PubMed
Physiological and metabolic changes during the transition from hyperthyroidism to euthyroidism in Graves' disease.
Physiological and metabolic changes during the transition from hyperthyroidism to euthyroidism in Graves' disease.
Thyroid. 2016 Jul 27;
Authors: Chng CL, Lim AY, Tan HC, Kovalik JP, Tham KW, Bee YM, Lim W, Acharyya S, Lai OF, Chong MF, Yen PM
Abstract
BACKGROUND: The serum metabolomic profile and its relationship to physiological changes during hyperthyroidism and restoration to euthyroidism are not known. We aimed at examining the physiological, adipokine, and metabolomic changes that occur when subjects with Graves' disease transit from hyperthyroidism to euthyroidism with medical treatment.
METHODS: Chinese women between age 21 and 50 years of age and with newly diagnosed Graves' disease attending the Endocrine outpatient clinics in a single institution were recruited between July 2012 and September 2014. All subjects were treated with thioamides to achieve euthyroidism. Clinical parameters (body weight, body composition via bioelectrical impedance analysis, resting energy expenditure and respiratory quotient via indirect calorimetry, reported total energy intake via 24 hr food diary), biochemical parameters (thyroid hormones, lipid profile, fasting insulin and glucose levels), serum leptin, adiponectin and metabolomics profiles were measured during hyperthyroidism and repeated in early euthyroidism.
RESULTS: Twenty four Chinese women with an average age of 36.3 ± 8.6 years were included in the study. The average duration of treatment that was required to reach euthyroidism for these subjects was 38 ± 16.3 weeks. There was a significant increase in body weight (52.6 ± 9.0 kg to 55.3 ± 9.4 kg, p<0.001) and fat mass (14.3 ± 6.9 kg to 16.8 ± 6.5 kg, p=0.005). There was a reduction in resting energy expenditure corrected for weight (28.7 ± 4.0 Kcal/Kg to 21.5 ± 4.1 Kcal/Kg, p<0.001) and an increase in respiratory quotient (0.76 to 0.81, p=0.037). Resting energy expenditure increased significantly with increasing FT3 levels (p=0.007). Significant increases in total cholesterol, LDL-cholesterol and HDL-cholesterol were noted. There was no significant change in leptin levels but adiponectin levels increased significantly (p=0.018). We observed significant reductions in fasting C2, medium, long chain, and total acylcarnitines, but no changes in the fat-free mass, branched chain amino acid levels, or insulin sensitivity during recovery from hyperthyroidism.
CONCLUSIONS: Serum metabolomics profile changes complemented the physiological changes observed during the transition from hyperthyroidism to euthyroidism. Our study provides a comprehensive and integrated view of the changes in fuel metabolism and energy balance that occur following treatment of hyperthyroidism.
PMID: 27465032 [PubMed - as supplied by publisher]
Gene Expression Profiling in Fish Toxicology: A Review.
Gene Expression Profiling in Fish Toxicology: A Review.
Rev Environ Contam Toxicol. 2016 Jul 28;
Authors: Kumar G, Denslow ND
Abstract
In this review, we present an overview of transcriptomic responses to chemical exposures in a variety of fish species. We have discussed the use of several molecular approaches such as northern blotting, differential display reverse transcription-polymerase chain reaction (DDRT-PCR), suppression subtractive hybridization (SSH), real time quantitative PCR (RT-qPCR), microarrays, and next-generation sequencing (NGS) for measuring gene expression. These techniques have been mainly used to measure the toxic effects of single compounds or simple mixtures in laboratory conditions. In addition, only few studies have been conducted to examine the biological significance of differentially expressed gene sets following chemical exposure. Therefore, future studies should focus more under field conditions using a multidisciplinary approach (genomics, proteomics and metabolomics) to understand the synergetic effects of multiple environmental stressors and to determine the functional significance of differentially expressed genes. Nevertheless, recent developments in NGS technologies and decreasing costs of sequencing holds the promise to uncover the complexity of anthropogenic impacts and biological effects in wild fish populations.
PMID: 27464848 [PubMed - as supplied by publisher]
[Toward understanding and regulation of gut ecosystem by metabologenomics].
Related Articles
[Toward understanding and regulation of gut ecosystem by metabologenomics].
Seikagaku. 2016 Feb;88(1):61-70
Authors: Fukuda S
PMID: 27459737 [PubMed - indexed for MEDLINE]
[Progress of Japanese Omics Reference Panels in Iwate Tohoku Medical Megabank Project].
Related Articles
[Progress of Japanese Omics Reference Panels in Iwate Tohoku Medical Megabank Project].
Seikagaku. 2016 Feb;88(1):36-43
Authors: Furukawa R, Shimizu A
PMID: 27025006 [PubMed - indexed for MEDLINE]
[Jananese Multi Omics Reference Panel].
Related Articles
[Jananese Multi Omics Reference Panel].
Seikagaku. 2016 Feb;88(1):25-30
Authors: Koshiba S
PMID: 27025004 [PubMed - indexed for MEDLINE]
Omics data input for metabolic modeling.
Related Articles
Omics data input for metabolic modeling.
Curr Opin Biotechnol. 2016 Feb;37:127-34
Authors: Rai A, Saito K
Abstract
Recent advancements in high-throughput large-scale analytical methods to sequence genomes of organisms, and to quantify gene expression, proteins, lipids and metabolites have changed the paradigm of metabolic modeling. The cost of data generation and analysis has decreased significantly, which has allowed exponential increase in the amount of omics data being generated for an organism in a very short time. Compared to progress made in microbial metabolic modeling, plant metabolic modeling still remains limited due to its complex genomes and compartmentalization of metabolic reactions. Herein, we review and discuss different omics-datasets with potential application in the functional genomics. In particular, this review focuses on the application of omics-datasets towards construction and reconstruction of plant metabolic models.
PMID: 26723010 [PubMed - indexed for MEDLINE]
Search for novel circulating cancer chemopreventive biomarkers of dietary rice bran intervention in Apc(Min) mice model of colorectal carcinogenesis, using proteomic and metabolic profiling strategies.
Related Articles
Search for novel circulating cancer chemopreventive biomarkers of dietary rice bran intervention in Apc(Min) mice model of colorectal carcinogenesis, using proteomic and metabolic profiling strategies.
Mol Nutr Food Res. 2015 Sep;59(9):1827-36
Authors: Norris L, Malkar A, Horner-Glister E, Hakimi A, Ng LL, Gescher AJ, Creaser C, Sale S, Jones DJ
Abstract
SCOPE: There is strong epidemiological evidence indicating that consumption by humans of whole-grain foods including rice bran may be associated with a low incidence of cancer, especially in the colorectum. Molecular processes associated with cancer development may be retarded by fiber consumption. Consequently, intervention with dietary fiber might be suitable as a cancer chemoprevention strategy in high-risk populations. Here, we searched for putative molecular mechanism-based efficacy biomarkers of rice fiber consumption in the plasma of mice characterized by a genetic propensity to develop gastrointestinal adenomas. The hypothesis was tested that metabolic and proteomic changes in blood reflect the chemopreventive activity of rice bran.
METHODS AND RESULTS: Apc(Min) mice received diet supplemented with rice bran at 5, 15, and 30%. Blood and tissue samples were taken. Plasma was subjected to MS-based proteomic and metabolic profiling analyses as well as assessment of hematocrit values. Gastrointestinal tracts were removed and adenomas were counted and their size was measured so that total tumor burden could be calculated. The hypothesis was tested that metabolic and proteomic changes in blood reflect chemopreventive activity.
CONCLUSION: Rice bran consumption reduced adenoma burden and number in a dose-related fashion when compared to controls. Metabolic profiling data demonstrated strong clustering of the groups indicating that metabolic pathways are perturbed. Proteomic analysis identified adiponectin as a molecule that was significantly altered, which may play a role in tumor suppression.
PMID: 26033951 [PubMed - indexed for MEDLINE]
The effect of plant sterols and different low doses of omega-3 fatty acids from fish oil on lipoprotein subclasses.
Related Articles
The effect of plant sterols and different low doses of omega-3 fatty acids from fish oil on lipoprotein subclasses.
Mol Nutr Food Res. 2015 Sep;59(9):1745-57
Authors: Jacobs DM, Mihaleva VV, van Schalkwijk DB, de Graaf AA, Vervoort J, van Dorsten FA, Ras RT, Demonty I, Trautwein EA, van Duynhoven J
Abstract
SCOPE: Consumption of a low-fat spread enriched with plant sterols (PS) and different low doses (<2 g/day) of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil reduces serum triglycerides (TGs) and low-density lipoprotein-cholesterol (LDL-Chol) and thus beneficially affects two blood lipid risk factors. Yet, their combined effects on TG and Chol in various lipoprotein subclasses have been investigated to a limited extent.
METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled, parallel study, we determined TG and Chol in 13 LP subclasses in fasting serum of 282 hypercholesterolemic subjects, who consumed either a placebo spread or one of the four spreads containing PS (2.5 g/day) and EPA+DHA (0.0, 0.9, 1.3, and 1.8 g/day) for 4 weeks. After PS treatment, total LDL-Chol was reduced, which was not further changed by EPA+DHA. No shift in the LDL-Chol particle distribution was observed. The addition of EPA+DHA to PS dose-dependently reduced VLDL-Chol and VLDL-TG mainly in larger particles. Furthermore, the two highest doses of EPA+DHA increased Chol and TG in the larger HDL particles, while these concentrations were decreased in the smallest HDL particles.
CONCLUSION: The consumption of a low-fat spread enriched with both PS and EPA+DHA induced shifts in the lipoprotein distribution that may provide additional cardiovascular benefits over PS consumption alone.
PMID: 26019023 [PubMed - indexed for MEDLINE]
metabolomics; +55 new citations
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metabolomics
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metabolomics; +16 new citations
16 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 2016/07/25PubMed 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.
Application of genomics for understanding plant virus-insect vector interactions and insect vector control.
Application of genomics for understanding plant virus-insect vector interactions and insect vector control.
Phytopathology. 2016 Jul 20;
Authors: Kaur N, Hasegawa DK, Ling KS, Wintermantel WM
Abstract
The relationships between plant viruses and their vectors have evolved over the millennia and yet, studies on viruses began <150 years ago and investigations into the virus and vector interactions even more recently. The advent of next generation sequencing (NGS), including rapid genome and transcriptome analysis, methods for evaluation of small RNAs and the related disciplines of proteomics and metabolomics offer a significant shift in the ability to elucidate molecular mechanisms involved in virus infection and transmission by insect vectors. Genomic technologies offer an unprecedented opportunity to examine the response of insect vectors to the presence of ingested viruses through gene expression changes and altered biochemical pathways. This review focuses on the interactions between viruses and their whitefly or thrips vectors, and potential applications of genomics-driven control of the insect vectors. Recent studies have evaluated gene expression in vectors during feeding on plants infected with begomoviruses, criniviruses, and tospoviruses, which exhibit very different types of virus-vector interactions. These studies demonstrate the advantages of genomics and the potential complementary studies that rapidly advance our understanding of the biology of virus transmission by insect vectors, and offer additional opportunities to design novel genetic strategies to manage insect vectors and the viruses they transmit.
PMID: 27442532 [PubMed - as supplied by publisher]
Metabolic traits of pathogenic streptococci.
Metabolic traits of pathogenic streptococci.
FEBS Lett. 2016 Jul 21;
Authors: Willenborg J, Goethe R
Abstract
Invasive and non-invasive diseases caused by facultative pathogenic streptococci depend on their equipment with virulence factors and on their ability to sense and adapt to changing nutrients in different host environments. The knowledge of the principal metabolic mechanisms which allow these bacteria to recognise and utilise nutrients in host habitats is a prerequisite for our understanding of streptococcal pathogenicity and the development of novel control strategies. This review aims to summarize and compare the central carbohydrate metabolic and amino acid biosynthetic pathways of a selected group of streptococcal species, all belonging to the naso-oropharyngeal microbiome in humans and/or animals. We also discuss the urgent need of comprehensive metabolomics approaches for a better understanding of the streptococcal metabolism during host-pathogen interaction. This article is protected by copyright. All rights reserved.
PMID: 27442496 [PubMed - as supplied by publisher]
Metabolic Profiles Reveal Changes in Wild and Cultivated Soybean Seedling Leaves under Salt Stress.
Metabolic Profiles Reveal Changes in Wild and Cultivated Soybean Seedling Leaves under Salt Stress.
PLoS One. 2016;11(7):e0159622
Authors: Zhang J, Yang D, Li M, Shi L
Abstract
Clarification of the metabolic mechanisms underlying salt stress responses in plants will allow further optimization of crop breeding and cultivation to obtain high yields in saline-alkali land. Here, we characterized 68 differential metabolites of cultivated soybean (Glycine max) and wild soybean (Glycine soja) under neutral-salt and alkali-salt stresses using gas chromatography-mass spectrometry (GC-MS)-based metabolomics, to reveal the physiological and molecular differences in salt tolerance. According to comparisons of growth parameters under the two kinds of salt stresses, the level of inhibition in wild soybean was lower than in cultivated soybean, especially under alkali-salt stress. Moreover, wild soybean contained significantly higher amounts of phenylalanine, asparagine, citraconic acid, citramalic acid, citric acid and α-ketoglutaric acid under neutral-salt stress, and higher amounts of palmitic acid, lignoceric acid, glucose, citric acid and α-ketoglutaric acid under alkali-salt stress, than cultivated soybean. Further investigations demonstrated that the ability of wild soybean to salt tolerance was mainly based on the synthesis of organic and amino acids, and the more active tricarboxylic acid cycle under neutral-salt stress. In addition, the metabolite profiling analysis suggested that the energy generation from β-oxidation, glycolysis and the citric acid cycle plays important roles under alkali-salt stress. Our results extend the understanding of mechanisms involved in wild soybean salt tolerance and provide an important reference for increasing yields and developing salt-tolerant soybean cultivars.
PMID: 27442489 [PubMed - as supplied by publisher]
Metabolite profiling study on the toxicological effects of polybrominated diphenyl ether in a rat model.
Metabolite profiling study on the toxicological effects of polybrominated diphenyl ether in a rat model.
Environ Toxicol. 2016 Jul 21;
Authors: Jung YS, Lee J, Seo J, Hwang GS
Abstract
Polybrominated diphenyl ethers (PBDEs) are commonly used to retard the combustion of materials such as foam padding, textiles, or plastics, and numerous studies have confirmed the accumulation thereof in the environment and in fish, mammals, and humans. In this study, we used metabolomics to conduct an environmental risk assessment of the PBDE-209. We profiled the urinary metabolites of control and PBDE-treated rats (exposed to PBDE-209) using nuclear magnetic resonance (NMR) and mass spectrometry (MS). Global metabolic profiling indicated that the effects of PBDE-209 on the urinary metabolic profile were not significant. However, targeted metabolic profiling revealed progressive effects of PBDE-209 over a 7-day PBDE-209 treatment. Moreover, despite the weak PBDE-209 effects, we observed that choline, acetylcholine, 3-indoxylsulfate, creatinine, urea, and dimethyl sulfone levels were decreased, whereas that of pyruvate was significantly increased. Furthermore, we suggest that the increased pyruvate level and decreased levels of choline, acetylcholine, and uremic toxins were suggestive of endocrine disruption and neurodevelopmental toxicity caused by PBDEs. © 2016 Wiley Periodicals, Inc. Environ Toxicol, 2016.
PMID: 27442109 [PubMed - as supplied by publisher]
Metabolic Profiling of Systemic Lupus Erythematosus and Comparison with Primary Sjögren's Syndrome and Systemic Sclerosis.
Metabolic Profiling of Systemic Lupus Erythematosus and Comparison with Primary Sjögren's Syndrome and Systemic Sclerosis.
PLoS One. 2016;11(7):e0159384
Authors: Bengtsson AA, Trygg J, Wuttge DM, Sturfelt G, Theander E, Donten M, Moritz T, Sennbro CJ, Torell F, Lood C, Surowiec I, Rännar S, Lundstedt T
Abstract
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease which can affect most organ systems including skin, joints and the kidney. Clinically, SLE is a heterogeneous disease and shares features of several other rheumatic diseases, in particular primary Sjögrens syndrome (pSS) and systemic sclerosis (SSc), why it is difficult to diagnose The pathogenesis of SLE is not completely understood, partly due to the heterogeneity of the disease. This study demonstrates that metabolomics can be used as a tool for improved diagnosis of SLE compared to other similar autoimmune diseases. We observed differences in metabolic profiles with a classification specificity above 67% in the comparison of SLE with pSS, SSc and a matched group of healthy individuals. Selected metabolites were also significantly different between studied diseases. Biochemical pathway analysis was conducted to gain understanding of underlying pathways involved in the SLE pathogenesis. We found an increased oxidative activity in SLE, supported by increased xanthine oxidase activity and an increased turnover in the urea cycle. The most discriminatory metabolite observed was tryptophan, with decreased levels in SLE patients compared to control groups. Changes of tryptophan levels were related to changes in the activity of the aromatic amino acid decarboxylase (AADC) and/or to activation of the kynurenine pathway.
PMID: 27441838 [PubMed - as supplied by publisher]
Comparative analysis of the proximate and elemental composition of the blue crab Callinectes sapidus, the warty crab Eriphia verrucosa, and the edible crab Cancer pagurus.
Comparative analysis of the proximate and elemental composition of the blue crab Callinectes sapidus, the warty crab Eriphia verrucosa, and the edible crab Cancer pagurus.
Heliyon. 2016 Feb;2(2):e00075
Authors: Zotti M, Coco LD, Pascali SA, Migoni D, Vizzini S, Mancinelli G, Fanizzi FP
Abstract
The proximate composition and element contents of claw muscle tissue of Atlantic blue crabs (Callinectes sapidus) were compared with the native warty crab (Eriphia verrucosa) and the commercially edible crab (Cancer pagurus). The scope of the analysis was to profile the chemical characteristics and nutritive value of the three crab species. Elemental fingerprints showed significant inter-specific differences, whereas non-significant variations in the moisture and ash contents were observed. In the blue crab, protein content was significantly lower than in the other two species, while its carbon content resulted lower than that characterizing only the warty crab. Among micro-elements, Ba, Cr, Cu, Li, Mn, Ni, and Pb showed extremely low concentrations and negligible among-species differences. Significant inter-specific differences were observed for Na, Sr, V, Ba, Cd and Zn; in particular, cadmium and zinc were characterized in the blue crab by concentrations significantly lower than in the other two species. The analysis of the available literature on the three species indicated a general lack of comparable information on their elemental composition. The need to implement extended elemental fingerprinting techniques for shellfish quality assessment is discussed, in view of other complementary profiling methods such as NMR-based metabolomics.
PMID: 27441254 [PubMed]
An Integrative Genetic Study of Rice Metabolism, Growth and Stochastic Variation Reveals Potential C/N Partitioning Loci.
An Integrative Genetic Study of Rice Metabolism, Growth and Stochastic Variation Reveals Potential C/N Partitioning Loci.
Sci Rep. 2016;6:30143
Authors: Li B, Zhang Y, Mohammadi SA, Huai D, Zhou Y, Kliebenstein DJ
Abstract
Studying the genetic basis of variation in plant metabolism has been greatly facilitated by genomic and metabolic profiling advances. In this study, we use metabolomics and growth measurements to map QTL in rice, a major staple crop. Previous rice metabolism studies have largely focused on identifying genes controlling major effect loci. To complement these studies, we conducted a replicated metabolomics analysis on a japonica (Lemont) by indica (Teqing) rice recombinant inbred line population and focused on the genetic variation for primary metabolism. Using independent replicated studies, we show that in contrast to other rice studies, the heritability of primary metabolism is similar to Arabidopsis. The vast majority of metabolic QTLs had small to moderate effects with significant polygenic epistasis. Two metabolomics QTL hotspots had opposing effects on carbon and nitrogen rich metabolites suggesting that they may influence carbon and nitrogen partitioning, with one locus co-localizing with SUSIBA2 (WRKY78). Comparing QTLs for metabolomic and a variety of growth related traits identified few overlaps. Interestingly, the rice population displayed fewer loci controlling stochastic variation for metabolism than was found in Arabidopsis. Thus, it is possible that domestication has differentially impacted stochastic metabolite variation more than average metabolite variation.
PMID: 27440503 [PubMed - in process]
Metabolomic analysis of percutaneous fine-needle aspiration specimens of thyroid nodules: Potential application for the preoperative diagnosis of thyroid cancer.
Metabolomic analysis of percutaneous fine-needle aspiration specimens of thyroid nodules: Potential application for the preoperative diagnosis of thyroid cancer.
Sci Rep. 2016;6:30075
Authors: Ryoo I, Kwon H, Kim SC, Jung SC, Yeom JA, Shin HS, Cho HR, Yun TJ, Choi SH, Sohn CH, Park S, Kim JH
Abstract
Thyroid nodules are a very common problem. Since malignant thyroid nodules should be treated surgically, preoperative diagnosis of thyroid cancer is very crucial. Cytopathologic analysis of percutaneous fine-needle aspiration (FNA) specimens is the current gold standard for diagnosing thyroid nodules. However, this method has led to high rates of inconclusive results. Metabolomics has emerged as a useful tool in medical fields and shown great potential in diagnosing various cancers. Here, we evaluated the potential of nuclear magnetic resonance (NMR) analysis of percutaneous FNA specimens for preoperative diagnosis of thyroid cancer. We analyzed metabolome of FNA samples of papillary thyroid carcinoma (n = 35) and benign follicular nodule (n = 69) using a proton NMR spectrometer. The metabolomic profiles showed a considerable discrimination between benign and malignant nodules. Receiver operating characteristic (ROC) curve analysis indicated that seven metabolites could serve as discriminators (area under ROC curve value, 0.64-0.85). These findings demonstrated that NMR analysis of percutaneous FNA specimens of thyroid nodules can be potentially useful in the accurate and rapid preoperative diagnosis of thyroid cancer.
PMID: 27440433 [PubMed - in process]
Biodiesel and poly-unsaturated fatty acids production from algae and crop plants - a rapid and comprehensive workflow for lipid analysis.
Biodiesel and poly-unsaturated fatty acids production from algae and crop plants - a rapid and comprehensive workflow for lipid analysis.
Biotechnol J. 2016 Jul 21;
Authors: Furuhashi T, Nakamura T, Fragner L, Roustan V, Schön V, Weckwerth W
Abstract
Fatty acid methyl ester analysis (FAME) by gas chromatography coupled to mass spectrometry (GC-MS) is a widely used technique in biodiesel/bioproduct (e.g. poly-unsaturated fatty acids (PUFA)) research but typically does not allow distinguishing between bound and free fatty acids. To understand and optimize biosynthetic pathways, however, the origin of the fatty acid is an important information. Furthermore the annotation of PUFAs is compromised in classical GC-EI-MS because the precursor molecular ion is missing. In the present protocol we combine an alkaline methyl esterification step with TMS derivatization enabling the simultaneous analysis of bound and free fatty acids but also further lipids such as sterols in one GC-MS chromatogram. We applied this protocol to different lipid extracts from single cell algae to higher plants: Chlorella vulgaris, Chlamydomonas reinhardtii, Coffea arabica, Pisum sativum and Cuscuta japonica. Further, field ionization (GC-FI-MS) is introduced for a better annotation of fatty acids and exact determination of the number of double bonds in PUFAs. The proposed workflow provides a convenient strategy to analyze algae and other plant crop systems with respect to their capacity for third generation biodiesel and high-quality bioproducts for nutrition such as PUFA's.
PMID: 27440175 [PubMed - as supplied by publisher]
Construction and Evaluation of an Organic Anion Transporter 1 (OAT1)-Centered Metabolic Network.
Construction and Evaluation of an Organic Anion Transporter 1 (OAT1)-Centered Metabolic Network.
J Biol Chem. 2016 Jul 20;
Authors: Liu HC, Jamshidi N, Chen Y, Eraly SA, Cho SY, Bhatnagar V, Wu W, Bush KT, Abagyan R, Palsson BO, Nigam SK
Abstract
There has been a recent interest in the broader physiological importance of multispecific drug transporters of the SLC and ABC transporter families. Here, a novel multi-tiered systems biology approach was used to predict metabolites and signaling molecules potentially affected by the in vivo deletion of organic anion transporter 1 (Oat1, Slc22a6, originally NKT), a major kidney-expressed drug transporter. Validation of some predictions in wet-lab assays, together with re-evaluation of existing transport and knockout metabolomics data, generated an experimentally-validated, confidence-ranked set of OAT1-interacting endogenous compounds enabling construction of an OAT1-centered metabolic interaction network. Pathway and enrichment analysis indicated an important role for OAT1 in metabolism involving: the TCA cycle, tryptophan and other amino acids, fatty acids, prostaglandins, cyclic nucleotides, odorants, polyamines, and vitamins. The partly-validated reconstructed network is also consistent with a major role for OAT1 in modulating metabolic and signaling pathways involving uric acid, gut microbiome products and so-called uremic toxins accumulating in chronic kidney disease (CKD). Together, the findings are compatible with the hypothesized role of drug transporters in remote inter-organ and inter-organismal communication (the Remote Sensing and Signaling Hypothesis, Nigam SK. 2015, Nature Rev Drug Disc 14:29). The fact that OAT1 can affect many systemic biological pathways suggests that drug-metabolite interactions (DMI) need to be considered beyond simple competition for the drug transporter itself and may explain aspects of drug-induced metabolic syndromes. Our approach should provide novel mechanistic insights into the role of OAT1 and other drug transporters implicated in metabolic diseases like gout, diabetes and CKD.
PMID: 27440044 [PubMed - as supplied by publisher]