PubMed

Omics studies for comprehensive understanding of immunoglobulin A nephropathy: state-of-the-art and future directions. Nephrol Dial Transplant. 2018 Jun 13;: Authors: Schena FP, Serino G, Sallustio F, Falchi M, Cox SN Abstract Immunoglobulin A nephropathy (IgAN) is the most common worldwide primary glomerulonephritis with a strong autoimmune component. The disease shows variability in both clinical phenotypes and endpoints and can be potentially subdivided into more homogeneous subtypes through the identification of specific molecular biomarkers. This review focuses on the role of omics in driving the identification of potential molecular subtypes of the disease through the integration of multilevel data from genomics, transcriptomics, epigenomics, proteomics and metabolomics. First, the identification of molecular biomarkers, including mapping of the full spectrum of common and rare IgAN risk alleles, could permit a more precise stratification of IgAN patients. Second, the analysis of transcriptomic patterns and their modulation by epigenetic factors like microRNAs has the potential to increase our understanding in the pathogenic mechanisms of the disease. Third, the specificity of urinary proteomic and metabolomic signatures and the understanding of their functional relevance may contribute to the development of new non-invasive biomarkers for a better molecular characterization of the renal damage and its follow-up. All these approaches can give information for targeted therapeutic decisions and will support novel clinical decision making. In conclusion, we offer a framework of omic studies and outline barriers and potential solutions that should be used for improving the diagnosis and treatment of the disease. The ongoing decade is exploiting novel high-throughput molecular technologies and computational analyses for improving the diagnosis (precision nephrology) and treatment (personalized therapy) of the IgAN subtypes. PMID: 29905852 [PubMed - as supplied by publisher]

Untargeted Profiling of Concordant/Discordant Phenotypes of High Insulin Resistance and Obesity To Predict the Risk of Developing Diabetes. J Proteome Res. 2018 Jun 15;: Authors: Marco-Ramell A, Tulipani S, Palau-Rodriguez M, Gonzalez-Dominguez R, Miñarro A, Jauregui O, Sanchez-Pla A, Macias-Gonzalez M, Cardona F, Tinahones FJ, Andres-Lacueva C Abstract This study explores the metabolic profiles of concordant/discordant phenotypes of high insulin resistance (IR) and obesity. Through untargeted metabolomics (LC-ESI-QTOF-MS), we analyzed the fasting serum of subjects with high IR and/or obesity ( n = 64). An partial least-squares discriminant analysis with orthogonal signal correction followed by univariate statistics and enrichment analysis allowed exploration of these metabolic profiles. A multivariate regression method (LASSO) was used for variable selection and a predictive biomarker model to identify subjects with high IR regardless of obesity was built. Adrenic acid and a dyglyceride (DG) were shared by high IR and obesity. Uric and margaric acids, 14 DGs, ketocholesterol, and hydroxycorticosterone were unique to high IR, while arachidonic, hydroxyeicosatetraenoic (HETE), palmitoleic, triHETE, and glycocholic acids, HETE lactone, leukotriene B4, and two glutamyl-peptides to obesity. DGs and adrenic acid differed in concordant/discordant phenotypes, thereby revealing protective mechanisms against high IR also in obesity. A biomarker model formed by DGs, uric and adrenic acids presented a high predictive power to identify subjects with high IR [AUC 80.1% (68.9-91.4)]. These findings could become relevant for diabetes risk detection and unveil new potential targets in therapeutic treatments of IR, diabetes, and obesity. An independent validated cohort is needed to confirm these results. PMID: 29905079 [PubMed - as supplied by publisher]

Metabolomics Profiling of Serum and Urine in Three Beef Cattle Breeds Revealed Different Levels of Tolerance to Heat Stress. J Agric Food Chem. 2018 Jun 15;: Authors: Liao Y, Hu R, Wang Z, Peng Q, Dong X, Zhang X, Zou H, Pu Q, Xue B, Wang L Abstract This study was to determine differences in the global metabolic profiles of serum and urine of Xuanhan yellow cattle, Simmental crossbred cattle (Simmental × Xuanhan yellow cattle) and cattle-yaks (Jersey × Maiwa yak) under heat stress (temperature-humidity index remained above 80 for 1 week). A total of 55 different metabolites associated with the three breeds were identified in the serum and urine samples by gas chromatography-mass spectrometry. The metabolic adaptations to heat stress are heterogeneous. Cattle-yaks mobilize a greater amount of body protein to release glucogenic amino acids to supply energy, whereas the tricarboxylic acid cycle is inhibited. Simmental crossbred cattle mobilize a greater amount of body fat to use free fatty acids as an energy source. In comparison with Simmental crossbred cattle and cattle-yaks, Xuanhan yellow cattle have higher glycolytic activity, and possess a stronger antioxidant defense system and are, in conclusion, more adapted to hot and humid environments. PMID: 29905066 [PubMed - as supplied by publisher]

Related Articles Metabolomic and transcriptomic data on major metabolic/biosynthetic pathways in workers and soldiers of the termite Prorhinotermes simplex (Isoptera: Rhinotermitidae) and chemical synthesis of intermediates of defensive (E)-nitropentadec-1-ene biosynthesis. Data Brief. 2018 Jun;18:1614-1627 Authors: Jirošová A, Jančařík A, Menezes RC, Bazalová O, Dolejšová K, Vogel H, Jedlička P, Buček A, Brabcová J, Majer P, Hanus R, Svatoš A Abstract Production of nitro compounds has only seldom been recorded in arthropods. The aliphatic nitroalkene (E)-nitropentadec-1-ene (NPD), identified in soldiers of the termite genus Prorhinotermes, was the first case documented in insects in early seventies. Yet, the biosynthetic origin of NPD has long remained unknown. We previously proposed that NPD arises through the condensation of amino acids glycine and/or l-serine with tetradecanoic acid along a biosynthetic pathway analogous to the formation of sphingolipids. Here, we provide a metabolomics and transcriptomic data of the Prorhinotermes simplex termite workers and soldiers. Data are related to NPD biosynthesis in P. simplex soldiers. Original metabolomics data were deposited in MetaboLights metabolomics database and are become publicly available after publishing the original article. Additionally, chemical synthesis of biosynthetic intermediates of NPD in nonlabeled and stable labeled forms are reported. Data extend our poor knowledge of arthropod metabolome and transcriptome and would be useful for comparative study in termites or other arthropods. The data were used for de-replication of NPD biosynthesis and published separately (Jirošová et al., 2017) [1]. PMID: 29904664 [PubMed]

Related Articles Oleocanthal-rich extra virgin olive oil demonstrates acute anti-platelet effects in healthy men in a randomized trial. J Funct Foods. 2017 Sep;36:84-93 Authors: Agrawal K, Melliou E, Li X, Pedersen TL, Wang SC, Magiatis P, Newman JW, Holt RR Abstract The phenolic profiles of extra virgin olive oils (EVOOs) may influence their cardiovascular benefits. In a randomized crossover of acute EVOO intake on platelet function, participants (n=9) consumed 40 mL of EVOO weekly. EVOOs were matched for total phenolic content and were either tyrosol-poor with 1:2 oleacein/oleocanthal (D2i0.5), or 2:1 oleacein/oleocanthal (D2i2), or predominantly tyrosol (D2i0). Ibuprofen provided a platelet inhibition control. Blood was collected pre- and 2 hr post-EVOO intake. D2i0.5 and D2i2 reduced 1 µg/mL collagen-stimulated maximum platelet aggregation (Pmax), with effects best correlated to oleocanthal intake (R=0.56, P=0.002). Total phenolic intake was independently correlated to eicosanoid production inhibition, suggesting that cyclooxygenase blockade was not responsible for the Pmax inhibition. Five participants exhibited >25% ΔPmax declines with D2i0.5 and D2i2 intake and plasma metabolomic profiles discriminated subjects by oil responsivity. Platelet responses to acute EVOO intake are associated with oil phenolic composition and may be influenced by diet. PMID: 29904393 [PubMed]

Related Articles Medium-Chain Fatty Acids, Beta-Hydroxybutyric Acid and Genetic Modulation of the Carnitine Shuttle Are Protective in a Drosophila Model of ALS Based on TDP-43. Front Mol Neurosci. 2018;11:182 Authors: Manzo E, O'Conner AG, Barrows JM, Shreiner DD, Birchak GJ, Zarnescu DC Abstract ALS patients exhibit dyslipidemia, hypermetabolism and weight loss; in addition, cellular energetics deficits have been detected prior to denervation. Although evidence that metabolism is altered in ALS is compelling, the mechanisms underlying metabolic dysregulation and the contribution of altered metabolic pathways to disease remain poorly understood. Here we use a Drosophila model of ALS based on TDP-43 that recapitulates hallmark features of the disease including locomotor dysfunction and reduced lifespan. We performed a global, unbiased metabolomic profiling of larvae expressing TDP-43 (wild-type, TDPWT or disease-associated mutant, TDPG298S) and identified several lipid metabolism associated alterations. Among these, we found a significant increase in carnitine conjugated long-chain fatty acids and a significant decrease in carnitine, acetyl-carnitine and beta-hydroxybutyrate, a ketone precursor. Taken together these data suggest a deficit in the function of the carnitine shuttle and reduced lipid beta oxidation. To test this possibility we used a combined genetic and dietary approach in Drosophila. Our findings indicate that components of the carnitine shuttle are misexpressed in the context of TDP-43 proteinopathy and that genetic modulation of CPT1 or CPT2 expression, two core components of the carnitine shuttle, mitigates TDP-43 dependent locomotor dysfunction, in a variant dependent manner. In addition, feeding medium-chain fatty acids or beta-hydroxybutyrate improves locomotor function, consistent with the notion that bypassing the carnitine shuttle deficit is neuroprotective. Taken together, our findings highlight the potential contribution of the carnitine shuttle and lipid beta oxidation in ALS and suggest strategies for therapeutic intervention based on restoring lipid metabolism in motor neurons. PMID: 29904341 [PubMed]

Related Articles Citrate usage in the leading causes of blindness: new possibilities for the old metabolite. Metabolomics. 2018;14(6):82 Authors: Michalczuk M, Urban B, Porowski T, Wasilewska A, Bakunowicz-Łazarczyk A Abstract Introduction: Citrate is an old metabolite which is best known for the role in the Krebs cycle. Citrate is widely used in many branches of medicine. In ophthalmology citrate is considered as a therapeutic agent and an useful diagnostic tool-biomarker. Objectives: To summarize the published literature on citrate usage in the leading causes of blindness and highlight the new possibilities for this old metabolite. Methods: We conducted a systematic search of the scientific literature about citrate usage in ophthalmology up to January 2018. The reference lists of identified articles were searched for providing in-depth information. Results: This systematic review included 30 articles. The role of citrate in the leading causes of blindness is presented. Conclusions: Citrate might help inhibit cataract progression, in case of questions confirm glaucoma diagnosis or improve cornea repair treatment as adjuvant agent (therapy of ulcerating cornea after alkali injury, crosslinking procedure). However, the knowledge about possible citrate usage in ophthalmology is not widely known. Promoting recent scientific knowledge about citrate usage in ophthalmology may not only benefit of medical improvement but may also limit economic costs caused by leading causes of blindness. Further studies on citrate usage in ophthalmology should continuously be the field of scientific interest. PMID: 29904332 [PubMed]

Related Articles Arabidopsis myrosinases link the glucosinolate-myrosinase system and the cuticle. Sci Rep. 2016 12 15;6:38990 Authors: Ahuja I, de Vos RC, Rohloff J, Stoopen GM, Halle KK, Ahmad SJ, Hoang L, Hall RD, Bones AM Abstract Both physical barriers and reactive phytochemicals represent two important components of a plant's defence system against environmental stress. However, these two defence systems have generally been studied independently. Here, we have taken an exclusive opportunity to investigate the connection between a chemical-based plant defence system, represented by the glucosinolate-myrosinase system, and a physical barrier, represented by the cuticle, using Arabidopsis myrosinase (thioglucosidase; TGG) mutants. The tgg1, single and tgg1 tgg2 double mutants showed morphological changes compared to wild-type plants visible as changes in pavement cells, stomatal cells and the ultrastructure of the cuticle. Extensive metabolite analyses of leaves from tgg mutants and wild-type Arabidopsis plants showed altered levels of cuticular fatty acids, fatty acid phytyl esters, glucosinolates, and indole compounds in tgg single and double mutants as compared to wild-type plants. These results point to a close and novel association between chemical defence systems and physical defence barriers. PMID: 27976683 [PubMed - indexed for MEDLINE]

Related Articles A capillary electrophoresis coupled to mass spectrometry pipeline for long term comparable assessment of the urinary metabolome. Sci Rep. 2016 10 03;6:34453 Authors: Boizard F, Brunchault V, Moulos P, Breuil B, Klein J, Lounis N, Caubet C, Tellier S, Bascands JL, Decramer S, Schanstra JP, Buffin-Meyer B Abstract Although capillary electrophoresis coupled to mass spectrometry (CE-MS) has potential application in the field of metabolite profiling, very few studies actually used CE-MS to identify clinically useful body fluid metabolites. Here we present an optimized CE-MS setup and analysis pipeline to reproducibly explore the metabolite content of urine. We show that the use of a beveled tip capillary improves the sensitivity of detection over a flat tip. We also present a novel normalization procedure based on the use of endogenous stable urinary metabolites identified in the combined metabolome of 75 different urine samples from healthy and diseased individuals. This method allows a highly reproducible comparison of the same sample analyzed nearly 130 times over a range of 4 years. To demonstrate the use of this pipeline in clinical research we compared the urinary metabolome of 34 newborns with ureteropelvic junction (UPJ) obstruction and 15 healthy newborns. We identified 32 features with differential urinary abundance. Combination of the 32 compounds in a SVM classifier predicted with 76% sensitivity and 86% specificity UPJ obstruction in a separate validation cohort of 24 individuals. Thus, this study demonstrates the feasibility to use CE-MS as a tool for the identification of clinically relevant urinary metabolites. PMID: 27694997 [PubMed - indexed for MEDLINE]

22 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 2018/06/15PubMed 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.

22 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 2018/06/15PubMed 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.

Metabolomic Profiling of Plasma Samples from Women with Recurrent Spontaneous Abortion. Med Sci Monit. 2018 Jun 13;24:4038-4045 Authors: Li X, Yin M, Gu J, Hou Y, Tian F, Sun F Abstract BACKGROUND Gas chromatography coupled with mass spectrometry (GC-MS) and liquid chromatography coupled with mass spectrometry (LC-MS) metabolomics have been deployed to detect novel differential metabolites in cases with recurrent spontaneous abortion (RSA). MATERIAL AND METHODS Fifty patients who had recurrent spontaneous abortions (RSAs) and 51 control patients (age, gestational age, and body mass index (BMI) match) were enrolled in this study. Untargeted GC-MS and targeted LC-MS were combined to discover and validate the different metabolomic profiles between groups. Score plots of orthogonal partial least-squares discriminant analysis (OPLS-DA) clearly separated the RSA group from the control group. The variable importance in projection (VIP) generated in OPLS-DA processing represented the contribution to the discrimination of each metabolite ion between groups. Variables with a VIP >1 and P<0.05 were considered to be different variables. We also used MetaboAnalyst 3.0 to analyze the pathway impact of potential metabolite biomarkers. RESULTS Fifty-four metabolites were significantly different between the two groups, as indicated by a VIP >1 and P<0.05. The metabolic pathways involving glycine, serine, threonine (P=0.00529, impact=0.26), beta-alanine (P=0.0284, impact=0.27), and phenylalanine metabolism (P=0.0217, impact=0.17), along with the tricarboxylic acid (TCA) cycle (P=0.0113, impact=0.19) and the glycolysis pathway (P=0.037, impact=0.1) are obviously related to RSA. Verification by LC-MS showed that the concentration of lactic acid in RSA was higher than that in the control group (P<0.05), while the concentration of 5-methoxytryptamine was significantly lower in the RSA group (P<0.05). CONCLUSIONS In our study, untargeted GC-MS was used to detect disturbance of metabolism occurs in RSA and targeted LC-MS further was used to show that plasma concentrations of two metabolites (lactic acid and 5-methoxytryptamine) were different in the RSA compared to the control group. PMID: 29898462 [PubMed - in process]

Comparative physiological and metabolomics analysis of wheat (Triticum aestivum L.) following post-anthesis heat stress. PLoS One. 2018;13(6):e0197919 Authors: Thomason K, Babar MA, Erickson JE, Mulvaney M, Beecher C, MacDonald G Abstract Genetic improvement for stress tolerance requires a solid understanding of biochemical processes involved with different physiological mechanisms and their relationships with different traits. The objective of this study was to demonstrate genetic variability in altered metabolic levels in a panel of six wheat genotypes in contrasting temperature regimes, and to quantify the correlation between those metabolites with different traits. In a controlled environment experiment, heat stress (35:28 ± 0.08°C) was initiated 10 days after anthesis. Flag leaves were collected 10 days after heat treatment to employ an untargeted metabolomics profiling using LC-HRMS based technique called IROA. High temperature stress produced significant genetic variations for cell and thylakoid membrane damage, and yield related traits. 64 known metabolites accumulated 1.5 fold of higher or lower due to high temperature stress. In general, metabolites that increased the most under heat stress (L-tryptophan, pipecolate) showed negative correlation with different traits. Contrary, the metabolites that decreased the most under heat stress (drummondol, anthranilate) showed positive correlation with the traits. Aminoacyl-tRNA biosysnthesis and plant secondary metabolite biosynthesis pathways were most impacted by high temperature stress. The robustness of metabolic change and their relationship with phenotypes renders those metabolites as potential bio-markers for genetic improvement. PMID: 29897945 [PubMed - in process]

Loss of Fnip1 alters kidney developmental transcriptional program and synergizes with TSC1 loss to promote mTORC1 activation and renal cyst formation. PLoS One. 2018;13(6):e0197973 Authors: Centini R, Tsang M, Iwata T, Park H, Delrow J, Margineantu D, Iritani BM, Gu H, Liggitt HD, Kang J, Kang L, Hockenbery DM, Raftery D, Iritani BM Abstract Birt-Hogg-Dube' Syndrome (BHDS) is a rare genetic disorder in humans characterized by skin hamartomas, lung cysts, pneumothorax, and increased risk of renal tumors. BHDS is caused by mutations in the BHD gene, which encodes for Folliculin, a cytoplasmic adapter protein that binds to Folliculin interacting proteins-1 and -2 (Fnip1, Fnip2) as well as the master energy sensor AMP kinase (AMPK). Whereas kidney-specific deletion of the Bhd gene in mice is known to result in polycystic kidney disease (PKD) and renal cell carcinoma, the roles of Fnip1 in renal cell development and function are unclear. In this study, we utilized mice with constitutive deletion of the Fnip1 gene to show that the loss of Fnip1 is sufficient to result in renal cyst formation, which was characterized by decreased AMPK activation, increased mTOR activation, and metabolic hyperactivation. Using RNAseq, we found that Fnip1 disruption resulted in many cellular and molecular changes previously implicated in the development of PKD in humans, including alterations in the expression of ion and amino acid transporters, increased cell adhesion, and increased inflammation. Loss of Fnip1 synergized with Tsc1 loss to hyperactivate mTOR, increase Erk activation, and greatly accelerate the development of PKD. Our results collectively define roles for Fnip1 in regulating kidney development and function, and provide a model for how loss of Fnip1 contributes to PKD and perhaps renal cell carcinoma. PMID: 29897930 [PubMed - in process]

A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice. Xenobiotica. 2018 Jun 13;:1-53 Authors: Wang YK, Yang XN, Liang WQ, Xiao Y, Zhao Q, Xiao XR, Gonzalez FJ, Li F Abstract 1. To elucidate the metabolism of pazopanib, a metabolomics approach was performed based on ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry. 2. A total of 22 pazopanib metabolites were identified in vitro and in vivo. Among these metabolites, 17 were novel, including several cysteine adducts and aldehyde derivatives. By screening using recombinant CYPs, CYP3A4 and CYP1A2 were found to be the main forms involved in the pazopanib hydroxylation. Formation of a cysteine conjugate (M3), an aldehyde derivative (M15) and two N-oxide metabolites (M18 and M20) from pazopanib could induce the oxidative stress that may be responsible in part for pazopanib-induced hepatotoxicity. 3. Morphological observation of the liver suggested that pazopanib (300 mg/kg) could cause liver injury. The aspartate transaminase and alanine aminotransferase in serum significantly increased after pazopanib (150, 300 mg/kg) treatment; this liver injury could be partially reversed by the broad-spectrum CYP inhibitor 1-aminobenzotriazole (ABT). Metabolomics analysis revealed that pazopanib could significantly change the levels of L-carnitine, proline and lysophosphatidylcholine 18:1 in liver. Additionally, drug metabolism-related gene expression analysis revealed that hepatic Cyp2d22 and Abcb1a (P-gp) mRNAs of were significantly lowered by pazopanib treatment. 4. In conclusion, this study provides a global view of pazopanib metabolism and clues to its influence on hepatic function. PMID: 29897827 [PubMed - as supplied by publisher]

Cortisol, cortisone, and 4-methoxyphenylacetic acid as potential plasma biomarkers for early detection of non-small cell lung cancer. Int J Biol Markers. 2018 Jun 01;:1724600818778754 Authors: Xiang C, Jin S, Zhang J, Chen M, Xia Y, Shu Y, Guo R Abstract BACKGROUND: Lung cancer is the most common cause of cancer-related deaths in men and women worldwide. Novel diagnostic biomarkers are urgently required to enable the early detection and treatment of lung cancer, and using novel methods to explore tumor-related biomarkers is a hot topic in lung cancer research. The purpose of this study was to use ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) metabolomics analysis technology combined with multivariate data processing methods to identify potential plasma biomarkers for non-small cell lung cancer (NSCLC). METHODS: Plasma samples from 99 NSCLC patients and 112 healthy controls were randomly divided into the screening group and the validation group, respectively. UPLC-MS metabolomics analysis technology combined with multivariate data processing methods were used to identify potential plasma biomarkers for NSCLC. RESULTS: A total of 254 metabolites were detected and validated in plasma. Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) modeling indicated that 28 endogenous metabolites were present at significantly different levels in patients with NSCLC than healthy controls (variable importance in projection (VIP)>1 and P<0.001 (independent samples t-test) in both the screening group and the validation group). Further analysis revealed that cortisol, cortisone, and 4-methoxyphenylacetic acid had high sensitivity and specificity values as biomarkers for discriminating between NSCLC and healthy controls. Significant associations between specific plasma metabolites and the pathological type or stage of NSCLC were also observed. CONCLUSIONS: Metabolomics has the potential to distinguish between NSCLC patients and healthy controls, and may reveal new plasma biomarkers for the early detection of NSCLC. PMID: 29896992 [PubMed - as supplied by publisher]

Related Articles Omics in Zebrafish Teratogenesis. Methods Mol Biol. 2018;1797:421-441 Authors: Piña B, Navarro L, Barata C, Raldúa D, Martínez R, Casado M Abstract The genome revolution represents a complete change on our view of biological systems. The quantitative determination of changes in all major molecular components of the living cells, the "omics" approach, opened whole new fields for all health sciences. Genomics, transcriptomics, proteomics, metabolomics, and others, together with appropriate prediction and modeling tools, will mark the future of developmental toxicity assessment both for wildlife and humans. This is especially true for disciplines, like teratology, which rely on studies in model organisms, as studies at lower levels of organization are difficult to implement. Rodents and frogs have been the favorite models for studying human reproductive and developmental disorders for decades. Recently, the study of the development of zebrafish embryos (ZE) is becoming a major alternative tool to adult animal testing. ZE intrinsic characteristics makes this model a unique system to analyze in vivo developmental alterations that only can be studied applying in toto approaches. Moreover, under actual legislations, ZE is considered as a replacement model (and therefore, excluded from animal welfare regulations) during the first 5 days after fertilization. Here we review the most important components of the zebrafish toolbox available for analyzing early stages of embryotoxic events that could eventually lead to teratogenesis. PMID: 29896707 [PubMed - in process]

Related Articles Exploratory lipidomics in patients with nascent Metabolic Syndrome. J Diabetes Complications. 2018 May 25;: Authors: Ramakrishanan N, Denna T, Devaraj S, Adams-Huet B, Jialal I Abstract BACKGROUND: Metabolic Syndrome (MetS) is a cardio-metabolic cluster that confers an increased risk of developing both diabetes and atherosclerotic cardiovascular disease (ASCVD). The mechanisms governing the increased ASCVD risk remains to be elucidated. Moreover, lipidomics poses as an exciting new tool that has potential to shed more light on the pathogenesis of MetS. OBJECTIVE: The aim of this study was to explore the lipidome in an unbiased fashion in patients with nascent MetS uncomplicated by diabetes and CVD. METHODS: Patients with nascent MetS (n = 30) without diabetes or ASCVD and controls (n = 20) who participated in the study had normal hepatic and renal function. Early morning urine samples from patients were collected and frozen at -70° until analysis. Lipidomic analyses were undertaken at the National Institute of Health Western Metabolomics Center. RESULTS: Phosphatidylcholine 34:2, PC (34:2) was significantly increased in patients with MetS compared to controls. PC (34:2) had a significant positive correlation with waist circumference, plasma glucose, free fatty acid, and triglyceride levels. It had a significant positive correlation with pro-inflammatory markers such as plasma hs CRP, IL-1b, and IL-8. Additionally, PC (34:2) significantly correlated positively with Leptin and inversely with adiponectin. Levels of various acyl carnitines and PC34:1 were not significantly altered. CONCLUSION: We propose that PC (34:2) could emerge as a novel biomarker in MetS that promotes a pro-inflammatory state. PMID: 29895440 [PubMed - as supplied by publisher]

Related Articles Non-targeted investigation of benthic invertebrates (Chironomus riparius) exposed to wastewater treatment plant effluents using nanoliquid chromatography coupled to high-resolution mass spectrometry. Chemosphere. 2018 Apr;196:347-353 Authors: Berlioz-Barbier A, Buleté A, Fildier A, Garric J, Vulliet E Abstract Nanoliquid chromatography (nanoLC) was coupled to high-resolution mass spectrometry (HRMS) to perform a non-targeted investigation on benthic invertebrates, Chironomus riparius exposed to wastewater treatment plant (WWTP) effluents. Insect larvae represent a complex and low-weight matrix that required the use of a miniaturized Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) method of extraction followed by nanoLC-HRMS to perform the analysis. The optimization of this coupling in terms of separation conditions including trapping step, detection conditions and data treatment provided reproducible fingerprints on insect larvae exposed to WWTP effluents with both in situ and ex-situ approaches. Statistical treatments such as principal component analysis highlighted the impact of WWTP effluents on the metabolome of insect larvae and showed the influence of exposure conditions. The identification of discriminating signals (m/z, tR) matched with several potential endogenous biomarkers. These are mainly fatty acids, indicating a change in lipid metabolism that can be correlated with exposure to WWTP effluents. Several xenobiotics have also been detected, including ibuprofen and propranolol, whose identities have been confirmed by analytical standards. This work demonstrates the effectiveness and sensitivity of nanoLC-HRMS based environmental non-targeted approaches in ecotoxicological studies and provides the first profiling data for a very small aquatic invertebrate. PMID: 29310071 [PubMed - indexed for MEDLINE]

Related Articles Bioenergetics of Monoterpenoid Essential Oil Biosynthesis in Nonphotosynthetic Glandular Trichomes. Plant Physiol. 2017 Oct;175(2):681-695 Authors: Johnson SR, Lange I, Srividya N, Lange BM Abstract The commercially important essential oils of peppermint (Mentha × piperita) and its relatives in the mint family (Lamiaceae) are accumulated in specialized anatomical structures called glandular trichomes (GTs). A genome-scale stoichiometric model of secretory phase metabolism in peppermint GTs was constructed based on current biochemical and physiological knowledge. Fluxes through the network were predicted based on metabolomic and transcriptomic data. Using simulated reaction deletions, this model predicted that two processes, the regeneration of ATP and ferredoxin (in its reduced form), exert substantial control over flux toward monoterpenes. Follow-up biochemical assays with isolated GTs indicated that oxidative phosphorylation and ethanolic fermentation were active and that cooperation to provide ATP depended on the concentration of the carbon source. We also report that GTs with high flux toward monoterpenes express, at very high levels, genes coding for a unique pair of ferredoxin and ferredoxin-NADP+ reductase isoforms. This study provides, to our knowledge, the first evidence of how bioenergetic processes determine flux through monoterpene biosynthesis in GTs. PMID: 28838953 [PubMed - indexed for MEDLINE]