PubMed

Related Articles Metabolomics of Rhabdomyosarcoma Cell During Echovirus 30 Infection. Virol J. 2017 Jul 27;14(1):144 Authors: Tiwari S, Dhole TN Abstract BACKGROUND: Echovirus 30 (E30) causes acute aseptic meningitis. Viral replication requires energy and macromolecular precursors derived from the metabolic network of the host cell. The effect of viral infection within a host cell metabolic activity remains unclear. METHODS: To gain an insight into cell-virus interaction during E30 infection we used a human rhabdomyosarcoma cell line. In a new approach to metabolomics, (1H) NMR was used to measure the level of various cellular metabolites at different times of infection and morphological examination of the cells. Statistical analysis was done by using Confidence interval (CI) 95% and One-way ANOVA test. RESULTS: The(1)H NMR metabolite spectrum signals were observed between mock infected and virus infected cells. Both mock infected and virus infected cells utilized glucose through metabolic pathways and released metabolic end products. Upon infection, the concentration of Alanine, Lactate, Acetate, Glutamate, Tyrosine, Histidine, Phenylalanine, Creatine, Choline and Formate, increased. Interestingly, all of these augmented metabolites were decreased during later stage of infection. The cells showed wide-ranging lipid signals at the end of infection, which correlates with the morphological changes as apoptosis (programmed cell death) of cells was observed. A significant association was found between time interval (12 h, 24 h, and 48 h) and metabolites likewise Alanin, Lactate, Acetate, Glutamate, Tyrosine, Histidine, Phenylalanine, Creatine, Choline and Formate respectively released by cell during infection, which is highly significant (p < 0.01). CONCLUSION: Progressive breakdown and utilization of all cellular components were observed as the infection increased. This study is useful for monitoring the cellular metabolic changes during viral infection. PMID: 28750646 [PubMed - in process]

Related Articles Metabolome alterations in severe critical illness and vitamin D status. Crit Care. 2017 Jul 28;21(1):193 Authors: Lasky-Su J, Dahlin A, Litonjua AA, Rogers AJ, McGeachie MJ, Baron RM, Gazourian L, Barragan-Bradford D, Fredenburgh LE, Choi AMK, Mogensen KM, Quraishi SA, Amrein K, Christopher KB Abstract BACKGROUND: Metabolic homeostasis is substantially disrupted in critical illness. Given the pleiotropic effects of vitamin D, we hypothesized that metabolic profiles differ between critically ill patients relative to their vitamin D status. METHODS: We performed a metabolomics study on biorepository samples collected from a single academic medical center on 65 adults with systemic inflammatory response syndrome or sepsis treated in a 20-bed medical ICU between 2008 and 2010. To identify key metabolites and metabolic pathways related to vitamin D status in critical illness, we first generated metabolomic data using gas and liquid chromatography mass spectroscopy. We followed this by partial least squares-discriminant analysis to identify individual metabolites that were significant. We then interrogated the entire metabolomics profile using metabolite set enrichment analysis to identify groups of metabolites and pathways that were differentiates of vitamin D status. Finally we performed logistic regression to construct a network model of chemical-protein target interactions important in vitamin D status. RESULTS: Metabolomic profiles significantly differed in critically ill patients with 25(OH)D ≤ 15 ng/ml relative to those with levels >15 ng/ml. In particular, increased 1,5-anhydroglucitol, tryptophan betaine, and 3-hydroxyoctanoate as well as decreased 2-arachidonoyl-glycerophosphocholine and N-6-trimethyllysine were strong predictors of 25(OH)D >15 ng/ml. The combination of these five metabolites led to an area under the curve for discrimination for 25(OH)D > 15 ng/ml of 0.82 (95% CI 0.71-0.93). The metabolite pathways related to glutathione metabolism and glutamate metabolism are significantly enriched with regard to vitamin D status. CONCLUSION: Vitamin D status is associated with differential metabolic profiles during critical illness. Glutathione and glutamate pathway metabolism, which play principal roles in redox regulation and immunomodulation, respectively, were significantly altered with vitamin D status. PMID: 28750641 [PubMed - in process]

Related Articles Comprehensive molecular tumor profiling in radiation oncology: How it could be used for precision medicine. Cancer Lett. 2016 Nov 01;382(1):118-126 Authors: Eke I, Makinde AY, Aryankalayil MJ, Ahmed MM, Coleman CN Abstract New technologies enabling the analysis of various molecules, including DNA, RNA, proteins and small metabolites, can aid in understanding the complex molecular processes in cancer cells. In particular, for the use of novel targeted therapeutics, elucidation of the mechanisms leading to cell death or survival is crucial to eliminate tumor resistance and optimize therapeutic efficacy. While some techniques, such as genomic analysis for identifying specific gene mutations or epigenetic testing of promoter methylation, are already in clinical use, other "omics-based" assays are still evolving. Here, we provide an overview of the current status of molecular profiling methods, including promising research strategies, as well as possible challenges, and their emerging role in radiation oncology. PMID: 26828133 [PubMed - indexed for MEDLINE]

Related Articles Differential metabolic profiles associated to movement behaviour of stream-resident brown trout (Salmo trutta). PLoS One. 2017;12(7):e0181697 Authors: Oromi N, Jové M, Pascual-Pons M, Royo JL, Rocaspana R, Aparicio E, Pamplona R, Palau A, Sanuy D, Fibla J, Portero-Otin M Abstract The mechanisms that can contribute in the fish movement strategies and the associated behaviour can be complex and related to the physiology, genetic and ecology of each species. In the case of the brown trout (Salmo trutta), in recent research works, individual differences in mobility have been observed in a population living in a high mountain river reach (Pyrenees, NE Spain). The population is mostly sedentary but a small percentage of individuals exhibit a mobile behavior, mainly upstream movements. Metabolomics can reflect changes in the physiological process and can determine different profiles depending on behaviour. Here, a non-targeted metabolomics approach was used to find possible changes in the blood metabolomic profile of S. trutta related to its movement behaviour, using a minimally invasive sampling. Results showed a differentiation in the metabolomic profiles of the trouts and different level concentrations of some metabolites (e.g. cortisol) according to the home range classification (pattern of movements: sedentary or mobile). The change in metabolomic profiles can generally occur during the upstream movement and probably reflects the changes in metabolite profile from the non-mobile season to mobile season. This study reveals the contribution of the metabolomic analyses to better understand the behaviour of organisms. PMID: 28750027 [PubMed - in process]

Related Articles A Metabolomics-Guided Exploration of the Phytochemical Constituents of Vernonia fastigiata with the Aid of Pressurized Hot Water Extraction and Liquid Chromatography-Mass Spectrometry. Molecules. 2017 Jul 27;22(8): Authors: Masike K, Khoza BS, Steenkamp PA, Smit E, Dubery IA, Madala NE Abstract Vernonia fastigiata is a multi-purpose nutraceutical plant with interesting biological properties. However, very little is known about its phytochemical composition and, thus the need for its phytochemical characterization. In the current study, an environmentally friendly method, pressurized hot water extraction (PHWE), was used to extract metabolites from the leaves of V. fastigiata at various temperatures (50 °C, 100 °C, 150 °C and 200 °C). Ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-qTOF-MS) analysis in combination with chemometric methods, particularly principal component analysis (PCA) and liquid/gas chromatography mass spectrometry (XCMS) cloud plots, were used to descriptively visualize the data and identify significant metabolites extracted at various temperatures. A total of 25 different metabolites, including hydroxycinnamic acid derivatives, clovamide, deoxy-clovamide and flavonoids, were noted for the first time in this plant. Overall, an increase in extraction temperature resulted in an increase in metabolite extraction during PHWE. This study is the first scientific report on the phytochemical composition of V. fastigiata, providing insight into the components of the chemo-diversity of this important plant. PMID: 28749445 [PubMed - in process]

Related Articles Evaluation of the Nutritional Quality of Chinese Kale (Brassica alboglabra Bailey) Using UHPLC-Quadrupole-Orbitrap MS/MS-Based Metabolomics. Molecules. 2017 Jul 27;22(8): Authors: Wang YQ, Hu LP, Liu GM, Zhang DS, He HJ Abstract Chinese kale (Brassica alboglabra Bailey) is a widely consumed vegetable which is rich in antioxidants and anticarcinogenic compounds. Herein, we used an untargeted ultra-high-performance liquid chromatography (UHPLC)-Quadrupole-Orbitrap MS/MS-based metabolomics strategy to study the nutrient profiles of Chinese kale. Seven Chinese kale cultivars and three different edible parts were evaluated, and amino acids, sugars, organic acids, glucosinolates and phenolic compounds were analysed simultaneously. We found that two cultivars, a purple-stem cultivar W1 and a yellow-flower cultivar Y1, had more health-promoting compounds than others. The multivariate statistical analysis results showed that gluconapin was the most important contributor for discriminating both cultivars and edible parts. The purple-stem cultivar W1 had higher levels of some phenolic acids and flavonoids than the green stem cultivars. Compared to stems and leaves, the inflorescences contained more amino acids, glucosinolates and most of the phenolic acids. Meanwhile, the stems had the least amounts of phenolic compounds among the organs tested. Metabolomics is a powerful approach for the comprehensive understanding of vegetable nutritional quality. The results provide the basis for future metabolomics-guided breeding and nutritional quality improvement. PMID: 28749430 [PubMed - in process]

Related Articles Protocols and Applications of Cellular Metabolomics in Safety Studies Using Precision-Cut Tissue Slices and Carbon 13 NMR. Methods Mol Biol. 2017;1641:259-279 Authors: Baverel G, El Hage M, Martin G Abstract Numerous xenobiotics are toxic to human and animal cells by interacting with their metabolism, but the precise metabolic step affected and the biochemical mechanism behind such a toxicity remain often unknown. In an attempt to reduce the ignorance in this field, we have developed a new approach called cellular metabolomics. This approach, developed in vitro, provides a panoramic view not only of the pathways involved in the metabolism of physiological substrates of any normal or pathological human or animal cell but also of the beneficial and adverse effects of xenobiotics on these metabolic pathways. Unlike many cell lines, precision-cut tissue slices, for which there is a renewed interest, remain metabolically differentiated for at least 24-48 h and allow to study the effect of xenobiotics during short-term and long-term incubations. Cellular metabolomics (or metabolic flux analysis), which combines enzymatic and carbon 13 NMR measurements with mathematical modeling of metabolic pathways, is illustrated in this brief chapter for studying the effect of insulin on glucose metabolism in rat liver precision-cut slices and of valproate on glutamine metabolism in human renal cortical precision-cut slices. The use of very small amounts of test compounds allows to predict their toxic effect and eventually their beneficial effects very early in the research and development processes. Cellular metabolomics is complementary to other omics approaches, but, unlike them, provides functional, mechanistic, and dynamic pieces of information by measuring enzymatic fluxes. PMID: 28748469 [PubMed - in process]

Related Articles NMR and MS Methods for Metabolomics. Methods Mol Biol. 2017;1641:229-258 Authors: Amberg A, Riefke B, Schlotterbeck G, Ross A, Senn H, Dieterle F, Keck M Abstract Metabolomics, also often referred as "metabolic profiling," is the systematic profiling of metabolites in biofluids or tissues of organisms and their temporal changes. In the last decade, metabolomics has become more and more popular in drug development, molecular medicine, and other biotechnology fields, since it profiles directly the phenotype and changes thereof in contrast to other "-omics" technologies. The increasing popularity of metabolomics has been possible only due to the enormous development in the technology and bioinformatics fields. In particular, the analytical technologies supporting metabolomics, i.e., NMR, UPLC-MS, and GC-MS, have evolved into sensitive and highly reproducible platforms allowing the determination of hundreds of metabolites in parallel. This chapter describes the best practices of metabolomics as seen today. All important steps of metabolic profiling in drug development and molecular medicine are described in great detail, starting from sample preparation to determining the measurement details of all analytical platforms, and finally to discussing the corresponding specific steps of data analysis. PMID: 28748468 [PubMed - in process]

Related Articles Confirmation that MAT1A p.Ala259Val mutation causes autosomal dominant hypermethioninemia. Mol Genet Metab Rep. 2017 Dec;13:9-12 Authors: Muriello MJ, Viall S, Bottiglieri T, Cusmano-Ozog K, Ferreira CR Abstract Methionine adenosyltransferase (MAT) I/III deficiency is an inborn error of metabolism caused by mutations in MAT1A, encoding the catalytic subunit of MAT responsible for the synthesis of S-adenosylmethionine, and is characterized by persistent hypermethioninemia. While historically considered a recessive disorder, a milder autosomal dominant form of MAT I/III deficiency occurs, though only the most common mutation p.Arg264His has ample evidence to prove dominant inheritance. We report a case of hypermethioninemia caused by the p.Ala259Val substitution and provide evidence of autosomal dominant inheritance by showing both maternal inheritance of the mutation and concomitant hypermethioninemia. The p.Ala259Val mutation falls in the dimer interface, and thus likely leads to dominant inheritance by a similar mechanism to that described in the previously reported dominant negative mutation, that is, by means of interference with subunits encoded by the wild-type allele. PMID: 28748147 [PubMed]

Related Articles NMR-based metabonomics and correlation analysis reveal potential biomarkers associated with chronic atrophic gastritis. J Pharm Biomed Anal. 2017 Jan 05;132:77-86 Authors: Cui J, Liu Y, Hu Y, Tong J, Li A, Qu T, Qin X, Du G Abstract Chronic atrophic gastritis (CAG) is one of the most important pre-cancerous states with a high prevalence. Exploring of the underlying mechanism and potential biomarkers is of significant importance for CAG. In the present work, (1)H NMR-based metabonomics with correlative analysis was performed to analyze the metabolic features of CAG. 19 plasma metabolites and 18 urine metabolites were enrolled to construct the circulatory and excretory metabolome of CAG, which was in response to alterations of energy metabolism, inflammation, immune dysfunction, as well as oxidative stress. 7 plasma biomarkers and 7 urine biomarkers were screened to elucidate the pathogenesis of CAG based on the further correlation analysis with biochemical indexes. Finally, 3 plasma biomarkers (arginine, succinate and 3-hydroxybutyrate) and 2 urine biomarkers (α-ketoglutarate and valine) highlighted the potential to indicate risks of CAG in virtue of correlation with pepsin activity and ROC analysis. Here, our results paved a way for elucidating the underlying mechanisms in the development of CAG, and provided new avenues for the diagnosis of CAG and presented potential drug targets for treatment of CAG. PMID: 27697573 [PubMed - indexed for MEDLINE]

Related Articles Quantitative metabolomics of a xylose-utilizing Saccharomyces cerevisiae strain expressing the Bacteroides thetaiotaomicron xylose isomerase on glucose and xylose. J Ind Microbiol Biotechnol. 2017 Jul 25;: Authors: Mert MJ, Rose SH, la Grange DC, Bamba T, Hasunuma T, Kondo A, van Zyl WH Abstract The yeast Saccharomyces cerevisiae cannot utilize xylose, but the introduction of a xylose isomerase that functions well in yeast will help overcome the limitations of the fungal oxido-reductive pathway. In this study, a diploid S. cerevisiae S288c[2n YMX12] strain was constructed expressing the Bacteroides thetaiotaomicron xylA (XI) and the Scheffersomyces stipitis xyl3 (XK) and the changes in the metabolite pools monitored over time. Cultivation on xylose generally resulted in gradual changes in metabolite pool size over time, whereas more dramatic fluctuations were observed with cultivation on glucose due to the diauxic growth pattern. The low G6P and F1,6P levels observed with cultivation on xylose resulted in the incomplete activation of the Crabtree effect, whereas the high PEP levels is indicative of carbon starvation. The high UDP-D-glucose levels with cultivation on xylose indicated that the carbon was channeled toward biomass production. The adenylate and guanylate energy charges were tightly regulated by the cultures, while the catabolic and anabolic reduction charges fluctuated between metabolic states. This study helped elucidate the metabolite distribution that takes place under Crabtree-positive and Crabtree-negative conditions when cultivating S. cerevisiae on glucose and xylose, respectively. PMID: 28744577 [PubMed - as supplied by publisher]

Related Articles Multi-omics Analysis of Periodontal Pocket Microbial Communities Pre- and Posttreatment. mSystems. 2017 May-Jun;2(3): Authors: Califf KJ, Schwarzberg-Lipson K, Garg N, Gibbons SM, Caporaso JG, Slots J, Cohen C, Dorrestein PC, Kelley ST Abstract Periodontitis is a polymicrobial infectious disease that causes breakdown of the periodontal ligament and alveolar bone. We employed a meta-omics approach that included microbial 16S rRNA amplicon sequencing, shotgun metagenomics, and tandem mass spectrometry to analyze sub- and supragingival biofilms in adults with chronic periodontitis pre- and posttreatment with 0.25% sodium hypochlorite. Microbial samples were collected with periodontal curettes from 3- to 12-mm-deep periodontal pockets at the baseline and at 2 weeks and 3 months. All data types showed high interpersonal variability, and there was a significant correlation between phylogenetic diversity and pocket depth at the baseline and a strong correlation (rho = 0.21; P = 0.008) between metabolite diversity and maximum pocket depth (MPD). Analysis of subgingival baseline samples (16S rRNA and shotgun metagenomics) found positive correlations between abundances of particular bacterial genera and MPD, including Porphyromonas, Treponema, Tannerella, and Desulfovibrio species and unknown taxon SHD-231. At 2 weeks posttreatment, we observed an almost complete turnover in the bacterial genera (16S rRNA) and species (shotgun metagenomics) correlated with MPD. Among the metabolites detected, the medians of the 20 most abundant metabolites were significantly correlated with MPD pre- and posttreatment. Finally, tests of periodontal biofilm community instability found markedly higher taxonomic instability in patients who did not improve posttreatment than in patients who did improve (UniFrac distances; t = -3.59; P = 0.002). Interestingly, the opposite pattern occurred in the metabolic profiles (Bray-Curtis; t = 2.42; P = 0.02). Our results suggested that multi-omics approaches, and metabolomics analysis in particular, could enhance treatment prediction and reveal patients most likely to improve posttreatment. IMPORTANCE Periodontal disease affects the majority of adults worldwide and has been linked to numerous systemic diseases. Despite decades of research, the reasons for the substantial differences among periodontitis patients in disease incidence, progressivity, and response to treatment remain poorly understood. While deep sequencing of oral bacterial communities has greatly expanded our comprehension of the microbial diversity of periodontal disease and identified associations with healthy and disease states, predicting treatment outcomes remains elusive. Our results suggest that combining multiple omics approaches enhances the ability to differentiate among disease states and determine differential effects of treatment, particularly with the addition of metabolomic information. Furthermore, multi-omics analysis of biofilm community instability indicated that these approaches provide new tools for investigating the ecological dynamics underlying the progressive periodontal disease process. PMID: 28744486 [PubMed]

Related Articles Metabolic Effects of Acibenzolar-S-Methyl for Improving Heat or Drought Stress in Creeping Bentgrass. Front Plant Sci. 2017;8:1224 Authors: Jespersen D, Yu J, Huang B Abstract Acibenzolar-S-methyl (ASM) is a synthetic functional analog of salicylic acid which can induce systemic acquired resistance in plants, but its effects on abiotic stress tolerance is not well known. The objectives of this study were to examine effects of acibenzolar-S-methyl on heat or drought tolerance in creeping bentgrass (Agrostis stolonifera) and to determine major ASM-responsive metabolites and proteins associated with enhanced abiotic stress tolerance. Creeping bentgrass plants (cv. 'Penncross') were foliarly sprayed with ASM and were exposed to non-stress (20/15°C day/night), heat stress (35/30°C), or drought conditions (by withholding irrigation) in controlled-environment growth chambers. Exogenous ASM treatment resulted in improved heat or drought tolerance, as demonstrated by higher overall turf quality, relative water content, and chlorophyll content compared to the untreated control. Western blotting revealed that ASM application resulted in up-regulation of ATP synthase, HSP-20, PR-3, and Rubisco in plants exposed to heat stress, and greater accumulation of dehydrin in plants exposed to drought stress. Metabolite profiling identified a number of amino acids, organic acids, and sugars which were differentially accumulated between ASM treated and untreated plants under heat or drought stress, including aspartic acid, glycine, citric acid, malic acid, and the sugars glucose, and fructose. Our results suggested that ASM was effective in improving heat or drought tolerance in creeping bentgrass, mainly through enhancing protein synthesis and metabolite accumulation involved in osmotic adjustment, energy metabolism, and stress signaling. PMID: 28744300 [PubMed]

Related Articles Metabolomic Analysis of Alfalfa (Medicago sativa L.) Root-Symbiotic Rhizobia Responses under Alkali Stress. Front Plant Sci. 2017;8:1208 Authors: Song T, Xu H, Sun N, Jiang L, Tian P, Yong Y, Yang W, Cai H, Cui G Abstract Alkaline salts (e.g., NaHCO3 and Na2CO3) causes more severe morphological and physiological damage to plants than neutral salts (e.g., NaCl and Na2SO4) due to differences in pH. The mechanism by which plants respond to alkali stress is not fully understood, especially in plants having symbotic relationships such as alfalfa (Medicago sativa L.). Therefore, a study was designed to evaluate the metabolic response of the root-nodule symbiosis in alfalfa under alkali stress using comparative metabolomics. Rhizobium-nodulized (RI group) and non-nodulized (NI group) alfalfa roots were treated with 200 mmol/L NaHCO3 and, roots samples were analyzed for malondialdehydyde (MDA), proline, glutathione (GSH), superoxide dismutase (SOD), and peroxidase (POD) content. Additionally, metabolite profiling was conducted using gas chromatography combined with time-of-flight mass spectrometry (GC/TOF-MS). Phenotypically, the RI alfalfa exhibited a greater resistance to alkali stress than the NI plants examined. Physiological analysis and metabolic profiling revealed that RI plants accumulated more antioxidants (SOD, POD, GSH), osmolytes (sugar, glycols, proline), organic acids (succinic acid, fumaric acid, and alpha-ketoglutaric acid), and metabolites that are involved in nitrogen fixation. Our pairwise metabolomics comparisons revealed that RI alfalfa plants exhibited a distinct metabolic profile associated with alkali putative tolerance relative to NI alfalfa plants. Data provide new information about the relationship between non-nodulized, rhizobium-nodulized alfalfa and alkali resistance. PMID: 28744296 [PubMed]

Related Articles Nuclear Magnetic Resonance-Based Metabolomics Approach to Evaluate the Prevention Effect of Camellia nitidissima Chi on Colitis-Associated Carcinogenesis. Front Pharmacol. 2017;8:447 Authors: Li MH, Du HZ, Kong GJ, Liu LB, Li XX, Lin SS, Jia AQ, Yuan ST, Sun L, Wang JS Abstract Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, occurring in the colon or rectum portion of large intestine. With marked antioxidant, anti-inflammation and anti-tumor activities, Camellia nitidissima Chi has been used as an effective treatment of cancer. The azoxymethane/dextran sodium sulfate (AOM/DSS) induced CRC mice model was established and the prevention effect of C. nitidissima Chi extracts on the evolving of CRC was evaluated by examination of neoplastic lesions, histopathological inspection, serum biochemistry analysis, combined with nuclear magnetic resonance (NMR)-based metabolomics and correlation network analysis. C. nitidissima Chi extracts could significantly inhibit AOM/DSS induced CRC, relieve the colonic pathology of inflammation and ameliorate the serum biochemistry, and could significantly reverse the disturbed metabolic profiling toward the normal state. Moreover, the butanol fraction showed a better efficacy than the water-soluble fraction of C. nitidissima Chi. Further development of C. nitidissima Chi extracts as a potent CRC inhibitor was warranted. PMID: 28744216 [PubMed]

Related Articles Circadian Metabolomics in Time and Space. Front Neurosci. 2017;11:369 Authors: Dyar KA, Eckel-Mahan KL Abstract Circadian rhythms are widely known to govern human health and disease, but specific pathogenic mechanisms linking circadian disruption to metabolic diseases are just beginning to come to light. This is thanks in part to the development and application of various "omics"-based tools in biology and medicine. Current high-throughput technologies allow for the simultaneous monitoring of multiple dynamic cellular events over time, ranging from gene expression to metabolite abundance and sub-cellular localization. These fundamental temporal and spatial perspectives have allowed for a more comprehensive understanding of how various dynamic cellular events and biochemical processes are related in health and disease. With advances in technology, metabolomics has become a more routine "omics" approach for studying metabolism, and "circadian metabolomics" (i.e., studying the 24-h metabolome) has recently been undertaken by several groups. To date, circadian metabolomes have been reported for human serum, saliva, breath, and urine, as well as tissues from several species under specific disease or mutagenesis conditions. Importantly, these studies have consistently revealed that 24-h rhythms are prevalent in almost every tissue and metabolic pathway. Furthermore, these circadian rhythms in tissue metabolism are ultimately linked to and directed by internal 24-h biological clocks. In this review, we will attempt to put these data-rich circadian metabolomics experiments into perspective to find out what they can tell us about metabolic health and disease, and what additional biomarker potential they may reveal. PMID: 28744188 [PubMed]

Related Articles Pharmacological PPARγ modulation regulates sebogenesis and inflammation in SZ95 human sebocytes. Biochem Pharmacol. 2017 Aug 15;138:96-106 Authors: Mastrofrancesco A, Ottaviani M, Cardinali G, Flori E, Briganti S, Ludovici M, Zouboulis CC, Lora V, Camera E, Picardo M Abstract The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) controls the expression of genes involved in the regulation of lipid and glucose metabolism, cell proliferation/differentiation as well as inflammatory pathways. Pivotal studies in human sebocytes and isolated sebaceous glands have raised the interesting possibility that compounds acting on PPARγ can modulate sebaceous lipids and inflammation and, as such, may be useful in the treatment of acne. To investigate the role of this receptor in the regulation of lipid synthesis, proliferation and inflammation, we used the SZ95 sebaceous gland cell line stimulated with insulin. In sebocytes, insulin signaling activated the phosphatidylinositide 3-kinase-Akt (PI3K/Akt) and mammalian target of rapamycin (mTOR) pathways, which, in turn, induced high protein/lipid synthesis, increased cell growth and proliferation as well as inflammation. As regards lipogenesis, insulin initially stimulated the formation of unsaturated lipids and then the neosynthesis of lipids. The results showed, that the modulation of PPARγ, counteracted the insulin-induced altered lipogenesis, evident through a decrease in gene expression of key enzymes responsible for the synthesis of fatty acids, and through a reduction of lipid species synthesis analyzed by Oil/Nile Red staining and GC-MS. PPARγ modulation also regulated the insulin-induced proliferation, inhibiting the cell cycle progression and p21WAF1/CIP1 (p21) protein reduction. Moreover, the expression of inflammatory cytokines, induced by insulin or lipopolysaccharide (LPS), was down-modulated. In PPARγ-deficient cells or in the presence of GW9662 antagonist, all these observed effects were abolished, indicating that PPARγ activation plays a role in regulating alteration of lipogenesis, cell proliferation and inflammatory signaling. We demonstrated that selective modulation of PPARγ activity is likely to represent a therapeutic strategy for the treatment of acne. PMID: 28461124 [PubMed - indexed for MEDLINE]

Related Articles Dietary supplementation of branched-chain amino acids increases muscle net amino acid fluxes through elevating their substrate availability and intramuscular catabolism in young pigs. Br J Nutr. 2017 Apr;117(7):911-922 Authors: Zheng L, Zuo F, Zhao S, He P, Wei H, Xiang Q, Pang J, Peng J Abstract Branched-chain amino acids (BCAA) have been clearly demonstrated to have anabolic effects on muscle protein synthesis. However, little is known about their roles in the regulation of net AA fluxes across skeletal muscle in vivo. This study was aimed to investigate the effect and related mechanisms of dietary supplementation of BCAA on muscle net amino acid (AA) fluxes using the hindlimb flux model. In all fourteen 4-week-old barrows were fed reduced-protein diets with or without supplemental BCAA for 28 d. Pigs were implanted with carotid arterial, femoral arterial and venous catheters, and fed once hourly with intraarterial infusion of p-amino hippurate. Arterial and venous plasma and muscle samples were obtained for the measurement of AA, branched-chain α-keto acids (BCKA) and 3-methylhistidine (3-MH). Metabolomes of venous plasma were determined by HPLC-quadrupole time-of-flight-MS. BCAA-supplemented group showed elevated muscle net fluxes of total essential AA, non-essential AA and AA. As for individual AA, muscle net fluxes of each BCAA and their metabolites (alanine, glutamate and glutamine), along with those of histidine, methionine and several functional non-essential AA (glycine, proline and serine), were increased by BCAA supplementation. The elevated muscle net AA fluxes were associated with the increase in arterial and intramuscular concentrations of BCAA and venous metabolites including BCKA and free fatty acids, and were also related to the decrease in the intramuscular concentration of 3-MH. Correlation analysis indicated that muscle net AA fluxes are highly and positively correlated with arterial BCAA concentrations and muscle net BCKA production. In conclusion, supplementing BCAA to reduced-protein diet increases the arterial concentrations and intramuscular catabolism of BCAA, both of which would contribute to an increase of muscle net AA fluxes in young pigs. PMID: 28446262 [PubMed - indexed for MEDLINE]

Related Articles Untargeted metabolomic profiling of seminal plasma in nonobstructive azoospermia men: A noninvasive detection of spermatogenesis. Biomed Chromatogr. 2017 Aug;31(8): Authors: Gilany K, Mani-Varnosfaderani A, Minai-Tehrani A, Mirzajani F, Ghassempour A, Sadeghi MR, Amini M, Rezadoost H Abstract Male factor infertility is involved in almost half of all infertile couples. Lack of the ejaculated sperm owing to testicular malfunction has been reported in 6-10% of infertile men, a condition named nonobstructive azoospermia (NOA). In this study, we investigated untargeted metabolomic profiling of the seminal plasma in NOA men using gas chromatography-mass spectrometry and advance chemometrics. In this regard, the seminal plasma fluids of 11 NOA men with TESE-negative, nine NOA men with TESE-positive and 10 fertile healthy men (as a control group) were collected. Quadratic discriminate analysis (QDA) technique was implemented on total ion chromatograms (TICs) for identification of discriminatory retention times. We developed multivariate classification models using the QDA technique. Our results revealed that the developed QDA models could predict the classes of samples using their TIC data. The receiver operating characteristic curves for these models were >0.88. After recognition of discriminatory retention time's asymmetric penalized least square, evolving factor analysis, correlation optimized warping and alternating least squares strategies were applied for preprocessing and deconvolution of the overlapped chromatographic peaks. We could identify 36 discriminatory metabolites. These metabolites may be considered discriminatory biomarkers for different groups in NOA. PMID: 28058728 [PubMed - indexed for MEDLINE]

Related Articles Covariation Analysis of Serumal and Urinary Metabolites Suggests Aberrant Glycine and Fatty Acid Metabolism in Chronic Hepatitis B. PLoS One. 2016;11(5):e0156166 Authors: Yang L, Yang X, Kong X, Cao Z, Zhang Y, Hu Y, Tang K Abstract BACKGROUND: Chronic hepatitis b (CHB) is one of the most serious viral diseases threatening human health by putting patients at lifelong risk of cirrhosis and hepatocellular carcinoma (HCC). Although some proofs of altered metabolites in CHB were accumulated, its metabolic mechanism remains poorly understood. Analyzing covariations between metabolites may provide new hints toward underlying metabolic pathogenesis in CHB patients. METHODS: The present study collected paired urine and serum samples from the same subjects including 145 CHB and 23 healthy controls. A large-scale analysis of metabolites' covariation within and across biofluids was systematically done to explore the underlying biological evidences for reprogrammed metabolism in CHB. Randomization and relative ranking difference were introduced to reduce bias caused by different sample size. More importantly, functional indication was interpreted by mapping differentially changed covariations to known metabolic pathways. RESULTS: Our results suggested reprogrammed pathways related to glycine metabolism, fatty acids metabolism and TCA cycle in CHB patients. With further improvement, the covariation analysis combined with network association study would pave new alternative way to interpret functional clues in clinical multi-omics data. PMID: 27228119 [PubMed - indexed for MEDLINE]