Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

metabolomics; +18 new citations

Tue, 11/06/2019 - 12:44
18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/06/11PubMed 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.

Metabolomics of the alimurgic plants Taraxacum officinale, Papaver rhoeas and Urtica dioica by combined NMR and GC-MS analysis.

Mon, 10/06/2019 - 12:36
Metabolomics of the alimurgic plants Taraxacum officinale, Papaver rhoeas and Urtica dioica by combined NMR and GC-MS analysis. Phytochem Anal. 2019 Jun 09;: Authors: Grauso L, Emrick S, Bonanomi G, Lanzotti V Abstract INTRODUCTION: The phytoalimurgic plants, common dandelion (Taraxacum officinale), corn poppy (Papaver rhoeas) and stinging nettle (Urtica dioica) are a source of nutraceuticals. OBJECTIVES: To apply a combined metabolomic fingerprinting approach by nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) to common dandelion, corn poppy and stinging nettles to obtain simultaneous identification and quantitation of the major classes of organic compounds. METHODOLOGY: The whole plants collected in the Cilento National Park were dried and then extracted to obtain non-polar and polar organic extracts. GC-MS was used for non-polar extracts while 1 H-NMR spectroscopy was used for polar extracts. In both cases, simultaneous identification and quantification of the bioactive metabolites was obtained. RESULTS: Non-polar organic extracts of all plants were mainly composed of palmitic, stearic and oleic acids. The two pentacyclic triterpenols α- and β-amyrin were detected in nettle extract. The analysis of polar organic extracts allowed to detect and quantify organic acids and sugars as main metabolites along with amino acids, caffeoyl derivatives, flavonoids, and nucleotides. In particular, corn poppy leaves contained a huge amount of glyceric acid (55.7% of the total extract). Stinging nettles, instead, exhibited a large amount of choline (19.5%). CONCLUSION: Metabolomic approach coupling GC-MS with NMR spectroscopy allowed to provide a detailed metabolite profile of three alimurgic plants, common dandelion, corn poppy and stinging nettle, from both a qualitative and quantitative point of view. PMID: 31177603 [PubMed - as supplied by publisher]

UPLC-QTOF/MS-based metabolomics reveals the mechanism of chronic unpredictable mild stress-induced hypertension in rats.

Mon, 10/06/2019 - 12:36
UPLC-QTOF/MS-based metabolomics reveals the mechanism of chronic unpredictable mild stress-induced hypertension in rats. Biomed Chromatogr. 2019 Jun 08;:e4619 Authors: Wu Q, Xia DM, Lan F, Wang YK, Tan X, Sun JC, Wang WZ, Wang R, Peng XD, Liu M Abstract Hypertension is a common chronic disease, and it is the strongest risk factor for cardiovascular diseases. Recently, the number of patients with hypertension-related complications has increased significantly, adding a heavy burden to the public health system. It is known that chronic stress plays an important role in the pathogenesis of cardiovascular diseases such as hypertension and stroke. However, the impact of hypertension on the dysfunctions induced by chronic stress remains poorly understood. In this study, using LC-MS-based metabolomics, we established a chronic stress model to demonstrate the mechanisms of stress-induced hypertension. We found that 30 metabolites in chronically stressed rats were changed; of these metabolites, 7 had been upregulated, and 23 had been downregulated, including amino acids, phospholipids, carnitines and fatty acids, many of which are involved in amino acid metabolism, cell membrane injury, ATP supply and inflammation. These metabolites are engaged in dysregulated pathways and will provide a targeted approach to study the mechanism of stress-induced hypertension. PMID: 31177559 [PubMed - as supplied by publisher]

Two-Week Aflibercept or Erlotinib Administration Does Not Induce Changes in Intestinal Morphology in Male Sprague-Dawley Rats But Aflibercept Affects Serum and Urine Metabolic Profiles.

Mon, 10/06/2019 - 12:36
Two-Week Aflibercept or Erlotinib Administration Does Not Induce Changes in Intestinal Morphology in Male Sprague-Dawley Rats But Aflibercept Affects Serum and Urine Metabolic Profiles. Transl Oncol. 2019 Jun 06;12(8):1122-1130 Authors: Forsgård RA, Marrachelli VG, Lindén J, Frias R, Collado MC, Korpela R, Monleon D, Spillmann T, Österlund P Abstract Gastrointestinal toxicity is a frequently observed adverse event during cancer treatment with traditional chemotherapeutics. Currently, traditional chemotherapeutics are often combined with targeted biologic agents. These biologics, however, possess a distinct toxicity profile, and they may also exacerbate the adverse effects of traditional chemotherapeutics. In this study, we aimed to characterize the gastrointestinal and metabolic changes after a 2-week treatment period with aflibercept, an antiangiogenic VEGFR decoy, and with erlotinib, a tyrosine-kinase inhibitor. Male rats were treated either with aflibercept or erlotinib for 2 weeks. During the 2-week treatment period, the animals in the aflibercept group received two subcutaneous doses of 25 mg/kg aflibercept. The erlotinib group got 10 mg/kg of erlotinib by oral gavage every other day. The control groups were treated similarly but received either saline injections or oral gavage of water. Intestinal toxicity was assessed by measuring intestinal permeability and by histological analyses of intestinal tissues. Metabolic changes were measured with 1H nuclear magnetic resonance in serum and urine. Neither aflibercept nor erlotinib induced changes in intestinal permeability or intestinal tissue morphology. However, aflibercept treatment resulted in stunted body weight gain and altered choline, amino acid, and lipid metabolism. Two-week treatment with aflibercept or erlotinib alone does not induce observable changes in gastrointestinal morphology and function. However, observed aflibercept-treatment related metabolic changes suggest alterations in intestinal microbiota, nutrient intake, and adipose tissue function. The metabolic changes are also interesting in respect to the systemic effects of aflibercept and their possible associations with adverse events caused by aflibercept administration. PMID: 31176994 [PubMed - as supplied by publisher]

Metabolomics, stunting and neurodevelopment.

Mon, 10/06/2019 - 12:36
Metabolomics, stunting and neurodevelopment. EBioMedicine. 2019 Jun 05;: Authors: van den Heuvel M PMID: 31176679 [PubMed - as supplied by publisher]

Mortality, growth and metabolic responses by 1H-NMR-based metabolomics of earthworms to sodium selenite exposure in soils.

Sun, 09/06/2019 - 15:23
Mortality, growth and metabolic responses by 1H-NMR-based metabolomics of earthworms to sodium selenite exposure in soils. Ecotoxicol Environ Saf. 2019 Jun 04;181:69-77 Authors: Shao X, He J, Liang R, Lu Y, Shi Y, Wang Y, Zheng X, Zhang S, Wang T Abstract The rapid development of selenium-enriched agriculture leads to the accumulation of selenium in the soil, which has an adverse impact on terrestrial ecosystems. In the present study, the mortality, growth inhibition rate and metabolism of earthworms were examined to investigate the toxicological effects of sodium selenite (Na2SeO3) on earthworms (Eisenia fetida) after exposuring for 14 days (d). We used 1H-NMR-based metabolomics to identify sensitive biomarkers and explored the metabolic responses of earthworms exposed to Na2SeO3. The mortality and growth inhibition rate of earthworms exposed to 70 and 90 mg/kg Na2SeO3 were significantly higher than the rate of control group. The LC50 (the median lethal concentration) of Na2SeO3 was 57.4 mg/kg in this artificial soil test of E. fetida exposed to Na2SeO3 for 14 d. However, there was no significant differences when earthworms were exposed to different concentrations of Na2SeO3. The selected metabolic markers were ATP, lactic acid, leucine, alanine, valine, glycine, glutamic acid, lysine, α-glucose and betaine. Na2SeO3 affected the metabolic level of earthworms, as the percentage of metabolic markers in the earthworm changes when exposed to different concentrations of Na2SeO3. The metabolic disturbances were greater with increasing concentrations of Na2SeO3. The differential metabolic markers were significantly changed when exposed to Na2SeO3 comparing to those in the control group, affecting the tricarboxylic acid cycle process and breaking the metabolic balance. This study showed that Na2SeO3 had toxic effect on the growth and development of earthworms. In addition, this study provided a biochemical insights for the development of selenium-enriched agriculture. PMID: 31176249 [PubMed - as supplied by publisher]

Extreme, but not moderate climate scenarios, impart sublethal effects on polyps of the Irukandji jellyfish, Carukia barnesi.

Sun, 09/06/2019 - 15:23
Extreme, but not moderate climate scenarios, impart sublethal effects on polyps of the Irukandji jellyfish, Carukia barnesi. Sci Total Environ. 2019 May 30;685:471-479 Authors: Boco SR, Pitt KA, Melvin SD Abstract Ocean acidification and warming, fueled by excess atmospheric carbon dioxide, can impose stress on marine organisms. Most studies testing the effects of climate change on marine organisms, however, use extreme climate projection scenarios, despite moderate projections scenarios being most likely to occur. Here, we examined the interactive effects of warming and acidification on reproduction, respiration, mobility and metabolic composition of polyps of the Irukandji jellyfish, Carukia barnesi, to determine the responses of a cubozoan jellyfish to moderate and extreme climate scenarios in Queensland, Australia. The experiment consisted two orthogonal factors: temperature (current 25 °C and future 28 °C) and pH (current (8.0) moderate (7.9) and extreme (7.7)). All polyps survived in the experiment but fewer polyps were produced in the pH 7.7 treatment compared to pH 7.9 and pH 8.0. Respiration rates were elevated in the lowest pH treatment throughout most of the experiment and polyps were approximately half as mobile in this treatment compared to pH 7.9 and pH 8.0, regardless of temperature. We identified metabolites occurring at significantly lower relative abundance in the lowest pH (i.e. glutamate, acetate, betaine, methylguanidine, lysine, sarcosine, glycine) and elevated temperature (i.e. proline, trigonelline, creatinine, mannose, acetate, betaine, methylguanidine, lysine, sarcosine) treatments. Glycine was the only metabolite exhibiting an interactive effect between pH and temperature. Our results suggest that C. barnesi polyps are unaffected by the most optimistic climate scenario and may tolerate even extreme climate conditions to some extent. PMID: 31176232 [PubMed - as supplied by publisher]

Comparing the disrupting effects of short-, medium- and long-chain chlorinated Paraffins on cell viability and metabolism.

Sun, 09/06/2019 - 15:23
Comparing the disrupting effects of short-, medium- and long-chain chlorinated Paraffins on cell viability and metabolism. Sci Total Environ. 2019 May 30;685:297-307 Authors: Ren X, Geng N, Zhang H, Wang F, Gong Y, Song X, Luo Y, Zhang B, Chen J Abstract With the phasing out of short-chain chlorinated paraffins (SCCPs), the production and emissions of medium- and long-chain chlorinated paraffins (MCCPs and LCCPs) are expected to increase. In this study, cell viability assay and pseudotargeted metabolomics approach were adopted to define and compare the toxic effects induced by SCCPs, MCCPs and LCCPs. The dose response curves indicated that three CP mixtures with comparable chlorine contents produced similar inhibitory effects on cell viability. At exposure concentration of 100 μg/L, three CP mixtures all induced significant increases in levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and a significant reduction in level of adenosine triphosphate production (ATP), and produced similar impact intensities on overall metabolism. A stronger perturbation in phospholipid and fatty acid metabolism was observed in all CP exposure groups. In comparison with SCCPs and MCCPs, LCCPs produced a stronger suppressive effect on amino acid transport across cell membrane and induced an opposite effect on purine metabolism. Furthermore, the toxicity mechanism and possible health risks of the three types of CPs were discussed. MCCPs shared the most similar cytotoxicity and metabolic perturbation with SCCPs, suggesting that there should be concern about using MCCPs as alternatives to SCCPs. PMID: 31176216 [PubMed - as supplied by publisher]

Lactulose: patient- and dose-dependent prebiotic properties in humans.

Sun, 09/06/2019 - 15:23
Lactulose: patient- and dose-dependent prebiotic properties in humans. Anaerobe. 2019 Jun 05;: Authors: Jakub R, Jacek M W Abstract Lactulose is a disaccharide used in clinical practice since 1957 and has since been tested in the treatment of many human disorders, including chronic constipation, hepatic encephalopathy, and chronic kidney disease. Its mode of action is based on the lactulose fermentation by intestinal microbiota. Based on in silico, in vitro and in vivo studies we comprehensively review here the impact of lactulose on human gut/fecal and vaginal microbiota composition and both fecal and blood metabolomes. However, both in vitro and in vivo studies summarized in this review have revealed that the effects of lactulose on human microbiota composition are both patient- and dose-dependent. This highlights the need of heterogeneity indication in clinical trials. PMID: 31176002 [PubMed - as supplied by publisher]

Whole-genome sequence of Arthrinium phaeospermum, a globally distributed pathogenic fungus.

Sun, 09/06/2019 - 15:23
Whole-genome sequence of Arthrinium phaeospermum, a globally distributed pathogenic fungus. Genomics. 2019 Jun 05;: Authors: Li S, Tang Y, Fang X, Qiao T, Han S, Zhu T Abstract Arthrinium phaeospermum (Corda) M.B. Ellis is a globally distributed pathogenic fungus with a wide host range; its hosts include not only plants, but also humans and animals. This study aimed to develop genomic resources for A. phaeospermum to provide solid data and a theoretical basis for further studies of its pathogenesis, transcriptomics, proteomics, metabolomics and RNA genomics. The genome was obtained from the mycelia of the strain AP-Z13 using a combination of analyses with the high-throughput Illumina HiSeq 4000 system and PacBio RSII LongRead sequencing platform. Functional annotation was performed by BLASTing protein sequences against those in different publicly available databases to obtain their corresponding annotations. The genome is 48.45 Mb in size, with an N90 scaffold size of 1,931,147 bp, and encodes 19,836 putative predicted genes. This is the first report of the genome-scale assembly and annotation for A. phaeospermum, the first species in the genus Arthrinium to be subjected to whole genome sequencing. PMID: 31175977 [PubMed - as supplied by publisher]

Metabolomics of Thrips Resistance in Pepper (Capsicum spp.) Reveals Monomer and Dimer Acyclic Diterpene Glycosides as Potential Chemical Defenses.

Sun, 09/06/2019 - 15:23
Related Articles Metabolomics of Thrips Resistance in Pepper (Capsicum spp.) Reveals Monomer and Dimer Acyclic Diterpene Glycosides as Potential Chemical Defenses. J Chem Ecol. 2019 Jun 08;: Authors: Macel M, Visschers IGS, Peters JL, Kappers IF, de Vos RCH, van Dam NM Abstract The development of pesticide resistance in insects and recent bans on pesticides call for the identification of natural sources of resistance in crops. Here, we used natural variation in pepper (Capsicum spp.) resistance combined with an untargeted metabolomics approach to detect secondary metabolites related to thrips (Frankliniella occidentalis) resistance. Using leaf disc choice assays, we tested 11 Capsicum accessions of C. annuum and C. chinense in both vegetative and flowering stages for thrips resistance. Metabolites in the leaves of these 11 accessions were analyzed using LC-MS based untargeted metabolomics. The choice assays showed significant differences among the accessions in thrips feeding damage. The level of resistance depended on plant developmental stage. Metabolomics analyses showed differences in metabolomes among the Capsicum species and plant developmental stages. Moreover, metabolomic profiles of resistant and susceptible accessions differed. Monomer and dimer acyclic diterpene glycosides (capsianosides) were pinpointed as metabolites that were related to thrips resistance. Sucrose and malonylated flavone glycosides were related to susceptibility. To our knowledge, this is the first time that dimer capsianosides of pepper have been linked to insect resistance. Our results show the potential of untargeted metabolomics as a tool for discovering metabolites that are important in plant - insect interactions. PMID: 31175497 [PubMed - as supplied by publisher]

Metabolomic study of the soybean pastes fermented by the single species Penicillium glabrum GQ1-3 and Aspergillus oryzae HGPA20.

Sun, 09/06/2019 - 15:23
Related Articles Metabolomic study of the soybean pastes fermented by the single species Penicillium glabrum GQ1-3 and Aspergillus oryzae HGPA20. Food Chem. 2019 Oct 15;295:622-629 Authors: Sun X, Lyu G, Luan Y, Yang H, Zhao Z Abstract Penicillium glabrum GQ1-3 and Aspergillus oryzae HGPA20 isolated from home-made soybean pastes were separately inoculated into soybean paste subjected to brine fermentation for 90 days. The amino acid nitrogen contents of the two fermentation systems were detected every 10 days, and both reached the maximum level at 40 days. The samples fermented for 40 days were analyzed via gas chromatography-time of flight mass spectrometry. Using univariate, multivariate and KEGG analyses, 72 differential metabolites were obtained, and 7 metabolic pathways closely related to fermentation were screened. The relative contents of 2-oxoglutarate, ornithine, glutamine, and citrulline were higher in GQ1-3, whereas those of l-homoserine, aspartic acid, and asparagine were higher in HGPA20. These findings indicate that α-ketoglutaric acid-derived amino acid synthesis is preponderant in GQ1-3, whereas oxaloacetate-derived type is predominant in HGPA20. The different pathways of amino acid synthesis lead to the distinct nutrients and umami substances in the fermented soybean pastes. PMID: 31174804 [PubMed - in process]

In silico annotation of discriminative markers of three Zanthoxylum species using molecular network derived annotation propagation.

Sun, 09/06/2019 - 15:23
Related Articles In silico annotation of discriminative markers of three Zanthoxylum species using molecular network derived annotation propagation. Food Chem. 2019 Oct 15;295:368-376 Authors: Lee J, da Silva RR, Jang HS, Kim HW, Kwon YS, Kim JH, Yang H Abstract In liquid chromatography-mass spectrometry (LC-MS) metabolomics, data matrices with up to thousands of variables for each ion peak are subjected to multivariate analysis (MVA) to assess the homogeneity between samples. The large dimensions of LC/MS datasets hinder the identification of the discriminant or the metabolic markers. In the present study, the molecular network (MN) approach and two in silico annotation tools, network annotation propagation (NAP) and the hierarchical chemical classification method, ClassyFire, were used to annotate the metabolites of three Zanthoxylum species, Z. bungeanum, Z. schinifolium and Z. piperitum. The in silico annotation results of the MN nodes and the MVA variables were combined and visualized in loading plots. This approach helped intuitive detection of the variables that greatly contributed to the separation of the samples in the score plot as discriminant or metabolic markers, thereby allowing rapid annotation of two flavanone derivatives. PMID: 31174771 [PubMed - in process]

Metabolomic studies as a tool for determining the post-mortem interval (PMI) in stillborn calves.

Sun, 09/06/2019 - 15:23
Related Articles Metabolomic studies as a tool for determining the post-mortem interval (PMI) in stillborn calves. BMC Vet Res. 2019 Jun 07;15(1):189 Authors: Jawor P, Ząbek A, Wojtowicz W, Król D, Stefaniak T, Młynarz P Abstract BACKGROUND: Perinatal mortality may vary between herds, but the cost of deaths are always higher than value of the calf. When diagnosing the cause of a calf's death it is important to determine when it occurred, before or after calving. Metabolomics is widely used to identify many human diseases, but quite rarely applied in veterinary science. The aim of this study was to compare the metabolic profiles of calves with different times of death and those of calves born alive. Into the study, twenty one healthy controls (singleton, normal assisted calving, born alive) and 75 stillborn (SB) calves (with a gestation length of ≥260 days, SB, or dead within 6 h of birth) were enrolled. Plasma and urine from SB and control calves were investigated by proton nuclear magnetic resonance based metabolomic methods. SB calves were divided into four PMI groups. One PMI group included calves that died after calving and the other groups - three comprised in utero deaths, based on pathophysiological changes (lung inflation, autolysis in internal organs, hemoglobin imbibition in the pleura and aortic arch). Partial Least Squares - Discriminant Analysis models based on plasma metabolites were calculated, reflecting assumed data clustering. RESULTS: Twenty six metabolites in plasma and 29 in urine changed significantly with PMI according to one way analysis of variance. Half the metabolites in plasma and the majority in urine increased with PMI. Six metabolites increased simultaneously in plasma and urine: acetate, sn-glycero-3-phosphocholine (GPC), leucine, valine, creatine, and alanine. CONCLUSIONS: Post-mortem changes in calves were associated with molecular variations in blood plasma and urine, showing the greatest differences for the group in which the post-mortem pathological changes were the most advanced. The results of the study show that evaluation of calf plasma or urine may be used as a diagnostic method for the determination of the PMI. Moreover, the metabolites, which unambiguously increased or decreased, can be used as potential biomarkers of PMI. PMID: 31174528 [PubMed - in process]

Translational Metabolomics: Current Challenges and Future Opportunities.

Sun, 09/06/2019 - 15:23
Related Articles Translational Metabolomics: Current Challenges and Future Opportunities. Metabolites. 2019 Jun 06;9(6): Authors: Pinu FR, Goldansaz SA, Jaine J Abstract Metabolomics is one of the latest omics technologies that has been applied successfully in many areas of life sciences. Despite being relatively new, a plethora of publications over the years have exploited the opportunities provided through this data and question driven approach. Most importantly, metabolomics studies have produced great breakthroughs in biomarker discovery, identification of novel metabolites and more detailed characterisation of biological pathways in many organisms. However, translation of the research outcomes into clinical tests and user-friendly interfaces has been hindered due to many factors, some of which have been outlined hereafter. This position paper is the summary of discussion on translational metabolomics undertaken during a peer session of the Australian and New Zealand Metabolomics Conference (ANZMET 2018) held in Auckland, New Zealand. Here, we discuss some of the key areas in translational metabolomics including existing challenges and suggested solutions, as well as how to expand the clinical and industrial application of metabolomics. In addition, we share our perspective on how full translational capability of metabolomics research can be explored. PMID: 31174372 [PubMed]

Tackling the Complexity of the Exposome: Considerations from the Gunma University Initiative for Advanced Research (GIAR) Exposome Symposium.

Sun, 09/06/2019 - 15:23
Related Articles Tackling the Complexity of the Exposome: Considerations from the Gunma University Initiative for Advanced Research (GIAR) Exposome Symposium. Metabolites. 2019 Jun 06;9(6): Authors: Zhang P, Arora M, Chaleckis R, Isobe T, Jain M, Meister I, Melén E, Perzanowski M, Torta F, Wenk MR, Wheelock CE Abstract The attempt to describe complex diseases by solely genetic determination has not been successful. There is increasing recognition that the development of disease is often a consequence of interactions between multiple genetic and environmental factors. To date, much of the research on environmental determinants of disease has focused on single exposures generally measured at a single time point. In order to address this limitation, the concept of the exposome has been introduced as a comprehensive approach, studying the full complement of environmental exposures from conception onwards. However, exposures are vast, dynamic, and diverse, and only a small proportion can be reasonably measured due to limitations in technology and feasibility. In addition, the interplay between genes and exposure as well as between different exposures is complicated and multifaceted, which leads to difficulties in linking disease or health outcomes with exposures. The large numbers of collected samples require well-designed logistics. Furthermore, the immense data sets generated from exposome studies require a significant computational investment for both data analysis and data storage. This report summarizes discussions during an international exposome symposium held at Gunma University in Japan regarding the concept of the exposome, challenges in exposome research, and future perspectives in the field. PMID: 31174297 [PubMed]

Perigestational low-dose BDE-47 exposure alters maternal serum metabolome and results in sex-specific weight gain in adult offspring.

Sat, 08/06/2019 - 12:07
Perigestational low-dose BDE-47 exposure alters maternal serum metabolome and results in sex-specific weight gain in adult offspring. Chemosphere. 2019 May 30;233:174-182 Authors: Gao H, Li P, Liu L, Yang K, Xiao B, Zhou G, Tian Z, Luo C, Xia T, Dong L, Zhao Q, Wang A, Zhang S Abstract Emerging evidence suggests environmental contaminant exposures during critical windows of development may contribute to the increasing prevalence of obesity. It has been shown that early life polybrominated diphenyl ethers exposures have critical impacts on child weight trajectories, however, little is known about their maternal mechanisms responsible for offspring obesity development. In this study, we investigated the effects of perigestational low-dose 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) exposure on maternal metabolome, and its possible link to adult offspring bodyweight changes. Female Sprague-Dawley rats were exposed to daily doses of 0.1, or 1 mg/kg BDE-47 from 10 days prior to conception until offspring were weaned on postnatal day 21, and then a gas chromatography-mass spectrometry based metabolomics analysis was used to uncover the global metabolic response in dams. The pups continued to grow into adulthood for measurements of bodyweight. Perigestational BDE-47 exposure caused increased adult bodyweight in male but not in female offspring and dams. Metabolomics revealed significant changes in maternal serum metabolites that clearly distinguish BDE-47 from control rats. These differentially expressed metabolites were primarily implicated in amino acid, lipid, carbohydrate, and energy metabolisms, which was confirmed by pathway analysis. Importantly, most of these identified metabolites were decreased, a state similar to maternal malnutrition that can predispose adult male offspring to weight increase and adiposity in a postnatal environment with abundant calories. Collectively, our data suggest that perigestational exposure to low-dose BDE-47 produces altered maternal serum metabolome, which may be an additional contributing factor to weight gain in adult male offspring. PMID: 31173955 [PubMed - as supplied by publisher]

α-Ketoglutarate inhibits autophagy.

Sat, 08/06/2019 - 12:07
α-Ketoglutarate inhibits autophagy. Aging (Albany NY). 2019 Jun 07;: Authors: Baracco EE, Castoldi F, Durand S, Enot DP, Tadic J, Kainz K, Madeo F, Chery A, Izzo V, Maiuri MC, Pietrocola F, Kroemer G Abstract The metabolite α-ketoglutarate is membrane-impermeable, meaning that it is usually added to cells in the form of esters such as dimethyl -ketoglutarate (DMKG), trifluoromethylbenzyl α-ketoglutarate (TFMKG) and octyl α-ketoglutarate (O-KG). Once these compounds cross the plasma membrane, they are hydrolyzed by esterases to generate α-ketoglutarate, which remains trapped within cells. Here, we systematically compared DMKG, TFMKG and O-KG for their metabolic and functional effects. All three compounds similarly increased the intracellular levels of α-ketoglutarate, yet each of them had multiple effects on other metabolites that were not shared among the three agents, as determined by mass spectrometric metabolomics. While all three compounds reduced autophagy induced by culture in nutrient-free conditions, TFMKG and O-KG (but not DMKG) caused an increase in baseline autophagy in cells cultured in complete medium. O-KG (but neither DMKG nor TFMK) inhibited oxidative phosphorylation and exhibited cellular toxicity. Altogether, these results support the idea that intracellular α-ketoglutarate inhibits starvation-induced autophagy and that it has no direct respiration-inhibitory effect. PMID: 31173576 [PubMed - as supplied by publisher]

Serum metabolites as predictive molecular markers of ovarian response to controlled stimulation: a pilot study.

Sat, 08/06/2019 - 12:07
Serum metabolites as predictive molecular markers of ovarian response to controlled stimulation: a pilot study. JBRA Assist Reprod. 2019 Jun 07;: Authors: Borges E, Montani DA, Setti AS, Zanetti BF, Figueira RCS, Iaconelli A, Oliveira-Silva D, Braga DPAF Abstract OBJECTIVE: This study aimed to look into the use of serum metabolites as potential biomarkers of response to controlled ovarian stimulation (COS) in patients undergoing intracytoplasmic sperm injection (ICSI) cycles. METHODS: This case-control study analyzed serum samples from 30 patients aged <36 years undergoing COS for ICSI in a university-affiliated assisted reproduction center from January 2017 to August 2017. The samples were split into three groups based on response to COS as follows: poor responders: <4 retrieved oocytes (PR group, n=10); normal responders: ≥ 8 and ≤ 12 retrieved oocytes (NR group, n=10); and hyper-responders: >25 retrieved oocytes (HR, n=10). The metabolic profiles of the serum samples were compared between the groups through Principal Component Analysis (PCA). Receiver Operating Characteristic (ROC) curves were built to assess the power of the model at predicting response to COS. RESULTS: PCA clearly distinguished between PR, NR and HR, and 10 ions were chosen as potential biomarkers of response to COS. These ions were more specific for PR than for NR. The ROC curve considering PR and NR had an area under the curve of 99.6% (95% CI: 88.9 - 100%). CONCLUSION: The preliminary evidence discussed in this study suggests that serum metabolites may be used as predictive molecular markers of ovarian response to controlled stimulation. The integration of clinical and "omics" findings may allow the migration toward an era of personalized treatment in reproductive medicine. PMID: 31173494 [PubMed - as supplied by publisher]

Emerging applications of metabolomics in clinical pharmacology.

Sat, 08/06/2019 - 12:07
Emerging applications of metabolomics in clinical pharmacology. Clin Pharmacol Ther. 2019 Jun 07;: Authors: Pang H, Jia W, Hu Z Abstract Metabolic disturbances have been associated with many human diseases, including cancer, diabetes, and cardiovascular disease. Metabolomics, a rapidly growing member of the 'omics family, investigates cellular metabolism by quantifying metabolites on a large-scale and provides a link between metabolic pathways and the upstream genome that governs them. With the advances in analytical technologies, metabolomics is becoming a powerful tool for identifying diagnostic biomarkers of diseases, elucidating the pathological mechanisms, discovering novel drug targets, predicting drug responses, interpreting the mechanisms of drug action, as well as enabling precision treatment of patients. In this review, we highlight the recent advances of technologies and methodologies in metabolomics and their applications to the field of clinical pharmacology. Recent publications from 2013 to 2018 are covered in the review, and current challenges and potential future directions in the field are also discussed. This article is protected by copyright. All rights reserved. PMID: 31173340 [PubMed - as supplied by publisher]

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