PubMed

25 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 2017/02/22PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles Dysregulation of Metabolic Pathways in a Mouse Model of Allergic Asthma. Allergy. 2017 Feb 18;: Authors: Quinn KD, Schedel M, Nkrumah-Elie Y, Joetham A, Armstrong M, Cruickshank-Quinn C, Reisdorph R, Gelfand EW, Reisdorph N Abstract BACKGROUND: Asthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function. METHODS: In this experimental model of allergic asthma, matched bronchoalveolar lavage (BAL) fluid and plasma were collected from three groups of C57BL6 mice (control vs sensitized and/or challenged with ovalbumin, n=3-5/group) 6h, 24h, and 48h after the last challenge. Samples were analyzed using liquid chromatography mass spectrometry-based metabolomics. Airway hyperresponsiveness (AHR) measurements and differential cell counts were performed. RESULTS: In total, 398 and 368 dysregulated metabolites in the BAL fluid and plasma of sensitized and challenged mice were identified, respectively. These belonged to four, interconnected pathways relevant to asthma pathogenesis: sphingolipid metabolism (p=6.6x10(-5) ), arginine and proline metabolism (p=1.12x10(-7) ), glycerophospholipid metabolism (p=1.3x10(-10) ), and the neurotrophin signaling pathway (p=7.0x10(-6) ). Furthermore, within the arginine and proline metabolism pathway, a positive correlation between urea-1-carboxyate and AHR was observed in plasma metabolites, while ornithine revealed a reciprocal effect. In addition, agmatine positively correlated with lung eosinophilia. CONCLUSION: These findings point to potential targets and pathways that may be central to asthma pathogenesis and can serve as novel therapeutic targets. This article is protected by copyright. All rights reserved. PMID: 28213886 [PubMed - as supplied by publisher]

Related Articles Prebiotic inulin-type fructans induce specific changes in the human gut microbiota. Gut. 2017 Feb 17;: Authors: Vandeputte D, Falony G, Vieira-Silva S, Wang J, Sailer M, Theis S, Verbeke K, Raes J Abstract OBJECTIVE: Contrary to the long-standing prerequisite of inducing selective (ie, bifidogenic) effects, recent findings suggest that prebiotic interventions lead to ecosystem-wide microbiota shifts. Yet, a comprehensive characterisation of this process is still lacking. Here, we apply 16S rDNA microbiota profiling and matching (gas chromatography mass spectrometry) metabolomics to assess the consequences of inulin fermentation both on the composition of the colon bacterial ecosystem and faecal metabolites profiles. DESIGN: Faecal samples collected during a double-blind, randomised, cross-over intervention study set up to assess the effect of inulin consumption on stool frequency in healthy adults with mild constipation were analysed. Faecal microbiota composition and metabolite profiles were linked to the study's clinical outcome as well as to quality-of-life measurements recorded. RESULTS: While faecal metabolite profiles were not significantly altered by inulin consumption, our analyses did detect a modest effect on global microbiota composition and specific inulin-induced changes in relative abundances of Anaerostipes, Bilophila and Bifidobacterium were identified. The observed decrease in Bilophila abundances following inulin consumption was associated with both softer stools and a favourable change in constipation-specific quality-of-life measures. CONCLUSIONS: Ecosystem-wide analysis of the effect of a dietary intervention with prebiotic inulin-type fructans on the colon microbiota revealed that this effect is specifically associated with three genera, one of which (Bilophila) representing a promising novel target for mechanistic research. TRIAL REGISTRATION NUMBER: NCT02548247. PMID: 28213610 [PubMed - as supplied by publisher]

Related Articles Drug discovery strategies in the field of tumor energy metabolism: Limitations by metabolic flexibility and metabolic resistance to chemotherapy. Biochim Biophys Acta. 2017 Feb 14;: Authors: Amoedo ND, Obre E, Rossignol R Abstract The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro. Such contradictory findings raised several questions concerning the optimization of drug discovery strategies in the field of cancer metabolism. For instance, the cell culture models in 2D or 3D might already show strong limitations to mimic the tumor micro- and macro-environment. The microenvironment of tumors is composed of cancer cells of variegated metabolic profiles, supporting local metabolic exchanges and symbiosis, but also of immune cells and stroma that further interact with and reshape cancer cell metabolism. The macroenvironment includes the different tissues of the organism, capable of exchanging signals and fueling the tumor 'a distance'. Moreover, most metabolic targets were identified from their increased expression in tumor transcriptomic studies, or from targeted analyses looking at the metabolic impact of particular oncogenes or tumor suppressors on selected metabolic pathways. Still, very few targets were identified from in vivo analyses of tumor metabolism in patients because such studies are difficult and adequate imaging methods are only currently being developed for that purpose. For instance, perfusion of patients with [(13)C]-glucose allows deciphering the metabolomics of tumors and opens a new area in the search for effective targets. Metabolic imaging with positron emission tomography and other techniques that do not involve [(13)C] can also be used to evaluate tumor metabolism and to follow the efficiency of a treatment at a preclinical or clinical stage. Relevant descriptors of tumor metabolism are now required to better stratify patients for the development of personalized metabolic medicine. In this review, we discuss the current limitations in basic research and drug discovery in the field of cancer metabolism to foster the need for more clinically relevant target identification and validation. We discuss the design of adapted drug screening assays and compound efficacy evaluation methods for the discovery of innovative anti-cancer therapeutic approaches at the level of tumor energetics. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. PMID: 28213330 [PubMed - as supplied by publisher]

Related Articles A method for the analysis of sugars in biological systems using reductive amination in combination with hydrophilic interaction chromatography and high resolution mass spectrometry. Talanta. 2017 May 01;166:75-80 Authors: Bawazeer S, Muhsen Ali A, Alhawiti A, Khalaf A, Gibson C, Tusiimire J, Watson DG Abstract Separation of sugar isomers extracted from biological samples is challenging because of their natural occurrence as alpha and beta anomers and, in the case of hexoses, in their pyranose and furanose forms. A reductive amination method was developed for the tagging of sugars with the aim of it becoming part of a metabolomics work flow. The best separation of the common hexoses (glucose, fructose, mannose and galactose) was achieved when (2)H5-aniline was used as the tagging reagent in combination with separation on a ZICHILIC column. The method was used to tag a range of sugars including pentoses and uronic acids. The method was simple to perform and was able to improve both the separation of sugars and their response to electrospray ionisation. The method was applied to the profiling of sugars in urine where a number of hexose and pentose isomers could be observed. It was also applied to the quantification of sugars in post-mortem brain samples from three control samples and three samples from individuals who had suffered from bipolar disorder. PMID: 28213261 [PubMed - in process]

Related Articles Epimetabolites: discovering metabolism beyond building and burning. Curr Opin Chem Biol. 2017 Feb 14;36:70-76 Authors: Showalter MR, Cajka T, Fiehn O Abstract Enzymatic transformations of primary, canonical metabolites generate active biomolecules that regulate important cellular and physiological processes. Roles include regulation of histone demethylation in epigenetics, inflammation in tissue injury, insulin sensitivity, cancer cell invasion, stem cell pluripotency status, inhibition of nitric oxide signaling and others. Such modified compounds, defined as epimetabolites, have functions distinct from classic hormones as well as removed from generic anabolism and catabolism. Epimetabolites are discovered by untargeted metabolomics using liquid- or gas chromatography-high resolution mass spectrometry and structurally annotated by in-silico fragmentation prediction tools. Their specific biological functions are subsequently investigated by targeted metabolomics methods. PMID: 28213207 [PubMed - as supplied by publisher]

Related Articles The pathogenesis and pathophysiology of gestational diabetes mellitus: Deductions from a three-part longitudinal metabolomics study in China. Clin Chim Acta. 2017 Feb 14;: Authors: Law KP, Zhang H Abstract Gestational diabetes mellitus (GDM) is a form of diabetes that is first recognised during pregnancy, with no evidence of pre-existing type 1 or type 2 diabetes. The prevalence of GDM has been rising steadily over the past few decades, coinciding with the ongoing epidemic of obesity and type 2 diabetes. Although GDM normally disappears after delivery, women who have been previously diagnosed with GDM are at a greater risk of developing gestational diabetes in subsequent pregnancies, and type 2 diabetes later in life. Infants born to mothers with GDM also have a higher risk of developing type 2 diabetes in their teens or early adulthood. There are many possible causes of insulin resistance, and multiple metabolic aberrants are known to be involved in the development of different forms of diabetes. Increasing evidence suggests that different forms of diabetes share common pathogenesis and pathophysiological dysregulation resulting from a progressive β-cell demise or dysfunction. The outcome manifests clinically as hyperglycaemia. The development of GDM may represent a very early stage of the progression to type 2 diabetes that is being manifested under the stresses of pregnancy. However, the exact mechanisms of GDM development are not clearly understood. Based on the results of a three-part longitudinal metabolomics study of Chinese pregnant women, in combination with the current literature, a new model of GDM development is proposed to outline the biomolecular mechanisms underpinning GDM. A possible cause of GDM is obesity, which is an important clinical risk factor for the development of diabetes. Women who develop GDM generally have higher body mass indices when compared with healthy pregnant women, and obesity can induce low-grade inflammation. Chronic low-grade inflammation induces the synthesis of xanthurenic acid, which is known to be associated with the development of type 2 diabetes, pre-diabetes and GDM. Hyperglycaemia accelerates purine nucleotide synthesis, which in turn stimulates nucleotide breakdown and increases the concentration of nucleotide degradation products, including superoxide molecules and uric acid. Reactive oxygen species and excessive intracellular uric acid may also have direct effects on the development of the disease or further deterioration of the condition. PMID: 28213010 [PubMed - as supplied by publisher]

Related Articles Understanding the response to endurance exercise using a systems biology approach: combining blood metabolomics, transcriptomics and miRNomics in horses. BMC Genomics. 2017 Feb 17;18(1):187 Authors: Mach N, Ramayo-Caldas Y, Clark A, Moroldo M, Robert C, Barrey E, López JM, Le Moyec L Abstract BACKGROUND: Endurance exercise in horses requires adaptive processes involving physiological, biochemical, and cognitive-behavioral responses in an attempt to regain homeostasis. We hypothesized that the identification of the relationships between blood metabolome, transcriptome, and miRNome during endurance exercise in horses could provide significant insights into the molecular response to endurance exercise. For this reason, the serum metabolome and whole-blood transcriptome and miRNome data were obtained from ten horses before and after a 160 km endurance competition. RESULTS: We obtained a global regulatory network based on 11 unique metabolites, 263 metabolic genes and 5 miRNAs whose expression was significantly altered at T1 (post- endurance competition) relative to T0 (baseline, pre-endurance competition). This network provided new insights into the cross talk between the distinct molecular pathways (e.g. energy and oxygen sensing, oxidative stress, and inflammation) that were not detectable when analyzing single metabolites or transcripts alone. Single metabolites and transcripts were carrying out multiple roles and thus sharing several biochemical pathways. Using a regulatory impact factor metric analysis, this regulatory network was further confirmed at the transcription factor and miRNA levels. In an extended cohort of 31 independent animals, multiple factor analysis confirmed the strong associations between lactate, methylene derivatives, miR-21-5p, miR-16-5p, let-7 family and genes that coded proteins involved in metabolic reactions primarily related to energy, ubiquitin proteasome and lipopolysaccharide immune responses after the endurance competition. Multiple factor analysis also identified potential biomarkers at T0 for an increased likelihood for failure to finish an endurance competition. CONCLUSIONS: To the best of our knowledge, the present study is the first to provide a comprehensive and integrated overview of the metabolome, transcriptome, and miRNome co-regulatory networks that may have a key role in regulating the metabolic and immune response to endurance exercise in horses. PMID: 28212624 [PubMed - in process]

18 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 2017/02/18PubMed 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.

Impaired HDL2-mediated cholesterol efflux is associated with metabolic syndrome in families with early onset coronary heart disease and low HDL-cholesterol level. PLoS One. 2017;12(2):e0171993 Authors: Paavola T, Kuusisto S, Jauhiainen M, Kakko S, Kangas-Kontio T, Metso J, Soininen P, Ala-Korpela M, Bloigu R, Hannuksela ML, Savolainen MJ, Salonurmi T Abstract OBJECTIVE: The potential of high-density lipoproteins (HDL) to facilitate cholesterol removal from arterial foam cells is a key function of HDL. We studied whether cholesterol efflux to serum and HDL subfractions is impaired in subjects with early coronary heart disease (CHD) or metabolic syndrome (MetS) in families where a low HDL-cholesterol level (HDL-C) predisposes to early CHD. METHODS: HDL subfractions were isolated from plasma by sequential ultracentrifugation. THP-1 macrophages loaded with acetyl-LDL were used in the assay of cholesterol efflux to total HDL, HDL2, HDL3 or serum. RESULTS: While cholesterol efflux to serum, total HDL and HDL3 was unchanged, the efflux to HDL2 was 14% lower in subjects with MetS than in subjects without MetS (p<0.001). The efflux to HDL2 was associated with components of MetS such as plasma HDL-C (r = 0.76 in men and r = 0.56 in women, p<0.001 for both). The efflux to HDL2 was reduced in men with early CHD (p<0.01) only in conjunction with their low HDL-C. The phospholipid content of HDL2 particles was a major correlate with the efflux to HDL2 (r = 0.70, p<0.001). A low ratio of HDL2 to total HDL was associated with MetS (p<0.001). CONCLUSION: Our results indicate that impaired efflux to HDL2 is a functional feature of the low HDL-C state and MetS in families where these risk factors predispose to early CHD. The efflux to HDL2 related to the phospholipid content of HDL2 particles but the phospholipid content did not account for the impaired efflux in cardiometabolic disease, where a combination of low level and poor quality of HDL2 was observed. PMID: 28207870 [PubMed - in process]

Novel approaches for the taxonomic and metabolic characterization of lactobacilli: Integration of 16S rRNA gene sequencing with MALDI-TOF MS and 1H-NMR. PLoS One. 2017;12(2):e0172483 Authors: Foschi C, Laghi L, Parolin C, Giordani B, Compri M, Cevenini R, Marangoni A, Vitali B Abstract Lactobacilli represent a wide range of bacterial species with several implications for the human host. They play a crucial role in maintaining the ecological equilibrium of different biological niches and are essential for fermented food production and probiotic formulation. Despite the consensus about the 'health-promoting' significance of Lactobacillus genus, its genotypic and phenotypic characterization still poses several difficulties. The aim of this study was to assess the integration of different approaches, genotypic (16S rRNA gene sequencing), proteomic (MALDI-TOF MS) and metabolomic (1H-NMR), for the taxonomic and metabolic characterization of Lactobacillus species. For this purpose we analyzed 40 strains of various origin (intestinal, vaginal, food, probiotics), belonging to different species. The high discriminatory power of MALDI-TOF for species identification was underlined by the excellent agreement with the genotypic analysis. Indeed, MALDI-TOF allowed to correctly identify 39 out of 40 Lactobacillus strains at the species level, with an overall concordance of 97.5%. In the perspective to simplify the MALDI TOF sample preparation, especially for routine practice, we demonstrated the perfect agreement of the colony-picking from agar plates with the protein extraction protocol. 1H-NMR analysis, applied to both culture supernatants and bacterial lysates, identified a panel of metabolites whose variations in concentration were associated with the taxonomy, but also revealed a high intra-species variability that did not allow a species-level identification. Therefore, despite not suitable for mere taxonomic purposes, metabolomics can be useful to correlate particular biological activities with taxonomy and to understand the mechanisms related to the antimicrobial effect shown by some Lactobacillus species. PMID: 28207855 [PubMed - in process]

Vitiligo susceptibility and catalase gene (CAT) polymorphisms in sicilian population. G Ital Dermatol Venereol. 2017 Feb 15;: Authors: Caputo V, Niceta M, Fiorella S, La Vecchia M, Bastonini E, Bongiorno MR, Pistone G Abstract BACKGROUND: Catalase gene (CAT) polymorphisms were analyzed as responsible for the deficiency of catalase enzyme activity and concomitant accumulation of excessive hydrogen peroxide in Vitiligo patients. Catalase is a well known oxidative stress regulator that could play an important role in the pathogenesis of Vitiligo. This study was conducted to evaluate three CAT gene polymorphisms (-89A/T, 389C/T, 419C/T) and their association with Vitiligo susceptibility in Sicilian population. METHODS: 60 out of 73 Sicilian patients with Vitiligo were enrolled and submitted to CAT gene analysis. RESULTS: Contrary to the Northern part of Europe but likewise to the Mediterranean area, the frequency of the CAT genotypes in Sicily is equally distributed. Out of all CAT genotypes, only CAT -89 T/T frequency was found to be significantly higher amongst Vitiligo patients than controls. CONCLUSIONS: Despite the involvement of the CAT enzyme in the pathogenesis of Vitiligo, the biological significance of CAT gene polymorphisms is still controversial. With the only exception for CAT variant -89A/T, the other studied CAT gene polymorphisms (389C/T and 419C/T) might not to be associated with Vitiligo in Sicilian population. PMID: 28206724 [PubMed - as supplied by publisher]

Nickel biopathways in tropical nickel hyperaccumulating trees from Sabah (Malaysia). Sci Rep. 2017 Feb 16;7:41861 Authors: van der Ent A, Callahan DL, Noller BN, Mesjasz-Przybylowicz J, Przybylowicz WJ, Barnabas A, Harris HH Abstract The extraordinary level of accumulation of nickel (Ni) in hyperaccumulator plants is a consequence of specific metal sequestering and transport mechanisms, and knowledge of these processes is critical for advancing an understanding of transition element metabolic regulation in these plants. The Ni biopathways were elucidated in three plant species, Phyllanthus balgooyi, Phyllanthus securinegioides (Phyllanthaceae) and Rinorea bengalensis (Violaceae), that occur in Sabah (Malaysia) on the Island of Borneo. This study showed that Ni is mainly concentrated in the phloem in roots and stems (up to 16.9% Ni in phloem sap in Phyllanthus balgooyi) in all three species. However, the species differ in their leaves - in P. balgooyi the highest Ni concentration is in the phloem, but in P. securinegioides and R. bengalensis in the epidermis and in the spongy mesophyll (R. bengalensis). The chemical speciation of Ni(2+) does not substantially differ between the species nor between the plant tissues and transport fluids, and is unambiguously associated with citrate. This study combines ion microbeam (PIXE and RBS) and metabolomics techniques (GC-MS, LC-MS) with synchrotron methods (XAS) to overcome the drawbacks of the individual techniques to quantitatively determine Ni distribution and Ni(2+) chemical speciation in hyperaccumulator plants. PMID: 28205587 [PubMed - in process]

System-wide detection of protein-small molecule complexes suggests extensive metabolite regulation in plants. Sci Rep. 2017 Feb 13;7:42387 Authors: Veyel D, Kierszniowska S, Kosmacz M, Sokolowska EM, Michaelis A, Luzarowski M, Szlachetko J, Willmitzer L, Skirycz A Abstract Protein small molecule interactions are at the core of cell regulation controlling metabolism and development. We reasoned that due to the lack of system wide approaches only a minority of those regulatory molecules are known. In order to see whether or not this assumption is true we developed an effective approach for the identification of small molecules having potential regulatory role that obviates the need of protein or small molecule baits. At the core of this approach is a simple biochemical co-fractionation taking advantage of size differences between proteins and small molecules. Metabolomics based analysis of small molecules co-fractionating with proteins identified a multitude of small molecules in Arabidopsis suggesting the existence of numerous, small molecules/metabolites bound to proteins representing potential regulatory molecules. The approach presented here uses Arabidopsis cell cultures, but is generic and hence applicable to all biological systems. PMID: 28205532 [PubMed - in process]

Related Articles Clinical Phenotyping of Heart Failure with Biomarkers: Current and Future Perspectives. Curr Heart Fail Rep. 2017 Feb 15;: Authors: Senthong V, Kirsop JL, Tang WH Abstract INTRODUCTION: Heart failure (HF) is a complex clinical syndrome with diverse risk factors and etiologies, differing underlying pathophysiology, and large phenotypic heterogeneity. RECENT FINDINGS: Advances in imaging techniques coupled with clinical trials that targeted only in those with impaired left ventricular ejection fraction (LVEF) have largely shaped the current management strategy for HF that focuses predominantly in patients with systolic HF. In contrast, there are no effective treatments for HF with preserved ejection fraction (HFpEF). Instead of this "one-size-fits-all" approach to treatment, better precision to define HF phenotypic classifications may lead to more efficient and effective HF disease management. CONCLUSION: Integrating variables-including clinical variables, HF biomarkers, imaging, genotypes, metabolomics, and proteomics-can identify different pathophysiologies, lead to more precise phenotypic classification, and warrant investigation in future clinical trials. PMID: 28205040 [PubMed - as supplied by publisher]

Related Articles Sunlight Modulates Fruit Metabolic Profile and Shapes the Spatial Pattern of Compound Accumulation within the Grape Cluster. Front Plant Sci. 2017;8:70 Authors: Reshef N, Walbaum N, Agam N, Fait A Abstract Vineyards are characterized by their large spatial variability of solar irradiance (SI) and temperature, known to effectively modulate grape metabolism. To explore the role of sunlight in shaping fruit composition and cluster uniformity, we studied the spatial pattern of incoming irradiance, fruit temperature and metabolic profile within individual grape clusters under three levels of sunlight exposure. The experiment was conducted in a vineyard of Cabernet Sauvignon cv. located in the Negev Highlands, Israel, where excess SI and midday temperatures are known to degrade grape quality. Filtering SI lowered the surface temperature of exposed fruits and increased the uniformity of irradiance and temperature in the cluster zone. SI affected the overall levels and patterns of accumulation of sugars, organic acids, amino acids and phenylpropanoids, across the grape cluster. Increased exposure to sunlight was associated with lower accumulation levels of malate, aspartate, and maleate but with higher levels of valine, leucine, and serine, in addition to the stress-related proline and GABA. Flavan-3-ols metabolites showed a negative response to SI, whereas flavonols were highly induced. The overall levels of anthocyanins decreased with increased sunlight exposure; however, a hierarchical cluster analysis revealed that the members of this family were grouped into three distinct accumulation patterns, with malvidin anthocyanins and cyanidin-glucoside showing contrasting trends. The flavonol-glucosides, quercetin and kaempferol, exhibited a logarithmic response to SI, leading to improved cluster uniformity under high-light conditions. Comparing the within-cluster variability of metabolite accumulation highlighted the stability of sugars, flavan-3-ols, and cinnamic acid metabolites to SI, in contrast to the plasticity of flavonols. A correlation-based network analysis revealed that extended exposure to SI modified metabolic coordination, increasing the number of negative correlations between metabolites in both pulp and skin. This integrated study of micrometeorology and metabolomics provided insights into the grape-cluster pattern of accumulation of 70 primary and secondary metabolites as a function of spatial variations in SI. Studying compound-specific responses against an extended gradient of quantified conditions improved our knowledge regarding the modulation of berry metabolism by SI, with the aim of using sunlight regulation to accurately modulate fruit composition in warm and arid/semi-arid regions. PMID: 28203242 [PubMed - in process]

Related Articles Gut Microbiota Promotes Obesity-Associated Liver Cancer through PGE2-Mediated Suppression of Antitumor Immunity. Cancer Discov. 2017 Feb 15;: Authors: Loo TM, Kamachi F, Watanabe Y, Yoshimoto S, Kanda H, Arai Y, Nakajima-Takagi Y, Iwama A, Koga T, Sugimoto Y, Ozawa T, Nakamura M, Kumagai M, Watashi K, Taketo MM, Aoki T, Narumiya S, Oshima M, Arita M, Hara E, Ohtani N Abstract Obesity increases the risk of cancers, including hepatocellular carcinomas (HCCs). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment. LTA enhances the senescence-associated secretory phenotype (SASP) of hepatic stellate cells (HSCs) collaboratively with an obesity-induced gut microbial metabolite, deoxycholic acid (DCA) to upregulate the expression of SASP factors and cyclooxygenase-2 (COX-2) through Toll-like receptor (TLR) 2. Interestingly, COX-2-mediated prostaglandin E2 (PGE2) production suppresses the antitumor immunity through EP4 receptor, thereby contributing to HCC progression. Moreover, COX-2 overexpression and excess PGE2 production were detected in HSCs in human HCCs with non-cirrhotic, non-alcoholic steatohepatitis (NASH), indicating that a similar mechanism could function in humans. PMID: 28202625 [PubMed - as supplied by publisher]

Related Articles Recurrent patterns of DNA copy number alterations in tumors reflect metabolic selection pressures. Mol Syst Biol. 2017 Feb 15;13(2):914 Authors: Graham NA, Minasyan A, Lomova A, Cass A, Balanis NG, Friedman M, Chan S, Zhao S, Delgado A, Go J, Beck L, Hurtz C, Ng C, Qiao R, Ten Hoeve J, Palaskas N, Wu H, Müschen M, Multani AS, Port E, Larson SM, Schultz N, Braas D, Christofk HR, Mellinghoff IK, Graeber TG Abstract Copy number alteration (CNA) profiling of human tumors has revealed recurrent patterns of DNA amplifications and deletions across diverse cancer types. These patterns are suggestive of conserved selection pressures during tumor evolution but cannot be fully explained by known oncogenes and tumor suppressor genes. Using a pan-cancer analysis of CNA data from patient tumors and experimental systems, here we show that principal component analysis-defined CNA signatures are predictive of glycolytic phenotypes, including (18)F-fluorodeoxy-glucose (FDG) avidity of patient tumors, and increased proliferation. The primary CNA signature is enriched for p53 mutations and is associated with glycolysis through coordinate amplification of glycolytic genes and other cancer-linked metabolic enzymes. A pan-cancer and cross-species comparison of CNAs highlighted 26 consistently altered DNA regions, containing 11 enzymes in the glycolysis pathway in addition to known cancer-driving genes. Furthermore, exogenous expression of hexokinase and enolase enzymes in an experimental immortalization system altered the subsequent copy number status of the corresponding endogenous loci, supporting the hypothesis that these metabolic genes act as drivers within the conserved CNA amplification regions. Taken together, these results demonstrate that metabolic stress acts as a selective pressure underlying the recurrent CNAs observed in human tumors, and further cast genomic instability as an enabling event in tumorigenesis and metabolic evolution. PMID: 28202506 [PubMed - in process]

Related Articles An integrative metabolomics and transcriptomics study to identify metabolic alterations in aged skin of humans in vivo. BMC Genomics. 2017 Feb 15;18(1):169 Authors: Kuehne A, Hildebrand J, Soehle J, Wenck H, Terstegen L, Gallinat S, Knott A, Winnefeld M, Zamboni N Abstract BACKGROUND: Aging human skin undergoes significant morphological and functional changes such as wrinkle formation, reduced wound healing capacity, and altered epidermal barrier function. Besides known age-related alterations like DNA-methylation changes, metabolic adaptations have been recently linked to impaired skin function in elder humans. Understanding of these metabolic adaptations in aged skin is of special interest to devise topical treatments that potentially reverse or alleviate age-dependent skin deterioration and the occurrence of skin disorders. RESULTS: We investigated the global metabolic adaptions in human skin during aging with a combined transcriptomic and metabolomic approach applied to epidermal tissue samples of young and old human volunteers. Our analysis confirmed known age-dependent metabolic alterations, e.g. reduction of coenzyme Q10 levels, and also revealed novel age effects that are seemingly important for skin maintenance. Integration of donor-matched transcriptome and metabolome data highlighted transcriptionally-driven alterations of metabolism during aging such as altered activity in upper glycolysis and glycerolipid biosynthesis or decreased protein and polyamine biosynthesis. Together, we identified several age-dependent metabolic alterations that might affect cellular signaling, epidermal barrier function, and skin structure and morphology. CONCLUSIONS: Our study provides a global resource on the metabolic adaptations and its transcriptional regulation during aging of human skin. Thus, it represents a first step towards an understanding of the impact of metabolism on impaired skin function in aged humans and therefore will potentially lead to improved treatments of age related skin disorders. PMID: 28201987 [PubMed - in process]

Related Articles 2015 Information Processing in Cells and Tissues (IPCAT 2015). Biosystems. 2016 Aug;146:1-2 Authors: Tyrrell AM, Lones MA, Smith SL, Fogel GB PMID: 27616167 [PubMed - indexed for MEDLINE]