PubMed

Related Articles Exploring Metabolism In Vivo Using Endogenous (11)C Metabolic Tracers. Semin Nucl Med. 2017 Sep;47(5):461-473 Authors: Neumann K, Flavell R, Wilson DM Abstract Cancer and other diseases are increasingly understood in terms of their metabolic disturbances. This thinking has revolutionized the field of ex vivo metabolomics and motivated new approaches to detect metabolites in living systems, including proton magnetic resonance spectroscopy ((1)H-MRS), hyperpolarized (13)C MRS, and PET. For PET, imaging abnormal metabolism in vivo is hardly new. Positron-labeled small-molecule metabolites have been used for decades in humans, including (18)F-FDG, which is used frequently to detect upregulated glycolysis in tumors. Many current (18)F metabolic tracers including (18)F-FDG have evolved from their (11)C counterparts, chemically identical to endogenous substrates and thus approximating intrinsic biochemical pathways. This mimicry has stimulated the development of new radiochemical methods to incorporate (11)C and inspired the synthesis of a large number of (11)C endogenous radiotracers. This is in spite of the 20-minute half-life of (11)C, which generally limits its use in patients to centers with an on-site cyclotron. Innovation in (11)C chemistry has persisted in the face of this limitation, because (1) the radiochemists involved are inspired, (2) the methods of (11)C incorporation are diverse, and (3) (11)C compounds often show more predictable in vivo behavior, thus representing an important first step in the validation of new tracer concepts. In this mini-review we will discuss some of the general motivations behind PET tracers, rationales for the use of (11)C, and some of the special challenges encountered in the synthesis of (11)C endogenous compounds. Most importantly, we will try to highlight the exceptional creativity used in early (11)C tracer syntheses, which used enzyme-catalyzed and other "green" methods before these concepts were commonplace. PMID: 28826521 [PubMed - in process]

Related Articles Quantitative profiling of 19 bile acids in rat plasma, liver, bile and different intestinal section contents to investigate bile acid homeostasis and the application of temporal variation of endogenous bile acids. J Steroid Biochem Mol Biol. 2017 Sep;172:69-78 Authors: Yang T, Shu T, Liu G, Mei H, Zhu X, Huang X, Zhang L, Jiang Z Abstract Bile acid homeostasis is maintained by liver synthesis, bile duct secretion, microbial metabolism and intestinal reabsorption into the blood. When drug insults result in liver damage, the variances of bile acids (BAs) are related to the physiological status of the liver. Here, we established a method to simultaneously quantify 19 BAs in rat plasma, liver, bile and different intestinal section contents (duodenum, jejunum, ileum, cecum and colon) using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) to reveal the pattern of bile acid homeostasis in the enterohepatic circulation of bile acids in physiological situations. Dynamic changes in bile acid composition appeared throughout the enterohepatic circulation of the BAs; taurine- and glycine-conjugated BAs and free BAs had different dynamic homeostasis levels in the circulatory system. cholic acid (CA), beta-muricholic acid (beta-MCA), lithocholic acid (LCA), glycocholic acid (GCA) and taurocholic acid (TCA) greatly fluctuated in the bile acid pool under physiological conditions. Taurine- and glycine-conjugated bile acids constituted more than 90% in the bile and liver, whereas GCA and TCA accounted for more than half of the total bile acids and the secretion of bile mainly via conjugating with taurine. While over 80% of BAs in plasma were unconjugated bile acids, CA and HDCA were the most abundant elements. Unconjugated bile acids constituted more than 90% in the intestine, and CA, beta-MCA and HDCA were the top three bile acids in the duodenum, jejunum and ileum content, but LCA and HDCA were highest in the cecum and colon content. As the main secondary bile acid converted by microflora in the intestine, LCA was enriched in the cecum and DCA mostly in the colon. As endogenous substances, the concentrations of plasma BAs were closely related to time rhythm and diet. In conclusion, analyzing detailed BA profiles in the enterohepatic circulation of bile acids in a single run is possible using LC-MS/MS. Based on the physiological characteristics of the metabolic profiling of 19 BAs in the total bile acid pool and the time rhythm variation of the endogenous bile acids, this study provided a new valuable method and theoretical basis for the clinical research of bile acid homeostasis. PMID: 28583875 [PubMed - indexed for MEDLINE]

Related Articles Diversity and association of phenotypic and metabolomic traits in the close model grasses Brachypodium distachyon, B. stacei and B. hybridum. Ann Bot. 2017 Mar 01;119(4):545-561 Authors: López-Álvarez D, Zubair H, Beckmann M, Draper J, Catalán P Abstract Background and Aims: Morphological traits in combination with metabolite fingerprinting were used to investigate inter- and intraspecies diversity within the model annual grasses Brachypodium distachyon, Brachypodium stacei and Brachypodium hybridum . Methods: Phenotypic variation of 15 morphological characters and 2219 nominal mass ( m / z ) signals generated using flow infusion electrospray ionization-mass spectrometry (FIE-MS) were evaluated in individuals from a total of 174 wild populations and six inbred lines, and 12 lines, of the three species, respectively. Basic statistics and multivariate principal component analysis and discriminant analysis were used to differentiate inter- and intraspecific variability of the two types of variable, and their association was assayed with the rcorr function. Key Results: Basic statistics and analysis of variance detected eight phenotypic characters [(stomata) leaf guard cell length, pollen grain length, (plant) height, second leaf width, inflorescence length, number of spikelets per inflorescence, lemma length, awn length] and 434 tentatively annotated metabolite signals that significantly discriminated the three species. Three phenotypic traits (pollen grain length, spikelet length, number of flowers per inflorescence) might be genetically fixed. The three species showed different metabolomic profiles. Discriminant analysis significantly discriminated the three taxa with both morphometric and metabolome traits and the intraspecific phenotypic diversity within B. distachyon and B. stacei . The populations of B. hybridum were considerably less differentiated. Conclusions: Highly explanatory metabolite signals together with morphological characters revealed concordant patterns of differentiation of the three taxa. Intraspecific phenotypic diversity was observed between northern and southern Iberian populations of B. distachyon and between eastern Mediterranean/south-western Asian and western Mediterranean populations of B. stacei . Significant association was found for pollen grain length and lemma length and ten and six metabolomic signals, respectively. These results would guide the selection of new germplasm lines of the three model grasses in ongoing genome-wide association studies. PMID: 28040672 [PubMed - indexed for MEDLINE]

Related Articles MicroRNA858 Is a Potential Regulator of Phenylpropanoid Pathway and Plant Development. Plant Physiol. 2016 Jun;171(2):944-59 Authors: Sharma D, Tiwari M, Pandey A, Bhatia C, Sharma A, Trivedi PK Abstract MicroRNAs (miRNAs) are endogenous, noncoding small RNAs that function as critical regulators of gene expression. In plants, miRNAs have shown their potential as regulators of growth, development, signal transduction, and stress tolerance. Although the miRNA-mediated regulation of several processes is known, the involvement of miRNAs in regulating secondary plant product biosynthesis is poorly understood. In this study, we functionally characterized Arabidopsis (Arabidopsis thaliana) miR858a, which putatively targets R2R3-MYB transcription factors involved in flavonoid biosynthesis. Overexpression of miR858a in Arabidopsis led to the down-regulation of several MYB transcription factors regulating flavonoid biosynthesis. In contrast to the robust growth and early flowering of miR858OX plants, reduction of plant growth and delayed flowering were observed in Arabidopsis transgenic lines expressing an artificial miRNA target mimic (MIM858). Genome-wide expression analysis using transgenic lines suggested that miR858a targets a number of regulatory factors that modulate the expression of downstream genes involved in plant development and hormonal and stress responses. Furthermore, higher expression of MYBs in MIM858 lines leads to redirection of the metabolic flux towards the synthesis of flavonoids at the cost of lignin synthesis. Altogether, our study has established the potential role of light-regulated miR858a in flavonoid biosynthesis and plant growth and development. PMID: 27208307 [PubMed - indexed for MEDLINE]

Related Articles Volatile organic compounds in breath as markers for irritable bowel syndrome: a metabolomic approach. Aliment Pharmacol Ther. 2016 Jul;44(1):45-56 Authors: Baranska A, Mujagic Z, Smolinska A, Dallinga JW, Jonkers DM, Tigchelaar EF, Dekens J, Zhernakova A, Ludwig T, Masclee AA, Wijmenga C, van Schooten FJ Abstract BACKGROUND: The diagnosis of irritable bowel syndrome (IBS) is challenging because of its heterogeneity and multifactorial pathophysiology. No reliable biomarkers of IBS have been identified so far. AIMS: In a case-control study, using a novel application of breath analysis to distinguish IBS patients from healthy controls based on the analysis of volatile organic compounds (VOCs). Subsequently, the diagnostic VOC-biomarker set was correlated with self-reported gastrointestinal (GI) symptoms of subjects of the Maastricht IBS clinical cohort and of a general population cohort, LifeLines DEEP. METHODS: Breath samples were collected from 170 IBS patients and 153 healthy controls in the clinical cohort and from 1307 participants in general population cohort. Multivariate statistics were used to identify the most discriminatory set of VOCs in the clinical cohort, and to find associations between VOCs and GI symptoms in both cohorts. RESULTS: A set of 16 VOCs correctly predicted 89.4% of the IBS patients and 73.3% of the healthy controls (AUC = 0.83). The VOC-biomarker set correlated moderately with a set of GI symptoms in the clinical (r = 0.55, P = 0.0003) and general population cohorts (r = 0.54, P = 0.0004). A Kruskal-Wallis test showed no influence from possible confounding factors in distinguishing IBS patients from healthy controls. CONCLUSIONS: A set of 16 breath-based biomarkers that distinguishes IBS patients from healthy controls was identified. The VOC-biomarker set correlated significantly with GI symptoms in two independent cohorts. We demonstrate the potential use of breath analysis in the diagnosis and monitoring of IBS, and a possible application of VOC analyses in a general population cohort. PMID: 27136066 [PubMed - indexed for MEDLINE]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/08/22PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Comparative study of single/combination use of Huang-Lian-Jie-Du decoction and berberine on their protection on sepsis induced acute liver injury by NMR metabolic profiling. J Pharm Biomed Anal. 2017 Aug 01;145:794-804 Authors: Lv Y, Wang J, Xu D, Liao S, Li P, Zhang Q, Yang M, Kong L Abstract Sepsis is a serious clinical disease with a high mortality rate all around the world. Liver organ dysfunction is an important sign for the severity and outcome of sepsis in patients. In this study, (1)H NMR-based metabolomics approach and biochemical assays were applied to investigate the metabolic profiling for cecal ligation and puncture (CLP) induced acute liver injury, the therapeutical effect of single/combination use of Huang-Lian-Jie-Du decoction (HLJDD) and berberine, and the interaction of them. Metabolomics analysis revealed significant perturbations in livers of septic rats, which could be ameliorated by HLJDD, berberine and their combination treatment. Berberine could better rectified glycolysis and nucleic acid metabolism in the liver. HLJDD had exceptional better anti-inflammatory, antibacterial and antioxidative effects than berberine. The interaction of berberine and HLJDD could further strengthen the anti-inflammation and anti-oxidation, but with poor effect on amino acids metabolism. These findings highlighted the feasibility of the integrated NMR based metabolomics approach to understand the pathogenesis of diseases, the action mechanisms of therapy and the herb-drug interaction. PMID: 28822346 [PubMed - as supplied by publisher]

[Metabolic fingerprint analysis of RAW264.7 inflammatory cell model by using UPLC-Q-TOF/MS]. Zhongguo Zhong Yao Za Zhi. 2017 Jun;42(12):2373-2379 Authors: Gao SS, Guo HQ, Zhang ZK, Bai GC, Gao XY, Ma CH Abstract In order to reveal the properties of polar metabolome in inflammatory cells, we selected LPS-induced RAW264.7 inflammatory cell models as the carrier for the research of metabolic fingerprint analysis. In this study, an ultra performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics protocol was optimized for the extraction of polar metabolites from RAW264.7 cell line. Then orthogonal partial least squares discriminant analysis (OPLS-DA) was used to process the metabolic data, and finally, a total of 17 metabolites were selected and identified. The results showed that MeOH-CHCl3-H2O (8∶1∶1) was chosen as the optimal extraction solvent to achieve higher number of chromatographic peaks, with the best relative extraction efficiency and stability. Comparing with the normal cells, the inflammatory cells presented an abnormal metabolism in protein, carbohydrate, nucleotide and phospholipids. In this study, a UPLC-Q-TOF/MS-based metabolomics protocol for the polar metabolites from RAW264.7 cell line was developed, which may provide important information for the study of mechanism of inflammation and the anti-inflammatory drugs. PMID: 28822196 [PubMed - in process]

[Mechanism of treatment effect of Huanglian-Huangqin herb pairs on cerebral ischemia rats based on metabolomic approach]. Zhongguo Zhong Yao Za Zhi. 2017 Jun;42(11):2159-2167 Authors: Cao HT, Zhu HX, Zhang QC, Guo LW Abstract The metabolic effect of Huanglian-Huangqin herb pairs on cerebral ischemia rats was studied by using metabolomic method. The rat model of ischemia reperfusion injury induced by introduction of transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Ultra high performance liquid chromatography-series four pole time of flight mass spectrometry method（UPLC-Q-TOF/MS）, Markerlynx software, and principal component analysis and partial least-squares discriminant analysis were used to analyze the different endogenous metabolites among the urine samples of sham rats, cerebral ischemia model rats, Huanglian groups (HL), Huangqin groups (HQ) and Huanglian-Huangqin herb pairs groups (LQ) was achieved, combined with accurate information about the endogenous metabolites level and secondary fragment ions, retrieval and identification of possible biological markers, metabolic pathway which build in MetPA database. The 20 potential biomarkers were found in the urine of rats with cerebral ischemia, which mainly involved in the neurotransmitter regulation, amino acid metabolism, energy metabolism, lipid metabolism and so on. Those metabolic pathways were disturbed in cerebral ischemia model rats, the principal component analysis showed that the normal and cerebral ischemia model is clearly distinguished, and the compound can be given to the normal state of change after HL, HQ, LQ administration. This study index the interpretation of cerebral ischemia rat metabolism group and mechanism, the embodiment of metabonomics can reflect the physiological and metabolic state, which can better reflect the traditional Chinese medicine as a whole view, system view and the features of multi ingredient synergistic or antagonistic effects. PMID: 28822163 [PubMed - in process]

Genome-Scale Modeling of Photorespiratory Pathway Manipulation. Methods Mol Biol. 2017;1653:195-202 Authors: Küken A, Nikoloski Z Abstract Quantifying the redistribution of metabolic reaction fluxes under experimental scenarios that affect the photorespiratory pathway can provide insights about the coupling of this pathway with other parts of metabolism. However, differential flux profiling on a genome-scale level remains the biggest challenge in modern systems biology. Here we present a protocol for applying a constraint-based approach, termed iReMet-Flux, that integrates data about relative metabolite levels in a stoichiometric metabolic model to predict differential fluxes at a genome-scale level under mild modeling assumptions. We demonstrate how iReMet-Flux can be employed to investigate the interplay between photorespiration and other pathways at a genome-scale level, and complements flux profiling methods based on radioactive tracer labeling. PMID: 28822134 [PubMed - in process]

Comparative metabonomics of Wenxin Keli and Verapamil reveals differential roles of gluconeogenesis and fatty acid β-oxidation in myocardial injury protection. Sci Rep. 2017 Aug 18;7(1):8739 Authors: Jiang M, Wang Q, Chen J, Wang Y, Fan G, Zhu Y Abstract Metabonomics/metabolomics is a rapid technology for comprehensive profiling of small molecule metabolites in cells, tissues, or whole organisms, the application of which has led to understanding pathophysiologic mechanisms of cardiometabolic diseases, defining predictive biomarkers for those diseases, and also assessing the efficacious effects of incident drugs. In this study, proton nuclear magnetic resonance (NMR)-based metabonomics was employed to identify the metabolic changes in rat plasma caused by myocardial ischemia-reperfusion injury (MIRI), and to compare the metabolic regulatory differences between traditional Chinese medicine Wenxin Keli (WXKL) and Western medicine verapamil. The results revealed that energy-substrate metabolism were significantly disturbed by ischemia-reperfusion (I/R) in myocardium and bulk of the key metabolites could be further modulated by verapamil and/or WXKL. Lipid metabolism and amino acid transamination occurred mainly following the treatment of verapamil, whereas glucose oxidation and BCAA degradation were prominently ameliorated by WXKL to content the energy demands of heart. Moreover, both WXKL and verapamil improved the secretions of taurine and ketone bodies to overcome the oxidative stress and the shortage of energy sources induced by ischemia-reperfusion. PMID: 28821850 [PubMed - in process]

Biogeography shaped the metabolome of the genus Espeletia: a phytochemical perspective on an Andean adaptive radiation. Sci Rep. 2017 Aug 18;7(1):8835 Authors: Padilla-González GF, Diazgranados M, Da Costa FB Abstract The páramo ecosystem has the highest rate of diversification across plant lineages on earth, of which the genus Espeletia (Asteraceae) is a prime example. The current distribution and molecular phylogeny of Espeletia suggest the influence of Andean geography and past climatic fluctuations on the diversification of this genus. However, molecular markers have failed to reveal subtle biogeographical trends in Espeletia diversification, and metabolomic evidence for allopatric segregation in plants has never been reported. Here, we present for the first time a metabolomics approach based on liquid chromatography-mass spectrometry for revealing subtle biogeographical trends in Espeletia diversification. We demonstrate that Espeletia lineages can be distinguished by means of different metabolic fingerprints correlated to the country of origin on a global scale and to the páramo massif on a regional scale. Distinctive patterns in the accumulation of secondary metabolites according to the main diversification centers of Espeletia are also identified and a comprehensive phytochemical characterization is reported. These findings demonstrate that a variation in the metabolic fingerprints of Espeletia lineages followed the biogeography of this genus, suggesting that our untargeted metabolomics approach can be potentially used as a model to understand the biogeographic history of additional plant groups in the páramo ecosystem. PMID: 28821838 [PubMed - in process]

Disease-syndrome combination modeling: metabolomic strategy for the pathogenesis of chronic kidney disease. Sci Rep. 2017 Aug 18;7(1):8830 Authors: Li S, Xu P, Han L, Mao W, Wang Y, Luo G, Yang N Abstract Conventional disease animal models have limitations on the conformity to the actual clinical situation. Disease-syndrome combination (DS) modeling may provide a more efficient strategy for biomedicine research. Disease model and DS model of renal fibrosis in chronic kidney disease were established by ligating the left ureter and by ligating unilateral ureteral combined with exhaustive swimming, respectively. Serum metabolomics was conducted to evaluate disease model and DS model by using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Potential endogenous biomarkers were identified by multivariate statistical analysis. There are no differences between two models regarding their clinical biochemistry and kidney histopathology, while metabolomics highlights their difference. It is found that abnormal sphingolipid metabolism is a common characteristic of both models, while arachidonic acid metabolism, linolenic acid metabolism and glycerophospholipid metabolism are highlighted in DS model. Metabolomics is a promising approach to evaluate experiment animal models. DS model are comparatively in more coincidence with clinical settings, and is superior to single disease model for the biomedicine research. PMID: 28821830 [PubMed - in process]

Metabolomics and genomics combine to unravel the pathway for the presence of fragrance in rice. Sci Rep. 2017 Aug 18;7(1):8767 Authors: Daygon VD, Calingacion M, Forster LC, Voss JJ, Schwartz BD, Ovenden B, Alonso DE, McCouch SR, Garson MJ, Fitzgerald MA Abstract Since it was first characterised in 1983, 2-acetyl-1-pyrroline (2AP) has been considered to be the most important aroma compound in rice. In this study, we show four other amine heterocycles: 6-methyl, 5-oxo-2,3,4,5-tetrahydropyridine (6M5OTP), 2-acetylpyrrole, pyrrole and 1-pyrroline, that correlate strongly with the production of 2AP, and are present in consistent proportions in a set of elite aromatic rice varieties from South East Asia and Australia as well as in a collection of recombinant inbred lines (RILs) derived from indica Jasmine-type varieties, Australian long grain varieties (temperate japonica) and Basmati-type rice (Grp V). These compounds were detected through untargeted metabolite profiling by two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOF-MS), and their identity were confirmed by comparison with authentic standards analysed using gas chromatography mass spectrometry (GC-MS) and High Resolution GC × GC-TOF-MS (GC × GC HRT-4D). Genome-wide association analysis indicates that all compounds co-localised with a single quantitative trait locus (QTL) that harbours the FGR gene responsible for the production of GABA. Together, these data provide new insights into the production of 2AP, and evidence for understanding the pathway leading to the accumulation of aroma in fragrant rice. PMID: 28821745 [PubMed - in process]

Twenty-four-hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes. FASEB J. 2017 Aug 18;: Authors: Isherwood CM, Van der Veen DR, Johnston JD, Skene DJ Abstract Metabolic profiling of individuals with type 2 diabetes mellitus (T2DM) has previously been limited to single-time-point samples, ignoring time-of-day variation. Here, we tested our hypothesis that body mass and T2DM affect daily rhythmicity and concentrations of circulating metabolites across a 24-h day in 3 age-matched, male groups-lean, overweight/obese (OW/OB), and OW/OB with T2DM-in controlled laboratory conditions, which were not confounded by large meals. By using targeted liquid chromatography/mass spectrometry metabolomics, we quantified 130 plasma metabolites every 2 h over 24 h, and we show that average metabolite concentrations were significantly altered by increased body mass (90 of 130) and T2DM (56 of 130). Thirty-eight percent of metabolites exhibited daily rhythms in at least 1 study group, and where a metabolite was rhythmic in >1 group, its peak time was comparable. The optimal time of day was assessed to provide discriminating biomarkers. This differed between metabolite classes and study groups-for example, phospholipids showed maximal difference at 5:00 AM (lean vs. OW/OB) and at 5:00 PM (OW/OB vs. T2DM). Metabolites that were identified with both robust 24-h rhythms and significant concentration differences between study groups emphasize the importance of controlling the time of day for diagnosis and biomarker discovery, offering a significant improvement over current single sampling.-Isherwood, C. M., Van der Veen, D. R., Johnston, J. D., Skene, D. J. Twenty-four-hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes. PMID: 28821636 [PubMed - as supplied by publisher]

Space-type radiation induces multimodal responses in the mouse gut microbiome and metabolome. Microbiome. 2017 Aug 18;5(1):105 Authors: Casero D, Gill K, Sridharan V, Koturbash I, Nelson G, Hauer-Jensen M, Boerma M, Braun J, Cheema AK Abstract BACKGROUND: Space travel is associated with continuous low dose rate exposure to high linear energy transfer (LET) radiation. Pathophysiological manifestations after low dose radiation exposure are strongly influenced by non-cytocidal radiation effects, including changes in the microbiome and host gene expression. Although the importance of the gut microbiome in the maintenance of human health is well established, little is known about the role of radiation in altering the microbiome during deep-space travel. RESULTS: Using a mouse model for exposure to high LET radiation, we observed substantial changes in the composition and functional potential of the gut microbiome. These were accompanied by changes in the abundance of multiple metabolites, which were related to the enzymatic activity of the predicted metagenome by means of metabolic network modeling. There was a complex dynamic in microbial and metabolic composition at different radiation doses, suggestive of transient, dose-dependent interactions between microbial ecology and signals from the host's cellular damage repair processes. The observed radiation-induced changes in microbiota diversity and composition were analyzed at the functional level. A constitutive change in activity was found for several pathways dominated by microbiome-specific enzymatic reactions like carbohydrate digestion and absorption and lipopolysaccharide biosynthesis, while the activity in other radiation-responsive pathways like phosphatidylinositol signaling could be linked to dose-dependent changes in the abundance of specific taxa. CONCLUSIONS: The implication of microbiome-mediated pathophysiology after low dose ionizing radiation may be an unappreciated biologic hazard of space travel and deserves experimental validation. This study provides a conceptual and analytical basis of further investigations to increase our understanding of the chronic effects of space radiation on human health, and points to potential new targets for intervention in adverse radiation effects. PMID: 28821301 [PubMed - in process]

Impact of novel palmitoylated prolactin-releasing peptide analogs on metabolic changes in mice with diet-induced obesity. PLoS One. 2017;12(8):e0183449 Authors: Pražienková V, Holubová M, Pelantová H, Bugáňová M, Pirník Z, Mikulášková B, Popelová A, Blechová M, Haluzík M, Železná B, Kuzma M, Kuneš J, Maletínská L Abstract Analogs of anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP), have a potential as new anti-obesity drugs. In our previous study, palmitic acid attached to the N-terminus of PrRP enabled its central anorexigenic effects after peripheral administration. In this study, two linkers, γ-glutamic acid at Lys11 and a short, modified polyethylene glycol at the N-terminal Ser and/or Lys11, were applied for the palmitoylation of PrRP31 to improve its bioavailability. These analogs had a high affinity and activation ability to the PrRP receptor GPR10 and the neuropeptide FF2 receptor, as well as short-term anorexigenic effect similar to PrRP palmitoylated at the N-terminus. Two-week treatment with analogs that were palmitoylated through linkers to Lys11 (analogs 1 and 2), but not with analog modified both at the N-terminus and Lys11 (analog 3) decreased body and liver weights, insulin, leptin, triglyceride, cholesterol and free fatty acid plasma levels in a mouse model of diet-induced obesity. Moreover, the expression of uncoupling protein-1 was increased in brown fat suggesting an increase in energy expenditure. In addition, treatment with analogs 1 and 2 but not analog 3 significantly decreased urinary concentrations of 1-methylnicotinamide and its oxidation products N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide, as shown by NMR-based metabolomics. This observation confirmed the previously reported increase in nicotinamide derivatives in obesity and type 2 diabetes mellitus and the effectiveness of analogs 1 and 2 in the treatment of these disorders. PMID: 28820912 [PubMed - in process]

Cell cycle-related metabolism and mitochondrial dynamics in a replication-competent pancreatic beta-cell line. Cell Cycle. 2017 Aug 18;:0 Authors: Montemurro C, Vadrevu S, Gurlo T, Butler AE, Vongbunyong KE, Petcherski A, Shirihai OS, Satin LS, Braas D, Butler PC, Tudzarova S Abstract Cell replication is a fundamental attribute of growth and repair in multicellular organisms. Pancreatic beta-cells in adults rarely enter cell cycle, hindering the capacity for regeneration in diabetes. Efforts to drive beta-cells into cell cycle have so far largely focused on regulatory molecules such as cyclins and cyclin-dependent kinases (CDKs). Investigations in cancer biology have uncovered that adaptive changes in metabolism, the mitochondrial network, and cellular Ca(2+) are critical for permitting cells to progress through the cell cycle. Here, we investigated these parameters in the replication-competent beta-cell line INS 832/13. Cell cycle synchronization of this line permitted evaluation of cell metabolism, mitochondrial network, and cellular Ca(2+) compartmentalization at key cell cycle stages. The mitochondrial network is interconnected and filamentous at G1/S but fragments during the S and G2/M phases, presumably to permit sorting to daughter cells. Pyruvate anaplerosis peaks at G1/S, consistent with generation of biomass for daughter cells, whereas mitochondrial Ca(2+) and respiration increase during S and G2/M, consistent with increased energy requirements for DNA and lipid synthesis. This synchronization approach may be of value to investigators performing live cell imaging of Ca(2+) or mitochondrial dynamics commonly undertaken in INS cell lines because without synchrony widely disparate data from cell to cell would be expected depending on position within cell cycle. Our findings also offer insight into why replicating beta-cells are relatively nonfunctional secreting insulin in response to glucose. They also provide guidance on metabolic requirements of beta-cells for the transition through the cell cycle that may complement the efforts currently restricted to manipulating cell cycle to drive beta-cells through cell cycle. PMID: 28820316 [PubMed - as supplied by publisher]

A cross-platform metabolomics workflow for volume-restricted tissue samples: application to an animal model for polycystic kidney disease. Mol Biosyst. 2017 Aug 18;: Authors: Sánchez-López E, Happé H, Steenvoorden E, Crego AL, Marina ML, Peters DJM, Mayboroda OA Abstract Metabolic profiling provides an unbiased view of the physiological status of an organism as a "function" of the metabolic composition of a measured sample. Here, we propose a simple LC-MS based workflow for metabolic profiling of volume-restricted samples, namely individual 20 μm-thick histological sections of a mouse kidney. The main idea of this workflow is to re-use the material after an RPLC-MS run, namely using the volume remaining in the vial after injection, and then introducing a phase changing step to enable HILIC-MS analysis. To test the applicability of the workflow and its ability to extract valuable biological information, we applied it to an animal model of polycystic kidney disease (PKD). PMID: 28820206 [PubMed - as supplied by publisher]

A metabolomics guided exploration of marine natural product chemical space. Metabolomics. 2016 Sep;12(9): Authors: Floros DJ, Jensen PR, Dorrestein PC, Koyama N Abstract INTRODUCTION: Natural products from culture collections have enormous impact in advancing discovery programs for metabolites of biotechnological importance. These discovery efforts rely on the metabolomic characterization of strain collections. OBJECTIVE: Many emerging approaches compare metabolomic profiles of such collections, but few enable the analysis and prioritization of thousands of samples from diverse organisms while delivering chemistry specific read outs. METHOD: In this work we utilize untargeted LC-MS/MS based metabolomics together with molecular networking to. RESULT: This approach annotated 76 molecular families (a spectral match rate of 28 %), including clinically and biotechnologically important molecules such as valinomycin, actinomycin D, and desferrioxamine E. Targeting a molecular family produced primarily by one microorganism led to the isolation and structure elucidation of two new molecules designated maridric acids A and B. CONCLUSION: Molecular networking guided exploration of large culture collections allows for rapid dereplication of know molecules and can highlight producers of uniques metabolites. These methods, together with large culture collections and growing databases, allow for data driven strain prioritization with a focus on novel chemistries. PMID: 28819353 [PubMed]