-
1.
Untargeted metabolomics reveals plasma metabolites predictive of ectopic fat in pancreas and liver as assessed by magnetic resonance imaging: the TOFI_Asia study.
Wu, ZE, Fraser, K, Kruger, MC, Sequeira, IR, Yip, W, Lu, LW, Plank, LD, Murphy, R, Cooper, GJS, Martin, JC, et al
International journal of obesity (2005). 2021;(8):1844-1854
-
-
Free full text
-
Abstract
BACKGROUND Excess visceral obesity and ectopic organ fat is associated with increased risk of cardiometabolic disease. However, circulating markers for early detection of ectopic fat, particularly pancreas and liver, are lacking. METHODS Lipid storage in pancreas, liver, abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from 68 healthy or pre-diabetic Caucasian and Chinese women enroled in the TOFI_Asia study was assessed by magnetic resonance imaging/spectroscopy (MRI/S). Plasma metabolites were measured with untargeted liquid chromatography-mass spectroscopy (LC-MS). Multivariate partial least squares (PLS) regression identified metabolites predictive of VAT/SAT and ectopic fat; univariate linear regression adjusting for potential covariates identified individual metabolites associated with VAT/SAT and ectopic fat; linear regression adjusted for ethnicity identified clinical and anthropometric correlates for each fat depot. RESULTS PLS identified 56, 64 and 31 metabolites which jointly predicted pancreatic fat (R2Y = 0.81, Q2 = 0.69), liver fat (RY2 = 0.8, Q2 = 0.66) and VAT/SAT ((R2Y = 0.7, Q2 = 0.62)) respectively. Among the PLS-identified metabolites, none of them remained significantly associated with pancreatic fat after adjusting for all covariates. Dihydrosphingomyelin (dhSM(d36:0)), 3 phosphatidylethanolamines, 5 diacylglycerols (DG) and 40 triacylglycerols (TG) were associated with liver fat independent of covariates. Three DGs and 12 TGs were associated with VAT/SAT independent of covariates. Notably, comparison with clinical correlates showed better predictivity of ectopic fat by these PLS-identified plasma metabolite markers. CONCLUSIONS Untargeted metabolomics identified candidate markers of visceral and ectopic fat that improved fat level prediction over clinical markers. Several plasma metabolites were associated with level of liver fat and VAT/SAT ratio independent of age, total and visceral adiposity, whereas pancreatic fat deposition was only associated with increased sulfolithocholic acid independent of adiposity-related parameters, but not age.
-
2.
Determination of the Absolute Configuration of Bioactive Indole-Containing Pyrazino[2,1-b]quinazoline-3,6-diones and Study of Their In Vitro Metabolic Profile.
Long, S, Furlani, IL, Oliveira, JM, Resende, DISP, Silva, AMS, Gales, L, Pereira, JA, Kijjoa, A, Cass, QB, Oliveira, RV, et al
Molecules (Basel, Switzerland). 2021;(16)
Abstract
In recent decades, fungi-derived naturally occurring quinazolines have emerged as potential drug candidates. Nevertheless, most studies are conducted for bioactivity assays, and little is known about their absorption, distribution, metabolism, and elimination (ADME) properties. To perform metabolic studies, the synthesis of the naturally occurring quinazolinone, fiscalin B (1), and its chloro derivative, 4-((1H-indol-3-yl)methyl)-8,10-dichloro-1-isobutyl-1,2-dihydro-6H-pyrazino[2,1-b]quinazoline-3,6(4H)-dione (2), disclosed as an antibacterial agent, was performed in a gram scale using a microwave-assisted polycondensation reaction with 22% and 17% yields, respectively. The structure of the non-natural (+)-fiscalin B was established, for the first time, by X-ray crystallography as (1R,4S)-1, and the absolute configuration of the naturally occurring fiscalin B (-)-1 was confirmed by comparison of its calculated and experimental electronic circular dichroism (ECD) spectra as (1S,4R)-1. in vitro metabolic studies were monitored for this class of natural products for the first time by ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS). The metabolic characteristics of 1 and 2 in human liver microsomes indicated hydration and hydroxylation mass changes introduced to the parent drugs.
-
3.
Metabolic imaging of human cumulus cells reveals associations among metabolic profiles of cumulus cells, patient clinical factors, and oocyte maturity.
Venturas, M, Yang, X, Kumar, K, Wells, D, Racowsky, C, Needleman, DJ
Fertility and sterility. 2021;(6):1651-1662
Abstract
OBJECTIVE To determine whether fluorescence lifetime imaging microscopy (FLIM) detects differences in metabolic state among cumulus cell samples and whether their metabolic state is associated with patient age, body mass index (BMI), and antimüllerian hormone (AMH) level and maturity of the oocyte. DESIGN Prospective observational study. SETTING Academic laboratory. PATIENT(S): Cumulus cell (CC) clusters from cumulus-oocyte complexes were collected from patients undergoing assisted reproductive technology treatment after oocyte retrieval and vitrified. INTERVENTION(S): Cumulus cell metabolism was assessed using FLIM to measure autofluorescence of nicotinamide adenine (phosphate) dinucleotide and flavine adenine dinucleotide, endogenous coenzymes essential for cellular respiration and glycolysis. Patient age, BMI, and AMH level and the maturity of the corresponding oocytes were recorded. MAIN OUTCOME MEASURE(S): Quantitative information from FLIM was obtained regarding metabolite concentrations from fluorescence intensity and metabolite enzyme engagement from fluorescence lifetimes. Associations were investigated between each FLIM parameter and oocyte maturity and patient age, BMI, and AMH. Variance between CC clusters within and between patients was determined. RESULT(S): Of 619 CC clusters from 193 patients, 90 were associated with immature oocytes and 505 with metaphase II oocytes. FLIM enabled quantitative measurements of the metabolic state of CC clusters. These parameters were significantly correlated with patient age and AMH independently, but not with BMI. Cumulus cell nicotinamide adenine (phosphate) dinucleotide FLIM parameters and redox ratio were significantly associated with maturity of the enclosed oocyte. CONCLUSION(S): FLIM detects variations in the metabolic state of CCs, showing a greater variance among clusters from each patient than between patients. Fluorescence lifetime imaging microscopy can detect CC metabolic associations with patient age and AMH and variations between mature and immature oocytes, suggesting the potential utility of this technique to help identify superior oocytes.
-
4.
Crosstalk among intestinal barrier, gut microbiota and serum metabolome after a polyphenol-rich diet in older subjects with "leaky gut": The MaPLE trial.
Peron, G, Gargari, G, Meroño, T, Miñarro, A, Lozano, EV, Escuder, PC, González-Domínguez, R, Hidalgo-Liberona, N, Del Bo', C, Bernardi, S, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(10):5288-5297
Abstract
BACKGROUND &AIM: The MaPLE study was a randomized, controlled, crossover trial involving adults ≥60 y.o. (n = 51) living in a residential care facility during an 8-week polyphenol-rich (PR)-diet. Results from the MaPLE trial showed that the PR-diet reduced the intestinal permeability (IP) in older adults by inducing changes to gut microbiota (GM). The present work aimed at studying the changes in serum metabolome in the MaPLE trial, as a further necessary step to depict the complex crosstalk between dietary polyphenols, GM, and intestinal barrier. METHODS Serum metabolome was monitored using a semi-targeted UHPLC-MS/MS analysis. Metataxonomic analysis (16S rRNA gene profiling) of GM was performed on faecal samples. Clinical characteristics and serum levels of the IP marker zonulin were linked to GM and metabolomics data in a multi-omics network. RESULTS Compared to the control diet, the PR-diet increased serum metabolites related to polyphenols and methylxanthine intake. Theobromine and methylxanthines, derived from cocoa and/or green tea, were positively correlated with butyrate-producing bacteria (the order Clostridiales and the genera Roseburia, Butyricicoccus and Faecalibacterium) and inversely with zonulin. A direct correlation between polyphenol metabolites hydroxyphenylpropionic acid-sulfate, 2-methylpyrogallol-sulfate and catechol-sulfate with Butyricicoccus was also observed, while hydroxyphenylpropionic acid-sulfate and 2-methylpyrogallol-sulfate negatively correlated with Methanobrevibacter. The multi-omics network indicated that participant's age, baseline zonulin levels, and changes in Porphyromonadaceae abundance were the main factors driving the effects of a PR-diet on zonulin. CONCLUSION Overall, these results reveal the complex relationships among polyphenols consumption, intestinal permeability, and GM composition in older adults, and they may be important when setting personalized dietary interventions for older adults. TRIAL REGISTRATION NUMBER ISRCTN10214981.
-
5.
Metabolite reanalysis revealed potential biomarkers for COVID-19: a potential link with immune response.
Chen, X, Gu, M, Li, T, Sun, Y
Future microbiology. 2021;:577-588
Abstract
Aim: To understand the pathological progress of COVID-19 and to explore the potential biomarkers. Background: The COVID-19 pandemic is ongoing. There is metabolomics research about COVID-19 indicating the rich information of metabolomics is worthy of further data mining. Methods: We applied bioinformatics technology to reanalyze the published metabolomics data of COVID-19. Results: Benzoate, β-alanine and 4-chlorobenzoic acid were first reported to be used as potential biomarkers to distinguish COVID-19 patients from healthy individuals; taurochenodeoxycholic acid 3-sulfate, glucuronate and N,N,N-trimethyl-alanylproline betaine TMAP are the top classifiers in the receiver operating characteristic curve of COVID-severe and COVID-nonsevere patients. Conclusion: These unique metabolites suggest an underlying immunoregulatory treatment strategy for COVID-19.
-
6.
ZnO nanoparticle-based seed priming modulates early growth and enhances physio-biochemical and metabolic profiles of fragrant rice against cadmium toxicity.
Li, Y, Liang, L, Li, W, Ashraf, U, Ma, L, Tang, X, Pan, S, Tian, H, Mo, Z
Journal of nanobiotechnology. 2021;(1):75
Abstract
BACKGROUND Cadmium (Cd) is amongst the most toxic heavy metals that severely affects crop growth, whereas application of nanoparticles (NPs) to negate the toxic effects of heavy metals could be an effective management approach. In the present study, the seeds of two fragrant rice varieties i.e., Yuxiangyouzhan and Xiangyaxiangzhan under normal and Cd stress conditions i.e., 0 and 100 mg L- 1 applied with four levels of ZnO NPs i.e., 0, 25, 50, and 100 mg L- 1. RESULTS Seed priming with ZnO NPs had no significant effect on the seed germination (p > 0.05) however, it substantially improved the seedling growth and other related physiological attributes under the Cd stress. The mean fresh weight of the shoot, and whole seedling was increased by 16.92-27.88% and by 16.92-27.88% after ZnO NPs application. The root fresh weight, root-shoot length was also substantially improved under ZnO NPs treatment. Moreover, application of ZnO NPs induced modulations in physiological and biochemical attributes e.g., the superoxide dismutase (SOD) activity in root and shoot, the peroxidase (POD) activity and metallothionein contents in root were increased under low levels of ZnO NPs. The α-amylase and total amylase activity were improved by ZnO NPs application under Cd Stress. Besides, modulation in Zn concentration and ZnO NPs uptake in the seedling were detected. The metabolomic analysis indicated that various pathways such as alanine, aspartate and glutamate metabolism, phenylpropanoid biosynthesis, and taurine and hypotaurine metabolism were possibly important for rice response to ZnO NPs and Cd. CONCLUSION Overall, application of ZnO NPs substantially improved the early growth and related physio-biochemical attributes in rice. Our findings provide new insights regarding the effects of ZnO NPs on seed germination, and early growth of rice, and its potential applications in developing crop resilience against Cd contaminated soils.
-
7.
Effect of Dapagliflozin on Urine Metabolome in Patients with Type 2 Diabetes.
Bletsa, E, Filippas-Dekouan, S, Kostara, C, Dafopoulos, P, Dimou, A, Pappa, E, Chasapi, S, Spyroulias, G, Koutsovasilis, A, Bairaktari, E, et al
The Journal of clinical endocrinology and metabolism. 2021;(5):1269-1283
-
-
Free full text
-
Abstract
CONTEXT Inhibitors of sodium-glucose cotransporters-2 have cardio- and renoprotective properties. However, the underlying mechanisms remain indeterminate. OBJECTIVE To evaluate the effect of dapagliflozin on renal metabolism assessed by urine metabolome analysis in patients with type 2 diabetes. DESIGN Prospective cohort study. SETTING Outpatient diabetes clinic of a tertiary academic center. PATIENTS Eighty patients with hemoglobin A1c > 7% on metformin monotherapy were prospectively enrolled. INTERVENTION Fifty patients were treated with dapagliflozin for 3 months. To exclude that the changes observed in urine metabolome were merely the result of the improvement in glycemia, 30 patients treated with insulin degludec were used for comparison. MAIN OUTCOME MEASURE Changes in urine metabolic profile before and after the administration of dapagliflozin and insulin degludec were assessed by proton-nuclear magnetic resonance spectroscopy. RESULTS In multivariate analysis urine metabolome was significantly altered by dapagliflozin (R2X = 0.819, R2Y = 0.627, Q2Y = 0.362, and coefficient of variation analysis of variance, P < 0.001) but not insulin. After dapagliflozin, the urine concentrations of ketone bodies, lactate, branched chain amino acids (P < 0.001), betaine, myo-inositol (P < 0001), and N-methylhydantoin (P < 0.005) were significantly increased. Additionally, the urine levels of alanine, creatine, sarcosine, and citrate were also increased (P < 0001, P <0.0001, and P <0.0005, respectively) whereas anserine decreased (P < 0005). CONCLUSIONS Dapagliflozin significantly affects urine metabolome in patients with type 2 diabetes in a glucose lowering-independent way. Most of the observed changes can be considered beneficial and may contribute to the renoprotective properties of dapagliflozin.
-
8.
Metabolomics in Diabetic Retinopathy: A Systematic Review.
Hou, XW, Wang, Y, Pan, CW
Investigative ophthalmology & visual science. 2021;(10):4
-
-
Free full text
-
Abstract
PURPOSE Diabetic retinopathy (DR), a common microvascular complication of diabetes, is the leading cause of acquired blindness in the working-age population. Individuals with diabetes still develop DR despite appropriate glycemic and blood pressure control, highlighting the pressing need to identify useful biomarkers for risk stratification. The purpose of this review is to systematically summarize potential metabolic biomarkers and pathways of DR, which could facilitate developing an understanding of the disease mechanisms, as well as new therapeutic measures. METHODS We searched PubMed and Web of Science for relevant metabolomics studies on humans published before September 30, 2020. Information regarding authors, title, publication date, study subjects, analytical platforms, methods of statistical analysis, biological samples, directions of change of potential metabolic biomarkers, and predictive values of metabolic biomarker panels was extracted, and the quality of the studies was assessed. Pathway analysis, including enrichment analysis and topology analysis, was derived from integrating differential metabolites using MetaboAnalyst 3.0, based on the Kyoto Encyclopedia of Genes and Genomes and Human Metabolome Database. RESULTS We found nine studies focused on the identification of potential biomarkers. Repeatedly identified metabolites including l-glutamine, l-lactic acid, pyruvic acid, acetic acid, l-glutamic acid, d-glucose, l-alanine, l-threonine, citrulline, l-lysine, and succinic acid were found to be potential biomarkers of DR. It was observed that l-glutamine and citrulline changed in all biological samples. Dysregulation of metabolic pathways involved amino acid and energy metabolism. CONCLUSIONS This review summarizes potential biomarkers and metabolic pathways, providing insights into new pathogenic pathways for this microvascular complication of diabetes.
-
9.
Resolving trained immunity with systems biology.
Koeken, VACM, van Crevel, R, Netea, MG, Li, Y
European journal of immunology. 2021;(4):773-784
Abstract
Trained immunity is characterized by long-term functional reprogramming of innate immune cells following challenge with pathogens or microbial ligands during infection or vaccination. This cellular reprogramming leads to increased responsiveness upon restimulation, and is mediated through epigenetic and metabolic modifications. In this review, we describe how molecular mechanisms underlying trained immunity, for example, induced by β-glucan or Bacille Calmette-Guérin (BCG) vaccination, can be investigated by using and integrating different layers of information including genome, epigenome, transcriptome, proteome, metabolome, microbiome, immune cell phenotyping, and function. We also describe the most commonly used experimental and computational techniques. Finally, we provide a number of examples of how a systems biology approach was applied to study trained immunity to understand interindividual variation or the complex interplay between molecular layers. In conclusion, trained immunity represents an opportunity for regulating innate immune function, and understanding the complex interplay of mechanisms that mediate trained immunity might enable us to employ it as a clinical tool in the future.
-
10.
Serum metabolite profiling yields insights into health promoting effect of A. muciniphila in human volunteers with a metabolic syndrome.
Depommier, C, Everard, A, Druart, C, Maiter, D, Thissen, JP, Loumaye, A, Hermans, MP, Delzenne, NM, de Vos, WM, Cani, PD
Gut microbes. 2021;(1):1994270
-
-
Free full text
-
Abstract
Reduction of A. muciniphila relative abundance in the gut microbiota is a widely accepted signature associated with obesity-related metabolic disorders. Using untargeted metabolomics profiling of fasting plasma, our study aimed at identifying metabolic signatures associated with beneficial properties of alive and pasteurized A. muciniphila when administrated to a cohort of insulin-resistant individuals with metabolic syndrome. Our data highlighted either shared or specific alterations in the metabolome according to the form of A. muciniphila administered with respect to a control group. Common responses encompassed modulation of amino acid metabolism, characterized by reduced levels of arginine and alanine, alongside several intermediates of tyrosine, phenylalanine, tryptophan, and glutathione metabolism. The global increase in levels of acylcarnitines together with specific modulation of acetoacetate also suggested induction of ketogenesis through enhanced β-oxidation. Moreover, our data pinpointed some metabolites of interest considering their emergence as substantial compounds pertaining to health and diseases in the more recent literature.