Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Bioaccumulation and metabolomics responses in oysters Crassostrea hongkongensis impacted by different levels of metal pollution.

Sun, 05/06/2016 - 12:30
Bioaccumulation and metabolomics responses in oysters Crassostrea hongkongensis impacted by different levels of metal pollution. Environ Pollut. 2016 Jun 1;216:156-165 Authors: Cao C, Wang WX Abstract Jiulong River Estuary, located in southern China, was heavily contaminated by metal pollution. In this study, the estuarine oysters Crassostrea hongkongensis were transplanted to two sites with similar hydrological conditions but different levels of metal pollution in Jiulong River Estuary over a six-month period. We characterized the time-series change of metal bioaccumulation and final metabolomics responses of oysters. Following transplantation, all metals (Cd, Cu, Cr, Ni, Pb, and Zn) in the oyster digestive glands had elevated concentrations over time. By the end of six-month exposure, Cu, Zn and Cd were the main metals significantly differentiating the two sites. Using (1)H NMR metabolite approach, we further demonstrated the disturbance in osmotic regulation, energy metabolism, and glycerophospholipid metabolism induced by metal contaminations. Six months later, the oysters transplanted in the two sites showed a similar metabolite variation pattern when compared with the initial oysters regardless of different metal levels in the tissues. Interestingly, by comparing the oysters from two sites, the more severely polluted oysters accumulated significantly higher amounts of osmolytes (betaine and homarine) and lower energy storage compounds (glycogen) than the less polluted oysters; these changes could be the potential biomarkers for different levels of metal pollution. Our study demonstrated the complexity of biological effects under field conditions, and NMR metabolomics provides an important approach to detect sensitive variation of oyster inner status. PMID: 27262129 [PubMed - as supplied by publisher]

Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target.

Sun, 05/06/2016 - 12:30
Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target. Asian Pac J Trop Med. 2016 Jun;9(6):525-534 Authors: Krungkrai SR, Krungkrai J Abstract Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum (P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria. PMID: 27262062 [PubMed - as supplied by publisher]

Establishment of local searching methods for orbitrap-based high throughput metabolomics analysis.

Sun, 05/06/2016 - 12:30
Establishment of local searching methods for orbitrap-based high throughput metabolomics analysis. Talanta. 2016 Aug 15;156-157:163-71 Authors: Tang H, Wang X, Xu L, Ran X, Li X, Chen L, Zhao X, Deng H, Liu X Abstract Our method aims to establish local endogenous metabolite databases economically without purchasing chemical standards, giving strong bases for following orbitrap based high throughput untargeted metabolomics analysis. A new approach here is introduced to construct metabolite databases on the base of biological sample analysis and mathematic extrapolation. Building local metabolite databases traditionally requires expensive chemical standards, which is barely affordable for most research labs. As a result, most labs working on metabolomics analysis have to refer public libraries, which is time consuming and limited for high throughput analysis. Using this strategy, a high throughput orbitrap based metabolomics platform can be established at almost no cost within a couple of months. It enables to facilitate the application of high throughput metabolomics analysis to identify disease-related biomarkers or investigate biological functions using orbitrap. PMID: 27260449 [PubMed - in process]

Genetic transformation of rare Verbascum eriophorum Godr. plants and metabolic alterations revealed by NMR-based metabolomics.

Sun, 05/06/2016 - 12:30
Genetic transformation of rare Verbascum eriophorum Godr. plants and metabolic alterations revealed by NMR-based metabolomics. Biotechnol Lett. 2016 Jun 3; Authors: Marchev A, Yordanova Z, Alipieva K, Zahmanov G, Rusinova-Videva S, Kapchina-Toteva V, Simova S, Popova M, Georgiev MI Abstract OBJECTIVES: To develop a protocol to transform Verbascum eriophorum and to study the metabolic differences between mother plants and hairy root culture by applying NMR and processing the datasets with chemometric tools. RESULTS: Verbascum eriophorum is a rare species with restricted distribution, which is poorly studied. Agrobacterium rhizogenes-mediated genetic transformation of V. eriophorum and hairy root culture induction are reported for the first time. To determine metabolic alterations, V. eriophorum mother plants and relevant hairy root culture were subjected to comprehensive metabolomic analyses, using NMR (1D and 2D). Metabolomics data, processed using chemometric tools (and principal component analysis in particular) allowed exploration of V. eriophorum metabolome and have enabled identification of verbascoside (by means of 2D-TOCSY NMR) as the most abundant compound in hairy root culture. CONCLUSION: Metabolomics data contribute to the elucidation of metabolic alterations after T-DNA transfer to the host V. eriophorum genome and the development of hairy root culture for sustainable bioproduction of high value verbascoside. PMID: 27259724 [PubMed - as supplied by publisher]

Compartmentation of metabolites in regulating epigenome of cancer.

Sat, 04/06/2016 - 14:44
Related Articles Compartmentation of metabolites in regulating epigenome of cancer. Mol Med. 2016 Apr 14;22 Authors: Zhao Z, Wang L, Di LJ Abstract Covalent modification of DNA and histones are important epigenetic events and the genome wide reshaping of epigenetic markers is common in cancer. The epigenetic markers are produced by enzymatic reactions and some of these reactions require the presence of metabolites as cofactors (termed Epigenetic Enzyme Required Metabolites, EERMs). Recent studies found that the abundance of these EERMs correlates with epigenetic enzymes activity. Also, the subcellular compartmentation, especially the nuclear localization of these EERMs may play a role in regulating the activities of epigenetic enzymes. Moreover, gene specific recruitment of enzymes which produce the EERMs in the proximity of the epigenetic modification events accompanying the gene expression regulation, were proposed. Therefore, it is of importance to summarize these findings of the EERMs in regulating the epigenetic modifications at both DNA and histone levels, and to understand how EERMs contribute to cancer development by addressing their global versus local distribution. PMID: 27258652 [PubMed - as supplied by publisher]

Development of Database Assisted Structure Identification (DASI) Methods for Nontargeted Metabolomics.

Sat, 04/06/2016 - 14:44
Related Articles Development of Database Assisted Structure Identification (DASI) Methods for Nontargeted Metabolomics. Metabolites. 2016;6(2) Authors: Menikarachchi LC, Dubey R, Hill DW, Brush DN, Grant DF Abstract Metabolite structure identification remains a significant challenge in nontargeted metabolomics research. One commonly used strategy relies on searching biochemical databases using exact mass. However, this approach fails when the database does not contain the unknown metabolite (i.e., for unknown-unknowns). For these cases, constrained structure generation with combinatorial structure generators provides a potential option. Here we evaluated structure generation constraints based on the specification of: (1) substructures required (i.e., seed structures); (2) substructures not allowed; and (3) filters to remove incorrect structures. Our approach (database assisted structure identification, DASI) used predictive models in MolFind to find candidate structures with chemical and physical properties similar to the unknown. These candidates were then used for seed structure generation using eight different structure generation algorithms. One algorithm was able to generate correct seed structures for 21/39 test compounds. Eleven of these seed structures were large enough to constrain the combinatorial structure generator to fewer than 100,000 structures. In 35/39 cases, at least one algorithm was able to generate a correct seed structure. The DASI method has several limitations and will require further experimental validation and optimization. At present, it seems most useful for identifying the structure of unknown-unknowns with molecular weights <200 Da. PMID: 27258318 [PubMed - as supplied by publisher]

Plant Metabolomics: An Indispensable System Biology Tool for Plant Science.

Sat, 04/06/2016 - 14:44
Related Articles Plant Metabolomics: An Indispensable System Biology Tool for Plant Science. Int J Mol Sci. 2016;17(6) Authors: Hong J, Yang L, Zhang D, Shi J Abstract As genomes of many plant species have been sequenced, demand for functional genomics has dramatically accelerated the improvement of other omics including metabolomics. Despite a large amount of metabolites still remaining to be identified, metabolomics has contributed significantly not only to the understanding of plant physiology and biology from the view of small chemical molecules that reflect the end point of biological activities, but also in past decades to the attempts to improve plant behavior under both normal and stressed conditions. Hereby, we summarize the current knowledge on the genetic and biochemical mechanisms underlying plant growth, development, and stress responses, focusing further on the contributions of metabolomics to practical applications in crop quality improvement and food safety assessment, as well as plant metabolic engineering. We also highlight the current challenges and future perspectives in this inspiring area, with the aim to stimulate further studies leading to better crop improvement of yield and quality. PMID: 27258266 [PubMed - as supplied by publisher]

Application of Two-Dimensional Nuclear Magnetic Resonance for Signal Enhancement by Spectral Integration Using a Large Dataset of Metabolic Mixtures.

Sat, 04/06/2016 - 14:44
Related Articles Application of Two-Dimensional Nuclear Magnetic Resonance for Signal Enhancement by Spectral Integration Using a Large Dataset of Metabolic Mixtures. Anal Chem. 2016 Jun 3; Authors: Misawa T, Wei F, Kikuchi J Abstract Nuclear magnetic resonance (NMR) spectroscopy has tremendous advantages of minimal sample preparation and inter-convertibility of data among different institutions; thus, large datasets are frequently acquired in metabolomics studies. Pre-viously, we used a novel analytical strategy, named signal enhancement by spectral integration (SENSI), to overcome the low signal to noise ratio (S/N ratio) problem in (13)C NMR by integration of hundreds of spectra without additional measure-ments. In this letter, the development of a SENSI 2D method and application to >1000 2D JRES NMR spectra are described. Remarkably, the obtained SENSI 2D spectrum had an approximate 14-fold increase in the S/N ratio and 80-250 additional peaks without any additional measurements. These results suggest that SENSI 2D is a useful method for assigning weak signals and that the use of coefficient of variation values can support the assignment information and extraction of features from the population characteristics among large datasets. PMID: 27257670 [PubMed - as supplied by publisher]

ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling.

Sat, 04/06/2016 - 14:44
Related Articles ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling. Science. 2016 Jun 3;352(6290):1221-5 Authors: Wright RH, Lioutas A, Le Dily F, Soronellas D, Pohl A, Bonet J, Nacht AS, Samino S, Font-Mateu J, Vicent GP, Wierer M, Trabado MA, Schelhorn C, Carolis C, Macias MJ, Yanes O, Oliva B, Beato M Abstract Key nuclear processes in eukaryotes, including DNA replication, repair, and gene regulation, require extensive chromatin remodeling catalyzed by energy-consuming enzymes. It remains unclear how the ATP demands of such processes are met in response to rapid stimuli. We analyzed this question in the context of the massive gene regulation changes induced by progestins in breast cancer cells and found that ATP is generated in the cell nucleus via the hydrolysis of poly(ADP-ribose) to ADP-ribose. In the presence of pyrophosphate, ADP-ribose is used by the pyrophosphatase NUDIX5 to generate nuclear ATP. The nuclear source of ATP is essential for hormone-induced chromatin remodeling, transcriptional regulation, and cell proliferation. PMID: 27257257 [PubMed - in process]

Identification of Rare Variants in Metabolites of the Carnitine Pathway by Whole Genome Sequencing Analysis.

Sat, 04/06/2016 - 14:44
Related Articles Identification of Rare Variants in Metabolites of the Carnitine Pathway by Whole Genome Sequencing Analysis. Genet Epidemiol. 2016 Jun 3; Authors: Yazdani A, Yazdani A, Liu X, Boerwinkle E Abstract We use whole genome sequence data and rare variant analysis methods to investigate a subset of the human serum metabolome, including 16 carnitine-related metabolites that are important components of mammalian energy metabolism. Medium pass sequence data consisting of 12,820,347 rare variants and serum metabolomics data were available on 1,456 individuals. By applying a penalization method, we identified two genes FGF8 and MDGA2 with significant effects on lysine and cis-4-decenoylcarnitine, respectively, using Δ-AIC and likelihood ratio test statistics. Single variant analyses in these regions did not identify a single low-frequency variant (minor allele count > 3) responsible for the underlying signal. The results demonstrate the utility of whole genome sequence and innovative analyses for identifying candidate regions influencing complex phenotypes. PMID: 27256581 [PubMed - as supplied by publisher]

Autophagy in acute brain injury.

Sat, 04/06/2016 - 14:44
Related Articles Autophagy in acute brain injury. Nat Rev Neurosci. 2016 Jun 3; Authors: Galluzzi L, Pedro JM, Blomgren K, Kroemer G Abstract Autophagy is an evolutionarily ancient mechanism that ensures the lysosomal degradation of old, supernumerary or ectopic cytoplasmic entities. Most eukaryotic cells, including neurons, rely on proficient autophagic responses for the maintenance of homeostasis in response to stress. Accordingly, autophagy mediates neuroprotective effects following some forms of acute brain damage, including methamphetamine intoxication, spinal cord injury and subarachnoid haemorrhage. In some other circumstances, however, the autophagic machinery precipitates a peculiar form of cell death (known as autosis) that contributes to the aetiology of other types of acute brain damage, such as neonatal asphyxia. Here, we dissect the context-specific impact of autophagy on non-infectious acute brain injury, emphasizing the possible therapeutic application of pharmacological activators and inhibitors of this catabolic process for neuroprotection. PMID: 27256553 [PubMed - as supplied by publisher]

Metabolic profiling of potential lung cancer biomarkers using bronchoalveolar lavage fluid and the integrated direct infusion/ gas chromatography mass spectrometry platform.

Sat, 04/06/2016 - 14:44
Related Articles Metabolic profiling of potential lung cancer biomarkers using bronchoalveolar lavage fluid and the integrated direct infusion/ gas chromatography mass spectrometry platform. J Proteomics. 2016 May 30; Authors: Callejón-Leblic B, García-Barrera T, Grávalos-Guzmán J, Pereira-Vega A, Gómez-Ariza JL Abstract Lung cancer is one of the ten most common causes of death worldwide, so that the search for early diagnosis biomarkers is a very challenging task. Bronchoalveolar lavage fluid (BALF) provides information on cellular and biochemical epithelial surface of the lower respiratory tract constituents and no previous metabolomic studies have been performed with BALF samples from patients with lung cancer. Therefore, this fluid has been explored looking for new contributions in lung cancer metabolism. In this way, two complementary metabolomics techniques based on direct infusion high resolution mass spectrometry (DI-ESI-QTOF-MS) and gas chromatography mass spectrometry (GC-MS) have been applied to compare statistically differences between lung cancer (LC) and control (C) BALF samples, using partial least square discriminant analysis (PLS-DA) in order to find and identify potential biomarkers of the disease. A total of 42 altered metabolites were found in BALF from LC. The metabolic pathway analysis showed that glutamate and glutamine metabolism pathway was mainly altered by this disease. In addition, we assessed the biomarker specificity and sensitivity according to the area under the receiver operator characteristic (ROC) curves, indicating that glycerol and phosphoric acid were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. BIOLOGICAL SIGNIFICANCE: The search for early diagnosis of lung cancer is a very challenging task because of the high mortality associated to this disease and its critical linkage to the initiation of treatment. Bronchoalveolar lavage fluid provides information on cellular and biochemical epithelial surface of the lower respiratory tract constituents and no previous metabolomic studies have been performed with BALF samples from patients with lung cancer. Since BALF is in close interaction with lung tissue it is a more representative sample of lung status than other peripheral biofluids as blood or urine studied in previous works. Therefore, this study represents an innovative contribution in this topic that complement previous investigations about lung cancer, opening up new possibilities for understanding the pathogenesis of this disease and the use of efficient biomarkers. Therefore, this fluid has been explored looking for new contributions in lung cancer metabolism. In this way, two complementary metabolomic techniques based on direct infusion high resolution mass spectrometry (DI-ESI-QTOF-MS) and gas chromatography mass spectrometry (GC-MS) have been applied to compare statistically sifnificant differences between lung cancer (LC) and control (C) BALF samples, using partial least square discriminant analysis (PLS-DA) in order to find and identify potential biomarkers of the disease. A total of 42 altered metabolites were found in BALF from LC. The metabolic pathway analysis showed that glutamate and glutamine metabolism pathway was mainly altered by this disease. In addition, we assessed the biomarker specificity and sensitivity according to the area under the receiver operator characteristic (ROC) curves, indicating that glycerol and phosphoric acid were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. PMID: 27255828 [PubMed - as supplied by publisher]

Medium-chain plasma acylcarnitines, ketone levels, cognition, and gray matter volumes in healthy elderly, mildly cognitively impaired, or Alzheimer's disease subjects.

Sat, 04/06/2016 - 14:44
Related Articles Medium-chain plasma acylcarnitines, ketone levels, cognition, and gray matter volumes in healthy elderly, mildly cognitively impaired, or Alzheimer's disease subjects. Neurobiol Aging. 2016 Jul;43:1-12 Authors: Ciavardelli D, Piras F, Consalvo A, Rossi C, Zucchelli M, Di Ilio C, Frazzini V, Caltagirone C, Spalletta G, Sensi SL Abstract Aging, amyloid deposition, and tau-related pathology are key contributors to the onset and progression of Alzheimer's disease (AD). However, AD is also associated with brain hypometabolism and deficits of mitochondrial bioenergetics. Plasma acylcarnitines (ACCs) are indirect indices of altered fatty acid beta-oxidation, and ketogenesis has been found to be decreased on aging. Furthermore, in elderly subjects, alterations in plasma levels of specific ACCs have been suggested to predict conversion to mild cognitive impairment (MCI) or AD. In this study, we assayed plasma profiles of ACCs in a cohort of healthy elderly control, MCI subjects, and AD patients. Compared with healthy controls or MCI subjects, AD patients showed significant lower plasma levels of several medium-chain ACCs. Furthermore, in AD patients, these lower concentrations were associated with lower prefrontal gray matter volumes and the presence of cognitive impairment. Interestingly, lower levels of medium-chain ACCs were also found to be associated with lower plasma levels of 2-hydroxybutyric acid. Overall, these findings suggest that altered metabolism of medium-chain ACCs and impaired ketogenesis can be metabolic features of AD. PMID: 27255810 [PubMed - in process]

Fatty acid and metabolomic profiling approaches differentiate heterotrophic and mixotrophic culture conditions in a microalgal food supplement 'Euglena'.

Sat, 04/06/2016 - 14:44
Related Articles Fatty acid and metabolomic profiling approaches differentiate heterotrophic and mixotrophic culture conditions in a microalgal food supplement 'Euglena'. BMC Biotechnol. 2016;16(1):49 Authors: Zeng M, Hao W, Zou Y, Shi M, Jiang Y, Xiao P, Lei A, Hu Z, Zhang W, Zhao L, Wang J Abstract BACKGROUND: Microalgae have been recognized as a good food source of natural biologically active ingredients. Among them, the green microalga Euglena is a very promising food and nutritional supplements, providing high value-added poly-unsaturated fatty acids, paramylon and proteins. Different culture conditions could affect the chemical composition and food quality of microalgal cells. However, little information is available for distinguishing the different cellular changes especially the active ingredients including poly-saturated fatty acids and other metabolites under different culture conditions, such as light and dark. RESULTS: In this study, together with fatty acid profiling, we applied a gas chromatography-mass spectrometry (GC-MS)-based metabolomics to differentiate hetrotrophic and mixotrophic culture conditions. CONCLUSIONS: This study suggests metabolomics can shed light on understanding metabolomic changes under different culture conditions and provides a theoretical basis for industrial applications of microalgae, as food with better high-quality active ingredients. PMID: 27255274 [PubMed - in process]

Differential Metabolic Profiles during the Albescent Stages of 'Anji Baicha' (Camellia sinensis).

Sat, 04/06/2016 - 14:44
Related Articles Differential Metabolic Profiles during the Albescent Stages of 'Anji Baicha' (Camellia sinensis). PLoS One. 2015;10(10):e0139996 Authors: Li CF, Yao MZ, Ma CL, Ma JQ, Jin JQ, Chen L Abstract 'Anji Baicha' is an albino tea cultivar with white shoots at low air temperature and green shoots at high air temperature in early spring. The metabolite contents in the shoots dynamically vary with the color changes and with shoot development. To investigate the metabolomic variation during the albescent and re-greening stages, gas chromatography-mass spectrometry combined with multivariate analysis were applied to analyze the metabolite profiles in the different color stages during the development of 'Anji Baicha' leaves. The metabolite profiles of three albescent stages, including the yellow-green stage, the early albescent stage, and the late albescent stage, as well as the re-greening stage were distinguished using principal component analysis, revealing that the distinct developmental stages were likely responsible for the observed metabolic differences. Furthermore, a group classification and pairwise discrimination was revealed among the three albescent stages and re-greening stage by partial least squares discriminant analysis. A total of 65 differential metabolites were identified with a variable influence on projection greater than 1. The main differential metabolic pathways of the albescent stages compared with the re-greening stage included carbon fixation in photosynthetic organisms and the phenylpropanoid and flavonoid biosynthesis pathways. Compared with the re-greening stage, the carbohydrate and amino acid metabolic pathways were disturbed during the albescent stages. During the albescent stages, the sugar (fructofuranose), sugar derivative (glucose-1-phosphate) and epicatechin concentrations decreased, whereas the amino acid (mainly glycine, serine, tryptophan, citrulline, glutamine, proline, and valine) concentrations increased. These results reveal the changes in metabolic profiling that occur during the color changes associated with the development of the albino tea plant leaves. PMID: 26444680 [PubMed - indexed for MEDLINE]

Changes in Glucose Metabolism in Vertical Sleeve Gastrectomy.

Sat, 04/06/2016 - 14:44
Related Articles Changes in Glucose Metabolism in Vertical Sleeve Gastrectomy. Obes Surg. 2015 Nov;25(11):2002-10 Authors: Lho Y, le Roux CW, Park HS, Kim GS, Jung J, Hwang GS, Seo YK, Ha TK, Ha E Abstract BACKGROUND: We evaluated metabolic changes after vertical sleeve gastrectomy (VSG) surgery in a rat model using proteomics and metabolomic profiling in liver and serum. METHODS: Rats were randomly divided into two groups: sham (n = 10) and VSG (n = 12). Food intake, body weight, blood glucose, insulin, and thyroid hormone levels were measured. Two-dimensional electrophoresis, nuclear resonance spectroscopy, mass spectroscopy, immunofluorescence, and immunoblot analyses were used to determine and validate changes in metabolites and proteins in liver tissue and serum samples. RESULTS: Food intake and body weight decreased after VSG group (p < 0.05 and p < 0.05, respectively). Random blood glucose (sham, 183.3 ± 5.6 mg/dL; VSG, 138.5 ± 3.7 mg/dL) decreased while random insulin (sham, 0.45 ± 0.16 μg/L; VSG, 1.05 ± 0.18 μg/L) increased after VSG (p < 0.05 and p < 0.01, respectively). We found that expressions of gluconeogenic enzymes (phosphoenolpyruvate carboxykinase-1 and glucose-6-phosphatase) and concentrations of pyruvate and malate decreased while lactate, NADH, NADPH, glucose, and AMP/ATP ratio increased after VSG. Thyroid hormones, triiodothyronine (T3) and free thyroxine (fT4), decreased after VSG. CONCLUSION: This study proves that VSG suppresses hepatic glucose production. PMID: 25726321 [PubMed - indexed for MEDLINE]

Highly repeatable dissolution dynamic nuclear polarization for heteronuclear NMR metabolomics.

Fri, 03/06/2016 - 14:17
Highly repeatable dissolution dynamic nuclear polarization for heteronuclear NMR metabolomics. Anal Chem. 2016 Jun 2; Authors: Bornet A, Maucourt M, Deborde C, Jacob D, Milani J, Vuichoud B, Ji X, Dumez JN, Moing A, Bodenhausen G, Jannin S, Giraudeau P Abstract At natural 13C abundance, metabolomics based on heteronuclear NMR is limited by sensitivity. We have recently demonstrated how hyperpolarization by dissolution dynamic nuclear polarization (D-DNP) assisted by cross-polarization (CP) provides a reliable way of enhancing the sensitivity of heteronuclear NMR in dilute mixtures of metabolites. In this Technical Note, we evaluate the precision of this experimental approach, a critical point for applications to metabolomics. The higher the repeatability, the greater the likelihood that one can detect small biologically relevant differences between samples. The average repeatability of our state-of-the-art D-DNP NMR equipment for samples of metabolomic relevance (20 mg dry weight tomato extracts) is 3.6% for signals above the limit of quantification (LOQ), and 6.4% when all the signals above the limit of detection (LOD) are taken into account. This first report on the repeatability of D-DNP highlights the compatibility of the technique with the requirements of metabolomics, and confirms its potential as an analytical tool for such applications. PMID: 27253320 [PubMed - as supplied by publisher]

Metabolomic Analysis in Brain Research: Opportunities and Challenges.

Fri, 03/06/2016 - 14:17
Metabolomic Analysis in Brain Research: Opportunities and Challenges. Front Physiol. 2016;7:183 Authors: Vasilopoulou CG, Margarity M, Klapa MI Abstract Metabolism being a fundamental part of molecular physiology, elucidating the structure and regulation of metabolic pathways is crucial for obtaining a comprehensive perspective of cellular function and understanding the underlying mechanisms of its dysfunction(s). Therefore, quantifying an accurate metabolic network activity map under various physiological conditions is among the major objectives of systems biology in the context of many biological applications. Especially for CNS, metabolic network activity analysis can substantially enhance our knowledge about the complex structure of the mammalian brain and the mechanisms of neurological disorders, leading to the design of effective therapeutic treatments. Metabolomics has emerged as the high-throughput quantitative analysis of the concentration profile of small molecular weight metabolites, which act as reactants and products in metabolic reactions and as regulatory molecules of proteins participating in many biological processes. Thus, the metabolic profile provides a metabolic activity fingerprint, through the simultaneous analysis of tens to hundreds of molecules of pathophysiological and pharmacological interest. The application of metabolomics is at its standardization phase in general, and the challenges for paving a standardized procedure are even more pronounced in brain studies. In this review, we support the value of metabolomics in brain research. Moreover, we demonstrate the challenges of designing and setting up a reliable brain metabolomic study, which, among other parameters, has to take into consideration the sex differentiation and the complexity of brain physiology manifested in its regional variation. We finally propose ways to overcome these challenges and design a study that produces reproducible and consistent results. PMID: 27252656 [PubMed]

Nutrigenomics and its Impact on Life Style Associated Metabolic Diseases.

Fri, 03/06/2016 - 14:17
Nutrigenomics and its Impact on Life Style Associated Metabolic Diseases. Curr Genomics. 2016 Jun;17(3):261-78 Authors: Rana S, Kumar S, Rathore N, Padwad Y, Bhushana S Abstract Post-human genome revelation observes the emergence of 'Nutigenomics' as one of the exciting scientific advancement influencing mankind around the world. Food or more precisely 'nutrition' has the major impact in defining the cause-response interaction between nutrient (diet) and human health. In addition to substantial understanding of nutrition-human-health interaction, bases of 'nutrigenomic' development foster on advent in transcriptomics, genomics, proteomics and metabolomics as well as insight into food as health supplement. Interaction of selected nutrient with associated genes in specific organ or tissue necessary to comprehend that how individual's genetic makeup (DNA transcribed into mRNA and then to proteins) respond to particular nutrient. It provided new opportunities to incorporate natural bioactive compounds into food for specific group of people with similar genotype. As inception of diabetes associated with change in gene expression of, not limited to, protein kinase B, insulin receptor, duodenal homeobox and glucokinase, thus, targeting such proteins by modifying or improving the nutritional availability or uptake may help to devise novel food, supplements, or nutraceuticals. In this article, various aspects of R&D in nutrigenomics are reviewed to ascertain its impact on human health, especially with life-style associated diseases. PMID: 27252592 [PubMed]

Molecular Approaches to Understand Nutritional Potential of Coarse Cereals.

Fri, 03/06/2016 - 14:17
Molecular Approaches to Understand Nutritional Potential of Coarse Cereals. Curr Genomics. 2016 Jun;17(3):177-92 Authors: Singh AK, Singh R, Subramani R, Kumar R, Wankhede DP Abstract Coarse grains are important group of crops that constitutes staple food for large population residing primarily in the arid and semi-arid regions of the world. Coarse grains are designated as nutri-cereals as they are rich in essential amino acids, minerals and vitamins. In spite of having several nutritional virtues in coarse grain as mentioned above, there is still scope for improvement in quality parameters such as cooking qualities, modulation of nutritional constituents and reduction or elimination of anti-nutritional factors. Besides its use in traditional cooking, coarse grains have been used mainly in the weaning food preparation and other malted food production. Improvement in quality parameters will certainly increase consumer's preference for coarse grains and increase their demand. The overall genetic gain in quality traits of economic importance in the cultivated varieties will enhance their industrial value and simultaneously increase income of farmers growing these varieties. The urgent step for improvement of quality traits in coarse grains requires a detailed understanding of molecular mechanisms responsible for varied level of different nutritional contents in different genotypes of these crops. In this review we have discussed the progresses made in understanding of coarse grain biology with various omics tool coupled with modern breeding approaches and the current status with regard to our effort towards dissecting traits related to improvement of quality and nutritional constituents of grains. PMID: 27252585 [PubMed]

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