PubMed

Nitro-fatty acid pharmacokinetics in the adipose tissue compartment. J Lipid Res. 2016 Dec 02;: Authors: Fazzari M, Khoo NK, Woodcock SR, Jorkasky DK, Li L, Schopfer FJ, Freeman BA Abstract Electrophilic nitro-fatty acids (NO2-FAs) promote adaptive and anti-inflammatory cell signaling responses as a result of an electrophilic character that supports post-translational protein modifications. A unique pharmacokinetic profile is expected for NO2-FAs because of an ability to undergo reversible reactions including Michael additions with biological cysteine-containing proteins and esterification into complex lipids. Herein we report via quantitative whole-body autoradiography analysis of rats gavaged with radiolabeled 10-nitro-[14C]oleic acid, preferential accumulation in adipose tissue over two weeks. To better define the metabolism and incorporation of NO2-FAs and their metabolites in adipose tissue lipids, adipocyte cultures were supplemented with 10-nitro-oleic acid (10-NO2-OA), nitro-stearic acid (NO2-SA), nitro-conjugated-linoleic acid (NO2-CLA) and nitro-linolenic acid (NO2-LnA). Then, quantitative HPLC-MS/MS analysis was performed on adipocyte neutral and polar lipid fractions, both before and after acidic hydrolysis of esterified fatty acids. NO2-FAs preferentially incorporated in the monoacyl- and diacyl-glycerides while reduced metabolites were highly enriched in triacylglycerides. This differential distribution profile was confirmed in vivo in the adipose tissue of NO2-OA-treated mice. This pattern of NO2-FA deposition lends new insight into the unique pharmacokinetics and pharmacologic actions that could be expected for this chemically-reactive class of endogenous signaling mediators and synthetic drug candidates. PMID: 27913584 [PubMed - as supplied by publisher]

Metabolomic Characterization of Hepatocellular Carcinoma in Patients with Liver Cirrhosis for Biomarker Discovery. Cancer Epidemiol Biomarkers Prev. 2016 Dec 02;: Authors: Di Poto C, Ferrarini A, Zhao Y, Varghese RS, Tu C, Zuo Y, Wang M, Nezami Ranjbar MR, Luo Y, Zhang C, Desai CS, Shetty K, Tadesse MG, Ressom HW Abstract BACKGROUND: Metabolomics plays an important role in providing insight into the etiology and mechanisms of hepatocellular carcinoma (HCC). This is accomplished by a comprehensive analysis of patterns involved in metabolic alterations in human specimens. This study compares the levels of plasma metabolites in HCC cases versus cirrhotic patients and evaluates the ability of candidate metabolites in distinguishing the two groups. Also, it investigates the combined use of metabolites and clinical covariates for detection of HCC in patients with liver cirrhosis. METHODS: Untargeted analysis of metabolites in plasma from 128 subjects (63 HCC cases and 65 cirrhotic controls) was conducted using gas chromatography coupled to mass spectrometry (GC-MS). This was followed by targeted evaluation of selected metabolites. LASSO regression was used to select a set of metabolites and clinical covariates that are associated with HCC. The performance of candidate biomarkers in distinguishing HCC from cirrhosis was evaluated through a leave-one-out cross-validation based on area under the receiver operating characteristics (ROC) curve. RESULTS: We identified 11 metabolites and three clinical covariates that differentiated HCC cases from cirrhotic controls. Combining these features in a panel for disease classification using support vector machines (SVM) yielded better area under the ROC curve compared to alpha-fetoprotein (AFP). CONCLUSIONS: This study demonstrates the combination of metabolites and clinical covariates as an effective approach for early detection of HCC in patients with liver cirrhosis. IMPACT: Further investigation of these findings may improve understanding of HCC pathophysiology and possible implication of the metabolites in HCC prevention and diagnosis. PMID: 27913395 [PubMed - as supplied by publisher]

To the Editor: Combined immunodeficiency and hypoglycemia associated with mutations in hypoxia up-regulated 1. J Allergy Clin Immunol. 2016 Nov 29;: Authors: Haapaniemi EM, Fogarty CL, Keskitalo S, Katayama S, Vihinen H, Ilander M, Mustjoki S, Krjutškov K, Lehto M, Hautala T, Eriksson O, Jokitalo E, Velagapudi V, Varjosalo M, Seppänen M, Kere J Abstract We describe recessive mutations in hypoxia up-regulated 1 (HYOU1) in a patient that presented with generalized susceptibility to bacterial and herpetic infections as well as hypoglycemic episodes. PMID: 27913302 [PubMed - as supplied by publisher]

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2016/12/03PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2016/12/02PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Comprehensive investigation of tobacco leaves during natural early senescence via multi-platform metabolomics analyses. Sci Rep. 2016 Nov 29;6:37976 Authors: Li L, Zhao J, Zhao Y, Lu X, Zhou Z, Zhao C, Xu G Abstract Senescence is the final stage of leaf growth and development. Many different physiological activities occur during this process. A comprehensive metabolomics analysis of tobacco middle leaves at 5 different developmental stages was implemented through multi-platform methods based on liquid chromatography, capillary electrophoresis and gas chromatography coupled with mass spectrometry. In total, 412 metabolites were identified, including pigments, sterols, lipids, amino acids, polyamines, sugars and secondary metabolites. Dramatic metabolic changes were observed. Firstly, membrane degradation and chlorophyll down-regulation occurred after the 50% flower bud stage. Levels of major membrane lipids decreased, including those of the glycolipids in chloroplast thylakoids and phospholipids in membrane envelopes. Clear decreases in free sterols and acylated sterol glucosides were detected along with the accumulation of sterol esters. The accumulation of alkaloids was found. The amino acid levels were significantly decreased, particularly those of N-rich amino acids (glutamine and asparagine), thus reflecting N translocation. Subsequently, the antioxidant system was activated. Sugar alcohols and polyphenols accumulated when the lower leaves turned yellow. These results comprehensively revealed the metabolic changes that occur during tobacco leaf development and senescence under natural conditions. PMID: 27897248 [PubMed - in process]

Changes in the Membrane-Associated Proteins of Exosomes Released from Human Macrophages after Mycobacterium tuberculosis Infection. Sci Rep. 2016 Nov 29;6:37975 Authors: Diaz G, Wolfe LM, Kruh-Garcia NA, Dobos KM Abstract Tuberculosis (TB) is the deadliest infectious disease worldwide. One obstacle hindering the elimination of TB is our lack of understanding of host-pathogen interactions. Exosomes, naturally loaded with microbial molecules, are circulating markers of TB. Changes in the host protein composition of exosomes from Mycobacterium tuberculosis (Mtb)-infected cells have not been described, can contribute to our understanding of the disease process, and serve as a direct source of biomarkers or as capture targets to enrich for exosomes containing microbial molecules. Here, the protein composition of exosomes from Mtb-infected and uninfected THP-1-derived macrophages was evaluated by tandem-mass-spectrometry and differences in protein abundances were assessed. Our results show that infection with Mtb leads to significant changes in the protein composition of exosomes. Specifically, 41 proteins were significantly more abundant in exosomes from Mtb-infected cells; 63% of these were predicted to be membrane associated. Thus, we used a novel biotinylation strategy to verify protein localization, and confirmed the localization of some of these proteins in the exosomal membrane. Our findings reveal another important scenario where Mtb could be influencing changes in host cells that unveil new features of the host-pathogen interaction and may also be exploited as a source of biomarkers for TB. PMID: 27897233 [PubMed - in process]

Versatile, sensitive liquid chromatography mass spectrometry - Implementation of 10 μm OT columns suitable for small molecules, peptides and proteins. Sci Rep. 2016 Nov 29;6:37507 Authors: Vehus T, Roberg-Larsen H, Waaler J, Aslaksen S, Krauss S, Wilson SR, Lundanes E Abstract We have designed a versatile and sensitive liquid chromatographic (LC) system, featuring a monolithic trap column and a very narrow (10 μm ID) fused silica open tubular liquid chromatography (OTLC) separation column functionalized with C18-groups, for separating a wide range of molecules (from small metabolites to intact proteins). Compared to today's capillary/nanoLC approaches, our system provides significantly enhanced sensitivity (up to several orders) with matching or improved separation efficiency, and highly repeatable chromatographic performance. The chemical properties of the trap column and the analytical column were fine-tuned to obtain practical sample loading capacities (above 2 μg), an earlier bottleneck of OTLC. Using the OTLC system (combined with Orbitrap mass spectrometry), we could perform targeted metabolomics of sub-μg amounts of exosomes with 25 attogram detection limit of a breast cancer-related hydroxylated cholesterol. With the same set-up, sensitive bottom-up proteomics (targeted and untargeted) was possible, and high-resolving intact protein analysis. In contrast to state-of-the-art packed columns, our platform performs chromatography with very little dilution and is "fit-for-all", well suited for comprehensive analysis of limited samples, and has potential as a tool for challenges in diagnostics. PMID: 27897190 [PubMed - in process]

(1)H NMR Metabolomic Profiling of Human and Animal Blood Serum Samples. Methods Mol Biol. 2017;1546:275-282 Authors: Pontes JG, Brasil AJ, Cruz GC, de Souza RN, Tasic L Abstract Nuclear magnetic resonance (NMR) spectroscopy techniques allow the acquisition of a large amount of data and when combined with multivariate statistical analysis, it is possible to process and interpret the obtained NMR data in accordance with the biological problem being investigated. In this chapter, the search for biologically relevant biomarkers is addressed using NMR spectroscopy-based metabolomics, due to their clinical relevance for either diagnosis or monitoring of diseases and disorders. PMID: 27896777 [PubMed - in process]

Multiplex Biomarker Approaches in Type 2 Diabetes Mellitus Research. Methods Mol Biol. 2017;1546:37-55 Authors: Ozanne SE, Rahmoune H, Guest PC Abstract Type 2 diabetes mellitus is a multifactorial condition resulting in high fasting blood glucose levels. Although its diagnosis is straightforward, there is not one set of biomarkers or drug targets that can be used for classification or personalized treatment of individuals who suffer from this condition. Instead, the application of multiplex methods incorporating a systems biology approach is essential in order to increase our understanding of this disease. This chapter reviews the state of the art in biomarker studies of human type 2 diabetes from a proteomic and metabolomic perspective. Our main focus was on biomarkers for disease prediction as these could lead to early intervention strategies for the best possible patient outcomes. PMID: 27896756 [PubMed - in process]

Application of Multiplex Biomarker Approaches to Accelerate Drug Discovery and Development. Methods Mol Biol. 2017;1546:3-17 Authors: Rahmoune H, Guest PC Abstract Multiplex biomarker tests are becoming an essential part of the drug development process. This chapter explores the role of biomarker-based tests as effective tools in improving preclinical research and clinical development, and the challenges that this presents. The potential of incorporating biomarkers in the clinical pipeline to improve decision making, accelerate drug development, improve translation, and reduce development costs is discussed. This chapter also discusses the latest biomarker technologies in use to make this possible and details the next steps that must undertaken to keep driving this process forwards. PMID: 27896754 [PubMed - in process]

High-throughput metabolomics approach reveals new mechanistic insights for drug response of phenotypes of geniposide towards alcohol-induced liver injury by using liquid chromatography coupled to high resolution mass spectrometry. Mol Biosyst. 2016 Nov 29; Authors: Zhang T, Zhang A, Qiu S, Sun H, Han Y, Guan Y, Wang X Abstract Alcohol-induced liver injury (ALD) shows obvious metabolic disorders, categorized by a wide range of metabolite abnormalities. High-throughput metabolomics technology appears to be an appropriate solution. In this study, a urine metabolic profile was assessed using a UPLC-Q-TOF/HDMS (liquid chromatography coupled to high resolution mass spectrometry) approach to investigate the underlying molecular mechanisms of ALD and the therapeutic effect of geniposide. The endogenous low-molecular-weight metabolites in the mouse model of ALD were observed and 48 specific biomarkers were identified. Geniposide was found to have a regulatory effect on 32 of them. Furthermore, targeted analysis of biomarkers showed clear separation between the model and geniposide treatment group. Fifteen biomarkers with high contribution to group differentiation were screened out. Also, a comprehensive analysis of a significant disturbance of multiple metabolic pathways indicated that geniposide could modify abnormal metabolism due to ethanol exposure, during which disorders relating to amino acid metabolism and the oxidative stress state could be alleviated. At the same time, accessory examinations, including plasma biochemical indicators and liver tissue pathological analysis, showed similar results. It was suggested that geniposide was effective as a hepatoprotective agent against ethanol-induced liver damage by re-balancing a wide range of metabolic disorders. PMID: 27896352 [PubMed - as supplied by publisher]

'Omics' and Plant Responses to Botrytis cinerea. Front Plant Sci. 2016;7:1658 Authors: AbuQamar SF, Moustafa K, Tran LP Abstract Botrytis cinerea is a dangerous plant pathogenic fungus with wide host ranges. This aggressive pathogen uses multiple weapons to invade and cause serious damages on its host plants. The continuing efforts of how to solve the "puzzle" of the multigenic nature of B. cinerea's pathogenesis and plant defense mechanisms against the disease caused by this mold, the integration of omic approaches, including genomics, transcriptomics, proteomics and metabolomics, along with functional analysis could be a potential solution. Omic studies will provide a foundation for development of genetic manipulation and breeding programs that will eventually lead to crop improvement and protection. In this mini-review, we will highlight the current progresses in research in plant stress responses to B. cinerea using high-throughput omic technologies. We also discuss the opportunities that omic technologies can provide to research on B. cinerea-plant interactions as an example showing the impacts of omics on agricultural research. PMID: 27895649 [PubMed - in process]

Glycoproteins and glycoproteomics in pancreatic cancer. World J Gastroenterol. 2016 Nov 14;22(42):9288-9299 Authors: Pan S, Brentnall TA, Chen R Abstract Aberrations in protein glycosylation and polysaccharides play a pivotal role in pancreatic tumorigenesis, influencing cancer progression, metastasis, immuno-response and chemoresistance. Abnormal expression in sugar moieties can impact the function of various glycoproteins, including mucins, surface receptors, adhesive proteins, proteoglycans, as well as their effectors and binding ligands, resulting in an increase in pancreatic cancer invasiveness and a cancer-favored microenvironment. Recent advance in glycoproteomics, glycomics and other chemical biology techniques have been employed to better understand the complex mechanism of glycosylation events and how they orchestrate molecular activities in genomics, proteomics and metabolomics implicated in pancreatic adenocarcinoma. A variety of strategies have been demonstrated targeting protein glycosylation and polysaccharides for diagnostic and therapeutic development. PMID: 27895417 [PubMed - in process]

UPLC-QTOF analysis reveals metabolomic changes in the flag leaf of wheat (Triticum aestivum L.) under low-nitrogen stress. Plant Physiol Biochem. 2016 Nov 18;111:30-38 Authors: Zhang Y, Ma XM, Wang XC, Liu JH, Huang BY, Guo XY, Xiong SP, La GX Abstract Wheat is one of the most important grain crop plants worldwide. Nitrogen (N) is an essential macronutrient for the growth and development of wheat and exerts a marked influence on its metabolites. To investigate the influence of low nitrogen stress on various metabolites of the flag leaf of wheat (Triticum aestivum L.), a metabolomic analysis of two wheat cultivars under different induced nitrogen levels was conducted during two important growth periods based on large-scale untargeted metabolomic analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF). Multivariate analyses-such as principle components analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA)-were used for data analysis. PCA yielded distinctive clustering information among the samples, classifying the wheat flag samples into two categories: those under normal N treatment and low N treatment. By processing OPLS-DA, eleven secondary metabolites were shown to be responsible for classifying the two groups. The secondary metabolites may be considered potential biomarkers of low nitrogen stress. Chemical analyses showed that most of the identified secondary metabolites were flavonoids and their related derivatives, such as iso-vitexin, iso-orientin and methylisoorientin-2″-O-rhamnoside, etc. This study confirmed the effect of low nitrogen stress on the metabolism of wheat, and revealed that the accumulation of secondary metabolites is a response to abiotic stresses. Meanwhile, we aimed to identify markers which could be used to monitor the nitrogen status of wheat crops, presumably to guide appropriate fertilization regimens. Furthermore, the UPLC-QTOF metabolic platform technology can be used to study metabolomic variations of wheat under abiotic stresses. PMID: 27894005 [PubMed - as supplied by publisher]

Resistance Training Improves Muscle Function and Cardiometabolic Risks But Not Quality of Life in Older People With Type 2 Diabetes Mellitus: A Randomized Controlled Trial. J Geriatr Phys Ther. 2016 Nov 23; Authors: Hsieh PL, Tseng CH, Tseng YJ, Yang WS Abstract BACKGROUND AND PURPOSE: In older people with type 2 diabetes mellitus (T2DM), the effects of aging and T2DM may compromise the function of skeletal muscle, deteriorate metabolic status, and jeopardize physical performance, aerobic capacity, and quality of life (QoL). The purpose of this study was to investigate the effects of 12 weeks of resistance training (RT) on muscle function, physical performance, cardiometabolic risks, and QoL in older people with T2DM. METHODS: This study was a randomized controlled trial that employed block randomization, assessor blinding, and the intention-to-treat principle. Thirty people 65 years or older with a diagnosis of T2DM were randomly assigned to either an exercise group or a control group and were further stratified by gender. The exercise group performed 8 RT exercises in 3 sets of 8 to 12 repetitions at 75% 1-repetition maximum (1-RM) 3 times per week for 12 weeks. The control group received usual care and maintained their daily activities and lifestyle. Muscle function (1-RM and muscle oxygenation responses), physical performance (5-repetition sit-to-stand test and Timed Up and Go test), cardiometabolic risks (aerobic capacity, blood pressure, body composition, glycemic control, lipids levels, and high-sensitivity C-reactive protein levels), and QoL (Audit of Diabetes-Dependent Quality of Life 19) were assessed at baseline (week 0) and after the 12-week interventions (week 12). RESULTS: The 1-RM chest-press and leg-press strength and physical performance in 5-repetition sit-to-stand test were significantly improved in the exercise group compared with the controls after the interventions. The exercise group had significantly lower resting systolic blood pressure (by -12.1 mm Hg, P = .036) than did the controls after 12 weeks of RT, without any significant within-group change in either group after intervention. The waist circumference, fasting glucose levels, and peak diastolic blood pressure tended to favor RT over usual care after the interventions. CONCLUSION: Twelve weeks of RT increased the maximal strength in chest-press and leg-press tests, and improved 5-repetition sit-to-stand performance in older people with T2DM. Our study demonstrated that supervised, structured RT was able to promote muscle function and alleviate cardiometabolic risks in people with T2DM 65 years or older. PMID: 27893563 [PubMed - as supplied by publisher]

A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2016 Nov 28;: Authors: Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, Chilloux J, Ottman N, Duparc T, Lichtenstein L, Myridakis A, Delzenne NM, Klievink J, Bhattacharjee A, van der Ark KC, Aalvink S, Martinez LO, Dumas ME, Maiter D, Loumaye A, Hermans MP, Thissen JP, Belzer C, de Vos WM, Cani PD Abstract Obesity and type 2 diabetes are associated with low-grade inflammation and specific changes in gut microbiota composition. We previously demonstrated that administration of Akkermansia muciniphila to mice prevents the development of obesity and associated complications. However, the underlying mechanisms of this protective effect remain unclear. Moreover, the sensitivity of A. muciniphila to oxygen and the presence of animal-derived compounds in its growth medium currently limit the development of translational approaches for human medicine. We have addressed these issues here by showing that A. muciniphila retains its efficacy when grown on a synthetic medium compatible with human administration. Unexpectedly, we discovered that pasteurization of A. muciniphila enhanced its capacity to reduce fat mass development, insulin resistance and dyslipidemia in mice. These improvements were notably associated with a modulation of the host urinary metabolomics profile and intestinal energy absorption. We demonstrated that Amuc_1100, a specific protein isolated from the outer membrane of A. muciniphila, interacts with Toll-like receptor 2, is stable at temperatures used for pasteurization, improves the gut barrier and partly recapitulates the beneficial effects of the bacterium. Finally, we showed that administration of live or pasteurized A. muciniphila grown on the synthetic medium is safe in humans. These findings provide support for the use of different preparations of A. muciniphila as therapeutic options to target human obesity and associated disorders. PMID: 27892954 [PubMed - as supplied by publisher]

Metabolic response induced by parasitic plant-fungus interactions hinder amino sugar and nucleotide sugar metabolism in the host. Sci Rep. 2016 Nov 28;6:37434 Authors: Lee DK, Ahn S, Cho HY, Yun HY, Park JH, Lim J, Lee J, Kwon SW Abstract Infestation by the biotrophic pathogen Gymnosporangium asiaticum can be devastating for plant of the family Rosaceae. However, the phytopathology of this process has not been thoroughly elucidated. Using a metabolomics approach, we discovered the intrinsic activities that induce disease symptoms after fungal invasion in terms of microbe-induced metabolic responses. Through metabolic pathway enrichment and mapping, we found that the host altered its metabolite levels, resulting in accumulation of tetrose and pentose sugar alcohols, in response to this fungus. We then used a multiple linear regression model to evaluate the effect of the interaction between this abnormal accumulation of sugar alcohol and the group variable (control/parasitism). The results revealed that this accumulation resulted in deficiency in the supply of specific sugars, which led to a lack of amino sugar and nucleotide sugar metabolism. Halting this metabolism could hamper pivotal functions in the plant host, including cell wall synthesis and lesion repair. In conclusion, our findings indicate that altered metabolic responses that occur during fungal parasitism can cause deficiency in substrates in pivotal pathways and thereby trigger pathological symptoms. PMID: 27892480 [PubMed - in process]

Metabolic signatures of birthweight in 18 288 adolescents and adults. Int J Epidemiol. 2016 Oct;45(5):1539-1550 Authors: Würtz P, Wang Q, Niironen M, Tynkkynen T, Tiainen M, Drenos F, Kangas AJ, Soininen P, Skilton MR, Heikkilä K, Pouta A, Kähönen M, Lehtimäki T, Rose RJ, Kajantie E, Perola M, Kaprio J, Eriksson JG, Raitakari OT, Lawlor DA, Davey Smith G, Järvelin MR, Ala-Korpela M, Auro K Abstract BACKGROUND: Lower birthweight is associated with increased susceptibility to cardiometabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birthweight with a comprehensive metabolic profile measured in adolescents and adults. METHODS: High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts from Finland and the UK, comprising altogether 18 288 individuals (mean age 26 years, range 15-75). Metabolic associations with birthweight were assessed by linear regression models adjusted for sex, gestational age and age at blood sampling. The metabolic associations with birthweight were compared with the corresponding associations with adult body mass index (BMI). RESULTS: Lower birthweight adjusted for gestational age was adversely associated with cardiometabolic biomarkers, including lipoprotein subclasses, fatty acids, amino acids and markers of inflammation and impaired liver function (P < 0.0015 for 46 measures). Associations were consistent across cohorts with different ages at metabolic profiling, but the magnitudes were weak. The pattern of metabolic deviations associated with lower birthweight resembled the metabolic signature of higher adult BMI (R(2) = 0.77) assessed at the same time as the metabolic profiling. The resemblance indicated that 1 kg lower birthweight is associated with similar metabolic aberrations as caused by 0.92 units higher BMI in adulthood. CONCLUSIONS: Lower birthweight adjusted for gestational age is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birthweight and higher adult adiposity suggest that shared molecular pathways may potentially underpin the metabolic deviations. However, the magnitudes of metabolic associations with birthweight are modest in comparison to the effects of adiposity, implying that birthweight is only a weak indicator of the metabolic risk profile in adulthood. PMID: 27892411 [PubMed - in process]

Short-term NO2 exposure is associated with long-chain fatty acids in prospective cohorts from Augsburg, Germany: results from an analysis of 138 metabolites and three exposures. Int J Epidemiol. 2016 Oct;45(5):1528-1538 Authors: Ward-Caviness CK, Breitner S, Wolf K, Cyrys J, Kastenmüller G, Wang-Sattler R, Schneider A, Peters A Abstract BACKGROUND: Short-term exposure to air pollution is associated with morbidity and mortality. Metabolites are intermediaries in biochemical processes, and associations between air pollution and metabolites can yield unique mechanistic insights. METHODS: We used independent cross-sectional samples with targeted metabolomics (138 metabolites across five metabolite classes) from three cohort studies, each a part of the Cooperative Health Research in the Region of Augsburg (KORA). The KORA cohorts are numbered (1 to 4) according to which survey they belong to, and lettered S or F according to whether the survey was a baseline or follow-up survey. KORA F4 (N = 3044) served as our discovery cohort, with KORA S4 (N = 485) serving as the primary replication cohort. KORA F4 and KORA S4 were primarily fasting cohorts. We used the non-fasting KORA F3 (N = 377) cohort to evaluate replicated associations in non-fasting individuals, and we performed a random effects meta-analysis of all three cohorts. Associations between the 0-4-day lags and the 5-day average of particulate matter (PM)2.5, NO2 and ozone were modelled via generalized additive models. All air pollution exposures were scaled to the interquartile range, and effect estimates presented as percent changes relative to the geometric mean of the metabolite concentration (ΔGM). RESULTS: There were 10 discovery cohort associations, of which seven were lysophosphatidylcholines (LPCs); NO2 was the most ubiquitous exposure (5/10). The 5-day average NO2-LPC(28:0) association was associated at a Bonferroni corrected P-value threshold (P < 1.2x10(-4)) in KORA F4 [ΔGM = 11.5%; 95% confidence interval (CI) = 6.60, 16.3], and replicated (P < 0.05) in KORA S4 (ΔGM = 21.0%; CI = 4.56, 37.5). This association was not observed in the non-fasting KORA F3 cohort (ΔGM = -5.96%; CI = -26.3, 14.3), but remained in the random effects meta-analysis (ΔGM = 10.6%; CI = 0.16, 21). CONCLUSIONS: LPCs are associated with short-term exposure to air pollutants, in particular NO2 Further research is needed to understand the effect of nutritional/fasting status on these associations and the causal mechanisms linking air pollution exposure and metabolite profiles. PMID: 27892410 [PubMed - in process]