PubMed

New insight on obesity and adipose-derived stem cells by comprehensive metabolomics. Biochem J. 2016 May 19; Authors: Mastrangelo A, Panadero MI, Pérez LM, Gálvez BG, García A, Barbas C, Rupérez FJ Abstract Obesity affects the functional capability of adipose-derived stem cells (ASCs) and their effective use in regenerative medicine through mechanisms still poorly understood. Here we employed a multiplatform (LC/MS, CE/MS, GC/MS) metabolomics untargeted approach to investigate the metabolic alteration underlying the inequalities observed in obese-derived ASCs. The metabolic fingerprint (metabolites within the cells) and footprint (metabolites secreted in the culture medium) from humans or mice, obese and non-obese derived ASCs, were characterized by providing valuable information. Metabolites associated to glycolysis, TCA, pentose phosphate pathway and polyol pathway were increased in the footprint of obese-derived human ASCs indicating alterations in the carbohydrate metabolism; whereas from the murine model, deep differences in lipid and amino acid catabolism were highlighted. Therefore, new insights on the ASCs metabolome were provided that enhance our understanding of the processes underlying the ASCs stemness capacity and its relationship with obesity, in different cell models. PMID: 27208167 [PubMed - as supplied by publisher]

Metabolic networks and metabolites underlie associations between maternal glucose during pregnancy and newborn size at birth. Diabetes. 2016 Apr 5; Authors: Scholtens DM, Bain JR, Reisetter AC, Muehlbauer MJ, Nodzenski M, Stevens RD, Ilkayeva O, Lowe LP, Metzger BE, Newgard CB, Lowe WL, HAPO Study Cooperative Research Group. Abstract Maternal metabolites and metabolic networks underlying associations between maternal glucose during pregnancy and newborn birth weight and adiposity demand fuller characterization. We performed targeted and non-targeted gas-chromatography/mass-spectrometry metabolomics on maternal serum collected at fasting and 1-hour following Trutol consumption during an oral glucose tolerance test for 400 Northern European mothers at ∼28 weeks gestation in the Hyperglycemia and Adverse Pregnancy Outcome Study. Amino acids, fatty acids, acylcarnitines and products of lipid metabolism decreased and triglycerides increased following glucose ingestion during the OGTT. Analyses of individual metabolites indicated limited maternal glucose associations at fasting, but broader associations including amino acids, fatty acids, carbohydrates and lipids at 1-hour. Network analyses modeling metabolite correlations provided context for individual metabolite associations and elucidated collective associations of multiple classes of metabolic fuels with newborn size and adiposity, including acylcarnitines, fatty acids, carbohydrates and organic acids. Random forest analyses indicated improved ability to predict newborn size outcomes using maternal metabolomics data beyond traditional risk factors including maternal glucose. Broad scale association of fuel metabolites with maternal glucose is evident during pregnancy, with unique maternal metabolites potentially contributing specifically to newborn birth weight and adiposity. PMID: 27207545 [PubMed - as supplied by publisher]

Metabolomic investigation of regional brain tissue dysfunctions induced by global cerebral ischemia. BMC Neurosci. 2016;17(1):25 Authors: Zhang T, Wang W, Huang J, Liu X, Zhang H, Zhang N Abstract BACKGROUND: To get a broader view of global ischemia-induced cerebral disorders at the metabolic level, a nuclear magnetic resonance-based metabolomic study was performed to evaluate the metabolic profile changes on regional brain tissues of female and male mice upon bilateral common carotid arteries occlusion (BCCAO) operation. RESULTS: Significant metabolic disorders were observed in both cerebral cortex and hippocampus tissues of the experimental mice upon global cerebral ischemic attack. Multiple amino acids were identified as the dominantly perturbed metabolites. It was also shown that although the metabolic profile change patterns in the brain tissues were quite similar in male and female BCCAO mice, metabolic disorders in the cortex tissues were more severe in the female mice than in the male mice. CONCLUSIONS: In the present study, significant changes in amino acid metabolic pathways were confirmed in the early stage of global ischemia. Meanwhile, cerebral metabolic dysfunctions were more severe in the female BCCAO mice than in the male mice, suggesting that gender may play a role in different metabolic responses to the ischemic attack, which may provide an important hypothesis for a better understanding of the clinically observed gender-dependent pathological outcome of cerebral ischemia. PMID: 27206925 [PubMed - as supplied by publisher]

Neurotransmitter and their metabolite concentrations in different areas of the HPRT knockout mouse brain. J Neurol Sci. 2016 Jun 15;365:169-74 Authors: Tschirner SK, Gutzki F, Schneider EH, Seifert R, Kaever V Abstract Lesch-Nyhan syndrome (LNS) is characterized by uric acid overproduction and severe neurobehavioral symptoms, such as recurrent self-mutilative behavior. To learn more about the pathophysiology of the disease, we quantified neurotransmitters and their metabolites in the cerebral hemisphere, cerebellum and the medulla oblongata of HPRT knockout mice, an animal model for LNS, in comparison to the corresponding wild-type. Our analyses included l-glutamate, 4-aminobutanoic acid (GABA), acetylcholine, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine, l-normetanephrine, epinephrine and l-metanephrine and were conducted via high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS). Among these neurotransmitter systems, we did not find any abnormalities in the HPRT knockout mouse brains. On one side, this might indicate that HPRT deficiency most severely affects dopamine signaling, while brain functioning based on other neurotransmitters is more or less spared. On the other hand, our findings may reflect a compensating mechanism for impaired purine salvage that protects the brain in HPRT-deficient mice but not in LNS patients. PMID: 27206901 [PubMed - in process]

The novel choline kinase inhibitor ICL-CCIC-0019 reprograms cellular metabolism and inhibits cancer cell growth. Oncotarget. 2016 May 19; Authors: Trousil S, Kaliszczak M, Schug Z, Nguyen Q, Tomasi G, Favicchio R, Brickute D, Fortt R, Twyman FJ, Carroll L, Kalusa A, Navaratnam N, Adejumo T, Carling D, Gottlieb E, Aboagye EO Abstract The glycerophospholipid phosphatidylcholine is the most abundant phospholipid species of eukaryotic membranes and essential for structural integrity and signaling function of cell membranes required for cancer cell growth. Inhibition of choline kinase alpha (CHKA), the first committed step to phosphatidylcholine synthesis, by the selective small-molecule ICL-CCIC-0019, potently suppressed growth of a panel of 60 cancer cell lines with median GI50 of 1.12 μM and inhibited tumor xenograft growth in mice. ICL-CCIC-0019 decreased phosphocholine levels and the fraction of labeled choline in lipids, and induced G1 arrest, endoplasmic reticulum stress and apoptosis. Changes in phosphocholine cellular levels following treatment could be detected non-invasively in tumor xenografts by [18F]-fluoromethyl-[1,2-2H4]-choline positron emission tomography. Herein, we reveal a previously unappreciated effect of choline metabolism on mitochondria function. Comparative metabolomics demonstrated that phosphatidylcholine pathway inhibition leads to a metabolically stressed phenotype analogous to mitochondria toxin treatment but without reactive oxygen species activation. Drug treatment decreased mitochondria function with associated reduction of citrate synthase expression and AMPK activation. Glucose and acetate uptake were increased in an attempt to overcome the metabolic stress. This study indicates that choline pathway pharmacological inhibition critically affects the metabolic function of the cell beyond reduced synthesis of phospholipids. PMID: 27206796 [PubMed - as supplied by publisher]

17 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 2016/05/21PubMed 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.

Metabolomic Biomarkers of Prostate Cancer: Prediction, Diagnosis, Progression, Prognosis, and Recurrence. Cancer Epidemiol Biomarkers Prev. 2016 Apr 6; Authors: Kelly RS, Vander Heiden MG, Giovannucci E, Mucci LA Abstract Metabolite profiling is being increasing employed in the study of prostate cancer as a means of identifying predictive, diagnostic, and prognostic biomarkers. This review provides a summary and critique of the current literature. Thirty-three human case-control studies of prostate cancer exploring disease prediction, diagnosis, progression, or treatment response were identified. All but one demonstrated the ability of metabolite profiling to distinguish cancer from benign, tumor aggressiveness, cases who recurred, and those who responded well to therapy. In the subset of studies where biomarker discriminatory ability was quantified, high AUCs were reported that would potentially outperform the current gold standards in diagnosis, prognosis, and disease recurrence, including PSA testing. There were substantial similarities between the metabolites and the associated pathways reported as significant by independent studies, and important roles for abnormal cell growth, intensive cell proliferation, and dysregulation of lipid metabolism were highlighted. The weight of the evidence therefore suggests metabolic alterations specific to prostate carcinogenesis and progression that may represent potential metabolic biomarkers. However, replication and validation of the most promising biomarkers is currently lacking and a number of outstanding methodologic issues remain to be addressed to maximize the utility of metabolomics in the study of prostate cancer. Cancer Epidemiol Biomarkers Prev; 25(6); 1-20. ©2016 AACR. PMID: 27197278 [PubMed - as supplied by publisher]

Impact of Pattern Recognition Receptors on the Prognosis of Breast Cancer Patients Undergoing Adjuvant Chemotherapy. Cancer Res. 2016 May 16; Authors: Vacchelli E, Enot DP, Pietrocola F, Zitvogel L, Kroemer G Abstract Pattern recognition receptors allow the innate immune system to perceive the presence of microbial products and to launch the first steps of the defense response. Some pattern recognition receptors also sense endogenous ligands that are released from uninfected dying cells, thereby activating immune responses against dead-cell antigens. This applies to toll-like receptors 3 and 4 (TLR3, TLR4), which sense double-stranded RNA and high-mobility group protein B1 (HMGB1), respectively, as well as to formyl peptide receptor-1 (FPR1), which interacts with Annexin A1 (ANXA1) from dead cells. Breast cancer patients who bear loss-of-function alleles in TLR3, TLR4, and FPR1 exhibit a reduced metastasis-free and overall survival after treatment with anthracycline-based adjuvant chemotherapy. These genetic defects are epistatic with respect to each other, suggesting that they act on the same pathway, linking chemotherapy to a therapeutically relevant anticancer immune response. Loss-of-function alleles in TLR4 and FPR1 also affect the prognosis of colorectal cancer patients treated with oxaliplatin-based chemotherapy. Altogether, these results support the idea that conventional anticancer treatments rely on stimulation of anticancer immune responses to become fully efficient. Cancer Res; 76(11); 1-5. ©2016 AACR. PMID: 27197163 [PubMed - as supplied by publisher]

Huangqi Decoction Alleviates Dimethylnitrosamine-induced Liver Fibrosis: an Analysis of Bile Acids Metabolic Mechanism. J Ethnopharmacol. 2016 May 16; Authors: Song YN, Zhang GB, Lu YY, Chen QL, Yang L, Wang ZT, Liu P, Su SB Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Decoction (HQD), a classical traditional Chinese medicine (TCM) formula, is used to treating liver injury in China. The aim of the study is to investigate mechanisms of HQD against dimethylnitrosamine (DMN)-induced liver fibrosis underlying metabolic profiles of bile acids. MATERIALS AND METHODS: DMN-induced liver fibrosis rats were administrated HQD and its compounds, astragalosides (AS), glycyrrhizic acid (GA) and their combination. The anti-fibrosis effects were evaluated and targeted metabolomics by UPLC-MS was used to examine whether HQD had an influence on bile acid metabolism. The levels of mRNAs associated with bile acid metabolism were expressed by RT-PCR. Chenodeoxycholic acid (CDCA)-induced hepatic stellate cells (HSCs) proliferation and activation were examined using MTS assay and Western blot. RESULTS: Histopathological changes and serum liver function in HQD group had significant improvements (P<0.01). Concentrations of free bile acids and taurine conjugates were significantly increased in DMN group (P<0.05). HQD and its compounds restored the increased bile acids to normal levels, and HQD was more effected on parts of bile acids. Furthermore, the levels of mRNAs related bile acid synthesis and reabsorption such as CYP7A1, CYP8B1, CYP27A1, OATP2, OATP3, OATP4 and NTCP were significantly down-regulated in DMN group (P<0.05), mRNAs related excretion such as MRP3 and BESP were up-regulated (P<0.01), and CYP7A1, CYP8B1, OATP3, OATP4, NTCP and MRP3 restored to normal levels by HQD treatment. Moreover, CDCA-induced HSCs proliferation and activation were weaken by HQD (P<0.05) with down-regulated α-SMA, TGF-β1, p-Smad2 and p-Smad3 expressions. CONCLUSIONS: HQD alleviated DMN-induced liver fibrosis with a better effect than its compounds, which may be involved in the regulation of bile acid metabolism enzyme. Moreover, HQD may inhibit CDCA-induced HSCs proliferation and activation. PMID: 27196295 [PubMed - as supplied by publisher]

Role of metabolism during viral infections, and crosstalk with the innate immune system. Intractable Rare Dis Res. 2016 May;5(2):90-6 Authors: González Plaza JJ, Hulak N, Kausova G, Zhumadilov Z, Akilzhanova A Abstract Viruses have been for long polemic biological particles which stand in the twilight of being living entities or not. As their genome is reduced, they rely on the metabolic machinery of their host in order to replicate and be able to continue with their infection process. The understanding of their metabolic requirements is thus of paramount importance in order to develop tailored drugs to control their population, without affecting the normal functioning of their host. New advancements in high throughput technologies, especially metabolomics are allowing researchers to uncover the metabolic mechanisms of viral replication. In this short review, we present the latest discoveries that have been made in the field and an overview of the intrinsic relationship between metabolism and innate immunity as an important part of the immune system. PMID: 27195191 [PubMed]

Serum Cortisol-to-Cortisone Ratio and Blood Pressure in Severe Obesity before and after Weight Loss. Cardiorenal Med. 2015 Dec;6(1):1-7 Authors: Byrd JB, Rothberg AE, Chomic R, Burant CF, Brook RD, Auchus RJ Abstract BACKGROUND/AIMS: The pathogenesis of obesity-associated hypertension is poorly understood. Serum cortisol-to-cortisone ratio (F/E ratio) is a marker of cortisol metabolism. Our objective was to determine whether the serum F/E ratio is associated with blood pressure (BP) in patients after significant weight loss (≥15% from baseline weight). METHODS: Sera from 43 nondiabetic, severely obese males participating in a weight management program were assayed for F and E by mass spectrometry. We assessed whether changes in the F/E ratio accompanying weight loss correlate with changes in the systolic (SBP) and diastolic BP (DBP). Linear regression was used to evaluate change in the F/E ratio as a predictor of change in BP. RESULTS: The body mass index decreased from 40.8 ± 5.6 to 33.7 ± 4.8 (p < 0.001); also, SBP (133.2 ± 13.8 vs. 124.1 ± 14.3 mm Hg; p < 0.001) and DBP (69.8 ± 8.0 vs. 66.6 ± 9.4 mm Hg; p = 0.026) decreased during the study. The baseline F/E ratio tended to associate with baseline DBP (Spearman's r = -0.29, p = 0.06), and change in the serum F/E ratio correlated with change in DBP (Spearman's r = -0.32, p = 0.036). Change in the F/E ratio also tended to associate with change in SBP (Spearman's r = -0.27, p = 0.08). A multiple linear regression model adjusted for change in the F/E ratio and age explained 22% of the variance in SBP change (R(2) = 0.22, p = 0.007). Change in the F/E ratio independently predicted change in SBP (p = 0.036). CONCLUSION: In our sample of nondiabetic, severely obese males, change in the serum F/E ratio was associated with change in BP after weight loss. PMID: 27194991 [PubMed]

Stepped collisional energy MS(All) : an analytical approach for optimal MS/MS acquisition of complex mixture with diverse physicochemical properties. J Mass Spectrom. 2016 May;51(5):328-41 Authors: Ye H, Wang L, Zhu L, Sun D, Luo X, Wang H, Wang G, Hao H Abstract The analysis of complex mixtures is becoming increasingly important in various fields, such as nutrition, medicinal plants and metabolomics. The components contained in such complex mixtures are always characterized with diverse physiochemical properties that pose a major challenge during the optimization of various parameters using liquid chromatography-mass spectrometer (LC-MS). The parameter 'CE energy' that is normally set at a fixed value with a moderate range of CE spread during data-dependent acquisition (DDA) analysis, a prevalent approach for untargeted identification, often fails to generate sufficient MS/MS fragment ions for untargeted identification of components from complex mixtures. Here we developed a simple and generally applicable acquisition method named stepped MS(All) (sMS(All) ) in this study, aiming to obtain optimal MS/MS spectra for identification of chemically diverse compounds from complex mixtures. sMS(All) collects serial MS(All) scans acquired at low CE to gradually ramped-up high CE values in a cycle that conventional DDA scans cannot afford. The resultant MS/MS spectra of each compound were compared and evaluated among serial MS(All) scans, and the optimal spectra were used for identification. An untargeted data analysis strategy was then employed to analyze these optimal MS/MS spectra by searching common diagnostic ions and connecting the diagnostic ion families into a network via bridging components. This sMS(All) -based route enables identification of 71 natural products from a herbal preparation, whereas only 53 out of 71 compounds were identified using the classical DDA approach. Therefore, the sMS(All) -based approach is expected to find its wide applications for characterization of vastly diverse compounds with no priori knowledge from various complex mixtures. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 27194517 [PubMed - in process]

Efficacy of Fluidized Bed Bioartificial Liver in Treating Fulminant Hepatic Failure in Pigs: A Metabolomics Study. Sci Rep. 2016;6:26070 Authors: Zhou P, Shao L, Zhao L, Lv G, Pan X, Zhang A, Li J, Zhou N, Chen D, Li L Abstract Bioartificial livers may act as a promising therapy for fulminant hepatic failure (FHF) with better accessibility and less injury compared to orthotopic liver transplantation. This study aims to evaluate the efficacy and safety of a fluidized bed bioartificial liver (FBBAL) and to explore its therapeutic mechanisms based on metabolomics. FHF was induced by D-galactosamine. Eighteen hours later, pigs were treated with an FBBAL containing encapsulated primary porcine hepatocytes (B group), with a sham FBBAL (containing cell-free capsules, S group) or with only intensive care (C group) for 6 h. Serum samples were assayed using ultra-performance liquid chromatography-mass spectrometry. The difference in survival time (51.6 ± 7.9 h vs. 49.3 ± 6.6 h) and serum metabolome was negligible between the S and C groups, whereas FBBAL treatment significantly prolonged survival time (70.4 ± 11.5h, P < 0.01) and perturbed the serum metabolome, resulting in a marked decrease in phosphatidylcholines, lysophosphatidylcholines, sphingomyelinase, and fatty acids and an increase in conjugated bile acids. The FBBAL exhibits some liver functions and may exert its therapeutic effect by altering the serum metabolome of FHF pigs. Moreover, alginate-chitosan capsules have less influence on serum metabolites. Nevertheless, the alterations were not universally beneficial, revealing that much should be done to improve the FBBAL. PMID: 27194381 [PubMed - as supplied by publisher]

Related Articles Metabolic profiling reveals altered pattern of central metabolism in navel orange plants as a result of boron deficiency. Physiol Plant. 2015 Apr;153(4):513-24 Authors: Liu G, Dong X, Liu L, Wu L, Peng S, Jiang C Abstract We focused on the changes of metabolite profiles in navel orange plants under long-term boron (B) deficiency using a gas chromatography-mass spectrometry (GC-MS) approach. Curling of the leaves and leaf chlorosis were observed only in the upper leaves (present before start of the treatment) of B-deficient plants, while the lower leaves (grown during treatment) did not show any visible symptoms. The metabolites with up-accumulation in B-deficient leaves were mainly proline, l-ornithine, lysine, glucoheptonic acid, fucose, fumarate, oxalate, quinate, myo-inositol and allo-inositol, while the metabolites with down-accumulation in B-deficient leaves were mainly serine, asparagine, saccharic acid, citrate, succinate, shikimate and phytol. The levels of glucose and fructose were increased only in the upper leaves by B deficiency, while starch content was increased in all the leaves and in roots. The increased levels of malate, ribitol, gluconic acid and glyceric acid occurred only in the lower leaves of B-deficient plants. The increased levels of phenols only in the upper leaves indicated that the effects of B on phenol metabolism in citrus plants may be a consequence of disruptions in leaf structure. Metabolites with opposite reactions in upper and lower leaves were mainly glutamine, glycine and pyrrole-2-carboxylic acid. To our knowledge, the phenomena of allo-inositol even higher than myo-inositol occurred characterized for the first time in this species. These results suggested that the altered pattern of central metabolism may be either specific or adaptive responses of navel orange plants to B deficiency. PMID: 25212059 [PubMed - indexed for MEDLINE]

UHPLC-HR-QTOF-MS based metabolomics reveals key differences between Brachiaria decumbens and B. brizantha, two similar pastures with different toxicity. J Agric Food Chem. 2016 May 18; Authors: Pérez AJ, Hussain SM, Pecio Ł, Kowalczyk M, Rodrigues V, Stochmal A Abstract Several species of Brachiaria (Poaceae) currently cover extensive grazing areas in Brazil, providing valuable source of feed for a large cattle population. However, numerous cases of toxicity outbreaks in livestock have raised concerns on safety of using these plants, especially B. decumbens. In this study, chemometric analysis of UHPLC-HR-QTOF-MS data has for the first time uncovered qualitative and quantitative differences between metabolomes of toxic B. decumbens and non-toxic B. brizantha. The steroidal saponin protoneodioscin was established as the main biomarker for B. decumbens when compared to B. brizantha, and therefore the key explanation for their phytochemical differentiation. Quantification of protodioscin in both plants showed no significant differences, consequently the idea that this compound is solely responsible for toxicity outbreaks must be discarded. Instead, we propose that the added occurrence of its stereoisomer, protoneodioscin, in B. decumbens, can be considered as the probable cause of these events. Interestingly, the greatest concentrations of saponins for both species were reached during winter (B. decumbens = 53.6 ± 5.1 mg·g(-1) D.W.; B. brizantha = 25.0 ± 1.9 mg·g(-1) D:W.) and spring (B. decumbens = 49.4 ± 5.0 mg·g(-1) D.W.; B. brizantha = 27.9 ± 1.4 mg·g(-1) D:W.), although in the case of B. decumbens these values do not vary significantly among seasons. PMID: 27192362 [PubMed - as supplied by publisher]

Related Articles Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort. BMC Med. 2015;13:242 Authors: Fages A, Duarte-Salles T, Stepien M, Ferrari P, Fedirko V, Pontoizeau C, Trichopoulou A, Aleksandrova K, Tjønneland A, Olsen A, Clavel-Chapelon F, Boutron-Ruault MC, Severi G, Kaaks R, Kuhn T, Floegel A, Boeing H, Lagiou P, Bamia C, Trichopoulos D, Palli D, Pala V, Panico S, Tumino R, Vineis P, Bueno-de-Mesquita HB, Peeters PH, Weiderpass E, Agudo A, Molina-Montes E, Huerta JM, Ardanaz E, Dorronsoro M, Sjöberg K, Ohlsson B, Khaw KT, Wareham N, Travis RC, Schmidt JA, Cross A, Gunter M, Riboli E, Scalbert A, Romieu I, Elena-Herrmann B, Jenab M Abstract BACKGROUND: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers. METHODS: To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort. RESULTS: A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis. CONCLUSION: Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer. PMID: 26399231 [PubMed - indexed for MEDLINE]

Related Articles Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain. PLoS One. 2015;10(8):e0136904 Authors: Lieblein-Boff JC, Johnson EJ, Kennedy AD, Lai CS, Kuchan MJ Abstract Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510) were excluded. In addition, moderate correlations with xenobiotic relationships (2) or those driven by single outliers (3) were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development. PMID: 26317757 [PubMed - indexed for MEDLINE]

Related Articles Direct Derivatization vs Aqueous Extraction Methods of Fecal Free Fatty Acids for GC-MS Analysis. Lipids. 2015 Jul;50(7):681-9 Authors: Amer B, Nebel C, Bertram HC, Mortensen G, Dalsgaard TK Abstract A comprehensive and accurate determination of free fatty acids (FFA) is required for fecal metabolomic investigations. The present study compares three aqueous extraction methods (1) ULTRA-TURRAX(®), (2) whirl mixing and (3) basic ULTRA-TURRAX extraction of fecal FFA with a direct derivatization approach using ethyl chloroformate as the derivatization reagent before determination by gas chromatography-mass spectrometry. The direct derivatization method resulted in significantly higher estimations (P < 0.01) of short- and long-chain fatty acids than was the case when applying the aqueous extraction methods using ULTRA-TURRAX, whirl mixing, or basic ULTRA-TURRAX extraction before the derivatization step. Thus, avoiding an aqueous extraction before derivatization reduces the loss of volatile short-chain FFA and the less water-soluble long-chain FFA. PMID: 26007321 [PubMed - indexed for MEDLINE]

44 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 2016/05/18PubMed 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.

(1)H NMR-based metabolite profiling workflow to reduce inter-sample chemical shift variations in urine samples for improved biomarker discovery. Anal Bioanal Chem. 2016 May 13; Authors: Gil RB, Lehmann R, Schmitt-Kopplin P, Heinzmann SS Abstract Metabolite profiling of urine has seen much advancement in recent years, and its analysis by nuclear magnetic resonance (NMR) spectroscopy has become well established. However, the highly variable nature of human urine still requires improved protocols despite some standardization. In particular, diseases such as kidney disease can have a profound effect on the composition of urine and generate a highly diverse sample set for clinical studies. Large variations in pH and the cationic concentration of urine play an important role in creating positional noise within datasets generated from NMR. We demonstrate positional noise to be a confounding variable for multivariate statistical tools such as statistical total correlation spectroscopy (STOCSY), thereby hindering the process of biomarker discovery. We present a two-dimensional buffering system using potassium fluoride (KF) and phosphate buffer to reduce positional noise in metabolomic data generated from urine samples with various levels of proteinuria. KF reduces positional noise in citrate peaks, by decreasing the mean relative standard deviation (RSD) from 0.17 to 0.09. By reducing positional noise with KF, STOCSY analysis of citrate peaks saw significant improvement. We further aligned spectral data using a recursive segment-wise peak alignment (RSPA) method, which leads to further improvement of the positional noise (RSD = 0.06). These results were validated using diverse selection of metabolites which lead to an overall improvement in positional noise using the suggested protocol. In summary, we provide an improved workflow for urine metabolite biomarker discovery to achieve higher data quality for better pathophysiological understanding of human diseases. Graphical abstract Citrate peaks in the range 2.75-2.5 ppm from datasets with different sample preparation protocols and with/without in silico alignment. A Citrate peaks with standard phosphate buffering and without in silico alignment. B citrate peaks with standard phosphate buffering and with in silico alignment. C citrate peak with additional potassium fluoride and standard phosphate buffering without in silico alignment. D citrate peaks with additional potassium fluoride and standard phosphate buffering with in silico alignment. Below the respective spectrum are displayed the percent relative standard deviation (RSD) of the respective citrate peaks. This is a measure of the positional noise of peaks within a (1)H NMR analysis. It can be seen that D performs the best in reducing positional noise of citrate peaks. E-H STOCSY analysis of correlating spectral features with the driver peak at 2.675 ppm (see red arrow) to identify structural correlations. As a, b, c, and d are known to be structurally correlated, STOCSY analysis should reveal r (2) = 1 if data is perfectly aligned and can therefore be used as a measure of peak alignment. E Strong positional noise does not allow identifying the c and d peaks of the AB system to be correlated. F, G Neither in silico alignment or KF addition alone can completely improve the alignment and therefore increase the correlations. H Highly improved alignment by combining both KF addition and in silico alignment reduces positional noise and elucidates all four citrate peaks to be strongly correlated. PMID: 27178551 [PubMed - as supplied by publisher]