PubMed

Related Articles Discovery of a novel amino acid racemase through exploration of natural variation in Arabidopsis thaliana. Proc Natl Acad Sci U S A. 2015 Aug 31; Authors: Strauch RC, Svedin E, Dilkes B, Chapple C, Li X Abstract Plants produce diverse low-molecular-weight compounds via specialized metabolism. Discovery of the pathways underlying production of these metabolites is an important challenge for harnessing the huge chemical diversity and catalytic potential in the plant kingdom for human uses, but this effort is often encumbered by the necessity to initially identify compounds of interest or purify a catalyst involved in their synthesis. As an alternative approach, we have performed untargeted metabolite profiling and genome-wide association analysis on 440 natural accessions of Arabidopsis thaliana. This approach allowed us to establish genetic linkages between metabolites and genes. Investigation of one of the metabolite-gene associations led to the identification of N-malonyl-d-allo-isoleucine, and the discovery of a novel amino acid racemase involved in its biosynthesis. This finding provides, to our knowledge, the first functional characterization of a eukaryotic member of a large and widely conserved phenazine biosynthesis protein PhzF-like protein family. Unlike most of known eukaryotic amino acid racemases, the newly discovered enzyme does not require pyridoxal 5'-phosphate for its activity. This study thus identifies a new d-amino acid racemase gene family and advances our knowledge of plant d-amino acid metabolism that is currently largely unexplored. It also demonstrates that exploitation of natural metabolic variation by integrating metabolomics with genome-wide association is a powerful approach for functional genomics study of specialized metabolism. PMID: 26324904 [PubMed - as supplied by publisher]

Related Articles [Chemical comparison of different Farfarae Flos by NMR-based metabolomic approaches]. Yao Xue Xue Bao. 2015 May;50(5):599-604 Authors: Zhang ZZ, Zhi HJ, Qin XM, Li ZY Abstract 1H NMR-based metabolomic approach combined with multivariate statistical analysis was used to evaluate the quality of 21 Farfarae Flos (FF) samples from different growth regions. Principal component analysis showed that wild and cultivated FF could be separated clearly, suggesting a big chemical difference existed between them. Supervised PLS-DA analysis indicated that the wild samples showed higher levels of secondary metabolites, such as bauer-7-ene-3β, 16α-diol, chlorogenic acid, rutin, 7-(3'-ethylcrotonoyloxy)-1α-(2'-methyl-butyryloxy)-3, 14-dehydro-Z-notonipetranone (EMDNT), tussilagone, β-sitosterol and sitosterone. This is consistent with traditional experience that the quality of wild samples are better than that of cultivated ones. The content of pyrrolizidine alkaloids senkirkine also differed greatly among samples from different habitats. The Pearson correlation analysis showed that senkirkine is positively correlated with 4, 5-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, 3,4-O-dicaffeoylquinic acid, rutin, kampferol analogues, to a statistically significant extent. The correlation between the toxic compounds and the bioactive components in FF should be further studied. PMID: 26234144 [PubMed - indexed for MEDLINE]

Related Articles [Metabolomic approach to evaluating the effect of the mixed decoction of kelp and licorice on system metabolism of SD rats]. Yao Xue Xue Bao. 2015 Mar;50(3):312-8 Authors: Sun RB, Yu XY, Mao Y, Ge C, Yang Na, A JY, Tang YP, Duan JA, Ma ZT, Wu XT, Zhu XX, Wang GJ Abstract The aim of the study is to evaluate the effects of the single and mixed decoction of Thallus laminariae (kelp) and Glycyrrhiza glabra (licorice) on the metabolism and their difference. The mixed decoction of kelp and licorice and the single decoction were made and intragastrically administered to the SD rats. The effect on system metabolism, the toxicity of liver and kidney were assessed by GC-MS profiling of the endogenous molecules in serum, routine biochemical assays and histographic inspection of tissues from SD rats, separately. The mixed decoction of kelp and licorice induced more obvious pathological abnormalities in SD rats than a single decoction of kelp, while the extracts of licorice did not show any pathological change. Neither the mixed, nor the single decoction showed abnormal histopathology. After intragastric administration of extracts for 5 days, the mixed decoction induced a decrease of ALT (no significant change in the groups of single decoction) and an increase of BUN (so did the single decoction of kelp). Metabolomic profile of the molecules in serum revealed that the metabolic patterns were all obviously affected for the three groups, i.e., the mixed and single decoction of kelp and licorice. The rats given with the single decoction of kelp showed a similar pattern to that of the mixed decoction, indicating that the kelp primarily contributed the perturbation of metabolism for the mixed decoction. All three groups induced a decrease of branched chain amino acids, TCA cycle intermediates and glycolysis intermediates (e.g., pyruvic acid and lactic acid) and an increase of 3-hydroxybutyric acid. Kelp decoction showed stronger potential in reducing TCA cycle intermediates and glycolysis intermediates than the other two groups, while the levels of branched chain amino acids were the lowest after licorice extracts were given. These results suggested that the effect of the mixed decoction on metabolism was closely associated with both kelp and licorice. The continuous administration of single decoction of kelp and the mixed decoction of licorice and kelp resulted in pathological abnormalities in kidney of SD rats. The mixed decoction of kelp and licorice distinctly perturbed sera molecules and hence system metabolism, which showed associated with those of kelp and licorice. Although the metabolic effect was associated with both kelp and licorice, the results suggested kelp contributed to it primarily. PMID: 26118110 [PubMed - indexed for MEDLINE]

Related Articles [metabonomics research on coronary heart disease patients of phlegm turbidity syndrome and qi deficiency syndrome]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2015 Feb;35(2):193-7 Authors: Cheng P, Chen ZQ, Wang DS Abstract OBJECTIVE: To study the correlation between Chinese medical types of coronary heart disease (CHD) [i.e., phlegm turbidity syndrome (PTS) and qi deficiency syndrome (QDS)] and their metabolites. METHODS: Recruited were 65 CHD patients including 37 cases of PTS and 28 cases of QDS. Serum endogenous metabolites in the two syndrome types were determined by gas chromatograph-mass spectrometer-computer (GC/MS), and their differences between their metabolic profiles analyzed. RESULTS: More than 100 chromatographic peaks were totally scanned. Chromatograms obtained was matched with mass spectrum bank, and finally we got the category contribution value of 46 kinds of substances. Results of MCTree analysis showed patients of PTS and patients of QDS could be effectively distinguished. Compounds contributing to identify the two syndromes were sequenced as serine, valine, 2 hydroxy propionic acid. Comparison of metabolites showed contents of serine and 2 hydroxy propionic acid were higher in patients of PTS than in patients of QDS (P<0.05). CONCLUSION: The differences in the metabonomics of CHD TCM syndrome types could provide material bases for TCM syndrome differentiation of CHD, indicating that metabonomics technologies might become a new research method for TCM syndrome typing. PMID: 25881465 [PubMed - indexed for MEDLINE]

Related Articles Thiobenzothiazole-modified Hydrocortisones Display Anti-inflammatory Activity with Reduced Impact on Islet β-Cell Function. J Biol Chem. 2015 May 22;290(21):13401-16 Authors: Burke SJ, May AL, Noland RC, Lu D, Brissova M, Powers AC, Sherrill EM, Karlstad MD, Campagna SR, Stephens JM, Collier JJ Abstract Glucocorticoids signal through the glucocorticoid receptor (GR) and are administered clinically for a variety of situations, including inflammatory disorders, specific cancers, rheumatoid arthritis, and organ/tissue transplantation. However, glucocorticoid therapy is also associated with additional complications, including steroid-induced diabetes. We hypothesized that modification of the steroid backbone is one strategy to enhance the therapeutic potential of GR activation. Toward this goal, two commercially unavailable, thiobenzothiazole-containing derivatives of hydrocortisone (termed MS4 and MS6) were examined using 832/13 rat insulinoma cells as well as rodent and human islets. We found that MS4 had transrepression properties but lacked transactivation ability, whereas MS6 retained both transactivation and transrepression activities. In addition, MS4 and MS6 both displayed anti-inflammatory activity. Furthermore, MS4 displayed reduced impact on islet β-cell function in both rodent and human islets. Similar to dexamethasone, MS6 promoted adipocyte development in vitro, whereas MS4 did not. Moreover, neither MS4 nor MS6 activated the Pck1 (Pepck) gene in primary rat hepatocytes. We conclude that modification of the functional groups attached to the D-ring of the hydrocortisone steroid molecule produces compounds with altered structure-function GR agonist activity with decreased impact on insulin secretion and reduced adipogenic potential but with preservation of anti-inflammatory activity. PMID: 25851902 [PubMed - indexed for MEDLINE]

Related Articles [A novel metabolomic data scaling method based on K-L divergence]. Guang Pu Xue Yu Guang Pu Fen Xi. 2014 Oct;34(10):2868-72 Authors: Deng LL, Cheng KK, Shen GP, Zhou L, Liu XZ, Dong JY, Chen Z Abstract A new scaling method in the current study based on Kullback-Leibler (K-L) divergence is proposed for NMR metabolomic data. The proposed method (called K-L scaling) is a supervised scaling method as group information is incorporated in the scaling procedure. Notably, K-L divergence measures the difference between two different datasets by their probability distributions, it can be used for the analysis of data that either follows Gaussian or non-Gaussian distributions. In K-L scaling, all variables were first standardized to unit variance, then their variance was adjusted using Kullback-Leibler divergence to highlight the significant variables. K-L scaling can tell effectively the difference in spectral data points between two experimental groups, and then enhances the weights of biological-relevant variables, and at the same time reduces the weight of noise and uninformative variables. The developed method was applied to a H-NMR metabolomic dataset acquired from human urine. Analysis results of the dataset showed that this new scaling method is efficient in suppressing the contribution of noise in the resulting multivariate model In addition, it can increase the weights of important variables, and improve the interpretability and predictability of subsequent principal component regression (PCR) and partial least squares discriminant analysis (PLS-DA). Furthermore, the scaling method facilitated the identification of metabolic signatures. The current result suggested that the developed K-L scaling method may become a useful alternative for the preprocessing of NMR-based metabolomic data. PMID: 25739240 [PubMed - indexed for MEDLINE]

Related Articles Multiple levels of regulation determine monoterpenoid essential oil compositional variation in the mint family. Mol Plant. 2015 Jan;8(1):188-91 Authors: Ahkami A, Johnson SR, Srividya N, Lange BM PMID: 25578282 [PubMed - indexed for MEDLINE]

Related Articles Polyunsaturated fatty acid metabolites as novel lipidomic biomarkers for noninvasive diagnosis of nonalcoholic steatohepatitis. J Lipid Res. 2015 Jan;56(1):185-92 Authors: Loomba R, Quehenberger O, Armando A, Dennis EA Abstract Lipotoxicity is a key mechanism thought to be responsible for the progression of nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). Noninvasive diagnosis of NASH is a major unmet clinical need, and we hypothesized that PUFA metabolites, in particular arachidonic acid (AA)-derived eicosanoids, in plasma would differentiate patients with NAFL from those with NASH. Therefore, we aimed to assess the differences in the plasma eicosanoid lipidomic profile between patients with biopsy-proven NAFL versus NASH versus normal controls without nonalcoholic fatty liver disease (NAFLD; based on MRI fat fraction <5%). We carried out a cross-sectional analysis of a prospective nested case-control study including 10 patients with biopsy-proven NAFL, 9 patients with biopsy-proven NASH, and 10 non-NAFLD MRI-phenotyped normal controls. We quantitatively compared plasma eicosanoid and other PUFA metabolite levels between NAFL versus NASH versus normal controls. Utilizing a uniquely well-characterized cohort, we demonstrated that plasma eicosanoid and other PUFA metabolite profiling can differentiate between NAFL and NASH. The top candidate as a single biomarker for differentiating NAFL from NASH was 11,12-dihydroxy-eicosatrienoic acid (11,12-diHETrE) with an area under the receiver operating characteristic curve (AUROC) of 1. In addition, we also found a panel including 13,14-dihydro-15-keto prostaglandin D2 (dhk PGD2) and 20-carboxy arachidonic acid (20-COOH AA) that demonstrated an AUROC of 1. This proof-of-concept study provides early evidence that 11,12-diHETrE, dhk PGD2, and 20-COOH AA are the leading eicosanoid candidate biomarkers for the noninvasive diagnosis of NASH. PMID: 25404585 [PubMed - indexed for MEDLINE]

Related Articles Enhanced formation of aromatic amino acids increases fragrance without affecting flower longevity or pigmentation in Petunia × hybrida. Plant Biotechnol J. 2015 Jan;13(1):125-36 Authors: Oliva M, Ovadia R, Perl A, Bar E, Lewinsohn E, Galili G, Oren-Shamir M Abstract Purple Petunia × hybrida V26 plants accumulate fragrant benzenoid-phenylpropanoid molecules and anthocyanin pigments in their petals. These specialized metabolites are synthesized mainly from the aromatic amino acids phenylalanine. Here, we studied the profile of secondary metabolites of petunia plants, expressing a feedback-insensitive bacterial form of 3-deoxy-di-arabino-heptulosonate 7-phosphate synthase enzyme (AroG*) of the shikimate pathway, as a tool to stimulate the conversion of primary to secondary metabolism via the aromatic amino acids. We focused on specialized metabolites contributing to flower showy traits. The presence of AroG* protein led to increased aromatic amino acid levels in the leaves and high phenylalanine levels in the petals. In addition, the AroG* petals accumulated significantly higher levels of fragrant benzenoid-phenylpropanoid volatiles, without affecting the flowers' lifetime. In contrast, AroG* abundance had no effect on flavonoids and anthocyanins levels. The metabolic profile of all five AroG* lines was comparable, even though two lines produced the transgene in the leaves, but not in the petals. This implies that phenylalanine produced in leaves can be transported through the stem to the flowers and serve as a precursor for formation of fragrant metabolites. Dipping cut petunia stems in labelled phenylalanine solution resulted in production of labelled fragrant volatiles in the flowers. This study emphasizes further the potential of this metabolic engineering approach to stimulate the production of specialized metabolites and enhance the quality of various plant organs. Furthermore, transformation of vegetative tissues with AroG* is sufficient for induced production of specialized metabolites in organs such as the flowers. PMID: 25283446 [PubMed - indexed for MEDLINE]

Related Articles [Mechanism research on the lupeol treatment on MCF-7 breast cancer cells based on cell metabonomics]. Se Pu. 2014 Mar;32(3):278-83 Authors: Shi D, Kuang Y, Wang G, Peng Z, Wang Y, Yan C Abstract The objective of this research is to investigate the suppressive effects of lupeol on MCF-7 breast cancer cells, and explore its mechanism on inhibiting the proliferation of MCF-7 cells based on cell metabonomics and cell cycle. Gas chromatography-mass spectrometry (GC-MS) was used in the cell metabonomics assay to identify metabolites of MCF-7 cells and MCF-7 cells treated with lupeol. Then, orthogonal partial least squares discriminant analysis (OPLS-DA) was used to process the metabolic data and model parameters of OPLS-DA were as follows: R2Ycum = 0.988, Q2Ycum = 0.964, which indicated that these two groups could be distinguished clearly. The metabolites (VIP (variable importance in the projection) > 1) were analyzed by t-test, and finally, metabolites (t < 0.05) were identified to be biomarkers. Eleven metabolites such as butanedioic acid, phosphoric acid, L-leucine and isoleucine which had a significant contribution to classification were selected and preliminarily identified due to the accurate mass. Cell cycle assay was analyzed by FACSCalibur. Since the cells in the phase of G1 were increased significantly after the treatment of lupeol, we speculated that lupeol has a blocking effect on the generation of succinyl-CoA and the reaction of substrate phosphorylation of tricarboxylic acid cycle of MCF-7 cells. This study provided a novel approach to the mechanism research on the lupeol treatment on MCF-7 breast cancer cells based on cell metabonomics. PMID: 24984468 [PubMed - indexed for MEDLINE]

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Related Articles Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways. PLoS Comput Biol. 2015 Aug;11(8):e1004321 Authors: King ZA, Dräger A, Ebrahim A, Sonnenschein N, Lewis NE, Palsson BO Abstract Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users can draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, ChIP)-in conjunction with metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics). Third, Escher harnesses the strengths of web technologies (SVG, D3, developer tools) so that visualizations can be rapidly adapted, extended, shared, and embedded. This paper provides examples of each of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools. PMID: 26313928 [PubMed - as supplied by publisher]

Related Articles How should we choose the 'best' embryo? A commentary on behalf of the British Fertility Society and the Association of Clinical Embryologists. Hum Fertil (Camb). 2015 Aug 27;:1-9 Authors: Bolton VN, Leary C, Harbottle S, Cutting R, Harper JC Abstract Embryo selection to improve pregnancy rates remains a significant challenge in IVF. Non-invasive and invasive methods of embryo selection include morphological assessment, metabolomics, time-lapse imaging and preimplantation genetic screening. To date, none has been shown conclusively to yield improved implantation and live birth rates. This review summarises current understanding of methods for embryo selection. PMID: 26313607 [PubMed - as supplied by publisher]

Related Articles Direct metabolomics for plant cells by live single-cell mass spectrometry. Nat Protoc. 2015 Sep;10(9):1445-1456 Authors: Fujii T, Matsuda S, Tejedor ML, Esaki T, Sakane I, Mizuno H, Tsuyama N, Masujima T Abstract Live single-cell mass spectrometry (live MS) provides a mass spectrum that shows thousands of metabolite peaks from a single live plant cell within minutes. By using an optical microscope, a cell is chosen for analysis and a metal-coated nanospray microcapillary tip is used to remove the cell's contents. After adding a microliter of ionization solvent to the opposite end of the tip, the trapped contents are directly fed into the mass spectrometer by applying a high voltage between the tip and the inlet port of the spectrometer to induce nanospray ionization. Proteins are not detected because of insufficient sensitivity. Metabolite peaks are identified by exact mass or tandem mass spectrometry (MS/MS) analysis, and isomers can be separated by combining live MS with ion-mobility separation. By using this approach, spectra can be acquired in 10 min. In combination with metabolic maps and/or molecular databases, the data can be annotated into metabolic pathways; the data analysis takes 30 min to 4 h, depending on the MS/MS data availability from databases. This method enables the analysis of a number of metabolites from a single cell with rapid sampling at sub-attomolar-level sensitivity. PMID: 26313480 [PubMed - as supplied by publisher]

Related Articles Investigating a signature of temozolomide resistance in GBM cell lines using metabolomics. J Neurooncol. 2015 Aug 28; Authors: St-Coeur PD, Poitras JJ, Cuperlovic-Culf M, Touaibia M, Morin PJ Abstract Glioblastoma multiforme (GBM) is the most common form of malignant glioma. Current therapeutic approach to treat this malignancy involves a combination of surgery, radiotherapy and chemotherapy with temozolomide. Numerous mechanisms contributing to inherent and acquired resistance to this chemotherapeutic agent have been identified and can lead to treatment failure. This study undertook a metabolomics-based approach to characterize the metabolic profiles observed in temozolomide-sensitive and temozolomide-resistant GBM cell lines as well as in a small sub-set of primary GBM tumors. This approach was also utilized to explore the metabolic changes modulated upon cell treatment with temozolomide and lomeguatrib, an MGMT inhibitor with temozolomide-sensitizing potential. Metabolites previously explored for their potential role in chemoresistance including glucose, citrate and isocitrate demonstrated elevated levels in temozolomide-resistant GBM cells. In addition, a signature of metabolites comprising alanine, choline, creatine and phosphorylcholine was identified as up-regulated in sensitive GBM cell line across different treatments. These results present the metabolic profiles associated with temozolomide response in selected GBM models and propose interesting leads that could be leveraged for the development of therapeutic or diagnostic tools to impact temozolomide response in GBMs. PMID: 26311249 [PubMed - as supplied by publisher]

Related Articles NMR-based metabolomic urinalysis: a rapid screening test for urinary tract infection. Clin Chim Acta. 2014 Sep 25;436:217-23 Authors: Lam CW, Law CY, To KK, Cheung SK, Lee KC, Sze KH, Leung KF, Yuen KY Abstract BACKGROUND: Urinary tract infection (UTI) is one of the most common bacterial infections in humans; however, there is no accurate and fast quantitative test to detect UTI. Dipstick urinalysis is semi-quantitative with a limited diagnostic accuracy, while urine culture is accurate but takes time. We described a quantitative biochemical method for the diagnosis of bacteriuria using a single marker. METHODS: We compared the urine metabolomes from 88 patients with bacterial UTI and 61 controls using (1)H NMR spectroscopy followed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The biomarker identified was subsequently validated using independent samples. RESULTS: The urine acetic acid/creatinine (mmol/mmol) level was determined to be the most discriminatory marker for bacterial UTI with an area-under-receiver operating characteristic curve=0.97, sensitivity=91% and specificity=95% at the optimal cutoff 0.03 mmol/mmol. For validation, 60 samples were recruited prospectively. Using the optimal cutoff for acetic acid/creatinine, this method showed sensitivity=96%, specificity=94%, positive predictive value=92%, negative predictive value=97% and an overall accuracy=95%. The diagnostic performance was superior to dipstick urinalysis or microscopy. In addition, we also observed an increase of urinary trimethylamine (TMA) in patients with Escherichia coli-associated UTI. TMA is a mammalian-microbial co-metabolite and the high level of TMA generated is related to the bacterial enzyme, trimethylamine N-oxide (TMAO) reductase which reduces TMAO to TMA. CONCLUSIONS: Urine acetic acid is a neglected metabolite that can be used for rapid diagnosis of UTI and TMA can be used for etiologic diagnosis of UTI. With the introduction of NMR-based clinical analyzers to clinical laboratories, NMR-based urinalysis can be translated for clinical use. PMID: 24909875 [PubMed - indexed for MEDLINE]

Related Articles Automated quantum mechanical total line shape fitting model for quantitative NMR-based profiling of human serum metabolites. Anal Bioanal Chem. 2014 May;406(13):3091-102 Authors: Mihaleva VV, Korhonen SP, van Duynhoven J, Niemitz M, Vervoort J, Jacobs DM Abstract An automated quantum mechanical total line shape (QMTLS) fitting model was implemented for quantitative nuclear magnetic resonance (NMR)-based profiling of 42 metabolites in ultrafiltrated human serum samples. Each metabolite was described by a set of chemical shifts, J-couplings, and line widths. These parameters were optimized for each metabolite in each sample by iteratively minimizing the difference between the calculated and the experimental spectrum. In total, 92.0 to 98.1 % of the signal intensities in the experimental spectrum could be explained by the calculated spectrum. The model was validated by comparison to signal integration of metabolites with isolated signals and by means of standard additions. Metabolites present at average concentration higher than 50 μM were quantified with average absolute relative error less than 10 % when using different initial parameters for the fitting procedure. Furthermore, the biological applicability of the QMTLS model was demonstrated on 287 samples from an intervention study in 37 human volunteers undergoing an exercise challenge. Our automated QMTLS model was able to cope with the large dynamic range of metabolite concentrations in serum and proved to be suitable for high-throughput analysis. PMID: 24722875 [PubMed - indexed for MEDLINE]

Rapid and noninvasive technique to assess the metabolomics profile of bovine embryos produced in vitro by Raman spectroscopy. Biomed Opt Express. 2015 Aug 1;6(8):2830-2839 Authors: Santos EC, Martinho HS, Annes K, Leite RF, Milazzotto MP Abstract Morphological assessments are used to select embryos with the highest implantation potential, however it is still very limited. The development of new technologies, such as Raman spectroscopy have improved quantitative and qualitative analysis, and consequently led to a better characterization of embryos and improvements on the prediction of their potential. Therefore, we propose a method based on the conventional in vitro culture system of bovine embryos, and the subsequent analysis of the culture media drops by Raman spectroscopy. Our results obtained by PCA analysis clearly showed a separation of the spectral profiles from culture media drops with and without embryos. PMID: 26309747 [PubMed - as supplied by publisher]

Alterations of plasma metabolite profiles related to adipose tissue distribution and cardiometabolic risk. Am J Physiol Endocrinol Metab. 2015 Aug 25;:ajpendo.00231.2015 Authors: Boulet MM, Chevrier G, Grenier-Larouche T, Pelletier M, Nadeau M, Scarpa J, Prehn C, Marette A, Adamski J, Tchernof A Abstract CONTEXT: Metabolomic profiling of obese individuals revealed altered concentrations of many metabolites, especially branched-chain amino acids (BCAA), possibly linked to altered adipose tissue BCAA catabolism. OBJECTIVE: We tested the hypothesis that some features of this metabolite signature relate closely to visceral obesity and concomitant alterations in cardiometabolic risk factors. We also postulated that alterations in BCAA-catabolizing enzymes are predominant in visceral adipose tissue. METHODS: Fifty-nine women (BMI 20-41 kg/m(2)) undergoing gynecologic surgery were recruited and characterized for overall and regional adiposity, blood metabolite levels using targeted metabolomics and cardiometabolic risk factors. Adipose samples (visceral and subcutaneous) were obtained and used for gene expression and western blot analyses. RESULTS: Obese women had significantly higher circulating BCAA and Kynurenine/Tryptophan (KYN/Trp) ratio than lean or overweight women (p<0.01). Principal component analysis confirmed that factors related to AA and the KYN/Trp ratio were positively associated with BMI, fat mass, visceral or subcutaneous adipose tissue area and subcutaneous adipocyte size (p≤0.05). AA-related factor was positively associated with HOMA-IR (p≤0.01). Factors reflecting glycerophospholipids and sphingolipids levels were mostly associated with altered blood lipid concentrations (p≤0.05). Glutamate level was the strongest independent predictor of visceral adipose tissue area (r=0.46, p<0.001). Obese women had lower expression and protein levels of BCAA-catabolizing enzymes in visceral adipose tissue compared to overweight or lean women (p≤0.05). CONCLUSIONS: Among metabolites altered in obesity, plasma concentrations of BCAA and the KYN/Trp ratio are closely related to increased adiposity. Alterations in expression and protein levels of BCAA-catabolizing enzymes are predominant in visceral adipose tissue. PMID: 26306599 [PubMed - as supplied by publisher]

Related Articles Low- and high-grade bladder cancer appraisal via serum-based proteomics approach. Clin Chim Acta. 2014 Sep 25;436:97-103 Authors: Bansal N, Gupta A, Sankhwar SN, Mahdi AA Abstract OBJECTIVE: To address the shortcomings of urine cytology and cystoscopy for screening and grading of urinary bladder cancer (BC) we applied a serum-based proteomics approach as a surrogate tactic for rapid BC probing. METHODS: This study was performed on 90 sera samples comprising of low-grade (LG, n=33) and high-grade (HG, n=32) BC, and healthy controls (HC, n=25). Two-dimensional gel electrophoresis (2DE) tactic was executed to describe serum proteome. MALDI-TOF-MS (MS) was used to identify the characteristics of aberrantly expressed proteins in 2DE and validated using Western blot (WB) and ELISA approach. Receiver operating characteristics (ROC) curve analysis was also performed to determine the clinical usefulness of these proteins to discriminate among LG, HG and HC cohorts. RESULTS: This comprehensive approach of 2DE, MS, WB and ELISA reveals five differentially expressed proteins. Among them two biomarkers (S100A8 and S100A9) were able to accurately (ROC, 0.946) distinguish 81% of BC (LG+HG) cases compared to HC with highest sensitivity and specificity. With a comparable tactic, two biomarkers (S100A8 and S100A4) were able to precisely (ROC, 0.941) discriminate 92% of LG cases from HG with utmost sensitivity and specificity. CONCLUSIONS: Serum proteomics probing appears to be an encouraging and least-invasive tactic for screening and grading of BC. PMID: 24875752 [PubMed - indexed for MEDLINE]