PubMed

Related Articles Gene-Diet Interaction and Precision Nutrition in Obesity. Int J Mol Sci. 2017 Apr 07;18(4): Authors: Heianza Y, Qi L Abstract The rapid rise of obesity during the past decades has coincided with a profound shift of our living environment, including unhealthy dietary patterns, a sedentary lifestyle, and physical inactivity. Genetic predisposition to obesity may have interacted with such an obesogenic environment in determining the obesity epidemic. Growing studies have found that changes in adiposity and metabolic response to low-calorie weight loss diets might be modified by genetic variants related to obesity, metabolic status and preference to nutrients. This review summarized data from recent studies of gene-diet interactions, and discussed integration of research of metabolomics and gut microbiome, as well as potential application of the findings in precision nutrition. PMID: 28387720 [PubMed - in process]

Related Articles Elucidating dynamic metabolic physiology through network integration of quantitative time-course metabolomics. Sci Rep. 2017 Apr 07;7:46249 Authors: Bordbar A, Yurkovich JT, Paglia G, Rolfsson O, Sigurjónsson ÓE, Palsson BO Abstract The increasing availability of metabolomics data necessitates novel methods for deeper data analysis and interpretation. We present a flux balance analysis method that allows for the computation of dynamic intracellular metabolic changes at the cellular scale through integration of time-course absolute quantitative metabolomics. This approach, termed "unsteady-state flux balance analysis" (uFBA), is applied to four cellular systems: three dynamic and one steady-state as a negative control. uFBA and FBA predictions are contrasted, and uFBA is found to be more accurate in predicting dynamic metabolic flux states for red blood cells, platelets, and Saccharomyces cerevisiae. Notably, only uFBA predicts that stored red blood cells metabolize TCA intermediates to regenerate important cofactors, such as ATP, NADH, and NADPH. These pathway usage predictions were subsequently validated through (13)C isotopic labeling and metabolic flux analysis in stored red blood cells. Utilizing time-course metabolomics data, uFBA provides an accurate method to predict metabolic physiology at the cellular scale for dynamic systems. PMID: 28387366 [PubMed - in process]

Related Articles Metabolic Response of Visceral White Adipose Tissue of Obese Mice Exposed for 5 Days to Human Room Temperature Compared to Mouse Thermoneutrality. Front Physiol. 2017;8:179 Authors: van der Stelt I, Hoevenaars F, Široká J, de Ronde L, Friedecký D, Keijer J, van Schothorst E Abstract Housing of laboratory mice at room temperature (22°C) might be considered a constant cold stress, which induces a thermogenic program in brown adipose tissue (BAT). However, the early adaptive response of white adipose tissue (WAT), the fat storage organ of the body, to a change from thermoneutrality to room temperature is not known. This was investigated here for various WAT depots, focusing on epididymal WAT (eWAT), widely used as reference depot. Male adult diet-induced obese (DIO) C57BL/6JOlaHsd mice housed at thermoneutrality (29°C), were for 5 days either switched to room temperature (22°C) or remained at thermoneutrality. Energy metabolism was continuously measured using indirect calorimetry. At the end of the study, serum metabolomics and WAT transcriptomics were performed. We confirmed activation of the thermogenic program in 22°C housed mice. Body weight and total fat mass were reduced. Whole body energy expenditure (EE) was increased, with a higher fatty acid to carbohydrate oxidation ratio and increased serum acylcarnitine levels, while energy intake was not significantly different between the two groups. Transcriptome analysis of eWAT identified tissue remodeling and inflammation as the most affected processes. Expression of pro-inflammatory M1 macrophage-related genes, and M1 over M2 macrophage ratio were decreased, which might be linked to an increased insulin sensitivity. Markers of thermogenesis were not altered in eWAT. Decreased expression of tryptophan hydroxylase 2 (Tph2) and cholecystokinin (Cck) might represent altered neuroendocrine signaling. eWAT itself does not show increased fatty acid oxidation. The three measured WATs, epididymal, mesenteric, and retroperitoneal, showed mainly similar responses; reduced inflammation (s100a8), decreased carbohydrate oxidation, and no or small differences in fatty acid oxidation. However, Ucp1 was only expressed and increased in rWAT in 22°C housed mice. Cck expression was decreased in the three WATs, significantly in eWAT and rWAT, in contrast to Tph2, which was decreased in eWAT while not expressed in mWAT and rWAT. Our data show that tissue remodeling, inflammation and neuroendocrine signaling are early responses in WAT to a moderate decrease in environmental temperature. PMID: 28386236 [PubMed - in process]

Related Articles Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity. Nature. 2017 01 05;541(7635):81-86 Authors: Wahl S, Drong A, Lehne B, Loh M, Scott WR, Kunze S, Tsai PC, Ried JS, Zhang W, Yang Y, Tan S, Fiorito G, Franke L, Guarrera S, Kasela S, Kriebel J, Richmond RC, Adamo M, Afzal U, Ala-Korpela M, Albetti B, Ammerpohl O, Apperley JF, Beekman M, Bertazzi PA, Black SL, Blancher C, Bonder MJ, Brosch M, Carstensen-Kirberg M, de Craen AJ, de Lusignan S, Dehghan A, Elkalaawy M, Fischer K, Franco OH, Gaunt TR, Hampe J, Hashemi M, Isaacs A, Jenkinson A, Jha S, Kato N, Krogh V, Laffan M, Meisinger C, Meitinger T, Mok ZY, Motta V, Ng HK, Nikolakopoulou Z, Nteliopoulos G, Panico S, Pervjakova N, Prokisch H, Rathmann W, Roden M, Rota F, Rozario MA, Sandling JK, Schafmayer C, Schramm K, Siebert R, Slagboom PE, Soininen P, Stolk L, Strauch K, Tai ES, Tarantini L, Thorand B, Tigchelaar EF, Tumino R, Uitterlinden AG, van Duijn C, van Meurs JB, Vineis P, Wickremasinghe AR, Wijmenga C, Yang TP, Yuan W, Zhernakova A, Batterham RL, Smith GD, Deloukas P, Heijmans BT, Herder C, Hofman A, Lindgren CM, Milani L, van der Harst P, Peters A, Illig T, Relton CL, Waldenberger M, Järvelin MR, Bollati V, Soong R, Spector TD, Scott J, McCarthy MI, Elliott P, Bell JT, Matullo G, Gieger C, Kooner JS, Grallert H, Chambers JC Abstract Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10(-7), range P = 9.2 × 10(-8) to 6.0 × 10(-46); n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10(-6), range P = 5.5 × 10(-6) to 6.1 × 10(-35), n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 × 10(-54)). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity. PMID: 28002404 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic profiling of breast tumors using ductal fluid. Int J Oncol. 2016 Dec;49(6):2245-2254 Authors: Matos Do Canto L, Marian C, Varghese RS, Ahn J, Da Cunha PA, Willey S, Sidawy M, Rone JD, Cheema AK, Luta G, Nezami Ranjbar MR, Ressom HW, Haddad BR Abstract Identification of new biomarkers for breast cancer remains critical in order to enhance early detection of the disease and improve its prognosis. Towards this end, we performed an untargeted metabolomic analysis of breast ductal fluid using an ultra-performance liquid chromatography coupled with a quadrupole time-of-light (UPLC-QTOF) mass spectrometer. We investigated the metabolomic profiles of breast tumors using ductal fluid samples collected by ductal lavage (DL). We studied fluid from both the affected breasts and the unaffected contralateral breasts (as controls) from 43 women with confirmed unilateral breast cancer. Using this approach, we identified 1560 ions in the positive mode and 538 ions in the negative mode after preprocessing of the UPLC‑QTOF data. Paired t-tests applied on these data matrices identified 209 ions (positive and negative modes combined) with significant change in intensity level between affected and unaffected control breasts (adjusted p-values <0.05). Among these, 83 ions (39.7%) showed a fold change (FC) >1.2 and 66 ions (31.6%) were identified with putative compound names. The metabolites that we identified included endogenous metabolites such as amino acid derivatives (N-Acetyl-DL-tryptophan) or products of lipid metabolism such as N-linoleoyl taurine, trans-2-dodecenoylcarnitine, lysophosphatidylcholine LysoPC(18:2(9Z,12Z)), glycerophospholipids PG(18:0/0:0), and phosphatidylserine PS(20:4(5Z,8Z,11Z,14Z). Generalized LASSO regression further selected 21 metabolites when race, menopausal status, smoking, grade and TNM stage were adjusted for. A predictive conditional logistic regression model, using the LASSO selected 21 ions, provided diagnostic accuracy with the area under the curve of 0.956 (sensitivity/specificity of 0.907/0.884). This is the first study that shows the feasibility of conducting a comprehensive metabolomic profiling of breast tumors using breast ductal fluid to detect changes in the cellular microenvironment of the tumors and shows the potential for this approach to be used to improve detection of breast cancer. PMID: 27748798 [PubMed - indexed for MEDLINE]

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 2017/04/07PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/04/06PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Cord Blood Metabolome Is Highly Associated with Birth Weight, but Less Predictive for Later Weight Development. Obes Facts. 2017 Apr 05;10(2):85-100 Authors: Hellmuth C, Uhl O, Standl M, Demmelmair H, Heinrich J, Koletzko B, Thiering E Abstract BACKGROUND/AIMS: Fetal metabolism may be changed by the exposure to maternal factors, and the route to obesity may already set in utero. Cord blood metabolites might predict growth patterns and later obesity. We aimed to characterize associations of cord blood with birth weight, postnatal weight gain, and BMI in adolescence. METHODS: Over 700 cord blood samples were collected from infants participating in the German birth cohort study LISAplus. Glycerophospholipid fatty acids (GPL-FA), polar lipids, non-esterified fatty acids (NEFA), and amino acids were analyzed with a targeted, liquid chromatography-tandem mass spectrometry based metabolomics platform. Cord blood metabolites were related to growth factors by linear regression models adjusted for confounding variables. RESULTS: Cord blood metabolites were highly associated with birth weight. Lysophosphatidylcholines C16:1, C18:1, C20:3, C18:2, C20:4, C14:0, C16:0, C18:3, GPL-FA C20:3n-9, and GPL-FA C22:5n-6 were positively related to birth weight, while higher cord blood concentrations of NEFA C22:6, NEFA C20:5, GPL-FA C18:3n-3, and PCe C38:0 were associated with lower birth weight. Postnatal weight gain and BMI z-scores in adolescents were not significantly associated with cord blood metabolites after adjustment for multiple testing. CONCLUSION: Potential long-term programming effects of the intrauterine environment and metabolism on later health cannot be predicted with profiling of the cord blood metabolome. PMID: 28376503 [PubMed - as supplied by publisher]

Delineation of molecular pathway activities of the chronic antidepressant treatment response suggests important roles for glutamatergic and ubiquitin-proteasome systems. Transl Psychiatry. 2017 Apr 04;7(4):e1078 Authors: Park DI, Dournes C, Sillaber I, Ising M, Asara JM, Webhofer C, Filiou MD, Müller MB, Turck CW Abstract The aim of this study was to identify molecular pathways related to antidepressant response. We administered paroxetine to the DBA/2J mice for 28 days. Following the treatment, the mice were grouped into responders or non-responders depending on the time they spent immobile in the forced swim test. Hippocampal metabolomics and proteomics analyses revealed that chronic paroxetine treatment affects glutamate-related metabolite and protein levels differentially in the two groups. We found significant differences in the expression of N-methyl-d-aspartate receptor and neuronal nitric oxide synthase proteins between the two groups, without any significant alterations in the respective transcript levels. In addition, we found that chronic paroxetine treatment altered the levels of proteins associated with the ubiquitin-proteasome system (UPS). The soluble guanylate cyclase-β1, proteasome subunit α type-2 and ubiquitination levels were also affected in peripheral blood mononuclear cells from antidepressant responder and non-responder patients suffering from major depressive disorder. We submit that the glutamatergic system and UPS have a crucial role in the antidepressant treatment response in both mice and humans. PMID: 28375208 [PubMed - in process]

Serum Metabolomic Profiles for Human Pancreatic Cancer Discrimination. Int J Mol Sci. 2017 Apr 04;18(4): Authors: Itoi T, Sugimoto M, Umeda J, Sofuni A, Tsuchiya T, Tsuji S, Tanaka R, Tonozuka R, Honjo M, Moriyasu F, Kasuya K, Nagakawa Y, Abe Y, Takano K, Kawachi S, Shimazu M, Soga T, Tomita M, Sunamura M Abstract This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC) from malignant diseases, such as biliary tract cancer (BTC), intraductal papillary mucinous carcinoma (IPMC), and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples (n = 41) of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples (n = 140). Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups (p < 0.05; Steel-Dwass test). Four multiple logistic regression models (MLR) were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC) of 0.970 (95% confidential interval (CI), 0.946-0.994, p < 0.0001). Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650-1.01, p = 0.0020) with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), pancreatic cancer-associated antigen (DUPAN2) and s-pancreas-1 antigen (SPAN1). Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases. PMID: 28375170 [PubMed - in process]

Sialylation is dispensable for early murine embryonic development in vitro. Chembiochem. 2017 Apr 04;: Authors: Abeln M, Borst K, Cajic S, Thiesler H, Kats E, Albers I, Kuhn M, Kaever V, Rapp E, Münster-Kühnel A, Weinhold B Abstract The negatively charged nonulose sialic acid (Sia) is essential for murine development in vivo. To elucidate the impact of sialylation on differentiation processes in the absence of maternal effects, we generated mouse embryonic stem cell (mESC) lines that lack CMP-Sia synthetase (CMAS) and thereby the capacity of activating Sia to CMP-Sia. Loss of CMAS activity resulted in an asialo cell surface, accompanied by an increase in glycoconjugates with terminal galactosyl and oligo-LacNAc residues as well as intracellular accumulation of free Sia. Remarkably, observed changes did neither impact intracellular metabolites nor the morphology and transcriptome of pluripotent mESC lines. Moreover, the capacity of Cmas-/- mESC for undirected differentiation into embryoid bodies, germ layer formation and even generation of beating cardiomyocytes provides first and doubtless evidence that pluripotency and differentiation of mESC in vitro can proceed in the absence of (poly)sialoglycans. PMID: 28374933 [PubMed - as supplied by publisher]

Urine metabolomics in neonates with late-onset sepsis in a case-control study. Sci Rep. 2017 Apr 04;7:45506 Authors: Sarafidis K, Chatziioannou AC, Thomaidou A, Gika H, Mikros E, Benaki D, Diamanti E, Agakidis C, Raikos N, Drossou V, Theodoridis G Abstract Although late-onset sepsis (LOS) is a major cause of neonatal morbidity and mortality, biomarkers evaluated in LOS lack high diagnostic accuracy. In this prospective, case-control, pilot study, we aimed to determine the metabolic profile of neonates with LOS. Urine samples were collected at the day of initial LOS evaluation, the 3(rd) and 10(th) day, thereafter, from 16 septic neonates (9 confirmed and 7 possible LOS cases) and 16 non-septic ones (controls) at respective time points. Urine metabolic profiles were assessed using non-targeted nuclear magnetic resonance spectroscopy and targeted liquid chromatography-tandem mass spectrometry analysis. Multivariate statistical models with data from either analytical approach showed clear separation between the metabolic profiles of septic neonates (both possible and confirmed) and the controls. Metabolic changes appeared to be related to disease progression. Overall, neonates with confirmed or possible LOS exhibited comparable metabolic profiles indicating similar metabolic alternations upon the onset of clinical manifestations. This methodology therefore enabled the discrimination of neonates with LOS from non-septic individuals, providing potential for further research toward the discovery of LOS-related biomarkers. PMID: 28374757 [PubMed - in process]

Related Articles Alzheimer's Disease: Biomarkers in the Genome, Blood, and Cerebrospinal Fluid. Front Neurol. 2017;8:102 Authors: Huynh RA, Mohan C Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder that slowly destroys memory and thinking skills, resulting in behavioral changes. It is estimated that nearly 36 million are affected globally with numbers reaching 115 million by 2050. AD can only be definitively diagnosed at autopsy since its manifestations of senile plaques and neurofibrillary tangles throughout the brain cannot yet be fully captured with current imaging technologies. Current AD therapeutics have also been suboptimal. Besides identifying markers that distinguish AD from controls, there has been a recent drive to identify better biomarkers that can predict the rates of cognitive decline and neocortical amyloid burden in those who exhibit preclinical, prodromal, or clinical AD. This review covers biomarkers of three main types: genes, cerebrospinal fluid-derived, and blood-derived biomarkers. Looking ahead, cutting-edge OMICs technologies, including proteomics and metabolomics, ought to be fully tapped in order to mine even better biomarkers for AD that are more predictive. PMID: 28373857 [PubMed - in process]

Related Articles Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity. Proc Natl Acad Sci U S A. 2017 Apr 03;: Authors: Nagata M, Izumi Y, Ishikawa E, Kiyotake R, Doi R, Iwai S, Omahdi Z, Yamaji T, Miyamoto T, Bamba T, Yamasaki S Abstract Sensing and reacting to tissue damage is a fundamental function of immune systems. Macrophage inducible C-type lectin (Mincle) is an activating C-type lectin receptor that senses damaged cells. Notably, Mincle also recognizes glycolipid ligands on pathogens. To elucidate endogenous glycolipids ligands derived from damaged cells, we fractionated supernatants from damaged cells and identified a lipophilic component that activates reporter cells expressing Mincle. Mass spectrometry and NMR spectroscopy identified the component structure as β-glucosylceramide (GlcCer), which is a ubiquitous intracellular metabolite. Synthetic β-GlcCer activated myeloid cells and induced production of inflammatory cytokines; this production was abrogated in Mincle-deficient cells. Sterile inflammation induced by excessive cell death in the thymus was exacerbated by hematopoietic-specific deletion of degrading enzyme of β-GlcCer (β-glucosylceramidase, GBA1). However, this enhanced inflammation was ameliorated in a Mincle-deficient background. GBA1-deficient dendritic cells (DCs) in which β-GlcCer accumulates triggered antigen-specific T-cell responses more efficiently than WT DCs, whereas these responses were compromised in DCs from GBA1 × Mincle double-deficient mice. These results suggest that β-GlcCer is an endogenous ligand for Mincle and possesses immunostimulatory activity. PMID: 28373578 [PubMed - as supplied by publisher]

Related Articles Nit1 is a metabolite repair enzyme that hydrolyzes deaminated glutathione. Proc Natl Acad Sci U S A. 2017 Apr 03;: Authors: Peracchi A, Veiga-da-Cunha M, Kuhara T, Ellens KW, Paczia N, Stroobant V, Seliga AK, Marlaire S, Jaisson S, Bommer GT, Sun J, Huebner K, Linster CL, Cooper AJ, Van Schaftingen E Abstract The mammalian gene Nit1 (nitrilase-like protein 1) encodes a protein that is highly conserved in eukaryotes and is thought to act as a tumor suppressor. Despite being ∼35% sequence identical to ω-amidase (Nit2), the Nit1 protein does not hydrolyze efficiently α-ketoglutaramate (a known physiological substrate of Nit2), and its actual enzymatic function has so far remained a puzzle. In the present study, we demonstrate that both the mammalian Nit1 and its yeast ortholog are amidases highly active toward deaminated glutathione (dGSH; i.e., a form of glutathione in which the free amino group has been replaced by a carbonyl group). We further show that Nit1-KO mutants of both human and yeast cells accumulate dGSH and the same compound is excreted in large amounts in the urine of Nit1-KO mice. Finally, we show that several mammalian aminotransferases (transaminases), both cytosolic and mitochondrial, can form dGSH via a common (if slow) side-reaction and provide indirect evidence that transaminases are mainly responsible for dGSH formation in cultured mammalian cells. Altogether, these findings delineate a typical instance of metabolite repair, whereby the promiscuous activity of some abundant enzymes of primary metabolism leads to the formation of a useless and potentially harmful compound, which needs a suitable "repair enzyme" to be destroyed or reconverted into a useful metabolite. The need for a dGSH repair reaction does not appear to be limited to eukaryotes: We demonstrate that Nit1 homologs acting as excellent dGSH amidases also occur in Escherichia coli and other glutathione-producing bacteria. PMID: 28373563 [PubMed - as supplied by publisher]

Related Articles Longitudinal analyses of the steroid metabolome in obese PCOS girls with weight loss. Endocr Connect. 2017 Apr 03;: Authors: Reinehr T, Kulle A, Rothermel J, Knop C, Lass N, Bosse C, Holterhus PM Abstract OBJECTIVE: The underlying mechanisms of polycystic ovarian syndrome (PCOS) are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics. DESIGN: This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13-16 years (50% with PCOS) participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI, and change of weight status. METHODS: We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendion-sulfate (DHEA-S), estrone, and estradiol by LC-MS/MS steroid profiling at baseline and one year later. RESULTS: At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, while the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens, and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol, and corticosterone concentrations. Weight loss in obese non PCOS girls was associated with a significant decrease of DHEA-S, cortisol, and corticosterone concentrations, while no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss. CONCLUSIONS: The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, while glucocorticoids, mineralocorticoids, estrogens, and precursors of androgens did not differ between obese girls with and without PCOS. PMID: 28373267 [PubMed - as supplied by publisher]

Related Articles Differential expression of novel metabolic and immunological biomarkers in oysters challenged with a virulent strain of OsHV-1. Dev Comp Immunol. 2017 Mar 31;: Authors: Young T, Kesarcodi-Watson A, Alfaro AC, Merien F, Nguyen TV, Mae H, Le DV, Villas-Bôas S Abstract Early lifestages of the Pacific oyster (Crassostrea gigas) are highly susceptible to infection by OsHV-1 μVar, but little information exists regarding metabolic or pathophysiological responses of larval hosts. Using a metabolomics approach, we identified a range of metabolic and immunological responses in oyster larvae exposed to OsHV-1 μVar; some of which have not previously been reported in molluscs. Multivariate analyses of entire metabolite profiles were able to separate infected from non-infected larvae. Correlation analysis revealed the presence of major perturbations in the underlying biochemical networks and secondary pathway analysis of functionally-related metabolites identified a number of prospective pathways differentially regulated in virus-exposed larvae. These results provide new insights into the pathogenic mechanisms of OsHV-1 infection in oyster larvae, which may be applied to develop disease mitigation strategies and/or as new phenotypic information for selective breeding programmes aiming to enhance viral resistance. PMID: 28373065 [PubMed - as supplied by publisher]

Related Articles Mung bean (Vigna radiata (L.)) coat extract modulates macrophage functions to enhance antigen presentation: A proteomic study. J Proteomics. 2017 Mar 31;: Authors: Hashiguchi A, Hitachi K, Zhu W, Tian J, Tsuchida K, Komatsu S Abstract The immunomodulatory effect of mung bean is mainly attributed to antioxidant properties of flavonoids; however, the precise machinery for biological effect on animal cells remains uncertain. To understand the physiological change produced by mung bean consumption, proteomic and metabolomic techniques were used. In vitro assay confirmed the importance of synergistic interaction among multiple flavonoids by IL-6 expression. Proteomic analysis detected that the abundance of 190 proteins was changed in lipopolysaccharide-stimulated RAW264.7 cells by treatment with coat extract. Pathway mapping revealed that a range of proteins were regulated including an interferon-responsive antiviral enzyme (2'-5'-oligoadenylate synthetase), antigen processing factors (immunoglobulin heavy chain-binding protein and protein disulfide-isomerase), and proteins related to proteasomal degradation. Major histocompatibility complex pathway was activated. These results suggest that mung bean consumption enhances immune response toward a Th2-promoting polarization. BIOLOGICAL SIGNIFICANCE: This study highlighted the immunomodulation of RAW264.7 cells in response to treatment with mung bean seed coat extract, using gel-free proteomic technique. The mechanism of immunomodulation by mung bean has not been described until today except for a report which identified HMGB1 suppression as a pathway underlying the protective effect against sepsis. This study suggested that the mung bean is involved in the regulation of antigen processing and presentation, and thus shifts immune response from acute febrile illness to specific/systemic and long-lasting immunity to protect the host. PMID: 28373035 [PubMed - as supplied by publisher]

Related Articles Targeting aggression in severe mental illness: The predictive role of genetic, epigenetic, and metabolomic markers. Prog Neuropsychopharmacol Biol Psychiatry. 2017 Mar 31;: Authors: Manchia M, Fanos V Abstract Human aggression is a complex and widespread social behavior that is overrepresented in individuals affected by severe mental illness (SMI), such as schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). A substantial proportion of the liability threshold for aggressive behavior is determined by genetic factors, and environmental moderators might facilitate the manifestation of this behavioral phenotype through modification of gene expression via the epigenetic machinery. These specific alterations in the genetic and epigenetic make-up of aggressive individuals might determine specific biochemical modifications detectable through metabolomics. An additional pathophysiological component playing a role in aggressive behavior might be determined by alterations of gut microbiota. Here, we present a selective review of the human data on genetic, epigenetic, and metabolomic markers of aggressive behavior in SMI, discussing also the available evidence on the role of microbiome alterations. Clinical implication of these evidences, as well as future perspectives, will be discussed. PMID: 28372995 [PubMed - as supplied by publisher]

Related Articles Simultaneous metabolomics and lipidomics analysis based on novel heart-cutting two-dimensional liquid chromatography-mass spectrometry. Anal Chim Acta. 2017 May 08;966:34-40 Authors: Wang S, Zhou L, Wang Z, Shi X, Xu G Abstract Increasing metabolite coverage by combining data from different platforms or methods can improve understanding of related metabolic mechanisms and the identification of biomarkers. However, no one method can obtain metabolomic and lipidomic information in a single analysis. In this work, aiming at collecting comprehensive information on metabolome and lipidome in a single analytical run, we developed an on-line heart-cutting two-dimensional liquid chromatography-mass spectrometry (2D-LC-MS) method. Complex metabolites from biological samples are divided into two fractions by using a precolumn. The first fraction is directly transferred and subjected to metabolomics analysis. Most lipids are retained on the precolumn until the mobile phases for lipidomics flow through; then they are subjected to lipidomics analysis. Up to 447 and 289 metabolites in plasma, including amino acids, carnitines, bile acids, free fatty acids, lyso-phospholipids, phospholipids, sphingomyelins etc. were identified within 30 min in the positive mode and negative mode, respectively. A comparison of the newly developed method with the conventional metabolomic and lipidomic approaches showed that approximately 99% features obtained by the two conventional methods can be covered with this 2D-LC method. Analytical characteristics evaluation showed the method had a wide linearity range, high sensitivity, satisfactory recovery and repeatability. These results demonstrate that this method is reliable, stable and well qualified in metabolomics analysis, particularly for large-scale metabolomics studies with small amount of samples. PMID: 28372724 [PubMed - in process]