PubMed

Related Articles Treatment Effects of Ischemic Stroke by Berberine, Baicalin, and Jasminoidin from Huang-Lian-Jie-Du-Decoction (HLJDD) Explored by an Integrated Metabolomics Approach. Oxid Med Cell Longev. 2017;2017:9848594 Authors: Zhang Q, Fu X, Wang J, Yang M, Kong L Abstract Berberine, baicalin, and jasminoidin were major active ingredients of Huang-Lian-Jie-Du-Decoction (HLJDD), a famous prescription of traditional Chinese medicine (TCM), which has been used for the treatment of ischemic stroke. The aim of the present study was to classify their roles in the treatment effects of ischemic stroke. A rat model of middle cerebral artery occlusion (MCAO) was constructed to mimic ischemic stroke and treatment effects of berberine, baicalin, and jasminoidin, and HLJDD was assessed by neurologic deficit scoring, infarct volume, histopathology, immunohistochemistry, biochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. In addition, the (1)H NMR metabolomics approach was used to assess the metabolic profiles, which combined with correlation network analysis successfully revealed metabolic disorders in ischemic stroke concerning the treatment of the three principal compounds from HLJDD for the first time. The combined results suggested that berberine, baicalin, and jasminoidin are responsible for the effectiveness of HLJDD on the treatment of ischemic stroke by amelioration of abnormal metabolism and regulation of oxidative stress, neuron autophagy, and inflammatory response. This integrated metabolomics approach showed its potential in understanding the function of complex formulae and clarifying the role of its components in the overall treatment effects. PMID: 28894512 [PubMed - in process]

Related Articles Effects of Combined Low Glutathione with Mild Oxidative and Low Phosphorus Stress on the Metabolism of Arabidopsis thaliana. Front Plant Sci. 2017;8:1464 Authors: Fukushima A, Iwasa M, Nakabayashi R, Kobayashi M, Nishizawa T, Okazaki Y, Saito K, Kusano M Abstract Plants possess highly sensitive mechanisms that monitor environmental stress levels for a dose-dependent fine-tuning of their growth and development. Differences in plant responses to severe and mild abiotic stresses have been recognized. Although many studies have revealed that glutathione can contribute to plant tolerance to various environmental stresses, little is known about the relationship between glutathione and mild abiotic stress, especially the effect of stress-induced altered glutathione levels on the metabolism. Here, we applied a systems biology approach to identify key pathways involved in the gene-to-metabolite networks perturbed by low glutathione content under mild abiotic stress in Arabidopsis thaliana. We used glutathione synthesis mutants (cad2-1 and pad2-1) and plants overexpressing the gene encoding γ-glutamylcysteine synthetase, the first enzyme of the glutathione biosynthetic pathway. The plants were exposed to two mild stress conditions-oxidative stress elicited by methyl viologen and stress induced by the limited availability of phosphate. We observed that the mutants and transgenic plants showed similar shoot growth as that of the wild-type plants under mild abiotic stress. We then selected the synthesis mutants and performed multi-platform metabolomics and microarray experiments to evaluate the possible effects on the overall metabolome and the transcriptome. As a common oxidative stress response, several flavonoids that we assessed showed overaccumulation, whereas the mild phosphate stress resulted in increased levels of specific kaempferol- and quercetin-glycosides. Remarkably, in addition to a significant increased level of sugar, osmolytes, and lipids as mild oxidative stress-responsive metabolites, short-chain aliphatic glucosinolates over-accumulated in the mutants, whereas the level of long-chain aliphatic glucosinolates and specific lipids decreased. Coordinated gene expressions related to glucosinolate and flavonoid biosynthesis also supported the metabolite responses in the pad2-1 mutant. Our results suggest that glutathione synthesis mutants accelerate transcriptional regulatory networks to control the biosynthetic pathways involved in glutathione-independent scavenging metabolites, and that they might reconfigure the metabolic networks in primary and secondary metabolism, including lipids, glucosinolates, and flavonoids. This work provides a basis for the elucidation of the molecular mechanisms involved in the metabolic and transcriptional regulatory networks in response to combined low glutathione content with mild oxidative and nutrient stress in A. thaliana. PMID: 28894456 [PubMed]

Related Articles A novel swine model for evaluation of dyslipidemia and atherosclerosis induced by human CETP overexpression. Lipids Health Dis. 2017 Sep 11;16(1):169 Authors: Chen T, Sun M, Wang JQ, Cui JJ, Liu ZH, Yu B Abstract BACKGROUND: The mechanism of cholesteryl ester transfer protein (CETP) in lipid metabolism is still unclear. Furthermore, the relationship of CETP and atherosclerosis (AS) has been controversial. As pigs are a good model for both lipid and AS research, we investigated the lipid metabolism of human CETP (hCETP) transgenic pigs and explored the mechanism of CETP in lipid modulation. METHODS: Plasmids expressing the hCETP gene were designed, successfully constructed, and transfected into porcine fetal fibroblasts by liposomes. Using somatic cell nuclear transfer technology and embryonic transfer, hCETP transgenic pigs were generated. After the DNA, RNA, and protein levels were identified, positive hCETP transgenic pigs were selected. Blood samples were collected at different ages to evaluate the phenotypes of biochemical markers, and the metabolomes of plasma samples were analyzed by liquid mass spectrometry. RESULTS: Eight positive hCETP transgenic pigs and five negative cloned pigs were generated by transgenic technology. Finally, five hCETP transgenic and five cloned pigs were grown healthily. After feeding with a normal diet, hCETP transgenic pigs compared with unmodified pigs had no significant differences in body weight, liver function, kidney function, or plasma ions, while total cholesterol and low-density lipoprotein were higher than in unmodified pigs, and high-density lipoprotein was significantly decreased. Metabolomics analysis showed that there were differences in metabolic components between hCETP transgenic pigs, cloned pigs, and unmodified pigs. CONCLUSIONS: In this study, we created hCETP transgenic pigs that could serve as an excellent model for lipid disorders and atherosclerosis. PMID: 28893253 [PubMed - in process]

Related Articles Integrated application of transcriptomics and metabolomics provides insights into glycogen content regulation in the Pacific oyster Crassostrea gigas. BMC Genomics. 2017 Sep 11;18(1):713 Authors: Li B, Song K, Meng J, Li L, Zhang G Abstract BACKGROUND: The Pacific oyster Crassostrea gigas is an important marine fishery resource, which contains high levels of glycogen that contributes to the flavor and the quality of the oyster. However, little is known about the molecular and chemical mechanisms underlying glycogen content differences in Pacific oysters. Using a homogeneous cultured Pacific oyster family, we explored these regulatory networks at the level of the metabolome and the transcriptome. RESULTS: Oysters with the highest and lowest natural glycogen content were selected for differential transcriptome and metabolome analysis. We identified 1888 differentially-expressed genes, seventy-five differentially-abundant metabolites, which are part of twenty-seven signaling pathways that were enriched using an integrated analysis of the interaction between the differentially-expressed genes and the differentially-abundant metabolites. Based on these results, we found that a high expression of carnitine O-palmitoyltransferase 2 (CPT2), indicative of increased fatty acid degradation, is associated with a lower glycogen content. Together, a high level of expression of phosphoenolpyruvate carboxykinase (PEPCK), and high levels of glucogenic amino acids likely underlie the increased glycogen production in high-glycogen oysters. In addition, the higher levels of the glycolytic enzymes hexokinase (HK) and pyruvate kinase (PK), as well as of the TCA cycle enzymes malate dehydrogenase (MDH) and pyruvate carboxylase (PYC), imply that there is a concomitant up-regulation of energy metabolism in high-glycogen oysters. High-glycogen oysters also appeared to have an increased ability to cope with stress, since the levels of the antioxidant glutathione peroxidase enzyme 5 (GPX5) gene were also increased. CONCLUSION: Our results suggest that amino acids and free fatty acids are closely related to glycogen content in oysters. In addition, oysters with a high glycogen content have a greater energy production capacity and a greater ability to cope with stress. These findings will not only provide insights into the molecular mechanisms underlying oyster quality, but also promote research into the molecular breeding of oysters. PMID: 28893177 [PubMed - in process]

Related Articles Protocol for Standardizing High-to-Moderate Abundance Protein Biomarker Assessments Through an MRM-with-Standard-Peptides Quantitative Approach. Adv Exp Med Biol. 2016;919:515-530 Authors: Percy AJ, Yang J, Chambers AG, Mohammed Y, Miliotis T, Borchers CH Abstract Quantitative mass spectrometry (MS)-based approaches are emerging as a core technology for addressing health-related queries in systems biology and in the biomedical and clinical fields. In several 'omics disciplines (proteomics included), an approach centered on selected or multiple reaction monitoring (SRM or MRM)-MS with stable isotope-labeled standards (SIS), at the protein or peptide level, has emerged as the most precise technique for quantifying and screening putative analytes in biological samples. To enable the widespread use of MRM-based protein quantitation for disease biomarker assessment studies and its ultimate acceptance for clinical analysis, the technique must be standardized to facilitate precise and accurate protein quantitation. To that end, we have developed a number of kits for assessing method/platform performance, as well as for screening proposed candidate protein biomarkers in various human biofluids. Collectively, these kits utilize a bottom-up LC-MS methodology with SIS peptides as internal standards and quantify proteins using regression analysis of standard curves. This chapter details the methodology used to quantify 192 plasma proteins of high-to-moderate abundance (covers a 6 order of magnitude range from 31 mg/mL for albumin to 18 ng/mL for peroxidredoxin-2), and a 21-protein subset thereof. We also describe the application of this method to patient samples for biomarker discovery and verification studies. Additionally, we introduce our recently developed Qualis-SIS software, which is used to expedite the analysis and assessment of protein quantitation data in control and patient samples. PMID: 27975233 [PubMed - indexed for MEDLINE]

Related Articles Changes in cellular glycosylation of leukemia cells upon treatment with acridone derivatives yield insight into drug action. Proteomics. 2016 Dec;16(23):2977-2988 Authors: Wang Y, Park D, Galermo AG, Gao D, Liu H, Lebrilla CB Abstract A new acridone derivative 2-aminoacetamido-10-(3, 5-dimethoxy)-benzyl-9(10H)-acridone hydrochloride (8a) has been shown to have potent antitumor activity. In order to understand the underlying action mechanism of 8a, three compounds of the same class with structures optimized step-by-step, 9(10H)-acridone (A), 10-(3,5-dimethoxy) benzyl-9(10H)-acridone (I) and 8a, were exposed to CCRF-CEM leukemia cell to determine the N-glycosylation changes using the microfluidic HPLC-chip-TOF MS platform. N-Glycans from whole cell lysates (WCL) and cell membranes (CM) were analyzed using isomer-sensitive chip-based porous graphitized carbon nano-LC/MS. A total of 223 N-glycan compositions and 398 N-glycan compounds were identified. Comparison of the two analyses showed that more apparent changes were observed in the CM compared with WCL, suggesting that CM may be a more sensitive indicator of changes in glycosylation. Upon 8a exposure to CCRF-CEM cells, a significant decrease in high-mannose-type glycans was observed. Different expressions of oligosaccharyltransferase subunits appear to play a key functional role in regulating the hypoglycosylation and contribute to the action mechanism of 8a. Taken together our findings suggest that glycosylation is strongly affected by therapeutic potency and can be used as possible biomarkers for monitoring toxicity and antitumor activity of 8a. PMID: 27717196 [PubMed - indexed for MEDLINE]

Early Embryogenesis of Brown Alga Fucus vesiculosus L. is Characterized by Significant Changes in Carbon and Energy Metabolism. Molecules. 2017 Sep 09;22(9): Authors: Tarakhovskaya E, Lemesheva V, Bilova T, Birkemeyer C Abstract Brown algae have an important role in marine environments. With respect to their broad distribution and importance for the environment and human use, brown algae of the order Fucales in particular became a model system for physiological and ecological studies. Thus, several fucoids have been extensively studied for their composition on the molecular level. However, research of fucoid physiology and biochemistry so far mostly focused on the adult algae, so a holistic view on the development of these organisms, including the crucial first life stages, is still missing. Therefore, we employed non-targeted metabolite profiling by gas chromatography coupled to mass spectrometry to create a non-biased picture of the early development of the fucoid alga Fucus vesiculosus. We found that embryogenic physiology was mainly dominated by a tight regulation of carbon and energy metabolism. The first dramatic changes of zygote metabolism started within 1 h after fertilization, while metabolism of 6-9 days old embryos appeared already close to that of an adult alga, indicated by the intensive production of secondary metabolites and accumulation of mannitol and citric acid. Given the comprehensive description and analysis we obtained in our experiments, our results exhibit an invaluable resource for the design of further experiments related to physiology of early algal development. PMID: 28891948 [PubMed - in process]

Glycosylated cell surface markers for the isolation of human cardiac progenitors. Stem Cells Dev. 2017 Sep 11;: Authors: Moerkamp AT, Leung HW, Bax NAM, Holst S, Lodder K, Berends T, Dingenouts CKE, Choo ABH, Smits AM, Goumans MJ Abstract The aim of stem cell therapy after cardiac injury is to replace damaged cardiac tissue. Human cardiac progenitor cells (CPCs) represent an interesting cell population for clinical strategies to treat cardiac disease and human CPC-specific antibodies would aid in the clinical implementation of cardiac progenitor based cell therapy. However, the field of CPC biology suffers from the lack of human CPC-specific markers. Therefore, we raised a panel of monoclonal antibodies (mAb) against CPCs Of this panel of antibodies, we show that mAb C1096 recognizes a progenitor-like population in the fetal and adult human heart and partially co-localize with reported CPC populations in vitro. Furthermore, mAb C1096 can be used to isolate a multipotent progenitor population from human heart tissue. Interestingly, the two lead candidates, mAb C1096 and mAb C19, recognize glycosylated residues on PECAM1 and GRP78, respectively, and de-N-glycosylation significantly abolishes their binding. Thereby, this report describes new clinical applicable antibodies against human CPCs, and for the first time demonstrates the importance of glycosylated residues as CPCs specific markers. PMID: 28891400 [PubMed - as supplied by publisher]

A comprehensive narrative review of diagnostic biomarkers in human primary membranous nephropathy. Biomark Med. 2017 Sep 11;: Authors: Kalantari S, Nafar M Abstract Membranous nephropathy (MN) is relatively major cause of nephrotic syndrome in adults which is recognized as an organ-specific autoimmune disease. The etiology of most cases is idiopathic, whereas the secondary MN is caused by systemic autoimmune diseases, infections, medications and malignancies. The idiopathic disease is developed by the formation of sub-epithelial immune complex deposits most likely due to binding the circulating auto-antibodies to intrinsic antigen on podocytes. The major auto antibody is the anti-phospholipase A2 receptor (anti-PLA2R), however, it is not enough sensitive. Several attempts for diagnostic biomarker identification by modern analytical technologies have been devoted recently. This article reviews the biomarker candidates for primary type of MN that are detected by different approaches on human subjects. PMID: 28891307 [PubMed - as supplied by publisher]

Related Articles Navigating freely-available software tools for metabolomics analysis. Metabolomics. 2017;13(9):106 Authors: Spicer R, Salek RM, Moreno P, Cañueto D, Steinbeck C Abstract INTRODUCTION: The field of metabolomics has expanded greatly over the past two decades, both as an experimental science with applications in many areas, as well as in regards to data standards and bioinformatics software tools. The diversity of experimental designs and instrumental technologies used for metabolomics has led to the need for distinct data analysis methods and the development of many software tools. OBJECTIVES: To compile a comprehensive list of the most widely used freely available software and tools that are used primarily in metabolomics. METHODS: The most widely used tools were selected for inclusion in the review by either ≥ 50 citations on Web of Science (as of 08/09/16) or the use of the tool being reported in the recent Metabolomics Society survey. Tools were then categorised by the type of instrumental data (i.e. LC-MS, GC-MS or NMR) and the functionality (i.e. pre- and post-processing, statistical analysis, workflow and other functions) they are designed for. RESULTS: A comprehensive list of the most used tools was compiled. Each tool is discussed within the context of its application domain and in relation to comparable tools of the same domain. An extended list including additional tools is available at https://github.com/RASpicer/MetabolomicsTools which is classified and searchable via a simple controlled vocabulary. CONCLUSION: This review presents the most widely used tools for metabolomics analysis, categorised based on their main functionality. As future work, we suggest a direct comparison of tools' abilities to perform specific data analysis tasks e.g. peak picking. PMID: 28890673 [PubMed]

Related Articles Multivariate strategy for the sample selection and integration of multi-batch data in metabolomics. Metabolomics. 2017;13(10):114 Authors: Surowiec I, Johansson E, Torell F, Idborg H, Gunnarsson I, Svenungsson E, Jakobsson PJ, Trygg J Abstract INTRODUCTION: Availability of large cohorts of samples with related metadata provides scientists with extensive material for studies. At the same time, recent development of modern high-throughput 'omics' technologies, including metabolomics, has resulted in the potential for analysis of large sample sizes. Representative subset selection becomes critical for selection of samples from bigger cohorts and their division into analytical batches. This especially holds true when relative quantification of compound levels is used. OBJECTIVES: We present a multivariate strategy for representative sample selection and integration of results from multi-batch experiments in metabolomics. METHODS: Multivariate characterization was applied for design of experiment based sample selection and subsequent subdivision into four analytical batches which were analyzed on different days by metabolomics profiling using gas-chromatography time-of-flight mass spectrometry (GC-TOF-MS). For each batch OPLS-DA(®) was used and its p(corr) vectors were averaged to obtain combined metabolic profile. Jackknifed standard errors were used to calculate confidence intervals for each metabolite in the average p(corr) profile. RESULTS: A combined, representative metabolic profile describing differences between systemic lupus erythematosus (SLE) patients and controls was obtained and used for elucidation of metabolic pathways that could be disturbed in SLE. CONCLUSION: Design of experiment based representative sample selection ensured diversity and minimized bias that could be introduced at this step. Combined metabolic profile enabled unified analysis and interpretation. PMID: 28890672 [PubMed]

Related Articles Metabolic profiles revealed anti-ischemia-reperfusion injury of Yangxinshi tablet in Rats. J Ethnopharmacol. 2017 Sep 07;: Authors: Zhang H, Zhao Y, Xia Z, Du H, Gao Y, Xue D, Zhu Z, Chai Y Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial ischemia-reperfusion (I/R) injury is a serious injury that is resulted from the recovery of blood supply after myocardial ischemia. Yangxinshi tablet is a compound Chinese herbal preparation and often used to alleviate the myocardial ischemia in clinical, but its protective mechanism of anti-myocardial ischemia reperfusion injury remains unclear. The objective of this study was to evaluate the anti-I/R injury effect of Yangxinshi tablet on a myocardial I/R rat model and to identify serum biomarker metabolites associated with I/R based on ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF/MS) metabolomic method, and explore the metabolic mechanism of anti-I/R injury of Yangxinshi tablet. MATERIALS AND METHODS: Unsupervised principle component analysis highlighted significant differences in the metabolome of the myocardial I/R, healthy control and drug-treated rats. Partial least squares-discriminant analysis revealed 25 metabolites as the most potential biomarker metabolites discriminating the myocardial I/R rats and control rats. Most of the metabolites were primarily involved in oxidative stress, energy metabolism, fatty acid metabolism, amino acid metabolism. These metabolites were validated by assessing the efficacy after intragastric administration of Yangxinshit ablet to the myocardial I/R rat model. RESULTS: Based on metabolomic results, the action mechanism of anti-I/R injury of Yangxinshi tablet was concluded as follows: (1) enhance the ability of scavenging free radicals and reactive oxygen species in vivo; (2) provide energy for myocardium via accelerating the intracellular carnitine transportion to accelerate the oxidation of fatty acid and (3) attenuate ceramide to reduce cardiomyocyte apoptosis. CONCLUSIONS: Yangxinshi tablet has cardio-protection effects on I/R rats via regulation of multiple metabolic pathways involving in oxidative stress, energy metabolism, fatty acid, and amino acid metabolisms. This study will be meaningful for its clinical application and valuable for further exploring the action mechanism of Yangxinshi tablet. PMID: 28889959 [PubMed - as supplied by publisher]

Related Articles α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat Immunol. 2017 Sep;18(9):985-994 Authors: Liu PS, Wang H, Li X, Chao T, Teav T, Christen S, Di Conza G, Cheng WC, Chou CH, Vavakova M, Muret C, Debackere K, Mazzone M, Huang HD, Fendt SM, Ivanisevic J, Ho PC Abstract Glutamine metabolism provides synergistic support for macrophage activation and elicitation of desirable immune responses; however, the underlying mechanisms regulated by glutamine metabolism to orchestrate macrophage activation remain unclear. Here we show that the production of α-ketoglutarate (αKG) via glutaminolysis is important for alternative (M2) activation of macrophages, including engagement of fatty acid oxidation (FAO) and Jmjd3-dependent epigenetic reprogramming of M2 genes. This M2-promoting mechanism is further modulated by a high αKG/succinate ratio, whereas a low ratio strengthens the proinflammatory phenotype in classically activated (M1) macrophages. As such, αKG contributes to endotoxin tolerance after M1 activation. This study reveals new mechanistic regulations by which glutamine metabolism tailors the immune responses of macrophages through metabolic and epigenetic reprogramming. PMID: 28714978 [PubMed - indexed for MEDLINE]

Related Articles Bioavailability of Microencapsulated Iron from Fortified Bread Assessed Using Piglet Model. Nutrients. 2017 Mar 13;9(3): Authors: Bryszewska MA, Laghi L, Zannoni A, Gianotti A, Barone F, Taneyo Saa DL, Bacci ML, Ventrella D, Forni M Abstract The aim of this study was to investigate the influence of oral iron supplementation, in the form of fortified breads, on the growth performance, health, iron status parameters, and fecal metabolome of anemic piglets. A study was conducted on 24 hybrid (Large White × Landrace × Duroc) piglets. From day 44, the post-natal 12 piglets were supplemented with 100 g of one of two experimental breads, each fortified with 21 mg of ferrous sulphate, either encapsulated or not. After one week of oral supplementation, hematological parameters (hematocrit value, hemoglobin, and red blood cells) showed statistically significant differences (p ≤ 0.05). Piglets fed with the fortified breads had higher iron concentrations in the heart, liver, and intestinal mucosa compared to anemic piglets fed with control bread. Gene expression of hepcidin, iron exporter ferroportin (IREG1), and divalent metal transporter 1 (DMT1), together with concentrations of plasma ferritin, showed no significant statistical differences between groups. Both fortified breads could be used as sources of bioavailable iron. The seven-day intervention trial showed microencapsulation to have only a mild effect on the effectiveness of iron supplementation in the form of fortified bread. PMID: 28335378 [PubMed - indexed for MEDLINE]

Related Articles Muscle Sympathetic Nerve Activity Is Associated With Elements of the Plasma Lipidomic Profile in Young Asian Adults. J Clin Endocrinol Metab. 2017 Jun 01;102(6):2059-2068 Authors: Eikelis N, Lambert EA, Phillips S, Sari CI, Mundra PA, Weir JM, Huynh K, Grima MT, Straznicky NE, Dixon JB, Schlaich MP, Meikle PJ, Lambert GW Abstract Background: Asian subjects are at increased cardio-metabolic risk at comparatively lower body mass index (BMI) compared with white subjects. Sympathetic nervous system activation and dyslipidemia, both characteristics of increased adiposity, appear to be related. We therefore analyzed the association of muscle sympathetic nerve activity (MSNA) with the plasma lipidomic profile in young adult Asian and white subjects. Methods: Blood samples were collected from 101 participants of either Asian or white background (age, 18 to 30 years; BMI, 28.1 ± 5.9 kg/m2). Lipids were extracted from plasma and analyzed using electrospray ionization-tandem mass spectrometry. MSNA was quantified using microneurography. The association of MSNA and obesity with lipid species was examined using linear regression analysis. Results: The plasma concentrations of total dihydroceramide, ceramide, GM3 ganglioside, lysoalkylphosphatidylcholine, alkenylphosphatidylethanolamine, and lysophosphatidylinositol were elevated in the Asian subjects relative to the white subjects. After adjustment for confounders, diacylglycerols and triacylglycerols, cholesterol esters, phosphatidylinositols, phosphatidylethanolamines, and phosphatidylglycerols bore significant associations with MSNA but only in the Asian subjects. These associations remained significant after further adjustment for the participants' degree of insulin resistance and appeared not to be related to differences in diet macronutrient content between groups. Conclusions: The lipidomic profile differs between Asian and white subjects. There exists a strong relationship between certain lipid species and MSNA. The association is stronger in Asian subjects, despite their lower BMI. This study demonstrates an association between circulating lipids and central sympathetic outflow. Whether the stronger association between the lipid profile and sympathetic activation underpins the apparent greater risk posed by increased adiposity in Asian individuals merits further attention. PMID: 28323975 [PubMed - indexed for MEDLINE]

Related Articles Randomized Controlled Trial of a MUFA or Fiber-Rich Diet on Hepatic Fat in Prediabetes. J Clin Endocrinol Metab. 2017 May 01;102(5):1765-1774 Authors: Errazuriz I, Dube S, Slama M, Visentin R, Nayar S, O'Connor H, Cobelli C, Das SK, Basu A, Kremers WK, Port J, Basu R Abstract Context: Increased prevalence of type 2 diabetes mellitus and prediabetes worldwide is attributed in part to an unhealthy diet. Objective: To evaluate whether 12 weeks of high monounsaturated fatty acid (MUFA) or fiber-rich weight-maintenance diet lowers hepatic fat and improves glucose tolerance in people with prediabetes. Design: Subjects underwent a [6, 6-2H2]-labeled 75-g oral glucose tolerance test to estimate hepatic insulin sensitivity and liver fat fraction (LFF) using magnetic resonance spectroscopy before and after intervention. Setting: Mayo Clinic Clinical Research Trials Unit. Participants: 43 subjects with prediabetes. Intervention: Subjects were randomized into three isocaloric weight-maintaining diets containing MUFA (olive oil), extra fiber, and standard US food (control-habitual diet). Outcome Measures: LFF, glucose tolerance, and indices of insulin action and secretion. Results: Body weight was maintained constant in all groups during the intervention. Glucose and hormonal concentrations were similar in all groups before, and unchanged after, 12 weeks of intervention. LFF was significantly lower after intervention in the MUFA group (P < 0.0003) but remained unchanged in the fiber (P = 0.25) and control groups (P = 0.45). After 12 weeks, LFF was significantly lower in the MUFA than in the control group (P = 0.01), but fiber and control groups did not differ (P = 0.41). Indices of insulin action and secretion were not significantly different between the MUFA and control groups after intervention (P ≥ 0.11), but within-group comparison showed higher hepatic (P = 0.01) and total insulin sensitivity (P < 0.04) with MUFA. Conclusions: Twelve weeks of a MUFA diet decreases hepatic fat and improves both hepatic and total insulin sensitivity. PMID: 28323952 [PubMed - indexed for MEDLINE]

Related Articles The Bactericidal Lectin RegIIIβ Prolongs Gut Colonization and Enteropathy in the Streptomycin Mouse Model for Salmonella Diarrhea. Cell Host Microbe. 2017 Feb 08;21(2):195-207 Authors: Miki T, Goto R, Fujimoto M, Okada N, Hardt WD Abstract The bactericidal lectin RegIIIβ is inducibly produced by intestinal epithelial cells as a defense against infection by enteropathogens. In the gut lumen, RegIIIβ kills not only certain enteropathogens, but also some commensal bacteria; thus, RegIIIβ is also thought to be an innate immune effector shaping microbiota composition and establishing intestinal homeostasis. Using the streptomycin mouse model for Salmonella colitis, we show that RegIIIβ can promote sustained gut colonization of Salmonella Typhimurium and prolong enteropathy. RegIIIβ expression was associated with suppression of Bacteroides spp. in the gut lumen, prolonged disease-associated alterations in colonic metabolism, and reduced luminal vitamin B6 levels. Supplementation with Bacteroides spp. or vitamin B6 accelerated pathogen clearance from the gut and remission of enteropathy. Our findings indicate that interventions at the level of RegIIIβ and supplementation with Bacteroides spp. or vitamin B6 might open new avenues for therapeutic intervention in the context of Salmonella colitis. PMID: 28111202 [PubMed - indexed for MEDLINE]

Related Articles A rabbit model for assessment of volatile metabolite changes observed from skin: a pressure ulcer case study. J Breath Res. 2017 Jan 09;11(1):016007 Authors: Schivo M, Aksenov AA, Pasamontes A, Cumeras R, Weisker S, Oberbauer AM, Davis CE Abstract Human skin presents a large, easily accessible matrix that is potentially useful for diagnostic applications based on whole body metabolite changes-some of which will be volatile and detected using minimally invasive tools. Unfortunately, identifying skin biomarkers that can be reliably linked to a particular condition is challenging due to a large variability of genetics, dietary intake, and environmental exposures within human populations. This leads to a paucity of clinically validated volatile skin biomarker compounds. Animal models present a very convenient and attractive way to circumvent many of the variability issues. The rabbit (Leporidae) is a potentially logistically useful model to study the skin metabolome, but very limited knowledge of its skin metabolites exists. Here we present the first comprehensive assessment of the volatile fraction of rabbit skin metabolites using polydimethylsiloxane sorbent patch sampling in conjunction with gas chromatography/mass spectrometry. A collection of compounds that are secreted from rabbit skin was documented, and predominantly acyclic long-chain alkyls and alcohols were detected. We then utilized this animal model to study differences between intact skin and skin with early pressure ulcers, as the latter are a major problem in intensive care units. Four New Zealand female white rabbits underwent ulcer formation on one ear with the other ear as a control. Early-stage ulcers were created with neodymium magnets. Histologic analysis showed acute heterophilic dermatitis, edema, and micro-hemorrhage on the ulcerated ears with normal findings on the control ears. The metabolomic analysis revealed subtle but noticeable differences, with several compounds associated with the oxidative stress-related degradation of lipids found to be present in greater abundances in ulcerated ears. The metabolomic findings correlate with histologic evidence of early-stage ulcers. We postulate that the Leporidae model recapitulated the vascular changes associated with ulcer formation. This study illustrates the potential usefulness of the Leporidae model for skin metabolome studies. Additionally, skin metabolome analysis may enhance an understanding of non-skin sources such as urine or breath. PMID: 28068292 [PubMed - indexed for MEDLINE]

A Time for Metabolism and Hormones Book. 2016 Authors: Sassone-Corsi P, Christen Y Abstract A biological “circadian” clock governs nearly all aspects of mammalian behavior and physiology. This control extends from activities of entire organ systems down to individual cells, all of which contain autonomous molecular clocks. Under this control, a significant fraction of the cellular metabolome—the collection of all small-molecule metabolites—varies in abundance according to time of day. Comparing the rhythmic expression of transcripts, proteins, and metabolites has yielded valuable insights into clock-controlled physiological mechanisms. In the future, their analysis could provide a glimpse of instantaneous clock phase, even providing notions of clock time based upon molecules within a single breath. Such knowledge could be important for disease diagnosis and for chronopharmacology. PMID: 28892341

Identification and Quantification of Cyclic Di-Guanosine Monophosphate and Its Linear Metabolites by Reversed-Phase LC-MS/MS. Methods Mol Biol. 2017;1657:45-58 Authors: Bähre H, Kaever V Abstract Cyclic dinucleotides such as bis-(3',5')-cyclic dimeric guanosine monophosphate (3',3'-c-di-GMP) represent an important class of second messengers in bacteria and are involved in numerous (patho)physiological settings. Here, we describe a sensitive and specific quantification method for 3',3'-c-di-GMP by HPLC-coupled tandem mass spectrometry (LC-MS/MS). Additionally, linear 3',3'-c-di-GMP metabolites, i.e., 5'-phosphoguanylyl-3',5'-guanosine (pGpG) and 5'-guanosine monophosphate (5'-GMP), as well as cyclic guanosine monophosphate (3',5'-cGMP) and 3',3' c-di-GMP analogues (2',3'-c-di-GMP and 2',2'-c-di-GMP) can be simultaneously determined by this method. PMID: 28889285 [PubMed - in process]