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

PubMed

metabolomics; +16 new citations

Wed, 09/11/2016 - 23:14
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 2016/11/09PubMed comprises more than 24 million 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.

Transcriptomic Analysis of Responses to Imbalanced Carbon: Nitrogen Availabilities in Rice Seedlings.

Tue, 08/11/2016 - 13:35
Transcriptomic Analysis of Responses to Imbalanced Carbon: Nitrogen Availabilities in Rice Seedlings. PLoS One. 2016;11(11):e0165732 Authors: Huang A, Sang Y, Sun W, Fu Y, Yang Z Abstract The internal C:N balance must be tightly controlled for the normal growth and development of plants. However, the underlying mechanisms, by which plants sense and balance the intracellular C:N status correspondingly to exogenous C:N availabilities remain elusive. In this study, we use comparative gene expression analysis to identify genes that are responsive to imbalanced C:N treatments in the aerial parts of rice seedlings. Transcripts of rice seedlings treated with four C:N availabilities (1:1, 1:60, 60:1 and 60:60) were compared and two groups of genes were classified: high C:low N responsive genes and low C:high N responsive genes. Our analysis identified several functional correlated genes including chalcone synthase (CHS), chlorophyll a-b binding protein (CAB) and other genes that are implicated in C:N balancing mechanism, such as alternative oxidase 1B (OsAOX1B), malate dehydrogenase (OsMDH) and lysine and histidine specific transporter 1 (OsLHT1). Additionally, six jasmonate synthetic genes and key regulatory genes involved in abiotic and biotic stresses, such as OsMYB4, autoinhibited calcium ATPase 3 (OsACA3) and pleiotropic drug resistance 9 (OsPDR9), were differentially expressed under high C:low N treatment. Gene ontology analysis showed that high C:low N up-regulated genes were primarily enriched in fatty acid biosynthesis and defense responses. Coexpression network analysis of these genes identified eight jasmonate ZIM domain protein (OsJAZ) genes and several defense response related regulators, suggesting that high C:low N status may act as a stress condition, which induces defense responses mediated by jasmonate signaling pathway. Our transcriptome analysis shed new light on the C:N balancing mechanisms and revealed several important regulators of C:N status in rice seedlings. PMID: 27820840 [PubMed - in process]

Regulation of autoantibody activity by the IL-23-TH17 axis determines the onset of autoimmune disease.

Tue, 08/11/2016 - 13:35
Regulation of autoantibody activity by the IL-23-TH17 axis determines the onset of autoimmune disease. Nat Immunol. 2016 Nov 07;: Authors: Pfeifle R, Rothe T, Ipseiz N, Scherer HU, Culemann S, Harre U, Ackermann JA, Seefried M, Kleyer A, Uderhardt S, Haugg B, Hueber AJ, Daum P, Heidkamp GF, Ge C, Böhm S, Lux A, Schuh W, Magorivska I, Nandakumar KS, Lönnblom E, Becker C, Dudziak D, Wuhrer M, Rombouts Y, Koeleman CA, Toes R, Winkler TH, Holmdahl R, Herrmann M, Blüml S, Nimmerjahn F, Schett G, Krönke G Abstract The checkpoints and mechanisms that contribute to autoantibody-driven disease are as yet incompletely understood. Here we identified the axis of interleukin 23 (IL-23) and the TH17 subset of helper T cells as a decisive factor that controlled the intrinsic inflammatory activity of autoantibodies and triggered the clinical onset of autoimmune arthritis. By instructing B cells in an IL-22- and IL-21-dependent manner, TH17 cells regulated the expression of β-galactoside α2,6-sialyltransferase 1 in newly differentiating antibody-producing cells and determined the glycosylation profile and activity of immunoglobulin G (IgG) produced by the plasma cells that subsequently emerged. Asymptomatic humans with rheumatoid arthritis (RA)-specific autoantibodies showed identical changes in the activity and glycosylation of autoreactive IgG antibodies before shifting to the inflammatory phase of RA; thus, our results identify an IL-23-TH17 cell-dependent pathway that controls autoantibody activity and unmasks a preexisting breach in immunotolerance. PMID: 27820809 [PubMed - as supplied by publisher]

Nutrigenomics in the modern era.

Tue, 08/11/2016 - 13:35
Nutrigenomics in the modern era. Proc Nutr Soc. 2016 Nov 7;:1-11 Authors: Mathers JC Abstract The concept that interactions between nutrition and genetics determine phenotype was established by Garrod at the beginning of the 20th century through his ground-breaking work on inborn errors of metabolism. A century later, the science and technologies involved in sequencing of the human genome stimulated development of the scientific discipline which we now recognise as nutritional genomics (nutrigenomics). Much of the early hype around possible applications of this new science was unhelpful and raised expectations, which have not been realised as quickly as some would have hoped. However, major advances have been made in quantifying the contribution of genetic variation to a wide range of phenotypes and it is now clear that for nutrition-related phenotypes, such as obesity and common complex diseases, the genetic contribution made by SNP alone is often modest. There is much scope for innovative research to understand the roles of less well explored types of genomic structural variation, e.g. copy number variants, and of interactions between genotype and dietary factors, in phenotype determination. New tools and models, including stem cell-based approaches and genome editing, have huge potential to transform mechanistic nutrition research. Finally, the application of nutrigenomics research offers substantial potential to improve public health e.g. through the use of metabolomics approaches to identify novel biomarkers of food intake, which will lead to more objective and robust measures of dietary exposure. In addition, nutrigenomics may have applications in the development of personalised nutrition interventions, which may facilitate larger, more appropriate and sustained changes in eating (and other lifestyle) behaviours and help to reduce health inequalities. PMID: 27819203 [PubMed - as supplied by publisher]

Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism.

Tue, 08/11/2016 - 13:35
Related Articles Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism. Cell Metab. 2016 Oct 21;: Authors: Chaurasia B, Kaddai VA, Lancaster GI, Henstridge DC, Sriram S, Galam DL, Gopalan V, Prakash KN, Velan SS, Bulchand S, Tsong TJ, Wang M, Siddique MM, Yuguang G, Sigmundsson K, Mellet NA, Weir JM, Meikle PJ, Bin M Yassin MS, Shabbir A, Shayman JA, Hirabayashi Y, Shiow ST, Sugii S, Summers SA Abstract Adipocytes package incoming fatty acids into triglycerides and other glycerolipids, with only a fraction spilling into a parallel biosynthetic pathway that produces sphingolipids. Herein, we demonstrate that subcutaneous adipose tissue of type 2 diabetics contains considerably more sphingolipids than non-diabetic, BMI-matched counterparts. Whole-body and adipose tissue-specific inhibition/deletion of serine palmitoyltransferase (Sptlc), the first enzyme in the sphingolipid biosynthesis cascade, in mice markedly altered adipose morphology and metabolism, particularly in subcutaneous adipose tissue. The reduction in adipose sphingolipids increased brown and beige/brite adipocyte numbers, mitochondrial activity, and insulin sensitivity. The manipulation also increased numbers of anti-inflammatory M2 macrophages in the adipose bed and induced secretion of insulin-sensitizing adipokines. By comparison, deletion of serine palmitoyltransferase from macrophages had no discernible effects on metabolic homeostasis or adipose function. These data indicate that newly synthesized adipocyte sphingolipids are nutrient signals that drive changes in the adipose phenotype to influence whole-body energy expenditure and nutrient metabolism. PMID: 27818258 [PubMed - as supplied by publisher]

Metabolomic analysis of urine with Nuclear Magnetic Resonance spectroscopy in patients with idiopathic sudden sensorineural hearing loss: A preliminary study.

Tue, 08/11/2016 - 13:35
Related Articles Metabolomic analysis of urine with Nuclear Magnetic Resonance spectroscopy in patients with idiopathic sudden sensorineural hearing loss: A preliminary study. Auris Nasus Larynx. 2016 Nov 3;: Authors: Carta F, Lussu M, Bandino F, Antonio N, Peppi M, Chuchueva N, Luigi A, Fanos V, Puxeddu R Abstract OBJECTIVE: Idiopathic sudden sensorineural hearing loss is a frequent emergency, with unknown aetiology and usually treated with empiric therapy. Steroids represent the only validated treatment but prognosis is unpredictable and the possibility to select the patients who will not respond to steroids could avoid unnecessary treatments. Metabolomic profiling of the biofluids target the analysis of the final product of genic expression and enzymatic activity, defining the biochemical phenotype of a whole biologic system. METHODS: We studied the metabolomics of the urine of a cohort of patients with idiopathic sudden sensorineural hearing loss, correlating the metabolic profiles with the clinical outcomes. Metabolomic profiling of urine samples was performed by (1)H Nuclear Magnetic Resonance spectroscopy in combination with multivariate statistical approaches. RESULTS: 26 patients were included in the study: 5 healthy controls, 13 patients who did not recover after treatment at 6 months while the remaining 8 patients recovered from the hearing loss. The orthogonal partial least square-discriminant analysis score plot showed a significant separation between the two groups, responders and non-responders after steroid therapy, R(2)Y of 0.83, Q(2) of 0.38 and p value <0.05. The resulting metabolic profiles were characterized by higher levels of urinary B-Alanine, 3-hydroxybutyrate and Trimethylamine N-oxide, and lower levels of Citrate and Creatinine in patients with worst outcome. CONCLUSION: Idiopathic sudden sensorineural hearing loss is a specific disease with unclear systemic changes, but our data suggest that there are different types of this disorder or patients predisposed to effective action of steroids allowing the recover after treatment. PMID: 27817938 [PubMed - as supplied by publisher]

[Effect of respiratory syncytial virus-related pulmonary infection on endogenous metabolites in large intestinal mucosa in mice].

Tue, 08/11/2016 - 13:35
Related Articles [Effect of respiratory syncytial virus-related pulmonary infection on endogenous metabolites in large intestinal mucosa in mice]. Zhongguo Dang Dai Er Ke Za Zhi. 2016 Nov;18(11):1166-1173 Authors: Meng X, Wang SC, Shan JJ, Xie T, Xu JY, Shen CS Abstract OBJECTIVE: To investigate the effect of respiratory syncytial virus (RSV)-related pulmonary infection on endogenous metabolites in large intestinal mucosa in BALB/c mice using metabolomics technology based on gas chromatography-mass spectrometry (GC-MS). METHODS: Mice were randomly divided into a control group and a RSV pneumonia model group (n=16 each). The mouse model of RSV pneumonia was established using intranasal RSV infection (100×TCID50, 50 μL/mouse, once a day). After 7 days of intranasal RSV infection, the mice were sacrificed and GC-MS was used to identify endogenous metabolites and measure the changes in their relative content in colon tissue. SMCA-P12.0 software was used to perform principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) for endogenous metabolites in colon tissue. The differentially expressed metabolites in colon tissue were imported into the metabolic pathway platform Metaboanalyst to analyze related metabolic pathways. RESULTS: PCA and OPLS-DA showed significant differences between the control and RSV pneumonia model groups. A total of 32 metabolites were identified in the colon tissue of the mice with RSV pneumonia. The RSV pneumonia model group had significant increases in the content of leucine, isoleucine, glycine, alanine, arachidonic acid, and lactic acid, which were related to the valine, leucine, isoleucine, arachidonic acid, and pyruvic acid metabolic pathways. CONCLUSIONS: RSV pneumonia might cause metabolic disorders in the large intestinal tissue in mice. PMID: 27817786 [PubMed - in process]

Bioanalytical techniques in nontargeted clinical lipidomics.

Tue, 08/11/2016 - 13:35
Related Articles Bioanalytical techniques in nontargeted clinical lipidomics. Bioanalysis. 2016 Feb;8(4):351-64 Authors: Hyötyläinen T, Orešič M Abstract Lipidomic analysis aims at comprehensive characterization of molecular lipids in biological systems. Due to the central role of lipid metabolism in many devastating diseases, lipidomics is being increasingly applied in biomedical research. Over the past years, advances in analytical techniques and bioinformatics enabled increasingly comprehensive and accurate coverage of lipids both in tissues and biofluids, yet many challenges remain. This review highlights recent progress in the domain of analytical lipidomics, with main emphasis on non-targeted methodologies for large scale clinical applications, as well as discusses some of the key challenges and opportunities in this field. PMID: 26856187 [PubMed - indexed for MEDLINE]

Metabolite profiling can change health-care delivery to obese patients with fatty liver disease: the search for biomarkers.

Mon, 07/11/2016 - 15:36
Related Articles Metabolite profiling can change health-care delivery to obese patients with fatty liver disease: the search for biomarkers. Clin Chem Lab Med. 2016 Nov 7;: Authors: Camps J, Joven J Abstract Comorbidities associated with obesity have become a worldwide public health concern. Obesity-associated hepatic steatosis is not benign, and the risk of developing severe liver disease is high. Currently, biopsy is the only clinical tool available for the diagnosis of pathological alterations in the liver. However, the procedure is painful and not without risk. As such, there is a need to identify non-invasive biomarkers of steatosis. There has been considerable progress in this area, but research appears to be limited to measurements of levels of certain parameters in patients with liver impairment relative to those of healthy controls. The clinically relevant aim should be to distinguish, at an early stage, those obese individuals with liver steatosis from those obese individuals without it. Plasma constituents that act as surrogates of altered hepatic energy metabolism in response to food intake are likely candidates. Targeted metabolomics, combined with quantitation of the metabolites involved, has been shown to be an efficient measurement tool. Indeed, the evaluation of exhaled volatile compounds might be sufficient, while other rapid, sensitive, and reproducible methods have been validated in preliminary studies in various clinical settings. Metabolomics methods are promising but require considerable expertise and sophisticated (and expensive) equipment not readily available in all centers. The challenge is to adapt this newly acquired, expanding knowledge to current, reasonably equipped clinical laboratories, while substantially reducing costs. Good outcomes are urgently required if effective prevention programs are to be developed to decrease the prevalence of liver disease. PMID: 27816954 [PubMed - as supplied by publisher]

Cognitive decline in type 2 diabetic db/db mice may be associated with brain region-specific metabolic disorders.

Mon, 07/11/2016 - 15:36
Related Articles Cognitive decline in type 2 diabetic db/db mice may be associated with brain region-specific metabolic disorders. Biochim Biophys Acta. 2016 Nov 2;: Authors: Zheng H, Zheng Y, Zhao L, Chen M, Bai G, Hu Y, Hu W, Yan Z, Gao H Abstract Type 2 diabetes has been associated with cognitive decline, but its metabolic mechanism remains unclear. In the present study, we attempted to investigate brain region-specific metabolic changes in db/db mice with cognitive decline and explore the potential metabolic mechanism linking type 2 diabetes and cognitive decline. We analyzed the metabolic changes in seven brain regions of two types of mice (wild-type mice and db/db mice with cognitive decline) using a (1)H NMR-based metabolomic approach. Then, a mixed-model analysis was used to evaluate the effects of mice type, brain region, and their interaction on metabolic changes. Compared with the wild-type mice, the db/db mice with cognitive decline had significant increases in lactate, glutamine (Gln) and taurine as well as significant decreases in alanine, aspartate, choline, succinate, γ-Aminobutyric acid (GABA), glutamate (Glu), glycine, N-acetylaspartate, inosine monophosphate, adenosine monophosphate, adenosine diphosphate, and nicotinamide adenine dinucleotide. Brain region-specific metabolic differences were also observed between these two mouse types. In addition, we found significant interaction effects of mice type and brain region on creatine/phosphocreatine, lactate, aspartate, GABA, N-acetylaspartate and taurine. Based on metabolic pathway analysis, the present study suggests that cognitive decline in db/db mice might be linked to a series of brain region-specific metabolic changes, involving an increase in anaerobic glycolysis, a decrease in tricarboxylic acid (TCA) and Gln-Glu/GABA cycles as well as a disturbance in lactate-alanine shuttle and membrane metabolism. PMID: 27816519 [PubMed - as supplied by publisher]

HPLC-based metabolomics to identify cytotoxic compounds from Plectranthus amboinicus (Lour.) Spreng against human breast cancer MCF-7Cells.

Mon, 07/11/2016 - 15:36
Related Articles HPLC-based metabolomics to identify cytotoxic compounds from Plectranthus amboinicus (Lour.) Spreng against human breast cancer MCF-7Cells. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Oct 22;: Authors: Yulianto W, Andarwulan N, Giriwono PE, Pamungkas J Abstract The objective of this study was to identify the active compounds in Plectranthus amboinicus (Lour.) Spreng which play a role to inhibit viability of breast cancer MCF-7 cells using HPLC-based metabolomics approach. Five fractions of the plant extract were observed including ethanol, hexane, chloroform, ethyl acetate and water fraction. There were 45 HPLC chromatograms resulted from 5 fractions with 3 replications and 3 wavelengths detection. The chromatograms were compared to the data of IC50 from MTT assay of each fraction against human breast cancer MCF-7 cells using metabolomics. The OPLS analysis result promptly pointed towards a chloroform fraction at retention time of 40.16-41.28min that has the greatest contribution to the cytotoxic activity. The data of mass spectra indicated that an abietane diterpene namely 7-acetoxy-6-hydroxyroyleanone was the main compound that contributed to the cytotoxic activity. This metabolomics application method can be used as a quick preliminary guideline to uncover the most dominant compound related to the bioactivity. PMID: 27816313 [PubMed - as supplied by publisher]

Evaluation of dilution and normalization strategies to correct for urinary output in HPLC-HRTOFMS metabolomics.

Mon, 07/11/2016 - 15:36
Related Articles Evaluation of dilution and normalization strategies to correct for urinary output in HPLC-HRTOFMS metabolomics. Anal Bioanal Chem. 2016 Nov 4; Authors: Vogl FC, Mehrl S, Heizinger L, Schlecht I, Zacharias HU, Ellmann L, Nürnberger N, Gronwald W, Leitzmann MF, Rossert J, Eckardt KU, Dettmer K, Oefner PJ, GCKD Study Investigators Abstract Reliable identification of features distinguishing biological groups of interest in urinary metabolite fingerprints requires the control of total metabolite abundance, which may vary significantly as the kidneys adjust the excretion of water and solutes to meet the homeostatic needs of the body. Failure to account for such variation may lead to misclassification and accumulation of missing data in case of less concentrated urine specimens. Here, different pre- and post-acquisition methods of normalization were compared systematically for their ability to recover features from liquid chromatography-mass spectrometry metabolite fingerprints of urine that allow distinction between patients with chronic kidney disease and healthy controls. Methods of normalization that were employed prior to analysis included dilution of urine specimens to either a fixed creatinine concentration or osmolality value. Post-acquisition normalization methods applied to chromatograms of 1:4 diluted urine specimens comprised normalization to creatinine, osmolality, and sum of all integrals. Dilution of urine specimens to a fixed creatinine concentration resulted not only in the least number of missing values, but it was also the only method allowing the unambiguous classification of urine specimens from healthy and diseased individuals. The robustness of classification could be confirmed for two independent patient cohorts of chronic kidney disease patients and yielded a shared set of 49 discriminant metabolite features. Graphical Abstract Dilution to a uniform creatinine concentration across urine specimens yields more comparable urinary metabolite fingerprints. PMID: 27815612 [PubMed - as supplied by publisher]

Corrigendum to "Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice" [Atherosclerosis 243/2 (2015) 598-608].

Mon, 07/11/2016 - 15:36
Related Articles Corrigendum to "Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice" [Atherosclerosis 243/2 (2015) 598-608]. Atherosclerosis. 2016 Nov;254:314-315 Authors: Rasmiena AA, Barlow CK, Stefanovic N, Huynh K, Tan R, Sharma A, Tull D, de Haan JB, Meikle PJ PMID: 27814884 [PubMed - in process]

Maternal urinary metabolic signatures of fetal growth and associated clinical and environmental factors in the INMA study.

Mon, 07/11/2016 - 15:36
Related Articles Maternal urinary metabolic signatures of fetal growth and associated clinical and environmental factors in the INMA study. BMC Med. 2016 Nov 4;14(1):177 Authors: Maitre L, Villanueva CM, Lewis MR, Ibarluzea J, Santa-Marina L, Vrijheid M, Sunyer J, Coen M, Toledano MB Abstract BACKGROUND: Maternal metabolism during pregnancy is a major determinant of the intra-uterine environment and fetal outcomes. Herein, we characterize the maternal urinary metabolome throughout pregnancy to identify maternal metabolic signatures of fetal growth in two subcohorts and explain potential sources of variation in metabolic profiles based on lifestyle and clinical data. METHODS: We used (1)H nuclear magnetic resonance (NMR) spectroscopy to characterize maternal urine samples collected in the INMA birth cohort at the first (n = 412 and n = 394, respectively, in Gipuzkoa and Sabadell cohorts) and third trimesters of gestation (n = 417 and 469). Metabolic phenotypes that reflected longitudinal intra- and inter-individual variation were used to predict measures of fetal growth and birth weight. RESULTS: A metabolic shift between the first and third trimesters of gestation was characterized by (1)H NMR signals arising predominantly from steroid by-products. We identified 10 significant and reproducible metabolic associations in the third trimester with estimated fetal, birth, and placental weight in two independent subcohorts. These included branched-chain amino acids; isoleucine, valine, leucine, alanine and 3 hydroxyisobutyrate (metabolite of valine), which were associated with a significant fetal weight increase at week 34 of up to 2.4 % in Gipuzkoa (P < 0.005) and 1 % in Sabadell (P < 0.05). Other metabolites included pregnancy-related hormone by-products of estrogens and progesterone, and the methyl donor choline. We could explain a total of 48-53 % of the total variance in birth weight of which urine metabolites had an independent predictive power of 12 % adjusting for all other lifestyle/clinical factors. First trimester metabolic phenotypes could not predict reproducibly weight at later stages of development. Physical activity, as well as other modifiable lifestyle/clinical factors, such as coffee consumption, vitamin D intake, and smoking, were identified as potential sources of metabolic variation during pregnancy. CONCLUSIONS: Significant reproducible maternal urinary metabolic signatures of fetal growth and birth weight are identified for the first time and linked to modifiable lifestyle factors. This novel approach to prenatal screening, combining multiple risk factors, present a great opportunity to personalize pregnancy management and reduce newborn disease risk in later life. PMID: 27814705 [PubMed - in process]

metabolomics; +24 new citations

Sat, 05/11/2016 - 13:51
24 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 2016/11/05PubMed comprises more than 24 million 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.

metabolomics; +20 new citations

Fri, 04/11/2016 - 19:31
20 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 2016/11/04PubMed comprises more than 24 million 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.

Lipids Reprogram Metabolism to Become a Major Carbon Source for Histone Acetylation.

Thu, 03/11/2016 - 12:20
Lipids Reprogram Metabolism to Become a Major Carbon Source for Histone Acetylation. Cell Rep. 2016 Nov 1;17(6):1463-1472 Authors: McDonnell E, Crown SB, Fox DB, Kitir B, Ilkayeva OR, Olsen CA, Grimsrud PA, Hirschey MD Abstract Cells integrate nutrient sensing and metabolism to coordinate proper cellular responses to a particular nutrient source. For example, glucose drives a gene expression program characterized by activating genes involved in its metabolism, in part by increasing glucose-derived histone acetylation. Here, we find that lipid-derived acetyl-CoA is a major source of carbon for histone acetylation. Using (13)C-carbon tracing combined with acetyl-proteomics, we show that up to 90% of acetylation on certain histone lysines can be derived from fatty acid carbon, even in the presence of excess glucose. By repressing both glucose and glutamine metabolism, fatty acid oxidation reprograms cellular metabolism, leading to increased lipid-derived acetyl-CoA. Gene expression profiling of octanoate-treated hepatocytes shows a pattern of upregulated lipid metabolic genes, demonstrating a specific transcriptional response to lipid. These studies expand the landscape of nutrient sensing and uncover how lipids and metabolism are integrated by epigenetic events that control gene expression. PMID: 27806287 [PubMed - in process]

The metabolomics and lipidomics window into thyroid cancer research.

Thu, 03/11/2016 - 12:20
The metabolomics and lipidomics window into thyroid cancer research. Biomarkers. 2016 Nov 2;:1-19 Authors: Farrokhi Yekta R, Rezaie Tavirani M, Arefi Oskouie A, Mohajeri Tehrani MR, Soroush AR Abstract CONTEXT: Thyroid carcinoma is the most common endocrine system malignancy with a fast rising incidence in the last decade for unknown reasons. Fine needle aspiration (FNA) biopsy, the gold standard in thyroid cancer screening has still its own challenges and in some cases needs a proceeding surgery. OBJECTIVE: This review highlights the role of the two most recent "omics" approaches, "metabolomics" and "lipidomics", in the field of thyroid cancer research. METHODS: All the previous studies have been extracted from the literature and major concepts were detailed in the field of thyroid cancer metabolomics and lipidomics. RESULTS: Metabolomics and lipidomics, have potential in finding biomarkers related to thyroid carcinoma. Among the previous studies, the most important introduced altered tissue metabolites and lipids included glucose and galactose, lactate, Scyllo- and Myo inositol, hypoxanthine, citrate, cholesterol, and choline. CONCLUSION: Metabolomics methods have been widely used in the field of biomarker discovery in thyroid cancer and attempts are still in progress to use these methods to find a reliable biomarker panel besides current diagnostic tools. PMID: 27805426 [PubMed - as supplied by publisher]

Urinary Biomarkers of Whole Grain Wheat Intake Identified by Non-targeted and Targeted Metabolomics Approaches.

Thu, 03/11/2016 - 12:20
Urinary Biomarkers of Whole Grain Wheat Intake Identified by Non-targeted and Targeted Metabolomics Approaches. Sci Rep. 2016 Nov 02;6:36278 Authors: Zhu Y, Wang P, Sha W, Sang S Abstract Mounting evidence suggests that whole grain (WG) intake plays an important role in chronic disease prevention. However, numerous human studies have failed to produce clear-cut conclusions on this topic. Here, a combination of non-targeted and targeted metabolomics approaches, together with kinetic studies, was used to investigate biomarkers of WG wheat intake and further explore the diet-disease associations. Via these integrated approaches, forty-one compounds were identified as the most discriminating endogenous metabolites after WG versus refined grain (RG) wheat bread consumption. The corresponding biological assessment of these endogenous changes suggests that, in contrast to RG consumption, WG wheat consumption may facilitate antioxidant defense systems and moderate the risk factors of cancer, cardiovascular diseases, and other chronic diseases. A panel of urinary markers consisting of seven alkylresorcinol metabolites and five benzoxazinoid derivatives as specific biomarkers, as well as five phenolic acid derivatives, was also established to cover multiple time points and longer time periods for correctly and objectively monitoring WG wheat intake. Through these findings, we have established a comprehensive biomarker pool to better assess WG wheat consumption, and to monitor the endogenous changes that are linked to health effects of WG wheat consumption. PMID: 27805021 [PubMed - in process]

Profiling of Altered Metabolomic States in Nicotiana tabacum Cells Induced by Priming Agents.

Thu, 03/11/2016 - 12:20
Related Articles Profiling of Altered Metabolomic States in Nicotiana tabacum Cells Induced by Priming Agents. Front Plant Sci. 2016;7:1527 Authors: Mhlongo MI, Steenkamp PA, Piater LA, Madala NE, Dubery IA Abstract Metabolomics has developed into a valuable tool for advancing our understanding of plant metabolism. Plant innate immune defenses can be activated and enhanced so that, subsequent to being pre-sensitized, plants are able to launch a stronger and faster defense response upon exposure to pathogenic microorganisms, a phenomenon known as priming. Here, three contrasting chemical activators, namely acibenzolar-S-methyl, azelaic acid and riboflavin, were used to induce a primed state in Nicotiana tabacum cells. Identified biomarkers were then compared to responses induced by three phytohormones-abscisic acid, methyljasmonate, and salicylic acid. Altered metabolomes were studied using a metabolite fingerprinting approach based on liquid chromatography and mass spectrometry. Multivariate data models indicated that these inducers cause time-dependent metabolic perturbations in the cultured cells and revealed biomarkers of which the levels are affected by these agents. A total of 34 metabolites were annotated from the mass spectral data and online databases. Venn diagrams were used to identify common biomarkers as well as those unique to a specific agent. Results implicate 20 cinnamic acid derivatives conjugated to (i) quinic acid (chlorogenic acids), (ii) tyramine, (iii) polyamines, or (iv) glucose as discriminatory biomarkers of priming in tobacco cells. Functional roles for most of these metabolites in plant defense responses could thus be proposed. Metabolites induced by the activators belong to the early phenylpropanoid pathway, which indicates that different stimuli can activate similar pathways but with different metabolite fingerprints. Possible linkages to phytohormone-dependent pathways at a metabolomic level were indicated in the case of cells treated with salicylic acid and methyljasmonate. The results contribute to a better understanding of the priming phenomenon and advance our knowledge of cinnamic acid derivatives as versatile defense metabolites. PMID: 27803705 [PubMed - in process]

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