from endothelial cells, astrocytes, macrophages, microglia, and non-stem-like tumor cells can stimulate peritumoral invasion of GSCs. Therefore, therapeutic efforts designed to target the invasive GSCs may enhance patient survival. In this review, we summarize the current understanding of extrinsic pathways and major stromal and immune players facilitating GSC maintenance and survival.

Quantitative proteomics and transcriptomics reveals metabolic differences in attracting and non-attracting human-in-mouse glioma stem cell xenografts and stromal cells

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Norelle C. Wildburger

2015-09-01

Full Text Available Bone marrow-derived human mesenchymal stem cells (BM-hMSCs show promise as cell-based delivery vehicles for anti-glioma therapeutics, due to innate tropism for gliomas. However, in clinically relevant human-in-mouse glioma stem cell xenograft models, BM-hMSCs tropism is variable. We compared the proteomic profile of cancer and stromal cells in GSCXs that attract BM-hMSCs (“attractors” with those to do not (“non-attractors” to identify pathways that may modulate BM-hMSC homing, followed by targeted transcriptomics. The results provide the first link between fatty acid metabolism, glucose metabolism, ROS, and N-glycosylation patterns in attractors. Reciprocal expression of these pathways in the stromal cells suggests microenvironmental cross-talk.

Dynamic optimal metabolic control theory: a cybernetic approach for modelling of the central nitrogen metabolism of S. cerevisiae

NARCIS (Netherlands)

Riel, van N.A.W.; Giuseppin, M.L.F.; Verrips, C.T.

2000-01-01

The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the

Metabolic control by S6 kinases depends on dietary lipids.

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Tamara R Castañeda

Full Text Available Targeted deletion of S6 kinase (S6K 1 in mice leads to higher energy expenditure and improved glucose metabolism. However, the molecular mechanisms controlling these effects remain to be fully elucidated. Here, we analyze the potential role of dietary lipids in regulating the mTORC1/S6K system. Analysis of S6K phosphorylation in vivo and in vitro showed that dietary lipids activate S6K, and this effect is not dependent upon amino acids. Comparison of male mice lacking S6K1 and 2 (S6K-dko with wt controls showed that S6K-dko mice are protected against obesity and glucose intolerance induced by a high-fat diet. S6K-dko mice fed a high-fat diet had increased energy expenditure, improved glucose tolerance, lower fat mass gain, and changes in markers of lipid metabolism. Importantly, however, these metabolic phenotypes were dependent upon dietary lipids, with no such effects observed in S6K-dko mice fed a fat-free diet. These changes appear to be mediated via modulation of cellular metabolism in skeletal muscle, as shown by the expression of genes involved in energy metabolism. Taken together, our results suggest that the metabolic functions of S6K in vivo play a key role as a molecular interface connecting dietary lipids to the endogenous control of energy metabolism.

Microenvironmental pH measurement during sodium naproxenate dissolution in acidic medium by UV/vis imaging

DEFF Research Database (Denmark)

Ostergaard, Jesper; Jensen, Henrik; Larsen, Susan W

2014-01-01

Variable dissolution from sodium salts of drugs containing a carboxylic acid group after passing the acidic environment of the stomach may affect oral bioavailability. The aim of the present proof of concept study was to investigate pH effects in relation to the dissolution of sodium naproxenate...... in 0.01M hydrochloric acid. For this purpose a UV/vis imaging-based approach capable of measuring microenvironmental pH in the vicinity of the solid drug compact as well as monitoring drug dissolution was developed. Using a pH indicating dye real-time spatially resolved measurement of pH was achieved....... Sodium naproxenate, can significantly alter the local pH of the dissolution medium, is eventually neutralized and precipitates as the acidic species naproxen. The developed approach is considered useful for detailed studies of pH dependent dissolution phenomena in dissolution testing....

Enhanced dissolution and bioavailability of Nateglinide by microenvironmental pH-regulated ternary solid dispersion: in-vitro and in-vivo evaluation.

Science.gov (United States)

Wairkar, Sarika; Gaud, Ram; Jadhav, Namdeo

2017-09-01

Nateglinide, an Antidiabetic drug (BCS II), shows pH-dependent solubility and variable bioavailability. The purpose of study was to increase dissolution and bioavailability of Nateglinide by development of its microenvironmental pH-regulated ternary solid dispersion (MeSD). MeSD formulation of Nateglinide, poloxamer-188 and Na 2 CO 3 was prepared by melt dispersion in 1 : 2 : 0.2 w/w ratio and further characterised for solubility, In-vitro dissolution, microenvironmental pH, crystallinity/amorphism, physicochemical interactions, bioavailability in Wistar rats. Solubility of Nateglinide was increased notably in MeSD, and its in-vitro dissolution study showed fourfold increase in the dissolution, particularly in 1.2 pH buffer. Prominent reduction in the peak intensity of X-ray powder diffraction (XRPD) and absence of endotherm in DSC thermogram confirmed the amorphism of Nateglinide in MeSD. Attenuated total reflectance Fourier transform infrared spectra revealed the hydrogen bond interactions between Nateglinide and poloxamer-188. In-vivo study indicated that MeSD exhibited fourfold increase in area under curve over Nateglinide. Tmax of MeSD was observed at 0.25 h, which is beneficial for efficient management of postprandial sugar. Instead of mere transformation of the Nateglinide to its amorphous form as evidenced by DSC and XRPD, formation of a soluble carboxylate compound of Nateglinide in MeSD was predominantly responsible for dissolution and bioavailability enhancement. The study demonstrates the utility of MeSD in achieving pH-independent dissolution, reduced T max and enhanced bioavailability of Nateglinide. © 2017 Royal Pharmaceutical Society.

Pre- and post-natal nutritional factors in the metabolic regulation of obesity

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E. Villanueva-Ortega

2017-04-01

Full Text Available In recent decades there has been a very significant increase in obesity in most developing countries. In addition to environmental, genetic and hormonal factors, nutritional and maternal environment factors influencing critical periods of foetal development have acquired increasing significance since the thrifty phenotype theory was described by Harles and Barker and epidemiological studies demonstrated that perinatal conditions may modify individuals’ future metabolic responses via genomic reprogramming. Perinatal programming corresponds to a critical and accelerated period of developmental plasticity from preconception through early postnatal life. This characteristic may also have a long-term influence on metabolic health and obesity. Epigenetic modifications favour the survival of the individual in critical periods when nutritional restriction is established, but exerts long-term risks, as metabolic programming tracks into infancy and adulthood and induces fat mass accumulation, particularly if energy consumption is exceeded. Although the mechanisms are not yet fully understood, it is evident that hormonal factors such as insulin and leptin may influence the programming of hypothalamic circuits for energy balance regulation. Nutritional interventions in animal models at critical stages of development have demonstrated that microenvironmental modifications might induce a permanent modulation of the progeny genome expression via epigenetic mechanisms. A transgenerational transmission of obesity has been proposed.

Cancer Metabolism and Tumor Heterogeneity: Imaging Perspectives Using MR Imaging and Spectroscopy

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Gigin Lin

2017-01-01

Full Text Available Cancer cells reprogram their metabolism to maintain viability via genetic mutations and epigenetic alterations, expressing overall dynamic heterogeneity. The complex relaxation mechanisms of nuclear spins provide unique and convertible tissue contrasts, making magnetic resonance imaging (MRI and magnetic resonance spectroscopy (MRS pertinent imaging tools in both clinics and research. In this review, we summarized MR methods that visualize tumor characteristics and its metabolic phenotypes on an anatomical, microvascular, microstructural, microenvironmental, and metabolomics scale. The review will progress from the utilities of basic spin-relaxation contrasts in cancer imaging to more advanced imaging methods that measure tumor-distinctive parameters such as perfusion, water diffusion, magnetic susceptibility, oxygenation, acidosis, redox state, and cell death. Analytical methods to assess tumor heterogeneity are also reviewed in brief. Although the clinical utility of tumor heterogeneity from imaging is debatable, the quantification of tumor heterogeneity using functional and metabolic MR images with development of robust analytical methods and improved MR methods may offer more critical roles of tumor heterogeneity data in clinics. MRI/MRS can also provide insightful information on pharmacometabolomics, biomarker discovery, disease diagnosis and prognosis, and treatment response. With these future directions in mind, we anticipate the widespread utilization of these MR-based techniques in studying in vivo cancer biology to better address significant clinical needs.

Metabolic Control and Illness Perceptions in Adolescents with Type 1 Diabetes

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Line Wisting

2016-01-01

Full Text Available Background. Disturbed eating behavior and psychosocial variables have been found to influence metabolic control, but little is known about how these variables interact or how they influence metabolic control, separately and combined. Objective. To explore associations between metabolic control (measured by HbA1c and eating disorder psychopathology, coping strategies, illness perceptions, and insulin beliefs in adolescents with type 1 diabetes. Methods. A total of 105 patients (41.9% males with type 1 diabetes (12–20 years were interviewed with the Child Eating Disorder Examination. In addition, self-report psychosocial questionnaires were completed. Clinical data, including HbA1c, was obtained from the Norwegian Childhood Diabetes Registry. Results. Significant gender differences were demonstrated. Among females, HbA1c correlated significantly with eating restriction (.29, p < .05, the illness perception dimensions consequences, personal control, coherence, and concern (ranging from .33 to .48, and the coping strategy ventilating negative feelings (−.26, p < .05. Illness perception personal control contributed significantly to HbA1c in a regression model, explaining 23% of the variance among females (β .48, p < .001. None of the variables were significantly associated with HbA1c among males. Conclusions. Illness perceptions appear to be important contributors to metabolic control in females, but not males, with type 1 diabetes.

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

Science.gov (United States)

Goforth, Paulette B; Myers, Martin G

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

Heart over mind: metabolic control of white adipose tissue and liver.

Science.gov (United States)

Nakamura, Michinari; Sadoshima, Junichi

2014-12-01

Increasing evidence suggests that the heart controls the metabolism of peripheral organs. Olson and colleagues previously demonstrated that miR‐208a controls systemic energy homeostasis through the regulation of MED13 in cardiomyocytes (Grueter et al, 2012). In their follow‐up study in this issue of EMBO Molecular Medicine, white adipose tissue (WAT) and liver are identified as the physiological targets of cardiac MED13 signaling, most likely through cardiac‐derived circulating factors, which boost energy consumption by upregulating metabolic gene expression and increasing mitochondrial numbers (Baskin et al, 2014). In turn, increased energy expenditure in WAT and the liver confers leanness. These findings strengthen the evidence of metabolic crosstalk between the heart and peripheral tissues through cardiokines and also set the stage for the development of novel treatments for metabolic syndrome.

Significance of family and peer support for metabolic control of type 1 diabetes in adolescents

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Đurović Dušanka

2009-01-01

Full Text Available The aim of the paper was to explore the significance of family and peer support for metabolic control of Type 1 diabetes in adolescents. Metabolic control refers to maintenance of acceptable blood glucose level thus diminishing risk for chronic complications. It involves regular insulin shots, measuring blood glucose and keeping diary, as the daily based self-control. Regular visits to endocrinologist and screening for chronic complications are compulsory. The sample comprised 79 adolescents age 10-17 years with diagnose of Type 1 diabetes and properly treated at the institute. The sample was divided in two groups - with good (N=40 and poor (N=39 metabolic control. A criterium for good metabolic control was glycosilated hemoglobin less than 7,6%. Social support was measured by Social Support Scale consisting of two parts - the first for estimation of registered family support (based upon modified Perceived Social Support Family Scale and the second for estimation of registered friends' support (modified Perceived Social Support Friend Scale. Adolescents with good metabolic control referred statistically more significant social support in the family, unlike the group with poor metabolic control. Considering peer social support, there was no statistically significant difference. Positive family history for diabetes also appeared to be directly linked to good metabolic control.

Metabolic control of puberty: roles of leptin and kisspeptins.

Science.gov (United States)

Sanchez-Garrido, Miguel A; Tena-Sempere, Manuel

2013-07-01

This article is part of a Special Issue "Puberty and Adolescence". Reproduction is an energy-demanding function. Accordingly, puberty is metabolically gated, as a means to prevent fertility in conditions of energy insufficiency. In addition, obesity has been shown to impact the timing of puberty and may be among the causes for the earlier trends of pubertal age reported in various countries. The metabolic control of puberty in such a spectrum of situations, ranging from energy deficit to extreme overweight, is the result of the concerted action of different peripheral hormones and central transmitters that sense the metabolic state of the organism and transmit this information to the various elements of the reproductive axis, mainly the GnRH neurons. Among the peripheral signals involved, the adipose hormone, leptin, is known to play an essential role in the regulation of puberty, especially in females. Yet, although it is clear that the effects of leptin on puberty onset are predominantly permissive and mainly conducted at central (hypothalamic) levels, the primary sites and mechanisms of action of leptin within the reproductive brain remain unsolved. In this context, neurons expressing kisspeptins, the products of the Kiss1 gene that have emerged recently as essential upstream regulators of GnRH neurons, operate as key sensors of the metabolic state and funnel of the reproductive effects of leptin. Yet, much debate has arisen recently on whether the putative actions of leptin on the Kiss1 system are actually indirect and/or may primarily target Kiss1-independent pathways, such as those originating from the ventral premmamilary nucleus. Moreover, evidence has been presented for extra-hypothalamic or peripheral actions of leptin, including direct gonadal effects, which may contribute to the metabolic control of reproduction in extreme body weight conditions. In this work, we will critically review the experimental evidence supporting a role of leptin, kisspeptin

Transcriptional switches in the control of macronutrient metabolism.

Science.gov (United States)

Wise, Alan

2008-06-01

This review shows how some transcription factors respond to alterations in macronutrients. Carbohydrates induce enzymes for their metabolism and fatty acid synthesis. Fatty acids reduce carbohydrate processing, induce enzymes for their metabolism, and increase both gluconeogenesis and storage of fat. Fat stores help control carbohydrate uptake by other cells. The following main transcription factors are discussed: carbohydrate response element-binding protein; sterol regulatory element-binding protein-1c, cyclic AMP response element-binding protein, peroxisome proliferator-activated receptor-alpha, and peroxisome proliferator-activated receptor-gamma.

Modified metabolic syndrome and second cancers in women: A case control study.

Science.gov (United States)

Ortiz-Mendoza, Carlos-Manuel; Pérez-Chávez, Ernesto; Fuente-Vera, Tania-Angélica De-la

2016-01-01

According to some studies, the metabolic syndrome causes diverse primary cancers; however, there is no evidence about metabolic syndrome impact on second cancers development in women. To find out the implication of the modified metabolic syndrome in women with second cancers. This was a case-control study, at a general hospital in Mexico City, in women with second cancers (cases) and age-matched women with only one neoplasm (controls). The analysis comprised: Tumor (s), anthropometric features, and body mass index (BMI); moreover, presence of diabetes mellitus, hypertension, and fasting serum levels of total cholesterol, triglycerides and glucose. The sample was of nine cases and 27 controls. In cases, the metabolic syndrome (diabetes mellitus or glucose > 99 mg/dL + hypertension or blood pressure ≥ 135/85 mm Hg + triglycerides > 149 mg/dL or BMI ≥ 30 kg/m 2 ) was more frequent (odds ratio 20.8, 95% confidence interval: 1.9-227.1). Our results suggest that in women, the modified metabolic syndrome may be a risk factor for second cancers.

Modified metabolic syndrome and second cancers in women: A case control study

Directory of Open Access Journals (Sweden)

Carlos-Manuel Ortiz-Mendoza

2016-01-01

Full Text Available Background: According to some studies, the metabolic syndrome causes diverse primary cancers; however, there is no evidence about metabolic syndrome impact on second cancers development in women. Aim: To find out the implication of the modified metabolic syndrome in women with second cancers. Materials and Methods: This was a case-control study, at a general hospital in Mexico City, in women with second cancers (cases and age-matched women with only one neoplasm (controls. The analysis comprised: Tumor (s, anthropometric features, and body mass index (BMI; moreover, presence of diabetes mellitus, hypertension, and fasting serum levels of total cholesterol, triglycerides and glucose. Results: The sample was of nine cases and 27 controls. In cases, the metabolic syndrome (diabetes mellitus or glucose > 99 mg/dL + hypertension or blood pressure ≥ 135/85 mm Hg + triglycerides > 149 mg/dL or BMI ≥ 30 kg/m 2 was more frequent (odds ratio 20.8, 95% confidence interval: 1.9-227.1. Conclusion: Our results suggest that in women, the modified metabolic syndrome may be a risk factor for second cancers.

Sense and nonsense in metabolic control of reproduction.

Science.gov (United States)

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

2012-01-01

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

Signed, Sealed, Delivered: Microenvironmental Modulation of Extracellular Vesicle-Dependent Immunoregulation in the Lung.

Science.gov (United States)

Schneider, Daniel J; Speth, Jennifer M; Peters-Golden, Marc

2016-01-01

Unconventional secretion and subsequent uptake of molecular cargo via extracellular vesicles (EVs) is an important mechanism by which cells can exert paracrine effects. While this phenomenon has been widely characterized in the context of their ability to promote inflammation, less is known about the ability of EVs to transfer immunosuppressive cargo. Maintenance of normal physiology in the lung requires suppression of potentially damaging inflammatory responses to the myriad of insults to which it is continually exposed. Recently, our laboratory has reported the ability of alveolar macrophages (AMs) to secrete suppressors of cytokine signaling (SOCS) proteins within microvesicles (MVs) and exosomes (Exos). Uptake of these EVs by alveolar epithelial cells (AECs) resulted in inhibition of pro-inflammatory STAT activation in response to cytokines. Moreover, AM packaging of SOCS within EVs could be rapidly tuned in response to exogenous or AEC-derived substances. In this article we will highlight gaps in knowledge regarding microenvironmental modulation of cargo packaging and utilization as well as EV secretion and uptake. Advances in these areas are critical for improving understanding of intercellular communication in the immune system and for therapeutic application of artificial vesicles aimed at treatment of diseases characterized by dysregulated inflammation.

Metabolic gene polymorphism frequencies in control populations

DEFF Research Database (Denmark)

Garte, Seymour; Gaspari, Laura; Alexandrie, Anna-Karin

2001-01-01

Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1...

An introduction to the indirect exposure assessment approach: modeling human exposure using microenvironmental measurements and the recent National Human Activity Pattern Survey.

Science.gov (United States)

Klepeis, N E

1999-01-01

Indirect exposure approaches offer a feasible and accurate method for estimating population exposures to indoor pollutants, including environmental tobacco smoke (ETS). In an effort to make the indirect exposure assessment approach more accessible to people in the health and risk assessment fields, this paper provides examples using real data from (italic>a(/italic>) a week-long personal carbon monoxide monitoring survey conducted by the author; and (italic>b(/italic>) the 1992 to 1994 National Human Activity Pattern Survey (NHAPS) for the United States. The indirect approach uses measurements of exposures in specific microenvironments (e.g., homes, bars, offices), validated microenvironmental models (based on the mass balance equation), and human activity pattern data obtained from questionnaires to predict frequency distributions of exposure for entire populations. This approach requires fewer resources than the direct approach to exposure assessment, for which the distribution of monitors to a representative sample of a given population is necessary. In the indirect exposure assessment approach, average microenvironmental concentrations are multiplied by the total time spent in each microenvironment to give total integrated exposure. By assuming that the concentrations encountered in each of 10 location categories are the same for different members of the U.S. population (i.e., the NHAPS respondents), the hypothetical contribution that ETS makes to the average 24-hr respirable suspended particle exposure for Americans working their main job is calculated in this paper to be 18 microg/m3. This article is an illustrative review and does not contain an actual exposure assessment or model validation. Images Figure 3 Figure 4 PMID:10350522

Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

Science.gov (United States)

2014-01-01

Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

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

Science.gov (United States)

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

2015-04-20

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

Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

International Nuclear Information System (INIS)

Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

2015-01-01

During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET- 18 FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal

Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.

Science.gov (United States)

Volkow, Nora D; Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S; Benveniste, Helene; Tomasi, Dardo

2015-02-18

During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-(18)FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal. Copyright © 2015 the authors 0270-6474/15/353248-08$15.00/0.

Metabolic control analysis of xylose catabolism in Aspergillus

NARCIS (Netherlands)

Prathumpai, W.; Gabelgaard, J.B.; Wanchanthuek, P.; Vondervoort, van de P.J.I.; Groot, de M.J.L.; McIntyre, M.; Nielsen, J.

2003-01-01

A kinetic model for xylose catabolism in Aspergillus is proposed. From a thermodynamic analysis it was found that the intermediate xylitol will accumulate during xylose catabolism. Use of the kinetic model allowed metabolic control analysis (MCA) of the xylose catabolic pathway to be carried out,

Signed, sealed, delivered: microenvironmental modulation of extracellular vesicle-dependent immunoregulation in the lung

Directory of Open Access Journals (Sweden)

Daniel J Schneider

2016-08-01

Full Text Available Unconventional secretion and subsequent uptake of molecular cargo via extracellular vesicles (EVs is an important mechanism by which cells can exert paracrine effects. While this phenomenon has been widely characterized in the context of their ability to promote inflammation, less is known about the ability of EVs to transfer immunosuppressive cargo. Maintenance of normal physiology in the lung requires suppression of potentially damaging inflammatory responses to the myriad of insults to which it is continually exposed. Recently, our laboratory has reported the ability of alveolar macrophages (AMs to secrete suppressors of cytokine signaling (SOCS proteins within microvesicles (MVs and exosomes (Exos. Uptake of these EVs by alveolar epithelial cells (AECs resulted in inhibition of pro-inflammatory STAT activation in response to cytokines. Moreover, AM packaging of SOCS within EVs could be rapidly tuned in response to exogenous or AEC-derived substances. In this article we will highlight gaps in knowledge regarding microenvironmental modulation of cargo packaging and utilization as well as EV secretion and uptake. Advances in these areas are critical for improving understanding of intercellular communication in the immune system and for therapeutic application of artificial vesicles aimed at treatment of diseases characterized by dysregulated inflammation.

Quantitative diagnosis of breast tumors by morphometric classification of microenvironmental myoepithelial cells using a machine learning approach.

Science.gov (United States)

Yamamoto, Yoichiro; Saito, Akira; Tateishi, Ayako; Shimojo, Hisashi; Kanno, Hiroyuki; Tsuchiya, Shinichi; Ito, Ken-Ichi; Cosatto, Eric; Graf, Hans Peter; Moraleda, Rodrigo R; Eils, Roland; Grabe, Niels

2017-04-25

Machine learning systems have recently received increased attention for their broad applications in several fields. In this study, we show for the first time that histological types of breast tumors can be classified using subtle morphological differences of microenvironmental myoepithelial cell nuclei without any direct information about neoplastic tumor cells. We quantitatively measured 11661 nuclei on the four histological types: normal cases, usual ductal hyperplasia and low/high grade ductal carcinoma in situ (DCIS). Using a machine learning system, we succeeded in classifying the four histological types with 90.9% accuracy. Electron microscopy observations suggested that the activity of typical myoepithelial cells in DCIS was lowered. Through these observations as well as meta-analytic database analyses, we developed a paracrine cross-talk-based biological mechanism of DCIS progressing to invasive cancer. Our observations support novel approaches in clinical computational diagnostics as well as in therapy development against progression.

Integration of Environmental and Developmental (or Metabolic) Control of Seed Mass by Sugar and Ethylene Metabolisms in Arabidopsis.

Science.gov (United States)

Meng, Lai-Sheng; Xu, Meng-Ke; Wan, Wen; Wang, Jing-Yi

2018-04-04

In higher plants, seed mass is an important to evolutionary fitness. In this context, seedling establishment positively correlates with seed mass under conditions of environmental stress. Thus, seed mass constitutes an important agricultural trait. Here, we show loss-of-function of YODA (YDA), a MAPKK Kinase, and decreased seed mass, which leads to susceptibility to drought. Furthermore, we demonstrate that yda disrupts sugar metabolisms but not the gaseous plant hormone, ethylene. Our data suggest that the transcription factor EIN3 (ETHYLENE-INSENSITIVE3), integral to both sugar and ethylene metabolisms, physically interacts with YDA. Further, ein3-1 mutants exhibited increased seed mass. Genetic analysis indicated that YDA and EIN3 were integral to a sugar-mediated metabolism cascade which regulates seed mass by maternally controlling embryo size. It is well established that ethylene metabolism leads to the suppression of drought tolerance by the EIN3 mediated inhibition of CBF1, a transcription factor required for the expression genes of abiotic stress. Our findings help guide the synthesis of a model predicting how sugar/ethylene metabolisms and environmental stress are integrated at EIN3 to control both the establishment of drought tolerance and the production of seed mass. Collectively, these insights into the molecular mechanism underpinning the regulation of plant seed size may aid prospective breeding or design strategies to increase crop yield.

Hematopoietic stem cell fate through metabolic control.

Science.gov (United States)

Ito, Kyoko; Ito, Keisuke

2018-05-25

Hematopoietic stem cells (HSCs) maintain a quiescent state in the bone marrow to preserve their self-renewal capacity, but also undergo cell divisions as required. Organelles such as the mitochondria sustain cumulative damage during these cell divisions, and this damage may eventually compromise the cells' self-renewal capacity. HSC divisions result in either self-renewal or differentiation, with the balance between the two directly impacting hematopoietic homeostasis; but the heterogeneity of available HSC-enriched fractions, together with the technical challenges of observing HSC behavior, has long hindered the analysis of individual HSCs, and prevented the elucidation of this process. However, recent advances in genetic models, metabolomics analyses and single-cell approaches have revealed the contributions made to HSC self-renewal by metabolic cues, mitochondrial biogenesis, and autophagy/mitophagy, which have highlighted mitochondrial quality as a key control factor in the equilibrium of HSCs. A deeper understanding of precisely how specific modes of metabolism control HSC fate at the single cell level is therefore not only of great biological interest, but will have clear clinical implications for the development of therapies for hematological disease. Copyright © 2018. Published by Elsevier Inc.

Association between metabolic control and oral health in adolescents with type 1 diabetes mellitus.

Science.gov (United States)

Saes Busato, Ivana Maria; Bittencourt, Mônica Sommer; Machado, Maria Angela Naval; Grégio, Ana Maria Trindade; Azevedo-Alanis, Luciana Reis

2010-03-01

The aim of this study was to evaluate the association between metabolic control and oral health of adolescents with type 1 diabetes mellitus (DM1). A case-control epidemiologic study was performed on adolescents allocated between 2 groups: DM1 group composed of 51 with DM1, and control group composed of 51 without diabetes. In the DM1 group, metabolic control data were observed (glycosylated hemoglobin (GHb) and capillary glucose), whereby GHb 8.0% poor metabolic control (DM1-B). Oral mucosal abnormalites, Community Periodontal Index (CPI), and decayed, missing, and filled (DMF) index were documented. Salivary flow was evaluated by means of stimulated saliva collection (SSFR). Glycosylated hemoglobin values of 8.0% (DM1-B) in 34 (76%) of the subjects. The average DMF indexes were 1.5 (control) and 3.3 (DM1-group) (P < or = .05). The average CPIs were 0.2 (control), 1.4 (DM1-A), and 2.0 (DM1-B) (P < or = .05). Average SSFRs were 0.997 (DM1-A), 0.903 (DM1-B), and 1.224 (control) mL/min. Oral health of adolescents with DM1 was impaired regardless of metabolic control. Copyright 2010 Mosby, Inc. All rights reserved.

Hypothalamic control of energy metabolism via the autonomic nervous system

NARCIS (Netherlands)

Kalsbeek, A.; Bruinstroop, E.; Yi, C. X.; Klieverik, L. P.; La Fleur, S. E.; Fliers, E.

2010-01-01

The hypothalamic control of hepatic glucose production is an evident aspect of energy homeostasis. In addition to the control of glucose metabolism by the circadian timing system, the hypothalamus also serves as a key relay center for (humoral) feedback information from the periphery, with the

[Metabolic control in children and adolescents with type 1 diabetes].

Science.gov (United States)

Díaz-Cárdenas, Claudia; Wong, Carolina; Vargas Catalán, Nelson A

2016-01-01

Type 1 diabetes mellitus (T1D) is an important disease in children and adolescent being a major risk factor for early morbidity and mortality. To know the degree of metabolic control and prevalence of cardiovascular risk factors in T1D patients. Retrospective study including patients under 19 years of age with T1D controlled at a Chilean hospital in 2011. 94 patients were evaluated (average age at diagnosis: 7.3 years; current age: 11,9 years; evolution time: 4.5 years). Seventy-nine percent (79.8%) of patients presented glycated hemoglobin (HbA1c) over the recommended level with an average of 8.9%. The group between 13 and 19 years of age exhibited the worst metabolic control (86% with HbA1c abnormal levels). Overweight or obesity occurred in 26.6% of patients, 20.3% had LDL >100mg/dl and 4.2% had hypertension. Only about twenty percent of patients had adequate metabolic control as measured by HbA1c, although cardiovascular risk profile was acceptable. Therapeutic and educational efforts must be reinforced mainly in adolescents, emphasizing the importance of adequate nutritional management as a primary method to treat this entity. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

A dual control mechanism synchronizes riboflavin and sulphur metabolism in Bacillus subtilis

Science.gov (United States)

Pedrolli, Danielle Biscaro; Kühm, Christian; Sévin, Daniel C.; Vockenhuber, Michael P.; Sauer, Uwe; Suess, Beatrix; Mack, Matthias

2015-01-01

Flavin mononucleotide (FMN) riboswitches are genetic elements, which in many bacteria control genes responsible for biosynthesis and/or transport of riboflavin (rib genes). Cytoplasmic riboflavin is rapidly and almost completely converted to FMN by flavokinases. When cytoplasmic levels of FMN are sufficient (“high levels”), FMN binding to FMN riboswitches leads to a reduction of rib gene expression. We report here that the protein RibR counteracts the FMN-induced “turn-off” activities of both FMN riboswitches in Bacillus subtilis, allowing rib gene expression even in the presence of high levels of FMN. The reason for this secondary metabolic control by RibR is to couple sulfur metabolism with riboflavin metabolism. PMID:26494285

Mitochondrial quality control pathways as determinants of metabolic health

NARCIS (Netherlands)

Held, Ntsiki M.; Houtkooper, Riekelt H.

2015-01-01

Mitochondrial function is key for maintaining cellular health, while mitochondrial failure is associated with various pathologies, including inherited metabolic disorders and age-related diseases. In order to maintain mitochondrial quality, several pathways of mitochondrial quality control have

Lansoprazole Is Associated with Worsening Asthma Control in Children with the CYP2C19 Poor Metabolizer Phenotype.

Science.gov (United States)

Lang, Jason E; Holbrook, Janet T; Mougey, Edward B; Wei, Christine Y; Wise, Robert A; Teague, W Gerald; Lima, John J

2015-06-01

Gastric acid blockade in children with asymptomatic acid reflux has not improved asthma control in published studies. There is substantial population variability regarding metabolism of and response to proton pump inhibitors based on metabolizer phenotype. How metabolizer phenotype affects asthma responses to acid blockage is not known. To determine how metabolizer phenotype based on genetic analysis of CYP2C19 affects asthma control among children treated with a proton pump inhibitor. Asthma control as measured by the Asthma Control Questionnaire (ACQ) and other questionnaires from a 6-month clinical trial of lansoprazole in children with asthma was analyzed for associations with surrogates of lansoprazole exposure (based on treatment assignment and metabolizer phenotype). Groups included placebo-treated children; lansoprazole-treated extensive metabolizers (EMs); and lansoprazole-treated poor metabolizers (PMs). Metabolizer phenotypes were based on CYP2C19 haplotypes. Carriers of the CYP2C19*2, *3, *8, *9, or *10 allele were PMs; carriers of two wild-type alleles were extensive metabolizers (EMs). Asthma control through most of the treatment period was unaffected by lansoprazole exposure or metabolizer phenotype. At 6 months, PMs displayed significantly worsened asthma control compared with EMs (+0.16 vs. -0.13; P = 0.02) and placebo-treated children (+0.16 vs. -0.23; P lansoprazole-treated PMs. Children with the PM phenotype developed worse asthma control after 6 months of lansoprazole treatment for poorly controlled asthma. Increased exposure to proton pump inhibitor may worsen asthma control by altering responses to respiratory infections. Clinical trial registered with www.clinicaltrials.gov (NCT00604851).

Metabolic Control and Academic Achievement over Time among Adolescents with Type 1 Diabetes

Science.gov (United States)

Winnick, Joel B.; Berg, Cynthia A.; Wiebe, Deborah J.; Schaefer, Barbara A.; Lei, Pui-Wa; Butner, Jonathan E.

2017-01-01

The relation between metabolic control (HbA1c) and achievement (grade point average [GPA]) was examined over a period of 2.5 years (every 6 months) employing a dynamical systems approach that allowed for the examination of whether HbA1c was associated with change in subsequent GPA and vice versa. Metabolic control tends to deteriorate (i.e., with…

Self-Efficacy, Self-Care, and Metabolic Control in Persons with Type 2, Diet and Exercised Controlled Diabetes

National Research Council Canada - National Science Library

Randall, Lisa

1998-01-01

... (Diabetes control and Complications Trial, 1993). Nurses' understanding of diabetes management coupled with a holistic view of person makes them the optimal professionals to facilitate patient movement toward tight metabolic control...

Metabolic sensing neurons and the control of energy homeostasis.

Science.gov (United States)

Levin, Barry E

2006-11-30

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

NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair.

Science.gov (United States)

Wang, Pei; Li, Wen-Lin; Liu, Jian-Min; Miao, Chao-Yu

2016-06-01

Vascular repair plays important roles in postischemic remodeling and rehabilitation in cardiovascular and cerebrovascular disease, such as stroke and myocardial infarction. Nicotinamide adenine dinucleotide (NAD), a well-known coenzyme involved in electron transport chain for generation of adenosine triphosphate, has emerged as an important controller regulating various biological signaling pathways. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for NAD biosynthesis in mammals. NAMPT may also act in a nonenzymatic manner, presumably mediated by unknown receptor(s). Rapidly accumulating data in the past decade show that NAMPT and NAMPT-controlled NAD metabolism regulate fundamental biological functions in endothelial cells, vascular smooth muscle cells, and endothelial progenitor cells. The NAD-consuming proteins, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38, may contribute to the regulatory effects of NAMPT-NAD axis in these cells and vascular repair. This review discusses the current data regarding NAMPT and NAMPT-controlled NAD metabolism in vascular repair and the clinical potential translational application of NAMPT-related products in treatment of cardiovascular and cerebrovascular disease.

Neuroendocrine control by kisspeptins: role in metabolic regulation of fertility.

Science.gov (United States)

Navarro, Victor M; Tena-Sempere, Manuel

2011-09-13

The neurohormonal control of reproduction involves a hierarchical network of central and peripheral signals in the hypothalamic-pituitary-gonadal (HPG) axis. Development and function of this neuroendocrine system is the result of a lifelong delicate balance between endogenous regulators and environmental cues, including nutritional and metabolic factors. Kisspeptins are the peptide products of KISS1, which operate via the G-protein-coupled receptor GPR54 (also known as Kiss1R). These peptides have emerged as essential upstream regulators of neurons secreting gonadotropin-releasing hormone (GnRH), the major hypothalamic node for the stimulatory control of the HPG axis. They are potent elicitors of gonadotropin secretion in various species and physiological settings. Moreover, Kiss1 neurons in the hypothalamus participate in crucial features of reproductive maturation and function, such as brain-level sex differentiation, puberty onset and the neuroendocrine regulation of gonadotropin secretion and ovulation. Cotransmitters of Kiss1 neurons, such as neurokinin B, with roles in controlling the HPG axis have been identified by genetic, neuroanatomical and physiological studies. In addition, a putative role has been proposed for Kiss1 neurons in transmitting metabolic information to GnRH neurons, although the precise mechanisms are as yet unclear. In this Review, we present the major reproductive features of kisspeptins, especially their interplay with neurokinin B and potential roles in the metabolic control of puberty and fertility, and suggest new avenues for research.

Role of Autophagy in the Control of Body Metabolism

Directory of Open Access Journals (Sweden)

Wenying Quan

2013-03-01

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

Bilateral Diabetic Papillopathy and Metabolic Control

DEFF Research Database (Denmark)

Ostri, Christoffer; Lund-Andersen, Henrik; Sander, Birgit

2010-01-01

OBJECTIVE: The pathogenesis of diabetic papillopathy largely is unknown, but case reports suggest that it may follow rapidly improved metabolic control. The present study was designed to investigate this hypothesis. DESIGN: Retrospective case-control study. PARTICIPANTS: Two thousand sixty......-six patients with type 1 diabetes. METHODS: Review of clinical, photographic, and clinical chemistry records from a large diabetology and ophthalmology unit between 2001 and 2008. MAIN OUTCOME MEASURES: Simultaneous, bilateral diabetic papillopathy. RESULTS: The mean follow-up was 4.9 years. During 10 020...... patient-years of observation, bilateral diabetic papillopathy developed in 5 patients. During the year preceding this incident, all 5 patients had experienced a decrease in glycosylated hemoglobin A(1c) (HbA(1C)) at a maximum rate of -2.5 (mean) percentage points per quarter year, which was significantly...

Iron metabolism in critically ill patients developing anemia of inflammation: a case control study.

Science.gov (United States)

Boshuizen, Margit; Binnekade, Jan M; Nota, Benjamin; van de Groep, Kirsten; Cremer, Olaf L; Tuinman, Pieter R; Horn, Janneke; Schultz, Marcus J; van Bruggen, Robin; Juffermans, Nicole P

2018-05-02

Anemia occurring as a result of inflammatory processes (anemia of inflammation, AI) has a high prevalence in critically ill patients. Knowledge on changes in iron metabolism during the course of AI is limited, hampering the development of strategies to counteract AI. This case control study aimed to investigate iron metabolism during the development of AI in critically ill patients. Iron metabolism in 30 patients who developed AI during ICU stay was compared with 30 septic patients with a high Hb and 30 non-septic patients with a high Hb. Patients were matched on age and sex. Longitudinally collected plasma samples were analyzed for levels of parameters of iron metabolism. A linear mixed model was used to assess the predictive values of the parameters. In patients with AI, levels of iron, transferrin and transferrin saturation showed an early decrease compared to controls with a high Hb, already prior to the development of anemia. Ferritin, hepcidin and IL-6 levels were increased in AI compared to controls. During AI development, erythroferrone decreased. Differences in iron metabolism between groups were not influenced by APACHE IV score. The results show that in critically ill patients with AI, iron metabolism is already altered prior to the development of anemia. Levels of iron regulators in AI differ from septic controls with a high Hb, irrespective of disease severity. AI is characterized by high levels of hepcidin, ferritin and IL-6 and low levels of iron, transferrin and erythroferrone.

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.

Microenvironmental Regulation of Chemokine (C-X-C-motif) Receptor 4 in Ovarian Carcinoma

Science.gov (United States)

Barbolina, Maria V.; Kim, Mijung; Liu, Yueying; Shepard, Jaclyn; Belmadani, Abdelhak; Miller, Richard J.; Shea, Lonnie D.; Stack, M. Sharon

2010-01-01

The majority of women diagnosed with epithelial ovarian carcinoma (EOC) succumb due to complications of metastatic disease, suggesting that anti-metastatic therapies may improve patient survival. EOC metastasis involves intra-peritoneal shedding of cells from the primary tumor, followed by adhesion and localized penetration of the submesothelial matrix to anchor metastatic implants. Accumulation of malignant ascites is also common. Thus, a unique microenvironmental niche is established, which includes malignant cells and a plethora of soluble factors secreted by – or in response to – tumor cells. As cells penetrating the sub-mesothelial surface encounter an interstitial collagen-rich ECM, we have used 3-dimensional type I collagen (3DCI) gels to model early events resulting from intra-peritoneal anchoring. In this study we demonstrate a novel pathway of CXCR4 upregulation through β1-integrin- and NFκB- dependent signaling pathways in response to 3DCI. We also demonstrate the involvement of CXCR4-SDF1 axis in collagen invasion and proliferation, relevant to the metastatic EOC. Our data show that CXCR4 expression in human EOCs, as well as SDF1 presence in the ascites, is correlated with disease progression and metastasis. These data emphasize the importance of CXCR4 – SDF1 axis in EOC metastasis and suggest that this mechanism should be accounted for when targeting EOC metastasis. PMID:20460402

Effect of metabolic control on parathyroid hormone secretion in diabetic patients

Directory of Open Access Journals (Sweden)

Paula F.J.A.

2001-01-01

Full Text Available The metabolic derangement caused by diabetes mellitus may potentially affect bone mineral metabolism. In the present study we evaluated the effect of diabetes metabolic control on parathyroid hormone (PTH secretion during stimulation with EDTA infusion. The study was conducted on 24 individuals, 8 of them normal subjects (group N: glycated hemoglobin - HbA1C = 4.2 ± 0.2%; range = 3.5-5.0%, 8 patients with good and regular metabolic control (group G-R: HbA1C = 7.3 ± 0.4%; range = 6.0-8.5%, and 8 patients with poor metabolic control (group P: HbA1C = 12.5 ± 1.0%; range: 10.0-18.8%. Blood samples were collected at 10-min intervals throughout the study (a basal period of 30 min and a 2-h period of EDTA infusion, 30 mg/kg body weight and used for the determination of ionized calcium, magnesium, glucose and intact PTH. Basal ionized calcium levels were slightly lower in group P (1.19 ± 0.01 mmol/l than in group N (1.21 ± 0.01 mmol/l and group G-R (1.22 ± 0.01 mmol/l. After EDTA infusion, the three groups presented a significant fall in calcium, but with no significant difference among them at any time. Basal magnesium levels and levels determined during EDTA infusion were significantly lower (P<0.01 in group P than in group N. The induction of hypocalcemia caused an elevation in PTH which was similar in groups N and G-R but significantly higher than in group P throughout the infusion period (+110 min, N = 11.9 ± 2.1 vs G-R = 13.7 ± 1.6 vs P = 7.5 ± 0.7 pmol/l; P<0.05 for P vs N and G-R. The present results show that PTH secretion is impaired in patients with poorly controlled diabetes.

Sense of coherence, self-esteem, and health locus of control in subjects with type 1 diabetes mellitus with/without satisfactory metabolic control.

Science.gov (United States)

Nuccitelli, C; Valentini, A; Caletti, M T; Caselli, C; Mazzella, N; Forlani, G; Marchesini, G

2018-03-01

Despite intensive training, a few individuals with Type 1 diabetes mellitus (T1DM) fail to reach the desired metabolic targets. To evaluate the association between disease-related emotional and cognitive aspects and metabolic control in subjects with T1DM. Health locus of control (HLOC), sense of coherence (SOC), and self-esteem were assessed in T1DM subjects using validated questionnaires. Sixty-seven consecutive subjects who did not attain the desired HbA1c target (mean HbA1c, 8.3% [67 mmol/mol]) were compared with 30 cases in satisfactory metabolic control (HbA1c levels satisfactory metabolic control tend to rely on significant others, trusting in the physicians' skills or on the efficiency of the health-care system. Strategies aimed at increasing self-efficacy and SOC, based on personal ability, are eagerly awaited to help patients improve diabetes care.

Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering.

Science.gov (United States)

He, Fei; Murabito, Ettore; Westerhoff, Hans V

2016-04-01

Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. © 2016 The Author(s).

Longitudinal Trajectories of Metabolic Control across Adolescence: Associations with Parental Involvement, Adolescents’ Psychosocial Maturity, and Health Care Utilization

Science.gov (United States)

King, Pamela S.; Berg, Cynthia A.; Butner, Jonathan; Drew, Linda M.; Foster, Carol; Donaldson, David; Murray, Mary; Swinyard, Michael; Wiebe, Deborah J.

2012-01-01

Purpose To predict trajectories of metabolic control across adolescence from parental involvement and adolescent psychosocial maturity, and to link metabolic control trajectories to health care utilization. Methods 252 adolescents (M age at study initiation = 12.5, SD=1.5, range 10–14 years) with type 1 diabetes (54.4% female, 92.8% Caucasian, length of diagnosis M=4.7 years, SD=3.0, range 1–12) participated in a 2-year longitudinal study. Metabolic control was gathered from medical records every three months. Adolescents completed measures of self-reliance (functional autonomy and extreme peer orientation), self-control (self-control and externalizing behavior), and parental involvement in diabetes care (acceptance, monitoring, and frequency of help). At the end of the study, mothers reported health care utilization (diabetes-related emergency room visits and hospitalizations) over the past six months. Results Latent class growth analyses indicated two distinct trajectories of metabolic control across adolescence: moderate control with slight deterioration (92% of the sample; average HbA1c = 8.18%) and poor control with rapid deterioration (8% of the sample; average HbA1c of 12.09%). Adolescents with poor and rapidly deteriorating metabolic control reported lower paternal monitoring and frequency of help with diabetes management, lower functional autonomy, and lower self-control than others. Those with poor and rapidly deteriorating metabolic control were 6.4 times more likely to report diabetes-related emergency room visits, and 9.3 times more likely to report diabetes-related hospitalizations near the end of the study. Conclusions Parental involvement and adolescents’ psychosocial maturity predict patterns of deteriorating metabolic control across adolescence and could be targeted for intervention. PMID:22525113

Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*.

Science.gov (United States)

Carrer, Michele; Liu, Ning; Grueter, Chad E; Williams, Andrew H; Frisard, Madlyn I; Hulver, Matthew W; Bassel-Duby, Rhonda; Olson, Eric N

2012-09-18

Obesity and metabolic syndrome are associated with mitochondrial dysfunction and deranged regulation of metabolic genes. Peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) is a transcriptional coactivator that regulates metabolism and mitochondrial biogenesis through stimulation of nuclear hormone receptors and other transcription factors. We report that the PGC-1β gene encodes two microRNAs (miRNAs), miR-378 and miR-378*, which counterbalance the metabolic actions of PGC-1β. Mice genetically lacking miR-378 and miR-378* are resistant to high-fat diet-induced obesity and exhibit enhanced mitochondrial fatty acid metabolism and elevated oxidative capacity of insulin-target tissues. Among the many targets of these miRNAs, carnitine O-acetyltransferase, a mitochondrial enzyme involved in fatty acid metabolism, and MED13, a component of the Mediator complex that controls nuclear hormone receptor activity, are repressed by miR-378 and miR-378*, respectively, and are elevated in the livers of miR-378/378* KO mice. Consistent with these targets as contributors to the metabolic actions of miR-378 and miR-378*, previous studies have implicated carnitine O-acetyltransferase and MED13 in metabolic syndrome and obesity. Our findings identify miR-378 and miR-378* as integral components of a regulatory circuit that functions under conditions of metabolic stress to control systemic energy homeostasis and the overall oxidative capacity of insulin target tissues. Thus, these miRNAs provide potential targets for pharmacologic intervention in obesity and metabolic syndrome.

Metabolic control of vesicular glutamate transport and release.

Science.gov (United States)

Juge, Narinobu; Gray, John A; Omote, Hiroshi; Miyaji, Takaaki; Inoue, Tsuyoshi; Hara, Chiaki; Uneyama, Hisayuki; Edwards, Robert H; Nicoll, Roger A; Moriyama, Yoshinori

2010-10-06

Fasting has been used to control epilepsy since antiquity, but the mechanism of coupling between metabolic state and excitatory neurotransmission remains unknown. Previous work has shown that the vesicular glutamate transporters (VGLUTs) required for exocytotic release of glutamate undergo an unusual form of regulation by Cl(-). Using functional reconstitution of the purified VGLUTs into proteoliposomes, we now show that Cl(-) acts as an allosteric activator, and the ketone bodies that increase with fasting inhibit glutamate release by competing with Cl(-) at the site of allosteric regulation. Consistent with these observations, acetoacetate reduced quantal size at hippocampal synapses and suppresses glutamate release and seizures evoked with 4-aminopyridine in the brain. The results indicate an unsuspected link between metabolic state and excitatory neurotransmission through anion-dependent regulation of VGLUT activity. Copyright © 2010 Elsevier Inc. All rights reserved.

Molecular, metabolic, and genetic control: An introduction

Science.gov (United States)

Tyson, John J.; Mackey, Michael C.

2001-03-01

The living cell is a miniature, self-reproducing, biochemical machine. Like all machines, it has a power supply, a set of working components that carry out its necessary tasks, and control systems that ensure the proper coordination of these tasks. In this Special Issue, we focus on the molecular regulatory systems that control cell metabolism, gene expression, environmental responses, development, and reproduction. As for the control systems in human-engineered machines, these regulatory networks can be described by nonlinear dynamical equations, for example, ordinary differential equations, reaction-diffusion equations, stochastic differential equations, or cellular automata. The articles collected here illustrate (i) a range of theoretical problems presented by modern concepts of cellular regulation, (ii) some strategies for converting molecular mechanisms into dynamical systems, (iii) some useful mathematical tools for analyzing and simulating these systems, and (iv) the sort of results that derive from serious interplay between theory and experiment.

Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion

Science.gov (United States)

Mitch, William E.; Sands, Jeff M.

2015-01-01

Renal nitrogen metabolism primarily involves urea and ammonia metabolism, and is essential to normal health. Urea is the largest circulating pool of nitrogen, excluding nitrogen in circulating proteins, and its production changes in parallel to the degradation of dietary and endogenous proteins. In addition to serving as a way to excrete nitrogen, urea transport, mediated through specific urea transport proteins, mediates a central role in the urine concentrating mechanism. Renal ammonia excretion, although often considered only in the context of acid-base homeostasis, accounts for approximately 10% of total renal nitrogen excretion under basal conditions, but can increase substantially in a variety of clinical conditions. Because renal ammonia metabolism requires intrarenal ammoniagenesis from glutamine, changes in factors regulating renal ammonia metabolism can have important effects on glutamine in addition to nitrogen balance. This review covers aspects of protein metabolism and the control of the two major molecules involved in renal nitrogen excretion: urea and ammonia. Both urea and ammonia transport can be altered by glucocorticoids and hypokalemia, two conditions that also affect protein metabolism. Clinical conditions associated with altered urine concentrating ability or water homeostasis can result in changes in urea excretion and urea transporters. Clinical conditions associated with altered ammonia excretion can have important effects on nitrogen balance. PMID:25078422

Effect of Microenvironmental pH Modulation on the Dissolution Rate and Oral Absorption of the Salt of a Weak Acid - Case Study of GDC-0810.

Science.gov (United States)

Hou, Hao Helen; Jia, Wei; Liu, Lichuan; Cheeti, Sravanthi; Li, Jane; Nauka, Ewa; Nagapudi, Karthik

2018-01-29

The purpose of this work is to investigate the effect of microenvironmental pH modulation on the in vitro dissolution rate and oral absorption of GDC-0810, an oral anti-cancer drug, in human. The pH-solubility profile of GDC-0810 free acid and pH max of its N-Methyl-D-glucamine (NMG) salt were determined. Precipitation studies were conducted for GDC-0810 NMG salt at different pH values. GDC-0810 200-mg dose NMG salt tablet formulations containing different levels of sodium bicarbonate as the pH modifier were tested for dissolution under the dual pH-dilution scheme. Three tablet formulations were evaluated in human as a part of a relative bioavailability study. A 200-mg dose of GDC-0810 was administered QD with low fat food. Intrinsic solubility of GDC-0810 free acid was found to be extremely low. The pH max of the NMG salt suggested a strong tendency for form conversion to the free acid under GI conditions. In vitro dissolution profiles showed that the dissolution rate and extent of GDC-0810 increased with increasing the level of sodium bicarbonate in the formulation. The human PK data showed a similar trend for the geometric mean of C max and AUC 0-t for formulations containing 5%, 10%, and 15% sodium bicarbonate, but the difference is not statistically significant. Incorporation of a basic pH modifier, sodium bicarbonate, in GDC-0810 NMG salt tablet formulations enhanced in vitro dissolution rate of GDC-0810 via microenvironmental pH modulation. The human PK data showed no statistically significant difference in drug exposure from tablets containing 5%, 10%, and 15% sodium bicarbonate.

A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC).

Science.gov (United States)

Sandoval, Imelda T; Delacruz, Richard Glenn C; Miller, Braden N; Hill, Shauna; Olson, Kristofor A; Gabriel, Ana E; Boyd, Kevin; Satterfield, Christeena; Remmen, Holly Van; Rutter, Jared; Jones, David A

2017-04-11

Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that mitochondrial pyruvate carrier 1 (MPC1) , a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, we found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation. Exogenous human MPC1 RNA rescued failed intestinal differentiation in zebrafish models of apc deficiency. Our data demonstrate a novel role for apc in pyruvate metabolism and that pyruvate metabolism dictates intestinal cell fate and differentiation decisions downstream of apc .

Self-Efficacy, Self-Care, and Metabolic Control in Persons with Type 2, Diet and Exercised Controlled Diabetes

National Research Council Canada - National Science Library

Randall, Lisa

1998-01-01

.... psychological determinants of self-care and metabolic control must be explored. Self-efficacy (Bandura, 1977) has demonstrated its importance in behavioral modification but has been minimally investigated in diabetes...

Effects of short- and long-term Mediterranean-based dietary treatment on plasma LC-QTOF/MS metabolic profiling of subjects with metabolic syndrome features: The Metabolic Syndrome Reduction in Navarra (RESMENA) randomized controlled trial.

Science.gov (United States)

Bondia-Pons, Isabel; Martinez, José Alfredo; de la Iglesia, Rocio; Lopez-Legarrea, Patricia; Poutanen, Kaisa; Hanhineva, Kati; Zulet, Maria de los Ángeles

2015-04-01

Adherence to the Mediterranean diet has been associated with a reduced risk of metabolic syndrome (MetS). Metabolomics approach may contribute to identify beneficial associations of metabolic changes affected by Mediterranean diet-based interventions with inflammatory and oxidative-stress markers related to the etiology and development of the MetS. Liquid chromatography coupled to quadrupole-time of flight-MS metabolic profiling was applied to plasma from a 6-month randomized intervention with two sequential periods, a 2-month nutritional-learning intervention period, and a 4-month self-control period, with two energy-restricted diets; the RESMENA diet (based on the Mediterranean dietary pattern) and the Control diet (based on the American Heart Association guidelines), in 72 subjects with a high BMI and at least two features of MetS. The major contributing biomarkers of each sequential period were lipids, mainly phospholipids and lysophospholipids. Dependency network analysis showed a different pattern of associations between metabolic changes and clinical variables after 2 and 6 month of intervention, with a highly interconnected network during the nutritional-learning intervention period of the study. The 2-month RESMENA diet produced significant changes in the plasma metabolic profile of subjects with MetS features. However, at the end of the 6-month study, most of the associations between metabolic and clinical variables disappeared; suggesting that adherence to healthy dietary habits had declined during the self-control period. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Vulnerability to stress, anxiety and depressive symptoms and metabolic control in Type 2 diabetes

Directory of Open Access Journals (Sweden)

Gois Carlos

2012-06-01

Full Text Available Abstract Background Vulnerability to stress has been associated to distress, emotional distress symptoms and metabolic control in type 2 diabetes mellitus (T2DM patients as well. Furthermore some conflicting results were noticed. We aimed to evaluate the effect over metabolic control in what concerns vulnerability to stress beyond depressive and anxiety symptoms. Findings This cross-sectional study assessed 273 T2DM patients with depressive and anxiety symptoms using the Hospital Anxiety Depression Scale (HADS and the 23 Questions to assess Vulnerability to Stress (23QVS, along with demographic and clinical diabetes-related variables. Hierarchical logistic regression models were used to investigate predictors of poor glycemic control. The results showed an association of depressive symptoms (odds ratio = 1.12, 95%CI = 1.01-1.24, P = 0.030 with increased risk of poor glycemic control. Anxiety symptoms and vulnerability to stress on their own were not predictive of metabolic control, respectively (odds ratio = 0.92, 95%CI = 0.84-1.00, P = 0.187 and odds ratio = 0.98, 95%CI = 0.95-1.01, P = 0.282. Conclusions Our data suggested that vulnerability to stress was not predictive of poor glycemic control in T2DM, but depressive symptoms were.

Perspectives in metabolic engineering: understanding cellular regulation towards the control of metabolic routes.

Science.gov (United States)

Zadran, Sohila; Levine, Raphael D

2013-01-01

Metabolic engineering seeks to redirect metabolic pathways through the modification of specific biochemical reactions or the introduction of new ones with the use of recombinant technology. Many of the chemicals synthesized via introduction of product-specific enzymes or the reconstruction of entire metabolic pathways into engineered hosts that can sustain production and can synthesize high yields of the desired product as yields of natural product-derived compounds are frequently low, and chemical processes can be both energy and material expensive; current endeavors have focused on using biologically derived processes as alternatives to chemical synthesis. Such economically favorable manufacturing processes pursue goals related to sustainable development and "green chemistry". Metabolic engineering is a multidisciplinary approach, involving chemical engineering, molecular biology, biochemistry, and analytical chemistry. Recent advances in molecular biology, genome-scale models, theoretical understanding, and kinetic modeling has increased interest in using metabolic engineering to redirect metabolic fluxes for industrial and therapeutic purposes. The use of metabolic engineering has increased the productivity of industrially pertinent small molecules, alcohol-based biofuels, and biodiesel. Here, we highlight developments in the practical and theoretical strategies and technologies available for the metabolic engineering of simple systems and address current limitations.

Correlating bilayer tablet delamination tendencies to micro-environmental thermodynamic conditions during pan coating.

Science.gov (United States)

Zacour, Brian M; Pandey, Preetanshu; Subramanian, Ganeshkumar; Gao, Julia Z; Nikfar, Faranak

2014-06-01

The objective of this study was to determine the impact that the micro-environment, as measured by PyroButton data loggers, experienced by tablets during the pan coating unit operation had on the layer adhesion of bilayer tablets in open storage conditions. A full factorial design of experiments (DOE) with three center points was conducted to study the impact of final tablet hardness, film coating spray rate and film coating exhaust temperature on the delamination tendencies of bilayer tablets. PyroButton data loggers were placed (fixed) at various locations in a pan coater and were also allowed to freely move with the tablet bed to measure the micro-environmental temperature and humidity conditions of the tablet bed. The variance in the measured micro-environment via PyroButton data loggers accounted for 75% of the variance in the delamination tendencies of bilayer tablets on storage (R(2 )= 0.75). A survival analysis suggested that tablet hardness and coating spray rate significantly impacted the delamination tendencies of the bilayer tablets under open storage conditions. The coating exhaust temperature did not show good correlation with the tablets' propensity to crack indicating that it was not representative of the coating micro-environment. Models created using data obtained from the PyroButton data loggers outperformed models created using primary DOE factors in the prediction of bilayer tablet strength, especially upon equipment or scale transfers. The coating micro-environment experienced by tablets during the pan coating unit operation significantly impacts the strength of the bilayer interface of tablets on storage.

Brain Ceramide Metabolism in the Control of Energy Balance

Directory of Open Access Journals (Sweden)

Céline Cruciani-Guglielmacci

2017-10-01

Full Text Available The regulation of energy balance by the central nervous system (CNS is a key actor of energy homeostasis in mammals, and deregulations of the fine mechanisms of nutrient sensing in the brain could lead to several metabolic diseases such as obesity and type 2 diabetes (T2D. Indeed, while neuronal activity primarily relies on glucose (lactate, pyruvate, the brain expresses at high level enzymes responsible for the transport, utilization and storage of lipids. It has been demonstrated that discrete neuronal networks in the hypothalamus have the ability to detect variation of circulating long chain fatty acids (FA to regulate food intake and peripheral glucose metabolism. During a chronic lipid excess situation, this physiological lipid sensing is impaired contributing to type 2 diabetes in predisposed subjects. Recently, different studies suggested that ceramides levels could be involved in the regulation of energy balance in both hypothalamic and extra-hypothalamic areas. Moreover, under lipotoxic conditions, these ceramides could play a role in the dysregulation of glucose homeostasis. In this review we aimed at describing the potential role of ceramides metabolism in the brain in the physiological and pathophysiological control of energy balance.

It must be my metabolism: Metabolic control of mind

Directory of Open Access Journals (Sweden)

Dana M Small

2014-07-01

relationship between the reinforcing potency of sugared solutions and the metabolic effects that follow their consumption (16, also see the abstract of I. de Araujo. We therefore hypothesized that metabolic response provides the critical signal necessary to condition preference. To test this prediction in humans we designed a flavor nutrient conditioning study in which participants first rated their liking for novel flavored beverages and then, over a three week-long conditioning protocol, alternately ingested one of the flavored beverages with 112.5 kcal from maltodextrin, a tasteless and odorless polysaccharide that breaks down into glucose, and another flavored beverage with no calories added. Plasma glucose was measured before and after each of the drinks’ consumption as a proxy measure of metabolic response, assuming that glucose oxidation depends upon the level of circulating glucose. For each participant flavor-calorie pairings were held constant but the identity of the conditioned flavors were counterbalanced across participants. Following the exposure phase, participants’ liking of, and brain responses to, non-caloric versions of the flavors were assessed. We predicted that change in plasma glucose produced by beverage consumption during the exposure sessions would be associated with neural responses in dopamine source and target regions to the calorie predictive flavor. As predicted, response in the ventral striatum and hypothalamus to the calorie-predictive flavor (CS+ vs. non the noncaloric-predictive flavor (CS- was strongly associated with the changes in plasma glucose levels produced by ingestion of these same beverages when consumed previously either with (CS+ or without (CS- calories (17. Specifically, the greater the increase in circulating glucose occurring post ingestion of the beverage containing 112.5 kcal from maltodextrin versus the noncaloric drink, the stronger was the brain response to the CS+ compared to the CS- flavor. Importantly, because each

Follow-the-leader cell migration requires biased cell–cell contact and local microenvironmental signals

International Nuclear Information System (INIS)

Wynn, Michelle L; Rupp, Paul; Trainor, Paul A; Kulesa, Paul M; Schnell, Santiago

2013-01-01

Directed cell migration often involves at least two types of cell motility that include multicellular streaming and chain migration. However, what is unclear is how cell contact dynamics and the distinct microenvironments through which cells travel influence the selection of one migratory mode or the other. The embryonic and highly invasive neural crest (NC) are an excellent model system to study this question since NC cells have been observed in vivo to display both of these types of cell motility. Here, we present data from tissue transplantation experiments in chick and in silico modeling that test our hypothesis that cell contact dynamics with each other and the microenvironment promote and sustain either multicellular stream or chain migration. We show that when premigratory cranial NC cells (at the pre-otic level) are transplanted into a more caudal region in the head (at the post-otic level), cells alter their characteristic stream behavior and migrate in chains. Similarly, post-otic NC cells migrate in streams after transplantation into the pre-otic hindbrain, suggesting that local microenvironmental signals dictate the mode of NC cell migration. Simulations of an agent-based model (ABM) that integrates the NC cell behavioral data predict that chain migration critically depends on the interplay of biased cell–cell contact and local microenvironment signals. Together, this integrated modeling and experimental approach suggests new experiments and offers a powerful tool to examine mechanisms that underlie complex cell migration patterns. (paper)

Follow-the-leader cell migration requires biased cell-cell contact and local microenvironmental signals

Science.gov (United States)

Wynn, Michelle L.; Rupp, Paul; Trainor, Paul A.; Schnell, Santiago; Kulesa, Paul M.

2013-06-01

Directed cell migration often involves at least two types of cell motility that include multicellular streaming and chain migration. However, what is unclear is how cell contact dynamics and the distinct microenvironments through which cells travel influence the selection of one migratory mode or the other. The embryonic and highly invasive neural crest (NC) are an excellent model system to study this question since NC cells have been observed in vivo to display both of these types of cell motility. Here, we present data from tissue transplantation experiments in chick and in silico modeling that test our hypothesis that cell contact dynamics with each other and the microenvironment promote and sustain either multicellular stream or chain migration. We show that when premigratory cranial NC cells (at the pre-otic level) are transplanted into a more caudal region in the head (at the post-otic level), cells alter their characteristic stream behavior and migrate in chains. Similarly, post-otic NC cells migrate in streams after transplantation into the pre-otic hindbrain, suggesting that local microenvironmental signals dictate the mode of NC cell migration. Simulations of an agent-based model (ABM) that integrates the NC cell behavioral data predict that chain migration critically depends on the interplay of biased cell-cell contact and local microenvironment signals. Together, this integrated modeling and experimental approach suggests new experiments and offers a powerful tool to examine mechanisms that underlie complex cell migration patterns.

NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells

International Nuclear Information System (INIS)

Santos, Nuno R. dos; Ghezzo, Marinella N.; Silva, Ricardo C. da; Fernandes, Mónica T.

2010-01-01

Two main NF-κB signaling pathways, canonical and noncanonical, performing distinct functions in organisms have been characterized. Identification of mutations in genes encoding components of these NF-κB signaling pathways in lymphoid malignancies confirmed their key role in leukemogenesis. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes that despite significant therapeutic advances can still be fatal. Although mutations in NF-κB genes have not been reported in T-ALL, NF-κB constitutive activation in human T-ALL and in acute T-cell leukemia mouse models has been observed. Although these studies revealed activation of members of both canonical and noncanonical NF-κB pathways in acute T-cell leukemia, only inhibition of canonical NF-κB signaling was shown to impair leukemic T cell growth. Besides playing an important pro-oncogenic role in leukemic T cells, NF-κB signaling also appears to modulate T-cell leukemogenesis through its action in microenvironmental stromal cells. This article reviews recent data on the role of these transcription factors in T-ALL and pinpoints further research crucial to determine the value of NF-κB inhibition as a means to treat T-ALL

NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells

Energy Technology Data Exchange (ETDEWEB)

Santos, Nuno R. dos, E-mail: nrsantos@ualg.pt; Ghezzo, Marinella N.; Silva, Ricardo C. da; Fernandes, Mónica T. [IBB-Institute for Biotechnology and Bioengineering, Centre for Molecular and Structural Biomedicine (CBME), University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal)

2010-11-05

Two main NF-κB signaling pathways, canonical and noncanonical, performing distinct functions in organisms have been characterized. Identification of mutations in genes encoding components of these NF-κB signaling pathways in lymphoid malignancies confirmed their key role in leukemogenesis. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes that despite significant therapeutic advances can still be fatal. Although mutations in NF-κB genes have not been reported in T-ALL, NF-κB constitutive activation in human T-ALL and in acute T-cell leukemia mouse models has been observed. Although these studies revealed activation of members of both canonical and noncanonical NF-κB pathways in acute T-cell leukemia, only inhibition of canonical NF-κB signaling was shown to impair leukemic T cell growth. Besides playing an important pro-oncogenic role in leukemic T cells, NF-κB signaling also appears to modulate T-cell leukemogenesis through its action in microenvironmental stromal cells. This article reviews recent data on the role of these transcription factors in T-ALL and pinpoints further research crucial to determine the value of NF-κB inhibition as a means to treat T-ALL.

How to determine control of growth rate in a chemostat. Using metabolic control analysis to resolve the paradox

DEFF Research Database (Denmark)

Snoep, Jacky L.; Jensen, Peter Ruhdal; Groeneveld, Philip

1994-01-01

how, paradoxically, one can determine control of growth rate, of growth yield and of other fluxes in a chemostat. We develop metabolic control analysis for the chemostat. this analysis does not depend on the particular way in which specific growth rate varies with the concentration of the growth...

Mitochondrial metabolism and the control of vascular smooth muscle cell proliferation

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Mario eChiong

2014-12-01

Full Text Available Differentiation and dedifferentiation of vascular smooth muscle cells (VSMCs are essential processes of vascular development. VSMCs have biosynthetic, proliferative and contractile roles in the vessel wall. Alterations in the differentiated state of the VSMCs play a critical role in the pathogenesis of a variety of cardiovascular diseases, including atherosclerosis, hypertension and vascular stenosis. This review provides an overview of the current state of knowledge of molecular mechanisms involved in the control of VSMC proliferation, with particular focus on mitochondrial metabolism. Mitochondrial activity can be controlled by regulating mitochondrial dynamics, i.e. mitochondrial fusion and fission, and by regulating mitochondrial calcium handling through the interaction with the endoplasmic reticulum (ER. Alterations in both VSMC proliferation and mitochondrial function can be triggered by dysregulation of mitofusin-2, a small GTPase associated with mitochondrial fusion and mitochondrial-ER interaction. Several lines of evidence highlight the relevance of mitochondrial metabolism in the control of VSMC proliferation, indicating a new area to be explored in the treatment of vascular diseases.

Diabetes in children and adolescents from ethnic minorities: barriers to education, treatment and good metabolic control

DEFF Research Database (Denmark)

Povlsen, Lene; Olsen, Birthe; Ladelund, Steen

2005-01-01

AIM: This paper reports an investigation to establish whether metabolic control is different in children and adolescents from ethnic minorities with type 1 diabetes compared with young Danish patients, and to learn about factors affecting their opportunities to achieve good metabolic control....... BACKGROUND: The prevalence of diabetes in children and adolescents from ethnic minorities in Denmark is increasing. Having a different ethnic background has frequently been described as a risk factor for poor metabolic control, but whether the risk is represented by the ethnicity and immigration itself...... the centres provided limited specialized knowledge and support. The questionnaires completed by the parents revealed limited schooling, lack of professional education and a major need for interpreters; these characteristics were especially prevalent among the mothers. CONCLUSIONS: Young patients from ethnic...

Estimation of occupational and nonoccupational nitrogen dioxide exposure for Korean taxi drivers using a microenvironmental model

International Nuclear Information System (INIS)

Son, Busoon; Yang, Wonho; Breysse, Patrick; Chung, Taewoong; Lee, Youngshin

2004-01-01

Occupational and nonoccupational personal nitrogen dioxide (NO 2 ) exposures were measured using passive samplers for 31 taxi drivers in Asan and Chunan, Korea. Exposures were also estimated using a microenvironmental time-weighted average model based on indoor, outdoor and inside the taxi area measurements. Mean NO 2 indoor and outdoor concentrations inside and outside the taxi drivers' houses were 24.7±10.7 and 23.3±8.3 ppb, respectively, with a mean indoor to outdoor NO 2 ratio of 1.1. Mean personal NO 2 exposure of taxi drivers was 30.3±9.7 ppb. Personal NO 2 exposures for drivers were more strongly correlated with interior vehicle NO 2 levels (r=0.89) rather than indoor residential NO 2 levels (r=0.74) or outdoor NO 2 levels (r=0.71). The main source of NO 2 exposure for taxi drivers was considered to be occupational driving. Interestingly, the NO 2 exposures for drivers' using LPG-fueled vehicles (26.3±1.3 ppb) were significantly lower than those (38.1±1.3 ppb) using diesel-fueled vehicle (P 2 exposure with indoor and outdoor NO 2 levels of the residence, and interior vehicle NO 2 levels (P 2 levels because they drive diesel-using vehicles outdoors in Korea

Role of glycolytic intermediate in regulation: Improving lycopene production in Escherichia coli by engineering metabolic control

Energy Technology Data Exchange (ETDEWEB)

Farmer, W.R.; Liao, J.C.

2001-06-01

Metabolic engineering in the postgenomic era is expected to benefit from a full understanding of the biosynthetic capability of microorganisms as a result of the progress being made in bioinformatics and functional genomics. The immediate advantage of such information is to allow the rational design of novel pathways and the elimination of native reactions that are detrimental or unnecessary for the desired purpose. However, with the ability to manipulate metabolic pathways becoming more effective, metabolic engineering will need to face a new challenge: the reengineering of the regulatory hierarchy that controls gene expression in those pathways. In addition to constructing the genetic composition of a metabolic pathway, they propose that it will become just as important to consider the dynamics of pathways gene expression. It has been widely observed that high-level induction of a recombinant protein or pathway leads to growth retardation and reduced metabolic activity. These phenotypic characteristics result from the fact that the constant demands of production placed upon the cell interfere with its changing requirements for growth. They believe that this common situation in metabolic engineering can be alleviated by designing a dynamic controller that is able to sense the metabolic state of the cell and regulate the expression of the recombinant pathway accordingly. This approach, which is termed metabolic control engineering, involves redesigning the native regulatory circuits and applying them to the recombinant pathway. The general goal of such an effort will be to control the flux to the recombinant pathway adaptively according to the cell's metabolic state. The dynamically controlled recombinant pathway can potentially lead to enhanced production, minimized growth retardation, and reduced toxic by-product formation. The regulation of gene expression in response to the physiological state is also essential to the success of gene therapy. Here they

Modulation of microenvironmental pH for dual release and reduced in vivo gastrointestinal bleeding of aceclofenac using hydroxypropyl methylcellulose-based bilayered matrix tablet.

Science.gov (United States)

Kang, Won-Ho; Nguyen, Hien Van; Park, Chulhun; Choi, Youn-Woong; Lee, Beom-Jin

2017-05-01

This study was designed to develop a once-daily controlled-release matrix tablet of aceclofenac 200mg (AFC-CR) with dual release characteristics and to investigate the role of an alkalizer in enhancing drug solubility and reducing the occurrence of gastroduodenal mucosal lesions. Two formulation approaches were employed, namely a monolithic matrix tablet and a bilayered tablet. In vitro dissolution studies of AFC-CR tablets were carried out in simulated intestinal fluid (pH6.8 buffer). The in vivo pharmacokinetic studies and drug safety of the immediate-release reference tablet Airtal® 100mg (Daewoong Co., Korea) and the optimized AFC-CR tablet were compared in beagle dogs under fasted condition. The optimally selected AFC-CR formulation displayed the desired dual release characteristics in simulated intestinal fluid with satisfactory micromeritic properties. The swelling action of the optimal matrix tablet, which was visualized by near-infrared (NIR) chemical imaging, occurred rapidly following hydration. Incorporation of sodium carbonate (Na 2 CO 3 ) was found to enhance the release rate of the AFC-CR bilayered tablets at early stages and increase the microenvironmental pH (pH M ). A pharmacokinetic study in beagle dogs indicated a higher drug plasma concentration and a sustained-release pattern for the AFC-CR tablet compared to the Airtal® tablet. AFC-CR was also superior to Airtal® in terms of in vivo drug safety, since no beagle dog receiving AFC-CR experienced gastrointestinal bleeding. The significant enhancement of drug safety was attributed to the size reduction and the increase of pH M of drug particles by means of incorporation of the alkalizer. These findings provide a scientific rationale for developing a novel controlled-release matrix tablet with enhanced patient compliance and better pain control. Copyright © 2017 Elsevier B.V. All rights reserved.

Metabolic control, self-care behaviors, and parenting in adolescents with type 1 diabetes: a correlational study.

Science.gov (United States)

Greene, Maia Stoker; Mandleco, Barbara; Roper, Susanne Olsen; Marshall, Elaine S; Dyches, Tina

2010-01-01

The purpose of this pilot study was to explore relationships among metabolic control, self-care behaviors, and parenting in adolescents with type 1 diabetes. Twenty-nine adolescents (mean age, 14.1 years) and their parents participated. Metabolic control was determined by an average of 4 A1C values taken prior to study enrollment; self-care behaviors were measured with a 12-item self-report questionnaire; parenting style was evaluated using the Parenting Practices Report. The mean for A1C values was 8.5%; the mean for overall self-care behaviors was 4.93 (5 = usually). Participants rated themselves highest on the self-care behaviors of giving insulin shots when indicated and adjusting insulin when eating a lot. They ranked themselves lowest on eating a low-fat diet and testing urine for ketones. Parents tended to be more authoritative in their approaches to parenting than either authoritarian or permissive. A significant relationship was found between authoritative mothering and adolescent self-care behaviors and metabolic control. Regression analyses controlling for age and length of time with diabetes confirmed the significance of these relationships. Authoritative fathering positively correlated with the self-care behaviors of monitoring blood glucose, taking insulin, and not skipping meals. A relationship was also noted between permissive parenting by mothers/fathers and poorer metabolic outcomes. However, the permissive parenting correlations did not remain significant when controlling for age and length of time with diabetes. Clinicians may help prevent declining participation in self-care behaviors and metabolic control in adolescents with type 1 diabetes by working with parents, particularly mothers, and encouraging authoritative parenting.

Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal

Science.gov (United States)

Ito, Kyoko; Ito, Keisuke

2016-01-01

Although the stem cells of various tissues remain in the quiescent state to maintain their undifferentiated state, they also undergo cell divisions as required, and if necessary, even a single stem cell is able to provide for lifelong tissue homeostasis. Stem cell populations are precisely controlled by the balance between their symmetric and asymmetric divisions, with their division patterns determined by whether the daughter cells involved retain their self-renewal capacities. Recent studies have reported that metabolic pathways and the distribution of mitochondria are regulators of the division balance of stem cells and that metabolic defects can shift division balance toward symmetric commitment, which leads to stem cell exhaustion. It has also been observed that in asymmetric division, old mitochondria, which are central metabolic organelles, are segregated to the daughter cell fated to cell differentiation, whereas in symmetric division, young and old mitochondria are equally distributed between both daughter cells. Thus, metabolism and mitochondrial biology play important roles in stem cell fate decisions. As these decisions directly affect tissue homeostasis, understanding their regulatory mechanisms in the context of cellular metabolism is critical. PMID:27482603

The relative contribution of insulin secretory capacity, insulin action, and incretins to metabolic control after islet transplantation in dogs

NARCIS (Netherlands)

van der Burg, MPM; van Suylichem, PTR; Guicherit, OR; Frolich, M; Lemkes, HHPJ; Gooszen, HG

Adequate metabolic control is central to the concept of islet transplantation, but has received limited attention. We studied metabolic control in 8 dogs at 6-9 months after intrasplenic autografting of similar to 25% of the normal mass islets - as compared to 30 controls. A similar posttransplant

FGF-dependent metabolic control of vascular development

Science.gov (United States)

Yu, Pengchun; Alves, Tiago C.; Fang, Jennifer S.; Xie, Yi; Zhu, Jie; Chen, Zehua; De Smet, Frederik; Zhang, Jiasheng; Jin, Suk-Won; Sun, Lele; Sun, Hongye; Kibbey, Richard G.; Hirschi, Karen K.; Hay, Nissim; Carmeliet, Peter; Chittenden, Thomas W.; Eichmann, Anne; Potente, Michael; Simons, Michael

2017-01-01

Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are of importance to these processes1. While much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism2,3, little is understood about the role of fibroblast growth factors (FGFs) in this context4. Here we identify FGF receptor (FGFR) signaling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signaling inputs results in decreased glycolysis leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/r3 double mutant mice while HK2 overexpression partially rescues the defects caused by suppression of FGF signaling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development. PMID:28467822

Impact of hypothalamic reactive oxygen species in the control of energy metabolism and food intake

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Anne eDrougard

2015-02-01

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

Metabolic control and bone health in adolescents with type 1 diabetes

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Mohan Subburaman

2011-10-01

Full Text Available Abstract Background Adults with type 1 diabetes (T1D have decreased bone mineral density (BMD and increased fracture risk, yet the etiologies remain elusive. Early detection of derangements in bone biomarkers during adolescence could lead to timely recognition. In adolescents with T1D, we evaluated the relationships between metabolic control, BMD, and bone anabolic and turnover markers. Methods Cross-sectional study of 57 adolescent subjects with T1D who had HbA1c consistently ≥ 9% (Poor Control, PC n = 27 or Results There were no differences between HbA1c groups in BMD, components of the IGF system, or 25-hydroxyvitamin D status. The prevalence of 25-hydroxyvitamin D abnormalities was similar to that seen in the general adolescent population. Few patients met the recommended dietary allowance (RDA for vitamin D or calcium. Conclusions These data provide no evidence of association between degree of metabolic control and BMD in adolescents with T1D. Adolescents with T1D have a high prevalence of serum 25-hydroxyvitamin D abnormalities. Longitudinal studies are needed to evaluate the predictive value of vitamin D abnormalities on fracture risk.

Effects of pistachio nuts on body composition, metabolic, inflammatory and oxidative stress parameters in Asian Indians with metabolic syndrome: a 24-wk, randomized control trial.

Science.gov (United States)

Gulati, Seema; Misra, Anoop; Pandey, Ravindra Mohan; Bhatt, Surya Prakash; Saluja, Shelza

2014-02-01

The aim of this study was to evaluate the effects of pistachio nuts as an adjunct to diet and exercise on body composition, metabolic, inflammatory, and oxidative stress parameters in Asian Indians with metabolic syndrome. In this 24-wk randomized control trial, 60 individuals with the metabolic syndrome were randomized to either pistachio (intervention group) or control group (diet as per weight and physical activity profile, modulated according to dietary guidelines for Asian Indians) after 3 wk of a diet and exercise run in. In the first group, unsalted pistachios (20% energy) were given daily. A standard diet and exercise protocol was followed for both groups. Body weight, waist circumference (WC), magnetic resonance imaging estimation of intraabdominal adipose tissue and subcutaneous abdominal adipose tissue, fasting blood glucose (FBG), fasting serum insulin, glycosylated hemoglobin, lipid profile, high-sensitivity C-reactive protein (hs-CRP), adiponectin, free fatty acids (FFAs), tumor necrosis factor (TNF)-α, leptin, and thiobarbituric acid reactive substances (TBARS) were assessed before and after the intervention. Statistically significant improvement in mean values for various parameters in the intervention group compared with control group were as follows: WC (P pistachios leads to beneficial effects on the cardiometabolic profile of Asian Indians with metabolic syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

Metabolic Control of Dendritic Cell Activation and Function: Recent Advances and Clinical Implications

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Bart eEverts

2014-05-01

Full Text Available Dendritic cells (DCs are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cell and regulatory T cell responses. Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to profound changes in cellular metabolism. Over the past decade there is a growing appreciation that these metabolic changes also underlie the capacity of immune cells to perform particular functions. This has led to the concept that the manipulation of cellular metabolism can be used to shape innate and adaptive immune responses. While most of our understanding in this area has been gained from studies with T cells and macrophages, evidence is emerging that the activation and function of DCs are also dictated by the type of metabolism these cells commit to. We here discuss these new insights and explore whether targeting of metabolic pathways in DCs could hold promise as a novel approach to manipulate the functional properties of DCs for clinical purposes.

Defining a novel leptin–melanocortin–kisspeptin pathway involved in the metabolic control of puberty

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Maria Manfredi-Lozano

2016-10-01

Full Text Available Objective: Puberty is a key developmental phenomenon highly sensitive to metabolic modulation. Worrying trends of changes in the timing of puberty have been reported in humans. These might be linked to the escalating prevalence of childhood obesity and could have deleterious impacts on later (cardio-metabolic health, but their underlying mechanisms remain unsolved. The neuropeptide α-MSH, made by POMC neurons, plays a key role in energy homeostasis by mediating the actions of leptin and likely participates in the control of reproduction. However, its role in the metabolic regulation of puberty and interplay with kisspeptin, an essential puberty-regulating neuropeptide encoded by Kiss1, remain largely unknown. We aim here to unveil the potential contribution of central α-MSH signaling in the metabolic control of puberty by addressing its role in mediating the pubertal effects of leptin and its potential interaction with kisspeptin. Methods: Using wild type and genetically modified rodent models, we implemented pharmacological studies, expression analyses, electrophysiological recordings, and virogenetic approaches involving DREADD technology to selectively inhibit Kiss1 neurons, in order to interrogate the physiological role of a putative leptin→α-MSH→kisspeptin pathway in the metabolic control of puberty. Results: Stimulation of central α-MSH signaling robustly activated the reproductive axis in pubertal rats, whereas chronic inhibition of melanocortin receptors MC3/4R, delayed puberty, and prevented the permissive effect of leptin on puberty onset. Central blockade of MC3/4R or genetic elimination of kisspeptin receptors from POMC neurons did not affect kisspeptin effects. Conversely, congenital ablation of kisspeptin receptors or inducible, DREADD-mediated inhibition of arcuate nucleus (ARC Kiss1 neurons resulted in markedly attenuated gonadotropic responses to MC3/4R activation. Furthermore, close appositions were observed between

Pyruvate Kinase Triggers a Metabolic Feedback Loop that Controls Redox Metabolism in Respiring Cells

NARCIS (Netherlands)

Grüning, N.M.; Rinnerthaler, M.; Bluemlein, K.; Mulleder, M.; Wamelink, M.M.C.; Lehrach, H.; Jakobs, C.A.J.M.; Breitenbach, M.; Ralser, M.

2011-01-01

In proliferating cells, a transition from aerobic to anaerobic metabolism is known as the Warburg effect, whose reversal inhibits cancer cell proliferation. Studying its regulator pyruvate kinase (PYK) in yeast, we discovered that central metabolism is self-adapting to synchronize redox metabolism

Changes in the isozymic pattern of phosphoenolpyruvate : An early step in photoperiodic control of crassulacean acid metabolism level.

Science.gov (United States)

Brulfert, J; Arrabaça, M C; Guerrier, D; Queiroz, O

1979-01-01

Two major isofunctional forms of phosphoenolpyruvate carboxylase (EC 4.1.1.31) have been separated from the leaves of Kalanchoe blossfeldiana Poelln. Tom Thumb by acrylamide gel electrophoresis and diethylaminoethyl cellulose techniques: one of the forms prevails under long-day treatment (low crassulacean acid metabolism level), the other develops under short-day treatment (high Crassulacean acid metabolism level). Molecular weights are significantly different: 175·10(3) and 186·10(3), respectively. These results indicate that two populations of phosphoenolyruvate carboxylase are present in the plant, one of which is responsible for Crassulacean acid metabolism activity under the control of photoperiod.The Crassulacean acid metabolism appears to depend on the same endogenous clock that governs other photoperiodically controlled events (e.g. flowering). The metabolic and energetic significance of this feature is discussed. It is suggested that modification in isozymic composition could be an early step in the response to photoperiodism at the metabolic level.

Leptin and the central nervous system control of glucose metabolism.

Science.gov (United States)

Morton, Gregory J; Schwartz, Michael W

2011-04-01

The regulation of body fat stores and blood glucose levels is critical for survival. This review highlights growing evidence that leptin action in the central nervous system plays a key role in both processes. Investigation into underlying mechanisms has begun to clarify the physiological role of leptin in the control of glucose metabolism and raises interesting new possibilities for the treatment of diabetes and related disorders.

Evaluation of empowerment model on indicators of metabolic control in patients with type 2 diabetes, a randomized clinical trial study.

Science.gov (United States)

Ebrahimi, Hossein; Sadeghi, Mahdi; Amanpour, Farzaneh; Vahedi, Hamid

2016-04-01

Diabetes education is a major subject in achieving optimal glycemic control. Effective empowerment approach can be beneficial for improving patients' health. The aim of this study was to evaluate the effect of empowerment model on indicators of metabolic control in patients with type 2 diabetes. a randomized controlled trial of 103 patients with type 2 diabetes were randomly assigned to either the intervention (empowerment approach training) or the control group (conventional training) 2014. Empowerment approach training were performed for the experimental group for eight weeks. Data collection tool included demographic information form and indicators of metabolic control checklist. Analysis was performed by one-way analysis of variance, chi-square test, paired t-test, independent t-test and multiple linear regression. Before the intervention, two groups were homogeneous in terms of demographic variables, glycosylated hemoglobin (HbA1C), and other indicators of metabolic control. After the intervention, average HbA1C and other metabolic indicators except for LDL showed significant differences in the experimental group compared to the control group. study results indicated the positive effects of applying the empowerment model on the metabolic control indicators. Therefore, applying this model is recommended to nurses and the relevant authorities in order to improve clinical outcomes in diabetic patients. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Sleep Control, GPCRs, and Glucose Metabolism.

Science.gov (United States)

Tsuneki, Hiroshi; Sasaoka, Toshiyasu; Sakurai, Takeshi

2016-09-01

Modern lifestyles prolong daily activities into the nighttime, disrupting circadian rhythms, which may cause sleep disturbances. Sleep disturbances have been implicated in the dysregulation of blood glucose levels and reported to increase the risk of type 2 diabetes (T2D) and diabetic complications. Sleep disorders are treated using anti-insomnia drugs that target ionotropic and G protein-coupled receptors (GPCRs), including γ-aminobutyric acid (GABA) agonists, melatonin agonists, and orexin receptor antagonists. A deeper understanding of the effects of these medications on glucose metabolism and their underlying mechanisms of action is crucial for the treatment of diabetic patients with sleep disorders. In this review we focus on the beneficial impact of sleep on glucose metabolism and suggest a possible strategy for therapeutic intervention against sleep-related metabolic disorders. Copyright © 2016. Published by Elsevier Ltd.

The Role of Monoaminergic Neurotransmission for Metabolic Control in the Fruit Fly Drosophila Melanogaster

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Yong Li

2017-08-01

Full Text Available Hormones control various metabolic traits comprising fat deposition or starvation resistance. Here we show that two invertebrate neurohormones, octopamine (OA and tyramine (TA as well as their associated receptors, had a major impact on these metabolic traits. Animals devoid of the monoamine OA develop a severe obesity phenotype. Using flies defective in the expression of receptors for OA and TA, we aimed to decipher the contributions of single receptors for these metabolic phenotypes. Whereas those animals impaired in octß1r, octß2r and tar1 share the obesity phenotype of OA-deficient (tβh-deficient animals, the octß1r, octß2r deficient flies showed reduced insulin release, which is opposed to the situation found in tβh-deficient animals. On the other hand, OAMB deficient flies were leaner than controls, implying that the regulation of this phenotype is more complex than anticipated. Other phenotypes seen in tβh-deficient animals, such as the reduced ability to perform complex movements tasks can mainly be attributed to the octß2r. Tissue-specific RNAi experiments revealed a very complex interorgan communication leading to the different metabolic phenotypes observed in OA or OA and TA-deficient flies.

Effect of strict metabolic control on regulation of subcutaneous blood flow in insulin-dependent diabetic patients

DEFF Research Database (Denmark)

Kastrup, J; Mathiesen, E R; Saurbrey, Nina

1987-01-01

washout technique. Mean arterial blood pressure was reduced by a maximum of 23 mmHg by elevating the limb above heart level and elevated to a maximum of 65 mmHg by head-up tilt; in the latter position venous pressure was kept constantly low by activation of the leg muscle vein pump (heel raising......The effect of 10 weeks of improved metabolic control on the impaired autoregulation of the subcutaneous blood flow was studied at the level of the lateral malleolus in eight long-term insulin-dependent diabetic patients with clinical microangiopathy. Blood flow was measured by the local 133-Xenon......). Improved metabolic control was achieved using either continuous subcutaneous insulin infusion or multiple insulin injections. The blood glucose concentration declined from (median) 12.7 to 6.8 mmol/l and the HbA1C level from 10.1 to 7.5% during strict metabolic control (p less than 0.01 and p less than 0...

Individual and family strengths: an examination of the relation to disease management and metabolic control in youth with type 1 diabetes.

Science.gov (United States)

Mackey, Eleanor Race; Hilliard, Marisa E; Berger, Sarah Shafer; Streisand, Randi; Chen, Rusan; Holmes, Clarissa

2011-12-01

We examined the association of youths' positive qualities, family cohesion, disease management, and metabolic control in Type 1 diabetes. Two-hundred fifty-seven youth-parent dyads completed the Family Cohesion subscale of the Family Environment Scale, the Diabetes Behavior Rating Scale, 24-hour diabetes interview, and youth completed the Positive Qualities subscale of the Youth Self Report (YSR-PQ). Structural equation modeling demonstrated that YSR-PQ scores were associated with metabolic control mediated by associations with more family cohesion and better disease management. That is, youth with higher YSR-PQ scores had more cohesive families, better disease management, and, indirectly, better metabolic control. Family cohesion was indirectly associated with better metabolic control mediated by its association with better disease management, but not mediated by its association with YSR-PQ scores. Youth who reported more positive qualities, as measured by the YSR-PQ subscale, had better disease management and metabolic control through the association with more family cohesion. However, the current results did not support an alternative hypothesis that cohesive families display better diabetes management mediated by higher YSR-PQ scores.

Space Station CMIF extended duration metabolic control test

Science.gov (United States)

Schunk, Richard G.; Bagdigian, Robert M.; Carrasquillo, Robyn L.; Ogle, Kathryn Y.; Wieland, Paul O.

1989-01-01

The Space Station Extended Duration Metabolic Control Test (EMCT) was conducted at the MSFC Core Module Integration Facility. The primary objective of the EMCT was to gather performance data from a partially-closed regenerative Environmental Control and Life Support (ECLS) system functioning under steady-state conditions. Included is a description of the EMCT configuration, a summary of events, a discussion of anomalies that occurred during the test, and detailed results and analysis from individual measurements of water and gas samples taken during the test. A comparison of the physical, chemical, and microbiological methods used in the post test laboratory analyses of the water samples is included. The preprototype ECLS hardware used in the test, providing an overall process description and theory of operation for each hardware item. Analytical results pertaining to a system level mass balance and selected system power estimates are also included.

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

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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

Effect of dietary regime on metabolic control in phenylketonuria: Is exact calculation of phenylalanine intake really necessary?

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Carmen Rohde

2015-12-01

Conclusion: Exact calculation of Phe content of all food is not necessary to achieve good metabolic control in children and adolescents with PKU. Excluding special low protein food, as well as fruit and vegetables from calculation of Phe-intake has no impact on metabolic control. However including protein rich food into the diet and simply estimating all Phe-intake appears insufficient. The simplification of dietary regime may be helpful in enhancing acceptability and feasibility.

Combined Effects of Ezetimibe and Phytosterols on Cholesterol Metabolism: A Randomized, Controlled Feeding Study in Humans

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Lin, Xiaobo; Racette, Susan B.; Lefevre, Michael; Ma, Lina; Spearie, Catherine Anderson; Steger-May, Karen; Ostlund, Richard E.

2011-01-01

Background Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that ezetimibe combined with phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism. Methods and Results Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo + phytosterol placebo, (2) 10 mg ezetimibe/day + phytosterol placebo, and (3) 10 mg ezetimibe/day + 2.5 g phytosterols/day, for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and LDL cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/day, 95% CI 368 to 828) relative to control (2161 mg/day, 1112 to 3209) and ezetimibe alone (1054 mg/day, 546 to 1561, both P phytosterols averaged 129 (95% CI: 116 to 142), 108 (97 to 119), and 101 (90 to 112) mg/dL (P phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma LDL cholesterol. The large cumulative action of combined dietary and pharmacologic treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia. PMID:21768544

Brain glucose sensing, glucokinase and neural control of metabolism and islet function.

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Ogunnowo-Bada, E O; Heeley, N; Brochard, L; Evans, M L

2014-09-01

It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel--emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases. © 2014 John Wiley & Sons Ltd.

Central nervous system control of triglyceride metabolism

NARCIS (Netherlands)

Geerling, Johanna Janetta (Janine)

2013-01-01

This thesis describes the role of the brain in the regulation of peripheral triglyceride metabolism, in the context of the metabolic syndrome. Based on various pharmacological studies we described the role of two hormones, insulin and glucagon-like peptide-1, in the production and clearance of

Micro-Environmental Stress Induces Src-Dependent Activation of Invadopodia and Cell Migration in Ewing Sarcoma

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Kelly M. Bailey

2016-08-01

Full Text Available Metastatic Ewing sarcoma has a very poor prognosis and therefore new investigations into the biologic drivers of metastatic progression are key to finding new therapeutic approaches. The tumor microenvironment is highly dynamic, leading to exposure of different regions of a growing solid tumor to changes in oxygen and nutrient availability. Tumor cells must adapt to such stress in order to survive and propagate. In the current study, we investigate how Ewing sarcoma cells respond to the stress of growth factor deprivation and hypoxia. Our findings reveal that serum deprivation leads to a reversible change in Ewing cell cytoskeletal phenotypes. Using an array of migration and invasion techniques, including gelatin matrix degradation invadopodia assays, we show that exposure of Ewing sarcoma cells to serum deprivation and hypoxia triggers enhanced migration, invadopodia formation, matrix degradation and invasion. Further, these functional changes are accompanied by and dependent on activation of Src kinase. Activation of Src, and the associated invasive cell phenotype, were blocked by exposing hypoxia and serum-deprived cells to the Src inhibitor dasatinib. These results indicate that Ewing sarcoma cells demonstrate significant plasticity in response to rapidly changing micro-environmental stresses that can result from rapid tumor growth and from necrosis-causing therapies. In response to these stresses, Ewing cells transition to a more migratory and invasive state and our data show that Src is an important mediator of this stress response. Our data support exploration of clinically available Src inhibitors as adjuvant agents for metastasis prevention in Ewing sarcoma.

PERT: A Method for Expression Deconvolution of Human Blood Samples from Varied Microenvironmental and Developmental Conditions

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Csaszar, Elizabeth; Yu, Mei; Morris, Quaid; Zandstra, Peter W.

2012-01-01

The cellular composition of heterogeneous samples can be predicted using an expression deconvolution algorithm to decompose their gene expression profiles based on pre-defined, reference gene expression profiles of the constituent populations in these samples. However, the expression profiles of the actual constituent populations are often perturbed from those of the reference profiles due to gene expression changes in cells associated with microenvironmental or developmental effects. Existing deconvolution algorithms do not account for these changes and give incorrect results when benchmarked against those measured by well-established flow cytometry, even after batch correction was applied. We introduce PERT, a new probabilistic expression deconvolution method that detects and accounts for a shared, multiplicative perturbation in the reference profiles when performing expression deconvolution. We applied PERT and three other state-of-the-art expression deconvolution methods to predict cell frequencies within heterogeneous human blood samples that were collected under several conditions (uncultured mono-nucleated and lineage-depleted cells, and culture-derived lineage-depleted cells). Only PERT's predicted proportions of the constituent populations matched those assigned by flow cytometry. Genes associated with cell cycle processes were highly enriched among those with the largest predicted expression changes between the cultured and uncultured conditions. We anticipate that PERT will be widely applicable to expression deconvolution strategies that use profiles from reference populations that vary from the corresponding constituent populations in cellular state but not cellular phenotypic identity. PMID:23284283

[Metabolic control in the critically ill patient an update: hyperglycemia, glucose variability hypoglycemia and relative hypoglycemia].

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Pérez-Calatayud, Ángel Augusto; Guillén-Vidaña, Ariadna; Fraire-Félix, Irving Santiago; Anica-Malagón, Eduardo Daniel; Briones Garduño, Jesús Carlos; Carrillo-Esper, Raúl

Metabolic changes of glucose in critically ill patients increase morbidity and mortality. The appropriate level of blood glucose has not been established so far and should be adjusted for different populations. However concepts such as glucose variability and relative hypoglycemia of critically ill patients are concepts that are changing management methods and achieving closer monitoring. The purpose of this review is to present new data about the management and metabolic control of patients in critical areas. Currently glucose can no longer be regarded as an innocent element in critical patients; both hyperglycemia and hypoglycemia increase morbidity and mortality of patients. Protocols and better instruments for continuous measurement are necessary to achieve the metabolic control of our patients. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Interaction of Pubertal Development and Metabolic Control in Adolescents with Type 1 Diabetes Mellitus

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M. Plamper

2017-01-01

Full Text Available Background. In T1DM, delayed pubertal development and reduced final height are associated with inadequate metabolic control. Objective. To assess whether T1DM affects pubertal growth spurt and whether metabolic control during puberty is gender-related. Methods. Using a large multicentre database, longitudinal data from 1294 patients were analysed. Inclusion criteria: complete records of height and HbA1c from the age of seven to 16 years. Exclusion criteria: other significant chronic diseases and medications, T1DM duration less than three months, and initial BMI 97th percentile. Results. Growth velocity (GV was impaired with a significant reduction of peak GV by 1.2 cm in boys. HbA1c increase during male puberty was lower except for a period of 1.5 years. The highest HbA1c increase in boys coincided with maximum growth spurt. In girls, the highest HbA1c increase was observed during late puberty. Even though there is impaired GV, both sexes reach a height at 16 years of age which corresponds to the background population height. Conclusion. Worsening of metabolic control is sex-discordant and associated with gender-specific alterations of GV. However, the vast majority of boys and girls with T1DM seems to reach normal height at the age of 16 years.

Linking metabolic QTLs with network and cis-eQTLs controlling biosynthetic pathways.

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Adam M Wentzell

2007-09-01

Full Text Available Phenotypic variation between individuals of a species is often under quantitative genetic control. Genomic analysis of gene expression polymorphisms between individuals is rapidly gaining popularity as a way to query the underlying mechanistic causes of variation between individuals. However, there is little direct evidence of a linkage between global gene expression polymorphisms and phenotypic consequences. In this report, we have mapped quantitative trait loci (QTLs-controlling glucosinolate content in a population of 403 Arabidopsis Bay x Sha recombinant inbred lines, 211 of which were previously used to identify expression QTLs controlling the transcript levels of biosynthetic genes. In a comparative study, we have directly tested two plant biosynthetic pathways for association between polymorphisms controlling biosynthetic gene transcripts and the resulting metabolites within the Arabidopsis Bay x Sha recombinant inbred line population. In this analysis, all loci controlling expression variation also affected the accumulation of the resulting metabolites. In addition, epistasis was detected more frequently for metabolic traits compared to transcript traits, even when both traits showed similar distributions. An analysis of candidate genes for QTL-controlling networks of transcripts and metabolites suggested that the controlling factors are a mix of enzymes and regulatory factors. This analysis showed that regulatory connections can feedback from metabolism to transcripts. Surprisingly, the most likely major regulator of both transcript level for nearly the entire pathway and aliphatic glucosinolate accumulation is variation in the last enzyme in the biosynthetic pathway, AOP2. This suggests that natural variation in transcripts may significantly impact phenotypic variation, but that natural variation in metabolites or their enzymatic loci can feed back to affect the transcripts.

Microenvironmental influence on pre-clinical activity of polo-like kinase inhibition in multiple myeloma: implications for clinical translation.

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Douglas W McMillin

Full Text Available Polo-like kinases (PLKs play an important role in cell cycle progression, checkpoint control and mitosis. The high mitotic index and chromosomal instability of advanced cancers suggest that PLK inhibitors may be an attractive therapeutic option for presently incurable advanced neoplasias with systemic involvement, such as multiple myeloma (MM. We studied the PLK 1, 2, 3 inhibitor BI 2536 and observed potent (IC50<40 nM and rapid (commitment to cell death <24 hrs in vitro activity against MM cells in isolation, as well as in vivo activity against a traditional subcutaneous xenograft mouse model. Tumor cells in MM patients, however, don't exist in isolation, but reside in and interact with the bone microenvironment. Therefore conventional in vitro and in vivo preclinical assays don't take into account how interactions between MM cells and the bone microenvironment can potentially confer drug resistance. To probe this question, we performed tumor cell compartment-specific bioluminescence imaging assays to compare the preclinical anti-MM activity of BI 2536 in vitro in the presence vs. absence of stromal cells or osteoclasts. We observed that the presence of these bone marrow non-malignant cells led to decreased anti-MM activity of BI 2536. We further validated these results in an orthotopic in vivo mouse model of diffuse MM bone lesions where tumor cells interact with non-malignant cells of the bone microenvironment. We again observed that BI 2536 had decreased activity in this in vivo model of tumor-bone microenvironment interactions highlighting that, despite BI 2536's promising activity in conventional assays, its lack of activity in microenvironmental models raises concerns for its clinical development for MM. More broadly, preclinical drug testing in the absence of relevant tumor microenvironment interactions may overestimate potential clinical activity, thus explaining at least in part the gap between preclinical vs. clinical efficacy in MM

Effect of oral cinnamon intervention on metabolic profile and body composition of Asian Indians with metabolic syndrome: a randomized double -blind control trial.

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Gupta Jain, Sonal; Puri, Seema; Misra, Anoop; Gulati, Seema; Mani, Kalaivani

2017-06-12

Nutritional modulation remains central to the management of metabolic syndrome. Intervention with cinnamon in individuals with metabolic syndrome remains sparsely researched. We investigated the effect of oral cinnamon consumption on body composition and metabolic parameters of Asian Indians with metabolic syndrome. In this 16-week double blind randomized control trial, 116 individuals with metabolic syndrome were randomized to two dietary intervention groups, cinnamon [6 capsules (3 g) daily] or wheat flour [6 capsules (2.5 g) daily]. Body composition, blood pressure and metabolic parameters were assessed. Significantly greater decrease [difference between means, (95% CI)] in fasting blood glucose (mmol/L) [0.3 (0.2, 0.5) p = 0.001], glycosylated haemoglobin (mmol/mol) [2.6 (0.4, 4.9) p = 0.023], waist circumference (cm) [4.8 (1.9, 7.7) p = 0.002] and body mass index (kg/m2 ) [1.3 (0.9, 1.5) p = 0.001] was observed in the cinnamon group compared to placebo group. Other parameters which showed significantly greater improvement were: waist-hip ratio, blood pressure, serum total cholesterol, low-density lipoprotein cholesterol, serum triglycerides, and high-density lipoprotein cholesterol. Prevalence of defined metabolic syndrome was significantly reduced in the intervention group (34.5%) vs. the placebo group (5.2%). A single supplement intervention with 3 g cinnamon for 16 weeks resulted in significant improvements in all components of metabolic syndrome in a sample of Asian Indians in north India. The clinical trial was retrospectively registered (after the recruitment of the participants) in ClinicalTrial.gov under the identification number: NCT02455778 on 25th May 2015.

Thyroid peroxidase antibodies in pregnant women with type 1 diabetes: impact on thyroid function, metabolic control and pregnancy outcome

DEFF Research Database (Denmark)

Vestgaard, Marianne; Nielsen, Lene Ringholm; Rasmussen, Åse Krogh

2008-01-01

In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome.......In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome....

Identification of microRNAs controlling hepatic mRNA levels for metabolic genes during the metabolic transition from embryonic to posthatch development in the chicken.

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Hicks, Julie A; Porter, Tom E; Liu, Hsiao-Ching

2017-09-05

The transition from embryonic to posthatch development in the chicken represents a massive metabolic switch from primarily lipolytic to primarily lipogenic metabolism. This metabolic switch is essential for the chick to successfully transition from the metabolism of stored egg yolk to the utilization of carbohydrate-based feed. However, regulation of this metabolic switch is not well understood. We hypothesized that microRNAs (miRNAs) play an important role in the metabolic switch that is essential to efficient growth of chickens. We used high-throughput RNA sequencing to characterize expression profiles of mRNA and miRNA in liver during late embryonic and early posthatch development of the chicken. This extensive data set was used to define the contributions of microRNAs to the metabolic switch during development that is critical to growth and nutrient utilization in chickens. We found that expression of over 800 mRNAs and 30 miRNAs was altered in the embryonic liver between embryonic day 18 and posthatch day 3, and many of these differentially expressed mRNAs and miRNAs are associated with metabolic processes. We confirmed the regulation of some of these mRNAs by miRNAs expressed in a reciprocal pattern using luciferase reporter assays. Finally, through the use of yeast one-hybrid screens, we identified several proteins that likely regulate expression of one of these important miRNAs. Integration of the upstream regulatory mechanisms governing miRNA expression along with monitoring the downstream effects of this expression will ultimately allow for the construction of complete miRNA regulatory networks associated with the hepatic metabolic switch in chickens. Our findings support a key role for miRNAs in controlling the metabolic switch that occurs between embryonic and posthatch development in the chicken.

[DiabeTIC website: a pilot study of satisfaction and impact on metabolic control].

Science.gov (United States)

Carral San Laureano, Florentino; Ayala Ortega, María del Carmen; Jiménez Millán, Ana Isabel; Piñero Zaldivar, Antonia; García Calzado, Concepción; Prieto Ferrón, Matilde; Silva Rodríguez, Juan José

2013-10-01

To evaluate satisfaction and short-term impact on metabolic control of diabetes monitoring through the DiabeTIC website. A prospective, uncontrolled intervention study was conducted in 32 patients aged 29.7±9.7 years (65% female) incorporated to the telemedicine platform DiabeTIC between March and September 2012. All patients completed a satisfaction questionnaire in the first month, and impact on metabolic control was evaluated at three and six months. In the satisfaction survey conducted in the first month of follow-up, the following mean scores (0-10) were obtained: overall impression with the platform: 8.6±1.8; ease of use: 8.1±1.5; intuitive navigation: 6.7±3.0; value of measurements: 9.1±1.1; importance of the platform in diabetes management: 9.5±0.9; sense of security: 9.5±0.8; value of the library: 9.4±1.1; value of messages: 9.1±1.4, and recommendation to use the platform: 9.4±0.9. Glycosilated hemoglobin concentrations significantly improved at six months as compared to study start (7.0±0.8 versus 8.1±1.9; p=0.007). Nine patients were discharged from DiabeTIC before completing six months of follow-up. Patients with diabetes monitored through the DiabeTIC website report a high degree of satisfaction, showing improved metabolic control at short-term follow-up. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Hypoglycemia in pregnant women with type 1 diabetes - Predictors and role of metabolic control

DEFF Research Database (Denmark)

Nielsen, L.R.; Johansen, M.; Pedersen-Bjergaard, U.

2008-01-01

OBJECTIVE- In pregnancy with type 1 diabetes, we evaluated occurrence of mild and severe hypoglycemia and analyzed the influence of strict metabolic control, nausea, Vomiting, and other potential predictors of occurrence of severe hypoglycemia. RESEARCH DESIGN AND METHODS- A prospective...... awareness or unawareness (3.2 [1.2-8.2]) as independent predictors for severe hypoglycemia. CONCLUSIONS - In pregnancy with type 1 diabetes, the incidence of mild and severe hypoglycemia was highest in early pregnancy, although metabolic control was tighter in the last part of pregnancy. Predictors...... observational study of 108 consecutive pregnant women with type 1 diabetes was conducted. At 8, 14, 21, 27, and 33 weeks of gestation, patients performed self-monitored plasma glucose (SMPG) (eight/day) for 3 days and completed a questionnaire on nausea, vomiting, hypoglycemia awareness, and history of mild...

Monitoring and robust adaptive control of fed-batch cultures of microorganisms exhibiting overflow metabolism [abstract

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Vande Wouwer, A.

2010-01-01

Full Text Available Overflow metabolism characterizes cells strains that are likely to produce inhibiting by-products resulting from an excess of substrate feeding and a saturated respiratory capacity. The critical substrate level separating the two different metabolic pathways is generally not well defined. Monitoring of this kind of cultures, going from model identification to state estimation, is first discussed. Then, a review of control techniques which all aim at maximizing the cell productivity of fed-batch fermentations is presented. Two main adaptive control strategies, one using an estimation of the critical substrate level as set-point and another regulating the by-product concentration, are proposed. Finally, experimental investigations of an adaptive RST control scheme using the observer polynomial for the regulation of the ethanol concentration in Saccharomyces cerevisiae fed-batch cultures ranging from laboratory to industrial scales, are also presented.

Metabolic Syndrome Increases the Risk of Sudden Sensorineural Hearing Loss in Taiwan: A Case-Control Study.

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Chien, Chen-Yu; Tai, Shu-Yu; Wang, Ling-Feng; Hsi, Edward; Chang, Ning-Chia; Wu, Ming-Tsang; Ho, Kuen-Yao

2015-07-01

Sudden sensorineural hearing loss has been reported to be associated with diabetes mellitus, hypertension, and hyperlipidemia in previous studies. The aim of this study was to examine whether metabolic syndrome increases the risk of sudden sensorineural hearing loss in Taiwan. A case-control study. Tertiary university hospital. We retrospectively investigated 181 cases of sudden sensorineural hearing loss and 181 controls from the Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, in southern Taiwan from 2010 to 2012, comparing their clinical variables. We analyzed the relationship between metabolic syndrome and sudden sensorineural hearing loss. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III with Asian modifications. The demographic and clinical characteristics, audiometry results, and outcome were reviewed. Subjects with metabolic syndrome had a 3.54-fold increased risk (95% confidence interval [CI] = 2.00-6.43, P diabetes mellitus, hypertension, and hyperlipidemia. With increases in the number of metabolic syndrome components, the risk of sudden sensorineural hearing loss increased (P for trend Vertigo was associated with a poor outcome (P = .02; 95% CI = 1.13~5.13, adjusted odds ratio = 2.39). The hearing loss pattern may influence the outcome of sudden sensorineural hearing loss (P Vertigo and total hearing loss were indicators of a poor outcome in sudden sensorineural hearing loss. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Role of Parenting Style in Achieving Metabolic Control in Adolescents With Type 1 Diabetes

OpenAIRE

Shorer, Maayan; David, Ravit; Schoenberg-Taz, Michal; Levavi-Lavi, Ifat; Phillip, Moshe; Meyerovitch, Joseph

2011-01-01

OBJECTIVE To examine the role of parenting style in achieving metabolic control and treatment adherence in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS Parents of 100 adolescents with type 1 diabetes completed assessments of their parenting style and sense of helplessness. Parents and patients rated patient adherence to the treatment regimen. Glycemic control was evaluated by HbA1c values. RESULTS An authoritative paternal parenting style predicted better glycemic control and...

Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock

DEFF Research Database (Denmark)

Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.

2014-01-01

Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-s...

Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study.

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Racette, Susan B; Lin, Xiaobo; Lefevre, Michael; Spearie, Catherine Anderson; Most, Marlene M; Ma, Lina; Ostlund, Richard E

2010-01-01

Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations. Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P phytosterol dose (-8.9 +/- 2.3%); a trend was observed with the 459-mg/d dose (-5.0 +/- 2.1%; P = 0.077). Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054.

Eating patterns in adolescents with type 1 diabetes: Associations with metabolic control, insulin omission, and eating disorder pathology.

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Wisting, Line; Reas, Deborah Lynn; Bang, Lasse; Skrivarhaug, Torild; Dahl-Jørgensen, Knut; Rø, Øyvind

2017-07-01

The purpose of this study was to investigate eating patterns among male and female adolescents with type 1 diabetes (T1D), and the associations with age, zBMI, eating disorder (ED) pathology, intentional insulin omission, and metabolic control. The sample consisted of 104 adolescents (58.6% females) with child-onset T1D, mean age of 15.7 years (SD 1.8) and mean zBMI of 0.4 (SD 0.8). The Child Eating Disorder Examination (ChEDE) assessed meal/snack frequency and ED pathology. T1D clinical data was obtained from the Norwegian Childhood Diabetes Registry. A significantly lower proportion of females than males (73.8% vs 97.7%) consumed breakfast on a daily basis. Approximately 50% of both genders ate lunch and 90% ate dinner daily. Among females, skipping breakfast was significantly associated with higher global ED psychopathology, shape concerns, self-induced vomiting, binge eating, insulin omission due to shape/weight concerns, and poorer metabolic control. Less frequent lunch consumption was significantly associated with poorer metabolic control. Skipping dinner was significantly associated with older age, higher dietary restraint, eating concerns, self-induced vomiting, and insulin omission. Among males, less frequent consumption of lunch and evening snacks was associated with attitudinal features of ED, including shape/weight concerns and dietary restraint. Among adolescents with T1D, irregular or infrequent meal consumption appears to signal potential ED pathology, as well as being associated with poorer metabolic control. These findings suggest the importance of routinely assessing eating patterns in adolescents with T1D to improve detection of ED pathology and to facilitate improved metabolic control and the associated risk of somatic complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exercise, Obesity and CNS Control of Metabolic Homeostasis: A Review

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Smith, John K.

2018-01-01

This review details the manner in which the central nervous system regulates metabolic homeostasis in normal weight and obese rodents and humans. It includes a review of the homeostatic contributions of neurons located in the hypothalamus, the midbrain and limbic structures, the pons and the medullary area postrema, nucleus tractus solitarius, and vagus nucleus, and details how these brain regions respond to circulating levels of orexigenic hormones, such as ghrelin, and anorexigenic hormones, such as glucagon-like peptide 1 and leptin. It provides an insight as to how high intensity exercise may improve homeostatic control in overweight and obese subjects. Finally, it provides suggestions as to how further progress can be made in controlling the current pandemic of obesity and diabetes.

Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta-analysis of randomized controlled clinical trials.

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Grossmann, Mathis; Hoermann, Rudolf; Wittert, Gary; Yeap, Bu B

2015-09-01

The effects of testosterone treatment on glucose metabolism and other outcomes in men with type 2 diabetes (T2D) and/or the metabolic syndrome are controversial. To perform a systematic review and meta-analysis of placebo-controlled double-blind randomized controlled clinical trials (RCT) of testosterone treatment in men with T2D and/or the metabolic syndrome. A systematic search of RCTs was conducted using Medline, Embase and the Cochrane Register of controlled trials from inception to July 2014 followed by a manual review of the literature. Eligible studies were published placebo-controlled double-blind RCTs published in English. Two reviewers independently selected studies, determined study quality and extracted outcome and descriptive data. Of the 112 identified studies, seven RCTs including 833 men were eligible for the meta-analysis. In studies using a simple linear equation to calculate the homeostatic model assessment of insulin resistance (HOMA1), testosterone treatment modestly improved insulin resistance, compared to placebo, pooled mean difference (MD) -1·58 [-2·25, -0·91], P treatment effect was nonsignificant for RCTs using a more stringent computer-based equation (HOMA2), MD -0·19 [-0·86, 0·49], P = 0·58). Testosterone treatment did not improve glycaemic (HbA1c) control, MD -0·15 [-0·39, 0·10], P = 0·25, or constitutional symptoms, Aging Male Symptom score, MD -2·49 [-5·81, 0·83], P = 0·14). This meta-analysis does not support the routine use of testosterone treatment in men with T2D and/or the metabolic syndrome without classical hypogonadism. Additional studies are needed to determine whether hormonal interventions are warranted in selected men with T2D and/or the metabolic syndrome. © 2014 John Wiley & Sons Ltd.

Engineering Cellular Metabolism

DEFF Research Database (Denmark)

Nielsen, Jens; Keasling, Jay

2016-01-01

Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

Clinical study on the prevalence and comparative analysis of metabolic syndrome and its components among Chinese breast cancer women and control population.

Science.gov (United States)

Wu, Yu-Tuan; Luo, Qing-Qing; Li, Xin; Arshad, Bilal; Xu, Zhou; Ran, Liang; Zhao, Chun-Xia; Wu, He; Shi, Yan-Ling; Chen, Hao-Ran; Li, Hao; Li, Hong-Yuan; Wu, Kai-Nan; Kong, Ling-Quan

2018-01-01

Metabolic syndrome has been previously identified as a risk factor for breast cancer and is increasingly a public health concern. This study aims to investigate the prevalence of metabolic syndrome and its components among primary breast cancer and control population. The clinical data of metabolic syndrome and its components in the breast cancer (605 cases) and control population (3212 cases), from Breast Cancer Center and Physical Examination Center of Chongqing, China, from July 2015 to February 2017, were collected for comparative analysis. This study was prospectively registered in Chinese Clinical Trial Registry (http://www.chictr.org.cn/, number: ChiCTR-OOB-15007543). The prevalence of metabolic syndrome in breast cancer (32.6%) was obviously higher than that in control population (18.2%) (pmetabolic syndrome in breast cancer group aged below 60 years (24.9%, pmetabolic syndrome and its components in Chinese breast cancer women, and metabolic syndrome is closely related with breast cancer. Therefore, screening and prevention strategy of metabolic syndrome should be carried out in the management of breast cancer.

Analysis of clock-regulated genes in Neurospora reveals widespread posttranscriptional control of metabolic potential

Science.gov (United States)

Hurley, Jennifer M.; Dasgupta, Arko; Emerson, Jillian M.; Zhou, Xiaoying; Ringelberg, Carol S.; Knabe, Nicole; Lipzen, Anna M.; Lindquist, Erika A.; Daum, Christopher G.; Barry, Kerrie W.; Grigoriev, Igor V.; Smith, Kristina M.; Galagan, James E.; Bell-Pedersen, Deborah; Freitag, Michael; Cheng, Chao; Loros, Jennifer J.; Dunlap, Jay C.

2014-01-01

Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation–based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset of ccg promoters, including those of many transcription factors. High temporal resolution (2-h) sampling over 48 h using RNA sequencing (RNA-Seq) identified circadianly expressed genes in Neurospora, revealing that from ∼10% to as much 40% of the transcriptome can be expressed under circadian control. Functional classifications of these genes revealed strong enrichment in pathways involving metabolism, protein synthesis, and stress responses; in broad terms, daytime metabolic potential favors catabolism, energy production, and precursor assembly, whereas night activities favor biosynthesis of cellular components and growth. Discriminative regular expression motif elicitation (DREME) identified key promoter motifs highly correlated with the temporal regulation of ccgs. Correlations between ccg abundance from RNA-Seq, the degree of ccg-promoter activation as reported by ccg-promoter–luciferase fusions, and binding of WCC as measured by ChIP-Seq, are not strong. Therefore, although circadian activation is critical to ccg rhythmicity, posttranscriptional regulation plays a major role in determining rhythmicity at the mRNA level. PMID:25362047

[Metabolic parameters in patients with steatosis non alcoholic liver and controlled diabetes type 2 versus uncontrolled diabetes type 2].

Science.gov (United States)

Miranda Manrique, Gonzalo

2016-01-01

Non-alcoholic fatty liver (NASH) is widely distributed around the world and is more common in subjects with dyslipidemia, metabolic syndrome obese and DM2 (34-74%). However, the prevalence of cirrhosis by NASH in general population is unknown which is still subject of research. To determine if there are significant differences between metabolic parameters of non-alcoholic fatty liver in controlled versus uncontrolled diabetes type 2 of recent diagnosis. retrospective case-control study, performed in the Hospital Guillermo Almenara Irigoyen, Lima, Peru from November 2014 to February 2015.This study included 231 patients: 147 patients (NASH with DM2 of recent diagnosis and poor control) and 84 patients (NASH with DM2 ofrecent diagnosis and adequate control). Levene test for evaluating homogeneity of variances intra groups and parametric test for independent samples. After applying Levene test of homogeneity and student test, significant metabolic parameters were the triglycerides, HbA1C level, metformin dose and gender. It is important in diabetic patients to diagnose NASH early for a tighter control, not only of glucose but other metabolic parameters mainly triglycerides which strongly supports existing concept of "multiple hits" which considers NASH affects glucose homeostasis, and it could be the starting point of new research to improve interventions for decreasing progression from to cirrhosis in diabetic patients and also to delay progression of diabetes mellitus in patients with non alcoholic steatohepatitis.

Fear of Hypoglycemia, Parenting Stress, and Metabolic Control for Children with Type 1 Diabetes and Their Parents.

Science.gov (United States)

Viaene, Ann-Sofie; Van Daele, Tom; Bleys, Dries; Faust, Kelly; Massa, Guy G

2017-03-01

This study sets out to extend current knowledge of parenting stress and fear of hypoglycemia (FoH) in parents of children with type 1 diabetes mellitus (T1DM). We examined if the relationship between parental and children's FoH and metabolic control, as reflected by HbA1c, is mediated by parenting stress. A total of 63 parents and children with T1DM were recruited during their routine physician's appointment. Parents completed questionnaires on parenting stress and FoH. Children eight years and older also completed a questionnaire on FoH. HbA1c values were obtained from all children. Mediation analysis revealed an indirect association between parental FoH and HbA1c values through parenting stress (Sobel's z = 2.42, p = .02), but no indirect association between children's FoH and HbA1c. We concluded that parental FOH has an indirect association with the child's metabolic control that is mediated by parenting stress. More simply, fear of hypoglycemia predicts parent stress, which in turn, predicts metabolic control.

Relationship between patients' perception of the importance of diabetes and metabolic control and pursuing chronic complications of disease

Directory of Open Access Journals (Sweden)

Mohammad Ebrahim Khamseh

2011-04-01

Full Text Available Introduction: Type II diabetes is a metabolic disorder. Environmental factors and patient awareness have major roles on chronic complications. The purpose of this study was to determine the association of patients' perception of t the importance of diabetes and metabolic- control and pursuing of chronic complications. Material and Methods: 194 patients with diabetes enrolled from diabetes clinic of Institute Endocrinology & Metabolism in a cross-sectional study, from February to March 2010. Data were collected using a questionnaire to assess the personal demographics, individual approach in pursuit of complications, and glycemic control, as well as patient perception and attitude toward the importance of disease process and follow-up. Level of perceptions was determined as well, moderate and weak. Results: Out of 194 patients, 77(39.7% were male and 117(60.3% female. Mean age was 52.18±10.17years. 69.2% did not know what the glycosylated hemoglobin was. In 71.4%, willing to participate in decisions making on medical treatment was good and they knew that with initiation of insulin therapy, they would have better metabolic control. 68.9% of patients had regular follow-up for eye complications, and 51% for cardiac complications. Follow-up for diabetic foot complication was poor. Patients with good perception had regular follow-up regarding cardiac, eye and renal complications. Conclusion: These results indicate that better perception of diabetic patients might improve their compliance for regular follow- up regarding the pursuit of chronic complications, especially cardiac, eye and renal problems. Although, the metabolic- control of patients had not the association with patient perception about the importance of diabetes

Dynamic optimal control of homeostasis: an integrative system approach for modeling of the central nitrogen metabolism in Saccharomyces cerevisiae.

Science.gov (United States)

van Riel, N A; Giuseppin, M L; Verrips, C T

2000-01-01

The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the source of the cellular amino acids and proteins, including flavors and potentially valuable biomolecules; therefore, it is also of industrial interest. In the DOMC approach the cell is regarded as an optimally controlled system. Given the metabolic genotype, the cell faces a control problem to maintain an optimal flux distribution in a changing environment. The regulation is based on strategies and balances feedback control of homeostasis and feedforward regulation for adaptation. The DOMC approach is an integrative, holistic approach, not based on mechanistic descriptions and (therefore) not biased by the variation present in biochemical and molecular biological data. It is an effective tool to structure the rapidly increasing amount of data on the function of genes and pathways. The DOMC model is used successfully to predict the responses of pulses of ammonia and glutamine to nitrogen-limited continuous cultures of a wild-type strain and a glutamine synthetase-negative mutant. The simulation results are validated with experimental data.

A soft sensor for bioprocess control based on sequential filtering of metabolic heat signals.

Science.gov (United States)

Paulsson, Dan; Gustavsson, Robert; Mandenius, Carl-Fredrik

2014-09-26

Soft sensors are the combination of robust on-line sensor signals with mathematical models for deriving additional process information. Here, we apply this principle to a microbial recombinant protein production process in a bioreactor by exploiting bio-calorimetric methodology. Temperature sensor signals from the cooling system of the bioreactor were used for estimating the metabolic heat of the microbial culture and from that the specific growth rate and active biomass concentration were derived. By applying sequential digital signal filtering, the soft sensor was made more robust for industrial practice with cultures generating low metabolic heat in environments with high noise level. The estimated specific growth rate signal obtained from the three stage sequential filter allowed controlled feeding of substrate during the fed-batch phase of the production process. The biomass and growth rate estimates from the soft sensor were also compared with an alternative sensor probe and a capacitance on-line sensor, for the same variables. The comparison showed similar or better sensitivity and lower variability for the metabolic heat soft sensor suggesting that using permanent temperature sensors of a bioreactor is a realistic and inexpensive alternative for monitoring and control. However, both alternatives are easy to implement in a soft sensor, alone or in parallel.

A Soft Sensor for Bioprocess Control Based on Sequential Filtering of Metabolic Heat Signals

Directory of Open Access Journals (Sweden)

Dan Paulsson

2014-09-01

Full Text Available Soft sensors are the combination of robust on-line sensor signals with mathematical models for deriving additional process information. Here, we apply this principle to a microbial recombinant protein production process in a bioreactor by exploiting bio-calorimetric methodology. Temperature sensor signals from the cooling system of the bioreactor were used for estimating the metabolic heat of the microbial culture and from that the specific growth rate and active biomass concentration were derived. By applying sequential digital signal filtering, the soft sensor was made more robust for industrial practice with cultures generating low metabolic heat in environments with high noise level. The estimated specific growth rate signal obtained from the three stage sequential filter allowed controlled feeding of substrate during the fed-batch phase of the production process. The biomass and growth rate estimates from the soft sensor were also compared with an alternative sensor probe and a capacitance on-line sensor, for the same variables. The comparison showed similar or better sensitivity and lower variability for the metabolic heat soft sensor suggesting that using permanent temperature sensors of a bioreactor is a realistic and inexpensive alternative for monitoring and control. However, both alternatives are easy to implement in a soft sensor, alone or in parallel.

Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21

Science.gov (United States)

Cornu, Marion; Oppliger, Wolfgang; Albert, Verena; Robitaille, Aaron M.; Trapani, Francesca; Quagliata, Luca; Fuhrer, Tobias; Sauer, Uwe; Terracciano, Luigi; Hall, Michael N.

2014-01-01

The liver is a key metabolic organ that controls whole-body physiology in response to nutrient availability. Mammalian target of rapamycin (mTOR) is a nutrient-activated kinase and central controller of growth and metabolism that is negatively regulated by the tumor suppressor tuberous sclerosis complex 1 (TSC1). To investigate the role of hepatic mTOR complex 1 (mTORC1) in whole-body physiology, we generated liver-specific Tsc1 (L-Tsc1 KO) knockout mice. L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner. Ectopic activation of mTORC1 also caused depletion of hepatic and plasma glutamine, leading to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α)–dependent fibroblast growth factor 21 (FGF21) expression in the liver. Injection of glutamine or knockdown of PGC-1α or FGF21 in the liver suppressed the behavioral and metabolic defects due to mTORC1 activation. Thus, mTORC1 in the liver controls whole-body physiology through PGC-1α and FGF21. Finally, mTORC1 signaling correlated with FGF21 expression in human liver tumors, suggesting that treatment of glutamine-addicted cancers with mTOR inhibitors might have beneficial effects at both the tumor and whole-body level. PMID:25082895

Female fibromyalgia patients: lower resting metabolic rates than matched healthy controls.

Science.gov (United States)

Lowe, John C; Yellin, Jackie; Honeyman-Lowe, Gina

2006-07-01

Many features of fibromyalgia and hypothyroidism are virtually the same, and thyroid hormone treatment trials have reduced or eliminated fibromyalgia symptoms. These findings led the authors to test the hypothesis that fibromyalgia patients are hypometabolic compared to matched controls. Resting metabolic rate (RMR) was measured by indirect calorimetry and body composition by bioelectrical impedance for 15 fibromyalgia patients and 15 healthy matched controls. Measured resting metabolic rate (mRMR) was compared to percentages of predicted RMR (pRMR) by fat-free weight (FFW) (Sterling-Passmore: SP) and by sex, age, height, and weight (Harris-Benedict: HB). Patients had a lower mRMR (4,306.31+/-1077.66 kJ vs 5,411.59+/-695.95 kJ, p=0.0028) and lower percentages of pRMRs (SP: -28.42+/-15.82% vs -6.83+/-12.55%, pBMI) best accounted for variability in controls' RMRs, age and fat weight (FW) did for patients. In the patient group, TSH level accounted for 28% of the variance in pain distribution, and free T3 (FT3) accounted for 30% of the variance in pressure-pain threshold. Patients had lower mRMR and percentages of pRMRs. The lower RMRs were not due to calorie restriction or low FFW. Patients' normal FFW argues against low physical activity as the mechanism. TSH, FT4, and FT3 levels did not correlate with RMRs in either group. This does not rule out inadequate thyroid hormone regulation because studies show these laboratory values do not reliably predict RMR.

The role of the autonomic nervous liver innervation in the control of energy metabolism

NARCIS (Netherlands)

Yi, Chun-Xia; la Fleur, Susanne E.; Fliers, Eric; Kalsbeek, Andries

2010-01-01

Despite a longstanding research interest ever since the early work by Claude Bernard, the functional significance of autonomic liver innervation, either sympathetic or parasympathetic, is still ill defined. This scarcity of information not only holds for the brain control of hepatic metabolism, but

SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion

DEFF Research Database (Denmark)

Anderson, Kristin A; Huynh, Frank K; Fisher-Wellman, Kelsey

2017-01-01

in leucine oxidation, and we show a primary role for SIRT4 in controlling this pathway in mice. Furthermore, we find that dysregulated leucine metabolism in SIRT4KO mice leads to elevated basal and stimulated insulin secretion, which progressively develops into glucose intolerance and insulin resistance....... These findings identify a robust enzymatic activity for SIRT4, uncover a mechanism controlling branched-chain amino acid flux, and position SIRT4 as a crucial player maintaining insulin secretion and glucose homeostasis during aging....

The impact of electronic education on metabolic control indicators in patients with diabetes who need insulin: a randomised clinical control trial.

Science.gov (United States)

Moattari, Marzieh; Hashemi, Maryam; Dabbaghmanesh, Mohammad H

2013-01-01

To determine the impact of electronic education on metabolic control indicators in patients with diabetes who were insulin dependent. Education can play an important role in controlling diabetes. Electronic (web-based, telehealth) education may be an efficient way to improve the patients' ability to control this disease. Randomised clinical control study. The participants in this clinical study were 48 insulin-dependent patients referred to diabetes centres in Shiraz, Iran. Serum concentrations of haemoglobin A(1C) , fasting blood sugar, triglycerides and high-density and low-density lipoprotein cholesterol were measured. Then the participants were divided randomly into control and experimental groups (n = 24). Participants in the experimental group received a specially designed electronic education programme for twelve weeks. The main components of the programme were a consultation service, quick answers to patients' questions, contact with the healthcare team and educational materials. At the end of the intervention period, all serum values were measured again in both groups. The data were compared using spss v 13·5 software. Serum concentrations of haemoglobin A(1C) (p education programme was useful in lowering two metabolic indicators of diabetes. Electronic education can be associated with increased health and patient satisfaction, and can eliminate the need to train personnel. © 2012 Blackwell Publishing Ltd.

The effect of metabolic control on hemodynamics in short-term insulin-dependent diabetic patients

DEFF Research Database (Denmark)

Mathiesen, E R; Hilsted, J; Feldt-Rasmussen, B

1985-01-01

Hemodynamics variables (heart rate, arterial blood pressure, cardiac output, hepato-splanchnic blood flow, forearm blood flow, and plasma catecholamines) were measured during good (median blood glucose 4.7 mmol/L) and poor (median blood glucose 16.3 mmol/L) metabolic control in eight young, short...

A qualitative study of young people's perspectives of living with type 1 diabetes: do perceptions vary by levels of metabolic control?

Science.gov (United States)

Scholes, Cheryl; Mandleco, Barbara; Roper, Susanne; Dearing, Karen; Dyches, Tina; Freeborn, Donna

2013-06-01

To explore if young people with higher and lower levels of metabolic control of type 1 diabetes have different perceptions about their lives and illness. Adolescence through emerging adulthood is a developmental stage made more challenging when the person has type 1 diabetes. Little research has investigated if individuals with high and low levels of metabolic control in this age group perceive their disease differently. Qualitative descriptive. In this study, 14 participants, ages 11-22 years were interviewed in 2008 about their perceptions of living with type 1 diabetes. Through a process of induction, major themes were identified. Participants with high and low metabolic control levels reported similar themes related to reactions of others, knowledge about type 1 diabetes, and believed healthcare providers used authoritarian interactions. However, high metabolic control level participants believed type 1 diabetes would be cured; had negative initial responses to being diagnosed; rarely received parental support in managing their diabetes; and were negligent in self-care activities. Participants with low metabolic control levels did not believe a cure was imminent or have negative responses to being diagnosed; received parental support in managing diabetes; and were diligent in self-care activities. Nurses should give information to young people with type 1 diabetes beyond initial diagnosis and help and support this age group learn appropriate ways to manage their disease, develop positive relationships with healthcare professionals, and participate in interactions with others their age successfully managing type 1 diabetes. © 2012 Blackwell Publishing Ltd.

A Multifunctional Bread Rich in Beta Glucans and Low in Starch Improves Metabolic Control in Type 2 Diabetes: A Controlled Trial.

Science.gov (United States)

Tessari, Paolo; Lante, Anna

2017-03-17

Functional foods may be useful for people with diabetes. The soluble fibers beta glucans can modify starch digestion and improve postprandial glucose response. We analyzed the metabolic effects of a specifically designed 'functional' bread, low in starch, rich in fibers (7 g/100 g), with a beta glucan/starch ratio of (7.6:100, g/g), in people with type 2 diabetes mellitus. Methods : Clinical and metabolic data from two groups of age-, sex- and glycated hemoglobin-matched diabetic subjects, taking either the functional bread or regular white bread, over a roughly six-month observation period, were retrieved. Bread intake did not change during the trial. The functional bread reduced glycated hemoglobin by ~0.5% (absolute units) vs. pre-treatment values ( p = 0.028), and by ~0.6% vs. the control group ( p = 0.027). Post-prandial and mean plasma glucose was decreased in the treatment group too. Body weight, blood pressure and plasma lipids did not change. The acceptance of the functional bread was good in the majority of subjects, except for taste. A starch-restricted, fiber-rich functional bread, with an increased beta glucan/starch ratio, improved long term metabolic control, and may be indicated in the dietary treatment of type 2 diabetes.

A Multifunctional Bread Rich in Beta Glucans and Low in Starch Improves Metabolic Control in Type 2 Diabetes: A Controlled Trial

Science.gov (United States)

Tessari, Paolo; Lante, Anna

2017-01-01

Design: Functional foods may be useful for people with diabetes. The soluble fibers beta glucans can modify starch digestion and improve postprandial glucose response. We analyzed the metabolic effects of a specifically designed ‘functional’ bread, low in starch, rich in fibers (7 g/100 g), with a beta glucan/starch ratio of (7.6:100, g/g), in people with type 2 diabetes mellitus. Methods: Clinical and metabolic data from two groups of age-, sex- and glycated hemoglobin-matched diabetic subjects, taking either the functional bread or regular white bread, over a roughly six-month observation period, were retrieved. Results: Bread intake did not change during the trial. The functional bread reduced glycated hemoglobin by ~0.5% (absolute units) vs. pre-treatment values (p = 0.028), and by ~0.6% vs. the control group (p = 0.027). Post-prandial and mean plasma glucose was decreased in the treatment group too. Body weight, blood pressure and plasma lipids did not change. The acceptance of the functional bread was good in the majority of subjects, except for taste. Conclusions: A starch-restricted, fiber-rich functional bread, with an increased beta glucan/starch ratio, improved long term metabolic control, and may be indicated in the dietary treatment of type 2 diabetes. PMID:28304350

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

Directory of Open Access Journals (Sweden)

Alexandre Fisette

2016-10-01

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

Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock★

Science.gov (United States)

Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.; Biensø, Rasmus S.; Tagliazucchi, Guidantonio M.; Patel, Vishal R.; Forcato, Mattia; Paz, Marcia I.P.; Gudiksen, Anders; Solagna, Francesca; Albiero, Mattia; Moretti, Irene; Eckel-Mahan, Kristin L.; Baldi, Pierre; Sassone-Corsi, Paolo; Rizzuto, Rosario; Bicciato, Silvio; Pilegaard, Henriette; Blaauw, Bert; Schiaffino, Stefano

2013-01-01

Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activity was also reduced due to altered expression of circadian genes Pdk4 and Pdp1, coding for PDH kinase and phosphatase, respectively. PDH inhibition leads to reduced glucose oxidation and diversion of glycolytic intermediates to alternative metabolic pathways, as revealed by metabolome analysis. The impaired glucose metabolism induced by muscle-specific Bmal1 knockout suggests that a major physiological role of the muscle clock is to prepare for the transition from the rest/fasting phase to the active/feeding phase, when glucose becomes the predominant fuel for skeletal muscle. PMID:24567902

LA sprouts randomized controlled nutrition and gardening program reduces obesity and metabolic risk in Latino youth.

Science.gov (United States)

Gatto, Nicole M; Martinez, Lauren C; Spruijt-Metz, Donna; Davis, Jaimie N

2015-06-01

To assess the effects of a 12-week gardening, nutrition, and cooking intervention ("LA Sprouts") on dietary intake, obesity parameters, and metabolic disease risk among low-income, primarily Hispanic/Latino youth in Los Angeles. The randomized controlled trial involved four elementary schools [two schools randomized to intervention (172 third-through fifth-grade students); two schools randomized to control (147 third-through fifth-grade students)]. Classes were taught in 90-minute sessions once a week to each grade level for 12 weeks. Data collected at pre- and postintervention included dietary intake via food frequency questionnaire (FFQ), anthropometric measures [BMI, waist circumference (WC)], body fat, and fasting blood samples. LA Sprouts participants had significantly greater reductions in BMI z-scores (0.1-vs. 0.04-point decrease, respectively; P = 0.01) and WC (-1.2 cm vs. no change; P < 0.001). Fewer LA Sprouts participants had the metabolic syndrome (MetSyn) after the intervention than before, while the number of controls with MetSyn increased. LA Sprouts participants had improvements in dietary fiber intake (+3.5% vs. -15.5%; P = 0.04) and less decreases in vegetable intake (-3.6% vs. -26.4%; P = 0.04). Change in fruit intake before and after the intervention did not significantly differ between LA Sprouts and control subjects. LA Sprouts was effective in reducing obesity and metabolic risk. © 2015 The Obesity Society.

Orphan Nuclear Receptor ERRα Controls Macrophage Metabolic Signaling and A20 Expression to Negatively Regulate TLR-Induced Inflammation.

Science.gov (United States)

Yuk, Jae-Min; Kim, Tae Sung; Kim, Soo Yeon; Lee, Hye-Mi; Han, Jeongsu; Dufour, Catherine Rosa; Kim, Jin Kyung; Jin, Hyo Sun; Yang, Chul-Su; Park, Ki-Sun; Lee, Chul-Ho; Kim, Jin-Man; Kweon, Gi Ryang; Choi, Hueng-Sik; Vanacker, Jean-Marc; Moore, David D; Giguère, Vincent; Jo, Eun-Kyeong

2015-07-21

The orphan nuclear receptor estrogen-related receptor α (ERRα; NR3B1) is a key metabolic regulator, but its function in regulating inflammation remains largely unknown. Here, we demonstrate that ERRα negatively regulates Toll-like receptor (TLR)-induced inflammation by promoting Tnfaip3 transcription and fine-tuning of metabolic reprogramming in macrophages. ERRα-deficient (Esrra(-/-)) mice showed increased susceptibility to endotoxin-induced septic shock, leading to more severe pro-inflammatory responses than control mice. ERRα regulated macrophage inflammatory responses by directly binding the promoter region of Tnfaip3, a deubiquitinating enzyme in TLR signaling. In addition, Esrra(-/-) macrophages showed an increased glycolysis, but impaired mitochondrial respiratory function and biogenesis. Further, ERRα was required for the regulation of NF-κB signaling by controlling p65 acetylation via maintenance of NAD(+) levels and sirtuin 1 activation. These findings unravel a previously unappreciated role for ERRα as a negative regulator of TLR-induced inflammatory responses through inducing Tnfaip3 transcription and controlling the metabolic reprogramming. Copyright © 2015 Elsevier Inc. All rights reserved.

Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study123

Science.gov (United States)

Lin, Xiaobo; Lefevre, Michael; Spearie, Catherine Anderson; Most, Marlene M; Ma, Lina; Ostlund, Richard E

2010-01-01

Background: Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. Objective: We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. Design: In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations. Results: Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P phytosterol dose (−8.9 ± 2.3%); a trend was observed with the 459-mg/d dose (−5.0 ± 2.1%; P = 0.077). Conclusions: Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054. PMID:19889819

Metabolic control of muscle blood flow during exercise in humans

DEFF Research Database (Denmark)

Boushel, Robert Christopher

2003-01-01

that combined blockade of NOS and PGI2, and NOS and cytochrome P450, both attenuate exercise-induced hyperemia in humans. Combined vasodilator blockade studies offer the potential to uncover important interactions and compensatory vasodilator responses. The signaling pathways that link metabolic events evoked...... to exert control of muscle vasodilation. Adenosine, nitric oxide (NO), prostacyclin (PGI2), and endothelial-derived hyperpolarization factor (EDHF) are possible mediators of muscle vasodilation during exercise. In humans, adenosine has been shown to contribute to functional hyperemia as blood flow...... by muscle contraction to vasodilatory signals in the local vascular bed remains an important area of study....

Prevalence and characteristics of metabolic syndrome in adults from the French childhood leukemia survivors’ cohort: a comparison with controls from the French population

Science.gov (United States)

Oudin, Claire; Berbis, Julie; Bertrand, Yves; Vercasson, Camille; Thomas, Frédérique; Chastagner, Pascal; Ducassou, Stéphane; Kanold, Justyna; Tabone, Marie-Dominique; Paillard, Catherine; Poirée, Marilyne; Plantaz, Dominique; Dalle, Jean-Hugues; Gandemer, Virginie; Thouvenin, Sandrine; Sirvent, Nicolas; Saultier, Paul; Béliard, Sophie; Leverger, Guy; Baruchel, André; Auquier, Pascal; Pannier, Bruno; Michel, Gérard

2018-01-01

The prevalence of the metabolic syndrome among adults from the French LEA childhood acute leukemia survivors’ cohort was prospectively evaluated considering the type of anti-leukemic treatment received, and compared with that of controls. The metabolic profile of these patients was compared with that of controls. A total of 3203 patients from a French volunteer cohort were age- and sex-matched 3:1 to 1025 leukemia survivors (in both cohorts, mean age: 24.4 years; females: 51%). Metabolic syndrome was defined according to the National Cholesterol Education Program’s Adult Treatment Panel III criteria. Metabolic syndrome was found in 10.3% of patients (mean follow-up duration: 16.3±0.2 years) and 4.5% of controls, (OR=2.49; Pmetabolic syndrome displayed a unique profile compared with controls: smaller waist circumference (91 vs. 99.6 cm; P=0.01), and increased triglyceride levels (3.99 vs. 1.5 mmol/L; Pmetabolic syndrome had a larger waist circumference (109 vs. 99.6 cm; P=0.007) than controls. Regardless of the anti-leukemic treatment, metabolic syndrome risk was higher among childhood leukemia survivors. Its presentation differed depending on the treatment type, thus suggesting a divergent pathophysiology. This study is registered at clinicaltrials.gov identifier: 01756599. PMID:29351982

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.

Cancer metabolism meets systems biology: Pyruvate kinase isoform PKM2 is a metabolic master regulator

OpenAIRE

Fabian V Filipp

2013-01-01

Pyruvate kinase activity is controlled by a tightly woven regulatory network. The oncofetal isoform of pyruvate kinase (PKM2) is a master regulator of cancer metabolism. PKM2 engages in parallel, feed-forward, positive and negative feedback control contributing to cancer progression. Besides its metabolic role, non-metabolic functions of PKM2 as protein kinase and transcriptional coactivator for c-MYC and hypoxia-inducible factor 1-alpha are essential for epidermal growth factor receptor acti...

Control of (pre-analytical aspects in immunoassay measurements of metabolic hormones in rodents

Directory of Open Access Journals (Sweden)

Maximilian Bielohuby

2018-04-01

Full Text Available The measurement of circulating hormones by immunoassay remains a cornerstone in preclinical endocrine research. For scientists conducting and interpreting immunoassay measurements of rodent samples, the paramount aim usually is to obtain reliable and meaningful measurement data in order to draw conclusions on biological processes. However, the biological variability between samples is not the only variable affecting the readout of an immunoassay measurement and a considerable amount of unwanted or unintended variability can be quickly introduced during the pre-analytical and analytical phase. This review aims to increase the awareness for the factors ‘pre-analytical’ and ‘analytical’ variability particularly in the context of immunoassay measurement of circulating metabolic hormones in rodent samples. In addition, guidance is provided how to gain control over these variables and how to avoid common pitfalls associated with sample collection, processing, storage and measurement. Furthermore, recommendations are given on how to perform a basic validation of novel single and multiplex immunoassays for the measurement of metabolic hormones in rodents. Finally, practical examples from immunoassay measurements of plasma insulin in mice address the factors ‘sampling site and inhalation anesthesia’ as frequent sources of introducing an unwanted variability during the pre-analytical phase. The knowledge about the influence of both types of variability on the immunoassay measurement of circulating hormones as well as strategies to control these variables are crucial, on the one hand, for planning and realization of metabolic rodent studies and, on the other hand, for the generation and interpretation of meaningful immunoassay data from rodent samples.

The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli.

Science.gov (United States)

Morin, Manon; Ropers, Delphine; Letisse, Fabien; Laguerre, Sandrine; Portais, Jean-Charles; Cocaign-Bousquet, Muriel; Enjalbert, Brice

2016-05-01

Metabolic control in Escherichia coli is a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation is uncertain. The post-transcriptional factor CsrA is stated as being the only regulator essential for the use of glycolytic substrates. A dozen enzymes in the central carbon metabolism (CCM) have been reported as potentially controlled by CsrA, but its impact on the CCM functioning has not been demonstrated. Here, a multiscale analysis was performed in a wild-type strain and its isogenic mutant attenuated for CsrA (including growth parameters, gene expression levels, metabolite pools, abundance of enzymes and fluxes). Data integration and regulation analysis showed a coordinated control of the expression of glycolytic enzymes. This also revealed the imbalance of metabolite pools in the csrA mutant upper glycolysis, before the phosphofructokinase PfkA step. This imbalance is associated with a glucose-phosphate stress. Restoring PfkA activity in the csrA mutant strain suppressed this stress and increased the mutant growth rate on glucose. Thus, the carbon storage regulator system is essential for the effective functioning of the upper glycolysis mainly through its control of PfkA. This work demonstrates the pivotal role of post-transcriptional regulation to shape the carbon metabolism. © 2016 John Wiley & Sons Ltd.

Energy Metabolism in the Liver

Science.gov (United States)

Rui, Liangyou

2014-01-01

The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

Hypothalamic control of energy and glucose metabolism.

Science.gov (United States)

Sisley, Stephanie; Sandoval, Darleen

2011-09-01

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

LA Sprouts Randomized Controlled Nutrition, Cooking and Gardening Program Reduces Obesity and Metabolic Risk in Latino Youth

Science.gov (United States)

Gatto, Nicole M.; Martinez, Lauren C.; Spruijt-Metz, Donna; Davis, Jaimie N.

2015-01-01

Objective To assess the effects of a 12-week gardening, nutrition, and cooking intervention (“LA Sprouts”) on dietary intake, obesity parameters and metabolic disease risk among low-income, primarily Hispanic/Latino youth in Los Angeles. Methods Randomized control trial involving four elementary schools [2 schools randomized to intervention (172, 3rd–5th grade students); 2 schools randomized to control (147, 3rd–5th grade students)]. Classes were taught in 90-minute sessions once a week to each grade level for 12 weeks. Data collected at pre- and post-intervention included dietary intake via food frequency questionnaire (FFQ), anthropometric measures [BMI, waist circumference (WC)], body fat, and fasting blood samples. Results LA Sprouts participants had significantly greater reductions in BMI z-scores (0.1 versus 0.04 point decrease, respectively; p=0.01) and WC (−1.2 cm vs. no change; p<0.001). Fewer LA Sprouts participants had the metabolic syndrome (MetSyn) after the intervention than before, while the number of controls with MetSyn increased. LA Sprouts participants had improvements in dietary fiber intake (+3.5% vs. −15.5%; p=0.04) and less decreases in vegetable intake (−3.6% vs. −26.4%; p=0.04). Change in fruit intake before and after the intervention did not significantly differ between LAS and control subjects. Conclusions LA Sprouts was effective in reducing obesity and metabolic risk. PMID:25960146

Metabolic Adaptation to Muscle Ischemia

Science.gov (United States)

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

2000-01-01

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

Association of neural tube defects in children of mothers with MTHFR 677TT genotype and abnormal carbohydrate metabolism risk: a case-control study.

Science.gov (United States)

Cadenas-Benitez, N M; Yanes-Sosa, F; Gonzalez-Meneses, A; Cerrillos, L; Acosta, D; Praena-Fernandez, J M; Neth, O; Gomez de Terreros, I; Ybot-González, P

2014-03-26

Abnormalities in maternal folate and carbohydrate metabolism have both been shown to induce neural tube defects (NTD) in humans and animal models. However, the relationship between these two factors in the development of NTDs remains unclear. Data from mothers of children with spina bifida seen at the Unidad de Espina Bífida del Hospital Infantil Virgen del Rocío (case group) were compared to mothers of healthy children with no NTD (control group) who were randomly selected from patients seen at the outpatient ward in the same hospital. There were 25 individuals in the case group and 41 in the control group. Analysis of genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with or without risk factors for abnormal carbohydrate metabolism revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism were more likely to have offspring with spina bifida and high levels of homocysteine, compared to the control group. The increased incidence of NTDs in mothers homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism stresses the need for careful metabolic screening in pregnant women, and, if necessary, determination of the MTHFR 677CT genotype in those mothers at risk of developing abnormal carbohydrate metabolism.

Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis

Science.gov (United States)

Zhang, Yumin; Liu, Gang; Yan, Jingqi; Zhang, Yalin; Li, Bo; Cai, Dongsheng

2015-01-01

Metabolic homeostasis is regulated by the brain, whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipids levels. Importantly, this function of metabolic learning requires not only the mushroom body but the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis. PMID:25848677

A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism

Directory of Open Access Journals (Sweden)

Meera Shah

2016-08-01

Full Text Available The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer.

microRNAs and lipid metabolism

Science.gov (United States)

Aryal, Binod; Singh, Abhishek K.; Rotllan, Noemi; Price, Nathan; Fernández-Hernando, Carlos

2017-01-01

Purpose of review Work over the last decade has identified the important role of microRNAs (miRNAS) in regulating lipoprotein metabolism and associated disorders including metabolic syndrome, obesity and atherosclerosis. This review summarizes the most recent findings in the field, highlighting the contribution of miRNAs in controlling low-density lipoprotein (LDL) and high-density lipoprotein (HDL) metabolism. Recent findings A number of miRNAs have emerged as important regulators of lipid metabolism, including miR-122 and miR-33. Work over the last two years has identified additional functions of miR-33 including the regulation of macrophage activation and mitochondrial metabolism. Moreover, it has recently been shown that miR-33 regulates vascular homeostasis and cardiac adaptation in response to pressure overload. In addition to miR-33 and miR-122, recent GWAS have identified single nucleotide polymorphisms (SNP) in the proximity of miRNAs genes associated with abnormal levels of circulating lipids in humans. Several of these miRNA, such as miR-148a and miR-128-1, target important proteins that regulate cellular cholesterol metabolism, including the low-density lipoprotein receptor (LDLR) and the ATP-binding cassette A1 (ABCA1). Summary microRNAs have emerged as critical regulators of cholesterol metabolism and promising therapeutic targets for treating cardiometabolic disorders including atherosclerosis. Here, we discuss the recent findings in the field highlighting the novel mechanisms by which miR-33 controls lipid metabolism and atherogenesis and the identification of novel miRNAs that regulate LDL metabolism. Finally, we summarize the recent findings that identified miR-33 as an important non-coding RNA that controls cardiovascular homeostasis independent of its role in regulating lipid metabolism. PMID:28333713

Differential effects of saturated fatty acids on the risk of metabolic syndrome: a matched case-control and meta-analysis study.

Science.gov (United States)

Yang, Wei-Sin; Chen, Pei-Chun; Hsu, Hsiu-Ching; Su, Ta-Chen; Lin, Hung-Ju; Chen, Ming-Fong; Lee, Yuan-Teh; Chien, Kuo-Liong

2018-06-01

We investigated the association between plasma saturated fatty acids (SFAs) and the risk of metabolic syndrome among ethnic Chinese adults in Taiwan who attended a health check-up center. A case-control study based on 1000 cases of metabolic syndrome and 1:1 matched control participants (mean age, 54.9 ± 10.7 y; 36% females) were recruited. Metabolic syndrome was defined according to the criteria of the International Diabetes Federation. Gas chromatography was used to measure the distribution of fatty acids in plasma (% of total fatty acids). Even-chain SFAs, including 14:0, 16:0, and 18:0, were associated with metabolic syndrome; the adjusted odds ratio [OR] and 95% confidence interval [CI] per standard deviation [SD] difference was 3.32, [1.98-5.59]; however, very-long-chain SFAs, including 20:0, 21:0, 22:0, 23:0, and 24:0, were inversely associated with metabolic syndrome. The adjusted OR [95% CI] per SD difference was 0.67 [0.58-0.78]. The area under the receiver operative characteristic curve increased from 0.814 in the basic model to 0.815 (p = 0.54, compared with the basic model), 0.818 (p metabolic syndrome, implying that SFAs are not homogenous for the effects. Copyright © 2018 Elsevier Inc. All rights reserved.

Metabolic control over the oxygen consumption flux in intact skeletal muscle: in silico studies.

Science.gov (United States)

Liguzinski, Piotr; Korzeniewski, Bernard

2006-12-01

It has been postulated previously that a direct activation of all oxidative phosphorylation complexes in parallel with the activation of ATP usage and substrate dehydrogenation (the so-called each-step activation) is the main mechanism responsible for adjusting the rate of ATP production by mitochondria to the current energy demand during rest-to-work transition in intact skeletal muscle in vivo. The present in silico study, using a computer model of oxidative phosphorylation developed previously, analyzes the impact of the each-step-activation mechanism on the distribution of control (defined within Metabolic Control Analysis) over the oxygen consumption flux among the components of the bioenergetic system in intact oxidative skeletal muscle at different energy demands. It is demonstrated that in the absence of each-step activation, the oxidative phosphorylation complexes take over from ATP usage most of the control over the respiration rate and oxidative ATP production at higher (but still physiological) energy demands. This leads to a saturation of oxidative phosphorylation, impossibility of a further acceleration of oxidative ATP synthesis, and dramatic drop in the phosphorylation potential. On the other hand, the each-step-activation mechanism allows maintenance of a high degree of the control exerted by ATP usage over the ATP turnover and oxygen consumption flux even at high energy demands and thus enables a potentially very large increase in ATP turnover. It is also shown that low oxygen concentration shifts the metabolic control from ATP usage to cytochrome oxidase and thus limits the oxidative ATP production.

Energy metabolism in the liver.

Science.gov (United States)

Rui, Liangyou

2014-01-01

The liver is an essential metabolic organ, and its metabolic function is controlled by insulin and other metabolic hormones. Glucose is converted into pyruvate through glycolysis in the cytoplasm, and pyruvate is subsequently oxidized in the mitochondria to generate ATP through the TCA cycle and oxidative phosphorylation. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and/or cholesterol esters in hepatocytes. These complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as very low-density lipoprotein particles. In the fasted state, the liver secretes glucose through both glycogenolysis and gluconeogenesis. During pronged fasting, hepatic gluconeogenesis is the primary source for endogenous glucose production. Fasting also promotes lipolysis in adipose tissue, resulting in release of nonesterified fatty acids which are converted into ketone bodies in hepatic mitochondria though β-oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver energy metabolism is tightly regulated by neuronal and hormonal signals. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis but suppresses gluconeogenesis, and glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze key steps of metabolic pathways, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases. © 2014 American Physiological Society.

Metabolic Control Analysis aimed at the ribose synthesis pathways of tumor cells: a new strategy for antitumor drug development

NARCIS (Netherlands)

Boren, Joan; Montoya, Antonio Ramos; de Atauri, Pedro; Comin-Anduix, Begoña; Cortes, Antonio; Centelles, Josep J.; Frederiks, Wilma M.; van Noorden, Cornelis J. F.; Cascante, Marta

2002-01-01

Metabolic control analysis predicts that effects on tumor growth are likely to be obtained with lower concentrations of drug, if an enzyme with a high control coefficient on tumor growth is being inhibited. Here we measure glucose-6-phosphate dehydrogenase (G6PDH) control coefficient on in vivo

Metabolic profiling reveals ethylene mediated metabolic changes and a coordinated adaptive mechanism of 'Jonagold' apple to low oxygen stress.

Science.gov (United States)

Bekele, Elias A; Beshir, Wasiye F; Hertog, Maarten L A T M; Nicolai, Bart M; Geeraerd, Annemie H

2015-11-01

Apples are predominantly stored in controlled atmosphere (CA) storage to delay ripening and prolong their storage life. Profiling the dynamics of metabolic changes during ripening and CA storage is vital for understanding the governing molecular mechanism. In this study, the dynamics of the primary metabolism of 'Jonagold' apples during ripening in regular air (RA) storage and initiation of CA storage was profiled. 1-Methylcyclopropene (1-MCP) was exploited to block ethylene receptors and to get insight into ethylene mediated metabolic changes during ripening of the fruit and in response to hypoxic stress. Metabolic changes were quantified in glycolysis, the tricarboxylic acid (TCA) cycle, the Yang cycle and synthesis of the main amino acids branching from these metabolic pathways. Partial least square discriminant analysis of the metabolic profiles of 1-MCP treated and control apples revealed a metabolic divergence in ethylene, organic acid, sugar and amino acid metabolism. During RA storage at 18°C, most amino acids were higher in 1-MCP treated apples, whereas 1-aminocyclopropane-1-carboxylic acid (ACC) was higher in the control apples. The initial response of the fruit to CA initiation was accompanied by an increase of alanine, succinate and glutamate, but a decline in aspartate. Furthermore, alanine and succinate accumulated to higher levels in control apples than 1-MCP treated apples. The observed metabolic changes in these interlinked metabolites may indicate a coordinated adaptive strategy to maximize energy production. © 2015 Scandinavian Plant Physiology Society.

Differential Effects of High-Carbohydrate and High-Fat Diet Composition on Metabolic Control and Insulin Resistance in Normal Rats

Science.gov (United States)

Ble-Castillo, Jorge L.; Aparicio-Trapala, María A.; Juárez-Rojop, Isela E.; Torres-Lopez, Jorge E.; Mendez, Jose D.; Aguilar-Mariscal, Hidemi; Olvera-Hernández, Viridiana; Palma-Cordova, Leydi C.; Diaz-Zagoya, Juan C.

2012-01-01

The macronutrient component of diets is critical for metabolic control and insulin action. The aim of this study was to compare the effects of high fat diets (HFDs) vs. high carbohydrate diets (HCDs) on metabolic control and insulin resistance in Wistar rats. Thirty animals divided into five groups (n = 6) were fed: (1) Control diet (CD); (2) High-saturated fat diet (HSFD); (3) High-unsaturated fat diet (HUFD); (4) High-digestible starch diet, (HDSD); and (5) High-resistant starch diet (HRSD) during eight weeks. HFDs and HCDs reduced weight gain in comparison with CD, however no statistical significance was reached. Calorie intake was similar in both HFDs and CD, but rats receiving HCDs showed higher calorie consumption than other groups, (p < 0.01). HRSD showed the lowest levels of serum and hepatic lipids. The HUFD induced the lowest fasting glycemia levels and HOMA-IR values. The HDSD group exhibited the highest insulin resistance and hepatic cholesterol content. In conclusion, HUFD exhibited the most beneficial effects on glycemic control meanwhile HRSD induced the highest reduction on lipid content and did not modify insulin sensitivity. In both groups, HFDs and HCDs, the diet constituents were more important factors than caloric intake for metabolic disturbance and insulin resistance. PMID:22754464

Individual differences in arsenic metabolism and lung cancer in a case-control study in Cordoba, Argentina

International Nuclear Information System (INIS)

Steinmaus, Craig; Yuan Yan; Kalman, Dave; Rey, Omar A.; Skibola, Christine F.; Dauphine, Dave; Basu, Anamika; Porter, Kristin E.; Hubbard, Alan; Bates, Michael N.; Smith, Martyn T.; Smith, Allan H.

2010-01-01

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although in most people this process is not complete. Previous studies have identified associations between the proportion of urinary MMA (%MMA) and increased risks of several arsenic-related diseases, although none of these reported on lung cancer. In this study, urinary arsenic metabolites were assessed in 45 lung cancer cases and 75 controls from arsenic-exposed areas in Cordoba, Argentina. Folate has also been linked to arsenic-disease susceptibility, thus an exploratory assessment of associations between single nucleotide polymorphisms in folate metabolizing genes, arsenic methylation, and lung cancer was also conducted. In analyses limited to subjects with metabolite concentrations above detection limits, the mean %MMA was higher in cases than in controls (17.5% versus 14.3%, p = 0.01). The lung cancer odds ratio for subjects with %MMA in the upper tertile compared to those in the lowest tertile was 3.09 (95% CI, 1.08-8.81). Although the study size was too small for a definitive conclusion, there was an indication that lung cancer risks might be highest in those with a high %MMA who also carried cystathionine β-synthase (CBS) rs234709 and rs4920037 variant alleles. This study is the first to report an association between individual differences in arsenic metabolism and lung cancer, a leading cause of arsenic-related mortality. These results add to the increasing body of evidence that variation in arsenic metabolism plays an important role in arsenic-disease susceptibility.

Cerebral metabolism and vascular reactivity during breath-hold and hypoxic challenge in freedivers and healthy controls

DEFF Research Database (Denmark)

Vestergaard, Mark B.; Larsson, Henrik B.W.

2017-01-01

blood flow (CBF) and metabolic rate of oxygen (CMRO2), and magnetic resonance spectroscopy was used to measure the cerebral lactate, glutamate+glutamine, N-acetylaspartate and phosphocreatine+creatine concentrations in the occipital lobe. Fifteen freedivers and seventeen non-diver controls participated...

Metabolic Diet App Suite for inborn errors of amino acid metabolism.

Science.gov (United States)

Ho, Gloria; Ueda, Keiko; Houben, Roderick F A; Joa, Jeff; Giezen, Alette; Cheng, Barbara; van Karnebeek, Clara D M

2016-03-01

An increasing number of rare inborn errors of metabolism (IEMs) are amenable to targeted metabolic nutrition therapy. Daily adherence is important to attain metabolic control and prevent organ damage. This is challenging however, given the lack of information of disorder specific nutrient content of foods, the limited availability and cost of specialty products as well as difficulties in reliable calculation and tracking of dietary intake and targets. To develop apps for all inborn errors of amino acid metabolism for which the mainstay of treatment is a medical diet, and obtain patient and family feedback throughout the process to incorporate this into subsequent versions. The Metabolic Diet App Suite was created with input from health care professionals as a free, user-friendly, online tool for both mobile devices and desktop computers (http://www.metabolicdietapp.org) for 15 different IEMs. General information is provided for each IEM with links to useful online resources. Nutrient information is based on the MetabolicPro™, a North American food database compiled by the Genetic Metabolic Dietitians International (GMDI) Technology committee. After user registration, a personalized dashboard and management plan including specific nutrient goals are created. Each Diet App has a user-friendly interface and the functions include: nutrient intake counts, adding your own foods and homemade recipes and, managing a daily food diary. Patient and family feedback was overall positive and specific suggestions were used to further improve the App Suite. The Metabolic Diet App Suite aids individuals affected by IEMs to track and plan their meals. Future research should evaluate its impact on patient adherence, metabolic control, quality of life and health-related outcomes. The Suite will be updated and expanded to Apps for other categories of IEMs. Finally, this Suite is a support tool only, and does not replace medical/metabolic nutrition professional advice. Copyright �

Colorectal cancer and its association with the metabolic syndrome: a Malaysian multi-centric case-control study.

Science.gov (United States)

Ulaganathan, V; Kandiah, M; Zalilah, M S; Faizal, J A; Fijeraid, H; Normayah, K; Gooi, B H; Othman, R

2012-01-01

Colorectal cancer (CRC) and the metabolic syndrome (MetS) are both on the rise in Malaysia. A multi-centric case-control study was conducted from December 2009 to January 2011 to determine any relationship between the two. Patients with confirmed CRC based on colonoscopy findings and cancer free controls from five local hospitals were assessed for MetS according to the International Diabetes Federation (IDF) definition. Each index case was matched for age, gender and ethnicity with two controls (140: 280). MetS among cases was highly prevalent (70.7%), especially among women (68.7%). MetS as an entity increased CRC risk by almost three fold independently (OR=2.61, 95%CI=1.53-4.47). In men MetS increased the risk of CRC by two fold (OR=2.01, 95%CI, 1.43-4.56), demonstrating an increasing trend in risk with the number of Mets components observed. This study provides evidence for a positive association between the metabolic syndrome and colorectal cancer. A prospective study on the Malaysian population is a high priority to confirm these findings.

Energy Metabolism in the Liver

OpenAIRE

Rui, Liangyou

2014-01-01

The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, p...

Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis.

Science.gov (United States)

Zhang, Yumin; Liu, Gang; Yan, Jingqi; Zhang, Yalin; Li, Bo; Cai, Dongsheng

2015-04-07

Metabolic homeostasis is regulated by the brain, but whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help in balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipid levels. Importantly, this function of metabolic learning requires not only the mushroom body but also the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting that the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate that the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis.

Geniposide regulates glucose-stimulated insulin secretion possibly through controlling glucose metabolism in INS-1 cells.

Directory of Open Access Journals (Sweden)

Jianhui Liu

Full Text Available Glucose-stimulated insulin secretion (GSIS is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM. Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion. Emerging evidence has suggested that other mechanisms are involved. The present study demonstrated that geniposide enhanced GSIS in response to the stimulation of low or moderately high concentrations of glucose, and promoted glucose uptake and intracellular ATP levels in INS-1 cells. However, in the presence of a high concentration of glucose, geniposide exerted a contrary role on both GSIS and glucose uptake and metabolism. Furthermore, geniposide improved the impairment of GSIS in INS-1 cells challenged with a high concentration of glucose. Further experiments showed that geniposide modulated pyruvate carboxylase expression and the production of intermediates of glucose metabolism. The data collectively suggest that geniposide has potential to prevent or improve the impairment of insulin secretion in β-cells challenged with high concentrations of glucose, likely through pyruvate carboxylase mediated glucose metabolism in β-cells.

Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics.

Science.gov (United States)

Geurts, L; Neyrinck, A M; Delzenne, N M; Knauf, C; Cani, P D

2014-03-01

Crosstalk between organs is crucial for controlling numerous homeostatic systems (e.g. energy balance, glucose metabolism and immunity). Several pathological conditions, such as obesity and type 2 diabetes, are characterised by a loss of or excessive inter-organ communication that contributes to the development of disease. Recently, we and others have identified several mechanisms linking the gut microbiota with the development of obesity and associated disorders (e.g. insulin resistance, type 2 diabetes, hepatic steatosis). Among these, we described the concept of metabolic endotoxaemia (increase in plasma lipopolysaccharide levels) as one of the triggering factors leading to the development of metabolic inflammation and insulin resistance. Growing evidence suggests that gut microbes contribute to the onset of low-grade inflammation characterising these metabolic disorders via mechanisms associated with gut barrier dysfunctions. We have demonstrated that enteroendocrine cells (producing glucagon-like peptide-1, peptide YY and glucagon-like peptide-2) and the endocannabinoid system control gut permeability and metabolic endotoxaemia. Recently, we hypothesised that specific metabolic dysregulations occurring at the level of numerous organs (e.g. gut, adipose tissue, muscles, liver and brain) rely from gut microbiota modifications. In this review, we discuss the mechanisms linking gut permeability, adipose tissue metabolism, and glucose homeostasis, and recent findings that show interactions between the gut microbiota, the endocannabinoid system and the apelinergic system. These specific systems are discussed in the context of the gut-to-peripheral organ axis (intestine, adipose tissue and brain) and impacts on metabolic regulation. In the present review, we also briefly describe the impact of a variety of non-digestible nutrients (i.e. inulin-type fructans, arabinoxylans, chitin glucans and polyphenols). Their effects on the composition of the gut microbiota and

A structured approach to the study of metabolic control principles in intact and impaired mitochondria.

Science.gov (United States)

Huber, Heinrich J; Connolly, Niamh M C; Dussmann, Heiko; Prehn, Jochen H M

2012-03-01

We devised an approach to extract control principles of cellular bioenergetics for intact and impaired mitochondria from ODE-based models and applied it to a recently established bioenergetic model of cancer cells. The approach used two methods for varying ODE model parameters to determine those model components that, either alone or in combination with other components, most decisively regulated bioenergetic state variables. We found that, while polarisation of the mitochondrial membrane potential (ΔΨ(m)) and, therefore, the protomotive force were critically determined by respiratory complex I activity in healthy mitochondria, complex III activity was dominant for ΔΨ(m) during conditions of cytochrome-c deficiency. As a further important result, cellular bioenergetics in healthy, ATP-producing mitochondria was regulated by three parameter clusters that describe (1) mitochondrial respiration, (2) ATP production and consumption and (3) coupling of ATP-production and respiration. These parameter clusters resembled metabolic blocks and their intermediaries from top-down control analyses. However, parameter clusters changed significantly when cells changed from low to high ATP levels or when mitochondria were considered to be impaired by loss of cytochrome-c. This change suggests that the assumption of static metabolic blocks by conventional top-down control analyses is not valid under these conditions. Our approach is complementary to both ODE and top-down control analysis approaches and allows a better insight into cellular bioenergetics and its pathological alterations.

Metabolic anatomy of paraneoplastic cerebellar degeneration

International Nuclear Information System (INIS)

Anderson, N.E.; Posner, J.B.; Sidtis, J.J.; Moeller, J.R.; Strother, S.C.; Dhawan, V.; Rottenberg, D.A.

1988-01-01

Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration [PCD]) were evaluated using neuropsychological tests and 18 F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a reverse cerebellar diaschisis

Presumptive binge eating disorder in type 2 diabetes mellitus patients and its effect in metabolic control

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Sandra Soares Melo

2009-09-01

Full Text Available Objective: This study sought to determine the presence of diagnosis suggestive of binge eating disorder in individuals with type 2 diabetes mellitus, and to evaluate the influence of such disorder on the metabolic control. Methods: sixty-three patients with type 2 diabetes mellitus and registered  at the Diabetes and Hypertension Program of a Health Unit in the town of Balneário Camboriú, Santa Catarina, Brazil, were evaluated. The diagnosis of binge eating disorder was made by analysis of the Questionnaire on Eating and Weight Patterms – Revised. For the evaluation of metabolic control, 10 ml of blood was collected, and the serum glucose, glycated hemoglobin, tryglicerides, cholestrol and fractions were determined. Weight and height were determined for evaluation of national nutritional state, according to the body mass index. Rresults: Among the evaluated individuals, 29% presented a diagnosis suggestive of binge eating disorder, with higher prevalence among females. The individuals with diagnosis suggestive of binge eating disorder presented a higher average body mass index value than the group without diagnosis. The serum concentrations of glycated hemoglobin (p = 0.02 and triglicerides (p = 0.03 were statistically higher in the group with diagnosis suggestive of binge eating disorder. Cconclusions: Based on the results of this study, it is possible to conclude that the presence of binge eating disorder in individuals with type 2 diabetes mellitus favors an increase in body weight and has a negative influence on metabolic control, contributing to the early emergence of complications related to the disease.

Metabolic effects of resistance or high-intensity interval training among glycemic control-nonresponsive children with insulin resistance.

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Álvarez, C; Ramírez-Campillo, R; Ramírez-Vélez, R; Martínez, C; Castro-Sepúlveda, M; Alonso-Martínez, A; Izquierdo, M

2018-01-01

Little evidence exists on which variables of body composition or muscular strength mediates more glucose control improvements taking into account inter-individual metabolic variability to different modes of exercise training. We examined 'mediators' to the effects of 6-weeks of resistance training (RT) or high-intensity interval training (HIT) on glucose control parameters in physically inactive schoolchildren with insulin resistance (IR). Second, we also determined both training-induce changes and the prevalence of responders (R) and non-responders (NR) to decrease the IR level. Fifty-six physically inactive children diagnosed with IR followed a RT or supervised HIT program for 6 weeks. Participants were classified based on ΔHOMA-IR into glycemic control R (decrease in homeostasis model assessment-IR (HOMA-IR) training-induced changes to glucose control parameters; and third the report of R and NR to improve body composition, cardiovascular, metabolic and performance variables. Mediation analysis revealed that improvements (decreases) in abdominal fat by the waist circumference can explain more the effects (decreases) of HOMA-IR in physically inactive schoolchildren under RT or HIT regimes. The same analysis showed that increased one-maximum repetition leg-extension was correlated with the change in HOMA-IR (β=-0.058; P=0.049). Furthermore, a change in the waist circumference fully mediated the dose-response relationship between changes in the leg-extension strength and HOMA-IR (β'=-0.004; P=0.178). RT or HIT were associated with significant improvements in body composition, muscular strength, blood pressure and cardiometabolic parameters irrespective of improvement in glycemic control response. Both glucose control RT-R and HIT-R (respectively), had significant improvements in mean HOMA-IR, mean muscular strength leg-extension and mean measures of adiposity. The improvements in the lower body strength and the decreases in waist circumference can explain more

A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism.

Science.gov (United States)

Shah, Meera; Su, Dan; Scheliga, Judith S; Pluskal, Tomáš; Boronat, Susanna; Motamedchaboki, Khatereh; Campos, Alexandre Rosa; Qi, Feng; Hidalgo, Elena; Yanagida, Mitsuhiro; Wolf, Dieter A

2016-08-16

The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Population-based family case-control proband study on familial aggregation of metabolic syndrome: finding from Taiwanese people involved in Keelung community-based integrated screening (KCIS no. 5).

Science.gov (United States)

Chiu, Yueh-Hsia; Lin, Wen-Yuan; Wang, Po-En; Chen, Yao-Der; Wang, Ting-Ting; Warwick, Jane; Chen, Tony Hsiu-Hsi

2007-03-01

A population-based case-control proband study was undertaken to elucidate familial aggregation, independent environmental factors, and the interaction between them. A total of 7308 metabolic syndrome (MET-S) cases were identified from the Keelung community-based integrated screening programme between 1999 and 2002. The study has a case-control/family sampling design. A total of 1417 case probands were randomly selected from 3225 metabolic syndrome cases and the corresponding 2458 controls selected from 16,519 subjects without metabolic syndrome by matching on sex, age (+/-3 years) and place of residence. The generalized estimation equation model was used to estimate odds ratios and corresponding 95% confidence intervals. The risk for having metabolic syndrome among family members for cases versus control probands was 1.56-fold (1.29-1.89) after controlling for significant environmental factors. Higher risk of metabolic syndrome was found in parents than spouse. Low education against high education had 2.06-fold (1.36-3.13) risk for metabolic syndrome. Betel quid chewing was positively associated with the risk of MET-S, with 1.99-fold (1.13-3.53) risk for 1-9 pieces and 1.76-fold (0.96-3.23) risk for >or=10 pieces compared with non-chewer. Moderate and high intensity of non-occupational exercise led to 21.0% (OR=0.79 (0.63-0.98)) and 26.0% (OR=0.74 (0.59-0.94)) reduction in the risk for metabolic syndrome, respectively. The frequent consumption of vegetable reduced 24.0% (OR=0.76 (0.62-0.92)) risk for MET-S. The frequent consumption of coffee was associated the increased risk for metabolic syndrome (OR=1.32 (1.07-1.64)). The present study confirmed the risk of metabolic syndrome not only has the tendency towards familial aggregation but is affected by independent effect of environmental or individual correlates.

Role of parenting style in achieving metabolic control in adolescents with type 1 diabetes.

Science.gov (United States)

Shorer, Maayan; David, Ravit; Schoenberg-Taz, Michal; Levavi-Lavi, Ifat; Phillip, Moshe; Meyerovitch, Joseph

2011-08-01

To examine the role of parenting style in achieving metabolic control and treatment adherence in adolescents with type 1 diabetes. Parents of 100 adolescents with type 1 diabetes completed assessments of their parenting style and sense of helplessness. Parents and patients rated patient adherence to the treatment regimen. Glycemic control was evaluated by HbA(1c) values. An authoritative paternal parenting style predicted better glycemic control and adherence in the child; a permissive maternal parenting style predicted poor adherence. A higher sense of helplessness in both parents predicted worse glycemic control and lesser adherence to treatment. Parental sense of helplessness was a significant predictor of diabetes control after correcting for other confounders (patient age, sex, and treatment method). An authoritative nonhelpless parenting style is associated with better diabetes control in adolescents. Paternal involvement is important in adolescent diabetes management. These results have implications for psychological interventions.

Risk of metabolic syndrome among children living in metropolitan Kuala Lumpur: A case control study

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Ismail Mohd N

2011-05-01

Full Text Available Abstract Background With the increasing prevalence of childhood obesity, the metabolic syndrome has been studied among children in many countries but not in Malaysia. Hence, this study aimed to compare metabolic risk factors between overweight/obese and normal weight children and to determine the influence of gender and ethnicity on the metabolic syndrome among school children aged 9-12 years in Kuala Lumpur and its metropolitan suburbs. Methods A case control study was conducted among 402 children, comprising 193 normal-weight and 209 overweight/obese. Weight, height, waist circumference (WC and body composition were measured, and WHO (2007 growth reference was used to categorise children into the two weight groups. Blood pressure (BP was taken, and blood was drawn after an overnight fast to determine fasting blood glucose (FBG and full lipid profile, including triglycerides (TG, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol (LDL-C and total cholesterol (TC. International Diabetes Federation (2007 criteria for children were used to identify metabolic syndrome. Results Participants comprised 60.9% (n = 245 Malay, 30.9% (n = 124 Chinese and 8.2% (n = 33 Indian. Overweight/obese children showed significantly poorer biochemical profile, higher body fat percentage and anthropometric characteristics compared to the normal-weight group. Among the metabolic risk factors, WC ≥90th percentile was found to have the highest odds (OR = 189.0; 95%CI 70.8, 504.8, followed by HDL-C≤1.03 mmol/L (OR = 5.0; 95%CI 2.4, 11.1 and high BP (OR = 4.2; 95%CI 1.3, 18.7. Metabolic syndrome was found in 5.3% of the overweight/obese children but none of the normal-weight children (p Conclusions We conclude that being overweight or obese poses a greater risk of developing the metabolic syndrome among children. Indian ethnicity is at higher risk compared to their counterparts of the same age. Hence, primary intervention strategies are

[Risk factors for metabolic syndrome in a case control study in Temuco, Chile].

Science.gov (United States)

Philco L, Patricia; Serón S, Pamela; Muñoz N, Sergio; Navia B, Pilar; Lanas Z, Fernando

2012-03-01

Metabolic syndrome is becoming an important public health problem in affluent societies. To identify factors associated to metabolic syndrome in a Southern Chilean city. Using a case control design, 200 participants, aged 35 to 70 years with at least three criteria for metabolic syndrome according to the National Cholesterol Education Program (NCEP_ATPIII) and 200 subjects with less than three criteria, were studied. Both groups were compared in terms of ethnic background, educational level, family history of diabetes and coronary artery disease, menopausal status, smoking, stress and depression, physical activity, changes in body mass index in the last five years and diet. Among subjects aged more than 54 years, among males and among overweight individuals, having a Mapuche origin was a risk factor with odds ratios (OR) of 7.2; 88 and 3.9 respectively. Among subjects aged more than 54 years, among women and among overweight individuals, a family history of diabetes was a risk factor with OR of 17.7; 3.2 and 3.9 respectively. Among subjects aged more than 54 years and among women a change in body mass index of more than three points was a risk factor with OR of 12.5 and 7.4, respectively. Depression also was a risk factor among subjects aged more than 54 years (OR 3.3). Regular consumption of wine was a protective factor among participants of more than 54 years, with an OR of 0.17. The risk factors for metabolic syndrome detected in this group of participants, were having a Mapuche origin, a family history of diabetes mellitus and depression. Wine consumption was associated with a lower risk.

Comparative genomics of metabolic capacities of regulons controlled by cis-regulatory RNA motifs in bacteria.

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Sun, Eric I; Leyn, Semen A; Kazanov, Marat D; Saier, Milton H; Novichkov, Pavel S; Rodionov, Dmitry A

2013-09-02

In silico comparative genomics approaches have been efficiently used for functional prediction and reconstruction of metabolic and regulatory networks. Riboswitches are metabolite-sensing structures often found in bacterial mRNA leaders controlling gene expression on transcriptional or translational levels.An increasing number of riboswitches and other cis-regulatory RNAs have been recently classified into numerous RNA families in the Rfam database. High conservation of these RNA motifs provides a unique advantage for their genomic identification and comparative analysis. A comparative genomics approach implemented in the RegPredict tool was used for reconstruction and functional annotation of regulons controlled by RNAs from 43 Rfam families in diverse taxonomic groups of Bacteria. The inferred regulons include ~5200 cis-regulatory RNAs and more than 12000 target genes in 255 microbial genomes. All predicted RNA-regulated genes were classified into specific and overall functional categories. Analysis of taxonomic distribution of these categories allowed us to establish major functional preferences for each analyzed cis-regulatory RNA motif family. Overall, most RNA motif regulons showed predictable functional content in accordance with their experimentally established effector ligands. Our results suggest that some RNA motifs (including thiamin pyrophosphate and cobalamin riboswitches that control the cofactor metabolism) are widespread and likely originated from the last common ancestor of all bacteria. However, many more analyzed RNA motifs are restricted to a narrow taxonomic group of bacteria and likely represent more recent evolutionary innovations. The reconstructed regulatory networks for major known RNA motifs substantially expand the existing knowledge of transcriptional regulation in bacteria. The inferred regulons can be used for genetic experiments, functional annotations of genes, metabolic reconstruction and evolutionary analysis. The obtained genome

Effect of growth regulators on 'Brookfield' apple gas diffusion and metabolism under controlled atmosphere storage

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Auri Brackmann

2014-05-01

Full Text Available The objective of this work was to evaluate the effect of growth regulators on gas diffusion and on metabolism of 'Brookfield' apple, and to determine their correlation with quality characteristics of fruit stored in controlled atmosphere. A completely randomized design was used with four replicates. After eight months of storage, the effects of water (control, aminoethoxyvinylglycine (AVG, AVG + ethephon, AVG + naphthaleneacetic acid (NAA, ethephon + NAA, sole NAA, 1-MCP, ethylene absorption by potassium permanganate (ABS, AVG + ABS, and of AVG + 1-MCP - applied at different rates and periods - were evaluated on: gas diffusion rate, ethylene production, respiratory rate, internal ethylene concentration, internal CO2 content, mealiness, and intercellular space. Fruit from the control and sole NAA treatments had the highest mealiness occurrence. Growth regulators significantly changed the gaseous diffusion through the pulp of 'Brookfield' apple, mainly in the treatment AVG + ABS, which kept the highest gas diffusion rate. NAA spraying in the field, with or without another growth regulator, increased ripening metabolism by rising ethylene production and respiration rate, and reduced gas diffusion during shelf life. AVG spraying cannot avoid the ethephon effect during the ripening process, and reduces both the internal space and mealiness incidence, but it is not able to induce ethylene production or to increase respiration rates.

Metabolic Syndrome and Breast Cancer Risk.

Science.gov (United States)

Wani, Burhan; Aziz, Shiekh Aejaz; Ganaie, Mohammad Ashraf; Mir, Mohammad Hussain

2017-01-01

The study was meant to estimate the prevalence of metabolic syndrome in patients with breast cancer and to establish its role as an independent risk factor on occurrence of breast cancer. Fifty women aged between 40 and 80 years with breast cancer and fifty controls of similar age were assessed for metabolic syndrome prevalence and breast cancer risk factors, including age at menarche, reproductive status, live births, breastfeeding, and family history of breast cancer, age at diagnosis of breast cancer, body mass index, and metabolic syndrome parameters. Metabolic syndrome prevalence was found in 40.0% of breast cancer patients, and 18.0% of those in control group ( P = 0.02). An independent and positive association was seen between metabolic syndrome and breast cancer risk (odds ratio = 3.037; 95% confidence interval 1.214-7.597). Metabolic syndrome is more prevalent in breast cancer patients and is an independent risk factor for breast cancer.

Nucleotide Metabolism and its Control in Lactic Acid Bacteria

DEFF Research Database (Denmark)

Kilstrup, Mogens; Hammer, Karin; Jensen, Peter Ruhdal

2005-01-01

Most metabolic reactions are connected through either their utilization of nucleotides or their utilization of nucleotides or their regulation by these metabolites. In this review the biosynthetic pathways for pyrimidine and purine metabolism in lactic acid bacteria are described including...... the interconversion pathways, the formation of deoxyribonucleotides and the salvage pathways for use of exogenous precursors. The data for the enzymatic and the genetic regulation of these pathways are reviewed, as well as the gene organizations in different lactic acid bacteria. Mutant phenotypes and methods...... for manipulation of nucleotide pools are also discussed. Our aim is to provide an overview of the physiology and genetics of nucleotide metabolism and its regulation that will facilitate the interpretation of data arising from genetics, metabolomics, proteomics, and transcriptomics in lactic acid bacteria....

Risk of metabolic syndrome among children living in metropolitan Kuala Lumpur: a case control study.

Science.gov (United States)

Wee, Bee S; Poh, Bee K; Bulgiba, Awang; Ismail, Mohd N; Ruzita, Abdul T; Hills, Andrew P

2011-05-18

With the increasing prevalence of childhood obesity, the metabolic syndrome has been studied among children in many countries but not in Malaysia. Hence, this study aimed to compare metabolic risk factors between overweight/obese and normal weight children and to determine the influence of gender and ethnicity on the metabolic syndrome among school children aged 9-12 years in Kuala Lumpur and its metropolitan suburbs. A case control study was conducted among 402 children, comprising 193 normal-weight and 209 overweight/obese. Weight, height, waist circumference (WC) and body composition were measured, and WHO (2007) growth reference was used to categorise children into the two weight groups. Blood pressure (BP) was taken, and blood was drawn after an overnight fast to determine fasting blood glucose (FBG) and full lipid profile, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). International Diabetes Federation (2007) criteria for children were used to identify metabolic syndrome. Participants comprised 60.9% (n = 245) Malay, 30.9% (n = 124) Chinese and 8.2% (n = 33) Indian. Overweight/obese children showed significantly poorer biochemical profile, higher body fat percentage and anthropometric characteristics compared to the normal-weight group. Among the metabolic risk factors, WC ≥90th percentile was found to have the highest odds (OR = 189.0; 95%CI 70.8, 504.8), followed by HDL-C≤1.03 mmol/L (OR = 5.0; 95%CI 2.4, 11.1) and high BP (OR = 4.2; 95%CI 1.3, 18.7). Metabolic syndrome was found in 5.3% of the overweight/obese children but none of the normal-weight children (p < 0.01). Overweight/obese children had higher odds (OR = 16.3; 95%CI 2.2, 461.1) of developing the metabolic syndrome compared to normal-weight children. Binary logistic regression showed no significant association between age, gender and family history of communicable diseases with the metabolic

mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation.

Science.gov (United States)

Sinclair, Charles; Bommakanti, Gayathri; Gardinassi, Luiz; Loebbermann, Jens; Johnson, Matthew Joseph; Hakimpour, Paul; Hagan, Thomas; Benitez, Lydia; Todor, Andrei; Machiah, Deepa; Oriss, Timothy; Ray, Anuradha; Bosinger, Steven; Ravindran, Rajesh; Li, Shuzhao; Pulendran, Bali

2017-09-08

Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working with mouse models of inflammation, we found that mechanistic target of rapamycin (mTOR)-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for dendritic cell (DC) homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103 + DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b + DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic T helper cell 2 (T H 2) to neutrophilic T H 17 polarity. The mechanism for this change was independent of translational control but dependent on inflammatory DCs, which produced interleukin-23 and increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

A real-time control system of gene expression using ligand-bound nucleic acid aptamer for metabolic engineering.

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Wang, Jing; Cui, Xun; Yang, Le; Zhang, Zhe; Lv, Liping; Wang, Haoyuan; Zhao, Zhenmin; Guan, Ningzi; Dong, Lichun; Chen, Rachel

2017-07-01

Artificial control of bio-functions through regulating gene expression is one of the most important and attractive technologies to build novel living systems that are useful in the areas of chemical synthesis, nanotechnology, pharmacology, cell biology. Here, we present a novel real-time control system of gene regulation that includes an enhancement element by introducing duplex DNA aptamers upstream promoter and a repression element by introducing a RNA aptamer upstream ribosome binding site. With the presence of ligands corresponding to the DNA aptamers, the expression of the target gene can be potentially enhanced at the transcriptional level by strengthening the recognition capability of RNAP to the recognition region and speeding up the separation efficiency of the unwinding region due to the induced DNA bubble around the thrombin-bound aptamers; while with the presence of RNA aptamer ligand, the gene expression can be repressed at the translational level by weakening the recognition capability of ribosome to RBS due to the shielding of RBS by the formed aptamer-ligand complex upstream RBS. The effectiveness and potential utility of the developed gene regulation system were demonstrated by regulating the expression of ecaA gene in the cell-free systems. The realistic metabolic engineering application of the system has also tested by regulating the expression of mgtC gene and thrombin cDNA in Escherichia coli JD1021 for controlling metabolic flux and improving thrombin production, verifying that the real-time control system of gene regulation is able to realize the dynamic regulation of gene expression with potential applications in bacterial physiology studies and metabolic engineering. Copyright © 2017. Published by Elsevier Inc.

Programming Post-Translational Control over the Metabolic Labeling of Cellular Proteins with a Noncanonical Amino Acid.

Science.gov (United States)

Thomas, Emily E; Pandey, Naresh; Knudsen, Sarah; Ball, Zachary T; Silberg, Jonathan J

2017-08-18

Transcriptional control can be used to program cells to label proteins with noncanonical amino acids by regulating the expression of orthogonal aminoacyl tRNA synthetases (aaRSs). However, we cannot yet program cells to control labeling in response to aaRS and ligand binding. To identify aaRSs whose activities can be regulated by interactions with ligands, we used a combinatorial approach to discover fragmented variants of Escherichia coli methionyl tRNA synthetase (MetRS) that require fusion to associating proteins for maximal activity. We found that these split proteins could be leveraged to create ligand-dependent MetRS using two approaches. When a pair of MetRS fragments was fused to FKBP12 and the FKBP-rapamycin binding domain (FRB) of mTOR and mutations were introduced that direct substrate specificity toward azidonorleucine (Anl), Anl metabolic labeling was significantly enhanced in growth medium containing rapamycin, which stabilizes the FKBP12-FRB complex. In addition, fusion of MetRS fragments to the termini of the ligand-binding domain of the estrogen receptor yielded proteins whose Anl metabolic labeling was significantly enhanced when 4-hydroxytamoxifen (4-HT) was added to the growth medium. These findings suggest that split MetRS can be fused to a range of ligand-binding proteins to create aaRSs whose metabolic labeling activities depend upon post-translational interactions with ligands.

The role of tryptophan 2,3-dioxygenase in the hormonal control of tryptophan metabolism in isolated rat liver cells. Effects of glucocorticoids and experimental diabetes.

OpenAIRE

Salter, M; Pogson, C I

1985-01-01

The metabolism of L-tryptophan by isolated liver cells prepared from control, adrenalectomized, glucocorticoid-treated, acute-diabetic, chronic-diabetic and insulin-treated chronic-diabetic rats was studied. Liver cells from adrenalectomized rats metabolized tryptophan at rates comparable with the minimum diurnal rates of controls, but different from rates determined for cells from control rats 4h later. Administration of dexamethasone phosphate increased the activity of tryptophan 2,3-dioxyg...

Correlation between resting state fMRI total neuronal activity and PET metabolism in healthy controls and patients with disorders of consciousness.

Science.gov (United States)

Soddu, Andrea; Gómez, Francisco; Heine, Lizette; Di Perri, Carol; Bahri, Mohamed Ali; Voss, Henning U; Bruno, Marie-Aurélie; Vanhaudenhuyse, Audrey; Phillips, Christophe; Demertzi, Athena; Chatelle, Camille; Schrouff, Jessica; Thibaut, Aurore; Charland-Verville, Vanessa; Noirhomme, Quentin; Salmon, Eric; Tshibanda, Jean-Flory Luaba; Schiff, Nicholas D; Laureys, Steven

2016-01-01

The mildly invasive 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established imaging technique to measure 'resting state' cerebral metabolism. This technique made it possible to assess changes in metabolic activity in clinical applications, such as the study of severe brain injury and disorders of consciousness. We assessed the possibility of creating functional MRI activity maps, which could estimate the relative levels of activity in FDG-PET cerebral metabolic maps. If no metabolic absolute measures can be extracted, our approach may still be of clinical use in centers without access to FDG-PET. It also overcomes the problem of recognizing individual networks of independent component selection in functional magnetic resonance imaging (fMRI) resting state analysis. We extracted resting state fMRI functional connectivity maps using independent component analysis and combined only components of neuronal origin. To assess neuronality of components a classification based on support vector machine (SVM) was used. We compared the generated maps with the FDG-PET maps in 16 healthy controls, 11 vegetative state/unresponsive wakefulness syndrome patients and four locked-in patients. The results show a significant similarity with ρ = 0.75 ± 0.05 for healthy controls and ρ = 0.58 ± 0.09 for vegetative state/unresponsive wakefulness syndrome patients between the FDG-PET and the fMRI based maps. FDG-PET, fMRI neuronal maps, and the conjunction analysis show decreases in frontoparietal and medial regions in vegetative patients with respect to controls. Subsequent analysis in locked-in syndrome patients produced also consistent maps with healthy controls. The constructed resting state fMRI functional connectivity map points toward the possibility for fMRI resting state to estimate relative levels of activity in a metabolic map.

The carbon storage regulator (Csr) system exerts a nutrient-specific control over central metabolism in Escherichia coli strain Nissle 1917.

Science.gov (United States)

Revelles, Olga; Millard, Pierre; Nougayrède, Jean-Philippe; Dobrindt, Ulrich; Oswald, Eric; Létisse, Fabien; Portais, Jean-Charles

2013-01-01

The role of the post-transcriptional carbon storage regulator (Csr) system in nutrient utilization and in the control of the central metabolism in E. coli reference commensal strain Nissle 1917 was investigated. Analysis of the growth capabilities of mutants altered for various components of the Csr system (csrA51, csrB, csrC and csrD mutations) showed that only the protein CsrA - the key component of the system - exerts a marked role in carbon nutrition. Attenuation of CsrA activity in the csrA51 mutant affects the growth efficiency on a broad range of physiologically relevant carbon sources, including compounds utilized by the Entner-Doudoroff (ED) pathway. Detailed investigations of the metabolomes and fluxomes of mutants and wild-type cells grown on carbon sources representative of glycolysis and of the ED pathway (glucose and gluconate, respectively), revealed significant re-adjusting of central carbon metabolism for both compounds in the csrA51 mutant. However, the metabolic re-adjusting observed on gluconate was strikingly different from that observed on glucose, indicating a nutrient-specific control of metabolism by the Csr system.

Plasma proteome profiles associated with diet-induced metabolic syndrome and the early onset of metabolic syndrome in a pig model.

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Marinus F W te Pas

Full Text Available Obesity and related diabetes are important health threatening multifactorial metabolic diseases and it has been suggested that 25% of all diabetic patients are unaware of their patho-physiological condition. Biomarkers for monitoring and control are available, but early stage predictive biomarkers enabling prevention of these diseases are still lacking. We used the pig as a model to study metabolic disease because humans and pigs share a multitude of metabolic similarities. Diabetes was chemically induced and control and diabetic pigs were either fed a high unsaturated fat (Mediterranean diet or a high saturated fat/cholesterol/sugar (cafeteria diet. Physiological parameters related to fat metabolism and diabetes were measured. Diabetic pigs' plasma proteome profiles differed more between the two diets than control pigs plasma proteome profiles. The expression levels of several proteins correlated well with (pathophysiological parameters related to the fat metabolism (cholesterol, VLDL, LDL, NEFA and diabetes (Glucose and to the diet fed to the animals. Studying only the control pigs as a model for metabolic syndrome when fed the two diets showed correlations to the same parameters but now more focused on insulin, glucose and abdominal fat depot parameters. We conclude that proteomic profiles can be used as a biomarker to identify pigs with developing metabolic syndrome (prediabetes and diabetes when fed a cafeteria diet. It could be developed into a potential biomarkers for the early recognition of metabolic diseases.

Association between Two Resistin Gene Polymorphisms and Metabolic Syndrome in Jilin, Northeast China: A Case-Control Study

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Yingli Fu

2017-01-01

Full Text Available Metabolic syndrome (MetS is a significant health care problem worldwide and is characterized by increased fasting glucose and obesity. Resistin is a protein hormone produced both by adipocytes and immunocompetent cells, including those residing in adipose tissue, and is believed to modulate glucose tolerance and insulin action. This study examined the association of resistin gene polymorphisms, rs1862513 and rs3745368, and related haplotypes with the development of metabolic syndrome in a Han Chinese population. This case-control study was performed on 3792 subjects, including 1771 MetS cases and 2021 healthy controls from the Jilin province of China. Metabolic syndrome was defined according to the criteria of the International Diabetes Federation (IDF. Logistic regression analysis was used to estimate the relationship between gene polymorphism and MetS. Our results showed that there were no significant associations between MetS and the genotype distributions in four kinds of inheritance models, allele frequencies, and related haplotypes of resistin gene polymorphisms rs1862513 and rs3745368 (all p values > 0.05. Based on our study findings, we concluded that mutations in resistin genes are not associated with the presence of MetS in a Han Chinese population from Jilin province in China.

A Controlled Trial of CPAP Therapy on Metabolic Control in Individuals with Impaired Glucose Tolerance and Sleep Apnea

Science.gov (United States)

Weinstock, Tanya G.; Wang, Xuelei; Rueschman, Michael; Ismail-Beigi, Faramarz; Aylor, Joan; Babineau, Denise C.; Mehra, Reena; Redline, Susan

2012-01-01

Study Objectives: To address whether treatment of sleep apnea improves glucose tolerance. Design: Randomized, double-blind crossover study. Setting: Sleep clinic referrals. Patients: 50 subjects with moderate to severe sleep apnea (AHI > 15) and impaired glucose tolerance. Interventions: Subjects were randomized to 8 weeks of CPAP or sham CPAP, followed by the alternate therapy after a one-month washout. After each treatment, subjects underwent 2-hour OGTT, polysomnography, actigraphy, and measurements of indices of glucose control. Measurements and Results: The primary outcome was normalization of the mean 2-h OGTT; a secondary outcome was improvement in the Insulin Sensitivity Index (ISI (0,120). Subjects were 42% men, mean age of 54 (10), BMI of 39 (8), and AHI of 44 (27). Baseline fasting glucose was 104 (12), and mean 2-h OGTT was 110 (57) mg/dL. Seven subjects normalized their mean 2-h OGTT after CPAP but not after sham CPAP, while 5 subjects normalized after sham CPAP but not after CPAP. Overall, there was no improvement in ISI (0,120) between CPAP and sham CPAP (3.6%; 95% CI: [-2.2%, 9.7%]; P = 0.22). However, in those subjects with baseline AHI ≥ 30 (n = 25), there was a 13.3% (95% CI: [5.2%, 22.1%]; P CPAP compared to sham CPAP. Conclusions: This study did not show that IGT normalizes after CPAP in subjects with moderate sleep apnea and obesity. However, insulin sensitivity improved in those with AHI ≥ 30, suggesting beneficial metabolic effects of CPAP in severe sleep apnea. Clinical Trials Information: ClinicalTrials.gov Identifier: NCT01385995. Citation: Weinstock TG; Wang X; Rueschman M; Ismail-Beigi F; Aylor J; Babineau DC; Mehra R; Redline S. A controlled trial of CPAP therapy on metabolic control in individuals with impaired glucose tolerance and sleep apnea. SLEEP 2012;35(5):617-625. PMID:22547887

Artificial Promoters for Metabolic Optimization

DEFF Research Database (Denmark)

Jensen, Peter Ruhdal; Hammer, Karin

1998-01-01

In this article, we review some of the expression systems that are available for Metabolic Control Analysis and Metabolic Engineering, and examine their advantages and disadvantages in different contexts. In a recent approach, artificial promoters for modulating gene expression in micro-organisms...

Hypothyroidism in metabolic syndrome

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Sunil Kumar Kota

2012-01-01

Full Text Available Aim: Metabolic syndrome (MetS and hypothyroidism are well established forerunners of atherogenic cardiovascular disease. Considerable overlap occurs in the pathogenic mechanisms of atherosclerotic cardiovascular disease by metabolic syndrome and hypothyroidism. Insulin resistance has been studied as the basic pathogenic mechanism in metabolic syndrome. [1] This cross sectional study intended to assess thyroid function in patients with metabolic syndrome and to investigate the association between hypothyroidism and metabolic syndrome. Materials and Methods: One hundred patients with metabolic syndrome who fulfilled the National Cholesterol Education Program- Adult Treatment Panel (NCEP-ATP III criteria [ 3 out of 5 criteria positive namely blood pressure ≥ 130/85 mm hg or on antihypertensive medications, fasting plasma glucose > 100 mg/dl or on anti-diabetic medications, fasting triglycerides > 150 mg/dl, high density lipoprotein cholesterol (HDL-C 102 cms in men and 88 cms in women] were included in the study group. [2] Fifty patients who had no features of metabolic syndrome (0 out of 5 criteria for metabolic syndrome were included in the control group. Patients with liver disorders, renal disorders, congestive cardiac failure, pregnant women, patients on oral contraceptive pills, statins and other medications that alter thyroid functions and lipid levels and those who are under treatment for any thyroid related disorder were excluded from the study. Acutely ill patients were excluded taking into account sick euthyroid syndrome. Patients were subjected to anthropometry, evaluation of vital parameters, lipid and thyroid profile along with other routine laboratory parameters. Students t-test, Chi square test and linear regression, multiple logistic regression models were used for statistical analysis. P value < 0.05 was considered significant. Results: Of the 100 patients in study group, 55 were females (55% and 45 were males (45%. Of the 50

Metabolic Control in Mammalian Fed-Batch Cell Cultures for Reduced Lactic Acid Accumulation and Improved Process Robustness

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Viktor Konakovsky

2016-01-01

Full Text Available Biomass and cell-specific metabolic rates usually change dynamically over time, making the “feed according to need” strategy difficult to realize in a commercial fed-batch process. We here demonstrate a novel feeding strategy which is designed to hold a particular metabolic state in a fed-batch process by adaptive feeding in real time. The feed rate is calculated with a transferable biomass model based on capacitance, which changes the nutrient flow stoichiometrically in real time. A limited glucose environment was used to confine the cell in a particular metabolic state. In order to cope with uncertainty, two strategies were tested to change the adaptive feed rate and prevent starvation while in limitation: (i inline pH and online glucose concentration measurement or (ii inline pH alone, which was shown to be sufficient for the problem statement. In this contribution, we achieved metabolic control within a defined target range. The direct benefit was two-fold: the lactic acid profile was improved and pH could be kept stable. Multivariate Data Analysis (MVDA has shown that pH influenced lactic acid production or consumption in historical data sets. We demonstrate that a low pH (around 6.8 is not required for our strategy, as glucose availability is already limiting the flux. On the contrary, we boosted glycolytic flux in glucose limitation by setting the pH to 7.4. This new approach led to a yield of lactic acid/glucose (Y L/G around zero for the whole process time and high titers in our labs. We hypothesize that a higher carbon flux, resulting from a higher pH, may lead to more cells which produce more product. The relevance of this work aims at feeding mammalian cell cultures safely in limitation with a desired metabolic flux range. This resulted in extremely stable, low glucose levels, very robust pH profiles without acid/base interventions and a metabolic state in which lactic acid was consumed instead of being produced from day 1. With

Nuclear receptors and metabolism: from feast to famine.

Science.gov (United States)

Hong, Suk-Hyun; Ahmadian, Maryam; Yu, Ruth T; Atkins, Annette R; Downes, Michael; Evans, Ronald M

2014-05-01

The ability to adapt to cycles of feast and famine is critical for survival. Communication between multiple metabolic organs must be integrated to properly metabolise nutrients. By controlling networks of genes in major metabolic organs, nuclear hormone receptors (NHRs) play central roles in regulating metabolism in a tissue-specific manner. NHRs also establish daily rhythmicity by controlling the expression of core clock genes both centrally and peripherally. Recent findings show that many of the metabolic effects of NHRs are mediated through certain members of the fibroblast growth factor (FGF) family. This review focuses on the roles of NHRs in critical metabolic organs, including adipose tissue, liver and muscle, during the fed and fasted states, as well as their roles in circadian metabolism and downstream regulation of FGFs.

Design and characterization of tunable hydrogels to examine microenvironmental regulation of breast cancer recurrence

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Sawicki, Lisa A.

Late recurrence of breast cancer within distant metastatic tissue sites is often difficult to diagnose and treat, resulting in poor prognosis for patients. It is hypothesized that cells may go dormant by interactions with or lack of adhesion to the extracellular matrix (ECM) within these tissues, which differs from native breast tissue. The metastatic ECM is a complex microenvironment, containing a mixture of mechanical and chemical cues to which cells respond. To investigate how the ECM regulates cancer recurrence, two-dimensional (2D, plates) and three-dimensional (3D, naturally-derived scaffolds) in vitro culture models have been used. However, lack of complexity (2D), mechanical property control (2D, 3D), and chemical property control (3D) makes it challenging to identify key factors involved in regulating dormancy or activation in these systems. The development of synthetic polymer-based scaffolds in recent years provides an alternate route to investigating cellular response to the presentation of microenvironmental cues in 3D. Initially bioinert, these scaffolds may be modified with chemical ligands to permit cell-matrix interactions and their mechanical properties may be precisely tuned to mimic different tissue sites. The goal of this dissertation is to develop and characterize a novel synthetic material for cell culture applications and to examine how physical and chemical factors in this microenvironment regulate breast cancer activation. Specifically, we have developed a novel poly(ethylene glycol) (PEG)-based hydrogel scaffold for in vitro cell culture. PEG modified with thiols and peptides containing alloxycarbonyl-protected lysines (containing a reactive vinyl) react rapidly upon the application of light in the presence of a photoinitiator, lithium acylphosphinate ( minutes). Scaffold mechanical properties are tuned by varying macromer concentration to mimic soft metastatic site tissue ECMs (Young's modulus 600 - 6000 Pa). These properties remain

Effects of lifestyle intervention using patient-centered cognitive behavioral therapy among patients with cardio-metabolic syndrome: a randomized, controlled trial.

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Zhang, Ying; Mei, Songli; Yang, Rui; Chen, Ling; Gao, Hang; Li, Li

2016-11-18

Cardio-metabolic syndrome (CMS) is a highly prevalent condition. There is an urgent need to identify effective and integrated multi-disciplinary approaches that can reduce risk factors for CMS. Sixty-two patients with a history of CMS were randomized 1:1 into two groups: a standard information -only group (control), or a self-regulated lifestyle waist circumference (patient-centered cognitive behavioral therapy) intervention group. A pretest and posttest, controlled, experimental design was used. Outcomes were measured at the baseline (week 0) and at the end of intervention (week 12). Comparisons were drawn between groups and over time. The mean (standard deviation) age of the subjects was 48.6 (5.8) years ranging from 32 to 63, and 56.9% of the participants were female. Both groups showed no significant differences in Demographic variables and the metabolic syndrome indicators at baseline. While the control group only showed modest improvement after 12 weeks, compared to baseline, the intervention group demonstrated significant improvement from baseline. This study controlled for patients' demographics and baseline characteristics when assessing the effects of intervention. After adjusting for age, education and baseline level, the experimental group and the control group were statistically significant different in the following post-treatment outcomes: WC (F = 35.96, P cognitive behavioral therapy can improve the physical and mental health conditions among individuals reporting a history of cardio-metabolic syndrome, and possibly provided preliminary benefits for the treatment of CMS. Chinese Clinical Trial Register #, ChiCTR15006148 .

Understanding Regulation of Metabolism through Feasibility Analysis

NARCIS (Netherlands)

Nikerel, I.E.; Berkhout, J.; Hu, F.; Teusink, B.; Reinders, M.J.T.; De Ridder, D.

2012-01-01

Understanding cellular regulation of metabolism is a major challenge in systems biology. Thus far, the main assumption was that enzyme levels are key regulators in metabolic networks. However, regulation analysis recently showed that metabolism is rarely controlled via enzyme levels only, but

Thyroid peroxidase antibodies in pregnant women with type 1 diabetes: impact on thyroid function, metabolic control and pregnancy outcome

DEFF Research Database (Denmark)

Vestgaard, Marianne; Nielsen, Lene Ringholm; Rasmussen, Åse Krogh

2008-01-01

In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome....

Comparative genomic reconstruction of transcriptional networks controlling central metabolism in the Shewanella genus

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Kovaleva Galina

2011-06-01

Full Text Available Abstract Background Genome-scale prediction of gene regulation and reconstruction of transcriptional regulatory networks in bacteria is one of the critical tasks of modern genomics. The Shewanella genus is comprised of metabolically versatile gamma-proteobacteria, whose lifestyles and natural environments are substantially different from Escherichia coli and other model bacterial species. The comparative genomics approaches and computational identification of regulatory sites are useful for the in silico reconstruction of transcriptional regulatory networks in bacteria. Results To explore conservation and variations in the Shewanella transcriptional networks we analyzed the repertoire of transcription factors and performed genomics-based reconstruction and comparative analysis of regulons in 16 Shewanella genomes. The inferred regulatory network includes 82 transcription factors and their DNA binding sites, 8 riboswitches and 6 translational attenuators. Forty five regulons were newly inferred from the genome context analysis, whereas others were propagated from previously characterized regulons in the Enterobacteria and Pseudomonas spp.. Multiple variations in regulatory strategies between the Shewanella spp. and E. coli include regulon contraction and expansion (as in the case of PdhR, HexR, FadR, numerous cases of recruiting non-orthologous regulators to control equivalent pathways (e.g. PsrA for fatty acid degradation and, conversely, orthologous regulators to control distinct pathways (e.g. TyrR, ArgR, Crp. Conclusions We tentatively defined the first reference collection of ~100 transcriptional regulons in 16 Shewanella genomes. The resulting regulatory network contains ~600 regulated genes per genome that are mostly involved in metabolism of carbohydrates, amino acids, fatty acids, vitamins, metals, and stress responses. Several reconstructed regulons including NagR for N-acetylglucosamine catabolism were experimentally validated in S

The efficiency of telemedicine to optimize metabolic control in patients with type 1 diabetes mellitus: Telemed study.

Science.gov (United States)

Esmatjes, Enric; Jansà, Margarida; Roca, Daria; Pérez-Ferre, Natalia; del Valle, Laura; Martínez-Hervás, Sergio; Ruiz de Adana, Marisol; Linares, Francisca; Batanero, Ricardo; Vázquez, Federico; Gomis, Ramon; de Solà-Morales, Oriol

2014-07-01

This study evaluated the impact of an Internet-based telematic system on the economic and clinical management of patients with type 1 diabetes mellitus. This 6-month prospective, randomized, comparative, open, multicenter study included patients with type 1 diabetes >18 years old treated with multiple insulin doses and with a glycated hemoglobin (HbA1c) level of >8%. We compared an intervention group (IG) (two face-to-face and five telematic appointments) with a control group (CG) (seven face-to-face appointments). The variables studied were (1) patient and healthcare team costs, (2) metabolic control, (3) knowledge of diabetes, (4) quality of life, and (5) self-care treatment adherence. Of the 154 patients included, 118 (76.6%) completed the study (IG, 54; CG, 64). The time used by the CG to follow the program was 823±645 min versus 353±222 min in the IG (Pknowledge and self-care treatment adherence. The use of interactive telematic appointments in subjects with type 1 diabetes and inadequate metabolic control is an efficient strategy, providing results comparable to those of face-to-face appointments in relation to improvement in glycemic control, knowledge acquisition, and self-care treatment adherence, with a significant reduction in the time used, especially by patients.

Coordinated and interactive expression of genes of lipid metabolism and inflammation in adipose tissue and liver during metabolic overload.

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Wen Liang

Full Text Available BACKGROUND: Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT, often accompanied by non-alcoholic fatty liver disease (NAFLD. In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated. METHODOLOGY/PRINCIPAL FINDINGS: ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters' with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks, inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks, genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT. CONCLUSION: In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by

The Effects of Mindfulness-Based Interventions on Diabetes-Related Distress, Quality of Life, and Metabolic Control Among Persons with Diabetes: A Meta-Analytic Review.

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Bogusch, Leah M; O'Brien, William H

2018-04-04

Mindfulness-based interventions (MBIs) have improved psychological outcomes for multiple chronic health conditions, including diabetes. A meta-analytic review of the literature was conducted on all located studies (n = 14) investigating MBIs that targeted diabetes-related distress (DRD) and diabetes-related outcomes among people with Type 1 and Type 2 diabetes. PsychInfo, PubMed, Medline, and Web of Science were searched for MBIs that were designed to improve DRD and other secondary outcomes, including quality of life and measures of metabolic control. A meta-analysis of these outcomes uncovered small-to-moderate effect sizes for intervention studies measuring pretreatment to posttreatment changes in DRD and metabolic control among treatment group participants. However, the pretreatment to follow-up comparisons for DRD and metabolic control were small and unreliable. For control groups, all pre-treatment to post-treatment and pre-treatment to follow-up comparisons were unreliable for all outcomes. A moderate effect size for treatment-control comparisons was found for intervention studies measuring quality of life outcomes at posttreatment, but not at follow-up comparisons. All other effect sizes for treatment-control comparisons were unreliable. Limitations and implications for MBIs among individuals with diabetes are discussed.

Metabolic Correction in the Management of Diabetic Peripheral Neuropathy: Improving Clinical Results Beyond Symptom Control

Science.gov (United States)

Miranda-Massari, Jorge R.; Gonzalez, Michael J.; Jimenez, Francisco J.; Allende-Vigo, Myriam Z.; Duconge, Jorge

2013-01-01

Current Clinical Management Guidelines of Diabetic Peripheral Neuropathy (DPN) are based on adequate glucose control and symptomatic pain relief. However, meticulous glycemic control could delay the onset or slow the progression of diabetic neuropathy in patients with DM type 2, but it does not completely prevent the progression of the disease. Complications of DPN as it continues its natural course, produce increasing pain and discomfort, loss of sensation, ulcers, infections, amputations and even death. In addition to the increased suffering, disability and loss of productivity, there is a very significant economic impact related to the treatment of DPN and its complications. In USA alone, it has been estimated that there are more than 5,000,000 patients suffering from DPN and the total annual cost of treating the disease and its complications is over $10,000 million dollars. In order to be able to reduce complications of DPN, it is crucial to improve or correct the metabolic conditions that lead to the pathology present in this condition. Pathophysiologic mechanisms implicated in diabetic neuropathy include: increased polyol pathway with accumulation of sorbitol and reduced Na+/K+-ATPase activity, microvascular damage and hypoxia due to nitric oxide deficit and increased oxygen free radical activity. Moreover, there is a decrease in glutathione and increase in homocysteine. Clinical trials in the last two decades have demonstrated that the use of specific nutrients can correct some of these metabolic derangements, improving symptom control and providing further benefits such as improved sensorium, blood flow and nerve regeneration. We will discuss the evidence on lipoic acid, acetyi-L-carnitine, benfotiamine and the combination of active B vitamins L-methylfolate, methylcobalamin and piridoxal-6-phosphate. In addition, we discuss the role of metforrnin, an important drug in the management of diabetes, and the presence of specific polymorphic genes, in the risk

Neural control of blood flow during exercise in human metabolic syndrome.

Science.gov (United States)

Limberg, Jacqueline K; Morgan, Barbara J; Sebranek, Joshua J; Proctor, Lester T; Eldridge, Marlowe W; Schrage, William G

2014-09-01

α-Adrenergic-mediated vasoconstriction is greater during simulated exercise in animal models of metabolic syndrome (MetSyn) when compared with control animals. In an attempt to translate such findings to humans, we hypothesized that adults with MetSyn (n = 14, 35 ± 3 years old) would exhibit greater α-adrenergic responsiveness during exercise when compared with age-matched healthy control subjects (n = 16, 31 ± 3 years old). We measured muscle sympathetic nerve activity (MSNA; microneurography) and forearm blood flow (Doppler ultrasound) during dynamic forearm exercise (15% of maximal voluntary contraction). α-Adrenergic agonists (phenylephrine and clonidine) and an antagonist (phentolamine) were infused intra-arterially to assess α-adrenergic receptor responsiveness and restraint, respectively. Resting MSNA was ∼35% higher in adults with MetSyn (P exercise. Clonidine-mediated vasoconstriction was greater in adults with MetSyn (P  0.05). Interestingly, exercise-mediated vasodilatation was greater in MetSyn (P exercise blood flow during low-intensity hand-grip exercise when compared with age-matched healthy control subjects. These results suggest that adults with MetSyn exhibit compensatory vascular control mechanisms capable of preserving blood flow responses to exercise in the face of augmented sympathetic adrenergic activity. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Phosphoinositide metabolism and metabolism-contraction coupling in rabbit aorta

International Nuclear Information System (INIS)

Coburn, R.F.; Baron, C.; Papadopoulos, M.T.

1988-01-01

The authors tested a hypothesis that metabolism-contraction coupling in vascular smooth muscle is controlled by the rate of delivery of energy to ATP-dependent reactions in the inositol phospholipid transduction system that generate second messengers exerting control on smooth muscle force. Rabbit aorta was contracted by norepinephrine (NOR) under conditions of normoxia and hypoxia, and changes in inositol phospholipid pool sizes and metabolic flux rates (J F ) were determined. J F was determined by labeling free cytosolic myo-inositol by incubation of unstimulated muscle with myo-[ 3 H]inositol and then measuring rates of incorporation of this isotope into inositol phospholipids and inositol phosphates when the muscle was activated by NOR. J F measured during maintenance of NOR-induced force was markedly inhibited during hypoxia to 40-50% of that determined during normoxia; rates of increases in inositol phosphate radioactivities were similarly depressed during NOR activation under hypoxia. The hypoxia-induced decrease in J F was associated with four- to fivefold increase in phosphatidylinositol 4-phosphate (PIP) total pool size, suggesting PIP kinase was inhibited and rate limiting. These data suggest that activation of inositol phospholipid metabolism, which generates inositol 1,4,5-trisphosphate (IP 3 ) and diacylglycerol, is blunted under conditions where aerobic energy production is inhibited. Data are consistent with rate-limiting effects of decreased ATP delivery, or decreased phosphate potential, on PIP kinase and reactions that control resynthesis of phosphatidylinositol

Metabolic control in type 1 diabetes patients practicing combat sports: at least two-year follow-up study.

Science.gov (United States)

Benbenek-Klupa, Teresa; Matejko, Bartlomiej; Klupa, Tomasz

2015-01-01

It is well recognized that physical activity should be an integral part of the management of diabetes. It remains controversial, however, whether combat sports, often preferred by young individuals type 1 diabetes mellitus (T1DM), may be performed without high risk of metabolic decompensation. The aim of this observational study was to summarize a two-year follow-up period of five young male patients with T1DM practicing combat sports under the care of a physical-activity oriented specialist diabetes outpatient clinic. Of the five patients, three mixed martial arts and two kick-boxing competitors were included in the study. To control glucose in each patient, an individual approach was used that took into consideration the type of training, the sequence of the exercises, and the relative proportion of different forms of exercise. During the follow-up, glycemic control was improved and maintained in all individuals. Neither an episode of hospitalization-requiring diabetic ketoacidosis nor severe hypoglycemia occurred in these patients during the follow-up. In conclusion, an individual approach for T1DM patients practicing combat sports may result in achieving and maintaining satisfactory glycemic control without increased risk of metabolic decompensation.

Thermodynamic and Probabilistic Metabolic Control Analysis of Riboflavin (Vitamin B₂) Biosynthesis in Bacteria.

Science.gov (United States)

Birkenmeier, Markus; Mack, Matthias; Röder, Thorsten

2015-10-01

In this study, we applied a coupled in silico thermodynamic and probabilistic metabolic control analysis methodology to investigate the control mechanisms of the commercially relevant riboflavin biosynthetic pathway in bacteria. Under the investigated steady-state conditions, we found that several enzyme reactions of the pathway operate far from thermodynamic equilibrium (transformed Gibbs energies of reaction below about -17 kJ mol(-1)). Using the obtained thermodynamic information and applying enzyme elasticity sampling, we calculated the distributions of the scaled concentration control coefficients (CCCs) and scaled flux control coefficients (FCCs). From the statistical analysis of the calculated distributions, we inferred that the control over the riboflavin producing flux is shared among several enzyme activities and mostly resides in the initial reactions of the pathway. More precisely, the guanosine triphosphate (GTP) cyclohydrolase II activity, and therefore the bifunctional RibA protein of Bacillus subtilis because it catalyzes this activity, appears to mainly control the riboflavin producing flux (mean FCCs = 0.45 and 0.55, respectively). The GTP cyclohydrolase II activity and RibA also exert a high positive control over the riboflavin concentration (mean CCCs = 2.43 and 2.91, respectively). This prediction is consistent with previous findings for microbial riboflavin overproducing strains.

Cholesterol Metabolism and Weight Reduction in Subjects with Mild Obstructive Sleep Apnoea: A Randomised, Controlled Study

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Maarit Hallikainen

2013-01-01

Full Text Available To evaluate whether parameters of obstructive sleep apnoea (OSA associate with cholesterol metabolism before and after weight reduction, 42 middle-aged overweight subjects with mild OSA were randomised to intensive lifestyle intervention (N=23 or to control group (N=18 with routine lifestyle counselling only. Cholesterol metabolism was evaluated with serum noncholesterol sterol ratios to cholesterol, surrogate markers of cholesterol absorption (cholestanol and plant sterols and synthesis (cholestenol, desmosterol, and lathosterol at baseline and after 1-year intervention. At baseline, arterial oxygen saturation (SaO2 was associated with serum campesterol (P<0.05 and inversely with desmosterol ratios (P<0.001 independently of gender, BMI, and homeostasis model assessment index of insulin resistance (HOMA-IR. Apnoea-hypopnoea index (AHI was not associated with cholesterol metabolism. Weight reduction significantly increased SaO2and serum cholestanol and decreased AHI and serum cholestenol ratios. In the groups combined, the changes in AHI were inversely associated with changes of cholestanol and positively with cholestenol ratios independent of gender and the changes of BMI and HOMA-IR (P<0.05. In conclusion, mild OSA seemed to be associated with cholesterol metabolism independent of BMI and HOMA-IR. Weight reduction increased the markers of cholesterol absorption and decreased those of cholesterol synthesis in the overweight subjects with mild OSA.

Cerebral Metabolic Changes Related to Oxidative Metabolism in a Model of Bacterial Meningitis Induced by Lipopolysaccharide

DEFF Research Database (Denmark)

Munk, Michael; Rom Poulsen, Frantz; Larsen, Lykke

2018-01-01

BACKGROUND: Cerebral mitochondrial dysfunction is prominent in the pathophysiology of severe bacterial meningitis. In the present study, we hypothesize that the metabolic changes seen after intracisternal lipopolysaccharide (LPS) injection in a piglet model of meningitis is compatible...... with mitochondrial dysfunction and resembles the metabolic patterns seen in patients with bacterial meningitis. METHODS: Eight pigs received LPS injection in cisterna magna, and four pigs received NaCl in cisterna magna as a control. Biochemical variables related to energy metabolism were monitored by intracerebral...... dysfunction with increasing cerebral LPR due to increased lactate and normal pyruvate, PbtO2, and ICP. The metabolic pattern resembles the one observed in patients with bacterial meningitis. Metabolic monitoring in these patients is feasible to monitor for cerebral metabolic derangements otherwise missed...

Serum Progranulin Levels in Type 2 Diabetic Patients with Metabolic Syndrome.

Science.gov (United States)

Shafaei, Azam; Marjani, Abdoljalal; Khoshnia, Masoud

2016-12-01

The role of progranulin in individuals with metabolic syndrome is not exactly clear.We aimed to assess the serum level of progranulin in type 2 diabetic patients with and without metabolic syndrome and compare them with healthy controls. The study included 60 patients with type 2 diabetes and 30 healthy individuals as control groups. Biochemical parameters and progranulin levels were determined. Subjects with metabolic syndrome showed significantly higher levels of triglyceride, waist circumference, BMI, systolic and diastolic blood pressure than subjects without metabolic syndrome and the control groups, while HDL-cholesterol level was significantly lower in subjects with metabolic syndrome. Fasting blood sugar was significantly higher in type 2 diabetic patients than in the control groups. Serum level of progranulin was slightly increased in subjects with metabolic syndrome. Serum progranulin level had no significant relationship with metabolic syndrome components. Serum progranulin was also not dependent on cardiometabolic risk factors for subjects with metabolic syndrome, but it could be considered for the management of type 2 diabetes mellitus. Further studies are recommended to explain the effect of progranulin on the pathogenesis of metabolic risk factors.

Epilepsy and astrocyte energy metabolism.

Science.gov (United States)

Boison, Detlev; Steinhäuser, Christian

2018-06-01

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

Albumin metabolism in health and disease

International Nuclear Information System (INIS)

Kirsch, R.E.; Saunders, S.J.; Brock, J.F.

1979-01-01

Studies performed at the University of Cape Town on the metabolism of albumin have been reviewed. The control of albumin metabolism in protein energy malnutrition, in acute exposure to alcohol and after partial hepatectomy in the rat is discussed

Albumin metabolism in health and disease

Energy Technology Data Exchange (ETDEWEB)

Kirsch, R E; Saunders, S J; Brock, J F [Cape Town Univ. (South Africa). Dept. of Medicine

1979-11-24

Studies performed at the University of Cape Town on the metabolism of albumin have been reviewed. The control of albumin metabolism in protein energy malnutrition, in acute exposure to alcohol and after partial hepatectomy in the rat is discussed.

HPLC-MS-Based Metabonomics Reveals Disordered Lipid Metabolism in Patients with Metabolic Syndrome

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Xinjie Zhao

2011-12-01

Full Text Available Ultra-high performance liquid chromatography/ quadrupole time of flight mass spectrometry-based metabonomics platform was employed to profile the plasma metabolites of patients with metabolic syndrome and the healthy controls. Data analysis revealed lots of differential metabolites between the two groups, and most of them were identified as lipids. Several fatty acids and lysophosphatidylcholines were of higher plasma levels in the patient group, indicating the occurrence of insulin resistance and inflammation. The identified ether phospholipids were decreased in the patient group, reflecting the oxidative stress and some metabolic disorders. These identified metabolites can also be used to aid diagnosis of patients with metabolic syndrome. These results showed that metabonomics was a promising and powerful method to study metabolic syndrome.

The consequences of being in an infectious biofilm – microenvironmental conditions governing antibiotic tolerance

DEFF Research Database (Denmark)

Sønderholm, Majken; Bjarnsholt, Thomas; Alhede, Maria

2017-01-01

The main driver behind biofilm research is the desire to understand the mechanisms governing the antibiotic tolerance of biofilm-growing bacteria found in chronic bacterial infections. Rather than genetic traits, several physical and chemical traits of the biofilm have been shown to be attributable...... to antibiotic tolerance. During infection, bacteria in biofilms exhibit slow growth and a low metabolic state due to O2 limitation imposed by intense O2 consumption of polymorphonuclear leukocytes or metabolically active bacteria in the biofilm periphery. Due to variable O2 availability throughout the infection......-growing bacteria. This review summarizes knowledge about the links between the microenvironment of biofilms in chronic infections and their tolerance against antibiotics...

Cardiovascular and metabolic syndrome risk among men with and without erectile dysfunction: case-control study

OpenAIRE

Zambon, João Paulo; Mendonça, Rafaela Rosalba de; Wroclawski, Marcelo Langer; Karam Junior, Amir; Santos, Raul D.; Carvalho, José Antonio Maluf de; Wroclawski, Eric Roger

2010-01-01

CONTEXT AND OBJECTIVE: Erectile dysfunction has been associated with cardiovascular diseases. The aim here was to evaluate cardiovascular risk through the Framingham Risk Score (FRS) criteria, C-reactive protein (CRP) assays and presence of metabolic syndrome (MS) in men with and without erectile dysfunction diagnosed within a healthcare program. DESIGN AND SETTING: A retrospective case-control study was conducted. The patients were selected from a healthcare program at the Hospital Israelita...

Management issues in the metabolic syndrome.

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Deedwania, P C; Gupta, R

2006-10-01

The metabolic syndrome or cardiovascular dysmetabolic syndrome is characterized by obesity, central obesity, insulin resistance, atherogenic dyslipidemia, and hypertension. The major risk factors leading to this syndrome are physical inactivity and an atherogenic diet and cornerstone clinical feature is abdominal obesity or adiposity. In addition, patients usually have elevated triglycerides, low HDL cholesterol, elevated LDL cholesterol, other abnormal lipid parameters, hypertension, and elevated fasting blood glucose. Impaired fibrinolysis, increased susceptibility to thrombotic events, and raised inflammatory markers are also observed. Given that India has the largest number of subjects with type-2 diabetes in the world it can be extrapolated that this country also has the largest number of patients with the metabolic syndrome. Epidemiological studies confirm a high prevalence. Therapeutic approach involves intervention at a macro-level and control of multiple risk factors using therapeutic lifestyle approaches (diet control and increased physical activity, pharmacotherapy - anti-obesity agents) for control of obesity and visceral obesity, and targeted approach for control of individual risk factors. Pharmacological therapy is a critical step in the management of patients with metabolic syndrome when lifestyle modifications fail to achieve the therapeutic goals. Anti-obesity drugs such as sibutramine and orlistat can be tried to reduce weight and central obesity and jointly control the metabolic syndrome components. Other than weight loss, there is no single best therapy and treatment should consist of treatment of individual components of the metabolic syndrome. Newer drugs such as the endocannabinoid receptor blocker,rimonabant, appear promising in this regard. Atherogenic dyslipidemia should be controlled initially with statins if there is an increase in LDL cholesterol. If there are other lipid abnormalities then combination therapy of statin with fibrates

Gut Microbiota and Metabolic Disorders

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Kyu Yeon Hur

2015-06-01

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

G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle

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Claire Laurens

2016-07-01

Full Text Available Objective: Recent data suggest that adipose triglyceride lipase (ATGL plays a key role in providing energy substrate from triglyceride pools and that alterations of its expression/activity relate to metabolic disturbances in skeletal muscle. Yet little is known about its regulation. We here investigated the role of the protein G0/G1 Switch Gene 2 (G0S2, recently described as an inhibitor of ATGL in white adipose tissue, in the regulation of lipolysis and oxidative metabolism in skeletal muscle. Methods: We first examined G0S2 protein expression in relation to metabolic status and muscle characteristics in humans. We next overexpressed and knocked down G0S2 in human primary myotubes to assess its impact on ATGL activity, lipid turnover and oxidative metabolism, and further knocked down G0S2 in vivo in mouse skeletal muscle. Results: G0S2 protein is increased in skeletal muscle of endurance-trained individuals and correlates with markers of oxidative capacity and lipid content. Recombinant G0S2 protein inhibits ATGL activity by about 40% in lysates of mouse and human skeletal muscle. G0S2 overexpression augments (+49%, p < 0.05 while G0S2 knockdown strongly reduces (−68%, p < 0.001 triglyceride content in human primary myotubes and mouse skeletal muscle. We further show that G0S2 controls lipolysis and fatty acid oxidation in a strictly ATGL-dependent manner. These metabolic adaptations mediated by G0S2 are paralleled by concomitant changes in glucose metabolism through the modulation of Pyruvate Dehydrogenase Kinase 4 (PDK4 expression (5.4 fold, p < 0.001. Importantly, downregulation of G0S2 in vivo in mouse skeletal muscle recapitulates changes in lipid metabolism observed in vitro. Conclusion: Collectively, these data indicate that G0S2 plays a key role in the regulation of skeletal muscle ATGL activity, lipid content and oxidative metabolism. Keywords: Lipid metabolism, Skeletal muscle, Lipolysis, Adipose triglyceride lipase

Melatonin for Atypical Antipsychotic-Induced Metabolic Adverse Effects: A Meta-Analysis of Randomized Controlled Trials

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Ashwin Kamath

2018-01-01

Full Text Available The objective of our study was to determine the effect of melatonin administration on atypical antipsychotic-induced metabolic adverse effects in patients with psychiatric disorders. A systematic search was performed in PUBMED, Cochrane Library, Scopus, Web of Science, and EBSCOhost electronic databases. Randomized controlled trials studying the effect of melatonin on antipsychotic-induced metabolic adverse effects were identified and subjected to meta-analysis. Four studies were included in the meta-analysis, including 57 patients on melatonin and 61 patients on placebo. Melatonin produced a significant decrease in the diastolic blood pressure compared with placebo (mean difference = −4.44 [95% CI, −7.00 to −1.88]; p=0.0007; I2 = 13%, but not the systolic blood pressure (mean difference = −4.23 [95% CI, −8.11 to −0.36]; p=0.03; I2 = 0%. Although a decrease in the body mass index was seen in the melatonin group, the difference was not significant in the random-effects analysis model. To conclude, in patients on atypical antipsychotics, melatonin at a dose of up to 5 mg/day for a treatment duration of up to 12 weeks attenuated the rise in diastolic blood pressure compared with placebo but had no significant effects on other metabolic parameters.

Melatonin for Atypical Antipsychotic-Induced Metabolic Adverse Effects: A Meta-Analysis of Randomized Controlled Trials.

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Kamath, Ashwin; Rather, Zahoor Ahmad

2018-01-01

The objective of our study was to determine the effect of melatonin administration on atypical antipsychotic-induced metabolic adverse effects in patients with psychiatric disorders. A systematic search was performed in PUBMED, Cochrane Library, Scopus, Web of Science, and EBSCOhost electronic databases. Randomized controlled trials studying the effect of melatonin on antipsychotic-induced metabolic adverse effects were identified and subjected to meta-analysis. Four studies were included in the meta-analysis, including 57 patients on melatonin and 61 patients on placebo. Melatonin produced a significant decrease in the diastolic blood pressure compared with placebo (mean difference = -4.44 [95% CI, -7.00 to -1.88]; p = 0.0007; I 2 = 13%), but not the systolic blood pressure (mean difference = -4.23 [95% CI, -8.11 to -0.36]; p = 0.03; I 2 = 0%). Although a decrease in the body mass index was seen in the melatonin group, the difference was not significant in the random-effects analysis model. To conclude, in patients on atypical antipsychotics, melatonin at a dose of up to 5 mg/day for a treatment duration of up to 12 weeks attenuated the rise in diastolic blood pressure compared with placebo but had no significant effects on other metabolic parameters.

The Central Nervous System and Bone Metabolism: An Evolving Story.

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Dimitri, Paul; Rosen, Cliff

2017-05-01

Our understanding of the control of skeletal metabolism has undergone a dynamic shift in the last two decades, primarily driven by our understanding of energy metabolism. Evidence demonstrating that leptin not only influences bone cells directly, but that it also plays a pivotal role in controlling bone mass centrally, opened up an investigative process that has changed the way in which skeletal metabolism is now perceived. Other central regulators of bone metabolism have since been identified including neuropeptide Y (NPY), serotonin, endocannabinoids, cocaine- and amphetamine-regulated transcript (CART), adiponectin, melatonin and neuromedin U, controlling osteoblast and osteoclast differentiation, proliferation and function. The sympathetic nervous system was originally identified as the predominant efferent pathway mediating central signalling to control skeleton metabolism, in part regulated through circadian genes. More recent evidence points to a role of the parasympathetic nervous system in the control of skeletal metabolism either through muscarinic influence of sympathetic nerves in the brain or directly via nicotinic receptors on osteoclasts, thus providing evidence for broader autonomic skeletal regulation. Sensory innervation of bone has also received focus again widening our understanding of the complex neuronal regulation of bone mass. Whilst scientific advance in this field of bone metabolism has been rapid, progress is still required to understand how these model systems work in relation to the multiple confounders influencing skeletal metabolism, and the relative balance in these neuronal systems required for skeletal growth and development in childhood and maintaining skeletal integrity in adulthood.

Krüppel-Like Factors in Metabolic Homeostasis and Cardiometabolic Disease

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Yumiko Oishi

2018-06-01

Full Text Available Members of the Krüppel-like factor (KLF family of transcription factors, which are characterized by the presence of three conserved Cys2/His2 zinc-fingers in their C-terminal domains, control a wide variety of biological processes. In particular, recent studies have revealed that KLFs play diverse and essential roles in the control of metabolism at the cellular, tissue and systemic levels. In both liver and skeletal muscle, KLFs control glucose, lipid and amino acid metabolism so as to coordinate systemic metabolism in the steady state and in the face of metabolic stresses, such as fasting. The functions of KLFs within metabolic tissues are also important contributors to the responses to injury and inflammation within those tissues. KLFs also control the function of immune cells, such as macrophages, which are involved in the inflammatory processes underlying both cardiovascular and metabolic diseases. This review focuses mainly on the physiological and pathological functions of KLFs in the liver and skeletal muscle. The involvement of KLFs in inflammation in these tissues is also summarized. We then discuss the implications of KLFs' control of metabolism and inflammation in cardiometabolic diseases.

Modelling of the metabolism of Zymomonas mobilis

Energy Technology Data Exchange (ETDEWEB)

Posten, C; Thoma, M

1986-01-01

In order to optimize fermentations with respect to media, reactor configuration, and control a structured model of the metabolism of Zymononas mobilis has been developed. The model is based on structure of metabolism, rate limiting steps, energy balance and metabolic elemental balances. A three-fold effect of ethanol has been observed concerning substrate-turnover, ammonia uptake and energy consumption. In addition to the metabolic view a structured cell-membrane-model should be considered.

Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism

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Laura ePaixão

2015-10-01

Full Text Available Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonised by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonisation to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc on this response at the transcriptional, physiological and metabolic levels. Galactose (Gal, N-acetylglucosamine (GlcNAc and mannose (Man affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo 13C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s was readily consumed and elicited a metabolic shift towards a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome. In central carbon metabolism (most represented category, Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

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

Science.gov (United States)

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

2015-01-01

Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonized by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonization to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological, and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc), and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo (13)C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s) was readily consumed and elicited a metabolic shift toward a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

Impact of Vitamin D Replacement on Markers of Glucose Metabolism and Cardio-Metabolic Risk in Women with Former Gestational Diabetes--A Double-Blind, Randomized Controlled Trial.

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Toh Peng Yeow

Full Text Available Gestational Diabetes Mellitus (GDM and vitamin D deficiency are related to insulin resistance and impaired beta cell function, with heightened risk for future development of diabetes. We evaluated the impact of vitamin D supplementation on markers of glucose metabolism and cardio metabolic risk in Asian women with former GDM and hypovitaminosis D. In this double blind, randomized controlled trial, 26 participants were randomized to receive either daily 4000 IU vitamin D3 or placebo capsules. 75 g Oral Glucose Tolerance Test (OGTT and biochemistry profiles were performed at baseline and 6 month visits. Mathematical models, using serial glucose, insulin and C peptide measurements from OGTT, were employed to calculate insulin sensitivity and beta cell function. Thirty three (76% women with former GDM screened had vitamin D level of <50 nmol/L at baseline. Supplementation, when compared with placebo, resulted in increased vitamin D level (+51.1 nmol/L vs 0.2 nmol/L, p<0.001 and increased fasting insulin (+20% vs 18%, p = 0.034. The vitamin D group also demonstrated a 30% improvement in disposition index and an absolute 0.2% (2 mmol/mol reduction in HbA1c. There was no clear change in insulin sensitivity or markers of cardio metabolic risk. This study highlighted high prevalence of vitamin D deficiency among Asian women with former GDM. Six months supplementation with 4000 IU of vitamin D3 safely restored the vitamin D level, improved basal pancreatic beta-cell function and ameliorated the metabolic state. There was no effect on markers of cardio metabolic risk. Further mechanistic studies exploring the role of vitamin D supplementation on glucose homeostasis among different ethnicities may be needed to better inform future recommendations for these women with former GDM at high risk of both hypovitaminosis D and future diabetes.

Coordinations between gene modules control the operation of plant amino acid metabolic networks

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Galili Gad

2009-01-01

Full Text Available Abstract Background Being sessile organisms, plants should adjust their metabolism to dynamic changes in their environment. Such adjustments need particular coordination in branched metabolic networks in which a given metabolite can be converted into multiple other metabolites via different enzymatic chains. In the present report, we developed a novel "Gene Coordination" bioinformatics approach and use it to elucidate adjustable transcriptional interactions of two branched amino acid metabolic networks in plants in response to environmental stresses, using publicly available microarray results. Results Using our "Gene Coordination" approach, we have identified in Arabidopsis plants two oppositely regulated groups of "highly coordinated" genes within the branched Asp-family network of Arabidopsis plants, which metabolizes the amino acids Lys, Met, Thr, Ile and Gly, as well as a single group of "highly coordinated" genes within the branched aromatic amino acid metabolic network, which metabolizes the amino acids Trp, Phe and Tyr. These genes possess highly coordinated adjustable negative and positive expression responses to various stress cues, which apparently regulate adjustable metabolic shifts between competing branches of these networks. We also provide evidence implying that these highly coordinated genes are central to impose intra- and inter-network interactions between the Asp-family and aromatic amino acid metabolic networks as well as differential system interactions with other growth promoting and stress-associated genome-wide genes. Conclusion Our novel Gene Coordination elucidates that branched amino acid metabolic networks in plants are regulated by specific groups of highly coordinated genes that possess adjustable intra-network, inter-network and genome-wide transcriptional interactions. We also hypothesize that such transcriptional interactions enable regulatory metabolic adjustments needed for adaptation to the stresses.

[Impact of metabolic syndrome in the control of blood pressure and dyslipemia].

Science.gov (United States)

Rodilla, Enrique; García, Luis; Merino, Consolación; Costa, José A; González, Carmen; Pascual, José M

2004-11-06

The objective of the study was to assess the influence of metabolic syndrome (MS) in the control of blood pressure (BP) and dyslipemia. A cross sectional study was performed with 1,320 (634 M and 686 F), 40.1 (13.3) years-old, BMI 29.8 (4.7) hypertensive non-diabetic patients. MS was diagnosed according to NCEP-ATP-III guidelines. Blood pressure control goal was BP 20% at 10 years). Goals of C-LDL levels were those of NCEP-ATP-III. 461 (35%) patients had MS and the remaining 859 became controls. Patients with MS had higher initial levels of hypertension and were receiving more antihypertensive drugs: 2.1 [1.3] vs. 1.7 [1.3]; p < 0.001), yet the average systolic and diastolic BP achieved and the degree of control was similar in both groups 53% vs. 52%; (p = ns). Patients with MS had higher CR at ten years than controls (10.7 [8.3] vs. 7.9 [6.8], p < 0.001) but achieved the C-LDL goals at fewer proportions than controls (57% vs. 74%; p < 0.001). In a regression analysis, patients with MS had 26% less probabilities of achieving both goals (p < 0.001). Hypertensive patients with MS have higher CR, and need more antihypertensive drugs to achieve the same BP goals. Yet it is more difficult for them to achieve LDL cholesterol goals. Patients with MS remain a target for cardiovascular prevention.

Dental caries and salivary status in children with type 1 diabetes mellitus, related to the metabolic control of the disease.

Science.gov (United States)

Siudikiene, Jolanta; Machiulskiene, Vita; Nyvad, Bente; Tenovuo, Jorma; Nedzelskiene, Irena

2006-02-01

The aim of this study was to investigate the relationship among type 1 diabetes mellitus, dental caries, and salivary status in children. The study comprised 68, 10-15-yr-old diabetics, and 68, age- and gender-matched non-diabetic controls. Diabetics were categorized into well-to-moderately controlled (HbA1c or= 9.0%) groups. Caries was recorded by assessing lesion activity at non-cavitated and cavity levels. Teeth were examined visually for the presence of dental plaque. Saliva was analyzed for unstimulated and stimulated flow rates, buffer effect, mutans streptococci, lactobacilli, and yeasts. Diabetics had fewer caries and plaque, lower salivary flow rates and buffer effect, and more frequent growth of yeasts than their non-diabetic controls. Well-to-moderately controlled diabetics had fewer decayed surfaces and lower counts of mutans streptococci and yeasts than poorly controlled diabetics, but the level of metabolic control of diabetes had no influence on salivary flow rates and buffer effect. High caries levels in diabetics were significantly associated with age, plaque score, and decreased unstimulated salivary flow rate, but were not associated with the level of metabolic control of diabetes. High caries experience in this study population could be related to plaque accumulation and/or to changes in saliva induced by diabetes mellitus.

Dysregulated metabolism contributes to oncogenesis

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Hirschey, Matthew D.; DeBerardinis, Ralph J.; Diehl, Anna Mae E.; Drew, Janice E.; Frezza, Christian; Green, Michelle F.; Jones, Lee W.; Ko, Young H.; Le, Anne; Lea, Michael A.; Locasale, Jason W.; Longo, Valter D.; Lyssiotis, Costas A.; McDonnell, Eoin; Mehrmohamadi, Mahya; Michelotti, Gregory; Muralidhar, Vinayak; Murphy, Michael P.; Pedersen, Peter L.; Poore, Brad; Raffaghello, Lizzia; Rathmell, Jeffrey C.; Sivanand, Sharanya; Vander Heiden, Matthew G.; Wellen, Kathryn E.

2015-01-01

Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review “Hallmarks of Cancer”, where the dysregulation of cellular metabolism was included as an emerging hallmark. While several lines of evidence suggest that metabolic rewiring is orchestrated by the concerted action of oncogenes and tumor suppressor genes, in some circumstances altered metabolism can play a primary role in oncogenesis. Recently, mutations of cytosolic and mitochondrial enzymes involved in key metabolic pathways have been associated with hereditary and sporadic forms of cancer. Together, these results suggest that aberrant metabolism, once seen just as an epiphenomenon of oncogenic reprogramming, plays a key role in oncogenesis with the power to control both genetic and epigenetic events in cells. In this review, we discuss the relationship between metabolism and cancer, as part of a larger effort to identify a broad-spectrum of therapeutic approaches. We focus on major alterations in nutrient metabolism and the emerging link between metabolism and epigenetics. Finally, we discuss potential strategies to manipulate metabolism in cancer and tradeoffs that should be considered. More research on the suite of metabolic alterations in cancer holds the potential to discover novel approaches to treat it. PMID:26454069

Locomotor Adaptation Improves Balance Control, Multitasking Ability and Reduces the Metabolic Cost of Postural Instability

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Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Brady, R. A.; Batson, C. D.; Miller, C. A.; Ploutz-Snyder, R. J.; Guined, J. R.; Buxton, R. E.; Cohen, H. S.

2011-01-01

During exploration-class missions, sensorimotor disturbances may lead to disruption in the ability to ambulate and perform functional tasks during the initial introduction to a novel gravitational environment following a landing on a planetary surface. The overall goal of our current project is to develop a sensorimotor adaptability training program to facilitate rapid adaptation to these environments. We have developed a unique training system comprised of a treadmill placed on a motion-base facing a virtual visual scene. It provides an unstable walking surface combined with incongruent visual flow designed to enhance sensorimotor adaptability. Greater metabolic cost incurred during balance instability means more physical work is required during adaptation to new environments possibly affecting crewmembers? ability to perform mission critical tasks during early surface operations on planetary expeditions. The goal of this study was to characterize adaptation to a discordant sensory challenge across a number of performance modalities including locomotor stability, multi-tasking ability and metabolic cost. METHODS: Subjects (n=15) walked (4.0 km/h) on a treadmill for an 8 -minute baseline walking period followed by 20-minutes of walking (4.0 km/h) with support surface motion (0.3 Hz, sinusoidal lateral motion, peak amplitude 25.4 cm) provided by the treadmill/motion-base system. Stride frequency and auditory reaction time were collected as measures of locomotor stability and multi-tasking ability, respectively. Metabolic data (VO2) were collected via a portable metabolic gas analysis system. RESULTS: At the onset of lateral support surface motion, subj ects walking on our treadmill showed an increase in stride frequency and auditory reaction time indicating initial balance and multi-tasking disturbances. During the 20-minute adaptation period, balance control and multi-tasking performance improved. Similarly, throughout the 20-minute adaptation period, VO2 gradually

Improved Metabolic Control in Diabetes, HSP60, and Proinflammatory Mediators

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Claudio Blasi

2012-01-01

Full Text Available The diabetes-atherosclerosis relationship remains to be fully defined. Repeated prolonged hyperglycemia, increased ROS production and endothelial dysfunction are important factors. One theory is that increased blood levels of heat shock protein (HSP60 are proinflammatory, through activation of innate immunity, and contribute to the progression of vascular disease. It was hypothesized that improvement of diabetes control in patients presenting with metabolic syndrome would lower HSP60, and anti-HSP60 antibody levels and decrease inflammatory markers. Paired sera of 17 Italian patients, before and after intensive treatment, were assayed for cytokines, HSP60 and anti-HSP60 antibodies. As expected, intensive treatment was associated with a decrease in HgbA1C (P<0.001 and BMI (P<0.001. After treatment, there was a significant decrease in IL-6 (P<0.05. HSP60 levels were before treatment −6.9+1.9, after treatment −7.1+2.0 ng/mL (P=ns. Overall HSP60 concentrations were lower than published reports. Anti-HSP60 antibody titers were high and did not decrease with treatment. In conclusion, improvement of diabetic control did not alter HSP60 concentrations or antiHSP60 antibody titers, but led to a reduction of IL-6 levels.

Determining the Control Circuitry of Redox Metabolism at the Genome-Scale

DEFF Research Database (Denmark)

Federowicz, Stephen; Kim, Donghyuk; Ebrahim, Ali

2014-01-01

-scale metabolic model to show that ArcA and Fnr regulate >80% of total metabolic flux and 96% of differential gene expression across fermentative and nitrate respiratory conditions. Based on the data, we propose a feedforward with feedback trim regulatory scheme, given the extensive repression of catabolic genes...

Pregnancy and lactation alter biomarkers of biotin metabolism in women consuming a controlled diet.

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Perry, Cydne A; West, Allyson A; Gayle, Antoinette; Lucas, Lauren K; Yan, Jian; Jiang, Xinyin; Malysheva, Olga; Caudill, Marie A

2014-12-01

Biotin functions as a cofactor for several carboxylase enzymes with key roles in metabolism. At present, the dietary requirement for biotin is unknown and intake recommendations are provided as Adequate Intakes (AIs). The biotin AI for adults and pregnant women is 30 μg/d, whereas 35 μg/d is recommended for lactating women. However, pregnant and lactating women may require more biotin to meet the demands of these reproductive states. The current study sought to quantify the impact of reproductive state on biotin status response to a known dietary intake of biotin. To achieve this aim, we measured a panel of biotin biomarkers among pregnant (gestational week 27 at study entry; n = 26), lactating (postnatal week 5 at study entry; n = 28), and control (n = 21) women who participated in a 10- to 12-wk feeding study providing 57 μg of dietary biotin/d as part of a mixed diet. Over the course of the study, pregnant women excreted 69% more (vs. control; P biotin-dependent methylcrotonyl-coenzyme A carboxylase is impaired. Interestingly, urinary excretion of 3-hydroxyisovaleryl-carnitine (3-HIA-carnitine), a downstream metabolite of 3-HIA, was 27% lower (P = 0.05) among pregnant (vs. control) women, a finding that may arise from carnitine inadequacy during gestation. No differences (P > 0.05) were detected in plasma biotin, urinary biotin, or urinary bisnorbiotin between pregnant and control women. Lactating women excreted 76% more (vs. control; P = 0.001) of the biotin catabolite bisnorbiotin, indicating that lactation accelerates biotin turnover and loss. Notably, with respect to control women, lactating women excreted 23% less (P = 0.04) urinary 3-HIA and 26% less (P = 0.05) urinary 3-HIA-carnitine, suggesting that lactation reduces leucine catabolism and that these metabolites may not be useful indicators of biotin status during lactation. Overall, these data demonstrate significant alterations in markers of biotin metabolism during pregnancy and lactation and

Microbiological changes after periodontal therapy in diabetic patients with inadequate metabolic control

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Carina Maciel Silva-Boghossian

2014-05-01

Full Text Available The present study investigated the effect of non-surgical periodontal treatment (SRP on the composition of the subgingival microbiota of chronic periodontitis (CP in individuals with type 2 diabetes (DM2 with inadequate metabolic control and in systemically healthy (SH individuals. Forty individuals (20 DM2 and 20 SH with CP underwent full-mouth periodontal examination. Subgingival plaque was sampled from 4 deep sites of each individual and tested for mean prevalence and counts of 45 bacterial taxa by the checkerboard method. Clinical and microbiological assessments were performed before and 3 months after SRP. At baseline, those in the DM2 group presented a significantly higher percentage of sites with visible plaque and bleeding on probing compared with those in the SH group (p < 0.01. Those in the DM2 group presented significantly higher levels of C. rectus and P. gingivalis, and lower prevalence of P. micra and S. anginosus, compared with those in the SH group (p ≤ 0.001. At the 3-month visit, both groups showed a significant improvement in all clinical parameters (p < 0.01. Those in the DM2 group showed significantly higher prevalence and/or levels of A. gerencseriae, A. naeslundii I, A. oris, A. odontolyticus, C. sputigena, F. periodonticum, and G. morbillorum compared with those in the SH group (p ≤ 0.001. However, those in the DM2 group showed a significant reduction in the levels of P. intermedia, P. gingivalis, T. forsythia, and T. denticola (p ≤ 0.001 over time. Those in the SRP group showed improved periodontal status and reduced levels of putative periodontal pathogens at 3 months’ evaluation compared with those in the DM2 group with inadequate metabolic control.

Semi-quantitative interpretation of the bone scan in metabolic bone disease

Energy Technology Data Exchange (ETDEWEB)

Fogelman, I; Turner, J G; Hay, I D; Boyle, I T [Royal Infirmary, Glasgow (UK). Dept. of Nuclear Medicine; Citrin, D L [Wisconsin Univ., Madison (USA). Dept. of Human Oncology; Bessent, G R

1979-01-01

Certain easily recognisable features are commonly seen in the bone scans of patients with metabolic bone disorders. Seven such features have been numerically graded by three independent observers in the scans of 100 patients with metabolic bone disease and of 50 control subjects. The total score for each patient is defined as the metabolic index. The mean metabolic index for each group of patients with metabolic bone disease is significantly greater than that for the control group (P < 0.001). (orig.).

Metabolic control analysis of biochemical pathways based on a thermokinetic description of reaction rates

DEFF Research Database (Denmark)

Nielsen, Jens Bredal

1997-01-01

Metabolic control analysis is a powerful technique for the evaluation of flux control within biochemical pathways. Its foundation is the elasticity coefficients and the flux control coefficients (FCCs). On the basis of a thermokinetic description of reaction rates it is here shown...... that the elasticity coefficients can be calculated directly from the pool levels of metabolites at steady state. The only requirement is that one thermodynamic parameter be known, namely the reaction affinity at the intercept of the tangent in the inflection point of the curve of reaction rate against reaction...... of the thermokinetic description of reaction rates to include the influence of effecters. Here the reaction rate is written as a linear function of the logarithm of the metabolite concentrations. With this type of rate function it is shown that the approach of Delgado and Liao [Biochem. J. (1992) 282, 919-927] can...

Cerebral Metabolism and the Role of Glucose Control in Acute Traumatic Brain Injury.

Science.gov (United States)

Buitrago Blanco, Manuel M; Prashant, Giyarpuram N; Vespa, Paul M

2016-10-01

This article reviews key concepts of cerebral glucose metabolism, neurologic outcomes in clinical trials, the biology of the neurovascular unit and its involvement in secondary brain injury after traumatic brain insults, and current scientific and clinical data that demonstrate a better understanding of the biology of metabolic dysfunction in the brain, a concept now known as cerebral metabolic energy crisis. The use of neuromonitoring techniques to better understand the pathophysiology of the metabolic crisis is reviewed and a model that summarizes the triphasic view of cerebral metabolic disturbance supported by existing scientific data is outlined. The evidence is summarized and a template for future research provided. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain PET substrate of impulse control disorders in Parkinson's disease: A metabolic connectivity study.

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Verger, Antoine; Klesse, Elsa; Chawki, Mohammad B; Witjas, Tatiana; Azulay, Jean-Philippe; Eusebio, Alexandre; Guedj, Eric

2018-04-10

Impulse control disorders (ICDs) have received increased attention in Parkinson's disease (PD) because of potentially dramatic consequences. Their physiopathology, however, remains incompletely understood. An overstimulation of the mesocorticolimbic system has been reported, while a larger network has recently been suggested. The aim of this study is to specifically describe the metabolic PET substrate and related connectivity changes in PD patients with ICDs. Eighteen PD patients with ICDs and 18 PD patients without ICDs were evaluated using cerebral 18F-fluorodeoxyglucose positron emission tomography. SPM-T maps comparisons were performed between groups and metabolic connectivity was evaluated by interregional correlation analysis (IRCA; p  130) and by graph theory (p < .05). PD patients with ICDs had relative increased metabolism in the right middle and inferior temporal gyri compared to those without ICDs. The connectivity of this area was increased mostly with the mesocorticolimbic system, positively with the orbitofrontal region, and negatively with both the right parahippocampus and the left caudate (IRCA). Moreover, the betweenness centrality of this area with the mesocorticolimbic system was lost in patients with ICDs (graph analysis). ICDs are associated in PD with the dysfunction of a network exceeding the mesocorticolimbic system, and especially the caudate, the parahippocampus, and the orbitofrontal cortex, remotely including the right middle and inferior temporal gyri. This latest area loses its central place with the mesocorticolimbic system through a connectivity dysregulation. © 2018 Wiley Periodicals, Inc.

LA sprouts randomized controlled nutrition, cooking and gardening programme reduces obesity and metabolic risk in Hispanic/Latino youth.

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Gatto, N M; Martinez, L C; Spruijt-Metz, D; Davis, J N

2017-02-01

Many programmes for children that involve gardening and nutrition components exist; however, none include experimental designs allowing more rigorous evaluation of their impact on obesity. The objective of this study is to explore the effects of a novel 12-week gardening, nutrition and cooking intervention {'LA Sprouts'} on dietary intake, obesity parameters and metabolic disease risk among low-income, primarily Hispanic/Latino youth in Los Angeles.. This study used a randomized control trial involving four elementary schools [two randomized to intervention {172, 3rd-5th grade students}; two randomized to control {147, 3rd-5th grade students}]. Classes were taught in 90-min sessions once per week for 12 weeks. Data collected at pre-intervention and post-intervention included dietary intake via food frequency questionnaire, anthropometric measures {body mass index, waist circumference}, body fat, and fasting blood samples. LA Sprouts participants compared with controls had significantly greater reductions in body mass index z-scores {-0.1 vs. -0.04, respectively; p = 0.01} and waist circumference {-1.2 vs. 0.1 cm; p obesity and metabolic risk; however, additional larger and longer-term studies are warranted. © 2016 World Obesity Federation.

Features of an altered AMPK metabolic pathway in Gilbert’s Syndrome, and its role in metabolic health

OpenAIRE

Christine Mölzer; Marlies Wallner; Carina Kern; Anela Tosevska; Ursula Schwarz; Rene Zadnikar; Daniel Doberer; Rodrig Marculescu; Karl-Heinz Wagner

2016-01-01

Energy metabolism, involving the ATP-dependent AMPK-PgC-Ppar pathway impacts metabolic health immensely, in that its impairment can lead to obesity, giving rise to disease. Based on observations that individuals with Gilbert?s syndrome (GS; UGT1A1 *28 promoter mutation) are generally lighter, leaner and healthier than controls, specific inter-group differences in the AMPK pathway regulation were explored. Therefore, a case-control study involving 120 fasted, healthy, age- and gender matched s...

The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity.

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Heimbucher, Thomas; Liu, Zheng; Bossard, Carine; McCloskey, Richard; Carrano, Andrea C; Riedel, Christian G; Tanasa, Bogdan; Klammt, Christian; Fonslow, Bryan R; Riera, Celine E; Lillemeier, Bjorn F; Kemphues, Kenneth; Yates, John R; O'Shea, Clodagh; Hunter, Tony; Dillin, Andrew

2015-07-07

FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and major determinants of aging in organisms ranging from worms to man. The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating enzyme MATH-33 as an essential DAF-16 regulator in IIS, which stabilizes active DAF-16 protein levels and, as a consequence, influences DAF-16 functions, such as metabolism, stress response, and longevity in C. elegans. MATH-33 associates with DAF-16 in cellulo and in vitro. MATH-33 functions as a deubiquitylase by actively removing ubiquitin moieties from DAF-16, thus counteracting the action of the RLE-1 E3-ubiquitin ligase. Our findings support a model in which MATH-33 promotes DAF-16 stability in response to decreased IIS by directly modulating its ubiquitylation state, suggesting that regulated oscillations in the stability of DAF-16 protein play an integral role in controlling processes such as metabolism and longevity. Copyright © 2015 Elsevier Inc. All rights reserved.

Increased prevalence of metabolic syndrome in patients with acne inversa.

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Robert Sabat

Full Text Available BACKGROUND: Acne inversa (AI; also designated as Hidradenitis suppurativa is a common chronic inflammatory skin disease, localized in the axillary, inguinal and perianal skin areas that causes painful, fistulating sinuses with malodorous purulence and scars. Several chronic inflammatory diseases are associated with the metabolic syndrome and its consequences including arteriosclerosis, coronary heart disease, myocardial infraction, and stroke. So far, the association of AI with systemic metabolic alterations is largely unexplored. METHODS AND FINDINGS: A hospital-based case-control study in 80 AI patients and 100 age- and sex-matched control participants was carried out. The prevalence of central obesity (odds ratio 5.88, hypertriglyceridemia (odds ratio 2.24, hypo-HDL-cholesterolemia (odds ratio 4.56, and hyperglycemia (odds ratio 4.09 in AI patients was significantly higher than in controls. Furthermore, the metabolic syndrome, previously defined as the presence of at least three of the five alterations listed above, was more common in those patients compared to controls (40.0% versus 13.0%; odds ratio 4.46, 95% confidence interval 2.02 to 9.96; P<0.001. AI patients with metabolic syndrome also had more pronounced metabolic alterations than controls with metabolic syndrome. Interestingly, there was no correlation between the severity or duration of the disease and the levels of respective parameters or the number of criteria defining the metabolic syndrome. Rather, the metabolic syndrome was observed in a disproportionately high percentage of young AI patients. CONCLUSIONS: This study shows for the first time that AI patients have a high prevalence of the metabolic syndrome and all of its criteria. It further suggests that the inflammation present in AI patients does not have a major impact on the development of metabolic alterations. Instead, evidence is given for a role of metabolic alterations in the development of AI. We recommend

Zinc Status Biomarkers and Cardiometabolic Risk Factors in Metabolic Syndrome: A Case Control Study

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Erika P. S. Freitas

2017-02-01

Full Text Available Metabolic syndrome (MS involves pathophysiological alterations that might compromise zinc status. The aim of this study was to evaluate zinc status biomarkers and their associations with cardiometabolic factors in patients with MS. Our case control study included 88 patients with MS and 37 controls. We performed clinical and anthropometric assessments and obtained lipid, glycemic, and inflammatory profiles. We also evaluated zinc intake, plasma zinc, erythrocyte zinc, and 24-h urinary zinc excretion. The average zinc intake was significantly lower in the MS group (p < 0.001. Regression models indicated no significant differences in plasma zinc concentration (all p > 0.05 between the two groups. We found significantly higher erythrocyte zinc concentration in the MS group (p < 0.001 independent from co-variable adjustments. Twenty-four hour urinary zinc excretion was significantly higher in the MS group (p = 0.008, and adjustments for age and sex explained 21% of the difference (R2 = 0.21, p < 0.001. There were significant associations between zincuria and fasting blood glucose concentration (r = 0.479, waist circumference (r = 0.253, triglyceride concentration (r = 0.360, glycated hemoglobin concentration (r = 0.250, homeostatic model assessment—insulin resistance (r = 0.223, and high-sensitivity C-reactive protein concentration (r = 0.427 (all p < 0.05 in the MS group. Patients with MS had alterations in zinc metabolism mainly characterized by an increase in erythrocyte zinc and higher zincuria.

Beneficial effects of viscous dietary fiber from Konjac-mannan in subjects with the insulin resistance syndrome: results of a controlled metabolic trial.

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Vuksan, V; Sievenpiper, J L; Owen, R; Swilley, J A; Spadafora, P; Jenkins, D J; Vidgen, E; Brighenti, F; Josse, R G; Leiter, L A; Xu, Z; Novokmet, R

2000-01-01

Dietary fiber has recently received recognition for reducing the risk of developing diabetes and heart disease. The implication is that it may have therapeutic benefit in prediabetic metabolic conditions. To test this hypothesis, we investigated the effect of supplementing a high-carbohydrate diet with fiber from Konjac-mannan (KJM) on metabolic control in subjects with the insulin resistance syndrome. We screened 278 free-living subjects between the ages of 45 and 65 years from the Canadian-Maltese Diabetes Study. A total of 11 (age 55+/-4 years, BMI 28+/-1.5 kg/m2) were recruited who satisfied the inclusion criteria: impaired glucose tolerance, reduced HDL cholesterol, elevated serum triglycerides, and moderate hypertension. After an 8-week baseline, they were randomly assigned to take either KJM fiber-enriched test biscuits (0.5 g of glucomannan per 100 kcal of dietary intake or 8-13 g/day) or wheat bran fiber (WB) control biscuits for two 3-week treatment periods separated by a 2-week washout. The diets were isoenergetic, metabolically controlled, and conformed to National Cholesterol Education Program Step 2 guidelines. Serum lipids, glycemic control, and blood pressure were the outcome measures. Decreases in serum cholesterol (total, 12.4+/-3.1%, PFasting blood glucose, insulin, triglycerides, HDL cholesterol, and body weight remained unchanged. A diet rich in high-viscosity KJM improves glycemic control and lipid profile, suggesting a therapeutic potential in the treatment of the insulin resistance syndrome.

Microenvironmental Modulation of Decorin and Lumican in Temozolomide-Resistant Glioblastoma and Neuroblastoma Cancer Stem-Like Cells.

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Cristiano Farace

Full Text Available The presence of cancer stem cells (CSCs or tumor-initiating cells can lead to cancer recurrence in a permissive cell-microenvironment interplay, promoting invasion in glioblastoma (GBM and neuroblastoma (NB. Extracellular matrix (ECM small leucine-rich proteoglycans (SLRPs play multiple roles in tissue homeostasis by remodeling the extracellular matrix (ECM components and modulating intracellular signaling pathways. Due to their pan-inhibitory properties against receptor tyrosine kinases (RTKs, SLRPs are reported to exert anticancer effects in vitro and in vivo. However, their roles seem to be tissue-specific and they are also involved in cancer cell migration and drug resistance, paving the way to complex different scenarios. The aim of this study was to determine whether the SLRPs decorin (DCN and lumican (LUM are recruited in cell plasticity and microenvironmental adaptation of differentiated cancer cells induced towards stem-like phenotype. Floating neurospheres were generated by applying CSC enrichment medium (neural stem cell serum-free medium, NSC SFM to the established SF-268 and SK-N-SH cancer cell lines, cellular models of GBM and NB, respectively. In both models, the time-dependent synergistic activation of DCN and LUM was observed. The highest DCN and LUM mRNA/protein expression was detected after cell exposure to NSC SFM for 8/12 days, considering these cells as SLRP-expressing (SLRP+ CSC-like. Ultrastructural imaging showed the cellular heterogeneity of both the GBM and NB neurospheres and identified the inner living cells. Parental cell lines of both GBM and NB grew only in soft agar + NSC SFM, whereas the secondary neurospheres (originated from SLRP+ t8 CSC-like showed lower proliferation rates than primary neurospheres. Interestingly, the SLRP+ CSC-like from the GBM and NB neurospheres were resistant to temozolomide (TMZ at concentrations >750 μM. Our results suggest that GBM and NB CSC-like promote the activation of huge

Microenvironmental Modulation of Decorin and Lumican in Temozolomide-Resistant Glioblastoma and Neuroblastoma Cancer Stem-Like Cells.

Science.gov (United States)

Farace, Cristiano; Oliver, Jaime Antonio; Melguizo, Consolacion; Alvarez, Pablo; Bandiera, Pasquale; Rama, Ana Rosa; Malaguarnera, Giulia; Ortiz, Raul; Madeddu, Roberto; Prados, Jose

2015-01-01

The presence of cancer stem cells (CSCs) or tumor-initiating cells can lead to cancer recurrence in a permissive cell-microenvironment interplay, promoting invasion in glioblastoma (GBM) and neuroblastoma (NB). Extracellular matrix (ECM) small leucine-rich proteoglycans (SLRPs) play multiple roles in tissue homeostasis by remodeling the extracellular matrix (ECM) components and modulating intracellular signaling pathways. Due to their pan-inhibitory properties against receptor tyrosine kinases (RTKs), SLRPs are reported to exert anticancer effects in vitro and in vivo. However, their roles seem to be tissue-specific and they are also involved in cancer cell migration and drug resistance, paving the way to complex different scenarios. The aim of this study was to determine whether the SLRPs decorin (DCN) and lumican (LUM) are recruited in cell plasticity and microenvironmental adaptation of differentiated cancer cells induced towards stem-like phenotype. Floating neurospheres were generated by applying CSC enrichment medium (neural stem cell serum-free medium, NSC SFM) to the established SF-268 and SK-N-SH cancer cell lines, cellular models of GBM and NB, respectively. In both models, the time-dependent synergistic activation of DCN and LUM was observed. The highest DCN and LUM mRNA/protein expression was detected after cell exposure to NSC SFM for 8/12 days, considering these cells as SLRP-expressing (SLRP+) CSC-like. Ultrastructural imaging showed the cellular heterogeneity of both the GBM and NB neurospheres and identified the inner living cells. Parental cell lines of both GBM and NB grew only in soft agar + NSC SFM, whereas the secondary neurospheres (originated from SLRP+ t8 CSC-like) showed lower proliferation rates than primary neurospheres. Interestingly, the SLRP+ CSC-like from the GBM and NB neurospheres were resistant to temozolomide (TMZ) at concentrations >750 μM. Our results suggest that GBM and NB CSC-like promote the activation of huge quantities

Measurement of microenvironmental ozone concentrations in Durham, North Carolina, using a 2B Technologies 205 Federal Equivalent Method monitor and an interference-free 2B Technologies 211 monitor.

Science.gov (United States)

Johnson, Ted; Capel, Jim; Ollison, Will

2014-03-01

During August and September of 2012, researchers conducted a microenvironmental (ME) monitoring study in Durham, North Carolina, using two 2B Technologies O3 monitors: a dual-beam model 205 Federal Equivalent Method (FEM) 254 nm photometer and a newly developed model 211 interference-free dual-beam photometer. The two monitors were mounted in a wheeled, fan-cooled suitcase together with a battery, a disposable N2O cartridge for the model 211 monitor and filtered sample lines. A scripted technician made paired O3 measurements in a variety of MEs within 2 miles of a fixed-site FEM O3 photometer at the Durham National GuardArmory. The ratio of the 211 to Armory O3 concentrations tended to be lowest (0.8) for 104 outdoor MEs. The mean values of the ratio for in-vehicle MEs tended to fall between 0.2 and 0.7--the mean for all 27 in-car tests was 0.3. The ratio values for indoor MEs tended to be higher when the enclosure was well ventilated. The outdoor ratios tended to be lower when the measurement was made downwind of nearby roadways, likely due to exhaust NO. The in-vehicle ratios tended to be larger with windows open than closed; the smallest occurred with closed windows, active air conditioning, and vent recirculation. The 205 - 211 measurement differences were generally small, with 94% of the 176 sample differences below 5 ppb. Five differences were above 10 ppb with the largest values (173.9 and 63.6 ppb) occurring inside a violin repair shop. Roadway proximity tended to increase the differences for outdoor locations. The largest in-vehicle difference (6 ppb) occurred at a convenience store service station. As addressed in regulatory models, such differences may reduce estimated population O3 exposure by 30-50% in indoor and in-vehicle MEs where individuals spend more than 80% of their time. Computer models used to estimate exposures of human populations-such as the Air Pollution Exposure Model (APEX) developed by the U.S. Environmental Protection Agency-can be

The Factor Inhibiting HIF Asparaginyl Hydroxylase Regulates Oxidative Metabolism and Accelerates Metabolic Adaptation to Hypoxia.

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Sim, Jingwei; Cowburn, Andrew S; Palazon, Asis; Madhu, Basetti; Tyrakis, Petros A; Macías, David; Bargiela, David M; Pietsch, Sandra; Gralla, Michael; Evans, Colin E; Kittipassorn, Thaksaon; Chey, Yu C J; Branco, Cristina M; Rundqvist, Helene; Peet, Daniel J; Johnson, Randall S

2018-04-03

Animals require an immediate response to oxygen availability to allow rapid shifts between oxidative and glycolytic metabolism. These metabolic shifts are highly regulated by the HIF transcription factor. The factor inhibiting HIF (FIH) is an asparaginyl hydroxylase that controls HIF transcriptional activity in an oxygen-dependent manner. We show here that FIH loss increases oxidative metabolism, while also increasing glycolytic capacity, and that this gives rise to an increase in oxygen consumption. We further show that the loss of FIH acts to accelerate the cellular metabolic response to hypoxia. Skeletal muscle expresses 50-fold higher levels of FIH than other tissues: we analyzed skeletal muscle FIH mutants and found a decreased metabolic efficiency, correlated with an increased oxidative rate and an increased rate of hypoxic response. We find that FIH, through its regulation of oxidation, acts in concert with the PHD/vHL pathway to accelerate HIF-mediated metabolic responses to hypoxia. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Simple anthropometric measures correlate with metabolic risk indicators as strongly as magnetic resonance imaging-measured adipose tissue depots in both HIV-infected and control subjects.

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Scherzer, Rebecca; Shen, Wei; Bacchetti, Peter; Kotler, Donald; Lewis, Cora E; Shlipak, Michael G; Heymsfield, Steven B; Grunfeld, Carl

2008-06-01

Studies in persons without HIV infection have compared percentage body fat (%BF) and waist circumference as markers of risk for the complications of excess adiposity, but only limited study has been conducted in HIV-infected subjects. We compared anthropometric and magnetic resonance imaging (MRI)-based adiposity measures as correlates of metabolic complications of adiposity in HIV-infected and control subjects. The study was a cross-sectional analysis of 666 HIV-positive and 242 control subjects in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study assessing body mass index (BMI), waist (WC) and hip (HC) circumferences, waist-to-hip ratio (WHR), %BF, and MRI-measured regional adipose tissue. Study outcomes were 3 metabolic risk variables [homeostatic model assessment (HOMA), triglycerides, and HDL cholesterol]. Analyses were stratified by sex and HIV status and adjusted for demographic, lifestyle, and HIV-related factors. In HIV-infected and control subjects, univariate associations with HOMA, triglycerides, and HDL were strongest for WC, MRI-measured visceral adipose tissue, and WHR; in all cases, differences in correlation between the strongest measures for each outcome were small (r HDL, WC appeared to be the best anthropometric correlate of metabolic complications, whereas, for triglycerides, the best was WHR. Relations of simple anthropometric measures with HOMA, triglycerides, and HDL cholesterol are approximately as strong as MRI-measured whole-body adipose tissue depots in both HIV-infected and control subjects.

Optogenetic control of mitochondrial metabolism and Ca2+ signaling by mitochondria-targeted opsins.

Science.gov (United States)

Tkatch, Tatiana; Greotti, Elisa; Baranauskas, Gytis; Pendin, Diana; Roy, Soumitra; Nita, Luliaoana I; Wettmarshausen, Jennifer; Prigge, Matthias; Yizhar, Ofer; Shirihai, Orian S; Fishman, Daniel; Hershfinkel, Michal; Fleidervish, Ilya A; Perocchi, Fabiana; Pozzan, Tullio; Sekler, Israel

2017-06-27

Key mitochondrial functions such as ATP production, Ca 2+ uptake and release, and substrate accumulation depend on the proton electrochemical gradient (ΔμH + ) across the inner membrane. Although several drugs can modulate ΔμH + , their effects are hardly reversible, and lack cellular specificity and spatial resolution. Although channelrhodopsins are widely used to modulate the plasma membrane potential of excitable cells, mitochondria have thus far eluded optogenetic control. Here we describe a toolkit of optometabolic constructs based on selective targeting of channelrhodopsins with distinct functional properties to the inner mitochondrial membrane of intact cells. We show that our strategy enables a light-dependent control of the mitochondrial membrane potential (Δψ m ) and coupled mitochondrial functions such as ATP synthesis by oxidative phosphorylation, Ca 2+ dynamics, and respiratory metabolism. By directly modulating Δψ m , the mitochondria-targeted opsins were used to control complex physiological processes such as spontaneous beats in cardiac myocytes and glucose-dependent ATP increase in pancreatic β-cells. Furthermore, our optometabolic tools allow modulation of mitochondrial functions in single cells and defined cell regions.

Teenage girls with type 1 diabetes have poorer metabolic control than boys and face more complications in early adulthood

DEFF Research Database (Denmark)

Samuelsson, Ulf; Anderzén, Johan; Gudbjörnsdottir, Soffia

2016-01-01

AIMS: To compare metabolic control between males and females with type 1 diabetes during adolescence and as young adults, and relate it to microvascular complications. METHODS: Data concerning 4000 adolescents with type 1 diabetes registered in the Swedish paediatric diabetes quality registry, an...

Analysis of the impact of environmental and social factors, with a particular emphasis on education, on the level of metabolic control in type 1 diabetes in children.

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Stefanowicz, Anna; Birkholz, Dorota; Myśliwiec, Małgorzata; Niedźwiecki, Maciej; Owczuk, Radosław; Balcerska, Anna

2012-01-01

Type 1 diabetes is a chronic, incurable childhood disease. Chronically uncontrolled diabetes is associated with eye, kidney, nerve, heart and blood vessel damage and function impairment. The aim of this study was to evaluate the impact of various social and environmental factors, with a particular emphasis on education, on the level of metabolic control in diabetes. The survey research was conducted in 102 children aged 0-18 years, diagnosed with type 1 diabetes. Based on the HbA(1c ) level, patients were divided into: group A (63 patients with fairly well and moderately controlled type 1 diabetes mellitus) and group B (39 patients with metabolically uncontrolled type 1 diabetes mellitus). The impact of various environmental and social factors on the degree of metabolic control of type 1 diabetes was analysed. No effect of typical environmental and social factors, such as: place of residence, gender, parents' education and their professional activity, on the level of metabolic control of type 1 diabetes was found. However, groups A and B significantly differed in the level of knowledge about diabetes and its treatment, in the regularity of meals, in possessing a nutrition scale and in the self-assessed preparation for taking care and custody of a child with type 1 diabetes. 1. Children with type 1 diabetes and their parents require ongoing education about the disease and its treatment. 2. The regularity of meals and the use of a nutrition scale have considerable impact on the level of metabolic control of the disease.

Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism.

Science.gov (United States)

Anandhan, Annadurai; Jacome, Maria S; Lei, Shulei; Hernandez-Franco, Pablo; Pappa, Aglaia; Panayiotidis, Mihalis I; Powers, Robert; Franco, Rodrigo

2017-07-01

The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

Regulators of nonsulfur purple phototrophic bacteria and the interactive control of CO2 assimilation, nitrogen fixation, hydrogen metabolism and energy generation.

Science.gov (United States)

Dubbs, James M; Tabita, F Robert

2004-06-01

For the metabolically diverse nonsulfur purple phototrophic bacteria, maintaining redox homeostasis requires balancing the activities of energy supplying and energy-utilizing pathways, often in the face of drastic changes in environmental conditions. These organisms, members of the class Alphaproteobacteria, primarily use CO2 as an electron sink to achieve redox homeostasis. After noting the consequences of inactivating the capacity for CO2 reduction through the Calvin-Benson-Bassham (CBB) pathway, it was shown that the molecular control of many additional important biological processes catalyzed by nonsulfur purple bacteria is linked to expression of the CBB genes. Several regulator proteins are involved, with the two component Reg/Prr regulatory system playing a major role in maintaining redox poise in these organisms. Reg/Prr was shown to be a global regulator involved in the coordinate control of a number of metabolic processes including CO2 assimilation, nitrogen fixation, hydrogen metabolism and energy-generation pathways. Accumulating evidence suggests that the Reg/Prr system senses the oxidation/reduction state of the cell by monitoring a signal associated with electron transport. The response regulator RegA/PrrA activates or represses gene expression through direct interaction with target gene promoters where it often works in concert with other regulators that can be either global or specific. For the key CO2 reduction pathway, which clearly triggers whether other redox balancing mechanisms are employed, the ability to activate or inactivate the specific regulator CbbR is of paramount importance. From these studies, it is apparent that a detailed understanding of how diverse regulatory elements integrate and control metabolism will eventually be achieved.

Attenuation of insulin-evoked responses in brain networks controlling appetite and reward in insulin resistance: the cerebral basis for impaired control of food intake in metabolic syndrome?

Science.gov (United States)

Anthony, Karen; Reed, Laurence J; Dunn, Joel T; Bingham, Emma; Hopkins, David; Marsden, Paul K; Amiel, Stephanie A

2006-11-01

The rising prevalence of obesity and type 2 diabetes is a global challenge. A possible mechanism linking insulin resistance and weight gain would be attenuation of insulin-evoked responses in brain areas relevant to eating in systemic insulin resistance. We measured brain glucose metabolism, using [(18)F]fluorodeoxyglucose positron emission tomography, in seven insulin-sensitive (homeostasis model assessment of insulin resistance [HOMA-IR] = 1.3) and seven insulin-resistant (HOMA-IR = 6.3) men, during suppression of endogenous insulin by somatostatin, with and without an insulin infusion that elevated insulin to 24.6 +/- 5.2 and 23.2 +/- 5.8 mU/l (P = 0.76), concentrations similar to fasting levels of the resistant subjects and approximately threefold above those of the insulin-sensitive subjects. Insulin-evoked change in global cerebral metabolic rate for glucose was reduced in insulin resistance (+7 vs. +17.4%, P = 0.033). Insulin was associated with increased metabolism in ventral striatum and prefrontal cortex and with decreased metabolism in right amygdala/hippocampus and cerebellar vermis (P reward. Diminishing the link be-tween control of food intake and energy balance may contribute to development of obesity in insulin resistance.

Comparative genome analysis of central nitrogen metabolism and its control by GlnR in the class Bacilli

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Kormelink Tom

2012-05-01

Full Text Available Abstract Background The assimilation of nitrogen in bacteria is achieved through only a few metabolic conversions between alpha-ketoglutarate, glutamate and glutamine. The enzymes that catalyze these conversions are glutamine synthetase, glutaminase, glutamate dehydrogenase and glutamine alpha-ketoglutarate aminotransferase. In low-GC Gram-positive bacteria the transcriptional control over the levels of the related enzymes is mediated by four regulators: GlnR, TnrA, GltC and CodY. We have analyzed the genomes of all species belonging to the taxonomic families Bacillaceae, Listeriaceae, Staphylococcaceae, Lactobacillaceae, Leuconostocaceae and Streptococcaceae to determine the diversity in central nitrogen metabolism and reconstructed the regulation by GlnR. Results Although we observed a substantial difference in the extent of central nitrogen metabolism in the various species, the basic GlnR regulon was remarkably constant and appeared not affected by the presence or absence of the other three main regulators. We found a conserved regulatory association of GlnR with glutamine synthetase (glnRA operon, and the transport of ammonium (amtB-glnK and glutamine/glutamate (i.e. via glnQHMP, glnPHQ, gltT, alsT. In addition less-conserved associations were found with, for instance, glutamate dehydrogenase in Streptococcaceae, purine catabolism and the reduction of nitrite in Bacillaceae, and aspartate/asparagine deamination in Lactobacillaceae. Conclusions Our analyses imply GlnR-mediated regulation in constraining the import of ammonia/amino-containing compounds and the production of intracellular ammonia under conditions of high nitrogen availability. Such a role fits with the intrinsic need for tight control of ammonia levels to limit futile cycling.

A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC.

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Neil Murphy

2016-04-01

Full Text Available Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI measurements to create four metabolic health/body size phenotype categories: (1 metabolically healthy/normal weight (BMI < 25 kg/m2, (2 metabolically healthy/overweight (BMI ≥ 25 kg/m2, (3 metabolically unhealthy/normal weight (BMI < 25 kg/m2, and (4 metabolically unhealthy/overweight (BMI ≥ 25 kg/m2. Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men] were used (instead of BMI to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was

Engineering microbial fatty acid metabolism for biofuels and biochemicals

DEFF Research Database (Denmark)

Marella, Eko Roy; Holkenbrink, Carina; Siewers, Verena

2017-01-01

microbial catalysis. This review summarizes the recent advances in the engineering of microbial metabolism for production of fatty acid-derived products. We highlight the efforts in engineering the central carbon metabolism, redox metabolism, controlling the chain length of the products, and obtaining...

Target setting in intensive insulin management is associated with metabolic control

DEFF Research Database (Denmark)

Swift, P G F; Skinner, T C; de Beaufort, C E

2010-01-01

Objective: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. Methods: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c...... was measured centrally. Results: A total of 2062 adolescents completed questionnaires (age 14.4 +/- 2.3 yr; diabetes duration 6.1 +/- 3.5 yr). Mean HbA 1c = 8.2 +/- 1.4% with significant differences between centres (F = 12.3; p ... (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant...

Metabolic Engineering of Chemical Defence Pathways in Plant Disease Control

DEFF Research Database (Denmark)

Rook, Frederik

2016-01-01

on each topic. The chapter reviews the some of the scientific and technical challenges in metabolic engineering and the new possibilities emerging from recent technological developments. It concludes by discussing the outlook for bioengineered chemical defences as part of crop protection strategies, also...... with antimicrobial properties for use in crop protection. It presents an overview of the metabolic engineering efforts made in the area of plant chemical defence. For in-depth information on the characteristics of a specific class of chemical defence compounds, the reader is referred to the specialized reviews...

Reduced Cortisol Metabolism during Critical Illness

Science.gov (United States)

Boonen, Eva; Vervenne, Hilke; Meersseman, Philippe; Andrew, Ruth; Mortier, Leen; Declercq, Peter E.; Vanwijngaerden, Yoo-Mee; Spriet, Isabel; Wouters, Pieter J.; Perre, Sarah Vander; Langouche, Lies; Vanhorebeek, Ilse; Walker, Brian R.; Van den Berghe, Greet

2015-01-01

BACKGROUND Critical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic–pituitary–adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism. METHODS In a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes. RESULTS Total and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (PCortisol production was 83% higher in the patients (P=0.02). There was a reduction of more than 50% in cortisol clearance during tracer infusion and after the administration of 100 mg of hydrocortisone in the patients (P≤0.03 for both comparisons). All these factors accounted for an increase by a factor of 3.5 in plasma cortisol levels in the patients, as compared with controls (Pcortisol clearance also correlated with a lower cortisol response to corticotropin stimulation. Reduced cortisol metabolism was associated with reduced inactivation of cortisol in the liver and kidney, as suggested by urinary steroid ratios, tracer kinetics, and assessment of liver-biopsy samples (P≤0.004 for all comparisons). CONCLUSIONS During critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically ill patients are unknown. (Funded by the Belgian

Oral cancer cells may rewire alternative metabolic pathways to survive from siRNA silencing of metabolic enzymes

International Nuclear Information System (INIS)

Zhang, Min; Chai, Yang D; Brumbaugh, Jeffrey; Liu, Xiaojun; Rabii, Ramin; Feng, Sizhe; Misuno, Kaori; Messadi, Diana; Hu, Shen

2014-01-01

Cancer cells may undergo metabolic adaptations that support their growth as well as drug resistance properties. The purpose of this study is to test if oral cancer cells can overcome the metabolic defects introduced by using small interfering RNA (siRNA) to knock down their expression of important metabolic enzymes. UM1 and UM2 oral cancer cells were transfected with siRNA to transketolase (TKT) or siRNA to adenylate kinase (AK2), and Western blotting was used to confirm the knockdown. Cellular uptake of glucose and glutamine and production of lactate were compared between the cancer cells with either TKT or AK2 knockdown and those transfected with control siRNA. Statistical analysis was performed with student T-test. Despite the defect in the pentose phosphate pathway caused by siRNA knockdown of TKT, the survived UM1 or UM2 cells utilized more glucose and glutamine and secreted a significantly higher amount of lactate than the cells transferred with control siRNA. We also demonstrated that siRNA knockdown of AK2 constrained the proliferation of UM1 and UM2 cells but similarly led to an increased uptake of glucose/glutamine and production of lactate by the UM1 or UM2 cells survived from siRNA silencing of AK2. Our results indicate that the metabolic defects introduced by siRNA silencing of metabolic enzymes TKT or AK2 may be compensated by alternative feedback metabolic mechanisms, suggesting that cancer cells may overcome single defective pathways through secondary metabolic network adaptations. The highly robust nature of oral cancer cell metabolism implies that a systematic medical approach targeting multiple metabolic pathways may be needed to accomplish the continued improvement of cancer treatment

Proton NMR metabolic profiling of CSF reveals distinct differentiation of meningitis from negative controls.

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Chatterji, Tanushri; Singh, Suruchi; Sen, Manodeep; Singh, Ajai Kumar; Agarwal, Gaurav Raj; Singh, Deepak Kumar; Srivastava, Janmejai Kumar; Singh, Alka; Srivastava, Rajeshwar Nath; Roy, Raja

2017-06-01

Cerebrospinal fluid (CSF) is an essential bio-fluid of the central nervous system (CNS), playing a vital role in the protection of CNS and performing neuronal function regulation. The chemical composition of CSF varies during onset of meningitis, neurodegenerative disorders (positive controls) and in traumatic cases (negative controls). The study design was broadly categorized into meningitis cases, negative controls and positive controls. Further differentiation among the three groups was carried out using Principal Component Analysis (PCA) followed by supervised Partial Least Square Discriminant Analysis (PLS-DA). The statistical analysis of meningitis vs. negative controls using PLS-DA model resulted in R 2 of 0.97 and Q 2 of 0.85. There was elevation in the levels of ketone bodies, total free amino acids, glutamine, creatine, citrate and choline containing compounds (choline and GPC) in meningitis cases. Similarly, meningitis vs. positive controls resulted in R 2 of 0.80 and Q 2 of 0.60 and showed elevation in the levels of total free amino acids, glutamine, creatine/creatinine and citrate in the meningitis group. Four cases of HIV were identified by PLS-DA model as well as by clinical investigations. On the basis of metabolic profile it was found that negative control CSF samples are more appropriate for differentiation of meningitis than positive control CSF samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Inter-regional comparison of land-use effects on stream metabolism

Science.gov (United States)

Melody J. Bernot; Daniel J. Sobota; Robert O. Hall; Patrick J. Mulholland; Walter K. Dodds; Jackson R. Webster; Jennifer L. Tank; Linda R. Ashkenas; Lee W. Cooper; Clifford N. Dahm; Stanley V. Gregory; Nancy B. Grimm; Stephen K. Hamilton; Sherri L. Johnson; William H. McDowell; Judith L. Meyer; Bruce Peterson; Geoffrey C. Poole; H. Maurice Valett; Clay Arango; Jake J. Beaulieu; Amy J. Burgin; Chelsea Crenshaw; Ashley M. Helton; Laura Johnson; Jeff Merriam; B.R. Niederlehner; Jonathan M. O' Brien; Jody D. Potter; Richard W. Sheibley; Suzanne M. Thomas; Kym. Wilson

2010-01-01

Rates of whole-system metabolism (production and respiration) are fundamental indicators of ecosystem structure and function. Although first-order, proximal controls are well understood, assessments of the interactions between proximal controls and distal controls, such as land use and geographic region, are lacking. Thus, the influence of land use on stream metabolism...

Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism

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Roze Ludmila V

2010-08-01

Full Text Available Abstract Background Filamentous fungi in the genus Aspergillus produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by Aspergillus parasiticus in an attempt to define the association of secondary metabolism with other metabolic and cellular processes. Results Volatile compounds were examined using solid phase microextraction - gas chromatography/mass spectrometry. In the wild type strain Aspergillus parasiticus SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine; we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator veA affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a veA disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation. Conclusions 1 Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2 VeA coordinates the

Classical and Non-Classical Roles for Pre-Receptor Control of DHT Metabolism in Prostate Cancer Progression.

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Zhang, Ailin; Zhang, Jiawei; Plymate, Stephen; Mostaghel, Elahe A

2016-04-01

Androgens play an important role in prostate cancer (PCa) development and progression. Accordingly, androgen deprivation therapy remains the front-line treatment for locally recurrent or advanced PCa, but patients eventually relapse with the lethal form of the disease termed castration resistant PCa (CRPC). Importantly, castration does not eliminate androgens from the prostate tumor microenvironment which is characterized by elevated tissue androgens that are well within the range capable of activating the androgen receptor (AR). In this mini-review, we discuss emerging data that suggest a role for the enzymes mediating pre-receptor control of dihydrotestosterone (DHT) metabolism, including AKR1C2, HSD17B6, HSD17B10, and the UGT family members UGT2B15 and UGT2B17, in controlling intratumoral androgen levels, and thereby influencing PCa progression. We review the expression of steroidogenic enzymes involved in this pathway in primary PCa and CRPC, the activity and regulation of these enzymes in PCa experimental models, and the impact of genetic variation in genes mediating pre-receptor DHT metabolism on PCa risk. Finally, we discuss recent data that suggests several of these enzymes may also play an unrecognized role in CRPC progression separate from their role in androgen inactivation.

Role of resting metabolic rate and energy expenditure in hunger and appetite control: a new formulation.

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Blundell, John E; Caudwell, Phillipa; Gibbons, Catherine; Hopkins, Mark; Naslund, Erik; King, Neil; Finlayson, Graham

2012-09-01

A long-running issue in appetite research concerns the influence of energy expenditure on energy intake. More than 50 years ago, Otto G. Edholm proposed that "the differences between the intakes of food [of individuals] must originate in differences in the expenditure of energy". However, a relationship between energy expenditure and energy intake within any one day could not be found, although there was a correlation over 2 weeks. This issue was never resolved before interest in integrative biology was replaced by molecular biochemistry. Using a psychobiological approach, we have studied appetite control in an energy balance framework using a multi-level experimental system on a single cohort of overweight and obese human subjects. This has disclosed relationships between variables in the domains of body composition [fat-free mass (FFM), fat mass (FM)], metabolism, gastrointestinal hormones, hunger and energy intake. In this Commentary, we review our own and other data, and discuss a new formulation whereby appetite control and energy intake are regulated by energy expenditure. Specifically, we propose that FFM (the largest contributor to resting metabolic rate), but not body mass index or FM, is closely associated with self-determined meal size and daily energy intake. This formulation has implications for understanding weight regulation and the management of obesity.

Role of resting metabolic rate and energy expenditure in hunger and appetite control: a new formulation

Directory of Open Access Journals (Sweden)

John E. Blundell

2012-09-01

Full Text Available A long-running issue in appetite research concerns the influence of energy expenditure on energy intake. More than 50 years ago, Otto G. Edholm proposed that “the differences between the intakes of food [of individuals] must originate in differences in the expenditure of energy”. However, a relationship between energy expenditure and energy intake within any one day could not be found, although there was a correlation over 2 weeks. This issue was never resolved before interest in integrative biology was replaced by molecular biochemistry. Using a psychobiological approach, we have studied appetite control in an energy balance framework using a multi-level experimental system on a single cohort of overweight and obese human subjects. This has disclosed relationships between variables in the domains of body composition [fat-free mass (FFM, fat mass (FM], metabolism, gastrointestinal hormones, hunger and energy intake. In this Commentary, we review our own and other data, and discuss a new formulation whereby appetite control and energy intake are regulated by energy expenditure. Specifically, we propose that FFM (the largest contributor to resting metabolic rate, but not body mass index or FM, is closely associated with self-determined meal size and daily energy intake. This formulation has implications for understanding weight regulation and the management of obesity.

Comparing metabolic control and complications in type 2 diabetes in two Pacific Islands at baseline and following diabetes care intervention

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Si Thu Win Tin

2016-06-01

Conclusions: This study indicates improved metabolic control but little change in diabetes complications 15 months after intervention. Efforts to improve and evaluate the ongoing quality and accessibility of diabetes care in Pacific Island settings need to be further strengthened.

Correlation of lipid metabolism characteristics with bile acid metabolism and placental hypoxia injury in patients with intrahepatic cholestasis of pregnancy

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Liang Tang

2017-05-01

Full Text Available Objective: To study the correlation of lipid metabolism characteristics with bile acid metabolism and placental hypoxia injury in patients with intrahepatic cholestasis of pregnancy (ICP. Methods: ICP pregnant women and healthy pregnant women who received antenatal care and delivered in Obstetrics Department of Panzhihua Maternal and Child Health Care Hospital between May 2013 and October 2016 were collected and included in ICP group and control group respectively. Serum lipid metabolism and bile acid metabolism indexes were measured at 20 weeks, 24 weeks, 28 weeks, 32 weeks and 36 weeks of gestation; mitochondria damage molecule expression levels in placenta were determined after childbirth. Results: Serum TC, LDL-C and HDL-C levels were not different between two groups of pregnant women at 20 weeks of gestation, and serum TC and LDL-C levels of ICP group at 24 weeks, 28 weeks, 32 weeks and 36 weeks of gestation were significantly higher than those of control group while HDL-C levels were significantly lower than those of control group; serum TBA, ALT and AST levels were not different between two groups of pregnant women at 20 weeks, 24 weeks and 28 weeks of gestation, and serum TBA, ALT and AST levels of ICP group at 32 weeks and 36 weeks of gestation were significantly higher than those of control group; CCO, ATPase, SDH and Bcl-2 protein expression in placenta tissue of ICP group were significantly lower than those of control group while Bax and Caspase-3 protein expression were significantly higher than those of control group. Serum LDL-C levels at 24 weeks, 28 weeks, 32 weeks and 36 weeks of gestation were positively correlated with TBA, ALT and AST levels in serum as well as Bax and Caspase-3 protein expression in placental tissue, and negatively correlated with CCO, ATPase, SDH and Bcl-2 protein expression in placental tissue. Conclusion: Midtrimester lipid metabolism characteristics can early predict the risk of ICP and evaluate the

A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers.

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Vance L Albaugh

Full Text Available Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT along with reduced plasma free fatty acids (FFA and leptin in animal models. It is unclear whether the same acute effects occur in humans.A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8 and female (7 subjects [18-30 years old, BMI 18.5-25]. Subjects received placebo or olanzapine (10 mg/day for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA. Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105 during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203 and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170, whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166 and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184, respectively after olanzapine. Other measures were unchanged.Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical antipsychotics.ClinicalTrials.gov NCT00741026.

ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch

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Steven Zhao

2016-10-01

Full Text Available Mechanisms of metabolic flexibility enable cells to survive under stressful conditions and can thwart therapeutic responses. Acetyl-coenzyme A (CoA plays central roles in energy production, lipid metabolism, and epigenomic modifications. Here, we show that, upon genetic deletion of Acly, the gene coding for ATP-citrate lyase (ACLY, cells remain viable and proliferate, although at an impaired rate. In the absence of ACLY, cells upregulate ACSS2 and utilize exogenous acetate to provide acetyl-CoA for de novo lipogenesis (DNL and histone acetylation. A physiological level of acetate is sufficient for cell viability and abundant acetyl-CoA production, although histone acetylation levels remain low in ACLY-deficient cells unless supplemented with high levels of acetate. ACLY-deficient adipocytes accumulate lipid in vivo, exhibit increased acetyl-CoA and malonyl-CoA production from acetate, and display some differences in fatty acid content and synthesis. Together, these data indicate that engagement of acetate metabolism is a crucial, although partial, mechanism of compensation for ACLY deficiency.

ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch.

Science.gov (United States)

Zhao, Steven; Torres, AnnMarie; Henry, Ryan A; Trefely, Sophie; Wallace, Martina; Lee, Joyce V; Carrer, Alessandro; Sengupta, Arjun; Campbell, Sydney L; Kuo, Yin-Ming; Frey, Alexander J; Meurs, Noah; Viola, John M; Blair, Ian A; Weljie, Aalim M; Metallo, Christian M; Snyder, Nathaniel W; Andrews, Andrew J; Wellen, Kathryn E

2016-10-18

Mechanisms of metabolic flexibility enable cells to survive under stressful conditions and can thwart therapeutic responses. Acetyl-coenzyme A (CoA) plays central roles in energy production, lipid metabolism, and epigenomic modifications. Here, we show that, upon genetic deletion of Acly, the gene coding for ATP-citrate lyase (ACLY), cells remain viable and proliferate, although at an impaired rate. In the absence of ACLY, cells upregulate ACSS2 and utilize exogenous acetate to provide acetyl-CoA for de novo lipogenesis (DNL) and histone acetylation. A physiological level of acetate is sufficient for cell viability and abundant acetyl-CoA production, although histone acetylation levels remain low in ACLY-deficient cells unless supplemented with high levels of acetate. ACLY-deficient adipocytes accumulate lipid in vivo, exhibit increased acetyl-CoA and malonyl-CoA production from acetate, and display some differences in fatty acid content and synthesis. Together, these data indicate that engagement of acetate metabolism is a crucial, although partial, mechanism of compensation for ACLY deficiency. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Caloric restriction alters the metabolic response to a mixed-meal: results from a randomized, controlled trial.

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Kim M Huffman

Full Text Available To determine if caloric restriction (CR would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to determine how any such changes relate to insulin sensitivity (S(I.Forty-six volunteers were randomized to a weight maintenance diet (Control, 25% CR, or 12.5% CR plus 12.5% energy deficit from structured aerobic exercise (CR+EX, or a liquid calorie diet (890 kcal/d until 15% reduction in body weightfor six months. Fasting and postprandial plasma samples were obtained at baseline, three, and six months. A targeted mass spectrometry-based platform was used to measure concentrations of individual free fatty acids (FFA, amino acids (AA, and acylcarnitines (AC. S(I was measured with an intravenous glucose tolerance test.Over three and six months, there were significantly larger differences in fasting-to-postprandial (FPP concentrations of medium and long chain AC (byproducts of FA oxidation in the CR relative to Control and a tendency for the same in CR+EX (CR-3 month P = 0.02; CR-6 month P = 0.002; CR+EX-3 month P = 0.09; CR+EX-6 month P = 0.08. After three months of CR, there was a trend towards a larger difference in FPP FFA concentrations (P = 0.07; CR-3 month P = 0.08. Time-varying differences in FPP concentrations of AC and AA were independently related to time-varying S(I (P<0.05 for both.Based on changes in intermediates of FA oxidation following a food challenge, CR imparted improvements in metabolic flexibility that correlated with improvements in S(I.ClinicalTrials.gov NCT00099151.

Metabolic effects of polycystic ovary syndrome in adolescents

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Han, Yejin; Lee, Hye-Jin; Oh, Jee-Young; Sung, Yeon-Ah

2015-01-01

Purpose Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenic anovulation in women of reproductive age. We investigated the metabolic effects of lean and overweight adolescents with PCOS. Methods Anthropometric measurements and biochemical parameters were evaluated in 49 adolescents with PCOS and 40 age- and body mass index (BMI)-matched controls. We further divided both PCOS and control groups into those having BMI within the normal range of less than 85th percentile and those being overweight and obese with a BMI greater than 85th percentile. Results Hemoglobin, gamma-glutamyl transferase (r-GT), total cholesterol, low-density lipoprotein-cholesterol and 2-hour postglucose load plasma insulin levels were significantly elevated in the lean PCOS group than in the lean control group. In the overweight/obese PCOS group, hemoglobin and r-GT levels were significantly elevated than in the overweight/obese control group. In the normal weight group, none of the subjects had metabolic syndrome according to the Adult Treatment Panel III criteria, but the incidence of metabolic syndrome in the overweight/obese PCOS group was 8.3% and that in the overweight/obese control group was 6.7%. Conclusion PCOS in adolescents causes metabolic abnormalities, underscoring the importance of early diagnosis of PCOS in oligomenorrheic adolescents. PMID:26512349

Metabolic effects of polycystic ovary syndrome in adolescents

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Yejin Han

2015-09-01

Full Text Available PurposePolycystic ovary syndrome (PCOS is characterized by hyperandrogenic anovulation in women of reproductive age. We investigated the metabolic effects of lean and overweight adolescents with PCOS.MethodsAnthropometric measurements and biochemical parameters were evaluated in 49 adolescents with PCOS and 40 age- and body mass index (BMI-matched controls. We further divided both PCOS and control groups into those having BMI within the normal range of less than 85th percentile and those being overweight and obese with a BMI greater than 85th percentile.ResultsHemoglobin, gamma-glutamyl transferase (r-GT, total cholesterol, low-density lipoprotein-cholesterol and 2-hour postglucose load plasma insulin levels were significantly elevated in the lean PCOS group than in the lean control group. In the overweight/obese PCOS group, hemoglobin and r-GT levels were significantly elevated than in the overweight/obese control group. In the normal weight group, none of the subjects had metabolic syndrome according to the Adult Treatment Panel III criteria, but the incidence of metabolic syndrome in the overweight/obese PCOS group was 8.3% and that in the overweight/obese control group was 6.7%.ConclusionPCOS in adolescents causes metabolic abnormalities, underscoring the importance of early diagnosis of PCOS in oligomenorrheic adolescents.

[Difficulties and concerns identified by Puerto Rican youth with insulin-dependent diabetes mellitus (IDDM): their relationship with metabolic control, hopelessness, social support, and depressive symptoms].

Science.gov (United States)

Rosselló, Jeannette; Maysonet Guzmán, Marielisa

2006-12-01

Insulin-dependent diabetes mellitus (IDDM) is a chronic health condition that affects 18 of every 100,000 Puerto Rican youth. Few research studies have been performed on the problems that youth with diabetes encounter and how they are related to adherence to treatment and adequate metabolic control. Adequate metabolic control is associated with fewer short and long-term medical complications, as well as better quality of life. Adapting to the demands and stressors associated with IDDM and its treatment is a task that can prove to be difficult for youth with diabetes due to having to make adjustments, alterations, and following a prescribed regimen in their daily activities. The main purpose of this investigation was to explore difficulties and worries identified by Puerto Rican youth with IDDM. This study examined whether there is a relationship between difficulties and worries, and adequate metabolic control, hopelessness, social support and depressive symptomatology. One hundred and one youth with IDDM between the ages of 8 and 17 (45 male, 56 female) were evaluated. Analysis of frequencies, correlations, and comparison tests were performed by group (gender, age, diabetes duration, and metabolic control. Results reveal that some of the difficulties identified by Puerto Rican youth with IDDM were: not eating candy and/or cake, self-monitoring blood glucose at school, doing things on time, and waking up early. Among the worries they reported were: insulin reactions and thinking that they might have to go to the hospital.

A randomized controlled trial: branched-chain amino acid levels and glucose metabolism in patients with obesity and sleep apnea.

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Barceló, Antonia; Morell-Garcia, Daniel; Salord, Neus; Esquinas, Cristina; Pérez, Gerardo; Pérez, Antonio; Monasterio, Carmen; Gasa, Merce; Fortuna, Ana Maria; Montserrat, Josep Maria; Mayos, Mercedes

2017-12-01

There is evidence that changes in branched-chain amino acid (BCAA) levels may correlate with the efficacy of therapeutic interventions for affecting improvement in metabolic control. The objective of this study was to evaluate whether serum concentrations of BCAAs (leucine, isoleucine, valine) could mediate in insulin sensitivity and glucose tolerance after continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). A prospective randomized controlled trial of OSA patients with morbid obesity was conducted. Eighty patients were randomized into two groups: 38 received conservative treatment and 42 received CPAP treatment for 12 weeks. Plasma levels of BCAA, glucose tolerance and insulin resistance were evaluated at baseline and after treatment. After treatment, significant decreases of leucine levels were observed in both groups when compared with baseline levels (P fasting plasma glucose and glycosylated haemoglobin values only in the conservative group (P < 0.05). In summary, we found that the treatment with CPAP for 12 weeks caused similar changes in circulating BCAAs concentrations to conservative treatment and a differential metabolic response of CPAP and conservative treatment was observed between the relationship of BCAAs and glucose homeostasis. Additional studies are needed to determine the interplay between branched-chain amino acids and glucose metabolism in patients with sleep apnea. © 2017 European Sleep Research Society.

[Effect of meal frequency and carbohydrate intake on the metabolic control of patients with type 2 diabetes mellitus].

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Leiva, Tamara; Basfi-Fer, Karen; Rojas, Pamela; Carrasco, Fernando; Ruz O, Manuel

2016-10-01

Increasing meal frequency is commonly used in the clinical practice as part of the nutritional treatment of patients with type 2 Diabetes Mellitus (DM2), although its effect on metabolic control parameters is controversial. To evaluate the association of energy intake, meal frequency, and amount of carbohydrates with fasting plasma glucose and glycosylated hemoglobin in a group of patients with DM2 without insulin therapy. Dietary intake was evaluated in 60 subjects with DM2 through three-day food records. The meal frequency was estimated establishing the main meal times considering snacks. Meal frequency was 4.7 ± 1.1 times per day. There was a positive association between glycosylated and fasting blood glucose levels (p Meal frequency was associated with energy intake (p meal frequency, available carbohydrates and energy intake, body mass index and fasting plasma glucose were analyzed in a multiple linear regression model, fasting blood glucose was the variable that best predicted changes in glycosylated hemoglobin (45.5%). Meal frequency had no association with glycosylated hemoglobin. Meal frequency showed no association with metabolic control parameters in DM2 patients.

Metabolic networks in epilepsy by MR spectroscopic imaging.

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Pan, J W; Spencer, D D; Kuzniecky, R; Duckrow, R B; Hetherington, H; Spencer, S S

2012-12-01

The concept of an epileptic network has long been suggested from both animal and human studies of epilepsy. Based on the common observation that the MR spectroscopic imaging measure of NAA/Cr is sensitive to neuronal function and injury, we use this parameter to assess for the presence of a metabolic network in mesial temporal lobe epilepsy (MTLE) patients. A multivariate factor analysis is performed with controls and MTLE patients, using NAA/Cr measures from 12 loci: the bilateral hippocampi, thalami, basal ganglia, and insula. The factor analysis determines which and to what extent these loci are metabolically covarying. We extract two independent factors that explain the data's variability in control and MTLE patients. In controls, these factors characterize a 'thalamic' and 'dominant subcortical' function. The MTLE patients also exhibit a 'thalamic' factor, in addition to a second factor involving the ipsilateral insula and bilateral basal ganglia. These data suggest that MTLE patients demonstrate a metabolic network that involves the thalami, also seen in controls. The MTLE patients also display a second set of metabolically covarying regions that may be a manifestation of the epileptic network that characterizes limbic seizure propagation. © 2012 John Wiley & Sons A/S.

The CD36-PPARγ Pathway in Metabolic Disorders

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Loïze Maréchal

2018-05-01

Full Text Available Uncovering the biological role of nuclear receptor peroxisome proliferator-activated receptors (PPARs has greatly advanced our knowledge of the transcriptional control of glucose and energy metabolism. As such, pharmacological activation of PPARγ has emerged as an efficient approach for treating metabolic disorders with the current use of thiazolidinediones to improve insulin resistance in diabetic patients. The recent identification of growth hormone releasing peptides (GHRP as potent inducers of PPARγ through activation of the scavenger receptor CD36 has defined a novel alternative to regulate essential aspects of lipid and energy metabolism. Recent advances on the emerging role of CD36 and GHRP hexarelin in regulating PPARγ downstream actions with benefits on atherosclerosis, hepatic cholesterol biosynthesis and fat mitochondrial biogenesis are summarized here. The response of PPARγ coactivator PGC-1 is also discussed in these effects. The identification of the GHRP-CD36-PPARγ pathway in controlling various tissue metabolic functions provides an interesting option for metabolic disorders.

Pregnancy and Lactation Alter Biomarkers of Biotin Metabolism in Women Consuming a Controlled Diet123

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Perry, Cydne A; West, Allyson A; Gayle, Antoinette; Lucas, Lauren K; Yan, Jian; Jiang, Xinyin; Malysheva, Olga; Caudill, Marie A

2014-01-01

Background: Biotin functions as a cofactor for several carboxylase enzymes with key roles in metabolism. At present, the dietary requirement for biotin is unknown and intake recommendations are provided as Adequate Intakes (AIs). The biotin AI for adults and pregnant women is 30 μg/d, whereas 35 μg/d is recommended for lactating women. However, pregnant and lactating women may require more biotin to meet the demands of these reproductive states. Objective: The current study sought to quantify the impact of reproductive state on biotin status response to a known dietary intake of biotin. Methods: To achieve this aim, we measured a panel of biotin biomarkers among pregnant (gestational week 27 at study entry; n = 26), lactating (postnatal week 5 at study entry; n = 28), and control (n = 21) women who participated in a 10- to 12-wk feeding study providing 57 μg of dietary biotin/d as part of a mixed diet. Results: Over the course of the study, pregnant women excreted 69% more (vs. control; P biotin-dependent methylcrotonyl–coenzyme A carboxylase is impaired. Interestingly, urinary excretion of 3-hydroxyisovaleryl-carnitine (3-HIA-carnitine), a downstream metabolite of 3-HIA, was 27% lower (P = 0.05) among pregnant (vs. control) women, a finding that may arise from carnitine inadequacy during gestation. No differences (P > 0.05) were detected in plasma biotin, urinary biotin, or urinary bisnorbiotin between pregnant and control women. Lactating women excreted 76% more (vs. control; P = 0.001) of the biotin catabolite bisnorbiotin, indicating that lactation accelerates biotin turnover and loss. Notably, with respect to control women, lactating women excreted 23% less (P = 0.04) urinary 3-HIA and 26% less (P = 0.05) urinary 3-HIA-carnitine, suggesting that lactation reduces leucine catabolism and that these metabolites may not be useful indicators of biotin status during lactation. Conclusions: Overall, these data demonstrate significant alterations in markers of

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.

Interdependence of nutrient metabolism and the circadian clock system: Importance for metabolic health

Science.gov (United States)

Ribas-Latre, Aleix; Eckel-Mahan, Kristin

2016-01-01

, can destroy synchrony between peripheral clocks and the central pacemaker in the brain as well as between peripheral clocks themselves. In addition, we review several studies looking at clock gene SNPs in humans and the metabolic phenotypes or tendencies associated with particular clock gene mutations. Major conclusions Targeted use of specific nutrients based on chronotype has the potential for immense clinical utility in the future. Macronutrients and micronutrients have the ability to function as zeitgebers for the clock by activating or modulating specific clock proteins or accessory proteins (such as nuclear receptors). Circadian clock control by nutrients can be tissue-specific. With a better understanding of the mechanisms that support nutrient-induced circadian control in specific tissues, human chronotype and SNP information might eventually be used to tailor nutritional regimens for metabolic disease treatment and thus be an important part of personalized medicine's future. PMID:26977390

Control of alanine metabolism in rat liver by transport processes or cellular metabolism.

OpenAIRE

Fafournoux, P; Rémésy, C; Demigné, C

1983-01-01

1. Factors governing hepatic utilization of alanine were studied in vivo and in vitro in rats adapted to increasing dietary protein. 2. Hepatic alanine utilization was enhanced 5-fold with a 90%-casein diet, compared with a 13%-casein diet. The increased uptake resulted from enhanced fractional extraction in the presence of high concentrations of alanine in the portal vein. 3. The increase in alanine metabolism on high-protein diets was associated with an increase in alanine aminotransferase ...

Fatty liver associated with metabolic derangement in patients with chronic kidney disease: A controlled attenuation parameter study

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Chang-Yun Yoon

2017-03-01

Full Text Available Background: Hepatic steatosis measured with controlled attenuation parameter (CAP using transient elastography predicts metabolic syndrome in the general population. We investigated whether CAP predicted metabolic syndrome in chronic kidney disease patients. Methods: CAP was measured with transient elastography in 465 predialysis chronic kidney disease patients (mean age, 57.5 years. Results: The median CAP value was 239 (202–274 dB/m. In 195 (41.9% patients with metabolic syndrome, diabetes mellitus was more prevalent (105 [53.8%] vs. 71 [26.3%], P < 0.001, with significantly increased urine albumin-to-creatinine ratio (184 [38–706] vs. 56 [16–408] mg/g Cr, P = 0.003, high sensitivity C-reactive protein levels (5.4 [1.4–28.2] vs. 1.7 [0.6–9.9] mg/L, P < 0.001, and CAP (248 [210–302] vs. 226 [196–259] dB/m, P < 0.001. In multiple linear regression analysis, CAP was independently related to body mass index (β = 0.742, P < 0.001, triglyceride levels (β = 2.034, P < 0.001, estimated glomerular filtration rate (β = 0.316, P = 0.001, serum albumin (β = 1.386, P < 0.001, alanine aminotransferase (β = 0.064, P = 0.029, and total bilirubin (β = −0.881, P = 0.009. In multiple logistic regression analysis, increased CAP was independently associated with increased metabolic syndrome risk (per 10 dB/m increase; odds ratio, 1.093; 95% confidence interval, 1.009–1.183; P = 0.029 even after adjusting for multiple confounding factors. Conclusion: Increased CAP measured with transient elastography significantly correlated with and could predict increased metabolic syndrome risk in chronic kidney disease patients.

Effects of rosiglitazone on metabolic parameters and large artery sclerosis in nondiabetic patients with metabolic sydrome

International Nuclear Information System (INIS)

Shen Zhenhai; Lu Yun; Feng Yinbo; Jin Xian

2010-01-01

Objective: To observe the effects of rosiglitazone on metabolic parameters, carotid intimamedia thickness (IMT), brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) in nondiabetic patients with metabolic syndrome. Methods: Seventy-nine nondiabetic patients with metabolic syndrome were randomly divided into treatment group (n = 41) and control group (n = 38). The patients in treatment group were treated with rosiglitazone on the basis of life-style intervention, those in control group were treated with life-style intervention for 9 months. All patients were followed up every 3 months. Body mass index (BMI) ,waist circumference(WC), systolic blood pressure (SBP), diastolic blood pressure(DBP), fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), highdendity lipoprotein (HDL-C), Low-density lipoprotein (LDL), high sensitivity C-reactive protein (hsCRP), HbA 1 C, fasting insulin (FIns), HOMA-IR, IMT, baPWV and ABI were measured in both groups before treatment and at the 6th, 9th month after treatment. Results: (1) After treatment with rosiglitazone for 6 months, FPG, TG, HDL-C, hsC RP, HbA 1 C, Fins and HOMA-IR in treatment group were improved (P 1 C, Fins and HOMA-IR got further improvement at the 9th month after treatment (P 1 C, Fins and HOMA-IR were changed significantly in treatment group compared to those in control group (P 1 C and HOMA-IR was independently related to the improvement of ABI by multivarient analysis. Conclusion: In nondiabetic patients with metabolic syndrome, rosiglitazone can significantly improve insulin resistance, correct metabolic disorders, has anti-inflammatory effect and retard atherosclerosis at some extent. (authors)

Contribution of family social support to the metabolic control of people with diabetes mellitus: A randomized controlled clinical trial.

Science.gov (United States)

Gomes, Lilian Cristiane; Coelho, Anna Claudia Martins; Gomides, Danielle Dos Santos; Foss-Freitas, Maria Cristina; Foss, Milton César; Pace, Ana Emilia

2017-08-01

This randomized controlled clinical trial aimed to evaluate the contribution of family social support to the clinical/metabolic control of people with type 2 diabetes mellitus. Diabetes mellitus is a chronic disease that requires continuous care in order for individuals to reach glycemic control, the primordial goal of treatment. Family social support is essential to the development of care skills and their maintenance. However, there are few studies that investigate the contribution of family social support to diabetes control. The study was developed between June 2011 and May 2013, and included 164 people who were randomized using simple randomization. The intervention group differed from the control group in that it included a family caregiver, who was recognized by the patient as a source of social support. The educational interventions received by people with diabetes mellitus were used as the basis of the education provided through telephone calls to patients' family members and caregivers, and their purpose was to encourage dialogue between the patients and their relatives about the topics related to diabetes. Regarding the clinical impact, the results showed that there was a greater reduction in blood pressure and glycated hemoglobin in the intervention group than in the control group, showing a positive effect on the control of the disease. Families should be incorporated into the care of people with diabetes mellitus and especially in health care programs, in particular those that can promote different forms of social support to strengthen the bond between family members. Copyright © 2017 Elsevier Inc. All rights reserved.

Reduced apolipoprotein glycosylation in patients with the metabolic syndrome.

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Olga V Savinova

Full Text Available The purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls.Very low density (VLDL, intermediate/low density (IDL/LDL, hereafter LDL, and high density lipoproteins (HDL fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays.Metabolic syndrome patients differed from healthy controls in the following ways: (1 total plasma--apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2 VLDL--apoB, apoC3, and apoE were increased; (3 LDL--apoC3 was increased, (4 HDL--associated constitutive serum amyloid A protein (SAA4 was reduced (p<0.05 vs. controls for all. In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all. Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all. Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001.Patients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined.

Effects of Tight Versus Non Tight Control of Metabolic Acidosis on Early Renal Function After Kidney Transplantation

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Farhad Etezadi

2012-09-01

Full Text Available Background Recently, several studies have been conducted to determine the optimal strategy for intraoperative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetatethat indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. Methods:120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE measurements to achieve the normal values of BE (5 to +5 mEq/L. In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE [less than or equal to] 15 mEq/L or bicarbonate [less than or equal to] 10 mEq/L or PH [less than or equal to] 7.15. Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. Results:In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Conclusion:Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

Effects of tight versus non tight control of metabolic acidosis on early renal function after kidney transplantation

Directory of Open Access Journals (Sweden)

Etezadi Farhad

2012-09-01

Full Text Available Abstract Background Recently, several studies have been conducted to determine the optimal strategy for intra-operative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetatethat indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. Methods 120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE measurements to achieve the normal values of BE (−5 to +5 mEq/L. In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE ≤ −15 mEq/L or bicarbonate ≤ 10 mEq/L or PH ≤ 7.15. Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. Results In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Conclusion Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

PHB Associates with the HIRA Complex to Control an Epigenetic-Metabolic Circuit in Human ESCs.

Science.gov (United States)

Zhu, Zhexin; Li, Chunliang; Zeng, Yanwu; Ding, Jianyi; Qu, Zepeng; Gu, Junjie; Ge, Laixiang; Tang, Fan; Huang, Xin; Zhou, Chenlin; Wang, Ping; Zheng, Deyou; Jin, Ying

2017-02-02

The chromatin landscape and cellular metabolism both contribute to cell fate determination, but their interplay remains poorly understood. Using genome-wide siRNA screening, we have identified prohibitin (PHB) as an essential factor in self-renewal of human embryonic stem cells (hESCs). Mechanistically, PHB forms protein complexes with HIRA, a histone H3.3 chaperone, and stabilizes the protein levels of HIRA complex components. Like PHB, HIRA is required for hESC self-renewal. PHB and HIRA act together to control global deposition of histone H3.3 and gene expression in hESCs. Of particular note, PHB and HIRA regulate the chromatin architecture at the promoters of isocitrate dehydrogenase genes to promote transcription and, thus, production of α-ketoglutarate, a key metabolite in the regulation of ESC fate. Our study shows that PHB has an unexpected nuclear role in hESCs that is required for self-renewal and that it acts with HIRA in chromatin organization to link epigenetic organization to a metabolic circuit. Copyright © 2017 Elsevier Inc. All rights reserved.

The Effects of Legumes on Metabolic Features, Insulin Resistance and Hepatic Function Tests in Women with Central Obesity: A Randomized Controlled Trial

OpenAIRE

Mohammad Alizadeh; Rasool Gharaaghaji; Bahram Pourghassem Gargari

2014-01-01

Background: The effect of high-legume hypocaloric diet on metabolic features in women is unclear. This study provided an opportunity to find effects of high-legume diet on metabolic features in women who consumed high legumes at pre-study period. Methods: In this randomized controlled trial after 2 weeks of a run-in period on an isocaloric diet, 42 premenopausal women with central obesity were randomly assigned into two groups: (1) Hypocaloric diet enriched in legumes (HDEL) and (2) hypoc...

A critique of the molecular target-based drug discovery paradigm based on principles of metabolic control: advantages of pathway-based discovery.

Science.gov (United States)

Hellerstein, Marc K

2008-01-01

Contemporary drug discovery and development (DDD) is dominated by a molecular target-based paradigm. Molecular targets that are potentially important in disease are physically characterized; chemical entities that interact with these targets are identified by ex vivo high-throughput screening assays, and optimized lead compounds enter testing as drugs. Contrary to highly publicized claims, the ascendance of this approach has in fact resulted in the lowest rate of new drug approvals in a generation. The primary explanation for low rates of new drugs is attrition, or the failure of candidates identified by molecular target-based methods to advance successfully through the DDD process. In this essay, I advance the thesis that this failure was predictable, based on modern principles of metabolic control that have emerged and been applied most forcefully in the field of metabolic engineering. These principles, such as the robustness of flux distributions, address connectivity relationships in complex metabolic networks and make it unlikely a priori that modulating most molecular targets will have predictable, beneficial functional outcomes. These same principles also suggest, however, that unexpected therapeutic actions will be common for agents that have any effect (i.e., that complexity can be exploited therapeutically). A potential operational solution (pathway-based DDD), based on observability rather than predictability, is described, focusing on emergent properties of key metabolic pathways in vivo. Recent examples of pathway-based DDD are described. In summary, the molecular target-based DDD paradigm is built on a naïve and misleading model of biologic control and is not heuristically adequate for advancing the mission of modern therapeutics. New approaches that take account of and are built on principles described by metabolic engineers are needed for the next generation of DDD.

Fulltext PDF

Indian Academy of Sciences (India)

PRAKASH KUMAR

with the wild-type sequence at position 3435, and so linkage disequilibrium was not ... of microenvironmental control of translation elongation rate in eukaryotic cells ... Synonymous codon substitutions affect ribosome traffic and protein folding.

Reduced Metabolism in Brain 'Control Networks' Following Cocaine-Cues Exposure in Female Cocaine Abusers

International Nuclear Information System (INIS)

Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Telang, F.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

2011-01-01

Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved. To test this we compared brain metabolism (using PET and 18 FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video. Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (-8.6% ± 10) whereas males tended to increase it (+5.5% ± 18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus). Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from 'control networks' (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.

What Is the Best Blood Sampling Time for Metabolic Control of Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients?

NARCIS (Netherlands)

van Dam, Esther; Daly, Anne; Venema-Liefaard, Gineke; van Rijn, Margreet; Derks, Terry G J; McKiernan, Patrick J; Heiner-Fokkema, Rebecca; MacDonald, Anita; van Spronsen, Francjan J

2017-01-01

BACKGROUND: Treatment of hereditary tyrosinemia type 1 with nitisinone and phenylalanine and tyrosine restricted diet has largely improved outcome, but the best blood sampling time for assessment of metabolic control is not known. AIM: To study diurnal and day-to-day variation of phenylalanine and

Impact of a structured multicomponent educational intervention program on metabolic control of patients with type 2 diabetes.

Science.gov (United States)

do Rosário Pinto, Maria; Parreira, Pedro Miguel Dinis Santos; Basto, Marta Lima; Dos Santos Mendes Mónico, Lisete

2017-12-15

Diabetes is one of the most common metabolic disorders, with a high prevalence of patients with poor metabolic control. Worldwide, evidence highlights the importance of developing and implementing educational interventions that can reduce this burden. The main objective of this study was to analyse the impact of a lifestyle centred intervention on glycaemic control of poorly controlled type 2 diabetic patients, followed in a Community Care Centre. A type 2 experimental design was conducted over 6 months, including 122 adults with HbA1c ≥ 7.5%, randomly allocated into Experimental group (EG) or Control Group (CG). EG patients attended a specific Educational Program while CG patients frequented usual care. Personal and health characterization variables, clinical metrics and self-care activities were measured before and after the implementation of the intervention. Analysis was done by comparing gains between groups (CG vs EG) through differential calculations (post minus pre-test results) and Longitudinal analysis. Statistical differences were obtained between groups for HbA1c and BMI: EG had a decrease in 11% more (effect-size r2 = .11) than CG for HbA1c (p values [Wilks' ʎ = .900; F(1,59) = 6.57; p = .013; ηp2 = .100; observed power = .713]; systolic Blood pressure [Wilks' ʎ = .735; F(1,61) = 21.94; p educational intervention program by itself, beyond standard educational approach alone, supported in a Longitudinal analysis that controlled variables statistically associated with clinical metrics in pre-test measures, has demonstrated its effectiveness in improving HbA1c, BMI and Blood pressure values. RBR-8ns8pb . (Retrospectively registered: October 30,2017).

Metabolic and cardiovascular risk in patients with a history of differentiated thyroid carcinoma: A case-controlled cohort study.

Science.gov (United States)

Giusti, Massimo; Mortara, Lorenzo; Degrandi, Roberta; Cecoli, Francesca; Mussap, Michele; Rodriguez, Guido; Ferone, Diego; Minuto, Francesco

2008-09-29

Hyperthyroidism seems to increase metabolic and cardiovascular risk, while the effects of sub-clinical hyperthyroidism are controversial. We evaluated metabolic and cardiovascular parameters in differentiated thyroid carcinoma (DTC) patients with suppressed thyrotropin (TSH) due to levo-thyroxine (L-T4) therapy. We studied DTC patients and, as a control group, patients with a history of surgery for non-malignant thyroid pathology. Significantly higher insulin and lower HDL-cholesterol levels were recorded in DTC subjects. In both groups, insulin levels were significantly related with body mass index (BMI) but not with age or L-T4 dosage. In DTC patients, a significant negative correlation was seen between HDL-cholesterol and BMI or L-T4 dosage. In both groups, intima-media thickness (IMT) correlated positively with age, BMI, glucose levels and systolic blood pressure. In DTC patients, increased IMT was significantly correlated with glycated hemoglobin (HbA1c), cholesterol and triglycerides. In DTC patients, C-reactive protein correlated positively with insulin, insulin resistance, triglycerides and systolic blood pressure, and negatively with HDL-cholesterol. In both DTC and control subjects, fibrinogen correlated positively with age, BMI, increased IMT, HbA1c and systolic blood pressure. In DTC subjects, plasma fibrinogen concentrations correlated positively with insulin resistance, cholesterol and LDL-cholesterol, and negatively with TSH levels. Our data confirm that the favorable evolution of DTC can be impaired by a high incidence of abnormal metabolic and cardiovascular data that are, at least in part, related to L-T4 therapy. These findings underline the need for adequate L-T4 titration.

Control of fluxes towards antibiotics and the role of primary metabolism in production of antibiotics

DEFF Research Database (Denmark)

Gunnarsson, Nina; Eliasson Lantz, Anna; Nielsen, Jacob

2004-01-01

Yield improvements in antibiotic-producing strains have classically been obtained through random mutagenesis and screening. An attractive alternative to this strategy is the rational design of producer strains via metabolic engineering, an approach that offers the possibility to increase yields...... in the metabolic network. Here we describe and discuss available methods for identification of these steps, both in antibiotic biosynthesis pathways and in the primary metabolism, which serves as the supplier of precursors and cofactors for the secondary metabolism. Finally, the importance of precursor...... and cofactor supply from primary metabolism in the biosynthesis of different types of antibiotics is discussed and recent developments in metabolic engineering towards increased product yields in antibiotic producing strains are reviewed....

Regional cerebral glucose metabolism in patients with Parkinson's disease with or without dementia

Energy Technology Data Exchange (ETDEWEB)

Sasaki, Masayuki; Ichiya, Yuichi; Hosokawa, Shinichi; Otsuka, Makoto; Kuwabara, Yasuo; Fukumura, Toshimitsu; Kato, Motohiro; Goto, Ikuo; Masuda, Kouji [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

1992-11-01

By means of positron emission tomography, the cerebral glucose metabolism in 5 patients with Parkinson's disease with dementia was compared with that in 9 patients without dementia, and that in 5 normal volunteers. The metabolic rates for glucose were measured by placing one hundred regions of interest. In the demented patients, cerebral glucose metabolism was diffusely decreased compared with that of the non-demented patients and the normal controls. The most significant decrease in glucose metabolism was observed in the angular gyrus (49.7% of the normal controls). The glucose metabolism in the cingulate, pre- and postcentral, occipital and subcortical regions was relatively spared (62.1 to 85.5% of the normal controls). In the patients without dementia, the glucose metabolism in each region was not significantly different from that in the normal controls. These results suggest that diffuse glucose hypometabolism in the cerebral cortex may correlate with that of patients with Parkinson's disease with dementia. (author).

Mineralogical controls on surface colonization by sulfur-metabolizing microbial communities

Science.gov (United States)

Jones, A. A.; Bennett, P.

2012-12-01

When characterizing microbial diversity and the microbial ecosystem of the shallow subsurface the mineral matrix is generally assumed to be homogenous and unreactive. We report here experimental evidence that microorganisms colonize rock surfaces according to the rock's chemistry and the organism's metabolic requirements and tolerances. We investigated this phenomenon using laboratory biofilm reactors with both a pure culture of sulfur-oxidizing Thiothrix unzii and a mixed environmental sulfur-metabolizing community from Lower Kane, Cave, WY, USA. Reactors contained rock and mineral chips (calcite, albite, microcline, quartz, chert, Madison Limestone (ML), Madison Dolostone (MD), and basalt) amended with one of the two inoculants. Biomass of attached microorganisms on each mineral surface was quantified. The 16S rRNA of attached microbial communities were compared using Roche FLX and Titanium 454 next generation pyrosequencing. A primary controlling factor on taxonomy of attached microorganisms in both pure and mixed culture experiments was mineral buffering capacity. In mixed culture experiments acid-buffering carbonates were preferentially colonized by neutrophilic sulfur-oxidizing microorganisms (~18% to ~27% of microorganisms), while acidophilic sulfur-oxidizing microorganisms colonized non-buffering quartz exclusively (~46% of microorganisms). The nutrient content of the rock was a controlling factor on biomass accumulation, with neutrophilic organisms selecting between carbonate surfaces of equivalent buffer capacities according to the availability of phosphate. Dry biomass on ML was 17.8 ± 2.3 mg/cm2 and MD was 20.6 ± 6.8 mg/cm2; while nutrient poor calcite accumulated 2.4 ± 0.3 mg/cm2. Biomass accumulation was minimal on non-buffering nutrient-limited surfaces. These factors are countered by the competitive exclusion of some populations. A pure culture of T. unzii preferentially colonizes carbonates while a very closely related Thiothrix spp is excluded

Vitamin C improves basal metabolic rate and lipid profile in alloxan ...

Indian Academy of Sciences (India)

MADU

3.1 Effect of vitamin C administration on basal metabolic rate. The basal metabolic rate values in diabetic rats and control are presented in figure 1. The basal metabolic rate (BMR) in diabetic rats was 1.19 ± 0.15 ml/h/g, while the BMR in control rats was 0.76 ± 0.89 ml/h/g. The BMR value in diabetic rats treated with vitamin ...

Applications of computational modeling in metabolic engineering of yeast

DEFF Research Database (Denmark)

Kerkhoven, Eduard J.; Lahtvee, Petri-Jaan; Nielsen, Jens

2015-01-01

a preferred flux distribution. These methods point to strategies for altering gene expression; however, fluxes are often controlled by post-transcriptional events. Moreover, GEMs are usually not taking into account metabolic regulation, thermodynamics and enzyme kinetics. To facilitate metabolic engineering......, it is necessary to expand the modeling of metabolism to consider kinetics of individual processes. This review will give an overview about models available for metabolic engineering of yeast and discusses their applications....

Obesogenic diets alter metabolism in mice.

Directory of Open Access Journals (Sweden)

Megan R Showalter

Full Text Available Obesity and accompanying metabolic disease is negatively correlated with lung health yet the exact mechanisms by which obesity affects the lung are not well characterized. Since obesity is associated with lung diseases as chronic bronchitis and asthma, we designed a series of experiments to measure changes in lung metabolism in mice fed obesogenic diets. Mice were fed either control or high fat/sugar diet (45%kcal fat/17%kcal sucrose, or very high fat diet (60%kcal fat/7% sucrose for 150 days. We performed untargeted metabolomics by GC-TOFMS and HILIC-QTOFMS and lipidomics by RPLC-QTOFMS to reveal global changes in lung metabolism resulting from obesity and diet composition. From a total of 447 detected metabolites, we found 91 metabolite and lipid species significantly altered in mouse lung tissues upon dietary treatments. Significantly altered metabolites included complex lipids, free fatty acids, energy metabolites, amino acids and adenosine and NAD pathway members. While some metabolites were altered in both obese groups compared to control, others were different between obesogenic diet groups. Furthermore, a comparison of changes between lung, kidney and liver tissues indicated few metabolic changes were shared across organs, suggesting the lung is an independent metabolic organ. These results indicate obesity and diet composition have direct mechanistic effects on composition of the lung metabolome, which may contribute to disease progression by lung-specific pathways.

Obesogenic diets alter metabolism in mice.

Science.gov (United States)

Showalter, Megan R; Nonnecke, Eric B; Linderholm, A L; Cajka, Tomas; Sa, Michael R; Lönnerdal, Bo; Kenyon, Nicholas J; Fiehn, Oliver

2018-01-01

Obesity and accompanying metabolic disease is negatively correlated with lung health yet the exact mechanisms by which obesity affects the lung are not well characterized. Since obesity is associated with lung diseases as chronic bronchitis and asthma, we designed a series of experiments to measure changes in lung metabolism in mice fed obesogenic diets. Mice were fed either control or high fat/sugar diet (45%kcal fat/17%kcal sucrose), or very high fat diet (60%kcal fat/7% sucrose) for 150 days. We performed untargeted metabolomics by GC-TOFMS and HILIC-QTOFMS and lipidomics by RPLC-QTOFMS to reveal global changes in lung metabolism resulting from obesity and diet composition. From a total of 447 detected metabolites, we found 91 metabolite and lipid species significantly altered in mouse lung tissues upon dietary treatments. Significantly altered metabolites included complex lipids, free fatty acids, energy metabolites, amino acids and adenosine and NAD pathway members. While some metabolites were altered in both obese groups compared to control, others were different between obesogenic diet groups. Furthermore, a comparison of changes between lung, kidney and liver tissues indicated few metabolic changes were shared across organs, suggesting the lung is an independent metabolic organ. These results indicate obesity and diet composition have direct mechanistic effects on composition of the lung metabolome, which may contribute to disease progression by lung-specific pathways.

The Bone Marrow-Derived Stromal Cells

DEFF Research Database (Denmark)

Tencerova, Michaela; Kassem, Moustapha

2016-01-01

Bone marrow (BM) microenvironment represents an important compartment of bone that regulates bone homeostasis and the balance between bone formation and bone resorption depending on the physiological needs of the organism. Abnormalities of BM microenvironmental dynamics can lead to metabolic bone...... diseases. BM stromal cells (also known as skeletal or mesenchymal stem cells) [bone marrow stromal stem cell (BMSC)] are multipotent stem cells located within BM stroma and give rise to osteoblasts and adipocytes. However, cellular and molecular mechanisms of BMSC lineage commitment to adipocytic lineage...

Translational control of aberrant stress responses as a hallmark of cancer.

Science.gov (United States)

El-Naggar, Amal M; Sorensen, Poul H

2018-04-01

Altered mRNA translational control is emerging as a critical factor in cancer development and progression. Targeting specific elements of the translational machinery, such as mTORC1 or eIF4E, is emerging as a new strategy for innovative cancer therapy. While translation of most mRNAs takes place through cap-dependent mechanisms, a sub-population of cellular mRNA species, particularly stress-inducible mRNAs with highly structured 5'-UTR regions, are primarily translated through cap-independent mechanisms. Intriguingly, many of these mRNAs encode proteins that are involved in tumour cell adaptation to microenvironmental stress, and thus linked to aggressive behaviour including tumour invasion and metastasis. This necessitates a rigorous search for links between microenvironmental stress and aggressive tumour phenotypes. Under stress, cells block global protein synthesis to preserve energy while maintaining selective synthesis of proteins that support cell survival. One highly conserved mechanism to regulate protein synthesis under cell stress is to sequester mRNAs into cytosolic aggregates called stress granules (SGs), where their translation is silenced. SGs confer survival advantages and chemotherapeutic resistance to tumour cells under stress. Recently, it has been shown that genetically blocking SG formation dramatically reduces tumour invasive and metastatic capacity in vivo. Therefore, targeting SG formation might represent a potential treatment strategy to block cancer metastasis. Here, we present the critical link between selective mRNA translation, stress adaptation, SGs, and tumour progression. Further, we also explain how deciphering mechanisms of selective mRNA translation occurs under cell stress holds great promise for the identification of new targets in the treatment of cancer. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland

Metabolic Surgery

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Pareek, Manan; Schauer, Philip R; Kaplan, Lee M

2018-01-01

The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown...... the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity....... Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further...

Alteration patterns of brain glucose metabolism: comparisons of healthy controls, subjective memory impairment and mild cognitive impairment.

Science.gov (United States)

Song, In-Uk; Choi, Eun Kyoung; Oh, Jin Kyoung; Chung, Yong-An; Chung, Sung-Woo

2016-01-01

Some groups have focused on the detection and management of subjective memory impairment (SMI) as the stage that precedes mild cognitive impairment (MCI). However, there have been few clinical studies that have examined biomarkers of SMI to date. To investigate the differences in glucose metabolism as a prodromal marker of dementia in patients with SMI, MCI, and healthy controls using brain F-18 fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Sixty-eight consecutive patients with SMI, 47 patients with MCI, and 42 age-matched healthy subjects were recruited. All subjects underwent FDG-PET and detailed neuropsychological testing. FDG-PET images were analyzed using the statistical parametric mapping (SPM) program. FDG-PET analysis showed glucose hypometabolism in the periventricular regions of patients with SMI and in the parietal, precentral frontal, and periventricular regions of patients with MCI compared with healthy controls. Interestingly, hypometabolism on FDG-PET was noted in the parietal and precentral frontal regions in MCI patients compared to SMI patients. The results suggest that hypometabolism in the periventricular regions as seen on FDG-PET may play a role as a predictive biomarker of pre-dementia, and the extension of reduced glucose metabolism into parietal regions likely reflects progression of cognitive deterioration. © The Foundation Acta Radiologica 2014.

Diabetes self-management, depressive symptoms, quality of life and metabolic control in youth with type 1 diabetes in China.

Science.gov (United States)

Guo, Jia; Whittemore, Robin; Grey, Margaret; Wang, Jing; Zhou, Zhi-Guang; He, Guo-Ping

2013-01-01

To assess diabetes self-management, depressive symptoms, quality of life and metabolic control in a cohort of youth with type 1 diabetes in mainland China. Predictors of self-management and depressive symptoms were also explored. Studies have shown that adaptation to childhood chronic illness is important in determining outcomes. Few studies have been reported on the behavioural, psychosocial and physiological adaptation processes and outcomes in Chinese youth with type 1 diabetes. This is a cross-sectional study as part of a multi-site longitudinal descriptive study. Data for this report were collected at baseline. A convenience sample of 136 eligible youth was recruited during follow-up visits in hospitals in 14 major cities of Hunan Province (located in central southern mainland China) from July 2009-October 2010. Data were collected on socio-demographic background, clinical characteristics, diabetes self-management, depressive symptoms, quality of life and metabolic control. Diabetes self-management was lower in Chinese youth compared with a US cohort and was associated with insulin treatment regimen, treatment location, depressive symptoms and gender. A total of 17·6% of youth reported high depressive symptoms, and depressive symptoms were correlated with family annual revenue, school attendance, peer relationship and parent-child relationship. The mean score of global satisfaction with quality of life was 17·14 ± 3·58. The mean HbA1c was 9·68%. Living with type 1 diabetes poses considerable challenges, and Chinese youth report lower self-management than US youth and high depressive symptoms. Metabolic control and quality of life were sub-optimal. More clinic visits, treatment for high depressive symptoms and an intensive insulin regimen may improve diabetes self-management for youth with type 1 diabetes in China. Culturally appropriate interventions aimed at helping them adapt to living with the disease and improving outcomes are urgently needed. © 2012

DNA methylation in metabolic disorders

DEFF Research Database (Denmark)

Barres, Romain; Zierath, Juleen R

2011-01-01

DNA methylation is a major epigenetic modification that controls gene expression in physiologic and pathologic states. Metabolic diseases such as diabetes and obesity are associated with profound alterations in gene expression that are caused by genetic and environmental factors. Recent reports...... have provided evidence that environmental factors at all ages could modify DNA methylation in somatic tissues, which suggests that DNA methylation is a more dynamic process than previously appreciated. Because of the importance of lifestyle factors in metabolic disorders, DNA methylation provides...... a mechanism by which environmental factors, including diet and exercise, can modify genetic predisposition to disease. This article considers the current evidence that defines a role for DNA methylation in metabolic disorders....

Protocols to Study Growth and Metabolism in Drosophila.

Science.gov (United States)

Strassburger, Katrin; Teleman, Aurelio A

2016-01-01

Signaling pathways such as the insulin/insulin-like growth factor pathway concurrently regulate organismal growth and metabolism. Drosophila has become a popular model system for studying both organismal growth and metabolic regulation. Care must be taken, however, when assessing such phenotypes because they are quantitative in nature, and influenced by environment. This chapter first describes how to control animal age and nutrient availability, since growth and metabolism are sensitive to these parameters. It then provides protocols for measuring tissue growth, cell size, and metabolic parameters such as stored lipids and glycogen, and circulating sugars.

Hormonal contraception in obesity, the metabolic syndrome, and diabetes

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Skouby, S.O.

2010-01-01

The rate of obesity worldwide is currently at epidemic proportions. As part of obesity, the metabolic syndrome describes a clustering of metabolic abnormalities that increase the cardiovascular and diabetes risk. In particular, women from developing countries have diabetes in the reproductive age...... diabetes, hormonal contraception should therefore be part of the highly needed preconception care and metabolic control...

Hormonal Contraception in obestiy, the metabolic syndrome, and diabetes

DEFF Research Database (Denmark)

Skouby, Sven O.

2010-01-01

The rate of obesity worldwide is currently at epidemic proportions. As part of obesity, the metabolic syndrome describes a clustering of metabolic abnormalities that increase the cardiovascular and diabetes risk. In particular, women from developing countries have diabetes in the reproductive age...... diabetes, hormonal contraception should therefore be part of the highly needed preconception care and metabolic control...

Leucine metabolism in patients with Hepatic Encephalopathy

International Nuclear Information System (INIS)

McGhee, A.S.; Kassouny, M.E.; Matthews, D.E.; Millikan, W.

1986-01-01

A primed continuous infusion of [ 15 N, 1- 13 C]leucine was used to determine whether increased oxidation and/or protein synthesis of leucine occurs in patients with cirrhosis. Five controls and patients were equilibrated on a metabolic balance diet [0.6 g protein per kg ideal body weight (IBW)]. An additional four patients were equilibrated in the same manner with the same type of diet with a protein level of 0.75 g per kg IBW. Plasma leucine and breath CO 2 enrichments were measured by mass spectrometry. Protein synthesis and leucine metabolism were identical in controls and patients when both were fed a diet with 0.6 g protein/kg IBW. Results indicate that systemic derangements of leucine metabolism are not the cause of Hepatic Encephalopathy

The metabolic profile of long-lived Drosophila melanogaster

DEFF Research Database (Denmark)

Sarup, Pernille Merete; Pedersen, Simon Metz; Nielsen, Niels Christian

2012-01-01

We investigated the age-related changes in the metabolic profile of male Drosophila melanogaster and compared the metabolic profile of flies selected for increased longevity to that of control flies of equal age. We found clear differences in metabolite composition between selection regimes...

Photoperiodism and enzyme activity: towards a model for the control of circadian metabolic rhythms in the crassulacean Acid metabolism.

Science.gov (United States)

Queiroz, O; Morel, C

1974-04-01

Metabolic readjustments after a change from long days to short days appear, in Kalanchoe blossfeldiana, to be achieved through the operation of two main mechanisms: variation in enzyme capacity, and circadian rhythmicity. After a lag time, capacity in phosphoenolpyruvate carboxylase and capacity in aspartate aminotransferase increase exponentially and appear to be allometrically linked during 50 to 60 short days; then a sudden fall takes place in the activity of the former. Malic enzyme and alanine aminotransferase behave differently. Thus, the operation of the two sections of the pathway (before and after the malate step) give rise to a continuously changing functional compartmentation in the pathway. Circadian rhythmicity, on the other hand, produces time compartmentation through phase shifts and variation in amplitude, independently for each enzyme. These characteristics suggest that the operation of a so-called biological clock would be involved. We propose the hypothesis that feedback regulation would be more accurate and efficient when applied to an already oscillating, clock-controlled enzyme system.

Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case-Control Study in EPIC.

Science.gov (United States)

Assi, Nada; Thomas, Duncan C; Leitzmann, Michael; Stepien, Magdalena; Chajès, Véronique; Philip, Thierry; Vineis, Paolo; Bamia, Christina; Boutron-Ruault, Marie-Christine; Sandanger, Torkjel M; Molinuevo, Amaia; Boshuizen, Hendriek C; Sundkvist, Anneli; Kühn, Tilman; Travis, Ruth C; Overvad, Kim; Riboli, Elio; Gunter, Marc J; Scalbert, Augustin; Jenab, Mazda; Ferrari, Pietro; Viallon, Vivian

2018-05-01

Background: The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (HLI) variables were related to targeted serum metabolites. Methods: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HLI to a set of 132 serum-measured metabolites and a liver function score. Mediation analysis evaluated whether metabolic profiles mediated the relationship between each lifestyle exposure and HCC risk. Results: Exposure-related metabolic signatures were identified. Particularly, the body mass index (BMI)-associated metabolic component was positively related to glutamic acid, tyrosine, PC aaC38:3, and liver function score and negatively to lysoPC aC17:0 and aC18:2. The lifetime alcohol-specific signature had negative loadings on sphingomyelins (SM C16:1, C18:1, SM(OH) C14:1, C16:1 and C22:2). Both exposures were associated with increased HCC with total effects (TE) = 1.23 (95% confidence interval = 0.93-1.62) and 1.40 (1.14-1.72), respectively, for BMI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HCC with natural indirect effects, respectively, equal to 1.56 (1.24-1.96) and 1.09 (1.03-1.15), accounting for a proportion mediated of 100% and 24%. Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk. Impact: The understanding of the biological basis for the relationship between modifiable exposures and cancer would pave avenues for clinical and public health interventions on metabolic mediators

Bile Acid Metabolism in Liver Pathobiology

Science.gov (United States)

Chiang, John Y. L.; Ferrell, Jessica M.

2018-01-01

Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver and other tissues and cells from cholesterol and bile acid toxicity. Bile acid metabolism is tightly regulated by bile acid synthesis in the liver and bile acid biotransformation in the intestine. Bile acids are endogenous ligands that activate a complex network of nuclear receptor farnesoid X receptor and membrane G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose metabolic homeostasis and energy metabolism. The gut-to-liver axis plays a critical role in the regulation of enterohepatic circulation of bile acids, bile acid pool size, and bile acid composition. Bile acids control gut bacteria overgrowth, and gut bacteria metabolize bile acids to regulate host metabolism. Alteration of bile acid metabolism by high-fat diets, sleep disruption, alcohol, and drugs reshapes gut microbiome and causes dysbiosis, obesity, and metabolic disorders. Gender differences in bile acid metabolism, FXR signaling, and gut microbiota have been linked to higher prevalence of fatty liver disease and hepatocellular carcinoma in males. Alteration of bile acid homeostasis contributes to cholestatic liver diseases, inflammatory diseases in the digestive system, obesity, and diabetes. Bile acid-activated receptors are potential therapeutic targets for developing drugs to treat metabolic disorders. PMID:29325602

Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder

International Nuclear Information System (INIS)

Swedo, S.E.; Schapiro, M.B.; Grady, C.L.; Cheslow, D.L.; Leonard, H.L.; Kumar, A.; Friedland, R.; Rapoport, S.I.; Rapoport, J.L.

1989-01-01

The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system

Impact of psychological stress on the associations between apolipoprotein E variants and metabolic traits: findings in an American sample of caregivers and controls.

Science.gov (United States)

Kring, Sofia I Iqbal; Brummett, Beverly H; Barefoot, John; Garrett, Melanie E; Ashley-Koch, Allison E; Boyle, Stephen H; Siegler, Ilene C; Sørensen, Thorkild I A; Williams, Redford B

2010-06-01

To examine the association between apolipoprotein E (APOE) gene variants and waist circumference, fasting plasma glucose, serum insulin, serum high-density lipoprotein cholesterol, and serum triglycerides, all metabolic traits known as cardiovascular disease (CVD) endophenotypes, in a population of stressed individuals and controls. Abdominal obesity, insulin resistance, elevated serum lipid concentration, and APOE polymorphisms have been associated with CVD risk. Current evidence supports the hypothesis that gene-environment interactions modulate serum lipid concentrations. The association between rs769450, rs405509, rs439401, and metabolic traits were analyzed in a U.S. sample of 126 white caregivers of a relative with Alzheimer';s disease or other major dementia and 122 white controls. The associations were analyzed, using multivariate analysis of variance adjusted for age, sex, and medications. Significant multivariate interactions were found, using both additive (p = .009) and dominant (p = .047) models between rs439401 (C/T) and caregiver stress in relation to a profile of metabolic variables. Univariate analyses found the TT genotype to be associated with more adverse levels of waist circumference (interaction, p = .026), triglycerides (interaction, p = .001) and high-density lipoprotein cholesterol (interaction, p = .001) among caregivers but with a more favorable profile of these endophenotypes among controls. There were no significant associations or interactions involving the other two single nucleotide polymorphisms. The APOE rs439401 TT genotype is associated with an adverse metabolic profile among chronically stressed individuals compared with individuals not similarly stressed in whom a more favorable profile is expressed. Confirmation of these results in further research would indicate that the TT genotype can be used to identify persons at high risk for CVD when subjected to chronic stress.

Reduced metabolism in brain "control networks" following cocaine-cues exposure in female cocaine abusers.

Directory of Open Access Journals (Sweden)

Nora D Volkow

2011-02-01

Full Text Available Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved.To test this we compared brain metabolism (using PET and ¹⁸FDG between female (n = 10 and male (n = 16 active cocaine abusers when they watched a neutral video (nature scenes versus a cocaine-cues video.Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05; females significantly decreased metabolism (-8.6%±10 whereas males tended to increase it (+5.5%±18. SPM analysis (Cocaine-cues vs Neutral in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001 whereas males showed increases in right inferior frontal gyrus (BA 44/45 (only at p<0.005. The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001 in frontal (BA 8, 9, 10, anterior cingulate (BA 24, 32, posterior cingulate (BA 23, 31, inferior parietal (BA 40 and thalamus (dorsomedial nucleus.Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from "control networks" (prefrontal, cingulate, inferior parietal, thalamus in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition. This highlights the importance of gender tailored interventions for cocaine addiction.

Is the rate of metabolic ageing and survival determined by Basal metabolic rate in the zebra finch?

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Bernt Rønning

Full Text Available The relationship between energy metabolism and ageing is of great interest because aerobic metabolism is the primary source of reactive oxygen species which is believed to be of major importance in the ageing process. We conducted a longitudinal study on captive zebra finches where we tested the effect of age on basal metabolic rate (BMR, as well as the effect of BMR on the rate of metabolic ageing (decline in BMR with age and survival. Basal metabolic rate declined with age in both sexes after controlling for the effect of body mass, indicating a loss of functionality with age. This loss of functionality could be due to accumulated oxidative damage, believed to increase with increasing metabolic rate, c.f. the free radical theory of ageing. If so, we would expect the rate of metabolic ageing to increase and survival to decrease with increasing BMR. However, we found no effect of BMR on the rate of metabolic ageing. Furthermore, survival was not affected by BMR in the males. In female zebra finches there was a tendency for survival to decrease with increasing BMR, but the effect did not reach significance (P<0.1. Thus, the effect of BMR on the rate of functional deterioration with age, if any, was not strong enough to influence neither the rate of metabolic ageing nor survival in the zebra finches.

Is the rate of metabolic ageing and survival determined by Basal metabolic rate in the zebra finch?

Science.gov (United States)

Rønning, Bernt; Moe, Børge; Berntsen, Henrik H; Noreen, Elin; Bech, Claus

2014-01-01

The relationship between energy metabolism and ageing is of great interest because aerobic metabolism is the primary source of reactive oxygen species which is believed to be of major importance in the ageing process. We conducted a longitudinal study on captive zebra finches where we tested the effect of age on basal metabolic rate (BMR), as well as the effect of BMR on the rate of metabolic ageing (decline in BMR with age) and survival. Basal metabolic rate declined with age in both sexes after controlling for the effect of body mass, indicating a loss of functionality with age. This loss of functionality could be due to accumulated oxidative damage, believed to increase with increasing metabolic rate, c.f. the free radical theory of ageing. If so, we would expect the rate of metabolic ageing to increase and survival to decrease with increasing BMR. However, we found no effect of BMR on the rate of metabolic ageing. Furthermore, survival was not affected by BMR in the males. In female zebra finches there was a tendency for survival to decrease with increasing BMR, but the effect did not reach significance (PBMR on the rate of functional deterioration with age, if any, was not strong enough to influence neither the rate of metabolic ageing nor survival in the zebra finches.

[Gut microbiota and immune crosstalk in metabolic disease].

Science.gov (United States)

Burcelin, Rémy

2017-01-01

The aim of the review is to discuss about the role played by the defence crosstalk between the gut microbiota and the intestinal immune system, in the development of metabolic disease focusing on obesity and diabetes. Starting from physiological and pathological stand points and based on the latest published data, this review is addressing how the concept of the hologenome theory of evolution can drive the fate of metabolic disease. The notion of "metabolic infection" to explain the "metabolic inflammation" is discussed. This imply comments about the process of bacterial translocation and impaired intestinal immune defense against commensals. Eventually this review sets the soil for personalized medicine. The monthly increase in the number of publications on the gut microbiota to intestinal immune defense and the control of metabolism demonstrate the importance of this field of investigation. The notion of commensal as "self or non-self" has to be reevaluated in the light of the current data. Furthermore, data demonstrate the major role played by short chain fatty acids, secondary bile acids, LPS, peptidoglycans, indole derivatives, and other bacteria-related molecules on the shaping of cells involved in the intestinal protection against commensals is now becoming a central player in the incidence of metabolic diseases. The literature demonstrates that the onset of metabolic diseases and some specific co-morbidities can be explained by a gut microbiota to intestinal immune system crosstalk. Therefore, one should now consider this avenue of investigation as a putative source of biomarkers and therapeutic targets to personalize the treatment of metabolic disease and its co-morbidities. Gut microbiota is considered as a major regulator of metabolic disease. This reconciles the notion of metabolic inflammation and the epidemic development of the disease. In addition to evidence showing that a specific gut microbiota characterizes patients with obesity, type 2 diabetes

Controlled sumoylation of the mevalonate pathway enzyme HMGS-1 regulates metabolism during aging

NARCIS (Netherlands)

Sapir, Amir; Tsur, Assaf; Koorman, Thijs; Ching, Kaitlin; Mishra, Prashant; Bardenheier, Annabelle; Podolsky, Lisa; Bening-Abu-Shach, Ulrike; Boxem, Mike; Chou, Tsui-Fen; Broday, Limor; Sternberg, Paul W

2014-01-01

Many metabolic pathways are critically regulated during development and aging but little is known about the molecular mechanisms underlying this regulation. One key metabolic cascade in eukaryotes is the mevalonate pathway. It catalyzes the synthesis of sterol and nonsterol isoprenoids, such as

Metabolic and cardiovascular risk in patients with a history of differentiated thyroid carcinoma: A case-controlled cohort study

Directory of Open Access Journals (Sweden)

Giusti Massimo

2008-09-01

Full Text Available Abstract Hyperthyroidism seems to increase metabolic and cardiovascular risk, while the effects of sub-clinical hyperthyroidism are controversial. We evaluated metabolic and cardiovascular parameters in differentiated thyroid carcinoma (DTC patients with suppressed thyrotropin (TSH due to levo-thyroxine (L-T4 therapy. We studied DTC patients and, as a control group, patients with a history of surgery for non-malignant thyroid pathology. Significantly higher insulin and lower HDL-cholesterol levels were recorded in DTC subjects. In both groups, insulin levels were significantly related with body mass index (BMI but not with age or L-T4 dosage. In DTC patients, a significant negative correlation was seen between HDL-cholesterol and BMI or L-T4 dosage. In both groups, intima-media thickness (IMT correlated positively with age, BMI, glucose levels and systolic blood pressure. In DTC patients, increased IMT was significantly correlated with glycated hemoglobin (HbA1c, cholesterol and triglycerides. In DTC patients, C-reactive protein correlated positively with insulin, insulin resistance, triglycerides and systolic blood pressure, and negatively with HDL-cholesterol. In both DTC and control subjects, fibrinogen correlated positively with age, BMI, increased IMT, HbA1c and systolic blood pressure. In DTC subjects, plasma fibrinogen concentrations correlated positively with insulin resistance, cholesterol and LDL-cholesterol, and negatively with TSH levels. Our data confirm that the favorable evolution of DTC can be impaired by a high incidence of abnormal metabolic and cardiovascular data that are, at least in part, related to L-T4 therapy. These findings underline the need for adequate L-T4 titration.

A Metabolic Study of Huntington's Disease.

Directory of Open Access Journals (Sweden)

Rajasree Nambron

Full Text Available Huntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington's disease gene carriers (premanifest and moderate stage II/III and controls.Control (n = 15, premanifest (n = 14 and stage II/III (n = 13 participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a, fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test.We found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington's disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine there is a suggestion (p values between 0.02 and 0.05 that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious.Contrary to previous studies that showed altered levels of metabolic markers in patients with Huntington's disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington's disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results, despite many being tested, suggests that

Preliminary examination of metabolic syndrome response to motivational interviewing for weight loss as compared to an attentional control and usual care in primary care for individuals with and without binge-eating disorder.

Science.gov (United States)

Barnes, Rachel D; Barber, Jessica A

2017-08-01

Motivational interviewing (MI) treatment for weight loss is being studied in primary care. The effect of such interventions on metabolic syndrome or binge eating disorder (BED), both highly related to excess weight, has not been examined in primary care. This study conducted secondary analyses from a randomized controlled trial to test the impact of MI for weight loss in primary care on metabolic syndrome. 74 adult participants with overweight/obesity recruited through primary care were randomized to 12weeks of either MI, an attentional control, or usual care. Participants completed measurements for metabolic syndrome at pre- and post-treatment. There were no statistically significant differences in metabolic syndrome rates at pre-, X 2 (2)=0.16, p=0.921, or post-, X 2 (2)=0.852, p=0.653 treatment. The rates in metabolic syndrome, however, decreased for MI (10.2%) and attentional control (13.8%) participants, but not for usual care. At baseline, metabolic syndrome rates did not differ significantly between participants with BED or without BED across treatments. At post-treatment, participants with BED were significantly more likely to meet criteria for metabolic syndrome than participants without BED, X 2 (1)=5.145, p=0.023, phi=0.273. Across treatments, metabolic syndrome remitted for almost a quarter of participants without BED (23.1%) but for 0% of those with BED. These preliminary results are based on a small sample and should be interpreted with caution, but they are the first to suggest that relatively low intensity MI weight loss interventions in primary care may decrease metabolic syndrome rates but not for individuals with BED. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of periodontal therapy on metabolic control and an inflammatory mediator in type 2 diabetic subjects: a report on 17 consecutive cases.

Science.gov (United States)

Serrano, Carlos; Pérez, Clara; Sabogal, Diego

2012-04-01

A reciprocal relationship between diabetes mellitus and chronic periodontitis has been described, whereby chronic periodontal infection could affect diabetic metabolic control. Therefore, periodontal therapy could influence metabolic control or systemic inflammation leading to diabetic complications. This case report series presents the effect of therapy on periodontal indices, glycated hemoglobin (HbA1c) and high-sensitivity C-reactive protein (hs-CRP) in a group of type 2 diabetic patients. Seventeen diabetic patients diagnosed with moderate to severe chronic periodontitis received periodontal therapy. All patients received a hygienic phase of treatment and were re-examined 3 months later. At re-examination, subjects judged to need periodontal surgery were treated and re-examined after a further 3 months. A complete clinical examination and measurements of HbA1c and hs-CRP were evaluated. Periodontal treatment led to a significant improvement in periodontal indices; only five patients required periodontal surgery. The percentage of bleeding on probing was reduced by nearly 40%; percentage of pockets > or = 5 mm was less than half baseline values; mean pocket depth reduction was 1.21 mm (0.58) and attachment level gain was 0.74 mm (0.69). Nevertheless, no changes were present for HbA1c; a reduction in hs-CRP of 1.37 mg/L (2.67) was present. Periodontal therapy in this case series group produced a significant improvement in the clinical condition, butdid not affect metabolic control. It led to a decrease in hs-CRP.

Effectiveness of physical activity intervention among government employees with metabolic syndrome.

Science.gov (United States)

Huei Phing, Chee; Abu Saad, Hazizi; Barakatun Nisak, M Y; Mohd Nasir, M T

2017-12-01

Our study aimed to assess the effects of physical activity interventions via standing banners (point-of-decision prompt) and aerobics classes to promote physical activity among individuals with metabolic syndrome. We conducted a cluster randomized controlled intervention trial (16-week intervention and 8-week follow-up). Malaysian government employees in Putrajaya, Malaysia, with metabolic syndrome were randomly assigned by cluster to a point-of-decision prompt group (n = 44), an aerobics group (n = 42) or a control group (n = 103) based on sample size calculation formula. Step counts were evaluated by Lifecorder e-STEP accelerometers for all participants. Metabolic syndrome was defined according to the 'harmonizing' definition, in which individuals who have at least three of the five metabolic risk factors (waist circumference, high-density lipoprotein cholesterol, triglycerides, fasting glucose levels, systolic and diastolic blood pressure) will be classified as having metabolic syndrome. A total of 80% of the enrolled government employees with metabolic syndrome completed the programme. Data were analyzed using SPSS for Windows (version 20, SPSS, Chicago, IL). There were significantly higher step counts on average in the aerobics group compared to the control group over assessments. Assessments at baseline, post-intervention and follow-up showed a significant difference in step counts between the intervention and control groups. The greatest reductions in the proportions of individuals with metabolic syndrome were observed in the aerobics group with a reduction of 79.4% in the post-intervention assessment compared to the assessment at baseline. The findings of this study suggest that physical activity intervention via aerobics classes is an effective strategy for improving step counts and reducing the prevalence of metabolic syndrome.

Endocrine control of bone and calcium metabolism. Vol. 8A - Formal sessions and abstracts

International Nuclear Information System (INIS)

Cohn, D.V.; Fujita, Takuo; Potts, J.T. Jr.; Talmage, R.V.

1984-01-01

This book contains papers of a conference about hormonal regulation of calcium metabolism. The pathophysiology and treatment of disorders of mineral metabolism is described in several chapters. A separate chapter is devoted to bone composition, development and remodelling. The same for the physiology of skeletal tissue. The other chapters deal with the secretion, metabolism and action of parathormone, vitamin D, calcitonin and new recognized calcium factors. refs.; figs.; tabs

Metabolism of allylnitrile to cyanide: in vitro studies.

Science.gov (United States)

Farooqui, M Y; Ybarra, B; Piper, J

1993-09-01

In liver fractions from male Sprague-Dawley rats, the metabolism of allylnitrile (ALN) to cyanide (CN-) was localized in the microsomal fraction and required NADPH and oxygen for maximal activity. The biotransformation of ALN to CN- was characterized with respect to time, microsomal protein concentration, pH and temperature. Metabolism of ALN was increased in microsomes obtained from phenobarbital-treated rats (160% of control) and decreased with cobaltous chloride and beta-diethyl aminoethyl-2,2-diphenyl pentanoate (SKF 525-A) treatments (48% of control). Addition of SKF 525-A to the incubation mixtures inhibited ALN metabolism to CN-. Addition of the epoxide hydrolase inhibitor, 1,1,1-trichloropropane 2,3-oxide, decreased the formation of CN- from ALN. Addition of glutathione, cysteine, D-penicillamine, and 2-mercaptoethanol enhanced the release of CN- from ALN. These findings indicate that ALN is metabolized to CN- via a cytochrome P-450-dependent mixed-function oxidase system.

Regulation of Metabolic Activity by p53

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Jessica Flöter

2017-05-01

Full Text Available Metabolic reprogramming in cancer cells is controlled by the activation of multiple oncogenic signalling pathways in order to promote macromolecule biosynthesis during rapid proliferation. Cancer cells also need to adapt their metabolism to survive and multiply under the metabolically compromised conditions provided by the tumour microenvironment. The tumour suppressor p53 interacts with the metabolic network at multiple nodes, mostly to reduce anabolic metabolism and promote preservation of cellular energy under conditions of nutrient restriction. Inactivation of this tumour suppressor by deletion or mutation is a frequent event in human cancer. While loss of p53 function lifts an important barrier to cancer development by deleting cell cycle and apoptosis checkpoints, it also removes a crucial regulatory mechanism and can render cancer cells highly sensitive to metabolic perturbation. In this review, we will summarise the major concepts of metabolic regulation by p53 and explore how this knowledge can be used to selectively target p53 deficient cancer cells in the context of the tumour microenvironment.

Effects of synbiotic food consumption on metabolic status of diabetic patients: a double-blind randomized cross-over controlled clinical trial.

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Asemi, Zatollah; Khorrami-Rad, Ashraf; Alizadeh, Sabihe-Alsadat; Shakeri, Hossein; Esmaillzadeh, Ahmad

2014-04-01

We are aware of no study indicating the effects of synbiotic food consumption on metabolic profiles, inflammation and oxidative stress among diabetic patients. The aim of the current study was to investigate the effects of synbiotic food consumption on metabolic profiles, hs-CRP and biomarkers of oxidative stress in diabetic patients. This randomized double-blinded cross-over controlled clinical trial was performed among 62 diabetic patients aged 35-70 y. After a 2-wk run-in period, subjects were randomly assigned to consume either a synbiotic (n = 62) or control food (n = 62) for 6 weeks. A 3-week washout period was applied following which subjects were crossed over to the alternate treatment arm for an additional 6 weeks. The synbiotic food consisted of a probiotic viable and heat-resistant Lactobacillus sporogenes (1 × 10(7) CFU), 0.04 g inulin (HPX) as prebiotic with 0.38 g isomalt, 0.36 g sorbitol and 0.05 g stevia as sweetener per 1 g. Control food (the same substance without probiotic bacteria and prebiotic inulin) was packed in identical 9-gram packages. Patients were asked to consume the synbiotic and control foods three times a day. Fasting blood samples were taken at baseline and after a 6-wk intervention to measure metabolic profiles, hs-CRP and biomarkers of oxidative stress. Consumption of a synbiotic food, compared to the control, resulted in a significant decrease in serum insulin levels (changes from baseline: -1.75 ± 0.60 vs. +0.95 ± 1.09 μIU/mL, P = 0.03). Although we failed to find a significant effect of synbiotic food consumption on total- and LDL-cholesterol levels and HOMA-IR, the effects on FPG (22.3 vs. 4.2 mg/dL, P = 0.09), serum triglycerides (45.9 vs. 20.6 mg/dL, P = 0.08) and HDL-cholesterol levels (3.1 vs. -2 mg/dL, P = 0.06) tended to be significant. A significant reduction in serum hs-CRP levels (-1057.86 ± 283.74 vs. 95.40 ± 385.38 ng/mL, P = 0.01) was found following the consumption of synbiotic food compared with the

Determining the control circuitry of redox metabolism at the genome-scale.

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Stephen Federowicz

2014-04-01

Full Text Available Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism Escherichia coli, established mechanisms only explain a small fraction of the hundreds of genes that are regulated during electron acceptor shifts. Here we propose a qualitative model that accounts for the full breadth of regulated genes by detailing how two global transcription factors (TFs, ArcA and Fnr of E. coli, sense key metabolic redox ratios and act on a genome-wide basis to regulate anabolic, catabolic, and energy generation pathways. We first fill gaps in our knowledge of this transcriptional regulatory network by carrying out ChIP-chip and gene expression experiments to identify 463 regulatory events. We then interfaced this reconstructed regulatory network with a highly curated genome-scale metabolic model to show that ArcA and Fnr regulate >80% of total metabolic flux and 96% of differential gene expression across fermentative and nitrate respiratory conditions. Based on the data, we propose a feedforward with feedback trim regulatory scheme, given the extensive repression of catabolic genes by ArcA and extensive activation of chemiosmotic genes by Fnr. We further corroborated this regulatory scheme by showing a 0.71 r(2 (p<1e-6 correlation between changes in metabolic flux and changes in regulatory activity across fermentative and nitrate respiratory conditions. Finally, we are able to relate the proposed model to a wealth of previously generated data by contextualizing the existing transcriptional regulatory network.

Body composition and basal metabolic rate in Hidradenitis Suppurativa

DEFF Research Database (Denmark)

Miller, I M; Rytgaard, Helene Charlotte; Mogensen, U B

2016-01-01

BACKGROUND: Several studies have suggested an association between Hidradenitis Suppurativa (HS) and obesity. Obesity is often expressed as Body Mass Index (BMI). However, BMI lacks information on body composition. General obesity is a predictor of health status and cardiovascular risk, but body...... composition (e.g. abdominal fat) may be more so. Basal metabolic rate (BMR) is an expression of resting metabolism and may serve as a complementary tool when assessing the possibly underlying metabolism behind a persons' body composition. OBJECTIVE: To investigate the body composition and basal metabolic rate...... in individuals with HS compared with healthy controls. METHODS: We performed a cross-sectional study on both a hospital-based and population-based HS group and compared with controls using Bioelectrical Impedance Analysis to assess body composition. RESULTS: We identified a hospital-based HS group of 32 hospital...

Dynamic modeling of lactic acid fermentation metabolism with Lactococcus lactis.

Science.gov (United States)

Oh, Euhlim; Lu, Mingshou; Park, Changhun; Park, Changhun; Oh, Han Bin; Lee, Sang Yup; Lee, Jinwon

2011-02-01

A dynamic model of lactic acid fermentation using Lactococcus lactis was constructed, and a metabolic flux analysis (MFA) and metabolic control analysis (MCA) were performed to reveal an intensive metabolic understanding of lactic acid bacteria (LAB). The parameter estimation was conducted with COPASI software to construct a more accurate metabolic model. The experimental data used in the parameter estimation were obtained from an LC-MS/ MS analysis and time-course simulation study. The MFA results were a reasonable explanation of the experimental data. Through the parameter estimation, the metabolic system of lactic acid bacteria can be thoroughly understood through comparisons with the original parameters. The coefficients derived from the MCA indicated that the reaction rate of L-lactate dehydrogenase was activated by fructose 1,6-bisphosphate and pyruvate, and pyruvate appeared to be a stronger activator of L-lactate dehydrogenase than fructose 1,6-bisphosphate. Additionally, pyruvate acted as an inhibitor to pyruvate kinase and the phosphotransferase system. Glucose 6-phosphate and phosphoenolpyruvate showed activation effects on pyruvate kinase. Hexose transporter was the strongest effector on the flux through L-lactate dehydrogenase. The concentration control coefficient (CCC) showed similar results to the flux control coefficient (FCC).

Metabolic Profiles of Brain Metastases

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Tone F. Bathen

2013-01-01

Full Text Available Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis. A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases. The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS to correlate the metabolic profiles to clinical and pathological information. Biopsy samples of human brain metastases (n = 49 were investigated. A significant correlation between lipid signals and necrosis in brain metastases was observed (p < 0.01, irrespective of their primary origin. The principal component analysis (PCA showed that brain metastases from malignant melanomas cluster together, while lung carcinomas were metabolically heterogeneous and overlap with other subtypes. Metastatic melanomas have higher amounts of glycerophosphocholine than other brain metastases. A significant correlation between microscopically visible lipid droplets estimated by Nile Red staining and MR visible lipid signals was observed in metastatic lung carcinomas (p = 0.01, indicating that the proton MR visible lipid signals arise from cytoplasmic lipid droplets. MRS-based metabolomic profiling is a useful tool for exploring the metabolic profiles of metastatic brain tumors.

Proteolytic regulation of metabolic enzymes by E3 ubiquitin ligase complexes: lessons from yeast.

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Nakatsukasa, Kunio; Okumura, Fumihiko; Kamura, Takumi

2015-01-01

Eukaryotic organisms use diverse mechanisms to control metabolic rates in response to changes in the internal and/or external environment. Fine metabolic control is a highly responsive, energy-saving process that is mediated by allosteric inhibition/activation and/or reversible modification of preexisting metabolic enzymes. In contrast, coarse metabolic control is a relatively long-term and expensive process that involves modulating the level of metabolic enzymes. Coarse metabolic control can be achieved through the degradation of metabolic enzymes by the ubiquitin-proteasome system (UPS), in which substrates are specifically ubiquitinated by an E3 ubiquitin ligase and targeted for proteasomal degradation. Here, we review select multi-protein E3 ligase complexes that directly regulate metabolic enzymes in Saccharomyces cerevisiae. The first part of the review focuses on the endoplasmic reticulum (ER) membrane-associated Hrd1 and Doa10 E3 ligase complexes. In addition to their primary roles in the ER-associated degradation pathway that eliminates misfolded proteins, recent quantitative proteomic analyses identified native substrates of Hrd1 and Doa10 in the sterol synthesis pathway. The second part focuses on the SCF (Skp1-Cul1-F-box protein) complex, an abundant prototypical multi-protein E3 ligase complex. While the best-known roles of the SCF complex are in the regulation of the cell cycle and transcription, accumulating evidence indicates that the SCF complex also modulates carbon metabolism pathways. The increasing number of metabolic enzymes whose stability is directly regulated by the UPS underscores the importance of the proteolytic regulation of metabolic processes for the acclimation of cells to environmental changes.

Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism.

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Xu, Minjun; Kitaura, Yasuyuki; Ishikawa, Takuya; Kadota, Yoshihiro; Terai, Chihaya; Shindo, Daichi; Morioka, Takashi; Ota, Miki; Morishita, Yukako; Ishihara, Kengo; Shimomura, Yoshiharu

2017-01-01

It is known that the catabolism of branched-chain amino acids (BCAAs) in skeletal muscle is suppressed under normal and sedentary conditions but is promoted by exercise. BCAA catabolism in muscle tissues is regulated by the branched-chain α-keto acid (BCKA) dehydrogenase complex, which is inactivated by phosphorylation by BCKA dehydrogenase kinase (BDK). In the present study, we used muscle-specific BDK deficient mice (BDK-mKO mice) to examine the effect of uncontrolled BCAA catabolism on endurance exercise performance and skeletal muscle energy metabolism. Untrained control and BDK-mKO mice showed the same performance; however, the endurance performance enhanced by 2 weeks of running training was somewhat, but significantly less in BDK-mKO mice than in control mice. Skeletal muscle of BDK-mKO mice had low levels of glycogen. Metabolome analysis showed that BCAA catabolism was greatly enhanced in the muscle of BDK-mKO mice and produced branched-chain acyl-carnitine, which induced perturbation of energy metabolism in the muscle. These results suggest that the tight regulation of BCAA catabolism in muscles is important for homeostasis of muscle energy metabolism and, at least in part, for adaptation to exercise training.

Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism.

Directory of Open Access Journals (Sweden)

Minjun Xu

Full Text Available It is known that the catabolism of branched-chain amino acids (BCAAs in skeletal muscle is suppressed under normal and sedentary conditions but is promoted by exercise. BCAA catabolism in muscle tissues is regulated by the branched-chain α-keto acid (BCKA dehydrogenase complex, which is inactivated by phosphorylation by BCKA dehydrogenase kinase (BDK. In the present study, we used muscle-specific BDK deficient mice (BDK-mKO mice to examine the effect of uncontrolled BCAA catabolism on endurance exercise performance and skeletal muscle energy metabolism. Untrained control and BDK-mKO mice showed the same performance; however, the endurance performance enhanced by 2 weeks of running training was somewhat, but significantly less in BDK-mKO mice than in control mice. Skeletal muscle of BDK-mKO mice had low levels of glycogen. Metabolome analysis showed that BCAA catabolism was greatly enhanced in the muscle of BDK-mKO mice and produced branched-chain acyl-carnitine, which induced perturbation of energy metabolism in the muscle. These results suggest that the tight regulation of BCAA catabolism in muscles is important for homeostasis of muscle energy metabolism and, at least in part, for adaptation to exercise training.

Metabolic control of the insecticides safety use

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L.I. Solomenko

2016-06-01

Full Text Available The results of the conducted research affirm that the phosphororganic insecticides utilization can lead to the break in the nitrogen metabolism, breaking the protein formation, reducing the protein molecules renewal, causing the amino acid and amides accumulation in the active state. It has been revealed that the translocation and transformation of the insecticides under consideration are more closely connected with the changes of insoluble protein fraction. The stagnation point of the Phosphamide and Kaunter impact on the plant has been determined. And only the use of the preparation in optimal norms can influence stimulatingly the course of the process under consideration.

THE METABOLIC SYNDROME AMONG PATIENTS WITH ...

African Journals Online (AJOL)

Objectives: To determine the frequency of occurrence of the Metabolic Syndrome among patients presenting with cardiovascular disease at the Korle Bu Teaching Hospital, Ghana. Methods: This was a case-control study of 100 con-secutive cardiovascular disease patients and 100 age- and sex- matched controls who ...

Euglena in time: Evolution, control of central metabolic processes and multi-domain proteins in carbohydrate and natural product biochemistry

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Ellis C. O’Neill

2015-12-01

Full Text Available Euglena gracilis is a eukaryotic microalgae that has been the subject of scientific study for hundreds of years. It has a complex evolutionary history, with traces of at least four endosymbiotic genomes and extensive horizontal gene transfer. Given the importance of Euglena in terms of evolutionary cell biology and its unique taxonomic position, we initiated a de novo transcriptome sequencing project in order to understand this intriguing organism. By analysing the proteins encoded in this transcriptome, we can identify an extremely complex metabolic capacity, rivalling that of multicellular organisms. Many genes have been acquired from what are now very distantly related species. Herein we consider the biology of Euglena in different time frames, from evolution through control of cell biology to metabolic processes associated with carbohydrate and natural products biochemistry.

Prevalence of chronic complications, metabolic control and nutritional intake in type 1 diabetes

DEFF Research Database (Denmark)

Toeller, M; Buyken, A E; Heitkamp, G

1999-01-01

and proliferative retinopathy were more common. Persons from the eastern European and the German centres consumed undesirably high amounts of cholesterol, total and saturated fat. Overall, improvements in the prevention, detection and management of diabetes complications in persons with type 1 diabetes......) and chronic diabetes complications (retinopathy, nephropathy, neuropathy, cardiovascular disease) were all considerably more frequent in the eastern European centres. HbA1c was lower in the German centres than in the total EURODIAB cohort or in the north-western European centres, but severe hypoglycaemia......This study compares the prevalence of chronic complications, the quality of metabolic control and the nutritional intake in people with type 1 diabetes in different European regions. The EURODIAB Complications Study included a sample of 3250 European patients with type 1 diabetes stratified...

Engineering Hydrogel Microenvironments to Recapitulate the Stem Cell Niche.

Science.gov (United States)

Madl, Christopher M; Heilshorn, Sarah C

2018-06-04

Stem cells are a powerful resource for many applications including regenerative medicine, patient-specific disease modeling, and toxicology screening. However, eliciting the desired behavior from stem cells, such as expansion in a naïve state or differentiation into a particular mature lineage, remains challenging. Drawing inspiration from the native stem cell niche, hydrogel platforms have been developed to regulate stem cell fate by controlling microenvironmental parameters including matrix mechanics, degradability, cell-adhesive ligand presentation, local microstructure, and cell-cell interactions. We survey techniques for modulating hydrogel properties and review the effects of microenvironmental parameters on maintaining stemness and controlling differentiation for a variety of stem cell types. Looking forward, we envision future hydrogel designs spanning a spectrum of complexity, ranging from simple, fully defined materials for industrial expansion of stem cells to complex, biomimetic systems for organotypic cell culture models.

A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate

DEFF Research Database (Denmark)

Wone, B W M; Madsen, Per; Donovan, E R

2015-01-01

Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection...... on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols...... and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR...

Interaction Between the Central and Peripheral Effects of Insulin in Controlling Hepatic Glucose Metabolism in the Conscious Dog

Science.gov (United States)

Ramnanan, Christopher J.; Kraft, Guillaume; Smith, Marta S.; Farmer, Ben; Neal, Doss; Williams, Phillip E.; Lautz, Margaret; Farmer, Tiffany; Donahue, E. Patrick; Cherrington, Alan D.; Edgerton, Dale S.

2013-01-01

The importance of hypothalamic insulin action to the regulation of hepatic glucose metabolism in the presence of a normal liver/brain insulin ratio (3:1) is unknown. Thus, we assessed the role of central insulin action in the response of the liver to normal physiologic hyperinsulinemia over 4 h. Using a pancreatic clamp, hepatic portal vein insulin delivery was increased three- or eightfold in the conscious dog. Insulin action was studied in the presence or absence of intracerebroventricularly mediated blockade of hypothalamic insulin action. Euglycemia was maintained, and glucagon was clamped at basal. Both the molecular and metabolic aspects of insulin action were assessed. Blockade of hypothalamic insulin signaling did not alter the insulin-mediated suppression of hepatic gluconeogenic gene transcription but blunted the induction of glucokinase gene transcription and completely blocked the inhibition of glycogen synthase kinase-3β gene transcription. Thus, central and peripheral insulin action combined to control some, but not other, hepatic enzyme programs. Nevertheless, inhibition of hypothalamic insulin action did not alter the effects of the hormone on hepatic glucose flux (production or uptake). These data indicate that brain insulin action is not a determinant of the rapid (<4 h) inhibition of hepatic glucose metabolism caused by normal physiologic hyperinsulinemia in this large animal model. PMID:23011594

Randomised controlled trial: Effects of aerobic exercise training programme on indices of adiposity and metabolic markers in hypertension

International Nuclear Information System (INIS)

Lamina, S.; Okoye, C.G.

2013-01-01

Objective: To investigate the effects of interval training programme on blood pressure, maximal oxygen consumption, indices of adiposity and metabolic markers in black African men with essential hypertension. Methods: The study was conducted at Murtala Muhammed Specialist Hospital, Kano, Nigeria, from October 24, 2007 to February 24, 2009. It comprised 245 male patients with mild to moderate (systolic blood pressure 140-179 and diastolic blood pressure 90-109 mmHg) essential hypertension who were age-matched and grouped into experimental and control groups. The experimental group was involved in an 8-week training programme of between 45 and 60 minutes, while the controls remained sedentary during the period. Cardiovascular parameters, maximal oxygen consumption, per cent body fat, waist-to-hip ratio, body mass index, fasting blood sugar, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein and artherogenic index were assessed. Analysis of co-variance and Pearson correlation tests were used in data analysis which was done using SPSS 16. Results: The study had 140 (57.1%) cases with a mean age of 58.90+-7.35 years, and 105 (42.9%) controls with a mean age of 58.27+-6.24 years. It revealed significant increased effect of interval training programme on maximal oxygen consumption and high-density lipoprotein. There was significant reduction in on all the other controls. Changes in maximal oxygen consumption as a result of interval training significantly and negatively correlated with the other variables except high-density lipoprotein. Conclusions: The therapeutic role of interval exercise training on blood pressure reduction may be mediated through elevation of high-density lipoprotein, reduction of other markers of metabolism, and reduction in bodyweight and fatness. (author)

Simple anthropometric measures correlate with metabolic risk indicators as strongly as magnetic resonance imaging–measured adipose tissue depots in both HIV-infected and control subjects2

Science.gov (United States)

Scherzer, Rebecca; Shen, Wei; Bacchetti, Peter; Kotler, Donald; Lewis, Cora E; Shlipak, Michael G; Heymsfield, Steven B

2008-01-01

Background Studies in persons without HIV infection have compared percentage body fat (%BF) and waist circumference as markers of risk for the complications of excess adiposity, but only limited study has been conducted in HIV-infected subjects. Objective We compared anthropometric and magnetic resonance imaging (MRI)–based adiposity measures as correlates of metabolic complications of adiposity in HIV-infected and control subjects. Design The study was a cross-sectional analysis of 666 HIV-positive and 242 control subjects in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study assessing body mass index (BMI), waist (WC) and hip (HC) circumferences, waist-to-hip ratio (WHR), %BF, and MRI-measured regional adipose tissue. Study outcomes were 3 metabolic risk variables [homeostatic model assessment (HOMA), triglycerides, and HDL cholesterol]. Analyses were stratified by sex and HIV status and adjusted for demographic, lifestyle, and HIV-related factors. Results In HIV-infected and control subjects, univariate associations with HOMA, triglycerides, and HDL were strongest for WC, MRI-measured visceral adipose tissue, and WHR; in all cases, differences in correlation between the strongest measures for each outcome were small (r ≤ 0.07). Multivariate adjustment found no significant difference for optimally fitting models between the use of anthropometric and MRI measures, and the magnitudes of differences were small (adjusted R2 ≤ 0.06). For HOMA and HDL, WC appeared to be the best anthropometric correlate of metabolic complications, whereas, for triglycerides, the best was WHR. Conclusion Relations of simple anthropometric measures with HOMA, triglycerides, and HDL cholesterol are approximately as strong as MRI-measured whole-body adipose tissue depots in both HIV-infected and control subjects. PMID:18541572

Radioiodinated free fatty acids; can we measure myocardial metabolism

International Nuclear Information System (INIS)

Visser, F.C.; Eenige, M.J. van; Duwel, C.M.B.; Roos, J.P.

1986-01-01

To investigate the feasibility of radioiodinated free fatty acids for ''metabolic imaging'', the kinetics and distribution pattern of metabolites of heptadecanoic acid I 131 (HDA I 131) were studied in canine myocardium throughout metabolic interventions. In control dogs and in dogs during glucose/insulin and sodium lactate infusion, biopsy specimens were taken during a go-min period after HDA I 131 administration and analyzed. Clearly distinct patterns of distribution and elimination were seen during the metabolic interventions, indicating the usefulness of iodinated fatty acids for metabolic studies. (orig.)

BEYOND GLYCEMIC CONTROL IN DIABETES MELLITUS: EFFECTS OF INCRETIN-BASED THERAPY ON BONE METABOLISM

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ELENA eCECCARELLI

2013-06-01

Full Text Available Diabetes mellitus (DM and osteoporosis (OP are common disorders with a significant health burden, and an increase in fracture risk has been described both in type 1 (T1DM and in type 2 (T2DM diabetes. The pathogenic mechanisms of impaired skeletal strength in diabetes remain to be clarified in details and they are only in part reflected by a variation in bone mineral density (BMD. In T2DM, the occurrence of low bone turnover together with a decreased osteoblast activity and compromised bone quality has been shown. Of note, some antidiabetic drugs (e.g. tiazolidinediones, insulin may deeply affect bone metabolism. In addition, the recently introduced class of incretin-based drugs (i.e. GLP-1 receptor agonists and DPP-4 inhibitors is expected to exert potentially beneficial effects on bone health, possibly due to a bone anabolic activity of GLP-1, that can be either direct or indirect through the involvement of thyroid C cells.Here we will review the established as well as the putative effects of incretin hormones and of incretin-based drugs on bone metabolism, both in preclinical models and in man, taking into account that such therapeutic strategy may be effective not only to achieve a good glycemic control, but also to improve bone health in diabetic patients.

Metabolic syndrome and atypical antipsychotics: Possibility of prediction and control.

Science.gov (United States)

Franch Pato, Clara M; Molina Rodríguez, Vicente; Franch Valverde, Juan I

Schizophrenia and other psychotic disorders are associated with high morbidity and mortality, due to inherent health factors, genetic factors, and factors related to psychopharmacological treatment. Antipsychotics, like other drugs, have side-effects that can substantially affect the physical health of patients, with substantive differences in the side-effect profile and in the patients in which these side-effects occur. To understand and identify these risk groups could help to prevent the occurrence of the undesired effects. A prospective study, with 24 months follow-up, was conducted in order to analyse the physical health of severe mental patients under maintenance treatment with atypical antipsychotics, as well as to determine any predictive parameters at anthropometric and/or analytical level for good/bad outcome of metabolic syndrome in these patients. There were no significant changes in the physical and biochemical parameters individually analysed throughout the different visits. The baseline abdominal circumference (lambda Wilks P=.013) and baseline HDL-cholesterol levels (lambda Wilks P=.000) were the parameters that seem to be more relevant above the rest of the metabolic syndrome constituents diagnosis criteria as predictors in the long-term. In the search for predictive factors of metabolic syndrome, HDL-cholesterol and abdominal circumference at the time of inclusion were selected, as such that the worst the baseline results were, the higher probability of long-term improvement. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate.

Science.gov (United States)

Wone, B W M; Madsen, P; Donovan, E R; Labocha, M K; Sears, M W; Downs, C J; Sorensen, D A; Hayes, J P

2015-04-01

Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR, and BMR was slightly, but not significantly, higher (2.5%). Compared with controls, MMR was significantly higher (5.3%) in antagonistically selected lines, and BMR was slightly, but not significantly, lower (4.2%). Analysis of breeding values revealed no positive genetic trend for elevated BMR in high-MMR lines. A weak positive genetic correlation was detected between MMR and BMR. That weak positive genetic correlation supports the aerobic capacity model for the evolution of endothermy in the sense that it fails to falsify a key model assumption. Overall, the results suggest that at least in these mice there is significant capacity for independent evolution of metabolic traits. Whether that is true in the ancestral animals that evolved endothermy remains an important but unanswered question.

Phase I to II cross-induction of xenobiotic metabolizing enzymes: A feedforward control mechanism for potential hormetic responses

International Nuclear Information System (INIS)

Zhang Qiang; Pi Jingbo; Woods, Courtney G.; Andersen, Melvin E.

2009-01-01

Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a

Phase I to II cross-induction of xenobiotic metabolizing enzymes: a feedforward control mechanism for potential hormetic responses.

Science.gov (United States)

Zhang, Qiang; Pi, Jingbo; Woods, Courtney G; Andersen, Melvin E

2009-06-15

Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a

Prevalence of metabolic syndrome in Chinese psoriasis patients: A hospital-based cross-sectional study.

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Gui, Xin-Yu; Yu, Xiao-Ling; Jin, Hong-Zhong; Zuo, Ya-Gang; Wu, Chao

2018-01-01

Psoriasis, a chronic autoimmune skin disorder, is believed to contribute to cardiovascular diseases and metabolic syndrome. Psoriasis's association with the components of metabolic syndrome has been reported previously. However, large-scale cross-sectional studies about psoriasis and metabolic syndrome are rare in China. We assessed the prevalence of metabolic syndrome in Chinese psoriasis patients and controls. A total of 859 psoriasis patients and 1,718 controls were recruited in an age- and sex-matched cross-sectional study. Metabolic syndrome occurred in 14.3% of the psoriasis patients as opposed to 10.0% of the control participants (P = 0.001). Psoriasis patients had a higher prevalence of overweight/obesity, hyperglycemia and dyslipidemia when compared with controls. Meanwhile, psoriasis patients with metabolic syndrome were older, and had an older age of onset and a longer disease duration when compared with those without metabolic syndrome. The prevalence of metabolic syndrome is higher in the Chinese psoriatic population, which can favor cardiovascular events. The present study strengthens the value of treating psoriasis patients not only dealing with the skin lesions, and we suggest appropriate screening and relevant health education be carried out in the treatment of psoriasis patients. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

MetAssimulo:Simulation of Realistic NMR Metabolic Profiles

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De Iorio Maria

2010-10-01

Full Text Available Abstract Background Probing the complex fusion of genetic and environmental interactions, metabolic profiling (or metabolomics/metabonomics, the study of small molecules involved in metabolic reactions, is a rapidly expanding 'omics' field. A major technique for capturing metabolite data is 1H-NMR spectroscopy and this yields highly complex profiles that require sophisticated statistical analysis methods. However, experimental data is difficult to control and expensive to obtain. Thus data simulation is a productive route to aid algorithm development. Results MetAssimulo is a MATLAB-based package that has been developed to simulate 1H-NMR spectra of complex mixtures such as metabolic profiles. Drawing data from a metabolite standard spectral database in conjunction with concentration information input by the user or constructed automatically from the Human Metabolome Database, MetAssimulo is able to create realistic metabolic profiles containing large numbers of metabolites with a range of user-defined properties. Current features include the simulation of two groups ('case' and 'control' specified by means and standard deviations of concentrations for each metabolite. The software enables addition of spectral noise with a realistic autocorrelation structure at user controllable levels. A crucial feature of the algorithm is its ability to simulate both intra- and inter-metabolite correlations, the analysis of which is fundamental to many techniques in the field. Further, MetAssimulo is able to simulate shifts in NMR peak positions that result from matrix effects such as pH differences which are often observed in metabolic NMR spectra and pose serious challenges for statistical algorithms. Conclusions No other software is currently able to simulate NMR metabolic profiles with such complexity and flexibility. This paper describes the algorithm behind MetAssimulo and demonstrates how it can be used to simulate realistic NMR metabolic profiles with

Functional roles of FgLaeA in controlling secondary metabolism, sexual development, and virulence in Fusarium graminearum.

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Hee-Kyoung Kim

Full Text Available Fusarium graminearum, the causal agent of Fusarium head blight in cereal crops, produces mycotoxins such as trichothecenes and zearalenone in infected plants. Here, we focused on the function of FgLaeA in F. graminearum, a homolog of Aspergillus nidulans LaeA encoding the global regulator for both secondary metabolism and sexual development. Prior to gene analysis, we constructed a novel luciferase reporter system consisting of a transgenic F. graminearum strain expressing a firefly luciferase gene under control of the promoter for either TRI6 or ZEB2 controlling the biosynthesis of these mycotoxins. Targeted deletion of FgLaeA led to a dramatic reduction of luminescence in reporter strains, indicating that FgLaeA controls the expression of these transcription factors in F. graminearum; reduced toxin accumulation was further confirmed by GC-MS analysis. Overexpression of FgLaeA caused the increased production of trichothecenes and additional metabolites. RNA seq-analysis revealed that gene member(s belonging to ~70% of total tentative gene clusters, which were previously proposed, were differentially expressed in the ΔFgLaeA strain. In addition, ΔFgLaeA strains exhibited an earlier induction of sexual fruiting body (perithecia formation and drastically reduced disease symptoms in wheat, indicating that FgLaeA seems to negatively control perithecial induction, but positively control virulence toward the host plant. FgLaeA was constitutively expressed under both mycotoxin production and sexual development conditions. Overexpression of a GFP-FgLaeA fusion construct in the ΔFgLaeA strain restored all phenotypic changes to wild-type levels and led to constitutive expression of GFP in both nuclei and cytoplasm at different developmental stages. A split luciferase assay demonstrated that FgLaeA was able to interact with FgVeA, a homolog of A. nidulans veA. Taken together, these results demonstrate that FgLaeA, a member of putative FgVeA complex

NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells.

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Ratajczak, Joanna; Joffraud, Magali; Trammell, Samuel A J; Ras, Rosa; Canela, Núria; Boutant, Marie; Kulkarni, Sameer S; Rodrigues, Marcelo; Redpath, Philip; Migaud, Marie E; Auwerx, Johan; Yanes, Oscar; Brenner, Charles; Cantó, Carles

2016-10-11

NAD + is a vital redox cofactor and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Supplementation with NAD + precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we show that nicotinamide riboside kinase 1 (NRK1) is necessary and rate-limiting for the use of exogenous NR and NMN for NAD + synthesis. Using genetic gain- and loss-of-function models, we further demonstrate that the role of NRK1 in driving NAD + synthesis from other NAD + precursors, such as nicotinamide or nicotinic acid, is dispensable. Using stable isotope-labelled compounds, we confirm NMN is metabolized extracellularly to NR that is then taken up by the cell and converted into NAD + . Our results indicate that mammalian cells require conversion of extracellular NMN to NR for cellular uptake and NAD + synthesis, explaining the overlapping metabolic effects observed with the two compounds.

Multidisciplinary Treatment of the Metabolic Syndrome Lowers Blood Pressure Variability Independent of Blood Pressure Control.

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Marcus, Yonit; Segev, Elad; Shefer, Gabi; Sack, Jessica; Tal, Brurya; Yaron, Marianna; Carmeli, Eli; Shefer, Lili; Margaliot, Miri; Limor, Rona; Gilad, Suzan; Sofer, Yael; Stern, Naftali

2016-01-01

Blood pressure (BP) variability (BPV) contributes to target organ damage independent of BP. The authors examined the effect of a 1-year multidisciplinary intervention on BPV in patients with the metabolic syndrome (MetS) as defined by criteria from the Third Report of the Adult Treatment Panel. Forty-four nondiabetic patients underwent clinical and biochemical profiling, 24-hour ambulatory BP monitoring (ABPM), body composition, carotid intima-media thickness, and carotid-femoral pulse wave velocity (PWV). The intervention targeted all MetS components. BPV was assessed by the standard deviation of daytime systolic BP derived from ABPM. Patients with low and high BPV (lower or higher than the median daytime standard deviation of 11.6 mm Hg) did not differ in regards to systolic and diastolic BP, age, fasting glucose, glycated hemoglobin, and body mass index, but the high-variability group had higher values of low-density lipoprotein and leg fat. The 1-year intervention resulted in weight reduction but not BP-lowering. BPV declined in the high-variability group in association with lowering of PWV, C-reactive protein, glycated hemoglobin, alanine aminotransferase, asymmetric dimethylarginine, and increased high-density lipoprotein cholesterol. A multidisciplinary intervention independent of BP-lowering normalized BPV, lowered PWV, and enhanced metabolic control. © 2015 Wiley Periodicals, Inc.

On the use of metabolic control analysis in the optimization of cyanobacterial biosolar cell factories.

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Angermayr, S Andreas; Hellingwerf, Klaas J

2013-09-26

Oxygenic photosynthesis will have a key role in a sustainable future. It is therefore significant that this process can be engineered in organisms such as cyanobacteria to construct cell factories that catalyze the (sun)light-driven conversion of CO2 and water into products like ethanol, butanol, or other biofuels or lactic acid, a bioplastic precursor, and oxygen as a byproduct. It is of key importance to optimize such cell factories to maximal efficiency. This holds for their light-harvesting capabilities under, for example, circadian illumination in large-scale photobioreactors. However, this also holds for the "dark" reactions of photosynthesis, that is, the conversion of CO2, NADPH, and ATP into a product. Here, we present an analysis, based on metabolic control theory, to estimate the optimal capacity for product formation with which such cyanobacterial cell factories have to be equipped. Engineered l-lactic acid producing Synechocystis sp. PCC6803 strains are used to identify the relation between production rate and enzymatic capacity. The analysis shows that the engineered cell factories for l-lactic acid are fully limited by the metabolic capacity of the product-forming pathway. We attribute this to the fact that currently available promoter systems in cyanobacteria lack the genetic capacity to a provide sufficient expression in single-gene doses.

Emerging opportunities for the treatment of metabolic diseases

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Finan, Brian; Clemmensen, Christoffer; Müller, Timo D

2015-01-01

with integrated activities derived from multiple hormones involved in the physiological control of metabolism have emerged as one of the more promising candidates for reversing obesity. The inclusion of glucagon-like peptide-1 (GLP-1) as one of the constituents is a unifying factor amongst the majority......Obesity is a pathogenic gateway to the metabolic syndrome and the complications thereof, thus interventions aimed at preventing or reversing the metabolic derangements underlying obesity hold great therapeutic promise. However, the complexity of energy balance regulation, combined...

[Blood-sugar self control. A means for the diabetic of controlling his metabolic management. Quality control of a battery-run pocket size reflectometer (glucose-meter)].

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Leidinger, F; Jörgens, V; Chantelau, E; Berchtold, P; Berger, M

1980-07-26

Home blood glucose monitoring by diabetic patients has recently been advocated as an effective means to improve metabolic control. The Glucocheck apparatus, a pocket-size battery-driven reflectance-meter (in Germany commercially available under the name Glucose-meter), has been evaluated for accuracy and practicability. In 450 blood glucose measurements, the variance between the values obtained using the Glucocheck apparatus and routine clinical laboratory procedures was +/- 11.7%. Especially in the low range of blood glucose concentrations, the Glucocheck method was very reliable. The quantitative precision of the Glucocheck method depends, however, quite considerably on the ability of the patient to use the apparatus correctly. In order to profit from Glucocheck in clinical practice, particular efforts to educate the patients in its use are necessary.

Diabetes Health, Residence & Metabolism in Asians: the DHRMA study, research into foods from the Indian subcontinent - a blinded, randomised, placebo controlled trial

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Patel Jeetesh V

2011-12-01

Full Text Available Abstract Background Coronary heart disease (CHD is highly prevalent amongst the South Asian communities in Britain. The reasons for this excess CHD risk are multifactorial, but in part relate to a susceptibility to diabetes mellitus - where the aberrant metabolism of non-esterified fatty acids (NEFA and glucose are likely to underpin vascular disease in this population. Dietary intervention is an important and first line approach to manage increased CHD risk. However, there is limited information on the impact of the South Asian diet on CHD risk. Methods/Design The Diabetes Health, Residence & Metabolism in Asians (DHRMA study is a blinded, randomised, placebo controlled trial that analyses the efficacy of reduced glycaemic index (GI staples of the South Asian diet, in relation to cardio-metabolic risk factors that are commonly perturbed amongst South Asian populations - primarily glucose, fatty acid and lipoprotein metabolism and central adiposity. Using a 10-week dietary intervention study, 50 healthy South Asians will be randomised to receive either a DHRMA (reduced GI supply of chapatti (bread, stone ground, high protein wheat flour and white basmati rice (high bran, unpolished or commercially available (leading brand versions chapatti wheat flour and basmati rice. Volunteers will be asked to complete a 75g oral glucose tolerance test at baseline and at 10-weeks follow-up, where blood metabolites and hormones, blood pressure and anthropometry will also be assessed in a standardised manner. Discussion It is anticipated that the information collected from this study help develop healthy diet options specific (but not exclusive for South Asian ethnic communities. Trial registration Current Controlled Trials ISRCTN02839188

Correlations between cerebral glucose metabolism and neuropsychological test performance in nonalcoholic cirrhotics.

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Lockwood, Alan H; Weissenborn, Karin; Bokemeyer, Martin; Tietge, U; Burchert, Wolfgang

2002-03-01

Many cirrhotics have abnormal neuropsychological test scores. To define the anatomical-physiological basis for encephalopathy in nonalcoholic cirrhotics, we performed resting-state fluorodeoxyglucose positron emission tomographic scans and administered a neuropsychological test battery to 18 patients and 10 controls. Statistical parametric mapping correlated changes in regional glucose metabolism with performance on the individual tests and a composite battery score. In patients without overt encephalopathy, poor performance correlated with reductions in metabolism in the anterior cingulate. In all patients, poor performance on the battery was positively correlated (p glucose metabolism in bifrontal and biparietal regions of the cerebral cortex and negatively correlated with metabolism in hippocampal, lingual, and fusiform gyri and the posterior putamen. Similar patterns of abnormal metabolism were found when comparing the patients to 10 controls. Metabolic abnormalities in the anterior attention system and association cortices mediating executive and integrative function form the pathophysiological basis for mild hepatic encephalopathy.

Plant-derived therapeutics for the treatment of metabolic syndrome.

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Graf, Brittany L; Raskin, Ilya; Cefalu, William T; Ribnicky, David M

2010-10-01

Metabolic syndrome is defined as a set of coexisting metabolic disorders that increase an individual's likelihood of developing type 2 diabetes, cardiovascular disease and stroke. Medicinal plants, some of which have been used for thousands of years, serve as an excellent source of bioactive compounds for the treatment of metabolic syndrome because they contain a wide range of phytochemicals with diverse metabolic effects. In order for botanicals to be effectively used against metabolic syndrome, however, botanical preparations must be characterized and standardized through the identification of their active compounds and respective modes of action, followed by validation in controlled clinical trials with clearly defined endpoints. This review assesses examples of commonly known and partially characterized botanicals to describe specific considerations for the phytochemical, preclinical and clinical characterization of botanicals associated with metabolic syndrome.

Plant metabolic modeling: achieving new insight into metabolism and metabolic engineering.

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Baghalian, Kambiz; Hajirezaei, Mohammad-Reza; Schreiber, Falk

2014-10-01

Models are used to represent aspects of the real world for specific purposes, and mathematical models have opened up new approaches in studying the behavior and complexity of biological systems. However, modeling is often time-consuming and requires significant computational resources for data development, data analysis, and simulation. Computational modeling has been successfully applied as an aid for metabolic engineering in microorganisms. But such model-based approaches have only recently been extended to plant metabolic engineering, mainly due to greater pathway complexity in plants and their highly compartmentalized cellular structure. Recent progress in plant systems biology and bioinformatics has begun to disentangle this complexity and facilitate the creation of efficient plant metabolic models. This review highlights several aspects of plant metabolic modeling in the context of understanding, predicting and modifying complex plant metabolism. We discuss opportunities for engineering photosynthetic carbon metabolism, sucrose synthesis, and the tricarboxylic acid cycle in leaves and oil synthesis in seeds and the application of metabolic modeling to the study of plant acclimation to the environment. The aim of the review is to offer a current perspective for plant biologists without requiring specialized knowledge of bioinformatics or systems biology. © 2014 American Society of Plant Biologists. All rights reserved.

Increased Risk of Metabolic Syndrome in Patients with Vitiligo.

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Ataş, Hatice; Gönül, Müzeyyen

2017-05-05

Inflammatory and immune processes can be triggered in vitiligo due to a decreased number of melanocytes and their anti-inflammatory effects. Because of the systemic nature of vitiligo, metabolic abnormalities such as insulin resistance and lipid profile disturbances as well as skin involvement may be observed in vitiligo. To investigate the association between metabolic syndrome and vitiligo. Case-control study. The demographic, clinical and laboratory features in the subjects were compared according to presence of vitiligo and metabolic syndrome [patients (n=63) vs. gender-age matched controls (n=65) and metabolic syndrome positive (n=38) vs. negative (n=90)]. A logistic regression analysis was also used. We identified metabolic syndrome in 24 (38.1%) subjects with vitiligo and 14 (21.5%) subjects without vitiligo (p=0.04). Active vitiligo, segmental vitiligo, an increased duration of vitiligo and an increased percentage in the affected body surface area were determined to be independent predictors of metabolic syndrome [activity of vitiligo: p=0.012, OR (95% CI)=64.4 (2.5-1672); type of vitiligo: p=0.007, OR (95% CI)=215.1 (4.3-10725.8); duration of vitiligo: p=0.03, OR (95% CI)=1.4 (1.1-2.0); percentage of affected body surface area: p=0.07, OR (95% CI)=1.2 (0.98-1.5)]. The risk of developing metabolic syndrome is increased in patients with vitiligo. The poor clinical features of vitiligo, such as active, extended and segmental vitiligo with an increased duration of time, are independent predictors for developing metabolic syndrome.

Impact of changes in metabolic control on progression to photocoagulation for clinically significant macular oedema:a 20 year study of type 1 diabetes

DEFF Research Database (Denmark)

Sander, B.; Larsen, M.; Andersen, Elisabeth Wreford

2013-01-01

Aims/hypothesis Although increasing hyperglycaemia, arterial hypertension and longer duration of diabetes raise the risk of progression of diabetic retinopathy, short-term benefits in terms of improved metabolic control and lowered blood pressure have not been demonstrated. We therefore examined ...

Rapid selection of a pyrethroid metabolic enzyme CYP9K1 by operational malaria control activities.

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Vontas, John; Grigoraki, Linda; Morgan, John; Tsakireli, Dimitra; Fuseini, Godwin; Segura, Luis; Niemczura de Carvalho, Julie; Nguema, Raul; Weetman, David; Slotman, Michel A; Hemingway, Janet

2018-05-01

Since 2004, indoor residual spraying (IRS) and long-lasting insecticide-impregnated bednets (LLINs) have reduced the malaria parasite prevalence in children on Bioko Island, Equatorial Guinea, from 45% to 12%. After target site-based (knockdown resistance; kdr ) pyrethroid resistance was detected in 2004 in Anopheles coluzzii (formerly known as the M form of the Anopheles gambiae complex), the carbamate bendiocarb was introduced. Subsequent analysis showed that kdr alone was not operationally significant, so pyrethroid-based IRS was successfully reintroduced in 2012. In 2007 and 2014-2015, mass distribution of new pyrethroid LLINs was undertaken to increase the net coverage levels. The combined selection pressure of IRS and LLINs resulted in an increase in the frequency of pyrethroid resistance in 2015. In addition to a significant increase in kd r frequency, an additional metabolic pyrethroid resistance mechanism had been selected. Increased metabolism of the pyrethroid deltamethrin was linked with up-regulation of the cytochrome P450 CYP9K1. The increase in resistance prompted a reversion to bendiocarb IRS in 2016 to avoid a resurgence of malaria, in line with the national Malaria Control Program plan. Copyright © 2018 the Author(s). Published by PNAS.

The Aging Clock and Circadian Control of Metabolism and Genome Stability

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Victoria P. Belancio

2015-01-01

Full Text Available It is widely accepted that aging is characterized by a gradual decline in the efficiency and accuracy of biological processes, leading to deterioration of physiological functions and development of age-associated diseases. Age-dependent accumulation of genomic instability and development of metabolic syndrome are well-recognized components of the aging phenotype, both of which have been extensively studied. Existing findings strongly support the view that the integrity of the cellular genome and metabolic function can be influenced by light at night (LAN and associated suppression of circadian melatonin production. While LAN is reported to accelerate aging by promoting age-associated carcinogenesis in several animal models, the specific molecular mechanism(s of its action are not fully understood. Here, we review literature supporting a connection between LAN-induced central circadian disruption of peripheral circadian rhythms and clock function, LINE-1 retrotransposon-associated genomic instability, metabolic deregulation, and aging. We propose that aging is a progressive decline in the stability, continuity and synchronization of multi-frequency oscillations in biological processes to a temporally disorganized state. By extension, healthy aging is the ability to maintain the most consistent, stable and entrainable rhythmicity and coordination of these oscillations, at the molecular, cellular, and systemic levels.

MicroRNAs in Metabolism

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Vienberg, Sara; Geiger, Julian; Madsen, Søren

2017-01-01

roles in cholesterol and lipid metabolism, whereas miR-103 and -107 regulates hepatic insulin sensitivity. In muscle tissue a defined number of miRNAs (miR-1, miR-133, mir-206) control myofiber type switch and induce myogenic differentiation programs. Similarly, in adipose tissue a defined number of mi...

Engineering of metabolic pathways by artificial enzyme channels

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Marlene ePröschel

2015-10-01

Full Text Available Application of industrial enzymes for production of valuable chemical compounds has greatly benefited from recent developments in Systems and Synthetic Biology. Both, in vivo and in vitro systems have been established, allowing conversion of simple into complex compounds. Metabolic engineering in living cells needs to be balanced which is achieved by controlling gene expression levels, translation, scaffolding, compartmentation and flux control. In vitro applications are often hampered by limited protein stability/half-life and insufficient rates of substrate conversion. To improve stability and catalytic activity, proteins are post-translationally modified and arranged in artificial metabolic channels. Within the review article we will first discuss the supramolecular organization of enzymes in living systems and secondly summarize current and future approaches to design artificial metabolic channels by additive manufacturing for the efficient production of desired products.

The compositional and evolutionary logic of metabolism

International Nuclear Information System (INIS)

Braakman, Rogier; Smith, Eric

2013-01-01

Metabolism is built on a foundation of organic chemistry, and employs structures and interactions at many scales. Despite these sources of complexity, metabolism also displays striking and robust regularities in the forms of modularity and hierarchy, which may be described compactly in terms of relatively few principles of composition. These regularities render metabolic architecture comprehensible as a system, and also suggests the order in which layers of that system came into existence. In addition metabolism also serves as a foundational layer in other hierarchies, up to at least the levels of cellular integration including bioenergetics and molecular replication, and trophic ecology. The recapitulation of patterns first seen in metabolism, in these higher levels, motivates us to interpret metabolism as a source of causation or constraint on many forms of organization in the biosphere. Many of the forms of modularity and hierarchy exhibited by metabolism are readily interpreted as stages in the emergence of catalytic control by living systems over organic chemistry, sometimes recapitulating or incorporating geochemical mechanisms. We identify as modules, either subsets of chemicals and reactions, or subsets of functions, that are re-used in many contexts with a conserved internal structure. At the small molecule substrate level, module boundaries are often associated with the most complex reaction mechanisms, catalyzed by highly conserved enzymes. Cofactors form a biosynthetically and functionally distinctive control layer over the small-molecule substrate. The most complex members among the cofactors are often associated with the reactions at module boundaries in the substrate networks, while simpler cofactors participate in widely generalized reactions. The highly tuned chemical structures of cofactors (sometimes exploiting distinctive properties of the elements of the periodic table) thereby act as ‘keys’ that incorporate classes of organic reactions

Metabolic alkalosis in adults with stable cystic fibrosis.

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Al-Ghimlas, Fahad; Faughnan, Marie E; Tullis, Elizabeth

2012-01-01

The frequency of metabolic alkalosis among adults with stable severe CF-lung disease is unknown. Retrospective chart review. Fourteen CF and 6 COPD (controls) patients were included. FEV1 was similar between the two groups. PaO2 was significantly higher in the COPD (mean ± 2 SD is 72.0 ± 6.8 mmHg,) than in the CF group (56.1 ± 4.1 mmHg). The frequency of metabolic alkalosis in CF patients (12/14, 86%) was significantly greater (p=0.04) than in the COPD group (2/6, 33%). Mixed respiratory acidosis and metabolic alkalosis was evident in 4 CF and 1 COPD patients. Primary metabolic alkalosis was observed in 8 CF and none of the COPD patients. One COPD patient had respiratory and metabolic alkalosis. Metabolic alkalosis is more frequent in stable patients with CF lung disease than in COPD patients. This might be due to defective CFTR function with abnormal electrolyte transport within the kidney and/ or gastrointestinal tract.

The Association of Arsenic Exposure and Metabolism With Type 1 and Type 2 Diabetes in Youth: The SEARCH Case-Control Study.

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Grau-Pérez, Maria; Kuo, Chin-Chi; Spratlen, Miranda; Thayer, Kristina A; Mendez, Michelle A; Hamman, Richard F; Dabelea, Dana; Adgate, John L; Knowler, William C; Bell, Ronny A; Miller, Frederick W; Liese, Angela D; Zhang, Chongben; Douillet, Christelle; Drobná, Zuzana; Mayer-Davis, Elizabeth J; Styblo, Miroslav; Navas-Acien, Ana

2017-01-01

Little is known about arsenic and diabetes in youth. We examined the association of arsenic with type 1 and type 2 diabetes in the SEARCH for Diabetes in Youth Case-Control (SEARCH-CC) study. Because one-carbon metabolism can influence arsenic metabolism, we also evaluated the potential interaction of folate and vitamin B12 with arsenic metabolism on the odds of diabetes. Six hundred eighty-eight participants iAs], monomethylated arsenic [MMA], dimethylated arsenic [DMA]), and one-carbon metabolism biomarkers (folate and vitamin B12) were measured in plasma. We used the sum of iAs, MMA, and DMA (∑As) and the individual species as biomarkers of arsenic concentrations and the relative proportions of the species over their sum (iAs%, MMA%, DMA%) as biomarkers of arsenic metabolism. Median ∑As, iAs%, MMA%, and DMA% were 83.1 ng/L, 63.4%, 10.3%, and 25.2%, respectively. ∑As was not associated with either type of diabetes. The fully adjusted odds ratios (95% CI), rescaled to compare a difference in levels corresponding to the interquartile range of iAs%, MMA%, and DMA%, were 0.68 (0.50-0.91), 1.33 (1.02-1.74), and 1.28 (1.01-1.63), respectively, for type 1 diabetes and 0.82 (0.48-1.39), 1.09 (0.65-1.82), and 1.17 (0.77-1.77), respectively, for type 2 diabetes. In interaction analysis, the odds ratio of type 1 diabetes by MMA% was 1.80 (1.25-2.58) and 0.98 (0.70-1.38) for participants with plasma folate levels above and below the median (P for interaction = 0.02), respectively. Low iAs% versus high MMA% and DMA% was associated with a higher odds of type 1 diabetes, with a potential interaction by folate levels. These data support further research on the role of arsenic metabolism in type 1 diabetes, including the interplay with one-carbon metabolism biomarkers. © 2017 by the American Diabetes Association.

Structured hypocaloric diet is more effective than behavioral therapy in reducing metabolic syndrome in Mexican postmenopausal women: a randomized controlled trial.

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Perichart-Perera, Otilia; Balas-Nakash, Margie; Muñoz-Manrique, Cinthya; Legorreta-Legorreta, Jennifer; Rodríguez-Cano, Ameyalli; Mier-Cabrera, Jennifer; Aguilera-Pérez, Jesús Rafael

2014-07-01

This study aims to compare the effects of a lifestyle intervention using a behavioral therapy (BT) approach with the effects of a cardioprotective structured hypocaloric diet on metabolic syndrome in Mexican postmenopausal women. This study is a randomized clinical trial (2006-2009) of Mexican postmenopausal women with metabolic syndrome (Adult Treatment Panel III criteria) who were recruited from the Postmenopause Clinic of the National Institute of Perinatology in Mexico City. Women were assigned to one of two groups--group 1 (structured hypocaloric diet; n = 63): energy restriction (-300 to -500 kcal/d) emphasizing cardioprotective dietary changes; and group 2 (BT; n = 55): goal setting, problem-solving, and stimulus control to achieve cardioprotective dietary and lifestyle recommendations. Metabolic syndrome prevalence, as well as weight, waist circumference, fat mass, and fasting biochemical markers (glucose and lipid profile), were measured at baseline and at 2, 4, and 6 months after the intervention. Metabolic syndrome risk (relative risk and absolute risk reduction), mean differences between groups, and logistic regression were evaluated using Statistical Package for the Social Sciences software, version 17.0. A total of 118 women were studied (mean [SD] age, 53.81 [6.43] y). No baseline differences were observed between groups. At the end of the study, a higher reduction in metabolic syndrome prevalence was observed in group 1 (-38.1%) compared with group 2 (-12.7%; relative risk, 0.237; 95% CI, 0.092-0.608; P = 0.003). The effect was maintained even when adjusted by age, hormone therapy and antihypertensive drug use. A cardioprotective structured hypocaloric diet is more effective than the BT approach in reducing metabolic syndrome after 6 months of intervention. Both strategies have positive effects on different individual cardiovascular risk factors.

Effects of metabolic syndrome on the functional outcomes of corticosteroid injection for De Quervain tenosynovitis.

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Roh, Y H; Noh, J H; Gong, H S; Baek, G H

2017-06-01

Metabolic syndrome is a constellation of medical conditions that arise from insulin resistance and abnormal adipose deposition and function. In patients with metabolic syndrome and De Quervain tenosynovitis this might affect the outcome of treatment by local corticosteroid injection. A total of 64 consecutive patients with De Quervain tenosynovitis and metabolic syndrome treated with corticosteroid injection were age- and sex-matched with 64 control patients without metabolic syndrome. The response to treatment, including visual analogue scale score for pain, objective findings consistent with De Quervain tenosynovitis (tenderness at first dorsal compartment, Finkelstein test result), and Disability of the Arm, Shoulder, and Hand score were assessed at 6, 12, and 24 weeks follow-up. Treatment failure was defined as persistence of symptoms or surgical intervention. Prior to treatment, patients with metabolic syndrome had mean initial pain visual analogue scale and Disability of the Arm, Shoulder, and Hand scores similar to those in the control group. The proportion of treatment failure in the metabolic syndrome group (43%) was significantly higher than that in the control group (20%) at 6 months follow-up. The pain visual analogue scale scores in the metabolic syndrome group were higher than the scores in the control group at the 12- and 24-week follow-ups. The Disability of the Arm, Shoulder, and Hand scores of the metabolic syndrome group were higher (more severe symptoms) than those of the control group at the 12- and 24-week follow-ups. Although considerable improvements in symptom severity and hand function will likely occur in patients with metabolic syndrome, corticosteroid injection for De Quervain tenosynovitis is not as effective in these patients compared with age- and sex-matched controls in terms of functional outcomes and treatment failure. III.

Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

Directory of Open Access Journals (Sweden)

Lucio Della Guardia

2018-05-01

Full Text Available Recent epidemiological findings suggest that high levels of dietary acid load can affect insulin sensitivity and glucose metabolism. Consumption of high protein diets results in the over-production of metabolic acids which has been associated with the development of chronic metabolic disturbances. Mild metabolic acidosis has been shown to impair peripheral insulin action and several epidemiological findings suggest that metabolic acid load markers are associated with insulin resistance and impaired glycemic control through an interference intracellular insulin signaling pathways and translocation. In addition, higher incidence of diabetes, insulin resistance, or impaired glucose control have been found in subjects with elevated metabolic acid load markers. Hence, lowering dietary acid load may be relevant for improving glucose homeostasis and prevention of type 2 diabetes development on a long-term basis. However, limitations related to patient acid load estimation, nutritional determinants, and metabolic status considerably flaws available findings, and the lack of solid data on the background physiopathology contributes to the questionability of results. Furthermore, evidence from interventional studies is very limited and the trials carried out report no beneficial results following alkali supplementation. Available literature suggests that poor acid load control may contribute to impaired insulin sensitivity and glucose homeostasis, but it is not sufficiently supportive to fully elucidate the issue and additional well-designed studies are clearly needed.

Physical Activity Enhances Metabolic Fitness Independently of Cardiorespiratory Fitness in Marathon Runners

Directory of Open Access Journals (Sweden)

M. J. Laye

2015-01-01

Full Text Available High levels of cardiovascular fitness (CRF and physical activity (PA are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run consistently >50 km/wk and/or >2 marathons/yr for the last 5 years have superior metabolic fitness compared to matched sedentary subjects (CRF, age, gender, and BMI. Case-control recruitment of 31 pairs of runner-sedentary subjects identified 10 matched pairs with similar VO2max (mL/min/kg (similar-VO2max. The similar-VO2max group was compared with a group of age, gender, and BMI matched pairs who had the largest difference in VO2max (different-VO2max. Primary outcomes that defined metabolic fitness including insulin response to an oral glucose tolerance test, fasting lipids, and fasting insulin were superior in runners versus sedentary controls despite similar VO2max. Furthermore, performance (velocity at VO2max, running economy, improved exercise metabolism (lactate threshold, and skeletal muscle levels of mitochondrial proteins were superior in runners versus sedentary controls with similar VO2max. In conclusion subjects with a high amount of PA have more positive metabolic health parameters independent of CRF. PA is thus a good marker against metabolic diseases.

Calcium metabolism in birds.

Science.gov (United States)

de Matos, Ricardo

2008-01-01

Calcium is one of the most important plasma constituents in mammals and birds. It provides structural strength and support (bones and eggshell) and plays vital roles in many of the biochemical reactions in the body. The control of calcium metabolism in birds is highly efficient and closely regulated in a number of tissues, primarily parathyroid gland, intestine, kidney, and bone. The hormones with the greatest involvement in calcium regulation in birds are parathyroid hormone, 1,25-dihydroxyvitamin D(3) (calcitriol), and estrogen, with calcitonin playing a minor and uncertain role. The special characteristics of calcium metabolism in birds, mainly associated with egg production, are discussed, along with common clinical disorders secondary to derangements in calcium homeostasis.

The neuropeptide allatostatin A regulates metabolism and feeding decisions in Drosophila

DEFF Research Database (Denmark)

Hentze, Julie Lilith; Carlsson, Mikael A.; Kondo, Shu

2015-01-01

Coordinating metabolism and feeding is important to avoid obesity and metabolic diseases, yet the underlying mechanisms, balancing nutrient intake and metabolic expenditure, are poorly understood. Several mechanisms controlling these processes are conserved in Drosophila, where homeostasis and en...

Metabolic drift in the aging brain.

Science.gov (United States)

Ivanisevic, Julijana; Stauch, Kelly L; Petrascheck, Michael; Benton, H Paul; Epstein, Adrian A; Fang, Mingliang; Gorantla, Santhi; Tran, Minerva; Hoang, Linh; Kurczy, Michael E; Boska, Michael D; Gendelman, Howard E; Fox, Howard S; Siuzdak, Gary

2016-05-01

Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energymetabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication.

The Mediator Complex and Lipid Metabolism.

Science.gov (United States)

Zhang, Yi; Xiaoli; Zhao, Xiaoping; Yang, Fajun

2013-03-01

The precise control of gene expression is essential for all biological processes. In addition to DNA-binding transcription factors, numerous transcription cofactors contribute another layer of regulation of gene transcription in eukaryotic cells. One of such transcription cofactors is the highly conserved Mediator complex, which has multiple subunits and is involved in various biological processes through directly interacting with relevant transcription factors. Although the current understanding on the biological functions of Mediator remains incomplete, research in the past decade has revealed an important role of Mediator in regulating lipid metabolism. Such function of Mediator is dependent on specific transcription factors, including peroxisome proliferator-activated receptor-gamma (PPARγ) and sterol regulatory element-binding proteins (SREBPs), which represent the master regulators of lipid metabolism. The medical significance of these findings is apparent, as aberrant lipid metabolism is intimately linked to major human diseases, such as type 2 diabetes and cardiovascular disease. Here, we briefly review the functions and molecular mechanisms of Mediator in regulation of lipid metabolism.

Coordinated balancing of muscle oxidative metabolism through PGC-1{alpha} increases metabolic flexibility and preserves insulin sensitivity

Energy Technology Data Exchange (ETDEWEB)

Summermatter, Serge [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland); Troxler, Heinz [Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University Children' s Hospital, University of Zurich, Steinwiesstrasse 75, CH-8032 Zurich (Switzerland); Santos, Gesa [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland); Handschin, Christoph, E-mail: christoph.handschin@unibas.ch [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland)

2011-04-29

Highlights: {yields} PGC-1{alpha} enhances muscle oxidative capacity. {yields} PGC-1{alpha} promotes concomitantly positive and negative regulators of lipid oxidation. {yields} Regulator abundance enhances metabolic flexibility and balances oxidative metabolism. {yields} Balanced oxidation prevents detrimental acylcarnitine and ROS generation. {yields} Absence of detrimental metabolites preserves insulin sensitivity -- Abstract: The peroxisome proliferator-activated receptor {gamma} coactivator 1{alpha} (PGC-1{alpha}) enhances oxidative metabolism in skeletal muscle. Excessive lipid oxidation and electron transport chain activity can, however, lead to the accumulation of harmful metabolites and impair glucose homeostasis. Here, we investigated the effect of over-expression of PGC-1{alpha} on metabolic control and generation of insulin desensitizing agents in extensor digitorum longus (EDL), a muscle that exhibits low levels of PGC-1{alpha} in the untrained state and minimally relies on oxidative metabolism. We demonstrate that PGC-1{alpha} induces a strictly balanced substrate oxidation in EDL by concomitantly promoting the transcription of activators and inhibitors of lipid oxidation. Moreover, we show that PGC-1{alpha} enhances the potential to uncouple oxidative phosphorylation. Thereby, PGC-1{alpha} boosts elevated, yet tightly regulated oxidative metabolism devoid of side products that are detrimental for glucose homeostasis. Accordingly, PI3K activity, an early phase marker for insulin resistance, is preserved in EDL muscle. Our findings suggest that PGC-1{alpha} coordinately coactivates the simultaneous transcription of gene clusters implicated in the positive and negative regulation of oxidative metabolism and thereby increases metabolic flexibility. Thus, in mice fed a normal chow diet, over-expression of PGC-1{alpha} does not alter insulin sensitivity and the metabolic adaptations elicited by PGC-1{alpha} mimic the beneficial effects of endurance training

Coordinated balancing of muscle oxidative metabolism through PGC-1α increases metabolic flexibility and preserves insulin sensitivity

International Nuclear Information System (INIS)

Summermatter, Serge; Troxler, Heinz; Santos, Gesa; Handschin, Christoph

2011-01-01

Highlights: → PGC-1α enhances muscle oxidative capacity. → PGC-1α promotes concomitantly positive and negative regulators of lipid oxidation. → Regulator abundance enhances metabolic flexibility and balances oxidative metabolism. → Balanced oxidation prevents detrimental acylcarnitine and ROS generation. → Absence of detrimental metabolites preserves insulin sensitivity -- Abstract: The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) enhances oxidative metabolism in skeletal muscle. Excessive lipid oxidation and electron transport chain activity can, however, lead to the accumulation of harmful metabolites and impair glucose homeostasis. Here, we investigated the effect of over-expression of PGC-1α on metabolic control and generation of insulin desensitizing agents in extensor digitorum longus (EDL), a muscle that exhibits low levels of PGC-1α in the untrained state and minimally relies on oxidative metabolism. We demonstrate that PGC-1α induces a strictly balanced substrate oxidation in EDL by concomitantly promoting the transcription of activators and inhibitors of lipid oxidation. Moreover, we show that PGC-1α enhances the potential to uncouple oxidative phosphorylation. Thereby, PGC-1α boosts elevated, yet tightly regulated oxidative metabolism devoid of side products that are detrimental for glucose homeostasis. Accordingly, PI3K activity, an early phase marker for insulin resistance, is preserved in EDL muscle. Our findings suggest that PGC-1α coordinately coactivates the simultaneous transcription of gene clusters implicated in the positive and negative regulation of oxidative metabolism and thereby increases metabolic flexibility. Thus, in mice fed a normal chow diet, over-expression of PGC-1α does not alter insulin sensitivity and the metabolic adaptations elicited by PGC-1α mimic the beneficial effects of endurance training on muscle metabolism in this context.